Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas.

We investigated the influence of interferons alpha, beta, and gamma (IFN-alpha, -beta, and -gamma) on the production of basic fibroblast growth factor (bFGF) by human renal carcinoma cells. The human renal carcinoma cell metastatic line SN12PM6 was established in culture from a lung metastasis and SN12PM6-resistant cells were selected in vitro for resistance to the antiproliferative effects of IFN-alpha or IFN-beta. IFN-alpha and IFN-beta, but not IFN-gamma, down-regulated the expression of bFGF at the mRNA and protein levels by a mechanism independent of their antiproliferative effects. Down-regulation of bFGF required a long exposure (> 4 days) of cells to low concentrations (> 10 units/ml) of IFN-alpha or IFN-beta. The withdrawal of IFN-alpha or IFN-beta from the medium permitted SN12PM6-resistant cells to resume production of bFGF. The incubation of human bladder, prostate, colon, and breast carcinoma cells with noncytostatic concentrations of IFN-alpha or IFN-beta also produced down-regulation of bFGF production.

Basic workweek of federal firefighters : hearing before the Subcommittee on Human Resources of the Committee on Post Office and Civil Service, House of Representatives, Ninety-sixth Congress, first session, on H.R. 2748 ... September 14, 1979.

"Serial no. 96-113."

A letter to Sir William Pulteney, bart., representative in Parliament for the borough of Shrewsbury : containing some observations on the Bill for the better support and maintenance of the poor, presented to the House of Commons by the Right Hon. William Pitt /

Goldsmiths'-Kress no. 17133.

Logic, or, The right use of reason in the enquiry after truth : with a variety of rules to guard against error in the affairs of religion and human life as well as in the sciences /

Mode of access: Internet.

Logic; or, the right use of reason in the enquiry after truth: with a variety of rules to guard against error, in the affairs of religion and human life, as well as in the sciences.

Mode of access: Internet.

Hand receipt covering contents of components of end item (COEI), basic issue items (BII), and additional authorization list (AAL) for 2-1/2 ton, 6X6, M44A1 and M44A2 series trucks (multifuel) : truck, cargo: M35A1, M35A2, M35A2C, M36A2; truck, tank, fuel: M49A1C, M49A2C; truck, tank water: M50A1, M50A2, M50A3; truck van, shop: M109A2, M109A3; truck, repair shop: M185A2, M185A3; truck, tractor: M275A1, M275A2; truck, dump: M342A2; truck, maintenance, pipeline construction: M756A2; truck, maintenance, earth boring and polesetting: M764.

"This manual supersedes TM 9-2320-209-20-2-HR, 8 March 1979"--P. i.

Hand receipt covering contents of components of end item (COEI), basic issue items (BII), and additional authorization list (AAL) for truck, telephone maintenance, utility, C/S, 36,000 GVW, 6x4, W/WN, W/E, M876 (NSN 2320-00-000-0114).

"June 1984."

Organizational, DS, GS, and depot maintenance manual : crane-shovel, basic unit, truck mounted, 20 ton, 3/4 cu. yd., gasoline engine, 6x6 (American Hoist and Derrick models) model 2360 (non-winterized) FSB 3810-989-0505, model W2360 (winterized) FSN 3810-989-0506.

"December 1974."

Operator and organizational maintenance manual : crane-shovel, basic unit, crawler mounted, 40 ton, 2 cu yd, diesel driven (w/Harnischfeger engine model 687C-18-ES) ... FSN 3810-786-5200.

"March 1969."

Hand receipt manual covering system components of end item (COEI), basic issue items (BII), and additional authorization list (AAL) for CHAPARRAL M48A2 Air Defense Guided Missile System, AN/TSM-95A organizational maintenance shop set, and AN/TSM-96A support maintenance shop set.

"December 1984."

Hand receipt covering contents of components of end items (COEI), basic issue items (BII), and additional authorization list (AAL) for truck, cargo, 1 1/4 ton, 4 x 4, M880 (2320-00-579-8942)...; truck, cargo, 1 1/4 ton, 4 x 2, M890 (2320-00-579-8991)...; truck, ambulance, 1 1/4 ton, 4 x 2, M886 (2310-00-579-9078); truck, ambulance, 1 1/4 ton, 4 x 4, M893 (2310-00-125-5679); truck, telephone maintenance, tactical, 1 1/4 ton, 4 x 4, M888 (2320-01-044-0333).

"May 1983."

Distinguished successful Americans of our day; containing biographies of prominent Americans now living, noteworthy as having achieved success in their chosen avocations in the various civil, military, educational, religious, industrial, commercial and other lines of human effort--men of thought and men of action who have been effective in the establishment and maintenance of our commonwealth, prominent citizens in all walks of life who are really the founders, makers and builders of our great republic as manifested in America's great institutions of finance, commerce and trade, and its unparalleled progress in education, literature, art, science, and in the development of our nation in all lines of human endeavor.

Mode of access: Internet.

Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart

Objective: This study investigated signaling pathways that may contribute to the potent positive inotropic effect of human urotensin-II (hU-II) in human isolated right atrial trabeculae obtained from patients with coronary artery disease. Methods: Trabeculae were set up in tissue baths and stimulated to contract at 1 Hz. Tissues were incubated with 20 nM hU-II with or without phorbol 12-myristate 13-acetate (PMA, 10 muM) to desensitize PKC, the PKC inhibitor chelerythrine (10 muM), 10 muM 4alpha-phorbol that does not desensitize PKC, the myosin light chain kinase inhibitor wortmannin (50 nM, 10 muM), or the Rho kinase inhibitor Y-27632 (0.1 - 10 muM). Activated RhoA was determined by affinity immunoprecipitation, and phosphorylation of signaling proteins was determined by SDS-PAGE. Results: hU-II caused a potent positive inotropic response in atrial trabeculae, and this was concomitant with increased phosphorylation of regulatory myosin light chain (MLC-2, 1.8 +/- 0.4-fold, P < 0.05, n = 6) and PKCalpha/betaII (1.4 +/- 0.2-fold compared to non-stimulated controls, P < 0.05, n = 7). Pretreatment of tissues with PMA caused a marked reduction in the inotropic effect of hU-II, but did not affect hU-II-mediated phosphorylation of MLC-2. The inotropic response was inhibited by chelerythrine, but not 4alpha-phorbol or wortmannin. Although Y-27632 also reduced the positive inotropic response to hU-II, this was associated with a marked reduction in basal force of contraction. RhoA. GTP was immunoprecipitated in tissues pretreated with or without hU-II, with findings showing no detectable activation of RhoA in the agonist stimulated tissues. Conclusions: The findings indicated that hU-II increased force of contraction in human heart via a PKC-dependent mechanism and increased phosphorylation of MLC-2, although this was independent of PKC. The positive inotropic effect was independent of myosin light chain kinase and RhoA-Rho kinase signaling pathways. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Functional serotonin 5-HT4 receptors in porcine and human ventricular myocardium with increased 5-HT4 mRNA in heart failure

Serotonin (5-hydroxytryptamine, 5-HT) increases contractile force and elicits arrhythmias through 5-HT4 receptors in porcine and human atrium, but its ventricular effects are unknown. We now report functional 5-HT4 receptors in porcine and human ventricle. 5-HT4 mRNA levels were determined in porcine and human ventricles and contractility studied in ventricular trabeculae. Cyclic AMP-dependent protein kinase (PKA) activity was measured in porcine ventricle. Porcine and human ventricles expressed 5-HT4 receptor mRNA. Ventricular 5-HT4(b) mRNA was increased by four times in 20 failing human hearts compared with five donor hearts. 5-HT increased contractile force maximally by 16% (EC50=890 nM) and PKA activity by 20% of the effects of (-)-isoproterenol (200 muM) in ventricular trabeculae from new-born piglets in the presence of the phosphodiesterase-inhibitor 3-isobutyl-1-methylxanthine. In ventricular trabeculae from adult pigs (3-isobutyl-1-methylxanthine present) 5-HT increased force by 32% (EC50=60 nM) and PKA activity by 39% of (-)-iso-proterenol. In right and left ventricular trabeculae from failing hearts, exposed to modified Krebs solution, 5-HT produced variable increases in contractile force in right ventricular trabeculae from 4 out of 6 hearts and in left ventricular trabeculae from 3 out of 3 hearts- range 1-39% of (-)-isoproterenol, average 8%. In 11 left ventricular trabeculae from the failing hearts of four beta-blocker-treated patients, pre-exposed to a relaxant solution with 0.5 mM Ca2+ and 1.2 mM Mg2+ followed by a switch to 2.5 mM Ca2+ and 1 mM Mg2+, 5-HT (1-100 muM, 3-isobutyl-1-melhylxanthine present) consistently increased contractile force and hastened relaxation by 46% and 25% of (-)-isoproterenol respectively. 5-HT caused arrhythmias in three trabeculae from 3 out of I I patients. In the absence of phosphodiesterase inhibitor, 5-HT increased force in two trabeculae, but not in another six trabeculae from 4 patients. All 5-HT responses were blocked by 5-HT4 receptor antagonists. We conclude that phosphodiesterase inhibition uncovers functional ventricular 5-HT4 receptors, coupled to a PKA pathway, through which 5-HT enhances contractility, hastens relaxation and can potentially cause arrhythmias.

The cytoskeleton and motor proteins of human schistosomes and their roles in surface maintenance and host-parasite interactions

Schistosomes are parasitic blood flukes, responsible for significant human disease in tropical and developing nations. Here we review information on the organization of the cytoskeleton and associated motor proteins of schistosomes, with particular reference to the organization of the syncytial tegument, a unique cellular adaptation of these and other neodermatan flatworms. Extensive EST databases show that the molecular constituents of the cytoskeleton and associated molecular systems are likely to be similar to those of other eukaryotes, although there are potentially some molecules unique to schistosomes and platyhelminths. The biology of some components, particular those contributing to host-parasite interactions as well as chemotherapy and immunotherapy are discussed. Unresolved questions in relation to the structure and function of the tegument relate to dynamic organization of the syncytial layer. (C) 2004 Wiley Periodicals, Inc.