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Biomedical subjects

C Masters

Publications and source records attributed to C Masters.

At least 73 records · Page 4Linked to original sources

Ontogenic variations in the interactions of lactate dehydrogenase isozymes with cellular structure.

The interactions of the LDH isozymes with cellular structure have been studied in the major tissues of the mouse during development. Overall, there is a clear indication that interactions between LDH and cellular structure are appreciable in all major tissues and at all stages of development, and an analysis of the isozyme status of the enzyme in both soluble and bound compartments has been effected. Information has been provided supporting the preferential binding of the A type activity to actin filaments. The data provided also support the concept of pelletable B type LDH in kidney and brain during the postnatal period. Binding was particularly extensive in the early embryonic stages, and the significance of this phenomenon, and the subcellular interactions observed to varying degrees in all the tissues throughout development, have been discussed in relation to the known metabolic characteristics of these separate tissue situations.

Animals↗

The influence of insulin on the flux of lipid metabolism in vivo.

The effects of insulin on the balance of lipid metabolism have been investigated by measuring the relative in vivo incorporation of 3H- and 14C-labelled glycerol into the major tissues and lipid classes of diabetic mice over a three day period. Several significant alterations in the relative uptake of label were caused by the insulin treatment. Generally, there were indications of decreased synthesis and degradation of lipids in most tissues, but with an increased synthesis of hepatic triacylglycerol being a notable exception to these trends. These data indicate that insulin treatment produces widespread changes in the relative emphasis of lipid metabolism, and allow a detailed description of these responses in relation to the individual tissues and lipid classes of the living animal. The implications of these metabolic changes have been discussed in relation to hormonal effects, and tissue specific and whole body aspects of the regulation of lipid metabolism.

Animals↗

On the role of catalase in the oxidation of tissue fatty acids.

The role of catalase in lipid metabolism has been studied by means of a comparison of the turnover characteristics of the major lipid classes in the normal mouse with those of animals in which the catalase activity had been inhibited and blocked by aminotriazole and allylisopropylacetamide. Double isotope ratios were determined in the lipid fractions of several tissues following the injection of labeled glycerol, and a number of significant differences were identified between these treatments. Since catalase is recognized as an integral component of the peroxisomal pathway of fatty acid oxidation, these results may be taken as indicating that interruption of the process of peroxisomal beta-oxidation in this manner cause extensive perturbations of lipid metabolism in the living animal, and these perturbations extend well beyond those tissues where the predominant localization of these organelles occurs. The concept which derives from these data--that of a significant regulatory role of peroxisomes in relation to the overall balance of lipid metabolism in the animal body--is described and discussed.

Adipose Tissue↗

On the role of peroxisomes in the metabolism of lipids--evidence from studies on mammalian tissues in vivo.

Recent investigations into the role of peroxisomes in mammalian lipid metabolism have employed double isotope methodologies to examine the influence of peroxisomal agents on lipid turnover in the liver and extra hepatic tissues of the living animal. The action of these agents, all of which caused extensive changes in the flux of lipid metabolism in the treated animals, may best be viewed in relation to their effects on the common pathway of fatty acid oxidation in peroxisomes. Clofibrate, for example, acts through induction of peroxisomal oxidases and catalase; glycolate and ethanol through activation of this pathway; and aminotriazole and allylisopropylacetamide through inhibition of the catalase step in the sequence. The data from these studies provide support for the concept of an important contributory and regulatory role of peroxisomes in relation to the overall balance of lipid metabolism, and emphasize that these organelles play a significant role in the oxidation of common fatty acids, as well as a potential for the elimination of fatty acids that are poorly oxidized by mitochondria. Additionally, the data raise intriguing questions on the extension of peroxisomal influence to include phospholipid metabolism and the substantial degree of inter-tissue communication which is involved in the balance of lipid metabolism in the whole animal.

Adipose Tissue↗

Sequential alterations in the micro-localization of catalase in mouse liver after treatment with hypolipidemic drugs.

A comparative study has been carried out on the micro-localization of catalase in mouse tissues subsequent to treatment with a representative range of hypolipidemic drugs. A commonality of effect was shown by clofibrate (ethyl-alpha-p-chlorophenoxyisobutyrate), Wy-14,643 (4-chloro-6-[2,3 xylidino)-2-pyrimidinylthio] acetic acid), RMI-15,414 (5-tetradecyloxy-2-furancarboxylic acid) and aspirin (acetyl salicylic acid), in that treatments with each of these drugs was associated with the release of peroxisomal catalase into the cytoplasmic compartment of liver and kidney. It was also noticeable that this increased cytosolic activity was characterized by the presence of an 'aged' form of the enzyme with different mobility and activity characteristics to that of the peroxisomal enzyme. Possible molecular bases for these effects and their relationship to peroxisomal biogenesis are discussed.

Animals↗

Interactions between glycolytic enzymes and components of the cytomatrix.

