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Biomedical subjects

H Wachter

Publications and source records attributed to H Wachter.

At least 181 records · Page 10Linked to original sources

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↗

Biliary and urinary neopterin concentrations in monitoring liver-allograft recipients.

Biliary neopterin concentrations were measured daily in nine liver-transplant recipients during the early post-transplant period (on average, 25 days). Concentrations increased strongly during rejection episodes and decreased quickly after successful antirejection therapy. Contrary to the changes of urinary neopterin, cytomegalovirus infection and hepatitis were not associated with an increase in biliary neopterin concentrations. Therefore, measurement of neopterin in bile fluid and in urine may aid in distinguishing rejection from infectious complications in liver-allograft recipients.

Adult↗

The role of neopterin in assessing disease activity in Crohn's disease: classification and regression trees.

Neopterin, a product of human monocytes/macrophages stimulated by gamma-interferon, was previously found to be correlated with clinical activity of Crohn's disease. The present investigation attempted to identify more precisely the role of neopterin for assessment of clinical activity in a multivariate setting. A broad panel of clinical and laboratory variables was obtained on 76 patients. Neopterin was determined in urine by high performance liquid chromatography. Using a 4-point clinical activity score as dependent variable, multivariate linear discriminant analyses were performed in order to identify subsets of statistically independent laboratory activity indices. Neopterin was shown to be an independent indicator for clinical activity. The significant variables were then tested together with the eight constituent variables of the Crohn's Disease Activity Index. The resulting model, which consisted of the three laboratory variables--erythrocyte sedimentation rate, serum protein and neopterin, together with pain score--was further subjected to two multivariate techniques for comparison: polychotomous logistic regression analysis and the technique of classification and regression trees. By all methods, neopterin was included into the multivariate models, confirming that its determination aids in the assessment of clinical activity in Crohn's disease.

Adult↗

Effects of D-penicillamine on human cell lines.

The effect of penicillamine on the proliferation and viability of human T, B and premacrophage/promyelocytic cell lines was evaluated. Whereas Raji cells and U937 cells were not negatively influenced by the addition of 0.03-0.97 mmol/l D-penicillamine (D-Pen, Trolovol, CAS 52-67-5), other cell lines such as H9, NC37 and HL60 were clearly impaired by concentrations between 0.12 and 0.49 mmol/l. Similar effects on the uptake of 3H-thymidine, 3H-uridine and 3H-leucine were observed with the addition of other stereoisomeric forms of penicillamine, D,L- and L-penicillamine to H9 cell cultures. The evaluation of cell number and viability by light microscopy revealed similar actions of penicillamine on cell cultures. By these means its repressing effect on Jurkat, NC37 and even on U937 became more transparent.

B-Lymphocytes↗

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↗

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↗

Stimulation of human nitric oxide synthase by tetrahydrobiopterin and selective binding of the cofactor.

To check the stimulatory potency of the tetrahydro forms of the two major pteridines occurring in human tissues, neopterin and biopterin, NO synthase was purified 6000-fold from human cerebellum. Tetrahydrobiopterin stimulated the activity up to 4.5-fold in a concentration dependent manner with a maximum above 1 microM, whereas tetrahydroneopterin was completely inactive in concentrations up to 100 microM. Tetrahydrobiopterin, but not neopterin derivatives, were copurified with the NO synthase activity. Our results demonstrate that human cerebellum contains a tetrahydrobiopterin dependent NO synthase activity.

Amino Acid Oxidoreductases↗

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↗