Hyperphenylalaninemia.
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Alcohol Oxidoreductases↗
Biomedical subjects
D Fuchs
Publications and source records attributed to D Fuchs.
Distinct distributions of D-erythro-neopterin in arteries and veins and its recovery by an enterohepatic circulation.
Large amounts of D-erythro-neopterin, a pteridine derivative, are formed from guanosine triphosphate (GTP) by human macrophages upon stimulation with interferon-gamma. In addition, in humans a basal neopterin level in all body fluids is evident also in absence of immunological stimuli. Extremely high concentrations of D-erythro-neopterin were detected in biliary fluid. We therefore investigated, if an enterohepatic circulation might exist for this substance. We quantified concentrations of pteridines in serum obtained from various vessels and in biliary fluid. Samples were collected during surgery of five patients with duodenal ulcer or adenocarcinoma of the stomach. Our data clearly demonstrate the existence of an enterohepatic circulation for the recovery of neopterin which seems to be specific for this substance. The relative distributions of neopterin concentrations in the gastrointestinal tract and vessels were seen invariably in all patients and were consistent with findings in five corpses examined post mortem. In addition, significantly higher neopterin concentrations, were found in arteries than in veins. The data indicate that neopterin derivatives are consumed in the peripheral capillary system and an enterohepatic circulation is established to maintain constant blood levels of neopterin derivatives. Furthermore, we suppose that the liver is the source of constitutive neopterin concentrations.
Adenocarcinoma↗
The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases.
The accumulated knowledge about the organization and function of the human immune system contributes to a better understanding of the pathogenesis of most diverse disorders and is opening new avenues for therapeutic regimens. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. The determination of neopterin concentrations in human body fluids allows to investigate sensitively the cell-mediated immune status to be investigated with considerable sensitivity. In recent years it was shown that production and release of neopterin is inducible in human monocytes/macrophages by interferon gamma. Increased neopterin levels indicate endogenous formation of gamma interferon, and monitoring of neopterin levels therefore permits the activation status of the cell-mediated immune system to be examined. Neopterin concentrations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and parasites. In patients with human immunodeficiency virus infection neopterin concentration in serum and urine is a significant predictor of disease progression, the statistical power being similar to CD4+ T-cell numbers. In patients with autoimmune disorders, neopterin levels correlate with the extent and the activity of the disease. Neopterin concentrations are also sensitive indicators of immunological complications in allograft recipients. In certain malignant diseases neopterin concentrations correlate with the stage of the disease and bear prognostic information. Results of neopterin measurements agree with the important role that the cellular immune system plays in these disorders.
Animals↗
Chemical abuse. An intervention program for the elderly.
Although chemical dependency has been identified as a problem in the geriatric population, the literature continues to focus on issues of problem identification; few authors address the issue of providing appropriate services for the chemically dependent elderly. A goal of the Elders Health Program was to design a process of intervention using strategies employed by current chemical dependency treatment facilities, and to interface this process with knowledge and respect for normal aging changes. The intervention involved creating a unified and informed intervention team. The Elders Health Program illustrates that all elders have a network that can be employed or created in an effort to move the client into accepting the need to change. The ultimate goal is to improve the well-being of the client.
Aged↗
[Infections after bone marrow transplantation in childhood].
In 66 children having undergone bone marrow transplantation (BMT) the occurrence of infections was studied retrospectively. Bacterial infections were mostly found in the early period after transplantation before marrow engraftment. The analysis of positive blood cultures showed a dominance of gram-positive bacteria, especially of coagulase-negative staphylococci. Cytomegalovirus (CMV) infections were most important, because of its high rate and the risk of CMV associated interstitial pneumonia (IP), two patients suffered from. Infections from herpes simplex virus (HSV), varizella zoster virus (VZV) and Epstein Barr virus (EBV) had no influence on prognosis. In fungal infections the systemic aspergillosis was the most important complication. To increase the effectiveness and safety of therapy the serum levels of antibiotics and antifungal drugs should be determined.
Adolescent↗
[Kinetics of vaccination antibodies against tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococcus after allogenic and autologous bone marrow transplantation and booster vaccination. 2: Kinetics of vaccination antibodies against diphtheria toxoid after allogenic and autologous bone marrow transplantation].
In the second part of the paper we report on the results of the diphtheria antitoxin valuation of 8 children after allogeneic bone marrow transplantation (BMT) with and without graft versus host disease (GvHD) as well as on the kinetics of the diphtheria antitoxin of 5 children after allogeneic BMT with and without GvHD and of 5 children after autologous transplantation. The antibody valuation was done by a cell-culture assay. Whereas the inspection of the isolated data gives the impression of a swift antibody decrease up to the non-protective level from the 7th month after BMT, the kinetic tests are more highly differentiated. Besides rapidly decreasing values below the accepted protection rate of 0.01 IU/ml in the allogeneic transplanted groups, there are patients with positive antibody titres within an observation period of up to 24 months after BMT in the allogeneic as well as in the autologous transplantation group.
