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Detection of rotavirus in faecal specimens with a monoclonal antibody enzyme-linked immunosorbent assay: Comparison with polyclonal antibody enzyme immuno-assays and a latex agglutination test

Monoclonal antibodies have been produced against the 81/36F strain of rotavirus. One of them, was chosen as diagnostic reagent: it showed high ELISA reactivity with all the bovine, human and porcine rotavirus strains tested and reacted with VP6, structural protein product known to support the common rotavirus antigen. A sandwich ELISA procedure using the chosen monoclonal as “capture and detecting” antibody was performed to detect rotavirus in faecal samples from experimentally inoculated newborn calves: it always gave a negative response with meconium and a positive response for the stool specimens which rotavirus have been isolated. This assay was compared with Enzygnost and Slidex Rota Kit tests and with a non-commercial sandwich ELISA test using polyclonal antibodies: it showed more sensitivity than the agglutination test and was as sensitive as the other two tests to detect rotavirus in routine diagnostic material. The test evaluated showed no equivocal results.

Clinical applications of antiviral agents for chemophrophylaxis and therapy of respiratory viral infections

Table III summarizes clinical applications of antiviral agents in respiratory viral infections. For influenza A virus infections, both oral amantadine and rimantadine are effectvive when used for seasonal prophylaxis and for prophylaxis in institutional populations. Both of these drugs, as well as aerosilized ribavirin, have antiviral and therapeutic effects in uncomplicated influenza. It remains to be determined whether any of these modalities or possibly their combined use [44] will be useful in treating severe influenza in hospitalized patients or whether they can prevent the development of complications in high risk patients. Unfortunately, there is no parenteral formulation of amantadine or rimantadine for use in critically in patients. Aerosolized ribavirin has also been shown to have modest therapeutic effects in influenza B virus infection. However, a major need exists for an antiviral which is active against influenza B virus and which can be used on an outpatient basis. Controlled clinical trials have shown that aerosolized ribavirin therapy improves arterial oxygenation and modifies the severity fo respiratory syncytil virus bronchiolitis and pneumonia [3,5]. Its role in treatinglife-threatening disease or in dodifying the long-term sequelae of RSV infections are unknown at the present time. Again, a specific antiviral agent is needed for out-patient use in preventing or treating RSV infections. Finally, after over a decade of work since the original observation that intranasal interferon could prevent experimental rhinoirus infection [11], recent studies have established that intranasal rIFN-a2 is effective in the postexposure prophylaxis of rhinovirus colds in families [42]. This strategy needs to be studied with regard to the prevention of infection and its complications in high risk patients and it remains to be determined whether intranasal interferen will have therapeutic activity in established colds.

Analysis of a hypervariable region in the 3' non-coding end of the infectious bronchitis virus genome()

Previous studies on infectious bronchitis virus (IBV) cDNA have identified a region of about 184 bases in the 3' non-coding terminus of both the U.S. prototype strain (Beaudette) and a Japanese strain (KB8523), that was not present in an antigenically closely related U.S. strain, Massachusetts (Mass) 41 (Boursnell et al., 1985; Sutou et al., 1988). In order to investigate the origin and function of this region and its occurrence in nature, the cDNA sequences of the 3' non-coding regions of three additional strains of IBV, Gray, Arkansas (Ark) 99 and Holland (Holl) 52, were determined and compared to the sequences of the Beaudette, KB8523 and Mass41 strains. Not only was this U-rich sequence absent from the 3' non-coding region of the Mass41 strain, it was also highly variable, especially in comparison to the highly conserved 3' non coding region downstream of this sequence. Computer analyses of the sequences adjacent to this hypervariable region (HVR) showed that the 3' end of the IBV genome was highly conserved downstream of this region, with 94.3 to 97.8% similarity. However, the similarities for the HVR ranged from 53.2% between Ho1152 and Ark99, to 92.8% between Beaudette and Gray. The flanking sequences were not only conserved but these sequences upstream and downstream of the HVR also formed mirrored images.

A viral subunit immunogen for porcine transmissible gastroenteritis

An immunogenic component was isolated from both the Illinois (propagated in young swine) and the Miller (cell culture-adapted) strains of porcine transmissible gastroenteritis (TGE) virus. The viral subunit was released from the virion by sonication and was separated from intact virus and other viral components by isopycnic centrifugation. It had a buoyant density in sucrose of 1.02 g/ml. Further purification consisted of gel filtration through Sephadex G200, in which process the immunogen, with a molecular weight of approximately 25 000, was the last component to be eluted. A group of ten young, weaned swine, inoculated intramuscularly with two or three 1-mg doses of the viral subunit were protected against challenge with virulent TGE virus, probably by the induction of secretory IgA. The immunogen also induced a humoral immune response of variable magnitude (titers ranging from 8 to 5 625) in the animals. These antibodies are not believed to be directly related to protection against infection. They can, however, be easily identified by serologic procedures and may serve as a convenient indicator of responsiveness to the TGE viral immunogen.

Studies on the survival of aerosolized bovine rotavirus (UK) and a murine rotavirus

The effect of relative humidity (RH) and temperature on the survival of airborne bovine rotavirus UK isolate (BRV-UK) and a murine rotavirus (MRV) was studied. In any one experiment, the virus under test was suspended in tryptose phosphate broth (TPB) supplemented with uranine (physical tracer) and an antifoam, was aerosolized using a Collison nebulizer into the rotating drum with the RH at either low (30 ± 5%), medium (50 + 5%) or high (80 ± 5%) level at 20 ± 1°C. Following a 15-min period of viral aerosol stabilization, sequential samples of drum air were collected using an All-Glass Impinger (AGI) for 24 h post-aerosolization. Both of the rotavirus isolates were found to survive best at medium RH level and high RH was found least favorable for the survival of these aerosolized rotaviruses. The survival pattern of aerosolized MRV was found to be the best when compared with survival pattern of all animal and human rotavirus isolates studies performed under aerosolized conditions in our laboratory. The findings of these experiments confirm and extend our previous reports on the survival of other animal and human aerosolized rotaviruses and emphasize the fact that air may be one of the vehicles for their dissemination and could explain why it is difficult to control nosocomial outbreaks of rotavirus gastroenteritis and to keep animal colonies rotavirus-free.

Chapter 4 Picornavirus infections

The oldest member of the Picornaviruses group is polio virus, which was recognized early by clinicians because of its characteristic paralytic disease. This chapter examines the polio virus in regard to its virology, disease, and prevention by vaccines and chemoprophylaxis. Polio has been well controlled in most developed countries using live or inactivated vaccines. Research work has intensified using genetic engineering techniques to produce live attenuated viruses with defined and stable mutations so as to prevent reversion to virulence, and also to produce immunogenic oligopeptides or proteins for a new generation of inactivated polio vaccines. Chemotherapy is therefore not required for polio infections. In contrast, neither vaccines have been developed against rhinovirus infections, nor are the vaccines thought to have a use, unless broadly reacting antigenic determinants can be located. Several interesting but only weakly effective antiviral compounds have been selected against rhinoviruses and this is a major research area at present. Studies continue also with interferon, but because of toxicity problems these look less interesting at present. Sequence and biochemical data is now available for several additional enterovirus strains and this could open new possibilities both with antivirals or vaccines (for example synthetic peptides) in the near future.

A continuous epitope from transmissible gastroenteritis virus S protein fused to E. coli heat-labile toxin B subunit expressed by attenuated Salmonella induces serum and secretory immunity

Antigenic site D from the spike protein of transmissible gastroenteritis virus (TGEV), which is a continuous epitope critical in neutralization, has been expressed as a fusion protein with E. coli heat-labile toxin B subunit (LT-B) in attenuated S. typhimurium. Synthetic peptides containing the sequence of site D induced TGEB neutralizing antibodies when inoculated subcutaneously in both rabbits and swine. A synthetic oligonucleotide encoding residues 373–398 of TGEV S protein, including antigenic site D, was cloned in frame with the 3′ end of LT-B gene, into a plasmid used to transform S. typhimurium Δasd (χ)3730. A collection of 6 recombinant plasmids designated pYALTB-D I–VI encoding LTB-site D fusions with a variable number of site D sequences were selected. Four of the 6 LTB-site D fusion products expressed in S. typhimurium(χ)3730 formed oligomers (pentamers) that dissociated at > 70°. S. typhimurium(χ)3730 (pYALTB-D) V and VI expressed the oligomer forming products with higher antigenicity. Partially purified LTB-site D fusion product expressed from S. typhimurium(χ)3730 (pYALTB-D) V induced anti-TGEV neutralizing antibodies in rabbits. Recombinant vaccine strain S. typhimuriumΔcyaΔcrpΔasd(χ)3987 transformed with plasmid pYALTB-D V expressed constitutively products that formed oligomers presumably containing 20 copies of site D, and showed a high stability in vitro. This recombinant strain was orally inoculated in rabbits and induced TGEV specific antibodies in both serum and intestinal secretion.

Epigenetic transmission of feline infectious peritonitis

Feline Infectious Peritonitis (F.I.P.) was diagnosed in the kittens of two successive litters born to a female presumed also infected. At the same time, the two fathers and the other subjects of the cattery remained asymptomatic of F.I.P. The clinical observations, supported by electrophoretic data, suggest the possibility of a direct transmission of the disease by the mother to her offspring, either by the transplacentary pathway (epigenetic transmission) or via the milk.

I, 1.Viral causes of gastroenteritis

This chapter discusses the causative viral agents, pathophysiology, and immunology of gastroenteritis. Acute gastroenteritis is among the most common illnesses of humans and is caused by a variety of agents, including bacteria, viruses, parasites, toxins, and chemicals. The clinical spectrum ranges from asymptomatic or mild infection to severe dehydrating illness with a fatal outcome; the latter occurs primarily in young children and in the elderly. The chapter concludes with a discussion on the prevention and treatment of gastroenteritis. For the prevention of epidemic viral gastroenteritis, efforts need to be focused on caliciviruses. No specific antiviral therapy is recommended for childhood viral gastroenteritis, emphasizing the importance of distinguishing it from the selected forms of bacterial and parasitic gastroenteritis that require treatment. Other than pertinent epidemiologic information, certain clinical features of illness may provide etiologic clues, but they are not highly discriminating. Standard therapy of viral enteric infections relies on maintenance of adequate hydration and electrolyte balance. Oral rehydration therapy (ORT) is the main treatment.

