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Maximal activities of glutaminase and some enzymes of glycolysis and ketone body utilization and rates of utilization of glutamine, glucose and ketone bodies by intestinal mucosa after burn injury.

1. The effects of burn injury (33 per cent of body surface area) on the activities of key enzymes in the metabolism of glucose, glutamine and ketone bodies in the epithelial cells of the small intestine and the rates of utilization of glucose, glutamine and ketone bodies by isolated enterocytes have been investigated. 2. Burn injury decreased the maximal activities of hexokinase and 6-phosphofructokinase and increased those of glucose 6-phosphatase plus fructose bisphosphatase (in duodenum, jejunum and ileum) over the first 5 days post-injury. 3. After injury there are decreases in the rates of glucose utilization and lactate formation by incubated enterocytes. 4. The maximal activities of citrate synthase and oxoglutarate dehydrogenase were increased during the first 5 days post-injury, whereas the ketone-body-utilizing enzymes were unchanged. 5. An increase in the maximal activity of phosphate-dependent glutaminase was observed during the whole of the post-injury period studied (20 days). 6. After burn injury there is an increased rate of glutamine utilization and increased rates of formation of glutamate and alanine by incubated enterocytes.

Animals↗

Adjunctive therapy (whole body hyperthermia versus lonidamine) to total body irradiation for the treatment of favorable B-cell neoplasms: a report of two pilot clinical trials and laboratory investigations.

Based on earlier clinical and preclinical investigations, we designed two different pilot trials for patients with nodular lymphoma or chronic lymphocytic leukemia. These studies evaluated the use of either 41.8 degrees C whole body hyperthermia (WBH), or the nonmyelosuppressive chemotherapeutic drug, lonidamine (LON), as an adjunct to total body irradiation (TBI) (12.5 cGy twice a week, every other week for a planned total dose of 150 cGy). Whole body hyperthermia was initiated approximately 10 min after total body irradiation; lonidamine was administered orally (420 mg/m2) on a daily basis. Although entry to the studies was nonrandomized, the two patient populations were accrued during the same time frame and were comparable in terms of histology, stage of disease, performance status, and prior therapy. Of 8 patients entered on the TBI/WBH study, we observed 3 complete responses (CR), 4 partial responses (PR), and 1 improvement (i.e., a 48% decrease in tumor burden). Of 10 patients entered in the TBI/LON study, there was 1 CR and 4 PR. For the TBI/WBH study, myelosuppression was not treatment-limiting; there were no instances of infection or bleeding and platelet support was never required. The median survival time for the TBI/WBH study is 52.5 months based on Kaplan Meir estimates. Two patients remain in a CR. The median time to treatment failure (MTTF) is 9.4 months (90% confidence interval = 7-15.4 months). In the TBI/LON study, 50% of patients receiving TBI required treatment modification due to platelet-count depression during therapy, but there were no instances of infection or bleeding. Frequently observed LON-related toxicities included myalgias, testicular pain, photophobia and ototoxicity. For the TBI/LON study, median survival is 7.6 months; MTTF was 2.4 months. In analyzing the results of these pilot studies, our subjective clinical impressions lead to the hypothesis that WBH protected against TBI-induced thrombocytopenia during therapy, whereas LON had no effect on TBI-induced myelosuppression. This speculation was tested and confirmed in a series of in vitro and in vivo experiments.

Adult↗

Spheres, coiled bodies and nuclear bodies.

Of several distinct aggregations or nuclear bodies in the nucleus, two of the most prominent are the sphere organelle and the coiled body. Recent molecular studies indicate that the coiled body found in interphase nuclei may be identical to the sphere organelle found in the amphibian oocyte nucleus. This is not the first time an interphase nuclear body has been suspected of being the same as a structure in the oocyte nucleus; the first such structure was the nucleolus. Both the sphere organelle and the nucleolus are attached to site-specific loci on oocyte lampbrush chromosomes. Because of their unique morphologies and utility in reproducibly identifying specific genetic elements, they have been referred to as lampbrush chromosomal landmarks. The discovery of the way nucleoli arise has led to an understanding of their function, and for this reason I discuss current models for the genesis of spheres.

Animals↗

Postmenopausal weight status, body composition and body fat distribution in relation to parameters of menstrual and reproductive history.

