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Biomedical subjects

R Zangerle

Publications and source records attributed to R Zangerle.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neopterin, beta 2-microglobulin, and acute phase proteins in HIV-1-seropositive and -seronegative Zambian patients with tuberculosis.

Neopterin is a biochemical marker for the activation of the cell-mediated immune system. We measured neopterin, beta 2-microglobulin, and acute phase proteins in 31 HIV-seropositive and -seronegative Zambian patients with tuberculosis, using stored sera that had been obtained at the beginning and at end of antituberculosis treatment. In both HIV-seropositive and -seronegative patients neopterin and acute phase proteins were elevated when tuberculosis was initially diagnosed and fell during treatment. In contrast, the mean beta 2-microglobulin level increased during antituberculous therapy in the HIV-seropositive group. Serum neopterin levels at diagnosis were correlated with other parameters of disease activity (fever, anemia, and weight loss). In both groups, patients with persistently elevated neopterin levels at the end of treatment were more likely to suffer relapse of tuberculosis or other adverse health events in the subsequent follow-up period. Neopterin can be used to monitor the response to antituberculous therapy in both HIV-seropositive and -seronegative patients and may have a prognostic value for the patients' wellbeing in the follow-up period.

AIDS-Related Opportunistic Infections↗
PubMed1997

Has the rate of progression to AIDS changed in recent years?

OBJECTIVES: To investigate whether the rate of progression to AIDS has changed over time by testing an effect of the year of seroconversion on AIDS onset (Centers for Disease Control and Prevention 1987 revised classification), next to an effect of the calendar period of follow-up. DESIGN: French multicentre prospective study of 385 homosexual and heterosexual subjects and 231 subjects from a multicentre study of European injecting drug users (IDU), all with a documented date of HIV-1 seroconversion. METHOD: The effect of the year of seroconversion was compared by the log-rank test. Crude and adjusted relative hazard (ARH) were quantified using the Cox model. Calendar period of follow-up was studied separately for sexual exposure group and IDU and treated as a time-dependent variable in a Cox model. RESULTS: In the 616 study subjects the year of seroconversion was not significantly related to AIDS occurrence (n = 108); the ARH was 0.88 [95% confidence interval (CI), 0.56-1.38] for those who seroconverted in 1988-1989, and 1.17 (95% CI, 0.61-2.25) for those who seroconverted after 1989, compared with those who seroconverted before 1988. In the sexual exposure group, a clear trend towards less rapid progression to AIDS was observed in subjects followed in 1991-1992 (ARH, 0.49; 95% CI, 0.24-0.99) and after 1992 (ARH, 0.54; 95% CI; 0.24-1.21), compared with those followed before 1991. This favorable trend was not observed in IDU despite a significant decrease over time of Pneumocystis carinii pneumonia as AIDS-defining illness. Conversely to sexual exposure groups, the frequency of antiretroviral treatment (mainly zidovudine) prescription was still low during the most recent calendar periods in IDU when the CD4 count threshold of 200 x 10(6)/l was reached. CONCLUSIONS: No evidence was found of a change in the rate of progression to AIDS in subjects who seroconverted in recent years. Furthermore, conversely to sexual exposure groups, the lack of favorable trends in IDU users followed in recent years suggest that health-care systems are not always adapted to their lifestyles.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin.

OBJECTIVES: Elucidation of the mechanisms of the previously shown growth-inhibitory action of human chorionic gonadotropin (hCG) on Kaposi's sarcoma (KS) cells and the role of the luteinizing hormone/hCG receptor (hCGR). DESIGN AND METHODS: Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCGR using 125I-hCG binding and reverse transcriptase-polymerase chain reaction; analysis of several hCG preparations (urinary, recombinant, isolated alpha and beta subunits); analysis of apoptosis mechanisms by several assays including using z-Val-Ala-Asp-fluoromethylketone (zVAD-FMK), a known apoptosis-inhibitory drug. RESULTS: First, we found that some urinary preparations of hCG (e.g., CG-10, Steris Profasi) were indeed KS-killing but others (such as Pregnyl, Choragon, Serono Profasi) were not. Secondly, recombinant subunits (alpha as well as beta) of hCG were KS cell-killing but recombinant intact hCG was not. Thirdly, the hCGR message and protein were undetectable in KS. Fourthly, CG10-induced cell death occurred by apoptosis and KS cells could be rescued by preincubation with zVAD-FMK. Finally, we also found that normal peripheral blood lymphocytes (PBL) were killed by CG-10. CONCLUSION: It is proposed that the action of subunits or subunit fragments of hCG, mediated by a putative orphan receptor (as opposed to the hCGR) and executed by interleukin-1-converting enzyme (ICE)-like protease(s), constitutes a novel apoptosis mechanism effective towards KS cells, but PBLs and possibly other cells as well. These results provide a basis for testing in vitro the therapeutic efficacy of hCG preparations which, in turn, should improve current clinical trials with 'hCG' in patients who have KS.