Effect of liposome-encapsulation on immunomodulating and antiviral activities of interferon-γ()

The effect of liposome-encapsulation on the immunomodulating and antiviral activities of interferon-γ (IFN-γ) was evaluated in this study. The immunomodulating activity was measured by increases in phagocytic activity and in nitric oxide production by peritoneal macrophages from mice treated with both free and LIP-IFN-γ (4000 U/mouse, intraperitoneal injection). Resident peritoneal macrophages harvested from mice treated with free unencapsulated IFN-γ or muramyl dipeptide showed significant increases in macrophage yield, and enhanced ability to phagocytize zymosan particles. In mice treated with liposome-encapsulated IFN-γ (LIP-IFN-γ), both macrophage yield and phagocytic activity further increased by 2-fold over unencapsulated IFN-γ. In addition, the activation of peritoneal macrophages with LIP-IFN-γ showed enhanced production of NO when the cells were cultured ex vivo. Using a murine respiratory influenza infection model, intranasally administered LIP-IFN-γ conferred protection to 70% in mice challenged intranasally with 10 LD(50) doses of influenza A/PR/8 virus compared with a 20% survival rate using free IFN-γ. Together these results suggest that liposome-encapsulation increases the immunomodulating and antiviral activities of IFN-γ. Liposome-encapsulation of IFN-γ may provide additional therapeutic advantages by reducing IFN-γ toxicity while prolonging its body retention.

Induction of class I and class II transplantation antigens in rat brain during fatal and non-fatal measles virus infection

Measles virus induced a marked increase in the expression of MHC-coded class I and class II antigens as detected by immunostaining during both fatal and non-fatal brain infections in rats. The distribution of these molecules in the brain was much more widespread than the occurence of viral antigen suggesting a soluble factor for their induction. In 14-day-old rats with a non-fatal infection there was a marked infiltration of T lymphocytes of ‘cytotoxic/suppressor’ phenotype in the brain parenchyma, whereas T ‘helper’ cell phenotypes mainly were located perivascularly. In brains from newborn rats with a fatal infection no or only few lymphocytes were detected.

Loss of cytomegalovirus infectivity after treatment with castanospermine or related plant alkaloids correlates with aberrant glycoprotein synthesis

Many plants contain polyhydroxyalkaloids which are potent inhibitors of glucosidases, enzymes involved in oligosaccharide trimming. These are important in determining the final configuration of specific glycoproteins. Human cytomegalovirus (CMV) encodes a number of glycoproteins, some of which ultimately reside in the outer envelope of the mature virion and are important for virus infectivity. Treatment with three polyhydroxyalkaloids, castanospermine (CAST), deoxynojirimycin (DNJ) and 2R,5R-dihydroxymethyl-3R, 4R-dihydroxypyrrolidine (DMDP) blocked the growth of infectious virus, as determined by yield reduction and plaque reduction assays. However, in the presence of CAST, CMV infected cells continued to shed virions into the extracellular medium, as determined by electron microscopy. Envelope glycoproteins of virions produced after treatment with CAST (2.5 mM) were immunoprecipitated with a monoclonal antibody (F5) specific for the gcI family of glycoproteins. Analysis by PAGE-SDS showed an absence of gcI complex 2 (gp52 disulphide-linked to gp130) with a proportional increase in gcI complex 1 (gp52 disulphide-linked to gp95). The results indicated that gp130 alone, or linked to gp52, was important for CMV infectivity. As well as being potential targets for antiviral agents against CMV, inhibitors of glycoprotein trimming reactions may define components of the virion surface important for infectivity.

Molecular determinants of rotavirus virulence: Localization of a potential virulence site in a murine rotavirus VP4

The molecular basis of pathogenesis in vivo for a virulent mouse rotavirus (MRV) and a less virulent bovine rotavirus (BRV) were compared under in vitro and in vivo conditions. Obvious differences in the mobility of several genomic RNA segments were observed in one-dimensional gels. Under in vitro conditions, partial proteolytic peptide mapping identified differences between the two outer capsid proteins of these virus and no difference in inner capsid protein was observed. Since it has been observed by us and others that the gene coding for VP4 protein plays a significant role in determining virulence, the variability observed in the present study between the 84 k proteins (VP4) provided a basis for further investigations in order to locate a potential virulence determinant. A comparison of the carboxypeptidase digests of the MRV- and BRV-VP4 revealed an area of variability between amino acids 307 and 407, which may represent a site of virulence determinant. Under in vivo conditions the virulence of both parenteral BRV and MRV isolates and their corresponding reassortants (with replaced gene 4) were studied in murine and bovine hosts. Like their parents, BRV and MRV isolates, reassortants obtained by replacement of gene 4 in BRV with MRV gene 4 indicated that the dose of the virus isolate used and the clinical outcome in vivo was determined by gene segment 4. The implications of these findings to elucidate the molecular basis of pathogenesis of rotaviruses are discussed.

Effect of husbandry methods on seropositivity to African swine fever virus in Sardinian swine herds

Multiple logistic regression was used on serological data collected in the context of the Sardinian African swine fever (ASF) eradication program from pig farms in the province of Nuoro, Sardinia. The monthly percentage of ASFV-positive herds decreased significantly from October 1994 through March 1996 (P < 0.001). The farm-level risk of seropositivity to African swine fever virus (ASFV) was higher in free-range farms than in partial-confinement farms (odds ratios (OR) varied between 4.9 in October 1994, and 5.7 in March 1996, P < 0.001). The risk of infection for total-confinement farms was one-fifth of the risk for partial-confinement farms in October 1994 (OR = 0.2, P < 0.001), whereas in March 1996, the estimated OR was 0.57 and not significant (upper confidence limit = 1.1). The maintenance of ASFV in Sardinia was primarily associated with free-range pig farms. The natural logarithm of the number of pigs tested per visit in a farm was positively associated with the risk of herd seropositivity (OR = 2.6, P < 0.001).

The need for new antiviral agents

Population density and immune status, vectors and virulence of infection, nutritional status, sanitation, genetic susceptibility and medical management of cases, are important factors influencing the incidence and/or severity of virus infections. Thus, the prevalence and clinical importance of virus infections and the need for antiviral drugs differ from place to place and from time to time. National and World Health Statistics of notifications of disease give some index of the incidence of infections but not all virus infections are notifiable. Such statistics can be misleading also through failures to notify from sloth on the part of the physician or, in the absence of pathognomonic symptoms or signs, from errors in diagnosis. Any assessment of the need for new antiviral drugs should consider the availability, safety, effectiveness and cost of alternative measures, including prevention of spread of infection by control of vectors, immunization by use of viral vaccines, or treatment with existing antiviral drugs. Early start of treatment of acute virus infections with existing drugs gives the best results and, where the clinical diagnosis is uncertain, accurate rapid virus diagnosis is of paramount importance. Many virus infections are asymptomatic or of trivial importance and without sequelae. However, new or improved antiviral drugs are needed for the prevention and/or treatment of a number of significant conditions caused by viruses which are not at present adequately controlled. These include upper and lower respiratory tract infections, influenza, chronic hepatitis, gastroenteritis, infectious mononucleosis, measles, rabies, haemorrhagic fevers and warts. Furthermore, such drugs might prove of therapeutic value in the prevention or treatment of virus-associated tumours, such as hepatoma, nasopharyngeal carcinoma, Burkitt's lymphoma, Kaposi's sarcoma and possibly carcinoma of the cervix.

Evolution des anticorps anti rota dans le lait de vaches traitees en fin de gestation soit par le vaccin anti rota complet, soit par l'adjuvant seul

The authors describe the evolution of the secretion of anti-Rotavirus antibodies vaccine given three weeks before and repeated at the moment of parturition. Rota virus antibodies were detected at a high level during the three months test period with the Indirect Immunofluorescence Test, the seroneutralisation test and the immunofluorescence test. The four untreated animals excreted only rota-antibodies till day 6 post partum. Seroneutralising antibodies were detected in the milk of the vaccinated animals at a level of 10–50% of the colostral level till day 90. The aspecific stimulation of the excretion of anti-Rotavirus antibodies in the milk after inoculation of the only adjuvant fraction of the vaccine is confirmed. The excretion level, however, was significantly lower than after Rotavirus vaccination.

Chapter 1 The need for chemotherapy and prophylaxis against viral diseases

The chapter discusses the need for chemotherapy and prophylaxis against viral diseases. It briefly mentions clinical diseases and syndromes such as influenza, respiratory tract infections, hepatitis, and arbovirus infections resulting from virus infections. Viruses causing respiratory diseases, as well as many other diseases in humans are also discussed in the chapter. It describes the vaccines that are used to check the attack of different viruses as well as their cost-effectiveness. There is a list of some viruses that have been ranked according to different variables in an attempt to select a good candidate for an antiviral drug. The incidence of the viral disease is naturally an important factor, as is the severity of the disease. The incidence can be obtained for diseases being reported in accordance with local regulations, but in many cases viral diseases are not reported and the incidence has to be calculated from different surveys. Also, a grading of the severity is not easy and an example is when herpesvirus infections are handled as a group, which includes both herpes encephalitis and cold sores. The greatest challenges and probably the most difficult and medically important areas for prophylaxis and therapy of viral diseases are the viruses that are rapidly changing in antigenic composition and/or viruses with animal reservoirs (influenza and arboviruses) and those forming latent infections (herpesviruses).

Alphavirus replication in cultured cells and infected animals is inhibited by antiproteinase agents

The influence of different antiproteinase agents on alphavirus replication was examined. Sindbis virus multicycle replication in cultured cells was suppressed by N-tosyl-phenylalanine chloromethyl ketone (TPCK), an inhibitor of chymotrypsin-like proteinases, and by aprotinin, an inhibitor of a wide spectrum of proteinases. Antiviral activity of TPCK was also demonstrated in Sindbis virus-infected animals. Parenteral injections of TPCK in infected mice reduced virus titers in brain and blood. The possible mechanism(s) of antiviral action of the antiproteinase agents are discussed.

Transmissibility of the contagious equine metritis organism for the cat

A group of SPF cats were moderately susceptible to the causal organism of contagious equine metritis (CEM) following intra-uterine or intrapreputial challenge with an Irish streptomycin resistant strain isolated from a clinically infected mare. Subclinical infections were established in only 50% of the cats, none of which became long-term carriers of the organism. Cytological examination of vaginal smears was of no diagnostic value in confirming infection in inapparently infected cats. Bacteriological responses after primary or secondary challenge with the CEM organism were essentially similar, with one exception, a female cat in which there was possible evidence of local immunity persisting after the primary infection. Efforts to reactivate shedding subsequent to the immediate post-challenge period were unsuccessful. Throughout the experimental period, the cats remained sero-negative to the complement-fixation test, and they failed to develop any significant increase in the levels of antibody activity as measured by the kinetics-based ELISA or KELA system. On day 89 after primary challenge, the cats were euthanized and various sites in the genitourinary tract and the internal iliac lymphatic glands subjected to bacteriological and pathological examination for evidence of CEM infection with negative results. The findings of this study, although establishing the transmissibility of the CEM organism for the cat, demonstrate the limited value of this species as an experimental model system for the disease in the horse.

