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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 19 recordsLinked to original sources
PubMed1992

Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific.

Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of beta 2-microglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Critical study of consensus analysis.

Consensus analysis has been proposed as a statistical method by which the efficacy of clinical and laboratory tests of inflammatory activity can be assessed. This technique is claimed to overcome the need for an external "gold standard" as a reference method; instead, the consensus of all tests is used as the gold standard. We have evaluated the reliability of consensus analysis using data collected from patients with Crohn's disease. Our results demonstrate that the technique depends strongly on the correlation structure underlying the set of measures of disease used for analysis. This observation was supported by a series of conventional cluster analyses of the same set of variables. Furthermore, slight modifications of the algorithm had profound effects on the final result. We conclude that for the evaluation of tests of inflammatory activity, an external reference method, albeit an imperfect one, remains indispensable.

Clinical Laboratory Techniques↗
PubMed1992

Association between serum-soluble CD8 levels and parameters of immune activation in patients with human immunodeficiency virus infection.

We compared the serum concentrations of soluble CD8 with the immune activation markers neopterin, interferon-gamma, tumour necrosis factor-alpha, soluble CD4, and with CD4+ and CD8+ T-cell counts in patients with human immunodeficiency virus (HIV) infection. The majority of patients had increased concentrations of soluble CD8, interferon-gamma and neopterin, and various significant correlations existed between them. Our results support the view that enhanced soluble CD8 levels indicate activated CD8+ T cells in patients with HIV infection.

Adult↗
PubMed1992

Immunization with tween-ether-treated SIV adsorbed onto aluminum hydroxide protects monkeys against experimental SIV infection.

In order to examine the efficiency of an AIDS vaccine potentially acceptable for human use we have investigated a split vaccine. Since such vaccines are safe and efficient, they have been in use for many years to protect man against enveloped RNA viruses, e.g., influenza and measles. Seven rhesus monkeys were immunized at Week 0, 4, 8, and 16 by im injection of 2 ml of vaccine containing 140 micrograms of Tween-ether-disrupted SIVmac251/32H adsorbed onto aluminum hydroxide. The immunized animals and three nonvaccinated control monkeys were challenged 2 weeks after the last immunization by iv injection of 10 to 50 minimal monkey infectious doses of SIVmac251/32H. Four of seven immunized animals did not show any signs of virus replication and therefore appeared to be protected. Nonvaccinated control animals and the vaccine failures showed a rise in their urinary neopterin concentrations 1 to 2 weeks after infection. At the end of the second week and thereafter, cocultures and polymerase chain reaction of their peripheral blood lymphocytes were positive. After the challenge, control animals and infected vaccinees showed a primary or secondary antibody response while antibody titers declined in virus-negative animals. Specific cytotoxic T-lymphocytes were not present prior to challenge, but were present in some animals thereafter. Therefore, these seem to reflect a response to viral replication rather than to immunization. Prior to challenge the CD4-positive lymphocytes of the peripheral blood of the four virus-negative animals only proliferated after exposure to the immunizing antigen. Thus, this reaction appears to predict protection.

Adjuvants, Immunologic↗
PubMed1992

Neopterin production in acute schizophrenic patients: an indicator of alterations of cell-mediated immunity.

This longitudinal study analyzed how the activation of cell-mediated immunity (CMI) was related to the severity of symptomatology in 25 acute schizophrenic inpatients (DSM-III-R, 295.31). Neopterin, which was used to monitor the activation of T-cells and macrophages, was found to be within the normal range, but the lowest neopterin concentrations were measured on day 0. By day 3, a significant increase of neopterin was observed. Compared with healthy controls, patients had significantly lower neopterin levels at baseline. The highest scores on the Clinical Global Impressions Scale and the Brief Psychiatric Rating Scale occurred on day 0 and decreased significantly over the observation period. In general, the increase of neopterin was accompanied by a decrease in psychopathological symptoms. These results' indicate that at study entry, when patients are acutely ill, activation of the CMI is reduced rather than increased. Possible pathophysiological mechanisms are discussed.

Adult↗
PubMed1992

Serum kynurenine and neopterin concentrations in patients with cardiomyopathy.

Serum kynurenine and neopterin concentrations were determined in patients with hypertrophic (n = 22) and dilated (n = 23) cardiomyopathy. Significantly increased kynurenine and neopterin levels have been observed in cases of dilated cardiomyopathy. In these patients we found a positive correlation between serum kynurenine and neopterin levels (RS = 0.52, P less than 0.001). There existed several associations between the laboratory parameters neopterin and kynurenine and clinical findings, such as left ventricle (LV) systolic volume and LV circumferential fiber shortening velocity in patients with dilated cardiomyopathy (all P less than 0.05). In vitro, interferon-gamma induces the formation of neopterin in human monocytes/macrophages. Also the degradation of tryptophan via the kynurenine pathway is induced by interferon-gamma. Our data show that increased kynurenine as well as neopterin accumulation in serum are associated with severity of dilated cardiomyopathy. Thus, the data point to a role of immune activation in the pathogenesis of the disease.

Biopterins↗
PubMed1992

[Cellular immunity in pregnancy-induced hypertensive diseases].

Cytokines (IL-1, sIL-2R, IL-3, IL-6, TNF-alpha, IFN-gamma, GM-CSF and neopterin) were measured in sera of 37 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy non-pregnant controls. With the exception of neopterin (p = 0.004) there were no statistically significant differences in cytokine concentrations between healthy pregnant and non-pregnant controls. No statistically relevant differences between healthy pregnant women and hypertensive patients could be found in cytokines of T-lymphocytic origin except GM-CSF in patients with HELLP syndrome (p = 0.02). Elevated levels of IL-6, TNF-alpha and neopterin were observed in hypertensive women. Differences to healthy pregnant controls were statistically significant for IL-6 (p = 0.008), TNF-alpha (p = 0.009) and neopterin (p = 0.04) and were more pronounced in severe forms of the disease. These 3 parameters of monocytic origin showed significant positive correlations amongst each other. A participation of cell-mediated immunity (especially monocytes/macrophages) in the pathomechanism of hypertensive disorders of pregnancy can thus be assumed.

Biopterins↗
PubMed1992

Immunization of rhesus monkeys with high- and low-dose Tween-ether-disrupted SIVMAC.

Two vaccine trials were conducted with low- and high-dose purified Twen-ether-treated SIVmac adsorbed onto aluminum hydroxide using rhesus macaques. In the first experiment 7 macaques were immunized with a total amount of 560 micrograms protein and 3 animals served as controls. After the immunization period the vaccinees exhibited ELISA titers up to 1:1280 and 5 immunized animals showed an antigen-specific proliferative response. After the virus challenge the 3 control animals and 3 vaccinees became infected. Four of the infected animals developed a cytotoxic T-cell response beginning 8 weeks postchallenge. The 4 protected animals were rechallenged 16 weeks later and all became infected. For the high-dose experiment 5 immunized animals receiving 2 mg of antigen and 2 control animals were used. The ELISA titers of the vaccinees reached 1:20480 and 4 animals exhibited an antigen-specific proliferative response. In response to virus challenge the 2 control and 1 immunized animal became infected. From these data it can be concluded that the high-dose immunization scheme elicited higher antibody titers and increased the fraction of protected animals.

Adjuvants, Immunologic↗