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Biomedical subjects

D A Roncari

Publications and source records attributed to D A Roncari.

At least 55 records · Page 3Linked to original sources
PubMed1981

Exaggerated replication in culture of adipocyte precursors from massively obese persons.

The characteristics of omental adipocyte precursors from massively obese patients, whose average body weights were 231% (range 70--369) of reference values, were studied in propagating culture. When compared to cells from lean subjects, the adipocyte precursors from 34 massively obese patients replicated at a significantly higher rate (p less than 0.001). Excessive replication persisted throughout the first five subcultures. Thus, this characteristic is inherent in the cells, and may reflect the operation of genetic factors in this subgroup of the obese population.

Adipose Tissue↗
PubMed1981

Effects of phenobarbital upon triacylglycerol metabolism in the guinea pig.

The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male guinea pigs injected intraperitoneally with 50 mg phenobarbital x kg-1 for 7 days. Enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity, cytochrome P450 content, and hepatic gamma-glutamyl-transferase activity. Increased activity of gamma-glutamyltransferase was also observed in the blood serum of treated animals. The phenobarbital-treated guinea pigs manifested increased hepatic triacylglycerol content and serum triacylglycerol concentration, accompanied by enhanced ability of cell-free fractions of liver to synthesize glycerolipids in vitro from sn-[14C]glycerol 3-phosphate and fatty acids. Microsomal phosphatidate phosphohydrolase accounted for 97% of the total liver activity of this enzyme, and its specific activity was 50-fold higher than that of the cytosolic enzyme when each was measured under optimal conditions. Activity of the cytosolic phosphohydrolase per liver doubled and that of the microsomal phosphohydrolase increased by 40% in the phenobarbital-treated guinea pigs. The microsomal, but not the cytosolic enzyme, showed a significant correlation with hepatic triacylglycerol content. Significant correlation was observed between the various parameters of hepatic microsomal enzyme induction and hepatic triacylglycerol content, suggesting that enzyme induction may promote triacylglycerol synthesis and consequent hypertriglyceridaemia in the guinea pig.

Aminopyrine N-Demethylase↗
PubMed1981

Enzyme induction and hepatic glycerolipid synthesis in rats treated with 3-methylcholanthrene.

Fasting male rats fed 3-methylcholanthrene in a daily dose of 40 mg . kg body weight-1 gave evidence of hepatic microsomal enzyme induction after 3 days through significantly increased hepatic aryl hydrocarbon hydroxylase activity, cytochrome P448 content, and characteristic changes in microsomal proteins analysed by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Concomitantly, activities of aminopyrine N-demethylase and microsomal gamma-glutamyltransferase, which are increased in phenobarbital-treated rats, significantly declined. In contrast to phenobarbital, which has been previously shown to increase hepatic triacylglycerol content and in vitro glycerolipid synthesis, 3-methylcholanthrene did not affect hepatic triacylglycerol content, but did inhibit glycerolipid synthesis by cell-free preparations of rat liver and significantly reduced serum triacylglycerol concentration. Thus, the two prototypical drugs inducing characteristically different changes in microsomal enzyme and hemoprotein response also seem to differ in their effect upon another important microsomal function, hepatic glycerolipid synthesis.

Animals↗
PubMed1981

Hormonal influences on the replication and maturation of adipocyte precursors.

The establishment of a propagating cell culture system of adipocyte precursors is facilitating the elucidation of the regulation of fat cell development by hormones and growth factors. 17 beta-Estradiol significantly enhances the replication of cultured human omental adipocyte precursors. Androgens do not influence their growth. These findings suggest that estrogens account, at least partly, for the changes that occur in certain adipose tissue regions at puberty. While the physiological role of fibroblast growth factor is unknown, the bovine polypeptide increases the replicative rate of skin fibroblasts to a greater extent than that of adipocyte precursors. On the other hand, partially purified, novel bovine pituitary polypeptides promote the replication of human adipocyte precursors to an appreciably greater extent than fibroblast growth factor. We are further characterizing these putative 'adipocyte growth factors'. Porcine pancreatic polypeptide significantly inhibits the multiplication of human omental adipocyte precursors. These findings may account for the scarcity of pancreatic fat tissue, and suggest that pancreatic polypeptide may control the growth of adipose tissue through its inhibitory effect.

