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Biomedical subjects

L Orci

Publications and source records attributed to L Orci.

At least 397 records · Page 22Linked to original sources

Human islet cell tumor storing pancreatic polypeptide: a light and electron microscopic study.

A 45-year-old man was operated for surgical treatment of a long-standing peptic ulcer disease and upon inspection of the pancreas for suspected Zollinger-Ellison syndrome, tumor nodules were found in this organ. The tumor tissue examined by immunofluorescence showed specific staining only after incubation with anti-pancreatic polypeptide. Negative results were obtained with antisera directed against insulin, pancreatic glucagon, somatostatin, GLI, VIP, secretin, and gastrin. Examination of the tissue by electron microscopy revealed a homogeneous population of small granule-containing cells. This case, therefore, illustrates a tumor composed of one single hormone-producing cell type and allows definition of the ultrastructural features of human pancreatic polypeptide-containing cells.

Fluorescent Antibody Technique↗

Alteration of islet cell populations in spontaneously diabetic mice.

Endocrine-cell populations in the islets of Langerhans of mutant mice with a severe hypoinsulinemic diabetes (ob/ob or db/db on the C57BL/KsJ background) or with a mild hyperinsulinemic diabetes (ob/ob or db/db on the C57BL/6J background) were studied quantitatively by immunofluorescence and morphometry. In severely diabetic mice, islets presented a reduced proportion of insulin containing cells but increased glucagon-, somatostatin-, and pancreatic polypeptide (PP)-containing cells, as compared with islets of control (+/+) mice. An inverse change was observed in islets of mildly diabetic mice: islets were hypertrophic and composed mostly of insulin-containing cells, with decreased proportions of glucagon-, somatostatin-, and PP-containing cells. In both types of diabetic syndromes, the changes in cell populations induced a qualitative alteration of cellular interrelationships in the affected islets.

Animals↗

Freeze-fracture of membrane fusions in phagocytosing polymorphonuclear leukocytes.

Freeze-fracture of rabbit polymorphonuclear leukocytes in the process of phagocytosing yeast cells shows changes in storage granule and phagosome membranes essentially similar to those described in mammalian secretroy cells during exocytosis. These changes consist of the clearing of intramembrane particle from limited zones of the fusing granule and phagosome membranes. After the completion of fusion, which leads to the incorporation of storage granule membrane into the phagosome membrane, particle-free patches are no longer visible, but the phagosome membrane contains some loose aggregates of particles. These data suggest that intracellular membrane fusion in polymorphonuclear leukocytes occurs through interaction of protein-depleted areas of the involved membranes.

Animals↗

Somatostatin: widespread abnormality in tissues of spontaneously diabetic mice.

Diabetic mice of the C57BL/6J obob and C57BL/Ks dbdb strains show a reduction in pancreatic somatostatin concentration accompanied in the obob strain by a striking decrease in the number of somatostatin-containing cells in the islets. Somatostatin concentration is also decreased in the stomach but increased in the hypothalamus. These findings suggest different control mechanisms for somatostatin in the hypothalamus compared to the gut and pancreas and exclude a primary genetic abnormality of somatostatin cells in the mutants.

Animals↗

Histochemical and ultrastructural identification of neurotensin cells in the dog ileum.

In the dog ileum, neurotensin cells stained with immunofluorescence or immunoperoxidase proved distinct from argentaffin (EC) cells, glucagon immunoreactive (GLI) cells and pancreatic peptide immunoreactive (PP) cells. Neurotensin cells showed various degrees of reactivity with Grimelius' silver. With electron microscopy, besides EC cells, large granule cells with a thin peripheral rim of Grimelius-reactivity (L cells) and large granule cells with variable Grimelius-reactivity of the core (N cells) were found. On distributive grounds, L cells were identified with GLI cells and N cells were interpreted as neurotensin cells.

Animals↗

Pancreatic polypeptide: a possible role in the regulation of food intake in the mouse. Hypothesis.

