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Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis.

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Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Both noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be isolated from persistently infected cattle suffering from the lethal mucosal

Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer.

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BACKGROUND PKC412 (N-benzoyl-staurosporine), an oral inhibitor of protein kinase C, is capable of cell cycle inhibition and is endowed with anti-angiogenic properties. This dose-finding phase I study was designed to establish the maximum tolerated dose (MTD) of PKC412 when combined with

Novel small molecule cyclin-dependent kinases modulators in human clinical trials.

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Aberrations in cell cycle control occurs in the majority of human malignancies due to inactivation of tumor suppressor gene Rb by the phosphorylation induced by "hyperactive" cyclin-dependent kinases. Thus, it is quite reasonable to design cdk modulators for the prevention and treatment of human

Characterization of an invasive phenotype associated with enteroaggregative Escherichia coli.

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Enteroaggregative Escherichia coli (EAggEc) strains are associated with persistent diarrhea in children in the developing world and exhibit a classic aggregative phenotype. We have demonstrated that EAggEc strains isolated from children with persistent diarrhea in Brazil, Bangladesh, and Pakistan

Shiga toxin (Stx)1B and Stx2B induce von Willebrand factor secretion from human umbilical vein endothelial cells through different signaling pathways.

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Diarrhea-associated hemolytic uremic syndrome (D(+)HUS) is caused by the ingestion of Escherichia coli that produce Shiga toxin (Stx), which is composed of a cytotoxic A subunit and pentameric B subunits that bind globotriaosylceramide on susceptible cells. Stx occurs in 2 types, Stx1 and Stx2. B

Edotecarin: a novel topoisomerase I inhibitor.

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Edotecarin (PHA-782615; formerly J-107088) is a derivative of NB-506, an indolocarbazole antitumor agent. It is a novel inhibitor of topoisomerase I that induces single-strand DNA cleavage more effectively than NB-506 or camptothecin (CPT) and at different DNA sequences. The DNA-topoisomerase I

IFN-gamma and TNF-alpha regulate human NHE3 gene expression by modulating the Sp family transcription factors in human intestinal epithelial cell line C2BBe1.

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Diarrhea associated with inflammatory bowel disease has been attributed to stimulated secretion of proinflammatory cytokines like IFN-gamma and TNF-alpha, which have been shown to downregulate the expression of the sodium-hydrogen exchanger-3 (NHE3) gene. In this study, we have investigated the

Stimulation of intestinal Cl- transport by heat-stable enterotoxin: activation of cAMP-dependent protein kinase by cGMP.

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Heat-stable enterotoxins activate guanylate cyclase, whereas heat-labile enterotoxins stimulate adenylate cyclase. Both classes of toxins cause secretory diarrhea at least in part by stimulating Cl- secretion in the intestine. The mechanism for regulation of Cl- secretion by guanosine 3',5'-cyclic

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.).

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The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains

Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C.

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OBJECTIVE N-Benzoyl staurosporine (PKC412) is a protein kinase C inhibitor with antitumor activity in laboratory models. We determined the toxicity of oral PKC412 administered daily for repeat cycles of 28 days. METHODS Thirty-two patients with advanced solid cancers were treated at seven dose

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