Type 1 diabetes (T1D) is an autoimmune disease in which immune cells, notably T-lymphocytes target and kill the insulin-secreting pancreatic beta cells. Elevated blood sugar levels and full blown diabetes result once a large enough fraction of these beta cells have been destroyed. Recent investigation of T1D in animals, the non-obese diabetic (NOD) mice, has revealed large cyclic fluctuations i...

Phosphodiesterase (PDE)4 inhibition attenuates neutrophilic inflammation in chronic obstructive pulmonary disease. The objective of the present study was to examine the efficacy and mechanism by which PDE4 inhibition blocks adhesion of beta(2)-integrin to an endothelial counterligand. Neutrophils (polymorphonuclear leukocytes (PMNs)) were isolated from humans receiving no medication. Adhesion w...

Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer in smokers and non-smokers that arises in most cases from small airway epithelial cells. PAC has a high mortality due to its aggressive behavior and resistance to cancer therapeutics. We have shown previously that the proliferation of human PAC cells NCI-H322 and immortalized human small airway epithelial cells HPL1D is stimulate...

Vasoactive intestinal peptide (VIP) stimulated cyclic AMP production in rat peritoneal macrophages. The stimulatory effect of VIP was dependent on time, temperature and cell concentration, and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). At 15 degrees C, the response occurred in the 0.1-1000 nM range of VIP concentrations. Half maximal stimulation of ce...

A protein kinase, which was produced from its proenzyme occurring in rat brain upon limited proteolysis by a Ca2+-dependent protease from the same tissue (Inoue, M., Kishimoto, A., Takai, Y., and Nishizlka, Y. (1977) J. Biol. Chem. 252, 7610-7616, was capable of phosphorylating alpha and beta subunits of rabbit skeletal muscle glycogen phosphorylase kinase, resulting in a marked enhancement of ...

In blood-perfused isolated canine atrium preparations, single injections of dibutyryl cyclic AMP at a dose range of 1 to 30 mg were made into the cannulated sinus node artery. At doses above 3 mg, dibutyryl cyclic AMP induced a biphasic chronotropic and inotropic response; there was a slight and rapid negative chronotropic and inotropic response, followed by a long-lasting positive chronotropic...

Part of this work was previously reported at the symposium "Diabetes Research Today," held in Capri, Italy, 13-15 April 1976, and published in Symposia Medica Hoechst 12, 223240 (1976), Friedrich-Karl Schattauer-Verlag GmbH, Stuttgart, West Germany. Dr. Cerasi's present address is the Department of Endocrinology and Metabolism, the Hebrew University Hadassah Medical School, Jerusalem, Israel. R...

We recently reported that cyclic AMP (cAMP) specifically inhibits lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1 beta) transcription initiation in astrocytic cells but enhances the LPS induction of IL-1 beta in monocytic cells. The purpose of this study was to determine how cAMP differentially regulates LPS-induced IL-1 beta transcription in these two cell types. Two essential compon...

1. The airway and metabolic responses to an intravenous beta 2-agonist salbutamol have been investigated in normal subjects before and after chronic administration of inhaled salbutamol, 1600 micrograms daily for 2 weeks. 2. Before chronic inhalation of salbutamol there was a dose-dependent increase in specific airway conductance after intravenous salbutamol in cumulative doses from 25 to 300 m...