Pancreatic polypeptide (PP) is a recently identified hormone produced by pancreatic endocrine cells. The islets of genetically obese mice (ob/ob, C57 BL/6J), which are suspected to lack a circulating satiety factor, contain relatively few of the PP-producing cells. Administration of bovine pancreatic polypeptide (bPP) reduces food intake and suppresses body weight gain in the hyperphagic obese mice. It is postulated that PP participates in the regulation of food intake in a manner as yet undefined.

Animals↗

Endocrine cells in oxyntic mucosa of a dog 5 years after pancreatectomy.

Immunofluorescence shows that the oxyntic mucosa of a dog depancreatized for 5 years and having a poorly-controlled diabetes has more glucagon- and somatostatin-containing cells than the mucosa of a control dog. At the ultrastructural level, 4 endocrine cell types are identified: A-, A-like, D- and enterochromaffin-like (ECL) cells, with increased numbers of A-, A-like and D-cells in gastric glands of the depancreatized dog, together with a higher concentration of immunoreactive glucagon in the gastric mucosa. The increase in A-, A-like and D-cells is compatible with: a) a change induced by the diabetic state itself; b) a hyperplasia secondary to the loss of corresponding pancreatic cells. At any rate, the fact that A-, A-like and D-cells increase parallely may indicate that these three cell types are functionally related one with another.

Animals↗

Pancreatic immunoreactive somatostatin release.

The location of the somatostatin-containing D-cells of the pancreatic islets between the A- and B-cells suggests that their function might be to inhibit insulin and/or glucagon secretion by these neighboring cells. To determine if insulin and/or glucagon, in concentrations that might be present in the extracellular space surrounding the D-cells, stimulate immunoreactive somatostatin (IRS) release, we perfused 10 microng of glucagon or 10 milliunits of insulin per ml in 11 isolated dog pancreases, for 40 min in seven experiments and for 100 min in four experiments. In eight of the nine experiments in which glucagon was perfused, a prompt and significant rise in mean IRS release, ranging from 71 to 128% above the control level, was observed. In the eight experiments in which insulin was perfused. IRS did not increase during the first 40 min; in the two 100-min insulin experiments, it did rise during the final 50 min, however. To determine the effect of an A- and B-cell secretogogue on IRS release, we perfused 20 mM arginine for 60 min in six experiments. In all, IRS rose within 3 min and reached a level 71-465% above the control, remaining significantly elevated throughout the perfusion, while glucagon and insulin rose to peak levels at 2 min and then declined somewhat despite continuing arginine perfusion. The results indicate that perfusion of the normal dog pancreas with high doses of glucagon or arginine is accompanied by a prompt increase in IRS release and are compatible with a local feedback circuit involving A- and D-cells. Insulin appears not to augment IRS release, at least not promptly, but IRS stimulated by local endogenous glucagon could inhibit the B-cell response to locally secreted glucagon and thereby influence the composition of the insulin/glucagon secretion mixture.

Animals↗

Morphological changes of the adipose cell plasma membrane during lipolysis.

Morphological changes of the plasma membrane in the white adipose cell associated with lipid mobilization were assessed qualitatively and quantitatively on freeze-fracture replicas of epididymal adipose tissue from fasted and from streptozotocin-diabetic rats. The number of plasma membrane invaginations and intramembranous particles were evaluated per square micrometer of membrane and per entire adipocyte. These two determinations show that the number per square micrometer (local concentration) of both structural features progressively increases with the duration of diabetes and fasting, while that at the same time their number per entire cell (total content) remains unchanged. These data thus show: (a) a reorganization of the adipose cell plasma membrane during lipolysis; and (b) that this reorganization can be detected only by determining the concentration and the total content of the structural features of the membrane involved.

Adipose Tissue↗

Membrane particle changes attending the acrosome reaction in guinea pig spermatozoa.

