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Biomedical subjects

R D Thomas

Publications and source records attributed to R D Thomas.

At least 91 records · Page 5Linked to original sources
PubMed1990

Ribonucleic acids may be catalysts for the preferential synthesis of L-amino acid peptides: a minireview.

This minireview is a summary of the basic concepts and pieces of experimental evidence supporting a hypothesis that suggests a mechanism whereby purine monoribonucleotides having D-ribose may be able to preferentially catalyze the synthesis of L-amino acid peptides. The proposed mechanism involves a 2'-3' diaminoacyl intermediate and the preference accrues from several factors that favor the L-isomer, principally for hydrophobic amino acids. Although the hypothesis has not been fully tested, some crucial evidence has been published. Other pieces of evidence are now being submitted or are in press for publication and still other experiments, principally on the step of peptide bond formation, are in the process of being carried out. The purpose of a review at this point is to present the hypothesis to the scientific community in hopes of generating discussion, suggestions, and evaluation by other workers. Should the hypothesis prove correct, it may represent the most primitive and fundamental relationship between the nucleic acid and protein systems. In addition, it would represent another important example of the catalytic ability of RNA.

Amino Acids↗
PubMed1990

11 beta-methoxy-, 11 beta-ethyl- and 17 alpha-ethynyl-substituted 16 alpha-fluoroestradiols: receptor-based imaging agents with enhanced uptake efficiency and selectivity.

We have prepared three analogues of 16 alpha-fluoroestradiol (FES) substituted either with an 11 beta-methoxy group (1, 11 beta-MeO-FES), an 11 beta-ethyl group (2, 11 beta-Et-FES), or a 17 alpha-ethynyl group (3, 17 alpha-ethynyl-FES). These substituents all lower the binding of FES to the serum proteins alphafetoprotein and sex steroid binding protein, but their effect on estrogen receptor binding varies: Receptor binding is increased by the 11 beta-ethyl and 17 alpha-ethynyl groups, but decreased by the 11 beta-methoxy group. These substituents also have a parallel effect on the lipophilicity, and hence the nonspecific binding estimated for these compounds. All three compounds were prepared in fluorine-18 labeled form, at effective specific activities of 90-1600 Ci/mmol, by fluoride ion displacement reactions as done previously with FES. Tissue distribution studies in immature rats show high uptake selectivity by target tissue (uterus) and effective competition by an excess of unlabeled estradiol. Percent injected dose per gram values (% ID/g) at 1 h are 6% for 11 beta-MeO-FES and 11-13% for 11 beta-Et-FES and 17 alpha-ethynyl-FES (FES itself has a % ID/g of 9%). Uptake selectivity in terms of uterus to blood or muscle ratios at 1 h is highest for 11 beta-MeO-FES and 17 alpha-ethynyl-FES (43-149). Metabolic consumption studies show that most activity in uterus is unmetabolized and in blood is rapidly and nearly completely metabolized. In muscle, FES and the substituted estrogens show intermediate levels of metabolic consumption; in some cases activity in muscle extracts is nearly unmetabolized. Thus, the substituents on FES cause major alterations in receptor and nonreceptor binding affinity, uptake efficiency and selectivity, and extent of metabolism. It is not readily clear, however, whether the alterations in uptake efficiency and selectivity are the result of differences in receptor or nonreceptor binding or lipophilicity, or altered patterns of metabolism. Nevertheless, these compounds should be useful in providing a spectrum of uptake properties that could be used for imaging different estrogen-receptor-containing structures.

Animals↗
PubMed1990

Cardiopulmonary resuscitation in a district general hospital: increased success over 7 years.

In a 12-month prospective survey of CPR (cardiopulmonary resuscitation), 32 out of 192 patients (16.6%) survived to go home. This is a clear improvement compared with 7 years previously. This is attributed to better training in the use and management of CPR and more widespread availability of defibrillators. Certain patients could not be resuscitated--those with electromechanical dissociation, carcinoma, or multiple pathology. Age by itself was not a bar to resuscitation. There is still a high rate of inappropriate calls, often because of uncertainty by nurses about the use of CPR. This could be improved with clearer guidelines in hospitals about the value of CPR in selected patients.

