Search PubMed⌕ Search

Biomedical subjects

J G Kral

Publications and source records attributed to J G Kral.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effect of calcium supplementation on rectal epithelial hyperproliferation in intestinal bypass subjects.

BACKGROUND/AIMS: Fatty acids and bile acids are tumor promoters of experimental colon cancer in rats. Calcium can inhibit their effects. After intestinal bypass (IB), fecal bile acid and lipid levels increase markedly. In rats, IB increases colonic cell proliferation and carcinogen-induced colon tumor incidence. Whether fecal bile acids and lipids influence rectal epithelial proliferation in humans is uncertain. This study compared rectal epithelial proliferation in IB subjects and in controls matched for age, sex, and body mass index and investigated the effects of calcium carbonate supplementation (2400 or 3600 mg Ca2+/day for 12 weeks) on proliferation indices in IB subjects. METHODS: Epithelial proliferation was studied by in vitro incubation of rectal biopsy specimens with [3H] thymidine. Twenty-four-hour stool collections were assayed for bile acids, lipids, and calcium. RESULTS: Whole crypt labeling index (LI) and upper crypt LI were increased in IB subjects compared with controls (P < 0.005). Calcium reduced whole crypt LI by 38% (P < 0.001) and upper crypt LI by 56% (P < 0.05). Levels of fecal bile acids (4.5 mmol/day) and lipids (131.9 g/day) were markedly elevated in IB subjects (P < 0.005). CONCLUSIONS: IB induces rectal hyperproliferation and expansion of the proliferative zone in association with excessive output of fecal bile acids and lipids. Oral calcium reverses the proliferative changes.

Administration, Oral↗
PubMed1994

Distribution of angiotensin II receptors in rat and human adipocytes.

Angiotensin II (AII) receptor binding assays were performed in rat adipocytes from three separate anatomic depots. Fat cells were isolated by collagenase digestion, and plasma membranes were prepared from the epididymal, mesenteric, and retroperitoneal fat depots of male Sprague-Dawley rats at 100 days of age. Binding of 125I-labeled [Sar1,Ile8]AII was rapid, saturable, and specific in membranes from all depots, identifying a receptor with a similar affinity of approximately 1 nM. Site-associated differences in receptor number were observed, with epididymal and mesenteric fat cell membranes exhibiting significantly more receptors than retroperitoneal fat cells when binding was expressed per unit of membrane protein. When corrected for cell volume, the number of receptors per cell ranked epididymal > retroperitoneal > mesenteric. Inhibitory constants for the peptide agonists AII and AIII and the peptide antagonist [Sar1,Ala8]AII indicated similar affinities in all three depots. Because the receptor has been classified pharmacologically into two subtypes, the AT1 selective antagonist losartan, and the AT2 selective antagonist PD 123,319 were used to classify the adipocyte receptor, indicating an AT1 subtype with an affinity for losartan in the mesenteric and retroperitoneal adipocytes that was significantly greater than the epididymal. Similar studies were performed in adipocyte membranes obtained from human omental and subcutaneous adipose tissue, revealing the presence of an AII receptor in both depots with an affinity of approximately 10 nM for losartan. These data indicate site-specific differences in AII receptor number in fat cell membranes from rats and the existence of human adipocyte AII receptors, suggesting that the adipocyte is significant for the peripheral metabolism of components of the renin-angiotensin system.

Adipocytes↗
PubMed1993

Lipolysis in intraabdominal adipose tissues of obese women and men.

Intraabdominal fat in humans is located in two major depots, the omental and mesenteric. We compared basal and stimulated lipolysis in adipose tissue from these two depots and the subcutaneous abdominal depot of obese women and men. Omental fat cells of women are smaller and have lower rates of basal lipolysis than in men. Basal lipolysis rates are significantly higher in subcutaneous than intraabdominal adipose tissues of both genders. In men, the incremental lipolytic response to norepinephrine is significantly greater in both intraabdominal fat depots than in the subcutaneous fat, while in women the response of the mesenteric is lower than the omental. In women, but not men, responsiveness to the beta agonist isoproterenol is also increased in omental tissue. Thus, in women, omental and mesenteric adipose tissues show distinctly different metabolic properties which may moderate the impact of intraabdominal obesity.

Abdomen↗
PubMed1993

Body fat topography as an independent predictor of fatty liver.