Antibody-mediated enhancement of disease in feline infectious peritonitis: Comparisons with dengue hemorrhagic fever()

Non-immune kittens passively immunized with feline serum containing high-titered antibodies reactive with feline infectious peritonitis virus (FIPV) developed a more rapid disease after FIPV challenge than did kittens pretreated with FIPV antibody-negative serum. Antibody-sensitized, FIPV challenged—kittens developed earlier clinical signs (including pyrexia, icterus, and thrombocytopenia) and died more rapidly than did non-sensitized, FIPV-challenged kittens. Mean survival time in sensitized kittens was significantly (P < 0.05) reduced compared to non-sensitized kittens (mean ± SEM, 10.0 ± 0.6 days vs. 28.8 ± 8.3 days, respectively). Lesions induced included fibrinous peritonitis, disseminated pyogranulomatous inflammation and necrotizing phlebitis and periphlebitis. FIPV antigen, immunoglobulin G, complement (C3) and fibrinogen were demonstrated in lesions by immunofluorescence microscopy. The pathogenesis of dengue hemorrhagic fever (DHF) in persons bears striking resemblance to that of FIP in experimental kittens. In both FIP and DHF, non-neutralizing antibody may promote acute disease by enhancement of virus infection in mononuclear phagocytes or by formation of immune complexes, activation of complement and secondary vascular disturbances.

A study of the efficacy of the bradykinin antagonist, NPC 567, in rhinovirus infections in human volunteers

In a double-blind placebo controlled trial intranasal NPC 567, a bradykinin antagonist, failed to alleviate the symptoms of experimental rhinovirus colds. Indeed, there was evidence that the drug enhanced the symptoms although no irritant effect was detected on the uninfected nasal mucosa.

Inhibition of human adenoviruses by 1-(2′-hydroxy-5′-methoxybenzylidene)amino-3-hydroxyguanidine tosylate

Antiviral activities of four Schiff bases of aminohydroxyguanidine, designated ML1, ML4, ATL14 and LK11, were tested against human adenovirus types 5 and 8 (Ad5 and Ad8) in A549 cells by plaque reduction and virus yield reduction methods. Compound ML1 1-(2′-hydroxy-5′-methoxybenzylidene)amino-3-hydroxyguanidine tosylate gave the best therapeutic indices (TC(50)/IC(50)) of 27.2 and 17.8 for Ad5 and Ad8, respectively. Pretreatment of cells with ML1 did not affect the adsorption nor the penetration of virus. Ultrastructure studies showed that only the drug treated infected cells had unidentified irregular shaped electron dense structures that might be drug altered viral macromolecules that were not assembled into complete infectious virus particles. Since these compounds have metal chelating properties, their antiviral activity may involve the early IA (EIA) gene which encodes a viral protein of 289 amino acid which has a zinc finger moiety that is required for its transactivation activity.

Inhibition of cell adhesion to the virus by synthetic peptides of fiber knob of human adenovirus serotypes 2 and 3 and virus neutralisation by anti-peptide antibodies

The fiber knob of adenovirus (Ad) causes the first step in the interaction of adenovirus with cell membrane receptors. To obtain information on the receptor binding site(s) several synthetic peptides derived from Ad2 and Ad3 fiber head sequences and their antisera were tested for interference with virus attachment to HeLa and FL cells and cell adhesion to viruses. The anti-peptide sera were also evaluated in ELISA and virus neutralisation test. Ad2 (of subgroup C) and Ad3 (of subgroup B) attachment was not significantly inhibited by peptides corresponding to the amino acid residues 535–554, 555–573, 562–582 of Ad2 fiber or 210–225, 267–283, 291–306 and 300–319 of Ad3 fiber. However, microplate pre-adsorbed Ad3 fiber residues 210–225 and 267–283 could bind FL and HeLa cells, and 1 mg/ml of Ad3 fiber residues 267–283 inhibited the cell adhesion to Ad3 virus to approximately 90%. This peptide may participate in the receptor binding site of Ad3 fiber. ELISA reactive anti-peptide antibodies against the homologous peptide and virus did not significantly reduce the cell adhesion to the immobilised virus or the virus attachment to cells, but in the neutralisation assay antibodies raised to Ad2 fiber residues 555–573 and 562–582 and Ad3 fiber residues 210–225 caused neutralisation of the homologous virus at serum dilutions of 1:500 and 1:32, respectively. The corresponding peptides and one further peptide of Ad2 fiber and two of Ad3 fiber seem to contain neutralisation epitopes.

Optimization of culture conditions for feline × murine heterohybridomas

Feline splenocytes were fused to the murine myeloma lines NSO or Ag8. Autologous serum and taurine were used as media supplements for the cat × mouse heterohybridomas. The best results were obtained by the use of NSO as fusion line with taurine-supported media.

Induction of autoimmune reactions to myelin basic protein in measles virus encephalitis in Lewis rats

Intracerebral inoculation of weanling Lewis rats with measles virus led to the development of subacute measles encephalomyelitis (SAME) 4–8 weeks after infection. The disease is characterized pathologically by an intense inflammatory infiltration within both the white and grey matter of the central nervous system (CNS) without apparent demyelination. Both during and after SAME splenic lymphocytes from these animals could be restimulated in vitro to proliferate in the presence of myelin basic protein (MBP). MBP-specific class II MHC-restricted T cell lines were isolated from this cell population. They were shown to exhibit no cross-reactivity with measles virus and to induce experimental allergic encephalitis (EAE) in naive syngeneic recipients following adoptive transfer. The clinical and histopathological signs of this T cell-mediated disease were identical to that seen in classical T cell-mediated EAE. A humoral immune response to MBP was only detected in a limited number of those rats with SAME. These results indicate that autoimmune reactions to brain antigen can arise during measles virus infection which may contribute to the pathogenesis of measles virus-associated encephalomyelitis.

Chapter 7 Orthomyxovirus infections

The earth is a unity for influenza A virus in a manner not yet found for probably any other parasite and epidemics occur in all inhabited parts of the globe regardless of latitude, longitude, altitude, climate, rainfall, temperature, humidity, race and sex. Influenza A is the classic pandemic virus infection of man and influenza B virus also can cause sharp outbreaks, resulting in significant mortality. An overwhelming amount of data has accumulated on the biochemistry, cell biology, and epidemiology of influenza, but prospects of control of epidemics in the near future are dim. Meanwhile, a holding operation can be achieved using inactivated vaccine and rimantadine (100 mg/daily) in special risk groups in the population until new more effective vaccines and broad spectrum antivirals (active against influenza A and B virus) are developed. Research work is centered on biotechnology to produce immunogenic peptides and proteins and more logical searches for antivirals using amino acid sequence data and also virus specific enzymes such as the virion transcriptase as targets.

Studies on the suitability of alpha-hybrid interferon application in cattle

Twelve cattle with body wts ranging from 100 to 250 kg were treated using various doses and routes for four days with an E. coli derived alpha-hybrid interferon. The lowest parenteral doses (10(4) units per kg body wt) and the orally administered interferon did not lead to any disturbances, whereas the higher dosages led to marked changes in body temperature, pulse and respiration rates. Animals with the highest dose (10(8) units per kg body wt) became extremely distressed. The blood picture showed distinct changes, with very low leukocyte counts during treatment, which took weeks to recover. It is suggested that the dosages that did not lead to clinical symptoms are best suited for prophylactic or therapeutic purposes.

Trans splicing in trypanosomes — archaism or adaptation?

In trypanosomes, a single transcription unit usually covers several protein-coding genes. The primary transcript is cut up by trans-splicing and polyadenylation machineries to generate individual mature mRNAs. All nuclear mRNAs acquire the same capped 39 nucleotide sequence at their 5′ end as a consequence of the trans-splicing event. Trans splicing is used in the synthesis of some mRNAs in nematodes and chloroplats. These unusual systems are clearly related to cis-splicing systems, but it remains an intriguing question whether they are merely exotic offshoots of cis splicing or archaic remnants of cis-splicing progenitors.

Brefeldin A inhibits the antiviral action of interferon against encephalomyocarditis virus

Brefeldin A (BFA), a unique fungal metabolite of a 13-membered lactone ring, exhibits various biological actions, including antitumor, antifungal and antiviral activities. In the present study, mouse L(B) cells were treated with various concentrations of interferon (IFN) and/or BFA overnight and infected with encephalomyocarditis virus (EMCV) after removal of IFN and BFA. Doses of BFA which neither inhibit the metabolism of the cell nor the infectivity of EMCV, decreased the IFN-induced antiviral activity against EMCV as demonstrated by virus titer from supernatants. Since 2–5A synthetase and double-stranded RNA (dsRNA)-dependent protein kinase (PKR) have been suggested to be involved in the antiviral action of IFN against EMCV, their activities were investigated in L(B) cells after BFA treatment. Northern blot analysis and in situ hybridization showed a decrease (2–3-fold) in the mRNA of 2′–5′ oligoadenylate (2–5A) synthetase after BFA treatment. BFA also inhibited the activity of 2–5A synthetase, 2–5A dependent RNase and phosphorylation of PKR in cellular extracts, indicating that BFA may be exerting its inhibitory effect both at the transcriptional and post-transcriptional levels. This study reports a new biological action of BFA, demonstrating that BFA antagonized the antiviral action of IFN by inhibiting IFN-induced enzymatic pathways. These studies also suggest that both 2–5A and PKR are important in the antiviral activity of IFN against EMCV.

Isolation and identification of avian rotavirus from pheasant chicks with signs of clinical enteritis

Three rotaviruses were isolated from intestinal contents obtained from a flock of 6–8-day-old pheasant chicks showing diarrhoea and increased mortality. The isolates were characterized as avian group A rotavirus by immunoenzymatic technique (ELISA) and polyacrylamide gel electrophoresis (PAGE).

The polymerase in its labyrinth: mechanisms and implications of RNA recombination

The wide variety of RNA viruses, and the diseases associated with them, may result in part from the capacity of RNA genomes to evolve through genetic recombination. Here we address the mechanism of RNA recombination, and ask questions about its prevalence and purpose in nature.

