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Biomedical subjects

R Gasser

Publications and source records attributed to R Gasser.

122 records · Page 7Linked to original sources
PubMed1986

Acute myocardial infarction: an episodic event of several coronary spasms followed by dilatation?

Acute myocardial infarction (AMI) can no longer be considered as a single event, but as a series of episodes. In most of the cases, the initial event may be the induction of a severe spasm of the coronary artery by vasoconstrictive substance released from aggregated platelets. These spasms are followed by dilatation, which is caused by substances set free from the ischemic tissue. Dilatation then results in a washing-out of vasoactive mediators (as well as myoglobin) and platelets, which is reflected as a peak in the blood myoglobin concentration-time curve. The local depletion of vasodilative metabolites allows a further contraction of the coronary vessel. A new accumulation of platelets then stimulates another spasm. This vicious circle (thrombo-ischemic re-entry-mechanism) is repeated several times and can be interrupted by the systemic administration of thrombolytic drugs (streptokinase).

Coronary Vasospasm↗
PubMed1985

Pathological findings in coronary arteries associated with sudden death in Austria.

50 witnessed sudden cardiac deaths in the age group between 20-50 years have been studied at autopsy. The most remarkable findings were a high percentage of stenosis and arteriosclerosis of the descending branch of the left coronary artery and a large amount of three vessel disease. It is clear that severe stenosis and sclerosis of the coronary arteries are not essentially related to sudden cardiac death, but a high number of vessels with moderate stenoses and sclerosis has been found. The severity of vessel disease has been evaluated by a coronary score, which takes the haemodynamic effects of the injured coronary arteries on the myocardium into account. We also noted that patients below 35 years of age who died of sudden cardiac death showed a very low coronary score.

Adult↗
PubMed1985

Cytochrome P450 of small intestinal epithelial cells. Immunochemical characterization of the increase in cytochrome P450 caused by phenobarbital.

We have studied total cytochrome P450 and the major form of cytochrome P450 increased by phenobarbital in small intestinal epithelial cells and livers of male Sprague-Dawley rats. Using an improved method for preparing microsomes from intestinal epithelial cells, we find that concentrations of total cytochrome P450 in intestinal cell microsomes are 10% of those in liver microsomes, and that this percentage is unchanged after phenobarbital treatment. In untreated rats, less than 5% of total cytochrome P450 of liver or intestinal epithelium is the form induced by phenobarbital, as measured by rocket immunoelectrophoresis. In phenobarbital-treated rats, the major phenobarbital-induced form accounts for approximately 50% of the total in both organs. In the small intestine of phenobarbital-treated rats, the concentrations of total cytochrome P450 and of the major phenobarbital-induced form increase concurrently as epithelial cells mature from crypt to upper villus. Concentrations of total cytochrome P450 and of the major phenobarbital-induced form in the proximal two-thirds of the rat small intestine are twofold higher than in the distal third. Immunoblotting performed with a monoclonal antibody to the major phenobarbital-induced form of cytochrome P450 from rat liver revealed a subtle difference between this form in liver and intestine.

Animals↗
PubMed1985

[Cerebrospinal fluid and plasma levels of vitamin C in children].

Vitamin C (ascorbic acid) levels in cerebrospinal fluid (CSF) and plasma from 67 children, in whom lumbar puncture had to be performed for medical reasons, are reported in this preliminary paper. 14 children of this group show normal CSF laboratory values and serve as controls. Vitamin C concentrations in CSF of controls are on average 2.5-3-times higher (30.1 +/- 6.3 mg/l) than the pertaining values in their plasma (12.2 +/- 4.9 mg/l). Significant differences are exhibited by premature and term babies, which have up to 16-times higher values of vitamin C in CSF than in plasma. Furthermore CSF vitamin C is 4-5 times higher in premature babies than in schoolchildren of our group (118.2 +/- 65.9 versus 28.3 +/- 3.0 mg/l). Another interesting finding in this study is a significant decrease of CSF vitamin C in cases of acute purulent meningitis (12.3 +/- 4.8 versus 30.1 +/- 6.3 mg/l, p less than 0.05). These results, in connection with reports about high vitamin C concentrations in brain tissue, particularly in prematures, make one suspect important functions of this vitamin in physiological and pathological mechanisms in the central nervous system.

Ascorbic Acid↗
PubMed1984

Characterization of a common genetic defect of cytochrome P-450 function (debrisoquine-sparteine type polymorphism)--increased Michaelis is Constant (Km) and loss of stereoselectivity of bufuralol 1'-hydroxylation in poor metabolizers.

In order to define the mechanism of the debrisoquine-sparteine type genetic polymorphism of drug oxidation we studied the kinetics of bufuralol 1'-hydroxylation in liver microsomes from extensive and poor metabolizers and in a purified reconstituted human cytochrome P-450 isozyme with high activity for bufuralol 1'-hydroxylation, P-450[buf]. In extensive metabolizer microsomes the enzymatic reaction displayed apparent Michaelis-Menten kinetics and the (+)-isomer was preferentially metabolized. By contrast, the enzymatic reaction in poor metabolizer microsomes was characterized by a 4- to 5-fold increase in Km and by a loss of stereoselectivity. In a non-membraneous reconstituted system containing NADPH cytochrome P-450 reductase, a NADPH regenerating system and phospholipids, P-450[buf] exhibited an almost complete substrate stereoselectivity for (+)-isomer 1'-hydroxylation. It is concluded that the purified cytochrome P-450[buf] is the target of the debrisoquine-sparteine type oxidation polymorphism and that poor metabolizers have a quantitative or qualitative deficiency of this isozyme.

