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Biomedical subjects

D Müller

Publications and source records attributed to D Müller.

At least 253 records · Page 14Linked to original sources

[Left ventricular catheter ablation of the AV conduction system with radiofrequency electric current].

We report on a 32-year-old female patient with a history of recurrent atrial fibrillation and rapid ventricular response (up to 240 beats/min) resistant to multiple drug therapy. In this patient, we successfully performed a radiofrequency catheter ablation of the atrioventricular (AV) junction from the left ventricle, after radiofrequency energy application in His-position above the tricuspid valve was unsuccessful. This technique offers an-alternative treatment in patients in whom the conventional right-sided catheter ablation of the AV junction proves ineffective.

Adult↗

Atrial natriuretic peptide (ANP) is a high-affinity substrate for rat insulin-degrading enzyme.

A cytosolic protein specifically binding to and degrading atrial natriuretic peptide (ANP) was purified from rat brain homogenate. Based on partial amino acid sequences and enzymatic properties, this protein with an apparent molecular mass of 112 kDa has been identified as the rat insulin-degrading enzyme (IDE). In addition to the known substrates, insulin and transforming-growth-factor alpha IDE binds also with high affinity (apparent Kd 60 nM) to ANP. Competition studies with structural variants of ANP demonstrate that both the C terminus and the disulfide loop of the molecule are essential for high-affinity binding. The data suggest that IDE might be involved in the cellular processing and/or metabolic clearance of ANP.

Affinity Labels↗

[Thyroid abscess caused by Salmonella enteritidis].

A 70-year-old diabetic woman with a nodular goitre developed a swelling in the right neck, increasing over two weeks, as well as fever (38.2 degrees C), increased tendency towards sweating, finger tremors and pain on swallowing. Ultrasound examination of the thyroid raised the suspicion of an abscess, 3.5 x 1.5 cm, at the upper pole of the right thyroid lobe. Material obtained by fine-needle puncture grew Salmonella enteritidis. There have been no symptoms of gastroenteritis at any time. Stool and sputum cultures and nasopharyngeal swabs revealed the sites from which haematogenous spread had come. The abscess regressed (as monitored by ultrasound) within four weeks during intravenous treatment with 1,600 mg/d sulphamethoxazole and 320 mg/d trimethoprim (antibiotics determined by drug sensitivity tests) and after several ultrasound-directed needle punctures. Initially manifest hyperthyroidism (fT4: 3.4 ng/dl; basal TSH: 0.03 microU/l) regressed during the treatment without antithyroid treatment. The patient has been symptom-free for 6 months.

Abscess↗

Lipid peroxidation in thioacetamide-induced macronodular rat liver cirrhosis.

Microsomes and isolated hepatocytes from thioacetamide (TAA)-induced macronodularly cirrhotic rat livers were analysed for their susceptibility to unstimulated and stimulated lipid peroxidation measured as malondialdehyde (MDA) formation. In microsomes from TAA-induced macronodularly cirrhotic livers the MDA production stimulated either by ascorbate-iron or by ADP-iron in a NADPH-regenerating system was decreased. Hepatic microsomes from TAA-treated rats exhibited a reduced cytochrome P450 content and lowered activities of ethylmorphine N-demethylase, ethoxycoumarin O-deethylase and epoxide hydrolase. Besides this, the microsomal fatty acid pattern of phosphatidylcholine and phosphatidylethanolamine was significantly changed after 6 months of TAA administration. The 18:2/20:4 ratio of phospholipid fatty acids was markedly increased. In contrast to the microsomes, in isolated hepatocytes from macronodularly cirrhotic livers the iron- and ascorbate-iron-stimulated MDA formation was increased. The hepatocellular GSH content was unaffected by TAA pretreatment, whereas the GSSG content exhibited a significant increase, thus leading to a pronounced reduction of the GSH/GSSG ratio. The calcium channel blocker verapamil (200 microM), known to be able to scavenge OH' radicals produced by the Fenton reaction, revealed an inhibitory effect on ascorbate-iron- and ADP-iron-stimulated lipid peroxidation in hepatocytes from normal as well as TAA-treated livers which is attributed to its antioxidative properties. In summary, lipid peroxidation is altered in TAA-induced macronodularly cirrhotic rat livers. Furthermore, the data clearly show that isolated microsomes and parenchymal cells prepared from cirrhotic livers react differently to prooxidant stimuli.

Animals↗

Biochemical and morphological studies on perivenous and periportal liver parenchymal cells from female rats isolated by digitonin-collagenase method.

Periportal (pp) or perivenous (pv) liver parenchymal cells from female adult Uje: WIST rats were isolated after retro- or antegrade digitonin infusion followed by collagenase perfusion in the opposite direction. The morphological results revealed a distinct acinar-related destruction of the pv- or pp-zone by digitonin. The remaining cells of the respective other zone showed a good structural maintenance. After subsequent conventional collagenase perfusion the yield, viability and structural integrity of the isolated hepatocytes were high. The zonal cell separation was indicated by significant differences in the pp marker glucose-6-phosphatase and the pv marker glutamine synthetase found in the isolated pp or pv cell populations. Under our experimental conditions including the use of female rats, the alanine aminotransferase and glutamate dehydrogenase as well as ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities were evenly distributed in both preparations. Under stimulating conditions the capacity for urea synthesis was similar in both pv and pp cells.

