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At least 19 recordsLinked to original sources

Calculating dose from remaining body activity: a comparison of two methods.

Two methods for calculating the radiation dose from remaining body activity have been suggested. One requires correction of the cumulated activities so that they reflect the activity uniformly distributed in the total body. The other method requires correction of the S values so that a value of S for the target organ from the remainder of the body is obtained. These two methods give the same answer. We have examined these methods and the number of steps required to calculate the radiation dose in each case. Our results show that the method of correcting the cumulated activities is preferred, especially if the number of source and target organs is large and a computer equipped with the necessary software is not available.

Humans

Quantitative evaluation of the loss of human platelet dense bodies following stimulation by thrombin or A23187.

1. Distributions of dense bodies per platelet were evaluated in unstimulated human platelets and in platelets stimulated to secrete by the addition of varying amounts of thrombin or the ionophore A23187. Since distributions were not Gaussian, they were compared by non-parametric methods. 2. Most distribution obtained following varying levels of dense-body release differed significantly from the control (unstimulated) distribution. In general, distribution from points widely separated in terms of per cent release of total dense-body content also differed significantly. Distributions obtained at points where the total number of dense bodies lost was approximately the same did not differ significantly, regardless of the drug and incubation conditions used to produce the dense-body loss. 3. Dense bodies were lose from platelets during the secretory process (measured as the release of either calcium or ATP), and the number of dense bodies lost correlated at a significant level with the amounts of both substances secreted. 4. Following maximal secretion produced by either thrombin or A23187, a population of dense bodies (refractory dense bodies) remained in platelets. The refractory dense bodies could not have been distributed uniformly among the control populations of either platelets or dense bodies. The distribution of refractory dense bodies could, however, be described by a model in which platelets containing large numbers of dense bodies had a greater proportion of their dense-body complement refractory than did platelets containing fewer dense bodies.

Adenosine Triphosphate

Role of skin temperature in the control of sweating.

In five male subjects tympanic membrane temperature (Tty), rectal temperature, skin temperatures at 12 sites were simultaneously recorded. Local sweating rate was measured at six sites using resistance hygrometry. After steady-state sweating was established, the lower body was heated at ambient temperatures of 50, 60, 70, and 80 degrees C or cooled at an ambient temperature of 29 degrees C while the upper body remained at a constant ambient temperature. During lower body heating or cooling, Tty was maintained constant by the drinking of cold (10 degrees C) or warm (45 degrees C) water. Sweating rate on both upper and lower body surfaces was proportional to lower body skin temperature. The regression coefficients for sweating rate versus mean lower body skin temperature varied from 0.03 to 0.09 mg/cm2.min. degrees C between subjects, but were not significantly different from each other (P greater than 0.05). This study demonstrates an influence of cutaneous thermoreceptors on sweating rate under steady-state conditions.

Humans

Assay of the heat-labile enterotoxin of Escherichia coli in infant rabbits.

Infant rabbits were shown to respond to Escherichia coli heat-labile enterotoxin by a consistent increase in intestinal fluid content, which was maximal 5 h after oral dosing. Infant rabbits could be used in a simple quantitative assay for heat-labile E. coli enterotoxin based on the ratios of gut weight to remaining body weight 5 h after oral dosing. Infant rabbits remained responsive to heat-labile enterotoxin up to 14 days of age, after which their gastric pH became low enough to destroy the enterotoxin. Rabbits that had been deprived of food before being dosed had a reduced gastric pH and a reduced response to the enterotoxin. Lincomycin andmitomycin C were found not to increase th e yield of heat-labile enterotoxin from E. coli strain P307.

Animals

Evidence for a functional role of RNA in centrioles.

Basal bodies, purified from Chlamydomonas and Tetrahymena, were exposed to various enzymatic treatments and then assayed for their ability to nucleate aster formation upon injection into eggs of Xenopus laevis. Untreated basal bodies injected into frog eggs act as centrioles and induce the formation of asters. The aster-inducing activity of basal bodies was eliminated by treatment with proteolytic enzymes and ribonucleases. Aster-inducing activity was not affected by DNAse and a number of other enzymes. The effect of proteolytic digestion on aster-inducing activity appeared to be directly correlated with the degree of structural damage to the basal body. Low concentrations of pancreatic ribonuclease A, ribonuclease T1, and S1 nuclease also completely abolished aster-inducing activity, although these enzymes had no effect on basal body structure. Ribonuclease-treated basal bodies remained capable of supporting microtubule elongation in vitro. Preliminary evidence indicates that basal bodies from Chlamydomonas and Tetrahymena contain about 5 x 10(-16) g of RNA which co-band with basal bodies and aster-inducing activity by equilibrium density gradient sedimentation. We conclude first, that centrioles contain RNA which is required for initiation of aster formation, and second, that the centriole activity or ability to assemble a mitotic aster is separable from the basal body activity, or ability to serve directly as a template for microtubule growth.

