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Biomedical subjects

R McCauley

Publications and source records attributed to R McCauley.

At least 37 records · Page 2Linked to original sources

Influence of branched chain amino acid infusions on wound healing.

Branched chain amino acids (BCAA) may serve as a major oxidative fuel for skeletal muscle during periods of starvation. This study compared the ability of protein-undernourished rats to heal musculo-aponeurotic wounds of the abdominal wall when they were infused with solutions containing 45% BCAA or 8% BCAA (conventional TPN). Although the provision of 45% BCAA tended to result in better nourished animals and significantly increased plasma glutamine concentrations, this was not associated with improved healing.

Amino Acids, Branched-Chain↗

Ubiquitin is involved in the in vitro insertion of monoamine oxidase B into mitochondrial outer membranes.

Monoamine oxidase B that has been synthesized by a reticulocyte lysate charged with bovine liver RNA will insert in a proteinase K-resistant form into isolated outer membranes from rat liver mitochondria. It appears that ubiquitin, a 76-amino acid polypeptide which is enzymatically conjugated to proteins, may be involved in the insertion process. Depletion of endogenous ubiquitin from the reticulocyte lysate with purified antibodies against this polypeptide inhibits the insertion of monoamine oxidase B, and this inhibition is relieved if ubiquitin is restored. On the other hand, a mutant form of ubiquitin which is unable to conjugate with proteins will not support insertion. Conjugation with ubiquitin is an ATP-dependent process. Not only does enzymatic depletion of ATP from the lysate prevent the insertion of monoamine oxidase, but ubiquitin will not restore insertion unless ATP is also present. These data indicate that the formation of a ubiquitin conjugate is involved in the insertion of newly synthesized monoamine oxidase B into the outer membranes.

Adenosine Triphosphate↗

Ultrasonography in the evaluation of wrist swelling in children.

We studied 15 children using high resolution ultrasonography. In all patients, ultrasound clearly demonstrated the nature of the soft tissue abnormality; 11/15 had thickening of the common synovial sheaths surrounding extensor tendons of the fingers, 1/15 had thickening of the flexor tendons and 3/15 had abnormalities consistent with ganglion cysts. These results indicate that ultrasound is an important yet noninvasive tool in the assessment of wrist swelling in children.

Arthritis, Juvenile↗

The in vitro insertion of monoamine oxidase B into mitochondrial outer membranes.

Bovine monoamine oxidase (MAO) B has been synthesized in vitro using a reticulocyte lysate translation system directed by bovine liver poly(A)+ RNA. The newly synthesized enzyme apparently lacks a cleavable N-terminal extension, but MAO B is readily incorporated into mitochondria or isolated mitochondrial outer membranes prepared from rat liver. ATP is not required for the binding of the newly synthesized enzyme to the outer membranes, but is necessary for the insertion of MAO B into these membrane vesicles. The ATP is not required to generate a mitochondrial membrane potential as assembly occurs under conditions that preclude either the formation or the maintenance of the potential. MAO B will bind to but not become incorporated into outer membrane vesicles which have been treated with trypsin, suggesting that the insertion of MAO B also depends on protein factors present on the outer membranes.

Animals↗

Effect of selective monoamine oxidase inhibitors on rat pineal melatonin synthesis in vitro.

Freshly cultured pineal glands respond to the monoamine oxidase A (MAO A) inhibitor clorgyline and to high concentrations of the MAO B inhibitor, deprenyl, with an increase in serotonin N-acetyltransferase activity and N-acetylated indoles and a fall in 5-hydroxylated serotonin degradation products. Glands cultured for 48 hours before challenge respond less. Response is absent in glands cultured for 72 hours and in glands from ganglionectomized animals cultured for 48 hours before challenge. These data are consistent with the hypothesis that these MAO inhibitors stimulate melatonin synthesis by protecting norepinephrine from degradation.

Animals↗

The effects of chronic ozone exposure on pulmonary collagen content and collagen synthesis in rats.

Male rats were exposed to 0.125, 0.25 or 0.5 ppm of ozone or clean air for up to 1 year. During this exposure period there was little evidence for collagen accumulation in the lungs. However, the rate of incorporation of tritiated proline into both lung collagen and total lung protein was accelerated. These data suggest that exposure to ozone under these conditions results in an increase in the turnover of collagen as well as other lung proteins.

Animals↗

The effect of chronic ozone exposure on lung benzo(a)pyrene oxidase, benzphetamine demethylase and monoamine oxidase.

Adult male Fischer 344 rats were exposed either to clean air or to a mixture of clean air and 0.5ppm ozone for up to one year. These populations were sampled after three and six months and when the exposure was completed. The activity of several oxidative enzymes in these rat lungs were compared. Although there was no significant increase in the ability of pulmonary microsomes to oxidize benzo[alpha]pyrene after three months of exposure to ozone, this activity and the oxidative demethylation of benzphetamine were increased after six months and a year of exposure. Aside from these enzymatic changes, electrophoretic analysis indicated that the microsomes from ozone exposed rats were enriched with a protein with an apparent molecular weight of 68,000. The activity of the two isoenzymic forms of monoamine oxidase, MAO A and MAO B, were also measured, and neither activity was affected by the ozone exposure.

Animals↗

Monoamine oxidase A and monoamine oxidase B activities are catalyzed by different proteins.

