Search PubMed⌕ Search

Biomedical subjects

M Marshall

Publications and source records attributed to M Marshall.

At least 163 records · Page 9Linked to original sources
PubMed1987

Electrocardiographic and electrophysiologic effects of pirmenol in ventricular tachycardia.

Twenty patients with ventricular tachycardia refractory to drug treatment underwent electrophysiologic study with pirmenol. Patients ranged in age from 39 to 84 years (mean 61); the presenting arrhythmia was sustained ventricular tachycardia in 15, nonsustained ventricular tachycardia in 3 and ventricular fibrillation in 2. After discontinuation of all antiarrhythmic drugs (for at least 5 half-lives) and assessment of electrocardiographic and electrophysiologic parameters in the drug-free state, patients underwent comprehensive intracardiac electrophysiologic evaluation with intravenous pirmenol (mean dose 195 +/- 46 mg). Programmed ventricular stimulation began at least 30 minutes after pirmenol infusion was started in each patient. There was significant shortening of sinus cycle length in all patients, from 746 +/- 155 to 683 +/- 107 ms (mean +/- standard deviation). In 7 patients in whom ventricular tachycardia could not be induced after intravenous pirmenol, an oral pirmenol regimen was begun. The dosage was 200 or 250 mg (both 3 times/day) in 2 and 5 patients, respectively. Seven hours after the third dose of oral drug was given, these patients underwent repeat electrophysiologic testing. Intravenous and oral pirmenol significantly prolonged the PR, QT, QTc and JT intervals compared with baseline. Intravenous pirmenol also significantly prolonged the QRS interval compared with baseline. Oral pirmenol significantly prolonged the sinus node recovery time compared with intravenous pirmenol. Intravenous pirmenol significantly increased the HV interval compared with control; oral pirmenol did not demonstrate a significant prolongation of the HV interval, but this is due to the smaller number of patients studied while taking oral drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Functional domains of SIR4, a gene required for position effect regulation in Saccharomyces cerevisiae.

The product of the Saccharomyces cerevisiae SIR4 gene, in conjunction with at least three other gene products, prevents expression of mating-type genes resident at loci at either end of chromosome III, but not of the same genes resident at the MAT locus in the middle of the chromosome. To address the mechanism of this novel position effect regulation, we have conducted a structural and genetic analysis of the SIR4 gene. We have determined the nucleotide sequence of the gene and found that it encodes a lysine-rich, serine-rich protein of 152 kilodaltons. Expression of the carboxy half of the protein complements a chromosomal nonsense mutation of sir4 but not a complete deletion of the gene. These results suggest that SIR4 protein activity resides in two portions of the molecule, but that these domains need not be covalently linked to execute their biological function. We also found that high-level expression of the carboxy domain of the protein yields dominant derepression of the silent loci. This anti-Sir activity can be reversed by increased expression of the SIR3 gene, whose product is normally also required for maintaining repression of the silent loci. These results are consistent with the hypothesis that SIR3 and SIR4 proteins physically associate to form a multicomponent complex required for repression of the silent mating-type loci.

Amino Acid Sequence↗
PubMed1986

Ultrastructural findings on platelet depositions in initial atherogenesis.

Morphological methods, especially scanning electron microscopy, were used in mini-pigs to prove that locally and systemically acting angiopathic stimuli caused an initial adhesion of platelets with altered shape to apparently intact arterial endothelium in a highly reproducible manner. These angiopathy models imitate the risk factors for human arteriosclerosis. Transmission electron microscopic studies, on the other hand, showed very early changes in endothelial and media cells subjected to suitable stimuli. The effective stimuli for angiopathy were local contact of the arteries with ice or epinephrine, the inhalation of cigarette smoke or carbon monoxide, a high-cholesterol diet, renovascular hypertension, and insulin-dependent diabetes. On acting over a longer period these stimuli caused intimal thickening, formation of microparietal thrombi consisting of platelets and fibrin on the endothelium. Within half a year the stimuli led to the formation of lipid-containing plaques of the intima. Several of these stimuli led to increased platelet aggregation. According to these findings we see the decisive mechanism for the pathogenesis of all stenosing, obliterative arteriopathies in a disturbed interaction between vessel wall and arterially circulating blood. Adherence of platelets to the arterial endothelium appears to play a key role in the initial phase of atherogenesis. This concept is supported and augmented by a multitude of partly very recent findings cited in the literature.

Animals↗
PubMed1986

Topographic aspects of prostacyclin-like and fibrinolytic activity and of biogenic amines in the arterial system of the mini-pig.

