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7,200 |
The Effect of Calfhood Diseases on Growth of Female Dairy Calves During the First 3 Months of Life in New York State
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Our objective was to study the effects of pneumonia (cumulative incidence, 25%), diarrhea (29%), umbilical infection (14%), and umbilical hernia (15%) on BW and height gains during the first 3 mo of life. Female dairy calves (n = 410) born from January to December 1990 in 18 commercial herds in New York state were used. Average daily gains during the 1st, 2nd, and 3rd mo were 374, 596, and 719 g, respectively; average gain was 565 g during the 3-mo period. Average monthly height gains during the 1st, 2nd, and 3rd mo were 4.4, 5.6, and 5.7 cm, respectively. Use of multiple linear regression, with farms treated as random effects, indicated that treated, verified pneumonia was associated with a reduction in average daily gain of 66 g and that failure of passive transfer reduced average daily gain by 48 g during the 1st mo. During the 2nd mo, neither disease nor failure of passive transfer affected average daily gain. During the 3rd mo, each additional week of pneumonia reduced average daily gain by 14 g, and umbilical infection reduced average daily gain by 96 g. Each additional week of diagnosed pneumonia reduced total BW gain during the first 3 mo by 0.8 kg. Similarly, each week of pneumonia reduced total height gain by 0.2 cm and failure of passive transfer by 0.9 cm. Prevention of chronic pneumonia and umbilical infection may improve average daily gain of calves.
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7,201 |
Interferon induction in swine lymphocyte antigen-defined miniature pigs
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Interferon was induced in two groups of swine lymphocyte antigen (SLA)-defined miniature pigs with polyinosinic: polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose. The group 1 pigs were low antibody-response phenotypes (SLA(a/a), SLA(a/c), SLA(c/c)), and the group 2 pigs were high antibody-response phenotypes (SLA(d/d), SLA(d/g), SLA(g/g)). Six hours after induction the antiviral titres were not influenced by the SLA group, but higher titres were observed in females. Higher antiviral titres were found in group 2 pigs before treatment and 24 hours after treatment, and higher titres were found in female pigs. The antiviral titres before and after treatment were also influenced by the sire. Group 2 pigs had lower total leucocyte counts before treatment, and there was a significant reduction in leucocyte numbers in both groups six hours after induction, due mainly to a large reduction in lymphocyte counts.
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7,202 |
Three-generation toxicity study of rats ingesting Brown HT in the diet
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Brown HT was fed to rats of both sexes over three generations at dietary concentrations designed to provide daily intakes of 0, 50, 250 and 500 mg Brown HT/kg body weight/day. During the study a number of females died or failed to nurse their litters. This was so severe following the first mating of F(1) adults that the animals were remated to provide the next generation. None of these effects were related to treatment. Body weight and food and water intakes were not adversely affected by treatment. No effects of treatment were seen on reproductive performance or foetal and pup development, apart from slight evidence of a treatment-related retarded ossification of the third sternebrae. Organ weights at autopsy showed two changes, one of which was increased kidney weights which, although not present in every generation, seemed to be related to treatment. The other, increased caecum weights, occurred in adult high-dose females of early generations, but not in males or later generations of the study. Apart from brown coloration of tissues, macroscopic and microscopic examination revealed no treatment-related changes. It was concluded that the no-untoward-effect level in the present study was 250 mg Brown HT/kg/day.
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7,203 |
Vaccines for preventing enterotoxigenic Escherichia coli infections in farm animals
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Fimbrial vaccines are routinely given parenterally to pregnant cattle, sheep and swine to protect suckling newborn calves, lambs and pigs against enterotoxigenic Escherichia coli (ETEC) infections. Such vaccines are practical and effective because (1) most fatal ETEC infections in farm animals occur in the early neonatal period when the antibody titres in colostrum and milk are highest; (2) more than 90% of the ETEC in farm animals belong to a small family of fimbrial antigen types: (3) fimbriae consist of good protein antigens on the bacterial surface where they are readily accessible to antibody; (4) fimbriae are required for a critical step (adhesion-colonization) early in the pathogenesis of the disease. ETEC infections continue to be a significant clinical problem in farm animals in spite of extensive use of fimbriae-based vaccines. Definitive data on the efficacy of the commercial vaccines in field use are not available. The prevailing perception among animal health professionals is that the vaccines are effective, that the problem occurs chiefly among non-vaccinated animals, and that in some herds vaccination moves peak prevalence of disease from the first to the second or third week after birth, when mortality is lower. It has been suggested that extensive use of vaccines will rapidly select for the emergence of novel or previously low prevalence fimbrial antigen types. There is no evidence that this has happened after a decade of routine vaccine use in the United States. However, there is no active direct surveillance for such emergence. In contrast to the rational development of vaccines to provide passive lacteal protection against ETEC in suckling neonates, comparatively little progress has been made in providing the knowledge required for development of vaccines to protect against postweaning ETEC infections in swine.
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7,204 |
Manure and Microbes: Public and Animal Health Problem?
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Most environmental concerns about waste management either have focused on the effects of nutrients, especially N and P, on water quality or have emphasized odor problems and air quality. Microbes from manure are often low on the priority list for control and remediation, despite the fact that several out-breaks of gastroenteritis have been traced to livestock operations. The pathogens discussed in this paper include protozoans (Cryptosporidium parvum, Giardia spp.), bacteria (Listeria monocytogenes, Escherichia coli O157:H7, Salmonella spp., and Mycobacterium paratuberculosis), and some enteric viruses. Clinical symptoms, prospects for zoonotic infection, and control methods other than the use of antimicrobials are considered. Recommendations to avoid disease transmission include taking steps to ensure the provision of clean, unstressful environments to reduce disease susceptibility and the careful handling and spreading of manure from animals at high risk for infection, especially young calves. Composting and drying of manure decrease the number of viable pathogens. Environmental controls, such as filter strips, also reduce the risk of water contamination.
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7,205 |
Regulation of t cell responses during central nervous system viral infection
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This chapter focuses on the contribution of T cells to the pathogenesis of neurologic disease and discusses specific examples of how individual T cell effector functions can be regulated during central nervous system's (CNS) viral infections. T cells can serve a variety of functions as part of the host immune response during CNS viral infection. They can participate directly in viral clearance from the brain, or they can promote the survival of the host without exerting any direct effect on virus replication. Only a small number of T cells infiltrate the brain under normal circumstances. This paucity of immune surveillance of baseline is one of several reasons why the CNS has often been characterized as an “immunologically privileged” site. T cell-mediated lysis of infected cells has been demonstrated to be an important mechanism of viral clearance from tissues other than the CNS. In several well-characterized animal models of CNS viral infection, part of the elicited T cell response actually contributes to the pathology and adverse outcome of disease. Neurotropic lymphocytic choriomeningitis virus infection of adult mice is the premier example of this phenomenon.
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7,206 |
Diagnosis of Cryptosporidium on a sheep farm with neonatal diarrhea by immunofluorescence assays
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An outbreak of diarrhea in neonatal lambs occurred on a a sheep farm in northern Ohio. Diarrhea commenced as early as 1 week of age and lasted for about 3–4 days. Although 100% of the newborn lambs were affected, most had recovered by 3 weeks of age. Cryptosporidium infection appeared to be the cause of diarrhea. Fecal examination of nine diarrheic newborn lambs (5–10 days old), 23 older lambs (2–3 weeks old, six with diarrhea) and 23 clinically normal ewes by immunofluorescence assays revealed infection rates of 100%, 78.3% and 17.4%, respectively. Most newborn lambs had high oocyst counts. Ewes were considered to be an important source of infection for lambs.
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7,207 |
Influence of Sodium Bicarbonate on Growth and Health of Young Calves
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Fifty-four Holstein and Jersey calves were assigned at 4 days of age within breed and sex to one of four treatments: control consisting of colostrum, milk replacer, and starter; buffered colostrum and replacer (.6% sodium bicarbonate) and starter (2% sodium bicarbonate); acidified colostrum (1% propionic), untreated replacer, and starter; and acidified, buffered colostrum (1% propionic, .6% sodium bicarbonate), buffered replacer (.6% sodium bicarbonate), and starter (2% sodium bicarbonate). The feeding regimen was colostrum once daily, day 4 to 14; milk replacer once daily, day 15 to 28; and calf starter ad libitum, day 4 to 84. Bull calves were fed for 42 days and heifers for 84 days. Calves fed acidified colostrum refused more feed and were less efficient from day 4 to 14 than calves fed buffered colostrum. Bulls were more sensitive to acidified colostrum than heifers. Starter intake, total dry matter intake, and average daily gains were similar for all calves during days 4 to 84. Rumen fluid from calves fed diets with sodium bicarbonate was higher in acetate and lower in propionate and lactate than that from calves fed diets without sodium bicarbonate. Sodium bicarbonate improved intake of acidified colostrum during the first 2 or 3 days of feeding but had no other effect on gain or feed intake.
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7,208 |
Virus-Induced Immunopathology
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Several viruses cause damage to the tissue by immunopathological mechanisms. This chapter presents the principal examples of immunopathogenesis caused by the viruses, accompanied by speculations about its management. The most common mechanism of lesion development in virus induced immunopathology involves T cells. Usually, it seems that when CD8(+) T cells act as the controlling cell type, lesions are acute and the outcome is decided quickly. The classic example is provided by LCM in mice. The newest candidate may turn out to be SNV infection in humans. Lesions orchestrated primarily by CD4(+) T cells can be either acute or long-lasting. Curiously, in the LCMV example, if CD8(+) T cells are removed from the scene, immunopathological responses may still occur and these involve CD4(+) T cells. Such responses are far more chronic and of lower grade than those mediated by CD8(+) T lymphocytes. One possible sequel to chronic inflammatory responses to viruses is that autoreactive inflammatory reactions are initiated and an autoimmune disease occurs. The adage that an ounce of prevention is worth a pound of cure is certainly true in the field of viral pathogenesis. Preventing viral infection or manipulating immune processes during the initial phases of infection is far more successful than attempting to counteract pathological events once underway.
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7,209 |
Proteolysis and antigen presentation by MHC class II molecules
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Proteolysis is the primary mechanism used by all cells not only to dispose of unwanted proteins but also to regulate protein function and maintain cellular homeostasis. Proteases that reside in the endocytic pathway are the principal actors of terminal protein degradation. The proteases contained in the endocytic pathway are classified into four major groups based on the active-site amino acid used by the enzyme to hydrolyze amide bonds of proteins: cysteine, aspartyl, serine, and metalloproteases. The presentation of peptide antigens by major histocompatibility complex (MHC) class II molecules is strictly dependent on the action of proteases. Class II molecules scour the endocytic pathway for antigenic peptides to bind and present at the cell surface for recognition by CD4(+) T cells. The specialized cell types that support antigen presentation by class II molecules are commonly referred to as professional antigen presenting cells (APCs), which include bone marrow-derived B lymphocytes, dendritic cells (DCs), and macrophages. In addition, the expression of certain endocytic proteases is regulated either at the level of gene transcription or enzyme maturation and their activity is controlled by the presence of endogenous protease inhibitors.
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7,210 |
Virus Entry into Animal Cells
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In addition to its many other functions, the plasma membrane of eukaryotic cells serves as a barrier against invading parasites and viruses. It is not permeable to ions and to low molecular weight solutes, let alone to proteins and polynucleotides. Yet it is clear that viruses are capable of transferring their genome and accessory proteins into the cytosol or into the nucleus, and thus infect the cell. While the detailed mechanisms remain unclear for most animal viruses, a general theme is apparent like other stages in the replication cycle; their entry depends on the activities of the host cell. In order to take up nutrients, to communicate with other cells, to control the intracellular ion balance, and to secrete substances, cells have a variety of mechanisms for bypassing and modifying the barrier properties imposed by their plasma membrane. It is these mechanisms, and the molecules involved in them, that viruses exploit.
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7,211 |
Monoclonal antibodies against bovine immunoglobulins and their use in isotype-specific ELISAs for rotavirus antibody
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Monoclonal antibodies (MCA) against bovine immunoglobulin (BIg) isotypes were produced and characterized. MCAs were obtained which react specifically with IgG, IgG(1), IgG(2) or IgA while MCAs against IgM showed a partial cross-reaction with affinity purified IgA. MCAs with optimal characteristics for application in ELISA were selected and used as conjugates in an indirect double antibody sandwich assay (IDAS) and as the capturing antibody in an antibody capture assay (ACA) for the isotype-specific detection of antibodies against rotavirus. Based on theoretical grounds, experimental analysis of inter- and intra-isotype competition in IDAS and ACA, respectively, and direct comparison of both tests, the IDAS was selected for the detection of IgG(1) and IgG(2) anti-rotavirus antibodies. The ACA was the test of choice for the detection of IgM and IgA anti-rotavirus antibodies. The isotype specificity of these tests relies on the specificity of the MCAs and was confirmed for each test by the observation that samples containing rotavirus antibodies of only 1 particular isotypee reacted only in the homologous assay. The MCAs against bovine Ig isotypes and isotype-specific ELISAs were found to be very useful in the study of humoral mucosal immunity in calves infected with rotavirus.
