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Biomedical subjects

J G Kral

Publications and source records attributed to J G Kral.

At least 37 records · Page 2Linked to original sources
PubMed1999

Synthesis and secretion of plasminogen activator inhibitor-1 by human preadipocytes.

To further investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue physiology, the production and regulation of PAI-1 was determined in primary cultures of human preadipocytes. When expressed as production per cell and cultured under identical conditions, human preadipocytes from both visceral (omental) and sc depots of lean and obese individuals released significant, yet similar, amounts of PAI-1 protein into the conditioned medium. High steady-state PAI-1 messenger RNA (mRNA) concentrations were observed in visceral and sc preadipocytes, with the relative level of expression equivalent to beta-actin mRNA. Tumor necrosis factor alpha significantly decreased PAI-1 production in a concentration-dependent manner in both visceral and sc cultures, whereas transforming growth factor beta significantly elevated PAI-1 production, but only in sc preadipocytes from obese individuals. Addition of insulin had no effect on antigen levels in conditioned medium of preadipocyte cultures. Stimulation of the preadipocyte cultures with a defined medium resulted in differentiation to the adipocyte phenotype, as determined by flow cytometric analysis, verifying the cultures as human preadipocyte. These studies are the first to observe significant PAI-1 mRNA expression and protein production in primary cultures of a human adipose tissue cellular component, and they suggest that nascent adipocytes contribute significantly to the elevated plasma PAI-1 observed in obesity.

Actins↗
PubMed1998

Identification of estrogen receptor beta RNA in human breast and abdominal subcutaneous adipose tissue.

This study reports the initial observation of the novel estrogen receptor, ER beta, in human subcutaneous adipose tissue. Human adipose tissue was obtained from various anatomic sites including the subcutaneous depots of lipectomy patients (healthy controls), and from subcutaneous abdominal and breast depots of lean and obese women with breast cancer. ER beta mRNA expression, determined by reverse transcription and polymerase chain reaction (RT-PCR), was present in each adipose tissue sample examined. Cloning and sequencing of the PCR product confirmed its identity as ER beta. Separation of adipose tissue into component fractions indicated that ER beta was expressed in both adipocytes and the stroma-vasculature. Primary culture of human preadipocytes indicated that ER beta mRNA was present only after differentiation to the adipocyte phenotype. This novel observation of ER beta mRNA indicates that this receptor subtype may have a role in ER-mediated responses in human adipose tissue.

Abdomen↗
PubMed1998

Preliminary results comparing the recovery of basic fibroblast growth factor (FGF-2) in adipose tissue and benign and malignant renal tissue.

PURPOSE: Basic fibroblast growth factor (bFGF or FGF-2) is mitogenic to numerous epithelial, mesodermal and endothelial cells, and thus may play a role in the neovascularity and progression of several tumors. Furthermore, FGF-2 is reported to be elevated in the serum and urine of patients with various cancers, including renal cancer. Obesity, with increased body fat, is a risk factor for renal cancer through unknown mechanisms. Since adipose tissue is a source of FGF-2, we determined the quantity and quality of activity of FGF-2 in omental adipose tissue and compared it to normal and cancerous renal tissue. MATERIALS AND METHODS: Using heparin-Sepharose chromatography we extracted proteins from human omental adipose tissue, renal cell carcinoma (RCC) and benign renal tissue (BRT). Using FGF-2 antisera we performed western blot analysis to confirm their homology to FGF-2. We also assessed recovery, mitogenicity and angiogenicity of each of the proteins using thymidine incorporation into human umbilical vein endothelial cells (HUVEC) and the chorioallantoic membrane (CAM) assay. RESULTS: Each of the three purified mitogenic proteins eluted with NaCl concentrations between 1.4 M. and 1.8 M., similar to control FGF-2. There was greater recovery of FGF-2 from omental adipose tissue compared with renal cell carcinoma or benign renal tissue (42 microg. vs. 24 microg. and 18 microg., respectively; ANOVA p <0.05). Moreover, FGF-2 from adipose tissue had greater mitogenic activity (96.% versus 68% and 38%; p <0.05) and greater angiogenic activity (5.5 vessels versus 2.7 and 1.6 vessels; p <0.05) on the CAM assay. CONCLUSIONS: We suggest that human omental adipose tissue FGF-2 may demonstrate greater mitogenic and angiogenic activity than either benign or cancerous renal tissue FGF-2. It is not known if FGF-2 from adipose tissue may play a role in the relationship between obesity and renal cancer.

