Biosynthetic meshes in contaminated fields: where are we now? A systematic review and meta-analysis in humans

Hernia - Selection of an appropriate mesh reinforcement for hernia repair in contaminated fields is a significant problem for surgeons. To date the proper mesh for contaminated fields has not been...     

Expression of bcl-xL can confer a multidrug resistance phenotype

It has been suggested that genes that regulate apoptotic cell death may play an important role in determining the sensitivity of tumor cells to chemotherapy. We have recently cloned a member of the bcl-2 family, bcl- x. To test whether bcl-XL expression affects the sensitivity of tumor cells to chemotherapy, we have created stable cell lines overexpressing bcl-XL and have tested these cells for resistance to cell death induced by metabolic inhibitors and chemotherapeutic agents. Bcl-XL expression dramatically reduces the cytotoxicity of bleomycin, cisplatin, etoposide, vincristine, hygromycin B, and mycophenolic acid for up to 4 days in culture. Bcl-XL does not prevent cells from undergoing cell cycle arrest in response to these drugs, but rather prevents treated cells from undergoing apoptosis. Cell-cycle analysis on cells treated with the chemotherapeutic agents bleomycin, cisplatin, etoposide, and vincristine, show that the drugs cause growth arrest in different positions within the cell cycle. Bcl-XL expressing cells treated with chemotherapeutic drugs retain their proliferative ability after the drugs are removed. Interestingly, vincristine-treated cells expressing bcl-XL become polyploid after drug removal. These data show that bcl-XL protects cells from a wide variety of apoptotic stimuli, acts in multiple positions within the cell cycle, and confers a multidrug resistance phenotype. The ability of bcl-XL to prevent apoptotic cell death in response to chemotherapy-induced DNA damage and cell-cycle arrest may contribute to the accumulation of chromosomal aberrations within tumors. The expression of bcl-XL in tumor cells is likely to be an important indicator of chemotherapeutic efficacy.     

Intravenous thrombolysis in stroke patients of > or = 80 versus < 80 years of age--a systematic review across cohort studies

OBJECTIVE: elderly stroke patients were excluded or underrepresented in the randomised controlled trials of intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) applied within 3 h. Cohort studies comparing intravenous rtPA in stroke patients of >/=80 versus <80 years of age were limited by small sample sizes and yielded conflicting results. Thus, we performed a systematic review across all such studies. METHODS: a systematic literature search (PubMed; Science Citation Index) was performed to retrieve all eligible studies. Two reviewers independently extracted data on 'death', 'favourable 3-month outcome (modified Rankin Scale /=80 years]. Significant differences in baseline characteristics to the disadvantage of older patients were present in all studies. Compared with younger patients, older patients had a 3.09-time (95% CI = 2.37-4.03; P < 0.001) higher 3-month mortality and were less likely to regain a 'favourable outcome' (OR = 0.53; 95% CI = 0.42-0.66; P<0.001). The likelihood for 'sICH' (OR = 1.22; 95% CI = 0.77-1.94; P = 0.34) was similar in both age groups. CONCLUSION: intravenous rtPA-treated stroke patients of >/=80 years of age have a less favourable outcome than younger ones. Imbalances in predictive baseline variables to the disadvantage of the older patients may contribute to this finding. Compared with the younger cohort, rtPA-treated stroke patients aged >/=80 years do not seem exceedingly prone to sICH. Thus, there is scope for benefit from thrombolysis for the older age group. Hence, to obtain reliable evidence on the balance of risk and benefit of intravenous rtPA for stroke patients aged >/=80 years, it is safe and reasonable to include such patients in randomised placebo-controlled trials.     

Role of GSTP1-1 in mediating the effect of As2O3 in the Acute Promyelocytic Leukemia cell line NB4

Arsenic trioxide (As₂O₃) is a highly effective agent in the treatment of acute promyelocytic leukemia (APL), whereas other hematopoietic tumors are less responsive to this agent and mechanisms underlying As₂O₃,-resistance are poorly understood. To better understand the complex network of GSH-related pathways in As₂O₃ sensitivity, we investigated the role of GSH and GSH-relevant enzymes in an APL cell line sensitive to As₂O₃ (NB4) and in a resistant subclone (AsR). Cell proliferation, viability, and apoptosis were investigated in NB4 cells before and after treatment with 1 μM As₂O₃ and in AsR cells. In these experimental cell models, GSTP1-1, JNK1 and JNK2 proteins were analyzed by immunoblotting, and a kinase assay for JNK1 was performed. GSH levels as well as the activities of the enzymes glutathione peroxidase, glutathione transferase, γ-Glutamylcysteynilsinthetase and superoxide dismutase were measured. NB4 cells treated with As₂O₃ showed a high level of oxidative stress and an increase of GSH levels. GSTP1-1 polymerization and JNK1 activation were detectable after 24 h and were followed by an increase of the apoptotic rate starting at 72 h. Neither GSTP1-1 polymerization nor JNK activation was found in AsR cells that showed a very low apoptotic rate. Our results suggest that APL sensitivity to As₂O₃ might be, at least in part, mediated by the balance between association and dissociation of JNK from GSTP1-1, depending on the redox status of the cell. Further investigation is warranted to find a way to interfere with this balance, whenever it might represent a mechanism of drug resistance.     

树突状细胞与肝脏疾病

免疫反应的产生首先是由抗原提呈细胞(antigenpresenting cells,APC)捕获抗原,经其加工处理后将抗原信息传递给T,B淋巴细胞,从而引发一系列的特异性免疫应答.APC包括树突状细胞(dendritic cells,DC)、巨噬细胞(MΦ)、B细胞等,其中DC是人体内最具潜能的抗原提呈细胞(APC),能在体内外直接激活纯真(naive)T细胞,提呈抗原给MHC-Ⅰ类限制性CD8+和MHC-Ⅱ类限制性CD4+T淋巴细胞,诱导特异性免疫应答[1-6].     

瑞典老年高血压试验(STOP-Hypertension)

标　　题　瑞典老年高血压试验中的发病率及病死率作　　者　ＤａｈｌｏｆＢ,ＬｉｎｄｈｏｌｍＬＨ,ＨａｎｓｓｏｎＬ,ｅｔａｌ.　　参考文献　Ｌａｎｃｅｔ,1991,338:1281～1285研究的疾病　高血压病。目　　的　是为了评估抗高血压药物治疗对70～84岁老年高血压患者的益处岁的高血压患者,基础血压≥180/90ｍｍＨｇ,或舒张压≥105ｍｍＨｇ。进入试验前12个月内有心肌梗死、脑卒中、体位性低血压及血压>230/120ｍｍＨｇ者已除外。随　　访　随访1～4年,平均25个月。治疗方案　患者被随机安排接受药物或安慰剂治疗,药物治疗任选下列四种方案…     

Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1)

Background  

After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission.     

Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton

Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation.