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Biomedical subjects

G Reibnegger

Publications and source records attributed to G Reibnegger.

At least 163 records · Page 9Linked to original sources

Interferon-gamma concentrations are increased in sera from individuals infected with human immunodeficiency virus type 1.

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.

Acquired Immunodeficiency Syndrome↗

Generalized likelihood ratio concept and logistic regression analysis for multiple diagnostic categories.

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.

Alanine Transaminase↗

Urinary neopterin concentrations vs total neopterins for clinical utility.

Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV-1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4+ T-cell counts and CD4+/CD8+ T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8-dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8-dihydro derivative.

Acquired Immunodeficiency Syndrome↗

Effects of interferon-alpha on macrophage activation in patients with ovarian carcinoma and cervical dysplasia.

Patients with progressive ovarian carcinoma and patients with dysplasia of the uterine cervix were studied in order to compare clinical efficacy, hematological toxicity and effects on macrophage activation of administered interferon-alpha for both patient groups. One of three patients with ovarian carcinoma showed a minor response. Four of six patients with cervical dysplasia had slight improvements of PAP-smears. Moderate hematological toxicity was observed in the former patient group while side effects were much more pronounced in the latter patients group. However, changes of hematological parameters were not statistically different. Interestingly, the administered interferon-alpha caused the same activation of macrophages in both patients groups as indicated by raised neopterin levels. This activation does not result in clinical improvement but appears to play a role for the hematological toxicity observed during therapy of patients with ovarian carcinoma. It has been suggested that suppression of hematopoiesis is mediated by interferon-gamma. The present neopterin data propose that this lymphokine is continuously produced through influence of the tumor and enhanced by interferon-alpha.

Adult↗

Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection.

We assessed the value of urinary neopterin concentrations for prognosis of disease progression in HIV-1-infected patients. Sixty-eight anti-HIV-1 seropositive homosexuals with lymphadenopathy syndrome were tested for urinary neopterin and T-cell subset counts in 1982-83, and the incidence rate at which they developed acquired immunodeficiency syndrome (AIDS) between then and May 1988 was evaluated. Overall, 21 of 68 (30.9%) cases progressed to AIDS, with a yearly progression rate of 4-9%. The predictive value of urinary neopterin concentrations was higher (P = 0.0042) than that of CD4+ T-cell counts (P = 0.015) or the CD4+/CD8+ T-cell ratio (P = 0.022). Counts of CD8+ T-cells failed to show predictive significance (P = 0.29). Similarly, multivariate-regression analysis indicated that neopterin concentrations and CD4+ T-cell numbers were significant copredictors. Produced by human macrophages activated by interferon gamma, neopterin is thus a marker of macrophage activation via T cells. We conclude that these data demonstrate a correlation between the amount of T-cell-macrophage activation, as measured by urinary neopterin concentrations, and the progression of the disease.

AIDS-Related Complex↗

Influence of interferon-gamma and extracellular tryptophan on indoleamine 2,3-dioxygenase activity in T24 cells as determined by a non-radiometric assay.

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.

Cell Line↗

Urinary neopterin excretion in pulmonary sarcoidosis: correlation to clinical course of the disease.

Urinary neopterin levels were determined by high pressure liquid chromatography in 36 patients with pulmonary sarcoidosis. Values were above normal range in 69.4% of all patients. Neopterin excretion was significantly higher in radiologic types II/III than in type I disease (p = 0.0265, Mann-Whitney U-test). Urinary neopterin showed a weak, but significant inverse correlation to disease duration (r = -0.36; p = 0.034, Spearman's rank correlation). No significant correlation could be found between neopterin and the presence of pulmonary or extrapulmonary symptoms, vital capacity, forced expiratory volume in the first second, steroid treatment, and serum angiotensin converting enzyme. Follow-up studies revealed that worsening or improvement of chest X-ray findings was invariably accompanied by rising or decreasing neopterin excretion, respectively. Patients with normal neopterin at initial evaluation had a higher tendency towards spontaneous healing, and none of them deteriorated during the follow-up period. We conclude that urinary neopterin excretion reflects one aspect of alveolitic "activity" in pulmonary sarcoidosis and that normal values probably indicate a favorable prognosis.

Adult↗

Immunological status and HIV antibodies in patients with haemophilia--a longitudinal study.

Various immunological parameters were investigated in 12 children suffering from severe haemophilia A or B receiving substitution therapy over a follow-up period of 3 1/2 years. At the beginning of the study, the therapy was changed to heat-treated concentrates of factors VIII or IX. Antibodies to HIV were found in 9 out of these patients. There were no AIDS-related clinical symptoms, but HIV antigen was detectable in one case. Abnormalities of immunological parameters were found independently of HIV infection, but were more pronounced in anti-HIV seropositive patients. Elevated levels of immunoglobulins gave evidence of polyclonal B-cell activation whilst increased levels of neopterin indicated activated T-cells and macrophages. There was no close association between these two types of activation. However, peak activation of both immune compartments was found approximately 1 year after changing the therapy. Thereafter a continuous tendency towards normalization of neopterin levels was observed. At the final visit immunoglobulin levels also tended to decrease. The HIV antigen seropositive child showed the highest neopterin levels during the whole study period. Our data indicate that the primarily high risk of developing AIDS in anti-HIV-seropositive haemophiliacs is declining.

Acquired Immunodeficiency Syndrome↗