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7,212 |
Immunosorbent Electron Microscopy For Detection Of Viruses
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This chapter discusses the newer modifications of immunosorbent electron microscopy (ISEM) methods in both plant and animal virology. ISEM methods presented in the chapter include all the techniques where the “solid phase principle” is essential in a way similar to other solid phase immunoassays. These methods include (1) the antibody-coated grid technique (AB-CGT); (2) the protein A-coated grid technique (PA-CGT); (3) the protein A-coated bacteria technique (PA-CBT); and (4) the antigen-coated grid technique (AG-CGT). In all ISEM methods, one of the components of the system is adsorbed to a solid phase. In AG-CGT, PA-CGT, and AB-CGT, one of the reagents is adsorbed to an electron microscopic grid, while in PA-CBT protein A is naturally present on the surface of a bacterium that serves as a solid support. In ISEM methods, the viruses can be statistically evaluated and numerically expressed as number of virions per unit of area, and can, therefore, be statistically evaluated. Thus, these methods optimize the results of a test by quantifying the effects of the quality of the supporting grid, the time of adsorption, the pH, the presence of salts, and the type of staining. The ISEM also permits a detailed study of antigenic variations in the same genus of virus, and thus would visually pinpoint the type or strain differences.
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7,213 |
Nucleotide sequence of the bean strain of southern bean mosaic virus()
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The genome of the bean strain of southern bean mosaic virus (SBMV-B) comprises 4109 nucleotides and thus is slightlyshorter than those of the two other sequenced sobemoviruses (southern bean mosaic virus, cowpea strain (SBMV-C) and rice yellow mottle virus (RYMV)). SBMV-B has an overall sequence similarity with SBMV-C of 55% and with RYMV of 45%. Three potential open reading frames (ORFs) were recognized in SBMV-B which were in similar positions in the genomes of SBMV-C and RYMV. However, there was no analog of SBMV-C and RYMV ORF 3. From a comparison of the predicted sequences of the ORFs of these three sobemoviruses and of the noncoding regions, it is suggested that the two SBMV strains differ from one another as much as they do from RYMV and that they should be considered as different viruses.
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7,214 |
Mouse hepatitis virus type 3 infection provokes a decrease in the number of sinusoidal endothelial cell fenestrae both in vivo and in vitro
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Fenestrations of hepatic endothelial cells play an active role as a sieving barrier allowing extensive exchange between the blood and liver parenchyma. Alteration of these structures may be induced in the course of various pathological events and provoke important perturbations of liver function. We demonstrate here that sinusoidal endothelial cells are permissive for mouse hepatitis virus 3 (MHV3) in vivo and in vitro and that this infection leads to a striking decrease in the number of fenestrae. The disappearance of these structures observed under scanning electron microscopy or in cryofracture preparations in vivo and in vitro cannot be reversed by the action of cytochalasin B on the microfilament network. The decrease in the porosity seems to be related directly to the productive infection of the endothelial cells, because it was not observed in A/J mice resistant to the virus and in susceptible BALB/c mice immunized with a thermosensitive mutant in which no viral replication occurs. In conclusion, a viral infection of liver endothelial cells may cause extensive loss of the fenestrations and thus lead to important functional pertubations.
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7,215 |
Pathology and toxicology of beluga whales from the St. Lawrence Estuary, Quebec, Canada. Past, present and future
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An indigenous population of 450–500 beluga whales (Delphinapterus leucas) inhabiting the St. Lawrence Estuary has been exposed chronically for more than 50 years to a complex mixture of industrial pollutants including organochlorinated compounds (OC), polycyclic aromatic hydrocarbons (PAH) and heavy metals. From 1983 to 1990, we have necropsied 45 well preserved carcasses out of a total of 120 beluga whales reported dead over this period. Of these 45 animals, nine were affected by 10 malignant neoplasms. Fifteen animals (33%) were affected by pneumonia. Milk production was compromised in eight of 17 mature females (41%), by inflammatory changes (seven animals) and cancer (one animal) which affected the mammary glands. Opportunistic bacteria were found in pure culture, and/or in significant amounts in at least two organs in 20 belugas (44%). The concentrations of both total PCBs and highly chlorinated PCB congeners were much higher in St. Lawrence animals than in Arctic beluga whales. OC-induced immunosuppression has been repeatedly demonstrated in a wide variety of animal species. Therefore, it is probable that the immune functions of St. Lawrence beluga whales are impaired. Benzo[α]pyrene adducts were detected in 10 of the 11 St. Lawrence beluga whales of which tissues (six livers, 10/11 brains) were analyzed by a method based on HPLC. No such adducts were found in four Arctic animals. Since benzo[α]pyrene is one of the most potent chemical carcinogens known to man, these compounds might be responsible for some of the cancers observed in that population. Overall, our findings contrast vividly with those of others who found that cancers are exceedingly rare in free-ranging odontocete populations and that the major causes for mortalities in these populations are bacteria, parasites, and trauma.
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7,216 |
Prevalence of Cryptosporidium and Giardia infections in cattle in Aragón (northeastern Spain)
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Faecal samples from 554 bovines randomly selected at 30 farms in Aragón were examined to investigate the prevalence of Cryptosporidium and Giardia infections. C. parvum oocysts were identified by using the Ziehl-Neelsen modified technique in 109 (19.7%) bovines ranging from 3 days old to adults. Positive animals were found in 19 (63.3%) farms. As much as 44.4% of calves aged 3–4 days were infected, but infection rates peaked at 6–15 days of age (76.7%). Nevertheless, prevalence was also high in weaning calves aged 1.5–4 months (14%), fattening calves and heifers 4–24 months old (7.7%) and adults (17.8%). Diarrhoea was recorded in 78.6% of suckling and 29.4% of weanling calves infected by C. parvum, but it was only found to be statistically associated with infection in suckling calves (P < 0.01). All calves shedding moderate or many oocysts had diarrhoea, whereas asymptomatic infection was always correlated with few oocysts in faeces. Cryptosporidial infections were always asymptomatic in bovines older than 4 months. Giardia cysts were identified in 65 bovines (11.7%) from 16 (53.3%) of the farms surveyed. Infection rates were significantly higher in suckling (14.1%) and weanling calves (38%) than in bovines older than 4 months (2.2%) (P < 0.001). Diarrhoea was recorded in 45.5% of suckling and 10.9% of weanling calves infected by Giardia, but it was not found to be statistically associated with infection. In fact, infection rates were higher in non-diarrhoeic than in diarrhoeic calves.
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7,217 |
Mouse hepatitis virus ORF 2a is expressed in the cytosol of infected mouse fibroblasts
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A 266-bp fragment of cDNA from within gene B, ORF 2a, of MHV-A59 was used to construct a vector encoding a bacterial/viral fusion protein. Antiserum raised against this fusion protein specifically immunoprecipitates a 30K protein from infected 17CI-1 mouse fibroblasts. The protein is localized primarily in the cytosol and not in the membranes. This is consistent with its predicted sequence and potential role as an RNA binding protein.
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7,218 |
Syndemics, sex and the city: Understanding sexually transmitted diseases in social and cultural context
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This paper employs syndemics theory to explain high rates of sexually transmitted disease among inner city African American and Puerto Rican heterosexual young adults in Hartford, CT, USA. Syndemic theory helps to elucidate the tendency for multiple co-terminus and interacting epidemics to develop under conditions of health and social disparity. Based on enhanced focus group and in-depth interview data, the paper argues that respondents employed a cultural logic of risk assessment which put them at high risk for STD infection. This cultural logic was shaped by their experiences of growing up in the inner city which included: coming of age in an impoverished family, living in a broken home, experiencing domestic violence, limited expectations of the future, limited exposure to positive role models, lack of expectation of the dependency of others, and fear of intimacy.
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7,219 |
Mapping of Linear Antigenic Sites on the S Glycoprotein of a Neurotropic Murine Coronavirus with Synthetic Peptides: A Combination of Nine Prediction Algorithms Fails To Identify Relevant Epitopes and Peptide Immunogenicity Is Drastically Influenced by the Nature of the Protein Carrier
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The elucidation of the antigenic structure of the S glycoprotein of murine coronaviruses will provide further understanding of the Complex pathogenicity of these viruses. In order to identify linear antigenic determinants, the primary structure of the S glycoprotein of murine hepatitis virus strain A59 was analyzed with a combination of nine epitope prediction algorithms. Fifteen potential epitopes were synthesized chemically and injected into BALB/c mice to study their biological relevance. This approach failed to identify novel important epitopes. Furthermore, the algorithms were unable to identify as antigenic the previously mapped immunodominant epitope A [C Daniel, R. Anderson, M. J. Buchmeier, J. O. Fleming, W. J. M. Spaan, H. Wege, and Talbot, P. J. (1993) J. Virol. 67, 1185-1194]. Interestingly, peptide A coupled to KLH induced an immune response that stimulated the immune response induced by the corresponding region of the protein much more accurately than when the same peptide was coupled to BSA. This included drastically enhanced competition with monoclonal antibodies and protection from virus challenge. These findings emphasize the shortcomings of amino acid sequence-based epitope prediction algorithms and demonstrate the critical importance of the carrier when synthetic peptides are considered as potential vaccines.
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7,220 |
An outbreak of rotavirus-associated neonatal necrotizing enterocolitis()
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An outbreak of necrotizing enterocolitis and hemorrhagic gastroenteritis occurred in two nurseries during 25 days in August 1982. Eleven of the 40 patients in these nurseries during that time developed disease (attack rate 27.5%). In seven of the 10 patients with gastrointestinal disease, stool samples tested for human rotavirus were positive by ELISA, whereas in 20 unaffected infants, no stools tested demonstrated HRV (P=0.0001). Eleven staff members had serologic evidence of recent HRV infection. Comparison of risk factors traditionally associated with the development of NEC between the affected and unaffected infants revealed no significant differences. Rotavirus infection was the only finding that was highly correlated with this epidemic.
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7,221 |
A simplified procedure for studies of intestinal immunity in rabbits
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As interest in the development of oral vaccines continues to rise, alternative animal models for studies of mucosal immunity are needed. The present study examines a simplified procedure for delivering antigen to rabbit Peyer's patches via an indwelling cannula. The cannula was placed 3–4 cm proximal to the Peyer's patch, and was used to deliver four weekly doses of the potent mucosal immunogen, cholera toxin (CT). Anti-CT specific fecal secretory IgA (S-IgA), serum IgG and serum IgA were found in essentially equal amounts in rabbits with cannulas and in rabbits fitted with Thiry-Vella (T-V) isolated ileal loops. In contrast to animals with T-V loops, the intestinal flora of animals with cannulas contained less bacterial overgrowth with Pseudomonas sp. Further, the villus architecture remained histologically normal in appearance and there were fewer post-surgical complications associated with this technique than with T-V loops. This simplified technique should allow wider use of rabbits in studies of mucosal immunity.
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7,222 |
A nose-brain pathway for psychotropic peptides: evidence from a brain evoked potential study with cholecystokinin
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The access of substances to the brain is of particular relevance for the etiology and treatment of psychiatric and neurologic diseases. This study provides functional evidence for a direct access of peptides to the human brain after intranasal administration. Effects were compared of intranasal (IN, 10 μg) and intravenous (IV, 0.25 and 2.5 μg) administered cholecystokinin-8 (CCK) on the auditory event related potential (AERP) in 20 healthy subjects. Also, plasma concentration of cortisol and ACTH were monitored. The study was designed as a placebo-controlled, double-blind within-subject cross-over comparison. AERPs were recorded while the subject performed on an attention task (oddball task). Plasma CCK concentrations after IN administration of CCK were comparable to those after IV administration of 0.25 μg CCK, but were substantially lower than those after 2.5 μg CCK. The P3 complex of the AERP was markedly increased following the IN administration of CCK (p < .01) compared to placebo and to the IV administration of 0.25 μg This pattern was more obvious in women than men. Increases in plasma ACTH concentrations after CCK reached significance selectively following the IN mode of administration (p < .01).
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7,223 |
Early interactions between animal viruses and the host cell: relevance to viral vaccines
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Viral recognition of specific receptors in the host cell plasma membrane is the first step in virus infection. Attachment is followed by a redistribution or capping of virus particles on the cell surface which may play a role in the uptake process. Certain viruses penetrate the plasma membrane directly but many, both enveloped and non-enveloped viruses, are endocytosed at coated pits and subsequently pass into endosomes. The low pH environment of the endosome facilitates passage of the viral genome into the cytoplasm. For some viruses the mechanism of membrane penetration is now known to be linked to a pH-mediated conformational change in external virion proteins. As a consequence of infection there are alterations in the permeability of the plasma membrane which may contribute to cellular damage. Recent advances in the understanding of these processes are reviewed and their relevance to the development of new strategies for vaccines emphasised.