OBJECTIVES: In the present study the association between menstrual and reproductive history patterns and weight status, fat distribution and body composition during postmenopause was tested. METHODS: In 106 healthy postmenopausal women ranging in age from 48 to 58 years (x = 53.7 year) the weight status was classified according to the recommendations of the WHO. Additionally body composition was estimated by dual energy X-ray absorptiometry and fat distribution was calculated using the fat distribution index. Weight status, body composition and fat distribution were correlated with self-reported parameters of menstrual and reproductive history (age at menarche, average cycle length, number of births, age at first and last birth, average pregnancy weight gain, age at menopause). RESULTS: It was shown that number of births, age at first birth and pregnancy weight gain were related significantly to the postmenopausal weight status, body composition and fat distribution. CONCLUSION: An early first birth a low number of births and a high weight gain during pregnancies can be assumed as risk factors for overweight, a higher amount of adipose tissue, android fat patterning and therefore for the development of the metabolic syndrome during postmenopause. In contrast no adverse effect of menstrual and reproductive parameters on postmenopausal bone mass was found.

Adipose Tissue↗

Initial body mass indexes have contrary effects on change in body weight and mortality of patients on maintenance hemodialysis treatment.

Malnutrition is a relevant risk factor for mortality for patients on maintenance hemodialysis treatment. In a retrospective study including 377 patients who began hemodialysis treatment between 1986 and 2001, we assessed the prevalence of different statuses of nutrition and the impact of the initial status of nutrition on the change in body weight and patient survival. We found an inverse relationship between body mass index (BMI, kg/m2) and the gain in body weight and BMI within 12 months of hemodialysis treatment. Underweight and normal weight patients had a substantial increase in these parameters, greatest in underweight subjects, whereas overweight and obese patients showed only a moderate increase or none (P =.0019, P =.00036). Adjusted mortality rates showed an inverse correlation with the initial BMI (P <.0001). There was a statistically significant difference in the mortality between patients with normal weight and overweight or obesity, respectively, showing a more favorable prognosis in overweight and obese patients (P =.0007; P =.022; log-rank, normal versus overweight, P =.012). Weight loss was the greatest independent risk factor for mortality in general. Adjusted hazard ratio of death was highest in underweight patients (3.999; CI, 2.708 to 5.905; P <.0001) and decreased to 2.251 (CI, 1.795 to 2.822; P <.0001) in normal weight, 1.927 (CI, 1.390 to 2.670; P <.0001) in overweight, and 1.651 (CI, 0.841 to 3.236; P =.1439) in obese subjects when patients with weight loss were compared with patients who preserved their initial weight or gained weight. Overall, the initial BMI has an influence on the change in body weight as well as on patient survival in general and in the case of weight loss in particular.

Adolescent↗

The body as object versus the body as subject: the case of disability.

This paper is prompted by the charge that the prevailing Western paradigm of medical knowledge is essentially Cartesian. Hence, illness, disease, disability, etc. are said to be conceived of in Cartesian terms. The paper attempts to make use of the critique of Cartesianism in medicine developed by certain commentators, notably Leder (1992), in order to expose Cartesian commitments in conceptions of disability. The paper also attempts to sketch an alternative conception of disability--one partly inspired by the work of Merleau-Ponty. In particular, three key Cartesian claims are identified and subjected to criticism. These are as follows: (a) The claim that the body is an object, (b) what is termed here 'the modularity thesis', and (c) the claim that the body cannot be constitutive of the self (i.e. since the soul/mind/brain is). In opposition to these claims, it is argued that the body is properly viewed as a subject; that there are neither purely mental, nor purely physical disabilities; and that selves are constituted, at least in part, by their bodies.

Persons with Disabilities↗

Low body mass index but high percent body fat in Taiwanese subjects: implications of obesity cutoffs.

OBJECTIVES: To compare the different correlations of body mass index (BMI) and percent body fat (BF%) with other ethnic groups and to evaluate the appropriateness of Asia-Pacific redefining obesity criteria in the Taiwanese population. The corresponding BF% to BMI cutoffs of overweight and obesity will also be studied. DESIGN: A cross-sectional epidemiological survey. SUBJECTS: A total of 509 male and 570 female Taiwanese subjects aged > or =20 y sampled by the systematic stratified clustering sampling method were analyzed. MEASUREMENTS: BMI was obtained by body weight (kg) divided by squared body height (m(2)). The estimated BMI (BMIe) was deduced from the Caucasian-based four-compartment equation (4C). BF% measured by the methods of dual-energy X-ray absorptiometry (DXA) or Caucasian-based 4C were used and abbreviated as DXA-BF and 4C-BF, respectively. RESULTS: The curvilinear relationship between age and BMI or DXA-BF was established. When compared by age-stratified groups, Taiwanese subjects had a higher BF% (4C-BF) in any given BMI than Caucasians. That is, the level of 4C-BF for BMI> or =25 kg/m(2) in Taiwanese subjects was similar to BMI> or =30 kg/m(2) in Caucasians. The BMIe values of 25 and 30 kg/m(2) were nearly equal to the BMIs of 23.6 and 25.3 kg/m(2) in males, and 22.7 and 24.8 kg/m(2) in females, respectively. The 4C-BF of 25% was nearly equal to a BMI of 26.2 kg/m(2) in males, and 35% was equal to a BMI of 24.4 kg/m(2) in females. Consequently, the DXA-BF cutoffs for BMIs of 23 and 25 kg/m(2) were compatible to 23 and 25% in males, and 35 and 38% in females, respectively. CONCLUSION: It was demonstrated that Taiwanese subjects had a relatively lower BMI but a higher BF% than Caucasians. In general, the newly proposed Asia-Pacific BMI cutoffs for overweight (> or =23 kg/m(2)) and obesity (> or =25 kg/m(2)) may be acceptable to both male and female Taiwanese subjects. The corresponding BF% (DXA-BF) cutoffs for obesity would be 25% in male and 38% in female Taiwanese subjects, respectively.

