Rheumatic fever and chronic rheumatic heart disease in Yarrabah aboriginal community, north Queensland.
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Humans↗
Biomedical subjects
S O'Rourke
Publications and source records attributed to S O'Rourke.
Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens.
CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 +/- 132/mm3) and AIDS patients (253 +/- 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 +/- 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cells numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects.
ADP-ribosyl Cyclase↗
A prospective randomized trial comparing manual and automated endoscope disinfection methods.
OBJECTIVE: To compare the efficacy of endoscope disinfection using automated and manual systems. DESIGN: Prospective randomized trial. SETTING: A 1,000-bed tertiary care referral center. METHODS: All endoscopes underwent a three-stage decontamination process including brushing and cleaning with water and detergent, manual or automated disinfection with 2% glutaraldehyde, and 70% alcohol rinse with forced air drying. Cultures were obtained from endoscopes from both groups before and after alcohol rinse and then after overnight storage. RESULTS: Cultures from 8/30 (27%) automated and 11/30 (37%) manually disinfected (P = 0.58) endoscopes grew gram-negative bacteria and/or nontuberculous mycobacteria before the alcohol rinse. After alcohol rinse, 3 (10%) of 30 automated and 8 (27%) of 30 manually disinfected endoscopes remained contaminated (P = 0.28). Manually disinfected endoscopes were contaminated more frequently with coliform bacteria, whereas endoscopes undergoing automated disinfection were more frequently contaminated with nontuberculous mycobacteria, but the differences were not statistically significant. After alcohol rinse and forced air drying, there was no difference in contamination rates between freshly disinfected endoscopes and those stored overnight (7/30 (23%) versus 4/30 (13%), P = 0.50). Colonoscopes and duodenoscopes were contaminated more often than gastroscopes (P = 0.00001). CONCLUSION: The persistent endoscope contamination after manual and automated disinfection indicates the importance of developing more reliable and effective disinfection methods.
Automation↗
Activation and differentiation antigens on T cells of healthy, at-risk, and HIV-infected children.
We examined the T-lymphocyte phenotypes of 67 human immunodeficiency virus (HIV)-infected children (P-1 or P-2) and 65 age-matched, healthy, control children stratified into four groups from < 1 to > or = 5 years of age to determine expression of antigens associated with cell activation/differentiation. Immunophenotyping was performed by laser flow cytometry using two-color immunofluorescent labeling. Although the control children showed a decline in total CD4 cell percent with age, the HIV-infected children in all age groups showed significantly decreased CD4 cell numbers compared with the age-matched controls. However, the slope of the CD4 cell decline with age was not significantly different in HIV-infected and control children. The CD4 cell decrease in infected children was reflected in both the CD45RA+ (naive) and CD45RA- (memory) CD4 cell subsets, although the CD45RA+ cells were decreased in greater proportion. Results assessing CD4 cells for expression of the L-selectin (Leu8) molecule were similar to those for CD45RA. The overall CD8 cell percentage was significantly increased in HIV-infected children compared with controls in all age groups. This was due primarily to increases in CD8 cells that were CD38+, CD57+, HLA-DR+, or CD45RA-. In a retrospective analysis of data from 23 P-0 children, we compared phenotype results from 5 children who were HIV+ with those 18 who were HIV-. Although the phenotypic changes seen in the 5 HIV+ children paralleled those described above for P-1 and P-2 subjects, there was no significant difference in the values for HIV+ compared with HIV P-0 children. Although the phenotypic alterations described did not appear to be diagnostic markers in P-0 children, they may serve as useful adjuncts for the evaluation of HIV-infected children.
ADP-ribosyl Cyclase↗
Hemolysis of transfused group O red blood cells in minor ABO-incompatible unrelated-donor bone marrow transplants in patients receiving cyclosporine without posttransplant methotrexate.
