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Biomedical subjects

C Weber

Publications and source records attributed to C Weber.

At least 289 records · Page 16Linked to original sources

Treatment of protracted acute type B hepatitis with recombinant alpha-A-interferon. A pilot study.

Six individuals with protracted acute type B hepatitis were treated with recombinant alpha-A-interferon for 12 weeks. Two females eliminated the HBV completely, while 4 males did not respond. Response was preceded by a flare-up of the liver disease. It appears that responses to interferon are not higher in protracted acute type B hepatitis than in progressed chronic active hepatitis B. This assumption has to be proven in larger studies on a statistical basis.

Acute Disease↗

Reduction of blood transfusion requirement in open heart surgery by administration of high doses of aprotinin--preliminary results.

Reduction of homologous blood requirement in cardiac surgery is of increasing interest and may be achieved by various technical and pharmacological means. High-dose aprotinin (about 840 mg, equivalent to 6 million Kallikrein inactivator units), a serine proteinase inhibitor, was administered during open heart surgery to 60 patients refusing homologous blood transfusions or suspected to have an increased risk of bleeding. As a significant decrease in donor blood requirement could be observed, a prospective, randomised double blind study in 80 male patients undergoing primary coronary surgery with high-dose aprotinin administration was performed. Mean blood loss was reduced by 45.9% (652 ml in the treated vs 1204 ml in the untreated group, p less than 0.01) and the mean amount transfused was decreased by 74.2% (242 ml vs 937 ml, p less than 0.01). No homologous blood was needed in 57.9% of the aprotinin-treated patients and in 31.6% of patients not treated with aprotinin.

Aprotinin↗

Coronary artery disease in a patient with a congenital pericardial defect.

This case report summarizes our experience with a 43 year old male patient with congenital pericardial defect, involving the left ventricular part of the pericardium, and additionally 2-vessel coronary-artery disease in the absence of any coronary risk factors. This patient underwent coronary-artery bypass grafting. Intraoperatively the heart was found to be rotated and herniated into the left pleural cavity, strangulated by the remaining pericardium causing a bridle stricture of the right as well as the left margin of the heart, with a subsequent local narrowing of the ventricle in these areas. Furthermore, assessment of the coronary arteries at operation by external palpation showed the location of an RCA- and LAD-stenosis to match exactly with the stricture area.

Adult↗

Pancreatic islet transplantation in cynomolgus monkeys. Initial studies and evidence that cyclosporine impairs glucose tolerance in normal monkeys.

Using a model of streptozotocin-induced, ketosis-prone, insulin-dependent diabetes mellitus (IDDM) in the cynomolgus monkey, we performed 11 intraportal transplants of collagenase-digested, Ficoll-purified pancreatic islets (9 ABO-compatible allografts and 2 concordant baboon xenografts). Islets were pretreated with ultraviolet-B irradiation and recipients received cyclosporine A immunosuppression. Two grafts never functioned, five grafts showed evidence of partial function, and four grafts (three allografts and one xenograft) showed evidence of good function, with the animals independent of exogenous insulin with morning fasting blood glucose levels less than 200 mg/dl. Because two grafts functioned only after CsA was either tapered or discontinued, we performed a related study that showed that therapeutic doses of CsA (morning trough serum level 150-250 ng/ml) impaired intravenous glucose tolerance tests (IVGTT) of normal monkeys and may contributed to graft dysfunction in our islet transplantation model. The results show that there is a decrease in release of serum insulin during an IVGTT leading to impairment of glucose utilization, while serum glucagon remains unaffected. After cessation of CsA, the IVGTT did not return to normal for 28 days. Oral glucose tolerance tests were unaffected in CsA-treated monkeys. These initial studies show that the streptozotocin-diabetic monkey is a valuable model to study IDDM and islet transplantation in nonhuman primates. We also confirm studies in rodents, dogs, and sheep by showing that CsA partially inhibits beta cell function in normal monkeys.

Animals↗

Inhibition of growth of human breast carcinomas in vivo by somatostatin analog SMS 201-995: treatment of nude mouse xenografts.

Minced tumor fragments were xenografted into subcutaneous tissue of the lateral thoracic regions of young adult, virgin female nude mice to study the effects of somatostatin analog SMS 201-995 on growth of estrogen-dependent (MCF-7) and estrogen-independent (BT-20) human breast carcinomas. When tumors became palpable (6 to 10 days), mice were assigned randomly to receive either SMS (4 to 50 micrograms) or acetate buffer (0.2 ml) subcutaneously twice a day. For MCF-7, mean tumor volume was significantly lower on day 20 and days 30 through 50 in SMS-treated mice than in controls (p less than 0.05), and tumor doubling time was increased from 13.2 to 19.0 days. Calculated growth increment was significantly lower with SMS than with buffer treatment (1.1 +/- 0.1 vs 1.9 +/- 0.2) (p less than 0.001). For BT-20, mean tumor volume of SMS-treated mice was slightly, but not significantly, lower than that of controls; however, calculated growth increment was significantly lower for SMS treatment (3.2 +/- 0.3 vs 3.9 +/- 0.4) (p +/- 0.001), and tumor doubling time was increased from 4.0 to 5.8 days. For MCF-7, flow cytometric DNA analysis of tumor biopsy samples demonstrated a reduced G2 + M phase with SMS treatment. We conclude that SMS slows the growth of both MCF-7 and BT-20 human breast cancer xenografts in nude mice and that SMS may be clinically useful in the management of patients with breast carcinoma.

