Biomedical subjects

C Gerdes

Publications and source records attributed to C Gerdes.

25 records · Page 2Linked to original sources

PubMed1995

Polymorphisms in the lipoprotein lipase gene and their associations with plasma lipid concentrations in 40-year-old Danish men.

BACKGROUND: In some previous studies, HindIII and Pvu II restriction fragment length polymorphisms (RFLPs) in the lipoprotein lipase (LPL) gene were associated with coronary heart disease and plasma concentrations of HDL cholesterol and triglycerides. However, the populations studied were relatively small and heterogeneous in regard to age, sex, and ethnic background. METHODS AND RESULTS: Associations of a HindIII (intron 8) and a Pvu II (intron 6) RFLP in the LPL gene with plasma concentrations of cholesterol, HDL cholesterol, non-HDL cholesterol, and triglycerides were studied in 457 randomly selected 40-year-old Danish men. The HindIII and the Pvu II sites were in strong linkage disequilibrium. The frequencies of the H+ and P+ alleles (+ denotes presence of cutting site) were 0.717 and 0.464, respectively. In multivariate analysis, there was a clear gene dosage effect of the H+ allele on HDL. The lowest HDL cholesterol concentration was in the H+H+ group, the highest concentration was in the H-H- group, and the H+H- group had intermediate HDL concentrations (P = .03). There was a similar, but not statistically significant gene dosage effect on triglyceride concentrations, with the highest value seen in the H+H+ group. There were no other associations between LPL RFLPs and lipoprotein components. In males reporting family history of premature ischemic heart disease, the H+H+ genotype was overrepresented (odds ratio, 2.75; 95% confidence interval, 1.37 to 5.53). CONCLUSIONS: The results suggest that genetic variation in or near the LPL gene plays a role in interindividual differences in HDL cholesterol concentration and in risk of atherosclerosis and ischemic heart disease in men.

Adult↗

PubMed1994

Lack of prophylactic or therapeutic efficacy of 5-HT2A receptor antagonists in halothane-induced porcine malignant hyperthermia.

During halothane-induced malignant hyperthermia (MH), plasma levels of serotonin (5-hydroxytryptamine, 5-HT) increase in pigs. Administration of 5-HT agonists which stimulate the 5-HT2A subreceptor triggers MH in susceptible pigs. A possible link between MH induced by 5-HT2A receptor agonists and halothane could be an increase of second messengers such as phosphoinositides (inositol polyphosphates), which have recently been implicated in the abnormal regulation of skeletal muscle calcium release in MH. If so, antagonists of 5-HT2A receptors which are linked to phosphoinositide turnover should be capable of preventing, retarding or attenuating halothane-induced MH. This possibility was investigated in the present study in MH susceptible pigs, using dantrolene for comparison, Development of MH triggered by a halothane challenge (inhalation of 3% halothane for 15 min) was completely prevented by dantrolene, 3.5 mg/i.v., whereas the 5-HT2A receptor antagonists ritanserin (0.5-10 mg/kg i.v.) or ketanserin (0.5-10 mg/kg i.v.) exerted no prophylactic effect. In pigs in which dantrolene, ritanserin or ketanserin where given in combination with hyperventilation after development of MH, dantrolene exerted therapeutic efficacy, whereas neither ritanserin nor ketanserin were effective treatments. The data indicate that 5-HT is not critically involved in the mechanisms of halothane-induced MH, at least under the conditions of the present experimental study.

Animals↗

PubMed1992

Increase of serotonin in plasma during onset of halothane-induced malignant hyperthermia in pigs.

The levels of serotonin (5-HT) were determined in platelet-free and platelet-rich plasma before and during the onset of halothane-induced malignant hyperthermia (MH) in genetically MH-susceptible pigs. During MH onset, the free (i.e. physiologically active) levels of 5-HT in plasma rose concomitantly with the increases in muscle tone, body temperature, venous pCO2 and plasma lactate. Since pharmacological stimulation of 5-HT2 receptors has recently been shown to trigger MH in susceptible pigs, the finding of increased 5-HT plasma levels during onset of halothane-induced MH may indicate that 5-HT is involved in the mechanisms by which volatile anesthetics trigger this myopathic syndrome.

Animals↗

PubMed1992

Generation of analytic plasma lipoprotein profiles using two prepacked superose 6B columns.

