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排序方式: 共有3003条查询结果,搜索用时 15 毫秒
91.
Buck BJ Kerman IA Burghardt PR Koch LG Britton SL Akil H Watson SJ 《Neuroscience letters》2007,421(2):178-183
Although alterations in the function of the neurotransmitter system have been implicated in the pathology of Alzheimer's disease (AD), the mechanisms that underlie this pathological change are not well understood. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key protease in the generation of beta-amyloid, an important trigger protein in the pathogenesis of AD. The expression and activity of BACE1 are increased in the brains of sporadic AD patients, and a role for BACE1 in neurotransmission has been suggested recently. This study examines whether BACE1 plays a role in regulated exocytosis in PC12 cells. Treatment of PC12 cells with a beta-secretase inhibitor reduced stimulus-dependent secretion of neurotransmitters, suggesting a potential role of BACE1 in regulated exocytosis. Using transfected human growth hormone as a reporter for a regulated secretory pathway in PC12 cells, we found that the transient overexpression of BACE1 increased basal secretion in the absence of a stimulus and reduced stimulus-dependent secretion in intact PC12 cells. In digitonin-permeabilized PC12 cells, an overexpression of BACE1 enhanced the Ca2+-independent and ATP-independent component of the secretory pathway. Furthermore, expression of the glycosylation-deficient mutant of BACE1, BACE1N354Q, led to an elevation of basal secretions over that by BACE1 wild-type, suggesting a role of BACE1 glycosylation in basal secretion. These results demonstrate an unknown role for BACE1 in secretion, and suggest that elevated levels of BACE1 in AD brains may contribute to the altered neurotransmitter pathology of AD through stimulation of spontaneous basal secretion under resting conditions. 相似文献
92.
Severe combined immunodeficiency (SCID) is a lethal disease unless allogeneic bone marrow transplantation (BMT), preferably
from a family related HLA identical donor (RID) is given. Previously, some patients received HLA-mismatched related donors
(MMRD) BMT, which often resulted in slow immune reconstitution and variable survival. Alternatively, HLA-matched unrelated
donors (MUD) BMT have been suggested. Recently, we have directly compared outcome of patients with SCID who received either
MMRD or MUD BMT. Survival after MUD BMT was significantly better than after MMRD BMT. Patients who received MUD BMT also had
better engraftment of donor cells and immune reconstitution. Recent reports from other centers confirm these results finding
that MUD BMT provides excellent survival and better immune reconstitution for patients with SCID. In conclusion, MUD BMT appears
vastly superior to MMRD BMT and should be offered as first choice of treatment for patients with SCID when RID is unavailable.
Presented at the First Robert A Good Society Symposium, St. Petersburg, FL 2006. 相似文献
93.
94.
Kent Ilan Geffen Noa Stein Assaf Rudnicki Yaron Friehmann Asaf Avital Shmuel 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2020,258(3):607-611
Graefe's Archive for Clinical and Experimental Ophthalmology - Colonoscopy is an endoscopic examination of the bowel. It requires insufflation of the large bowel lumen with gas which leads to... 相似文献
95.
Avivit Cahn MD Stephen D. Wiviott MD Ofri Mosenzon MD Sabina A. Murphy MPH Erica L. Goodrich MS Ilan Yanuv MSc Aliza Rozenberg MA John P. H. Wilding MD Lawrence A. Leiter MD Deepak L. Bhatt MD Darren K. McGuire MD Leon Litwak MD Adriaan Kooy MD Ingrid A. M. Gause-Nilsson MD Martin Fredriksson MD Anna Maria Langkilde MD Marc S. Sabatine MD Itamar Raz MD 《Diabetes, obesity & metabolism》2021,23(1):29-38
96.
97.
