Correlations between human portal and peripheral venous insulin and proinsulin concentrations under glucose infusion]

In 8 female patients carbohydrate tolerance was proved by means of glucose infusion test 3 days after cholecystectomy. Parameters analyzed in portal and peripheral vein blood are compared with that of 47 healthy persons. All patients demonstrate a pathological carbohydrate tolerance after cholecystectomy, further characterized by an increased lipolysis, a paradoxical rise of HGH, a diminished insulin secretion during the early and increased IRI output in the second phase. There is a significant positive correlation between portal and peripheral vein IRI concentration despite the rising portalperipheral venous IRI difference with raised portal venous IRI concentration. Corresponding differences for proinsulin concentrations can be established in the early phase only. Relations existing between blood glucose and IRI are shown by multiple regression analysis. They suggest that the altitude of IRI concentration is determined by previous blood glucose concentration.     

Results of long-term biguanide therapy as a preventive measure in protodiabetes]

55 patients with pathological glucose tolerance received a long term treatment with buformin (200 mg daily). In 43 of the protodiabetics the duration of treatment was one year, in 29 of them two years and in 11 three years. The age of the patients was 38 years and the mean relative body weight was 118 per cent. The effect of buformin on glucose tolerance and insulin secretion was tested with the glucose infusion test before and after the periods of treatment. After one year we found in 58 per cent, after two years in 69 per cent and after three years in 64 per cent of the protodiabetics an improvement of glucose tolerance. In these groups the results showed a rise of the IRI in the low responder and a decrease of the IRI in the high responder. The good effects on glucose tolerance were not demonstrable in the compared groups with long-term treatment of diet only.     

Studies of glutamate dehydrogenase. Regulation of glutamate dehydrogenase from Candida utilis by a pH and temperature-dependent conformational transition.

Glutamate dehydrogenase from Candida utilis undergoes a reversible conformational transition between an active and an inactive state at low pH AND low temperature. This conformational transition can also be followed by fluorescence measurements. The temperature-dependent equilibrium between the active and the inactive state is characterized by a transition temperature of 10.7 degrees C and a delta H value of 148 kcal/mol (620 kJ/mol). The temperature dependence of the enzymic activity above 15 degrees C yields an activation energy of 15 kcal/mol (63 kJ/mol), a larger value than that for the beef liver enzyme (9 kcal/mol; 38 kJ/mol). In contrast to the yeast enzyme the Arrhenius plot is linear and, therefore, the beef liver enzyme is not transformed into an inactive conformation at low temperatures. Sedimentation analysis shows that the inactivation of the Candida utilis enzyme is not caused by change in the quaternary structure. The pH dependence of the conformational transition at low pH measured by fluorescence change is characterized by a pK value of 7.01 for the enzyme in the absence and of 6.89 for the enzyme in the presence of 2-oxoglutarate with a Hill coefficient of 3.4 in both cases. Similar results are found when the pH dependence of the enzymic activity is analyzed. With the beef liver enzyme the same pK value is obtained but with a Hill coefficient of 1 indicating cooperativity only in the case of the Candida utilis enzyme. The best fit of the pH dependence of the rate constants of the fluorescence changes was obtained with pK values of 7.45 and 6.45 for the active and the inactive state respectively. In this model the lowest time constant which is obtained at the pH of the equilibrium was found to be 0.05 s-1. Preincubation experiments with the substrate 2-oxoglutarate but not with the coenzyme shift the equilibrium to the active conformation. The coenzyme obviously reduces the rate constant of the conformational transition. The sedimentation coefficient (SO20, w) and the molecular weight were found to be 11.0 S and 276 000, respectively. The enzyme molecule is built up by six polypeptide chains each having a molecular weight of 47 000.     

The myofibroblast: Paradigm for a mechanically active cell

Tissues lose mechanical integrity when our body is injured. To rapidly restore mechanical stability a multitude of cell types can jump into action by acquiring a reparative phenotype—the myofibroblast. Here, I review the known biomechanics of myofibroblast differentiation and action and speculate on underlying mechanisms. Hallmarks of the myofibroblast are secretion of extracellular matrix, development of adhesion structures with the substrate, and formation of contractile bundles composed of actin and myosin. These cytoskeletal features not only enable the myofibroblast to remodel and contract the extracellular matrix but to adapt its activity to changes in the mechanical microenvironment. Rapid repair comes at the cost of tissue contracture due to the inability of the myofibroblast to regenerate tissue. If contracture and ECM remodeling become progressive and manifests as organ fibrosis, the outcome of myofibroblast activity will have more severe consequences than the initial damage. Whereas the pathological consequences of myofibroblast occurrence are of great interest for physicians, their mechano-responsive features render them attractive for physicists and bioengineers. Their well developed cytoskeleton and responsiveness to a plethora of cytokines fascinate cell biologists and biochemists. Finally, the question of the myofibroblast origin intrigues stem cell biologists and developmental biologists—what else can you ask from a truly interdisciplinary cell?     

Mitochondrial haplogroup N1a phylogeography,with implication to the origin of European farmers

Background  

Tracing the genetic origin of central European farmer N1a lineages can provide a unique opportunity to assess the patterns of the farming technology spread into central Europe in the human prehistory. Here, we have chosen twelve N1a samples from modern populations which are most similar with the farmer N1a types and performed the complete mitochondrial DNA genome sequencing analysis. To assess the genetic and phylogeographic relationship, we performed a detailed survey of modern published N1a types from Eurasian and African populations.     

Über die direkte und indirekte Strahlenwirkung auf Enzyme in der Zelle

Zusammenfassung Es wurde die Röntgenstrahleninaktivierung von Laktatdehydrogenase in Rattenleber und Invertase in Hefe untersucht. Die Inaktivierung war in den feuchten lebenden Zellen und in den getrockneten Zellen praktisch gleich, obwohl ein Beitrag der indirekten Strahlenwirkung in den feuchten Zellen zu erwarten war.Auszugsweise vorgetragen auf dem XI. Internationalen Kongreß für Radiologie, Rom, September 1965