Adipose Tissue↗
PubMed1998

The impact of liposuction on body fat.

Routine liposuction has very low perioperative complication rates and is thus considered to be innocuous. Some authors have even proposed that large-volume liposuction could be therapeutic. However, because subcutaneous adipose tissue has nutritional and thermodynamic metabolic functions proportional to the absolute amount and the distribution of fat, it is possible that removal of subcutaneous adipose tissue might be detrimental. We measured the amount of fat removed by large-volume (>1000 cc) liposuction and expressed the results in terms of absolute and relative changes in total body fat and in visceral adipose tissue (nonsubcutaneous adipose tissue) in 63 normal weight to mildly obese women (n = 51) and men (n = 12). Aspiration of 1.5 +/- 0.7 kg (mean +/- SD) of lipid in women removed 9.2 +/- 3.2 percent of body fat or 10.5 percent of subcutaneous adipose tissue corresponding to a 12-percent increase in the ratio of visceral to subcutaneous adipose tissue. One third of the women (n = 17) had a mean increase of 16 percent (range 13 to 21 percent) in the proportion of visceral fat. In the 12 men, aspiration of 1.7 +/- 0.6 kg of lipid removed 9.8 +/- 2.9 percent of body fat or 12.7 +/- 3.6 percent of subcutaneous adipose tissue, resulting in a 14-percent increase in the ratio of visceral to subcutaneous fat. The correlation between aspirate and body mass index was 0.57 (p < 0.001). Although large-volume subcutaneous liposuction removed relatively little body fat, it led to significant increases in the proportion of visceral adipose tissue. Because the proportion of visceral adipose tissue is a risk factor for metabolic complications of obesity, the metabolic effects of large-volume liposuction need to be evaluated.

Adipose Tissue↗
PubMed1998

Obesity surgery: a model of programmed undernutrition.

Surgical treatment of obesity (bariatric surgery) is the only effective long term solution for many patients. The procedures are designed to produce reduced intake, various degrees of malabsorption of nutrients, or both. Micronutrient deficiencies, especially those involved in erythropoiesis and bone metabolism, are common to nearly all bariatric surgery. They are inconsistently responsive to supplementation. The pattern of deficiency associated with gastrointestinal bypass procedures suggests that absorption of micronutrients is more dependent upon the functioning of the gut as a whole than the capacity of any single segment.

Calcium↗
PubMed1998

Management of T tubes for common bile duct stones: a new technique.

BACKGROUND: The optimal treatment of common bile duct (CBD) stones is controversial, and depends on local expertise, the patient's medical condition and the time of diagnosis. Current practice entails a wide variation in the duration of leaving T tubes in place, anywhere from 7 to 30 days, and in the time to postoperative cholangiogram. Here we present a new technique for T-tube placement and management of secondary or retained CBD calculi that reduces T-tube duration to </= 5 days. MATERIALS AND METHODS: After CBD exploration and clearance, we place a 10- to 18-French T tube through a 22- to 34-French straight rubber catheter with side holes acting as a sheath. The two tubes are exteriorized together, with the sheath protruding 1-2 cm. We place a colostomy bag for collecting possible abdominal drainage over the site and run the T tube through the colostomy bag into a bile bag. RESULTS: Our method allows early removal of the T tube in patients with cleared ducts and early radiologic instrumentation of the CBD through the sheath to extract retained calculi. This obviates the need for postoperative endoscopic retrograde cholangiopancreaticography. CONCLUSION: This method reduces the length of hospital stay, the number of outpatient office visits and postoperative studies, and the duration of T-tube drainage, potentially decreasing the incidence of complications of T tubes, improving patient satisfaction.

