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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 307 records · Page 17Linked to original sources
PubMed1993

Stimulated cellular immune system in patients with congestive heart failure.

In this cross-sectional study, we analysed serum concentrations of soluble markers of cellular immune activation, namely, interferon-gamma, neopterin (a product of activated macrophages), soluble interleukin-2 receptor, and soluble CD8, in 25 patients with congestive heart failure. Ten (40%) patients showed increased concentrations (i.e. above the reference ranges of healthy controls) of neopterin, 14 (56%) showed increased soluble interleukin-2 receptor, and 6 (24%) showed increased soluble CD8. Endogenous interferon-gamma was detectable in 10 patients (40%). In addition, we found significant correlations between neopterin and interferon-gamma (rs = 0.417, p < 0.05), and between neopterin and soluble CD8 concentrations (rs = 0.430, p < 0.05). All patients with increased soluble CD8 also had increased soluble interleukin-2 receptor. However, no significant correlations of soluble interleukin-2 receptor with soluble CD8 or any of the other quantities were observed. Increased concentrations of soluble interleukin-2 receptors, soluble CD8 and neopterin indicate that cellular immunity is stimulated in patients with congestive heart failure. Activated CD8-positive T-lymphocytes may represent the source of increased soluble CD8. Endogenous interferon-gamma, which is derived from activated T-cells, may induce neopterin release by monocytes/macrophages.

Adult↗
PubMed1993

Comparative effects of heme and metalloporphyrins on interferon-gamma-mediated pathways in monocytic cells (THP-1).

Previous results have demonstrated links between cell-mediated immunity, interferon (IFN)-gamma and neopterin production with heme, porphyrins, and iron metabolism. In this study, we compared the effects of heme, several metalloporphyrins, protoporphyrin IX, and iron on the signal or IFN-gamma-mediated pathways, such as the expression of major histocompatibility complex class II antigens, neopterin formation, and the degradation of tryptophan. Using the human monocytic cell line, THP-1, we found that heme, Zn-mesoporphyrin, Zn-deuteroporphyrin, Co-protoporphyrin, and iron reduced the efficiency of the IFN-gamma signal. In addition, Zn-mesoporphyrin almost fully inhibited IFN-gamma-induced degradation of tryptophan by the heme protein, indoleamine 2,3-dioxygenase. In contrast, tin-protoporphyrin enhanced the IFN-gamma effects as seen by increased neopterin production, enhanced tryptophan degradation, and elevated HLA-DR antigen expression on cells. These effects are considered to be due to the action of heme, metalloporphyrins, iron, or heme byproducts on the IFN-gamma signal, rather than to direct effects on IFN-gamma-induced enzymatic pathways. Heme and metalloporphyrins were previously shown to affect heme oxygenase activity, T cell growth, and lipid peroxidation and to modulate interleukin 2 activity. These pathways are also known to be influenced by IFN-gamma, and our data suggest that heme and metalloporphyrins may directly modulate the efficiency of the IFN-gamma signal.

Biopterins↗
PubMed1993

Elevated concentrations of circulating intercellular adhesion molecule 1 (ICAM-1) in HIV-1 infection.

The membrane-bound glycoprotein intercellular adhesion molecule 1 (ICAM-1) plays an important role for many cell-contact-dependent immune functions. A soluble, circulating form of ICAM-1 (cICAM-1) has been detected in the serum of healthy persons and increased concentrations in tumor patients have been reported. We measured serum levels of cICAM-1 in HIV-1-infected individuals with a recently developed ELISA. In contrast to HIV-seronegative controls (median value of 294 ng/ml, range of 185-408 ng/ml; n = 22), significantly elevated concentrations were detected in 76 HIV-1-infected persons (median of 487 ng/ml, range of 231-1,524 ng/ml; p < 0.0001). In HIV-1-infected individuals, cICAM-1 values did not correlate with the absolute number of CD4+ T cells or with disease progression according to the Walter Reed staging classification. Concentrations of cICAM-1 correlated with the serum concentrations of IL-6 (p = 0.0015; Spearman's rank correlation analysis) and with urinary neopterin (p = 0.005), but not with the C-reactive protein. Since there is evidence that cICAM-1 can interfere with immunological functions, the high amounts circulating in HIV-1-positive individuals could contribute to the disturbance of the immune system in HIV-1 infection.

Adult↗
PubMed1993

Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation.

The objectives of this prospective randomized trial were to quantify immunosuppressive effects of cardiopulmonary bypass, to identify mechanisms responsible for postoperative immunosuppression, and to investigate the effects of immunomodulatory intervention on these mechanisms. Sixty patients were studied after cardiopulmonary bypass. Immunomodulatory therapy consisted of the cyclooxygenase inhibitor indomethacin, which blocks the downregulating agent prostaglandin E2, and thymopentin, which enhances T-lymphocytic activity. Twenty patients each received indomethacin either alone or combined with thymopentin. Twenty patients served as the control population. Our in vitro studies showed a decrease of CD4+ helper/inducer T cells and interleukin-2 receptor expression on T lymphocytes, while CD8+ suppressor/cytotoxic T cells and monocytes increased. Additionally, a depression of interleukin-1 and interleukin-2 synthesis as well as concurrent low gamma-interferon serum concentrations could be documented. These results indicate a downregulation of cell-mediated immune response. As an in vivo correlate of the immunomechanistic alterations, patients demonstrated an impaired delayed-type hypersensitivity response to an antigen skin test battery. These changes in immunoreactivity could be successfully counteracted by the combined immunomodulatory regimen, whereas sole indomethacin treatment could only partially restore depressed host defense parameters. With this study we could demonstrate for the first time that human lymphocytic interleukin-2 synthesis, which represents the key event among forward regulatory immune mechanisms, can be protected via in vivo immunoaugmentatory therapy and that this therapy can successfully counteract immunosuppressive effects of cardiopulmonary bypass.

Aged↗
PubMed1993

Association between neopterin and beta-2-microglobulin levels and HIV status in Romanian orphanage children.

Serologic markers of immune activation, neopterin and beta-2-microglobulin (B2M), have been shown to predict progressive human immunodeficiency virus type 1 (HIV-1) disease based on cohort studies in adults. Both parameters appear also to be valuable in distinguishing HIV-1 infants with progressive disease from asymptomatic infants and HIV-1 seronegative infants. In a cross-sectional study we examined the utility of neopterin and B2M testing in 135 infants of an orphanage in Romania, 69 of the infants (51%) were found to be HIV-1 antibody seropositive; 95% of the 135 infants were either hepatitis B virus (HBV) antigen or antibody seropositive. In the HIV-1 seronegative infants B2M was higher in those with HBV antigenaemia. Serum neopterin and B2M concentrations were higher in HIV-1 seropositive than in seronegative infants (p = 7 x 10(-12) and 1 x 10(-6)). Children with CDC stage P2 had only slightly higher neopterin and B2M values as compared to stage P1 (P = 0.04 and 0.08). Our study indicates that measurement of neopterin and B2M is useful to monitor HIV-1 infection, particularly in areas where laboratory facilities are limited. Both parameters continue to be associated with HIV-1 infection even when there is a high background rate of other infections.

Biopterins↗
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↗