Hemolysis most commonly occurs following bone marrow transplant when there is "minor" ABO blood group incompatibility between donor and recipient. The hemolysis has been attributed to destruction of the patient's incompatible erythrocytes by donor-derived anti-A and/or anti-B antibody produced from "passenger" immunocompetent donor lymphocytes. Extraordinary transfusion requirements of group O erythrocytes in a series of patients receiving unrelated minor ABO-incompatible marrow grafts led us to investigate whether this mechanism could account for the extent of hemolysis observed. In seven consecutive minor ABO-incompatible unrelated-donor bone marrow transplant recipients receiving cyclosporine without posttransplant methotrexate, we observed excessive hemolysis. For cases in this index group, a strongly reactive donor-derived ABO blood group antibody was identified coincident with development of hemolysis. Transfusion requirements in the first three patients (26 U of group O erythrocytes each) greatly exceeded the recipient's volume of incompatible erythrocytes, indicating that lysis of transfused group O erythrocytes was also occurring. Pretransplant erythrocyte exchange transfusion with group O erythrocytes performed in the four subsequent patients decreased the severity of hemolysis, but did not prevent it. Among minor ABO-incompatible marrow graft recipients, an analysis of variance demonstrated effects on transfusion requirements due to donor-recipient relationship being unrelated (P less than .002) and the use of posttransplant methotrexate (P = .0001), and there was interaction between these two factors (P less than .001). Bone marrow transplants from unrelated donors resulted in an exaggerated immune response to ABO blood group antigens, which was associated with hemolysis of transfused group O erythrocytes, as well as the patient's ABO-incompatible erythrocytes. This serious complication may be prevented by posttransplant immunosuppression with methotrexate.
ABO Blood-Group System↗
A recombinant vaccinia virus expressing hepatitis A virus structural polypeptides: characterization and demonstration of protective immunogenicity.
A recombinant vaccinia virus containing most of the P1 region of hepatitis A virus (HAV) was constructed. Cell lysates of cultures infected with the virus contained HAV proteins detectable by radioimmunoassay. Western blot analysis revealed the presence of a single protein of Mr 60K to 62K, bearing epitopes from structural polypeptides VP4, -3 and -2, and the N terminus of VP1. The size of the protein suggests that at least some of the vaccinia virus thymidine kinase is also expressed. Inoculation of tamarin monkeys with the recombinant virus resulted in the development of a specific anti-HAV immune response which was protective against challenge with a virulent strain of HAV. Recombinant viruses expressing the above region of HAV or the proteins expressed by such viruses may be useful in the development of a vaccine suitable for use in man.
Animals↗
Characterization of the airborne concentrations of lead in U.S. industry.
Occupational exposure to lead represents a continuing problem of significant magnitude in the United States. To characterize the problem for surveillance purposes, an analysis of the airborne concentrations of lead identified in OSHA compliance inspections was conducted for the years 1979 to 1985. The five specific objectives of the study were: 1) to examine the distribution of air lead concentration in industrial environments; 2) to determine the secular trends in air lead concentrations for high lead industries; 3) to assess which job titles had excessive airborne lead concentrations; 4) to evaluate whether there was a relationship between lead overexposure and company size, unionization, or type of inspection; and 5) to investigate the prevalence of respirator violations for lead. Fifty-two industries were identified which had more than 1/3 of their inspection medians greater than the permissible exposure limit. These included primary and secondary lead smelting, battery manufacture, pigment manufacture, brass/bronze foundries, as well as 46 other industries. There has been little if any improvement in the prevalence and severity of airborne lead concentrations for the high lead industries, battery manufacture, secondary smelting, pigment manufacture, and brass/bronze foundries. Specific high exposure job titles are identified for certain high lead industries. The job title of painting stands out as an especially problematical job title across a number of industries. The prevalence of respirator violations is approximately 20% of all lead inspections.
Air Pollutants, Occupational↗
The inhibition of 5-lipoxygenase by RG 6866.
The generation of leukotrienes C4, D4 and E4 from arachidonic acid is dependent upon the activity of 5-lipoxygenase (5-LOX). The effects of RG 6866 (N-methyl-4-benzyloxyphenylacetohydroxamic acid) on the activity of guinea pig 5-LOX in vitro and in vivo were determined in the present study. The generation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) from arachidonic acid by isolated guinea pig peritoneal polymorphonuclear (PMN) cells was inhibited by incubation with RG 6866 (IC50 = 0.20 microM). A similar effect (IC50 = 0.23 microM) was observed when 5-HETE production was measured in a supernatant fraction from PMNs. Additionally, the compound did not inhibit 3H-LTD4 binding to guinea pig membranes. In actively sensitized guinea pigs pretreated with indomethacin, propranolol and pyrilamine, RG 6866 inhibited antigen-induced systemic anaphylaxis and LTD4-dependent bronchoconstriction in a dose-dependent manner following oral administration. In the pulmonary anaphylaxis model, significant (p less than 0.05) inhibition of the mortality was observed within 30 min and maintained through four hours after treatment with RG 6866 (50 mg/kg i.g.). Finally, orally administered RG 6866 inhibited the formation of LTC4 in these animals with an ED50 = 24.0 mg/kg. These findings indicate that RG 6866 is an inhibitor of 5-LOX both in vitro and in vivo.
