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Biomedical subjects

C Richter

Publications and source records attributed to C Richter.

At least 163 records · Page 9Linked to original sources

Extrapulmonary tuberculosis--a simple diagnosis? A retrospective study at Dar es Salaam, Tanzania.

Data from the national tuberculosis programme show that extrapulmonary tuberculosis is increasing rapidly in Tanzania, most likely caused by the human immunodeficiency virus (HIV) epidemic. Retrospective data from 271 patients admitted to Muhimbili Medical Centre (MMC), Dar es Salaam between January 1, 1987 and December 31, 1988 with the diagnosis of extrapulmonary tuberculosis reveal that in only 18% of the cases a bacteriological or histological confirmation of the diagnosis had been made. This figure is only 3% when the tuberculous lymphadenitis cases are excluded. The most common diagnosis was tuberculous pleuritis (119 cases), followed by tuberculous lymphadenitis (67 cases), tuberculosis of the spine (47 cases), tuberculous pericarditis (16 cases) and others. The mean clinical features are presented. In 79 patients the HIV ELISA test was performed, of which 52% were positive. There is an urgent need for improving the diagnosis of extrapulmonary tuberculosis requiring prospective studies.

Adult↗

Cyclosporine A inhibits mitochondrial pyridine nucleotide hydrolysis and calcium release.

Mitochondria participate in the maintenance of cellular Ca2+ homeostasis. Here we show that the immunosuppressive drug cyclosporine A at low concentrations inhibits release but not uptake of Ca2+ by mitochondria. Prevention of Ca2+ release is due to inhibition of intramitochondrial enzymatic hydrolysis of NAD to ADP-ribose and nicotinamide. These findings suggest a mechanism by which cyclosporine A interferes with cellular Ca2+ homeostasis, and may be related to the immunosuppressive and cytotoxic properties of the drug.

Alloxan↗

Inhibition of pro-oxidant-induced mitochondrial pyridine nucleotide hydrolysis and calcium release by 4-hydroxynonenal.

Intra- and extra-mitochondrial Ca2+ participates in vital cellular processes. This work investigates the influence of 4-hydroxynonenal (HNE) on pro-oxidant-induced Ca2+ release from rat liver mitochondria. Ca2+ movements across the mitochondrial inner membrane, the pyridine nucleotide redox state and pyridine (nicotinamide) nucleotide hydrolysis were analysed. HNE did not influence Ca2+ uptake by mitochondria, but inhibited in a concentration-dependent manner Ca2+ release induced by t-butylhydroperoxide (tbh). Total inhibition was achieved with about 50 microM-HNE. Ca2+ release induced by the pro-oxidant alloxan was also inhibited by HNE. Oxidation of pyridine nucleotides, induced by tbh through the concerted action of glutathione peroxidase, glutathione reductase and the energy-linked transhydrogenase, was not affected by up to 50 microM-HNE. In contrast, HNE inhibited pyridine nucleotide hydrolysis in a concentration-dependent manner. The data suggest that HNE toxicity may be in part attributed to an impaired intramitochondrial Ca2+ homeostasis.

Adenosine Diphosphate Ribose↗

No measurable increase in thymidine glycol or 8-hydroxydeoxyguanosine in liver DNA of rats treated with nafenopin or choline-devoid low-methionine diet.

Male rats were treated for 2 months with 1000 ppm nafenopin in the diet or for 4 or 7 days with a choline-devoid low-methionine diet. DNA was isolated from the livers and analyzed for the presence of cis-thymidine glycol-3'-phosphate (cis-dTGp) by 32P-postlabeling and for the level of 8-hydroxy-deoxyguanosine (8-OH-dG) by electrochemical detection (ECD). In no DNA sample was the level of cis-dTGp above the limit of detection of 1 modified thymidine per 10(6) nucleotides. With 8-OH-dG, a background level of this modification of 20 8-OH-dG per 10(6) nucleosides was found in liver DNA of control rats, which was not affected by either treatment. It is postulated for thymidine glycol that a potential increase was below the limit of detection or was rapidly repaired in vivo and that the steady-state level of endogenous 8-hydroxydeoxyguanosine appears not to be influenced by the treatments chosen.

8-Hydroxy-2'-Deoxyguanosine↗

Resting chondrocytes in culture survive without growth factors, but are sensitive to toxic oxygen metabolites.

Chondrocytes in dense suspension culture in agarose survive in serum-free DME because they secrete low molecular mass compounds supporting their own viability. This activity can be replaced by pyruvate, or sulfhydryl compounds, e.g., cysteine or dithioerythritol. Catalase, an enzyme decomposing H2O2, also protects the cells, whereas superoxide dismutase has no effect. Therefore, chondrocytes in culture are sensitive to toxic compounds derived from molecular oxygen, i.e., hydroxyl radicals or hydrogen peroxide spontaneously generated in DME containing ascorbate and ferrous ions. Poly-ADP-ribosylation is an important step in the cascade of events triggered by these compounds. To survive, chondrocytes do not require stimulation by growth factors. They remain resting cells in fully defined, serum-free culture also at low density. Proliferation and hypertrophy can be induced by serum, but not by low cell density alone.

Animals↗

The prooxidant-induced and spontaneous mitochondrial calcium release: inhibition by meta-iodo-benzylguanidine (MIBG), a substrate for mono (ADP-ribosylation).

The norepinephrine analogue meta-iodo-benzylguanidine (MIBG), a substrate for mono(ADP-ribosylation) and inhibitor of eukaryotic ADP-ribosyltransferases, inhibits the prooxidant-induced and spontaneous calcium release from intact rat liver mitochondria without affecting pyridine nucleotide oxidation and hydrolysis. This finding strongly suggests regulation of calcium release by ADP-ribosylation in mitochondria, and may be relevant for the cellular and pharmacological effects of MIBG.

