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Biomedical subjects

H Wachter

Publications and source records attributed to H Wachter.

At least 307 records · Page 17Linked to original sources
PubMed1989

Recombinant peptides derived from the env-gene of HIV-2 in the serodiagnosis of HIV-2 infections.

We produced recombinant envelope-derived peptides of HIV-2 for use in a diagnostic enzyme-linked immunosorbent assay (ELISA) or Western blot by expressing several restriction enzyme fragments from the env gene of HIV-2 in the bacterial fusion vector pEX-3. On Western blots, 17 out of 18 anti-HIV-2-positive sera available to us reacted strongly with those recombinant peptides which were derived from, or extended into, the transmembrane protein of HIV-2. In contrast, recombinant peptides derived from the external envelope glycoprotein were only weakly recognized by two sera. We observed a cross-reactivity of some human sera containing antibodies to HIV-1 with the HIV-2 peptides derived from the transmembrane protein of HIV-2. In spite of this cross-reactivity, a serological distinction between anti-sera to HIV-1 and HIV-2 can be attempted by simultaneous testing in ELISA on recombinant peptides derived from the transmembrane protein of HIV-1 and HIV-2.

AIDS Serodiagnosis↗
PubMed1989

Neopterin concentrations in cerebrospinal fluid and serum of individuals infected with HIV-1.

Neopterin, a biochemical marker for the activation of cell-mediated immune reactions, was determined in serum and cerebrospinal fluid (CSF) from patients infected with HIV-1. A significant correlation was found between serum and CSF neopterin concentrations, although concentrations of neopterin in serum were more closely correlated with the clinical severity of HIV-1 infection than those in CSF. However, higher CSF levels were observed in patients with neurologic/psychiatric symptoms than in unaffected patients. Also, quotients of CSF neopterin versus serum neopterin concentrations were increased, indicating intrathecal production of neopterin. Positive HIV-1 isolation from peripheral blood mononuclear cells (PBMC) was associated with higher neopterin concentrations in serum, when compared with negative HIV-1 isolation. Neopterin in CSF appears to be a suitable biochemical marker in patients with HIV-1 infection for detecting overt neurologic/psychiatric disturbances. The data suggest that in HIV-1 infected patients, cell-mediated immune reactions might be activated intrathecally and might contribute to neuropsychiatric disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Urinary neopterin concentrations in rhesus monkeys after infection with simian immunodeficiency virus (SIVmac 251).

Two rhesus monkeys were infected with SIVmac 251. Elevated urinary neopterin concentrations were observed as the first sign of infection. Virus-specific antibodies were detected 14 days after infection, when neopterin concentrations were already decreasing. The neopterin levels of one animal remained elevated and the virus was repeatedly isolated. Urinary or serum neopterin concentrations appear to be early markers for SIV infection and viremia in rhesus monkeys.

Animals↗
PubMed1989

Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells.

The capacity of recombinant interferon-alpha, -beta and -gamma, of bacterial lipopolysaccharide and of recombinant tumour necrosis factor-alpha to induce indoleamine 2,3-dioxygenase and synthesis of pteridines was studied in human peripheral blood mononuclear cells, human macrophages and normal dermal fibroblasts. The action of interferon-alpha and -beta on macrophages was supported by lymphocyte factors as indicated by the effect of these mediators in the absence or presence of lymphocytes. Tumour necrosis factor-alpha alone was ineffective in peripheral blood mononuclear cells and macrophages, but it significantly increased the action of all three interferon species on macrophages and fibroblasts. Lipopolysaccharide directly affected macrophages or dermal fibroblasts and enhanced the effect of interferon-gamma. However, in the presence of lymphocytes, the action of lipopolysaccharide was mediated via interferon-gamma.

Biopterins↗
PubMed1989

Interferon-gamma concentrations are increased in sera from individuals infected with human immunodeficiency virus type 1.