To examine the freeze-fracture appearance of membrane alterations accompanying the preparation of sperm membranes for fusions-the first preparatory stage occurring before physiological release of the acrosomal content, the second afterward-we induced the acrosome reaction in capacitated guinea pig spermatozoa by adding calcium to the mixture. The most common features observed before fusion of the acrosomal and plasma membranes were the deletion of fibrillar intramembranous particles from the E-fracture faces of both membranes, and the clearance of globular particles from the P face of the plasma membrane-events taking place near the terminus of the equatorial segment. Large particles, >12nm, remained not far from the cleared E-face patches. The P face of the outer acrosomal membrane is virtually clear from the outset. In addition, when fusion was completed, occasional double lines of large particles transiently embossed the P face of the plasma membrane (postacrosomal) side of the fusion zone. Behind the line of fusion, another series of particle-cleared foci emerged. We interpreted these postfusion membrane clearances as a second adaptation for sperm-egg interaction. Induction of the acrosome reaction in media containing phosphatidylcholine liposomes resulted in their apparent attachment, incorporation, or exchange in both the originally and secondarily cleared regions. Our observations support the concepts that membranes become receptive to union at particle- deficient interfaces, and that the physiologically created barren areas in freeze-fracture replicas may herald incipient membrane fusion.

Acrosome↗

Freeze-fracture of membrane fusions during exocytosis in pancreatic B-cells.

To examine the freeze-fracture appearance of membrane alterations at sites of exocytosis in mammalian cells, we studied the secretory granule and plasma membrane of rat pancreatic B-cells during glucose-stimulated insulin secretion. Constant features observed were the scarcity of particles in secretory-granule P-fracture faces and the almost total clearance of intramembranous particles in P-and E fracture faces of the plasma membrane in areas of close apposition of these two membranes preceding fusion; also observed was the temporary persistence of particle-cleared regions after the fusion was completed. Our observations thus support the concept that membranes fuse at sites of closely apposed, particle-free regions and that the physiologically created clear areas found in freeze-fracture replicas of the plasma membrane are the hallmarks of incipient or recent membrane fusion.

Animals↗

The effects of anoxia on the morphology and composite metabolism of the intact aortic intima-media preparation.

Paired samples of an intact rabbit aortic intima-media preparation were incubated for short periods under aerobic or anoxic conditions in Krebsbicarbonate buffer containing 6% albumin and 5 mM glucose. During aerobic incubation for as long as 1 h the preparation retained an electron microscopic (EM) appearance similar to that of tissue fixed in situ, and scanning EM confirmed the presence of an uninterrupted endothelial surface. After 2.5 min of anoxia there was widespread endothelial swelling, but the alterations in the EM appearance of these cells were not striking and did not progress during a subsequent 30 min aerobic incubation in fresh medium. After 10 min of anoxia there were marked and widespread alterations in endothelial cell structure, including loss of cell integrity, and numerous discrete interruptions in the endothelium were consistently observed on both transmission and scanning EM. After a subsequent 30 min aerobic incubation in fresh buffer, a major fraction of the luminal surface was denuded of endothelium. The aortic vascular smooth muscle cells did not exhibit evidence of irreversible anoxic injury after 2.5 or 10 min of anoxia or after subsequent aerobic incubation for 30 min. Exposure to anoxia for 10 min induced persistent alterations in the composite metabolism of the preparation during subsequent aerobic incubation in fresh medium; O(2) uptake was reduced, and the fraction of the glucose uptake that was accounted for by lactate production increased approximately 100%. The observations suggest that aortic endothelial cells are dependent upon respiration for the preservation of normal ultrastructure and cell integrity, and probably derive the major fraction of their energy requirements from reactions linked to respiration. Under the conditions employed in these experiments, short periods of anoxia did not induce EM evidence of irreversible anoxic injury in aortic vascular smooth muscle cells; this negative result is not incompatible with other data suggesting that these cells normally derive the major fraction of their energy requirements from respiration. Aortic intima-media does not exhibit a high rate of aerobic glycolysis under aerobic conditions which preserve a normal EM appearance of the preparation, but this pattern of metabolism can be induced by prior anoxic exposure.

Aerobiosis↗