Abdominal (truncal) fat distribution reflected by an elevated waist to hip ratio (WHR) predicts metabolic abnormalities such as diabetes and dyslipidemia as well as hypertension and stroke, all of which are associated with obesity. The pathogenesis is not known, although elevated splanchnic serum free fatty acid levels and reduced hepatic insulin clearance have been implicated. WHR and body fat (BF) by 40K-counting and 3H2O were measured before liver biopsy during antiobesity surgery in 68 severely obese women (body mass index [BMI], 48.9 +/- 1.1 SEM) and 15 men (BMI, 49.0 +/- 3.1) without histories of liver disease, diabetes, or hepatotoxic exposure. Biopsies were graded for fat content semiquantitatively (0 to 4+) by the hepatologist who was blinded to the patients' clinical characteristics. All 15 men had fatty infiltration (score, 2.5 +/- 0.3 v 1.4 +/- 0.1 in women; P < .001). The correlation between WHR and liver fat was .44 (P < .0005), while BF (-.16), weight (.15), or BMI (.04) did not correlate significantly with steatosis (all NS). As expected, percentage body fat (BF%) was greater in women than in men (40.3 +/- 0.8 kg v 33.9 +/- 2.0, P < .007), and accordingly liver fat was inversely related to BF% (r = -.32, P < .002). Steatosis was significantly greater in 14 men (2.5 +/- 0.3) than in 20 women (1.7 +/- 0.3, P < .04) matched for BF%. In multiple regression analysis R2 = .49, P < .0001), WHR and sex accounted for the variance in liver fat content without any further contribution from weight, BMI, BF, or BF%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

In vitro lipid synthesis in human adipose tissue from three abdominal sites.

The association between abdominal deposition of adipose tissue and morbidities accompanying obesity may be related to high rates of free fatty acid release from enlarged intra-abdominal stores. To investigate cellular mechanisms that might contribute to enlargement of intra-abdominal adipocytes, lipolysis, triacylglycerol (TG), and diacylglycerol (DG) synthesis from [14C]glucose was measured in abdominal subcutaneous, omental, and mesenteric adipose tissue from severely obese women and men. Subcutaneous adipose tissue from women showed the highest rates of TG synthesis compared with the intra-abdominal site, or any site in men. isoproterenol stimulated TG synthesis more in intra-abdominal than subcutaneous adipose tissue. In the basal state, intra-abdominal adipose tissue from both men and women showed rates of [14C]DG accumulation approximately 50% total [14C]acylglyceride accumulation, whereas, in subcutaneous adipose tissue, [14C]DG accumulation was approximately 25% of total. Basal lipolysis was lower in intra-abdominal than subcutaneous adipocytes. Stimulation of lipolysis reduced [14C]DG accumulation more in intra-abdominal than subcutaneous adipose tissue. Low rates of acylglyceride synthesis in intra-abdominal adipocytes may prevent accumulation of large intra-abdominal fat stores in women.

Abdomen↗
PubMed1992

Assessment of quality of life before and after surgery for severe obesity.

Quality of life is poor in obese people because of poor physical health and mental well-being and impaired psychosocial functioning. Obese people perceive discrimination and prejudice against them as their heaviest burden. Reports of absence of psychopathology in obese people reflect adaptation to chronic disease or failure of assessment instruments to detect disturbances. We present information on the extraordinary suffering and perceived discrimination of obese people and discuss econometric assessment of quality of life. The Swedish national population study of obese subjects (SOS) is presented as well as studies of effects of surgical weight loss on quality of life. Most studies lack adequate controls and extrapolations from surgical populations are uncertain. Psychosocial factors are important predictors of outcome in terms of physical as well as mental health. Operated patients with significant weight loss after surgery demonstrate dramatic improvement in quality of life. This alone justifies treating severely obese patients surgically.

Humans↗
PubMed1992

Overview of surgical techniques for treating obesity.

Nonsurgical methods fail to maintain clinically significant weight loss greater than or equal to 5 y in severely obese patients. Vertical banded gastroplasty and Roux-Y gastric bypass are the main operations for obesity. Modifications of intestinal bypass reserved for special cases require particular expertise in long-term management. Operations function by inducing satiety, nimiety, or aversion. Optimal weight loss or goal weights have not been defined and outcome predictors are inadequate. Results depend more on motivation and behavior than on metabolic, gastrointestinal, or technical factors. New approaches such as adding vagotomy or using inflatable cuffs to adjust outlet size in gastroplasty or modifying outlets or segment lengths in gastric bypass might improve long-term results. A staged approach to surgical treatment of obesity is proposed. Surgery will persist as a viable treatment alternative for severe obesity until effective preventive measures are taken to reduce the prevalence of this serious disease.