Serum concentrations of interferon-gamma were measured in individuals seropositive for human immunodeficiency virus type 1 (HIV-1). According to the CDC classification system, 6 presented with stage IV-C, 5 with stage IV-A, 8 with stage III, and the remaining 24 individuals with stage II. A modified radioimmunoassay procedure for detection of interferon-gamma was used with a detection limit of 18 U/L. Approximately one-half (22/43) of the seropositives exhibited increased serum interferon-gamma concentrations compared with seronegative blood donors (n = 76). There was a significant association between serum interferon-gamma concentrations and CDC stages of the patients; patients classified as CDC IV-C had the highest concentrations. Further, a significant positive correlation was observed between serum interferon-gamma and serum neopterin concentrations in seropositive study participants. We conclude that interferon-gamma is present in increased concentrations in HIV-1 seropositives compared to seronegative blood donors. Diminished in vitro production of interferon-gamma by T-lymphocytes on stimulation with specific soluble antigens contrasts with increased levels of circulating interferon-gamma in patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Generalized likelihood ratio concept and logistic regression analysis for multiple diagnostic categories.

Albert (Clin Chem 1982;28:1113-9) has proposed estimation of likelihood ratios by logistic regression analysis. The usual likelihood-ratio approach for estimation of post-test probability of disease from sensitivity and specificity data of a diagnostic test has been extended by Birkett (J Clin Epidemiol 1988; 41:491-4) for situations with more than two diagnostic categories. We suggest here a combination of these ideas, demonstrating this by a re-evaluation of previously published data on the validity of neopterin as a tool for differential diagnosis between chronic non-A, non-B hepatitis and fatty liver. Analysis of neopterin data in combination with the ratio between serum concentrations of aspartate aminotransferase and of alanine aminotransferase yielded a good discrimination between three mutually exclusive diagnostic categories, namely, fatty liver and chronic persistent and chronic aggressive non-A, non-B hepatitis. The approach is flexibly applicable to situations with different pre-test probabilities. The sum of estimated post-test probabilities deviates slightly from the sum of pre-test probabilities. This deviation is a function of the coefficients obtained in logistic regression, and an analytical expression for the deviation is given. The generalized likelihood-ratio approach appears promising in complex diagnostic situations when multiple diagnostic tests are available.

Alanine Transaminase↗
PubMed1989

Neopterin excretion after liver transplantation and its value in differential diagnosis of complications.

The aim of this study was to investigate patterns and clinical utility of a neopterin marker in liver allograft recipients. Urinary neopterin levels were studied in 59 transplant patients daily until discharge. During the early postoperative period (days +1 to +20) neopterin excretion exhibited a liver-specific pattern that clearly differed from that seen in renal and bone marrow transplant recipients. Neopterin concentrations increased and reached peak values on day +7. The height of this early peak varied in context with complications such as infection or rejection, and was correlated with an unfavorable prognosis. In contrast to the early phase, no liver-specific pattern was observed after day 20. As seen in all other transplant patient populations, values normalized in patients with an uncomplicated course but again increased during infection or rejection episodes. Neopterin levels were particularly high during CMV infection, and their increments were directly related to the severity of CMV disease. The neopterin marker, although not specific, enables discrimination between patients with a complicated and uncomplicated clinical course. High neopterin values early after transplantation are associated with unfavorable prognosis and correlate with an increased risk of developing CMV disease.

Biopterins↗
PubMed1989

Neopterin: a predictive marker of acquired immune deficiency syndrome in human immunodeficiency virus infection.

In 79 homosexual men infected with human immunodeficiency virus (HIV), urinary neopterin was significantly higher as compared with 70 HIV-seronegative men in the same cohort (p less than 0.0001). This highly significant association was found both for naturally occurring oxidized (native) neopterin and for total neopterin (native plus chemically oxidized forms). In prospective follow-up for 18 months, the odds that the acquired immune deficiency syndrome (AIDS) would develop were elevated 25-fold among those whose native neopterin levels were in the highest quartile compared with those with lower neopterin levels, and the corresponding odds ratio for total neopterin was 7.8. Logistic regression analyses indicated that neopterin added useful information to T4-cell count in predicting AIDS onset and that both are statistically significant in the multivariate model. A cross-sectional survey revealed that neopterin levels were correlated with number of receptive anal intercourse partners in the year before HIV seroconversion (r = 0.60, p = 0.0005). Since neopterin may serve as a marker of monocyte/macrophage activation by soluble factors such as gamma-interferon, these data support a growing body of virologic and immunologic evidence that highlights the important role of the monocyte/macrophage in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Urinary neopterin concentrations vs total neopterins for clinical utility.

Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV-1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4+ T-cell counts and CD4+/CD8+ T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8-dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8-dihydro derivative.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Effects of interferon-alpha on macrophage activation in patients with ovarian carcinoma and cervical dysplasia.

Patients with progressive ovarian carcinoma and patients with dysplasia of the uterine cervix were studied in order to compare clinical efficacy, hematological toxicity and effects on macrophage activation of administered interferon-alpha for both patient groups. One of three patients with ovarian carcinoma showed a minor response. Four of six patients with cervical dysplasia had slight improvements of PAP-smears. Moderate hematological toxicity was observed in the former patient group while side effects were much more pronounced in the latter patients group. However, changes of hematological parameters were not statistically different. Interestingly, the administered interferon-alpha caused the same activation of macrophages in both patients groups as indicated by raised neopterin levels. This activation does not result in clinical improvement but appears to play a role for the hematological toxicity observed during therapy of patients with ovarian carcinoma. It has been suggested that suppression of hematopoiesis is mediated by interferon-gamma. The present neopterin data propose that this lymphokine is continuously produced through influence of the tumor and enhanced by interferon-alpha.

Adult↗
PubMed1989

Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection.

We assessed the value of urinary neopterin concentrations for prognosis of disease progression in HIV-1-infected patients. Sixty-eight anti-HIV-1 seropositive homosexuals with lymphadenopathy syndrome were tested for urinary neopterin and T-cell subset counts in 1982-83, and the incidence rate at which they developed acquired immunodeficiency syndrome (AIDS) between then and May 1988 was evaluated. Overall, 21 of 68 (30.9%) cases progressed to AIDS, with a yearly progression rate of 4-9%. The predictive value of urinary neopterin concentrations was higher (P = 0.0042) than that of CD4+ T-cell counts (P = 0.015) or the CD4+/CD8+ T-cell ratio (P = 0.022). Counts of CD8+ T-cells failed to show predictive significance (P = 0.29). Similarly, multivariate-regression analysis indicated that neopterin concentrations and CD4+ T-cell numbers were significant copredictors. Produced by human macrophages activated by interferon gamma, neopterin is thus a marker of macrophage activation via T cells. We conclude that these data demonstrate a correlation between the amount of T-cell-macrophage activation, as measured by urinary neopterin concentrations, and the progression of the disease.

AIDS-Related Complex↗
PubMed1989

Effect of D-penicillamine on the expression and propagation of the human immunodeficiency virus by H9 T-lymphoblastoid cells.

The effect of D-penicillamine on the replication of the Human Immunodeficiency Virus (HIV) in H9 T-lymphoblastoid cells was evaluated. HIV-infected and uninfected H9 cells were incubated for a period of 6 weeks with various concentrations of D-penicillamine. During the first 8 days, D-penicillamine (at concentrations of 0-150 micrograms/ml) did not influence growth and viability of H9/H9-IIIB cells. However, long term cultures and higher doses of the drug caused a decay in cell number and viability of the cultured cells. Up to the 8th day of culture, D-penicillamine did not exert an inhibiting effect on the number of HIV-infected cells but did suppress HIV-antigen production by up to 29%. After 6 weeks, in addition to a decrease of the relative viral antigen concentration from 390-500 ng/ml in the medium control to 210-320 ng/ml in cultures containing 150 micrograms D-penicillamine/ml, D-penicillamine also reduced the percentage of HIV-positive cells. Thus our results demonstrate an antiviral effect of D-penicillamine in H9 cultures.

Cells, Cultured↗