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Biomedical subjects

R D Thomas

Publications and source records attributed to R D Thomas.

At least 19 recordsLinked to original sources

Metastatic malignant struma ovarii. Two case reports.

Struma ovarii is an ovarian germ cell tumor consisting mainly of thyroid tissue. Five percent of struma ovarii are malignant, and of these only five percent metastasize. The rarity of this disease has resulted in difficulty in agreeing on treatment regimes and in limited imaging experience. The authors report two cases and highlight the imaging and monitoring difficulties encountered in their management. The authors conclude that I-131 has a role to play both therapeutically and in monitoring these patients, but that biochemical testing is a more reliable indicator of disease status.

Adolescent

Carcinogenic mixtures.

Human populations are generally exposed simultaneously to a number of toxicants present in the environment, including complex mixtures of unknown and variable origin. While scientific methods for evaluating the potential carcinogenic risks of pure compounds are relatively well established, methods for assessing the risks of complex mixtures are somewhat less developed. This article provides a report of a recent workshop on carcinogenic mixtures sponsored by the Committee on Toxicology of the U.S. National Research Council, in which toxicological, epidemiological, and statistical approaches to carcinogenic risk assessment for mixtures were discussed. Complex mixtures, such as diesel emissions and tobacco smoke, have been shown to have carcinogenic potential. Bioassay-directed fractionation based on short-term screening test for genotoxicity has also been used in identifying carcinogenic components of mixtures. Both toxicological and epidemiological studies have identified clear interactions between chemical carcinogens, including synergistic effects at moderate to high doses. To date, laboratory studies have demonstrated over 900 interactions involving nearly 200 chemical carcinogens. At lower doses, theoretical arguments suggest that risks may be near additive. Thus, additivity at low doses has been invoked as as a working hypothesis by regulatory authorities in the absence of evidence to the contrary. Future studies of the joint effects of carcinogenic agents may serve to elucidate the mechanisms by which interactions occur at higher doses.

Animals

Helping those in need.

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Dental Care for Persons with Disabilities

Echocardiography and genetic counselling in tuberous sclerosis.

OBJECTIVE: To assess echocardiography as an investigation for the detection of occult gene carriers in tuberous sclerosis. PATIENTS: Sixty parents of children with tuberous sclerosis who had been extensively investigated for signs of the disease and 60 age and sex matched controls. PROCEDURE: Blind study by two experienced echocardiographers and blind interpretation of video recordings by an adult cardiologist. SETTING: Cardiology department of a district general hospital. RESULTS: Two parents and three controls had bright echodense areas interpreted as possible rhabdomyomas. CONCLUSIONS: In our hands echocardiography of adults is not an investigation with a high specificity for gene detection in tuberous sclerosis.

Adult

Stereoselective formation of bis(alpha-aminoacyl) esters of 5'-AMP suggests a primitive peptide synthesizing system with a preference for L-amino acids.

In the biosynthesis of proteins, each amino acid passes from the aminoacyl adenylate to become an amino acid ester and finally a 2' (3') peptidyl ester of the AMP residue at the end of a tRNA. Consequently, the chemistry of protein synthesis is the chemistry of aminoacyl and peptidyl AMP. Our data has revealed properties of 5'-AMP and its esters which should allow the preferential catalytic synthesis of L-amino acid peptides via a bis(2', 3'-aminoacyl) ester intermediate. Results in this paper concern one step in the proposed process and show that preexisting Ac-L-Phe monoester reacts about 2.5-times faster to form diester than preexisting Ac-D-Phe monoester.

Adenosine Monophosphate

Double duty.

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Career Choice

Chemical esterification of 5'-AMP occurs predominantly at the 2' position.

We describe experiments here which show that chemical esterification of 5'-adenylic acid (5'-AMP) with N-acetyl D- or L-phenylalanine (Ac-D- or Ac-L-Phe) imidazolide occurs principally, if not exclusively, at the 2' position. Furthermore, in experiments with the formation of the 2'-3' diester with butyric acid and N-acetyl glycine (Ac-Gly), we found the second esterification was also predominantly at the 2' position. This means that mixed diesters can be predictably prepared with the positions of the substituents known. The results are consistent with a model for the preferential catalytic synthesis of L-based peptides via a 2'-3' diester intermediate of purine monoribonucleotides.

Adenosine Monophosphate

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

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

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

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