Macrocyclic Hedgehog Pathway Inhibitors: Optimization of Cellular Activity and Mode of Action Studies

Chris Dockendorff; Marek M. Nagiec; Michel Weïwer; Sara Buhrlage; Amal Ting; Partha P. Nag; Andrew Germain; Han-Je Kim; Willmen Youngsaye; Christina Scherer; Melissa Bennion; Linlong Xue; Benjamin Z. Stanton; Timothy A. Lewis; Lawrence MacPherson; Michelle Palmer; Michael A. Foley; José R. Perez; Stuart L. Schreiber

doi:10.1021/ml300172p

Macrocyclic Hedgehog Pathway Inhibitors: Optimization of Cellular Activity and Mode of Action Studies

ACS Medicinal Chemistry Letters ◽

10.1021/ml300172p ◽

2012 ◽

Vol 3 (10) ◽

pp. 808-813 ◽

Cited By ~ 30

Author(s):

Chris Dockendorff ◽

Marek M. Nagiec ◽

Michel Weïwer ◽

Sara Buhrlage ◽

Amal Ting ◽

...

Keyword(s):

Mode Of Action ◽

Hedgehog Pathway ◽

Cellular Activity

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Effects of 5-5'-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine on the Ultrastructure and Chemical Composition of Rat Liver

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066917 ◽

1971 ◽

Vol 29 ◽

pp. 570-571

Author(s):

E. A. Elfont ◽

R. B. Tobin ◽

D. G. Colton ◽

M. A. Mehlman

Keyword(s):

Chemical Composition ◽

Rat Liver ◽

Future Study ◽

Mode Of Action ◽

Liver Mitochondria ◽

Rat Liver Mitochondria ◽

Effective Inhibitor ◽

Biochemical Effects ◽

Glycerophosphate Dehydrogenase ◽

Stimulation Of

Summary5,-5'-diphenyl-2-thiohydantoin (DPTH) is an effective inhibitor of thyroxine (T4) stimulation of α-glycerophosphate dehydrogenase in rat liver mitochondria. Because this finding indicated a possible tool for future study of the mode of action of thyroxine, the ultrastructural and biochemical effects of DPTH and/or thyroxine on rat liver mere investigated.Rats were fed either standard or DPTH (0.06%) diet for 30 days before T4 (250 ug/kg/day) was injected. Injection of T4 occurred daily for 10 days prior to sacrifice. After removal of the liver and kidneys, part of the tissue was frozen at -50°C for later biocheailcal analyses, while the rest was prefixed in buffered 3.5X glutaraldehyde (390 mOs) and post-fixed in buffered 1Z OsO4 (376 mOs). Tissues were embedded in Araldlte 502 and the sections examined in a Zeiss EM 9S.Hepatocytes from hyperthyroid rats (Fig. 2) demonstrated enlarged and more numerous mitochondria than those of controls (Fig. 1). Glycogen was almost totally absent from the cytoplasm of the T4-treated rats.

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The effects of Cyclosporin-A (CYA) on the Ultrastructure of Gingival Mast Cells (GMC) in Behcet's disease (BD)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159333 ◽

1990 ◽

Vol 48 (3) ◽

pp. 358-359

Author(s):

Oktay Arda ◽

Ulkü Noyan ◽

Selgçk Yilmaz ◽

Mustafa Taşyürekli ◽

İsmail Seçkin ◽

...

Keyword(s):

Unknown Etiology ◽

Control Group ◽

Target Cells ◽

Gingival Hyperplasia ◽

Cellular Activity ◽

Direct Relation ◽

Immune Disease ◽

Genital Ulceration ◽

Functional Changes ◽

The Third

Turkish dermatologist, H. Beheet described the disease as recurrent triad of iritis, oral aphthous lesions and genital ulceration. Auto immune disease is the recent focus on the unknown etiology which is still being discussed. Among the other immunosupressive drugs, CyA included in it's treatment newly. One of the important side effects of this drug is gingival hyperplasia which has a direct relation with the presence of teeth and periodontal tissue. We are interested in the ultrastructure of immunocompetent target cells that were affected by CyA in BD.Three groups arranged in each having 5 patients with BD. Control group was the first and didn’t have CyA treatment. Patients who had CyA, but didn’t show gingival hyperplasia assembled the second group. The ones displaying gingival hyperplasia following CyA therapy formed the third group. GMC of control group and their granules are shown in FIG. 1,2,3. GMC of the second group presented initiation of supplementary cellular activity and possible maturing functional changes with the signs of increased number of mitochondria and accumulation of numerous dense cored granules next to few normal ones, FIG. 4,5,6.

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