Absorptiometry, Photon↗

Basal metabolic rate, body composition and whole-body protein turnover in Indian men with differing nutritional status.

1. Three groups of adult men were studied in Bangalore, India: two groups were controls who had been receiving an adequate diet. Of these, one group, designated 'normal weight controls', had a mean body mass index of 22; the other group, 'underweight controls', had a mean body mass index of 16.7. The third group consisted of poor labourers, whose daily food intake had been less than 10 MJ and whose mean body mass index was 16.6. Previous studies had shown that such men had a lower basal metabolic rate than well-nourished Indian control subjects. 2. The object of the present study was to find out whether a reduced rate of protein turnover, measured after a single dose of [15N]glycine, contributed to a lower basal metabolic rate. It was found, however, that after adjusting for body weight and fat-free mass by analysis of co-variance there was no significant difference in basal metabolic rate between the three groups. Adjusted rates of protein synthesis were higher in the underweight controls and the undernourished labourers than in the normal weight controls, but not significantly so. 3. Estimates based on creatinine excretion showed that within the fat-free mass the underweight groups had a higher proportion of non-muscle to muscle mass. This may explain the somewhat higher rates of protein turnover in these groups. 4. Nitrogen flux (Q) was determined from 15N abundance in two end products, urea (QU) and ammonia (QA). In the underweight and undernourished groups the ratio QU/QA was increased compared with the normal weight group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men.

A weight-reducing effect of metformin has been demonstrated in obese subjects with and without diabetes. The mechanisms of this action are unclear, which may be partly due to the fact that in obese and diabetic patients the substance's effects result from a complex interaction with the distinct endocrine and metabolic disturbances in these patients. To dissociate primary from secondary action of metformin, we examined effects of the substance in normal-weight healthy subjects. Fifteen normal-weight men were treated with metformin (850 mg twice daily) or placebo for a 15-day period in a double-blind, placebo-controlled, cross-over study. Anthropometric, psychologic, cardiovascular, endocrine, and metabolic parameters were assessed before and at the end of the treatment period. Metformin did not affect body weight (P =.838) and body fat mass (P =.916). Yet, serum leptin concentration was distinctly reduced after metformin (P <.001). Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P <.001). There were no effects of metformin on feelings of hunger, blood pressure, heart rate, resting energy expenditure, the respiratory quotient, free fatty acids, beta-hydroxybutyrate, glycerol, triglycerides, cholesterol, and uric acid (all P >.1). Data indicate that metformin decreases the serum leptin concentration even without affecting body weight and body composition in normal-weight men.

Adipose Tissue↗

Tissue transglutaminase-induced aggregation of alpha-synuclein: Implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies.

Proteinaceous aggregates containing alpha-synuclein represent a feature of neurodegenerative disorders such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Despite extensive research, the mechanisms underlying alpha-synuclein aggregation remain elusive. Previously, tissue transglutaminase (tTGase) was found to contribute to the generation of aggregates by cross-linking pathogenic substrate proteins in Huntington's and Alzheimer's diseases. In this article, the role of tTGase in the formation of alpha-synuclein aggregates was investigated. Purified tTGase catalyzed alpha-synuclein cross-linking, leading to the formation of high molecular weight aggregates in vitro, and overexpression of tTGase resulted in the formation of detergent-insoluble alpha-synuclein aggregates in cellular models. Immunocytochemical studies demonstrated the presence of alpha-synuclein-positive cytoplasmic inclusions in 8% of tTGase-expressing cells. The formation of these aggregates was significantly augmented by the calcium ionophore and prevented by the inhibitor cystamine. Immunohistochemical studies on postmortem brain tissue confirmed the presence of transglutaminase-catalyzed epsilon (gamma-glutamyl)lysine cross-links in the halo of Lewy bodies in Parkinson's disease and dementia with Lewy bodies, colocalizing with alpha-synuclein. These findings, taken together, suggest that tTGase activity leads to alpha-synuclein aggregation to form Lewy bodies and perhaps contributes to neurodegeneration.

