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Kyoto, Japan

Tabata T.,University of California at San Francisco | Petitt M.,University of California at San Francisco | Fang-Hoover J.,University of California at San Francisco | Rivera J.,San Francisco General Hospital | And 5 more authors.
American Journal of Pathology | Year: 2012

We investigated human cytomegalovirus pathogenesis by comparing infection with the low-passage, endotheliotropic strain VR1814 and the attenuated laboratory strain AD169 in human placental villi as explants in vitro and xenografts transplanted into kidney capsules of SCID mice (ie, mice with severe combined immunodeficiency). In this in vivo human placentation model, human cytotrophoblasts invade the renal parenchyma, remodel resident arteries, and induce a robust lymphangiogenic response. VR1814 replicated in villous and cell column cytotrophoblasts and reduced formation of anchoring villi in vitro. In xenografts, infected cytotrophoblasts had a severely diminished capacity to invade and remodel resident arteries. Infiltrating lymphatic endothelial cells proliferated, aggregated, and failed to form lymphatic vessels. In contrast, AD169 grew poorly in cytotrophoblasts in explants, and anchoring villi formed normally in vitro. Likewise, viral replication was impaired in xenografts, and cytotrophoblasts retained invasive capacity, but some partially remodeled blood vessels incorporated lymphatic endothelial cells and were permeable to blood. The expression of both vascular endothelial growth factor (VEGF)-C and basic fibroblast growth factor increased in VR1814-infected explants, whereas VEGF-A and soluble VEGF receptor-3 increased in those infected with AD169. Our results suggest that viral replication and paracrine factors could undermine vascular remodeling and cytotrophoblast-induced lymphangiogenesis, contributing to bleeding, hypoxia, and edema in pregnancies complicated by congenital human cytomegalovirus infection. © 2012 American Society for Investigative Pathology.

Yagi Y.,Kyoto University | Yagi Y.,Nagasaki University | Muroga E.,Kyoto University | Naitoh M.,Kyoto University | And 7 more authors.
Journal of Investigative Dermatology | Year: 2013

The most distinctive feature of keloid is the extreme deposition of extracellular matrix, including collagens and proteoglycans (PGs). The focus of this study was the PG versican, which presumably defines keloid volume because of its ability to retain large amounts of water through its component glycosaminoglycans (GAGs). The excessive deposition of versican in keloids was examined by immunohistochemical analysis and by upregulation of the versican gene in these lesions by real-time PCR. The latter showed that mesenchymal cells derived from keloid lesion (KL) cells continue to exhibit above-normal versican production in culture. To establish a model of GAG deposition in keloids, collagen sponges seeded with KL cells (KL-SPos) were implanted in the subcutaneous space of nude mice. After 1 month, the KL-SPos were significantly heavier than the fibroblast (Fb)-seeded sponges (Fb-SPos). This ex vivo model was subsequently used to examine an inhibitory ability of IL-1β that was identified to reduce versican in vitro. IL-1β or chondroitinase ABC, when injected directly, successfully reduced the weight of the KL-SPos. Thus, on the basis of the change in weight of the seeded sponges, this ex vivo model can be used to test therapies aimed at reducing or inhibiting keloid formation and to study the pathogenesis of this aberrant response. © 2013 The Society for Investigative Dermatology.

Maruho Co. | Date: 2011-07-22

The purpose is to provide a tacrolimus-containing pharmaceutical composition which is a creamy preparation for external application having good feeling upon use and has high stability of a main ingredient contained therein (high main ingredient residual ratio), and allows easy control of skin concentration of the main ingredient. The present invention relates to an oil-in-water type creamy composition comprising (A) tacrolimus, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, (B) an oil prepared by mixing (a) a medium-chain fatty acid triglyceride with (b) ethylene glycol salicylate and/or diisopropyl sebacate, (C) an emulsifying agent having a HLB value of 12 or more, and (D) a hydrophilic polymer, and having a pH value of 4 to 7.

Maruho Co. | Date: 2012-12-20

It is an object to provide a topical composition that is excellent in texture and feeling upon use. The present invention is a topical composition without water, satisfying the following: (A) the composition includes a silicone base in a proportion of 80% by weight or more; (B) the silicone base includes (b1) a silicone elastomer, (b2) a cyclic volatile methylsiloxane having 3 to 6 silicon atoms, and (b3) a linear dimethylpolysiloxane and/or linear methylphenylpolysiloxane; (C) the composition includes therein an active ingredient present in a dispersed or dissolved type; and (D) the composition does not contain any non-silicone thickener.

The present invention provides a dermal composition comprising a polymeric reversed micelle that allows a water-soluble drug to be efficiently encapsulated and that is superior in percutaneous absorptiveness and very safe, and provides a method that can produce the composition in simple steps. The dermal composition comprises a polymeric reversed micelle composed of an amphipathic polymer having a hydrophilic segment and a hydrophobic segment, wherein the polymeric reversed micelle has a configuration in which the hydrophilic segment is the core and the hydrophobic segment is the shell, and a water-soluble drug is encapsulated therein. The composition can be produced by blending an oil phase comprising the amphipathic polymer in an oily base agent with an aqueous phase comprising the water-soluble drug in an aqueous solvent, or by blending an oily base agent with an aqueous phase comprising the amphipathic polymer and the water-soluble drug in an aqueous solvent.

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