Diagnosis of Feline Viral Infection

The methods of diagnosis of the common feline viral infections are discussed. Specific diagnosis involves a combination of an accurate history, careful observation of disease signs, demonstration of characteristic clinicopathologic changes, and isolation or identification of the etiologic agent. The laboratory tests for virus identification—including virus isolation, cytology, electron microscopy, virus neutralization, immunofluorescent microscopy, and enzyme-linkedimmunosorbent-assay (ELISA)—are briefly described.

Myelitis and Meningitis

The inflammatory diseases most commonly affecting the spinal cord meninges and parenchyma of dogs and cats are discussed. Clinical signs, lesion localization, differential diagnoses, diagnostic procedures, therapeutic regimens, and prognosis are described.

Canine Vaccination

New technologies for vaccine development and infectious disease diagnosis are likely to be introduced in the near future. With this new technology comes the opportunity to vaccinate companion animals against even more infectious agents than is currently practiced in the United States. As we look forward, it becomes particularly important to review current vaccination standards applied to dogs with respect to current knowledge of duration of immunity, awareness of incidence, and likelihood of injurious or even fatal adverse events associated with vaccination, and individual risk factors that dictate which vaccines are most appropriate at which stage of life.

A Major Role of Macrophage Activation by Interferon-Gamma during Mouse Hepatitis Virus Type 3 Infection. I. Genetically Dependent Resistance()

Resistance of mice to mouse hepatitis virus type 3 (MHV3) infection is genetically determined. Normal adult A/J mice are resistant, and BALB/c mice are susceptible. Higher titers of virus and interferon (IFN) in vivo were found in MHV3-infected BALB/c mice compared with A/J mice. In vitro activation of macrophages (MФ) by lipopolysaccharide (LPS) delayed MHV3 replication only in cells that originated from A/J mice, although cell populations from both A/J, and BALB/c mice were able to synthesize comparable amounts of IFN-α/β. Using specific antibodies, we have shown that the delayed MHV3 replication in LPS-activated A/J MФ was due, in part, to IFN-α/β. A/J MФ were found to be more sensitive to IFN-γ than to IFN-α/β, and BALB/c MФ did not develop an antiviral state to either IFN. Cultured spleen cells from A/J mice synthesized more IFN-γ than BALB/c spleen cells after specific or non-specific stimulation. The results indicate that IFN-activated MФ may play a crucial role in the resistance to MHV3 infection. Since IFN-γ is produced in large amounts by A/J spleen cells after specific stimulation with MHV3 and is efficient in activating the A/J MФ, a T cell-dependent mechanism- is likely to be involved.

An unique CD4(+)CD8(+) intestinal intraepithelial Lymphocyte Specific for DnaK (Escherichia coli HSP70) may be selected by intestinal microflora of rats

We have previously shown an age-associated increase in unique CD4+CD8+ intestinal intraepithelial lymphocytes (i-IEL) in rats. To elucidate the potential causes of the increase in CD4+CD8+ i-IEL with age, we analyzed the specificity of the CD4+CD8+ i-IEL and influence of intestinal microflora on the increase in this subset in aged rats. The purified CD4+CD8+ i-IEL proliferated in response to DnaK [Escherichia colt (E. coli) HSP70] in the presence of mitomycin-c (MMC)-treated syngeneic, spleen cells. The proportion of CD4+CD8+ T cells in whole i-IEL were significantly increased in aged rats fed commercial (CL-2) diet but not in those fed home-made (purified) diet under conventional condition. No CD4+CD8+ i-IEL were detected in aged rats under germfree condition, irrespective of diet feeding. A larger number of Enterobacteriaceae, especially E. coli, were detected in the intestinal contents and feces from aged rats with CD4+CD8+ i-IEL compared with those from aged rats fed without CD4+CD8+ i-IEL. The unique CD4+CD8+ i-IEL population specific for E. coli HSP may be associated with long term exposure to intestinal E. coli in aged rats.

Feline Infectious Peritonitis

Feline infectious peritonitis (FIP) occurs most frequently in young animals from multicat households. Ocular manifestations of FIP are extremely common with the noneffusive form of the disease. All cats suspected of having FIP should undergo a thorough ophthalmic examination. Uveitis (inflarrunation of the iris, ciliary body, and choroid) is the primary clinical sign of ocular FIP. Treatment with anti-inflammatory medications is only supportive and aimed at disease palliation.

Nutrition and Management of Reproduction in the Cat

The successful long-term maintenance of catteries for reproductive purposes necessitates careful consideration of many facets of feline health, nutrition, and management. This article discusses control of infectious and parasitic diseases, proper nutrition and feeding, management of reproduction, and general management procedures.

The Epidemiology of Viral Infections in Dogs and Cats

Understanding the epidemiology of an infectious disease is a prerequisite to be being able to suggest the most appropriate methods for prevention and control of the disease. This article reviews some important epidemiologic concepts.

Significance of viral glycoproteins for infectivity and pathogenicity()

Disease resulting from virus infection is a complex event depending on the close interaction of viral and cellular factors. Through the application of biochemical and genetic methods, it is now possible to gain an insight into the molecular basis of these interactions. Thus, it has been shown that the glycoproteins of enveloped viruses play a central role in the initiation of infection. They are responsible not only for the adsorption of virions to cellular receptors, but are also for the entry of the genome into the cell by the fusion of viral envelopes with cellular membranes. Evidence is growing that the fusogenic glycoproteins are frequently activated by cellular proteases. The structure of the proteins at the cleavage site and the availability of a suitable protease are critical for tissue tropism, spread of the virus in the infected organism and, thus, for pathogenicity. This will be demonstrated here by the example of the haemagglutinin of influenza viruses.

Canine Parvovirus

Canine parvovirus type-2 is a new canine pathogen that emerged in the late 1970s. The origin, spread, and evolution of the virus are reviewed. The present pattern of disease and current concepts of diagnosis, clinical management, and prevention are discussed.

Human immunodeficiency virus—associated vitiligo: Expression of autoimmunity with immunodeficiency?

Persistent viral infections have been postulated to be trigger factors for the development of autoimmune disease. We report the development of vitiligo in four patients with human immunodeficiency virus (HIV)—related conditions and in one patient with hepatitis who later developed both psoriasis and acquired immunodeficiency syndrome (AIDS). Other common features were hepatitis and multiple other viral infections. Ribavirin was associated with repigmentation in one patient. Vitiligo may be an example of an autoimmune disease triggered by viral infection in a genetically predisposed host.

Protection of Mice against Infection with Mouse Hepatitis Virus Type 3 by Injection of Silica

Injection of silica did not brake the resistance against MHV3 conferred to C57BL/6 mice by injection of C. parvum. However, silica itself had a marked protective effect against MHV3 infection that was maximal when injecting 1 mg 2 hrs before virus infection. The protective effect of silica was observed in a number of inbred mouse strains that differ in their relative resistance to MHV3 infection. No viral titers were observed in the spleen and liver of mice which had received MHV3 plus silica, whereas high titers were observed in the virus-infected controls. Injection of silica caused a marked decrease in the number of esterase-positive macrophages in the peritoneal wash-out population, that may be compatible with the possibility that the cause of the protection is the depletion of target cells for the viral infection. This latter effect, however, was short-lived and 24–48 hrs after injection of silica, high numbers of esterase-positive cells were again observed. This may explain why only little protection was observed when silica was administered 2 days before virus infection.

Rapid mitogen-induced aminopeptidase N surface expression in human T cells is dominated by mechanisms independent of de novo protein biosynthesis

The membrane bound metalloprotease aminopeptidase N (APN, CD13, EC 3.4.11.2) is a well established marker of normal and malignant cells of the myelo-monocytic lineage. It is also expressed by leukaemic blasts of a small group of patients suffering from acute or chronic lymphoid leukaemia. Recently, the expression of the APN gene in T cell lines as well as the induction of APN gene and surface expression in human peripheral T cells by mitogenic activation have been demonstrated. Here, by means of cytofluorimetric analysis evidence is provided, that the induction of APN surface expression is partially resistent to the action of the inhibitors of protein biosynthesis, puromycin and cycloheximide, and is not prevented by tunicamycin, an inhibitor of glycosylation. These data suggest that the rapid mitogen-induced surface expression of APN, detectable 20 hours after stimulation is dominated by mechanisms not dependent on de novo protein biosynthesis or glycosylation. As shown by simultaneous analyses, the inhibitors used did also differently modify the induction of surface expression of other inducible glycosylated leukocyte surface antigens, namely CD25, CD69 and CD95.

Persistent Viral Infection: The Carrier State

A persistent viral infection is one in which the virus in a replicating or non-replicating form persists in the host beyond the normal recovery and elimination period for that particular viral infection. The clinical significance and mechanisms of persistence, when known, are discussed for the important viral infections of dogs and cats. Particular emphasis is given to feline viral rhinotracheitis, feline calicivirus, canine distemper, and feline leukemia.

Pet Rabbits

Pet rabbits are becoming more common, and rabbit owners are demanding quality veterinary care. This article provides a broad overview of pet rabbit medicine, which is a relatively new field compared to laboratory and farm rabbit medicine. The most common differential diagnoses for presenting complaints are summarized in table form. Disease conditions are reviewed individually in the text. Sources of further information on veterinary care of rabbits are listed throughout the text, in an appendix, and in the references.

Possible Association of Thymus Dysfunction with Fading Syndromes in Puppies and Kittens

This article focuses on the role of the thymus gland in maintaining the health of young animals and on how thymus dysfunction may contribute to some cases of wasting and death. Current knowledge about thymus hormones is reviewed briefly, and one form of a wasting syndrome in pups that is responsive to thymus hormone therapy is described.

Inflammatory Disease of the Central Nervous System

Inflammatory conditions affecting the central nervous system are discussed. Clinical signs, diagnostic procedures, therapeutic regimeris, and prognosis are described.

In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to mouse hepatitis virus 3 infection

The possible role of interferon-gamma (IFN-γ) in the resistance of A/J mice to MHV3 infection was investigated. Monoclonal antibodies specific for IFN-γ, CD4 and CD8 molecules were administered in vivo to deplete selectively the IFN-y synthesized or the appropriate subset of T cells. The animals were then infected with MHV3 and the course of infection was followed by studying different parameters, such as, the mortality, the virus growth in the tissues and the IFN-γ synthesis in sera and peritoneal exudates. After MHV3 infection, a full resistance of control A/J mice was observed, in contrast to the high mortality rate observed among the depleted animals, where higher virus titers were found in different tissues. The IFN-γ synthesis in sera and peritoneal exudates of depleted mice, after MHV3 infection, drastically decreased when compared to that detected in control mice. The data presented are consistent with the hypothesis that IFN-γ plays an essential role in the resistance of A/J mice to MHV3 infection.

