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Biomedical subjects

A Hausen

Publications and source records attributed to A Hausen.

At least 55 records · Page 3Linked to original sources
PubMed1989

Neopterin and viral infections: diagnostic potential in virally induced liver disease.

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.

Biopterins↗
PubMed1989

Stability analysis of simple models for immune cells interacting with normal pathogens and immune system retroviruses.

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.

HIV↗
PubMed1989

Retroviral infections (HIV-1, HIV-2, and HTLV-I) in rural northwestern Tanzania. Clinical findings, epidemiology, and association with infections common in Africa.

During a three-week period in March/April 1987, the authors examined 253 consecutive patients referred to a rural hospital in northwestern Tanzania. Sera were tested for antibodies to human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and human T-lymphotropic virus type I (HTLV-I), as well as for various parasites, hepatitis B virus, and Treponema pallidum. Neopterin (urinary and serum) was chosen as the immunologic parameter. In eight of the 253 patients (3.2%), a clinical diagnosis of acquired immunodeficiency syndrome (AIDS) was established. Three of the AIDS patients had HIV-1 antibodies, two had HIV-1 antigen, one had both HIV-1 and HIV-2 antibodies, and in one patient, only HIV-2 antibodies were found. The total HIV-1 and HIV-2 seroprevalence (antibodies plus antigen) was 4.3%; HTLV-I seroprevalence was 9.9%. No correlation could be found between HIV (or HTLV-I) seropositivity and raised levels of antibody to the above pathogens. There was, however, a significantly positive correlation between HIV seropositivity and history of gonorrhea, whereas a history of operations, injections, vaccinations, blood transfusions, or scarification did not influence the level of HIV seropositivity. The most frequently noted epidemiologic association with HIV seropositivity was traveling to or coming from Uganda or Rwanda. Two thirds of the studied Tanzanians had elevated neopterin levels, and all seven HIV-seropositive patients with clinical signs of AIDS had extremely high serum and urinary neopterin levels compared with HIV-seropositive patients without signs of AIDS. Increased neopterin levels reflect a stimulation of the T-cell/macrophage system.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Neopterin concentrations in cerebrospinal fluid and serum of individuals infected with HIV-1.

Neopterin, a biochemical marker for the activation of cell-mediated immune reactions, was determined in serum and cerebrospinal fluid (CSF) from patients infected with HIV-1. A significant correlation was found between serum and CSF neopterin concentrations, although concentrations of neopterin in serum were more closely correlated with the clinical severity of HIV-1 infection than those in CSF. However, higher CSF levels were observed in patients with neurologic/psychiatric symptoms than in unaffected patients. Also, quotients of CSF neopterin versus serum neopterin concentrations were increased, indicating intrathecal production of neopterin. Positive HIV-1 isolation from peripheral blood mononuclear cells (PBMC) was associated with higher neopterin concentrations in serum, when compared with negative HIV-1 isolation. Neopterin in CSF appears to be a suitable biochemical marker in patients with HIV-1 infection for detecting overt neurologic/psychiatric disturbances. The data suggest that in HIV-1 infected patients, cell-mediated immune reactions might be activated intrathecally and might contribute to neuropsychiatric disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells.

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.

Biopterins↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