Insulin activation of phosphatidylinositol 3-kinase in human skeletal muscle in vivo

Hickey, Matthew S., Charles J. Tanner, D. Sean O'Neill,Lydia J. Morgan, G. Lynis Dohm, and Joseph A. Houmard. Insulin activation of phosphatidylinositol 3-kinase in human skeletal muscle invivo. J. Appl. Physiol. 83(3):718-722, 1997.The purpose of this investigation was to determinewhether insulin-stimulated phosphatidylinositol 3-kinase (PI3-kinase)activity is detectable in needle biopsies of human skeletal muscle.Sixteen healthy nonobese males matched for age, percent fat, fastinginsulin, and fasting glucose participated in one of two experimentalprotocols. During an intravenous glucose tolerance test (IVGTT)protocol, insulin-stimulated PI3-kinase activity was determined frompercutaneous needle biopsies at 2, 5, and 15 min post-insulinadministration (0.025 U/kg). In the second group, a 2-h, 100 mU · m² · min¹euglycemic hyperinsulinemic clamp was performed, and biopsies wereobtained at 15, 60, and 120 min after insulin infusion was begun.Insulin stimulated PI3-kinase activity by 1.6 ± 0.2-, 2.2 ± 0.3-, and 2.2 ± 0.4-fold at 2, 5, and 15 min, respectively, duringthe IVGTT. During the clamp protocol, PI3-kinase was elevated by 5.3 ± 1.3-, 8.0 ± 2.6-, and 2.7 ± 1.4-fold abovebasal at 15, 60, and 120 min, respectively. Insulin-stimulatedPI3-kinase activity at 15 min post-insulin administration wassignificantly greater during the clamp protocol vs. the IVGTT(P < 0.05). These observations suggest that insulin-stimulated PI3-kinase activity is detectable inneedle biopsies of human skeletal muscle, and furthermore, that theeuglycemic, hyperinsulinemic clamp protocol may be a useful tool toassess insulin signaling in vivo.

     

Characterization of two new facultative methanotrophs

Two new facultative methane-oxidizing bacteria have been isolated from lake water enrichments. The organisms have been characterized in terms of colony types, growth characteristics, the guanine plus cytosine content of their deoxyribonucleic acid, thin sections, oxidation rates, and carbon assimilation pathways. Methane-grown cells of both organisms contained intracytoplasmic membranes similar to those described as type II in other methanotrophic bacteria. Neither organism had such membranes when grown heterotrophically. Both organisms assimilated methane by way of the isocitrate lyase-negative serine pathway for formaldehyde incorporation. The enzymes of this pathway were high in specific activity in cells grown on methane and were at low levels in cells grown either on heterotrophic substrates or on heterotrophic substrates plus methane. It is proposed that both organisms be classified in the genus Methylobacterium as two new species, Methylobacterium ethanolicum and Methylobacterium hypolimneticum.     

Irgasan-induced pigmentation in Serratia marcescens and Pseudomonas aeruginosa.

Two irgasan-resistant micro-organisms (P. aeruginosa and S. marcescens) were used to study the effects of various antibiotic and chemotherapeutic agents on pigment production. These agents included streptomycin, thallium acetate, polymyxin B, hexachlorophene, irgasan, prodigiosin and DMSO (dimethyl sulphoxide). Only irgasan, compared to other drugs and membrane-active agents showed the unique property of inducing pigmentation in both P. aeruginosa and S. marcescens, i.e. prodigiosin in S. marcescens and pyocyanin in P. aeruginosa.     

Idiotype-specific transplantation resistance to MOPC-315: abrogation by post-immunization thymectomy.

The idiotype-specific myeloma transplantation resistance induced in BALB/c mice by immunization with the DNP-binding IgAlambda2 protein produced by plasmacytoma MOPC-315 is ablated by post-immunization thymectomy. Sham-thymectomy has no effect. The ablative effect of thymectomy is observed is observed in mice challenged subcutaneously with MOPC-315 cells either 3 days after thymectomy, or after a rest period of 44 days after thymectomy. These observations suggest that short-lived, thymic-dependent suppressive factors may play a role in the idiotype-specific myeloma graft resistance.     

Adriamycin extravasation.

Adriamycin extravasation creates a severe tissue necrosis which is unusual, because it may not appear until several weeks later, and may continue to worsen for several months. As soon as the progressive nature of the tissue necrosis is established, we recommend that an early wide excision be performed in an attempt to remove the necrotic area and the surrounding tissues containing the extravasated drugs--before it has had an opportunity to diffuse even further. Adequate debridement requires removal of any adjacent tissue that is indurated, reddened, edematous, or pale. Skin grafts take poorly if there are small amounts of Adriamycin left in the tissue of the recipient site. Synergistic effects with radiotherapy, and continued systemic Adriamycin therapy, can aggravate or recall necrosis. The administration of more dilute solutions of Adriamycin may decrease the hazard of extravasation necrosis.     

Fibrinolytic activator activity in human neoplasms

The results of this study suggest that many malignant tumors contain low levels of fibrinolytic activator activity. Evidence is presented to suggest that this low activity may be due to the presence of an inhibitor of fibrinolysis. The presence or absence of measurable fibrinolytic activator activity, and/or inhibitor in neoplastic growths may enable one to predict the probability of viable metastases to a distant site.