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排序方式: 共有649条查询结果,搜索用时 15 毫秒
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CA von Arnim R Spoelgen ID Peltan M Deng S Courchesne M Koker T Matsui H Kowa SF Lichtenthaler MC Irizarry BT Hyman 《The Journal of neuroscience》2006,26(39):9913-9922
The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD. 相似文献
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R D Dillard F P Carr D McCullough K D Haisch L E Rinkema J H Fleisch 《Journal of medicinal chemistry》1987,30(5):911-918
A series of [[(tetrazol-5-ylaryl)oxy]methyl]acetophenones was synthesized and evaluated as antagonists of leukotriene D4 induced contractions of guinea pig ileum. Substitutions at the 3-position of the acetophenone with ethyl (66), propyl (68), butyl (83), and isobutyl (84) gave -log IC50 values of 7.9, 8.0, 7.8, and 7.7, respectively. Equally potent compounds were obtained when the tetrazol-5-yl group was connected to the second benzene ring in the para position with a chemical bond (67), methylene (68), or ethylene (71). For retention of high antagonist activity, the acetophenone should be substituted in the 2-position by a hydroxyl group and the tetrazole ring should have an acidic hydrogen atom. 1-[2-Hydroxy-3-propyl-4-[[4-(1H-tetrazol-5-ylmethy) phenoxy]methyl]phenyl]ethanone (68, LY1632443) has undergone extensive pharmacologic evaluation for its potential as an antiasthma agent. 相似文献
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应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位,该结合位点可以满足特异结合部位的基本条件:1.低结合容量;2.高亲和力;3.可饱和性;4.可逆性;5.对降黑素高度特异性。此外,该特异结合位点具昼夜节律;亚细胞分布的研究表明以细胞核含量最高,线粒体次之,并具有年龄依赖性降低,以出生时最高。 相似文献
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Kung FT; Chen WJ; Chou HH; Ko SF; Chang SY 《Human reproduction (Oxford, England)》1997,12(8):1649-1653
We report a rare case of early-stage endometrial adenocarcinoma in a 22
year old nullipara with polycystic ovaries undergoing conservative
treatment. Pretreatment evaluation including tumour grade, depth of
myometrial invasion, tumour size, hormone receptor status and flow
cytometric analysis indicated a favourable prognosis. The patient underwent
repeat endometrial curettage and a 6 month period of therapy with megestrol
acetate and tamoxifen. A combination contraceptive pill was then prescribed
to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after
the last curettage, there is no evidence of disease. During the treatment
period, hysteroscopy allowed for a more precise approach in panoramically
examining the tumour nest in the endometrial cavity, and the subsequent
endometrial response to hormone therapy. Laparoscopy using bulldog clamps
applied to the isthmic portion of the Fallopian tubes prevented i.p. spread
of endometrial tissue from retrograde regurgitation during hysteroscopy.
Laparoscopic ovarian electrocautery resulted in the reduction of abnormal
hypervascularization on the surface of polycystic ovaries postoperatively
but caused a peri-ovarian adhesion complication. It is interesting that
this case posed a unique opportunity to demonstrate the tumour regression
under the assistance of laparoscopy and hysteroscopy.
相似文献
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Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity 总被引:2,自引:0,他引:2
Nicole C. Johnson Miriam E. Dillard Peter Baluk Donald M. McDonald Natasha L. Harvey Sharon L. Frase Guillermo Oliver 《Genes & development》2008,22(23):3282-3291
The activity of the homeobox gene Prox1 is necessary and sufficient for venous blood endothelial cells (BECs) to acquire a lymphatic endothelial cell (LEC) fate. We determined that the differentiated LEC phenotype is a plastic, reprogrammable condition that depends on constant Prox1 activity for its maintenance. We show that conditional down-regulation of Prox1 during embryonic, postnatal, or adult stages is sufficient to reprogram LECs into BECs. Consequently, the identity of the mutant lymphatic vessels is also partially reprogrammed as they acquire some features typical of the blood vasculature. siRNA-mediated down-regulation of Prox1 in LECs in culture demonstrates that reprogramming of LECs into BECs is a Prox1-dependent, cell-autonomous process. We propose that Prox1 acts as a binary switch that suppresses BEC identity and promotes and maintains LEC identity; switching off Prox1 activity is sufficient to initiate a reprogramming cascade leading to the dedifferentiation of LECs into BECs. Therefore, LECs are one of the few differentiated cell types that require constant expression of a certain gene to maintain their phenotypic identity. 相似文献
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Jerome H. Fleisch Lynn E. Rinkema Klaus D. Haisch Doris McCullough F. Patrick Carr Robert D. Dillard 《Naunyn-Schmiedeberg's archives of pharmacology》1986,333(1):70-77
Summary LY163443,1-[2-hydroxy-3-propyl-4-{[4-(1H-tetrazol-5-ylmethyl)-phenoxy]methyl}phenyl]ethanone, antagonized LTD4-induced contractions of guinea pig ileum, trachea, and lung parenchyma. Tracheal contractions to LTE4 were also inhibited by LY163443. The compound had minimal effect against ileal responses to LTC4 and parenchymal contractions to LTB4. Furthermore, LY163443.had little to no effect against contractions of isolated smooth muscles to histamine, bradykinin, PGF2, carbachol, serotonin or U46619. LY163443, given by oral administration to guinea pigs, blocked LTD4-induced increases in total pulmonary impedance (TPI). Similar responses elicited by histamine or U46619 were unaffected. Increases in TPI in response to i.v. administration of LTC4 were antagonized by LY163443 given by the same route. Ovalbumin challenge also increased TPI in guinea pigs previously sensitized against this antigen. In such animals, pretreated with pyrilamine, propranolol, and indomethacin, oral administration of LY163443 blocked the increase in TPI caused by ovalbumin. Additionally, LTD4 given intradermally to guinea pigs caused a vascular leakage which was suppressed by prior oral administration of LY163443. Finally, LY163443 relaxed isolated guinea pig trachea previously contracted with LTD4, histamine, or carbachol. Relaxation of tissues contracted by these latter two agonists suggested some inherent airway smooth muscle relaxant properties of the molecule. This was further demonstrated by showing some bronchodilator activity in an in vivo setting. Thus, this pharmacologic profile indicates that LY163443, or a member of the same chemical family, warrants consideration as a possible therapeutic agent in the treatment of asthma and in diseases characterized by an overproduction of LTD4 and LTE4.Presented in part at the meeting of The Federation of American Societies for Experimental Biology, April 1985, Anaheim, California. 相似文献
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OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age. 相似文献