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S Smith

Publications and source records attributed to S Smith.

At least 991 records · Page 55Linked to original sources
PubMed1979

Evaluation of the toxicologic and teratogenic potentials of sodium fluorescein in the rat.

Sodium fluorescein (10%) when injected intravenously (5 ml/kg) in pregnant albino rats crossed the placental barrier and appeared to be distributed throughout the fetus within 15 min. It was detectable in the fetus up to 4 h after injection but not beyond 24 h. A single intravenous administration of sodium fluorescein did not produce embryotoxic or teratogenic effects. Oral LD50 studies using sodium phenobarbital on rats which received sodium fluorescein during their fetal development showed no apparent effects of sodium fluorescein on their drug detoxification systems.

Abnormalities, Drug-Induced↗
PubMed1979

Effect of paracetamol on amylobarbitone hydroxylation in man: a gas chromatographic method for simultaneous estimation of underivatized paracetamol and barbiturates.

A rapid and specific technique for the simultaneous gas chromatographic estimation of underivatized paracetamol and barbiturates using an alkali flame ionization detector is described which is suitable for both forensic and pharmacokinetic investigations. An improved method for estimation of 3-hydroxyamylobarbitone is also detailed. These techniques were used in an investigation of the effects of oral administration of 1 g paracetamol 8 hourly on the formation of 3-hydroxyamylobarbitone from a single oral dose of 200 mg sodium amylobarbitone. No significant changes were found in the plasma concentrations and total body clearance of amylobarbitone nor was there any alteration in the urinary elimination of 3-hydroxyamylobarbitone.

Acetaminophen↗
PubMed1979

Bone marrow culture in vitro. A technique for analysis and permanent recording of cellular composition.

The in vitro cloning of haematopoietic progenitor cells derived from blood or bone marrow is now an established technique for the study of normal and abnormal blood formation. In semi-solid agar the results are conventionally recorded as the number of clusters or colonies that grow on the plate under controlled culture conditions. However, the demonstration of detailed morphology within these cellular aggregates remains unsatisfactory. Aspiration techniques are cumbersome and invariably disturb cellular relationships within the supporting matrix while supravital staining is limited by variable uptake of dye by the agar. We describe a method in which the entire cell-containing layer is removed from the Petri dish, fixed, and after mounting on a glass-slide, is air-dried. This preparation stains well with a wide variety of biological dyes, is minimally influenced by background colouration of the culture medium and excellent demonstration of morphologic detail is possible. A permanent record of the cellular composition of the culture is easily obtained by mounting the stained agar disc.

Animals↗
PubMed1978

Release of two thioesterase domains from fatty acid synthetase by limited digestion with trypsin.

Limited digestion, with trypsin, of the fatty acid synthetase from rat mammary gland releases an enzymically active thioesterase component that, under denaturing conditions, consists of two major species of mol.wts. 35000 and 17500 and a minor species, mol.wt. 15,000. The 17500- and 150000-mol.wt. species are shown to originate from the 35000-mol.wt. species as a result of nicking by trypsin. The nicked polypeptides are enzymically active. The fatty acid synthetase is inhibited by [1,3-14C]di-isopropyl phosphorofluoridate, which is shown to bind to, and inactivate, two thioesterase active sites. When the [1,3-14C]di-isopropyl phosphate-labelled fatty acid synthetase is subjected to limited digestion with trypsin, all of the radioactivity is recovered in the isolated thioesterase component, i.e. in the 35000-mol.wt. polypeptide and its nicked products. Since the isolated thioesterase is shown to bind only one di-isopropyl phosphate residue per 35000-mol.wt. polypeptide, we conclude that the fatty acid synthetase has two thioesterase domains, both of which are removed by limited trypsin treatment.

Chromatography, Gel↗
PubMed1978

Properties of the thioesterase component obtained by limited trypsinization of the fatty acid synthetase multienzyme complex.

The fatty acid synthetase from lactating rat mammary gland is shown to consist of two polyfunctional polypeptides of similar molecular weight (about 220,000); a 4'-phosphopantetheine residue is covalently bound to one, or both subunits. Limited trypsinization of the fatty acid synthetase releases on enzymatically active thioesterase component which has been purified and its properties studied. The thioesterase sediments in the ultracentrifuge as a single component of molecular weight 32,000; its sedimentation coefficient is 2.9 x 10-(13) s its diffusion coefficient 5.0 x 10-(7) cm2 s-(1). The thioesterase also elutes from a column of Sephadex G-75 as a single, symmetrical peak of constant specific activity. However, electrophoresis of the denatured thioesterase in the presence of sodium dodecyl sulfate reveals that the enzyme has been partially nicked during isolation. The kinetic data of the enzyme reaction were studied using palmityl-CoA as a model substrate. Solvent pH was found to affect both Vmax and Km (Km = 0.5 micron at pH 6.6, 2.5 micron at pH 8.0) wereas solvent ionic strength affected Vmax but no Km. The thioesterases from the fatty acid synthetases of rat liver and lactating mammary gland have identical physical properties, identical amino acid compositions, and are immunologically indistinguishable. Both thioesterases hydrolyze long chain, in preference to short chain, thioesters of CoA, an observation consistent with their role in regulation of the chain-terminating step in fatty acid synthesis by the parent multienzyme complexes.

Amino Acids↗
PubMed1978

Purification and properties of a thioesterase from lactating rat mammary gland which modifies the product specificity of fatty acid synthetase.

