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PMID:13425 | Packaging of genomes in bacteriophages: a comparison of ssRNA bacteriophages and dsDNA bacteriophages. | In complex DNA bacteriophages like lambda, T4, T7, P22, P2, the DNA is packaged into a preformed precursor particle which sometimes has a smaller size and often a shape different from that of the phage head. This packaging mechanism is different from the one suggested for the RNA phages, according to which RNA nucleates the shell formation. The different mechanisms could be understood by comparing the genomes to be packaged: single stranded fII RNA has a very compact structure with high helix content. It might easily form quasispherical structures in solution (as seen in the electron microscope by Thach & Thach (1973)) around which the capsid could assemble. Double stranded phage DNA, on the other hand, is a rigid molecule which occupies a large volume in solution and has to be concentrated 15-fold during packaging into the preformed capsid, and the change in the capsid structure observed hereby might provide the necessary DNA condensation energy. | Packaging of genomes in bacteriophages: a comparison of ssRNA bacteriophages and dsDNA bacteriophages. In complex DNA bacteriophages like lambda, T4, T7, P22, P2, the DNA is packaged into a preformed precursor particle which sometimes has a smaller size and often a shape different from that of the phage head. This packaging mechanism is different from the one suggested for the RNA phages, according to which RNA nucleates the shell formation. The different mechanisms could be understood by comparing the genomes to be packaged: single stranded fII RNA has a very compact structure with high helix content. It might easily form quasispherical structures in solution (as seen in the electron microscope by Thach & Thach (1973)) around which the capsid could assemble. Double stranded phage DNA, on the other hand, is a rigid molecule which occupies a large volume in solution and has to be concentrated 15-fold during packaging into the preformed capsid, and the change in the capsid structure observed hereby might provide the necessary DNA condensation energy. | [
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PMID:13426 | Studies on the maturation of the head of bacteriophage T4. | The presentation focuses on the structural rearrangements of the subunits and the processing of the various protein constituents which accompany the maturation events of the head of bacteriophage T4. The major features of the maturation steps of the head are the following: (a) the viral DNA is pulled into an empty head in a series of events; (b) cleavage of two core proteins, P22 (mol. mass = 31000), to small fragments and the internal protein IPIII (mol. mass = 23000) to IPIII (mol. mass = 21000) appears to be intimately linked to the DNA packaging event, whereas the cleavage of the major head protein of the viral coat, P23 (mol. mass = 55000), to P23 (mol. mass = 45000) precedes the DNA packaging event. Recently, we have obtained information about the mechanism by which the viral DNA is pulled into a preformed empty head. Our evidence suggests that the DNA becomes attached to the inside of the empty head and is subsequently collapsed in the interior by the so-called internal peptides. These are highly acidic and derived from a large precursor protein by cleavage. | Studies on the maturation of the head of bacteriophage T4. The presentation focuses on the structural rearrangements of the subunits and the processing of the various protein constituents which accompany the maturation events of the head of bacteriophage T4. The major features of the maturation steps of the head are the following: (a) the viral DNA is pulled into an empty head in a series of events; (b) cleavage of two core proteins, P22 (mol. mass = 31000), to small fragments and the internal protein IPIII (mol. mass = 23000) to IPIII (mol. mass = 21000) appears to be intimately linked to the DNA packaging event, whereas the cleavage of the major head protein of the viral coat, P23 (mol. mass = 55000), to P23 (mol. mass = 45000) precedes the DNA packaging event. Recently, we have obtained information about the mechanism by which the viral DNA is pulled into a preformed empty head. Our evidence suggests that the DNA becomes attached to the inside of the empty head and is subsequently collapsed in the interior by the so-called internal peptides. These are highly acidic and derived from a large precursor protein by cleavage. | [
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|
PMID:13427 | Assembly of tobacco mosaic virus. | The assembly of tobacco mosaic virus requires the presence of a particular protein aggregate, the disk. During the nucleation, a specific region of the RNA interacts with a single disk, to bring about a necessarily cooperative transition from the paired two-layer structure to a short segment of nucleo-protein helix. There is a high selectivity for this region of the TMV RNA, because of the many nucleotides bound at once, and other nucleotide sequences appear only to bind by a different mechanism. Elongation of the nucleated rods can continue with either further disks or the less aggregated 'A-protein' as the protein source, but the continued cooperativity inherent with disks would have some advantages. The rates of the two processes have been separately determined and growth is faster when disks are still present. New experiments show that the breakdown of disks to yield A-protein is relatively slow and it is concluded that virus growth from disks could not proceed through a prior breakdown in solution, but must involve the direct interaction of the disk with the growing nucleoprotein rod. The detailed mechanism of disk addition is not understood but it may involve a directed breakdown, since there is also evidence for the existence of a non-equilibrium form of A-protein which has aggregation kinetics distinct from those of equilibrium A-protein. Some implications for the general assembly pathways of viruses both of the specificity and of the assembly/disassembly cycle during the viral infection are considered. | Assembly of tobacco mosaic virus. The assembly of tobacco mosaic virus requires the presence of a particular protein aggregate, the disk. During the nucleation, a specific region of the RNA interacts with a single disk, to bring about a necessarily cooperative transition from the paired two-layer structure to a short segment of nucleo-protein helix. There is a high selectivity for this region of the TMV RNA, because of the many nucleotides bound at once, and other nucleotide sequences appear only to bind by a different mechanism. Elongation of the nucleated rods can continue with either further disks or the less aggregated 'A-protein' as the protein source, but the continued cooperativity inherent with disks would have some advantages. The rates of the two processes have been separately determined and growth is faster when disks are still present. New experiments show that the breakdown of disks to yield A-protein is relatively slow and it is concluded that virus growth from disks could not proceed through a prior breakdown in solution, but must involve the direct interaction of the disk with the growing nucleoprotein rod. The detailed mechanism of disk addition is not understood but it may involve a directed breakdown, since there is also evidence for the existence of a non-equilibrium form of A-protein which has aggregation kinetics distinct from those of equilibrium A-protein. Some implications for the general assembly pathways of viruses both of the specificity and of the assembly/disassembly cycle during the viral infection are considered. | [
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|
PMID:13428 | Tobacco rattle virus RNA-protein interactions. | For the purpose of attempting to generalize the rules concerning morphogenesis of helical viruses, the in vitro reconstitution of the CAM strain of TRV was studied. The conditions for reconstitution and the importance of the aggregation state of the protein for initiation and elongation are compared with those of TMV. The initiation step consisting of the binding of RNA with the 36S disk of protein was easily accomplished. The polarity and the specificity of encapsidation of TRV RNA by homologous and heterologous viral protein is discussed. | Tobacco rattle virus RNA-protein interactions. For the purpose of attempting to generalize the rules concerning morphogenesis of helical viruses, the in vitro reconstitution of the CAM strain of TRV was studied. The conditions for reconstitution and the importance of the aggregation state of the protein for initiation and elongation are compared with those of TMV. The initiation step consisting of the binding of RNA with the 36S disk of protein was easily accomplished. The polarity and the specificity of encapsidation of TRV RNA by homologous and heterologous viral protein is discussed. | [
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|
PMID:13429 | Assembly of flexuous plant viruses and their proteins. | Recent experiments on the disassembly and assembly of some flexuous plant viruses and their proteins are described. The properties of reconstituted potato virus X and those of assembled potato virus Y protein are considered as well as the suitability of other flexuous viruses for reconstitution studies. | Assembly of flexuous plant viruses and their proteins. Recent experiments on the disassembly and assembly of some flexuous plant viruses and their proteins are described. The properties of reconstituted potato virus X and those of assembled potato virus Y protein are considered as well as the suitability of other flexuous viruses for reconstitution studies. | [
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PMID:13430 | Specific encapsidation of fragments of TMV RNA. | The in vitro reconstitution of tobacco mosaic virus (TMV) is initiated by the binding of a disk of TMV protein to the 'disk recognition site', a region of the RNA chain at or near the 5'-terminus for which the disk has special affinity. In order to gain insight into the recognition process, we have studied the ability of disks to encapsidate short RNA fragments produced by partial pancreatic or T1 RNase digestion of TMV RNA. The disk is capable of dicriminating among such fragments, encapsidating only a few of the many present in the digest. The products of encapsidation are short nucleoprotein rods of the same diameter as TMV and of length proportional to that of the encapsidated RNA fragment. The particles differ from TMV, however, in one significant aspect (apart from their length): they possess rings of RNA-free protein at one or both extremities of the rod. In the case of T1 RNase digestion the principal encapsidated fragments were fragments T1 (105 nucleotides) and a family of smaller fragments containing elements of the same sequence. Partial digestion with pancreatic RNase generated only one major fragment (fragment P1; 150 nucleotides) with affinity for the disk. Fragment T1 has been sequenced and shown to represent a portion of the coat protein cistron. Fragment P1 has been partially sequenced but its function is not yet known. Several lines of evidence indicate that fragment T1 is not the disk recognition site. The portion of the TMV RNA chain from which fragment P1 is derived, on the other hand, is encapsidated early in the reconstitution process; thus fragment P1 may contain the disk recognition site. Fragment T1 and fragment P1 both have purine-rich and cytosine-poor sequences near their termini. In addition, fragment T1, and possibly fragment P1, possess a periodicity of order three in purine residues. It seems likely that one or both of the aforesaid properties are largely responsible for the affinity of these fragments for the disk. | Specific encapsidation of fragments of TMV RNA. The in vitro reconstitution of tobacco mosaic virus (TMV) is initiated by the binding of a disk of TMV protein to the 'disk recognition site', a region of the RNA chain at or near the 5'-terminus for which the disk has special affinity. In order to gain insight into the recognition process, we have studied the ability of disks to encapsidate short RNA fragments produced by partial pancreatic or T1 RNase digestion of TMV RNA. The disk is capable of dicriminating among such fragments, encapsidating only a few of the many present in the digest. The products of encapsidation are short nucleoprotein rods of the same diameter as TMV and of length proportional to that of the encapsidated RNA fragment. The particles differ from TMV, however, in one significant aspect (apart from their length): they possess rings of RNA-free protein at one or both extremities of the rod. In the case of T1 RNase digestion the principal encapsidated fragments were fragments T1 (105 nucleotides) and a family of smaller fragments containing elements of the same sequence. Partial digestion with pancreatic RNase generated only one major fragment (fragment P1; 150 nucleotides) with affinity for the disk. Fragment T1 has been sequenced and shown to represent a portion of the coat protein cistron. Fragment P1 has been partially sequenced but its function is not yet known. Several lines of evidence indicate that fragment T1 is not the disk recognition site. The portion of the TMV RNA chain from which fragment P1 is derived, on the other hand, is encapsidated early in the reconstitution process; thus fragment P1 may contain the disk recognition site. Fragment T1 and fragment P1 both have purine-rich and cytosine-poor sequences near their termini. In addition, fragment T1, and possibly fragment P1, possess a periodicity of order three in purine residues. It seems likely that one or both of the aforesaid properties are largely responsible for the affinity of these fragments for the disk. | [
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|
PMID:13431 | The region of tobacco mosaic virus RNA involved in the nucleation of assembly. | The interaction of TMV RNA with the disk aggregate of TMV protein at the initiation of assembly has been studied by using the techniques of RNA sequencing. The 5' end group has been identified, and shown not to be protected in the early stages of assembly from accessibility to nuclease digestion. A population of RNA fragments of average length 250 nucleotides, originating from a unique region of TMV RNA, is encapsidated by limited assembly, and sufficient sequence information is available to identify certain unusual features. The protected region does not contain highly reiterated simple repeating sequences, but may contain more complicated repeats. The length and complexity of the nucleation region may reflect adaptation to the efficient mediation of the conformational change from disk to helix of TMV protein, besides a requirement for binding to the disk, and this may be an important part of the mechanism of specificity in the nucleation of assembly. | The region of tobacco mosaic virus RNA involved in the nucleation of assembly. The interaction of TMV RNA with the disk aggregate of TMV protein at the initiation of assembly has been studied by using the techniques of RNA sequencing. The 5' end group has been identified, and shown not to be protected in the early stages of assembly from accessibility to nuclease digestion. A population of RNA fragments of average length 250 nucleotides, originating from a unique region of TMV RNA, is encapsidated by limited assembly, and sufficient sequence information is available to identify certain unusual features. The protected region does not contain highly reiterated simple repeating sequences, but may contain more complicated repeats. The length and complexity of the nucleation region may reflect adaptation to the efficient mediation of the conformational change from disk to helix of TMV protein, besides a requirement for binding to the disk, and this may be an important part of the mechanism of specificity in the nucleation of assembly. | [
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|
PMID:13432 | Structure and assembly of phage phi29. | Bacteriophage phi29 is a small, morphologically complex, virus with a DNA of molecular mass 12 X 10(6). The most likely structure of the head of phi29 consists of two fivefold symmetric end-caps based on T = 1 icosahedral symmetry, separated by an equatorial row of 5 hexamers. The eighteen genes identified in phi29 genome have been mapped and, in some cases, the gene products have been identified. Five linked genes, four coding for structural proteins (G, A, E, H) and one coding for a non-structural protein (J), are essential to determine the normal shape of the capsid. Protein pJ may be a scaffolding protein. An account of the effects of mutations in phi29 genes is given. | Structure and assembly of phage phi29. Bacteriophage phi29 is a small, morphologically complex, virus with a DNA of molecular mass 12 X 10(6). The most likely structure of the head of phi29 consists of two fivefold symmetric end-caps based on T = 1 icosahedral symmetry, separated by an equatorial row of 5 hexamers. The eighteen genes identified in phi29 genome have been mapped and, in some cases, the gene products have been identified. Five linked genes, four coding for structural proteins (G, A, E, H) and one coding for a non-structural protein (J), are essential to determine the normal shape of the capsid. Protein pJ may be a scaffolding protein. An account of the effects of mutations in phi29 genes is given. | [
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PMID:13433 | DNA viruses: cooperativity and regulation through conformational changes as features of phage assembly. | The assembly of bacteriophages provides experimental model systems for the study of regulation at the level of gene products. We discuss the hypothesis of regulation through sequentially induced conformational changes by which precursor-assemblies become ready at a specific stage of maturation to interact with an additional gene product or nucleic acids. Phage mutants provide excellent experimental model systems for studying, for example, the role and fate of the core in the prehead assembly. The conservative maturation of the prehead to the final, stable head consists of several steps whose complexity reflect that of the virus. It includes packaging of DNA. The surface lattice of maturing preheads apparently undergoes several steps characterized by different conformational states as suggested by in vitro studies on a morphological variant of the prehead, the polyhead of phage T4 (Steven, Couture, Aebi & Showe 1976; Laemmli, Amos & Klug 1976). Addition of a partly purified, enriched proteolytic fraction--which is gene 21-dependent--to empty purified polyheads leads to different conformational states. These seem to go in a direction approaching the structure of the surface of finished capsids as studied by Aebi et al. on gene 24 related (Bijlenga, Aebi & Kellenberger 1976) and other genetically defined giant-variants of T4 phage (Doermann, Eiserling & Boehner 1973). We show some experiments which suggest that high cooperativity is responsible for the stabilization of capsids. The activation energy necessary for dissociation of capsids is very high, 247 kJ for T4 capsids, and 10% smaller for T2. Once the energy barrier has been overcome, the capsids are first structurally modified before they undergo partial and finally complete dissociation. | DNA viruses: cooperativity and regulation through conformational changes as features of phage assembly. The assembly of bacteriophages provides experimental model systems for the study of regulation at the level of gene products. We discuss the hypothesis of regulation through sequentially induced conformational changes by which precursor-assemblies become ready at a specific stage of maturation to interact with an additional gene product or nucleic acids. Phage mutants provide excellent experimental model systems for studying, for example, the role and fate of the core in the prehead assembly. The conservative maturation of the prehead to the final, stable head consists of several steps whose complexity reflect that of the virus. It includes packaging of DNA. The surface lattice of maturing preheads apparently undergoes several steps characterized by different conformational states as suggested by in vitro studies on a morphological variant of the prehead, the polyhead of phage T4 (Steven, Couture, Aebi & Showe 1976; Laemmli, Amos & Klug 1976). Addition of a partly purified, enriched proteolytic fraction--which is gene 21-dependent--to empty purified polyheads leads to different conformational states. These seem to go in a direction approaching the structure of the surface of finished capsids as studied by Aebi et al. on gene 24 related (Bijlenga, Aebi & Kellenberger 1976) and other genetically defined giant-variants of T4 phage (Doermann, Eiserling & Boehner 1973). We show some experiments which suggest that high cooperativity is responsible for the stabilization of capsids. The activation energy necessary for dissociation of capsids is very high, 247 kJ for T4 capsids, and 10% smaller for T2. Once the energy barrier has been overcome, the capsids are first structurally modified before they undergo partial and finally complete dissociation. | [
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PMID:13434 | Structure and assembly of the capsid of bacteriophage P22. | Identification of the genes and proteins involved in phage P22 formation has permitted a detailed analysis of particle assembly, revealing some unexpected aspects. The polymerization of the major coat protein (gene 5 product) into an organized capsid is directed by a scaffolding protein (gene 8 product) which is absent from mature phage. The resulting capsid structure (prohead) is the precursor for DNA encapsidation. All of the scaffolding protein exits from the prohead in association with DNA packaging. These molecules then recycle, directing further rounds of prohead assembly. The structure of the prohead has been studied by electron microscopy of thin sections of phage infected cells, and by low angle X-ray scattering of concentrated particles. The results show that the prohead is a double shell structure, or a ball within a shell. The inner ball or shell is composed of the scaffolding protein while the outer shell is composed of coat protein. The conversion from prohead to mature capsid is associated with an expansion of the coat protein shell. It is possible that the scaffolding protein molecules exit through the capsid lattice. When DNA encapsidation within infected cells is blocked by mutation, scaffolding protein is trapped in proheads and cannot recycle. Under these conditions, the rate of synthesis of gp8 increases, so that normal proheads continue to form. These results suggest that free scaffolding protein negatively regulates its own further synthesis, providing a coupling between protein synthesis and protein assembly. | Structure and assembly of the capsid of bacteriophage P22. Identification of the genes and proteins involved in phage P22 formation has permitted a detailed analysis of particle assembly, revealing some unexpected aspects. The polymerization of the major coat protein (gene 5 product) into an organized capsid is directed by a scaffolding protein (gene 8 product) which is absent from mature phage. The resulting capsid structure (prohead) is the precursor for DNA encapsidation. All of the scaffolding protein exits from the prohead in association with DNA packaging. These molecules then recycle, directing further rounds of prohead assembly. The structure of the prohead has been studied by electron microscopy of thin sections of phage infected cells, and by low angle X-ray scattering of concentrated particles. The results show that the prohead is a double shell structure, or a ball within a shell. The inner ball or shell is composed of the scaffolding protein while the outer shell is composed of coat protein. The conversion from prohead to mature capsid is associated with an expansion of the coat protein shell. It is possible that the scaffolding protein molecules exit through the capsid lattice. When DNA encapsidation within infected cells is blocked by mutation, scaffolding protein is trapped in proheads and cannot recycle. Under these conditions, the rate of synthesis of gp8 increases, so that normal proheads continue to form. These results suggest that free scaffolding protein negatively regulates its own further synthesis, providing a coupling between protein synthesis and protein assembly. | [
