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Biomedical subjects

H Wachter

Publications and source records attributed to H Wachter.

At least 163 records · Page 9Linked to original sources
PubMed1993

Increased immune activation during and after physical exercise.

The present study has been performed to examine the pattern of immune response during and following a long-duration of physical exercise. We have measured plasma concentrations of serum soluble immune activation markers namely soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8), soluble intercellular adhesion molecule 1 (sICAM-1), soluble CD23 (sCD23), soluble tumor necrosis factor receptor (sTNF-R) and neopterin in 18 individuals before, during (ascent: 3 h, descent: 2 h) and after an alpine tour. Compared to baseline levels, all the parameters were significantly increased on top of the mountain and/or after descent. Within 36 hours after the tour sIL-2R, sCD8 and sICAM-1 decreased. In contrast, sTNF-R and neopterin levels remained higher than baseline throughout the study, only partially decreasing 24 and 36 hours from start. These data show immune system activation induced by physical exercise. The increase of parameters sTNF-R and neopterin, reflecting activation of macrophages, was sustained. The data suggest that immune activation phenomena may be involved in the pathogenesis of impaired immune function after exercise and the exercise-induced asthma.

Adult↗
PubMed1993

Cerebrospinal fluid neopterin concentrations in central nervous system infection.

Cerebrospinal fluid (CSF) neopterin levels were determined by RIA in individuals with central nervous system (CNS) or human immunodeficiency virus (HIV) infections and in healthy controls. The mean CSF neopterin concentrations were 63.0 nmol/L in 15 patients with acute bacterial meningitis, 54.9 nmol/L in 15 patients with Lyme neuroborreliosis, 32.5 nmol/L in 10 patients with viral meningitis, 130.9 nmol/L in 8 patients with viral encephalitis, 13.9 nmol/L in 15 patients with asymptomatic HIV infection, 26.0 nmol/L in 11 patients with AIDS without dementia, 65.4 nmol/L in 4 patients with AIDS dementia, and 4.2 nmol/L in 24 healthy controls. Although patients with viral encephalitis had higher mean neopterin levels than any other patient category studied, the CSF neopterin concentrations cannot be used to discriminate between viral and bacterial infections. Analysis of CSF levels of neopterin may be useful as guidance in following clinical course and effect of treatment and can provide information of value in addition to CSF cell count as a measurement of CNS immune stimulation.

Adolescent↗
PubMed1993

Weight loss in HIV-1 infection is associated with immune activation.

OBJECTIVE: To assess the risk of developing weight loss, a decline in CD4+ T-cell count and AIDS-defining infections using urinary neopterin levels and CD4+ T-cell count. DESIGN: Retrospective record review. SETTING: A primary care clinic for patients at any stage of HIV infection at the University Hospital in Innsbruck, Austria, to which all patients with HIV-related diseases from the Austrian Tyrol are referred. PATIENTS, PARTICIPANTS: Seventy-nine out of the 311 HIV-seropositive individuals attending our clinic between July 1985 and December 1991 participated in the study. The selection was made after complete examination (clinical and laboratory) and follow-up of at least 6 months, up to 48 months (median, 28 months). Patients with severe diarrhoea were excluded. MAIN OUTCOME MEASURES: Correlation between body mass index, urinary neopterin and CD4+ T-cell count; development of AIDS-defining infections, weight loss, and a decline in CD4+ T-cells. Weight loss was recognized if > 10% of body weight, and there had been no concomitant AIDS-defining infection for at least 2 months. RESULTS: Initial urinary neopterin (P = 0.04), but not initial CD4+ T-cell count (P = 0.94), correlated with the body mass index obtained at the end of follow-up. Using the product-limit method, urinary neopterin predicted weight loss (P < 0.0001), decline in CD4+ T-cell count to < 200 x 10(6)/l (P = 0.006) and AIDS-defining infections (P = 0.009). CD4+ T-cell count was a better predictor of AIDS-defining infections (P < 0.0001) than of weight loss (P = 0.002). Results were confirmed by multivariate analysis. CONCLUSIONS: Weight loss > 10% of body weight is associated with immune activation.

AIDS-Related Opportunistic Infections↗
PubMed1993

Association between immune activation, changes of iron metabolism and anaemia in patients with HIV infection.

The pathogenesis of anaemia associated with human immunodeficiency virus infection is still far from being understood. It cannot be explained by direct effects of the virus on the haematopoietic system. Recent data suggest a role for immune activation. In a cross-sectional study we compared blood cell counts, haemoglobin and erythropoietin levels of 63 HIV-seropositive individuals with immune activation markers (interferon-gamma, serum and urine neopterin, and beta 2-microglobulin) and with parameters or iron metabolism (serum iron, transferrin, free iron binding capacity, ferritin). We found significant correlations between the concentrations of haemoglobin and the immune activation markers and erythropoietin concentrations. Additional significant correlations existed between the parameters of iron metabolism and haemoglobin levels, and ferritin correlated inversely with transferrin. In sum, low haemoglobin levels in patients were associated with enhanced cellular immune activation, as seen by increased interferon-gamma, neopterin and beta 2-microglobulin, and with changes of iron metabolism: low haemoglobin was associated with low transferrin and free iron binding capacity and high ferritin levels. Endogenous release of cytokines such as interferon-gamma-inhibiting erythropoiesis may be one underlying cause of anaemia in these patients.

Adolescent↗
PubMed1993

Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus.

