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Biomedical subjects

M L Kaplan

Publications and source records attributed to M L Kaplan.

At least 55 records · Page 3Linked to original sources

Oxygen consumption and oxidative capacity of muscles from young obese and nonobese Zucker rats.

The contribution of muscle tissue to the increased metabolic efficiency of the obese (fa/fa) Zucker rat at 6 wk of age was examined. In vitro O2 consumption was similar in obese and nonobese soleus and extensor digitorum longus (EDL) muscles, whether the animals were fed ad libitum, fasted, or treated with triiodothyronine. No phenotypic difference in the in vitro O2 consumption was seen when the muscles were preincubated with or without exogenous insulin. Pyruvate kinase, citrate synthase, succinate dehydrogenase, and cytochrome oxidase activities were similar in the soleus and the EDL muscles of both phenotypes. Phosphofructokinase and lactate dehydrogenase activities were higher in the soleus muscles from the obese rats, whereas hexokinase activities were higher in the EDL muscles from the nonobese rats. Mitochondrial and whole muscle homogenate respiration rates were similar in both phenotypes. The soleus and EDL muscles from the obese animals weighed less than those from the nonobese, but empty carcass weights were similar. Taken together these data suggest that muscle mass, muscle O2 consumption, and muscle oxidative capacity are similar in 6-wk-old obese and nonobese rats. Therefore other tissues are probably responsible for the increased metabolic efficiency of the young obese rat.

Animals↗

Alterations in skeletal muscle proteins in obese and nonobese rats.

Skeletal muscle proteins (myofibrillar, sarcoplasmic, and stromal) were assayed in the gastrocnemius muscles from Zucker obese rats (fa/fa) at 3, 8, and 52 weeks of age. Total muscle weights were similar in obese and nonobese rats at 3 weeks, but reduced in the obese rats by 8 weeks of age. When the muscle proteins were expressed per 100 mg of muscle, the obese rats had lower concentrations of all three muscle proteins, with a greater loss of sarcoplasmic proteins than the nonobese rats at 8 and 52 weeks of age. By 8 weeks of age total muscle proteins were also reduced in obese compared with nonobese rats. With increasing age, the amount of total proteins continued to rise in both obese and nonobese rats with concomitant increases in myofibrillar, sarcoplasmic, and stromal proteins. The increase in muscle proteins was greater between 3 and 8 weeks than between 8 and 52 weeks of age. It is suggested that the inactivity of the obese rat may contribute to the reduction in muscle proteins observed during their early development.

Age Factors↗

The relationship of the eye uptake of N-isopropyl-p-[123I]iodoamphetamine to melanin production.

Eye uptake has been a potential concern with N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) because it has been observed in certain animal species. We have investigated the cause of the eye uptake and its relationship to melanin synthesis. In a 1-yr-old cynomolgus monkey, high concentration of the tracer was seen in the eyes regardless of the type of anesthesia (pentobarbital or ketamine) or the oral administration of Lugol's solution. The eye uptake at 24 hr after injection of I-123 IMP was equally high in an 8-yr-old rhesus monkey. The ratio of radioactivity in the eye of black compared with white albino mice was 10:1 at 30 min, 18:1 at 2 hr and 36:1 at 24 hr after injection of I- 123 IMP. No eye uptake above soft-tissue background was seen in five patients at 2, 24, and 48 hr after injection. I-123 IMP is avidly incorporated into melanocytes actively producing melanin, but substantially less in melanocytes where production of melanin has ceased as in the human eye.

Amphetamines↗

Effects of high fat and high carbohydrate diets on development of hepatic and adipose lipogenesis in fa/fa and non-fa/fa rats.

Non-fa/fa and fa/fa rats were weaned at 18 days of age and fed either a high fat or high carbohydrate diet. At 6 weeks of age some of the rats fed high fat were fed the high carbohydrate diet until 10 weeks of age. Food consumption was equalized between all treatment groups. Epididymal fat pads were heavier in the fa/fa rats in all treatment groups. Fat pad weight and cellularity increased in the non-fa/fa rats fed the high fat diet. Cellularity was actually less in the fa/fa than in the non-fa/fa rats, but high fat feeding resulted in higher proportions of larger adipocytes in both phenotypes. Rates of epididymal fat pad lipogenesis and enzymatic activities were similar in both non-fa/fa and fa/fa rats in all treatment groups. Hepatic fatty acid synthesis and enzymatic activities were consistently greater in the fa/fa rats. Carbohydrate feeding resulted in increased hepatic fatty acid synthesis regardless of the earlier feeding of the fat diet, but the fa/fa rats were more responsive to the carbohydrate diet than the non-fa/fa rats. A delay in introduction of carbohydrate to the diet did not alter the eventual lipogenic capacity of fa/fa rats. Lipogenesis appeared responsive to the most recent diet.

Adipose Tissue↗

Biodistribution and dosimetry of N-isopropyl-p-[123I]iodoamphetamine in the primate.

