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D Fuchs

Publications and source records attributed to D Fuchs.

At least 55 records · Page 3Linked to original sources
PubMed1992

Iron modulates interferon-gamma effects in the human myelomonocytic cell line THP-1.

This investigation demonstrates that low concentrations (25 microM) of free and transferrin-bound iron reduce the efficiency of the interferon-gamma (IFN-gamma) signal in the human myelomonocytic cell line THP-1, as seen by decreased production of neopterin, reduced degradation of tryptophan, and impaired expression of major histocompatibility complex (MHC) class II antigens. This inhibitory effect of iron, which is not due to an enhanced cytotoxicity towards THP-1 cells, is increased by enhancement of iron concentrations in a dose-dependent relationship and can be partially reversed by increasing amounts of the cytokine. The iron-mediated inhibition of the effects of IFN-gamma is fully reversed when iron is administered concomitantly with equimolar concentrations of the iron chelator deferoxamine. Furthermore, deferoxamine alone is even able to enhance the efficiency of the IFN-gamma signal. Our data provide evidence that there is an inverse correlation between the intracellular amount of iron, which is not bound to ferritin, and the activity of the IFN-gamma signal. This suggests that iron withholding by the immune cells in the course of inflammatory disorders may also contribute to the enhancement of the cytopathic effect of IFN-gamma. This speculation is confirmed by the observation of high concentrations of immune activation markers such as IFN-gamma and neopterin and low serum iron levels in patients with hypoferric anemia in the course of chronic inflammation.

Biopterins↗
PubMed1992

[Results of allogenic and autologous bone marrow transplantation in children with acute myeloid leukemia].

We report on our experience of bone marrow transplantation (BMT) in children with acute myeloblastic leukaemia (AML) and high risk of relapse (initial WBC greater than 20 x 10(9)/l, FAB M 5, M 6, M 7). 32 children were grafted between november 1982 and october 1991 at the Children's Hospital of the University of Jena. Two patients underwent an allogenous BMT in relapse and died from progressive disease. In 13 children an allogeneic BMT was performed in first complete remission. One patient relapsed, two patients died from severe acute graft-versus-host disease, and two patients died from encephalopathy and cardiomyopathy. Eight of the 13 patients are living and well 18 months to eight and a half year after BMT. Seventeen patients received an autologous (unpurged) BMT. Four of them relapsed four to seven months after BMT. The disease free survival (DFS) for the 29 patients grafted in remission was 0.65. There was no statistical significant difference in DFS between patients with allogeneic and autologous BMT. We conclude that in children with AML and high risk for relapse BMT offers a real chance for better survival. Autologous BMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.

Adolescent↗
PubMed1991

Impact of tumour necrosis factor-alpha and interferon-gamma on tetrahydrobiopterin synthesis in murine fibroblasts and macrophages.

Tumour necrosis factor-alpha causes an up to 30-fold induction of GTP cyclohydrolase I (EC 3.5.4.16) activity in murine dermal fibroblasts in a dose-dependent manner. Owing to the high constitutive activities of 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase (EC 1.1.1.153), this potentiates biosynthesis of tetrahydrobiopterin. Murine macrophages already contain high activities of GTP cyclohydrolase I when unstimulated, and this is further augmented up to 4-fold by tumour necrosis factor-alpha/interferon-gamma. In Western blots an antiserum to murine liver GTP cyclohydrolase I does not stain cell extracts with high enzyme activities, suggesting that the cytokine induced peripheral form of GTP cyclohydrolase I might differ from the liver form.

Animals↗
PubMed1991

6-Pyruvoyl tetrahydropterin synthase assay in extracts of cultured human cells using high-performance liquid chromatography with fluorescence detection of biopterin.

An assay for 6-pyruvoyl tetrahydropterin synthase, the second enzyme in the conversion of guanosine triphosphate into tetrahydrobiopterin, has been developed. Cell extracts were incubated with enzymatically prepared dihydroneopterin triphosphate (80 microM) in the presence of Mg2+ (12 mM), excess sepiapterin reductase (EC 1.1.1.153) (2 nmol/min) and NADPH (2 mM). 6-Pyruvoyl tetrahydropterin, the product of the reaction, was thus converted into tetrahydrobiopterin. After oxidation of the reduced biopterin derivatives in acidic iodine solution, biopterin was enriched and separated from the abundant neopterin phosphates by solid-phase extraction on a strong cation exchanger. Biopterin was then directly eluted on a reversed-phase liquid chromatographic column and detected fluorimetrically using excitation at 353 nm and emission at 438 nm. The biopterin concentrations formed by the coupled enzyme reaction increased linearly with incubation times up to 90 min. The assay allows the quantification of 6-pyruvoyl tetrahydropterin synthase in cultured human cells.

Alcohol Oxidoreductases↗
PubMed1991

[Cognitive training in psycho-organic syndromes].

Seven of fourteen elderly female patients (mean age 82.3 [75-89] years) with abnormalities of cognition, memory and affect of organic causation were randomly assigned to be given cognitive training, especially relating to memory, as part of rehabilitation measures for medical or orthopaedic diseases. The other seven served as controls. Training extended over 15 days, cognitive training given on 9 days for 45 min each. The control group had sessions of nonspecific attention. All patients were given psychological tests of memory and attention before and after cognitive training (or nonspecific attention). Behavioural changes were also assessed. The patients with cognitive training scored significantly higher than the controls, both in the individual exercises of the training programme and in the various tests of performance. The cognitive training also favourably influenced social behaviour, mood and level of volition. Maintaining and improving still present mental capacity in this type of patient is an essential task within a hospital setting, which otherwise provides little stimulus. Cognitive training is simple and effective, yet of great social importance.

Aged↗
PubMed1991

Correlation of the percentage of activated, CD3 + DR + lymphocytes to serum neopterin level in HIV-seropositive haemophiliacs.

The percentage of activated, CD3+ DR+ and CD8+ Leu7+ lymphocytes and the serum neopterin concentration were determined in 17 HIV-seropositive and 10 HIV-seronegative haemophiliacs and in 11 healthy control subjects. All three parameters tested were found to be significantly higher in the seropositive patients than in the seronegative controls. In the seropositive group, a significant positive correlation was found between the neopterin levels and the percentage of CD3+ DR+ cells. By contrast, no significant negative or positive correlation was observed between the neopterin levels and the percentage of the CD8+ Leu7+ subset. These data suggest that in the HIV-infected patients the activated T cells responsible for the stimulation of macrophages to produce neopterin are those that do not carry CD8.

Adolescent↗
PubMed1991

Induction of indoleamine 2,3-dioxygenase in human cells in vitro.

IFN-gamma is the most effective principle responsible for IDO induction in human cells in vitro. Lymphocyte factors support the effect of other IFN species. Induction of IDO and influence of various factors on IDO is correlated to pteridine synthesis. Cooperative effects of several mediators may account for in vivo observations concerning enhanced excretion of neopterin and tryptophan metabolites in certain disease states.

Biopterins↗
PubMed1991

Postmortem neopterin concentrations: comparison of diagnoses with and without cellular immunological background.

Increased neopterin levels in urine and serum of living humans indicate an activation of the cellular immune system. We investigated 119 urine and 48 serum samples from 129 corpses taken at necropsy; 29 cases with a background of cellular immune activation were compared to 100 corpses with no such indication. Our investigations show the feasibility of postmortem neopterin measurements. However, different kinetics of serum and urine concentrations after death were observed. In addition, the data show that urine and serum neopterin concentrations were significantly higher when cellular immunological abnormalities were present when compared to the control group and to living healthy controls. The findings suggest, that increased postmortem urine neopterin concentrations in necropsy indicate pathological processes linked with cellular immune activation.

Adolescent↗
PubMed1991

Neopterin and beta 2-microglobulin as prognostic indices in human immunodeficiency virus type 1 infection.

The great majority of individuals with human immunodeficiency virus type 1 (HIV-1) infection presents with no signs or symptoms, or only lymphadenopathy. To initiate prophylactic measures in time it is necessary to establish risk criteria. CD4+ cell counts are significant predictors. Supplementary methods to improve the predictive information of CD4+ cell counts are still required. In addition, CD4+ cell counting is laborious, expensive, and restricted to specialized laboratories. Thus, there is also a place for more easily performed laboratory tests with similar predictive value as CD4+ cell counts. Neopterin and beta 2-microglobulin levels proved to be significant predictors of AIDS risk in HIV-1 seropositives. The predictive value of both parameters is equal to CD4+ cell counts and both markers are significant joint predictors in addition to CD4+ cell counts. Measurement of the parameters is done in serum (neopterin and beta 2-microglobulin) or urine (neopterin) specimens which reduces the risk of HIV-1 transmission compared to handling of whole-blood samples as it is required for cell counting. Although more studies are needed, especially in developing countries and in persons receiving zidovudine, it can be recommended to use neopterin and beta 2-microglobulin as additional marker to estimate AIDS risk in HIV-1 seropositive individuals. Moreover, both markers may be useful for this purpose without CD4+ cell counts if cell counting is not available.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Nocturnal sleep EEG in patients with HIV infection.

