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2.
PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells 总被引:65,自引:10,他引:55
PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM. 相似文献
3.
This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing." 相似文献
4.
Did you ever think, “If we just had a little money we could…”? The current health care environment is wrought with financial stressors that can be overwhelming and take up most of our time. Such stress can limit the development of a professional practice environment if you let it. How do you not only survive but thrive in this financial climate? 相似文献
5.
Martin C. Robson MD ; Diane M. Cooper PhD RN ; Rummana Aslam MD ; Lisa J. Gould MD PhD ; Keith G. Harding MBChB MRCGP FRCS ; David J. Margolis MD MSCE PhD ; Diane E. Ochs RN ; Thomas E. Serena MD ; Robert J. Snyder DPM ; David L. Steed MD ; David R. Thomas MD ; Laurel Wiersema-Bryant RN BC ANP 《Wound repair and regeneration》2008,16(2):147-150
6.
Thomas Barba Romain Fort Vincent Cottin Steeve Provencher Isabelle Durieu Sabine Jardel Arnaud Hot Quitterie Reynaud Jean-Christophe Lega 《Autoimmunity reviews》2019,18(2):113-122
Objective
Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD.Methods
Studies were selected from MEDLINE up to July 2017. Two investigators independently extracted data on study design, patient characteristics, clinical features, treatment, follow-up and outcomes. Global survival rates and objectively confirmed lung function improvements were extracted as the main outcome for rapidly progressive IIM-related ILD (RP-ILD) and chronic forms of ILD (C-ILD), respectively, and pooled using the weighted mean proportion with fixed or random-effects models in case of significant heterogeneity (I2?>?50%).Results
Twenty-seven studies encompassing 553 patients (male: 30.5%, age: 53.5?±?5.5?years) were included in the meta-analysis. Globally, retrieved studies were of limited methodological quality (no controlled studies and only 2 prospective studies). Dermatomyositis (40%) and anti-tRNA synthetase syndrome (45%) were the most represented IIM subtypes. In C-ILD, functional improvement rates were 89.2% (95%CI 82.5–93.6; 7 studies, n?=?124) for corticosteroids alone, 80.7% (95%CI 49.6–94; 6 studies, n?=?38) for cyclosporine A, 64.1% (95%CI 46.3–78.7; 4 studies, n?=?32) for azathioprine, 86.2% (95%CI 61.5–96; 2 studies, n?=?23) for tacrolimus, 56.4% (95%CI 44–68.0; 8 studies, n?=?71) for cyclophosphamide, and 76.6% (95%CI 50.4–96.0; 2 studies, n?=?20) for rituximab. In RP-ILD, survival rates at 3?months were 51.7% (95%CI 24.2–78.1; 2 studies, n?=?11) for corticosteroids alone, 69.2% (95%CI 55.0–80.5; 8 studies, n?=?146) for cyclosporine A and 72.4% (95%CI 6.4–99.0, 2 studies, n?=?16) for cyclophosphamide.Conclusion
Despite aggressive immunosuppressive therapies, the short-term mortality of RP-ILD remains high. While immunosuppressive therapies are associated with significant functional improvements in most patients with C-ILD, substantial uncertainty remains about the best treatment strategy in the absence of good quality evidence. 相似文献7.
8.
Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung 总被引:1,自引:0,他引:1
Prahalad AK; Ross JA; Nelson GB; Roop BC; King LC; Nesnow S; Mass MJ 《Carcinogenesis》1997,18(10):1955-1963
Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic
hydrocarbon, is the most potent carcinogen ever tested in mouse skin and
rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction,
tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in
strain A/J mouse lung. Groups of mice received a single i.p. injection of
0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment,
DNA adducts were measured at times between 1 and 28 days, while tumors were
counted at 250 days and analyzed for the occurrence of point mutations in
codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung
induced six major and four minor DNA adducts. Maximal levels of adduction
occurred between 5 and 10 days after injection followed by a gradual
decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti-
and syn-11,12- dihydroxy-13,14-epoxy-
11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both
deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed
by cochromatography. The major adduct was identified as a product of the
reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced
significant numbers of lung adenomas in a dose- dependent manner, with the
highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In
tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based
on the administered dose, DB[a,l]P was more active than other environmental
carcinogens including benzo[a]pyrene. As a function of time-integrated DNA
adduct levels, DB[a,l]P induced lung adenomas with about the same potency
as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar
in carcinogenic potency to other PAHs in the strain A/J mouse lung model.
Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors
revealed the predominant mutations to be G-->T transversions in the
first base of codon 12, A-->G transitions in the second base of codon
12, and A-->T transversions in the second or third base of codon 61,
concordant with the DNA adduct profile.
相似文献
9.
10.
目的分析中国不同人群及不同胃部疾病病例来源的幽门螺杆菌致病相关基因cagA、iceA、vacA及HP0519的分布.方法采用特异引物聚合酶链式反应(PCR)方法分析150株幽门螺杆菌上述基因的多态性分布特点,并对其分布作初步统计分析.结果93%(139/150)中国菌株cagA基因3′端重复序列的PCR产物具有东方菌株特征.75%(113/150)菌株iceA基因为iceA1,19%(29/150)为iceA2,不同地区间iceA基因的分布差异无统计学意义.云南菌株iceA1、iceA2的分布与菌株分离个体的种族特点及临床疾病类型无显著关系.96%中国菌株(144/150)vacA基因s区的等位基因为s1;m区等位基因m2、m1b和m1b-m2的比例分别为57%(85/150)、27%(41/150)和11%(16/150),仅2株福建菌株为m1a.不同地区间vacA s1、m2、m1b分布的差异无统计学意义.云南菌株m1b-m2的分布高于福建和北京菌株.云南菌株vacA s区等位基因的多样性与分离个体的种族及临床疾病类型无显著关系.vacA m区等位基因的多样性与分离个体的临床疾病类型无显著关系,但不同民族间m2的分布有显著差异,白族人群m2的分布显著少于汉族和纳西族.93%(140/150)的中国菌株HP0519基因具有24 bp和15 bp DNA插入和缺失的多态性特点.不同地区间HP0519基因的多态性无显著不同.云南菌株HP0519的多态性与菌株分离个体的临床疾病类型无显著关系,但来源不同民族菌株的HP0519基因存在差异.结论幽门螺杆菌中国菌株cagA 3′端JF/TR特异引物的扩增结果具有东亚菌株特点.中国菌株vacA基因多为s1,其分布与菌株分离个体的临床疾病类型无关.中国菌株vacA基因m区的分布具有多样性.中国菌株HP0519基因具有24 bp和15 bp插入和缺失的多态性特点. 相似文献