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Biomedical subjects

H Wachter

Publications and source records attributed to H Wachter.

At least 343 records · Page 19Linked to original sources
PubMed1988

Approach to define "normal aging" in man. Immune function, serum lipids, lipoproteins and neopterin levels.

In 53 healthy women with mean age 25.1 years (age range 21-34 years) and in 51 healthy women with mean age 82.1 years (age range 75-91 years), a panel of immunological and biochemical tests was performed. These tests, comprising lymphocyte mitogen responsiveness, phenotyping of lymphocytes, uptake of low density lipoprotein by T cells, serum levels of neopterin, lipids and lipoproteins, as well as routine blood chemistry, were investigated for a possible effect of age and of the classification according to the SENIEUR Protocol of admission criteria by the European Economic Community's Concerted Action Program on Aging (EURAGE). A highly significant effect of age on serum levels of neopterin, lipids and lipoproteins was found. No clear effects, however, of SENIEUR status on these variables was detected. As expected, age had a significant impact on mitogen responsiveness of T cells. Proportional numbers of helper/inducer and cytotoxic/suppressor T cells (as well as antigen density on these cells) were not influenced by age. SENIEUR classification did not affect these immunologic variables. Thus, most of the tested variables that are not included in the SENIEUR admission criteria appear to present information not yet covered by the SENIEUR variables. Various ways for a possible revision or extension of the SENIEUR Protocol are discussed.

Adult↗
PubMed1988

Selective induction of mononuclear phagocytes to produce neopterin by interferons.

Interferon-gamma (IFN-gamma) has been shown to be a potent inducer of neopterin secretion by human peripheral blood monocytes/macrophages (1). In this paper, it is shown that other known stimuli of monocytes (e.g., to secrete proteases or to migrate) such as zymosan-activated human serum, lipopolysaccharide, human C3/iC3 and zymosan coated with complement were unable to trigger monocytes/macrophages to release neopterin. Monocytes/macrophages could be stimulated solely by IFN-gamma (25 U/ml) and IFN-alpha at very high concentrations (10,000 U/ml). In the case of human peripheral blood mononuclear cells (PBMNC), basically the same pattern was observed. If however, in the buffer controls PBMNC showed some neopterin release, all stimuli triggered an increase of neopterin secretion: 10,000 U/ml IFN-alpha induced the same amount of secreted neopterin as did 25 U/ml of IFN-gamma. Both caused higher levels of neopterin secretion than ZAS, LPS and C3/iC3. Amongst the supernatants from PBMNC, only those which were obtained from cells activated with IFN-gamma or -alpha stimulated monocytes/macrophages to produce neopterin. Supernatants from lymphocytes activated with zymosan, lipopolysaccharide and interferon did not contain neopterin, nor did the latter induce monocytes/macrophages to generate and secrete neopterin. Antibodies against IFN-gamma inhibited the triggering effect of the supernatants except when generated by IFN-alpha at 10,000 U/ml. These results demonstrate that both interferons, IFN-gamma and IFN-alpha, the latter only at a 400-fold higher concentration, can trigger monocytes/macrophages directly to secrete neopterin. ZAS, LPS and C3/iC3 are weakly effective only on a mixture of lymphocytes and monocytes/macrophages, provided this cell mixture shows already a basic spontaneous neopterin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Urinary neopterin in infants with primary immunodeficiency.

Neopterin is produced in large amounts specifically from macrophages upon stimulation with interferon-gamma (IFN-gamma). Measurement of neopterin allows a direct in vivo quantification of T cell activation. This is particularly useful, e.g., in early diagnosis of graft rejection. Since disease states with elevated neopterin levels in some cases are coupled with an impaired cellular immunity, we decided to investigate the possible influence that severely diminished cellular immunity might have on urinary neopterin levels. Our investigation on six children with severe primary immunodeficiency presents some evidence that immunodeficiency itself does not account for an increase in neopterin when patients are free from infections. Neopterin was also normal in an SCID patient who was completely lacking T cells and was suffering from severe infections. Two patients with primary immunodeficiency and residual T lymphocytes suffered from severe infections and showed elevated neopterin. The data support the hypothesis that elevated neopterin levels are dependent on the presence of activated T lymphocytes. Residual T lymphocytes of SCID patients have the capacity to induce neopterin in vivo when patients suffer from infections.

Adenosine Deaminase↗
PubMed1988

Comparison of Western blot (immunoblot) based on recombinant-derived p41 with conventional tests for serodiagnosis of human immunodeficiency virus infections.

