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Biomedical subjects

W R Hiatt

Publications and source records attributed to W R Hiatt.

At least 127 records · Page 7Linked to original sources

Attenuation of exercise conditioning by low dose beta-adrenergic receptor blockade.

Because it has been shown that high doses of propranolol (40 to 80 mg orally, four times daily) markedly attenuate cardiovascular response to exercise training in healthy subjects, the effects of lower doses of this nonselective beta-adrenergic receptor antagonist on the conditioning response were investigated. Twelve normal men underwent maximal treadmill testing before and after a 6 week intensive exercise program. After an initial test, six men were randomized in a paired fashion to receive low dose propranolol and the others received no drug. The average propranolol dose +/- standard error was 22 +/- 4 mg four times daily, and the average decrease in maximal heart rate due to propranolol was 32 +/- 4 beats/min. Both groups trained at comparable intensities. At the end of the training period, propranolol was stopped and testing was repeated so that the effect of beta-receptor blockade was no longer present but the training effects still persisted. Maximal oxygen consumption increased in control subjects from 47.5 +/- 1.1 to 51.4 +/- 0.4 ml/kg per min (p less than 0.05) but was unchanged in those receiving propranolol (47.2 +/- 1.9 versus 47.4 +/- 1.5). Exercise duration increased in both groups but the increment was greater in the control group (+2.4 versus +1.1 min, p less than 0.05). It is concluded that low level beta-receptor blockade attenuates cardiovascular conditioning in normal subjects in exercise training programs. High levels of sympathetic stimulation during training appear to be important, if not essential, to the conditioning process.

Adrenergic beta-Antagonists↗

Factors modifying the early nondiuretic vascular effects of furosemide in man. The possible role of renal prostaglandins.

Animal experiments have suggested that salt-balance, prostaglandin synthesis, and renal function are important determinants of the nondiuretic vascular effects of furosemide. To investigate the influence of these factors in humans, we studied 10 normal volunteers and five anephric patients. The volunteers were studied on three occasions: when on a 10 mEq/day sodium diet, on a 250 mEq/day sodium diet, and on a 10 mEq/day sodium diet with indomethacin, 200 mg/day. The anephric patients were studied immediately after dialysis. Plethysmographic methods were used to measure venous capacitance and blood flow in the calf before, and at 5, 10, and 15 minutes after furosemide, 80 mg, iv. Blood was obtained before and 15 minutes after furosemide for determination of plasma renin activity by radioimmunoassay and of plasma 6-keto-prostaglandin F1 alpha by chromatography-mass spectrometry. We found that furosemide significantly increased venous capacitance in the calf of the normal volunteers on a low salt diet. Indomethacin, high salt intake, or lack of renal function was sufficient to inhibit this effect. Plasma renin activity increased only in the group that had the increase in venous capacitance. Limb blood flow decreased gradually in the 15 minutes following administration of furosemide in the normal volunteers, regardless of salt balance or indomethacin, but remained unchanged in the anephric patients. Plasma 6-keto-prostaglandin F1 alpha was less than 30 pg/ml in all samples. Indomethacin concentration averaged 1.3 micrograms/ml in volunteers on the drug. To determine whether indomethacin, salt intake or renal function affected another venodilator, we studied an additional group of normal and uremic volunteers who received 0.6 mg nitroglycerin sublingually.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Methylation of elongation factor 1 alpha from the fungus Mucor.

A basic protein from the dimorphic fungus Mucor racemosus, found to be highly methylated, is shown to be protein synthesis elongation factor 1 alpha. This protein is the most abundant protein in hyphal cells but is less abundant in yeast cells. It is post-translationally methylated with the formation of mono-, di-, and trimethyllysine at as many as 16 sites. Nearly 20% of the 44 lysine residues of elongation factor 1 alpha from mycelia are modified while those from sporangiospores are virtually unmethylated.

Amino Acids↗

Differential synthesis of polypeptides during morphogenesis of Mucor.

The extent of differential gene expression during morphogenesis of Mucor racemosus was investigated by two-dimensional polyacrylamide gel electrophoresis of neutral and acidic polypeptides. Cellular proteins were labeled with [35S]methionine in cells growing in either the yeast or hyphal form, or in yeast cells undergoing the transition of hyphae. The results showed that of the 400 to 500 polypeptides resolved by electrophoresis, relatively few were specific to one or the other morphological form. The major change in the patterns of proteins synthesized during morphogenesis was a change in rates of synthesis of individual polypeptides. Experiments in which morphogenesis was affected under aerobic or anaerobic conditions showed that the majority of changes in the protein patterns were associated with morphogenesis and were not a specific response to O2.

Anaerobiosis↗

S-adenosylmethionine levels and protein methylation during morphogenesis of Mucor racemosus.

The intracellular level of S-adenosylmethionine increased as the yeast-phase cells of Mucor racemosus were induced to convert to hyphae. This increase correlated well with time course of the conversion in cell type and was independent of the metabolic changes caused by the shift to aerobic conditions. There was no significant change in the intracellular level of spermidine, a polyamine synthesized from putrescine and the propylamine group of S-adenosylmethionine. Spermine was not detected. An examination of protein methylation revealed an increase in the methylation of total protein during the shift in cell type and possible qualitative as well as quantitative changes in specific base proteins.

