An erythroid chaperone that facilitates folding of alpha-globin subunits for hemoglobin synthesis

Erythrocyte precursors produce abundant alpha- and beta-globin proteins, which assemble with each other to form hemoglobin A (HbA), the major blood oxygen carrier. alphaHb-stabilizing protein (AHSP) binds free alpha subunits reversibly to maintain their structure and limit their ability to generate reactive oxygen species. Accordingly, loss of AHSP aggravates the toxicity of excessive free alpha-globin caused by beta-globin gene disruption in mice. Surprisingly, we found that AHSP also has important functions when free alpha-globin is limited. Thus, compound mutants lacking both Ahsp and 1 of 4 alpha-globin genes (genotype Ahsp(-/-)alpha-globin*(alpha/alphaalpha)) exhibited more severe anemia and Hb instability than mice with either mutation alone. In vitro, recombinant AHSP promoted folding of newly translated alpha-globin, enhanced its refolding after denaturation, and facilitated its incorporation into HbA. Moreover, in erythroid precursors, newly formed free alpha-globin was destabilized by loss of AHSP. Therefore, in addition to its previously defined role in detoxification of excess alpha-globin, AHSP also acts as a molecular chaperone to stabilize nascent alpha-globin for HbA assembly. Our findings illustrate what we believe to be a novel adaptive mechanism by which a specialized cell coordinates high-level production of a multisubunit protein and protects against various synthetic imbalances.     

Mixed chimerism following in utero hematopoietic stem cell transplantation in murine models of hemoglobinopathy

OBJECTIVE: Mixed hematopoietic chimerism after bone marrow transplantation can provide effective treatment for beta-thalassemia because of the selective advantage that exists for donor erythropoiesis. In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism, particularly when a selective advantage exists for donor cells. To investigate the biology of IUHSCTx in hemoglobinopathies, we performed fully allogeneic IUHSCTx in murine models of beta-thalassemia (Thal) and sickle cell disease (SCD). MATERIALS AND METHODS: We serially assessed and compared levels of mononuclear cell (MNC) and erythroid chimerism after IUHSCTx of either adult bone marrow (BM)- or fetal liver (FL)-derived allogeneic donor cells in the two hemoglobinopathy models, which differ significantly in their degree of anemia (Thal>SCD) and red cell half-life (Thal相似文献   

A case report: Cecal volvulus caused by Meckel's diverticulum

INTRODUCTION

Meckel''s diverticulum is the most common congenital anomaly of the small intestine. Common complications related to Meckel''s diverticulum include hemorrhage, intestinal obstruction and inflammation. Acute large bowel obstruction is a rare complication of Meckel''s diverticulum and in the presented case it is caused by volvulus.

PRESENTATION OF CASE

We report a 39 year old female who presented with the diagnosis of a large bowel obstruction occurring as a result of cecal volvulus caused by adhesions of a perforated diverticulum.

DISCUSSION

The reported case presents one of the rare complications of MD, which is volvulus. The case described above presented with signs and symptoms suggestive of acute intestinal obstruction and radiological findings suggestive of cecal volvulus. The patient was taken to the operation room for exploration and we discovered the presence of a perforated MD. The main treatment of such case is to perform diverticulectomy in all symptomatic patients.

CONCLUSION

MD is mostly identified intraoperatively. Knowledge of the pathophysiologies by which MD can cause complications such as volvulus is important in order to plan management.     

解脲脲原体生物被膜形成与耐药性的相关性研究

目的 研究解脲脲原体(Ureaplasma urealyticum,Uu)标准株及临床分离株体外形成生物被膜的能力及游离状态与形成生物被膜后药物敏感性的差异.方法 对Uu标准株3、8血清型(Uu3、Uu8)及从女性患者宫颈中分离鉴定的21株Uu临床株进行体外培养后,扫描电镜、激光共聚焦显微镜鉴定生物被膜形成,并在生物被膜形成前后进行约敏测定(四环素、红霉素、环丙沙星).配对秩和检验及x2检验分别比较Uu游离状态及形成生物被膜后最低抑菌浓度间及耐药率间的差异.结果 Uu3、Uu8及21株Uu临床株均具有体外形成生物被膜的能力.Uu形成牛物被膜后对四环素、红霉素及环丙沙星的最低抑菌浓度较游离状态明显增高(P<0.001).Uu形成生物被膜后对红霉素及环丙沙星的耐药率增高具有统计学意义(P值分别为<0.001及0.035),但对四环素的耐药率增高无统计学意义(P=0.293).结论 Uu标准株及临床株均具有体外形成生物被膜的能力,Uu形成生物被膜后对抗菌素的抵抗力增加,出现了多重耐药现象.

Abstract：

Objective To study the ability of standard strain and clinical isolates of Ureaplasma spp. to form biofilms in vitro and to compare the antibiotic susceptibility of sessile cells and their planktonic counterparts. Methods A total of 21 Ureaplasma wealyticum(Uu) isolates recovered from female patients diagnosed with cervicitis and Uu serovar 3 and Uu serovar 8( Uu3, Uu8) were included. Scanning electron microscope and confocal scanning laser microscopy were used to identify biofilm formation. Conventional antibiotic susceptibility tests and biofilm susceptibility assays for tetracycline, erythromycin and ciprofloxacin were carried out. The paired rank sum test and was applied to analyze the statistical differences between the MIC and the minimal biofilm inhibitory concentration. The x2 test was applied to analyze the statistical differences of global resistance percentages between planktonic cells and sessile cells. Results Uu3, Uu8 and 21 Uu isolates all can form biofilms in vitro. Minimal inhibitory concentration of sessile cells compared with planktonic cells were obviously higher for tetracycline, erythromycin and ciprofloxacin (P <0.001). Global resistance percentages between planktonic cells and sessile cells were different for erythromycin (9.52% vs 61.90% , P < 0. 001), ciprofloxacin ( 80. 95% vs 100% , P = 0. 035 ) and tetracycline (4. 76% vs 14.29% , P =0.293). Conclusion Uu isolates and Uu1, Uu8 all can form biofilms in vitro, and biofilm formation can strengthen resistance of Uu to antibiotics, even multidrug resistance was observed.     

