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Biomedical subjects

H Wachter

Publications and source records attributed to H Wachter.

At least 289 records · Page 16Linked to original sources
PubMed1989

Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma.

In all of eight tested human cells and cell lines with inducible indoleamine 2,3-dioxygenase (EC 1.13.11.17) tetrahydrobiopterin biosynthesis was activated by interferon-gamma. This was demonstrated by GTP cyclohydrolase I (EC 3.5.4.16) activities and intracellular neopterin and biopterin concentrations. Pteridine synthesis was influenced by extracellular tryptophan. In T 24-cell extracts, submillimolar concentrations of tetrahydrobiopterin stimulated the indoleamine 2,3-dioxygenase reaction.

Biopterins↗
PubMed1989

Characteristics of interferon induced tryptophan metabolism in human cells in vitro.

Interferon-gamma-induced tryptophan metabolism of human macrophages was compared to ten human neoplastic cell lines of various tissue origin and to normal dermal human fibroblasts. Tryptophan and metabolites were determined in supernatants of cultures, after incubation for 48 h, by high-performance liquid chromatography with ultraviolet and fluorescence detection. With the exception of two cell lines (Hep G 2, hepatoma and CaCo 2, colon adenocarcinoma) in all of the ten other cells and cell lines tryptophan degradation was induced by interferon-gamma. Five of these ten formed only kynurenine (SK-N-SH, neuroblastoma; T 24, J 82, bladder carcinoma; A 431, epidermoid carcinoma; normal dermal fibroblasts), three formed kynurenine and anthranilic acid (U 138 MG, glioblastoma; SK-HEP-1, hepatoma; A 549, lung carcinoma). Only one line, A 498 (kidney carcinoma) showed the same pattern of metabolites as macrophages (kynurenine, anthranilic acid and 3-hydroxyanthranilic acid). Interferon-gamma regulated only the activity of indoleamine 2,3-dioxygenase. All other enzyme activities detected were independent of interferon-gamma, as shown by the capacity of the cells to metabolize L-kynurenine or N-formyl-L-kynurenine. Increasing the extracellular L-tryptophan concentration resulted in a marked induction of tryptophan degradation by macrophages. Contrarily, a significant decrease of the tryptophan degrading activity was observed when the extracellular L-tryptophan concentration was increased 2-fold with SK-N-SH, T 24 and J 82, 4-fold with A 431 and A 549 and 10-fold with U 138 MG and SK-HEP-1. The activity was unaffected by extracellular L-tryptophan with dermal fibroblasts and A 498. Though interferon-gamma was the most potent inducer of tryptophan metabolism, interferon-alpha and/or -beta showed small but distinct action on some of the cells. In all cells which reacted to interferon-gamma by enhanced expression of class I and/or class II major histocompatibility complex antigens tryptophan degradation was also inducible. These results demonstrate that induction of indoleamine 2,3-dioxygenase is a common feature of interferon-gamma action, that the extent of this induction is influenced by extracellular L-tryptophan concentrations and that indoleamine 2,3-dioxygenase is the only enzyme in the formation of 3-hydroxyanthranilic acid from tryptophan which is regulated by interferon-gamma.

Cell Line↗
PubMed1989

AIDS incidence rates in Austria.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Serum neopterin determination for the additional safeguarding of blood transfusions. Our experiences with 76,587 blood donors].

Since October 1986, all volunteer blood donors in the Tirol of Austria have been tested for neopterin. Serum neopterin levels were raised in 1242 donors (1.6%), 650 of whom (52.3%) consented to another test four weeks after the donation. In retrospect, 148 of these donors (22.8%) had an illness or abnormal symptoms at the time of donation or within a few days of it: according to the "guidelines for blood group testing and blood transfusion" of the Federal German Chamber of Doctors (Deutsche Bundesärztekammer) 25 of these (16.9%) should be permanently excluded as blood donors. The other 123 donors would have been temporarily excluded, according to the guidelines, if their illness had been known at the time of donation. Since the beginning of 1988, all donated blood with increased serum neopterin levels also had an IgM test for cytomegalovirus (CMV): nine of 243 samples tested (3.7%) indicated an acute CMV infection. The neopterin assay thus detects a variety of potentially harmful diseases or conditions which would not be revealed by the usually employed battery of routine tests.

Adolescent↗
PubMed1989

Endogenous release of interferon-gamma and diminished response of peripheral blood mononuclear cells to antigenic stimulation.

The capacity of T lymphocytes to proliferate in response to stimulation and the amount of representative lymphokines produced in vitro often correlate with the immunocompetence of patients. However, direct and indirect measurement of endogenous interferon-gamma (IFN-gamma) brings some evidence that decreased in vitro production of IFN-gamma by T lymphocytes is associated with increased concentrations in vivo. The data indicate that both a functional inhibition of IFN-gamma and its continuous presence at high levels may result in hyporesponsiveness or unresponsiveness of immune cells. A possible role of IFN-gamma in the induction of tolerance is discussed.

Animals↗
PubMed1989

Anti-viral antibodies in HIV (HTLV-III) infection possess auto-antibody activity against a CH1 domain determinant in human IgG: possible immunological consequences.

Two regions of the envelope glycoprotein gp120 of the human immunodeficiency virus were shown to have a significant degree of homology to human immunoglobulin-gamma heavy-chain constant domains. We have now synthesized three short linear peptides, the first representing a sequence within the CH1 domain, the second an analogue of it, and the third representative of a region within the viral gp120. Polyclonal antibodies against these peptides were raised in rabbits and used to demonstrate that they all reacted well with human native IgG. Vice-versa, we observed the reaction of these antisera to the virus in an ELISA system. The proportion of sera reacting with the human gamma-chain peptide was significantly higher in HIV-positive individuals than in HIV-negative individuals, suggesting production of anti-viral antibodies in AIDS patients with auto-antibody activity against a CH1 domain determinant in human IgG.

Acquired Immunodeficiency Syndrome↗
PubMed1989

HIV and HIV-infected cells differentially activate the human complement system independent of antibody.

The human retroviruses HTLV-I and HIV-I have previously been shown not to be lysed by human serum. An interaction between HIV and the complement system, however, has not been investigated in any detail. In this report we show that purified HIV as well as HIV-infected cells activate the complement system. In the case of virus-infected cells this activation is mediated by the alternative pathway of complement, whereas the classical pathway seems to be in operation for the triggering of the complement system by purified virus and recombinant envelope glycoprotein (gp 160). We demonstrate that this leads to the deposition of C3b and/or C3bi on the surface of infected cells. But the HIV-infected cells are not lysed by human complement. C3 fragments deposited on the surface of HIV-infected cells are capable of mediating immune adherence to complement receptor-bearing cells, such as human erythrocytes and phagocytes. Whether this might have an influence on infectivity of HIV for certain cells bearing complement receptors has yet to be shown.

Cell Line↗
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↗