Evidence is provided that enzymes absorb to cellular structures in a wide range of tissues. In particular, the interactions between glycolytic enzymes and the microfilaments of the cytoplasm are described. The relevance of these interactions to the compartmentation of carbohydrate metabolism is discussed. Examples are given of the variations in degree of binding during alteration of tissue metabolism and, for individual glycolytic enzymes, during fetal development and differentiation. Overall, these data support the concept that metabolic activities in the cytoplasm have an organized structure. Just as the structural elements of the cytosolic compartment have evolved with the capacity to assemble and disassemble in response to the changing requirements of the organism, so the metabolic elements appear to have evolved a parallel system that provides for the appropriate positioning of an energy-producing sequence in relation to the specific, dynamic requirements of the cytoskeleton.

Actins↗

Relationships between the flux of lipid metabolism in vivo and the uncoupling of respiratory control.

The influence of dinitrophenol treatment on the balance of lipid metabolism in mouse tissues has been studied by measuring the incorporation in vivo of 3H- and 14C-labelled glycerol. Several significant alterations in the relative utilization of these labels were observed in treated animals, with the greatest influence being evident in liver lipids, and diverse responses occurring in kidney, heart, muscle and adipose tissue. These data establish that dinitrophenol perturbs lipid metabolism in all the major tissues of the animal, and point to the detailed nature of this response in the individual classes of neutral and phospholipids. The implications of individual changes have been discussed in relation to the relative roles of mitochondria and peroxisomes in the regulation of mammalian lipid metabolism.

Adipose Tissue↗

On the flux of lipid metabolism in diabetic animals.

The influence of diabetes on the balance of lipid metabolism has been studied by measuring the simultaneous incorporation in vivo of 3H- and 14C-labelled glycerol into all the major tissues and lipid classes of diabetic mice. The induction of the diabetic condition caused significant alterations in the relative utilization of these labels, with double isotope ratios (3H/14C) being increased in the total lipid fractions of all tissues, but most extensively in muscle and adipose tissue. A degree of individuality was evident in relation to the response of tissue phospholipids, particularly in regard to the incorporation of tritium label into phosphatidyl choline fractions. These data establish that diabetes causes widespread and major perturbations of lipid metabolism in these animals, and indicate the detailed nature of the responses in relation to individual tissues and lipid classes. The implications of these alterations have been discussed with respect to tissue-specific and whole body aspects of the regulation of lipid metabolism.

Adipose Tissue↗

On the synthesis and incorporation of catalase and urate oxidase into the peroxisomes of mouse liver.

The processes associated with the biogenesis of peroxisomes in mouse liver have been studied by following the incorporation of radiolabelled leucine into major enzymic components of this organelle. Maximal incorporation of label into peroxisomal catalase and urate oxidase occurred within 2 hr, with the urate oxidase being labelled before catalase, but subsequent to the incorporation of phospholipid into this organelle. Subsequently, immunoprecipitation of catalase from the large granular fraction of mouse liver was shown to result in the isolation of a catalase molecule which had lost a peptide of approx. 2000 dalton from each subunit by comparison with the newly-synthesized enzyme. It was observed that the modification of catalase was obviated by the presence of leupeptin and iodoacetamide and this information has enabled the purification of both modified and unmodified forms of the enzyme. The possible significance of these data has been discussed and the major features incorporated into a working model of peroxisomal biogenesis.

Animals↗

Brain monoamine abnormalities in the two types of Creutzfeldt-Jakob disease.

Analysis of monoamine concentrations in brain tissue was carried out on the two types of Creutzfeldt-Jakob disease (CJD). The results showed decreased levels of catecholamines compared to control cases in a number of areas, and the reductions were most pronounced for dopamine. In general, the case classified as the amyotrophic form of CJD showed a greater degree of a monoamine loss than the case with spongiform encephalopathy, which is the typical transmissible form of CJD. These findings support the scarce available data indicating disturbances in the catecholaminergic systems in these types of brain diseases, and may have therapeutic implications.

Aged↗

Changes in expression of glial antigens M1 and C1 after cerebellar injury.

In response to mechanical injury in the adult mouse cerebellum, Bergmann glia and astrocytes of the granular layer exhibit abnormally increased expression of M1 antigen, while expression of C1 antigen in Bergmann glia is reduced. these reciprocal changes in two different astrocytic antigenic determinants (each recognized by monoclonal antibodies) are easily detected in the immediate area of the wound 4 days after the lesion. Although loss of C1 antigen from Bergmann glia remains localized to the area of the wound, abnormal M1 expression becomes widespread in cerebellar astrocytes, also affecting the contralateral side of the injured cerebellum at its peak 8 to 12 days after injury. These findings suggest that previous observations of abnormal expression of the two antigens in the cerebellum of mutant mice (Sommer, I., and M. Schachner (1981) J. Supramol. Struct. 16: 53-74) might be interpreted with the view that a glial reaction to pathological state might be induced by genetically programmed neuronal cell death and/or abnormal development. We therefore postulate that expression of M1 in astrocytes that normally do not express this antigen and repression of C1 in normally positive astrocytes are indicative of a distinct functional state of astroglia, reactive gliosis.

Animals↗