Cardiopulmonary Resuscitation↗
PubMed1990

Antibodies to xanthine oxidase: elevated levels in patients with acute myocardial infarction.

Circulating antibodies to whole dried cows' milk, previously reported to be elevated in patients with myocardial infarction, have been shown to be directed mainly to the bovine milk fat globule membrane. Human antibodies against the bovine milk fat globule membrane themselves interact primarily with the enzyme, xanthine oxidase. Comparison of anti-(xanthine oxidase) antibody levels in 107 patients, who had suffered a myocardial infarction, with those in 86 control subjects showed significantly higher IgM levels in the patients with myocardial infarction. No corresponding differences were found for IgG or IgA anti-(xanthine oxidase) antibodies. Total levels of IgM class immunoglobulins did not differ between patients and controls. Serial assays following myocardial infarction showed no evidence that raised levels of IgM anti-(xanthine oxidase) antibodies result from the infarction itself.

Antibodies↗
PubMed1989

Use of laboratory animal models in investigating emphysema and cigarette smoking in humans.

To increase our understanding of biological systems, the first step is to make an observation at the level of organization that we wish to understand. It has yet to be conclusively shown that any laboratory animal has contracted emphysema solely as a result of exposure to cigarette smoke. Available mechanism-of-response studies at the tissue, cellular, or biochemical level of organization are not useful in elucidating the relationship between emphysema and exposure to cigarette smoke without an animal model for the disease. If progress in understanding the etiology of emphysema from cigarette smoking is judged to be important to the scientific and regulatory communities, the highest priority should be given to discovering a suitable animal model.

Animals↗
PubMed1988

Mitral stenosis in systemic lupus erythematosus. Successful management by mitral valve replacement.

A female Caucasian with a history of 18 years of systemic lupus erythematosus (SLE) developed symptoms and signs of mitral stenosis, but had no history of rheumatic fever. Investigations confirmed severe stenosis, and the diseased valve was replaced by a pericardial xenograft. Histological examination was compatible with steroid-modified Libman-Sacks endocarditis. She remains well 24 months postoperatively.

Adult↗
PubMed1988

Differential distribution of D and L amino acids between the 2' and 3' positions of the AMP residue at the 3' terminus of transfer ribonucleic acid.

Amino acids esterified to the ribose group of 5'-adenylic acid (AMP) constantly migrate between the 2' and 3' positions of the ribose at a rate of several times per second, which is slower than the rate of peptide-bond synthesis (15-20 per sec). Because the contemporary protein-synthesizing system only incorporates amino acids into protein when they are at the 3' position of the AMP at the terminus of tRNA, the value of the equilibrium constant relative to the 2' and 3' positions is of considerable interest. Differences between D and L isomers in this regard might be especially revealing. We have used N-acetylaminoacyl esters of AMP as models for the 3' terminus of tRNA and find that glycine and the L amino acids consistently distribute predominantly to the 3' position (approximately equal to 67% 3', approximately equal to 33% 2'), but D amino acids distribute to that position generally to a lesser extent and in a manner inversely related to the hydrophobicity of the amino acid side chain. This consistency of the L amino acid preference for the 3' position, combined with the inconsistency of the D amino acid preference, may be one reason for the origin of our contemporary protein-synthesizing system, which forms the peptide bond preferentially with L amino acids and only when they are in the 3' position of the ribose moiety of the AMP residue at the 3' terminus of every tRNA.

Adenosine Monophosphate↗
PubMed1987

Long term use of enalapril in the treatment of patients with congestive heart failure.

Fifty-five patients of both sexes, aged 39-72, suffering from congestive heart failure of varying aetiology were admitted to a double blind study in which enalapril given in a dose of 5-10 mg twice daily or placebo was added to existing medication. A significant increase in exercise performance (P less than 0.004) was seen in the group treated with enalapril, an improvement which was still evident after 24 weeks of therapy. No significant difference was seen between the mean ejection fractions but subjective assessment suggested improvement in the enalapril-treated group.

Adult↗
PubMed1986

Cardiovascular toxicity of local anesthetics: an alternative hypothesis.

