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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 379 records · Page 21Linked to original sources
PubMed1986

Some poststimulatory effects on the whole nerve action potential.

Short-term poststimulatory effects on the N1 component of the auditory-nerve compound action potential (CAP) were investigated in Mongolian gerbils. Some effects of conditioner level, conditioner frequency and probe level were assessed. In most cases, poststimulatory decrements occurred. The decrements were independent of probe intensity when the conditioner was close in frequency and of equal or less intensity than the probe. At some other conditioner frequencies, decrements decreased as probe intensity increased. Departures from these relationships occurred when a more intense conditioner was applied. In some instances, increases in CAP amplitude were also observed. The roles of single unit responses including spread of cochlear excitation, and possible mechanisms for poststimulatory facilitation are discussed.

Acoustic Stimulation↗
PubMed1986

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 4. Side chain ester derivatives of mevinolin.

Modification of the 2(S)-methylbutyryl moiety of mevinolin led to a series of side chain ester derivatives. A systematic exploration of the structure-activity relationships showed that the introduction of an additional aliphatic group on the carbon alpha to the carbonyl group increased potency. This observation led to the synthesis of compound 16, which has about 2.5 times the intrinsic inhibitory activity of mevinolin.

Hydroxymethylglutaryl-CoA Reductase Inhibitors↗
PubMed1986

Synthesis and biological activity of 3-amino-5-(3,5-diamino-6-chloropyrazin-2-yl)-1,2,4-oxadiazole: an amiloride prodrug.

The pyrazinyl-1,2,4-oxadiazoles 4a and 4b were synthesized by two different approaches. The corresponding N-methyloxadiazolium salts 13a and 13b were also prepared. These compounds were evaluated for their diuretic and saluretic activity in rats and dogs. All compounds exhibited electrolyte excretion profiles similar to amiloride 1. The facile conversion of 4a to 1 was demonstrated chemically and in vivo in both rats and dogs.

Amiloride↗
PubMed1986

Adenocarcinoma of the lower esophagus. A disease primarily of white men with Barrett's esophagus.

Sex and racial predilection, social history, and histology were analyzed in a biopsy-proven adenocarcinoma of the lower esophagus/esophagogastric junction collected over a 5-year period in two teaching institutions with different patient populations. Adenocarcinoma occurred in 11% of patients with biopsy-proven esophageal cancer. The disease occurred only in males at one center, and in a 7:1 ratio of males to females at the other center. Clear racial predilection was seen, since 12 of 13 patients with adenocarcinoma of the esophagus were white, whereas less than 20% of patients with squamous carcinoma of the esophagus were white. The finding of Barrett's epithelium in eight of the 13 cases strongly supports the theory that in white males, Barrett's epithelium is a precursor lesion of adenocarcinoma of the esophagus/esophagogastric junction.

Adenocarcinoma↗
PubMed1986

Phosphorylase kinase isozymes in normal and electrically stimulated skeletal muscles.

Phosphorylase kinase was quantitatively immunoprecipitated from extracts of different rabbit skeletal muscles, subjected to electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate, and stained with silver. Amounts of the two isozymes, enzymes r and w. were determined by the staining intensities of the alpha'- and alpha -subunits, respectively. The kinase in muscles composed primarily of slow oxidative fibers was almost entirely enzyme r, but several times more of this isozyme was found in muscles with a high proportion of fast oxidative-glycolytic fibers. Enzyme w predominated in muscles composed mostly of fast glycolytic fibers. To investigate the possible role of muscle activity in controlling isozyme levels, tibialis anterior muscles were activated by chronic electrical stimulation of the peroneal nerves. After 10 wk of continuous stimulation, the amount of phosphorylase kinase was decreased by approximately 80%, and the ratio of enzyme r to enzyme w was doubled. These results demonstrate that increased muscle activity can decrease levels of phosphorylase kinase and suggest that activity may regulate the expression of the isozymes in different muscle fiber types.

Animals↗
PubMed1986

The metabolism of aspirin in man: a population study.

The metabolism of a 900 mg oral dose of aspirin has been investigated in 129 healthy volunteers. For this purpose, the 0-12 h urine was collected and analysed for the following excretion products: salicylic acid, its acyl and phenolic glucuronides, salicyluric acid, its phenolic glucuronide and gentisic acid. The total excretion of salicylate and metabolites was normally distributed within the population group studied, showing a 2.5-fold variation: a mean of 68.1% of the dose was recovered in 12 h. The excretion of salicylic acid was found to be highly variable within the study panel (1.3-31% of dose in 12 h), and was related to both urine volume and pH. Salicyluric acid was the major metabolite in the majority of the volunteers and its excretion was normally distributed amongst the study panel. The elimination of this metabolite ranged from 19.8 to 65% of the dose and was related to the total recovery of salicylate. The excretion of the two salicyl glucuronides was highly variable, ranging from 0.8 to 42% of the dose. The elimination of the glucuronides was inversely related to that of salicyluric acid. Gentisic acid and salicyluric acid phenolic glucuronide were minor metabolites of salicylate, accounting for 1 and 3% of the dose, respectively. The recovery of gentisic acid was statistically significantly greater in female subjects than in males, whilst the opposite was found for salicyluric acid and total salicylate. However, these differences were small in magnitude.

