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Biomedical subjects

J Provost

Publications and source records attributed to J Provost.

At least 19 recordsLinked to original sources
PubMed2000

RPR112378 and RPR115781: two representatives of a new family of microtubule assembly inhibitors.

A screening program aimed at the discovery of new antimicrotubule agents yielded RPR112378 and RPR115781, two natural compounds extracted from the Indian plant Ottelia alismoides. We report their isolation, structural determination, and mechanisms of action. RPR112378 is an efficient inhibitor of tubulin polymerization (IC(50) = 1.2 microM) and is able to disassemble preformed microtubules. Regarding tubulin activity, RPR115781 is 5-fold less active than RPR112378. Tubulin-RPR112378 complexes, when isolated by gel filtration, were able to block further tubulin addition to growing microtubules, a mechanism that accounts for the substoichiometric effect of the drug. RPR112378 was found to prevent colchicine binding but not vinblastine binding to tubulin. Although colchicine binding is known to induce an increase of tubulin GTPase activity, no such increase was observed with RPR112378. We show that RPR112378 is a highly cytotoxic compound and that RPR115781 is 10, 000-fold less active as an inhibitor of KB cell growth. Part of the cytotoxicity of RPR112378 is probably caused by a reaction of addition with sulfhydryl groups, an observation that has not been made with RPR115781. In conclusion, these molecules represent a new class of inhibitors of microtubule assembly with potential therapeutic value.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Five new flavone 5-O-glycosides from Lethedon tannaensis: lethedosides and lethediosides.

Five new 7-methoxy-flavone 5-O-glycosides were isolated from a cytotoxic MeOH extract of Lethedon tannaensis, and the structures were elucidated by 2D NMR spectral analysis and by chemical methods. Lethedosides A (1), B (2), and C (3) were 5-O-glucosides of 7,3', 4'-tri-O-methylluteolin, 7,3',4',5'-tetra-O-methyltricetin, and 7,3', 4'-tri-O-methytricetin, respectively; lethediosides A (4) and B (5) and a known compound 6 were 5-O-xylosylglucosides of 7,3', 4'-tri-O-methylluteolin, 7,3',4',5'-tetra-O-methyltricetin, and 7, 4'-di-O-methylapigenin, respectively. These flavonoids were either inactive or weakly active against KB tumor cells, in contrast to previously isolated flavones from the same plant.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Glycosylated flavones as selective inhibitors of topoisomerase IV.

Three flavonoids which promoted Escherichia coli topoisomerase IV-dependent DNA cleavage were isolated from cottonseed flour and identified as quercetin 3-O-beta-D-glucose-[1,6]-O-alpha-L-rhamnose (rutin), quercetin 3-O-beta-D-galactose-[1,6]-O-alpha-L-rhamnose, and quercetin 3-O-beta-D-glucose (isoquercitrin). The most active one (rutin) also inhibited topoisomerase IV-dependent decatenation activity (50% inhibitory concentration, 64 microg/ml) and induced the SOS response of a permeable E. coli strain. Derivatives of quercetin glycosylated at position C-3 were shown to induce two site-specific DNA cleavages of pBR322 DNA, which were mapped by DNA sequence analysis to the gene encoding resistance to tetracycline. Cleavage at these sites was hardly detectable in cleavage reactions with quercetin or fluoroquinolones. None of the three flavonoids isolated from cottonseeds had any stimulatory activity on E. coli DNA gyrase-dependent or calf thymus topoisomerase II-dependent DNA cleavage, and they were therefore specific to topoisomerase IV. These results show that selective inhibitors of topoisomerase IV can be derived from the flavone structure. This is the first report on a DNA topoisomerase inhibitor specific for topoisomerase IV.

Base Sequence↗
PubMed1997

The PsyScope experiment-building system.

PsyScope is a system for building behavioral experiments on the Apple Macintosh computer using a graphic user interface that requires no computer programming. The program supports a wide variety of experimental designs, multimedia formats, and stimulus control. A freeware version is available at the author's web site.

