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Biomedical subjects

H Wachter

Publications and source records attributed to H Wachter.

At least 361 records · Page 20Linked to original sources
PubMed1987

Clinical significance of neopterin for prognosis and follow-up in ovarian cancer.

Neopterin, a pyrazinopyrimidine compound, is a marker of activation of cell-mediated immunity. The prognostic value of pretherapeutically and of serially measured urinary neopterin levels in patients with ovarian cancer was assessed, in a blinded manner, by analysis of 658 urine specimens from 74 women. The specimens were collected during a 5-year period (January 1981 to January 1986). Thirty-one deaths due to cancer were observed during the study period. By statistical analysis, a significant predictive value of pretherapeutic neopterin levels was found and compared with that of other possible prognostic clinical and laboratory findings. Multivariate analysis, using stratification by tumor stage, demonstrated that this predictive information was independent of other variables. A significant association was found between serial neopterin measurements and the current risk of death during follow-up (P less than 0.0001). In addition, current death risk was correlated with neopterin levels measured 6 months previously (P = 0.026). The histological outcome at surgical reexamination was correlated with the current neopterin levels (P = 0.016). Further, normal neopterin levels in women with evidence of tumor at surgical reexamination were shown to be a sign of better prognosis than elevated levels. Measurement of urinary neopterin levels during follow-up of women with ovarian cancer appears to be a valuable adjunct to conventional techniques, particularly in patients refusing explorative surgery.

Biopterins↗
PubMed1987

Neopterin as discriminating and prognostic parameter in healthy homosexuals, ARC and AIDS patients.

Urinary neopterin, a sensitive marker for activation of cell mediated immunity, is compared to clinical and laboratory data in 5 patients with AIDS, in 15 patients with ARC and in 40 male subjects without AIDS-related clinical signs attending an AIDS outpatient clinic. The sensitivity of neopterin for AIDS-related diseases was higher than that of the CD4+/CD8+ subset ratio. The differences in neopterin levels between the controls, ARC and AIDS patients were found to be more significant than the T-cell subset data. The observation that the 3 AIDS patients with the highest neopterin levels have died whereas the two others with the lower levels are still alive also underlines the prognostic potential of urinary neopterin level determinations. Measurement of urinary neopterin is thus recommended as an additional criterion for monitoring ARC and AIDS patients.

AIDS-Related Complex↗
PubMed1987

Human macrophages degrade tryptophan upon induction by interferon-gamma.

Human peripheral blood mononuclear cells, monocytes-macrophages and T-cells were stimulated with human recombinant interferon-gamma, interferon-alpha and phytohemagglutinin. The culture supernatants were analyzed for tryptophan, kynurenine, 3-hydroxyanthranilic acid, anthranilic acid and neopterin by high performance liquid chromatography. Tryptophan was decreased and the four other compounds were increased in supernatants of peripheral blood mononuclear cells activated by interferon-gamma (250 U/ml), interferon-alpha (10.000 U/ml) and phytohemagglutinin (1 microgram/ml). After splitting of peripheral blood mononuclear cells by adherence, the monocytes and macrophages but not the T-cells degraded tryptophan upon stimulation by interferon-gamma in a dose dependent manner. Supernatants of phytohemagglutinin stimulated but not of resting T-cells were found to induce tryptophan degradation by macrophages, the active principle being neutralized by an antiserum for interferon-gamma. Thus phytohemagglutinin acts by activating T-cells to release interferon-gamma which in turn induces macrophages to degrade tryptophan. In all experiments the appearance of neopterin in the culture media was correlated to the observed tryptophan degradation.

Cells, Cultured↗
PubMed1987

[Detection of antibodies to HTLV-III: a comparison of various ELISA methods as screening tests and the Western Blot with immunofluorescence as confirmatory procedures].

386 sera were examined with three commercially available ELISAs for antibodies to HTLV-III. Western Blot and an indirect immunofluorescence assay were performed on sera showing a positive reaction in one or more ELISAs as confirmatory assay. 299 sera reacted negatively in all ELISAs, 48 were positive in all ELISAs and the confirmatory assays, whilst 33 ELISA positive sera reacted negatively in the confirmatory assays. In the case of 5 sera both Western Blot as well as the immunofluorescence assay had to be undertaken to obtain conclusive results.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Role of activated T lymphocytes in mycosis fungoides.

A patient with mycosis fungoides was treated effectively with the immunosuppressant cyclosporine A. Excretion of urinary neopterin, a marker of activation of the cellular immune system, fell immediately at the start of therapy. This result argues in support of a central role of activated T lymphocytes in this disease as has already been proposed by other authors.

Adult↗
PubMed1987

The dependence of cell-mediated immune activation in malaria on age and endemicity.

In vitro, neopterin, a pyrazino-[2, 3-d]-pyrimidine compound, is produced by human monocytes-macrophages following induction by either supernatants from activated T lymphocytes or by recombinant gamma interferon. In vivo, its determination in urine or serum provides a sensitive and specific test for the activation grade of cell-mediated immune reactions. Urinary neopterin levels were measured in 128 Tanzanian individuals (age 6 months to 54 years) with parasitologically proven malaria. Levels in a subgroup of 117 previously untreated patients were compared with those previously reported from 19 untreated malarial patients from Bangkok, Thailand (age 7 to 62 years). The influence of concomitant variables such as age, fever, parasitaemia, duration of symptoms and local endemicity of malaria upon neopterin excretion levels was analysed. In the Thai patients, levels were considerably higher than in Tanzanian subjects of similar age. Among the Tanzanian patients, an overwhelming influence of age was detected, children showing extremely high neopterin excretion levels. The other variables did not influence neopterin levels significantly. Our findings are in accord with recent data on the prevalence and mean titres of antibodies to the circumsporozoite protein of Plasmodium falciparum, which indicate that in endemic areas acquired humoral immunity develops slowly with increasing age, while prevalence and severity of disease decline.

