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Biomedical subjects

K Müller

Publications and source records attributed to K Müller.

At least 379 records · Page 21Linked to original sources

Solubilization of imipramine-binding protein from human blood platelets.

Various procedures for the solubilization of the imipramine-binding protein (IBP) of human platelets were compared. An IBP of a molecular weight of 300 000-400 000, as determined by exclusion chromatography on Sepharose 6B, was obtained with high amounts of digitonin and with lysolecithin. With smaller amounts of digitonin the molecular weight varied between more than 1 million and about 550 000 depending on the batch of detergent. The KD values and the IC50 values of drugs inhibiting imipramine binding were similar in the soluble preparation and in intact membranes. CHAPS and CHAPSO, even in high amounts, yielded solubilized IBP of high molecular weight (greater than 1 million). Membrane preparations of human platelets solubilized with high amounts of digitonin and with lysolecithin would therefore seem to be the most suitable for further purification of IBP.

Blood Platelets↗

A triglobular model for the polypeptide chain of aspartokinase I-homoserine dehydrogenase I of Escherichia coli.

Limited proteolysis of aspartokinase I-homoserine dehydrogenase I from Escherichia coli by type VI protease from Streptomyces griseus yields five proteolytic fragments, three of which are dimeric, the other two being monomeric. One of the monomeric fragments (27 kilodaltons) exhibits residual aspartokinase activity, while the second one (33 kilodaltons) possesses residual homoserine dehydrogenase activity. The smallest of the dimeric species (2 X 25 kilodaltons) is inactive; the two other dimers exhibit either only homoserine dehydrogenase activity (2 X 59 kilodaltons) or both activities (hybrid fragment, 89 + 59 kilodaltons). This characterization of the proteolytic species in terms of molecular weight, subunit structure, and activity leads to the proposal of a triglobular model for the native enzyme. In addition, the time course of the formation of the various fragments was followed by measuring enzymatic activity and performing gel electrophoretic analysis of the protein mixture at defined time intervals during proteolysis. On the basis of the results of these studies, a reaction scheme describing the succession of events during proteolysis is given.

Aspartokinase Homoserine Dehydrogenase↗

Temperature-sensitive mutants of fowl plague virus (influenza A) generated by undiluted passages at 33 degrees C.

Temperature-sensitive (ts) mutants obtained by undiluted passages of fowl plague virus at 33 degrees C have their defects located mainly in RNA segments 3, 4 and 8 as determined by rescue to wild-type with standard ts mutants. This result is different from that obtained after treatment of virus with mutagens, where the frequency of mutations follows roughly the target size of the RNA segments. Many isolates generated after undiluted passages at 33 degrees C, which seem to have mutations in RNA segments 3 and 4, can be rescued to wild-type. This occurs, however, with certain defined standard ts mutants having a defect in RNA segment 4, but not by other segment 4 mutants. One such mutant, ts 1/93 (ts defect in segment 3), interferes with the multiplication of ts 227 (ts defect in segment 4) at the permissive temperature, presumably at the level of vRNA synthesis, preventing reassortment to wild-type. Similarly, ts 263 (ts defect in segment 3) interferes with the multiplication of ts 1/1 (ts defect in segment 4). For other such interfering mutants, the mechanism preventing reassortment to wild-type is different from that of ts 1/93 or ts 1/1, but is not yet understood. Thus, the number of mutations as determined by rescue with standard ts mutants in isolates obtained by undiluted passages is overestimated due to intrinsic interference.

Animals↗

[Use of electronic data processing for quality control in perinatal medicine].

Pregnancy, delivery and neonatal period are influenced by many factors, which effect on perinatal and neonatal mortality and morbidity on the other-hand. Numerous parameters are to be recorded and analyzed for control of quality. With conventional technic of data processing this is only possible in large perinatological centers on a restricted scale. Therefore the electronic data processing project "perinatal medicine" was developed for recording important perinatological efficiency parameters. It was introduced in the practice of gynecological and infant hospital in Karl-Marx-Stadt.

Computers↗

Precision scanning calorimetry of bile salt-phosphatidylcholine micelles.

Precision scanning calorimetry has been used to examine the thermal behavior of mixed micelles formed between bile salts and dipalmitoylphosphatidylcholine (DPPC). Complex thermal transitions are observed which change dramatically with the mole ratio of bile salt to DPPC, dilution, and ionic strength. Comparison of the behavior of sodium taurocholate (TC) mixed micelles with sodium taurodeoxy-cholate (TDC) mixed micelles indicates similarity in the thermal transitions at high dilution or when the actual micellar composition is similar. It was found through equilibrium dialysis that considerably less TC than TDC is incorporated into mixed micelles with DPPC at a given bile salt concentration. Accounting for these concentration differences provides a means for more direct analysis of changes in the thermal transitions with mole ratio and dilution for the two bile salt components. Resolution of the thermal transitions into several component contributions is employed as an aid to interpretation of the differential scanning calorimetry curves. The curve resolutions lead to estimates of van't Hoff and calorimetric enthalpies of the individual contributions. The results of the curve resolutions, along with the behavior of the total enthalpies of the transitions, are consistent with a transformation in micellar structure occurring when the actual micellar composition is a mole ratio of bile salt to DPPC of about 1 to 1. The transformation region is near that found from X-ray evidence and is thought to correspond to a change from disk-shaped to spherical micelles.