Computer Communication Networks↗
PubMed1996

The Current State of Solar Modeling

Data from the Global Oscillation Network Group (GONG) project and other helioseismic experiments provide a test for models of stellar interiors and for the thermodynamic and radiative properties, on which the models depend, of matter under the extreme conditions found in the sun. Current models are in agreement with the helioseismic inferences, which suggests, for example, that the disagreement between the predicted and observed fluxes of neutrinos from the sun is not caused by errors in the models. However, the GONG data reveal subtle errors in the models, such as an excess in sound speed just beneath the convection zone. These discrepancies indicate effects that have so far not been correctly accounted for; for example, it is plausible that the sound-speed differences reflect weak mixing in stellar interiors, of potential importance to the overall evolution of stars and ultimately to estimates of the age of the galaxy based on stellar evolution calculations.

Journal Article↗
PubMed1996

Differential Rotation and Dynamics of the Solar Interior

Splitting of the sun's global oscillation frequencies by large-scale flows can be used to investigate how rotation varies with radius and latitude within the solar interior. The nearly uninterrupted observations by the Global Oscillation Network Group (GONG) yield oscillation power spectra with high duty cycles and high signal-to-noise ratios. Frequency splittings derived from GONG observations confirm that the variation of rotation rate with latitude seen at the surface carries through much of the convection zone, at the base of which is an adjustment layer leading to latitudinally independent rotation at greater depths. A distinctive shear layer just below the surface is discernible at low to mid-latitudes.

Journal Article↗
PubMed1996

DNA topoisomerase I inhibitors: cytotoxic flavones from Lethedon tannaensis.

From ethyl acetate and methanolic extracts of Lethedon tannaensis leaves, which were cytotoxic against murine leukemia (P-388) and human nasopharynx carcinoma (KB) cells, one new and six known 5-hydroxy-7-methoxyflavones variously substituted on the B ring were isolated and their structures determined by spectral analysis. Compounds active against KB cells were velutin (4) (IC50 4.8 microM), 7,3',5'-tri-O-methyltricetin (2) (IC50 22.2 microM), genkwanin (6) (IC50 30.6 microM), and the novel compound, 7,3',4'-tri-O-methyltricetin, named lethedocin (1) (IC50 47.6 microM). These flavones required the presence of hydroxyl groups at C-5 and C-4' and methoxyl groups at C-7 and C-3' for inhibition of calf thymus DNA topoisomerase I activity.

Animals↗
PubMed1990

Hypoglycaemic effect of Momordica charantia extracts.

The hypoglycaemic effect of orally administered extracts of fruits of cultivated Momordica charantia (karela) was examined in normal and streptozotocin diabetic mice. In normal mice, an aqueous extract (A) lowered the glycaemic response to both oral and intraperitoneal glucose, without altering the insulin response. This aqueous extract (A) and the residue after alkaline chloroform extraction (B) reduced the hyperglycaemia in diabetic mice at 1 hour. Material recovered by acid water wash of the chloroform extract remaining after an alkaline water wash (D) produced a more slowly generated hypoglycaemic effect. The results suggest that orally administered karela extracts lower glucose concentrations independently of intestinal glucose absorption and involve an extrapancreatic effect. Two types of hypoglycaemic substances with different time dependent effects are indicated.

Animals↗
PubMed1976

Total avascular necrosis of the capital femoral epiphysis in congenital dislocated hips.

Ninety-four hips involved with total avascular necrosis in the treatment of congenital dislocation of the hips were reviewed in a search for etiological factors and effective salvage procedures. Pre-reduction traction and adductor tenotomy did not prevent avascular necrosis. Abduction of the hip in the "frog" position was the incriminating common denominator. This position may cause (1) interference of the blood supply to the femoral head by compression of the medial branch of the deep profundus artery; and (2) pressure on the intraepiphyseal grooves by the glenoid labrum. The containment of the femoral head by acetabuloplasty (preferably) below age 8, followed at a later date (over age 10) by transfer distally of the greater trochanter, with the abductor muscles, offers a satisfactory salvage procedure.

Acetabulum↗