The biodistribution of N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) in the Macaca fascicularis monkey was determined at 15 min and at 1, 4, 24, and 48 hr after intravenous injection. Brain uptake was 7.8% of the injected dose at 1 hr, with little change in concentration between 15 min and 1 hr, falling thereafter. Eye uptake reached a maximum of 0.23% of injected dose at 24 hr, with activity primarily in the pigmented layers. The human absorbed radiation dose was calculated on the basis of biodistribution data. The critical organ is the eye (0.407 rad/mCi of I-123 IMP). The eye dose increased to 1.11 rad/mCi with 4% contamination from I-124 IMP and to 0.535 rad/mCi with 0.4% contamination from I-125 IMP. The absorbed dose to the liver was 0.127 rad/mCi for pure I-123 IMP and the thyroid dose was 0.120 rad/mCi, both increasing with either I-124 or I-125 contamination. While delayed eye uptake has not yet been reported in the human, care should be exercised in limiting the amount of contaminating I-124 or I-125 to the lowest practical level.

Absorption↗

Chemical and in vivo studies of the anion oxo[N,N'-ethylenebis(2-mercaptoacetimido)]Technetate(V).

Studies of the anionic coordination complex 99Tc-oxo[N,N'-ethylene-bis(2-mercaptoacetimido)]technetate(V) ([TcO(ema)]-) are described. Syntheses performed both at carrier levels (10(-5)M) and with no carrier added (less than 10(-8)M) indicate that the complex is formed virtually quantitatively from pertechnetate ion over this range. Tissue distributions in normal rats are similar at both concentrations up to one hour after administration. It has been shown--using a combination of high-pressure liquid chromatography and field-desorption mass spectrometry--that the anion is excreted unchanged into both urine and bile. The effectiveness of this N2S2 donor set in sequestering Tc-99m, and the in vivo stability of the resulting complex, suggest that modified chelates of this structural class could provide a series of useful diagnostic agents.

Animals↗

Development of lipogenesis and insulin sensitivity in tissues of the ob/ob mouse.

Lipogenesis and insulin sensitivity are evaluated in adipose tissue, liver, and diaphragm of ob/ob and non-ob/ob mice. In ob/ob mice, hepatic fatty acid synthesis from [U-14C]glucose is elevated by 4 wk of age, and adipose tissue fatty acid synthesis increases at approximately 7 wk. Hepatic activities in ob/ob mice of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), malate dehydrogenase (EC 1.1.1.40), and alpha-glycerophosphate dehydrogenase (EC 1.1.1.8) are dramatically increased by 7 wk of age. Diminished insulin-stimulated glycogen synthesis is first noted in the diaphragm of ob/ob mice at 7 wk of age. Insulin-stimulated glycogen synthesis in adipose tissue of ob/ob mice is impaired at 3 wk. At 7 wk, insulin-stimulated fatty acid synthesis in adipose tissue of ob/ob mice is markedly increased. Adipose tissue glyceride-glycerol synthesis continues to increase throughout development, whereas fatty acid synthesis decreases after 7 wk. The data suggest that alterations in lipid synthesis occur very early in the development of ob/ob mouse, prior to expression to overt obesity, at which time a major contribution to lipogenesis is made by the liver. The altered de novo lipogenesis does not precede the reported diminution in energy metabolism.

Adipose Tissue↗

Oxygen consumption by Zucker obese rats, obese yellow mice, and obese hyperglycemic mice with body protein used for metabolic mass.

Oxygen consumption was determined in three varieties of genetically-obese rodents and their lean littermates; the Zucker obese rat (fa/fa), the obese hyperglycemic mouse (ob/ob), and the yellow obese mouse (Ay/a). Values were expressed with both live body weight and total body protein as the unit of metabolic body size. When oxygen consumptions were expressed on the basis of live body weight, all three obese varieties exhibited lower values than their age-matched non-obese littermates. When values of oxygen consumption were expressed with total body protein as the unit of metabolic size, only the ob/ob mice had lower oxygen consumptions than their non-ob/ob littermates. The fa/fa rats and the Ay/a mice had similar values of oxygen consumption as their non-obese controls. Much better correlations between whole-animal resting oxygen consumption, reported values of maintenance energy requirements, and tissue oxygen consumption are obtained when body protein content rather than live body weight is used as the unit of metabolic mass.

Animals↗

Adipocyte size distribution in fa/fa rats during development.

Epididymal fat pad adipocyte frequency distributions of obese (fa/fa) and nonobese (non-fa/fa) Zucker rats were determined from 2 to 20 wk of age. The fa/fa rats consistently displayed a higher proportion of larger adipocytes than the non-fa/fa rats of all ages studied. Increased adipocyte size preceded an increase in the number of adipocytes during the early phases of obese development. Among the fa/fa rats, the frequency of small cells continued to increase, which resulted in a bimodal distribution by 20 wk of age. Discriminant analysis suggests that the differences in adipocyte size frequency distributions at 2 wk of age may be another useful means to identify fa/fa and non-fa/fa pups prior to expression of overt obesity. Increased fat storage may reflect the lower energy expended by the very young fa/fa rats.

Adipose Tissue↗

Consumption of O2 and early detection of fa/fa genotype in rats.

Oxygen consumption was determined in 10--12-wk-old fa/fa and non-fa/fa rats at ambient temperatures of 10 degrees--40 degrees C. The fa/fa rats exhibited a lower oxygen consumption than non-fa/fa rats from 10 degrees--30 degrees C, but not at 35 degrees C and 40 degrees C. A lower oxygen consumption was also observed among fa/fa rats as early as 18 days of age, prior to the phenotypic expression of apparent obesity. Fourteen hundred microliter O2 consumed/hr/g body weight at STP was used as a value, below which future obese rats could be identified among 18-day-old pups from fa/+ X fa/+ crosses. Only a 10% error was found in the use of this value for the early identification of the fa/fa genotype.

Animals↗