Bile Acids and Salts↗

Thermodynamics and mechanism of high-pressure deactivation and dissociation of porcine lactic dehydrogenase.

Lactic dehydrogenase (LDH) from pig heart and pig skeletal muscle can be reversibly dissociated into monomers at high hydrostatic pressure. The reaction can be quantitatively fitted by a reversible consecutive dissociation-unfolding mechanism according to N in equilibrium 4M in equilibrium 4M (where N is the native tetramer, and M and M two different conformations of the monomer) (K. Müller, et al., Biophys. Chem. 14 (1981) 101.). At p less than or equal to 1 kbar, the pressure deactivation of both isoenzymes (H4 and M4) is described by the two-state equilibrium N in equilibrium 4M. From the respective equilibrium constant and the temperature and pressure dependence of the change in free energy, the thermodynamic parameters of the dissociation/deactivation may be determined, e.g., for LDH-M4: delta GDiss = 110 kJ/mol, delta SDiss =-860 J/K per mol, delta HDiss= -124 kJ/mol (enzyme concentration 10 microgram/ml, in Tris-HCl buffer, pH 7.6, I = 0.16 M, 293 K, 0.8 kbar); the dissociation volume is found to be delta VDiss =-420 ml/mol (0.7 less than p less than 0.9 kbar). Measurements using 8-anilino-1-naphthalenesulfonic acid (ANS) as extrinsic fluorophore demonstrate that the occurrence of hydrophobic surface area upon dissociation parallels the decrease in reactivation yield after pressurization beyond 1 kbar. Within the range of reversible deactivation (p less than 1 kbar) no increase in ANS fluorescence is detectable, thus indicating compensatory effects in the process of subunit dissociation. 2H2O is found to stabilize the enzyme towards pressure dissociation, in accordance with the involvement of hydrophobic interactions in the subunit contact of both isoenzymes of LDH.

Anilino Naphthalenesulfonates↗

Plasminogen activator activity in the aorta of strains of rats with genetically determined different patterns of lipids in the blood. Induction of increased activity by streptozotocin.

In a strain of genetically hypercholesterolemic rats (RICO), developed from an albino mutant of Rattus norvegicus (Sprague-Dawley, Tif: RAIf, SPF) by selective breeding, the intimal plasminogen activator activity (PAA) at the nonbranching regions of the aorta was markedly lower than at the nonbranching regions of the aorta in the control strain (Sprague-Dawley). At the branching regions of the aorta the intimal PAA showed no difference between the two strains of rats. In another strain of rats (HBC; hyper-beta-cholesterolemic) with a slightly elevated level of total cholesterol in the blood, a high concentration of LDL-cholesterol and a low concentration of triglycerides, the intimal PAA showed no difference from that in the control strain (Sprague-Dawley) at the branching and nonbranching regions of the aorta. 6 weeks after a single injection of streptozotocin at a diabetogenic dose (45 mg/kg) into RICO rats and the control strain, the intimal PAA was found to be increased by 280% in RICO rats, but only by 140% in controls, compared to that in the corresponding nontreated rats.

Animals↗

The antenatal use of ambroxol (bromhexine metabolite VIII) to prevent hyaline membrane disease: a controlled double-blind study.

A prospective double-blind clinical trial was carried out to determine whether ambroxol (bromhexine metabolite VIII) treatment (1000 mg/day for a period of 5 days) reduces the risk of hyaline membrane disease (HMD) in potentially premature infants. Amniocentesis was performed before the first and 24 h after the last application of ambroxol or placebo to assess the development of the total phospholipid phosphorus content, the L/S ratio, the P/S ratio, and the properties of the surface tension of the amniotic fluid after ambroxol or placebo. There were 246 infants born to 224 mothers. Of the 116 infants with less than or equal to 36 completed weeks' gestation, 56 were in the ambroxol and 60 in the placebo group. No differences between groups occurred in risk factors for HMD (diabetes, asphyxia, male sex, cesarean section). Statistically significant differences in favor of the infants in the ambroxol group were found in the HMD incidence: 23.2% in the ambroxol group compared with 41.7% in the placebo group (p less than 0.05). There was no reduction of the HMD incidence in the less than or equal to 32-week gestational age category in the ambroxol group compared with the placebo group inspite of the fact that all the examined parameters for determining lung maturity reflected a stimulatory effect of ambroxol compared with the results of the placebo group, particularly before the 33rd week of gestation. Prolonged rupture of the membranes played no protective role against HMD.

Ambroxol↗

[Community mental health in Israel].

The current state of mental health care in Israel is described, considering the historical and sociodemographic background. Predominating are community out-patient clinics and cooperation of out-patient and in-patient services, whereas the number of beds and the size of wards is comparatively small. The country is consequently divided into catchment areas with a flexible adjustment according to the geographical characteristics and practical means. Generally the centres are richly staffed instead of expensive buildings. In a short amount of time and by comparatively small means, a modern and humane psychiatric and psychotherapeutic care has been established, fairly meeting the needs of the patient concerned.

Adult↗