Biomedical subjects
Publications and source records attributed to G Werner-Felmayer.
AIDS incidence rates were calculated for Austria based on cumulative data up to October 31st 1988. Geographical differences are obvious, provinces of the northwest showing higher incidence rates than south-east provinces. An association of high AIDS incidence rates with intravenous drug abuse is suggested by the data.
D-erythro-neopterin is excreted in high amounts from human monocytes/macrophages responding to stimulation with gamma interferon. In vivo, the determination of neopterin offers a convenient possibility for monitoring the activation state of the cell-mediated immune system. Neopterin concentrations in body fluids also are raised with high sensitivity in viral diseases, irrespective of the specific nature of the virus. Thus, neopterin concentrations also are raised in viral diseases the causative agent of which has not yet been characterized such as non-A, non-B hepatitis. Determination of neopterin concentrations is easily accomplished by chromatographic or immunological techniques. Clinical studies showing the behaviour of neopterin levels in viral diseases are reviewed with special emphasis laid on the behaviour of neopterin concentrations in body fluids during virus-induced liver diseases, particularly non-A, non-B hepatitis. The possibilities offered by this marker to reduce the risk of disease transmission via transfusion of blood or blood components are discussed.
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A mathematical analysis is presented for several simple dynamical systems that might be considered as crude descriptions for the situation when an immune system retrovirus, immune cells, and normal autonomously replicating pathogens interact. By stability analysis of the steady-state solutions, the destabilizing effect of the immune system retrovirus is described. The qualitative behavior of the solutions depending on the system parameters is analyzed in terms of trajectories moving in a phase space in which the axes are defined by the population numbers of the interacting biological entities.
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The capacity of recombinant interferon-alpha, -beta and -gamma, of bacterial lipopolysaccharide and of recombinant tumour necrosis factor-alpha to induce indoleamine 2,3-dioxygenase and synthesis of pteridines was studied in human peripheral blood mononuclear cells, human macrophages and normal dermal fibroblasts. The action of interferon-alpha and -beta on macrophages was supported by lymphocyte factors as indicated by the effect of these mediators in the absence or presence of lymphocytes. Tumour necrosis factor-alpha alone was ineffective in peripheral blood mononuclear cells and macrophages, but it significantly increased the action of all three interferon species on macrophages and fibroblasts. Lipopolysaccharide directly affected macrophages or dermal fibroblasts and enhanced the effect of interferon-gamma. However, in the presence of lymphocytes, the action of lipopolysaccharide was mediated via interferon-gamma.
Serum concentrations of interferon-gamma were measured in individuals seropositive for human immunodeficiency virus type 1 (HIV-1). According to the CDC classification system, 6 presented with stage IV-C, 5 with stage IV-A, 8 with stage III, and the remaining 24 individuals with stage II. A modified radioimmunoassay procedure for detection of interferon-gamma was used with a detection limit of 18 U/L. Approximately one-half (22/43) of the seropositives exhibited increased serum interferon-gamma concentrations compared with seronegative blood donors (n = 76). There was a significant association between serum interferon-gamma concentrations and CDC stages of the patients; patients classified as CDC IV-C had the highest concentrations. Further, a significant positive correlation was observed between serum interferon-gamma and serum neopterin concentrations in seropositive study participants. We conclude that interferon-gamma is present in increased concentrations in HIV-1 seropositives compared to seronegative blood donors. Diminished in vitro production of interferon-gamma by T-lymphocytes on stimulation with specific soluble antigens contrasts with increased levels of circulating interferon-gamma in patients.
Albert (Clin Chem 1982;28:1113-9) has proposed estimation of likelihood ratios by logistic regression analysis. The usual likelihood-ratio approach for estimation of post-test probability of disease from sensitivity and specificity data of a diagnostic test has been extended by Birkett (J Clin Epidemiol 1988; 41:491-4) for situations with more than two diagnostic categories. We suggest here a combination of these ideas, demonstrating this by a re-evaluation of previously published data on the validity of neopterin as a tool for differential diagnosis between chronic non-A, non-B hepatitis and fatty liver. Analysis of neopterin data in combination with the ratio between serum concentrations of aspartate aminotransferase and of alanine aminotransferase yielded a good discrimination between three mutually exclusive diagnostic categories, namely, fatty liver and chronic persistent and chronic aggressive non-A, non-B hepatitis. The approach is flexibly applicable to situations with different pre-test probabilities. The sum of estimated post-test probabilities deviates slightly from the sum of pre-test probabilities. This deviation is a function of the coefficients obtained in logistic regression, and an analytical expression for the deviation is given. The generalized likelihood-ratio approach appears promising in complex diagnostic situations when multiple diagnostic tests are available.
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The indoleamine 2,3-dioxygenase (EC 1.13.11.17) activity in human T24 cells has been investigated in cell extracts by using a non-radioactive assay. It is enhanced in a dose-dependent manner up to 25-fold by interferon-gamma. The maximum reaction velocity is increased rather than the Km, which remains at 4 mumol/l. Induction of activity starts 3 h after stimulation and reaches a plateau at 21-48 h. Decreased stimulation was observed in the presence of high L-tryptophan concentrations.
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Hybrid cell lines producing monoclonal antibodies against Bacteroides forsythus or Wolinella recta were generated by fusion of SP2/0 or FO myeloma cells with splenocytes from Balb/c mice immunized with formalinized cells of B. forsythus FDC 331 or W. recta D13a-g, respectively. Enzyme-linked immunosorbent assays and indirect immunofluorescence tests were used to analyze the distribution of the recognized antigens on a panel of 70 strains representing 35 taxa, most of which are members of the oral flora. All monoclonal antibodies--eight against B. forsythus and six against W. recta--proved specific for the immunizing species. Four of the monoclonal antibodies against W. recta recognized antigens expressed by only some of the tested W. recta strains, thus confirming the earlier noted antigenic heterogeneity of this species. Antibody binding patterns consistent with those previously described or distinct for new serogroups could not, however, be observed. Four of the eight anti-B. forsythus monoclonal antibodies bound to only two of the three tested B. forsythus strains. All the remaining monoclonal antibodies detected every strain tested of the respective species against which they were raised. Preliminary results indicated that several of these antibodies should be very useful for the direct identification and quantification of these organisms in subgingival plaque.
Tryptophan and kynurenine were measured retrospectively in sera of 11 male patients with advanced human immunodeficiency virus (HIV) infection (Walter Reed stages 4 and 6). Tryptophan levels are significantly reduced to less than 50% in patients with HIV infection and kynurenine levels significantly elevated when compared to sex and age matched controls. The decrease of tryptophan levels might contribute to neurologic symptoms often associated with HIV infection. Since interferon-gamma induces degradation of tryptophan via the kynurenine pathway, the present results may be consistent with enhanced endogenous production of interferon-gamma in advanced HIV infection.
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