Adipose Tissue↗
PubMed1980

Alcohol and high-density lipoproteins.

High-density lipoproteins (HDL) have been shown to be negatively associated with coronary heart disease; some epidemiologic evidence also suggests that alcohol may protect against coronary heart disease, but other evidence shows the opposite. Alcohol ingestion and even alcoholism may be associated with higher serum HDL levels, but the levels tend to return to normal within 2 weeks with abstinence from alcohol. The relation between HDL and alcoholism, however, is complex, since in addition to alcohol itself several other factors have to be considered. Liver disease and cigarette smoking tend to decrease the serum HDL level in alcoholic persons, while certain hormonal and nutritional influences and the concomitant use of other microsomal-enzyme-inducing drugs may lead to increased HDL levels. On balance, while alcohol per se may increase the serum HDL level, alcoholism--particularly alcoholic liver disease--probably negates the HDL-related protection against coronary heart disease.

Alcohol Drinking↗
PubMed1980

Effects of phenobarbital upon triacylglycerol metabolism in the rabbit.

1. The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male rabbits (2kg body wt.) injected intra-peritoneally with 50 mg of phenobarbital per kg for 10 days. 2. Occurrence of enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity and cytochrome P-450 content, as well as a doubling of microsomal protein per g of liver and a 54% increase in liver weight. Parallel increments in hepatic gamma-glutamyltransferase (EC 2.3.2.2) activity occurred; these were more pronounced in the whole homogenate than in the microsomes, which only accounted for 12.5% of the total enzyme activity in the controls and 17.0% in the animals given phenobarbital. Increased activity of gamma-glutamyltransferase activity was also observed in the blood serum of the test animals. 3. The rabbits given phenobarbital manifested increased hepatic triacylglycerol content and the triacylglycerol concentration of blood serum was also elevated. These changes were accompanied by a significantly enhanced ability of cell-free fractions of liver from the test animals (postmitochondrial supernatant and microsomal fractions) to synthesize glycerolipids in vitro from sn-[14C] glycerol 3-phosphate and fatty acids, when expressed per whole liver. Relative to the protein content of the fraction, glycerolipid synthesis in vitro was significantly decreased in the microsomes, presumably consequent upon the dramatic increase in their total protein content, whereas no change occurred in the postmitochondrial supernatant, possibly due to the protective effect of cytosolic factors present in this fraction and known to enhance glycerolipid synthesis. 4. Microsomal phosphatidate phosphohydrolase accounted for 85% of the total liver activity of this enzyme and its specific activity was 20-fold higher than that of the cytosolic phosphatidate phosphohydrolase (EC 3.1.3.4), when each was measured under optimal conditions. A significant increase in the activity of both enzymes per whole liver occurred in the rabbits given phenobarbital. A closer correlation between hepatic triacylglycerol content and and microsomal phosphatidate phosphohydrolase, as well as the above observation, suggest that this, rather than the cytosolic enzyme, may be rate-limiting for triacylglycerol synthesis in rabbit liver. 5. Significant correlations were observed between the various factors of hepatic microsomal-enzyme induction (aminopyrine N-demethylase and gamma-glutamyltransferase activity as well as cytochrome P-450 content) and hepatic triacylglycerol content, suggesting that that microsomal enzyme induction may promote hepatic triacylglycerol synthesis and consequently hypertriglyceridaemia in the rabbit.

Animals↗
PubMed1980

Cyclic AMP metabolism and lipolysis in cultured human adipocyte precursors.