Monoamine oxidases A and B (amino: oxygen oxidoreductase (deaminating) (flavin-containing), EC 1.4.3.4) have been identified in the outer membranes of rat liver mitochondria by their covalent reaction with the inhibitor, [3H]pargyline. On analysis by polyacrylamide gel electrophoresis under denaturing conditions. Monoamine oxidase A was found to migrate more slowly that monoamine oxidase B. Proteins which correspond to monoamine oxidases A and B (as identified by the electrophoretic distribution of covalently bound [3H]pargyline) were excised from the gels. Subsequent analysis showed that both monoamine oxidase A and monoamine B had been highly purified by this procedure. Electrophoretic analysis of the peptides produced by limited proteolysis with bovine trypsin, alpha-chymotrypsin, Staphylococcus aureus V8 proteinase and cyanogen bromide indicate that monoamine oxidases A and B have different amino acid sequences.

Amino Acid Sequence↗

Selective inhibition of MAO-A but not MAO-B activity increases rat pineal melatonin.

Clorgyline, a selective MAO-A inhibitor, increased (5 times) rat pineal melatonin and N-acetyl-serotonin (NAS) content, and decreased 5-HIAA level by 80%. Deprenyl, a selective MAO-B inhibitor, did not change melatonin or other pineal indoles content. The data obtained show that inhibition of MAO-A but not B enzyme is responsible for pineal melatonin increase caused by MAO inhibitors. It is suggested that the stimulation of melatonin synthesis caused by MAO inhibitors may contribute to their antidepressive effect.

Animals↗

Gallium-67 scintigraphy in well-differentiated lymphocytic lymphoma of the skin.

Skin lymphomas are now divided into "T" or thymic cell lymphomas (mycosis fungoides being the principal type) and "B" cell lymphomas after the bursa of Fabricius. The "T" cell lymphomas all are identified by the thymic or cerebriform cell. Those lymphomas of the skin which do not contain these characteristic cells are derived from the bursa cells and are termed "B" cell lymphomas. A large percentage of these non "T" cell lymphomas have been histologically diagnosed as lymphocytic lymphoma of the skin (1). The authors had an opportunity to scan a patient with histologically proven lymphocytic lymphoma of the skin with Ga-67 and obtained on excellent correlation between gallium accumulation in the skin lesions and histologic confirmation of lymphocytic lymphoma.

Gallium Radioisotopes↗

The effect of in vivo exposure to diesel exhaust on rat hepatic and pulmonary microsomal activities.

The effect of exposure to three concentrations of diesel exhaust on several heptic and pulmonary activities has been tested. After one year of exposure, the ability of liver microsomes to oxidize benzo[alpha]pyrene to more polar metabolites was not increased. Further studies with liver microsomes showed that, after several months of exposure, there was no evidence for the induction of either cytochrome P-450, cytochrome P-448 or NADPH dependent cytochrome c reductase. The ability of pulmonary microsomes to generate polar metabolites from benzo[alpha]pyrene was impaired after one year of exposure to the highest concentration of exhaust (1500 micrograms m-3). The process by which the exposure causes this inhibition is not clear.

Aerosols↗

Studies on the flavins in rat liver mitochondrial outer membranes.

The incorporation of radioactivity derived from [2-14C] riboflavin into the flavins of rat liver mitochondrial outer membranes was studied. These membranes were found to contain about 0.6 nmol of non-covalently bound flavins per mg protein; the majority is in the form of FAD (73%) and FMN (24%). The membranes also contain about 1.5 nmol per mg of covalently bound flavins. After labeling, radioactive flavins appeared in the non-covalently bound flavins for about 4 h. Most of this radioactivity was in FAC (77%). Neither the rate nor extent of this labeling was affected by cycloheximide (1 mg/kg) administered 30 min prior to the radioactive riboflavin. With the covalently bound flavins, radioactivity was incorporated into the coenzymes for at least 18 h, but the rate of incorporation was much slower. After cycloheximide, radioactive flavins continued to appear in covalently bound flavins for about 2 h, but then stopped. Labeling of both types of flavins after [14C] riboflavin was considerably slower than the incorporation of [3H] leucine into outer membrane proteins. These results suggest that with flavoproteins from the mitochondrial outer membranes, the incorporation of flavins occurs after synthesis of the various apoenzymes is complete.

Animals↗

Effect of phenobarbitone on the nucleocytoplasmic transport of ribonucleic acid in vitro.

The transport of nucleic acids from the nucleus to the cytoplasm is a potential site for modification of normal cellular processes by drugs and hormones. In this study the effect of phenobarbitone on nucleocytoplasmic transport of ribosomes was measured in an assay system in vitro. The transport of radioactive ribosomes from isolated rat hepatic nuclei to unlabelled post-microsomal supernatant was measured in rats treated with 80 mg of phenobarbitone/kg body wt. or saline 3h before death. With either treatment, transport was linear with time, and dependent on temperature and the presence of ATP. However, phenobarbitone treatment increased transport of ribonucleoproteins over saline-treated animals nearly twofold. The effect of phenobarbitone was mediated through the cytosol, but was not the result of altered stability of the RNA transported to the cytosol. Cycloheximide (5 mg/kg body wt.) given 3.5 h before death inhibited the stimulation of transport by phenobarbitone. The data indicate that phenobarbitone increased the transport of RNA by stimulating the synthesis of cytosol factors that regulate transport of RNA from the nucleus.

Animals↗