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Biomedical subjects

R S Bar

Publications and source records attributed to R S Bar.

At least 55 records · Page 3Linked to original sources
PubMed1985

Receptors for insulin-like growth factor-I (IGF-I) in myocardial capillary endothelium of the intact perfused heart.

Isolated intact, beating hearts were perfused with HPLC-pure [125]-IGF-I (1 ng/ml) alone or [125]-IGF-I (1 ng/ml) plus varying concentrations of unlabeled IGF-I (10-3,000 ng/ml) or unlabeled insulin (1,000-100,000 ng/ml). After 1 min of perfusion with peptides, the hearts were rapidly fixed, sectioned and analyzed for radioautographic [125I] grain counts. Greater than 90% of [125I] grains were shown to represent intact [125I]-IGF. Maximal grain counts over capillaries occurred after perfusion with [125I]-IGF-I alone and decreased in a dose-dependent manner when unlabeled IGF-I was coperfused. Coperfusion of [125I]-IGF-I with unlabeled insulin also decreased 125I grains over capillaries but less potently than unlabeled IGF-I. EM radioautography demonstrated that [125I]-IGF-I grains were localized over capillary endothelial cells. Thus, specific IGF-I receptors are present in the capillary endothelium of the intact heart and have properties similar to IGF-I receptors in cultured capillary endothelial cells.

Adipose Tissue↗
PubMed1985

Neoplastic pathology of oncogenic osteomalacia/rickets.

Reported are two cases of oncogenic osteomalacia, each caused by a small mesenchymal tumor, with detailed assessment of the tumors by light microscopy, electron microscopy, and immunohistochemistry. One tumor was a primitive mesenchymal tumor with prominent giant cell and vascular components, and the second resembled the giant cell variant of soft parts chondroma. Osteoclast-like, multinucleated giant cells and vascularity were prominent features in both tumors. Although the literature documents a histologically heterogeneous group of tumors as causing this syndrome, most have multinucleated giant cells and/or extensive vascularity. The high incidence of these two histologic features in this group of tumors suggests that either or both may be related to the pathogenesis and/or metabolic consequences of oncogenic osteomalacia/rickets.

Adult↗
PubMed1985

Morphological alterations in cultured endothelial cells induced by arachidonic acid.

The addition of arachidonic acid (20:4), but not other fatty acids, including the structurally similar eicosapentaenoic acid (20:5), induced specific morphological changes in cultured endothelial cells derived from bovine aorta and pulmonary artery. Cells exhibited a time- and dose-dependent change from their normal, epithelioid morphology to become elongated, polygonal, and spindle-shaped. Cells isolated from aorta appeared more sensitive to these changes than those from pulmonary artery. The effect was observed as early as 12 h after exposure to 20:4, required 48 h for maximal expression, and could be reversed in 2-5 h after change to normal media. The morphological alteration was not observed in cells treated with leukotrienes or PGE2. When cells were pretreated with ibuprofen, aspirin, or indomethacin to block prostaglandin synthesis and then exposed to 20:4, the dose-response effect was shifted to the left. This increased sensitivity to 20:4 suggests either a direct effect of 20:4 on cell morphology or an indirect effect due to metabolites of 20:4 which are not dependent on the cyclooxygenase pathway.

Animals↗
PubMed1985

Sulfated glycosaminoglycans in cultured endothelial cells from capillaries and large vessels of human and bovine origin.

The [35S]glycosaminoglycans ([35S]GAG) synthesized by capillary endothelial cells were analyzed and compared to GAG synthesized by endothelial cells cultured from 4 larger vessels. Two separate cultures of endothelial cells were established from bovine fat capillaries and from 4 larger vessels of human origin (umbilical vein) and bovine origin (pulmonary artery, pulmonary vein and aorta). After incubation with 35SO4 for 72 h, the [35S]glycosaminoglycans (GAG) composition of the media, pericellular and cellular fractions of each culture were determined by selective degradation with nitrous acid, chondroitinase ABC and chondroitinase AC. All endothelial cells produced large amounts of [35S]GAG with increased proportions of heparinoids (heparan sulfate and heparin) in the cellular and pericellular fractions. Each culture showed a distinct distribution of [35S]GAG in the media, pericellular and cellular fractions with several specific differences found among the 5 cultures. The differences in GAG content were confirmed in a second group of separate cultures from each of the 5 vessels indicating that, although having several features of GAG metabolism in common, each endothelial cell culture demonstrated a characteristic complement of synthesized, secreted and cell surface-sulfated glycosaminoglycans.