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PMID:13435 | Capsid transformation during packaging of bacteriophage lambdaDNA. | Assembly pathways of complex viruses might not be simple additions of one protein after another with rigid tertiary structure. It might in fact involve shifts in subunit structure, movement of subunits relative to each other to form new arrangements, transient action of proteins and protein segments, involvement of structure forming 'microenvironments' of the host. Thus morphogenesis of the bacteriophage lambda head starts with the formation of a core-containing DNA-free petit lambda particle. In a first transition, and dependent on a host function, the core is released, minor protein components of the capsid are processed and the particle's structure is altered, as shown by a change of its hydrodynamic properties. The resulting 'prehead' undergoes a second transition triggered by a complex of DNA and recognition protein (A-protein). This transition is more drastic than the first one. The particle doubles its volume without increasing in protein mass, the shell becomes thinner, and the surface structure is changed. Concomitantly with this process, the DNA becomes packaged and the particle becomes able to bind the small 'D-protein' in amounts equimolar to the capsid protein, which it could not do before. The D-protein addition probably causes another shift of the capsid structure. DNA packaging is completed, and the DNA is cut from concatemeric precursors to unit length molecules. Binding sites are created for the tail connector molecules which in turn allow the independently assembled tail to attach. Research on these processes proceeds along several lines: comparison of physical and chemical properties of particles accumulating in mutants; pulse-chase experiments on assembly precursors; morphogenesis in vitro; and model transitions of aberrant lambda polyheads. | Capsid transformation during packaging of bacteriophage lambdaDNA. Assembly pathways of complex viruses might not be simple additions of one protein after another with rigid tertiary structure. It might in fact involve shifts in subunit structure, movement of subunits relative to each other to form new arrangements, transient action of proteins and protein segments, involvement of structure forming 'microenvironments' of the host. Thus morphogenesis of the bacteriophage lambda head starts with the formation of a core-containing DNA-free petit lambda particle. In a first transition, and dependent on a host function, the core is released, minor protein components of the capsid are processed and the particle's structure is altered, as shown by a change of its hydrodynamic properties. The resulting 'prehead' undergoes a second transition triggered by a complex of DNA and recognition protein (A-protein). This transition is more drastic than the first one. The particle doubles its volume without increasing in protein mass, the shell becomes thinner, and the surface structure is changed. Concomitantly with this process, the DNA becomes packaged and the particle becomes able to bind the small 'D-protein' in amounts equimolar to the capsid protein, which it could not do before. The D-protein addition probably causes another shift of the capsid structure. DNA packaging is completed, and the DNA is cut from concatemeric precursors to unit length molecules. Binding sites are created for the tail connector molecules which in turn allow the independently assembled tail to attach. Research on these processes proceeds along several lines: comparison of physical and chemical properties of particles accumulating in mutants; pulse-chase experiments on assembly precursors; morphogenesis in vitro; and model transitions of aberrant lambda polyheads. | [
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|
PMID:13436 | Structure and assembly of lipid-containing viruses, with special reference to bacteriophage PM2 as one type of model system. | The simpler lipid-containing viruses (influenza, Semliki Forest, PM2) may have a phospholipid bilayer sandwiched between an outer shell of protein and an internal nucleocapsid possessing helical or icosahedral symmetry. Extensive physical and chemical studies have enabled us to form a more detailed picture of the structure of bacteriophage PM2 and controlled stepwise degradation of the virion has helped us to localize the four viral proteins. The surface protein (II) of PM2 is basic and interacts with the acidic phosphatidylglycerol of the bilayer to stabilize the membrane. The nucleocapsid protein (III) has proteolipid characteristics and may interact with the phospholipids in a hydrophobic fashion. The spikes are formed from protein I and the fourth protein (IV) is closely associated with the DNA. It is possible to reassemble the virus by reversing the degradation steps. Assembly has been especially useful in revealing the processes whereby the proteins and lipids interact to form the bilayer. Furthermore, results of in vivo studies of phospholipid synthesis and both in vivo and in vitro studies of viral protein synthesis have enabled us to form a reasonably complete picture of the biosynthesis of PM2. | Structure and assembly of lipid-containing viruses, with special reference to bacteriophage PM2 as one type of model system. The simpler lipid-containing viruses (influenza, Semliki Forest, PM2) may have a phospholipid bilayer sandwiched between an outer shell of protein and an internal nucleocapsid possessing helical or icosahedral symmetry. Extensive physical and chemical studies have enabled us to form a more detailed picture of the structure of bacteriophage PM2 and controlled stepwise degradation of the virion has helped us to localize the four viral proteins. The surface protein (II) of PM2 is basic and interacts with the acidic phosphatidylglycerol of the bilayer to stabilize the membrane. The nucleocapsid protein (III) has proteolipid characteristics and may interact with the phospholipids in a hydrophobic fashion. The spikes are formed from protein I and the fourth protein (IV) is closely associated with the DNA. It is possible to reassemble the virus by reversing the degradation steps. Assembly has been especially useful in revealing the processes whereby the proteins and lipids interact to form the bilayer. Furthermore, results of in vivo studies of phospholipid synthesis and both in vivo and in vitro studies of viral protein synthesis have enabled us to form a reasonably complete picture of the biosynthesis of PM2. | [
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|
PMID:13437 | Structure and assembly of filamentous bacterial viruses. | Filamentous bacterial viruses are flexible nucleoprotein rods, about 6 nm in diameter by 1000-2000 nm in length (depending on the virus strain). A protein shell encloses a central core of single-stranded circular DNA. The coat protein subunits forming the shell are largely alpha-helix, elongated in an axial direction, and also sloping radially, so as to overlap each other and give an arrangement of subunits reminiscent of scales on a fish. This arrangement of alpha-helices is rather like some models of myosin filaments. An early step in assembly of the virion is the formation of a complex between the viral DNA and an intracellular packaging protein that is not found in completed virions. Newly synthesized coat protein becomes associated with the plasma membrane of the cell. During the final steps of assembly, the packaging protein is displaced from the DNA and replaced by coat protein as the virion passes out through the plasma membrane of the host cell. | Structure and assembly of filamentous bacterial viruses. Filamentous bacterial viruses are flexible nucleoprotein rods, about 6 nm in diameter by 1000-2000 nm in length (depending on the virus strain). A protein shell encloses a central core of single-stranded circular DNA. The coat protein subunits forming the shell are largely alpha-helix, elongated in an axial direction, and also sloping radially, so as to overlap each other and give an arrangement of subunits reminiscent of scales on a fish. This arrangement of alpha-helices is rather like some models of myosin filaments. An early step in assembly of the virion is the formation of a complex between the viral DNA and an intracellular packaging protein that is not found in completed virions. Newly synthesized coat protein becomes associated with the plasma membrane of the cell. During the final steps of assembly, the packaging protein is displaced from the DNA and replaced by coat protein as the virion passes out through the plasma membrane of the host cell. | [
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|
PMID:13438 | RNA viruses: stabilization of brome mosaic virus. | The relative importances of protein-protein and RNA-protein interactions in stabilizing the architecture of brome mosaic virus particles are discussed in the light of the following experimental evidence: (a) disassembly pathways of the virus particles, (b) reassembly of the virus and self-association capacity of the protein moiety, and (c) the role of divalent cations in virus stabilization, and their relevance to localization of the RNA in the virus particles. Evidence is given that the capsid of BMV is primarily stabilized by hydrophobic bonds at low pH, but not around and above neutrality where RNA-protein electrostatic interactions are essential to the integrity of the virus particles. A model is proposed for the structure of BMV in the different configurational states. | RNA viruses: stabilization of brome mosaic virus. The relative importances of protein-protein and RNA-protein interactions in stabilizing the architecture of brome mosaic virus particles are discussed in the light of the following experimental evidence: (a) disassembly pathways of the virus particles, (b) reassembly of the virus and self-association capacity of the protein moiety, and (c) the role of divalent cations in virus stabilization, and their relevance to localization of the RNA in the virus particles. Evidence is given that the capsid of BMV is primarily stabilized by hydrophobic bonds at low pH, but not around and above neutrality where RNA-protein electrostatic interactions are essential to the integrity of the virus particles. A model is proposed for the structure of BMV in the different configurational states. | [
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|
PMID:13439 | Fluorescent probe studies of haptoglobin type 2-1. | Haptoglobin is an alpha2 serum protein that forms an irreversible complex with hemoglobin. The combination between these two macromolecules resembles the binding of an antigen to its antibody except that the complex remains soluble. This investigation was undertaken to determine the nature of the hydrophobic sites on haptoglobin type 2-1. The interaction of 1-anilinonphthalene-8-sulfonate (ANS) with haptoglobin type 2-1 is characterized by a flourescence intensity in solutions containing ANS and haptoglobin as the pH is decreased from 9 to 4. The dissociation constant for the ANS interaction with haptoglobin 2-1 is 5.8 x 10--5 M at pH 7.0, 5.2 X 10--5 M at pH 5.0 AND 30.3 X 10--5 M at pH 4.0. Fmax shows no change in the pH range 6-9 but does show an increase at pH 4.0 when compared to the neutral region. | Fluorescent probe studies of haptoglobin type 2-1. Haptoglobin is an alpha2 serum protein that forms an irreversible complex with hemoglobin. The combination between these two macromolecules resembles the binding of an antigen to its antibody except that the complex remains soluble. This investigation was undertaken to determine the nature of the hydrophobic sites on haptoglobin type 2-1. The interaction of 1-anilinonphthalene-8-sulfonate (ANS) with haptoglobin type 2-1 is characterized by a flourescence intensity in solutions containing ANS and haptoglobin as the pH is decreased from 9 to 4. The dissociation constant for the ANS interaction with haptoglobin 2-1 is 5.8 x 10--5 M at pH 7.0, 5.2 X 10--5 M at pH 5.0 AND 30.3 X 10--5 M at pH 4.0. Fmax shows no change in the pH range 6-9 but does show an increase at pH 4.0 when compared to the neutral region. | [
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|
PMID:13440 | Models for biological ion exchangers. I. Proton magnetic resonance studies of water structure in Bio-Rex 70. | Bio-Rex 70, a carboxylic acid cation exchanger, is studied as a biological ion-exchanger resin model for cellular cytoplasm. High-resolution proton magnetic resonance spectra of 1l ionic forms of Bio-Rex 70 are determined. From measured cation exchange capacities, water contents, and chemical shifts for the resin-phase water protons, the dependence of the chemical shift on the counter ion is calculated. The observed chemical shifts (Hz/geq/kg internal water, referred to the Ba2+ form) for each ionic form are: H+, --0.5; Li+, --0.2; Na+, 1.2; K+, 2; Rb+, 2.1; Ag+, --0.4; NH4+, --2.0; NMe4+, 1.2; NEt4+, 1.8; Mg2+, --2.0; Ca2+, --1.5; Sr2+, --0.6; Ba2+, 0.0 Zn2+, --2.3; Cd2+, --4.7; and La3+, --3.3. The results are in good agreement with earlier studies on Dowex 50, indicating that the carboxylate ion exchanger behaves like a concentrated polyelectrolyte. The widths at half-height for the internal water peaks of the polyvalent forms are quite large, ranging from 40 to 100 Hz. | Models for biological ion exchangers. I. Proton magnetic resonance studies of water structure in Bio-Rex 70. Bio-Rex 70, a carboxylic acid cation exchanger, is studied as a biological ion-exchanger resin model for cellular cytoplasm. High-resolution proton magnetic resonance spectra of 1l ionic forms of Bio-Rex 70 are determined. From measured cation exchange capacities, water contents, and chemical shifts for the resin-phase water protons, the dependence of the chemical shift on the counter ion is calculated. The observed chemical shifts (Hz/geq/kg internal water, referred to the Ba2+ form) for each ionic form are: H+, --0.5; Li+, --0.2; Na+, 1.2; K+, 2; Rb+, 2.1; Ag+, --0.4; NH4+, --2.0; NMe4+, 1.2; NEt4+, 1.8; Mg2+, --2.0; Ca2+, --1.5; Sr2+, --0.6; Ba2+, 0.0 Zn2+, --2.3; Cd2+, --4.7; and La3+, --3.3. The results are in good agreement with earlier studies on Dowex 50, indicating that the carboxylate ion exchanger behaves like a concentrated polyelectrolyte. The widths at half-height for the internal water peaks of the polyvalent forms are quite large, ranging from 40 to 100 Hz. | [
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|
PMID:13444 | [Effects of antianxiety drugs on the water intake in trained and untrained rats and mice (author's transl)]. | In water-deprived rats and mice, animals trained to the test situation spent more time in drinking than naive animals (first exposure to the test situation). The time spent in drinking, either during 5 min or during 10 min was recorded. As compared to controls, benzodiazepines, phenobarbital, meprobamate, and mecloqualone increased drinking time whether the experiments were run on naive or on experienced animals [5 or 10 (in mice) and 9 (in rats) exposures in the test situation]. All drugs were injected i.p. 30 min before testing. This release of the drinking behavior was more pronounced during the last 5 min than during the first 5 min of the 10 min test session. These results suggest that: 1. The inhibition of water intake of naive animals as compared to trained rats and mice, could be related to some emotional factors elicited by the first exposure to an unknown situation. 2. The increase in drinking time induced by the antianxiety drugs in a novel and in a familiar situation seems difficult to correlate only with the antianxiety action of these compounds. 3. Antianxiety drugs could interfere with the regulatory mechanism of thirst. | [Effects of antianxiety drugs on the water intake in trained and untrained rats and mice (author's transl)]. In water-deprived rats and mice, animals trained to the test situation spent more time in drinking than naive animals (first exposure to the test situation). The time spent in drinking, either during 5 min or during 10 min was recorded. As compared to controls, benzodiazepines, phenobarbital, meprobamate, and mecloqualone increased drinking time whether the experiments were run on naive or on experienced animals [5 or 10 (in mice) and 9 (in rats) exposures in the test situation]. All drugs were injected i.p. 30 min before testing. This release of the drinking behavior was more pronounced during the last 5 min than during the first 5 min of the 10 min test session. These results suggest that: 1. The inhibition of water intake of naive animals as compared to trained rats and mice, could be related to some emotional factors elicited by the first exposure to an unknown situation. 2. The increase in drinking time induced by the antianxiety drugs in a novel and in a familiar situation seems difficult to correlate only with the antianxiety action of these compounds. 3. Antianxiety drugs could interfere with the regulatory mechanism of thirst. | [
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|
PMID:13445 | Operant behavioural and neurochemical effects after neonatal 6-hydroxydopamine treatment. | Newborn rats were treated at 1 and 2 days after birth with 100 mg/kg 6-hydroxydopamine (60HDA), s.c. Testing on several operant behavioural tasks was begun at 6 months of age. On a fixed ratio 30 (FR 30) schedule of food reinforcement, the neonatal 60HDA treated rats responded at a significantly higher rate. Further analysis of the FR 30 response pattern indicated that the higher rate was due to a decrease in the amount of time spent pausing after the receipt of each reinforcer. The 60HDA treatment failed to alter the rat's behaviour during the extinction of the FR 30 response and on the progressive ratio or variable interval schedules of food reinforcement. Biochemical analysis of several brain areas at 9 months of age showed a decrease in noradrenaline (NA) levels in the cerebral cortex and hippocampus, while in the pons-medulla NA content was doubled. The tyrosine hydroxylase activity in these same brain areas was not significantly altered, but there appeared to be some decrease in the activity of this enzyme in the hippocampus. Comparison of the operant behavioural effects seen after various lesioning procedures in this and other studies, suggest the effects on FR performance are a result of destruction of NA neurons in the hippocampus and/or the apparent regeneration of neurons in the pons-medulla. | Operant behavioural and neurochemical effects after neonatal 6-hydroxydopamine treatment. Newborn rats were treated at 1 and 2 days after birth with 100 mg/kg 6-hydroxydopamine (60HDA), s.c. Testing on several operant behavioural tasks was begun at 6 months of age. On a fixed ratio 30 (FR 30) schedule of food reinforcement, the neonatal 60HDA treated rats responded at a significantly higher rate. Further analysis of the FR 30 response pattern indicated that the higher rate was due to a decrease in the amount of time spent pausing after the receipt of each reinforcer. The 60HDA treatment failed to alter the rat's behaviour during the extinction of the FR 30 response and on the progressive ratio or variable interval schedules of food reinforcement. Biochemical analysis of several brain areas at 9 months of age showed a decrease in noradrenaline (NA) levels in the cerebral cortex and hippocampus, while in the pons-medulla NA content was doubled. The tyrosine hydroxylase activity in these same brain areas was not significantly altered, but there appeared to be some decrease in the activity of this enzyme in the hippocampus. Comparison of the operant behavioural effects seen after various lesioning procedures in this and other studies, suggest the effects on FR performance are a result of destruction of NA neurons in the hippocampus and/or the apparent regeneration of neurons in the pons-medulla. | [
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|
PMID:13446 | Anticholinergic properties of antipsychotic drugs and their relation to extrapyramidal side-effects. | The effects of haloperidol, alone and in combination with atropine, were compared with the effects of clozapine, alone and in combination with physostigmine, in a variety of tests commonly used to characterize neuroleptic compounds. It was found that clozapine in combination with physostigmine did not present the profile of activity of a classical neuroleptic agent; neither did haloperidol in combination with atropine present that of clozapine. In fact, some effects of haloperidol (catalepsy) were antagonized by atropine, while others (induction of striatal DA-receptor hypersensitivity) were enhanced. It is concluded that the interaction between dopaminergic and cholinergic systems in the striatum is highly complex, and that a neuroleptic possessing both potent DA-receptor blocking and muscarinic anticholinergic activity, while being less likely to cause parkinsonism in patients, would be more likely to induce tardive dyskinesias. | Anticholinergic properties of antipsychotic drugs and their relation to extrapyramidal side-effects. The effects of haloperidol, alone and in combination with atropine, were compared with the effects of clozapine, alone and in combination with physostigmine, in a variety of tests commonly used to characterize neuroleptic compounds. It was found that clozapine in combination with physostigmine did not present the profile of activity of a classical neuroleptic agent; neither did haloperidol in combination with atropine present that of clozapine. In fact, some effects of haloperidol (catalepsy) were antagonized by atropine, while others (induction of striatal DA-receptor hypersensitivity) were enhanced. It is concluded that the interaction between dopaminergic and cholinergic systems in the striatum is highly complex, and that a neuroleptic possessing both potent DA-receptor blocking and muscarinic anticholinergic activity, while being less likely to cause parkinsonism in patients, would be more likely to induce tardive dyskinesias. | [
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|
PMID:13447 | Alterations of mouse adrenal medullary catecholamines and enzymes in response to attack: effect of pre- and post-treatment with phenobarbital. | Group-housed male C57BR/cdJ mice (victims) were exposed to attack for 10 min daily for up to 14 days by male Swiss-Webster mice, made aggressive by prolonged isolation. Their adrenal glands were analyzed for tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) activities and for norepinephrine (NE) and epinephrine (EPI) concentrations. TH was increased to 41 per cent above control after two exposures and remained elevated through 14 exposures to attack. PNMT was increased to 29 per cent above control after 2 days and increased further to 50 per cent above control after 14 days of attack. Both NE and EPI increased to 88 per cent and 51 per cent above control, respectively, after 7 days. In victim mice recuperating after 1 week of daily stress, EPI levels and PNMT activities were back to normal after 4 days whereas NE levels and TH activities returned to normal only after 1 week. Phenobarbital (40 mg/kg, i.m.) was effective in preventing the biochemical changes when given 2 h prior to each daily attack but was ineffective when given immediately after each daily stress. | Alterations of mouse adrenal medullary catecholamines and enzymes in response to attack: effect of pre- and post-treatment with phenobarbital. Group-housed male C57BR/cdJ mice (victims) were exposed to attack for 10 min daily for up to 14 days by male Swiss-Webster mice, made aggressive by prolonged isolation. Their adrenal glands were analyzed for tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) activities and for norepinephrine (NE) and epinephrine (EPI) concentrations. TH was increased to 41 per cent above control after two exposures and remained elevated through 14 exposures to attack. PNMT was increased to 29 per cent above control after 2 days and increased further to 50 per cent above control after 14 days of attack. Both NE and EPI increased to 88 per cent and 51 per cent above control, respectively, after 7 days. In victim mice recuperating after 1 week of daily stress, EPI levels and PNMT activities were back to normal after 4 days whereas NE levels and TH activities returned to normal only after 1 week. Phenobarbital (40 mg/kg, i.m.) was effective in preventing the biochemical changes when given 2 h prior to each daily attack but was ineffective when given immediately after each daily stress. | [
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|
PMID:13448 | Cyclic GMP in the CSF of patients with schizophrenia before and after neuroleptic treatment. | Cerebrospinal fluid (CSF) cyclic GMP may derive from central cholinergic neurotransmission. Measurement of CSF cyclic GMP may allow evaluation of possible implications of the dopaminergic hyperactivity in schizophrenia proposed by the dopamine hypothesis. The CSF cyclic GMP levels in 27 drug-free schizophrenic patients was measured and compared to that in 9 psychiatrically-healthy individuals. The mean CSF cyclic GMP level of the schizophrenic patients was 23 per cent lower than that of the control group, but this difference did not attain statistical significance. In addition the CSF cyclic GMP levels in a group of 10 schizophrenic patients were compared before and after 2 months of neuroleptic treatment. The mean level of cyclic GMP rose 50 per cent after treatment with phenothiazines (P less than 0.05). These results could indicate some tendency for decreased activity of central cholinergic neurons in schizophrenia as well as a restored dopaminergic-cholinergic balance after neuroleptic treatment. | Cyclic GMP in the CSF of patients with schizophrenia before and after neuroleptic treatment. Cerebrospinal fluid (CSF) cyclic GMP may derive from central cholinergic neurotransmission. Measurement of CSF cyclic GMP may allow evaluation of possible implications of the dopaminergic hyperactivity in schizophrenia proposed by the dopamine hypothesis. The CSF cyclic GMP levels in 27 drug-free schizophrenic patients was measured and compared to that in 9 psychiatrically-healthy individuals. The mean CSF cyclic GMP level of the schizophrenic patients was 23 per cent lower than that of the control group, but this difference did not attain statistical significance. In addition the CSF cyclic GMP levels in a group of 10 schizophrenic patients were compared before and after 2 months of neuroleptic treatment. The mean level of cyclic GMP rose 50 per cent after treatment with phenothiazines (P less than 0.05). These results could indicate some tendency for decreased activity of central cholinergic neurons in schizophrenia as well as a restored dopaminergic-cholinergic balance after neuroleptic treatment. | [