An acyl coenzyme A hydrolase (thioesterase II) has been purified to near homogeneity from lactating rat mammary gland. The enzyme is a monomer of molecular weight 33,000 and contains a single active site residue. The enzyme is specific for acyl groups, as acyl-CoA thioesters, containing eight or more carbon atoms and can also hydrolyze oxygen esters. Thioesterase II is capable of shifting the product specificity of rat mammary gland fatty acid synthetase from predominately long chain fatty acids (C14, C16, and C18) to mainly medium chain fatty acids (C8, C10, and C12). Thioesterase II can restore the capacity for fatty acid synthesis to fatty acid synthetase in which the thioesterase component (thioesterase I) has been inactivated with phenylmethanesulfonyl fluoride or removed by trypsinization. No evidence was found of significant levels of thioesterase II in lactating rat liver. The presence of thioesterase II in the lactating mammary gland and the ability of the enzyme to hydrolyze acyl-fatty acid synthetase thioesters of intermediate chain length, are indicative of a major role for this enzyme in the synthesis of the medium chain fatty acids characteristic of milk fat.

Amino Acids↗
PubMed1978

Decreased glucagon receptors in diabetic rat hepatocytes. Evidence for regulation of glucagon receptors by hyperglucagonemia.

The effects of endogenous and exogenous hyperglucagonemia on the specific binding of glucagon to hepatocyte receptors was studied, as was the response of cAMP to glucagon. In streptozotocin diabetic rats, blood glucose and plasma glucagon increased and plasma insulin decreased as compared with controls. Insulin treatment in diabetic rats restored blood glucose and plasma glucagon toward normal and elevated plasma insulin. Specific binding of (125)I-glucagon to isolated hepatocytes (10(6) cells) decreased in diabetic rats (8.17+/-0.38%) compared to controls (14.05+/-0.87%) and was restored by insulin treatment (12.25+/-0.93%). Specific binding of (125)I-insulin in controls was 7.30+/-10.16%; it increased in diabetic rats to 12.50+/-0.86%, and decreased in diabetic rats after insulin treatment (9.08+/-0.87%). Scatchard analysis and the competition plots of the data indicate that decreased glucagon binding and increased insulin binding in diabetes were due to change in the number of receptors rather than a change in their affinity. Hepatocyte cAMP response to glucagon (0.25-5.0 ng/ml) was almost abolished in diabetic rats and was restored with insulin treatment. Specific glucagon binding by hepatocytes from chronically hyperglucagonemic (glucagon injected) rats was decreased (P < 0.005) to 8.76+/-0.61% compared with controls (13.20+/-0.74%) and acutely hyperglucagonemic animals (13.53+/-1.33%). The decreased binding was associated with a 70% decrease in hepatocyte cAMP response to glucagon compared with a normal response in acutely hyperglucagonemic rats.These data appear to support the concept of receptor regulation by ambient hormone level. In both endogenous and exogenous hyperglucagonemia, however, there was a disproportionately large decrease in cAMP response to glucagon compared to the decrease in glucagon binding.

Animals↗
PubMed1978

Effects of processing and cooking on PBB residues.

To study the effect of processing on polybrominated biphenyl (PBB) levels, milk from four dairy herds containing less than 0.3 ppm (fat basis) of physiologically incorporated PBBs was presented individually into cream, skim milk, butter, and stirred curd cheese. Pasteurized and freeze-dried whole milk, skim milk, and cream, spray-dried whole milk and skim milk, and condensed whole milk were also made. PBBs were concentrated in the high-fat products. Spray-drying reduced PBBs in whole milk and skim milk while pasteurization, freeze-drying, aging of cheese, and condensation were not effective. To study the effect of cooking on PBB levels, thigh meat, thigh skin, drumstick and breast (with skin) from half of chickens fed PBBs were analyzed raw, and pieces from the other halves were analysed following separate pressure cooking. The level of PBBs expressed as parts per million on a solids basis was lower in the cooked sample than in the corresponding raw piece and part of the PBBs lost were found in the drip. Recoveries of PBBs in cooked tissue and broth ranged from 68.1% in the thigh skin to 84.6% in the drumstick, with approximately two-thirds of the recovered PBBs found in the cooked meat itself. Therefore, pressure cooking resulted in a loss ranging from 36% for the drumstick to 53% for the thigh skin.

Animals↗
PubMed1978

Small towns need big-time tactics to find physicians.

Successful placement of new physicians in small-community hospitals involves a four-phase strategy: assessing the need, conducting the search, arranging the visit, and negotiating the agreement.

Hospital Bed Capacity↗
PubMed1978

Comparative analgetic testing of various compounds in mice using writhing techniques.

Anti-writhing assays to detect analgesia or specific activity against selected agonists were performed on albino mice. Acetylcholine Cl, bradykinin triacetate, phenylquinone, and serotonin creatinine sulfate were used as agonists. 10 compounds, including 5 standard analgetics, were tested against each agonist. Attempts to study histamine phosphate as an agonist were not successful. Results of these investigations showed satisfactory analgetic acitivity for codeine phosphate and acteyl salicylic acid (ASA) in all assays. weaker analgetics displayed varying degrees of activity depending on the agonist tested. Acute oral toxicities were determined for the 10 test compounds and the analgetic ED50 vs the LD50 of each compound was compared. The data confirmed the nonspecificity for writhing assays as well as a variability in activity of the test compounds against the various agonist.

Acetylcholine↗