To evaluate the performance of a serological test for human immunodeficiency virus type 1 (HIV-1) infections based on the use of a recombinant envelope gene-derived protein as the antigen, we caused expression of a 1.4-kilobase fragment of HIV.DNA that codes for the complete gp41 transmembrane protein in an Escherichia coli expression vector and used Western blots (WB; immunoblots) prepared with recombinant material (pEX-41) to detect antibodies to HIV-1. This test detected all 339 sera which were positive by a combination of conventional serodiagnostic assays and produced no false-positive results with 311 negative samples. Also no false-positive results were obtained with 20 sera from systemic lupus erythematosus patients which had high titers of cross-reactive autoantibodies. In six cases, the pEX-41 WB proved to be more sensitive than individual assays applied on their own, and in five cases it was even more sensitive than a combination of conventional assays. We tested 221 sera in both our pEX-41 WB and a commercially available recombinant enzyme immunoassay (EIA [Abbott]). The results were identical in 188 cases. A total of 27 sera containing antibodies to gp41 as demonstrated in the pEX-41 WB, as well as the Abbott recombinant EIA, had no antibodies to the recombinant core antigen as measured in the Abbott EIA. However, 25 of these sera did stain the 24-kilodalton band on a WB with purified virus. Six sera that were positive in all of the conventional confirmatory assays and reacted strongly with the pEX-41 WB did not recognize the surface antigen used in the Abbott recombinant EIA. We conclude that the use of WB prepared with recombinant-derived p41 offers a very sensitive and specific method to detect antibodies to HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Tryptophan degradation in patients infected by human immunodeficiency virus.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Neopterin levels in long-term hemodialysis.

We studied 20 patients on long-term hemodialysis. Concentrations of neopterin and creatinine were quantified in serum and in exchange buffers before, during and after treatment sessions. Neopterin is a low molecular weight product released by human macrophages upon stimulation with interferon gamma. It permits the quantification of the level of cellular immune activation in vivo. Neopterin and neopterin/creatinine ratios were found to be significantly increased in all patients. When comparing 15 patients treated with acetate exchange fluid buffers versus 5 patients treated with hydrogencarbonate, neopterin levels did not differ. Statistical computations revealed that the length of time on dialysis contributed to the increase of neopterin concentrations. Higher grade of cellular immune activation was preferentially detectable in those patients who had been on dialysis for more than 1 year. The demonstrated state of enhanced immune activation in dialysis patients might also help to explain accelerated development of AIDS in dialysis patients when infected with HIV.

Acetates↗
PubMed1988

Preactivated T cells in cancer patients with poor prognosis.

We investigated the outcome of disease in correlation with pretherapeutic urinary neopterin levels in 161 patients suffering from cervical carcinoma and 51 patients suffering from ovarian cancer. Neopterin is produced by human macrophages upon stimulation with interferon gamma and is therefore a measure for activated T cells. In both types of cancer, neopterin levels before therapy were of predictive significance. Patients with pretherapeutically high neopterin levels were more likely to die earlier. Even 12-18 months after the start of therapy this effect was significant. The data indicate that primary events in the immune surveillance are intact in those patients but effector mechanisms might be diminished. Persistent activation of cell-mediated immunity appears to be unfavorable in cancer patients.

Biopterins↗
PubMed1988

Is T-cell activation an unfavourable sign in i.v.-drug addicts infected with HIV?

In a longitudinal study, we examined 183 parenteral drug addicts who were imprisoned in Innsbruck, Austria, from March 1985 to March 1987. Thirty-seven percent of the patients had anti-HIV-antibodies. A 2-year follow-up of 43 seropositive patients revealed some evidence that urinary neopterin levels are of predictive value. Neopterin is produced from human macrophages upon stimulation with interferon gamma and, therefore, represents a sensitive parameter of activated T-cells. Eight patients who developed AIDS-related complex and one of them who contracted AIDS had significantly higher neopterin levels during the previous follow-up than the other groups of patients. Our data support the view that T-cell activation might be a crucial event in the induction of HIV reproduction in vivo.

AIDS-Related Complex↗
PubMed1988

Neopterin estimation compared with the ratio of T-cell subpopulations in persons infected with human immunodeficiency virus-1.

We measured neopterin, a biochemical indicator for the activation of cell-mediated immune reactions, in urines from 105 individuals at risk of infection with human immunodeficiency virus-1 (HIV-1), 83 of whom were seropositive for antibody to HIV-1. We compared absolute numbers of T-cell subsets (CD4+ helper/inducer T-cells, CD8+ suppressor/cytotoxic T-cells), and the ratio of CD4+ T-cells to CD8+ T-cells with the urinary neopterin concentrations. Concentrations of neopterin in urine were inversely correlated with absolute numbers of CD4+ T-cells and with CD4+/CD8+ ratios in anti-HIV-1 seropositive subjects but not in those seronegative. Various statistical comparisons of the data further demonstrated that neopterin concentrations showed larger differences between anti-HIV-1 seronegative and seropositive subjects than absolute numbers of CD4+ T-cells or CD4+/CD8+ ratios. These results seem to indicate that neopterin concentrations increase earlier in the course of HIV-1 infection, before effects on T-cell subpopulations are detectable, and may further support the suggestion that neopterin measurement could be of use for monitoring infected subjects or predicting the progression of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Potential of urinary neopterin excretion in differentiating chronic non-A, non-B hepatitis from fatty liver.

Urinary neopterin excretion was measured in 26 patients with histologically proven chronic non-A, non-B hepatitis (16 chronic persistent hepatitis, 10 chronic active hepatitis) and in 16 patients with steatosis. The potential of neopterin levels to discriminate between the two patient groups was compared with that of standard laboratory variables. Neopterin levels and triglycerides were shown to be the best variables for discriminating between the hepatitis and fatty liver patients, neopterin being the more specific of the two. Neopterin excretion in chronic persistent hepatitis was not statistically different from that in chronic active hepatitis. In the absence of specific tests, increased neopterin excretion seems to be a useful marker for diagnosing chronic non-A, non-B hepatitis and particularly in differentiating it from fatty liver.

Adult↗