The current study examined the possibility that high local anesthetic concentrations within the central nervous system could contribute to the toxic cardiovascular effects observed clinically after an accidental intravenous injection. Equal numbers of molecules of lidocaine (1.6 microliter of a 2% solution) and bupivacaine (1.0 microliter of a 4% solution) were injected at three vasomotor and cardioactive areas in the rat medulla by means of a 28-gauge hypodermic needle and a microsyringe. These areas were the C1 region, the intermediolateral column (IML), and the nucleus tractus solitarius (NTS). Both lidocaine and bupivacaine at C1 significantly decreased mean arterial pressure and, at IML, resulted in significant bradycardia and hypotension. At NTS, both lidocaine and bupivacaine caused significant bradycardia and hypotension, which were accompanied by ventricular arrhythmias in 55% of the animals. In all animals in whom ventricular arrhythmias were associated with lidocaine, the arrhythmias spontaneously reverted to normal sinus rhythm. In 50% of animals developing ventricular arrhythmias after bupivacaine, the arrhythmias resulted in death. Using an equal number of molecules of lidocaine and bupivacaine, all three regions studied demonstrated that bupivacaine was 2-4 times more potent than lidocaine in producing cardiovascular effects. These data demonstrate that direct application of local anesthetics within the medullary region of the central nervous system can result in hypotension, bradycardia, and ventricular arrhythmias similar to what may be seen in humans after accidental intravenous injections of local anesthetics. Moreover, the sites and mechanisms of action appear to be identical for bupivacaine and lidocaine. Thus bupivacaine does not appear to be an aberrant local anesthetic, as some have suggested, but rather produces more profound effects related to its potency and physicochemical properties.

Animals↗
PubMed1985

Constructional morphology: the analysis of constraints in evolution dedicated to A. Seilacher in honour of his 60. birthday.

Evolutionary change is opportunistic, but its course is strongly constrained in several fundamental ways. These constraints (historical/phylogenetic, functional/adaptive, constructional/morphogenetic) and their dynamic relationships are discussed here and shown to constitute the conceptual framework of Constructional Morphology. Notwithstanding recent published opinions which claim that the "discovery" of constraints renders Neodarwinian selection theory obsolete, we regard the insights of Constructional Morphology as being entirely consistent with this theory. As is shown here in the case of the Hyracoidea, formal analysis of the constraints which have framed the evolution of various characters extends our understanding of the evolution of a taxon.

Adaptation, Physiological↗
PubMed1983

Ventricular fibrillation and initial plasma potassium in acute myocardial infarction.

In a retrospective review of patients admitted to a coronary care unit, 809 patients had a definite myocardial infarction and plasma potassium was measured within 48 hr. The mean (+/- s.d.) plasma potassium was 4.04 (+/- 0.56) mmol/litre. A potassium concentration of less than 4.0 mmol/litre was found in 383 patients, of whom 14 had ventricular fibrillation. A potassium concentration of 4.0 mmol/litre or greater was found in 426 patients, of whom 3 had ventricular fibrillation, a difference significant at the 0.4% level (chi 2 test). Preceding diuretic therapy did not appear to be relevant and there appeared to be no other difference between the two groups. The maintenance of a high-normal plasma potassium, or the prevention of its reduction, in patients with an acute myocardial infarction may be important.

Humans↗
PubMed1982

Chronic stable angina: comparison of verapamil and propranolol.

The effect of verapamil 120 mg t.d.s. was compared with propranolol 160 mg b.d. in the treatment of stable angina pectoris. Nineteen patients were studied in a randomized, double-blind, crossover trial, using patient diaries, exercise-testing and ambulatory electrocardiographic monitoring. Both drugs were given for 1 month. On average the number of attacks of angina was reduced equally by verapamil and propranolol. The degree of electrocardiographic evidence of myocardial ischaemia was decreased by the same amount, but verapamil was significantly more effective in prolonging the exercise time. Both drugs reduced the number of episodes of ST-segment depression during 24 hours of ambulatory electrocardiographic monitoring, which was analyzed in nine patients. It is concluded that verapamil compares very favourably with propranolol in the treatment of stable angina, and is more beneficial in improving exercise capacity.

Adult↗