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Biomedical subjects

C Richter

Publications and source records attributed to C Richter.

At least 73 records · Page 4Linked to original sources
PubMed1999

Failure to demonstrate postpartum functional iron deficiency using quantitative red blood cell analysis.

OBJECTIVE: The aim of this prospective study was to assess erythropoiesis and test for functional iron deficiency in the postpartum period using quantitative red blood cell analysis. STUDY DESIGN: Parameters were determined on admission for delivery and postpartum from 82 obstetric patients at Zurich University Hospital: full blood count, hypochromic and microcytic red cells, reticulocyte count (including subsets), reticulocyte mean corpuscular volume, reticulocyte mean hemoglobin content and reticulocyte mean corpuscular hemoglobin concentration. RESULTS: Microcytic cells increased from 0.9% prepartum to 1.4% on day 42 postpartum; hypochromic cells decreased from 4.3 to 1.9%; reticulocyte mean corpuscular volume decreased from 134 to 125 fl; reticulocyte mean hemoglobin content was unchanged. CONCLUSION: To our knowledge, this is the first medium scale application of quantitative red blood cell analysis to normal pre- and postpartum women. Our data show no evidence of functional iron deficiency or increased erythropoiesis in the postpartum period.

Adult↗
PubMed1999

Determination of sugar conformation in large RNA oligonucleotides from analysis of dipole-dipole cross correlated relaxation by solution NMR spectroscopy.

A new experiment, the forward directed quantitative gamma-HCCH-TOCSY for the measurement of the conformation of the five-membered ribosyl unit in RNA oligonucleotides, is presented. The experiment relies on quantification of cross peak intensities caused by evolution of CH, CH-dipole-dipole cross correlated relaxation in non-evolution periods and the resolution enhancement obtainable in forward directed HCC-TOCSY transfer. Cross correlated relaxation rates are interpreted to reveal the sugar conformation of 22 out of 25 nucleotides in an isotopically labelled 25-mer RNA. The results obtained with this new method are in agreement with the conformational analysis derived from 3J(H,H) coupling constants.

Carbohydrate Conformation↗
PubMed1999

Subclinical alveolar bleeding in pulmonary vasculitides: correlation with indices of disease activity.

Haemosiderin-laden alveolar macrophages are a common finding in patients with alveolar bleeding. Iron-positive macrophages, suggestive of subclinical alveolar bleeding, were found to be fairly common in bronchoalveolar lavage (BAL) fluid in primary systemic vasculitis but uncommon in collagen vascular diseases (CVDs) and rheumatoid arthritis (RA). To substantiate the impression that subclinical alveolar bleeding may be a feature distinguishing between these disorders, fibreoptic bronchoscopy and BAL were performed in 49 patients with active Wegener's granulomatosis or Churg-Strauss syndrome and 44 patients with CVDs or RA, all of them without clinically manifest alveolar bleeding. The percentage of iron-positive cells was compared with clinical and radiological findings. Only a minority of the CVD and RA patients had iron-positive alveolar macrophages; the 95th percentile of the median number of such cells was 5%. Fifty-three per cent of the patients in the vasculitis group had >5% iron-positive cells, with individual counts ranging up to 95%. Patients with iron-positive macrophages had more extensive disease, more frequent microhaematuria, a higher antineutrophil cytoplasmic antibody titre, a higher myeloperoxidase concentration in the BAL fluid and somewhat more frequent low-attenuation opacities in pulmonary high-resolution computed tomography than the patients with a low iron-positive cell count. In conclusion, subclinical alveolar bleeding was, indeed, a common finding in antineutrophil cytoplasmic antibody-associated vasculitis, which distinguished these disorders from lung disease due to collagen vascular diseases or rheumatoid arthritis. Its association with indices of disease activity, although weak in this cross-sectional study, merits a longitudinal study of its value for the long-term monitoring of vasculitis patients.

Aged↗
PubMed1999

Ceramide induces cytochrome c release from isolated mitochondria.