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|
PMID:13470 | Pulmonary function in premature lambs during the first few hours of life. | This study establishes the mean values, variations, and trend of pulmonary function during the first few hours of life in premature lambs. Measurements of intraesophaheal and tracheal pressure, air flow, tidal volume, and functional residual capacity enabled calculations of lung compliance, specific lung compliance, and inspiratory and expiratory resistance of the lungs. Arterial carbon dioxide tension and pH were maintained within a physiologic range. Mean arterial oxygen tension (PO2) at elevated inspired oxygen tension, varied in the individual animals from 51 to 185 mm Hg at an inspired oxygen concentration of 46 to 71%. It was found that the lungs of premature lambs delivered by cesarean section were mechanically unstable; the lambs were all ineffectual at breathing and required some form of mechanical ventilation. During the first 6 hours of postnatal life the lungs of premature lambs are characterized by a wide range of mechanical values and blood gas tensions. | Pulmonary function in premature lambs during the first few hours of life. This study establishes the mean values, variations, and trend of pulmonary function during the first few hours of life in premature lambs. Measurements of intraesophaheal and tracheal pressure, air flow, tidal volume, and functional residual capacity enabled calculations of lung compliance, specific lung compliance, and inspiratory and expiratory resistance of the lungs. Arterial carbon dioxide tension and pH were maintained within a physiologic range. Mean arterial oxygen tension (PO2) at elevated inspired oxygen tension, varied in the individual animals from 51 to 185 mm Hg at an inspired oxygen concentration of 46 to 71%. It was found that the lungs of premature lambs delivered by cesarean section were mechanically unstable; the lambs were all ineffectual at breathing and required some form of mechanical ventilation. During the first 6 hours of postnatal life the lungs of premature lambs are characterized by a wide range of mechanical values and blood gas tensions. | [
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|
PMID:13472 | Calculations for pH during CO2 and O2 exchange with blood. | New mathematical formulas are presented to calculate directly the change in blood pH during CO2, and O2 exchange with blood. pH changes are calculated from changes in blood PCO2 and saturation values or from changes in blood PCO2 and blood PO2 values. Computational results agree well with information obtained from a Dill nomogram. These new formulas have applicability to the modelling of gas exchange in blood oxygenators as well as to estimating blood acid-base parameters following the mixing of blood samples. | Calculations for pH during CO2 and O2 exchange with blood. New mathematical formulas are presented to calculate directly the change in blood pH during CO2, and O2 exchange with blood. pH changes are calculated from changes in blood PCO2 and saturation values or from changes in blood PCO2 and blood PO2 values. Computational results agree well with information obtained from a Dill nomogram. These new formulas have applicability to the modelling of gas exchange in blood oxygenators as well as to estimating blood acid-base parameters following the mixing of blood samples. | [
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PMID:13477 | [Biochemistry of collagen and the locomoter apparatus (Hereditary connective tissue diseases and rheumatic diseases. Part I]. | The elementary collagen molecule consists of three chains rolled into a spiral and ending in nonhelical telopeptides. In cutaneous collagen, there are two types of chains, in cartilaginous collagen there is only one. In the synthesis, several enzymes play successive parts: proline hydroxylase, lysine hydroxylase, then pro-collagen peptidase and finally, lysine oxidase and hydroxylysine oxidase; their coordinated actions ultimately allow the chains to establish the transverse intra and intermolecular links which give the collagen fiber its cohesion. The type and number of these transverse links vary from one tissue to another. Specific collagenases make collagen degradation possible. | [Biochemistry of collagen and the locomoter apparatus (Hereditary connective tissue diseases and rheumatic diseases. Part I]. The elementary collagen molecule consists of three chains rolled into a spiral and ending in nonhelical telopeptides. In cutaneous collagen, there are two types of chains, in cartilaginous collagen there is only one. In the synthesis, several enzymes play successive parts: proline hydroxylase, lysine hydroxylase, then pro-collagen peptidase and finally, lysine oxidase and hydroxylysine oxidase; their coordinated actions ultimately allow the chains to establish the transverse intra and intermolecular links which give the collagen fiber its cohesion. The type and number of these transverse links vary from one tissue to another. Specific collagenases make collagen degradation possible. | [
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|
PMID:13478 | The van Slyke equation. | The Henderson-Hasselbalch equation has always occupied a central place in the description of the acid-base status of the blood. An equation of similar importance is the equation for the CO2 equilibration curve of blood in vitro. It is proposed to name this the Van Slyke equation: a - 24.4 = - (2.3 X b + 7.7) X (c - 7.40) + d/(1 - 0.023 X b), where a = bicarbonate concentration in plasma/(mmol/l), b = hemoglobin concentration in blood/(mmol/l), c = pH of plasma at 37 degrees C, d = base excess concentration in blood/(mmol/l). These two equations provide an arithmetic algorithm for calculation of the various acid-base variables of the blood after measuring the pH, the pCO2, and the hemoglobin concentration. | The van Slyke equation. The Henderson-Hasselbalch equation has always occupied a central place in the description of the acid-base status of the blood. An equation of similar importance is the equation for the CO2 equilibration curve of blood in vitro. It is proposed to name this the Van Slyke equation: a - 24.4 = - (2.3 X b + 7.7) X (c - 7.40) + d/(1 - 0.023 X b), where a = bicarbonate concentration in plasma/(mmol/l), b = hemoglobin concentration in blood/(mmol/l), c = pH of plasma at 37 degrees C, d = base excess concentration in blood/(mmol/l). These two equations provide an arithmetic algorithm for calculation of the various acid-base variables of the blood after measuring the pH, the pCO2, and the hemoglobin concentration. | [
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PMID:13479 | Physiological viewpoints on clinical acid-base diagnostics. | Acid-base physiology is concerned with sources, extent, and control of hydrogen ion donation in the body, at the organ-physiological as well as the molecular level of study. With the introduction of Van Slyke's methods for quantitative carbon dioxide measurements in biological fluids, one important source of hydrogen ion donation became identifiable; and these and derived methods have permitted of fairly precise quantitative descriptions of transport and pulmonary elimination of carbon dioxide. However, the inevitable operational concept of non-carbonic (non-volatile) contributions to the titratable acidity of the body fluids has been a cause of considerable methodological and conceptual difficulties; and whereas it is now possible by means of the micro-equilibration technique to make accurate assessments of the concentration of non-volatile titratable acid (base) in blood, the question of the physiological relevance of the concept of 'base excess' remains open. In particular, the concept of non-carbonic acid does not possess a specific relevance with respect to the acid-base physiology of kidney, bone, and gastro-intestinal tract comparable to the 'substrate-specificity of carbon dioxide with respect to the lung. Our studies indicate that a subdivision of the titratable non-carbonic acid of any biological medium in two subcomponents will provide an improvement of specificity, adequate for a system physiological approach at the organ level. Thus, a distinction should be made between (1) processes of hydrogen ion donation, reversible by endogenous metabolic means (quantitated in terms of the component MA = metabolizable non-carbonic acid) and (2) processes of hydrogen ion donation associated with gastro-intestinal, skeletal, and renal transport, storage, and control of non-metabolizable non-carbonic acid (NA). Some implications of this distinction for acid-base physiology and acid-base diagnostics are discussed. | Physiological viewpoints on clinical acid-base diagnostics. Acid-base physiology is concerned with sources, extent, and control of hydrogen ion donation in the body, at the organ-physiological as well as the molecular level of study. With the introduction of Van Slyke's methods for quantitative carbon dioxide measurements in biological fluids, one important source of hydrogen ion donation became identifiable; and these and derived methods have permitted of fairly precise quantitative descriptions of transport and pulmonary elimination of carbon dioxide. However, the inevitable operational concept of non-carbonic (non-volatile) contributions to the titratable acidity of the body fluids has been a cause of considerable methodological and conceptual difficulties; and whereas it is now possible by means of the micro-equilibration technique to make accurate assessments of the concentration of non-volatile titratable acid (base) in blood, the question of the physiological relevance of the concept of 'base excess' remains open. In particular, the concept of non-carbonic acid does not possess a specific relevance with respect to the acid-base physiology of kidney, bone, and gastro-intestinal tract comparable to the 'substrate-specificity of carbon dioxide with respect to the lung. Our studies indicate that a subdivision of the titratable non-carbonic acid of any biological medium in two subcomponents will provide an improvement of specificity, adequate for a system physiological approach at the organ level. Thus, a distinction should be made between (1) processes of hydrogen ion donation, reversible by endogenous metabolic means (quantitated in terms of the component MA = metabolizable non-carbonic acid) and (2) processes of hydrogen ion donation associated with gastro-intestinal, skeletal, and renal transport, storage, and control of non-metabolizable non-carbonic acid (NA). Some implications of this distinction for acid-base physiology and acid-base diagnostics are discussed. | [
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|
PMID:13480 | Stoichiometric concentration and chemical potential. | It has been recommended to use SI units in clinical chemistry. A consequence of this is that pH is reported as the excess chemical potential (or standard chemical potential) of hydrogen ions with the unit kJ/mol. On the basis of the excess chemical potential of H+ it is possible to calculate the hydrogen ion concentration in the system = the equilibrium concentration of H+ = the concentration of free H+. This quantity must be clearly distinguished from the stoichiometric concentration of H+ = the excess concentration of total H+, which indicates the amount of added or removed H+. The latter quantity with opposite sign has been called the excess concentration of base, but the designation "stoichiometric concentration of H+" seems to be more logical. The general principles for description of a component in a chemical system are based on (1) an extensive quantity (the stoichiometric amount of substance), and (2) an intensive quantity (the excess chemical potential); the product of these has the dimension of energy. | Stoichiometric concentration and chemical potential. It has been recommended to use SI units in clinical chemistry. A consequence of this is that pH is reported as the excess chemical potential (or standard chemical potential) of hydrogen ions with the unit kJ/mol. On the basis of the excess chemical potential of H+ it is possible to calculate the hydrogen ion concentration in the system = the equilibrium concentration of H+ = the concentration of free H+. This quantity must be clearly distinguished from the stoichiometric concentration of H+ = the excess concentration of total H+, which indicates the amount of added or removed H+. The latter quantity with opposite sign has been called the excess concentration of base, but the designation "stoichiometric concentration of H+" seems to be more logical. The general principles for description of a component in a chemical system are based on (1) an extensive quantity (the stoichiometric amount of substance), and (2) an intensive quantity (the excess chemical potential); the product of these has the dimension of energy. | [
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|
PMID:13481 | Gastrin, antral g cells, and gastric acid in secretagogue-induced and antihistamine-inhibited duodenal ulcers. | In fasting control rats there was continuous basal gastric acid secretion, with a low plasma gastrin and antral G-cells full or immunofluroescent gastrin. After subcutaneous infusion of the gastric secretagogues, pentagastrin + carbachol, there was a six-hour period of gastric hypersecretion, but no change in plasma and G-cell gastrin. Pretreatment with the antihistamine derivative, Pfizer UK-9040, decreased both basal and stimulated acid secretion, whereas plasma gastrin levels increased and the antral G-cells were emptied of gastrin. These results suggest that this antihistamine derivative decreases gastric acid secretion by a direct action on the parietal cells and not by reducing gastrin release from the G-cells. The increased release of gastrin from the G-cells may be secondary to decreased gastric acid production, or more probably by a direct stimulation of the antral G-cells. | Gastrin, antral g cells, and gastric acid in secretagogue-induced and antihistamine-inhibited duodenal ulcers. In fasting control rats there was continuous basal gastric acid secretion, with a low plasma gastrin and antral G-cells full or immunofluroescent gastrin. After subcutaneous infusion of the gastric secretagogues, pentagastrin + carbachol, there was a six-hour period of gastric hypersecretion, but no change in plasma and G-cell gastrin. Pretreatment with the antihistamine derivative, Pfizer UK-9040, decreased both basal and stimulated acid secretion, whereas plasma gastrin levels increased and the antral G-cells were emptied of gastrin. These results suggest that this antihistamine derivative decreases gastric acid secretion by a direct action on the parietal cells and not by reducing gastrin release from the G-cells. The increased release of gastrin from the G-cells may be secondary to decreased gastric acid production, or more probably by a direct stimulation of the antral G-cells. | [
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|
PMID:13482 | Effect of resection of antrum and duodenal bulb on sham-feeding-induced inhibition of canine gastric secretion. | In dogs with Heidenhain pouches and oesophageal and gastric fistulae, sham feeding inhibited pentagastrin-stimulated Heidenhain pouch acid output. Resection of the antrum and the duodenalbulb reduced oin stomach was diverted through the gastric cannula. The present results are conid secretion at least partly by inducing a vagal release of an inhibitory hormone. The results suggest that this hormone is released from the antrum and the duodenal bulb. | Effect of resection of antrum and duodenal bulb on sham-feeding-induced inhibition of canine gastric secretion. In dogs with Heidenhain pouches and oesophageal and gastric fistulae, sham feeding inhibited pentagastrin-stimulated Heidenhain pouch acid output. Resection of the antrum and the duodenalbulb reduced oin stomach was diverted through the gastric cannula. The present results are conid secretion at least partly by inducing a vagal release of an inhibitory hormone. The results suggest that this hormone is released from the antrum and the duodenal bulb. | [
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PMID:13488 | [Exercise hemodynamics and renin before and after acute beta block in patients with essential hypertension]. | Hemodynamic and renin studies at rest and during graded upright ergometry were performed in 21 patients with essential hypertension before and after propranolol. Beta-adrenergic receptor blockade reduced exercise-stimulated cardiac and renin responses significantly more when compared with the corresponding effects at rest. Propranolol increased peripheral resistance at rest but not during exercise. The degree of the individual hemodynamic changes after propranolol correlated better with the corresponding control values than with age or renin. A direct relationship between the percent reduction of heart rate and renin responses after acute beta-blockade indicates a parallel suppression of cardiac and renal receptor functions. | [Exercise hemodynamics and renin before and after acute beta block in patients with essential hypertension]. Hemodynamic and renin studies at rest and during graded upright ergometry were performed in 21 patients with essential hypertension before and after propranolol. Beta-adrenergic receptor blockade reduced exercise-stimulated cardiac and renin responses significantly more when compared with the corresponding effects at rest. Propranolol increased peripheral resistance at rest but not during exercise. The degree of the individual hemodynamic changes after propranolol correlated better with the corresponding control values than with age or renin. A direct relationship between the percent reduction of heart rate and renin responses after acute beta-blockade indicates a parallel suppression of cardiac and renal receptor functions. | [
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|
PMID:13489 | [The burden of a general medical clinic with patients after suicide attempts]. | All 125 patients who entered the "suicide ward" of the Medical Department of a large public hospital during 1974 were analyzed according to age and sex distribution, duration of hospital stay, motivation and method of committing suicide and fate after recovering from the acute phase of intoxication. Motivation to commit suicide was mainly due to conflicting interpersonal relations. Suicide attempts were 3 times more frequent in women than in men. 49% of all suicide attempts were considered to be of the "cry for help" variety and 29% were classified as obviously ineffective but serious attempts of self-killing. The remaining 22% of patients wanted to mark a "caesura" in their lives. Since the early phase of recovery is of utmost importance for the patient's future, medical and nursing staff have to be trained and experienced in coping with the suicide patient's numerous problems. The permanent collaboration of an experienced psychiatrist within the staff of larger acute-phase hospitals is highly desirable in order to analyze the underlying social and medical problems, assess the danger of a renewed suicide attempt, start early and appropriate therapy and train hospital staff and nurses. | [The burden of a general medical clinic with patients after suicide attempts]. All 125 patients who entered the "suicide ward" of the Medical Department of a large public hospital during 1974 were analyzed according to age and sex distribution, duration of hospital stay, motivation and method of committing suicide and fate after recovering from the acute phase of intoxication. Motivation to commit suicide was mainly due to conflicting interpersonal relations. Suicide attempts were 3 times more frequent in women than in men. 49% of all suicide attempts were considered to be of the "cry for help" variety and 29% were classified as obviously ineffective but serious attempts of self-killing. The remaining 22% of patients wanted to mark a "caesura" in their lives. Since the early phase of recovery is of utmost importance for the patient's future, medical and nursing staff have to be trained and experienced in coping with the suicide patient's numerous problems. The permanent collaboration of an experienced psychiatrist within the staff of larger acute-phase hospitals is highly desirable in order to analyze the underlying social and medical problems, assess the danger of a renewed suicide attempt, start early and appropriate therapy and train hospital staff and nurses. | [
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|
PMID:13491 | [Drug-induced lung diseases]. | Adverse drug reactions involving different organs, including the lung, are numerous; much more numerous, however, are the offending drugs. According to the results of the Boston Collaborative Drug Surveillance Program, adverse reactions occur in about 6% of all drug exposures and 28% of all patients. Drug-induced lung diseases may present as bronchial reactions (e.g. bronchial asthma), diseases of the parenchyma (e.g. pulmonary infiltrates with eosinophilia, diffuse fibrosing alveolitis), of the pulmonary vasculature (vasculitis) and of the pleura (e.g. pleurisy or pleural fibrosis). Pathogenetically the two most pertinent types of reaction are hypersensitivity or toxic reactions, and less often biologic reactions such as opportunistic infections after cytotoxic and immunosuppressive therapy. Many drug-induced respiratory diseases are reversible upon withdrawal of the offending agent; others may be irreversibly or even progress. | [Drug-induced lung diseases]. Adverse drug reactions involving different organs, including the lung, are numerous; much more numerous, however, are the offending drugs. According to the results of the Boston Collaborative Drug Surveillance Program, adverse reactions occur in about 6% of all drug exposures and 28% of all patients. Drug-induced lung diseases may present as bronchial reactions (e.g. bronchial asthma), diseases of the parenchyma (e.g. pulmonary infiltrates with eosinophilia, diffuse fibrosing alveolitis), of the pulmonary vasculature (vasculitis) and of the pleura (e.g. pleurisy or pleural fibrosis). Pathogenetically the two most pertinent types of reaction are hypersensitivity or toxic reactions, and less often biologic reactions such as opportunistic infections after cytotoxic and immunosuppressive therapy. Many drug-induced respiratory diseases are reversible upon withdrawal of the offending agent; others may be irreversibly or even progress. | [
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|
PMID:13495 | Mode of action of beta blockers in angina pectoris. | The therapeutic effect of beta adrenoceptor blockers in angina pectoris can be ascribed to an inhibition of beta1 receptor mediated stimulation of heart rate and myocardial contractility, resulting in an improved oxygen supply-demand balance in the myocardium. When given in equipotent beta1 blocking doses, the nonselective blocker propranolol and the beta1 selective blocker metoprolol differ markedly as regards inhibition of adrenaline induced beta2 mediated vasodilatation. Only propranolol will inhibit this effect. After propranolol, adrenaline therefore elicits a haemodynamic effect pattern characterized by high peripheral vascular resistance, high arterial blood pressure, low cardiac output and increased cardiac size. In view of these findings it is suggested that a beta1 selective blocker may be a more efficient antianginal agent than a nonselective blocker in those patients in which the anginal attack is associated with a significant release of adrenaline. The clinical relevance of this hypothesis has not been tested. | Mode of action of beta blockers in angina pectoris. The therapeutic effect of beta adrenoceptor blockers in angina pectoris can be ascribed to an inhibition of beta1 receptor mediated stimulation of heart rate and myocardial contractility, resulting in an improved oxygen supply-demand balance in the myocardium. When given in equipotent beta1 blocking doses, the nonselective blocker propranolol and the beta1 selective blocker metoprolol differ markedly as regards inhibition of adrenaline induced beta2 mediated vasodilatation. Only propranolol will inhibit this effect. After propranolol, adrenaline therefore elicits a haemodynamic effect pattern characterized by high peripheral vascular resistance, high arterial blood pressure, low cardiac output and increased cardiac size. In view of these findings it is suggested that a beta1 selective blocker may be a more efficient antianginal agent than a nonselective blocker in those patients in which the anginal attack is associated with a significant release of adrenaline. The clinical relevance of this hypothesis has not been tested. | [
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|
