Search PubMed⌕ Search

Biomedical subjects

R C Smith

Publications and source records attributed to R C Smith.

At least 289 records · Page 16Linked to original sources

Regulation of myosin filament assembly by light-chain phosphorylation.

Myosins isolated from vertebrate smooth muscles and non-muscle cells such as lymphocytes and platelets contain regulatory light chains (Mr = 20000), which are phosphorylated by a Ca2+-calmodulin-dependent kinase and dephosphorylated by a Ca2+-insensitive phosphatase. Phosphorylation of the regulatory light chains of these myosins in vitro regulates not only their interactions with actin but also their assembly into filaments. Under approximately physiological conditions (0.15 M NaCl, pH 7.0) stoichiometric levels of Mg-ATP disassemble these non-phosphorylated myosin filaments into species with sedimentation coefficients (So20,w) of approximately 11S. Hydrodynamic and electron microscope observations have indicated that this 11S species is a monomer with a folded conformation (Trybus et al., Proc. natn. Acad. Sci. U.S.A. 79, 6151 (1982)). Rotary shadowing reveals that the tails of disassembled gizzard and thymus myosins are folded twice at two hinge points to form a folded three-segment structure. Phosphorylation of the regulatory light chains of these myosins causes these folded 11S molecules to unfold into the conventional extended monomeric form (6S), which is able to assemble into filaments. Thus in vitro these myosin filaments can be assembled or disassembled by phosphorylation or dephosphorylation of their light chains. Whether these results have any relevance to the situation within living non-muscle and smooth muscle cells remains to be established.

Actins↗

Studies on the effect of phosphorylation of the 20,000 Mr light chain of vertebrate smooth muscle myosin.

Myosin was rapidly prepared from turkey gizzard muscle to a high level of purity, in high yield and in a non-phosphorylated state. It was consistently observed that the actin-activated Mg2+ ATPase activity of this myosin was dependent on the level of phosphorylation of the 20,000 Mr light chain, for example, in the non-phosphorylated state, the myosin Mg2+ ATPase activity was not activated by actin whereas, when the light chains were phosphorylated, the Mg2+ ATPase activity of the myosin was activated approximately ninefold by actin. Using the "desensitized" scallop myosin test system (Kendrick-Jones et al., 1976; Sellers et al., 1980) it was further demonstrated that phosphorylation of the 20,000 Mr gizzard light chain has a regulatory role. These results also suggest that the regulatory mechanisms mediated by smooth muscle myosin light chains and molluscan myosin regulatory light chains are similar, i.e. in the absence of Ca2+, both types of light chain inhibit myosin interaction with actin and this inhibition is relieved by either phosphorylation in smooth muscle or by direct calcium binding in molluscan myosins. The basis of regulation exerted by these light chains is therefore repression derepression. Using a variety of techniques, i.e. turbidity measurements, quantitative high speed centrifugation, electron microscopy and dark field light microscopy, it was observed that the stability of gizzard myosin filaments at approximately physiological conditions (0.15 M-NaCl, 1 mM-MgATP, pH 7.0) was dependent on the level of light chain phosphorylation. Using purified calmodulin-dependent light chain kinase and phosphatase, it was further shown that these gizzard myosin filaments can be reversibly assembled and disassembled as a result of phosphorylation-dephosphorylation of the 20,000 Mr light chain.

Actins↗

A computerized nasal analysis system.

Critical analysis of an aesthetic surgeon's presurgical and postsurgical photographs may provide an excellent tool for self-assessment, research, and teaching. Techniques are presented that allowed precise definition by personnel other than the surgeon of each patient's deformities and the effects of surgery on them. Trigonometric formulas were developed and a computer was programmed to use the X and Y coordinates for facial landmarks to perform many calculations providing distances, angles, projections, and rotations relating to the rhinoplastic surgery. Cases are reported showing typical changes and some results not readily apparent in the photographs. Such data provide not only current analysis of individual cases, but they eventually will become a large data base that may be used to select groups of rhinoplastic cases having common degrees of deformity or of postoperative changes.

Anthropometry↗

Antioxidant activity of uric acid and 3-N-ribosyluric acid with unsaturated fatty acids and erythrocyte membranes.