Nocturnal sleep was studied in 14 human immunodeficiency virus (HIV)-positive patients without opportunistic infections of the central nervous system. Seven patients had no bodily complaints at the time of the investigation. Patients exhibited an impaired nocturnal sleep with longer sleep onset latency, reduced total sleep time, reduced sleep efficiency, and more time spent awake and in stage 1. Stage 2 sleep was significantly decreased; in 2 cases, sleep spindle density was extremely low. REM latency was reduced and correlated negatively with depressive symptomatology, while the percentages of REM and slow wave sleep were normal. No significant differences in sleep parameters were present among patients in different stages of the illness, or between patients with and without bodily complaints. Ventricular size and sulcal width on computed tomography scans correlated with sleep variables indicating reduced sleep quality, and with REM density. Decreased tryptophan plasma levels were associated with shorter and less efficient sleep, and with reduced stage 2 sleep. The findings demonstrate that sleep EEG investigations can be valuable for detecting and monitoring central nervous system affection in HIV-positive individuals.

AIDS Dementia Complex↗
PubMed1991

Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection.

Reduced tryptophan and increased kynurenine concentrations have been reported in patients with human immunodeficiency virus type 1 (HIV-1) infection. From in vitro data it appears that activated indoleamine 2,3-dioxygenase (IDO) is involved in this metabolic change. IDO is inducible by interferon-(IFN)-gamma. We compared serum concentrations of IFN-gamma and neopterin (the biosynthesis of which is also inducible by IFN-gamma) with serum, tryptophan and kynurenine of 42 patients with HIV-1 infection. IFN-gamma, neopterin and kynurenine levels were significantly increased compared to HIV-1 seronegative controls whereas tryptophan was significantly decreased. Various significant correlations were found between tryptophan, kynurenine, IFN-gamma and neopterin concentrations. Highest degree of correlation was found between neopterin, IFN-gamma and the kynurenine per tryptophan quotient which is the ratio between the product and the substrate concentration of IDO. The data indicate that decreased tryptophan in HIV-1 seropositives may result from chronic immune activation and can be referred to increased activation of IDO.

Adult↗
PubMed1991

Immunomodulatory therapy with thymopentin and indomethacin. Successful restoration of interleukin-2 synthesis in patients undergoing major surgery.

Prostaglandin E2 (PGE2)-mediated monocyte (M phi) suppressor activity and inadequate T-helper cell function represent the mechanistic keystones of trauma-induced impairment of cell-mediated immunity (CMI). In a prospective randomized trial, the immunorestorative potential of a combined therapy with the thymomimetic substance Thymopentin (TP-5; Timunox, Cilag GMBH, Sulzbach, FRG) and the cyclooxygenase inhibitor indomethacin (Indo) in 60 patients (mean age, 63 +/- 2 years) undergoing open heart surgery was studied. Perioperative immunologic screening was carried out on days -2, 3, 1, 5, and 7 and included the in vivo delayed type hypersensitivity (DTH) skin response, phenotyping for peripheral blood mononuclear cell (PBMC)-specific and nonspecific induction of lymphoproliferative responses, in vitro interleukin-2 (IL-2) synthesis, as well as the serum concentration of D-erythro-Neopterin (NPT) and of gamma interferon (gamma-IFN). The study protocol comprised three groups (n = 20): PA (Indo 150 mg administered intravenously on days 0 to 5), PB (TP-5 administered subcutaneously on days 0, 2, 4, and Indo), and PC (control). In contrast to PC, significant immunorestoration could be demonstrated in PB, as DTH scores on day 7, as well as proliferative responses in cell cultures were not depressed after operation (p less than 0.05). Cell-surface receptor expression for the CD3+, CD4+, and IL-2 receptor-positive (IL-2R+) lymphocyte subpopulations following surgery was reduced to 75% of baseline values in PC, while in PB, receptor protection for CD4+ and IL-2R+ subpopulations (more than 15% above baseline) was observed. Interleukin-2 synthesis (average baseline value, 0.7 + 0.08 U/mL) in cell cultures of PC was massively suppressed, with lymphokine concentrations in the supernatants never more than 0.27 +/- 0.05 U/mL. In PA cultures, IL-2 synthesis was impaired as well but not as precipitously as in PC. In contrast, in PB cultures, the average IL-2 production on consecutive postoperative days was never below baseline values. This study clearly demonstrates that the combined Indo/TP-5 therapy is superior to single Indo administration and can adequately preserve and/or restore intact M phi T-cell interaction and thus appears to be a feasible approach to maintain normal host defense activity in traumatized individuals.

Adjuvants, Immunologic↗