Airway Resistance↗
The immune response to hepatitis B virus.
Cell-mediated immune response to nucleocapsid determinants, including HBcAg and HBeAg, are important in the clearance of HBV-infected hepatocytes. This process is modulated by interferon and humoral responses to these antigens. Antibodies to the envelope proteins contribute to protective immunity, but the relative importance of pre-S and S determinants in evoking a response and the relative contributions of these antibodies in virus neutralization remains unclear. It is known, however, that antibodies binding to the RFHBs1 epitope on the HBs sequence 124-137 are capable of protecting against further infection and are present in convalescent subjects and in recipients of the plasma-derived and recombinant hepatitis B vaccines. Detailed analysis of the specificity of the anti-HBs response in vaccinees shows it to be qualitatively similar to that seen during recovery from natural infection.
Animals↗
Subcutaneous myxopapillary ependymoma.
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Adult↗
Immunogenicity of hepatitis B vaccine in renal transplant recipients.
To evaluate the immunogenicity of hepatitis B vaccine in renal transplant recipients, we administered three 40-microgram doses of vaccine to 17 patients who had previously undergone transplantation and were on immunosuppressive therapy. Life-table analysis revealed a cumulative antibody response rate of only 17.6% at 12 months, and the three responders had low titers of antibody to hepatitis B surface antigen. There were no serious adverse effects and no episodes of graft rejection in responders or nonresponders. In addition, the ratio of helper/inducer (T4) to suppressor/cytotoxic (T8) T cells in vaccinees bore no relationship to the immunogenicity of the vaccine. These data indicate that hepatitis B vaccine is weakly immunogenic in renal transplant recipients and illustrate the need for vaccination prior to transplantation for maximal protection against hepatitis B virus infection.
Adult↗
Immunogenicity of hepatitis B vaccine in oncology patients receiving chemotherapy.
We evaluated the immunogenicity and safety of three 40 micrograms doses of hepatitis B vaccine in oncology patients receiving chemotherapy. Of 76 patients screened for entry into the study, 13 (17%) already had been exposed to hepatitis B and were ineligible; 26 chose to join the study. The cumulative life-table response rate during the 12-month observation period was 70.8%; adequate immune response was linked to survival, 73% in survivors completing the study and 9% in nonsurvivors. Adverse effects were minor. We conclude that hepatitis B vaccine is safe and usually effective in inducing immunity in oncology patients younger than 60 years of age who are receiving chemotherapy.
Adult↗
Bacterial formation of aldosterone metabolites.
The experiments described in this paper demonstrate that most of the metabolic alterations of the aldosterone molecule, hitherto attributed to hepatic enzymes, equally well may be carried out by enzymes synthesized by anaerobic bacteria from the human gut. The steroid reductases synthesized by Clostridium paraputrificum, Clostridium J-1, and Clostridium innocuum convert aldosterone to the 3 alpha, 5 beta tetrahydroaldosterone (THA), 3 beta, 5 alpha-THA, and 3 alpha, 5 alpha-THA, respectively. All three enzymes metabolize 5 alpha.dihydroaldosterone to a single compound: 3 beta, 5 alpha-THA. Bifidobacterium adolescentis reduces aldosterone to 20 beta-dihydroaldosterone. In mixed cultures of B. adolescentis and clostridia, the individual enzymes operate independently of each other; however, about half of the aldosterone metabolites are in the free form and half in the acetal form. By appropriate selection of substrate and bacterial strains, therefore, it is possible to biosynthesize not only three of the THA isomers but also the hexahydroisomers in free form as well as in the acetal form.