Adolescent↗
PubMed1987

Theoretical implications of cellular immune reactions against helper lymphocytes infected by an immune system retrovirus.

The breakdown of the immune system induced by the human immunodeficiency virus might be due to the active immune destruction of human immunodeficiency virus-infected helper T lymphocytes expressing viral antigens. By numerical simulation, we have studied possible consequences that a hypothetical immunodeficiency virus (IDV) may have on the cellular immune response by using a mathematical model. In this model, IDV infects CD4+ (helper) T cells and is actively synthesized by the immunologically activated helper T cells. Infected helper T cells synthesizing IDV express antigenic determinants specific for IDV and trigger a cellular immune response against themselves that is mediated by cytotoxic T cells and cytotoxic macrophages. The dynamic evolution of the model in the case of mixed-type infections with IDV and with another pathogen that evokes a cell-mediated immune response shows strong interactions between both simultaneous infections. The model might be of value to elucidate the dynamics leading to opportunistic infections. Furthermore, a pivotal role for immunological stimulation in the progressive exacerbation of the disease can be demonstrated.

Antigens, Viral↗
PubMed1987

Interferon-gamma-induced degradation of tryptophan by human cells in vitro.

Several human cells were investigated for their ability to degrade tryptophan and to synthesize neopterin upon induction by interferon-gamma (500 units/ml for 48 h). Concentrations of tryptophan, kynurenine, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, 7,8-dihydroneopterin and neopterin were assessed in the culture supernatants by HPLC. Fibroblasts, A-22 arachnoidea, HK-2351 scalp, T-2346 meningeom and HeLa cervical carcinoma cells but not HL-60 promyelocytic leukaemia cells were found to degrade tryptophan upon induction by interferon-gamma. Tryptophan is converted to kynurenine by fibroblasts, A-22 arachnoidea and HK-2351 scalp cells and to kynurenine and anthranilic acid by HeLa cervical carcinoma and T-2346 meningeom cells. Kynurenine and anthranilic acid always make up more than 82% of the tryptophan degraded. None of these cells synthesizes 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 7,8-dihydroneopterin or neopterin. Human macrophages form 3-hydroxyanthranilic acid and neopterin, but not 3-hydroxykynurenine, beside kynurenine and anthranilic acid upon activation by interferon-gamma. These data indicate that several human cells can be induced by interferon-gamma to degrade tryptophan. The interferon-gamma induced synthesis of 3-hydroxyanthranilic acid and neopterin, however, appears to be restricted to human macrophages. A hypothesis explaining these findings is presented.

Biopterins↗
PubMed1987

Simultaneous determination of neopterin and creatinine in serum with solid-phase extraction and on-line elution liquid chromatography.

This is a method for the simultaneous determination of neopterin, a product of interferon-gamma-activated macrophages, and creatinine in serum. Acidified, but not deproteinized serum is applied to a 4-propylbenzene sulfonic acid-modified silica sorbent cartridge, which quantitatively retains the analytes but not the serum proteins. The retained analytes are then eluted from the cartridge directly onto the liquid-chromatography column. Elution from the cartridge is facilitated by a pulse of 0.4 mol/L, pH 6.8 potassium phosphate buffer. On isocratic elution from an octadecylsilica column with potassium phosphate buffer (15 mmol/L, pH 6.0), neopterin is detected by its native fluorescence, creatinine by ultraviolet absorption. Detection limits are 0.5 nmol/L for neopterin, 1 mumol/L for creatinine at a sample volume of 100 microL. The standard curve is linear over the range of concentrations encountered in sera. For both neopterin and creatinine in serum, concentrations so measured agree well with results by established methods.

Adult↗
PubMed1987

Activated T cells in addition to LAV/HTLV-III infection: a necessary precondition for development of AIDS.

Urinary neopterin levels are raised with a high incidence in all risk groups for AIDS. Neopterin elevations reflect activated cellular immunity in risk group members, in some cases independently of LAV/HTLV-III infection. Moreover, we are able to show that in patients receiving multiple blood transfusions at least a transient challenge of cell-mediated immunity occurs, which is indicated in part by increasing neopterin levels. We conclude that neopterin levels are a reliable index for assessment of susceptibility for AIDS when infection with LAV/HTLV-III occurs. Activated status of cell-mediated immunity might predispose infected persons to an overwhelming infection and secondary spreading of LAV/HTLV-III, thus leading to the development of full-blown AIDS or ARC. As a consequence of these observations, T-cell-stimulatory actions and agents should intentionally be avoided. Treatment of AIDS patients with immunosuppressants should be examined. The success of therapeutic regimens should be monitored by measurement of neopterin levels.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Determination of neopterin in serum and urine.

Concentrations of neopterin, a product of activated macrophages, in serum from 662 apparently healthy individuals (ages 1 to 97 years, median 22 years) were measured by radioimmunoassay and the results statistically analyzed. Consistent with prior investigations on the urinary excretion of neopterin, we found no significant sex dependence, but values for subjects younger than 18 or older than 75 years were significantly higher. Renal clearance of neopterin in nine healthy individuals was 218 (SD 44) mL/min, which suggests that the kidneys have an active role in neopterin excretion. Results for neopterin concentrations measured in serum by RIA and "high-performance" liquid chromatography (HPLC) are consistent, but for urinary neopterin the concordance between methods was weak. Therefore, the RIA should be used only for measuring neopterin in serum. In comparison of the clinical utility of serum neopterin and urinary neopterin/creatinine concentrations, in patients with gynecological tumors, the latter values (measured by HPLC) discriminated slightly better between patients with favorable and unfavorable prognoses.

Adolescent↗