Animals↗
PubMed1985

Oncogenic osteomalacia: strange tumours in strange places.

Two patients presented with hypophosphataemic osteomalacia and were subsequently found to have small tumours unusual histopathology and location causing the osteomalacia. Each tumour was found after an intensive search for occult masses. Studies of vitamin D metabolism and renal tubular function before and after surgery yielded further insight into the pathophysiology of oncogenic osteomalacia. These cases demonstrate that microscopic quantities of tumour are capable of causing the syndrome and further illustrate the high index of suspicion often necessary to locate causative tumours in patients with hypophosphataemic osteomalacia.

Adult↗
PubMed1985

Processing of cell-bound insulin by capillary and macrovascular endothelial cells in culture.

The processing of cell-bound insulin was determined in endothelial cells cultured from three large blood vessels (human umbilical vein, bovine pulmonary artery, and bovine aorta) and one microvascular source (bovine fat capillaries). Cells were exposed to monoiodinated TyrA14-insulin, the rates of dissociation of cell-bound TyrA14-insulin determined, and cell alteration of insulin assessed by gel filtration and high-performance liquid chromatography analysis. We found that 1) overall degradation rates of insulin are low for all cultured endothelial cells, 2) cell-bound insulin is rapidly processed to a nonreceptor compartment and then rapidly dissociated from all cells, primarily as biologically intact insulin, and 3) degradation of cell-bound insulin, although relatively low, does occur in endothelial cells with the least degradation by capillary cells. The presence of specific surface receptors for insulin on endothelial cells coupled with rapid cellular processing of intact insulin is consistent with a potential role for endothelial cells in either the transport of intact insulin out of the bloodstream or as a regional storage site for intact hormone.

Animals↗
PubMed1985

GIP increases insulin receptor affinity and cellular sensitivity in adipocytes.

Glucose ingestion has been previously shown to rapidly increase both the affinity of the insulin receptor and the cellular sensitivity of target tissues for insulin. We now demonstrate that gastric inhibitory polypeptide (GIP), a gastrointestinal hormone released by glucose ingestion, can mimic these effects in vitro. Incubation of rat adipocytes with GIP (10-100 ng/ml) resulted in both a displacement to the left of the insulin binding isotherm (i.e., increased receptor affinity) and potentiated insulin-mediated glucose uptake at insulin concentrations less than 1 ng/ml (i.e., increased cellular insulin sensitivity). Cholecystokinin, another gastrointestinal hormone, did not alter the insulin receptor binding characteristics or glucose uptake of the adipocytes in vitro. We suggest that GIP, a known potentiator of glucose-stimulated insulin secretion, may also modulate the effects of insulin by directly altering target tissue sensitivity to insulin.

Adipose Tissue↗
PubMed1984

Distinct receptors for IGF-I, IGF-II, and insulin are present on bovine capillary endothelial cells and large vessel endothelial cells.

Endothelial cells were cultured from bovine fat capillaries, aortae and pulmonary arteries and their interactions with 125I-IGF-I, 125I-MSA (an IGF-II), 125I-insulin and the corresponding unlabeled hormones were evaluated. Each endothelial culture showed similar binding parameters. With 125I-insulin, unlabeled insulin competed with high affinity while IGF-I and MSA were approximately 1% as potent. With 125I-MSA, MSA was greater than or equal to IGF-I in potency and insulin did not compete for binding. Using 125I-IGF-I, IGF-I was greater than or equal to MSA whereas insulin decreased 125I-IGF-I binding by up to 72%. Exposing cells to anti-insulin receptor antibodies inhibited 125I-insulin binding by greater than 90%, did not change 125I-MSA binding, while 125I-IGF-I binding was decreased by 30-44%, suggesting overlapping antigenic determinants between IGF-I and insulin receptors that were not present on MSA receptors. We conclude that cultured capillary and large vessel endothelial cells have distinct receptors for insulin, IGF-I and MSA (IGF-II).