Animals↗

Total body glucose metabolism in the conscious, unrestrained piglet and its relation to body- and organ weight.

1. Neonatal hypoglycaemia is a relatively common clinical problem in children but ethical constraints limit the investigations that may be made in the newborn. 2. As a preliminary step to assess the suitability of the piglet as a model for glucose metabolism in man, whole-body glucose turnover and glucose pool size were measured using [2-3H]glucose in forty piglets from ten litters. 3. Glucose pool size was linearly related to brain weight. However, multiple regression showed that the most useful predictors of pool size were body-weight and resting plasma glucose concentaration. 4. Glucose turnover was related to both brain weight and body-weight alone, but multiple regression showed that better predictors of turnover were liver weight, spleen weight and pancreas weight. 5. Similarities between our own results in piglets and those obtained in human neonates by Bier et al. (1977) extend not only to glucose turnover, but also to its relationship with body- and brain weight. These findings suggest that the piglet may be a useful model for the study of glucose metabolism in babies.

Animals↗

Attitudinal body-image assessment: factor analysis of the Body-Self Relations Questionnaire.

This article presents an analysis of the factor structure of the Body-Self Relations Questionnaire (BSRQ), an attitudinal body-image instrument. Random stratified samples, drawn from a national survey, included 1,064 females and 988 males. In order to evaluate the replicability of the BSRQ factor structure, separate split-sample factor analyses (principal components with varimax rotation) were conducted for each sex. Largely consistent with the conceptual basis of the BSRQ, the resultant factors derived from each analysis were: Appearance Evaluation, Appearance Orientation, Fitness Evaluation, Fitness Orientation, Health Evaluation, Health Orientation, and Illness Orientation. Subsequent concordance analyses revealed marked stability of the factor structure both within and between sexes. Females demonstrated somewhat greater differentiation of body-image attitudes than did males. The utility of the BSRQ is discussed relative to extant body-image measures.

Adolescent↗

Body composition analysis of cachectic rabbits by total body electrical conductivity.

A simple formula (1.536 x TOBEC + 475.146 = LBM, where TOBEC is total body electrical conductivity and LBM is lean body mass) to estimate LBM in grams was developed on the basis of the total body fat data obtained by ether extraction and TOBEC in normal rabbits. The formula was also applicable to rabbits with cachexia induced by inoculation of VX2 carcinoma or by starvation. We were able to assess the losses of body fat in the rabbits with cachexia at 10-day intervals by using TOBEC.

Animals↗

Body circumferences as alternatives to skinfold measures of body fat distribution in children.

The ratios of circumferences (waist/hip, waist/thigh) have been proposed in lieu of skinfold measurements for studies of obesity and body fat distribution in adults. The skinfold method has been used successfully in children to study the growth and development of patterns of body fat distribution, but circumferences have not. We studied the relationship between these two methodologies as indicators of body fat and its anatomical distribution among 365 normal children aged 6-11 years, using canonical correlation analysis. With this method, weighted vectors of four body circumferences on the one hand and five skinfolds on the other are formed in such a way that the correlation between the two sets of variables is maximized. Weights (regression coefficients) are assigned each variable and their strength and sign help us to select the best combination of circumferences which describe a component of centralised obesity. A first canonical correlation was substantial in both boys and girls (0.84) and was independent of age. It appeared to relate to fatness level. A second canonical correlation was low (0.34 in boys, 0.35 in girls) (p less than 0.01). It too was age independent and in both sexes it reflected differences between fat on the trunk and on the lower extremity, and was thus a component of centralised fat distribution. The simple waist/thigh ratio correlated better with this canonical variable (0.67-0.88) than the more commonly used waist/hip ratio (0.45-0.79). The 'best' index of centralised fat in children is therefore, the waist/thigh circumference ratio, the same one that has been suggested for adults.

Adipose Tissue↗

Body fat and fat-free mass in infants: new and classic anthropometric indexes and prediction equations compared with total-body electrical conductivity.