Animals

The influence of reserpine and ethylenediaminetetraacetic acid (EDTA) on serotonin storage organelles of blood platelets.

The present investigation has evaluated the influence of reserpine on the serotonin-rich organelles bodies) in platelets from dogs, rabbits, and humans. Reserpine markedly depresses the levels of stored serotonin in human and animal platelets, accompanied by a small decrease in platelet ATP but no change in platelet ADP content. Thin sections of human platelets showed no change in the number or morphology of serotonin storage organelles during reserpine therapy, whereas a profound decrease in the size and number of dense bodies occurred in platelets from rabbits treated with reserpine. Dog platelets also showed a decrease in the number and density of serotonin storage organelles after reserpine therapy. The basis for the difference between rabbit and human platelets was explored by fixing platelets in glutaraldehyde and osmium in the presence or absence of the chelating agent ethylenediaminetetraacetic acid (EDTA). Most of the dense bodies in fixed human platelets were removed by EDTA while rabbit platelet dense bodies remained essentially intact. The results suggested that the opacity of rabbit platelet dense bodies following fixation with glutaraldehyde and osmium relate primarily to their serotonin content, while the electron density of human serotonin storage organelles in fixed cells is due primarily to their calcium content. Further confirmation of this concept came from studies of platelets using the whole mount technique. Rabbit platelet serotonin storage organelles were found to lack the inherent opacity of the human dense bodies, a finding consistent with the lower concentration of calcium in the rabbit organelles.

Animals

Intramitochondrial bodies in bovine adrenocortical cells.

Electron dense, homogeneous, mostly round intramitochondrial bodies were found in bovine adrenal glands, predominantly in the zona glomerulosa. The histochemical results obtained suggest that these bodies might contain a considerable amount of protein, although the possibility that substances other than proteins are contained in these bodies cannot be completely ruled out. The physiological significance of the intramitochondrial bodies remains unclear.

Adrenal Cortex

The role of the kidney in the removal of ketone bodies under different acid-base status of the rat.

Arterial blood concentrations of ketone bodies, pyruvate, lactate, citrate, and oxoglutarate were measured in normal and in nephrectomized rats. The rate of removal from the circulation of an infused acetoacetate load has been studied in both groups of animals. Blood oxoglutarate and ketone bodies remained unchanged in nephrectomized rats. Blood citrate level rose rapidly. In rats with normal blood pH the contribution of the kidneys to the removal of ketone bodies is 28%, whereas in metabolic alkalosis, it is less than 2%. In nephrectomized rats with normal blood pH and in rats with metabolic alkalosis the ratio between beta-hydroxybutyrate and acetoacetate is very high in comparison with rats having metabolic acidosis. These data suggest that in metabolic alkalosis the kidneys are not able to utilize ketone bodies.

Acetoacetates

PaCO2 for optimum washout of inhalational anesthetics from the brain. A model study.

A hypothesis was established that, during emergence of inhalational anesthesia, hyperventilation and accompanying hypocapnia beyond a certain limit may actually disturb rather than enhance the washout of inhalational anesthetics from the brain because of a decreased cerebral blood flow. Two mathematical models were constructed and the washout of nitrous oxide, halothane and methoxyflurane were studied. In model I, the whole body consisted of a single compartment, and blood flow to this compartment was assumed to change proprotionally with the PaCO2. In model 2, the body was divided into two compartments, brain and the rest of the body. It was assumed that the blood flow to the brain compartment varies proportionally with the PaCO2, while that to the rest of the body remains constant. The analysis indicated that there indeed existed the PaCO2 values at which the washout of anesthetics from the brain can be maximally achieved. In model 1, they were 49.0, 22.1 and 9.7 mmHg for nitrous oxide, halothane, and methoxyflurane, respectively. In model 2, these PaCO2 values varied with time. While the hypothesis was proven to be valid, we conclude that it is of limited clinical significance. For halothane and methoxyflurane, these theoretically optimum PaCO2 values are sufficiently low. For nitrous oxide, the variation of PaCO2 makes little difference clinically, because its washout is fast enough regardless of PaCO2.

Anesthesia, Inhalation

Evidence of state dependent learning of brightness discrimination in hypothermic mice.