Animals↗
PubMed1984

Effects of membrane lipid unsaturation on the interactions of insulin and multiplication stimulating activity with endothelial cells.

Modification of plasma membrane fatty acyl composition has resulted in major changes in insulin binding and insulin action in several cell types. In the present study, endothelial cells, which in vivo are directly bathed by the changing fatty acid and insulin environment of the bloodstream, were grown in media enriched in specific saturated, monounsaturated and polyunsaturated fatty acids. These media conditions resulted in major and specific alteration in fatty acyl unsaturation of both neutral lipids and phospholipids of the endothelial cells. Despite the extensive fatty acyl changes, the lipid-modified cells demonstrated no change in the binding of insulin or the insulin-like growth factor, multiplication stimulating activity, and little alteration in insulin-induced down-regulation of the insulin receptor, or in cell processing of insulin. We suggest that the insulin receptor of the endothelial cell responds in a different manner than other cell types to similar alterations of membrane fatty acyl composition.

Animals↗
PubMed1984

Multiplication-stimulating activity (MSA) stimulates proteoglycan synthesis in cultured endothelial cells.

Cultured endothelial cells have previously been shown to have specific binding sites for certain insulin-like growth factors (IGFs) and insulin. In the present study, the IGF, Multiplication Stimulating Activity (MSA), at concentrations of 100-1000 ng/ml, stimulated 35SO4 incorporation into proteoglycans by endothelial cells cultured from bovine pulmonary arteries. The stimulatory effect on proteoglycan synthesis was not accompanied by changes in cell number, total protein synthesis, nor collagen synthesis and was not mimicked by insulin. These findings suggest that MSA specifically stimulated accumulation of proteoglycans in the cultured endothelial cells, with the effect mediated through an IGF receptor.

Animals↗
PubMed1984

Rapid transport of biologically intact insulin through cultured endothelial cells.

Mono A14-[125I]-iodoinsulin was incubated with cultured endothelial cells derived from bovine pulmonary arteries at physiologic conditions. The processing of the cell-bound A14-[125I]-iodoinsulin was evaluated by trichloroacetic acid precipitation, gel filtration and high performance liquid chromatography. In contrast to insulin processing in many other cell types, approximately 95% of cell bound insulin was dissociated from the cells in less than 15 minutes, and biologically intact insulin rapidly passed through the endothelial cells. The unique location of endothelial cells coupled with the ability of rapid transport of intact insulin are consistent with an endothelial role for either the transport of insulin out of the bloodstream or as an extra-pancreatic storage area for insulin.

Animals↗
PubMed1983

Factors that control insulin action at the receptor.

The binding of insulin to its plasma membrane receptors is an important component of insulin action at the cellular level. Insulin binding is altered in a number of clinical disease states in humans, and several specific regulators of the receptor have been identified. Recent in vitro studies of receptor regulators have furthered our understanding of the interaction of insulin with its receptors and also increased our awareness of the complexity of this interaction. The importance of the plasma membrane environment around the receptor, the potential importance of receptor microaggregation to information transfer, and the coupling of receptor binding to insulin action are reviewed.

Autoantibodies↗
PubMed1983

Insulin binding to microvascular endothelium of intact heart: a kinetic and morphometric analysis.

We have studied insulin binding to blood vessels of the intact, beating heart. The beating hearts were perfused with [125I]iodoinsulin (3 X 10(-10) M) followed by perfusion with unlabeled insulin. The unlabeled insulin displaced the bound [125I]iodoinsulin in direct proportion to the concentration of the unlabeled hormone. Perfusion with unlabeled insulin at 10(-11) M elicited a significant displacement of [125I]iodoinsulin, with a maximal effect at 10(-6) M. Unlabeled proinsulin also displaced [125I]iodoinsulin in a dose-dependent manner, being 1% as potent as insulin. Perfusion with unrelated peptides had no effect. Radioautographic counting of 125I grains indicated that greater than 95% of the grain counts over blood vessels were within the microvessels. When [125I]iodoinsulin perfusion was followed by perfusion with unlabeled insulin at 10(-6) M, there was a 50% decrease in grain counts over the microvessels (versus perfusion with [125I]iodoinsulin alone); with coperfusion of [125I]iodoinsulin and 10(-6) M unlabeled insulin, an 80% decrease in grain counts occurred. Electron microscopic radioautography indicated that the 125I grains were associated with the vascular endothelial cells. We conclude that specific insulin receptors are present on endothelial cells of microvessels in the intact heart.