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7,224 |
Passive immunity to bovine rotavirus in newborn calves fed colostrum supplements from cows immunized with recombinant SA11 rotavirus core-like particle (CLP) or virus-like particle (VLP) vaccines
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Heterotypic passive immunity to IND (P[5]G6) bovine rotavirus (BRV) was evaluated. Three groups of calves (n = 5 per group) were fed 1% pooled colostrum supplements (birth to 7 days of age) from BRV seropositive cows vaccinated with recombinant SA11(P[2]G3) rotavirus-like particles (VLPs), recombinant SA11 rotavirus core-like particles (CLPs), or inactivated SA11 rotavirus (SA11). Control calves (n = 5 per group) received either pooled colostrum from unvaccinated (BRV field exposure seropositive) control cows, or no colostrum. IgG1 antibody titers to IND BRV for the pooled colostrum were: 1048576 (VLP); 1048576 (CLP); 262144 (SA11); and 16384 (control colostrum). Elevated titers of BRV neutralizing (VN) antibodies were present in VLP colostrum (98 000), and SA11 colostrum (25 000), but not in CLP colostrum (1400), compared to colostrum from nonvaccinates (2081). Calves were orally inoculated with virulent IND BRV at 2 days of age and challenged at post-inoculation day (PID) 21. Calves were monitored daily for diarrhea and faecal BRV shedding through PID 10 and post-challenge day (PCD) 10. After colostrum feeding, the IgG1 antibody titers were highest in serum and faeces of calves fed VLP and CLP colostrum, but VN and IgA antibodies were highest in calves fed VLP colostrum. After BRV inoculation, calves fed colostrum from vaccinated cows had significantly fewer days of BRV-associated diarrhea and BRV shedding than control calves. All calves fed VLP colostrum were protected from diarrhea after BRV inoculation; two calves shed BRV. In the CLP colostrum group, one calf developed BRV-associated diarrhea and all calves shed virus. In the SA11 colostrum group, three calves developed BRV-associated diarrhea and four calves shed virus. BRV-associated diarrhea and shedding occurred in 9 of 10 control calves. Active IgM antibody responses occurred in faeces and/or serum of most calves after BRV inoculation. However, the highest active antibody responses (IgM and IgG1 in serum, and IgM, IgG1 or IgA in faeces) after BRV inoculation were in calves fed control or no colostrum, in association with clinical diarrhea in most of these calves. After challenge at PID 21, BRV-associated diarrhea and shedding were of short duration or absent, in all groups. These results demonstrate the efficacy of colostrum from VLP vaccinated cows to provide heterologous, passive protection against BRV diarrhea and shedding in calves. In comparison, calves fed CLP or SA11 colostrum were only partially protected against BRV diarrhea or shedding.
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7,225 |
Evaluation of free or liposome-encapsulated ribavirin for antiviral therapy of experimentally induced feline infectious peritonitis
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Ribavirin, either free in aqueous solution or incorporated into liposomes, was evaluated in 50 specific-pathogen-free kittens after experimental challenge exposure with feline infectious peritonitis virus (fipv). Ribavirin was administered daily for 10 to 14 days at 16·5 mg kg(−1) bodyweight given per os, intramuscularly or intravenously beginning 18 hours after kittens were challenge-exposed with fipv. All kittens, including ribavirin-treated and untreated kittens, succumbed to FIP. Clinical signs of disease were more severe in the ribavirin-treated kittens and their mean survival times were shortened. The clinical efficacy of free ribavirin given intravenously at a reduced dosage (5·5 mg kg(−1) bodyweight) was compared to that of ribavirin incorporated into lecithin-containing liposomes (5 mg kg(−1)) intravenously. Drugs were given once daily for three consecutive days of each week for three weeks, beginning 18 hours after virus challenge exposure. There was no significant difference either in survival rate or severity of disease between kittens given free ribavirin, liposomal ribavirin or saline only. Because of its intrinsic toxicity and low therapeutic index against fipv and its marginal antiviral activities in vivo at maximal doses, ribavirin cannot presently be recommended as primary antiviral chemotherapy against fip.
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7,226 |
Identification of a sorting signal for the regulated secretory pathway at the N-terminus of pro-opiomelanocortin
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The N-terminal 26 amino acids of the prohormone pro-opiomelanocortin (POMC) were investigated to determine whether this region has the capacity to act as a sorting signal for the regulated secretory pathway. Constructs were made using the N-terminal 101, 50, 26 or 10 amino acids of POMC fused to the chloramphenicol acetyltransferase (CAT) reporter protein and expressed in AtT20 cells to show that at least the first 26 amino acids were required to sort CAT to the regulated secretory pathway. Full length POMC was mutated by deleting amino acids 2–26 from the N-terminal region. Analysis of Neuro-2a cells expressing this mutation compared to wild type POMC indicated that these 26 amino acids contain information essential for sorting POMC to the regulated secretory pathway. The results presented here suggest the presence of a conformation-dependent signal in the N-terminal 26 amino acids of POMC responsible for sorting POMC to the regulated secretory pathway.
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7,227 |
A new pharyngitis model using capsaicin in rats
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1. 1. Application of capsaicin solution onto the rat pharyngeal mucosa caused a well-reproducible increase in vascular permeability in the pharynx. 2. 2. Capsaicin-induced pharyngeal inflammation was unaffected by a histamine H(1) blocker and non-steroidal anti-inflammatory agents, whereas dexamethasone was effective in its inhibition. 3. 3. FK224, a dual antagonist of tachykinin NK(1) and NK(2) receptors, and FK888, a selective antagonist of NK(1) receptor, significantly inhibited capsaicin-induced plasma exudation in the pharynx. 4. 4. In capsaicinized animals, the application of capsaicin solution in the pharyngeal mucosa did not induce pharyngitis. 5. 5. These results suggest that the mechanism of the capsaicin-induced pharyngitis primarily involves tachykinins.
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7,228 |
Necrotizing Enterocolitis: Treatment Based on Staging Criteria
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Neonatal necrotizing enterocolitis is the most important cause of acquired gastrointestinal morbidity or mortality among low birthweight infants. Prematurity alone is probably the only identifiable risk factor. Although the etiology is unknown NEC has many similarities to an infectious disease. Proper staging helps improve reporting and the management of NEC.
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Effect of Soy Protein on Calves’ Intestinal Absorptive Ability and Morphology Determined by Scanning Electron Microscopy
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Neonatal calves were fed whole milk (control) or one of three milk replacers with one-third of the total protein supplied by casein, Promocaf (a commercial soy protein concentrate), or an experimental soy flour. Xylose absorption was studied at 3 and 8 wk after a 12-h fast. Urine was collected for 5 h, and jugular blood was sampled at 0, 2.5, and 5 h after administration of xylose. Urinary excretions of xylose at 8 wk were 3.4, 5.3, 7.8, and 21.3% of xylose administered, respectively, for calves fed Promocaf, soy flour, casein, and milk. Increases in plasma xylose 2.5 h after administration were 7.7, 21.3, 31.8, and 46.5 mg/dl. Calves were sacrificed at 12 or 14 wk and duodenal tissues sampled for scanning electron microscopy. Micrographs revealed normal intestinal morphology with long, round, tapering villi when milk was fed. Casein feeding produced shorter, broader villi than did feeding whole milk. Abnormalities included absence of villi and short, blunted, convoluted villi on mucosal surfaces of calves fed soy proteins. Reduced surface area for intestinal absorption probably resulted from villous atrophy in calves with abnormal mucosae. Impairment of absorptive ability appears to be associated with morphological changes in intestinal structure.
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Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)()()
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A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.
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7,231 |
Viral vectors for malaria vaccine development
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A workshop on viral vectors for malaria vaccine development, organized by the PATH Malaria Vaccine Initiative, was held in Bethesda, MD on October 20, 2005. Recent advancements in viral-vectored malaria vaccine development and emerging vector technologies were presented and discussed. Classic viral vectors such as poxvirus, adenovirus and alphavirus vectors have been successfully used to deliver malaria antigens. Some of the vaccine candidates have demonstrated their potential in inducing malaria-specific immunity in animal models and human trials. In addition, emerging viral-vector technologies, such as measles virus (MV), vesicular stomatitis virus (VSV) and yellow fever (YF) virus, may also be useful for malaria vaccine development. Studies in animal models suggest that each viral vector is unique in its ability to induce humoral and/or cellular immune responses. Those studies have also revealed that optimization of Plasmodium genes for mammalian expression is an important aspect of vaccine design. Codon-optimization, surface-trafficking, de-glycosylation and removal of toxic domains can lead to improved immunogenicity. Understanding the vector's ability to induce an immune response and the expression of malaria antigens in mammalian cells will be critical in designing the next generation of viral-vectored malaria vaccines.
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7,232 |
Modification of Membrane Permeability by Animal Viruses
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Animal viruses permeabilize cells at two well-defined moments during infection: (1) early, when the virus gains access to the cytoplasm, and (2) during the expression of the virus genome. The molecular mechanisms underlying both events are clearly different; early membrane permeability is induced by isolated virus particles, whereas late membrane leakiness is produced by newly synthesized virus protein(s) that possess activities resembling ionophores or membrane-active toxins. Detailed knowledge of the mechanisms, by which animal viruses permeabilize cells, adds to our understanding of the steps involved in virus replication. Studies on early membrane permeabilization give clues about the processes underlying entry of animal viruses into cells; understanding gained on the modification by viral proteins of membrane permeability during virus replication indicates that membrane leakiness is required for efficient virus release from infected cells or virus budding, in the case of enveloped viruses. In addition, the activity of these membrane-active virus proteins may be related to virus interference with host cell metabolism and with the cytopathic effect that develops after virus infection.
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7,233 |
Diagnostic Virology Using Electron Microscopic Techniques
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This chapter illustrates the development of the use of electron microscopy in viral diagnosis. The field covered is confined to medical viral diagnosis, but parallel developments have taken place in both veterinary and botanical fields and techniques derived from both these sources are also included where relevant. It is reported that the scanning transmission mode of operation, which can induce image contrast changes electronically, may enhance studies with unstained sections and perhaps facilitate thin section immune electron microscopy (IEM). The application of negative stain IEM has been particularly useful for the study of the antigenic nature of some of the newly discovered noncultivable viruses. Viral antigens can also be detected in thin sections of infected cells by IEM with suitably labeled specific antibodies. Confirmation of viral infection by electron microscopy on tissues originally processed for light microscopy is also frequently useful.
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7,234 |
Isotype-specific antibody responses to rotavirus and virus proteins in cows inoculated with subunit vaccines composed of recombinant SA11 rotavirus core-like particles (CLP) or virus-like particles (VLP)
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The isotype antibody responses to bovine IND P(5), G6 and simian SA11 P(2), G3 rotavirus and SA11 rotavirus proteins (VP4, VP6 and VP7) in serum, colostrum and milk were analysed by ELISA in three groups of vaccinated cows and nonvaccinated controls. Pregnant cows were vaccinated intramuscularly and intramammarily with recombinant baculovirus-expressed SA11 rotavirus VLP (triple-layered virus-like particles containing rotavirus VP2, VP4, VP6 and VP7); CLP (double-layered core-like particles containing rotavirus VP2 and VP6); or inactivated SA11 rotavirus, respectively. Rotavirus antigen titers were highest (30–200-fold) in ELISA in the VLP vaccine compared to the inactivated SA11 vaccine. The IgG1, IgG2 and IgM geometric mean antibody titers (GMT) to rotavirus (titers to bovine rotavirus vs SA11 rotavirus did not differ significantly for any isotype or group) and the IgG2 GMT to VP6 in serum at calving in the vaccinated groups were significantly (P <0.05) higher than in the control group. In colostrum, IgG1 and IgA rotavirus antibody titers were significantly elevated for VLP (IgG1 GMT 832225; IgA GMT 16384), CLP (IgG1 GMT 660561; IgA GMT 10321) and SA11 (IgG1 GMT 131072; IgA GMT 1448) vaccinated cows compared to control cows (IgG1 GMT 11585; IgA GMT 45). The IgG1 and IgA GMT to rotavirus were significantly elevated (6–100-fold) in milk of VLP and CLP vaccinated cows compared to SA11 vaccinated or control cows. The isotype antibody responses to VP6 in serum, colostrum and milk paralleled the responses to rotavirus, but titers were ∼2–10-fold lower. Only cows vaccinated with VLP had significantly enhanced serum, colostral and milk antibody titers to rotavirus VP4 and VP7. These results demonstrate that rotavirus antibody titers in serum, colostrum and milk are significantly enhanced by use of non-infectious VLP, CLP and inactivated SA11 rotavirus vaccines, but the VLP or CLP vaccines induced the highest antibody responses, corresponding to their higher rotavirus antigen titers measured by ELISA.
