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D'Alessio, Silvia,Ferrari, Giovanni,Cinnante, Karma,Scheerer, William,Galloway, Aubrey C,Roses, Daniel F,Rozanov, Dmitri V,Remacle, Albert G,Oh, Eok-Soo,Shiryaev, Sergey A,Strongin, Alex Y,Pintucci, G American Society for Biochemistry and Molecular Bi 2008 The Journal of biological chemistry Vol.283 No.1
<P>Membrane-type 1 matrix metalloproteinase (MT1-MMP), a transmembrane proteinase with a short cytoplasmic domain and an extracellular catalytic domain, controls a variety of physiological and pathological processes through the proteolytic degradation of extracellular or transmembrane proteins. MT1-MMP forms a complex on the cell membrane with its physiological protein inhibitor, tissue inhibitor of metalloproteinases-2 (TIMP-2). Here we show that, in addition to extracellular proteolysis, MT1-MMP and TIMP-2 control cell proliferation and migration through a non-proteolytic mechanism. TIMP-2 binding to MT1-MMP induces activation of ERK1/2 by a mechanism that does not require the proteolytic activity and is mediated by the cytoplasmic tail of MT1-MMP. MT1-MMP-mediated activation of ERK1/2 up-regulates cell migration and proliferation in vitro independently of extracellular matrix proteolysis. Proteolytically inactive MT1-MMP promotes tumor growth in vivo, whereas proteolytically active MT1-MMP devoid of cytoplasmic tail does not have this effect. These findings illustrate a novel role for MT1-MMP-TIMP-2 interaction, which controls cell functions by a mechanism independent of extracellular matrix degradation.</P>
Low-Dose Acetazolamide in the Treatment of Premenstrual Dysphoric Disorder: A Case Series
Gabriele Sani,Georgios D. Kotzalidis,Isabella Panaccione,Alessio Simonetti,Lavinia De Chiara,Antonio Del Casale,Elisa Ambrosi,Flavia Napoletano,Delfina Janiri,Emanuela Danese,Nicoletta Girardi,Chiara 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.1
The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do notrespond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergictransmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder andone with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergicmechanisms may be involved in counteracting PMDD symptoms.
The role of the transcription factor ETV5 in insulin exocytosis.
Gutierrez-Aguilar, Ruth,Kim, Dong-Hoon,Casimir, Marina,Dai, Xiao-Qing,Pfluger, Paul T,Park, Jongsun,Haller, April,Donelan, Elizabeth,Park, Jisoo,D'Alessio, David,Woods, Stephen C,MacDonald, Patrick E Springer Verlag 2014 Diabetologia Vol.57 No.2
<P>Genome-wide association studies have revealed an association of the transcription factor ETS variant gene 5 (ETV5) with human obesity. However, its role in glucose homeostasis and energy balance is unknown.</P>