Animals↗
PubMed1982

Insulin decreases phosphoenolpyruvate carboxykinase (GTP) mRNA activity by a receptor-mediated process.

The mRNA that codes for phosphoenolpyruvate carboxykinase accounts for approximately 0.2% of the protein synthesized in H4IIEC3 hepatoma cells maintained for 24 h in serum-free medium containing N6,O2'-dibutyryl cAMP and theophylline. This value decreases to 0.04% within 3 h after the addition of insulin. Maximal effects are produced by 10(-10) M insulin, and half-maximal deinduction of both the relative rate of synthesis of P-enolpyruvate carboxykinase and mRNA coding for P-enolpyruvate carboxykinase activity occurs at approximately 2 X 10(-12) M insulin. Porcine proinsulin is 4% as potent as porcine insulin since half-maximal deinduction of mRNA coding for P-enolpyruvate carboxykinase occurs at 5 X 10(-11) M. The concentration of proinsulin required to inhibit 125I-insulin binding by 50% is 2 X 10(-7) M, as compared to 6 X 10(-9) M for insulin; thus, the decreased sensitivity of this deinduction to proinsulin parallels the decreased binding affinity H4IIEC3 cells have for proinsulin as compared to insulin. These data indicate that insulin regulates P-enolpyruvate carboxykinase synthesis through a receptor-mediated process, that the effect occurs when less than 2% of the insulin receptors are occupied, and that this effect is exerted prior to the level of mRNA translation.

Animals↗
PubMed1982

Hyperthyroidism caused by inappropriate thyrotropin hypersecretion: studies in patients with selective pituitary resistance to thyroid hormone.

We have identified the condition of thyrotropin (thyroid-stimulating hormone [TSH])-induced hyperthyroidism secondary to selective pituitary insensitivity to thyroid hormone in three patients. Each patient was clinically hyperthyroid, with elevated serum levels of thyroxine (T4) and triiodothyronine (T3) and detectable levels of serum TSH before therapy. After therapy each patient had notably elevated TSH levels at a time that peripheral levels of thyroid hormones were in the hyperthyroid range. Before and after therapy, serum levels of TSH were suppressed by therapy with liothyronine sodium and were stimulated by protirelin (thyrotropin-releasing hormone) both before and after liothyronine and dexamethasone treatment. Dexamethasone therapy decreased the levels of TSH, protirelin-stimulated TSH, and circulating T4 and T3. Serum levels of glycoprotein alpha-subunit were 0.6 to 2.4 ng/ml, values considerably lower than found in patients with TSH-secreting pituitary tumors. We suggest that the frequency of TSH-induced hyperthyroidism secondary to pituitary insensitivity to thyroid hormone may be higher than presently indicated in the medical literature.

Adolescent↗
PubMed1982

Interactions of multiplication-stimulating activity with bovine endothelium: comparative studies in primary, passaged, and cloned cultures from the pulmonary and systemic circulations.

Endothelial cells were prepared from adult bovine pulmonary and systemic vessels and maintained as primary cultures, passaged cultures, and cloned cell strains. All cultures were shown to contain endothelial cells on the basis of several endothelial-specific and endothelial-associated traits. Both primary and passaged cells demonstrated specific receptors for the insulin-like growth factor, multiplication-stimulating activity (MSA). [125I]Iodo-MSA binding was greatest in cells derived from aortas, least in pulmonary venous cells, and intermediate in pulmonary arterial cells. When compared to MSA receptors on primary endothelial cell cultures derived from human umbilical veins or arteries, the bovine cells bound 4-10 times more MSA per cell. In all bovine cells, insulin competed weakly or not at all with [125I]iodo-MSA binding. The presence of MSA receptors on primary and passaged cells from five different vascular sources (three bovine and two human) suggests that receptors for the insulin-like growth factors may be an intrinsic component of the vascular endothelium.

Animals↗