Cytochrome P-450 Enzyme System↗
PubMed1984

Biosynthesis of rat liver cytochrome P-450 in mitochondria-associated rough endoplasmic reticulum and in rough microsomes in vivo.

The hypothesis of a preferential biosynthesis of a major phenobarbital inducible form of hepatic cytochrome P-450 (P-450b) in mitochondria-associated rough endoplasmic reticulum (RERmito) was tested by measuring incorporation rates of [35S]methionine and delta-amino[3H]levulinate into the hemoprotein in adult rats. RERmito, rough microsomes (RM representing RER not associated with mitochondria) and smooth microsomes (SM) were quantitatively isolated from the same homogenate by rate zonal centrifugation and their content of P-450b determined by rocket immunoelectrophoresis. P-450b was isolated by immunoprecipitation from detergent-solubilized membrane fractions. The time course and rate of incorporation of [35S] methionine into immunoprecipitable P-450b of RERmito and of RM were similar at all time points studied (2-15 min) both under conditions of maximal induction (4 injections of phenobarbital in 4 days) and after a single injection of phenobarbital. The incorporation of [35S]methionine into P-450b of SM was slower at early time points (2-8 min) but similar to RERmito and RM after 15 min. In contrast, at short labeling periods (less than 8 min) more delta-amino[3H]levulinate was incorporated into P-450b of RERmito than into P-450b of RM and SM. No significant accumulation of free apocytochrome P-450b was found in either membrane fraction. These data indicate a close coordination of the biosynthesis and assembly of apocytochrome P-450b and its prosthetic heme but do not support the hypothesis of a major functional role of MITO X RER complexes in the synthesis of microsomal cytochrome P-450b.

Animals↗
PubMed1984

Debrisoquine-type polymorphism of drug oxidation: purification from human liver of a cytochrome P450 isozyme with high activity for bufuralol hydroxylation.

Indirect evidence suggests that the genetically defective metabolism of drugs such as debrisoquine and bufuralol observed in up to 10% of the population (poor metabolizers) is caused by the absence or functional deficiency of a cytochrome P450 isozyme. Using bufuralol-1'-hydroxylation to carbinol to optimize the procedure, 3 cytochrome P450 isozymes (P450A, P450buf, P450C) were purified to apparent electrophoretic homogeneity from human liver microsomes. P450buf had a specific activity of 20.3 nmol carbinol X nmol P450-1 X 15 min-1 as compared to microsomes (10.0 nmol carbinol X nmol P450(-1) X 15 min-1) when (+)-bufuralol was used as substrate. The stereoselective metabolism of (-)- and (+)-bufuralol to carbinol by purified P450buf [(-)/(+) ratio: 0.13] was strikingly different from that in the microsomes of either an extensive [(-)/(+) ratio: 0.4] or poor metabolizer [(-)/(+) ratio: 0.83] of bufuralol. We propose that this isozyme is the major bufuralol and debrisoquine hydroxylating species and is the target of the genetic deficiency.

Adrenergic beta-Antagonists↗
PubMed1982

The turnover of cytochrome P450b.

The turnover of the heme and apocytochrome moieties of phenobarbital-inducible microsomal cytochrome P450 (P450b) was investigated. Adult male Sprague-Dawley rats were treated with phenobarbital for 5 days and injected with [35S]methionine and the heme precursor delta-[3H]-aminolevulinic acid. P450b was isolated by immunoprecipitation and quantitated by rocket immunoelectrophoresis. The isotope disappearance curves revealed a mean half-life (T1/2) of 12.4 h for the heme moiety and a T1/2 of 19.1 h for the apoprotein moiety of P450b. The apparently slower catabolic rate of the apoprotein may be due to reutilization of [35S]methionine and does not exclude synchronous turnover of the two moieties. Our data are consistent with the kinetics of the drug-mediated induction of cytochrome P450b.

Animals↗
PubMed1976

Investigations on the sodium dependence of bile acid fluxes in the isolated perfused rat liver.

At [Na+]o = 118 mM the concentrative transfer of cholic and taurocholic acid from the perfusate into the isolated rat liver displays saturation kinetics (taurocholate: V = 299 nmol-min-1-g-1, Km = 61 muM; Cholate: V=327 nmol-min-1-g-1, Km = 436 muM). Perfusion with an isotonic sodium-free medium did not change the feature of a carrier-mediated transport but did markedly reduce V without affecting Km (taurocholate: V = 65 nmol-min-1-g-1, Km = 78 muM; cholate: V = 104 nmol-min-1-g-1, Km = 354 muM). It was experimentally assured that the observed reduction of bile salt uptake was not a consequence of regurgitation of bile salts or due to an excessive intracellular accumulation during cholestasis in the sodium-free state. The rate of taurocholate efflux is very low when compared with the rapid rate of the uptake. A stimulatory action of extracellular sodium on this pathway was also observed. Inhibition of the (Na+ + K+)-ATPase by 1 mM ouabain resulted in a decrease of bile salt uptake. Activation of the enzyme by potassium readmission to a K+-deprived liver enhanced bile salt uptake. The immediate response to alteration of the enzyme activity suggests a close association of a fraction of bile acid active transport with the sodium pump.

Adenosine Triphosphatases↗