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Biomedical subjects

D A Roncari

Publications and source records attributed to D A Roncari.

At least 37 records · Page 2Linked to original sources

Possible mechanisms in the pathogenesis of virus-induced diabetes mellitus.

Insulin-dependent diabetes mellitus results from destruction of pancreatic beta cells. Viruses and autoimmunity have been implicated as possible causes of beta cell destruction in genetically predisposed individuals. The evidence for viruses comes largely from experiments in animals, but several studies in humans point to viruses as triggers in the pathogenesis of diabetes in some cases. In animal models, at least 4 different possible mechanisms for virus-induced diabetes have been proposed. The first mechanism is direct cytolytic infection of pancreatic beta cells. One group of viruses, including encephalomyocarditis virus, Mengovirus 2T, and Coxsackie B viruses, can directly infect and destroy pancreatic beta cells independent of autoimmune processes. The second mechanism is triggering of autoimmune responses. In contrast to the encephalomyocarditis virus-induced diabetes, reovirus type 1 and rubella virus seem to be somehow associated with autoimmunity in the genesis of a diabetes-like syndrome in a certain strain of suckling mice and hamsters, respectively. The third mechanism is cumulative environmental insults. The cumulative environmental insults with viruses and beta cell toxic chemicals can result in diabetes in genetically predisposed non-human primates and certain inbred strains of mice. The fourth mechanism is persistent infection. A certain virus, such as lymphocytic choriomeningitis virus, persistently infects murine pancreatic beta cells and produces hyperglycemia. The evidence that viruses cause diabetes in humans is more circumstantial.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Usefulness of gas chromatographic profiles of plasma total lipids in diagnosis of phytosterolemia.

A Cambodian male (aged 5 years and 9 months) presented with subcutaneous and tendon xanthomas in association with hypercholesterolemia. He was erroneously diagnosed as having familial hypercholesterolemia and treated with a low cholesterol diet (+/- cholestyramine) to which he did not respond. A determination of plasma total lipid profile by high-temperature gas chromatography revealed elevated plasma levels of free and esterified plant sterols along with the hypercholesterolemia. Introduction and maintenance of a diet low in cholesterol and plant sterols resulted in significant reduction in the blood concentration of these sterols, which returned to pretreatment level upon discontinuation of the low sterol regimen. The rapid identification and quantitation of the plant sterols by high-temperature gas chromatography provides a sensitive means of distinguishing phytosterolemia, which might be more common than previously suspected, from other forms of dyslipidemia, and for following the course of any treatment.

Adult↗

Fatty acid composition of individual plasma steryl esters in phytosterolemia and xanthomatosis.

The bulk of the plasma plant sterol in phytosterolemia occurs in the esterified form and is carried mostly in the low and high density lipoproteins. We have determined the fatty acid composition of the individual plasma steryl esters from a newly discovered subject with phytosterolemia and xanthomatosis. For this purpose the intact steryl esters were subject to high temperature gas liquid chromatography (GLC) on a polar capillary column, which separated the major esters on the basis of molecular weight and degree of unsaturation of the fatty acids. The saturated and unsaturated sterols esterified to saturated, monoenic, dienoic and tetraenoic fatty acids were identified by GLC analysis of the sterol moieties of the corresponding AgNO3-TLC fractions of the steryl esters. The GLC results were confirmed by reversed phase high performance liquid chromatography combined with mass spectrometry via direct liquid inlet interface. It was found that, in general, each fatty acid was esterified to the same complement of sterols, and that the esterified sterols possessed a composition comparable to that of the free plasma sterols, which was comprised of about 75% cholesterol, 6% campesterol, 4% 22,23-dihydrobrassicasterol and 15% beta-sitosterol. The fatty acid composition of the steryl esters differed from that of the 2-position of the plasma phosphatidylcholines, which contained significantly less palmitic and oleic and more linoleic acid. On the basis of these results and a review of the literature it is suggested that the plasma cholesteryl and plant steryl esters in phytosterolemia originate from both synthesis in plasma via the lecithin-cholesterol acyltransferase and synthesis in tissues via the acylCoA-cholesterol acyltransferase.

Chromatography, Gas↗

Excessive proliferation in culture of reverted adipocytes from massively obese persons.