PMID:13496 | Haemodynamic effects of different beta blockers in angina pectoris. | Beta-blocking agents with partial agonist activity seem to reduce heart rate at rest slightly less than those without this property. Cardio-selective drugs have no effect on stroke volume at rest contrary to the non-selective ones which will reduce it somewhat. This difference is abolished during exercise. The only difference seen during work between different beta-blockers is the effect on the peripheral vascular resistance. The selective drugs lower the arterial pressure with unchanged resistance. | Haemodynamic effects of different beta blockers in angina pectoris. Beta-blocking agents with partial agonist activity seem to reduce heart rate at rest slightly less than those without this property. Cardio-selective drugs have no effect on stroke volume at rest contrary to the non-selective ones which will reduce it somewhat. This difference is abolished during exercise. The only difference seen during work between different beta-blockers is the effect on the peripheral vascular resistance. The selective drugs lower the arterial pressure with unchanged resistance. | [
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|
PMID:13492 | Inorganic photoreduction of nicotinamide adenine dinucleotide phosphate. I. Photoreduction by certain oxide semiconductors in the near ultraviolet. | The action of chloroplasts in the light reactions of photosynthesis is the reduction of NADP to NADPH and phosphorylation of ADP to ATP by light energy. According to the electron theory of catalysis of photosynthesis, these functions of chloroplasts can be mimicked by any inorganic semiconductors. This paper reports that with ZnO instead of chloroplasts NADP can be photoreduced to NADPH in the near ultraviolet. | Inorganic photoreduction of nicotinamide adenine dinucleotide phosphate. I. Photoreduction by certain oxide semiconductors in the near ultraviolet. The action of chloroplasts in the light reactions of photosynthesis is the reduction of NADP to NADPH and phosphorylation of ADP to ATP by light energy. According to the electron theory of catalysis of photosynthesis, these functions of chloroplasts can be mimicked by any inorganic semiconductors. This paper reports that with ZnO instead of chloroplasts NADP can be photoreduced to NADPH in the near ultraviolet. | [
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|
PMID:13497 | Observations in man of hypoglycaemia during selective and non-selective beta-blockade. | The acute hypoglycaemic reaction is accompanied by a rise in systolic and a slight fall in diastolic blood pressure and a tachycardia. In contrast, during beta-blockade with propranolol there is a rise of both systolic and diastolic blood pressures and bradycardia. Restoration of blood glucose to normal is delayed. With metoprolol there is a lesser increase in diastolic blood pressure and a slight tachycardia. Restoration of the blood glucose to normal is little delayed. When patients liable to hypoglycaemia require a beta-blocking agent, it is suggested that a selective blocker such as metoprolol should be used. | Observations in man of hypoglycaemia during selective and non-selective beta-blockade. The acute hypoglycaemic reaction is accompanied by a rise in systolic and a slight fall in diastolic blood pressure and a tachycardia. In contrast, during beta-blockade with propranolol there is a rise of both systolic and diastolic blood pressures and bradycardia. Restoration of blood glucose to normal is delayed. With metoprolol there is a lesser increase in diastolic blood pressure and a slight tachycardia. Restoration of the blood glucose to normal is little delayed. When patients liable to hypoglycaemia require a beta-blocking agent, it is suggested that a selective blocker such as metoprolol should be used. | [
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|
PMID:13499 | Dopamine-sensitive adenylate cyclase: location in substantia nigra. | A dopamine-sensitive adenylate cyclase with characteristics similar to those measured in the striatum is present in the rat substantia nigra. Destruction of dopamine cell bodies by intranigral 6-hydroxydopamine application failed to abolish the response of nigral adenylate cyclase to dopamine. In contrast, brain hemitransection between the striatum and substantia nigra, or a more circumscribed lesion of striatonigral pathways, abolished the dopamine stimulation of adenylate cyclase in the substantia nigra. These results suggest that dopamine receptors within the substantia nigra are not located on dopamine cell bodies but are associated with a pathway, containing gamma-aminobutyric acid or substance P, which projects from forebrain structures to the substantia nigra. | Dopamine-sensitive adenylate cyclase: location in substantia nigra. A dopamine-sensitive adenylate cyclase with characteristics similar to those measured in the striatum is present in the rat substantia nigra. Destruction of dopamine cell bodies by intranigral 6-hydroxydopamine application failed to abolish the response of nigral adenylate cyclase to dopamine. In contrast, brain hemitransection between the striatum and substantia nigra, or a more circumscribed lesion of striatonigral pathways, abolished the dopamine stimulation of adenylate cyclase in the substantia nigra. These results suggest that dopamine receptors within the substantia nigra are not located on dopamine cell bodies but are associated with a pathway, containing gamma-aminobutyric acid or substance P, which projects from forebrain structures to the substantia nigra. | [
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|
PMID:13501 | Uterine and cardiovascular effects of beta2-selective sympathomimetic drugs administered as an intravenous infusion. | The uterine and cardiovascular effects of fenoterol, hexoprenaline, ritodrine and salbutamol, given as intravenous infusions in equivalent and therapeutic dosages in oxytocin-induced labour, were studied and compared. All the drugs were effective in reducing the uterine activity to less than 30% of the original. The effect on the cardiovascular system was to produce a moderate tachycardia and a widening of the pulse pressure by raising the systolic and decreasing the diastolic blood pressures. | Uterine and cardiovascular effects of beta2-selective sympathomimetic drugs administered as an intravenous infusion. The uterine and cardiovascular effects of fenoterol, hexoprenaline, ritodrine and salbutamol, given as intravenous infusions in equivalent and therapeutic dosages in oxytocin-induced labour, were studied and compared. All the drugs were effective in reducing the uterine activity to less than 30% of the original. The effect on the cardiovascular system was to produce a moderate tachycardia and a widening of the pulse pressure by raising the systolic and decreasing the diastolic blood pressures. | [
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|
PMID:13502 | Studies of the pharmacology of a new antidepressant, S1694. | A new antidepressive drug, S1694, produces increased locomotor activity (LA) in mice, but less so than d-amphetamine. This effect is decreased by pimozide, phenoxybenzamine, as well as by pretreatment of the animals with reserpine or alpha-methyl-p-tyrosine methyl ester (H44/68). S1694 inhibits active dopamine (DA) uptake into rat striatal synaptosomes, but not noradrenaline (NA) uptake into rat hypothalamic synaptosomes, or serotonin (5-HT) uptake into rat midbrain synaptosomes, in the concentrations used. The inhibition of DA uptake appears tp be competitive and the inhibition constant estimated is 1,3 X 10(-6) M. In addition, S1694 releases DA in the same concentrations, and NA as well as 5HT at higher concentrations. It is concluded that S1694 activates LA primarily by inhibitionof DA re-uptake and DA release. The central DA system activation may be important in the antidepressive effect. | Studies of the pharmacology of a new antidepressant, S1694. A new antidepressive drug, S1694, produces increased locomotor activity (LA) in mice, but less so than d-amphetamine. This effect is decreased by pimozide, phenoxybenzamine, as well as by pretreatment of the animals with reserpine or alpha-methyl-p-tyrosine methyl ester (H44/68). S1694 inhibits active dopamine (DA) uptake into rat striatal synaptosomes, but not noradrenaline (NA) uptake into rat hypothalamic synaptosomes, or serotonin (5-HT) uptake into rat midbrain synaptosomes, in the concentrations used. The inhibition of DA uptake appears tp be competitive and the inhibition constant estimated is 1,3 X 10(-6) M. In addition, S1694 releases DA in the same concentrations, and NA as well as 5HT at higher concentrations. It is concluded that S1694 activates LA primarily by inhibitionof DA re-uptake and DA release. The central DA system activation may be important in the antidepressive effect. | [
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|
PMID:13503 | Enzymatic and hemodynamic changes after short term hepatic outflow occlusion in the dog. | In normal mongrel dogs, outflow occlusion of 15 or 30 minutes duration was produced by clamping both the suprahepatic and suprarenal portions of the vena cava. One dog died immediately after release of occlusion; two dogs died from recurrent hypotension between six and 24 hours postoperatively. The other five dogs survived for three days, at which time an autopsy was done. During outflow occlusion, the blood pressure fell in all dogs, as did the central venous pressure. The pulse rate decreased during, and after, occlusion but toward a tendency of gradual recovery. A significant drop in pH and base excess of arterial blood was seen after occlusion. Although a steady, but not substantial, increase in hemoglobin and hematocrit values was noted, there were no remarkable changes in the blood coagulation system. Significant increases in serum glutamic-oxalacetic transaminase, glutamic-pyruvic-transaminase, lactic dehydrogenase, acid phosphatase and beta-glucuronidase activities were observed from immediately after release of occlusion, but alkaline phosphatase values increased much later than did these. Thus, hepatic outflow occlusion, even if it is short, seems to be dangerous in the dog, since it produces hypotension, metabolic acidosis and diffuse damage as well as disruption of the parenchyma of the liver. | Enzymatic and hemodynamic changes after short term hepatic outflow occlusion in the dog. In normal mongrel dogs, outflow occlusion of 15 or 30 minutes duration was produced by clamping both the suprahepatic and suprarenal portions of the vena cava. One dog died immediately after release of occlusion; two dogs died from recurrent hypotension between six and 24 hours postoperatively. The other five dogs survived for three days, at which time an autopsy was done. During outflow occlusion, the blood pressure fell in all dogs, as did the central venous pressure. The pulse rate decreased during, and after, occlusion but toward a tendency of gradual recovery. A significant drop in pH and base excess of arterial blood was seen after occlusion. Although a steady, but not substantial, increase in hemoglobin and hematocrit values was noted, there were no remarkable changes in the blood coagulation system. Significant increases in serum glutamic-oxalacetic transaminase, glutamic-pyruvic-transaminase, lactic dehydrogenase, acid phosphatase and beta-glucuronidase activities were observed from immediately after release of occlusion, but alkaline phosphatase values increased much later than did these. Thus, hepatic outflow occlusion, even if it is short, seems to be dangerous in the dog, since it produces hypotension, metabolic acidosis and diffuse damage as well as disruption of the parenchyma of the liver. | [
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|
PMID:13504 | A review of recent advances in vascular smooth muscle pharmacology. | An understanding of the physiology of vascular smooth muscle and knowledge of the reaction of such muscle to certain drugs are essential for the development of a means of treating cerebral arterial spasm. The role of cyclic nucleotides in vascular smooth muscle activity is reviewed and possible therapeutic approaches are listed. Probably the safest and most effective treatment would be 1) stimulation of the adenyl cyclase-cyclic adenosine monophosphate system by a beta(2)-adrenergic drug combined with 2) inhibition of the phosphodiesterase system. | A review of recent advances in vascular smooth muscle pharmacology. An understanding of the physiology of vascular smooth muscle and knowledge of the reaction of such muscle to certain drugs are essential for the development of a means of treating cerebral arterial spasm. The role of cyclic nucleotides in vascular smooth muscle activity is reviewed and possible therapeutic approaches are listed. Probably the safest and most effective treatment would be 1) stimulation of the adenyl cyclase-cyclic adenosine monophosphate system by a beta(2)-adrenergic drug combined with 2) inhibition of the phosphodiesterase system. | [
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|
PMID:13505 | Bioavailability and generic prescribing. | Although oral drug bioinequivalence has been attributed to a number of causes (excipients, dosage form, variation in dissolution time, and aging) less is known about bioavailability problems of topical medications in ophthalmology. Factors that can alter drug absorption from solutions (pH, partition coefficient, container impurities, contact time, etc.) are noted, and cases in which bioavailability problems should be considered as causes of therapeutic failure are discussed. Various attitudes representing pharmaceutical companies, the federal government, pharmacists, consumers and physicians toward the related problems of bioinequivalence and generic prescribing are examined. Techniques for in vivo and in vitro drug testing and for establishing uniform conditions of drug manufacture and storage can contribute to identification and minimization of bioavailability problems. A rational program based on a combination of such techniques could, ultimately, lead to establishment of the terms "generic equivalency" and "therapeutic equivalency" as synonymous. | Bioavailability and generic prescribing. Although oral drug bioinequivalence has been attributed to a number of causes (excipients, dosage form, variation in dissolution time, and aging) less is known about bioavailability problems of topical medications in ophthalmology. Factors that can alter drug absorption from solutions (pH, partition coefficient, container impurities, contact time, etc.) are noted, and cases in which bioavailability problems should be considered as causes of therapeutic failure are discussed. Various attitudes representing pharmaceutical companies, the federal government, pharmacists, consumers and physicians toward the related problems of bioinequivalence and generic prescribing are examined. Techniques for in vivo and in vitro drug testing and for establishing uniform conditions of drug manufacture and storage can contribute to identification and minimization of bioavailability problems. A rational program based on a combination of such techniques could, ultimately, lead to establishment of the terms "generic equivalency" and "therapeutic equivalency" as synonymous. | [
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|
PMID:13510 | Total body potassium in cor pulmonale. | Total body potassium was measured in 12 patients with cor pulmonale, by determination of potassium-40, a naturally occurring radioisotope. In all subjects the observed value of total body potassium showed no significant depletion when compared with that predicted from height and age. All previous studies in similar groups of patients have been confined to the estimation of exchangeable potassium by the technique of isotope dilution. Results using the latter technique have shown gross potassium depletion. It is suggested that the apparent disparity between total body potassium and exchangeable potassium could be explained by the requirement for a longer equilibration period when using isotope dilution techniques in patients who are in chronic hypoxaemic state. | Total body potassium in cor pulmonale. Total body potassium was measured in 12 patients with cor pulmonale, by determination of potassium-40, a naturally occurring radioisotope. In all subjects the observed value of total body potassium showed no significant depletion when compared with that predicted from height and age. All previous studies in similar groups of patients have been confined to the estimation of exchangeable potassium by the technique of isotope dilution. Results using the latter technique have shown gross potassium depletion. It is suggested that the apparent disparity between total body potassium and exchangeable potassium could be explained by the requirement for a longer equilibration period when using isotope dilution techniques in patients who are in chronic hypoxaemic state. | [
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|
PMID:13511 | Arterial blood gas tensions, hydrogen ion, and electroencephalogram during sleep in patients with chronic ventilatory failure. | We have studied arterial PO2, PCO2, and hydrogen ion and electroencephalogram during sleep in 10 patients with stable severe chronic respiratory failure. As a group the patients slept badly. Sleep was associated with a worsening of hypoxia and no significant change in PCO2 and H+. Two patients were restudied, receiving oxygen therapy overnight. Both had improved sleep but one, who had an intact hypoxic drive to breathing, developed marked hypercapnia and acidosis when his PO2 was restored to normal during sleep; the other, who had no hypoxic drive to breathing, developed no more hypercapnia or acidosis during sleep when breathing oxygen than when breathing air. Oxygen therapy may improve sleep disturbance in these patients, but its effect on the drive to breathing during sleep should be considered if severe hypercapnia and acidosis are to be avoided. | Arterial blood gas tensions, hydrogen ion, and electroencephalogram during sleep in patients with chronic ventilatory failure. We have studied arterial PO2, PCO2, and hydrogen ion and electroencephalogram during sleep in 10 patients with stable severe chronic respiratory failure. As a group the patients slept badly. Sleep was associated with a worsening of hypoxia and no significant change in PCO2 and H+. Two patients were restudied, receiving oxygen therapy overnight. Both had improved sleep but one, who had an intact hypoxic drive to breathing, developed marked hypercapnia and acidosis when his PO2 was restored to normal during sleep; the other, who had no hypoxic drive to breathing, developed no more hypercapnia or acidosis during sleep when breathing oxygen than when breathing air. Oxygen therapy may improve sleep disturbance in these patients, but its effect on the drive to breathing during sleep should be considered if severe hypercapnia and acidosis are to be avoided. | [
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|
PMID:13516 | Studies on the properties of the immunologically effective anti-tumor substance from spleen cells of tumor-resistant rats. | The influence of physical and chemical treatments upon the immunologically effective subcellular fractions (5,000 X g supernatant and 105,000 X g sediment), which were prepared from the spleen cells of Yoshida sarcoma (YS)-resistant Donryu rats, was studied. The immunological activity of the 5,000 X g supernatant was stable to heating at 80 degrees C for 30 min. It was stable to alkali (pH 10) and less stable to acid (pH 2). It was labile to a ten-day storage at 4 degrees C, but relatively stable to a 30-day storage at -20 degrees C. When the 105,000 X g sediment was lyophilized and stored at -20 degrees C for 95 days, its immunological activity was well maintained. It was labile to 95% ethanol, 90% phenol and 2 M NaNO2, but relatively stable to 10% as well as 100% acetone, 10% phenol and 10% ethanol. It was labile to 0.1 M NaIO4 and relatively stable to 0.1 M K2Cr2O7 solution. It was labile to RNase but relatively stable to DNase. | Studies on the properties of the immunologically effective anti-tumor substance from spleen cells of tumor-resistant rats. The influence of physical and chemical treatments upon the immunologically effective subcellular fractions (5,000 X g supernatant and 105,000 X g sediment), which were prepared from the spleen cells of Yoshida sarcoma (YS)-resistant Donryu rats, was studied. The immunological activity of the 5,000 X g supernatant was stable to heating at 80 degrees C for 30 min. It was stable to alkali (pH 10) and less stable to acid (pH 2). It was labile to a ten-day storage at 4 degrees C, but relatively stable to a 30-day storage at -20 degrees C. When the 105,000 X g sediment was lyophilized and stored at -20 degrees C for 95 days, its immunological activity was well maintained. It was labile to 95% ethanol, 90% phenol and 2 M NaNO2, but relatively stable to 10% as well as 100% acetone, 10% phenol and 10% ethanol. It was labile to 0.1 M NaIO4 and relatively stable to 0.1 M K2Cr2O7 solution. It was labile to RNase but relatively stable to DNase. | [
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|
PMID:13520 | Minor and trace sterols in marine invertebrates. 1. General methods of analysis. | 3beta-Hydroxy sterols occurring at a concentration of at least 0.001% of the sterol mixtures of Pseudoplexaura porosa and Plexaura homomalla have been fractionated using a series of refined techniques and subsequently analyzed using combined gas chromatography-mass spectrometry (GC-MS) in the development of a procedure for examining the minor and trace components of marine sterol mixtures. A total of 49 sterols were found which spanned a molecular weight range of 274 to 440. In addition delta4-3-keto analogs of cholesterol, 24-methylcholesterol and gorgosterol were found in the extracts of P. homomalla. Initial separation of various natural sterol-containing conjugates and free sterols was found to have a number of advantages. Fractional digitonin precipitation and alumina column chromatography were found to possess greater sterol separation abilities than previously recognized. Many of the minor sterols were found to possess novel structures including a series of short side chain sterols, 19-nor sterols, 5beta-stanols and 4-monomethyl sterols for which structure elucidation work is continuing. | Minor and trace sterols in marine invertebrates. 1. General methods of analysis. 3beta-Hydroxy sterols occurring at a concentration of at least 0.001% of the sterol mixtures of Pseudoplexaura porosa and Plexaura homomalla have been fractionated using a series of refined techniques and subsequently analyzed using combined gas chromatography-mass spectrometry (GC-MS) in the development of a procedure for examining the minor and trace components of marine sterol mixtures. A total of 49 sterols were found which spanned a molecular weight range of 274 to 440. In addition delta4-3-keto analogs of cholesterol, 24-methylcholesterol and gorgosterol were found in the extracts of P. homomalla. Initial separation of various natural sterol-containing conjugates and free sterols was found to have a number of advantages. Fractional digitonin precipitation and alumina column chromatography were found to possess greater sterol separation abilities than previously recognized. Many of the minor sterols were found to possess novel structures including a series of short side chain sterols, 19-nor sterols, 5beta-stanols and 4-monomethyl sterols for which structure elucidation work is continuing. | [
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|
PMID:13523 | Detection of serum-blocking factors by inhibition of allorosette formation in rats with long-surviving renal allografts following short-term postoperative ALS treatment. | Thirty-nine (LEW x BN)F1 kidneys were transplanted to LEW rats. Twenty-four untreated recipients survived for a mean time of 16.1 +/- 1.7 days (group 1). Fifteen recipients received 4 ml of antilymphocytic serum per rat (group 3). In the last group 10 recipients survived for more than 4 months. The spleen cells of these permanently surviving 10 rats were obtained by splenectomy and used in a graft-versus-host assay, and this assay showed that the reactivity of these cells was normal. Following splenectomy the animals were given an (LEW x BN)F1 skin allograft, followed 18 days by a second. After another 18 days (LEW x Buf)F1 "third party" skin allografts were transplanted to the same animals. Animals of group 2 rejected their first grafts with a mean survival time of 12.2 +/- 1.2 days, whereas the second grafts were rejected normally as were the third party grafts. Attempts were made to detect lymphocytotoxic antibodies and haemagglutinins before and after the transplantation of skin grafts and none could be found up to day 53. The sera of group 2 inhibited allorosette formation by 38%. This serum-blocking factor was donor specific. It is probable that the survival of the kidney transplants following antilymphocytic serum treatment was brought about by the development of blocking antibodies. | Detection of serum-blocking factors by inhibition of allorosette formation in rats with long-surviving renal allografts following short-term postoperative ALS treatment. Thirty-nine (LEW x BN)F1 kidneys were transplanted to LEW rats. Twenty-four untreated recipients survived for a mean time of 16.1 +/- 1.7 days (group 1). Fifteen recipients received 4 ml of antilymphocytic serum per rat (group 3). In the last group 10 recipients survived for more than 4 months. The spleen cells of these permanently surviving 10 rats were obtained by splenectomy and used in a graft-versus-host assay, and this assay showed that the reactivity of these cells was normal. Following splenectomy the animals were given an (LEW x BN)F1 skin allograft, followed 18 days by a second. After another 18 days (LEW x Buf)F1 "third party" skin allografts were transplanted to the same animals. Animals of group 2 rejected their first grafts with a mean survival time of 12.2 +/- 1.2 days, whereas the second grafts were rejected normally as were the third party grafts. Attempts were made to detect lymphocytotoxic antibodies and haemagglutinins before and after the transplantation of skin grafts and none could be found up to day 53. The sera of group 2 inhibited allorosette formation by 38%. This serum-blocking factor was donor specific. It is probable that the survival of the kidney transplants following antilymphocytic serum treatment was brought about by the development of blocking antibodies. | [