Animals↗

Purification and characterization of DNA polymerase alpha from plasmodia of Physarum polycephalum.

DNA polymerase alpha from Physarum polycephalum has been purified from freshly harvested microplasmodia. An inhibitory activity was removed by precipitation with poly(ethyleneimine) and interfering type-beta-like DNA polymerase by chromatography on phosphocellulose. The preparation was free of endonucleases and exonucleases. The DNA-polymerizing polypeptide had a molecular mass of 140 kDa by polyacrylamide gel electrophoresis under denaturing conditions. It was contained in purified samples and in crude cell extracts. Peptides of smaller size that reacted with antibodies against this protein were generated during purification and prolonged standing. Molecular sizing under non-denaturing conditions resulted in high-molecular-mass forms. The type of isolated DNA polymerase was established on the basis of inhibition and template-primer utilization experiments underlying the classification of DNA polymerases from higher eucaryotes. The majority of the DNA-polymerizing activity was contained in the cell nucleus fraction and was inhibited by aphidicolin. The isoelectric point (pI) was 6.7 +/- 0.2, the pH optimum at pH 6.8, and the temperature optimum at 40 degrees C. Monovalent salts, Li+, Na+, NH+4, K+, were inhibitory except for small activation maxima at 10 mM, 75 mM and 100 mM in the case of Na+, NH+4 and K+ respectively. The bivalent cations Mg2+ and Mn2+ had broad activity maxima at 3-20 mM concentrations, which were shifted to 0.05-0.1 mM in the case of Mn2+ and synthetic DNA homopolymers. The numbers of molecules of DNA polymerases in Physarum nuclei were calculated and compared with the established number of replicons in plasmodia and with the number of molecules of DNA polymerases in higher eucaryotes.

Cell Nucleus↗

Reactivation of chronic type B hepatitis: the effect on expression of serum HBV-DNA and pre-S encoded proteins.

Hepatitis B markers were studied in seven patients with reactivated liver disease. Reactivation of chronic type B hepatitis, as indicated by the reappearance of hepatitis B e antigen (HBeAg) in the serum, was characterised by the appearance of hepatitis B virus-DNA (HBV-DNA) in the serum. The expression of pre-S 1 encoded protein remained unchanged in five of seven patients, and poly-HSA as a marker for pre-S 2 encoded protein remained detectable in six of seven patients before and after reactivation of chronic hepatitis. The level of serum HBV-DNA correlated well with the level of liver enzymes, which rose from normal to various levels after reactivation of the liver disease. The data suggest that inflammatory activity of the liver disease is not related to the expression of pre-S encoded protein but to viral replication. Possibly pre-C and C-gene encoded antigens, which are produced together with viral nucleic acid and expressed on the surface of HBV-infected liver cells, play the key role in liver damage believed to be mediated by cytotoxic T cells.

Adolescent↗

Transdifferentiation from striated muscle of medusae in vitro.

We have established an in vitro transdifferentiation and regeneration system which is based entirely on mononucleated striated muscle cells. The muscle tissue is isolated from anthomedusae and activated by various means to undergo cell cycles and transdifferentiation to several new cell types. In all cases DNA-replication is initiated and the division products are smooth muscle cells, characterized by their ultrastructure and monoclonal antibodies, and nerve/sensory cells, characterized by their ultrastructure and FMRFamide-staining. Both cell types are found at a 1:1 ratio after the first division. The nerve cells stop to replicate, whereas the smooth muscle cells continue and keep producing in each successive division a smooth muscle cell and a nerve cell. The observed data indicate that smooth muscle cells behave like stem cells. Depending on the destabilization and culturing methods, some isolated muscle tissue will form a bilayered fragment and within only two cell cycles manubria (the feeding and sexual organ) or tentacles will regenerate. In this case six to eight new non-muscle cell types have been formed by transdifferentiation.

Animals↗

Expression of Pre-S-encoded proteins in sera of individuals chronically infected with hepatitis D virus.

The sera of 16 individuals chronically infected with the hepatitis D virus were analyzed for hepatitis B virus (HBV) markers. The majority of these patients had a non-replicative form of viral type B hepatitis as indicated by negative tests for HBeAg and HBV-DNA. Pre-S-encoded proteins were detected in 13/16 sera. Sera that were negative for polymerized serum albumin did also not contain pre-S1-encoded proteins. The presence of pre-S-encoded proteins is probably predominantly associated with 22-nm HBsAg forms present in large amounts in sera of individuals with chronic type D hepatitis.

Chronic Disease↗