Differentiated omental adipocytes from lean and massively obese persons lost their spherical shape in culture and regained the ability to replicate. In propagating culture, reverted cells from each group multiplied to a greater extent than corresponding stromal adipocyte precursors. Reverted adipocytes from the massively obese proliferated at significantly higher rates than those from lean subjects. Reverted cells derived from 1-2 adipocytes also revealed these differences.

Adipose Tissue↗

Adipocyte precursor clones vary in capacity for differentiation.

Adipocyte precursor populations derived from rat perirenal or epididymal fat were found to be composed of clones varying in capacity for differentiation. Perirenal tissue contained a greater proportion of those clones that differentiated extensively. It is hypothesized that differences between regions and individuals in growth of adipose tissue may be due to differences in the frequency within adipocyte precursor pools of clones with unusual capacities for replication and differentiation.

Adipose Tissue↗

Hypercalcemia associated with cancer of prostate without bony metastases.

Although hypercalcemia is sometimes found in carcinoma of the prostate with osseous metastases, it is rarely seen as a paraneoplastic manifestation of this neoplasm. We present a patient with such a tumor in whom severe hypercalcemia developed in the absence of detectable osseous metastases.

Adenocarcinoma↗

Purification of a pituitary polypeptide that stimulates the replication of adipocyte precursors in culture.

A bovine anterior pituitary polypeptide that stimulates the replication of rat and human adipocyte precursors has been purified. Its Mr is 44 000-53 000 and its isoelectric point is 9.8-10.3. While pituitary basic fibroblast growth factor is equally mitogenic on adipocyte precursors and skin fibroblasts, the polypeptide described here is selectively more active on the precursors. We postulate that this adipocyte growth factor plays a physiological role by modulating the number of adipocyte precursors.

Adipose Tissue↗

Effects of glucocorticoid hormones on lipid-synthetic enzymes from different adipose tissue regions and from liver.

The regional diversity of adipose tissue is dramatically accentuated in states of glucocorticoid excess, in which certain fat depots expand, while others contract. We have studied the molecular basis of this redistribution by determining the activity of fatty acid synthetase and enzymes catalyzing di- and tri-acylglycerol synthesis, in subcellular fractions from four adipose depots of rats injected with dexamethasone and from interscapular and epididymal adipocyte precursors after addition of either dexamethasone or corticosterone to confluent monolayers in secondary culture. Subcellular fractions from cervical and interscapular adipose tissue, as well as from cultured interscapular precursors, revealed a general increase in specific enzyme activity. The opposite trend was observed for retroperitoneal and epididymal fat tissue, as well as cultured epididymal precursors. Fatty acid synthetase and cytosolic phosphatidate phosphohydrolase appeared to be most responsive. The findings in culture indicate that the regional effects of glucocorticoids are partly independent of other circulating or neural factors. Injections of dexamethasone led to significantly enhanced specific activity of all the lipid-synthetic enzymes assayed in subcellular fractions from liver. Differences in hormonal influences between liver and certain fat tissue regions represent tissue specificity. In addition, the diverse effects of glucocorticoids on various adipose tissue depots indicate regional or "intratissue" specificity.

Acyltransferases↗

Complete differentiation in vivo of implanted cultured adipocyte precursors from adult rats.

The formation of fully differentiated fat cells from adipocyte precursors, implanted into the same adult rats from which they were derived, is described. Precursor strains of rat epididymal adipocyte strains were grown through five subcultures, some in the presence of radioactive thymidine. While still at a relatively undifferentiated stage, the precursors were re-implanted into a superficial intramuscular location. At the time of resection six months later, "fat pads" were observed at the sites of implantation. These pads contained sheets of cells morphologically identical to mature epididymal adipocytes. The fat cells in pads developing from precursors grown in the presence of [3H]thymidine, were radiolabelled. Therefore, they represent fat cells that have differentiated in vivo from the implanted cultured precursors. Implanted skin fibroblasts did not lead to the formation of adipocytes. The finding that cultured adipocyte precursors from adult rats can differentiate fully not only in vitro, but also in adult animals, supports the probable physiological significance of these cells. The precursors probably participate in fat cell turnover, which likely persists throughout adulthood.

Adipose Tissue↗

Characterization of compounds shed from the surface of human leukemic myeloblasts in vitro.