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7,235 |
Pathogenesis of Virus-Induced Demyelination
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Demyelination is a component of several viral diseases of humans. The best known of these are subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML). There are a number of naturally occurring virus infections of animals that involve demyelination and many of these serve as instructive models for human demyelinating diseases. In addition to the naturally occurring diseases, many viruses have been shown to be capable of producing demyelination in experimental situations. In discussing virus-associated demyelinating disease, the chapter reviews the architecture and functional organization of the CNS and considers what is known of the interaction of viruses with CNS cells. It also discusses the immunology of the CNS that differs in several important aspects from that of the rest of the body. Experimental models of viral-induced demyelination have also been considered. Viruses capable of producing demyelinating disease have no common taxonomic features; they include both DNA and RNA viruses, enveloped and nonenveloped viruses. The chapter attempts to summarize the important factors influencing viral demyelination, their common features, and possible mechanisms.
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7,236 |
Peptidases in human bronchoalveolar lining fluid, macrophages, and epithelial cells: Dipeptidyl (amino)peptidase IV, aminopeptidase N, and dipeptidyl (carboxy)peptidase (angiotensin-converting enzyme)()
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The modulation of proteolytic activity is an important factor in regulating the metabolism and function of peptide hormones. In this study, the activities of dipeptidyl (carboxy)peptidase (angiotensin-converting enzyme (ACE)), aminopeptidase N (APN), and dipeptidyl (amino)peptidase IV (DPP IV) were measured in the blood, the human bronchial epithelial and alveolar cells, bronchoalveolar macrophages, and the soluble phase of bronchoalveolar lavage (BAL) samples obtained from normal human volunteers and patients with pulmonary pathologic conditions. BAL fluid expressed ACE activity and very low levels of APN and DPP IV activities in the volunteer population, but higher levels could be measured in samples from patients. In patients, increased APN corresponded to a high granulocyte count, while DPP IV and ACE were associated with a high percentage of lymphocytes. Neither AIDS nor smoking induced an increased level of these enzymes. Immunohistochemical staining of bronchoalveolar smears with anti-human ACE monoclonal antibody showed that only macrophages expressed this enzyme. Enzyme histochemistry for DPP IV and APN showed that all leukocytes expressed these activities. APN, DPP IV, and ACE activities were also found in cell extracts of bronchoalveolar macrophages. In extracts of bronchial epithelial and alveolar cells, only APN and DPP IV activities were detected. Kinetic properties of the soluble enzymes in lavage supernatants were comparable to those of serum enzymes. These results demonstrate that soluble forms of cellular enzymes found in BAL fluid are regulated independently of blood and that different cell types may release these enzymes.
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7,237 |
Efficacy of infectious bronchitis virus vaccines against heterologous challenge
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Twenty-four-week-old white Leghorn layers were inoculated subcutaneously with a killed Newcastle disease-infectious bronchitis (Massachusetts type) virus (mibv) vaccine. Twenty-eight weeks after vaccination, the birds were challenged intraocularly with the Arkansas strain of infectious bronchitis virus (aibv) to determine the effects of heterologous virus exposure on egg production, egg quality and serum antibody response of the birds. The challenged hens laid significantly (P<0·005) fewer eggs than the unchallenged layers. Eggs laid by the unchallenged groups weighed significantly more (P<0·005) than those laid by the challenged groups. Further, the internal quality (Haugh units) and shell quality of eggs laid by the aibv-challenged hens was significantly (P<0·005) inferior to those from the unchallenged hens. In addition, the aibv-challenged hens laid more soft-shell, misshapen and small eggs than the unchallenged hens. The Arkansas serum haemagglutination inhibition (aibv-hi) titres of aibv challenged birds increased up to four weeks after challenge. The corresponding mibv haemagglutination-inhibition (mibv-hi) titres decreased during the same period. The study indicates that killed mibv vaccine offered no protection to birds exposed to heterologous aibv.
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7,238 |
Investigation of the effects and aftereffects of naturally occurring upper respiratory tract illnesses on mood and performance
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This study examined the effects and aftereffects of naturally occurring upper respiratory tract illnesses on mood and performance. Twenty-six subjects (12 males, 14 females, mean age 23 years 10 months, age range 18–39 years) were tested once a week for a period of a month. Fifteen subjects were suffering from a common cold on the first week and the other 11 subjects were matched healthy controls. Subjects attended for an initial 3-h testing period that consisted of a set of practice trials and two test sessions involving mood rating and performance of a battery of tests measuring psychomotor functions, attention, and memory. Sessions 3, 4, and 5 took place 1, 2, and 3 weeks later, respectively. In addition to measuring mood and mental performance, symptom severity was rated on a subjective checklist. The results showed that subjects with a cold reported an increase in negative mood and that this was only significant in the first week. Impairments of psychomotor function (simple reaction time and tracking) were also observed at this time. Performance of sustained and selective attention tasks was also impaired in subjects with colds but this effect was only significant in the second week. Other functions such as working and semantic memory were unimpaired in subjects with colds at any point in the experiment. Overall, the present results confirm many of the earlier results obtained in studies of experimentally induced upper respiratory tract illnesses. Indeed, these results are both of great practical importance and theoretical interest and further studies must now elucidate the mechanisms underlying these effects.
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7,239 |
Construction of tobacco mosaic virus subgenomic replicons that are replicated and spread systemically in tobacco plants
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Two tobacco mosaic virus (TMV)derived replicons, created by deletion of most of the 126/183-kDa open reading frame (ORF), replicated and systemically invaded tobacco plants when supported by wild type TMV. One RNA replicon contained an internal direct repeat of 476 nucleotides from the 3′ end of the 30-kDa ORF. Although this RNA was replicated, most of the progeny were heterogeneous in size and smaller than the original transcript. A second TMV-derived RNA replicon, without any internally repeated sequences and containing a deletion of the 5′ portion of the 30-kDa ORF as well as most of the 126/183-kDa ORF, was created and coinoculated with wild type TMV as helper. This RNA also was replicated efficiently and systemically invaded tobacco plants. An examination of the sequences of cDNA clones obtained after PCR amplification of the progeny population of this RNA replicon demonstrated that the observed size heterogeneity was due to deletions and insertions adjacent to the artificially created deletion junction. These data demonstrate that a TMV infection is capable of supporting an artificially created RNA replicon, similar to defective interfering RNAs or satellites. However, these dependent RNAs were replicated without noticeably interfering with wild type TMV symptoms or replication.
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7,240 |
Studies on canine parvovirus infection: preparation of challenge virus
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Two techniques, adsorption on to hydroxylapatite and density gradient centrifugation, were investigated as prospective methods for the large scale purification of canine parvovirus from faecal suspensions. Adsorption with hydroxylapatite successfully removed virus from faecal material. However, the resultant virus was contaminated and some virus was left behind in the faecal suspension. Repeated adsorption with hydroxylapatite appeared to result in some damage to the virus particles. In contrast, density gradient centrifugation provided a simple, economical method of purification which yielded uncontaminated, infectious virus. The final method, using both isopyknic and rate zonal centrifugation is described.
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7,241 |
Immunosuppression And Experimental Virus Infection Of The Nervous System
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This chapter describes the current views of the pathogenesis of virus infections of the nervous system, with particular attention to certain aspects of virus-host interactions. Following invasion of the central nervous system, infection can follow a variety of patterns, as to number and distribution of neuronal and non-neuronal cells involved. There is a corresponding diversity in the pathological lesions of the central nervous system (CNS) produced by acute virus infection. Infection can be pictured as a race between virus and host defenses, where many factors, acting through different mechanisms, can influence the outcome. Outcome is always determined by multiple virus and host variables, although single variables can be independently studied under experimentally controlled conditions in the laboratory. The chapter demonstrates that in many virus-host combinations, the immune response plays an important role in recovery from primary infections. It mentions that an immunopathological process mediates the disease which follows certain CNS virus infections.
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7,242 |
Proposed Calfhood Immunization Program for the Commercial Dairy Herd
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Immunization programs never will usurp the central role of sound management practices and good nutrition in the disease prevention program of the commercial dairy operation. However, certain immunizations against disease such as brucellosis, leptospirosis, and clostridial infections should be routine. Other disease such as infectious bovine rhinotracheitis, bovine virus diarrhea, parainfluenza-3, colibacillosis, and pasteurellosis should be considered if it can be determined that the herd is infected chronically. The present knowledge of other disease conditions, vaccine effectiveness and safety makes the use of vaccines for other diseases of questionable value.
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7,243 |
A transient transfection system for identifying biosynthesized proteins processed and presented to class I MHC restricted T lymphocytes
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CD8(+) cytotoxic T lymphocytes (CTL) constitute a major portion of immune responses to foreign and self antigens. CTL recognize class I major histocompatibility complex molecules complexed to peptides of 8–10 residues derived from cytosolic proteins. To understand CTL responses to these antigens to manipulate CTL responses optimally, it is necessary to identify the specific peptides recognized by CTL. The methods currently used for this purpose have significant drawbacks. We describe a plasmid transfection method that results in significant lysis of histocompatible target cells. Influenza virus-specific CTLs specifically lysed target cells that were transfected with plasmids bearing cDNAs encoding full length gene products, fragments containing the region that encodes the CTL epitope, or even a ten residue peptide. This significantly lessens the time and effort required todefine genes, and gene segments that contain CTL epitopes.
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7,244 |
Rabies virus glycoprotein is a trimer
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The oligomerization state of the rabies virus envelope glycoprotein (G protein) was determined using electron microscopy and sedimentation analysis of detergent solubilized G. Most of the detergents used in this study solubilized G in a 4 S monomeric form. However, when CHAPS was used, G had a sedimentation coefficient of 9 S. This high sedimentation coefficient allowed its further separation from M1 and M2. Using electron microscopy of negatively stained samples, we studied the morphology of G on virus and after detergent extraction. End-on views of G on virus clearly showed triangles consisting of three dots indicating the trimeric nature of native G. End-on views of CHAPS-isolated G showed very similar triangles confirming that, using this detergent, G was solubilized in its native trimeric structure. Electron microscopy also showed that G had a “head” and a “stalk” and provided the basis for a low-resolution model of the glycoprotein structure.
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7,245 |
Cryptosporidiosis and the follicle-associated epithelium over the ileal Peyer’s patch in calves
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Three calves were studied in stages of spontaneous cryptosporidial infection with particular reference to the relation of the cryptosporidia to the follicle-associated epithelium (fae) over the ileal Peyer’s patch (ipp). In early infection scanning electron microscopy and streptavidin immunoperoxidase staining showed marked predilection of cryptosporidia for the fae. Cryptosporidial antigen was also found in subepithelial tissue, both in the domes over the ipp and in villi, apparently in macrophages, where the parasites seemed to be progressively degraded. The fae showed long tightly spaced microvilli, replacing normal low folds and protrusions, particularly in late infection. Endocytosis of indian ink was restricted to the cell periphery in late infection, contrasting the normal, more even distribution of endocytosis in the fae apical cytoplasm. Few parasites were seen in the intestinal mucosa at this stage. At convalescence the fae was normal, but all stages of infection were characterised by elongation of microvilli in absorptive cells.
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7,246 |
Transmissible gastroenteritis in piglets:A model of infantile viral diarrhea()
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Piglets infected with transmissible gastroenteritis virus, compared to matched-fed littermates, had massive diarrhea characterized by increased quantities and concentrations of sodium, potassium, and chloride. Determinations of Na-K-ATPase in mucosal homogenates from small and large intestine revealed decreased activity of this enzyme in the upper small bowel. Our data indicate that a defect in active sodium transport in this region may be an important factor in the pathogenesis of the diarrhea. Further studies using this model should help to define the mechanisms producing diarrhea in acute infantile gastroenteritis.
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7,247 |
Diagnostic Virology
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Diagnostic virology services are increasingly available and pertinent as the number of useful antiviral agents grows. In this article, current methods of diagnosis are reviewed with special emphasis on rapid procedures. Guidelines for interpretation of cultures and other tests are provided
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7,248 |
Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children()
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Between January, 1974, and June, 1975, infection with a human reovirus-like agent was detected in 47% of 152 infants and children hospitalized with acute gastroenteritis. Certain epidemiologic, clinical, and laboratory findings appear to be helpful in distinguishing gastroenteritis due to HRVLA from other causes in those children sick enough to require hospitalization. Age: 76% of infants and children seven through 12 months of age and 76% of those 13 through 24 months of age had infection with the HRVLA, whereas such infection was found in only 21% of infants under six months of age and 23% of children 25 through 60 months of age. Time of Year: 61% of patients studied during the cooler months had HRVLA infection and such infection was not found from June to October. Frequency of vomiting and dehydration: Twice as many patients infected with HRVLA as those who were not had vomiting (92%) and significant dehydration (83%).