Humans↗
PubMed1992

Body composition and surgical treatment of obesity. Effects of weight loss on fluid distribution.

Obesity is associated with absolute and relative expansion of the extracellular water compartment (ECW). The effects of substantial and prolonged weight reduction on body water distribution are unknown, however. The authors studied total body water (TBW) by tritiated water dilution, ECW by 35SO4 dilution, exchangeable sodium (Na(e)) by 24Na, and total body potassium (TBK) by 40K whole-body counting in 25 severely obese women (body mass index [BMI] = 48 +/- 7 kg.m-2, mean +/- standard deviation) aged 36 +/- 8 years before and at intervals after gastric restrictive (GR; n = 12) and malabsorptive (MA; n = 13) operations for obesity. Results are compared with a control group of 26 healthy normal-weight women (BMI = 21 +/- 2). Before operation, the obese patients had absolute elevations of all water compartments compared with controls, with significantly higher ratios of Na(e) to TBK (1.17 +/- 0.13 versus 0.91 +/- 0.10; p less than 0.05) and ECW to intracellular water (ICW) (E/I = 0.82 +/- 0.17 versus 0.63 +/- 0.06; p less than 0.05). After weight loss of 52 +/- 20 kg in MA and 47 +/- 19 kg in GR patients (nonsignificant between groups) to a stable level 22 +/- 8 months after operation, there were statistically significant reductions in TBW, ICW, TBK, and Na(e) in both groups, but a significant reduction in ECW only after GR. Adjusting for preoperative weight, duration of follow-up, and rate of weight loss, E/I was greater after MA than GR (1.09 +/- 0.25 versus 0.82 +/- 0.14; p less than 0.05). The elevated preoperative E/I ratio did not normalize with weight loss after surgery, and the response was related to the type of operation. The finding remains to be explained although the increased E/I after MA may reflect mild protein-calorie malnutrition not detectable in the blood. The persistence of elevated E/I with significant weight loss after GR might imply an intrinsic or irreversible imbalance of fluid distribution in obese patients.

Adult↗
PubMed1992

Transforming growth factor alpha and atrial natriuretic peptide in white adipose tissue depots in rats.

To detect the presence in adipose tissue of peptides known to affect tissue growth and to investigate potential regional differences, epididymal and perirenal adipose tissue depots from male Sprague-Dawley rats were separated into adipocyte and stroma-vascular fractions by collagenase digestion, sequential centrifugation and filtration. Identity and integrity of the fractions were demonstrated by light and electron microscopy, while dose-response curves for angiotensin-converting enzyme (ACE) were performed, revealing maintained functional capacity of the stroma-vascular fraction. ACE, atrial natriuretic peptide (ANP), and transforming growth factor-alpha (TGF-alpha) concentrations were significantly greater in epididymal than perirenal stroma-vascular tissue. Adipocyte fractions from both depots contained significant concentrations of ANP and TGF-alpha. There was no detectable ACE in the adipocyte fractions, indicating that no contaminating stromal-vascular cells were present in these fractions. These data show significant concentrations of peptides with effects on growth in subfractions of adipose tissue and demonstrate regional differences in concentrations between fat depots.

Adipose Tissue↗
PubMed1991

Crack-related perforated gastropyloric ulcer.

Cocaine is a potent topical vasoconstrictor that causes nasal mucosal and dermal ulceration. Use of the purified cocaine derivative "crack" has reached epidemic proportions in large cities. In 18 months we operated on 24 patients with perforated peptic ulcers. Five of the patients were young (27-38 years) male crack users without prior history of gastric symptoms who presented with a perforated gastric ulcer related to smoking crack. Three had had symptoms for only 1-5 days before admission. All five were afebrile, had a rigid abdomen, normal leukocyte count, and free intraabdominal air upon radiography. Five other age-matched, non-crack-using patients served as case controls. Their duration of symptoms was 1-24 months, they had elevated leukocyte counts on admission, and, in contrast to the crack users, four of these patients had duodenal perforations. The clinical presentation of the crack smokers and the unusual localization of the perforations imply different pathogenetic mechanisms than are commonly seen in perforated ulcer disease. With increasing abuse of crack, greater numbers of patients with this new complication may be expected to present to emergency services in urban areas.

Adult↗
PubMed1991

Relative expansion of extracellular fluid in obese vs. nonobese women.

