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Biomedical subjects

D A Roncari

Publications and source records attributed to D A Roncari.

At least 19 recordsLinked to original sources
PubMed1992

Augmented production of heparin-binding mitogenic proteins by preadipocytes from massively obese persons.

Basic fibroblast growth factor (bFGF) stimulates the replication of preadipocytes and inhibits their differentiation. In this study we explored whether the same or related polypeptides were produced locally and acted by paracrine/autocrine mechanisms in adipose tissue. Omental preadipocytes from 7 lean and 10 massively obese (> 170% reference) subjects were grown to confluence in subculture. Total RNA was hybridized with a synthetic deoxynucleotide for human bFGF. In the case of all cell strains, there was expression of two major bFGF transcripts, 7.0 and 3.7 kb. Although there was considerable variation in the degree of expression, preadipocytes from massively obese subjects revealed much greater expression than did cells from the lean (P < 0.001). In studies of conditioned media prepared with preadipocytes, the presence of proteins belonging to the heparin-binding (fibroblast) growth factor family was indicated by Western blot analysis, for a 66-kD protein with anti-(1-24)bFGF, and for a 32-kD protein with anti-(40-63)bFGF antibodies. The relative quantity of the 66-kD protein correlated with body mass index at r = 0.72. bFGF-related proteins probably function normally to maintain an appropriate complement of adipocyte precursors. The augmented expression of heparin-binding growth factors in preadipocytes from some massively obese people probably contributes to the excessive cellularity of their fat depots.

Adipose Tissue↗
PubMed1991

Relationships between the hypothalamus and adipose tissue mass.

The brain, particularly certain nuclei of the hypothalamus and their neural connections, have a major influence on energy balance, through effects on both food intake and energy expenditure. As summarized in Table 1, there are indeed extensive interactions between the hypothalamus and adipose tissue, the predominate site of storage of chemical energy. Structural, and possibly functional, abnormalities of the neural structures facilitate the development of obesity. This review has described four components of the interactive system. Two of these components are still partly conjectural; while we have increasing experimental support, the hypothalamic-pituitary-adipose axis and the hypothalamic-efferent neural-cytoskeletal pathway are the subject of continuing intense investigation. More complete knowledge of the pathophysiology of obesity will, in turn, facilitate prevention and treatment of corpulence, as well as such frequent associations as non-insulin dependent diabetes mellitus.

Adipose Tissue↗
PubMed1991

The C/EBP-binding region and adjacent sites regulate expression of the adipose P2 gene in human preadipocytes.

Human preadipocytes contain nuclear factors that specifically bind to the AE-1 sequence, previously demonstrated as an enhancer element in the regulation of adipose P2 gene expression during 3T3 adipose differentiation. By transient transfection and in vivo competition experiments, the trans-acting factors were found to bind either to the C/EBP recognition site in the AE-1 sequence and act as a negative regulator or to the adjacent site (termed 3' AE-1) and act as a positive regulator of adipose P2 gene activity in human preadipocytes.

Adipose Tissue↗
PubMed1990

Inhibition of rat perirenal preadipocyte differentiation.

The process of adipose differentiation uniquely endows fat cells to accrue triacylglycerols under conditions of nutrient energy surfeit and to release fatty acids during energy deprivation. The object of this investigation was to study influences on this process in perirenal preadipocytes, grown in primary culture or first subculture and derived from male Sprague-Dawley rats, 180-200 g. Supplementation of the culture medium with 1-methyl-3-isobutylxanthine, corticosterone, and insulin induced differentiation in practically all perirenal preadipocytes, as indicated morphologically and by rising glycerophosphate dehydrogenase activity. Appreciable differentiation was induced even in the absence of methylisobutylxanthine. Transforming growth factor beta (1-1000 pM), cachectin (tumour necrosis factor alpha) (1-1000 pM), and basic fibroblast growth factor (0.063-63 nM) inhibited adipose differentiation significantly, almost completely at the higher concentrations. Direct inhibition, rather than a persisting mitogenic effect of fibroblast growth factor, was confirmed using demecolcine (Colcemid). The fact that transforming growth factor beta and cachectin inhibit differentiation in preadipocytes from postpubertal rats suggests that this effect probably also occurs in vivo, thus diverting energy from adipose depots in certain neoplastic and inflammatory states. We propose that the anterior pituitary, through fibroblast growth factor(s), modulates the pool of preadipocytes and other mesenchymal cells. The mitogenic effect would be complemented by a concerted function, inhibition of adipose differentiation, resulting in the retention of a greater number of potentially replicative cells. Then, depending on the subject's nutritional and endocrine status, extrapituitary factors would regulate the specific process of differentiation.

Adipose Tissue↗
PubMed1990

Purification and partial characterization of a mitogenic protein released from preadipocytes of massively obese subjects.

A protein released into the culture medium by omental preadipocytes of massively obese persons, which stimulates the replication of rat perirenal preadipocytes, has been purified to a high degree. By gel filtration chromatography, the molecular mass of the mitogenic protein was approximately 66,000 daltons (Da), while on sodium dodecyl sulfate - polyacrylamide gel electrophoresis, two subunits were obtained, relative masses (Mr) of approximately 31,000 and approximately 35,000. The isoelectric point of the approximately 66,000 Da entity was 5.6 +/- 0.2. By specific radioreceptor assay, the purified protein was related to epidermal growth factor and transforming growth factor alpha. It was not related to insulin-like growth factors I and II by radioimmunoassay and radioreceptor assay. We propose that the approximately 66,000 Mr protein, and other mitogenic proteins released by preadipocytes from massively obese persons, act through paracrine-autocrine mechanisms and may play a role in the development of the hyperplasia of enlarged fat cells characteristic of massive corpulence.

Adipose Tissue↗
PubMed1990

Abnormalities of adipose cells in massive obesity.

Adipose cells grown in sub-culture are useful to elucidate genetic factors in obesity. Most omental adipose cell strains from 140 massively obese (greater than 170 percent of reference body weight) subjects replicated, in successive sub-cultures, to a significantly higher degree than cells from lean or moderately obese persons. The difference was due to a greater number of rapidly dividing clones. Adipose cells from the massively obese related into the culture medium proteins, native Mr 20,000-65,000, mitogenic on rat preadipocytes. Mitogenic activity of the medium was much less evident with cells from the lean. In the case of several cell strains, culture with 17-beta-estradiol increased the mitogenic activity of the medium. Omental adipose tissue of the massive obese also contained a greater number of adipose cell clones susceptible to differentiation. Hybrids of adipose cells from the massively obese fused with murine renal adenocarcinoma cells (RAG) revealed more prominent differentiation than hybrids comprised of adipose cells from the lean. Further, only those comprised of adipose cells from the obese could recapitulate differentiation in sub-cultures. These findings in culture probably reflect major heritable factors that facilitate the development of massive obesity in humans.

Adipose Tissue↗
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↗
PubMed1977

Ribonuclease activity in renal failure: evidence for toxicity.

The normal level of serum or plasma poly C-avid ribonuclease activity is 1047 +/- 247 U/mL. Serum levels increase proportionately with elevations in serum creatinine, reaching levels of 9,500-35,000 in patients undergoing dialysis. The levels can be normalised by successful renal transplantation but not by dialysis. Purified human urinary ribonuclease, a glycoprotein enzyme similar to the serum ribonuclease, was capable of: 1) inhibiting the incorporation of 3H-thymidine into mitogen-stimulated lymphocytes; 2) inhibiting the proliferation and growth of bone marrow red cell colonies; and 3) adversely affecting the growth and viability of precursor fat cells.

Cell Division↗