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7,249 |
Characterization of aminopeptidase N from Torpedo marmorata kidney
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A major antigen of the brush border membrane of Torpedo marmorata kidney was identified and purified by immunoprecipitation. The sequence of its 18 N terminal amino acids was determined and found to be very similar to that of mammalian aminopeptidase N (EC 3.4.11.2). Indeed aminopeptidase N activity was efficiently immunoprecipitated by monoclonal antibody 180K1. The purified antigen gives a broad band at 180 kDa after SDS-gel electrophoresis, which, after treatment by endoglycosidase F, is converted to a thinner band at 140 kDa. This antigen is therefore heavily glycosylated. Depending on solubilization conditions, both the antigen and peptidase activity were recovered either as a broad peak with a sedimentation coefficient of 18S (2% CHAPS) or as a single peak of 7.8S (1% CHAPS plus 0.2 % C(12)E(9)), showing that Torpedo aminopeptidase N behaves as an oligomer stabilized by hydrophobic interactions, easily converted into a 160 kDa monomer. The antigen is highly concentrated in the apical membrane of proximal tubule epithelial cells (600 gold particles/μm(2) of brush border membrane) whereas no labeling could be detected in other cell types or in other membranes of the same cells (basolatéral membranes, vacuoles or vesicles). Monoclonal antibodies prepared here will be useful tools for further functional and structural studies of Torpedo kidney aminopeptidase N.
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7,250 |
Recognition of correct reading frame by the ribosome
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The translation frame-monitoring mechanism has been suggested earlier, based on transient complementary contacts, between mRNA and rRNA. Recent studies related to the frame-monitoring mechanism are reviewed. The mechanism is well supported by both new experimental and sequence analysis data. Experiments are suggested for further elucidation of the structural details of the mRNA-rRNA interaction in the ribosome.
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7,251 |
Domains of Virus Glycoproteins
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This chapter reviews current information about the structure and function of virus glycoproteins. There are few virus glycoproteins that provide prototypes for illustrating important relationships between the functions and glycoprotein structure. The discussion presented in the chapter concentrates on those viral glycoproteins that (1) span the lipid bilayer once, (2) are oriented such that the carboxy terminus comprises the cytoplasmic domain, and (3) contain asparagine-linked oligosaccharides. There are also viral glycoproteins with extensive O-linked glycosylation, some of which are also presented in the discussion. The chapter also focuses on the studies involving directed mutagenesis and construction of chimeric proteins. The effects of altering specific amino acid sequences, of swapping domains, and of adding a new domain to a protein serve to define the functions of a domain and to show that a domain can be independently associated with a specific function. The experiments described have been carried out by inserting the genes of particular viral glycoproteins—such as cDNAs—into expression vectors and transcribing the cDNAs from the promoter provided by the expression vector. This approach established that localization and functions such as the fusogenic activity are properties of the viral glycoprotein per se and do not require other viral-coded components.
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7,252 |
Enzyme-Linked Immunoassays for the Detection of Microbial Antigens and Their Antibodies
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Antibodies could be labeled with enzymes for use in histochemical staining procedures by enzyme-immunoassay (EIA). The use of EIA is an extension of previously used serological tests, using enzyme-labeled antibody or antigen to determine antibody content. Direct detection of antigen by EIA represents a more dramatic departure from previous methods based on culture. Also, the method has enabled detection of infectious agents that are difficult to cultivate, such as hepatitis A virus and rotavirus, or agents that cannot be cultivated, such as hepatitis B. The use of EIA tests for detection of microbial antigens provides an alternative to culture as a means for direct identification of a specific microbial agent. It also provides a means to detect microbial agents which have not been successfully propagated. The detection of circulating antigen or detection of antigen in other body fluids by EIA is more difficult than detection of antibody because of the sensitivity required, and because of interfering substances in specimens such as feces and respiratory secretions. For this reason, very few antigen detection assays have the sensitivity and specificity required to be used as a primary diagnostic test. The number of tests that have been developed, however, is impressive and because of the possibilities for rapid, specific diagnosis, the interest in antigen detection by EIA remains high.
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7,253 |
The effect of halofuginone lactate on experimental Cryptosporidium parvum infections in calves
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The chemoprophylactic effects of halofuginone lactate were tested against calf experimental cryptosporidiosis. Twenty 2-day-old calves, divided into four groups, were orally inoculated with 1 × 10(6) oocysts of Cryptosporidium parvum. The infected control group was unmedicated whereas the three other groups were medicated with the drug at 30, 60 and 120 μg kg(−1) day(−1), respectively, for 7 days, from Day (D) 2 to D8 post-inoculation (D 0 was inoculation day). The calves were weighed twice weekly and disease development and drug efficacy were assessed daily from D0 to D30 from consistency of feces, shedding of oocysts and mortality. Experimental C. parvum infection caused a severe clinical disease with profuse watery diarrhea, high oocyst shedding and mortality (3 out of 5) in the unmedicated group. The results clearly demonstrated the efficacy of halofuginone lactate in reducing the severity of clinical cryptosporidiosis. This efficacy was dose-dependent. The lowest dose (30 μg kg(−1) day(−1)) was not able to prevent clinical disease and mortality (3 out of 5). No clinical signs were observed with the 60 and 120 μg kg(−1) day(−1) doses, but the animals shed oocysts after drug withdrawal. This shedding was more delayed the higher the dose of drug administered, but the delayed shedding had no effect on the growth of the animals.
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7,254 |
Protection against feline infectious peritonitis by intranasal inoculation of a temperature-sensitive FIPV vaccine
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Cats vaccinated intranasally (i.n.) with a temperature sensitive feline infectious peritonitis virus (ts-FIPV) vaccine were protected against an FIP-inducing challenge. Seventeen of 20 vaccinated cats (85%) survived a rigorous virulent FIPV challenge that caused FIP in 12 of 12 non-vaccinated cats (100%), 10 (83%) of which died. Intranasal vaccination stimulated serum IgG and serum and salivary IgA antibody responses (measured by ELISA), FIPV-neutralizing antibody (VN), and a cell-mediated immune (CMI) response as measured by lymphocyte proliferation. The serum antibody response to vaccination was not associated with protection. In fact, the IgG, IgA and VN titres were much higher in control cats than in vaccinated cats following challenge suggesting an immune-mediated pathogenesis. In contrast, stimulation of a mucosal IgA response to vaccination was related to protection. The in vitro proliferation of peripheral blood lymphocytes in response to virulent FIPV was observed in vaccinated cats, in vaccinated and challenged cats but not in non-vaccinated challenged cats.
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7,255 |
Guías de recomendaciones sobre diagnóstico, tratamiento y prevención de infecciones en pacientes con cáncer 2013
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Cancer patients pose an increased risk of infectious complications due to their underlying disease and its treatment. The present guidelines, developed by the Commission of Infections in the Immunocompromised Host of the Argentine Society of Infectious Diseases are an updated version of those published in 2008. For the elaboration of these guidelines, both the scientific evidence and the local experience were thoroughly evaluated. This Consensus includes an overview of the risk factors and the epidemiology of infections in both adult and pediatric cancer patients. It deals with the management of the febrile neutropenic patient, the risk categorization, the initial empirical therapy in the multiresistant era and its subsequent management. It includes a section dedicated to the antifungal empirical and directed therapy as well as the diagnosis and treatment of the most frequent fungal infections. Prevention strategies, both general and for high-risk patients, including those receiving biologic response modifiers, are herein shown. These guidelines should be applied in conjunction with a careful clinical evaluation and taking into account local epidemiological factors.
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7,256 |
Recombination and gene conversion
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Recombination is an important aspect of DNA metabolism. It leads to rearrangements of DNA sequences within genomes. Such genome rearrangements seem to be ubiquitous, since they play a role in evolution, human health and biotechnology. In medicine one important aspect of recombination is its role as one possible step in the multistep process of carcinogenesis. Since recombination may occur as a cellular response to DNA damage, the protection of cells from recombination-inducing agents, so-called recombinagen, should eliminate possible deleterious effects resulting from damage-induced DNA recombination. During the last few years, the awareness of the importance of recombination phenomena has substantially increased and the development of assay systems detecting recombinagens has progressed. The need for considering recombinagenic effects as a safety aspect of chemicals has gained ground in the field of genetic toxicology. This paper summarizes present knowledge concerning the occurence, inducibility, detection and toxicological interpretation of DNA recombination.
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7,257 |
Neonatal rotavirus-associated necrotizing enterocolitis: Case control study and prospective surveillance during an outbreak()
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After the death of a premature infant from rotavirus-associated necrotizing enterocolitis, we instituted prospective surveillance for this disease in our neonatal intensive care unit. During the 4-month study period an additional six cases of necrotizing enterocolitis and eight cases of hemorrhagic gastroenteritis occurred. Rotavirus infection was documented in 11 of these 15 symptomatic infants, in comparison with only eight rotavirus infections in 147 asymptomatic or minimally symptomatic bables (P<0.0001). Stools from 110 nursery personnel tested during the outbreak did not contain rotavirus. However, 12 of 59 staff members had serum IgM antibody against rotavirus, suggesting recent infection. In a case-control study we compared babies with severe gastrointestinal illness with a control group randomly selected from asymptomatic babies in the nursery during the time of the outbreak. Univariate analysis found six categorical variables and nine continuous variables that were significantly associated with disease. Multivariate logistic regression analysis, however, found only birth weight (P<0.0001), rotavirus infection (P<0.0001), and age at time of first nonwater feeding (P<0.02) to be associated with gastrointestinal illness. This study provides further evidence for the role of infection in some cases of neonatal necrotizing enterocolitis and hemorrhagic gastroenteritis.
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7,258 |
Recognition ability and cytotoxicity of some oligosaccharidylsubstituted β-cyclodextrins
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This paper reports a chemico-enzymatic synthesis of β-CD derivatives. The recognition properties of these derivativeswere tested using flocculating yeast and isolated lectins. It was observed that the substitution of β-cyclodextrins with galactose end arms induces the better recognition by a cell-linked galactose-specific lectin. The physicochemical effects of the β-CD derivatives on membranes were estimated using red blood cells and the effects on the viability of yeast and human rectal tumor cells were appreciated by measuring the mitochondrial deshydrogenase activity. The substitutions of the β-CD ring by sugar antennae decrease the negative physicochemical effects of the β-CD, ie their, hemolytic properties. However, these substitutions induce significant modifications of the biological properties of the molecules, particularly the cytotoxicity and the growth of eukaryotic cells.
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7,259 |
Potential viral vectors for the stimulation of mucosal antibody responses against enteric viral antigens in pigs
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Four viruses were compared for their ability to induce an intestinal antibody response in piglets. Antibodies were not detected in response to oral vaccination with either fowlpox virus or a baculovirus (BV). Simultaneous oral dosing and parenteral inoculation with high concentrations of BV in an oil emulsion adjuvant induced high levels of circulating virus neutralising (VN) antibodies, and also low levels of intestinal antibodies when booster doses of virus were given. In response to oral vaccination with swinepox virus (SPV), low levels of circulating and intestinal VN antibodies, and higher titres of antibodies reactive in an enzyme immunoassay, including intestinal antibodies of the IgA class, were detected. Oral vaccination with porcine adenovirus type 3 (PAV-3) stimulated both circulating and intestinal VN antibodies, and IgA antibodies were demonstrated in the intestinal contents. It was concluded that SPV and PAV-3 might be suitable vectors for the expression of genes encoding the protective antigens of porcine enteric viruses.
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Effect of Protein Source in Calf Milk Replacers on Morphology and Absorptive Ability of Small Intestine
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Holstein calves were fed milk or one of four milk replacers with one-third of the total protein supplied by casein, soy protein concentrate, soy flour, or fish protein concentrate. The remainder of the protein in each replacer was from milk sources. Milk and milk replacers (13% solids) were fed at 10% of body weight daily. No dry feed or bedding was provided. Absorptive ability of small intestine was evaluated by xylose absorption test at 2-wk intervals. With calves under general anesthesia, a biopsy of small intestine was taken after each xylose test to examine morphological changes in mucosa by scanning electron microscopy. Villi were long, tapering, and uniform in calves fed milk. Calves fed casein had greater variation in size and conformation of villi. Gradual deterioration in villous integrity was seen in calves fed soy proteins. Calves fed fish protein concentrate performed poorly and had abnormal villi. Diets were changed to milk to test for reversal of effects after marked alterations in intestinal structure had been observed. Atrophy was reversed as villi returned toward normal size and shape within 2 wk after milk feeding began. The surgical procedure apparently did not cause harmful effects of villi. Absorption of xylose and daily gain were greater, and feces firmer, in calves fed milk than in those fed milk replacers.
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7,261 |
Acute respiratory infections
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In conclusion, the purpose of this dissertation has been to review the data on acute respiratory infections as to etiology, pathogenicity, clinical syndromes and treatment. It would take volumes to adequately discuss respiratory infections in all their complexity, and by the time any manuscript gets into print, it is likely to be outdated because of the rapid advances in the area of virology and antimicrobial agents. This review in no way claims completeness for any one subject, but an attempt has been made to bring into focus and with some sort of organization the vast amount of information in the literature, recent and old, relative to acute respiratory infections. Perhaps the most encouraging aspects of acute respiratory infections are the mildness and short duration of the vast majority of these diseases, aspects which have been well expressed by A. A. Milne: Christopher Robin Had wheezles And sneezles,… Christopher Robin Got up in the morning, The sneezles had vanished away. And the look in his eye Seemed to say to the sky, “Now, how to amuse them today?” (From Now We Are Six [New York: E. P. Dutton & Co., Inc., 1950] pp. 12–14).