Aldosterone↗
Inactivation of contraceptive steroid hormones by human intestinal clostridia.
Steroid hormones reduced in ring-A are devoid of hormonal activity. In metabolic experiments we found that human fecal flora reduced the delta 4-3-keto structure of natural progestins to 3 alpha-hydroxy, 5 beta-steroid metabolites (3 alpha,5 beta) and of synthetic progestins to a mixture of 3 alpha,5 beta and 3 beta,5 beta compounds. 3 alpha,5 beta-Reductase was synthesized by Clostridium paraputrificum and had a strong affinity for natural progestins such as progesterone. 3 beta,5 beta-Reductase was synthesized by Clostridium innoculin and had a stronger affinity for synthetic progestins. A third enzyme, 3 beta,5 alpha-reductase, was synthesized by St. Luke's strain 209 (Clostridium species "J-1") but was only observed when pure cultures were used. Ring-A reduction of synthetic progestins was 3 to 10 times slower than that of natural progestins, thus explaining the pharmacological superiority of synthetic progestins over naturally occurring analogs.
Clostridium↗
16 alpha-dehydration of corticoids by bacteria isolated from rat fecal flora.
Two strains (No. 144 and No. 146) of rat intestinal anaerobic bacteria, phenotypically similar to Eubacterium lentum, were isolated and found capable of 16 alpha-dehydrating corticoids. The initial step in the 16 alpha-dehydration of 16 alpha-hydroxyprogesterone was dehydration at the C-16 and C-17 position with the accumulation of 16-dehydroprogesterone. This step required the side chain at C-17. In bacterial cultures the 16-dehydroprogesterone was then slowly reduced to iso-progesterone. 16 alpha-Hydroxypregnanolone was also converted to iso-pregnanolone by these bacteria. 16 alpha-Dehydratase was easily demonstrated in cell fractions of strain No. 144 incubated either aerobically or anaerobically. The same extracts did not convert 16-dehydroprogesterone to iso-progesterone under similar assay conditions. 16 alpha-Dehydration occurred at all substrate concentrations tested (20 to 200 micrograms/ml) provided the pH of the growth medium was between 6 abd 8 and the Eh below -130 mV. Strain No. 146 had both 16 alpha-dehydration and 21-dehydroxylation activities. The two enzymes functioned independently. A role for intestinal bacteria in the biotransformation of biliary 16 alpha-hydroxylated steroids and subsequent excretion in the urine is proposed.
Adrenal Cortex Hormones↗
Formation of 20 beta-dihydrosteroids by anaerobic bacteria.
Cortisol was metabolized to a variety of products, among them small amounts of cortol by fecal flora of humans and rats. A microorganism, Bifidobacterium adolescentis, isolated from both sources, synthesized a 20-hydroxysteroid dehydrogenase which reduced cortisol to 20 beta-dihydrocortisol. The metabolite was reduced to cortol by Clostridium paraputrificum. The 20-hydroxysteroid dehydrogenase showed a wide substrate specificity; it was independent of the 4-ene and the configuration at C3, C-11, C-17 and C-21. Cortol was resistant to any further alteration by human fecal flora, i.e. it is a metabolic end product. As expected, B. adolescentis effectively prevented 21-dehydroxylation of cortisol by Eubacterium lentum.
Adrenal Cortex Hormones↗
Isolation and characterization of fecal bacteria capable of 16 alpha-dehydroxylating corticoids.
For more than a decade it has been known that the fecal flora of humans and rats includes organisms capable of 16 alpha-dehydroxylating corticoids, but their identity has remained unknown. To isolate these organisms, Mueller-Hinton agar plates were seeded with fresh feces from Proteus-free rats and incubated anaerobically. On an average, 1 of every 35 colonies consisted of organisms synthesizing 16 alpha-dehydroxylase. Isolation of the individual colonies yielded two obligate anerobes, strains 144 and 146, which elaborated the enzyme. The steroid transformation could be attained by the microbial culture alone in prereduced media or in aerobic media in the presence of Escherichia coli. Although both strains were phenotypically similar to Eubacterium lentum, they differed between themselves in their enzymatic equipment.
Adrenal Cortex Hormones↗
Control of behavioral circadian rhythms for nesting and wheel running in mice.
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Animals↗