This chapter addresses the role of mitochondria in apoptosis. Emphasis is put on the recently observed influence of ceramides on mitochondrial functions. We report here that N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide) and, to a much lesser extent, C2-dihydroceramide, induce cytochrome c (cyt c) release from isolated rat liver mitochondria. Ceramide-induced cyt c release is prevented by a low concentration of Bcl-2. The release takes place when cyt c is oxidized, but not when it is reduced. Upon cyt c release mitochondrial oxygen consumption, mitochondrial transmembrane potential (delta psi m) and Ca2+ retention are diminished. Bcl-2 prevents, and addition of cyt c reverses, the alteration of these mitochondrial functions. In ATP-energized mitochondria ceramides do not alter delta psi m, neither when cyt c is oxidized nor when it is reduced. This rules out a non-specific disturbance by ceramides of mitochondrial-membrane integrity. It is concluded that some of the apoptogenic properties of ceramides are mediated via their interaction with mitochondrial cyt c followed by its release.

Animals↗
PubMed1999

Contribution of a prosegment lysine residue to the function and structure of porcine pepsinogen A and its active form pepsin A.

A conserved lysine residue, Lys36p, on the prosegment of pepsinogen was replaced with a positively charged arginine (K36pR), a negatively charged glutamic acid (K36pE), and a neutral side chain methionine (K36pM). K36pM and K36pE mutants were extremely unstable and degraded rapidly, especially K36pE, which was inactivated during purification. This instability was confirmed by microcalorimetry where the denaturing temperatures for K36pM and K36pE were 6 degrees C and 10 degrees C lower than the wild-type, respectively. As a function of pH, K36pM and K36pR were activated over a broader range of pH as compared with wild-type. The mutant pepsinogens were activated faster than wild-type with K36pM being activated approximately 10 times faster. The activated pepsins from the various mutant pepsinogens showed lower kinetic efficiency than wild-type enzyme. Catalytic rate constants were reduced by half. The results suggested Lys36p is important for the correct folding of the active-centre residues. The molecular modeling calculation suggested that the position of Asp215 was substantially altered. In conclusion, the above results would suggest that Lys36p was important not only for stability of the prosegment and pepsinogen, but also for the correct alignment of the active-centre residues.

Animals↗
PubMed1999

Prevalence of resistance to clarithromycin and its clinical impact on the efficacy of Helicobacter pylori eradication.

BACKGROUND: Triple therapy with a proton-pump inhibitor (PPI) in combination with metronidazole and clarithromycin is the method of choice for eradication of Helicobacter pylori. Failures have been primarily blamed on the development of resistance to clarithromycin. The present study investigated the prevalence and clinical significance of resistance to clarithromycin and metronidazole in determining therapeutic success of both triple therapy as a primary eradication method and high-dose dual therapy in non-responders. METHODS: On the basis of prior therapy, H. pylori-positive patients were assigned to one of two groups in the present prospective study. Group A (n = 93) included patients who had not undergone any prior eradication treatment, whereas group B (n = 15) consisted of patients who had received clarithromycin but in whom eradication had been unsuccessful. All patients underwent endoscopy with biopsy for bacterial culture and resistance studies. Patients in group A were treated with a 7-day regimen of pantoprazole (40 mg twice daily), metronidazole (500 mg twice daily), and clarithromycin (250 mg twice daily), whereas those in group B received omeprazole (40 mg three times a day) and amoxycillin (1000 mg three times a day ) for 14 days. Success of the eradication treatment was ascertained by means of the 13C urea breath test. RESULTS: In group A resistance to clarithromycin and metronidazole was identified in 3 patients (4.9%) and in 14 patients (22.9%), respectively. Eradication proved successful in 78 of 84 patients (92.6%) followed up. Two of the 3 patients with primary clarithromycin resistance and 1 of the 14 patients with metronidazole resistance did not respond to treatment. In group B isolated or combined resistance to clarithromycin was found in seven patients, whereas another four showed isolated resistance to metronidazole. Eradication proved successful in 10 of 13 controlled patients (76.9%) followed up, and only 2 patients reported severe side effects. CONCLUSION: Determination of antibiotic resistance before initiating therapy is not necessary, since primary resistance to clarithromycin is rare. The Italian triple therapy remains a highly effective primary therapeutic method. Further, routine determination of resistance in non-responders also seems to be superfluous because high-dose dual therapy is an effective and well-tolerated second-line therapy regardless of the patients' resistance status.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Insights into Escherichia coli RNA polymerase structure from a combination of x-ray and electron crystallography.

