Dissociation of obesity,hypercholesterolemia and diabetes from atherosclerosis in ob/ob mice

Summary Genetically obese, diabetic and hypercholesterolemic C57BL/6J-ob/ob mice were placed on Purina Laboratory Chow containing 2% cholesterol for up to 4 months. They developed higher plasma cholesterol levels and accumulated an increased quantity of cholesterol in the liver but failed to develop atherosclerotic lesions in the aorta as would be expected in an obese, diabetic and hypercholesterolemic human adult.Acknowledgments. We wish to thank Mr. Willis M. Overton for his excellent technical assistance.     

Histochemical demonstration of reductase activity in the nucleus of chicken erythrocyte

Zusammenfassung Dehydrase- und Succinodehydraseaktivität werden mittels histochemischer Methode durch Tetrazoliumsalze in Kernen der Hühnererythrocyten dargestellt. Das Vorhandensein der Formazankristalle beschränkt sich vor allem auf die innere Oberfläche der Kernmembrane. Die Bedeutung dieser Entdeckungen im Zusammenhang mit dem Succinodehydrase-Mitochondrien-Verhältnis wird kurz besprochen.

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This work was supported in part by a Research Grant from the National Cancer Institute, U. S. Department of Health, Education and Welfare, and in part by an Institutional Grant to the Detroit Institute of Cancer Research from the American Cancer Society.     

Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli

The recognition and phagocytosis of microbes by macrophages is a principal aspect of innate immunity that is conserved from insects to humans. Drosophila melanogaster has circulating macrophages that phagocytose microbes similarly to mammalian macrophages, suggesting that insect macrophages can be used as a model to study cell-mediated innate immunity. We devised a double-stranded RNA interference-based screen in macrophage-like Drosophila S2 cells, and have defined 34 gene products involved in phagocytosis. These include proteins that participate in haemocyte development, vesicle transport, actin cytoskeleton regulation and a cell surface receptor. This receptor, Peptidoglycan recognition protein LC (PGRP-LC), is involved in phagocytosis of Gram-negative but not Gram-positive bacteria. Drosophila humoral immunity also distinguishes between Gram-negative and Gram-positive bacteria through the Imd and Toll pathways, respectively; however, a receptor for the Imd pathway has not been identified. Here we show that PGRP-LC is important for antibacterial peptide synthesis induced by Escherichia coli both in vitro and in vivo. Furthermore, totem mutants, which fail to express PGRP-LC, are susceptible to Gram-negative (E. coli), but not Gram-positive, bacterial infection. Our results demonstrate that PGRP-LC is an essential component for recognition and signalling of Gram-negative bacteria. Furthermore, this functional genomic approach is likely to have applications beyond phagocytosis.     

Control of enzyme secretion by non-cholinergic, non-adrenergic nerves in guinea pig pancreas

Depolarization of pancreatic cells by exposure to high potassium solutions is associated with release of amylase. In the guinea pig, but not the mouse or cat, this Ca-dependent amylase secretion is resistant to atropine blockade, thus Scheele and Haymovits concluded that the enzyme secretion evoked by K depolarization does not involve release of transmitter from intrapancreatic nerves but is a consequence of Ca uptake into acinar cells mediated by the membrane depolarization. This hypothesis is inconsistent with current concepts of stimulus--secretion coupling in electrically non-excitable cells. The observation of Scheele and Haymovits could, however, also be explained by the release of a non-cholinergic, secretomotor transmitter as a consequence of the depolarization of intrapancreatic nerves. By adapting the technique of electrical field stimulation of isolated pancreatic segments to our studies of amylase secretion, we have now been able to demonstrate both cholinergic and non-cholinergic, non-adrenergic secretomotor nerves in the guinea pig pancreas. Excitation of the non-cholinergic nerves stimulates amylase secretion by a different intracellular coupling mechanism from that activated by cholinergic nerves or by peptides belonging to the cholecystokinin, gastrin or bombesin families.