Although arteriosclerosis is a systemic disease, it nevertheless exhibits noticeable topographical preference and particularities. The reason for this could be lie with certain biochemical features of the arterial wall. We therefore examined prostacyclin-like and fibrinolytic activity in mini-pigs, as well as the concentration of various biogenic amines in the thoracic and abdominal aorta, in coronary arteries and in the carotid and femoral artery. There was a similar behaviour between PG I2-like release and biogenic amines in the different arteries, whereas fibrinolytic activity behaved differently in some cases. In the femoral artery particularly low fibrinolytic activity was confronted by a particularly high level of PG I2-like activity and biogenic amines, while the reverse was the case in the abdominal aorta. In older animals PG I2-like activity considerably decreased.

Animals↗
PubMed1986

Interrenal function in larval Ambystoma tigrinum. I. Responses to alterations in external electrolyte concentrations.

Larval Ambystoma tigrinum were acclimated to distilled water, 150 mM NaCl, or 100 mM KCl to alter electrolyte balance. The effects on electrolyte balance and circulating interrenal steroids were observed by analysis of plasma and urine samples. Steroid titers were measured by radioimmunoassay. Acclimation to distilled water decreased plasma and urinary [Na+] and elevated circulating aldosterone (sixfold) and corticosterone (45%) but did not affect cortisol. Larvae acclimated to 150 mM NaCl experienced increases in plasma and urinary [Na+]. In this group aldosterone titer was depressed (47%), corticosterone was elevated (100%), and cortisol was unchanged. Salamanders acclimated to 100 mM KCl increased plasma and urinary [K+] and shifted to net renal K+ secretion. This group elevated aldosterone (150%); however, corticosterone was not significantly affected. Reciprocity between the Na+-loaded and K+-loaded groups was observed. Acclimation to high potassium stimulated fractional renal Na+ reabsorption while Na+ loading stimulated fractional K+ reabsorption. These findings are consistent with aldosterone having opposite effects on renal Na+ and K+ transport, stimulating the reabsorption of the former and the net secretion of the latter.

Adaptation, Physiological↗
PubMed1985

Proximate sulfhydryl groups in the acetylglutamate complex of rat carbamylphosphate synthetase I: their reaction with the affinity reagent 5'-p-fluorosulfonylbenzoyladenosine.

A preparation of rat carbamylphosphate synthetase I, isolated in the presence of antipain and stable without glycerol, has been used to investigate the effect of the allosteric activator, N-acetyl-L-glutamate (AcGlu), on the sulfhydryl chemistry of the enzyme. The enzyme X AcGlu complex was rapidly inactivated by several sulfhydryl group reagents and the ATP analog, 5'-p-fluorosulfonylbenzoyladenosine (FSO2BzAdo), with the loss of two sulfhydryl groups per monomer. Inactivation was much slower without AcGlu, and ATP/Mg2+/K+ provided complete protection. Reaction with a 1.1 molar excess of 4,4'-dipyridyldisulfide resulted in an intramonomer disulfide bond between groups that are probably juxtaposed in the activated enzyme, because 1.1 equivalents of the vicinal dithiol reagent, phenylarsine oxide, eliminated the rapid reaction with the disulfide. Evidence is presented that the same disulfide bond was formed in the reactions with 5-thiocyano-2-nitrobenzoic acid and FSO2BzAdo. Inactivation by FSO2BzAdo was a pseudo-first-order reaction. The concentration dependence of the rate is consistent with the reaction proceeding through a noncovalent complex (KI = 67 microM and k2 = 0.23 min-1 at pH 7.0, 30 degrees C). Protection from FSO2BzAdo by ATP required Mg2+ in excess of ATP with KMgATP = 4.5 microM at saturating free Mg2+ (0.1 M K+) and KMg2+ = 6.5 mM. KMgATP is close to Kd for the molecule of ATP that contributes the phosphoryl group of carbamylphosphate (H.B. Britton, V. Rubio, and S. Grisolia, (1979) Eur. J. Biochem. 102, 521-530]; KMg2+ agrees with the minimum value for the steady-state kinetic parameter, Ki,Mg2+, obtained under the same conditions. Dissociation constants for adenosine (320 microM), MgADP (110 microM) at 10 mM Mg2+, and AcGlu (100 microM) were also estimated.

Adenosine↗
PubMed1985

Regulation of aminotransferase-glutamate dehydrogenase interactions by carbamyl phosphate synthase-I, Mg2+ plus leucine versus citrate and malate.

