Antigen detection in primary HIV infection.
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Biomedical subjects
Publications and source records attributed to D Fuchs.
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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)
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.
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.
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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.
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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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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.
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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.