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Chemical linkage of erythrocytes and viral antigen in the hemolysis-in-gel (HIG) test for viral antibodies
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The sensitivity of the hemolysis-in-gel (HIG) test with rubella antigen is not improved by chemical linkage of the virus to the erythrocytes, and after such modification, IgM specific antibodies are not detectable. In the influenza HIG test with tetraazotized o-dianisidine (TOD), chromic chloride and potassium periodate as coupling reagents, increased sensitivity was observed with allantoic fluid of infected eggs as antigen. If Tween-ether treated hemagglutinin is used in the HIG test, zones of hemolysis are detectable only after treatment of the erythrocytes with TOD, chromic chloride and potassium periodate.
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Intrauterine latent herpes simplex virus infection(): I. Spontaneous abortion
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Herpes simplex virus (HSV, probably type 2) antigen was detected in nonpregnant and pregnant endometria, placentae, umbilical cords, and neonatal tissues (companion paper) by avidinbiotin complex immunohistochemical studies. HSV cytologic abnormalities were not detected in any of the 380 cases examined: included were specimens from therapeutic and spontaneous abortions (200 cases) and endometrial curettage (180 cases). The presence of inflammation was not correlated with HSV positivity. Endometrial HSV positivity was significantly correlated with normal late secretory phase (40 per cent of specimens positive), abnormal secretory phase (67 per cent positive), and therapeutic (33 per cent positive) versus spontaneous (26 per cent positive) abortions. Placental HSV positivity was significantly correlated with spontaneous (39 per cent positive) versus therapeutic (14 per cent positive) abortions and with blighted ova (67 per cent positive). No significant correlation was found between HSV positivity and a clinical history of oral or genital HSV infection in either the patient or the male partner. The data support the concept of a subclinical latent intrauterine endometrial HSV infection that is hormonally regulated and can produce transplacental infection of the embryo or fetus, with variable consequences.
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7,264 |
Biology of Natural Killer Cells
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Studies of cytotoxicity by human lymphocytes revealed not only that both allogeneic and syngeneic tumor cells were lysed in a non-MHC-restricted fashion, but also that lymphocytes from normal donors were often cytotoxic. Lymphocytes from any healthy donor, as well as peripheral blood and spleen lymphocytes from several experimental animals, in the absence of known or deliberate sensitization, were found to be spontaneously cytotoxic in vitro for some normal fresh cells, most cultured cell lines, immature hematopoietic cells, and tumor cells. This type of nonadaptive, non-MHC-restricted cellmediated cytotoxicity was defined as “natural” cytotoxicity, and the effector cells mediating natural cytotoxicity were functionally defined as natural killer (NK) cells. The existence of NK cells has prompted a reinterpretation of both the studies of specific cytotoxicity against spontaneous human tumors and the theory of immune surveillance, at least in its most restrictive interpretation. Unlike cytotoxic T cells, NK cells cannot be demonstrated to have clonally distributed specificity, restriction for MHC products at the target cell surface, or immunological memory. NK cells cannot yet be formally assigned to a single lineage based on the definitive identification of a stem cell, a distinct anatomical location of maturation, or unique genotypic rearrangements.
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Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by simian immunodeficiency virus
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Human CD4 was expressed on a range of mammalian cell lines. CD4(+) non-primate cells, derived from rat, hamster, mink, cat, and rabbit, bind recombinant gp120 of human immunodeficiency virus type 1 (HIV-1) but are resistant to HIV-1 infection. CD4 expression on various human, rhesus, and African green monkey cell lines confers differential susceptibilities for HIV-1, HIV-2, and simian immunodeficiency (SIV) strains. For example, CD4(+)TE671 rhabdomyosarcoma cells are sensitive to HIV-1 and HIV-2 but resistant to SIV, whereas CD4+ U87 glioma cells are resistant to HIV-1 infection but sensitive to HIV-2 and SIV. HIV-1 infection was not dependent on human major histocompatibility class I expression. Studies of cell fusion and of infection by vesicular stomatitis virus pseudotypes bearing HIV-1 and HIV-2 envelopes showed that the differential cell tropisms of HIV-1, HIV-2, and SIV are determined at the cell surface.
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7,266 |
Structures and mechanisms in flavivirus fusion
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This chapter focuses on the work carried out with tick-borne encephalitis (TBE) virus, the structurally best characterized of the flaviviruses. The data is related to those obtained with other flaviviruses, which are assumed to have a conserved structural organization, and compare the characteristics of flavivirus fusion to those of other enveloped viruses. Fusion proteins from several different virus families, including Orthomyxoviridae, Paramyxoviridae, Retroviridae, and Filoviridae have been shown to exhibit striking structural similarities; they all use a common mechanism for inducing membrane fusion, and the same general model applies to all of these cases. The flavivirus genome is a positive-stranded RNA molecule consisting of a single, long open reading frame of more than 10,000 nucleotides flanked by noncoding regions at the 5′ and 3′ ends. The fusion properties of flaviviruses have been investigated using several different assay systems, including virus-induced cell–cell fusion and virus–liposome fusion. All of these studies indicate that flaviviruses require an acidic pH for fusion, consistent with their proposed mode of entry.
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7,267 |
The Application Of Monoclonal Antibodies In The Study Of Viruses
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This chapter discusses the applications of monoclonal antibodies in virology. A single monoclonal antibody can provide information on protein “relatedness,” structure, function, synthesis, processing, and cellular or tissue distribution and on the association among molecules. The use of monoclonal antibodies provides valuable insight into the working of the protein both as an enzyme and as a target for the host immune response, evolving in reaction to that response. Monoclonal antibodies find application in two main areas: (1) in the field of rapid diagnosis of virus disease in man, animals, and plants and (2) in the extension of virus taxonomy. Monoclonal antibodies may be used to analyze the role of a protein. This ability to distinguish related proteins can be used to provide a genetic marker in recombination experiments. Monoclonal antibodies can detect low amounts of individual virus proteins within the infected cell. They can, thus, provide information concerning the temporal and spatial separation of protein formation and accumulation, and data on protein modification and processing in the infected cell.
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7,268 |
The Regulation of Pulmonary Immunity
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Thechapter describes the cells and structures of the lung that participate in pulmonary immunity and how the lung responds to challenges fromforeign antigens, with particular emphasis on animal models that have been developed to explore these issues. Some ligands-receptor interactions are specific while others are not, and it is the particular pattern of surface molecules and secreted factors expressed by interacting immune cells that determines the type of immune response that develops during central processing. The cells that are the major initiators and regulators of immunity in the lung include macrophages, dendritic cells (DCs), and lymphocytes, each expressing surface molecules and secretory products that depend on perturbations in the environments. Immune cells and structures of the lung and lung immunity to noninfectious particulate and soluble antigens are discussed. Several models for regulation of pulmonary immunity such as models for immunity in lung infections, models for hypersensitivity lung disease, models for lung transplantation, and graft versus host are also presented. Demonstration that lung cells regulate both nonspecific inflammation and immunity through the expression of adhesion molecules and the secretion of cytokines offers hope for ways to design more effective vaccines, enhance microbial clearance in immune-suppressed hosts, and to suppress manifestations of immunologically mediated lung disease.
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7,269 |
Concurrent infections of Giardia and Cryptosporidium on two Ohio farms with calf diarrhea
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Giardia and Cryptosporidium infections were diagnosed by immunofluorescence assay on two Ohio dairy farms with calf diarrhea problems. On the first farm, all nine diarrheic calves sampled once in June had Giardia cysts in their feces. On the second farm, all five diarrheic calves examined at the beginning of the diarrhea outbreak in March had Giardia infection. When resampled, the overall infection rate of normal and diarrheic calves was 82.4% in April, and 40.0% in August after the diarrhea subsided. Positive calves ranged from 11 to 164 days of age, and 22.2% of them were as young as 1 to 3 weeks of age. Eight of nine diarrheic calves (88.8%) on the first farm had Cryptosporidium infection. Lower infection rates (<30%) were found on the second farm. Six of 10 positive calves were 11–22 days old, three were 164–177 days old, and one was 71 days old. Five of these 10 positive calves were also positive for Giardia infection. Five diarrheic calves on the northern Ohio farm and one diarrheic calf on the central Ohio farm were treated with metronidazole after failing to respond to antibiotic therapy. Clinical improvement was observed in all calves within 48 h after the start of treatment. The high Giardia infection rates and intensities in calves of a wide age range and the clinical response to metronidazole suggest that Giardia infection contributed to the outbreaks of diarrhea.
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7,270 |
Human Immunodeficiency Virus Type 1-Associated Cd4 Downmodulation
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This chapter discusses human immunodeficiency virus type 1 (HIV-1) associated with CD4 downmodulation. It also discusses the structure and function of CD4 and p56(lck) and factors involved in hiv-1-associated cd4 downmodulation. There are, at present, at least three HIV-1 gene products known to be involved in cell surface CD4 downmodulation. These are Nef, Vpu, and gp160. Whereas Nef is expressed during the early phase of HIV-1 gene expression, both Vpu and gp160, which appear to act coordinately, are expressed during the late phase. This functional convergence of HIV-1 proteins on cell surface CD4 downmodulation, whether specific or nonspecific in activity, suggests that this event is of critical importance in the life cycle of HIV-1. Further elucidation of the mechanisms that underlie CD4 cell surface downmodulation may lead to the development of novel strategies aimed at preventing such events, and potentially to the development of new therapeutic approaches.
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7,271 |
Glucose trimming and mannose trimming affect different phases of the maturation of Sindbis virus in infected BHK cells
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The roles of glucose and mannose trimming in the maturation of Sindbis virus in BHK cells have been investigated using inhibitors of glycoprotein oligosaccharide processing. In the presence of the glucosidase inhibitor N-methyl-1-deoxynojirimycin the viral glycoproteins were equipped with oligosaccharides of the composition GIc(3)Man(8,9)(GIcNAc)(2) and the yield of virus in the extracellular medium was reduced as a result of a block in the proteolytic cleavage of the precursor (pE2) of the E2 viral envelope glycoprotein. The mannosidase I inhibitor 1-deoxymannojirimycin (dMM) also inhibited the appearance of virus in the medium and the oligosaccharides on the viral glycoproteins had the composition Man(9)(GIcNAc)(2). However, pE2 was cleaved to E2 under these conditions, and it was found that when the yield of virus from the cells and medium together was considered, there was no difference between untreated and dMM-treated cultures, suggesting the presence of intracellular virus particles in the dMM-treated cultures. When examined by electron microscopy, the dMM-treated cultures were found to contain intracellular virus particles. In addition, nucleocapsids were found lining intracellular membranes. These observations taken together with the plaque test data intimate that Sindbis virus preferentially buds from internal membranes in BHK cells treated with dMM. The results confirm the essential role of glucose trimming in the Sindbis virus-BHK cell system and suggest that the initial stages of mannose removal maybe important too.
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7,272 |
Clinical Virology of Rhinoviruses
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This chapter discusses the various aspects of the clinical virology of rhinoviruses. Some attributes of the virus and epidemiology of disease that have clinical relevance, the efficiency of methods for detecting the presence of the virus in the human respiratory tract, and the means by which symptomatic illness is produced by rhinovirus infection of the respiratory tract are described Rhinoviruses cause more infections in humans than any other microorganism. The chapter also discusses the attributes of virus and the epidemiology of disease. These acid-sensitive picornaviruses infect epithelial cells following inoculation onto the nasal mucosa and are detected reliably in nasopharyngeal secretions. Rhinovirus colds occur year round, with a peak of illness in the fall. Type-specific serum antibody correlates with protection against infection. The fact that there are at least 100 different immunotypes makes development of an effective vaccine unlikely. The chapter presents various techniques for the detection of rhinovirus, such as sampling and cell culture, and polymerase chain reaction.
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7,273 |
Selection of and evasion from cytotoxic T cell responses in the central nervous system
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Cytotoxic CD8 T lymphocytes (CTLs) are critical for the clearance of noncytopathic viruses from infected cells. This chapter discusses one mechanism used by viruses to persist—namely, the selection of a variant virus in which changes in the sequence of a CTL epitope abrogate recognition. The unique features of cytotoxic CD8 T cell function in the central nervous system (CNS) are discussed. The role of CTL escape mutants in the viral evasion of the immune system and subsequent disease progression in non-CNS infections are summarized. The immune response in the CNS is similar to the response in extraneural tissue, but several aspects of the activation of the immune response, cellular trafficking, and antigen presentation are unique to the CNS. Although the CNS has classically been considered a site of immune privilege, surveillance of the normal CNS by circulating, activated lymphocytes occurs, with a limited number of lymphocytes being present in the normal CNS at any given time. In mice infected with mouse hepatitis virus and in some humans persistently infected with human immunodeficiency virus type1, hepatitis B virus or hepatitis C virus, CTL escape mutants play an important role in virus amplification and disease progression.