Our goal is to understand the mechanism of transcription and its regulation. Determining structures of RNA polymerase and transcription complexes is an essential step. Because of their large size and complexity, determination of these structures will require a combination of electron microscopy, biophysical methods, and biochemical methods to identify functionally and structurally relevant subassemblies and domains and x-ray crystallography to determine high-resolution structures of RNA polymerase components and accessory factors. We recently solved the 2.5-A crystal structure of the Escherichia coli RNA polymerase alpha subunit N-terminal domain, which is the first high-resolution structure of a core component required for RNA polymerase assembly and basal transcription. This structure, combined with a new 19-A resolution structure determined by cryo-electron microscopy of helical crystals of E. coli core RNAP embedded in vitreous ice, leads to a model for the organization of the RNAP subunits.

Crystallography, X-Ray↗
PubMed1998

Mechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin.

The gastric aspartic proteinases (pepsin A, pepsin B, gastricsin and chymosin) are synthesized in the gastric mucosa as inactive precursors, known as zymogens. The gastric zymogens each contain a prosegment (i.e. additional residues at the N-terminus of the active enzyme) that serves to stabilize the inactive form and prevent entry of the substrate to the active site. Upon ingestion of food, each of the zymogens is released into the gastric lumen and undergoes conversion into active enzyme in the acidic gastric juice. This activation reaction is initiated by the disruption of electrostatic interactions between the prosegment and the active enzyme moiety at acidic pH values. The conversion of the zymogen into its active form is a complex process, involving a series of conformational changes and bond cleavage steps that lead to the unveiling of the active site and ultimately the removal and dissociation of the prosegment from the active centre of the enzyme. During this activation reaction, both the prosegment and the active enzyme undergo changes in conformation, and the proteolytic cleavage of the prosegment can occur in one or more steps by either an intra- or inter-molecular reaction. This variability in the mechanism of proteolysis appears to be attributable in part to the structure of the prosegment. Because of the differences in the activation mechanisms among the four types of gastric zymogens and between species of the same zymogen type, no single model of activation can be proposed. The mechanism of activation of the gastric aspartic proteinases and the contribution of the prosegment to this mechanism are discussed, along with future directions for research.

Amino Acid Sequence↗
PubMed1998

Bax-induced cytochrome C release from mitochondria is independent of the permeability transition pore but highly dependent on Mg2+ ions.

Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is a pore-forming, mitochondria-associated protein whose mechanism of action is still unknown. During apoptosis, cytochrome C is released from the mitochondria into the cytosol where it binds to APAF-1, a mammalian homologue of Ced-4, and participates in the activation of caspases. The release of cytochrome C has been postulated to be a consequence of the opening of the mitochondrial permeability transition pore (PTP). We now report that Bax is sufficient to trigger the release of cytochrome C from isolated mitochondria. This pathway is distinct from the previously described calcium-inducible, cyclosporin A-sensitive PTP. Rather, the cytochrome C release induced by Bax is facilitated by Mg2+ and cannot be blocked by PTP inhibitors. These results strongly suggest the existence of two distinct mechanisms leading to cytochrome C release: one stimulated by calcium and inhibited by cyclosporin A, the other Bax dependent, Mg2+ sensitive but cyclosporin insensitive.

Animals↗
PubMed1998

Visualization of the binding site for the transcript cleavage factor GreB on Escherichia coli RNA polymerase.

The structure of Escherichia coli core RNA polymerase (RNAP) complexed with the transcript cleavage factor GreB was determined from electron micrographs of negatively stained, flattened helical crystals. A binding assay was developed to establish that GreB was incorporated into the RNA polymerase crystals with high occupancy through interactions between the globular C-terminal domain and the RNA polymerase. Comparison of the core RNAP:GreB structure with the previously determined structure of core RNAP located the GreB binding site on one face of the RNA polymerase, next to but not in the 25 A-diameter channel of RNA polymerase.