Amino Acid Chloromethyl Ketones↗
PubMed1995

Survival differences in Austrian patients with the acquired immunodeficiency syndrome.

We investigated the association of clinical and demographic factors on survival of the 901 AIDS cases diagnosed until 31 December 1992 and reported to the Austrian Health Authorities up to 20 January 1994. The overall estimated median survival of patients with AIDS increased substantially from 8 months in 1987 to 16 months in 1988, although this increase was not significant by the log-rank test. However, the differences in hazard rates were larger at the beginning of the survival curve: between 1987 and 1988 the proportion surviving at 1 year increased from 41 to 62%, compared to an increase of the proportion surviving at 2 years from 30 to 35% (Breslow test, p value 0.008). AIDS patients diagnosed between 1988 and 1992 (n = 755) were analyzed in more detail. Multivariate survival analysis revealed a shorter survival for those with residence in Eastern Austria, recipients of blood products, individuals with unknown transmission risk, those presenting with two AIDS indicator diseases and those with higher age at AIDS diagnosis. Candidal esophagitis as AIDS indicator disease was associated with longer survival. One hundred eighty-eight of the 755 AIDS patients (24.9%) died within the first 3 months after diagnosis of AIDS. We conclude that the survival time for AIDS patients has improved considerably after 1987, but survival is still very poor. Several factors have been shown to predict survival of patients with AIDS in Austria. Death within the first 3 months after the diagnosis of AIDS occurred at a relatively high frequency in Austrian AIDS patients. This may be caused by difficulties in the use of health care facilities or by the lack of awareness of HIV infection before diagnosis of AIDS either by patient or care provider.

AIDS-Related Opportunistic Infections↗
PubMed1995

Sera from HIV-1 infected individuals in all stages of disease preferentially recognize the V3 loop of the prototypic macrophage-tropic glycoprotein gp120 ADA.

The outer membrane glycoprotein gp120 and the transmembrane glycoprotein gp41 are predominant targets of the humoral immune response to infection by human immunodeficiency virus type 1. The third hypervariable region (V3 loop) is the principal neutralizing domain and is the primary target of neutralizing antibodies directed against the envelope proteins of HIV-1. The V3 loop is also the major determinant for HIV-1 cell-specific tropism. To further characterize the humoral immune response directed against the gp120 envelope proteins, we expressed two prototypic gp120 envelope proteins (LAI/HXB2 and ADA) and chimeric gp120 envelope proteins in stable transfected Drosophila melanogaster Schneider 2 cells. Sera from four infected adults over the course of infection [McNearney et al. (1992) Proc. natn. Acad. Sci. U.S.A. 89, p. 10,242] were assayed for reactivity with the respective envelope proteins. Sera obtained at early stages preferentially recognized the gp120 envelope protein ADA, whereas in later stages of infection the sera showed diminished reactivity with both gp120 LAI/HXB2 and gp120 ADA. Chimeric envelope proteins revealed that the humoral response was directed primarily against the V3 loop of gp120 ADA. Furthermore, 22 sera from HIV-1 infected individuals in different stages of the disease were tested. Reactivity of sera with the gp120 envelope protein ADA was seven-fold higher than with the gp120 envelope protein LAI/HXB2. Our results suggest that the humoral immune response is preferentially elicited against the V3 loop of the prototypic macrophage-tropic gp120 envelope protein ADA.

Adult↗
PubMed1995

Serum nitrite plus nitrate in infection with human immunodeficiency virus type-1.

To get a measure of the extent of induction of nitric oxide synthase in infection with human immunodeficiency virus type-1 (HIV-1) in vivo, we estimated serum nitrite plus nitrate concentrations in 110 HIV-1 infected individuals compared to 76 blood donors. To monitor cytokine action and to measure induction of pteridine synthesis, we determined in parallel neopterin, biopterin, soluble tumor necrosis factor-alpha receptor 55 and 75, and beta 2-microglobulin. Serum nitrite plus nitrate concentrations were elevated in patients as compared to blood donor controls. In sera of patients, nitrite plus nitrate levels correlated significantly with neopterin, soluble tumor necrosis factor receptor 55 and 75, and beta 2-microglobulin. Nitrite plus nitrate levels were higher and correlations were stronger in groups of patients with lower CD4+ cell count. These results suggest that cytokine-mediated nitric oxide synthesis occurs in individuals with HIV-1 infection.

Adult↗
PubMed1995

Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis.