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7,274 |
Western and dot immunoblotting analysis of viral antigens and antibodies: Application to murine hepatitis virus
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Viral proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and transferred quantitatively to nitrocellulose by electroblotting in SDS-containing buffer. Monoclonal antibodies directed against previously defined epitopes on the viral proteins were used as probes to detect viral protein synthesis and processing, as well as expression in animal tissues. Circulating polyclonal antibodies were also probed and characterized for their polypeptide specificities. Under appropriate conditions, this Western immunoblotting technique was quantitative. Finally, a highly sensitive dot immunoblotting assay was used to analyze the sensitivity to denaturation of various epitopes on the viral proteins. This assay detected picogram quantities of viral antigens and antibodies.
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7,275 |
Molecular Biology of Rubella Virus
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This chapter summarizes the present medical significance of rubella virus. Rubella virus infection is systemic in nature and the accompanying symptoms are generally benign, the most pronounced being a mild rash of short duration. The most common complication of rubella virus infection is transient joint involvement such as polyarthralgia and arthritis. The primary health impact of rubella virus is that it is a teratogenic agent. The vaccination strategy is aimed at elimination of rubella and includes both universal vaccination of infants at 15 months of age with the trivalent measles, mumps, rubella (MMR) vaccine and specific targeting with the rubella vaccine of seronegative women planning pregnancy and seronegative adults who could come in contact with women of childbearing age, although it is recommended that any individual over the age of 12 months without evidence of natural infection or vaccination be vaccinated. Medically, the current challenge posed by rubella virus is to achieve complete vaccination coverage to prevent resurgences.
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7,276 |
Chemokines and viral diseases of the central nervous system
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This chapter discusses chemokines and their receptors in the evolution of viral infectious diseases of the central nervous system (CNS). Infection of the human CNS with many different viruses or infection of the rodent CNS induces vigorous host-inflammatory responses with recruitment of large numbers of leukocytes, particularly T lymphocytes and macrophages. Chemokines coordinate trafficking of peripheral blood leukocytes by stimulating their chemotaxis, adhesion, extravasation, and other effector functions. In view of these properties, research efforts have turned increasingly to the possible involvement of chemokines in regulating both peripheral tissue and CNS leukocyte migration during viral infection. The biological effects of chemokines are mediated via their interaction with receptors belonging to the family of seven transmembrane (7TM)-spanning, G-protein coupled receptors (GPCRs). In the normal mammalian CNS, the number of leukocytes present in the brain is scant. However, these cells are attracted to, and accumulate in, a variety of pathologic states, many involving viral infection. Although leukocyte migration into local tissue compartments, such as the CNS, is a multifactorial process, it has become clear that chemokines are pivotal components of this process, providing a necessary chemotactic signal for leukocyte recruitment.
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7,277 |
Bacteria, viruses, yeasts and protozoans associated with diarrheal disease in Singapore
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Labile toxin producing enterotoxic E. coil(ETEC) were the commonest pathogen isolated from diarrheal stools of hospitalized children (21%) and adults (26%) in Singapore. Salmonellas ranked a close second in children (19%), Other bacterial pathogens were isolated from less than 5% of subjects. Blastocystis hominis was detected in 4.3% of diarrheal stools when a simple sedimentation technique was used. Cryptosporidium was not detected at all. An analysis of yeast counts in smears of diarrheal and nondiarrheal stools suggested they were etiologically associated with at least 6% of diarrhea in children and 19% in adults. Testing for rotaviruses by Latex agglutination and for adenovirus by electronmicroscopy showed an association with 6 per cent and 3 per cent diarrhea respectively. The study highlighted a need for: case control studies on ETEC and B. hominis; studies on the epidemiology of diarrhea by yeasts; establishing the true incidence of adenovirus diarrhea; studies on the prevalence and seasonality of rotavirus infection in Singapore.
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7,278 |
Role of viruses in etiology and pathogenesis of multiple sclerosis
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Multiple sclerosis (MS) is the most prevalent demyelinating disease of young adults, affecting an estimated 300,000 individuals in the United States alone. The majority of affected individuals have a relapsing–remitting course while a smaller subset has a more chronic–progressive presentation. Women are affected more often than men, a phenomenon associated with a number of auto-immune diseases. Although the etiology of MS is unknown, it is generally believed that genetic, immunologic, and environmental factors are involved. This chapter discusses these issues as they suggest that exogenous factors are associated with the pathogenesis of this disorder. Recently, the human herpes virus 6 (HHV-6) has received considerable attention as an infectious agent candidate that might be associated with the pathogenesis of MS. The chapter focuses on this agent and the data that support the role of this virus in MS disease pathogenesis. A model is proposed, whereby in genetically susceptible individuals, multiple viruses may trigger either a virus-specific or a cross-reactive auto-immune response that results in clinical MS. Epidemiologic evidence suggests that it is a multifactorial disease that develops as a result of host genetics, immune response, and environment.
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7,279 |
Structural characteristics of the M2 protein of influenza a viruses: Evidence that it forms a tetrameric channe
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The evidence presented shows that the M2 protein of influenza A viruses exists in infected cells as a homotetramer composed of two disulfide-linked dimers held together by noncovalent interactions. The amphiphilic nature of the transmembrane α-helical domain is consistent with the protein forming a transmembrane channel with which amantadine, the specific anti-influenza A drug, interacts. Together these features provide a structural basis for the hypothesis that M2 has a proton translocation function capable of regulating the pH of vesicles of the trans-Golgi network, a role important in promoting the correct maturation of the hemagglutinin glycoprotein.
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7,280 |
Immunoelectron microscopic single and double labelling of aminopeptidase N (CD 13) and dipeptidyl peptidase IV (CD 26)
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Using ultrathin cryosections and immunogold labelling, aminopeptidase N (CD 13) and dipeptidyl peptidase IV (CD 26) were localized on the luminal side of the brush border membrane of proximal tubular cells in human kidney as well as of enterocytes from rat small intestine. Furthermore, both enzymes could be detected on the cell surface of human T lymphocytes and especially aminopeptidase N on human synovial fibroblasts. Gold labelled vesicular structures were also found in the cytoplasm in the apical part of renal proximal tubular cells and synovial fibroblasts. In human kidney the colocalization of the two membrane antigens was possible by using several double labelling methods.
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7,281 |
Special techniques in diagnostic electron microscopy()
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The power of electron microscopy as a diagnostic tool can be amplified considerably by the application of ancillary preparative and analytic methods. Subcellular chemistry and structure can be examined by various forms of microprobe analysis and by special staining methods, including cytochemical, immunocytochemical, and negative staining. Qualitative ultrastructural examination can be augmented by morphometric analysis. Correlative microscopic survey methods can be used as a means of targeting ultrastructural investigations. This article provides an overview of the use of these special techniques in the diagnosis and classification of tumors and other selected pathologic processes.
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7,282 |
Plaque/focus immunoassay: a simple method for detecting antiviral monoclonal or other antibodies and viral antigens in cells
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A new, simple enzyme-linked immunosorbent assay (ELISA) is described which is performed directly on infected and fixed cell cultures in microtitre plates. It permits large scale screening of antiviral monoclonal antibodies and differentiation of specific antibodies from those usually responsible for high background reactions in other ELISA techniques. Time consuming purification of antigens is thus avoided. The plaque/focus immunoassay is also applicable to titration of antibodies in patients' sera and antigens in lytically or non-lytically virus-infected cells. It may also be used to localize antigens in different cell compartments. This immunoassay requires no special equipment and results may be evaluated either with the naked eye or using a light microscope.
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7,283 |
Direct-from-Specimen Pathogen Identification: Evolution of Syndromic Panels
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This article describes the current state of the art with regards to commercially available syndromic panels for blood stream infections, gastrointestinal pathogen detection, respiratory tract infections, and central nervous system infections, while providing a provocative and speculative look into the future of syndromic panel testing for infectious diseases.
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7,284 |
Molecular Studies of Genetic RNA–RNA Recombination in Brome Mosaic Virus
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It is well known that DNA-based organisms rearrange and repair their genomic DNA through recombination processes, and that these rearrangements serve as a powerful source of variability and adaptation for these organisms. In RNA viruses' genetic recombination is defined as any process leading to the exchange of information between viral RNAs. There are two types of recombination events: legitimate and illegitimate. While legitimate (homologous) recombination occurs between closely related sequences at corresponding positions, illegitimate (nonhomologous) recombination could happen at any position among the unrelated RNA molecules. In order to differentiate between the symmetrical and asymmetrical homologous crosses, Lai defined the former as homologous recombination and the latter as aberrant homologous recombination. This chapter uses brome mosaic virus (BMV), a multicomponent plant RNA virus, as an example to discuss the progress in studying the mechanism of genetic recombination in positive-stranded RNA viruses. Studies described in this chapter summarize the molecular approaches used to increase the frequency of recombination among BMV RNA segments and, more importantly, to target the sites of crossovers to specific BMV RNA regions. It demonstrates that the latter can be accomplished by introducing local complementarities to the recombining substrates.
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7,285 |
Adrenal Hemorrhage in Neonates: Report of 5 Cases and Review of the Literature
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The differential diagnosis of masses in the suprarenal area in neonates is discussed in relation to clinical, laboratory and radiologic findings. Neonatal adrenal hemorrhage can be accurately diagnosed clinically. In the neonate neuroblastoma in situ is self-limiting and exploration to exclude it is unnecessary. Operative intervention should be reserved for controlling massive adrenal hemorrhage or if an abscess forms
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7,286 |
Structure and Function of the Hef Glycoprotein of Influenza C Virus
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Soon after the first isolation of an influenza C virus from a patient, it became obvious that this virus differs from other myxoviruses in several aspects. Pronounced differences have been observed in the interactions between the virus and cell surfaces, suggesting that influenza C virus attaches to the receptors different from those recognized by other myxoviruses. While influenza A and B viruses agglutinate erythrocytes from many species, including humans, the spectrum of erythrocytes agglutinated by influenza C virus is much more restricted. Erythrocytes from rats, mice, and adult chickens are suitable for hemagglutination and hemadsorption tests; cells from other species, however, react not at all or only poorly with influenza C virus. Differences are also observed so far as hemagglutination inhibitors are concerned. A variety of glycoproteins have been shown to prevent influenza A and B viruses from agglutinating erythrocytes. In the case of influenza C virus, rat serum was for a long time the only known hemagglutination inhibitor. A difference in the receptors for influenza C virus and other myxo-viruses was also suggested by studies on the receptor-destroying enzyme. The ability of influenza C virus to inactivate its own receptors was reported soon after the first isolation of this virus from a patient. However, the influenza C enzyme did not affect the receptors of other myxoviruses and, conversely, the receptor-destroying enzyme of either of the latter viruses was unable to inactivate the receptors for influenza C virus on erythrocytes. While the enzyme of influenza A and B virus was characterized as a neuraminidase in the 1950s, even with refined methodology no such activity was detectable with influenza C virus. It is now known that both the receptor-binding and receptor-destroying activities, as well as the fusion activity of influenza C virus are mediated by the only glycoprotein present on the surface of the virus particle. The structure and functions of this protein, which is designated as HEF, are reviewed in this chapter.
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7,287 |
Australia (Hepatitis-Associated) Antigen: Physicochemical And Immunological Characteristics
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This chapter discusses the discovery, characterization, immunology, and etiological significance of “Australia antigen (Au),” a new antigenic specificity appearing in the serum of patients with serum hepatitis, and carried on characteristic lipoprotein particles. In addition to its original name, given before its relationship to viral hepatitis became known, the antigen has also been given the designations, including Au(1) , SH antigen, Au/SH antigen, hepatitis antigen, and hepatitis-associated antigen (HAA). The synthesis of Au antigen, and its appearance in the serum, is specifically associated with infection by the causal agent of the SH type of viral hepatitis. The chapter discusses properties of the antigen, and of the particles which carry the Au specificity. It also discusses various serological techniques for Au antigen, such as two-dimensional double immunodiffusion (ID), complement fixation (CF), immunofluorescence (IF), reversed passive hemagglutination (RPHA) of antibody-coated red cells, immune electron microscopy (IEM), immunoelectroosmophoresis (IEOP), and radioimmunoassay (RIA).
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7,288 |
Viral and cellular mRNA capping: Past and prospects
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This chapter focuses on the history of the discovery of cap and an update of research on viral and cellular-messenger RNA (mRNA) capping. Cap structures of the type m(7) GpppN(m)pN(m)p are present at the 5′ ends of nearly all eukaryotic cellular and viral mRNAs. A cap is added to cellular mRNA precursors and to the transcripts of viruses that replicate in the nucleus during the initial phases of transcription and before other processing events, including internal N(6)A methylation, 3′-poly (A) addition, and exon splicing. Despite the variations on the methylation theme, the important biological consequences of a cap structure appear to correlate with the N(7)-methyl on the 5′-terminal G and the two pyrophosphoryl bonds that connect m(7)G in a 5′–5′ configuration to the first nucleotide of mRNA. In addition to elucidating the biochemical mechanisms of capping and the downstream effects of this 5′- modification on gene expression, the advent of gene cloning has made available an ever-increasing amount of information on the proteins responsible for producing caps and the functional effects of other cap-related interactions. Genetic approaches have demonstrated the lethal consequences of cap failure in yeasts, and complementation studies have shown the evolutionary functional conservation of capping from unicellular to metazoan organisms.