Zaza Iakobishvili Tal Hasin Robert Klempfner Nir Shlomo Ilan Goldenberg Ronen Brenner Ran Kornowski Yariv Gerber 《Mayo Clinic proceedings. Mayo Clinic》2019,94(7):1171-1179
ObjectiveTo evaluate the association between bezafibrate, a drug used to treat hypertriglyceridemia, and long-term cancer incidence in patients with coronary artery disease (CAD).Patients and MethodsThe study comprised 2980 patients with CAD (mean age, 60 years; 2729 [91.6%] men) who were free of cancer and were enrolled in the Bezafibrate Infarction Prevention study, a double-blind trial conducted between May 1, 1990, and January 31, 1993, in 18 cardiology departments in Israel. Patients randomized to receive 400 mg of bezafibrate (n=1486) or placebo (n=1494) daily for a median of 6.2 years (range, 4.7-7.6 years) were followed up for incidence of cancer through the Israeli National Cancer Registry and all-cause death through the Population Registry of the State of Israel until December 31, 2013. Cox proportional hazards and Fine and Gray survival models were used to assess the bezafibrate-cancer association.ResultsClinical characteristics and laboratory values were well balanced between the 2 groups at the study entry. Over a median follow-up of 22.5 years (range, 21.2-23.9 years), cancer developed in 753 patients. With death considered a competing event, the cumulative incidence of cancer at the end of the follow-up was lower in the bezafibrate vs the placebo group (23.9%; 95 CI, 21.9%-26.1% vs 27.2%; 95 CI, 25.1%-29.4%; P=.04). The hazard ratio for cancer in the bezafibrate vs placebo groups was 0.86 (95% CI, 0.74-0.99). In mediation analysis, the association between bezafibrate treatment and cancer incidence was not sensitive to adjustment for on-trial lipid levels but was attenuated on adjustment for on-trial fibrinogen levels.ConclusionBezafibrate treatment is associated with reduced risk of cancer among patients with CAD. Fibrinogen, but not lipid lowering, is linked to this association. 相似文献
98.
Goldenberg I Matetzky S Halkin A Roth A Di Segni E Freimark D Elian D Agranat O Har Zahav Y Guetta V Hod H 《American heart journal》2003,145(5):862-867
Background
Prior studies have yielded conflicting data on the advantage of primary angioplasty compared with thrombolysis in elderly patients with acute myocardial infarction (AMI). These studies, however, were performed before the contemporary widespread use of intracoronary stents and glycoprotien IIb/IIIa antagonists.Methods
We prospectively compared the outcome of 130 consecutive elderly patients (aged ≥70 years) with ST-elevation AMI who were admitted to 2 similar neighboring medical centers. Patients were assigned to receive either thrombolytic therapy with accelerated tissue-type plasminogen activator (center I) or primary angioplasty with routine stenting (center II).Results
Of the patients assigned to receive primary angioplasty, 91% underwent stenting. At 6 months, patients treated with primary angioplasty, compared with those treated with thrombolytic therapy, had a lower incidence of reinfarction (2% vs 14%, P = .053) and revascularization for recurrent ischemia (9% vs 61%, P < .001) and a significant reduction in the prespecified combined end point of death, reinfarction, or revascularization for recurrent ischemia (29% vs 93%, P < .01). Primary angioplasty remained an independent predictor of the triple combined end point after controlling for potential covariables (relative risk 0.63, 95% CI 0.38-0.84). Major bleeding complications were also significantly reduced in the primary angioplasty group (0% vs 17%, P = .03).Conclusions
Compared with thrombolysis, primary angioplasty with routine stenting in elderly patients with AMI is associated with better clinical outcomes and a lower risk of bleeding complications. 相似文献99.
100.
Simmy Bank M.B. Ch.B. F.R.C.P. B. H. Novis M.B. Ch.B. M.R.C.P. D. G. Burns F.C.P. Ph.D. I. N. Marks M.B. F.R.C.P. 《Diseases of the colon and rectum》1973,16(6):459-467
Summary The dissecting-microscopic appearance of the human rectal mucosa was studied in 147 biopsy specimens. The normal mucosa is
divided into mucosal units by a “honeycomb” pattern of the rectal microvasculature, the center of each unit containing a refractile
“pit” which may represent the mouth of the rectal crypt. The changes occurring in ulcerative colitis were graded according
to severity of disturbance of the vascular channels, ranging from dilatation, neoformation and tortuosity of the individual
vessels to complete disorganization of the “honeycomb” pattern. The vascular and “pit” changes in ulcerative colitis and other
diseases of the rectum are described. The pathogenesis of the dissecting-microscopic changes is discussed in relation to the
normal vascular pattern of the human colonic mucosa.
Supported by the Medical Research Council of South by the Medical Research Council of South Africa and the University of Cape
Town Staff Research Fund. 相似文献