Adult↗
PubMed1998

An analysis of microvessel density, androgen receptor, p53 and HER-2/neu expression and Gleason score in prostate cancer . preliminary results and therapeutic implications.

OBJECTIVES: To investigate relationships between microvessel density (MVD), androgen receptors (AR), mutant p53 and HER-2/neu expression and Gleason score (GS) to further understand the tumor biology of prostate cancer (CAP). METHODS: Slides of CAP from patients who underwent radical prostatectomy or channel transurethral resection of the prostate (TURP) were tested for androgen receptors by immunocytochemical assay and MVD was analyzed by staining with antibodies to the endothelial cell membrane molecule PECAM-1/CD-31. The p53 monoclonal antibody D07 and HER-2 9G6 mouse monoclonal antibody were used to assess p53 and HER-2/neu expression, respectively. The results were correlated with GS and clinical stage by multivariate analysis. RESULTS: We found a fourfold greater expression of MVD in prostate cancer specimens compared to neighboring normal prostate tissue. We observed a greater concentration of MVD in the higher Gleason scores (r = 0.40, p = 0. 06), and a correlation of Gleason score with mutant p53 expression (r = 0.57, p <0.05). We did not observe any associations between AR or HER-2/neu to Gleason score. More than half of the patients with specimens with 50% or greater expression of mutant p53 were in stage D2 (T4NxM1b) at the time of biopsy. CONCLUSIONS: We observed a correlation between mutant p53 and GS, and a greater concentration of MVD in the higher GS. Since the neovascularity of prostate tumors can be attenuated by radiation and hormones, while mutant p53 may confer resistance to such treatment, it appears that p53 expression may also play an important role in addition to angiogenesis in the virulence of prostate cancer. These data may aid in allocating patients to different treatment modalities.

Adenocarcinoma↗
PubMed1997

Differences in prostate and adipose tissue basic fibroblast growth factor: analysis of preliminary results.

OBJECTIVES: Basic fibroblast growth factor (bFGF or FGF-2) is mitogenic to human prostate epithelial and stromal cells, and it is reported to be elevated in the serum and urine of patients with various cancers, including prostate cancer. Obesity, with increased body fat, is a risk factor for prostate cancer through unknown mechanisms. Because adipose tissue is a source of FGF-2, we determined the quantity and quality of activity of FGF-2 in omental adipose tissue and compared it with normal and cancerous prostate tissues. METHODS: Using heparin-Sepharose chromatography, we extracted proteins from human omental adipose tissue, adenocarcinoma of the prostate, and benign prostatic hypertrophic (BPH) tissues. Each of the mitogenic proteins eluted with NaCl concentrations between 1.4 M and 1.8 M, similar to control FGF-2. Using FGF-2 antisera (which inhibited the mitogenic activity of the proteins), we performed Western blot analysis to confirm their homology to FGF-2. We also assessed recovery, mitogenicity, and angiogenicity of each of the proteins using thymidine incorporation into human umbilical vein endothelial cells and the chorioallantoic membrane assay. RESULTS: There was greater recovery of FGF-2 from omental adipose tissue compared with cancerous or BPH homogenates (40 micrograms [2.0 micrograms/g] versus 25 micrograms [1.25 micrograms/g] and 20 micrograms [1.0 microgram/g], respectively). Moreover. FGF-2 from adipose tissue had greater mitogenic activity (96.2% versus 74.8% and 54%; P < 0.05) and a greater angiogenic activity (5.1 vessels versus 2.9 and 1.8 vessels; P < 0.05) on the chorioallantoic assay. CONCLUSIONS: We suggest that human omental adipose tissue FGF-2 may demonstrate greater mitogenic and angiogenic activity than either BPH or prostate cancer tissue FGF-2. It is not known whether FGF-2 from adipose tissue qualitatively or quantitatively may underlie the relationship between obesity and prostate cancer.