7-Alkoxycoumarin O-Dealkylase↗

The influence of "essential" phospholipids (EPL) on phase-I- and phase-II-reactions and on the glutathione status in the liver of aging rats.

"Essential" phospholipids (EPL; polyene-phosphatidylcholine) were administered orally to aging male rats in doses of 100 and 300 mg/kg b.wt. over 10 weeks. One and 7 days after the last treatment cytochrome P-450 concentration, epoxide hydrolase and glutathione-S-transferases were found to be unchanged, but ethylmorphine N-demethylation, ethoxycoumarin O-deethylation and UDP-glucuronosyltransferase activities were enhanced, as were the concentrations of both reduced and oxidized glutathione, the values being similar to those in young adult rats. These results are discussed in terms of an increase in endoplasmic reticulum membrane fluidity.

7-Alkoxycoumarin O-Dealkylase↗

The influence of the radiation syndrome on cytochrome P450-dependent monooxygenation in rat liver.

Cytochrome P-450 concentration and the monooxygenation activities of some cytochrome P-450 forms were determined in rat liver in the course of the acute radiation sickness. Ethylmorphine N-demethylation, ethoxycoumarin, ethoxyresorufin, and pentoxyresorufin O-dealkylation were used as indicator reactions. After radiation a distinct decrease in the hepatic biotransformation capacity can be observed, most pronounced at the climax of the radiation syndrome. Phenobarbital treatment (60 mg/kg b. m. at 3 consecutive days each) increases the concentration and the monooxygenase activities of some cytochrome P-450 forms. The degree of this induction effect is not altered at the third day after radiation, whereas at day 7 no significant inducibility can be observed.

7-Alkoxycoumarin O-Dealkylase↗

Influence of aging, training and acute physical exercise on plasma glutathione and lipid peroxides in man.

In trained (long-distance runners) and untrained volunteers aged 22 to 57 years, basal plasma glutathione (GSH) concentration decreased significantly with increasing age. In most age groups basal GSH concentration of oxidized glutathione (GSSG) and lipid peroxides (LPO) was not influenced either by age or by training. Following acute physical exercise (bicycle ergometric test), which was maximal for each person and thus different in trained and untrained persons, plasma GSH, GSSG, and LPO concentrations were not changed at all in untrained volunteers. In trained persons, however, GSH concentration was significantly decreased by about 30%. Surprisingly, we observed a decrease in plasma LPO content by about 40%. GSSG content was not altered. The comparison with some physical-physiological parameters indicates that the changes in GSH and LPO concentrations depend on the extent of acute physical exercise rather than on previous training. Alterations of GSH and LPO in plasma could be of physiologic significance.

Adult↗

[Three-dimensional reconstructions in neuroanatomy].

Computer-aided 3D reconstructions of neurofunctional systems and structures are generated as a reference for neuroimaging (CT, MRI, PET). The clinical application of these 3D reconstructions requires a coordinate system and conditions resembling the intravital neuroanatomy as far as possible. In this paper the neuroanatomical Reference System (NeuRef) of the Department of Neuroanatomy of Hannover Medical School is presented. This consists of methods to record brain structures from serial sections with minimal error (less than 1 mm) and to display 3D brain models derived from such a data base. In addition, NeuRef is able to generate sections through, for instance, the visual and pyramidal system and to transfer these data onto a corresponding CT image. Therefore, this method can serve as a diagnostic aid in neuroradiology, in operation planning, and radiotherapy. It can also be used in PACS.

Brain↗

Domain structure of the endothelial cell receptor thrombomodulin as deduced from modulation of its anticoagulant functions. Evidence for a glycosaminoglycan-dependent secondary binding site for thrombin.

Rabbit thrombomodulin (TM) influences blood coagulation by serving as a cofactor for thrombin-induced protein C activation (activity a), by directly affecting the procoagulant activity of thrombin (activity b) and by accelerating the inhibition of thrombin by antithrombin III (AT III) (activity c). Although high molecular weight cationic compounds, such as poly-L-lysine and the ionophore-releasate from human platelets, only partly affected activity a in a concentration-dependent manner, activities b and c, however, were almost totally inhibited by these cationic compounds. Likewise, a heparin- and dermatan sulfate-binding peptide which represents a portion of the glycosaminoglycan-binding domain of vitronectin (VN) selectively inhibited activities b and c, indicating the presence of clustered acidic domain(s) in TM responsible for these activities. While heparinase or heparitinase did not affect rabbit TM function at all, digestion of rabbit TM with chondroitin ABC-lyase abolished activities b and c, whereas activity a remained unaffected. Modification of rabbit TM with chondroitin ABC-lyase was associated with a decrease in molecular mass of the receptor by about 10 kDa and a 2- to 3-fold decrease in affinity to thrombin as deduced from direct binding studies. These results suggest that at least two acidic thrombin binding domains are present in rabbit TM, whereby a dermatan sulfate-like glycosaminoglycan moiety constitutes the secondary binding domain for thrombin, eliciting both the direct as well as the AT III-dependent anticoagulant function of rabbit TM (activities b and c) but not protein C activation (activity a). In contrast to rabbit TM, human TM isolated from placenta only showed weak activities b and c. These differences in reactivity of TM from different sources appeared to be due to the masking (or absence) of the proposed secondary thrombin binding site in human TM, since VN could be identified as a major contamination in the human TM preparation as revealed by enzyme-linked immunosorbent assay and Western blot analysis. In addition, the major part of human TM could be immunoprecipitated by monospecific antibodies to VN. These findings indicate a possible modulatory function for VN in the human thrombin-TM system.