Anthropometry is frequently used for nutritional assessment. Little is known in infants about the validity of anthropometric measurements in relation to whole-body fat (TBF) and fat-free mass (FFM) composition. We compared TBF and FFM estimations by total-body electrical conductivity (TOBEC) with anthropometry in 435 healthy infants ages 21-365 d. TBF was best correlated with weight-for-length and calf circumference (r2 = 0.84, r2 = 0.83). FFM was best correlated with body weight (r2 = 0.93). Upper-arm anthropometry, skinfold thickness, and Quetelet's and Ponderal indexes were poorly correlated with TBF and FFM (r2 < 0.65). New anthropometry-based prediction equations were calculated (r2 = 0.90 for TBF and r2 = 0.95 for FFM). New simple indexes (analogous to Quetelet's index) were calculated for TBF (weight x calf circumference/length; r2 = 0.87) and for FFM (square root of weight x length; r2 = 0.95). Prediction equations and indexes were cross-validated in a second population by a second observer. Interobserver variation was largest for equations with skinfold thicknesses included. We conclude that anthropometry can be used for rough estimations of infant body composition, although indexes different than those used in children and adults are preferred.

Adipose Tissue↗

Is percentage body fat differentially related to body mass index in Hispanic Americans, African Americans, and European Americans?

BACKGROUND: Limited research has been done to explore differences between ethnic groups, including Hispanic Americans (HAs), in the association between percentage body fat (PBF) and body mass index (BMI; in kg/m(2)); the numbers of HAs are increasing in the US population. OBJECTIVE: We investigated whether the relation between PBF and BMI in adult HAs differed from that of African Americans (AAs) and European Americans (EAs). DESIGN: We used a multiple regression model in which PBF measured with dual energy X-ray absorptiometry was predicted by the reciprocal of BMI (1/BMI; in m(2)/kg) in a sample of 487 men (n(EA) = 192, n(AA) = 148, and n(HA) = 147) and 933 women (n(EA) = 448, n(AA) = 304, and n(HA) = 181). RESULTS: For men, our results showed no significant differences between HAs and EAs, AAs and EAs, or HAs and AAs in the slope of the line relating 1/BMI to PBF. In women, there were significant differences in PBF as predicted by BMI between HAs and EAs (P < 0.002) and AAs and HAs (P = 0.020), but not between AAs and EAs. When PBF was estimated on the basis of predicting equations, the trend of the predicted PBF value in women differed according to ethnic group and BMI category. At a BMI < 30, HAs tended to have more body fat than did EAs and AAs, and at a BMI > 35, EAs tended to have more body fat than did the other groups. CONCLUSIONS: Our results show that the relation between PBF and BMI in HA women differs from that of EA and AA women.

Absorptiometry, Photon↗

Body mass index and body girths as predictors of mortality in black and white men.

Anthropometric measurements collected from black and white men in the 1960 (n = 946) and 1963 (n = 456) examinations of the Charleston Heart Study cohort (Charleston County, South Carolina) were examined as predictors of all cause and coronary heart disease mortality. Anthropometric measurements included body mass index, chest girth (at the third intercostal space), abdominal girth (at the umbilicus) and midarm circumference. Vital status of 98 percent of the cohort was determined through 1988. Body mass index was not associated with mortality in the white men; however, it was predictive of all cause and coronary heart disease mortality in the black men. Analyses conducted separately in the lower and upper range of body mass index in black men showed the adjusted relative hazard at the 50th versus the 10th percentile of body mass index was 0.54 for all cause mortality, but was not significant for coronary heart disease mortality; whereas the adjusted relative hazard for the 90th relative to the 50th percentile was 1.7 for coronary heart disease deaths, but not significant for deaths from all causes. The circumference measurements were not predictive of all cause or coronary heart disease mortality in the white men. In the black men, the adjusted relative hazard ratios for all cause mortality for the 85th relative to the 15th percentiles were 0.22 for midarm circumference and 2.0 for abdominal circumference.

Age Factors↗

Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson's disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity.

A mutation in the alpha-synuclein gene has recently been linked to some cases of familial Parkinson's disease (PD). We characterized the expression of this presynaptic protein in the midbrain, striatum, and temporal cortex of control, PD, and dementia with Lewy bodies (DLB) brain. Control brain showed punctate pericellular immunostaining. PD brain demonstrated alpha-synuclein immunoreactivity in nigral Lewy bodies, pale bodies and abnormal neurites. Rare neuronal soma in PD brain were immunoreactive for alpha-synuclein. DLB cases demonstrated these findings as well as alpha-synuclein immunoreactivity in cortical Lewy bodies and CA2-3 neurites. These results suggest that, even in sporadic cases, there is an early and direct role for alpha-synuclein in the pathogenesis of PD and the neuropathologically related disorder DLB.

Aged↗