Binding Sites↗
PubMed1998

Mitochondrial creatine kinase is a prime target of peroxynitrite-induced modification and inactivation.

The reaction of peroxynitrite (PN) with sarcomeric mitochondrial creatine kinase (Mib-CK; EC 2.7.3.2) was observed at different stages of complexity (i) with purified Mi-CK, (ii) with enzyme bound on isolated mitoplasts, and (iii) within intact respiring mitochondria. Creatine-stimulated respiration was abolished by PN concentrations likely to be physiological and far before the respiratory chain itself was affected, thus demonstrating that Mi-CK is a prime target for inactivation by PN in intact mitochondria. The inactivation by PN of Mi-CK was reversed by 22% with 2-mercaptoethanol. More remarkable protective effects were noticed with the full set of CK substrates, e.g. 30 and 50% protection with MgATP plus creatine and MgADP plus phosphocreatine, respectively, but not with each substrate alone. These data indicate an involvement of the active-site Cys-278 residue of Mi-CK in this process. Furthermore, changes in endogenous tryptophan fluorescence intensity and spectral changes after reaction of Mi-CK with PN suggest additional modifications of Trp and Tyr residues. PN-inactivated Mi-CK can no longer be efficiently converted into dimers by incubation with reagents inducing a transition state analog complex at the active site. Thus, obviously, upon reaction of octameric Mi-CK with PN, the octamer-dimer equilibrium of Mi-CK is also affected. The consequences for cellular energy homeostasis and calcium handling are discussed.

Animals↗
PubMed1998

[Oxygenation status of squamous cell carcinoma of the head and neck: comparison of primary tumors, their neck node metastases and normal tissue].

AIM: Investigation of the relationship between the pO2-status of primary tumors, their cervical neck node metastases and normal tissues in squamous cell carcinomas of the head and neck. PATIENTS AND METHODS: Pretreatment oxygenation of primary tumors, their neck node metastases and of the contralateral sternocleidomastoid muscle was assessed in 16 patients with histologically proven advanced squamous cell carcinomas of head and neck. Oxygenation was measured with a polarographic microelectrode system (Eppendorf-pO-Histograph). Using CT/MRT additionally the volume of the tumors was estimated. RESULTS: A highly significant correlation existed between the median pO2 of primary tumors and their neck node metastases and between the relative proportion of hypoxic values (< 5 mm Hg) of both anatomic sites (both p = 0.0001) (Figure 1). Primary tumors were not different from their neck node metastases, neither regarding the pO2 median values nor in view of the relative frequency of hypoxic values (Table 1). No correlation was found between the volume of primary tumors and the one of their neck node metastases. For volume of tumors and the oxygenation status no relationship was found as well. Significantly different was the median pO2 in the muscles from the one of the malignant tissues (p = 0.0004). CONCLUSION: The results suggest that for to estimate the oxygenation status of squanious cell carcinomas of the head and neck pO2 measurements of primary tumors and neck node metastases are equally sufficient.

Carcinoma, Squamous Cell↗
PubMed1998

Acute radiation reaction and local control in breast cancer patients treated with postmastectomy radiotherapy.