Shock-elicited escape behavior of C57Bl mice in a brightness discrimination task was examined to investigate the effects of hypothermia on acquisition and reversal. Neither acquisition nor reversal was impaired by 7 degrees C or 13 degrees C decreases in central body temperature when body temperature remained at those levels throughout testing. However, body temperature changes from acquisition to reversal were accompanied by memory deficits during reversal if acquisition occurred at body temperature decreased by 13 degrees and reversal occurred at normal body temperature or body temperature decreased by 7 degrees and reversal at body temperature decreased by 13 degrees. This finding suggests the occurrence of a state dependent discrimination response: an instance of asymmetrical dissociation. In addition, during acquisition, latency of the escape response was longer in hypothermic animals than in controls, and should be interpreted as a performance deficit, rather than failure or delayed rate of learning. Depressed intertrial activity also was observed in hypothermic animals.

Animals

Protein malnutrition following intestinal bypass for morbid obesity.

Intestinal bypass surgery, performed for weight reduction in the morbidly obese patient, is frequently complicated by the development and hepatic complications. In 44 morbidly obese individuals, 55 inches of proximal jejunum were anastomosed, end to side, to 5 inches of distal ileum. All the patients were followed with body composition measurements, performed by multiple isotope dilution, prior to and at regular time intervals following bypass surgery. In 33 patients a decrease in body fat accounted for the entire postbypass weight loss, while the lean body mass remained normal in both size and composition. In these patients, at 1 year, body weights had decreased by 24.4 +/- 2.1%, while the body cell masses had decreased by 2.1 +/- 7.1%. In the remaining 11 patients, the postbypass weight loss resulted from a loss of both body fat and body cell mass. Their body weights at 1 year had decreased by 27.0 +/- 3.0%, while the body fat and body cell mass. Their body weights at 1 year had decreased by 27.0 +/- 3.0%, while the body cell masses decreased by 22.0 +/- 6.1%. Furthermore, their body compositions were characteristic of protein malnutrition with a contracted body cell mass and an expanded extracellular mass. Six of these 11 patients have required admission to hospital on 10 occasions because of malaise, anorexia, debilitating weakness, hypokalemia, and abnormal liver function. They were treated for 14.5 +/- 1.9 days with an intravenous infusion of amino acids without additional nonprotein calories. The body composition, initially characteristic of malnutrition, became normal. Their symptoms disappeared and hepatic function returned to normal. Subsequently a high-protein diet was required to prevent a recurrence of symptoms and to maintain a normal body composition. The data indicate that protein malnutrition developed in 11 of 44 patients undergoing jejunoileal bypass for weight reduction.

Adult

Metabolic studies in rats under glucose and glycerol loading.

It has been found in rats that 40% glycerol, when added to standard diet, reduces the food intake and thus prevents weight gain. The subcutaneous application (40 mg/kg three times daily) has no effect. Under pair feeding conditions the oxygen consumption, the RQ value and body weight remain unaffected as compared with controls receiving glucose. It is concluded that reduction of body weight induced by glycerol feeding is due to reduced amount of food intake and not due to any alterations of energy metabolism.

Animals

[Effect of clofibrate on glucose tolerance and insulin secretion in patients with endogenous hypertriglyceridemia (author's transl)].

In 22 patients with endogenous hypertriglyceridemia, oral and intravenous glucose tolerance showed significant improvement under clofibrate treatment which was in no way correlated to the fall in triglycerides. Basal and stimulated insulin, cholesterol and fasting blood sugar did not change, body weight remained constant and was not correlated to the degree of hypertriglyceridemia. On the other hand a positive correlation between body weight and insulin concentrations was found. Improvement of glucose tolerance independently of body weight and insulin may be due to a direct effect of clofibrate on glucose metabolism without any correlation to its triglyceride-lowering.

Administration, Oral

Activities of enzymes of fat and ketone-body metabolism and effects of starvation on blood concentrations of glucose and fat fuels in teleost and elasmobranch fish.