Human leukemic myeloblasts shed glycoproteins from the cell surface during short-term in vitro culture. Shed surface glycoproteins yield a characteristic profile when studied by gel chromatography, isoelectric focusing, immune precipitation, and polyacrylamide gel electrophoresis. Isolation of immunologically active material yields a compound to approximately 75,000--80,000 daltons, with an isoelectric point of 7.6 to 7.9. Various morphological subtypes of acute myelogenous leukemia shed these compounds, but they are most easily obtained from the more differentiated M2 and M4 types as compared to the undifferentiated M1 type. The shed compounds appear to be quantitatively and qualitatively different from compounds shed by other leukemic cells or nonleukemic cells.

Cells, Cultured↗

Triacylglycerol metabolism in the phenobarbital-treated rat.

1. Various aspects of triacylglycerol metabolism were compared in rats given phenobarbital at a dose of 100mg/kg body wt. per day by intraperitoneal injection; controls were injected with an equal volume of 0.15m-NaCl by the same route. Animals were killed after 5 days of treatment. 2. Rats injected with phenobarbital demonstrated increased liver weight, and increased microsomal protein per g of liver. Other evidence of microsomal enzyme induction was provided by increased activity of aminopyrine N-demethylase and cytochrome P-450 content. Increased hepatic activity of gamma-glutamyltransferase (EC 2.3.2.2) occurred in male rats, but not in females, and was not accompanied by any detectable change in the activity of this enzyme in serum. 3. Phenobarbital treatment increased the hepatic content of triacylglycerol after 5 days in starved male and female rats, as well as in non-starved male rats; non-starved females were not tested in this regard. At 5 days after withdrawal of the drug, there was no difference in hepatic triacylglycerol content or in hepatic functions of microsomal enzyme induction between the treated and control rats. 4. After 5 days, phenobarbital increased the synthesis in vitro of glycerolipids in cell-free liver fractions fortified with optimal concentrations of substrates and co-substrates when results were expressed per whole liver. The drug caused a significant increment in the activity of hepatic diacylglycerol acyltransferase (EC 2.3.1.20), but did not affect the activity per liver of phosphatidate phosphohydrolase (EC 3.1.3.4) in cytosolic or washed microsomal fractions. A remarkable sex-dependent difference was observed for this latter enzyme. In female rats, the activity of the microsomal enzyme per liver was 10-fold greater than that of the cytosolic enzyme, whereas in males, the activities of phosphohydrolases per liver from both subcellular fractions were similar. 5. The phenobarbital-mediated increase in hepatic triacylglycerol content could not be explained by a decrease in the hepatic triacylglycerol secretion rate as measured by the Triton WR1339 technique. Since the hepatic triacylglycerol showed significant correlation with microsomal enzyme induction functions, with hepatic glycerolipid synthesis in vitro and with diacylglycerol acyltransferase activity, it is likely to be due to enhanced triacylglycerol synthesis consequent on hepatic microsomal enzyme induction. 6. In contrast with rabbits and guinea pigs, rats injected with phenobarbital showed a decrease in serum triacylglycerol concentration in the starved state; this decrease persisted for up to 5 days after drug administration stopped, and did not occur in non-starved animals. It seems to be independent of the microsomal enzyme-inducing properties of the drug, and may be due to the action of phenobarbital at an extrahepatic site.

Animals↗

Acute myeloblastic leukemia-associated antigens: detection and clinical importance.

Antigenic compounds from the surface of leukemic myeloblasts are shed in vitro on short-term culture. Blast cells radiolabeled by lactoperoxidase iodination release soluble compounds that react immunologically with alloantisera to leukemia-associated antigens. Partially characterized soluble antigens were used to raise heteroantisera in monkeys that are selectively reactive with leukemic myeloblasts and unreactive with nonleukemic cells. Monkey heteroantisera were used to further characterize soluble leukemia antigens. Sera from patients with acute myeloblastic leukemia inhibit the reactivity of the heteroantisera, suggesting that soluble leukemic antigen is released in vivo as well.

Antibodies, Neoplasm↗

High-density lipoprotein cholesterol in male alcoholics with and without severe liver disease.

In a study of 26 male alcoholics, the subgroup without severe liver disease showed significant elevation in high-density lipoprotein cholesterol (HDL) in the immediate post-intoxication period: HDL levels decreased to control levels after one to two weeks of abstinence. Those patients with advanced liver disease failed to show this ethanol-induced rise in HDL. We were not able to correlate these observations with any variation in sex hormone levels, nutritional indices, age or quantity of alcohol intake. We concluded that ethanol consumption in alcoholics is associated with an increase in HDL levels, which is offset by the development of alcoholic liver disease.

Adult↗