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|
PMID:13521 | Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. | As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH. | Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH. | [
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|
PMID:13525 | Deficiency in the thymus-dependent immunity in "lethargic" mutant mice. | T cell function of "lethargic" mutant mice which exhibit spontaneous thymic involution was evaluated by skin transplantation and graft-versus-host reaction tests. At 15 to 30 days of age, the mutant mice did not reject skin allografts, but by 45 days of age their response was normal. Spleen cells from 24-day-old mutant donors demonstrated delayed appearance of graft-versus-host induced splenomegaly in F1 recipients. Implications of these results in understanding the immunological status of lethargic mice were considered. | Deficiency in the thymus-dependent immunity in "lethargic" mutant mice. T cell function of "lethargic" mutant mice which exhibit spontaneous thymic involution was evaluated by skin transplantation and graft-versus-host reaction tests. At 15 to 30 days of age, the mutant mice did not reject skin allografts, but by 45 days of age their response was normal. Spleen cells from 24-day-old mutant donors demonstrated delayed appearance of graft-versus-host induced splenomegaly in F1 recipients. Implications of these results in understanding the immunological status of lethargic mice were considered. | [
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|
PMID:13526 | Epidemiologic study of arboviruses in the Arba-Minch district of Ethiopia. | A yellow fever outbreak occurred in 1966 in Arba-Minch District, east of Abaya Lake, in Ethiopia. The present study was undertaken to assess the southern limits of that epidemic and to contribute to the inventory of arboviruses and potential vectors in that area. In the highlands 90 sera were collected, in the lowlands 140. With regard to Group B the sera reacted only with yellow fever, Wesselsbron and Spondweni antigens. In the highlands 17.8%, in the lowlands 22.2%, were positive for group B. In two sera only the titers against yellow fever were high. The absence of reactivity to West Nile virus was striking. A wide variety of Culicidae was present and differentiated. Potential or proven vectors were collected. At the time of the survey yellow fever was not active in the region. Because of an only partly immune human population, and of the presence of non-immune monkeys and some potential vectors, the area should, however, be considered to be receptive. | Epidemiologic study of arboviruses in the Arba-Minch district of Ethiopia. A yellow fever outbreak occurred in 1966 in Arba-Minch District, east of Abaya Lake, in Ethiopia. The present study was undertaken to assess the southern limits of that epidemic and to contribute to the inventory of arboviruses and potential vectors in that area. In the highlands 90 sera were collected, in the lowlands 140. With regard to Group B the sera reacted only with yellow fever, Wesselsbron and Spondweni antigens. In the highlands 17.8%, in the lowlands 22.2%, were positive for group B. In two sera only the titers against yellow fever were high. The absence of reactivity to West Nile virus was striking. A wide variety of Culicidae was present and differentiated. Potential or proven vectors were collected. At the time of the survey yellow fever was not active in the region. Because of an only partly immune human population, and of the presence of non-immune monkeys and some potential vectors, the area should, however, be considered to be receptive. | [
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|
PMID:13530 | [Experience with the use of viadril anesthesia]. | Based on experimental and clinical findings the authors concluded that a combination of viadril with neuroleptanalgesics shows a number of advantages over purely viadril anesthesia or its combination with other drugs for inhalation and intravenous anesthesia. The technic of thalmonal-viadril anesthesia is reported. | [Experience with the use of viadril anesthesia]. Based on experimental and clinical findings the authors concluded that a combination of viadril with neuroleptanalgesics shows a number of advantages over purely viadril anesthesia or its combination with other drugs for inhalation and intravenous anesthesia. The technic of thalmonal-viadril anesthesia is reported. | [
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|
PMID:13537 | [Adaptation to oxygen breathing]. | Controlled, dosed, uninterrupted and continuous oxygen treatment was applied in 63 patients with global respiratory insufficiency, through a nasopharyngeal catheter in concentrations to 30 per cent. PaO2, is elevated with and average of 12 mm mercury column after 30 minutes 25% oxygen breathing and PaCO2--at an average of 8 mm mercury column. PaO2 level was kept after 24 hours whereas PaCO2 decreased at an average of 4 mm mercury column. Besides, respiration and pulse rate are decelerated, secondary polyglobulia decreases, cardiac and renal function is improved. Those changes are interpreted as patients' adaptation to oxygen breathing. The adaptation to oxygen breathing decreases the danger of critical intensification of the respiratory depression in the course of the treatment and conditions for a successful application of O2 treatment at home are created. | [Adaptation to oxygen breathing]. Controlled, dosed, uninterrupted and continuous oxygen treatment was applied in 63 patients with global respiratory insufficiency, through a nasopharyngeal catheter in concentrations to 30 per cent. PaO2, is elevated with and average of 12 mm mercury column after 30 minutes 25% oxygen breathing and PaCO2--at an average of 8 mm mercury column. PaO2 level was kept after 24 hours whereas PaCO2 decreased at an average of 4 mm mercury column. Besides, respiration and pulse rate are decelerated, secondary polyglobulia decreases, cardiac and renal function is improved. Those changes are interpreted as patients' adaptation to oxygen breathing. The adaptation to oxygen breathing decreases the danger of critical intensification of the respiratory depression in the course of the treatment and conditions for a successful application of O2 treatment at home are created. | [
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|
PMID:13541 | [Postural hypotension: pathophysiology and clinical features (author's transl)]. | Circulatory regulation in response to postural changes follows mechanical rules, whereby the shifts in volume in the various organs of the body play an essential role. The change from the horizontal to the vertical position is accompanied by a decrease in pressure above the hydrostatic neutral point, i.e. in the cephalic vessels, whereas the capacious vessels in the caudal region are dilated and the venous return becomes sluggish. As a consequence of the different time courses followed by the various circulatory parameters in the wake of counter-regulatory measures, a distinction can be made between an early orthostatic instant regulatory response and a late orthostatic response. Prominent clinical features do not necessarily always consist of non-systemic dizziness, tinnitus, pallor cold sweat and, finally, orthostatic collapse, but general subjective symptoms such as deafness and tingling of the extremities, a chilly sensation and cardiac symptoms may frequently predominante. In the case of development of an autonomic neurotic symptom complex, psychoautonomic symptoms such as general sleep disturbance are observed. Apart from investigations carried out on a surgical tilting table in general practice, other procedures such as the Valsalva manoeuvre, the squatting test and, in most cases, the erect test are performed. Broadly speaking four different reaction types can be distinguished amongst cases of postural hypotension. Drugs with different therapeutic actions are selectively administered according to the pathophysiological characteristics of the individual patient and the sympathetic adrenal counter-regulatory response. Medico-mechanical measures and physical training should not be neglected. | [Postural hypotension: pathophysiology and clinical features (author's transl)]. Circulatory regulation in response to postural changes follows mechanical rules, whereby the shifts in volume in the various organs of the body play an essential role. The change from the horizontal to the vertical position is accompanied by a decrease in pressure above the hydrostatic neutral point, i.e. in the cephalic vessels, whereas the capacious vessels in the caudal region are dilated and the venous return becomes sluggish. As a consequence of the different time courses followed by the various circulatory parameters in the wake of counter-regulatory measures, a distinction can be made between an early orthostatic instant regulatory response and a late orthostatic response. Prominent clinical features do not necessarily always consist of non-systemic dizziness, tinnitus, pallor cold sweat and, finally, orthostatic collapse, but general subjective symptoms such as deafness and tingling of the extremities, a chilly sensation and cardiac symptoms may frequently predominante. In the case of development of an autonomic neurotic symptom complex, psychoautonomic symptoms such as general sleep disturbance are observed. Apart from investigations carried out on a surgical tilting table in general practice, other procedures such as the Valsalva manoeuvre, the squatting test and, in most cases, the erect test are performed. Broadly speaking four different reaction types can be distinguished amongst cases of postural hypotension. Drugs with different therapeutic actions are selectively administered according to the pathophysiological characteristics of the individual patient and the sympathetic adrenal counter-regulatory response. Medico-mechanical measures and physical training should not be neglected. | [
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|
PMID:13542 | [Early clinical symptoms and therapy of haemorrhages in old age (author's transl)]. | There is hardly a bleeding, where the extrinsic-and/or the intrinsic-system of the coagulation does not take part in. Haemorrhages represent a symptom only, and it is always to clear, if they are come from a local process of illness or from a general tendency of haemorrhage. There is point to the clinical differences of great bleeding (coagulopathy) and bleedings like points (the causes lie in the thrombocytes or in a vascular damage). The early clinical symptoms and the therapy of haemorrhages by the old human without the primary disturbance of the coagulate-system are discussed. | [Early clinical symptoms and therapy of haemorrhages in old age (author's transl)]. There is hardly a bleeding, where the extrinsic-and/or the intrinsic-system of the coagulation does not take part in. Haemorrhages represent a symptom only, and it is always to clear, if they are come from a local process of illness or from a general tendency of haemorrhage. There is point to the clinical differences of great bleeding (coagulopathy) and bleedings like points (the causes lie in the thrombocytes or in a vascular damage). The early clinical symptoms and the therapy of haemorrhages by the old human without the primary disturbance of the coagulate-system are discussed. | [
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|
PMID:13543 | [Duodenogastric reflux and anastomosis abscess. Experimental study]. | Different types of duodenal by-pass operations with and without duodenogastric reflux were performed on 54 male Wistar rats. The results of our investigation show that following duodenal by-pass with reflux peptic anastomotic ulcer regularly occurs. The constant reflux of bile and pancreas juice is the most important aetiologic factor in the development of ulcer in the vicinity of the anastomosis between the stomach and small intestine. Stasis in the by-passed duodenum (afferent loop syndrome) promotes ulcerogenic action of reflux. In the absence of the pylorus the effects of reflux and stasis potentiate, resulting in a high frequency of ulcer (greater than 90%). With intact pylorus the incidence is low. Duodenogastric reflux prevents hydrochloric acid secretion significantly (p less than o,o1); hydrochloric acid thus plays a minor role in the development of experimental anastomotic ulcer of the rat. -- In considering the prophylaxis against anastomotic ulcer, these findings support the claim of avoiding surgical techniques involving duodenal by-pass and reflux (Billroth II with short loop GE). Gastric resection should, therefore, aim at the reconstruction of the orthograde peristalsis. | [Duodenogastric reflux and anastomosis abscess. Experimental study]. Different types of duodenal by-pass operations with and without duodenogastric reflux were performed on 54 male Wistar rats. The results of our investigation show that following duodenal by-pass with reflux peptic anastomotic ulcer regularly occurs. The constant reflux of bile and pancreas juice is the most important aetiologic factor in the development of ulcer in the vicinity of the anastomosis between the stomach and small intestine. Stasis in the by-passed duodenum (afferent loop syndrome) promotes ulcerogenic action of reflux. In the absence of the pylorus the effects of reflux and stasis potentiate, resulting in a high frequency of ulcer (greater than 90%). With intact pylorus the incidence is low. Duodenogastric reflux prevents hydrochloric acid secretion significantly (p less than o,o1); hydrochloric acid thus plays a minor role in the development of experimental anastomotic ulcer of the rat. -- In considering the prophylaxis against anastomotic ulcer, these findings support the claim of avoiding surgical techniques involving duodenal by-pass and reflux (Billroth II with short loop GE). Gastric resection should, therefore, aim at the reconstruction of the orthograde peristalsis. | [
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|
PMID:13547 | [Histopathological study of the mosquito-bite infiltrate in patients with various underlying diseases and different medications]. | A histologic study was carried out on tissue-reactions after insect bits in 9 patients with various primary diseases. The clinical and cellular reactions to the bite in the epidermis varied, according to the length, intensity of toxity of the insect bit. The dermal infiltrate was similar in almost all cases and corresponded to a cellular immunologic reaction of the early or late type, as is also to be seen in trichophytin and tuberculin-reactions. Tere was clearly no relationship between the character of the dermal infiltrate and the basic disease. We also found no change in the dermal infiltrate due to special medicaments. Even corticosteroids did not suppress the dermal cellular reactions. There was also a striking absence of eosinophil leucocytes in the dermal infiltrate. | [Histopathological study of the mosquito-bite infiltrate in patients with various underlying diseases and different medications]. A histologic study was carried out on tissue-reactions after insect bits in 9 patients with various primary diseases. The clinical and cellular reactions to the bite in the epidermis varied, according to the length, intensity of toxity of the insect bit. The dermal infiltrate was similar in almost all cases and corresponded to a cellular immunologic reaction of the early or late type, as is also to be seen in trichophytin and tuberculin-reactions. Tere was clearly no relationship between the character of the dermal infiltrate and the basic disease. We also found no change in the dermal infiltrate due to special medicaments. Even corticosteroids did not suppress the dermal cellular reactions. There was also a striking absence of eosinophil leucocytes in the dermal infiltrate. | [
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|
PMID:13548 | Non-equivalence and inverse allosteric response of the alpha and beta chains in haemoglobins. An electron spin resonance study of NO-ligated Hb Kansas. | The electron spin resonance (ESR) spectra of 15NO- and 14NO-ligated Hb Kansas have been measured at 77 K in the range of pH 5 TO 10. At low pH the ESR spectrum is the composite of a type I and a type II spectrum which changes to another composite of type I and type II spectrum at high pH. For the definition of type I and type II spectra and the correlation of these types with two tertiary conformation states see Overkamp et al., Z. Naturforsch. 31 c, 524 [1976]. Both, the type I and the type II spectra observed at low and high pH respectively are different with regard to g-tensors and hyperfine-splitting constants. Therefore at intermediate pH values the ESR spectra of NO-Hb Kansas are the composites of four spectral components. The assignments of the four spectral components to the alpha and the beta chains are arrived at from the comparison of the ESR spectra of the alpha2Mmet beta2NO and of the alpha2MNObeta2NO species of Hb M Iwate. alpha and beta chains are both characterized by a pH-dependent spectral transition from a type I to a type II spectrum. The chains are non-equivalent with regard to both the type I and the type II spectra. The type I spectra assigned to the alpha and the beta chains are characterized by G*ZZ=2.0095 with a hyperfine splitting of alpha*ZZ(15NO)=2.36 mT and gZZ-2.0085 with a hyperfine splitting of aZZ(15NO)=2.41 mT respectively. The type II spectra assigned to the alpha and the beta chains are characterized by g*'ZZ-2.005 and a hyperfine splitting of alpha*'ZZ(15NO)-3.07 mT and g'ZZ-2.005 and a hyperfine splitting of alpha'ZZ(15NO)=3.31 mT. The change of the hyperfine splitting at gZZ during the transition from type I to type II corresponds to an increase of the spin density at the NO by about 25% in both types of chains. Comparison of type I spectra of the NO-ligated alpha and beta chains respectively demonstrates that the spin density at the NO is larger in the beta chains that in the alpha chains. The spectral types are correlated with functional states defined by the kinetics of N0-binding. Binding of inosital hexaphosphate has no influence on the ESR spectra in the whole range of pH as it is expected if NO-Hb Kandas is in the quaternary T structure. | Non-equivalence and inverse allosteric response of the alpha and beta chains in haemoglobins. An electron spin resonance study of NO-ligated Hb Kansas. The electron spin resonance (ESR) spectra of 15NO- and 14NO-ligated Hb Kansas have been measured at 77 K in the range of pH 5 TO 10. At low pH the ESR spectrum is the composite of a type I and a type II spectrum which changes to another composite of type I and type II spectrum at high pH. For the definition of type I and type II spectra and the correlation of these types with two tertiary conformation states see Overkamp et al., Z. Naturforsch. 31 c, 524 [1976]. Both, the type I and the type II spectra observed at low and high pH respectively are different with regard to g-tensors and hyperfine-splitting constants. Therefore at intermediate pH values the ESR spectra of NO-Hb Kansas are the composites of four spectral components. The assignments of the four spectral components to the alpha and the beta chains are arrived at from the comparison of the ESR spectra of the alpha2Mmet beta2NO and of the alpha2MNObeta2NO species of Hb M Iwate. alpha and beta chains are both characterized by a pH-dependent spectral transition from a type I to a type II spectrum. The chains are non-equivalent with regard to both the type I and the type II spectra. The type I spectra assigned to the alpha and the beta chains are characterized by G*ZZ=2.0095 with a hyperfine splitting of alpha*ZZ(15NO)=2.36 mT and gZZ-2.0085 with a hyperfine splitting of aZZ(15NO)=2.41 mT respectively. The type II spectra assigned to the alpha and the beta chains are characterized by g*'ZZ-2.005 and a hyperfine splitting of alpha*'ZZ(15NO)-3.07 mT and g'ZZ-2.005 and a hyperfine splitting of alpha'ZZ(15NO)=3.31 mT. The change of the hyperfine splitting at gZZ during the transition from type I to type II corresponds to an increase of the spin density at the NO by about 25% in both types of chains. Comparison of type I spectra of the NO-ligated alpha and beta chains respectively demonstrates that the spin density at the NO is larger in the beta chains that in the alpha chains. The spectral types are correlated with functional states defined by the kinetics of N0-binding. Binding of inosital hexaphosphate has no influence on the ESR spectra in the whole range of pH as it is expected if NO-Hb Kandas is in the quaternary T structure. | [
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|
PMID:13549 | Kinetic analysis of the catalytic properties of peptides in ester hydrolysis. | The catalytic properties of peptides containing histidine, cysteine and aspartic acid in ester hydrolysis were studied. Saturation kinetics were found for the reaction of p-nitrophenyl acetate (NPA) with Z-His-Ala-Asp-Gly-Cys-NH2 and Z-His-Ala-Gly-Cly-Cys-NH2. The Brönsted equation for the hydrolysis of tert-butyloxcarbonyl-L-alanine-p-nitrophenylester (Bos-Ala-ONp) catalyzed by simple imidazole and SH-compounds was determined. The catalytic behaviour of the peptides in ester hydrolysis could not be described by the Brönsted equations for imidazole o thiole catalyzed hydrolysis of NPA and Boc-Ala-ONp. The pH dependence of the rate constants of the catalyzed ester hydrolysis gave no linear plots in 1/k versus H+ diagrrams. | Kinetic analysis of the catalytic properties of peptides in ester hydrolysis. The catalytic properties of peptides containing histidine, cysteine and aspartic acid in ester hydrolysis were studied. Saturation kinetics were found for the reaction of p-nitrophenyl acetate (NPA) with Z-His-Ala-Asp-Gly-Cys-NH2 and Z-His-Ala-Gly-Cly-Cys-NH2. The Brönsted equation for the hydrolysis of tert-butyloxcarbonyl-L-alanine-p-nitrophenylester (Bos-Ala-ONp) catalyzed by simple imidazole and SH-compounds was determined. The catalytic behaviour of the peptides in ester hydrolysis could not be described by the Brönsted equations for imidazole o thiole catalyzed hydrolysis of NPA and Boc-Ala-ONp. The pH dependence of the rate constants of the catalyzed ester hydrolysis gave no linear plots in 1/k versus H+ diagrrams. | [
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|
PMID:13550 | Light-dependent interactions of phenazine methosulfate with 3-(3,4-dichlorophenyl)-1,1-dimethylurea-poisoned chloroplasts. | The chlorophyll fluorescence of isolated chloroplasts in the presence of phenazine methosulfate (PMS) and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) can be quenched in a light-depentdent reaction. This phenomenan has been studied and the following observations were made: 1. Quenching occurs under non-phosphorylating conditions and is stimulated by Mg2+ ions. 2. Under the same conditions, a light-dependent, Mg2+ stimulated transient decrease of absorption at change and binding of PMS. Others, such as methylamine, ammonia, gramicidin and nigericin do not. It is suggested that fluorescence quenching, transient absorption change and binding of PMS are casually related. The concept, postulated by others, that a high-energy state of the chloroplast membrane is involved in the fluorescence lowering is questioned. | Light-dependent interactions of phenazine methosulfate with 3-(3,4-dichlorophenyl)-1,1-dimethylurea-poisoned chloroplasts. The chlorophyll fluorescence of isolated chloroplasts in the presence of phenazine methosulfate (PMS) and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) can be quenched in a light-depentdent reaction. This phenomenan has been studied and the following observations were made: 1. Quenching occurs under non-phosphorylating conditions and is stimulated by Mg2+ ions. 2. Under the same conditions, a light-dependent, Mg2+ stimulated transient decrease of absorption at change and binding of PMS. Others, such as methylamine, ammonia, gramicidin and nigericin do not. It is suggested that fluorescence quenching, transient absorption change and binding of PMS are casually related. The concept, postulated by others, that a high-energy state of the chloroplast membrane is involved in the fluorescence lowering is questioned. | [
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|