Vaccines and Principles of Immunization

This article discusses the production of the various classes of vaccines and compares the advantages and disadvantages of each. Adjuvants, combination vaccines, heterologous viral vaccines, and vaccination failure are discussed briefly. Reported adverse reactions to vaccination are described at length. Essential vaccination for several exotic species is given.

Demonstration of CD13/Aminopeptidase N on Synovial Fluid T Cells from Patients with Different Forms of Joint Effusions

Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the synovial fluid (SF) and the peripheral blood (PB) from patients suffering from juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA). The most obvious difference could be found in expression of the surface protease aminopeptidase N (AP N/CD13). Whereas monoclonal antibodies specific to CD13 failed to reveal surface expression on lymphocytes of the PB; 63 ± 15% of SF T cells gave positive staining for CD 13 using Leu-M7. No correlation between CD13 expression and joint disease could be found in patients who had different types of inflammatory joint effusions. CD13 expression of T cells was also found in synovial tissue and inflammatory serous cavity effusions. Fixation of T cells revealed the presence of intracellular CD13 antigen already located in the PB T cells of healthy individuals. Induction of CD13 expression on PB T cells could be demonstrated after incubation with Con A/IL-2 or SF from patients with RA. Our findings suggest a role for AP N as a new activation-associated molecule of T lymphocytes.

A Major Role of Macrophage Activation by Interferon-Gamma During Mouse Hepatitis Virus Type 3 Infection: II. Age-Dependent Resistance

In contrast to adult mice, young AJ/mice, developed an acute hepatitis following infection with Mouse Hepatitis virus type 3. 100 % of the young animals died 4 to 5 days after the infection and high levels of virus were found in the liver and peritoneal exudate. Very low levels of IFN-$#x03B3; were found in the serum and peritoneal exudate of infected young mice. This was in contrast to the levels observed in adult mice. Spleen cells and macrophage cultures from young A/J mice, again in contrast to adult A/J mice, were shown to be unable to synthesize IFN-$#x03B3; and IFN-α/β respectively. Macrophages from either young or adult A/J mice were able to be activated with exogenous recombinant IFN-$#x03B3; or IFN-α/β, enabling both sets of cells to restrict MHV3 replication. The results indicate that the ability of the immune system to synthesize IFN-$#x03B3; and IFN-α/β may playa major role in the age-dependent resistance of A/J mice to MHV3.

Inflammatory Oral Cavity Diseases of the Cat

This article reviews the classification and characterization of specific and nonspecific inflammatory disease entities of the feline mouth. Special emphasis is placed on their etiology, pathogenesis, and comparison to related disorders of humans.

Diseases of Quail

An increasing number and variety of quail are being kept for food production, experimental use, release on hunting preserves, preservation of endangered species, zoological display, and as companion birds. Quail are susceptible to a variety of noninfectious, infectious, and parasitic diseases. Because they are related to chickens and turkeys, many of the diseases in quail are similar to those in poultry. In this article, the diagnostic characteristics of diseases affecting quail are presented along with information on their prevention, control, and treatment.

Non-linear Dynamics of Two-Patch Model Incorporating Secondary Dengue Infection

In this paper, the impact of human migration on the dynamics of dengue epidemic has been discussed. The vector-host model considers two patches with different dengue serotype in each patch. The model considers the constant rate of migration in susceptible and recovered class from one patch to other. Recovered migrants from prior infection are exposed to secondary infection in the patch where different serotype is present. The basic reproduction number is computed and analyzed in terms of migration parameters. The model is analyzed for the existence and local stability of various equilibrium states in terms of migration parameters. The numerical simulations for the choice of relevant data from literature have been performed to verify analytical results and to further explore the dynamics of the system. The sensitivity analysis of basic reproduction number with respect to migration parameters is carried out. It is found that immigration in a patch increases the basic reproduction in respective patch and vice-versa. The basic reproduction number has been estimated for the two states of Brazil which verifies the occurrence of severe epidemic in one of the states of Brazil.

Dynamics of an [Formula: see text] Epidemic Model with Vaccination and Saturated Incidence Rate

Measles and influenza are two major diseases–caused an epidemic in India. Therefore, in this paper, a [Formula: see text] epidemic mathematical model for measles and influenza is proposed and analyzed, where pre and post vaccinations are considered as control strategies with waning natural, vaccine-induced immunity and saturation incidence rate. The dissection of the proposed model is conferred in terms of the associated reproduction number [Formula: see text] , which is determined by the next-generation approach and obtained that if [Formula: see text] , the disease-free equilibrium exists and it is locally as well as globally asymptotically stable. Further for [Formula: see text] , a unique endemic equilibrium exists and it is also locally as well as globally asymptotically stable under certain conditions, which shows the prevalence and persistence of the disease in the population.

BALKAN (ENDEMIC) NEPHROPATHY AND A TOXIN-PRODUCING STRAIN OF PENICILLIUM VERRUCOSUM VAR CYCLOPIUM: AN EXPERIMENTAL MODEL IN RATS

Cultures of an isolate of Penicillium verrucosum var. cyclopium, obtained from stored maize in an area of Balkan (endemic) nephropathy—Vratza, Bulgaria—has consistently induced renal tubular lesions when force-fed to rats for 20 days. The lesions, confined to the lower reaches of the proximal convoluted tubules (pars recta and junctional zone), closely resemble the tubular changes in patients with Balkan nephropathy. Preliminary evidence suggests that this nephrotoxin-producing strain of P. verrucosum var. cyclopium may be implicated in the ætiology of Balkan nephropathy.

A bacterial pathogenicity determinant associated with necrotizing enterocolitis()

Predominant enterobacteria from infants with necrotizing enterocolitis (NEC) were examined for an unusual ability to ferment lactose. One such isolate, a Klebsiella pneumoniae strain, was partially induced for lactose operon expression in tryptone containing media, and was also pathogenic in a rabbit ileal loop model for NEC. A spontaneous segregant of this strain was no longer partially induced for lactose operon expression, and was no longer pathogenic in the rabbit model. The gene responsible for this phenotype was cloned. The resulting plasmid was shown to cause both partially induced lactose operon expression and pathogenicity when introduced into a laboratory K. pneumoniae strain. A K. pneumoniae mutant deficient in lactose repressor synthesis was also pathogenic in the rabbit model. These results and previous studies on the intraluminal biochemistry of infants with NEC support the hypothesis that an increased ability for lactose fermentation may be a bacterial pathogenic trait with respect to NEC.

Lymphocytic sialadenitis of Sjögren's syndrome associated with chronic hepatitis C virus liver disease

Viral infection has often been suggested as a possible cause of Sjögren's syndrome or chronic lymphocytic sialadenitis, and Epstein-Barr virus has been found in the salivary glands of patients with this condition. After we had noted Sjögren's syndrome in several patients infected with hepatitis C virus (HCV), a virus also excreted in saliva, we set up a prospective study to investigate the association of chronic lymphocytic sialadenitis, with or without symptoms, to chronic HCV liver disease. The histological appearances of labial salivary glands in patients with proven HCV hepatitis or cirrhosis were compared with those in dead controls. Histological changes characteristic of Sjögren's syndrome were significantly more common in HCV-infected patients (16 of 28, 57%) compared with controls (1 of 20, 5%). Focal lymphocytic sialadenitis characteristic of Sjögren's syndrome (though only 10 patients had xerostomia and none complained of xerophthalmia) appears to be common in patients with chronic HCV liver disease; if this association is confirmed, identification of the underlying mechanism may improve our understanding of both disorders.

1 Viruses, virulence and pathogenicity

Pathogenicity is a complex process with stringent requirements of both the host cell and the infecting virion. Among these requirements are a port of entry into host cells, a means of replication for the virus, and a means by which infection damages host cells. Damage to the host can result from multiple mechanisms including transformation, suppression of cellular metabolism, apoptosis, autoimmune responses directed against infected or uninfected tissues, or by molecular mimicry. In the attempt to identify new associations between viral infection and disease, investigators should be mindful that variable host factors as well as viral infection may be required for pathogenesis. Efforts to associate specific viral infections with specific diseases may be obscured by final common pathways through which multiple agents damage host cells in similar ways.

Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens

Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate > 30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis (P < 0.05). The current data provide relevant information about pathogen distribution and antimicrobial resistance of major pathogens of CAP as well as clinical outcomes of illness in Asian countries.

The Immunology of the Bovine Respiratory Disease Complex

The bovine respiratory disease complex continues to be an economically important syndrome in an era when immunologic control is likely to become increasingly important. Recent studies have yielded a better understanding of the interaction, at the molecular level, of various pathogens with the bovine immune system. Improved challenge models for important viral pathogens such as bovine viral diarrhea virus and bovine respiratory syncytial virus have provided evidence of the efficacy of immune responses stimulated by vaccination. This article highlights recent advances in understanding of the role of the immune response in the pathogenesis and prophylaxis of bovine respiratory disease complex.

A novel apparatus for non-contact measurement of heart rate variability: a system to prevent secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, in monitoring sepsis or in predicting multiple organ dysfunction syndrome

BACKGROUND. The impaired balance of the low-frequency/high-frequency ratio obtained from spectral components of RR intervals can be a diagnostic test for sepsis. In addition, it is known that a reduction of heart rate variability (HRV) is useful in identifying septic patients at risk of the development of multiple organ dysfunction syndrome (MODS). We have reported a non-contact method using a microwave radar to monitor the heart and respiratory rates of a healthy person placed inside an isolator or of experimental animals exposed to toxic materials. APPARATUS DESIGN AND TESTING. With the purpose of preventing secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, we designed a novel apparatus for non-contact measurement of HRV using a 1215 MHz microwave radar, a high-pass filter, and a personal computer. The microwave radar monitors only the small reflected waves from the subject's chest wall, which are modulated by the cardiac and respiratory motion. The high-pass filter enhances the cardiac signal and attenuates the respiratory signal. In a human trial, RR intervals derived from the non-contact apparatus significantly correlated with those derived from ECG (r=0.98, P<0.0001). The non-contact apparatus showed a similar power spectrum of RR intervals to that of ECG. CONCLUSIONS. Our non-contact HRV measurement apparatus appears promising for future pre-hospital monitoring of septic patients or for predicting MODS patients, inside isolators or in the field for mass casualties under biochemical hazard circumstances.

