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Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have(More)
The long-term effects of varying concentrations and frequencies of injectable, exogenous prostaglandin E2 (PGE2) on the rate of tooth movement and the amount of root resorption were evaluated. There were 132 male Sprague-Dawley rats 8 weeks old that initially weighed 225 to 250 gm. Five animals were in a pilot study, while seven were baseline controls and(More)
BACKGROUND In posterior uveitis the blood-retinal barrier (BRB) plays an important role in the pathogenesis of the disease. However, the morphologic correlate of BRB breakdown and the route of leukocyte migration remain poorly defined. EXPERIMENTAL DESIGN Using an experimental model of autoimmune uveoretinitis in the rat, we have examined the(More)
This study evaluated the amount and depth of root resorption associated with varying concentrations and frequencies of injectable, exogenous prostaglandin E2 (PGE2) in conjunction with orthodontic tooth movement in rats. The sample consisted of 155 maxillary right and left first molars from 88, 8-week old, male Sprague-Dawley rats. The animals were divided(More)
Novel piperazinyl, morpholino and piperidyl derivatives of the pyrazole-based Hsp90 inhibitor CCT018159 are described. Structure-activity relationships have been elucidated by X-ray co-crystal analysis of the new compounds bound to the N-terminal domain of human Hsp90. Key features of the binding mode are essentially identical to the recently reported(More)
Enamel microabrasion using hydrochloric acid and pumice is an effective method to remove superficial enamel discoloration. This procedure is used in many dental offices but little is known about how different treatment combinations of hand applicator pressure on the tooth, number of applications, and duration of application affect the amount of enamel loss.(More)
The purpose of this investigation was to study the changes in temporomandibular joint tissues, in particular the disc and its attachments, associated with muscle-powered continuous posterior displacement of the mandible for 33 days. After measurement of incisal relationships, food and water consumption, histologic and morphometric analysis, and radiologic(More)
In the second part of an experimental study of the behavior and fate of the roots of ectopically transplanted frog teeth the comparative aspects of the tooth root and its tissue composition were examined. Experimental results showed that the root or pedicel area of the frog tooth was an intrinsic part of the tooth. The tooth was capable of growth to normal(More)