Triacylglycerol breakdown (lipolysis) results from a series of reactions culminated by activation of "hormone-stimulated" triacylglycerol lipase, an enzyme unique to adipose tissue. We have studied various components of the lipolytic process in human omental adipocyte precursors differentiating in culture. The levels of cyclic AMP, the "second messenger" of lipolytic hormones, were about sixfold higher in fat cell precursors than those in abdominal skin fibroblasts. L-Isoproterenol resulted in significant elevation of cyclic AMP levels in both cell types. Preincubation of intact adipocyte precursors with insulin resulted in significant enhancement of "low Km" cyclic AMP phosphodiesterase activity; in contrast, this hormone had no effect on fibroblast phosphodiesterase activity, a distinctive biochemical difference despite the morphological similarities between the two cell types during the early stages of adipocyte precursor maturation. Incubation of adipocyte precursors with isoproterenol resulted in the release of fatty acids into the medium, findings indicative of "hormone-stimulated" lipase activity and, hence, the operation of the entire "lipolytic cascade"; isoproterenol-stimulated lipolysis was inhibited by insulin. Release of fatty acids from fibroblasts was not observed. Thus, "hormone-stimulated" lipolysis and insulin stimulation of cyclic AMP phosphodiesterase activity are expressed during early stages of human adipocyte precursor differentiation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

Serologic characterization of a monkey antiserum to human leukemic myeloblasts.

We have raised a monkey antiserum that is selectively reactive with human leukemic myeloblasts by immunization with a glycoprotein antigen (AMLSGA) released from myeloblasts in short-term culture. Antimyeloblast activity can be demonstrated using complement-dependent cytotoxicity or indirect immunofluorescence. Selective antimyeloblast activity is retained following absorption with leukemic lymphoblasts or lymphocytes, nonleukemic lymphocytes, neutrophils, or mononuclear cells from nonleukemic bone marrow. Anti-AMLSGA antisera are not reactive with B-cell-enriched cell populations, and antaimyeloblast activity is not reduced by absorption with Ia-positive cells. Anti-AMLSGA is a useful reagent for identification of human leukemic myeloblasts.

Animals↗
PubMed1978

Complete differentiation of adipocyte precursors. A culture system for studying the cellular nature of adipose tissue.

Evidence for the complete morphological maturation of precursor cells into adipocytes in vitro is presented. Cells were isolated from the stromal fraction of adipose tissue from adult humans and from rats and were grown in culture. Abdominal skin fibroblasts were used as controls. All cell strains were initially fusiform and replicated. On reaching monolayer confluency, they were transferred to an enriched growth medium in which the human and rat adipocyte precursors differentiated into a homogeneous population of cells, morphologically indistinguishable from mature adipocytes. In contrast, skin fibroblasts from the same person or animal, and grown under identical culture conditions, did not accumulate lipid and retained their fusiform contour. The same results were obtained in the first six subcultures that were studied. Thus, there is firm evidence that fat tissue of adult humans and rats contains adipocyte precursors that differentiate into mature fat cells. The culture system that has been described will facilitate the elucidation of the factors involved in replication and differentiation of adipocyte precursors.

Adipose Tissue↗
PubMed1978

Medical complications of obesity.

Obesity leads to several complications that affect many body systems. This paper focuses mainly on the cardiovascular complications, which include coronary heart disease, cerebrovascular disease and stroke, and congestive heart failure; the last may be secondary not only to advanced coronary atherosclerosis, but also to other pathogenetic factors. The increased frequency of coronary heart disease in the obese is largely attributable to the commonly associated hypertension, diabetes mellitus and lipoprotein abnormalities, rather than the adiposity. The lipoprotein disorders that have a role in atherogenesis are decreased plasma concentrations of high-density lipoproteins and elevated plasma concentrations of low-density lipoproteins. Abnormalities in cholesterol metabolism are responsible for the increased frequency of cholelithiasis in obese persons. The factors that mediate the development of cardiovascular and gallbladder complications are correctable by an appropriate program of meal planning and physical activity.