Bone Marrow Transplantation↗
[The kinetics of vaccine antibodies against tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococcus after allogeneic and autologous bone marrow transplantation and revaccination. 3: The kinetics of vaccine antibodies against tetanus toxoid and diphtheria toxoid after allogeneic and autologous bone marrow transplantation and combined revaccination against diphtheria and tetanus].
The 3rd part of the paper deals with the results of a combined revaccination against diphtheria and tetanus in a group of 25 children after allogeneic bone marrow transplantation (BMT) with and without graft versus host disease (GvHD) and after autologous transplantation. It can be shown that in the allogeneic transplanted groups with and without GvHD it is possible to build up a tetanus and diphtheria antitoxin titre in a safe protective cause by a 2nd basic immunisation consisting of 3 single vaccinations starting about 9 to 12 months later. For autologous transplanted children only 1 to 2 vaccinations at a later term than for the allogeneic transplanted children may possibly be sufficient.
Bone Marrow Transplantation↗
[Kinetics of vaccine antibodies to tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococci after allogenic and autologous bone marrow transplantation and booster immunization. 1: The kinetics of vaccine antibodies to tetanus toxoid after allogenic and autologous bone marrow transplantation].
Today BMT belongs to the established methods of treatment in haematology and oncology. Because of the constant increase of healthy long-term survivors after BMT the problem of immunological reconstitution and eventual possible late effects gets more and more importance. One problem, which til now has been few attention paid to, is that of the protection by vaccination after BMT. We report on the kinetics of the tetanus-antitoxin in 20 patients after allogeneic or autologous BMT and demonstrate the influence of a graft-versus-host disease and its therapy on the antibody kinetics. In the group of allogeneic transplanted children without a GvHD the tetanus-antitoxin titers felt below their detection range after a time of about 8 months whereas in the group with GvHD this effect already occurred after nearly 4 months. The autologous transplanted patients have a positive antibody level til the time of 20 months after BMT. As a consequence of the lost protection by vaccination after BMT follows the necessity of revaccinations respectively of boostering after immunological reconstitution.
Adolescent↗
Pathogenesis of chronic fatigue syndrome.
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Fatigue Syndrome, Chronic↗
Trends in HIV infection among intravenous drug users in Innsbruck, Austria.
The first HIV test among intravenous drug users (IVDUs) at the AIDS clinic and/or the drug dependency clinic of the University of Innsbruck was the basis for the calculation of the proportions of those testing HIV seropositive annually over the period 1985-1990. The numbers testing HIV seropositive at the drug dependency clinic declined drastically, from 72.2% in 1985 to 12.5% in 1990 (chi 2 = 29.62, p less than 0.0001), whereas they rose at the AIDS clinic during this period, from 48.4% to 100% (chi 2 = 5.82, p = 0.016). Overall 132 of the 268 (49.2%) individuals examined tested HIV seropositive. There were 102 individuals of the original 146 seronegative IVDUs who were retested, for an overall incidence rate of HIV seroconversion of 5.8/100 persons-years. Risk of seroconversion was associated with a steady sexual partnership with an HIV seropositive IVDU and with an age of less than or equal to 25 years at study entry (13.1 versus 8.7/100 persons-years). No seroconversions occurred in the subgroup of patients treated by the methadone maintenance treatment program. The cumulative incidence (Kaplan-Meier) rate for HIV seropositivity after 64 months was 22%, lower than the proportions testing HIV seropositive found in 1985 at each of the two clinics, which suggests that the speed of the spread of the epidemic of HIV infection among IVDUs has slowed in our region. Counseling of IVDUs should emphasize the risks of sexual acquisition, particularly among persons with steady relationships who may not perceive their risk.
Adult↗
Increased interferon-gamma and reduced hemoglobin in patients with human immunodeficiency virus type 1 infection.
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Acquired Immunodeficiency Syndrome↗
Patterns of serological markers for cellular immune activation in patients with dilated cardiomyopathy and chronic myocarditis.
We determined serum concentrations of neopterin and beta 2-microglobulin, soluble markers of cellular immune activation, in 27 patients with either dilated cardiomyopathy (DCM) or chronic myocarditis. Neopterin and beta 2-microglobulin concentrations were respectively increased in 2 and 5 of 11 patients with DCM and in 11 and 9 of 16 patients with chronic myocarditis. A higher cardiac functional class (according to the New York Heart Association) was associated with greater neopterin and beta 2-microglobulin concentrations. During follow-up of patients, both neopterin and beta 2-microglobulin concentrations in serum correlated with the course of disease. Additionally, correlations were significant between left ventricular functional tests (end-diastolic volume, end-systolic volume, and ejection fraction) and neopterin and beta 2-microglobulin concentrations. We conclude that measurement of neopterin and beta 2-microglobulin are useful to monitor disease development in patients with myocardial inflammation.
Adult↗
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↗
[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↗
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↗
Immune activation and psoriasis.
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Biopterins↗
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↗