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J Graf

Publications and source records attributed to J Graf.

187 records · Page 11Linked to original sources

A clinico-pathological study of 163 untreated cases of chronic hepatitis C.

We performed a clinico-pathological study of 163 untreated cases of chronic hepatitis C. Eighty five percent of the patients were clinically asymptomatic and their physical examinations showed unremarkable or minimal changes at the time of the liver biopsy. Liver function tests tended to present slight abnormalities, involving mild elevations of the activity of the aminotransferases and gamma-glutamil transferase levels. In spite of these mild abnormalities, advanced chronic liver disease was histologically detected in eighty nine percent of the patients, mainly showing chronic active hepatitis. The most characteristic histological finding was an interlobular bile duct damage, which correlated with the presence of lymphoid aggregates in the portal tracts and with the development of fibrosis.

Adult↗

Inhibition of rhodamine 123 secretion by cyclosporin A as a model of P-glycoprotein mediated transport in liver.

The interaction between P-glycoprotein modulators and P-glycoprotein mediated transport was investigated using rhodamine 123 in the isolated perfused rat liver of a mutant (TR-) rat strain. TR- rats, deficient in the canalicular multispecific anion transport system, are unable to extrude organic anions (glucuronides) and therefore excrete solely unconjugated rhodamine 123 via P-glycoprotein. Cyclosporin A, a modulator of multidrug resistance in tumor cells, inhibited the biliary secretion of rhodamine 123 dose dependently in a non-competitive manner. Both cyclosporin A and rhodamine inhibited photoaffinity labeling of immunoprecipitated P-glycoprotein with azidopine, indicating binding to hepatic P-glycoprotein. Our results indicate that monitoring the biliary rhodamine 123 secretion in the isolated perfused liver of TR- rats offers a new system for testing modulators of P-glycoprotein like cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Intra-articular treatment with hyaluronic acid in osteoarthritis of the knee joint: a controlled clinical trial versus mucopolysaccharide polysulfuric acid ester.

In a single-blind, randomized clinical trial, both the efficacy and safety of hyaluronic acid (HA) were compared with that of mucopolysaccharide polysulfuric acid ester (MPA) in patients with osteoarthritis of the knee joint. Both agents were administered intra-articularly over six weeks. Patients received either seven injections of HA or 13 injections of MPA. Joint function, range of motion, severity of pain, the general condition of the bony structure and soft tissue of the joint area, and the global clinical efficacy and safety of the medication were assessed. The mean improvement in the modified total Larson rating score was 22% (SD = 28) after HA treatment and 7% (SD = 17) after treatment with MPA (analysis of variance: p = 0.02). This change was mainly caused by a reduction of pain. The onset of pain relief was more rapid in the HA group. The therapeutic effect increased in both treatment groups during the follow-up period. During this interval, lasting six months after the start of treatment, a further reduction of pain and an improvement of knee joint function could be observed. At the end of the study, 25 out of 33 (76%) patients in the HA group and 11 out of 24 (46%) patients in the MPA group were symptom-free or markedly improved (Chi-square test: p = 0.02). Both agents were tolerated very well.

Adult↗

Is intracellular pH and/or intracellular bicarbonate a determinant of bile salt independent canalicular bile formation? The subject revisited.

Canalicular bile formation is a complex process that involves basolateral and apical cell membrane transport, paracellular transport and vesicular transport, all of which may be subject to regulation by pH. We review the concept that apical cell membrane bicarbonate secretion promotes bile salt independent canalicular bile formation. We show that the presence of paracellular electrolyte transport imposes a severe restriction in interpreting data from ion substitution experiments aimed at demonstrating pH or bicarbonate dependent bile formation. Furthermore, we report on experiments that all show stimulation of bile flow under three disparate experimental conditions: i) intracellular alkalinization in the absence of [HCO3-]i or associated with a decrease of [HCO3-]i, ii) intracellular alkalinization with an increase of [HCO3-]i, and iii) intracellular acidification with increase of [HCO3-]i. It is suggested that both, intracellular pH and intracellular bicarbonate may modulate canalicular bile salt independent bile formation, but it remains conjectural which mechanism is the prevailing one under a given experimental setting.

Animals↗