Adipose Tissue↗
PubMed1997

Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects.

To determine the interrelationship among insulin action, total or regional adiposity, and sex, we measured insulin-mediated glucose disposal by the euglycemic insulin clamp and adipose distribution using computed axial tomography (22 scans) in 32 black men and 20 black women with non-insulin-dependent diabetes mellitus (age 48 +/- 9 and 54 +/- 9 yr, body mass index 26.3 +/- 2.3 and 27.2 +/- 2.6 kg/m2, respectively). Women had approximately 80% more total and subcutaneous fat volume than men (31.8 +/- 8.3 vs. 18.6 +/- 6.1 and 28.5 +/- 7.3 vs. 14.7 +/- 4.6 liters) and less muscle volume (22.9 +/- 3.7 vs. 35.1 +/- 3.8 liters). Visceral fat volume did not differ between men and women (3.49 +/- 1.65 vs. 2.96 +/- 1.22 liters). Despite these body composition differences, an inverse nonlinear relationship existed between glucose disposal and visceral fat independent of sex (r = -0.58, P < 0.0001; men r = -0.60 and women r = -0.59; the slope and intercept were not different in men and women). Visceral fat explained a significant portion (34%) of variance in insulin-mediated glucose disposal, whereas total or subcutaneous fat and sex did not. Visceral fat appears to affect glucose disposal over a restricted range (up to approximately 2.5 l/m2 body surface area.

Adipose Tissue↗
PubMed1997

A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives.

Adipose tissue microcirculation is unique within the vascular system because of a capacity for this tissue to grow throughout most of adult life. A review of the microcirculation of adipose tissue has included a historical review of the early studies, which served as a foundation for later investigations on this topic, including basic hemodynamic measurements in mammalian adipose tissue. The various methods for measuring blood flow in white and brown adipose tissue are discussed with respect to studies of transport of substrates involved in adipose tissue metabolism. The role of innervation and vascular adrenergic receptors and the effects of diet and exercise on adipose tissue blood flow are also included. An in-depth analysis of the development of adipose tissue microvasculature indicates that angiogenesis often precedes adipogenesis. The clinical effects of hemodynamic adaptations to adipose tissue expansion are discussed in view of an epidemic increase in the prevalence of obesity and its co-morbidities. The recent discovery of sites of nuclear regulation of adipocyte differentiation, together with the identification of growth factors in adipose tissue, is an indication of the progress that is being made in the further understanding of molecular and cellular events that affect adipose tissue growth and, ultimately, adipose tissue microcirculation.

Adipose Tissue↗
PubMed1996

Calcium carbonate treatment of diarrhoea in intestinal bypass patients.

OBJECTIVE: To study the effect of supplemental calcium carbonate on faecal water, calcium, bile acid and lipid concentration and output in intestinal bypass subjects with diarrhoea. DESIGN: Prospective, single-arm treatment trial of oral calcium carbonate, 2400 or 3600 mg Ca2+ per day, given for 12 weeks. METHODS: Faecal constituents were determined in wet or lyophilized stool of 24-h collections at baseline and at 12 weeks of study. Calcium was measured by absorption spectrophotometry. Bile acids, long-chain fatty acids and short-chain fatty acids were analysed by gas chromatography. RESULTS: In 15 subjects, calcium supplementation reduced bowel frequency by a mean of 49%, faecal wet weight by a mean of 50% (1292 to 646 g per day), and dry weight by a mean of 36%, P < 0.001. Faecal water concentration was reduced from 76.4 +/- 1% to 70.2 +/- 2%, P < 0.01. Faecal water concentration was inversely correlated with dry faecal calcium concentration (r = -0.75 P = 0.00001). CONCLUSION: Calcium reduces the diarrhoea of intestinal bypass patients. It is suggested that the constipating effect of calcium may be related to reduction in faecal water.