1. Activities of 3-oxo acid CoA-transferase and carnitine palmitoyltransferase together with tri- and di-acylglycerol lipase were present in red and heart muscles of the teleost fish. However, d-3-hydroxybutyrate dehydrogenase activity was not detectable. These results suggest that the heart and red muscles of the teleosts should be able to utilize the fat fuels triacylglycerol, fatty acids or acetoacetate, but not hydroxybutyrate. The muscles from the elasmobranchs differed in that d-3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities were present, but carnitine palmitoyltransferase activity was not detectable. This suggests that ketone bodies are the most important fat fuels in elasmobranchs. 2. The concentrations of acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids and triacylglycerols were measured in blood or plasma of several species of fish (teleosts and elasmobranchs) in the fed state. Teleosts have a 10-fold higher concentration of plasma non-esterified fatty acids, but a lower blood concentration of ketone bodies; both acetoacetate and 3-hydroxybutyrate are present in blood of elasmobranchs, whereas 3-hydroxybutyrate is absent from that of the teleosts. 3. The effects of starvation (up to 150 days) on the concentrations of blood metabolites were studied in a teleost (bass) and an elasmobranch (dogfish). In the bass there was a 60% decrease in blood glucose after 100 and 150 days starvation. In dogfish there was a large increase in the concentration of ketone bodies, whereas in bass the concentration of acetoacetate (the only ketone body present) remained low (<0.04mm) throughout the period of starvation. The concentration of plasma non-esterified fatty acids increased in bass, but decreased in dogfish. These changes are consistent with the predictions based on the enzyme-activity data. 4. Starvation did not change the activities of ketone-body-utilizing enzymes or that of phosphoenolpyruvate carboxykinase in heart and red skeletal muscles of both fish, but it decreased markedly the activity of phosphoenolpyruvate carboxykinase in white skeletal muscle of both fish. However, in the liver of the dogfish, starvation resulted in a twofold increase in the activities of 3-hydroxybutyrate dehydrogenase and acetoacetyl-CoA thiolase, whereas in bass liver it decreased the activity of acetoacetyl-CoA thiolase and increased that of 3-oxo acid CoA-transferase. The activity of phosphoenolpyruvate carboxykinase was increased twofold in the liver of bass, but was unchanged in that of the dogfish. 5. The difference in changes in concentrations of blood metabolites and enzyme activities in the two fish support the suggestion that, in starvation, ketone bodies, but not non-esterified fatty acids, are an important fuel for muscle in elasmobranchs, whereas non-esterified fatty acids, but not ketone bodies, are an important fuel in teleosts. The results are discussed in relation to the evolution of a discrete lipid-storing adipose tissue in teleosts and higher vertebrates.

Animals

Anatomical location defines distinct molecular subtypes of mucosal melanoma.

BACKGROUND: Mucosal melanoma (MM) is a rare and aggressive melanoma subtype that is understudied. The relationships between anatomical location, genomic alterations, stage at presentation, and survival remain incompletely characterized. METHODS: We carried out a retrospective single tertiary center study of 105 patients with histologically confirmed MM diagnosed between 1996 and 2025. Clinical and genomic data were analyzed to evaluate associations between anatomical location, mutational profile, stage at presentation, and survival outcomes, including melanoma-specific mortality. RESULTS: Lower-body tumors arising in the anus or genital areas were enriched for KIT and splicing factor 3 subunit B1 alterations, whereas NRAS mutations were distributed across anatomical regions. Among the two most common mutated genes, NRAS-mutant tumors were more likely than KIT-mutant tumors to present with metastatic disease [53% versus 19%; P = 0.046, odds ratio (OR) 4.7, 95% confidence interval (CI) 1.15-19.41]. Lower-body tumors were associated with worse overall survival (OS) than upper-body tumors (median 2.81 versus 8.40 years; OR = 0.05) and with higher melanoma-specific mortality. In multivariable analyses, upper-body location remained independently associated with improved OS (hazard ratio 0.14, 95% CI 0.05-0.36, P < 0.001). CONCLUSIONS: Anatomical location of MMs and genomic alterations define biologically and clinically distinct subtypes.

KIT mutation

Potentiation of hyperphagia and relief of hypothermia in the genetically obese mouse (genotype, ob/ob) by alpha-methyl tyrosine.

DL-alpha-methyl-p-tyrosine methyl ester hydrochloride affected the hyperphagia and hypothermia characteristic of the genetically obese mouse (genotype, ob/ob) throughout an experimental period of 5 days. Intraperitoneal injections of 100 mg/kg body weight, daily, resulted in a significant increase in the average daily food consumption by 60 per cent, already elevated 35 per cent above that of lean litter-mates. The drug, administered at the same dose, caused a similar percentage elevation of food intake in the lean litter-mates. Rectal temperatures of obese mice were raised significantly throughout the 5-day period by an average of 0.95 degrees C, following administration of the drug. There was a significant rise of 0.75 degrees C in the rectal temperature of lean mice on 2 of the 5 days in the period. Body weight remained unchanged. Further experiments are necessary to determine the site of action at which DL-alpha-methyl-p-tyrosine brings about these effects at this dose in lean and obese mice.

Animals