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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 487 records · Page 27Linked to original sources

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↗

[Cryopreservation of bone marrow for the autologous transplantation in children].

In preparing the autologous transplantation of children a method for cryoconservation of bone-marrow was developed by means of investigating the donor's bone-marrow. This method is adapted to our conditions, can easily be practised and is cell-preserving. Quantity and quality of the stored bone-marrow cells were evaluated concerning their proliferation capability by means of CFU-c assays. The highest recovery in CFU-c (78%) and cells (98%) was observed if isolated mononuclear cells with cryoprotective addition of 5% DMSO, 20% of human albumin, and 20% of serum were slowly frozen at a controllable rate, stored in liquid oxygen and thawed very quickly. According to the elaborated method the remission marrow was taken from 15 children affected with malignant diseases for autologous reinfusion. The data gained here confirm the experimental experiences.

Adolescent↗

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↗

Immune status of drug abusers.

This study followed 184 drug abusers. Examined in all of them were urinary neopterin levels, HBV, SGOT, and Luestest. Seventy-three percent of IV drug addicts showed elevated neopterin levels reflecting activated cellular immunity. Statistically, no correlation of neopterin levels with, eg, excessive alcohol consumption, duration of drug abuse, or studied laboratory parameters was found. Individuals using cocaine revealed higher neopterin levels than those not doing so. Twenty-one of twenty-two patients with no parenteral drug use had normal neopterin excretion. In 34 drug detoxification patients, we examined in addition: T-lymphocyte subsets (T4/T8 ratio) and serum neopterin levels. Thirty-eight of ninety-four parenteral drug addicts presented with anti-LAV/HTLV-III antibodies (ELISA + Western blot + IFT). Our data demonstrate an activated cellular immune status in parenteral drug addicts that cannot be attributed to LAV/HTLV-III infection in all cases. The development of AIDS seems to depend not only on the exposure to LAV/HTLV-III but also on activated cellular immunity, which is easily assessed by neopterin measurement.

Antibodies, Viral↗

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↗

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↗

Who will get AIDS?

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Acquired Immunodeficiency Syndrome↗

[Activation of the macrophage/lymphocyte system in AIDS, ARC and AIDS risk groups].

Elevated neopterin levels are indicative of activation of the cellular immune system. Studies on excretion of neopterin in patients with AIDS and ARC, as well as in members of risk groups have demonstrated repeated or permanent stimulation of the immune system. This stimulation can be observed in all risk groups independent of LAV/HTLV-III infection. Additionally, in vitro replication of LAV/HTLV-III has been observed to be quantitatively greatest in activated CD4+-lymphocytes. Hence, we conclude that activation of the cellular immune system represents the central cofactor for progressive LAV/HTLV-III infection. These findings seem to contrast with most reports in the literature to date, but observations of other authors corroborate them. As consequence of these studies, therapeutic regimens using immunostimulatory strategies should be prevented in AIDS and ARC patients. Immunosuppressive treatment should be considered.

Acquired Immunodeficiency Syndrome↗

[HTLV-III in persons with intravenous drug abuse. Correlation of antibodies against HTLV-III with neopterin and TH/TS].

Antibodies against HTLV-III, neopterin levels in blood and urine, TH/TS ratio and hepatitis marker were determined in 34 clinically symptom-free persons known to be intravenous drug abusers. 15 persons were positive in the ELISA and Western-blot tests. There was a strong reaction to protein p24 compared with that to protein p41. In 12 of 14 persons who were antibody-positive the neopterin level in morning urine was elevated; an abnormal TH/TS ratio was present in nine of 13 persons. In future, determination of neopterin and of antibodies against certain proteins of HTLV-III may make it possible to provide a simple way of prognosticating on the course of an HTLV-III infection.

Acquired Immunodeficiency Syndrome↗

Urinary neopterin, a marker of clinical activity in patients with Crohn's disease.

Urinary neopterin excretion was measured in 34 patients with Crohn's disease. Neopterin excretion showed a significant correlation with disease activity using a clinical activity score. An interacting effect of previous medical or surgical therapy on neopterin excretion could be ruled out. Disease localization and extent did not exert any influence on neopterin excretion. Neopterin values were significantly correlated with disease duration, body weight and the presence of a palpable abdominal mass. Multiple stepwise regression analyses identified the combination of neopterin, hematocrit, weekly stool frequency, palpable abdominal mass and related symptoms as predicting clinical activity better than Crohn's Disease Activity Index (CDAI). Thus, neopterin determination may be introduced as an additional biochemical parameter in the assessment of disease activity.

Adolescent↗

Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis.

Neopterin is a marker for activation of cellular immunity. Urinary neopterin levels were measured in 106 patients with rheumatoid arthritis (RA) and in 45 patients with osteoarthritis. Levels were significantly higher in RA patients than in osteoarthritis patients and were strongly dependent on stage and activity of RA. Correlations with other laboratory parameters were weak. Multivariate analysis demonstrated that urinary neopterin levels reflected clinical activity better than did other laboratory findings. Thus, urinary neopterin determination might be useful in monitoring RA patients.

Aged↗