过氧化物酶体增殖物激活受体γ基因转染对小鼠骨髓基质细胞向心肌细胞分化影响的研究

目的 探讨过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPAR γ)基因表达对骨髓基质细胞(marrow stroma cell,MSC)向心肌细胞分化的影响及其调控作用。方法 原代培养Balb/c纯系小鼠MSC,应用脂质体转染法将pEGFP-N1-PPARγ表达载体转入MSC中,CA18筛选。RT-PCR检测mRNA表达,Western blot法检测蛋白表达。结果 未分化的MSC中PPARγmRNA不表达,GATA4、MEF2C、Nkx2.5表达呈阳性。经pEGFP-N1-PPARγ2转染后,调控成心肌细胞方向分化的转录因子GATA4(0.172±0.034对0.053±0.022,P<0.01)、MEF2C(0.164±0.041对0)、Nkx2.5(0.156±0.029对0)mRNA表达明显下调。MSC向成脂肪细胞方向分化,而向成心肌细胞分化受阻。结论 PPARγ抑制MSC分化过程中GATA4、MEF2C、Nkx2.5 mRNA的表达,抑制MSC向成心肌细胞分化,并促进其向脂肪细胞分化。     

腹腔镜胆总管探查T管引流术后胆漏的发生原因及对策

目的:探讨腹腔镜胆总管探查T管引流术后胆漏的发生原因、预防方法及处理措施。方法:对395例腹腔镜胆总管探查T管引流术后21例胆漏患者的临床资料进行回顾性分析。结果:胆管切口漏胆13例,其中4例经术中常规放置的腹腔引流管引流自愈,9例联合内镜乳头切开和鼻胆管引流治愈。术后T管早期滑脱4例和常规拔T管4例均导致胆汁性腹膜炎,经再次手术置T管和腹腔引流管治愈。结论:腹腔镜胆总管探查T管引流术后胆管切口漏胆、术后T管早期滑脱和T管瘘道形成不全是胆漏发生的主要原因,保持或建立通畅的腹腔引流和胆管引流是治疗胆漏的主要处理措施。     

对氧磷酯酶基因多态性与糖尿病肾病的关系

目的探讨对氧磷酯酶2(PON2)基因A148G多态性与糖尿病肾病的关系.方法(1)用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法探查PON2基因A148G多态性在正常对照组、单纯2型糖尿病组、糖尿病肾病组中的基因频率分布;(2)放射免疫法检测血清免疫反应性胰岛素(IRI)、C肽(C-P)水平.结果(1)糖尿病肾病组GG基因型和G等位基因频率明显高于单纯2型糖尿病组(X2=4.26 P＜0.05,X2=4.89P＜0.05)和正常对照组(X2=4.79 P＜0.05,X2=5.49P＜0.01);(2)基因型为GG的糖尿病患者空腹血糖浓度高于基因型为GA和AA的糖尿病患者的空腹血糖浓度(F=3.90 P＜0.05,F=4.23 P＜0.05);(3)Logistic回归分析表明GG基因型是糖尿病肾病的独立变异危险因素(P＜0.05).结论PON2基因多态性与糖尿病肾病的发生有关.     

Small bowel obstruction at a Filshie clip applicator port site

Laparoscopic Filshie clip sterilisation remains a common method of permanent female contraception. Worldwide, approximately 190 million couples use tubal occlusion (United Nations world population monitoring. United Nations, 2002). Trocar site incisional hernia has been reported as a complication of laparoscopic surgery where a 10-mm port was employed (Tonouchi et al. Arch Surg 139(11):1248–1256, 2004). It is common practice to repair port sites of 10 mm or more to prevent herniation. Port sites of 5 mm are not routinely repaired by most surgeons because it is thought that such iatrogenic fascial defects are not large enough to predispose to hernia (Reardon et al. J Laparoendosc Adv Surg Tech A 9(6):523–525, 1999). We report a rare case of early Filshie clip applicator port site intestinal obstruction following laparoscopic sterilisation. The mechanism of hernia formation and a preventive strategy are discussed.     

螺旋CT增强扫描在胆囊癌诊断中的价值

目的探讨螺旋CT多期增强扫描在胆囊癌诊断中的作用。方法对23例经病理证实的胆囊癌患者的多期螺旋CT表现进行回顾性分析。结果胆囊癌主要CT表现为胆囊壁的不规则增厚和结节状突起以及胆囊内的肿块，增强扫描强化明显且持续时间长。结论螺旋CT多期增强扫描在胆囊癌的定性诊断及了解胆囊癌的侵犯范围上具有重要作用。     

胰腺类癌7例临床分析

目的 分析胰腺类癌的临床特点及诊断.方法 回顾性分析该院7例胰腺类癌的临床资料.结果 4例患者表现为上腹部不适、饱胀或疼痛,1例为腰背部疼痛伴消瘦、乏力,1例表现为类癌综合征,1例为检查时意外发现.出现肝转移者2例,淋巴结肿大者4例.免疫组化:NSE阳性者5例,Syn阳性者5例,CgA阳性者6例.能准确定位的影像学检查有CT(5/7)、超声内镜(3/4).结论 胰腺类癌临床以缺乏特征性的上腹不适为主,典型类癌综合征少见,确诊主要依据病理及免疫组化,超声内镜及CT在定位诊断上有重要意义.