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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 163 records · Page 9Linked to original sources

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

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

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

Children's expected interpersonal consequences of communicating their affective state and reported likelihood of expression.

This study explored several factors associated with expected outcome of emotional expression and likelihood of expression among children. These variables were posited to be a reflection of children's affective display rules. Differences in outcome expectancies and likelihood of expression were assessed as a function of sex of parent, sex of subject, grade, and type of affect. 125 first-, fourth-, and sixth-grade children (mean ages, 6-9, 9-2, and 11-7, respectively) were randomly assigned to 1 of 2 experimental conditions involving either sad or angry affect inductions. Older boys reported less positive expectancies and lower likelihood of expression than younger boys; and boys had less positive expectancies and lower likelihood of expression for sadness than girls. A high correlation was obtained between outcome expectancy and likelihood of expression; the correlation was higher for sadness than anger, and higher among males than females. These results suggest that socialization practices tend to be directed toward the suppression of sadness among males.

Age Factors

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

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.

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