Adult↗
PubMed1986

The metabolism of debrisoquine in man: (1) regioselectivity of hydroxylation and (2) aberrant oxidative metabolism in two sibling patients with carbimazole-induced agranulocytosis.

The regioselectivity of the metabolic hydroxylation of debrisoquine has been determined in 43 healthy British white volunteers and the priority was found to be in the order 4 greater than 7 greater than 6 greater than 5 greater than 8. The order of preference for hydroxylation position was independent of debrisoquine 4-hydroxylation phenotype. The extent of total aromatic hydroxylation varied widely between individuals and was largely independent of the extent of 4-hydroxylation, and thus of the influence of the DH/DL locus. Two sisters and their blood relations all excreted comparatively large amounts of the phenolic metabolites in their urine, indicating some genetic basis for the control of aromatic oxidation of debrisoquine in man. These same two sisters had previously developed agranulocytosis in association with carbimazole therapy.

Adolescent↗
PubMed1986

Assessment of intra-aortic balloon pumping by ocular pneumoplethysmography.

The ocular pneumoplethysmograph (OPG-Gee) has been used to screen for unsuspected carotid disease in candidates for cardiac operations. This article demonstrates that the validity of such screening is maintained, even if the patient is sustained by an intra-aortic balloon pump (IABP). An unexpected observation is the apparent reduction of ocular blood flow during IABP, which was reduced in this series of 56 patients by an average of 11.6 per cent.

Blood Circulation↗
PubMed1985

Persistent ST-segment elevation in patients with anterior myocardial infarctions. Evaluation by exercise electrocardiography, echocardiography and Holter monitoring.

One hundred and seventy patients who suffered an acute myocardial infarction (MI) were followed up at 3-monthly intervals by a full clinical evaluation, exercise electrocardiography and ambulatory Holter monitoring. Fifty-eight patients (34%) had anterior MIs, and of these 23 (40%) had persistent ST-segment elevation over the infarct zone, reflected by leads presenting with Q-S configuration. Fifteen (65,2%) of the latter demonstrated further ST-segment elevation during exercise. They were further investigated by cross-sectional echocardiography. Left ventricular (LV) dysfunction was diagnosed in 87% of patients with persistent ST-segment elevation, and in 93% of the patients with additional exercise-induced ST-segment elevation. Organized thrombi occurred in 2 patients (8,7%) and 1 experienced a transient ischaemic attack. Ventricular arrhythmias occurred frequently (ventricular ectopy--91,3%, ventricular tachycardia--17,4%, and couplets--47,8%). Death occurred in 3 patients (13,1%) and 1 patient (4,3%) had a second MI over a mean follow-up period of 83,6 months. This study suggests that persistent ST-segment elevation on the resting ECG of patients with anterior MIs is a reliable indicator of LV wall motion abnormalities, and that this correlation further increases if it is associated with exercise-induced ST-segment elevation. Furthermore, the role of echocardiography as a diagnostic tool in evaluating LV function is stressed. The prognosis of patients with post-infarction LV dysfunction is notably poor and may be the result of frequent complex ventricular arrhythmias.

Arrhythmias, Cardiac↗
PubMed1985

Insulin action in denervated skeletal muscle. Evidence that the reduced stimulation of glycogen synthesis does not involve decreased insulin binding.

The motor nerves to rat soleus and epitrochlearis muscles were sectioned 1-3 days before the muscles were incubated in vitro to assess insulin action and binding. The hormonal stimulation of [U-14C]glucose into glycogen in both muscles was decreased by over 80% after 3 days of denervation. Associated with the reductions in glycogen synthesis were losses in the ability of insulin to activate glycogen synthase. Even so, denervated and control muscles bound the same amounts of 125I-labeled insulin over a wide range of insulin concentrations. Scatchard analysis indicates that denervation changed neither receptor numbers nor affinities. The results presented strongly suggest that the loss of the ability of insulin to stimulate glycogen synthesis following denervation is the result of a postreceptor defect.

Animals↗
PubMed1985

Separation of plasma fibronectin from associated hemagglutinating activity by elution from gelatin-agarose at pH 5.5.

Human plasma fibronectin prepared by elution of the adsorbed protein from gelatin-agarose by pH 5.5 citrate buffer is very low in hemagglutinating activity toward trypsinized rabbit erythrocytes, an activity previously associated with the purified plasma protein. Hemagglutinating activity is present, however, in a subsequent fibronectin-poor 4M urea eluate which contains plasma immunoglobulins and/or other unidentified gelatin-binding proteins. This activity is partially inhibited by antibodies to human immunoglobulins, and the inhibition is reversed by excess non-specific human immunoglobulin.

Animals↗