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Biomedical subjects

S M Shaw

Publications and source records attributed to S M Shaw.

At least 19 recordsLinked to original sources

Regulation of the mammalian carbamoyl-phosphate synthetase II by effectors and phosphorylation. Altered affinity for ATP and magnesium ions measured using the ammonia-dependent part reaction.

We have measured the 'core' mammalian carbamoyl-phosphate synthetase II (CPSII) activity, using NH4Cl as the nitrogen-donating substrate and trapping carbamoyl phosphate as urea through its reaction with ammonium ions. When ATP and magnesium ion concentrations are close to those found in the cell, the substrate saturation curves for ammonia and bicarbonate are hyperbolic, giving Km (NH3) values of 166 microM at high ATP concentrations and 26 microM at low ATP concentrations, while the Km (bicarbonate) is 1.4 mM at both ATP concentrations used. These values for the Km (NH3) are lower than previously reported for CPS II, and closer to the values for the mitochondrial counterpart. The Km for ammonia and bicarbonate are not altered by phosphorylation of the multienzyme polypeptide CAD, which contains the first three enzyme activities of pyrimidine biosynthesis. The CPS II activity is lower with an excess of either ATP or magnesium ions, causing the apparently sigmoid dependence of activity upon ATP concentration to be enhanced at low concentrations of free magnesium ions. The feedback inhibitor, UTP, acts by stabilising a state with a low affinity for magnesium ions and for ATP. In the presence of the activator, 5-phosphoribosyl diphosphate (PRibPP), the enzyme has a higher affinity for magnesium ions and thus the ATP dependence of the activity is hyperbolic. Phosphorylation of CAD similarly activates the CPS II enzyme by increasing the affinity for magnesium ions and by pushing the equilibrium away from the low-affinity UTP-stabilised state. Using our improved assay procedure, we observe a very large activation by PRibPP of carbamoylphosphate synthesis at low concentrations of magnesium ions, and we find that unlike UTP, the activator PRibPP is able to act on the phosphorylated enzyme.

Adenosine Triphosphate

The biodistribution of [75Se]bis-[beta-(N,N,N-trimethylamino)ethyl]selenide diiodide in adult guinea pigs.

The biodistribution of [75Se]BISTAES was studied in guinea pigs. A higher concentration of radioactivity was observed in articular cartilage than in other tissues or organs. A minimal amount of radioactivity was found in the blood, muscle and bone. The compound was excreted rapidly in urine. The target to background ratios were encouraging. [75Se]BISTAES has potential as an articular cartilage imaging agent and further studies in osteoarthritic animals are merited.

Animals

Fitness promotion for adolescent girls: the impact and effectiveness of promotional material which emphasizes the slim ideal.

This study looks at techniques for promoting fitness participation among adolescent girls, in particular those which emphasize the "slim ideal." Various promotional posters were designed which systematically used different models (slim, average, and overweight) and different messages (slimness, activity, and health). The relative effectiveness of these posters was tested using a probability sample of 627 female high school students. The slim model was found to be the most effective poster, while slimness was the least effective of the messages. Demographic and self- and body-image factors had relatively little effect on the ratings of the posters. Focus group interviews conducted with the student sample indicated that they were concerned about their body weight, and that they associated slimness with fitness. However, the slimness message was not thought to encourage participation in fitness because overt emphasis on body image may lead to self-consciousness and fear of social rejection. The idea that participation would lead to a slim physique was also thought to be unrealistic. The students were more critical of the slimness message than of the slim model in the posters. Overall, the data indicate that promoting fitness through messages relating fitness to slimness is not an effective approach with adolescent girls. The use of very slim models in promotional material may be effective, but this approach may not be desirable because it reinforces the dominant cultural stereotype of the "ideal" slim female form.

Adolescent

Influence of complex charge and size on the uptake of 99mTc-diphosphonates in osteogenic tissue.

The biodistributions of six chromatographically pure 99mTc-HEDP complexes have been determined in soft tissues, normal bone and osteogenic lesions (induced with a Walker 256 tumor) in Fisher 344 rats. The physical properties of each 99mTc-HEDP complex including anionic charge, partial molar volume, molecular weight and spectral characteristics are known; thus allowing structure-activity relationships to be drawn. The results indicate that the smallest, low charged, mononuclear 99mTc-HEDP complexes have the greatest uptake in bone lesions, and the highest lesion to muscle and lesion to normal bone ratios.

Animals

Deterioration of stannous ion in radiopharmaceutical kits during storage.

