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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 145 records · Page 8Linked to original sources
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

Antiretroviral therapy in sporadic adult amyotrophic lateral sclerosis.

Clinical and experimental findings in idiopathic amyothrophic lateral sclerosis (ALS) would be compatible with a retroviral involvement. In 35 adult patients with non-familial ALS we observed elevated circulating immune complexes, a decrease in IgG3 isotype and enzyme-linked sorbent assay (ELISA) serum antibodies against human spuma retrovirus (HSRV), confirmed by specific human foamy virus immunoblots. All 35 were negative for IgM or relevant IgG anti-ganglioside antibodies. We treated 12 HIV-negative, immune-complex-positive ALS patients with 500 mg d-1 zidovudine p.o. over 2-10 months and found reductions of serum creatine kinase and circulating immune complexes from two days to two weeks after the beginning of medication.

Adult↗
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

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↗