PMID:13588 | Kinetics and properties of L-glutaminase and L-asparaginase activities of Pseudomonas ovalis. | Pseudomonas ovalis produces L-glutaminase and L-asparaginase activities simultaneously upon induction by L-glutamine or L-asparagin in the growth medium. Both activities are confined to the cell during active growth and are not released into the medium. The apparent Km values are 1.4 X 10(-2) M and 6 X 10(-3) M for L-glutamine and L-asparagine substrates, respectively. Induction of both activities is substantially favoured in media with initial pH values higher than 7. In buffered yeast extract L-asparagine medium, significant amounts of L-glutaminase and L-asparaginase activities appeared towards the end of the exponential phase and along the stationary phase. The process of enzyme formation showed a firm link to the cell active growth, as evidenced by the use of growth inhibitors. | Kinetics and properties of L-glutaminase and L-asparaginase activities of Pseudomonas ovalis. Pseudomonas ovalis produces L-glutaminase and L-asparaginase activities simultaneously upon induction by L-glutamine or L-asparagin in the growth medium. Both activities are confined to the cell during active growth and are not released into the medium. The apparent Km values are 1.4 X 10(-2) M and 6 X 10(-3) M for L-glutamine and L-asparagine substrates, respectively. Induction of both activities is substantially favoured in media with initial pH values higher than 7. In buffered yeast extract L-asparagine medium, significant amounts of L-glutaminase and L-asparaginase activities appeared towards the end of the exponential phase and along the stationary phase. The process of enzyme formation showed a firm link to the cell active growth, as evidenced by the use of growth inhibitors. | [
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|
PMID:13589 | [Comparison in vitro between farm-yard manure and liquid manure (author's transl)]. | Spreading of liquid manure in a grassland ecosystem, stable since a long time when treated with farm-yard manure, brings out a great unbalance in the soil. In comparison of farm-yard manure, the liquid manure involves -- a decrease of C and N in the soil, -- a deterioration of the soil structure, -- a dangerous change in the CEC for K+ and Na+, -- an excessive stimulation of the microflora. In brief, through its composition the liquid manure involves a hyperactivity of the microglora. This heterotropic microflora is particularly mineralizing and breaks down the organic matter. The result is a temporary increase in fertility. But this stimulation of the soil life disbalances the eco-system in which -- the pool of organic matter decreases without replacement, -- the content in Ca++ and Mg++ decreases to the benefit of K+ and Na+. | [Comparison in vitro between farm-yard manure and liquid manure (author's transl)]. Spreading of liquid manure in a grassland ecosystem, stable since a long time when treated with farm-yard manure, brings out a great unbalance in the soil. In comparison of farm-yard manure, the liquid manure involves -- a decrease of C and N in the soil, -- a deterioration of the soil structure, -- a dangerous change in the CEC for K+ and Na+, -- an excessive stimulation of the microflora. In brief, through its composition the liquid manure involves a hyperactivity of the microglora. This heterotropic microflora is particularly mineralizing and breaks down the organic matter. The result is a temporary increase in fertility. But this stimulation of the soil life disbalances the eco-system in which -- the pool of organic matter decreases without replacement, -- the content in Ca++ and Mg++ decreases to the benefit of K+ and Na+. | [
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|
PMID:13590 | [Lymphogenic osteomyelitis of the foot (author's transl)]. | The special way of infection of the lymphogenic osteomyelitis caused by trivial trauma is demonstrated in 4 cases. Germ ascension is done by lymphatics or fissures in the tissue, as it is well known in the panaritium ossale. The treatment consists in removing the focus of infection, irrigation-suction drainage and specific antibiotic therapy. Trivial trauma of the lower extremity should be treated according to the principles of asepsis. | [Lymphogenic osteomyelitis of the foot (author's transl)]. The special way of infection of the lymphogenic osteomyelitis caused by trivial trauma is demonstrated in 4 cases. Germ ascension is done by lymphatics or fissures in the tissue, as it is well known in the panaritium ossale. The treatment consists in removing the focus of infection, irrigation-suction drainage and specific antibiotic therapy. Trivial trauma of the lower extremity should be treated according to the principles of asepsis. | [
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|
PMID:13591 | Effect of cholera enterotoxin preparations on cutaneous response in rabbit under varied conditions. | Enterotoxic activity of two preparations obtained from Vibrio cholerae, B-53-6 Inaba and B-53-10 Ogawa was tested in ligated ileal loops of rabbit. The biologically active enterotoxic preparations were further used to study the permeability reaction in rabbit skin. Cutaneous response tended to be linear only with higher concentrations of the toxin and showed maximum blueing intensity between 16 and 24 hrs of intracutaneous inoculation. Exposure of enterotoxin preparations to elevated temperatures greatly reduced the cutaneous response and the activity was completely lost at 100 degrees C. Change in pH towards alkaline side lowered the permeability activity to lesser extent as compared to a shift on acidic side. However, a residual activity could still be detected when pH of the enterotoxins was lowered to 3 at 30 degrees C for 4 hrs. | Effect of cholera enterotoxin preparations on cutaneous response in rabbit under varied conditions. Enterotoxic activity of two preparations obtained from Vibrio cholerae, B-53-6 Inaba and B-53-10 Ogawa was tested in ligated ileal loops of rabbit. The biologically active enterotoxic preparations were further used to study the permeability reaction in rabbit skin. Cutaneous response tended to be linear only with higher concentrations of the toxin and showed maximum blueing intensity between 16 and 24 hrs of intracutaneous inoculation. Exposure of enterotoxin preparations to elevated temperatures greatly reduced the cutaneous response and the activity was completely lost at 100 degrees C. Change in pH towards alkaline side lowered the permeability activity to lesser extent as compared to a shift on acidic side. However, a residual activity could still be detected when pH of the enterotoxins was lowered to 3 at 30 degrees C for 4 hrs. | [
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|
PMID:13594 | Pyruvate metabolism in rat brain mitochondria. | 1. Oxidation of pyruvate by rat brain mitochondria was stimulated in state 3 by malate or succinate up to 250 nmoles O2/mg protein/min. Oxidation of malate, succinate, 2-oxoglutarate or glutamate as the sole substrates, was 1/4 - 1/5 that observed with pyruvate. 2. Maximum oxygen consumption in state 3 was observed at pH 6.90 - 7.20, whereas in state 4 it was not affected by changes in pH. 3. In state 4, in the absence of exogenous acceptor or acetyl residues, acetate was the main oxidation product, corresponding to about 80% of the amount of pyruvate utilized. Malate did not affect the rate of pyruvate utilization but lowered acetate concentration and raised concentration of citrate and 2-oxoglutarate. 4. In state 3, pyruvate and malate were converted mainly to 2-oxoglutarate, its concentration being three times as high as that of citrate. 5. Formation of citrate, 2-oxoglutarate and acetate from pyruvate in brain is considered as a function of availability of the acceptor of acetyl residues and the energy state of mitochondrion. | Pyruvate metabolism in rat brain mitochondria. 1. Oxidation of pyruvate by rat brain mitochondria was stimulated in state 3 by malate or succinate up to 250 nmoles O2/mg protein/min. Oxidation of malate, succinate, 2-oxoglutarate or glutamate as the sole substrates, was 1/4 - 1/5 that observed with pyruvate. 2. Maximum oxygen consumption in state 3 was observed at pH 6.90 - 7.20, whereas in state 4 it was not affected by changes in pH. 3. In state 4, in the absence of exogenous acceptor or acetyl residues, acetate was the main oxidation product, corresponding to about 80% of the amount of pyruvate utilized. Malate did not affect the rate of pyruvate utilization but lowered acetate concentration and raised concentration of citrate and 2-oxoglutarate. 4. In state 3, pyruvate and malate were converted mainly to 2-oxoglutarate, its concentration being three times as high as that of citrate. 5. Formation of citrate, 2-oxoglutarate and acetate from pyruvate in brain is considered as a function of availability of the acceptor of acetyl residues and the energy state of mitochondrion. | [
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|
PMID:13595 | Purification and properties of two protease inhibitors from rat skin inhibiting papain and other SH-proteases. | Two papain inhibitors, I1 and I2, from rat skin extract were purified by affinity chromatography on KSCN-modified papain-agarose gel and by gel filtration on Sephadex G-100. I1 had a molecular weight of 74 000, a pI of 4.6, and it contained 4% of carbohydrates. I1 inhibited papain, ficin, bromelain, rat skin benzoylarginine-2-naphthylamide hydrolase, and to a minor extent, rat skin cathepsin C and bovine trypsin. Bovine chymotrypsin or rat skin cathepsin D were not inhibited and benzoylarginine-2-naphthylamide hydrolase was inhibited only at alkaline pH. An inhibitor corresponding to I1 was present in various rat tissues and also in serum. A similar inhibitor was present in the skin of cat, rabbit, guinea pig, and man. I2 had a molecular weight of 13 400, a pI of 4.9 and it contained no carbohydrates. I2 inhibited all thiol proteases tested, but not trypsin, chymotrypsin, or rat skin cathepsin D. I2 formed an equimolar complex with papain and benzoylarginine-2-naphthylamide hydrolase. I2 was present in rat skin, muscle, lung, and small intestine, but not in kidney, liver, or serum. A similar inhibitor was found in skin extracts of cat, rabbit, guinea pig, and man. | Purification and properties of two protease inhibitors from rat skin inhibiting papain and other SH-proteases. Two papain inhibitors, I1 and I2, from rat skin extract were purified by affinity chromatography on KSCN-modified papain-agarose gel and by gel filtration on Sephadex G-100. I1 had a molecular weight of 74 000, a pI of 4.6, and it contained 4% of carbohydrates. I1 inhibited papain, ficin, bromelain, rat skin benzoylarginine-2-naphthylamide hydrolase, and to a minor extent, rat skin cathepsin C and bovine trypsin. Bovine chymotrypsin or rat skin cathepsin D were not inhibited and benzoylarginine-2-naphthylamide hydrolase was inhibited only at alkaline pH. An inhibitor corresponding to I1 was present in various rat tissues and also in serum. A similar inhibitor was present in the skin of cat, rabbit, guinea pig, and man. I2 had a molecular weight of 13 400, a pI of 4.9 and it contained no carbohydrates. I2 inhibited all thiol proteases tested, but not trypsin, chymotrypsin, or rat skin cathepsin D. I2 formed an equimolar complex with papain and benzoylarginine-2-naphthylamide hydrolase. I2 was present in rat skin, muscle, lung, and small intestine, but not in kidney, liver, or serum. A similar inhibitor was found in skin extracts of cat, rabbit, guinea pig, and man. | [
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|
PMID:13596 | Histochemical studies on the mucins of the vertebrate tongues. VII. Histochemical analysis of mucosubstances in the tongues of some fishes. | The tongues of three fishes were investigated histochemically to determine the distribution and nature of mucosubstances by employing recent techniques and the results were considered comparatively with the lingual mucosubstances of other vertebrates. A heterogenous distribution of neutral mucosubstances, sulfomucins and sialomucins in various lingual sites was noted. The taste buds and/or free nerve endings were found to be restricted in the areas containing abundance of goblet cells. In non-gustatory areas of tongue, the goblet cells were very few or absent. Importance of lingual histology in establishing phylogenetic relationships and the possible functional significance of the mucosubstances in the physiology of gustation is discussed in detail. | Histochemical studies on the mucins of the vertebrate tongues. VII. Histochemical analysis of mucosubstances in the tongues of some fishes. The tongues of three fishes were investigated histochemically to determine the distribution and nature of mucosubstances by employing recent techniques and the results were considered comparatively with the lingual mucosubstances of other vertebrates. A heterogenous distribution of neutral mucosubstances, sulfomucins and sialomucins in various lingual sites was noted. The taste buds and/or free nerve endings were found to be restricted in the areas containing abundance of goblet cells. In non-gustatory areas of tongue, the goblet cells were very few or absent. Importance of lingual histology in establishing phylogenetic relationships and the possible functional significance of the mucosubstances in the physiology of gustation is discussed in detail. | [
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|
PMID:13597 | Histochemistry of Centroorhynchus falconis (Das, 1950). | With a view to augment the understanding of the animal mucosubstances in general and Acanthocephalan mucosubstances in particular, Acanthocephalan worms of (Centrorhynchus falconis, Das, 1950) were investigated histochemically by employing recent techniques. Variations in the intensity of histochemical reactions in different tissues revealed a heterogenous distribution of mucosubstances. The cuticle contained a mixture of periodate reactive neutral mucosubstances and sulfomucins, whereas the subcuticle contained only glycogen. Retractor muscles contained glycogen together with some acidic mucosubstances which exhibited alcianophilia only at high pH. Cement glands elaborated a mixture of glycogen and galactogen. Histochemical methods revealed two types of acanthors: Some contained only glycogen, whereas others contained glycogen and galactogen. | Histochemistry of Centroorhynchus falconis (Das, 1950). With a view to augment the understanding of the animal mucosubstances in general and Acanthocephalan mucosubstances in particular, Acanthocephalan worms of (Centrorhynchus falconis, Das, 1950) were investigated histochemically by employing recent techniques. Variations in the intensity of histochemical reactions in different tissues revealed a heterogenous distribution of mucosubstances. The cuticle contained a mixture of periodate reactive neutral mucosubstances and sulfomucins, whereas the subcuticle contained only glycogen. Retractor muscles contained glycogen together with some acidic mucosubstances which exhibited alcianophilia only at high pH. Cement glands elaborated a mixture of glycogen and galactogen. Histochemical methods revealed two types of acanthors: Some contained only glycogen, whereas others contained glycogen and galactogen. | [
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|
PMID:13599 | Intramuscular premedication with lorazepam. | Lorazepam is recognized as a tranquillizer. It is presented for intramuscular and intravenous injection. In a study of this drug's possible effects in premedication, its action was studied systematically when it was used for preoperative premedication. The drug has no side-effects other than drowsiness, which occurs in almost all cases. It produces very good premedication, sometimes with anterograde amnesia in the doses used. This anterograde amnesia is dependent on the dosage used but it is always accompanied by profound drowsiness, from which the patient can be roused verbally. The dose will be selected in relation to whether amnesia is desired or not. However, whatever the dose administered (over 2.5 mg), the tranquillizing effect is always of high quality. | Intramuscular premedication with lorazepam. Lorazepam is recognized as a tranquillizer. It is presented for intramuscular and intravenous injection. In a study of this drug's possible effects in premedication, its action was studied systematically when it was used for preoperative premedication. The drug has no side-effects other than drowsiness, which occurs in almost all cases. It produces very good premedication, sometimes with anterograde amnesia in the doses used. This anterograde amnesia is dependent on the dosage used but it is always accompanied by profound drowsiness, from which the patient can be roused verbally. The dose will be selected in relation to whether amnesia is desired or not. However, whatever the dose administered (over 2.5 mg), the tranquillizing effect is always of high quality. | [
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|
PMID:13600 | The amnesic action of diazepam, flunitrazepam and lorazepam in man. | Studies in man show that it is possible to reliably study the incidence, degree and duration of amnesia produced by drugs by showing patients 10 postcards and testing their ability to recall or recognise them six hours later. Using this method of study it was found that 1 mg flunitrazepam produced a comparable degree of amnesia to 10 mg diazepam, although its action was slightly longer. This difference was more marked when double doses were studied. The onset of the amnesic action of both drugs occurred within 2 minutes of their intravenous injection and rarely persisted for more than 10-15 minutes. In contrast, with 4 mg lorazepam the onset of amnesia was slower and persisted for up to 270 minutes. This was accompanied by a moderate but not excessive amount of drowsiness. Possible clinical uses for such a drug deserve serious consideration. | The amnesic action of diazepam, flunitrazepam and lorazepam in man. Studies in man show that it is possible to reliably study the incidence, degree and duration of amnesia produced by drugs by showing patients 10 postcards and testing their ability to recall or recognise them six hours later. Using this method of study it was found that 1 mg flunitrazepam produced a comparable degree of amnesia to 10 mg diazepam, although its action was slightly longer. This difference was more marked when double doses were studied. The onset of the amnesic action of both drugs occurred within 2 minutes of their intravenous injection and rarely persisted for more than 10-15 minutes. In contrast, with 4 mg lorazepam the onset of amnesia was slower and persisted for up to 270 minutes. This was accompanied by a moderate but not excessive amount of drowsiness. Possible clinical uses for such a drug deserve serious consideration. | [
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|
PMID:13601 | Comparative evaluation of neuromuscular blockade and reversibility of AH 8165 and pancuronium bromide in man. | The neuromuscular properties of AH 8165 were compared to those of pancuronium bromide in 66 patients during analgesic anesthesia procedures. Administration of 0.5 mg/kg AH 8165 and 0.04 mg/kg pancuronium bromide produced very similar degrees of non-depolarizing block. AH 8165 acted quicker and therefore gave better conditions for intubation. Spontaneous recovery of muscle twitch tension was slightly shorter for AH 8165 than for pancuronium bromide, whether small or larger amounts of drugs were used. Administration of neostigmine caused rapid and complete return of muscle twitch tension, well-maintained tetanus and insignificant posttetanic potentiation within 20 minutes, with a similar efficiency of competitive neuromuscular block reversal for both drugs. | Comparative evaluation of neuromuscular blockade and reversibility of AH 8165 and pancuronium bromide in man. The neuromuscular properties of AH 8165 were compared to those of pancuronium bromide in 66 patients during analgesic anesthesia procedures. Administration of 0.5 mg/kg AH 8165 and 0.04 mg/kg pancuronium bromide produced very similar degrees of non-depolarizing block. AH 8165 acted quicker and therefore gave better conditions for intubation. Spontaneous recovery of muscle twitch tension was slightly shorter for AH 8165 than for pancuronium bromide, whether small or larger amounts of drugs were used. Administration of neostigmine caused rapid and complete return of muscle twitch tension, well-maintained tetanus and insignificant posttetanic potentiation within 20 minutes, with a similar efficiency of competitive neuromuscular block reversal for both drugs. | [
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|
PMID:13602 | Turku sugar studies XX. Microbiological findings and plaque index values in relation to 1-year use of xylitol chewing gum. | The aim was to study possible alterations in the microbial flora of plaque and saliva in relation to partial substitution of dietary sucrose with xylitol. The development of plaque index values was observed simultaneously. These observations were carried out during a 1-year clinical trial, the effects of sucrose (S) and xylitol (X) chewing gum on the incidence of dental caries being observed in 100 young adults. Paraffin-stimulated saliva samples were diluted stepwise and cultivated on Rogosa S.L. agar and Sabouraud agar aerobically. Lyophilized dental plaque samples were cultivated on phenol red agar under anaerobic and aerobic conditions. The pH-values were measured after incubating the mixed plaque flora for 1 and 7 days in the presence of various sugars. Both the arithmetic and geometric means of the total CFU values on Rogosa S.L. agar decreased in the S-group at the 6-month phase but returned to the starting level after one year, whereas in the X-group they decreased or remained on the starting level. At the 6-month phase the difference between the groups was significant (U-test, p = 0.0013) and almost significant (U-test, p = 0.0569) at the end of the study. No significant differences or changes could be seen between or within the groups on Sabouraud agar. The geometric mean values of S. sanguis and S. mutans as well as the total CFU values on phenol red agar decreased considerably in both the S- and X-groups, but no significant differences could be detected in any of the streptococcal counts between the groups. The pH of the carbohydrate-containing culture media infected with mixed dental plaque significantly decreased, with the exception of the xylitol containing ones in which the pH values were not lowered even after 7 days' incubation. A significant decrease in plaque formation in relation of chewing per se was demonstrable. The difference in the plaque index values equalling or exceeding 2 was significant between the S- and X-groups. No bacterial adaptation to utilize xylitol occurred during the trial. | Turku sugar studies XX. Microbiological findings and plaque index values in relation to 1-year use of xylitol chewing gum. The aim was to study possible alterations in the microbial flora of plaque and saliva in relation to partial substitution of dietary sucrose with xylitol. The development of plaque index values was observed simultaneously. These observations were carried out during a 1-year clinical trial, the effects of sucrose (S) and xylitol (X) chewing gum on the incidence of dental caries being observed in 100 young adults. Paraffin-stimulated saliva samples were diluted stepwise and cultivated on Rogosa S.L. agar and Sabouraud agar aerobically. Lyophilized dental plaque samples were cultivated on phenol red agar under anaerobic and aerobic conditions. The pH-values were measured after incubating the mixed plaque flora for 1 and 7 days in the presence of various sugars. Both the arithmetic and geometric means of the total CFU values on Rogosa S.L. agar decreased in the S-group at the 6-month phase but returned to the starting level after one year, whereas in the X-group they decreased or remained on the starting level. At the 6-month phase the difference between the groups was significant (U-test, p = 0.0013) and almost significant (U-test, p = 0.0569) at the end of the study. No significant differences or changes could be seen between or within the groups on Sabouraud agar. The geometric mean values of S. sanguis and S. mutans as well as the total CFU values on phenol red agar decreased considerably in both the S- and X-groups, but no significant differences could be detected in any of the streptococcal counts between the groups. The pH of the carbohydrate-containing culture media infected with mixed dental plaque significantly decreased, with the exception of the xylitol containing ones in which the pH values were not lowered even after 7 days' incubation. A significant decrease in plaque formation in relation of chewing per se was demonstrable. The difference in the plaque index values equalling or exceeding 2 was significant between the S- and X-groups. No bacterial adaptation to utilize xylitol occurred during the trial. | [
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|
PMID:13603 | Turku sugar studies XXI. Xylitol, sorbitol-, fructose- and sucrose-induced physico-chemical changes in saliva. | The aim was to study eventual physico-chemical changes occurring in whole saliva due to sweetened and unsweetened stimulators. The assay was carried out in 10 female subjects with regard to changes of pH, buffering capacity and electrolytes in saliva as influenced by chewing of fructose, sucrose, sorbitol and xylitol gum, gum base and paraffin. The flow rate of saliva was measured in relation to use of xylitol and sucrose chewing gum and unsweetened gum base. These sweeteners increased significantly the salivary flow rate in comparison to the unsweetened gum base. Generally, xylitol and sorbitol on one hand, and sucrose and fructose on the other, behaved in an almost similar way. Increased buffering capacity and elevation of pH saliva was found in the presence of the polyols tested. | Turku sugar studies XXI. Xylitol, sorbitol-, fructose- and sucrose-induced physico-chemical changes in saliva. The aim was to study eventual physico-chemical changes occurring in whole saliva due to sweetened and unsweetened stimulators. The assay was carried out in 10 female subjects with regard to changes of pH, buffering capacity and electrolytes in saliva as influenced by chewing of fructose, sucrose, sorbitol and xylitol gum, gum base and paraffin. The flow rate of saliva was measured in relation to use of xylitol and sucrose chewing gum and unsweetened gum base. These sweeteners increased significantly the salivary flow rate in comparison to the unsweetened gum base. Generally, xylitol and sorbitol on one hand, and sucrose and fructose on the other, behaved in an almost similar way. Increased buffering capacity and elevation of pH saliva was found in the presence of the polyols tested. | [