Adult↗
PubMed1995

Intestinal B-cell isotype response in relation to local bacterial load: evidence for immunoglobulin A subclass adaptation.

BACKGROUND & AIMS: In experimental animals, the indigenous microbiota modulates mucosal immunity. In humans, such direct evidence is scarce. The aim of this study was to examine the effect of intestinal bacteria on the local immunoglobulin (Ig) response. METHODS: The numbers of IgA-, IgM-, and IgG-producing immunocytes per defined mucosal length unit were determined, and the local IgA subclass response was studied using immunohistochemistry in jejunal segments from adults with bacterial overgrowth and in sterile ileal urinary conduits from children. RESULTS: The ileal bladder mucosa showed atrophy, but the number of immunocytes only tended to be decreased. The jejunal segments with bacterial overgrowth showed minor histological changes; the numbers of IgA and IgG immunocytes were fairly normal, whereas the number of IgM immunocytes was significantly reduced (P < 0.05) (12 cells/U) compared with control mucosa (24 cells/U). The number of IgA2 immunocytes was significantly decreased (P < 0.01) in ileal conduits (7 cells/U or 30% of total IgA) but increased (P < 0.05) in jejunal segments with bacterial overgrowth (42 cells/U or 43% of total IgA) compared with normal ileum (15 cells/U or 40% of total IgA) and jejunum (24 cells/U or 23% of total IgA). CONCLUSIONS: An association exists between bacterial load and IgA subclass production. An increase in IgA2 may enhance mucosal protection and probably reflects immunomodulation caused by lipopolysaccharides.

Adolescent↗
PubMed1995

Does intra-abdominal adipose tissue in black men determine whether NIDDM is insulin-resistant or insulin-sensitive?

Insulin resistance in black Americans with non-insulin-dependent diabetes mellitus (NIDDM) is found in only 60% of those with a body mass index (BMI) of < 30 kg/m2, suggesting that NIDDM can occur independent of peripheral insulin resistance. When insulin resistance is present, it is not necessarily correlated with obesity. Numerous studies have shown that increased amounts of intra-abdominal adipose tissue are associated with various metabolic abnormalities. We therefore investigated whether the occurrence of insulin resistance in black NIDDM men could be explained by the pattern of body adipose tissue distribution rather than total adiposity. Twenty-two near-normoglycemic black men (fasting plasma glucose [mean +/- SD] = 104 +/- 10 mg/dl, HbA1c = 4.6 +/- 0.78%, age 48.9 +/- 9.2 years, and BMI 26.5 +/- 2.4 kg/m2) were studied. The euglycemic insulin clamp with 1 mU.kg-1.min-1 insulin infusion and D-[3-3H]glucose was used to measure insulin action. Whole-body computed tomography with 22 scans was used to determine body composition. Total body adipose tissue was 19.6 +/- 7.51, and the percentage of body fat was 27 +/- 7. Glucose disposal ranged from 2.5 to 8.1 mg.kg-1.min-1 (10 men were insulin-sensitive and 12 were insulin-resistant). There was a strong inverse correlation between glucose disposal and the proportion of total adipose tissue in the intra-abdominal region (r = -0.78, P < 0.001), while there was no correlation between glucose disposal and total muscle volume, BMI, total adipose tissue volume, or total subcutaneous adipose tissue volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1995

The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity.

Angiotensin II exerts its action via at least two distinct receptor subtypes designated AT1 and AT2. AT1 receptors seem to be responsible for most of the known angiotensin II effects while the role of AT2 receptors is not yet clear. Adipocytes of adult rats express exclusively the AT1 subtype. Angiotensin II stimulates prostacyclin release in adult rat adipocytes and in mouse preadipocytes. In the latter prostacyclin release is completely blocked by an AT2 receptor antagonist. Adipocyte angiotensin II receptors seem to be regulated by age and fat mass. Blockade of these receptors by an AT1 antagonist seems to prevent adipose tissue hypertrophy. Moreover, adipose tissue contains all the main components of the renin-angiotensin system such as angiotensinogen, angiotensin converting enzyme, angiotensin II and angiotensin II receptors. Angiotensinogen expression in adipocytes is stimulated by a high fat diet concurrent with enlargement of fat mass, associated with insulin resistance. Angiotensin converting enzyme inhibitors improve insulin sensitivity. Taken together, there is evidence of interaction between insulin and angiotensin II in regulation of adipose tissue metabolism and cellularity. Clarification of these interactions could lead to significant progress in pharmacological treatment of obesity and its comorbidity.