Fungal Proteins↗

A technique for simultaneous fracture repair and augmentation of the atrophic edentulous mandible.

A technique that uses autogenous rib grafts for repair of fractures of an atrophic, edentulous mandible and augmentation of the ridge has been presented. Nine cases have been treated in this manner. We advocate this treatment to promote healing of the fractures and to provide necessary mandibular bone for future vestibuloplasty and, ultimately, restoration of function with denture construction.

Adult↗

Role of the 21,000 molecular weight polypeptide of Bacillus subtilis RNA polymerase in RNA synthesis.

DNA-dependent RNA polymerase from Bacillus subtilis contains a 21,000 molecular weight (21K) peptide subunit. This subunit was purified and added to 21K-depleted polymerase isolated from both uninfected and SP85-infected B. subtilis. The effect of the subunit on total RNA synthesis, on enzyme-DNA binding, on RNA chain initiation and elongation, and on enzymatic specificity were examined. A comparison was made of the effects of the 21K peptide and NaCl on polymerase activity, RNA chain elongation, and symmetry of transcription of SP82 DNA. The addition of the 21K peptide to enzyme preparations lacking this subunit stimulated total polymerase activity 20 to 40%. In contrast, addition of NaCl at concentrations greater than 0.1 M significantly reduced polymerase activity. The 21K peptide appeared to alter the general affinity of the polymerase for DNA. The rate of RNA chain initiation was not affected by the 21K peptide, but RNA chain elongation was stimulated. Both the 21K peptide and NaCl increased the asymmetry of transcription of SP82 DNA by phage-modified polymerase. The 21K effect was related to the stimulation of elongation while high concentrations of NCl appeared to act at RNA chain initiation. RNAs synthesized in vitro by polymerase lacking and supplemented with the 21K peptide were translated by a Escherichia coli cell-free system. The 21K peptide had little direct effect on the selection of promoters in vitro as measured by this technique, but it dramatically increased the translatability of the product.

Bacillus subtilis↗

Translation of RNAs synthesized in vivo and in vitro from bacteriophage SP82 DNA.

The synthesis of 69 phage-specific polypeptides during the infection of Bacillus subtilis with bacteriophage SP82 was detected by pulse-labeling, one-dimensional electrophoresis, and autoradiography. SP82 virions were found to contain approximately 22 polypeptides, most of which were synthesized late in infection; evidence was obtained for the processing of the major virion protein. RNAs extracted at different times during infection were translated by using an Escherichia coli cell-free extract. Only smaller-molecular-weight peptides were produced efficiently in vitro; in the 9,000- to 60,000-molecular-weight range, 50 to 60% of the peptides synthesized in vivo were produced by translation of RNAs extracted from infected cells. Eight of the virion peptides were produced by in vitro translation of RNAs extracted from infected cells. RNAs were synthesized under defined conditions by RNA polymerase extracted from uninfected B. subtilis and by polymerases isolated from cells 8 and 20 min after infection with SP82. Translation of these RNAs yielded characteristic and different patterns of polypeptides. Nine of the 12 polypeptides produced by translation of RNAs synthesized by the host polymerase corresponded in mobility to peptides appearing in vivo in the 0 to 3 and 3 to 6 min intervals of pulse-labeling after infection; 12 of the 25 peptides synthesized from RNAs produced by polymerase extracted 8 min after infection corresponded in mobility to peptides detected in vivo 8 min after infection, and 15 of the 22 peptides directed by RNAs made by the polymerase isolated 20 min after infection corresponded to peptides present in vivo late in infection. Five of the peptides produced in vitro from the latter RNA corresponded to virion peptides.

Bacillus subtilis↗

Apertognathia: its challenge and conquest. Report of a case.

Apertognathia or open-bite deformity is the cause of poor speech, loss of masticatory function, and the resultant embarrassment of patients. The treatment of these malocclusions embodies the use of our own technical, scientific, and physiologic knowledge, coupled with the research of others. This article gives a solution to an unusual case and points out the present techniques and research are only building blocks for the future.

Adolescent↗

The use of velocity wave form analysis in the diagnosis of carotid artery occlusive disease.

Velocity wave form analysis (VWFA) was carried out on 75 velocity tracings recorded from the common carotid artery with a continuous wave Doppler. Grouped according to clinical status, there were 20 young "normals" (I), 18 old "normals" (II), 15 stenoses of less than 50% diameter (III), 13 stenoses of greater than 50% (IV), and nine complete occlusions (V). Five of the nine dimesnions analyzed were found to be more discriminating than the others. Using these dimensions in an equation derived by discriminant analysis, the "score" of each tracing placed it into the appropriate clinical category with 95% accuracy. The accuracy rate of separating normal, stenosed, and occluded carotids was 100%. The accuracy of VWFA was limited (82%) only in discriminating between greater than and less less than 50% stenosis by diameter. Twenty-one of the 37 patients identified by VWFA as having carotid artery occlusive disease (CAOD) had normal supraorbital artery Doppler tests. Highly significant improvements in the velocity wave form of 10 carotid arteries were produced by endarterectomy.

Adult↗

Oral psoriasis.

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Diagnosis, Differential↗