Soluble tumour necrosis factor receptors (sTNF-Rs) play a role as modulators of the biological function of tumour necrosis factor-alpha (TNF-alpha) in an agonist/antagonist pattern. In various pathologic states the production and release of sTNF-Rs may mediate host response and determine the course and outcome of disease by interacting with TNF-alpha and competing with cell surface receptors. The determination of sTNF-Rs in body fluids such as plasma or serum is a new tool to gain information about immune processes and provides valuable insight into a variety of pathological conditions. Regarding its immediate clinical use, sTNF-Rs levels show high accuracy in the follow-up and prognosis of various diseases. In HIV infection and sepsis, sTNF-Rs concentrations strongly correlate with the clinical stage and the progression of disease and can be of predictive value. Determination of sTNF-Rs also gives useful information for monitoring cancer and autoimmune diseases. The information provided is often even superior to that obtained with classical disease markers, probably due to the direct involvement of the "TNF system" in the pathogenetic mechanisms in these patients. The available data imply that the measurement of sTNF-Rs, especially of the sTNF-R 75kD type, is a useful adjunct for quantification of the Th1-type immune response, similar to other immune activation markers such as neopterin and beta 2-microglobulin. Endogenous sTNF-Rs concentrations appear to reflect the activation state of the TNF-alpha/TNF receptor system.

Communicable Diseases↗
PubMed1994

Serum concentrations of circulating endogenous granulocyte-macrophage colony-stimulating factor in HIV-1-seropositive injecting drug users.

OBJECTIVES: We compared serum concentrations cytokines in seronegative and seropositive HIV-I intravenous drug abusers. METHODS: The cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and the immune activation markers soluble interleukin-2 receptor (sIL-2R) and neopterin were determined in sera of HIV-1-seropositive and HIV-1-seronegative injecting drug users (IDUs). RESULTS: HIV-1-seropositive IDUs showed significantly lower serum concentrations of GM-CSF (p = 0.0064) and significantly higher concentrations of neopterin (p = 0.0005) than HIV-1-seronegative IDUs. All HIV-1-seropositive IDUs had neopterin levels above the normal range. Levels of TNF-alpha in HIV-1-seronegative IDUs did not differ from HIV-1-seropositive IDUs. Increased levels of IL-1 beta were found in 83.3% HIV-1-seronegative and in 94.4% HIV-1-seropositive IDUs with no significant difference between the two groups. An increase of serum levels of sIL-2R was found in 60% HIV-1-seronegative and in 63.6% HIV-1-seropositive IDUs. Again, no difference was found between the two groups. Neopterin concentrations correlated with TNF-alpha in HIV-1-seropositive as well as in HIV-1-seronegative IDUs, neopterin concentrations correlated with sIL-2R only in the HIV-1-seropositive IDUs. No correlations were found for GM-CSF. CONCLUSIONS: An impaired production of GM-CSF may contribute to the loss of the myelopoetic progenitor cells and to the functional abnormalities of leukocytes associated with HIV-1 infection. Injecting drug use contributes to the levels of immune activation markers, therefore their use in HIV-1 infection may be limited in IDUs. However, neopterin remains a useful marker for HIV-1 infected IDUs.

Adult↗
PubMed1994

Increased concentrations of soluble tumor necrosis factor receptor 75 but not of soluble intercellular adhesion molecule-1 are associated with the decline of CD4+ lymphocytes in HIV infection.

Immune activation seems to be involved in the pathogenesis of human immunodeficiency virus (HIV) infection. The immune activation markers neopterin and beta 2-microglobulin can predict the future rate of the decrease in CD4+ T cells. In a longitudinal study, we assessed whether the decline in the CD4+ T-cell count is associated with increased concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble tumor necrosis factor receptor 75 (sTNFR 75), compared to increased concentrations of beta 2-microglobulin and urinary neopterin. Forty-seven individuals representing all stages of HIV infection were followed-up for a mean of 12.7 months (range, 8 to 16 months). The percentage of the change of the CD4+ T-cell count from study entry to study end ranged from -97 to +98%; the median was -33%. Concentrations of urinary neopterin, sTNFR 75, and beta 2-microglobulin correlated with the percentage of the change of the CD4+ T-cell count from study entry to study end (r = -0.45, confidence interval (CI) -0.65 to -0.19; r = -0.42, 95% CI -0.63 to -0.15; and r = -0.416, 95% CI -0.62 to -0.15), but those of sICAM-1 did not. This difference was found despite significant correlations between sICAM-1 and sTNFR 75 and beta 2-microglobulin. Levels of sICAM-1 obtained at study entry correlated with levels of sICAM-1 obtained at study end (r = 0.46, 95% CI 0.17 to 0.68). In a multivariate linear regression analysis, urinary neopterin and sTNFR 75 were jointly significant for the percentage of the change of the CD4+ T-cell count. These results suggest that sTNFR 75 is a useful marker to estimate disease progression in HIV infection, whereas sICAM-1 does not seem to provide any information related to the decline of the CD4+ T-cell count.