There is a conflict in previous studies with regard to the relation between adipose tissue mass and total body fluid distribution. This study tested the hypothesis that obesity is accompanied by an increase in the extracellular-to-intracellular fluid ratio above that observed in nonobese subjects. Extracellular fluid was evaluated in obese (n = 39) and nonobese (n = 26) healthy women, using two different dilution volumes, 35SO4 [extracellular water (ECW)] and 24NaCl [exchangeable sodium (Nae)]. Intracellular water (ICW = 3H2O dilution volume-ECW) and total body potassium (TBK; 40K whole body counting) were assumed to represent intracellular fluid. Two independent markers of relative fluid distribution were formulated as ECW/ICW and Nae/TBK. Obese and nonobese women were of similar age and height but differed in body weight and TBW by 67.7 kg and 12.9 liters, respectively. The obese women had significantly larger absolute ECW, Nae, ICW, and TBK compared with the nonobese women (all P less than 0.001). The ratios ECW/ICW and Nae/TBK were significantly higher in obese vs. nonobese women and were highly correlated with each other (r = 0.54, P less than 0.001) in the pooled group of subjects. Fluid volumes are thus increased in obese women, and the expansion is relatively greater for the extracellular compartment. These results have implications in the study of human body composition and may also account in part for the fluid-overload states that often accompany severe obesity.

Adult↗
PubMed1990

Metabolic abnormalities in bulimia nervosa.

Resting metabolic rate was measured in a group of 22 women of normal body weight with bulimia nervosa and in 19 age-, sex-, and weight-matched control subjects. Mean resting metabolic rate of patients was significantly lower than that of controls (5162 +/- 928 vs 5636 +/- 449 kJ/24 h [1229 +/- 221 vs 1342 +/- 107 kcal/24 h]), as was mean fasting blood glucose level (4.0 +/- 0.6 vs 4.6 +/- 0.6 mmol/L). Mean basal thyrotropin level was significantly lower in patients than controls, but other thyroid indexes did not differ. There were no group differences in body fat mass, fat cell size, or lipoprotein lipase activity. These data suggest that there is a disturbance in energy regulation in bulimia nervosa. However, the origins and role of this disturbance in the pathophysiology of bulimia are unclear.

Adipose Tissue↗
PubMed1990

Truncal vagotomy reduces food and liquid intake in man.

Truncal vagotomy reduces food and liquid intake in laboratory animals but has not been studied in man. Seven (6F) morbidly obese patients kept 4-day dietary diaries with validation by urine nitrogen analysis before and 3 and 9 months after truncal vagotomy without drainage. Significant reductions in body weight were accompanied by reductions in self-reported total calorie intake from 2800 kcal/day to 1800 at 3 months and 2000 kcal/day at 9 months. The correlation between reported and validated protein intake was .72 (p less than 0.001) with a mean underreporting of protein intake by at least 27%. Macronutricant postoperative reductions in total volume and calorie density of liquid intake. Liquid calories were reduced by 47% at 3 months and 50% at 9 months and solid calories by 33% at 3 months and 27% at 9 months. It is concluded that truncal vagotomy reduces food and liquid intake in man preferentially through liquid reduction. These results have implications for surgical treatment of morbid obesity.

Adolescent↗
PubMed1990

Androgen binding to ammonium sulfate precipitates of human adipose tissue cytosols.

Although androgens are believed to influence the distribution of human adipose tissue and have been detected in human fat, receptors for these sex hormones have yet to be identified. These studies demonstrate that a high-affinity, limited-capacity binding component for the synthetic androgen methyltrienolone (R1881) exists in ammonium sulfate precipitates of human adipose tissue cytosols. The equilibrium dissociation constant (Kd = 0.1 to 0.4 nmol/L, n = 6) and the number of binding sites (2 to 26 fmol/mg protein, n = 22) are consistent with those reported for androgen receptors in rat prostate, human prostatic carcinoma, MCF-7 cells, and baboon myocardium. The relative steroid-binding specificities of the human adipose tissue androphile (R1881 approximately 5 alpha-dihydrotestosterone greater than testosterone greater than estradiol approximately progesterone much greater than dexamethasone) are similar, but not identical, to those reported for androgen receptors in rat prostate (R1881 greater than 5 alpha-dihydrotestosterone approximately testosterone greater than estradiol greater than progesterone much greater than cortisol) and baboon myocardium (R1881 greater than 5 alpha-dihydrotestosterone greater than testosterone greater than progesterone greater than estradiol much greater than cortisol). The function of the androgen-binding component in human adipose tissue is not known.

Adipose Tissue↗