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|
PMID:13604 | Reduced inactivation of tyrosine aminotransferase in the prefused rat liver in the presence of ethanol. | The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally -- 4 hrs potentiates the effects induced by pimozide (0.04 mg/kg intraperitoneally -- 6 hrs) which preferentially blocks central dopamine (DA) receptors, but not the effects induced by phenoxybenzamine (0.5 mg/kg intraperitoneally -- 30 min.) which blocks central noradrenaline (NA) receptors. Furthermore, the behavioural suppression induced by chlorpromazine (0.5 mg/kg intraperitoneally -- 15 min.), thioridazine (1.5 mg/kg intraperitoneally -- 15 min.), or haloperidol (0.02 mg/kg intraperitoneally -- 15 min.) were not potentiated by the administration of the inhibitor of DA-beta-hydroxylase, bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA-63) 4 mg/kg subcutaneously -- 1 hr). The potentiation by alpha-MT of the clinical effects of antipsychotic drugs and of their behavioural effects in animal experiments is in all probability due to a blockade by alpha-MT of a feed-back mediated compensatory increase in the catecholamine synthesis as a result of a blockade of central NA and/or DA receptors by the antipsychotic drugs. Since, in the present experiments, the behavioural effects induced by drugs which block central DA but not NA receptors were potentiated by the simultaneous administration of alpha-MT, it seemed probable that the disruption of conditioned behaviours by antipsychotic drugs is due to a blockade of central DA receptors. In view of the fact that the ability to selectively disrupt conditioned behaviours is shared by a wide range of antipsychotic drugs differing in chemical structure and also in their mode of action, it is possible that a blockade of DA neurotransmission is also of primary importance for the clinical effects induced by antipsychotic drugs. | Reduced inactivation of tyrosine aminotransferase in the prefused rat liver in the presence of ethanol. The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally -- 4 hrs potentiates the effects induced by pimozide (0.04 mg/kg intraperitoneally -- 6 hrs) which preferentially blocks central dopamine (DA) receptors, but not the effects induced by phenoxybenzamine (0.5 mg/kg intraperitoneally -- 30 min.) which blocks central noradrenaline (NA) receptors. Furthermore, the behavioural suppression induced by chlorpromazine (0.5 mg/kg intraperitoneally -- 15 min.), thioridazine (1.5 mg/kg intraperitoneally -- 15 min.), or haloperidol (0.02 mg/kg intraperitoneally -- 15 min.) were not potentiated by the administration of the inhibitor of DA-beta-hydroxylase, bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA-63) 4 mg/kg subcutaneously -- 1 hr). The potentiation by alpha-MT of the clinical effects of antipsychotic drugs and of their behavioural effects in animal experiments is in all probability due to a blockade by alpha-MT of a feed-back mediated compensatory increase in the catecholamine synthesis as a result of a blockade of central NA and/or DA receptors by the antipsychotic drugs. Since, in the present experiments, the behavioural effects induced by drugs which block central DA but not NA receptors were potentiated by the simultaneous administration of alpha-MT, it seemed probable that the disruption of conditioned behaviours by antipsychotic drugs is due to a blockade of central DA receptors. In view of the fact that the ability to selectively disrupt conditioned behaviours is shared by a wide range of antipsychotic drugs differing in chemical structure and also in their mode of action, it is possible that a blockade of DA neurotransmission is also of primary importance for the clinical effects induced by antipsychotic drugs. | [
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|
PMID:13605 | Potentiation by alpha-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs. | The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally - 4 hrs potentiates the effects induced by pimace, causing an alteration of the neuronal function. | Potentiation by alpha-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs. The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally - 4 hrs potentiates the effects induced by pimace, causing an alteration of the neuronal function. | [
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|
PMID:13606 | Characterization of the adrenergic beta-receptor in the urinary bladder of man and cat. | The corpus-fundus of the urinary bladder of man and cat was studied in vitro with respect to type of beta-adrenergic receptors. In both species beta-adrenergic stimulation produced marked relaxation but species differences were apparent. In the cat bladder only beta1-receptors were found. In the human bladder the beta-receptors had neither beta1- nor beta2-characteristics. It is suggested that the beta-adrenergic receptors in the corpus-fundus of the human bladder are of a third type. | Characterization of the adrenergic beta-receptor in the urinary bladder of man and cat. The corpus-fundus of the urinary bladder of man and cat was studied in vitro with respect to type of beta-adrenergic receptors. In both species beta-adrenergic stimulation produced marked relaxation but species differences were apparent. In the cat bladder only beta1-receptors were found. In the human bladder the beta-receptors had neither beta1- nor beta2-characteristics. It is suggested that the beta-adrenergic receptors in the corpus-fundus of the human bladder are of a third type. | [
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|
PMID:13607 | Cholinergic mechanisms in the learning and memory facilitating effect of caffeine. | Experiments are made to train rats in a maze involving memory tests 24 hours and 14 days after training. As it was established in previous studies of the authors, caffeine introduced in low doses (5 mg/kg) 5 min before training facilitates learning and memory. Applied immediately after training, caffeine even in higher doses (20 mg/kg) also improves the memory indices 24 hours and 14 days after the experiment. The anticholinergic agents spasmolytine and scopolamine in higher doses (20 and 2 mg/kg respectively) have a markedly deteriorating effect on learning, while scopolamine deteriorates retention as well. Introduced after training, both drugs deteriorate memory even in smaller doses - 2 and 0,25 mg/kg, respectively. On the background of the anticholinergic agents (especially in the higher doses), the learning and memory facilitating effects of caffeine are not manifested in any of the experimental setups (administration before and after train. The results obtained show that cholinergic mechanisms play an important role in the learning and memory facilitating effect of caffeine. A necessary condition for the manifestation of this effect is the optimum functional level of these cholinergic mechanisms in the central nervous system. | Cholinergic mechanisms in the learning and memory facilitating effect of caffeine. Experiments are made to train rats in a maze involving memory tests 24 hours and 14 days after training. As it was established in previous studies of the authors, caffeine introduced in low doses (5 mg/kg) 5 min before training facilitates learning and memory. Applied immediately after training, caffeine even in higher doses (20 mg/kg) also improves the memory indices 24 hours and 14 days after the experiment. The anticholinergic agents spasmolytine and scopolamine in higher doses (20 and 2 mg/kg respectively) have a markedly deteriorating effect on learning, while scopolamine deteriorates retention as well. Introduced after training, both drugs deteriorate memory even in smaller doses - 2 and 0,25 mg/kg, respectively. On the background of the anticholinergic agents (especially in the higher doses), the learning and memory facilitating effects of caffeine are not manifested in any of the experimental setups (administration before and after train. The results obtained show that cholinergic mechanisms play an important role in the learning and memory facilitating effect of caffeine. A necessary condition for the manifestation of this effect is the optimum functional level of these cholinergic mechanisms in the central nervous system. | [
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|
PMID:13609 | Amylase, hepatic enzymes and bilirubin in serum of chronic alcoholics. | The serum concentration of bilirubin and the activities of aspartate aminotransferase (ASAT, GOT), alanine aminotransferase (ALAT, GPT), gamma-glutamyltransferase (GT), total amylase and pancreatic isoamylase have been determined in serum of 182 male chronic alcoholics. Twelve per cent had abnormally high levels of bilirubin, 73% increased activity of S-ASAT, 50% increased S-ALAT, and 69% increased S-GT. The highest values were often found after 5-20 years of well documented alcoholism. Some patients with alcoholism of more than 20 years' duration displayed a slight tendency towards normalization of the activities. For all parameters the scatter around the mean was greater in the patients than in the controls. Patients who had had attacks of delirium showed slightly higher S-ASAT and S-ALAT than other alcoholics. Determination of S-ALAT and S-bilirubin did not add to the cases with abnormal laboratory tests demonstrated by the combination of S-ASAT and S-GT. In 14 patients the above mentioned parameters were within normal limits, even though severe alcoholism had lasted for many years. Isoamylase determination disclosed 20% to have decreased activity of pancreatic isoamylases in serum, whereas only 6% had low total serum amylase activity. | Amylase, hepatic enzymes and bilirubin in serum of chronic alcoholics. The serum concentration of bilirubin and the activities of aspartate aminotransferase (ASAT, GOT), alanine aminotransferase (ALAT, GPT), gamma-glutamyltransferase (GT), total amylase and pancreatic isoamylase have been determined in serum of 182 male chronic alcoholics. Twelve per cent had abnormally high levels of bilirubin, 73% increased activity of S-ASAT, 50% increased S-ALAT, and 69% increased S-GT. The highest values were often found after 5-20 years of well documented alcoholism. Some patients with alcoholism of more than 20 years' duration displayed a slight tendency towards normalization of the activities. For all parameters the scatter around the mean was greater in the patients than in the controls. Patients who had had attacks of delirium showed slightly higher S-ASAT and S-ALAT than other alcoholics. Determination of S-ALAT and S-bilirubin did not add to the cases with abnormal laboratory tests demonstrated by the combination of S-ASAT and S-GT. In 14 patients the above mentioned parameters were within normal limits, even though severe alcoholism had lasted for many years. Isoamylase determination disclosed 20% to have decreased activity of pancreatic isoamylases in serum, whereas only 6% had low total serum amylase activity. | [
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|
PMID:13613 | Oxygen transport and hemodynamics of stroma-free hemoglobin solutions. | The intravascular persistence of hb-W is significantly longer than of pyridoxylated hb (hb-PLP), however, no significant differences in BV were observed after isovolemic exchange of 20 ml/kg b.w. Even though the oxygen affinity of hb-PLP in vitro was reduced when compared to the affinity of hb-W significant differences in vivo were lacking. The development of hypovolemia and thus the lack of an adequate increase in cardiac output have been recognized as the most relevant causes to explain the changes observed. Neither of the solutions is yet to be recommended for clinical blood replacement therapy. | Oxygen transport and hemodynamics of stroma-free hemoglobin solutions. The intravascular persistence of hb-W is significantly longer than of pyridoxylated hb (hb-PLP), however, no significant differences in BV were observed after isovolemic exchange of 20 ml/kg b.w. Even though the oxygen affinity of hb-PLP in vitro was reduced when compared to the affinity of hb-W significant differences in vivo were lacking. The development of hypovolemia and thus the lack of an adequate increase in cardiac output have been recognized as the most relevant causes to explain the changes observed. Neither of the solutions is yet to be recommended for clinical blood replacement therapy. | [
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|
PMID:13615 | Problems in determination of oxygen dissociation of avian blood. | No appreciable errors are expected in determination of blood gas values and pH using classical techniques provided time of anaerobic storage is kept small and is, if unavoidable performed on ice. In particular, dissociation curves may safely be analyzed with the Van Slyke technique which is in disagreement with the conclusions of Lutz et al. (1973). For measurement of PO2 and PCO2, delay time is mainly dictated by response time of the electrodes; measurements may have to be corrected for metabolism, particularly in high PO2 range. | Problems in determination of oxygen dissociation of avian blood. No appreciable errors are expected in determination of blood gas values and pH using classical techniques provided time of anaerobic storage is kept small and is, if unavoidable performed on ice. In particular, dissociation curves may safely be analyzed with the Van Slyke technique which is in disagreement with the conclusions of Lutz et al. (1973). For measurement of PO2 and PCO2, delay time is mainly dictated by response time of the electrodes; measurements may have to be corrected for metabolism, particularly in high PO2 range. | [
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PMID:13616 | A theoretical model of the respiratory function of blood. | The model of the respiratory function of blood as outlined here is judged to be a powerful tool for the evaluation of the potential effects of changes in blood as well as tissue parameters upon the supply of oxygen to tissue. The erythrocyte-plasma disequilibria in lung and systemic capillaries which is a consequence of the slowness of plasma CO2 hydrolysis are not significant in terms of the delivery of oxygen to tissue, but result in slightly lower unloading of CO2 in the lungs compared to that which might occur at full equilibration. However, the effects might be of greater interest when relating pH values measured by in vivo sampling to actual values prevailing within the capillaries. The physiological importances of hyperventilation and elevated DPG levels in anemia cannot as yet be clarified. If anything, it appears that increased DPG is a compensatory mechanism to restore proper O2-Hb affinity in alkalosis, while the purpose for an alkalosis is not obvious. | A theoretical model of the respiratory function of blood. The model of the respiratory function of blood as outlined here is judged to be a powerful tool for the evaluation of the potential effects of changes in blood as well as tissue parameters upon the supply of oxygen to tissue. The erythrocyte-plasma disequilibria in lung and systemic capillaries which is a consequence of the slowness of plasma CO2 hydrolysis are not significant in terms of the delivery of oxygen to tissue, but result in slightly lower unloading of CO2 in the lungs compared to that which might occur at full equilibration. However, the effects might be of greater interest when relating pH values measured by in vivo sampling to actual values prevailing within the capillaries. The physiological importances of hyperventilation and elevated DPG levels in anemia cannot as yet be clarified. If anything, it appears that increased DPG is a compensatory mechanism to restore proper O2-Hb affinity in alkalosis, while the purpose for an alkalosis is not obvious. | [
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|
PMID:13627 | Control of prolactin secretion by the hypothalamic catecholamines. | The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion. | Control of prolactin secretion by the hypothalamic catecholamines. The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion. | [
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|
PMID:13630 | [Immunologic relations between cattle and ticks, specifically between cattle and Boophilus microplus]. | In the present investigation, it has been demonstrated that cattle become resistant to ticks after several heavy infestations, particularly with B. microplus. During development of the infestations, antibodies against salivary glands of B. microplus were detected using 2 techniques: indirect immunofluorescence and immunoelectrophoresis. There is a positive causal relationship between antibody titer and resistance development. Two precipitating systems against B. microplus in infested cattle and 7 systems in immunized rabbits were studied. The systems 1 and 2 are similar in cattle and rabbits, but system 2 does not show any specificity, as it has been detected in cattle completely lacking tick infestations. Two one-day calves were treated with the antigen of B. microplus by injection of salivary glands and repeated infestations with a small number of larvae. They developed a pronounced resistance to the usual subsequent infestations by the ticks of the same species. Specific antibodies were found before the first usual infestation. This suggests that they might be responsible for resistance. | [Immunologic relations between cattle and ticks, specifically between cattle and Boophilus microplus]. In the present investigation, it has been demonstrated that cattle become resistant to ticks after several heavy infestations, particularly with B. microplus. During development of the infestations, antibodies against salivary glands of B. microplus were detected using 2 techniques: indirect immunofluorescence and immunoelectrophoresis. There is a positive causal relationship between antibody titer and resistance development. Two precipitating systems against B. microplus in infested cattle and 7 systems in immunized rabbits were studied. The systems 1 and 2 are similar in cattle and rabbits, but system 2 does not show any specificity, as it has been detected in cattle completely lacking tick infestations. Two one-day calves were treated with the antigen of B. microplus by injection of salivary glands and repeated infestations with a small number of larvae. They developed a pronounced resistance to the usual subsequent infestations by the ticks of the same species. Specific antibodies were found before the first usual infestation. This suggests that they might be responsible for resistance. | [
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PMID:13631 | The occurrence of an intraerythrocytic microorganism Neitziella rezendei gen. nov. sp. nov. (Microtatobiotes, Rickettsiales) of poultry in Brazil. | An extremely polymorphous intraerythrocytic microorganism occurring in naturally infected turkeys, ducks and fowls has been discovered in the states of Minas Gerais, Rio de Janeiro and Espirito Santo. 2. Studies on the morphology and biology have shown that it is a hitherto undescribed heteroxenous parasite for which the name Neitziella rezendei gen. nov., sp. nov. is proposed. 3. Its morphological features permit its inclusion in the class Microtatobiotes and order Rickettsiales. 4. Microscopical examination of blood films have shown that the parasitic carrier state in turkeys persists for more than 200 days (endpoint not determined). 5. The natural mode of transmission needs to be determined. 6. The suspicion that the parasite may cause illthrift and deaths in poultry requires confirmation. | The occurrence of an intraerythrocytic microorganism Neitziella rezendei gen. nov. sp. nov. (Microtatobiotes, Rickettsiales) of poultry in Brazil. An extremely polymorphous intraerythrocytic microorganism occurring in naturally infected turkeys, ducks and fowls has been discovered in the states of Minas Gerais, Rio de Janeiro and Espirito Santo. 2. Studies on the morphology and biology have shown that it is a hitherto undescribed heteroxenous parasite for which the name Neitziella rezendei gen. nov., sp. nov. is proposed. 3. Its morphological features permit its inclusion in the class Microtatobiotes and order Rickettsiales. 4. Microscopical examination of blood films have shown that the parasitic carrier state in turkeys persists for more than 200 days (endpoint not determined). 5. The natural mode of transmission needs to be determined. 6. The suspicion that the parasite may cause illthrift and deaths in poultry requires confirmation. | [
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PMID:13632 | Protease activity in female Ornithodoros tholozani ticks. | The protease activity in guts of Ornithodoros tholozani females was studied in vitro. The intracellular protease in Ornithodoros tholozani guts has a pH optimum of about 3.0. Hemoglobin is the preferred substrate, and bovine serum albumin is digested very slowly. In this respect the protease resembles cathepsin D. Unfed ticks contain a small amount of protease in the gut. After feeding the level of protease increases gradually for several days until peak protease activity is attained. The level of gut protease activity depends on the size of the blood meal taken and on the interval after feeding. After a period of peak protease activity, the level of protease declines. The level of gut protease in unmated females (kept at 27 degrees C) did not reach prefeeding levels within 100 days. The level of gut proteolytic activity, as determined by in vitro protease assays, does not reflect the degree of blood digestion which takes place in vivo. After a period of rapid digestion, lasting for about two weeks, the undigested part of the blood meal remains unchanged in the lumen of the gut. At that time the gut tissue contains considerable levels of protease, which can be demonstrated by in vitro assays. Presumably, the protease remains active inside the gut cells, although the uptake of hemoglobin from the gut lumen has ceased. The results are compared to those obtained in other tick species. | Protease activity in female Ornithodoros tholozani ticks. The protease activity in guts of Ornithodoros tholozani females was studied in vitro. The intracellular protease in Ornithodoros tholozani guts has a pH optimum of about 3.0. Hemoglobin is the preferred substrate, and bovine serum albumin is digested very slowly. In this respect the protease resembles cathepsin D. Unfed ticks contain a small amount of protease in the gut. After feeding the level of protease increases gradually for several days until peak protease activity is attained. The level of gut protease activity depends on the size of the blood meal taken and on the interval after feeding. After a period of peak protease activity, the level of protease declines. The level of gut protease in unmated females (kept at 27 degrees C) did not reach prefeeding levels within 100 days. The level of gut proteolytic activity, as determined by in vitro protease assays, does not reflect the degree of blood digestion which takes place in vivo. After a period of rapid digestion, lasting for about two weeks, the undigested part of the blood meal remains unchanged in the lumen of the gut. At that time the gut tissue contains considerable levels of protease, which can be demonstrated by in vitro assays. Presumably, the protease remains active inside the gut cells, although the uptake of hemoglobin from the gut lumen has ceased. The results are compared to those obtained in other tick species. | [
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|
PMID:13637 | Human sleeping sickness in the Gboko endemic area of Nigeria. | Human infection with Trypanosoma gambiense in the Gboko endemic area was first reported in May, 1974 although T. gambiense sleeping sickness had been present there since the turn of the century. The disease is associated with the presence of the tsetse Glossina tachinoides and Glossina palpalis which is plentiful and widespread throughout the division as well as in thickets along the streams in the area. No successful attempt has been made to control the tsetse vector in the Division. The incidence and geographical distribution of cases of T. gambiense sleeping sickness in the Gboko area are described in this report. Cases were treated with Antrypol Tryparsamide mixture and Mel B. The highest number of cases of infection is usually picked up just before the start of the rains in early April. It is suggested that, for meaningful control of the disease a quick method should be devised to rid the area of the insect vector. | Human sleeping sickness in the Gboko endemic area of Nigeria. Human infection with Trypanosoma gambiense in the Gboko endemic area was first reported in May, 1974 although T. gambiense sleeping sickness had been present there since the turn of the century. The disease is associated with the presence of the tsetse Glossina tachinoides and Glossina palpalis which is plentiful and widespread throughout the division as well as in thickets along the streams in the area. No successful attempt has been made to control the tsetse vector in the Division. The incidence and geographical distribution of cases of T. gambiense sleeping sickness in the Gboko area are described in this report. Cases were treated with Antrypol Tryparsamide mixture and Mel B. The highest number of cases of infection is usually picked up just before the start of the rains in early April. It is suggested that, for meaningful control of the disease a quick method should be devised to rid the area of the insect vector. | [