Adult↗
PubMed1994

Tumor necrosis factor alpha and soluble tumor necrosis factor receptors in individuals with human immunodeficiency virus infection.

There is some ongoing debate as to whether tumor necrosis factor (TNF) alpha levels are elevated in human immunodeficiency virus infection (HIV), however TNF alpha is rapidly cleared from the circulation and long-term markers have to be analyzed. Two distinct TNF alpha receptors have been identified, which also exist in soluble forms. The aim of this study was to investigate whether an association in HIV infection exists between the serum levels of TNF alpha, the two soluble TNF receptors (sTNFRs) and other soluble immune activation markers, namely neopterin and beta 2-microglobulin, and the number of CD4+ T-cells. We investigated 63 individuals with HIV infection for serum levels of TNF alpha, sTNFR 55, sTNFR 75, beta 2-microglobulin and urinary neopterin. The study population comprised all stages of HIV infection: 35 were asymptomatic, 8 had oral candidiasis, 4 had constitutional signs and 16 had AIDS. Circulating levels of TNF alpha were detectable in 22 of 63 (34.9%) individuals. For those with detectable TNF alpha levels the median concentration was 40 pg/ml. The frequency and extent of TNF alpha levels found in those with advanced HIV infection as defined by a CD4+ T-cell count below 320 x 10(6)/l did not differ significantly compared to those with a higher CD4+ T-cell count. Increased concentrations were found in 69.8% of the patients for sTNFR 55 and in 87.3% for sTNFR 75. Serum concentrations of sTNFR 55 and sTNFR 75 were higher in the group with the lower CD4 T-cell count (P = 0.006 and P = 0.0003). TNF alpha correlated with sTNFR 75 and weakly with sTNFR 55 and beta 2-microglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Correlation of body mass index with urinary neopterin in individuals infected with human immunodeficiency virus.

We assessed correlations between body mass index and plasma lipids, immune activation markers and the CD4+ T-cell count. The subjects of this cross-sectional study were randomly selected and comprised all those who attended the AIDS Out-Patient Clinic at the University Hospital in Innsbruck in March and April 1992. Patients with signs and symptoms of acute bacterial and secondary opportunistic infections were excluded. We investigated 63 individuals with HIV infection of whom 35 were asymptomatic, 8 had oral candidiasis, 4 had constitutional signs and symptoms and 16 had AIDS, for an association among body mass index, urinary neopterin, soluble tumor necrosis factor receptors (sTNFRs), plasma lipids, and the numbers of CD4+ T cells. The body mass index correlated inversely with urinary neopterin (rs = -0.42, p = 0.0009) and weakly with the numbers of CD4+ T cells (rs = 0.29, p = 0.02) but not with plasma lipids, sTNFRs and beta 2-microglobulin. The results show that body mass index correlates with immune activation. The data suggest that endogenous formation of interferon-gamma may be an important mediator of wasting in HIV infection, since this cytokine is responsible for the observed elevation of neopterin concentrations in body fluids.

Adult↗
PubMed1994

Increased serum concentrations of soluble tumor necrosis factor receptors in HIV-infected individuals are associated with immune activation.

Serum concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) were measured in 61 human immunodeficiency virus (HIV)-infected individuals. Thirty-five percent of these had increased serum concentrations of sTNF-R type I (p55) (sTNF-R55) and 82% had increased concentrations of sTNF-R type II (p75) (sTNF-R75). The extent of the increase of sTNF-R75 was greater in more advanced HIV infection (p = 0.046) as it was measured by dividing the 61 individuals into two groups according to the median of the CD4+ T-cell count. However, the increase in concentrations of sTNF-R55 in the group with a CD4+ T-cell count below the median was only moderate and did not reach statistical significance. A strong correlation was found between sTNF-R75 and the soluble immune activation markers beta 2-microglobulin (rs = 0.74, p < 0.0001) and urinary neopterin (rs = 0.67, p < 0.0001), and a less strong correlation was found with interferon-gamma (rs = 0.51, p = 0.0001). The correlations observed for sTNF-R55 were also significant but were always weaker than that of sTNF-R75. A weak inverse correlation was found between the number of CD4+ T cells and sTNF-R75 (rs = -0.33, p = 0.012), but no such correlation was observed with sTNF-R55. Our findings suggest that increased concentrations of serum sTNF-Rs in HIV infection are linked to immune activation, in which synergistic actions of interferon-gamma and the TNF-alpha system are likely to play an important role.

Adolescent↗