MULTISITE INTRADERMAL ANTIRABIES VACCINATION: Immune Responses in Man and Protection of Rabbits Against Death from Street Virus by Postexposure Administration of Human Diploid-Cell-Strain Rabies Vaccine

Lymphocyte transformation, production of neutralising antibody, and the development of antirabies IgG antibody were studied in ten healthy volunteers in response to 0·8 ml of human diploid-cell strain (HDCS) rabies vaccine administered on one occasion in divided doses in 8 intradermal (i.d.) sites. All ten volunteers rapidly developed substantial titres of rabies antibody, and eight of the ten had T lymphocytes that were immunologically stimulated by HDCS rabies-virus antigen. Postexposure treatment with 0·8 ml of HDCS vaccine given at 4 i.d. sites completely protected fourteen rabbits from death by street virus. The results suggest that in developing countries patients could be protected with small volumes of potent tissue-culture vaccine administered intradermally shortly after exposure.

Treatment of Diarrhea of Neonatal Calves

Enterotoxigenic Escherichia coli, Salmonella spp, and Giardia duodena are causes of diarrhea of neonatal calves that may be treated by specific antimicrobial or antiprotozoal therapy. Treatment to correct physiologic abnormalities resulting from diarrhea is most successful because the causative agent does not have to be identified prior to treatment. Some agents, such as orally administered antimicrobials, kaolin-pectin, and parasympatholytic drugs, have detrimental effects that make them inappropriate for treatment of diarrheic calves.

A knowledge base for predicting protein localization sites in eukaryotic cells

To automate examination of massive amounts of sequence data for biological function, it is important to computerize interpretation based on empirical knowledge of sequence-function relationships. For this purpose, we have been constructing a knowledge base by organizing various experimental and computational observations as a collection of if—then rules. Here we report an expert system, which utilizes this knowledge base, for predicting localization sites of proteins only from the information on the amino acid sequence and the source origin. We collected data for 401 eukaryotic proteins with known localization sites (subcellular and extracellular) and divided them into training data and testing data. Fourteen localization sites were distinguished for animal cells and 17 for plant cells. When sorting signals were not well characterized experimentally, various sequence features were computationally derived from the training data. It was found that 66% of the training data and 59% of the testing data were correctly predicted by our expert system. This artificial intelligence approach is powerful and flexible enough to be used in genome analyses.

Examples of expression systems based on animal RNA viruses: Alphaviruses and influenza virus

Successful recovery of RNA viruses and functional RNA replicons from cDNA has greatly facilitated molecular genetic analyses of viral proteins and cis-regulatory elements. This technology allows the use of RNA virus replication machinery to express heterologous sequences. Both positive-strand and negative-strand animal RNA viruses have been engineered to produce chimeric viruses expressing protective epitopes from other pathogens and for transient expression of heterologous sequences.

Mouse hepatitis virus A59-induced demyelination can occur in the absence of CD8(+) T cells

Mouse hepatitis virus causes a chronic demyelinating disease in C57BL/6 mice. While early studies suggested demyelination is due to direct cytolytic effects of virus on oligodendrocytes, there is increasing evidence for the involvement of the immune system in the mechanism of demyelination. In this study we have asked whether demyelination can occur in the absence of functional MHC class I expression and CD8(+) T cells. We infected transgenic mice lacking expression of β(2) microglobulin (β(2)M(−/−) mice) with MHV-A59. In β(2)M(−/−) mice, virus was much more lethal than in either of the parental strains used to produce the mice; furthermore, while clearance from the CNS did occur in β(2)M(−/−) mice, it was slower than in C57BL/6 mice. This is consistent with the importance of CD8(+) cells in viral clearance. Because of the increased sensitivity of the β(2)M(−/−) mice to infection, only low levels of virus could be used to evaluate chronic disease. Even at these low levels, demyelination did occur in some animals. To compare infection in β(2)M(−/−) and C57BL/6 mice we used a higher dose of an attenuated variant of MHV-A59, C12. The attenuated variant induced less demyelination in C57BL/6 mice compared to wild type A59, but the levels observed were not significantly different from those seen in β(2)M(−/−) mice. Thus, MHV-induced demyelination can occur in some animals in the absence of MHC class I and CD8(+) cells.

Activation of autoreactive T cells by peptides from human pathogens

Activation of autoreactive T cells is a necessary — but not sufficient — step in the development of T cell mediated autoimmunity. Autoreactive T cells can be activated by viral and bacterial peptides that meet the structural requirements for MHC molecule binding and T cell receptor recognition. Due to the degenerate nature of MHC class II molecule binding motifs and a certain degree of flexibility in T cell receptor recognition, such microbial peptides have been found to be quite distinct in their primary sequence from the self-peptide they mimic.

Within-and between-strain variability in longevity of inbred and outbred rats under the same environmental conditions

The analysis of 26 longevity curves of different populations of inbred (Fischer 344) and outbred (Sprague-Dawley) rats highlighted a remarkable between-populations variability in survival parameters. This variability is independent of the breeding characteristics of the strain. The two strains differed in the slope of the survival curves, with Fischer 344 rats showing a higher survival over the second year of life as well as a lower interindividual variability. A model-free approach based on principal component analysis allowed us to quantify these differences and to highlight some limitations of the classical Gompertzian approach.

Differentiation of Gastrointestinal Diseases of Calves

Bovine practitioners are commonly faced with gastrointestinal problems in calves. Being able to diagnose gastrointestinal problems properly is pivotal in developing proper preventive and treatment strategies. This article discusses the common gastrointestinal diseases, including diarrhea of calves, with the focus on antemortem diagnosis and differentiation of these diseases.

3 Pathogenesis of feline panleukopenia virus and canine parvovirus

Feline panleukopenia virus (FPV) and canine parvovirus (CPV) are autonomous parvoviruses which infect cats or dogs, respectively. Both viruses cause an acute disease, with virus replicating for less than seven days before being cleared by the developing immune responses. The viruses have a broad tropism for mitotically active cells. In neonatal animals the viruses replicate in a large number of tissues, and FPV infection of the germinal epithelium of the cerebellum leads to cerebellar hypoplasia, while CPV may infect the hearts of neonatal pups, causing myocarditis. In older animals the virus replicates systemically, primarily in the primary and secondary lymphoid tissues, and also in the rapidly replicating cells of the small intestinal epithelial crypts. A transient panleukopenia or relative lymphopenia is often observed after FPV or CPV infection, respectively. Whether the reduction in cell numbers in vivo is due to virus replicating in and killing cells, or due to other indirect effects, is not known. However, FPV kills both erythroid and myeloid colony progenitors in in vitro bone marow cultures, and it has been suggested that virus replication in the myeloid cells in vivo could lead to the reduced neutrophil levels seen after FPV infection of cats.

INFECTION CONTROL CHALLENGES IN CHILD-CARE CENTERS

Current social and economic factors have resulted in increasing numbers of children attending child-care facilities outside of the home. In the United States over 13 million children less than 5 years of age and 60% of children less than 13 years of age are enrolled in some form of out-of-home child care.85, 108 Children attending out-of-home care settings are at increased risk for a variety of infections.25, 62, 79, 88 The incidence of respiratory tract infections, diarrheal disease, cytomegalovirus, hepatitis A, and bacterial meningitis is higher in children cared for outside of the home.54, 88 Increased rates of infections result in increased morbidity of children attending child-care facilities and significant economic impact because of loss of work and cost of medical care. These costs have been estimated at 1.8 billion dollars per year in the United States.(47) Parents of children attending child-care facilities miss from 1 to 4 weeks of work per year caring for ill children.(28) Increased risk for infections in child-care settings is of public health significance because of potential transmission to adult contacts and dissemination into the community.(88) Infections acquired in child-care settings that are mild or asymptomatic in children may be severe in adults.(85)

Aging-related morphological changes in the main olfactory bulb of the fischer 344 rat

—Aging-related changes in several structural characteristics of the main olfactory bulb (MOB) were evaluated using Fischer 344 rats 3, 18, 30 or 36 months of age. Histological examination of the nasal mucosa revealed no evidence of concurrent rhinitis in any of the animals studied. The internal granular layer of the MOB exhibited continual growth, increasing in volume by a factor of 63% over the range of ages studied. The sizes of MOB mitral cell perikarya and nuclei, expressed either as observed cross-sectional areas or as estimated mean volumes, did not change significantly as a function of age. The numbers of mitral cells exhibiting 2 nucleoli in the plane of section decreased from about 22% in the youngest animals to about 4% in the 18- and 30-month old animals and to nil in the oldest animals. These results are discussed in relation to findings of other investigators using Sprague-Dawley or Wistar rats. It is concluded that major structural age changes in the rat MOB are strain dependent.

Virus-induced interferon production in leukocyte cultures from children with recurrent respiratory infections. A follow-up study

Background: Lowered yields of virus-induced interferon (IFN) by leukocyte cultures were previously suggested to be associated with recurrent respiratory infections in children (Pitkäranta et al. (1993) Clin. Diagn. Virol. 1, 101–108) Objectives: To investigate if the observed lowered IFN producing capacity was secondary to the underlying disease and, consequently, would be normalized after recovery of the child from the chain of infections. Study design: Forty-eight 3–12-year-old children suffering from recurrent upper respiratory tract infections (acute otitis media included) were followed-up for 2 years. Their clinical condition and virus-induced interferon production in cultures of peripheral blood leukocytes were examined at the beginning and end of this period. Results: In 24 children the health improved strikingly during the follow-up, in 12 children a mild improvement took place, while 12 children remained constantly ill. IFN yields in cultures stimulated with corona- and respiratory syncytical viruses improved along with the clinical situation of the children. Parallel cultures induced with adeno-, influenza A or rhinoviruses did not show a similar correlation. Conclusion: These results suggest that the relationship between interferon production by leukocyte cultures and recurrent infections is complex and may be virus-specific.

Clinical considerations in the diagnosis of viral respiratory infections

Recent advances are allowing the transfer of sensitive and precise rapid viral antigen detection technology from sophisticated research laboratories to standardly equipped clinical diagnostic facilities. It is now possible to identify many viral respiratory pathogens directly from clinical specimens in <1 hr. Rapid antigen detection promises to be of the most value in the identification of respiratory viruses 1) for which antiviral therapy is available, 2) which can be prevented by employing isolation precautions, chemoprophylaxis, and/or immunization. 3) whose presence usually is associated with acute respiratory disease, not just asymptomatic colonization, and 4) which ordinarily are not associated with concomitant bacterial infection, and thus, whose early detection may allow withholding or withdrawing antibiotics. Based on these considerations, the relative usefulness of rapid viral antigen detection of commonly encountered respiratory pathogens will be discussed. In addition, the role of rapid viral detection in diagnosis of respiratory infections in high risk versus otherwise healthy individuals will be explored.