Citrate, malate, and high levels of ATP dissociate the mitochondrial aspartate aminotransferase-glutamate dehydrogenase complex and have an inhibitory effect on the latter enzyme. These effects are opposed by Mg2+, leucine, Mg2+ plus ATP, and carbamyl phosphate synthase-I. In addition, Mg2+ directly facilitates formation of a complex between glutamate dehydrogenase and the aminotransferase and displaces the aminotransferase from the inner mitochondrial membrane which could enable it to interact with glutamate dehydrogenase in the matrix. Zn2+ also favors an aminotransferase-glutamate dehydrogenase complex. It, however, is a potent inhibitor of and has a high affinity for glutamate dehydrogenase. Leucine, however, enhances binding of Mg2+ and decreases binding of and the effect of Zn2+ on the enzyme. Thus, since both metal ions enhance enzyme-enzyme interaction and Zn2+ is a more potent inhibitor, the addition of leucine in the presence of both metal ions results in activation of glutamate dehydrogenase without disruption of the enzyme-enzyme complex. Furthermore, the combination of leucine plus Mg2+ produces slightly more activation than leucine alone. These results indicate that leucine, carbamyl phosphate synthase-I, and its substrate and cofactor, ATP and Mg2+, operate synergistically to facilitate glutamate dehydrogenase activity and interaction between this enzyme and the aminotransferase. Alternatively, Krebs cycle intermediates, such as citrate and malate, have opposing effects.

Adenosine Triphosphate↗
PubMed1985

Alcohol research in Papua New Guinea: implications for health care workers.

Over the last 5 years a substantial amount of research and publication has been completed on the subject of alcoholic beverage consumption and its consequences for Papua New Guinea. This work can be grouped under four topical headings: anthropological, epidemiological (including public health), psychological and sociological. These recent findings will be summarized below and their relevance for health care personnel in helping to prevent some of the negative results of alcohol abuse will then be discussed.

Adolescent↗
PubMed1984

[The importance of peripheral venous diseases. Incidence and risk factors].

Comprehensive epidemiological studies in the last few years came concordantly to the conclusion, that peripheral venous diseases have a considerable social-medical importance. 70% of the adult population have some kind of alteration in the veins, 15% of which are serious. The main risk factors were the branch and trunk varices. Important risk factors were generally age and familial predisposition; apart from these, there were also relations between the existence of hernias (male), of flatfootedness and splayfootedness (female) and the practice of a "standing" career (male) and overweight (female). The female sex, positive auto-anamnesis relating to venous diseases, surgical interventions, pregnancy and lying-in proved to be important risk factors or indicators for deep phlebothromboses. The administration of a primary or if necessary a secondary prophylactic treatment should be given bearing these factors in mind.

Female↗
PubMed1984

[Vascular diseases and occupation. Incidence and significance of circulatory diseases in occupational medicine].

The high incidence and socio-medical significance of vascular diseases--which often manifest during the working lifetime of the patient--mean that doctors in occupational medical practice have more and more frequently to deal with these lesions, irrespective of whether they are causally linked to the patient's occupation or not. For diseases of the circulatory system usually have a direct effect on the patient's efficiency and fitness for work. Depending on the localisation of the lesion, certain precautionary measures may be needed at work, or it may no longer be possible for the affected person to carry out certain jobs--or at least not without risk. This applies not merely to arterial, but also to venous and lymphatic diseases. Further, there are a number of recognised occupational diseases that manifest, or may manifest, as circulatory disorders. A range of occupation-related effects or exposures of a physical, chemical or possibly immunological-allergic nature can lead to vascular lesions including premature attrition of the vascular system. The early detection and prevention of circulatory disorders may become a major task of occupational medicine in the future.

Adult↗
PubMed1984

[Varicose vein drugs--new attempts at objectivation of the effects of therapy].

The ultrasound Doppler examination has proved itself to be a very promising non-invasive method for the trials of vein medication under defined test conditions. In patients with postthrombotic syndrome the medium blood stream velocity in the V. femoralis increased on the diseased side two hours after oral application of a high-dosed combination of ruscogenin, trimethyl-hesperidin-chalkon and ascorbic acid (1 X 6 capsules Phlebodril) by the mean of 24%. If one observes the quotients from the middle arterial inflow and venous outflow velocity in the femoral vessels, in order to comprehend the relation between both these necessarily correlated hemodynamic parameters, one sees that this quotient shows a decrease after medication of 40%, which was significant on the 5% level. Corresponding drug effects in the early phase after getting upright could also be proved. The importance of these results, which are from an acute trial, must still be tested in a practical long-term therapy.

Blood Flow Velocity↗