A simple, low-priced chromatographic system to generate plasma lipoprotein profiles from total human plasma was tested with plasma from normolipidemic subjects and patients with heterozygous familial hypercholesterolemia, hyper-alpha-lipoproteinemia, lipoprotein lipase deficiency, familial dysbetalipoproteinemia and familial lecithin-cholesterol-acyl-transferase deficiency. The system appears to be a good alternative to more expensive high-pressure liquid chromatography systems, notably in lipoprotein laboratories already provided with equipment for column chromatography. If a microplate photometer and a computer is available in the laboratory, the measurement of various lipids in 70-80 eluant fractions from the columns can be simplified.

Adult↗

PubMed1992

Atypical reactions to halothane in a subgroup of homozygous malignant hyperthermia(MH)-susceptible pigs: indication of a heterogenous genetic basis for the porcine syndrome.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In genetically susceptible pigs, MH can be induced by volatile, halogenated anaesthetics such as halothane. Within a series of pharmacological investigations, a fulminant MH could be induced in 59 of 66 homozygous halothane-susceptible pigs by a challenge with 3% halothane for 15 minutes. The typical MH was characterized by sudden appearance of tachycardia, muscle rigidity with typical extension of the hindlimbs, increase of body temperature, acidosis-caused by rapid increase of CO2 and lactate production-, hyperkalaemia and increased activity of creatine kinase (CK) and aspartate transaminase (AST). In seven homozygous MH-susceptible pigs, this typical MH could not be induced by halothane. These animals responded with sudden appearance of bradyarrhythmia and decrease of arterial pressure. In these MH-atypical pigs (MHA) neither the typical extension of hindlimbs nor a hyperthermia occurred. Compared to a group of 6 MH-susceptible pigs with typical reactions to halothane (MHS), the biochemical alterations were significantly retarded in MHA-pigs. These atypical reactions to halothane could be the effect of decreased cardiac output. Concerning the atypical reactions, we observed a familiar predisposition in MH-susceptible pigs. Although atypical reactions were not found in a group of homozygous halothane-nonsusceptible pigs (MHN), a possible explanation for atypical reactions could be a MH-independent halothane-susceptibility of the myocardium+ in MHA-pigs. On the other side the data may indicate that a primary defect in both the skeletal muscle and also the myocardium is involved in MH. The different reactions to halothane in MH-susceptible pigs could point to a genetic heterogeneity.

Animals↗

PubMedDate not supplied

Electrophysiologic properties of intercostal muscle fibers in human neuromuscular diseases.

Electrophysiologic properties of biopsied normal and diseased intercostal muscle fibers were examined using intracellular microelectrode techniques. The resting potentials of all diseased muscle fibers were found to be depolarized. Those from Duchenne dystrophy patients showed the largest depolarization, followed by those from patients with myotonic muscular dystrophy, myotonia congenita, and motor neuron disease. All of the diseased fibers except those from myotonia congenita patients demonstrated an imparied ability to generate action potentials. In the latter fibers, the higher-than-normal membrane resistance was associated with hyperexcitability. When the membrane was hyperpolarized to the normal range, however, action potential characteristics in all fibers were near normal, except in motor neuron disease. All action potentials were blocked by tetrodotoxin. These findings--i.e., that all fibers were capable of generating action potentials when hyperpolarized, and that all action potentials were blocked by tetrodotoxin--suggest the relative intactness, in the disease studied here of the regenerative sodium conductance mechanism.

Action Potentials↗

PubMedDate not supplied

Proteolysis in heterocyst-forming cyanobacteria: characterization of a further enzyme with trypsin-like specificity, and of a prolyl endopeptidase from Anabaena variabilis.

Soluble extracts of the cyanobacterium Anabaena variabilis ATCC 29413 and an engineered mutant that lacks an intracellular protease cleaving after Lys and Arg (Maldener, Lockau, Cai, and Wolk, Mol. Gen, Genet. 225, 113-120 (1991)) were separated by ion exchange chromatography, and protease profiles determined using azocasein, N alpha-benzoyl-D,L-arginine-4-nitroanilide and N-carbobenzoxy-glycyl-L-proline-4-nitroanilide as substrates. A second enzyme cleaving at the carboxyl side of lysine and arginine, and a prolyl endopeptidase were detected, enriched and characterized. Both proteolytic enzymes appear to be located in the periplasm.

Amino Acid Sequence↗