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排序方式: 共有420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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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
4.
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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Anticoagulant Use in Patients with Chronic Renal Impairment 总被引:3,自引:0,他引:3
Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment. 相似文献
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Pierre Robin sequence (PRS) describes a small mandible with retrognathia, an elevated and posteriorly positioned tongue, and an associated U-shaped cleft palate. The retracted tongue may obstruct the airway leading to respiratory failure, with failure to thrive and adverse neurodevelopmental outcomes if not addressed. If the airway obstruction cannot be overcome with conservative measures, there are non-surgical and surgical options. A nasopharyngeal prong (NPP) is a non-surgical, temporary treatment that avoids the complications inherent in an operation, especially given the natural history of mandibular growth and improved airway obstruction in PRS. Although the use of a prong requires training, support, and follow up, it effectively bypasses the obstruction in the majority of children with PRS, and allows the child to outgrow the airway obstruction until the prong is no longer required. On average, the prong can be removed between 6 and 12 months of age. 相似文献
9.
Fabrice Extramiana Pierre Maison‐Blanche Fabio Badilini Philippe Beaufils Antoine Leenhardt 《Annals of noninvasive electrocardiology》2005,10(2):169-178
Background: Universal QT correction formulae have been shown to under or overcorrect the QT interval duration. Individual QT–R‐R modeling has been proposed as a preferable solution for heart rate correction of QT intervals. However, the QT–R‐R relationship stability over time needs to be evaluated. Methods: The present report is part of randomized, double‐dummy, and placebo‐controlled 4‐way crossover phase 1 study (48 healthy volunteers). Each randomized period included a run‐in placebo day followed the day after by drug administration, with moxifloxacin as a positive control for QT interval measurement. Digital Holter ECG data were analyzed using the “bin” approach. For each period, individual QT–R‐R relationship were calculated using two different models (linear and parabolic log–log models). Results: The mean intrasubject variability for the α coefficient of the linear modeling (SDintra = 0.011 ± 0.005) reached 28.6 ± 10.2%. When the parabolic model was considered, the SDintra was 0.026 ± 0.009 for the α coefficient. The QT–R‐R relationship variability was in part related to long‐term RR changes (R2= 30%, P < 0.05). However, no significant time effect (ANOVA) was evidenced for QT–R‐R coefficients. Moxifloxacin significantly increased the α coefficient of the QT–R‐R relationship from 0.07 ± 0.018 to 0.085 ± 0.019, P < 0.05 (linear model). Conclusions: The individual QT–R‐R relationship shows a residual variability in part related to long‐term autonomic changes. In addition, the QT–R‐R relationship might be modulated by the drug tested. As a consequence, pretherapy QT–R‐R relationship obtained in a given patient cannot be used as a fingerprint throughout a drug trial. 相似文献
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