3-Iodobenzylguanidine↗

Significant X-ray patterns in cardiomyopathy--an approach improving noninvasive diagnosis.

To identify their characteristic patterns, the X-ray dorso-ventral chest images of 118 patients with cardiomyopathy (63--dilated cardiomyopathy, 25--hypertrophic obstructive cardiomyopathy, 30--hypertrophic nonobstructive cardiomyopathy) were analyzed and compared with those of 22 patients without cardiac abnormalities. All 140 patients underwent comprehensive invasive cardiac examinations. In dilated and hypertrophic nonobstructive cardiomyopathy transvasal endomyocardial biopsy was performed. Irrespective of the type and the aetiology of cardiomyopathy, 4 characteristic patterns of X-ray findings could be identified: a class of left heart abnormality (class L) and 3 types of bilateral cardiac abnormalities with various stages of left heart failure (class L + R). An association between the image patterns and haemodynamic parameters (left ventricular end-diastolic pressure, wall mass index, pulmonary mean pressure) was demonstrated which was most obvious in dilated and less evident in hypertrophic obstructive cardiomyopathy. Mitral insufficiency in all types and classes frequently corresponded with the X-ray findings of left atrial enlargement. The X-ray classification method proved to be an efficient approach and superior to the heart-to-lung ratio.

Adult↗

Identification of the membrane anchor of microsomal rat liver cytochrome P-450.

Cytochrome P450IIB1 isolated from rat liver microsomes was incorporated into phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine (10:5:1 w/w) liposomes. Trypsinolysis of proteoliposomes and sequencing of the membrane-bound domains revealed that only one peptide, comprising amino acid residues 1-21, spans the membrane. Modification of the N-terminal methionine by membrane-impermeable fluorescein isothiocyanate occurred with the protein in solution but not in proteoliposomes. We conclude that in proteoliposomes cytochrome P-450 spans the membrane only with amino acid residues 1-21, the N-terminal methionine facing the lumen.

Animals↗

[Cytomegalovirus infection acquired in The Netherlands and in the tropics; a retrospective study in previously healthy adults].

Clinical and laboratory data of 44, previously healthy patients with cytomegalovirus (CMV) infections were analysed in a retrospective study (1975-1986). Eighteen (41%) were probably infected in the (sub)tropics. 33 (75%) patients showed symptoms and signs of CMV-mononucleosis: fever, malaise, absolute and relative lymphocytosis with atypical lymphocytes and liver function disturbance without jaundice. Enlargement of lymph-nodes was present in only 20% of the patients, distinct from mononucleosis caused by the Epstein-Barr virus. The clinical picture caused by CMV-infection in the tropics was not different from autochthonous CMV-infections.

Adolescent↗

Microsomal cytochrome P-450: substrate binding, membrane interactions, and topology.

The microsomal monoxygenase system is of paramount importance for the metabolism of endogenous substrates and xenobiotics. It is capable of detoxifying many compounds, but also activates procarcinogens to carcinogens. Cytochrome P-450 is the terminal enzyme of the monoxygenase system. In this article we briefly review current knowledge of the nature of its active site, its interaction with the membrane, and its topology in the membrane. In contrast to previous proposals there is now strong evidence that cytochrome P-450 spans the membrane with only one short segment. Analysis of tryptophan fluorescence gives further evidence that most of the protein's mass protrudes from the membrane into the cytosolic space.

Animals↗

[Sequential alternating chemotherapy of highly malignant non-Hodgkin's lymphomas with VIM-Bleo and CHOP. Initial results].

54 patients with high grade malignant NHL (stage II 19, stage III 10, stage IV 25 patients, medium age 56 years) were treated in an ongoing study with the VIM-Bleo/CHOP-regimen: Etoposide 100 mg/m2 i.v. days 1-3, Ifosfamide 1.5 g/m2 i.v. days 1-5 with Mesna for prophylaxis of cystitis, Methotrexate 30 mg/m2 i.v. day 3, Bleomycin 10 mg i.v. days 8 and 15, Cyclophosphamide 750 mg/m2 day 22, Adriamycin 50 mg/m2 day 22, Vincristine 1.4 mg/m2 day 22 and prednisolone 100 mg po days 1-5 and 22-26. Cycles were repeated on day 43. After completion of therapy (4 cycles of VIM-Bleo/CHOP), 27 out of 35 patients (77%) were in complete remission. 6 patients (17%) had a partial remission and 2 (6%) progressive disease. After a median follow up of 8 months so far, 6 relapses occurred. Probability of survival at 12 months is 82%. Toxicity of treatment was very low with leukopenia being the main side effect. Only in 2 cycles (3%), major infections were observed. Nausea and vomiting were severe only in 4% of patients. We conclude that VIM-Bleo/CHOP is a well tolerated regimen with good remission rates in high grade malignant NHL. However, longer follow up is necessary for a final evaluation.

Adult↗

[Electromagnetic articulography (EMA) studies on orofacial movement functions].

For judging the influence of orofacial motor functions on the development and function of the dentoalveolar system objective methods are required. Electromagnetic Articulography (EMA) is a new device based on an inductive measuring principle. Using miniature receiver coils placed on the tongue dorsum or the velar margin, movements of multiple points on orofacial structures in the midsagittal plane can be recorded. The application of EMA on the examination of tongue and velum motor activity during speech production and deglutition is demonstrated. First results of sagittal tongue movement during swallowing in normals are reported. Examples from current studies, using EMA in the field of tongue dysfunction, orofacial motor coordination and velopharyngeal closure are demonstrated and the possible perspective of EMA-application is discussed for dental research and functional treatment of CLP-patient.

Deglutition↗