Interaction of Mycoplasma hyopneumoniae and Pasteurella multocida infections in swine

To investigate the interaction between Mycoplasma hyopneumoniae and Pasteurella multocida infection, 32 pigs were randomly assigned by litter, sex, and weight to 4 treatment groups. Group-1 pigs were inoculated with M hyopneumoniae and allowed to recover from M hyopneumoniae infection. Group-2 pigs were vaccinated against M hyopneumoniae and then inoculated with M hyopneumoniae. Group-3 pigs were inoculated with M hyopneumoniae and developed clinical signs of mycoplasmosis. Group-4 pigs had never been exposed to M hyopneumoniae. All pigs were initially seronegative for M hyopneumoniae. All pigs were subsequently inoculated with P multocida and euthanatized 2 weeks later. Pasteurella multocida was isolated only from the lungs of group-3 pigs, and these pigs had a significantly higher median percentage of lung surface area affected by pneumonia than did pigs in the other groups. For group-3 pigs, percentage of lung surface area affected by pneumonia was positively correlated with the number of P multocida colonies isolated. We concluded that P multocida is not a primary respiratory pathogen in pigs, but that M hyopneumoniae infection can render the lungs susceptible to P multocida colonization and infection. Pigs recovered from or vaccinated against infection with M hyopneumoniae were resistant to P multocida infection.     

Effects of the carcinogen, acrylonitrile, on forestomach cell proliferation and apoptosis in the rat: comparison with methacrylonitrile

Acrylonitrile (AN) and methacrylonitrile (MAN) are two major industrial nitriles used in the production of plastics and acrylic fibers. Whereas AN is a potent acute toxin and carcinogenic in rats, little is known regarding MAN. Current work is part of an overall effort designed to assess the potential toxicity/carcinogenicity of MAN. The present study compares the ability of the two chemicals to induce epithelial proliferation and apoptosis in the forestomach (FS; a target of AN carcinogenicity), liver and glandular stomach (non-targets of AN carcinogenicity) of male F344 rats. AN was administered to rats daily, by gavage, for 6 weeks, at 0.43 and 0.22 mmol/kg. MAN was administered at 0.87 and 0.43 mmol/kg. Both AN and MAN induced a dose-dependent increase in epithelial cell proliferation in the FS of male F344 rats as determined by bromodeoxyuridine (BrdU) incorporation into DNA. In contrast, AN, but not MAN caused a dose-dependent increase in the thickness of the forestomach squamous mucosa. This increased thickness (hyperplasia) was reflected by an increase in the number of total epithelial cells per unit length of mucosa. At doses of AN and MAN which induced a 2.3-fold increase in BrdU incorporation, apoptosis was 5- and 18-fold greater than controls, respectively. Although both MAN and AN caused a similar increase in cell proliferation, the relatively more prominent increase in the apoptotic index of the squamous epithelium of rats exposed to MAN may explain the lack of a detectable increase in the thickness of the mucosa compared to that seen with AN. The disruption of the balance between FS mucosal cell proliferation and apoptosis in favor of a net increase in the number of FS epithelial cells per unit length may contribute to the carcinogenicity of AN. In conclusion, present work demonstrated that AN selectively induced a net enhancement in FS cell proliferation, a site of its carcinogenicity. On the other hand, MAN-induced FS cell proliferation was associated with a parallel increase in apoptosis. The relatively greater increase in apoptosis by MAN may have compensated for the increase in FS mucosal cell proliferation and the lack of observable change in the FS thickness.     

Immunologic events during the incubation period of hepatitis C virus infection: the role of antibodies to E2 glycoprotein. Multicentre Hemodialysis Cohort Study on Viral Hepatitis

BACKGROUND: The study of the sensitivity of screening assays is greatly facilitated by testing the sequential changes in seroconverting individuals. The aim of this study was to investigate the early immunologic response after hepatitis C virus (HCV) infection and to evaluate whether HCV envelope (E2) recombinant antigen would provide a significant increase in sensitivity for detection of anti-HCV. STUDY DESIGN AND METHODS: Twenty hemodialysis patients who were seroconverting to anti-HCV were included in this study. They were followed up for a mean period (+/- SD) of 10.5 +/- 3.3 months, in which 13 to 46 serum samples per case were collected. Each sample was tested for anti-HCV by second- and third-generation enzyme immunoassay (EIA-2 and EIA-3) and recombinant immunoblot assay (RIBA-3). E2 antibodies were tested by a prototype EIA in which E2 was expressed as a recombinant antigen in Chinese hamster ovary cells. RESULTS: Alanine aminotransferase elevation was observed in 18 of 20 cases. Reactivity against c100, c33c, c22, NS5, and E2 was detected in 15 (75%), 19 (95%), 15 (75%), 2 (10%), and 17 (85%) patients, respectively; c33c was the most immunogenic antigen, followed in descending order by E2, c22, c100, and NS5. E2 antibody reactivity resolved the two RIBA-3-indeterminate cases. However, there was no case in which E2 reactivity preceded all other HCV antigens. Anti-E2 was found to react in all patients of genotypes 1a, 1b, and 3a but in only 2 of 4 patients of genotype 4a. CONCLUSION: In this group of seroconverting individuals, E2 antigen was shown to be highly immunoreactive and did resolve some RIBA-3-indeterminate samples as being positive, on the basis of reactivity to multiple antigens, but it did not improve early detection of seroconversion.     