The importance of the vpr gene for simian immunodeficiency virus (SIV) replication, persistence, and disease progression was examined by using the infectious pathogenic molecular clone called SIVmac239. The ATG start codon of the vpr gene was converted to TTG by site-specific mutagenesis. The constructed Vpr- mutant virus is identical with the parental SIVmac239/nef-stop virus with the exception of this one nucleotide. These viruses replicated with similar kinetics and to similar extents in rhesus monkey lymphocyte cultures and in the human CEMX174 cell line. Five rhesus monkeys were inoculated with the Vpr- variant of SIVmac239/nef-stop, and two monkeys received SIVmac239/nef-stop as controls. Both controls showed reversion of the TAA stop signal in nef by 2 weeks postinfection, as has been observed previously. Reversion of the TAA stop codon in nef also occurred in the five monkeys that received the Vpr- variant, but reversion was delayed on average to about 4 weeks. Thus, the mutation in vpr appeared to delay the rapidity with which reversion occurred in the nef gene. Reversion of the TTG sequence in vpr to ATG was observed in three of the five test animals. Reversion in vpr was first observed in these three animals 4 to 8 weeks postinfection. No vpr revertants were found over the entire 66 weeks of observation in the other two test animals that received the vpr mutant. Antibodies to vpr developed in those three animals in which reversion of vpr was documented, but antibodies to vpr were not observed in the two animals in which reversion of vpr was not detected. Antibody responses to gag and to whole virus antigens were of similar strength in all seven animals. Both control animals and two of the test animals in which vpr reverted maintained high virus loads and developed progressive disease. Low virus burden and no disease have been observed in the two animals in which vpr did not revert and in the one animal in which vpr reversion was first detected only at 8 weeks. The reversion of vpr in three of the five test animals indicates that there is significant selective pressure for functional forms of vpr in vivo. Furthermore, the results suggest that both vpr and nef are important for maximal SIV replication and persistence in vivo and for disease progression.

Amino Acid Sequence↗
PubMed1993

Neopterin, biochemistry and clinical use as a marker for cellular immune reactions.

Large amounts of neopterin are produced and released from human macrophages on stimulation with interferon-gamma. Neopterin is biologically stable, and it can be easily quantified in human body fluids. Neopterin measurements are useful to monitor allograft recipients to detect immunological complications. In autoimmune diseases, neopterin concentrations reflect the extent and activity of the disease. In infectious syndromes and in patients with cancer, neopterin concentrations provide prognostic information. In addition to providing clinically useful information, neopterin monitoring allows insight into the immunopathogenesis of a variety of diseases.

Biomarkers↗
PubMed1993

Increased levels of serum intercellular adhesion molecule 1 in HIV infection are related to immune activation.

Cytopathic mechanisms in human immunodeficiency virus type 1 (HIV-1) infection involve syncytia formation, and it appears likely that increased expression of intracellular adhesion molecule 1 (ICAM-1) is involved in these cell adhesion phenomena. In this study, we determined serum concentrations of soluble ICAM-1 (sICAM-1) in 27 patients with HIV-1 infection and a control group. In addition, we compared sICAM-1 values to CD4+ T-cell counts, serum beta 2-microglobulin (beta 2M) and serum neopterin levels. HIV-1-infected patients had significantly higher sICAM-1, beta 2M and neopterin levels than controls. The subgroup of patients with Walter-Reed stages 3-6 had only slightly higher sICAM-1 concentrations in serum than Walter-Reed stages 1-2. The sICAM-1 concentrations in HIV-1-seropositive patients correlated with beta 2M levels but neither with neopterin nor with CD4+ T-cell counts. Increased sICAM-1 may result from immune activation, which enhances the expression of ICAM-1 in patients with HIV-1 infection.

Adult↗
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

Self-organizing neural networks as a means of cluster analysis in clinical chemistry.

Connectionist systems (often termed "neural networks") are an alternative way to solve data processing tasks. They differ radically from conventional "von-Neumann" computing devices. Recent work on neural networks in clinical chemistry was done using supervised learning schemes, resulting in models which resemble classical discriminant analysis. The aim of the present study is to make clinical chemists familiar with basic concepts of self-organizing neural networks employing unsupervised learning schemes. Using a benchmark data set on the composition of milk from 22 different mammals, it is demonstrated that self-organizing neural networks are capable of performing tasks similar to classical cluster analysis and principal component analysis. Self-organizing neural networks could be envisaged to provide an alternative way for reducing the dimensionality of complex multivariate data sets, thus producing easily comprehensible low-dimensional "maps" of essential features.

Animals↗
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

Tetrahydrobiopterin and cytokines.

Biosynthesis of tetrahydrobiopterin starts from guanosine triphosphate by the action of guanosine triphosphate cyclohydrolase I, which yields the first intermediate, 7,8-dihydroneopterin triphosphate. This compound is then converted by subsequent enzymes, 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase, to tetrahydrobiopterin, the biologically active metabolite. Cytokines such as gamma-interferon or tumor necrosis factor-alpha strongly stimulate the activity of guanosine triphosphate cyclohydrolase I in murine and human cells, yielding a potentiation of intracellular tetrahydrobiopterin concentrations. In human cells, particularly in human monocytes and macrophages, the low activity of 6-pyruvoyl tetrahydropterin synthase leads to the additional accumulation of neopterin derivatives, which leak from the cells after dephosphorylation and are found increased in body fluids of humans with diseases challenging cell-mediated immunity. A functional role for the stimulation of tetrahydrobiopterin biosynthesis by cytokines is the formation of a limiting cofactor required for the enzymatic conversion of L-arginine to citrulline and nitric oxide.

Alcohol Oxidoreductases↗