Effects of 3,3′-iminodipropionitrile on acquisition and performance of spatial tasks in rats

3,3′-Iminodipropionitrile (IDPN) has been reported to disrupt learning and memory in rats (24). The present work addressed the effects of IDPN on tasks requiring the use of spatial information. Separate groups of male rats were dosed with IDPN (IP, in 1 ml/kg saline) for 3 consecutive days and tested in the following procedures: (a) step-through passive avoidance conditioning (0, 100, 150, and 200 mg/kg/day); (b) Morris water maze (MWM) acquisition and retention (0, 125, 150, 175, and 200 mg/kg/day); (c) radial arm maze (RAM) acquisition (0, 100, 200, and 400 mg/kg/day); (d) RAM steady-state performance (0, 200, and 400 mg/kg/day); (e) repeated acquisition in the RAM (0, and 200 mg/kg/day). The vestibular toxicity of IDPN resulted in alterations in spontaneous behavior or swimming deficits in 5 of 8 rats treated with 175 mg/kg/day and in all the animals dosed with 200 or 400 mg/kg/day. IDPN increased step-through PA latencies at 200 mg/kg/day but not at lower doses. In the MWM, no performance deficits were observed at the dose levels preserving the swimming ability of the animals. In both the acquisition and the steady-state RAM tasks, IDPN (400 mg/kg/day) induced an increase in both choice errors and perseverative errors. In the RAM repeated acquisition paradigm, IDPN (200 mg/kg/day) induced performance deficits that included a decreased rate of within-session reduction in errors. The present data show that IDPN disrupts performance of tasks requiring spatial learning and memory and indicate that these deficits can be in part caused by an acquisition deficit.

Deficiency in interferon production by leukocytes from children with recurrent respiratory infections

In vitro interferon production by peripheral blood mononuclear cells from 50 children suffering from recurrent upper respiratory tract infections was examined, and compared with that of 50 healthy children. Five respiratory pathogenic viruses and Mycoplasma pneumoniae were used as inducers. Cells from every child responded to at least three out of the six inducers by interferon production. As a group, cultures prepared from patient cells showed decreased production of IFN when stimulated with adeno, rhino, corona or RS viruses or with the mycoplasma. Similar trend between the two groups of children was seen as regards influenza A virus induced IFN production in leukocyte cultures. These results corroborate our previous findings that relative deficiency in interferon production appears to be inducer-specific, and suggest that this phenomenon may have a role in the pathogenesis of recurrent respiratory infections.

Comparison of monoclonal biotin-avidin enzyme immunoassay and monoclonal time-resolved fluoroimmunoassay in detection of respiratory virus antigens

Background: Detection of respiratory viruses by time-resolved fluoroimmunoassay based on monoclonal antibodies were developed in our laboratories in the late 1980s and they have been successfully used in daily diagnosis for more than seven years. Later, similar Biotin-EIAs were developed but the sensitivities were unsatisfactory. Objectives: Further optimization of monoclonal Biotin-EIAs and comparison of the optimized assays with TR-FIAs. Study design: Variations in test format, diluents, incubation times and temperatures, and different monoclonal antibodies were tested, and the final comparisons were made with TR-FIA using stored nasopharyngeal aspirates. Results: The improvements in Biotin-EIA featured four changes which increased sensitivity in the assay: (a) test diluent contained diethylenetriamino-pentaacetic acid; (b) antigen and biotinylated detector antibody were added simultaneously; (c) reaction time was extended from 1 h at 37°C to overnight at 4°C; (d) from the thirteen monoclonal antibodies used in TR-FIA, ten were optimal also in Biotin-EIA, but in the parainfluenza 1 and 2 assays other monoclonals proved more sensitive. Out of 257 originally positive specimens tested in the comparison studies, 192 (74.7%) were again positive and 54 (21.0%) were negative in both assays; nine were negative in TR-FIA but positive in Biotin-EIA, while two specimens were negative in Biotin-EIA but positive in TR-FIA. The overall agreement between the two assays was 95.7%. Conclusions: All monoclonal Biotin-EIAs can be optimized to the same sensitivity as TR-FIAs for the detection of respiratory viruses. Laboratories which have no TR-FIA expertise may use Biotin-EIA in the diagnosis of acute respiratory infections.

Virus-induced autoimmune disease

The braking of tolerance or unresponsiveness to self-antigens, involving the activation of autoreactive lymphocytes, is a critical event leading to autoimmune diseases. The precise mechanisms by which this can occur are mostly unknown. Viruses have been implicated in this process, among other etiological factors, such as genetic predisposition and cytokine activity. Several ways have been proposed by which a viral infection might break tolerance to self and trigger an autoreactive cascade that ultimately leads to the destruction of a specific cell type or an entire organ. The process termed ‘molecular mimicry’ and the use of transgenic models in which viral and host genes can be manipulated to analyze their effects in causing autoimmunity have been particular focuses for research. For example, there is a transgenic murine model of virus-induced autoimmune disease, in which a known viral gene is selectively expressed as a self-antigen in β cells of the pancreas. In these mice, insulin-dependent diabetes develops after either a viral infection, the release of a cytokine such as IFN-γ, or the expression of the costimulatory molecule B7.1 in the islets of Langerhans. Recent studies using this model have contributed to the understanding of the pathogenesis of virus-induced autoimmune disease and have furthered the design and testing of novel immunotherapeutic approaches.

Unidentified viral particles could be associated with enteritis of various commercial bird species

La microscopie électronique nous a permis d'observer, chez des oiseaux domestiques présentant une entérite (pintades, canards, poulets, dindes), des images de particules virales enveloppées et spiculées dont l'aspect est identique d'une espèce aviaire à l'autre et qui n'ont pas été, jusqu'à présent, identifiées.

The pattern of proteins synthesized in the liver is profoundly modified upon infection of susceptible mice with mouse hepatitis virus 3

Susceptible BALB/c mice, after experimental infection with mouse hepatitis virus 3 (MHV3), revealed virus titres in the liver that increased gradually to a peak of 8 × 10(5) PFU/g of tissue after 3 days' infection, when the mice died of acute hepatitis. BALB/c mice were infected with MHV3, subsequently labelled in vivo with (35)S-methionine, and then the liver preparations from both infected and non-infected animals were subjected to two-dimensional gel electrophoresis. Comparisons of the patterns by computer image analysis revealed 17 gene products which increased, and 8 gene products which decreased, upon virus infection in their two-dimensional gel spot intensity. We conclude that during MHV3 infection of a susceptible strain of mice, a major modification in protein synthesis occurs. The pattern alterations were not related to the virus gene products but were mostly endogenous mouse proteins. Whether these proteins are a result of a defence attempt by the animal, or are dictated by the virus in order to prevent a protective response from happening, remains to be shown.

Cytokine network in the central nervous system and its roles in growth and differentiation of glial and neuronal cells

Cells resident within the central nervous system (CNS) can synthesize, secrete and respond to inflammatory cytokines not only contributing to the responses to injury or immunological challenge within the CNS, but also regulating their own growth and differentiation potential. The actions and cell communication via cytokines in the CNS are designated as the CNS cytokine network, in which microglia and astrocytes play the central roles. To further characterize the CNS cytokine network we investigated the differences in roles of these cells, and found that microglia might contribute to the early phase of cytokine production reaction and that astrocytes might contribute the late phase of the reaction. We also investigated roles of inhibitory cytokines such as TGF β, IL-4, and IL-10, and showed that each might play a distinct role in the inhibitory regulation in the CNS. We summarized our previous report about cellular distribution of cytokine receptors in the CNS cells and discussed their roles in the CNS cytokine network. Finally, we investigated that expression of IL-6 and IL-2 receptors in neuronal and oligodendrocytic differentiation, respectively. From these results, we discussed the features of the CNS cytokine network.

ClinMicroNet — Sharing experiences and building knowledge virtually

ClinMicroNet is a closed Internet discussion group, where doctoral-level clinical and public health microbiologists from many countries share their knowledge and experience. This collaborative approach to resolving issues and questions in the field of clinical microbiology transcends organizational, institutional, state and national boundaries. Based upon observations of list communications during 10 weeks and a small group user survey, this study analyzed the nature of communications and member's perceptions of the network. An explicit-tacit knowledge quadrant identifies distinct ways in which knowledge is transferred and created. Empirical evidence shows that ClinMicroNet complements other resources by encouraging members to share experiences and collaborate in establishing the best practices. Driven by a core group of active members, the network is highly participative and strongly supported. In turn, members maintain professional relationships beyond the list, which reinforces the network and its members' capacity to confront new threats and challenges in clinical microbiology.

Analysis of overlapping T- and B-Cell antigenic sites on rubella virus E1 envelope protein influence of HLA-DR4 polymorphism on T-cell clonal recognition

A CTL antigenic site located between residues 273 and 291 of the E1 envelope protein of RV was identified by (51)Cr-release assays employing SPs. Two E1-specific CTL clones were examined for immune recognition of RV wild-type and attenuated vaccine strains and recombinant E1 protein. The exact sequence (273–284) recognized by both clones was delineated by using truncated and overlapping SPs covering these residues. The defined T-cell site overlapped almost completely with a virus neutralizing antibody-binding site previously identified with mouse monoclonal and human antibodies. A series of single aa-substituted SP analogues of E1(273–284) was used to define residues critical for T-cell recognition. Using EBV-Bl displaying different HLA-DR haplotypes and -DR4 subtypes as targets to determine MHC class II restriction elements, immune recognition by both T-cell clones was shown to be associated with HLA-DR4. Three HLA-DR4 subtypes (DR4Dw 13A, DR4Dw13B, and DR4KT2) sharing a common residue, glutamic acid at position 74 in their β 1 chains, were able to present SP E1(273–284) to the T-cell clones.

Occupational Health Update: Focus on Preventing the Acquisition of Infections with Pre-exposure Prophylaxis and Postexposure Prophylaxis

Health care personnel are commonly exposed to infectious agents via sharp injuries (eg, human immunodeficiency virus, hepatitis B virus, and hepatitis C virus), direct patient care (eg, pertussis and meningococcus), and the contaminated environment (eg, Clostridium difficile). An effective occupational program is a key aspect of preventing acquisition of an infection by offering the following: (1) education of health care personnel regarding proper handling of sharps, early identification and isolation of potentially infectious patients, and hand hygiene; (2) assuring immunity to vaccine-preventable diseases; and, (3) immediate availability of a medical evaluation after a nonprotected exposure to an infectious disease.