Amino Acid Sequence↗

Biochemical and ultrastructural studies on the effect of verapamil on formation and secretion of lipoproteins in rat hepatocyte suspensions.

The effect of the calcium channel blocker verapamil on structure, formation and secretion of very-low-density lipoproteins (VLDL) from rat hepatocytes in suspension was examined. After 30 min incubation at a verapamil dose of 200 microM neither free fatty acid (FFA) uptake nor triglyceride (TG) and phospholipid (PL) secretion into the incubation medium were significantly changed. After 90 min incubation the TG secretion was inhibited by about 60%, whereas the PL output was only insignificantly lowered, indicating the secretion of abnormally composed lipoprotein particles. Morphologically, after 30 min incubation the hepatocytes had lost their microvillous border and exhibited a 2-3-fold increase in volume density and average size of the lysosomes. In the Golgi-containing regions an accumulation of smooth-surfaced microvesicles was regularly evident. The configuration of the Golgi complexes was normal. After 90 min incubation the lysosomes showed a further significant elevation in volume and size. The Golgi complexes exhibited only minor changes, but their content in VLDL particles was reduced per microns 2 Golgi complex by about 75%. Commonly, the VLDL were larger and more heterogenous in size. The diameter of those VLDL secreted into the incubation medium ranged from 31 to 84 nm, thus surpassing the control values by 2-3 times. The secretion of large-sized VLDL was regularly associated with the intracytoplasmic appearance of dilated smooth-surfaced vesicles filled with size-modified VLDL. These vesicles were concentrated within Golgi-containing areas from where they were widely dispersed towards the cell periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of xenobiotics on drug metabolism and its sensitive detection.

Biotransformation of drugs and other xenobiotics in the liver plays an important role intoxication and detoxication processes, i.e. changes in biotransformation activity have significant biological consequences. For that reason the determination of biotransformation activity is useful. The rate of some biotransformation reactions can be markedly changed by very small doses of xenobiotics. These changes may be used for the sensitive detection of the exposure to xenobiotics. Among biotransformation reactions cytochrome P-450-dependent monooxygenation is very important. It can be induced and inhibited by xenobiotics. Induction of P-450 forms can be detected by various methods, e.g. by using model reactions. Ethoxycoumarin O-deethylation, ethoxyresorufin O-deethylation, pentoxyresorufin O-depentylation and ethylmorphine N-demethylation are catalyzed at different P-450 forms, and their determination is described in detail.

Animals↗

Purine nucleotides and AMP deamination during maximal and endurance swimming exercise in heart and skeletal muscle of rats.

The purine nucleotides, phosphocreatine (PCr), ammonia, and lactic acid were investigated in skeletal muscles of rats with prominent type I, type IIa, type IIb fibers, and the heart after exhaustive and endurance swimming tests. ATP, ADP, AMP, IMP, and PCr were determined by HPLC with UV detection in controls after maximal and endurance training for 6 weeks with or without a respective final test and also after final exhaustive or endurance test without preceding training. The swimming time in these tests was longer with than without training. A pronounced ATP decrease and a large increase in IMP, up to 4.9 mumol/g wet weight, were found in type IIb fibers after the maximal final test without preceding training. Compared with skeletal muscle, the IMP concentration in the heart was significantly lower after all exercise bouts, even though after maximal exercise AMP augmentation was highest, ATP reduction was greatest, and energy charge was lowest. The difference between the heart and skeletal muscle in the production of IMP indicates that despite AMP and ADP accumulation, myoadenylate deaminase (MAD) activity in the heart is considerably lower than in skeletal muscle, especially in type IIb fibers. The smaller amount of MAD per tissue, and also the different MAD isozyme pattern of the heart as reported in the literature, may be attributed to lower activation. The difference between MAD activation of the soleus muscle and of the iliacus muscle, both consisting predominantly of type I fibers, suggests that MAD activity may be influenced by biochemical demand and oxygen supply, varying with the anatomical localization. Even though ammonia and lactic acid were highly correlated, it is questionable whether the H+ ion increase due to the lactate accumulation itself triggers MAD activation, as has been found for AMP and ADP in skeletal muscle.

AMP Deaminase↗