BACKGROUND: We have investigated the variation of acute radiation reactions in medium-risk patients with postmastectomy radiotherapy with regard to a possible correlation between radiation reaction of normal tissues and local tumor control. MATERIAL AND METHODS: From 1985 through 1991, a total number of 194 patients received postmastectomy radiotherapy for breast cancer pT1-2pN0-2M0 at the University of Halle-Wittenberg. The lymphatics were irradiated by an anterior 9-MV photon field and the chest wall by an individually shaped anterior field with 9-MV electrons. Both fields received single doses of 2 Gy 5 times weekly up to a total dose of 44 Gy to the chest wall and 50 Gy to the lymphatics. All patients were routinely evaluated once weekly during radiotherapy for acute side effects by one examiner. Skin erythema was classified as mild, moderate or severe, esophagitis as being present in form of dysphagia or not and pneumonitis, if present, as asymptomatic (visible only on repeated chest X-rays) or clinically symptomatic. A differential blood count was also carried out once weekly. For this analysis, the records of all patients were retrospectively reviewed. The median follow-up at the time of analysis was 4.2 years. RESULTS: Of the patients, 98 (51%) had a mild, 53 (27%) moderate and 43 (22%) a severe erythema. Furthermore, 38 patients (20%) had signs of esophagitis, 13 (7%) had asymptomatic and 26 (13%) symptomatic pneumonitis. Patients with severe erythema or erythema plus esophagitis and pneumonitis had a more pronounced decrease in lymphocyte count during treatment than patients with mild erythema: the lymphocyte nadir was 0.14 vs 0.73 Gpt/l in patients with severe vs mild erythema, and 0.36 vs 0.69 Gpt/l in patients with erythema plus esophagitis plus pneumonitis vs patients with erythema only, p < 0.05. Of the patients, 44 (22%) developed chronic side effects, mostly arm edema. There was no correlation between acute and late effects. An overall number of seven local recurrences (3.6%) occurred. The risk of developing a local recurrence within 5 years after treatment was 0% in patients with severe erythema or erythema plus esophagitis/pneumonitis vs 7% in patients with mild erythema only; this difference was marginally significant, p = 0.055. CONCLUSIONS: This analysis showed a trend towards better local control in patients with severe acute radiation reaction of normal tissue. The data support a recent publication by Dahl and coworkers showing a linkage between acute radiation reaction of normal tissue and tumor response in patients with preoperative radiotherapy for rectal cancer. The correlation between acute normal tissue reaction and local control might be explained by interindividual variations in the intrinsic, genetically determined radiosensitivity. However, local factors might also be involved, e.g. induction of a cytokin cascade in cases of acute reactions in normal tissues.

Adult↗
PubMed1998

The early phase of glucose-stimulated insulin secretion requires nitric oxide.

Nitric oxide (nitrogen monoxide, NO) acts as a signal transducer in a variety of cells. In the present study rat pancreatic islets were perifused with physiologically relevant glucose concentrations in the presence or absence of various NO-modulating agents. Perifusion in the presence of 0.1-1 mmol/l of the NO synthase inhibitor, NG-monomethyl-L-arginine or of 10 micromol/l of the NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), resulted in an inhibition of the early phase of glucose-stimulated insulin secretion by 60-65% and 46%, respectively. Light- and electron-microscopic studies revealed that pancreatic islets constitutively express NO-synthase in alpha and delta cells, where it is confined to the secretory granules. Therefore, these data indicate that NO may be important in the signal transduction pathway of the early phase of glucose-stimulated insulin secretion.

Animals↗
PubMed1998

Autofluorescence of living cells.

We have investigated the autofluorescence of viable mammalian cells (DU-145 and V79) with a confocal laser scanning microscope equipped with a UV laser. Our aim was to investigate the autofluorescence dependence on different treatments in mitochondria and lysosomes by using different reagents and to improve the confocal laser scanning microscope image quality by deconvolution. The following conclusions were drawn from the results: (1) not all of the autofluorescence comes from mitochondria; (2) one can significantly affect the signal which comes from the mitochondria; (3) the other organelles involved are probably lysosomes; (4) it is harder to affect the autofluorescence signal from the lysosomes than that from the mitochondria, and (5) deconvoluted autofluorescence images provide better information than undeconvoluted ones.

Animals↗
PubMed1998

[Leishmaniasis of the lips mimicking a mycotic infection].

A 24-year old German man was complaining of painful ulcers with infiltration of the lips without alteration of the oral mucosa and swelling of the regional lymph nodes. Three months earlier he had visited Israel, Italy, Romania and Bulgaria. He was treated with penicillin, doxycyclin, ciprofloxacin, itraconazole and prednisolone after detection of Candida spec. and staphylococci in another town without any effect. The smear and biopsy were sent to the Robert Koch Institute Berlin. Giemsa stain by phase contrast light microscopy with oil immersion showed extracellular amastigote leishmaniae with clearly stained kinetoplasts. Leishmania major could be detected by PCR investigation. The IgE was elevated, other investigations of the blood and from the lips were inconspicuous. The ulcers healed promptly under the treatment with Pentostam (antimony derivative) 0,1 ml/kg body weight i.m. for 12 days and 15% Paromomycin ointment.

Adult↗