HIV infection and HIV-1 clades among pregnant women in Harare, Zimbabwe

Official figures indicate that at least 1 million of Zimbabwe's 11 million population are infected with HIV, while the most recent survey results indicate that about 24% of apparently healthy women in the country are HIV seropositive. 60 (29.1%) of 206 pregnant women attending Edith Opperman and Budiriro clinics in Harare who were screened for infection with HIV were found to be HIV-1 seropositive. 66.6% of the HIV-1-infected women were infected with subtype C, 48.3% with subtype A, and 33.3% with subtype B. 45% of the infected were infected with subtypes A and C, 10% with A and D, 30% with B and C, and 6.6% with subtypes A, B, C, and D. 2 samples (3.3%) were nonreactive. The high prevalence rate of HIV-1 infection in this study population points to the urgent need to implement more aggressive approaches to controlling HIV/AIDS among women in Zimbabwe.     

Ornithine decarboxylase and polyamines in familial adenomatous polyposis

The effects of concanavalin A (Con A) on liver cytokine gene expression was studied in mice. The CD4 mRNA expression in normal liver suggests the presence of CD4+ T cells. The administration of Con A induced interleukin (IL)-1beta, IL-2 and IL-2 receptor mRNAs, which implies lymphocyte activation in the liver. Interferon-gamma and tumor necrosis factor-alpha mRNA expressions were increased gradually. The present results showed that Con A induced liver cytokine genes. This cytokine gene induction might have been the result of lymphocyte activation in the liver.     

The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials

BACKGROUND: In two double-blind trials conducted in North America, 513 patients with chronic schizophrenia received risperidone, haloperidol, or placebo. In the present study, combined data from the two trials were analyzed. METHOD: Patients were randomly assigned to receive placebo, fixed doses of risperidone (2, 6, 10, and 16 mg/day) or 20 mg/day of haloperidol for 8 weeks. Factor analysis of scores on the Positive and Negative Syndrome Scale (PANSS) produced five dimensions (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression), similar to the five dimensions of previous factor-analytic studies of PANSS data. RESULTS: Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncontrolled hostility/excitement, and anxiety/depression. Even at the lowest dose, 2 mg/day, risperidone was significantly (p < or = .05) superior to haloperidol in reducing negative symptoms. The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms. CONCLUSION: Risperidone produced significantly (p < or = .05) greater improvements than haloperidol on all five dimensions. The large between-group differences on negative symptoms, hostility/excitement, and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents.     

alpha IIb beta 3 redistribution triggered by receptor cross-linking

Fibrinogen binding to alpha IIb beta 3 on adherent, spread platelets triggers active, cytoskeletally-directed redistribution of fibrinogen/alpha IIb beta 3 complexes on the platelet surface. Gold-conjugated fibrinogen, unlabeled, soluble fibrinogen, and individual fibrinogen molecules have been demonstrated to trigger receptor redistribution. Here we examine the respective roles of receptor cross-linking and ligand occupancy of receptors in initiating this movement. Monovalent, alpha IIb beta 3-binding fibrinogen fragments RGDS and HHLGGAKQAGDV did not trigger receptor redistribution, suggesting that ligand binding to a single receptor is an insufficient stimulus. Binding of monoclonal antibodies 10E5, AP2, and AP3 to the receptor did not trigger receptor movement. However, cross-linking these receptor-bound monoclonal antibodies by polyclonal anti-mouse IgG or by conjugation of the anti-receptor antibody to large colloidal gold particles triggered receptor redistribution identical in rate, pattern, and final distribution to that previously seen with fibrinogen binding. We conclude that receptor cross-linking provides the signal for initiation of fibrinogen/alpha IIb beta 3 complex redistribution on platelet surfaces.     

In-house board-certified surgeons improve outcome for severely injured patients: a comparison of two university centers

The benefit derived from in-house board-certified attending surgeons (IHBCS) staffing trauma centers has recently been questioned. We compared the outcomes and provider-related complications of patients with severe injuries who were treated at two university trauma centers, one with IHBCS, and one with PGY-4 or PGY-5 residents in house (RIH). The RIH center had a significantly longer resuscitation time (160 vs. 58.8 minutes; p < 0.01). Except in cases of vascular injury, the odds ratio of dying at the RIH institution was significantly greater in all groups when the variables of transport time, Revised Trauma Score, and ISS were controlled. Errors in judgment were significantly more likely to have been made at the RIH institution in all groups. It is concluded that the management and ultimate outcome are significantly improved when IHBCS are involved with the resuscitation and early care of specific cohorts of severely injured patients.     

Autopsy. A crucial component of human clinical investigation

OBJECTIVE: To determine the proper role of human clinical investigation, including autopsy, in public health research policy. DATA SOURCES: Medical reports and reviews, and literature concerning the philosophy of medicine. CONCLUSIONS: Autopsy has always been a cornerstone of medical research. Although many pathologists appreciate the research value of autopsies, many other physicians do not. Declining federal support for human clinical research in general, and autopsy in particular, party reflects the popular view that laboratory experimentation-especially that performed on nonhuman animals-can reliably model human conditions. Human clinical research is often difficult, expensive, and time-consuming, but there seems to be no adequate substitute for studies of naturally occurring human conditions. Such studies address many critical medical questions. Autopsy remains an invaluable complement to evolving molecular biology techniques.