The deterioration of stannous ion (Sn++) in inhouse-prepared and commercial radiopharmaceutical kits was studied. Sn++ content of three types of nonlyophilized, deoxygenated, aqueous inhouse-prepared kits [diethylenetriamine pentaacetic acid (DTPA), pyrophosphate and glucoheptonate] and of three commercially prepared kits (two lyophilized pyrophosphate kits and one diphosphonate in sealed glass ampul kit) was measured by differential pulse polarography. Inhouse-prepared kits were assayed initially and after storage for 6, 12, 24 and 48 days at 24, 5 and -18 C. Commercial kits were assayed initially and after storage for 12, 24 and 48 days at 5 and 24 C. Of the inhouse-prepared kits, Sn++ stability when stored for 48 days at 5 and 24 C. Freezer storage should be used, when possible, to insure maximum stability of Sn++ in inhouse-prepared, nonlyophilized ratiopharmaceutical kits. The commercial procedures of lyophilization and of sealing the reagent in a sealed glass ampul prolong Sn++ stability.

Drug Stability

Cadmium induced endothelial cell alterations in the fetal brain from prenatal exposure.

Pregnant rats received a single administration of 0.5, 1.0, or 2.0 mg/kg of cadmium on day 18 or 20 or gestation. Maternal animals were killed on day 21 and samples of the caudate nucleus from fetal brains were examined using the transmission electron microscope. A 2.0 mg/kg dose of cadmium administered to maternal rats on day 20 of gestation caused the formation of vacuoles in the endothelial cells of capillaries in the fetal brain. Significant endothelial cell vacuolization was not observed in the brain of fetuses from other treatment groups. The vacuoles occurred singly, were spherical in shape, were located adjacent to the intercellular junctions and caused focal distortion of the endothelial cell. Vacuoles were the only ultrastructural alteration observed in the caudate nucleus of fetal brains.

Animals

Preferential localization of radiolabeled liposomes in liver.

Liposome formulations were studied to achieve an efficient entrapment procedure for the production of liposomes of 99mTc-pentetic acid. The entrapment efficiency was studied by separation of the product using column chromatography. The particle-size range of the prepared liposomes was evaluated using electron microscopy. Entrapment techniques and separation procedures led to a liposome preparation with particles in the colloidal size range (0.001-0.5 micron). Dramatic differences in the organ distribution of the liposome preparation in mice were produced when different particle-size ranges were injected. Liposomes eluted in the first fraction after the void volume led to a maximum uptake by the liver and spleen 10 min after intravenous injection. Liposomes from pooled fractions provided less than half of the activity in the liver, as did the narrow size range liposome preparation.

Animals

Fetal effects of cadmium in pregnant rats on normal and zinc deficient diets.

This investigation has shown that not only the extent of fetal resoprtion and malformation but also the types of malformation seen in rats depend upon the strain used and day of gestation. Furthermore, the effects of zinc deficiency and cadmium administration on the fetus can be at least additive, as was seen for malformations. For fetal resorption, zinc deficiency potentiated the action of cadmium.

Abnormalities, Drug-Induced

The maternal distribution and placental transfer of cadmium in zinc deficient rats.

Although a transitory maternal zinc deficiency has been shown to result in an increased cadmium-induced fetotoxicity, the results of the present investigation indicated that a maternal zinc deficiency apparently did not affect the placental transfer of cadmium. However, a zinc deficiency did alter the maternal distribution of cadmium. The increased cadmium fetotoxicity associated with a maternal zinc deficiency may be caused by a maternal alteration rather than a direct effect on the fetus. Further study is necessary prior to any definitive statement concerning the effects of a maternal zinc deficiency on cadmium fetotoxicity.

Animals

Absorption, distribution, and excretion of 14C-meglumine in rats and dogs after administration of 14C-meglumine salicylate.

Meglumine labeled with carbon-14 was administered orally as 14C-meglumine salicylate to rats and dogs to study its distribution and excretion. The compound was incompletely absorbed; that which was absorbed was rapidly excreted in the urine. Peak blood levels were about 5-10 mug/ml in rats and 2-8 mug/ml in dogs. Tissue levels were negligible at the end of the experimental periods. No evidence for N-demethylation or oxidation to carbon dioxide was obtained.

Animals

Use of microcapsules as timed-release parenteral dosage form: application as radiopharmaceutical imaging agent.

The development of a new type of parenteral dosage form is described. A system of microencapsulation was formulated which produced microcapsules containing a water-soluble core material. The basic microencapsulation system could be altered to produce microcapsules with varied timed-release characteristics. Tracer methodology was employed as a sensitive and versatile analytical tool for the development and evaluation of the microencapsulation system. The core material was labeled by neutron activation after microcapsule formulation, which eliminated the radiation hazard and contamination problems that could occur during formulation with a labeled core material. Both in vitro and in vivo testing showed that the release patterns of labeled core material could be altered and detected. The microcapsules developed have potential as a timed-release parenteral dosage form and as an organ-imaging radiopharmaceutical.

Animals