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PMID:13638 | Mel B toxicity in human trypanosomiasis in the Gboko endemic area of Nigeria. | Nine cases of Mel B (a melaminyl arsenical used in treating sleeping sickness patients who have developed central nervous system involvement) treated patients who developed reactions to the drug are described. They all developed high temperatures, pyrexia, diarrhoea, vomitting or itching and some had convulsions. Three of the nine described patients died. It is recommended that extra care and caution is needed while treating patients with Mel B. | Mel B toxicity in human trypanosomiasis in the Gboko endemic area of Nigeria. Nine cases of Mel B (a melaminyl arsenical used in treating sleeping sickness patients who have developed central nervous system involvement) treated patients who developed reactions to the drug are described. They all developed high temperatures, pyrexia, diarrhoea, vomitting or itching and some had convulsions. Three of the nine described patients died. It is recommended that extra care and caution is needed while treating patients with Mel B. | [
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|
PMID:13639 | Principles of complementation interaction of ts mutants of orthomyxoviruses. | The possibility of complementation between ts mutants of fowl plague virus (FPV) belonging to 5 different complementation groups was studied using various time intervals between inoculation of the cells with two complementation partners. The structural proteins of virions formed on complementation of individual ts mutants with wild virus were analysed by polyacrylamide gel electrophoresis after amino acid pulse label followed by pulse chase. The features of complementation interactions between the mutants are discussed. | Principles of complementation interaction of ts mutants of orthomyxoviruses. The possibility of complementation between ts mutants of fowl plague virus (FPV) belonging to 5 different complementation groups was studied using various time intervals between inoculation of the cells with two complementation partners. The structural proteins of virions formed on complementation of individual ts mutants with wild virus were analysed by polyacrylamide gel electrophoresis after amino acid pulse label followed by pulse chase. The features of complementation interactions between the mutants are discussed. | [
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|
PMID:13640 | Influence of host cell type on the density of herpes simplex virus particles. | The densities of purified herpes simplex virus (HSV) particles prepared from infected rabbit lung (ZP) and baby hamster kidney (BHK-21) cells were investigated in potassium tartrate (PT) and potassium citrate (PC) density gradients. Virions obtained from ZP cells exhibited a higher density than those from BHK-21 cells. In PT and PC gradients, the former banded at densities of 1.226 and 1.267, while tha latter at 1.194 and 1.233, respectively. Deenveloped viral particles prepared by Nonidet P-40 treatment from purified virions of either origin were found in PT and PC gradients at the densities of 1.263 and 1.320, respectively. The possible causes of the density change of virions propagated in different hosts are discussed. | Influence of host cell type on the density of herpes simplex virus particles. The densities of purified herpes simplex virus (HSV) particles prepared from infected rabbit lung (ZP) and baby hamster kidney (BHK-21) cells were investigated in potassium tartrate (PT) and potassium citrate (PC) density gradients. Virions obtained from ZP cells exhibited a higher density than those from BHK-21 cells. In PT and PC gradients, the former banded at densities of 1.226 and 1.267, while tha latter at 1.194 and 1.233, respectively. Deenveloped viral particles prepared by Nonidet P-40 treatment from purified virions of either origin were found in PT and PC gradients at the densities of 1.263 and 1.320, respectively. The possible causes of the density change of virions propagated in different hosts are discussed. | [
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|
PMID:13641 | Reversible inhibition of interferon-induced antiviral state by deoxyadenosine. | Deoxyadenosine reversibly inhibited the development of antiviral state (AVS) in chick embryo fibroblasts stimulated by interferon. Studies on cellular macromolecular syntheses in deoxyadenosine-treated cells suggested that the inhibition was related to nucleolar RNA synthesis. Reference experiments with actinomycin D and cordycepin (3'deoxyadenosine) also implied causal- or interrelation between AVS development and nucleolar RNA synthesis. | Reversible inhibition of interferon-induced antiviral state by deoxyadenosine. Deoxyadenosine reversibly inhibited the development of antiviral state (AVS) in chick embryo fibroblasts stimulated by interferon. Studies on cellular macromolecular syntheses in deoxyadenosine-treated cells suggested that the inhibition was related to nucleolar RNA synthesis. Reference experiments with actinomycin D and cordycepin (3'deoxyadenosine) also implied causal- or interrelation between AVS development and nucleolar RNA synthesis. | [
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|
PMID:13642 | Study of the priming effect of interferon in L cells. I. The primed interferon response and the kinetics of development of priming. | Interferon was detected one hour earlier, its production followed an enhanced pattern and became resistant to actinomycin D 30 minutes sooner in cultures primed by interferon pretreatment before stimulation by polyriboinosinic-polyribocytidylic acid than in unprimed cultures. The kinetics of development of the primed state was found to be a time and dose dependent phenomenon. The continuous presence of interferon during the pretreatment period was not required for the development of the primed state. | Study of the priming effect of interferon in L cells. I. The primed interferon response and the kinetics of development of priming. Interferon was detected one hour earlier, its production followed an enhanced pattern and became resistant to actinomycin D 30 minutes sooner in cultures primed by interferon pretreatment before stimulation by polyriboinosinic-polyribocytidylic acid than in unprimed cultures. The kinetics of development of the primed state was found to be a time and dose dependent phenomenon. The continuous presence of interferon during the pretreatment period was not required for the development of the primed state. | [
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|
PMID:13643 | Phenothiazine-induced alterations of immune response in experimental tick-borne encephalitis: morphological model analysis of events. | The depressive effect of trifluoperazine (TFP), a phenothiazine derivative, on the morphology of the development of immune response (IR) (humoral and cell-mediated component) was studied in mice given tick-borne encephalitis (TBE) virus, sheep red blood cells (SRBC) or the BCG vaccine. This effect was manifested by a decrease in the mitotic activity of lymphocytes and in the number of blastic transformations after antigenic stimulation. In virus-infected and TFP-given mice, lowered levels of specific virus neutralizing antibody (VNA), together with a pronounced reduction of the inflammatory response in the brain were found. No signs of cytotoxicity following administration of the drug were observed. The mechanism of the immunodepressive action of TFP are discussed. | Phenothiazine-induced alterations of immune response in experimental tick-borne encephalitis: morphological model analysis of events. The depressive effect of trifluoperazine (TFP), a phenothiazine derivative, on the morphology of the development of immune response (IR) (humoral and cell-mediated component) was studied in mice given tick-borne encephalitis (TBE) virus, sheep red blood cells (SRBC) or the BCG vaccine. This effect was manifested by a decrease in the mitotic activity of lymphocytes and in the number of blastic transformations after antigenic stimulation. In virus-infected and TFP-given mice, lowered levels of specific virus neutralizing antibody (VNA), together with a pronounced reduction of the inflammatory response in the brain were found. No signs of cytotoxicity following administration of the drug were observed. The mechanism of the immunodepressive action of TFP are discussed. | [
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|
PMID:13644 | Influence of temperatures corresponding to those of the host animals on Tahyna virus. | The influence of temperature of 36.5 and 39.2 degrees C on uncloned low passage Tahyna virus in chick embryo cell cultures was studied in the course of 10 passages. At a high multiplicity of infection, the virus titres showed a considerable variability, especially at 39.2 degrees C. The cytopathic effect (CPE) apparent at both temperatures started later and was of lower intensity at 39.2 degrees C than at 36.5 degrees C. The temperature of 39.2 degrees C intensified the thermostable character of the virus. Changes in plaque size and virulence were connected mainly with the cultivation substrate of the virus. | Influence of temperatures corresponding to those of the host animals on Tahyna virus. The influence of temperature of 36.5 and 39.2 degrees C on uncloned low passage Tahyna virus in chick embryo cell cultures was studied in the course of 10 passages. At a high multiplicity of infection, the virus titres showed a considerable variability, especially at 39.2 degrees C. The cytopathic effect (CPE) apparent at both temperatures started later and was of lower intensity at 39.2 degrees C than at 36.5 degrees C. The temperature of 39.2 degrees C intensified the thermostable character of the virus. Changes in plaque size and virulence were connected mainly with the cultivation substrate of the virus. | [
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|
PMID:13645 | Influence of temperature corresponding to that of the vector on Tahyna virus. | The behaviour of uncloned, low-passage Tahyna virus in an Aedes albopictus (AA) cell line at 28 and 20 degrees C was studied in the course of 10 passages. The virus multiplied at both temperatures without any apparent effect on the host cell. At 28 and 20 degrees C reduction of plaque size, decrease of peripheral virulence and weakening of thermostability were observed. Differences between both temperatures were only in the intensity of these changes. | Influence of temperature corresponding to that of the vector on Tahyna virus. The behaviour of uncloned, low-passage Tahyna virus in an Aedes albopictus (AA) cell line at 28 and 20 degrees C was studied in the course of 10 passages. The virus multiplied at both temperatures without any apparent effect on the host cell. At 28 and 20 degrees C reduction of plaque size, decrease of peripheral virulence and weakening of thermostability were observed. Differences between both temperatures were only in the intensity of these changes. | [
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|
PMID:13646 | Cultivation of Lednice (Yaba 1) virus in goose, duck, and chick embryo cells. | Lednice (Yaba 1) virus was found to multiply in primary cultures of goose, duck and chick embryo cells. The size of inoculum and age of embryos used for preparation of primary cultures was decisive for the amount of multiplied virus. One strain (110) of Lednice virus showed reduced ability to induce a cytopathic effect in the first passage in chick embryo cells. Virus multiplication in all three kinds of cells was confirmed by immunofluorescence. | Cultivation of Lednice (Yaba 1) virus in goose, duck, and chick embryo cells. Lednice (Yaba 1) virus was found to multiply in primary cultures of goose, duck and chick embryo cells. The size of inoculum and age of embryos used for preparation of primary cultures was decisive for the amount of multiplied virus. One strain (110) of Lednice virus showed reduced ability to induce a cytopathic effect in the first passage in chick embryo cells. Virus multiplication in all three kinds of cells was confirmed by immunofluorescence. | [
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|
PMID:13648 | Systematic management of the anxious patient. | The patient usually consults his family physician because of the physical symptoms of anxiety, usually cardiorespiratory, but often gastrointestinal or musculoskeletal. An organized, systematic approach includes these steps: an invitation to talk; identifying the problem; understanding the patient's wishes; choosing an appropriate drug (if necessary); involving the family, and behavioral modification techniques. | Systematic management of the anxious patient. The patient usually consults his family physician because of the physical symptoms of anxiety, usually cardiorespiratory, but often gastrointestinal or musculoskeletal. An organized, systematic approach includes these steps: an invitation to talk; identifying the problem; understanding the patient's wishes; choosing an appropriate drug (if necessary); involving the family, and behavioral modification techniques. | [
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|
PMID:13650 | Observations of plasma secretin levels by radioimmunoassay in response to duodenal acidification and to a meat meal in humans. | The endogenous release of secretin in healthy human subjects was studied by measuring plasma secretin levels by radioimmunoassay (RIA) before, during, and following duodenal acidification and eating a meal. The sensitivity of our RIA was assessed by measuring plasma secretin levels during constant intravenous infusions of 4 graded doses of secretin. Our RIA detected significant increases (P less than 0.001) in plasma secretin with each dose, including a low dose of 0.125 U (41.3 ng)/kg hr. Intraduodenal infusion of 0.1 N HCl resulted in marked increases (P less than 0.001) in plasma secretin levels whenever pH in the second portion of the duodenum was reduced to less than 3.5. In contrast, following a meal, pH in the second portion of the duodenum remained consistently greater than 4.5 and plasma secretin levels showed no changes from basal levels. These studies confirm that endogenous release of secretin depends on an acidic pH of the duodenum, and insigificant changes in the plasma secretin level following ingestion of a meal suggest that endogenous release of secretin in the postprandial period is probably to small in quantity to be detected by the present radioimmunoassay method. | Observations of plasma secretin levels by radioimmunoassay in response to duodenal acidification and to a meat meal in humans. The endogenous release of secretin in healthy human subjects was studied by measuring plasma secretin levels by radioimmunoassay (RIA) before, during, and following duodenal acidification and eating a meal. The sensitivity of our RIA was assessed by measuring plasma secretin levels during constant intravenous infusions of 4 graded doses of secretin. Our RIA detected significant increases (P less than 0.001) in plasma secretin with each dose, including a low dose of 0.125 U (41.3 ng)/kg hr. Intraduodenal infusion of 0.1 N HCl resulted in marked increases (P less than 0.001) in plasma secretin levels whenever pH in the second portion of the duodenum was reduced to less than 3.5. In contrast, following a meal, pH in the second portion of the duodenum remained consistently greater than 4.5 and plasma secretin levels showed no changes from basal levels. These studies confirm that endogenous release of secretin depends on an acidic pH of the duodenum, and insigificant changes in the plasma secretin level following ingestion of a meal suggest that endogenous release of secretin in the postprandial period is probably to small in quantity to be detected by the present radioimmunoassay method. | [
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|
PMID:13651 | Lower esophageal sphincter pressure and serum motilin levels. | The gastrointestinal hormone motilin has recently been proposed as having a physiological role in the determination of lower esophageal sphincter (LES) strength. The present study was performed to evaluate the effect of gastric alkalinization of LES pressure and serum motilin levels. Instillation of 0.1N NaHCO3 into the stomach resulted in a significant increase in LES pressure (P less than 0.01) without affecting serum motilin levels. No correlation was found between fasting serum motilin levels and resting LES pressure (r = -0.31). These observations do not support the theory that LES pressure increases during gastric alkalinization are mediated through motilin release. | Lower esophageal sphincter pressure and serum motilin levels. The gastrointestinal hormone motilin has recently been proposed as having a physiological role in the determination of lower esophageal sphincter (LES) strength. The present study was performed to evaluate the effect of gastric alkalinization of LES pressure and serum motilin levels. Instillation of 0.1N NaHCO3 into the stomach resulted in a significant increase in LES pressure (P less than 0.01) without affecting serum motilin levels. No correlation was found between fasting serum motilin levels and resting LES pressure (r = -0.31). These observations do not support the theory that LES pressure increases during gastric alkalinization are mediated through motilin release. | [
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|
PMID:13647 | Imminent shock; a useful diagnosis in drug pathology. | A research has been carried out on a total of 121 persons with survival post-drug shock (DS), which registered 192 DS. Mention should be made of their predominance in the feminine sex (85 per cent) and their maximum frequency between the ages of 21-50 (average age 34). DS was the first adverse reaction to drugs in 71 per cent of the cases. Therefore DS unpredictability is very frequent. A retrospective study suggested the role of risk factors which should help the doctor to prevent DS (personal allergic antecedents, antecedents of adverse reactions to drugs, neuroses, disorders of endocrine glands, feminine sex, etc.). In 1970, the clinical concept of shock imminence (SI) was formulated and it is applied to various etiologies (drugs, insect stings, food). The existence of SI was identified in the case history of 14 per cent of the persons with DS. SI is a syndrome which includes all clinical manifestations with imminent potential of transformation into shock condition, and represents the stage precursory to the setting up of shock. The utility of SI diagnosis is maximum if it also includes the causal factor (e.g. SI by penicillin or aspirin). The clinical image of SI may vary from the monosymptomatic aspect (urticaria, vomiting, diarrhoea, headaches, etc.) to the one with complex symptomatology (mixed form). Usually the symptoms are dramatic and depend on the administration of a certain drug (often in SI of allergic origin) or of various drugs (mainly on non-immunologic form). The absence of vascular collapse differentiates SI from shock. Differential diagnosis is more difficult in border cases with a slight diminution of blood pressure. SI can be diagnosed especially in several circumstances: when the first adverse drug reaction is dramatic; when the first allergic-type reaction to a drug occurs; when the repetition of drug reactions is amplified in intensity or frequency; when it occurs in persons with risk factors. The differential diagnosis of SI is made with a crude or minimum shock and with pre-shock condition. The advantages of SI diagnosis are the institution of efficient treatment with rapid recoverability and the prevention of subsequent shock to the respective drug. | Imminent shock; a useful diagnosis in drug pathology. A research has been carried out on a total of 121 persons with survival post-drug shock (DS), which registered 192 DS. Mention should be made of their predominance in the feminine sex (85 per cent) and their maximum frequency between the ages of 21-50 (average age 34). DS was the first adverse reaction to drugs in 71 per cent of the cases. Therefore DS unpredictability is very frequent. A retrospective study suggested the role of risk factors which should help the doctor to prevent DS (personal allergic antecedents, antecedents of adverse reactions to drugs, neuroses, disorders of endocrine glands, feminine sex, etc.). In 1970, the clinical concept of shock imminence (SI) was formulated and it is applied to various etiologies (drugs, insect stings, food). The existence of SI was identified in the case history of 14 per cent of the persons with DS. SI is a syndrome which includes all clinical manifestations with imminent potential of transformation into shock condition, and represents the stage precursory to the setting up of shock. The utility of SI diagnosis is maximum if it also includes the causal factor (e.g. SI by penicillin or aspirin). The clinical image of SI may vary from the monosymptomatic aspect (urticaria, vomiting, diarrhoea, headaches, etc.) to the one with complex symptomatology (mixed form). Usually the symptoms are dramatic and depend on the administration of a certain drug (often in SI of allergic origin) or of various drugs (mainly on non-immunologic form). The absence of vascular collapse differentiates SI from shock. Differential diagnosis is more difficult in border cases with a slight diminution of blood pressure. SI can be diagnosed especially in several circumstances: when the first adverse drug reaction is dramatic; when the first allergic-type reaction to a drug occurs; when the repetition of drug reactions is amplified in intensity or frequency; when it occurs in persons with risk factors. The differential diagnosis of SI is made with a crude or minimum shock and with pre-shock condition. The advantages of SI diagnosis are the institution of efficient treatment with rapid recoverability and the prevention of subsequent shock to the respective drug. | [
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|
PMID:13652 | Effect of methylated PGE2 analogs given orally on pancreatic response to secretin in man. | The effect of two methylated PGE2 analogs given orally on the pancreatic response to intravenous secretin has been studied in 8 healthy subjects. The secretion of bicarbonate was not changed by these PGE2 analogs. The secretion of enzymes during infusion of PGE2 analogs was significantly greater than in the control. | Effect of methylated PGE2 analogs given orally on pancreatic response to secretin in man. The effect of two methylated PGE2 analogs given orally on the pancreatic response to intravenous secretin has been studied in 8 healthy subjects. The secretion of bicarbonate was not changed by these PGE2 analogs. The secretion of enzymes during infusion of PGE2 analogs was significantly greater than in the control. | [
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|
PMID:13653 | Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria. | A patient with paroxysmal nocturnal hemoglobinuria, who required many blood transfusions for hemolytic episodes, had a persistent hyperchloremic metabolic acidosis. Bicarbonate infusion demonstrated a large fractional excretion of bicarbonate (28.6 per cent at a plasma bicarbonate level of 23 meq/liter) which was consistent with proximal renal tubular acidosis. Generalized aminoaciduria and decreased tubular reabsorption of phosphate were also present. Marked deposition of iron in renal proximal tubules was associated with these functional abnormalities. We believe that, as systemic acidosis can promote hemolysis in patients with paroxysmal nocturnal hemoglobinuria, hemolysis can lead, by way of iron deposition in renal tubules, to further acidosis. This cycle should be interrupted with appropriate doses of bicarbonate. | Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria. A patient with paroxysmal nocturnal hemoglobinuria, who required many blood transfusions for hemolytic episodes, had a persistent hyperchloremic metabolic acidosis. Bicarbonate infusion demonstrated a large fractional excretion of bicarbonate (28.6 per cent at a plasma bicarbonate level of 23 meq/liter) which was consistent with proximal renal tubular acidosis. Generalized aminoaciduria and decreased tubular reabsorption of phosphate were also present. Marked deposition of iron in renal proximal tubules was associated with these functional abnormalities. We believe that, as systemic acidosis can promote hemolysis in patients with paroxysmal nocturnal hemoglobinuria, hemolysis can lead, by way of iron deposition in renal tubules, to further acidosis. This cycle should be interrupted with appropriate doses of bicarbonate. | [
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0.00719942944124341
]
|
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