Differentiation of Gastrointestinal Diseases in Adult Cattle

An understanding of diagnostic tests and procedures for gastrointestinal diseases of adult cattle assists the practitioner in differentiating the more common gastrointestinal disturbances. A systematic approach to differentiating these conditions is used, targeting abdominal distention, anterior abdominal pain, and diarrhea.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

OBJECTIVE: To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. METHODS: Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. RESULTS: ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. CONCLUSIONS: GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

Fluid Therapy for Diarrheic Calves: What, How, and How Much

The pathophysiologic consequences of neonatal diarrhea in calves are presented. A brief discussion of intestinal nmction, nutrient absorption, and osmolar effects follows. A rationale for appropriate fluid therapy is presented, and comparisons of some currently marketed products are made.

Molecular Biology of Bovine Viral Diarrhea Virus and its Interactions with the Host

The contributions of pestivirus molecular biology research to our understanding of Bovine Viral Diarrhea Virus (BVDV) biology and disease have been remarkable. Completion of nucleotide sequence information for genomes of NCP and CP-BVDV isolates was an important milestone. Subsequent work on the protein map of BVDV and polyprotein processing pathways paved the way for the interpretation of many other virologic and immunologic studies. Discovery of a correlation between genotype II and virulence (hemorrhagic syndrome) will help to clarify previously controversial data and to improve disease control. Description of multiple pathways of p80 expression in CP-BVDV offered insight into the pathogenesis of mucosal disease. Identification of gp53/E2 as the target of neutralizing antibodies and source of antigenic hypervariability helped us to understand immunity to BVDV. Collectively, the advances described contribute to the implementation of improved diagnostic and control strategies to reduce losses inflicted by the bovine pestivirus.

In vivo and in vitro models of demyelinating diseases XXIV. The infectious process in cyclosporin A treated Wistar Lewis rats inoculated with JHM virus()

In the present study we investigated age related effects of inoculum size and cellular immunity on the CNS disease caused by JHM virus (JHMV) in Wistar Lewis (WL) rats. Onset of resistance normally becomes evident by the 10th day when inoculation is made with 10(6) pfu or less. The resistance could be abrogated in 15 day old animals by increasing the dose two-fold, but with rare exceptions, in 35 day old rats an 80-fold increase in pfu fails to surmount resistance. However, treatment with the immunosuppressant drug cyclosporin A (CsA) abolished resistance, whereby rats challenged at 35 days of age were susceptible to JHMV. The histopathological evidence and disease symptoms in the CsA treated group resembled closely those observed in our previous study with athymic, nude rats. Microscopic examination of the CNS from untreated, infected rats revealed extensive inflammatory responses characterized by perivascular cuffing and mononuclear infiltrates into the neuropile. The parallel CsA treated group showed that inflammatory responses of this type in the CNS were either minimal or absent. From the present evidence, we conclude that JHMV infection, which involves both neuronal and oligodendrocytic elements, is kept in check by the cellular immune system. When cellular immunity is suppressed or absent the disease process is altered from one in which white matter demyelination predominates to another form of disease in which neuronal involvement is prominent.

Necessity of a more standardized virological characterization of rodents for aging studies

Characterization of the microbiological status is an important facet of a quality assurance program for laboratory animals. This paper addresses basic issues with regard to standardization of the characterization of murine viral status. Methods for such characterization include clinical signs, virus isolation, and serological tests. Significant considerations are screening profiles; sample collection, processing, and s shipment; and sampling schedules. International standardization of programs and methods to control and characterize the microbiological status of laboratory animals is being developed, and will be highly significant in future efforts to produce, control, and maintain laboratory animals free of viral infections.

ROTAVIRUS INFECTIONS OF NEONATES

Fæcal specimens from 628 newborn babies in the nurseries of six metropolitan hospitals were examined by electron microscopy for rotaviruses. 304 babies (49%) were found to be excreting virus. All those infected were in five nurseries; viruses were not detected in specimens from the sixth nursery. Two nurseries were studied for 9 mo and another for 11 mo and rotaviruses were found consistently in 40-50% of stools examined. There was no seasonal variation. None of the neonates under the age of one day were infected but by the age of three to four days approximately 50% were excreting virus. Most of those shedding virus were symptom-free but 84 (28%) had diarrhœa. Persisting endemic rotavirus infection is apparently common in hospital nurseries in Sydney. The virus is probably transmitted by environmental spread from neonate to neonate.

AIDS, alcohol, endothelium, and immunity

Analogies are drawn between important unknowns in AIDS and alcohol research, related to underlying common pathogenetic mechanisms, immunodysregulation, cofactors, and prominent vascular manifestations. The central role of the blood and lymphatic vasculatures and specifically their endothelial lining in many facets of the immune response is reviewed. Evidence is presented that both alcohol and HIV (as well as other coinfecting viruses in AIDS) target and alter endothelial cells and the angiogenic process. These concepts are further illustrated by a serendipitous viral epidemic among rats on continuous long-term alcoholic and control nonalcoholic diets, where synergism between alcohol and virus appeared to underlie multiple vascular proliferative lesions in the liver. In AIDS and alcoholism/alcoholic liver disease (ALD), the prominent features of dysregulated angiogenesis point to the endothelium as a key player in pathogenesis of these seemingly disparate disorders and potentially in immunomodulation.

Quantifying the roles of vomiting, diarrhea, and residents vs. staff in norovirus transmission in U.S. nursing home outbreaks

The role of individual case characteristics, such as symptoms or demographics, in norovirus transmissibility is poorly understood. Six nursing home norovirus outbreaks occurring in South Carolina, U.S. from 2014 to 2016 were examined. We aimed to quantify the contribution of symptoms and other case characteristics in norovirus transmission using the reproduction number (R(Ei)) as an estimate of individual case infectivity and to examine how transmission changes over the course of an outbreak. Individual estimates of R(Ei) were calculated using a maximum likelihood procedure to infer the average number of secondary cases generated by each case. The associations between case characteristics and R(Ei) were estimated using a weighted multivariate mixed linear model. Outbreaks began with one to three index case(s) with large estimated R(Ei)’s (range: 1.48 to 8.70) relative to subsequent cases. Of the 209 cases, 155 (75%) vomited, 164 (79%) had diarrhea, and 158 (76%) were nursing home residents (vs. staff). Cases who vomited infected 2.12 (95% CI: 1.68, 2.68) times the number of individuals as non-vomiters, cases with diarrhea infected 1.39 (95% CI: 1.03, 1.87) times the number of individuals as cases without diarrhea, and resident-cases infected 1.53 (95% CI: 1.15, 2.02) times the number of individuals as staff-cases. Index cases tended to be residents (vs. staff) who vomited and infected considerably more secondary cases compared to non-index cases. Results suggest that individuals, particularly residents, who vomit are more infectious and tend to drive norovirus transmission in U.S. nursing home norovirus outbreaks. While diarrhea also plays a role in norovirus transmission, it is to a lesser degree than vomiting in these settings. Results lend support for prevention and control measures that focus on cases who vomit, particularly if those cases are residents.

Packaging and unpackaging the sea urchin sperm genome

Two species of histones in sea urchin sperm (Sp H1 and Sp H2B) are chimeric molecules whose highly basic amino-terminal domains are dephosphorylated at the last stage of sperm cell differentiation, and rephosphorylated immediately following fertilization. The phosphorylated regions consist largely of repeating tetrapeptides with two basic residues flanking Ser-Pro residues (‘SPKK’ motifs) and are predicted to have β-turn secondary structures. Alteration of the charge and structure of the SPKK sites may play a role in the unusually dense DNA packaging of the mature sperm chromatin. The motif resembles the target site of cell-cycle-associated cdc2 kinases and is found in several other proteins whose nucleic acid affinities may be altered during the cell cycle.

Bovine Enteric Colibacillosis

In this article, the author discusses procedures used to determine enteropathogenic strains of Escherichia coli, the history of the development of prophylactic procedures, including cow vaccination and specific monoclonal antibody, and other preventative measures such as proper management, nutrition, and sanitation.

Biological response modifiers and infectious diseases: Actual and potential therapeutic agents

Biological response modifiers (BRMs) are agents which can modify the immune response to cancer or invasion of the organism by infectious agents. An explosive appearance of new BRMs has resulted from the development of recombinant gene technology and the availability of monoclonal antibodies. Colony-stimulating factors first became available for the prevention of neutropenia but may also have a role in the treatment of infections. Interleukin-1 is being tested as a modular of hematopoiesis and may be useful as a helper factor for T- and B-cell function. Immunoglobulins are being used against viral and bacterial infections while interferons can prevent viral upper respiratory infections and suppress or irradicate some viral hepatitides. Other BRMs which show promise include chemical agents and traditional herbal medicines.

Increased susceptibility to mouse hepatitis virus type 3 (MHV3) infection induced by a hypercholesterolaemic diet with increased adsorption of MHV3 to primary hepatocyte cultures

The administration of a hypercholesterolaemic (HC) diet rendered genetically resistant A/J mice susceptible to mouse hepatitis 3 (MHV3) infection. The animals died cf acute hepatitis with high viral titres in the liver accompanied by many necrotic foci and high serum transaminase levels. Resistance to virus was re-established by refeeding HC mice with a normal diet for 2 weeks. This of modification by pathogenesis was accompanied by an increase in the susceptibility of hepatocyte cultures from HC mice to MHV3 and could be explained by an enhancement in virus adsorption. We hypothesize that the incorporation of cholesterol into the plasma membranes of hepatocytes of HC mice, thereby decreasing the membrane fluidity, may lead to an increase in the availability of virus receptors.

Acute bronchitis in the community: clinical features,infective factors, changes in pulmonary function and bronchial reactivity to histamine

A descriptive study of acute bronchitis in patients without pre-existing pulmonary disease was undertaken in the community during the winter months of 1986–87. Forty-two episodes were investigated in 40 individuals. The cardinal symptom was the acute onset of cough (100%), usually productive (90%). Wheezing was noted by 62% of patients, but heard on ausculation in only 31%. A potential pathogen was isolated in 29% of cases with a virus (eight cases) being identified more frequently than either Mycoplasma pneumoniae (three cases) or a bacterium (three cases). The acute illness was associated with significant reductions in forced expired volume in 1 second (P<0·02) and peak expiratory flow (P<0·001) but not forced vital capacity compared to 6 weeks later. Ten of the 27 (37%) patients who had a histamine challenge test performed at 6 weeks had a PD(20) of <7·8 μmol histamine. Thirty-nine episodes (93%) were treated with antibiotics by the general practitioner, the clinical course being unremarkable apart from one patient who developed a lingular pneumonia despite antibiotic therapy. Further studies are required to assess whether acute bronchitis causes an acute increase in bronchial hyperresponsiveness and whether either antibiotics or inhaled bronchodilators or anti-inflammatory therapy has a useful role in the management of this predominantly viral illness.