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7,289 |
Emergence, Natural History, and Variation of Canine, Mink, and Feline Parvoviruses
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This chapter discusses the emergence of canine parvovirus (CPV), the evidence concerning the previous emergence of mink enteritis virus (MEV) as the cause of a new disease in minks in the 1940s, and the mechanisms that determine the host ranges and other specific properties of the viruses of cats, minks, and dogs. The viruses are classified as the feline parvovirus subgroup of the genus Parvovirus, within the family Parvoviridae. Feline panleukopenia virus (FPV), MEV, and CPV are classified as “host range variants.” In addition to the viruses of cats, minks, and dogs, similar viruses naturally infect many species within the families Felidae, Canidae, Procyonidae, Mustelidae, and possibly the Viverridae. The differences in virulence for minks observed after inoculation of MEV or FPV suggests that there are subtle differences between FPV and MEV that have yet to be defined. Genetic mapping studies indicate that only three or four sequence differences between the FPV and CPV-2 isolates within the VP-1 lVP-2 gene determine all of the specific properties of CPV that have been defined: the pH dependence of hemagglutination, the CPV-specific epitope, and the host range for canine cells and dogs.
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7,290 |
Effects of Defective Interfering Viruses on Virus Replication and Pathogenesis In Vitro and In Vivo
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Defective interfering (DI) particles are subgenomic deletion mutants generated from the infectious virus genomes, generally by replicase errors. DI particles and related satellite genomes of the plant RNA viruses are generated by a wide variety of animal, plant, and fungal viruses. The ubiquity of DI viruses was first clearly recognized by Huang and Baltimore. They proposed and defined the term “DI particle” to include defective viruses containing only some portion of the infectious virus genome, requiring homologous parental virus as a helper for the replication, containing virus structural proteins and antigens, and exhibiting the capacity to replicate preferentially at the expense of infectious helper virus in cells infected by both. Satellite RNAs of plants are small RNAs that usually share little or no homology with their helper viruses, although some do exhibit some sequence homology with their helper viruses, and thus resemble DI particles in at least a portion of their genomes. Depending on the leaving sites and resumption sites, DI particles can be produced that are simple internal deletions of the virus genome, simple deletions with a new terminus, or complex or bizarre genomes with multiple rearrangements of the virus segments. DI viruses and defective viruses generally are widespread in nature. Laboratory studies show that they can sometimes exert powerful disease-modulating effects (either attenuation or intensification of symptoms). Their role in nature remains largely unexplored, despite the recent suggestive evidence for their importance in a number of systems.
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7,291 |
Regulation of Protein Synthesis in Virus-Infected Animal Cells
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This chapter summarizes the structural features that govern the translation of viral mRNAs: where the synthesis of a protein starts and ends, how many proteins can be produced from one mRNA, and how efficiently. It focuses on the interplay between viral and cellular mRNAs and the translational machinery. That interplay, together with the intrinsic structure of viral mRNAs, determines the patterns of translation in infected cells. It also points out some possibilities for translational regulation that can only be glimpsed at present, but are likely to come into focus in the future. The mechanism of selecting the initiation site for protein synthesis appears to follow a single formula. The translational machinery displays a certain flexibility that is exploited more frequently by viral than by cellular mRNAs. Although some of the parameters that determine efficiency have been identified, how efficiently a given mRNA will be translated cannot be predicted by summing the known parameters.
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7,292 |
Synthesis of the Putative Red Clover Necrotic Mosaic Virus RNA Polymerase by Ribosomal Frameshifting in Vitro
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The red clover necrotic mosaic virus (RCNMV) genome is split between two single-stranded RNA species termed RNA-1 and RNA-2. RNA-1 directs the synthesis of 88-kDa (p88), 57-kDa (p57), 37-kDa (p37), and 27-kDa (p27) polypeptides and RNA-2 a 35-kDa (p35) polypeptide in vitro. The coding order of the RNA-1 products was determined to be 5′-p27-p57-p37-3′. Antibodies to synthetic peptides representing the carboxyl terminal portions of p27 and p57 immunoprecipitated their respective polypeptides in addition to p88, suggesting that p88 is a fusion protein. A frameshift heptanucleotide sequence element has been identified in RCNMV RNA-1. In addition, a stable stem-loop secondary structure adjacent to the heptanucleotide sequence is predicted. Together, these sequence elements suggest that a ribosomal frameshifting event occurs which allows translational readthrough of the p27 open reading frame into the p57 open reading frame, generating the observed p88 product. An RNA-1 expression construct fusing the p57 and the CP open reading frame was engineered to investigate the ribosomal frameshifting event. CP antibodies immunoprecipitated a fusion protein of the predicted size containing the carboxyl portion of CP. Site-directed mutagenesis of the frameshift element indicates that in vitro, p88 can also be expressed alternatively by suppression of an amber termination codon. Based on these data, we propose that the putative RCNMV RNA polymerase is an 88-kDa polypeptide expressed by a ribosomal frameshifting mechanism similar to those utilized by retroviruses.
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7,293 |
Morphological changes in the jejunum of calves naturally infected with Giardia spp. and Cryptosporidium spp.
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Giardiosis and cryptosporidiosis are frequently diagnosed in calves at the large animal clinic of the veterinary school. Few studies have been reported in the literature regarding pathogenesis of these two intestinal protozoa. The aims of this study were to follow the histological changes in the villi and crypts and the changes in the number of intraepithelial lymphocytes in the jejunum of naturally infected calves during the acute phase of infection. For this purpose, 29 calves aged between 7 and 10 days were bought at a local auction. The animals were housed in individual pens to avoid cross-contamination. Fecal samples were examined microscopically for the presence of Giardia cysts and Cryptosporidium oocysts, three times per week for a period of 45 days. Six calves did not pass any cysts or oocysts and were used as controls. Fifteen calves passed Giardia cysts only, five passed both cysts and oocysts, and three passed oocysts only. The villus to crypt ratio index was 1.76 in the control group and 1.08 in the Giardia-infected group. In the Cryptosporidium-infected calves, the ratio was 1.18 and calves infected with both parasites had an index of 1.37. The number of intraepithelial lymphocytes per millimeter of jejunum tissue was 21 in the control group. This number was doubled in the calves infected with Giardia, but was slightly lower in the other infected groups. All of the infected calves had intermittent diarrhea and mucus was seen in many fecal samples.
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7,294 |
Correlation Among Cystometry, Urethral Pressure Profilometry and Pelvic Floor Electromyography in the Evaluation of Female Patients with Voiding Dysfunction Symptoms
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We herein evaluate the correlation among cystometry, urethral pressure profilometry and pelvic floor electromyography in 137 female patients. The predominant symptom was frequency in 40 patients, urge incontinence in 31 and stress incontinence in 66. There appeared to be a correlation between urge incontinence and a hyperreflexic cystometrogram but no correlation was noted between either frequency or stress incontinence and the cystometrogram profile. The urethral pressure profile showed a correlation between stress incontinence and the lowest profile measurements. Frequency and urge incontinence had similar profile measurements except for maximum urethral planimetry. Electromyography showed that the external urethral sphincter had a different finding than the levator ani or the external anal sphincters in all 3 groups of female patients. The external urethral sphincter had a higher percentage of denervation than the other 2 muscles, especially in the stress incontinence group.
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7,295 |
Pneumonia in pediatric outpatients: Cause and clinical manifestations
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The cause and clinical manifestations of pneumonia were studied in 98 pediatric outpatients. A viral diagnosis was established in 38 (39%) of the 98 patients, and a bacterial diagnosis in 19 (19%). Ten (53%) of the 19 patients with bacterial pneumonia had a concurrent viral infection. No clinical, laboratory, or radiographic findings that would reliably differentiate viral from bacterial infection were identified. This study suggests that bacterial pneumonia is more common in pediatric outpatients than previously reported, and that the clinical, laboratory, and radiographic findings in patients with bacterial infection may be indistinguishable from findings in patients with viral infection.
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7,296 |
Genetics of Resistance of Animals to Viruses: I. Introduction and Studies in Mice
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Inherited resistance to animal viruses may be conveniently classified into three types: monogenetic, following simple mendelian ratios; polygenetic; and cytoplasmic. A virus is a unique cellular parasite, dependent upon the host for reproduction and nourishment in a variety of different ways. Since, as with the other types of parasites, the host and the parasite have necessarily evolved together. It is a distortion to consider the resistance of the host, without considering the evolutionary steps in the development of this extreme form of parasitism; therefore, this chapter reviews some of the ideas put forward about host-agent interactions in plants as well as in animals. The importance of genes in regulating the resistance to disease, including parasites and parasitoids, is apparent if the disease is considered to be an important evolutionary force. The selective effects of viruses have not yet been adequately studied. Continued attempts to find a correlation between the different blood groups and differing severity of smallpox infection clearly searched for selective forces, but the results were inconclusive. Most of the knowledge of genetic resistance to virus disease rests on the study of resistance to selected agents in various inbred strains of mice and chickens, rather than on any knowledge of the effects of genetic resistance in a natural heterozygous population. The increasing frequency, however, with which genetic resistance is found, is in itself an evidence that these genes are important in natural outbred populations. In addition, there are increasing numbers of virus diseases, in which the viral agent seems to be inherited in a mendelian fashion.
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7,297 |
Molecular Basis of Human Leukocyte Antigen Class II
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This chapter focuses strictly on the HLA MHC class II genes and molecules with regard to how they contribute to better delineation of the genetic associations and how the current knowledge of their structure, expression, and functions can be used to speculate on their role in the pathogenesis of disease. Because of the strong linkage disequilibrium between loci and alleles, the chapter restricts the description of the genetic associations to only the most recent data, mainly generated by molecular means, and because they supercede in precision and accuracy the previous data obtained by serological methods. Because the HLA system displays the unusual feature of strong linkage disequilibrium between loci and alleles, the genetic traits found to be associated with disease do not emerge at random. The pattern of genetic associations follow an almost constant trend. The associations gain strength each time an additional locus centromeric to the precedent is individualized. The advances made in this respect almost parallel the introduction of progressively more refined typing procedures, which allow the division of former genetic entities (loci and alleles) into additional subtypes. Among the HLA-associated diseases, or at least for those diseases in which an autoimmune process is suspected to be directly relevant to the pathogenesis, the associations are with genes and molecules of the HLA-D region (HLA class II genes and products). The most recent data assigns the disease susceptibility to common amino acid sequences present on an HLA class II molecule within its “active” site.
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7,298 |
Effects of cattle tick (Boophilus microplus) infestation on the bovine immune system
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The immunosuppressive effect of experimental Boophilus microplus infestation on bovine peripheral blood lymphocytes (PBL) and on host antibody production to a protein antigen (ovalbumin) was examined. Boophilus microplus infestation caused a marginal decrease in the percentage of T lymphocytes in PBL, which was observed in both lightly (5000 larvae) and heavily (40 000 larvae) infested cattle, and began at the second infestation and continued until the end of the fourth infestation. The percentage of B lymphocytes in heavily tick-infested cattle was less than that in non-infested control cattle after the fourth infestation. The response of PBL from tick-infested cattle to phytohemagglutinin (PHA) was always less than that of tick-free cattle after the second infestation. No noteworthy differences were detected between the three stages of tick infestation, that is, 1 week before the peak of adult engorgement, the middle of the peak and 1 week after all ticks had dropped. Boophilus microplus saliva (100 μl ml(−1)) suppressed 47% of the response of bovine PBL to PHA in vitro. This suppressive effect of saliva may contribute to the lowerresponsiveness of PBL from tick-infested cattle. Antibody production by tick-infested cattle was examined during the third and fourth heavy tick infestation. Tick-infested cattle showed a diminished response against ovalbumin after the second immunization. The immunosuppressive effects of tick infestation may play an important role in tick survival or in the transmission of tick-borne diseases in the field.
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7,299 |
Translational Suppression in Retroviral GENE Expression
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This chapter summarizes the present state of knowledge concerning translational suppression in retroviruses. Other viruses, using similar mechanisms, are mentioned only briefly and tangentially. Retroviruses are a unique class of viruses that have been found in all classes of vertebrates but not in other organisms. Perhaps, their most distinctive properties are the flow of information from RNA to DNA early in the infectious process, and the subsequent integration of the viral DNA into the chromosomal DNA of the host cell. Retroviruses are the causative agents of acquired immunodeficiency syndrome (AIDS) and of a variety of neoplastic diseases in man and domestic animals. Elements with striking similarities to retroviruses, termed retrotransposons, occur in yeast and many other eukaryotes; elements sharing some characteristics with retroviruses have also recently been observed in prokaryotes. Because of the apparent relationship between retroviruses and retrotransposons, this chapter discusses of retrotransposons as well as retroviruses. Though all retroviruses utilize translational suppression in pol-protein synthesis, different groups of retroviruses use two completely distinct types of translational suppression. One of these is in-frame or readthrough suppression and the other is ribosomal frameshifting.
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