Uric acid and 3-N-ribosyluric acid have been proposed to be important antioxidants in human plasma and in the bovine erythrocyte, respectively. In this study both of these compounds at 0.2 mM protected linolenate and arachidonate from air oxidation in the presence of 5 microM copper sulfate. The unsaturated fatty acids were protected when the urates were added at the beginning of the incubation or at 12 and 24 h of incubation for linolenate and at 3, 6, and 12 h for arachidonate. Both urates protected human and bovine erythrocyte membranes from peroxidation by t-butylhydroperoxide. These data support the proposal that urates are important antioxidants and free radical scavengers.

Animals↗

Synthesis of 3-N-ribosyluric acid 5'-monophosphate by red cells of the bovine fetus.

Although 3-N-ribosyluric acid (3-RUA) was not detected in the red cells of bovine fetuses, 3-N-ribosyluric acid 5'-monophosphate, the immediate precursor of 3-RUA, was synthesized from uric acid and 5-phosphoribosyl-1-pyrophosphate (PRPP) by hemolysates of fetal red cells. These preparations also synthesized 3-N-ribosylxanthine 5'-monophosphate from xanthine and PRPP. Partially purified extracts of fetal and adult erythrocytes of cattle had similar enzyme activity and the same specificity toward xanthine and orotic acid. Therefore, it was concluded that the absence of 3-RUA in fetal red cells was not a result of lack of the enzyme orotate phosphoribosyltransferase (EC 2.4.2.10).

Aging↗

Gastric antisecretory 9H-xanthen-9-amines.

A series of 9H-xanthen-9-amines possessing a wide variety of nitrogen substituents at C-9 was prepared for evaluation of gastric antisecretory activity. These substituents included the acetamidine, imidate, pyrimidine, thiazoline, quinuclidine, 2-hydrazinopyridine, aminopiperidine, aminoalkylimidazole, and aminoalkylpyridine moieties. The majority of compounds in this series inhibited gastric acid secretion when tested orally in the pylorus-ligated rat. Potency was increased by intraduodenal administration and diminished by incubation with gastric juice, suggesting partial degradation of the compounds in the gastric environment. A representative example, 3-(9H-xanthen-9-ylamino)-1-ethylpiperidine, exhibited similar activity in dogs, although no free compound could be detected in the blood. It is therefore hypothesized that this compound is either rapidly bound to tissue and/or metabolized to an active species.

Animals↗

Adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma is a rare malignant tumour of the breast. It usually presents as a painful, apparently benign lump near the nipple. The tumour has an interesting histology, natural history and mammographic appearance. Mastectomy is usually curative.

Breast Neoplasms↗

The relationship of placental grade by ultrasound to markers of fetal lung maturity.

Seventy-two amniocenteses with concurrent placental grading by ultrasound were performed during 66 pregnancies. No relationship was observed between placental grade and the mean ratio of lecithin to sphingomyelin (L/S) or the phosphatidylglycerol concentration. Both placental grade and fetal lung maturity were interrelated by the independent variable of gestational age. The latter may explain the trend observed between a mature L/S ratio and the placental grade. Grade 3 placentas were present in only 20% of patients studied at 37 weeks of gestation or later (12 of 61 patients), and in every instance a Grade 3 placenta was associated with an absence of neonatal respiratory distress.

Amniocentesis↗

Blood levels of haloperidol in schizophrenic patients.

Plasma and red blood cell levels of haloperidol were measured in psychotic patients after an acute dose of haloperidol and during treatment with fixed doses for several weeks. There was wide variability of haloperidol plasma and red blood cell levels at a given dose and a nonlinear relationship between haloperidol dose and blood levels. The red blood cell/plasma ratio (0.40) had a narrow range among different patients. Haloperidol blood levels were not correlated with the age of the patient. Concomitant administration of benztropine mesylate did not decrease plasma haloperidol levels. Steady state plasma or red cell haloperidol levels could not be predicted from levels 24 hours after the acute dose.

Adolescent↗

Age affects dopamine receptor changes during chronic administration of fluphenazine.

The effects of age on the alteration of brain dopaminergic receptors (spiperone binding) during chronic administration of fluphenazine was studied in young (7-month) and old (25-month) rats. Compared to age-matched saline controls, the old fluphenazine rats showed an earlier on-set and quantitatively greater decrease in specific binding of spiperone and increase in the KD of spiperone binding than young rats. Young rats showed an increase in the Bmax of spiperone binding at 6-weeks which was not shown by old rats.

Age Factors↗