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Monocrotaline (MCT) is an 11-membered macrocyclic pyrrolizidine alkaloid (PA) that causes a pulmonary vascular syndrome in rats characterized by proliferative pulmonary vasculitis, pulmonary hypertension, and cor pulmonale. Current hypotheses of the pathogenesis of MCT-induced pneumotoxicity suggest that MCT is activated to a reactive metabolite(s) in the(More)
This report describes the isolation and identification of a monocrotaline-derived, glutathione-conjugated pyrrole obtained from the bile of male Sprague-Dawley rats. Bile obtained from rats given an intravenous bolus of 14C-monocrotaline was fractionated using a series of chromatographic separations. Initial purification with cholestyramine resin removed(More)
In the monocrotaline (MCT) rat model of pulmonary hypertension, the pulmonary vascular endothelium is thought to be the early target of the bifunctionally reactive metabolite monocrotaline pyrrole (MCTP). In previous studies, bovine pulmonary arterial endothelial cells (BPAEC) exposed to MCTP exhibited inhibition of proliferation. Since other compounds that(More)
Glioblastomas are among the most incurable cancers. Our past findings indicated that glioblastoma cells, but not neurons or glia, require the transcription factor ATF5 (activating transcription factor 5) for survival. However, it was unknown whether interference with ATF5 function can prevent or promote regression/eradication of malignant gliomas in vivo.(More)
The pattern of sensitivity of mice from three inbred strains were compared on measures of morphine-induced analgesia (hot plate), locomotor activity, hypothermia, Straub tail (muscular rigidity), antidiuresis and constipation. The DBA/2J strain emerged as the most sensitive strain for analgesia, retention of a water load (antidiuresis) and hypothermia. In(More)
OBJECTIVE Elevation of triglyceride-rich lipoproteins (TGRLs) contributes to the risk of atherosclerotic cardiovascular disease. Our work has shown that TGRL lipolysis products in high physiological to pathophysiological concentrations cause endothelial cell injury; however, the mechanisms remain to be delineated. APPROACH AND RESULTS We analyzed the(More)
Three cytosolic glutathione S-transferase (GST, EC isozymes were purified from livers of male CD-1 mice to homogeneity using affinity chromatography and gradient elution. Isozyme molecular masses and purities were determined using electrospray ionization mass spectrometry (ESI/MS), HPLC, and electrophoretic methods. Isozymes were assigned to(More)
Glioblastoma multiforme is an extremely aggressive and clinically unresponsive form of cancer. Transformed neoplastic neural stem cells, resistant to chemotherapy and radiation therapy, are thought to be responsible for the initial tumor formation and the recurrence of disease following surgical resection. These stem cells express multidrug resistance(More)
Two carboxylesterases (GPL1 and GPH1) were isolated from guinea pig hepatic microsomes and assayed for activity using the following pyrrolizidine alkaloids (PAs): seneciphylline (SNP), monocrotaline (MCT), and a mixture of senecionine (SEN) and integerrimine (INT) referred to as SEN-INT. GPH1 was able to effect the hydrolysis of all PAs, however, only(More)
One of the earliest morphologic changes evident in the monocrotaline (MCT) model of pulmonary hypertension in rats is microvascular leak. Whether this represents a direct effect of MCT metabolites or is secondary to inflammatory and thrombotic changes remains uncertain. To determine whether MCT directly affects endothelial cell permeability barrier(More)