Adipose Tissue↗
PubMed1995

The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects.

OBJECTIVE: To determine whether fatty liver impairs insulin clearance and contributes to insulin resistance in obese and lean healthy non-diabetic men and women. DESIGN: Cross-sectional, descriptive. SETTING: Medical outpatient clinic; university hospital. SUBJECTS: Twenty-seven (14 men) non-diabetic obese (Body fat % = 31.5 +/- 9.3; mean +/- s.d.) and 19 (13 men) non-diabetic non-obese (body fat % = 19.0 +/- 6.8; P < 0.01 vs obese) healthy subjects aged 31-64 without liver disease. MAJOR OUTCOME MEASURES: Liver density relative to the spleen on CT scan (LFS), glucose infusion rate (GIR) and metabolic insulin clearance rate (MIC) during euglycemic hyperinsulinemic clamp; anthropometric (waist-hip ratio: WHR) and CT-determined (visceral fat area: VFA) measures of fat distribution. RESULTS: Fatty liver was inversely related to MIC (r = -0.39; P < 0.01) with a positive correlation with fasting p-insulin (r = 0.39; P < 0.01). There were no statistically significant correlations between BMI, body fat % or WHR and MIC. GIR was inversely related to body fat % (r = -0.49; P < 0.01), VFA (r = -0.56; P < 0.01) and WHR (r = -0.36; P < 0.01) in all subjects, with an inverse relationship to fatty liver in men (r = -0.43; P < 0.05). CONCLUSION: Increased steatosis of the liver is associated with reduced insulin clearance, contributing to insulin resistance in non-diabetic Japanese men and women.

Adipose Tissue↗
PubMed1995

Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NIDDM.

OBJECTIVE: We investigated the relationship of liver fat to visceral adipose tissue, serum triglyceride levels and glucose disposal. DESIGN: Cross-sectional, prospective. SUBJECTS: 21 lean to moderately obese black NIDDM men (mean +/- s.d. age 48.9 +/- 9.4 years, body mass index 26.3 +/- 2.4, fasting plasma glucose 104 +/- 10 mg/dl, HBA1C 4.6 +/- 0.8% and body fat 26 +/- 6%) with no evidence of liver disease or alcohol abuse. Eleven were insulin-sensitive (glucose disposal > 5.5 mg/kg/min) and ten were insulin-resistant subjects during euglycemic insulin clamps. MEASUREMENTS: Body composition and liver density were determined by whole body computed tomography using 22 scans. Liver fat score was defined as 100 minus the absolute liver density. Glucose disposal was measured during 1 mU/kg/min euglycemic insulin clamp with 3-3H glucose. RESULTS: Visceral adipose tissue volume was 3.54 +/- 1.87 litres. The liver fat score was 48.8 +/- 5.0 (not in the range of clinical hepatic steatosis). Glucose disposal ranged from 2.5 to 8.1 mg/kg/min. The liver fat score was correlated with visceral/total adipose tissue ratio (r = 0.65, P = 0.001) and to fasting serum triglyceride levels (r = 0.47, P = 0.032). Fasting serum triglyceride levels were related to visceral adipose tissue (r = 0.52, P = 0.016). Liver fat was inversely related to glucose disposal (r = -0.42, 1 tail P = 0.036). CONCLUSIONS: In non-insulin-dependent diabetes mellitus, liver fat may contribute to insulin resistance and be a link between visceral adipose tissue mass and serum triglyceride levels.

Adipose Tissue↗