Adult↗
PubMed1978

Behavioural treatment of obesity.

Behaviour modification is a promising method of therapy for obesity. Helping the patient to gain control over environmental stimuli and positive reinforcement for the acquisition of appropriate eating and exercise habits are the basis of most treatment programs. While behavioural approaches have, on the average, resulted in greater weight loss than traditional measures during active therapy, responses have been highly variable, and the eventual outcome remains to be established by long-term follow-up studies. The best results are probably achieved with a combination of behavioural therapy and other measures such as a formal exercise program. Since primary prevention may be critical to the overall control of obesity, behavioural approaches may also be applied to young children.

Adult↗
PubMed1978

Promotion of human adipocyte precursor replication by 17beta-estradiol in culture.

The influence of 17beta-estradiol and 17alpha-estradiol on adult human omental adipocyte precursors grown in a propagating culture system was studied. Cells were grown in subculture in the presence or absence of hormone. 17beta-estradiol resulted in significant promotion of adipocyte precursor replication, as determined by cell counting and incorporation of radioactive thymidine into DNA. The hormone stimulated cell multiplication in the concentration range 0.5--500 ng/ml growth medium. The highest level tested was 500 ng/ml. The maximal effects were obtained at 50 ng/ml (P less than 0.001 by paired t test, 48 h after hormone addition). All 10 cell strains (five were derived from men and five from women) that were tested responded similarly to the hormone. 17beta-estradiol did not affect cell size. 17alpha-estradiol did not promote the replication of adipocyte precursors, nor did it influence cell size. Thus, 17beta-estradiol, which is the active isomer in known target tissues, stimulates the multiplication of human adipocyte precursors in culture.

Adipose Tissue↗
PubMed1978

Isolation and partial characterization of radioiodinated myeloblastic leukemia-associated cell surface glycoprotein antigen.

Peripheral blood myeloblasts from five patients with acute myeloblastic leukemia and peripheral remission leukocytes from two of these patients were radiolabeled by the lactoperoxidase-catalyzed surface radioiodination technique and incubated in a nutrient medium at 37 degrees. Radioactive materials shed from viable cells into the supernatant at 24 hr were purified by gel filtration and by DEAE-cellulose chromatography. The radiolabeled leukemic cells shed relatively few molecular species into the culture medium. The DEAE-cellulose eluate usually contained one major peak in which radioactivity and protein levels were coincident; the molecular weight of this compound was 350,000 to 400,000, and it contained carbohydrate as well as protein. Glycoprotein shed from leukemic cells was specifically reactive in a coprecipitation assay with defined antimyeloblast alloantisera obtained from leukemic patients receiving immunotherapy. No reaction was seen with antisera directed against HLA or B-cell antigens. Material shed from remission cells did not coprecipitate with antileukemic antisera. The isolation of radioactively labeled antigen derived from myeloblasts may ultimately allow the monitoring of human antigen levels in leukemic blood by radioimmunoassay.

Antigens, Neoplasm↗
PubMed1977

Isolation of fat cell precursors from adult rat adipose tissue.

The possible existence of adipocyte precursors in adult rat adipose tissue was investigated. Cells were isolated from the stromal fraction of adipose tissue and were grown in culture. Skin fibroblasts were used as controls. The stromal fraction cells were initially fusiform and proliferated; in culture, they accumulated lipid inclusions, became rounder and acquired an eccentric nucleus. In contrast, the skin fibroblasts from the same rat grown under identical culture conditions, did not exhibit any appreciable lipid accumulation. The doubling time for both the stromal fraction cells and skin fibroblasts was 40-60 h. At confluency, the stromal fraction cells contained 5-7 times more glyceride-glycerol than skin fibroblasts. Thus, adipose tissue of adult rats contains cells with the potential to proliferate and acquire morphological characteristics similar to those of adipocytes.

Adipose Tissue↗