Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule

Park C‐S, Kim K‐H, Im S‐A, Song S, Lee C‐K. Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule. Xenotransplantation 2012; 19: 317–322. © 2012 John Wiley & Sons A/S. Abstract: Indirect recognition of xenoantigens has been implicated as the major mechanism underlying xenospecific CD4⁺ T‐cell activation in chronic rejection. We identified swine leukocyte antigen (SLA)‐derived immunogenic peptides that are presented in the context of human HLA‐DR4 molecules. The SLA class I‐derived peptides that bind HLA‐DRB1*0401, a representative of the DR4 supertype, were predicted using a computer‐assisted algorithm. The candidate peptides were synthesized, and their binding capacities to HLA‐DRB1*0401 were compared in a competitive ELISA using biotinylated hemagglutinin reporter peptides [HA_307‐319]. Peptide‐11 (LRSWTAADTAAQISK) was determined to exhibit the most potent binding capacity to HLA‐DRB1*0401 in vitro and thus selected for in vivo immunization. Immunization of HLA‐DRB1*0401‐transgenic mice with peptide‐11 elicited potent CD4⁺ Th1 responses. Peptide‐11 shares homology to α2 domains of three SLA‐1 alleles, six SLA‐2 alleles, and 14 SLA‐3 alleles. Thus, this study has important implications not only for the identification of an immunogenic indirect epitope shared by diverse SLA class I alleles, but also for the development of epitope‐specific immunoregulation strategies.     

Notch1在人乳腺癌细胞中的表达及其与乳腺癌耐药的关系

目的 检测乳腺癌细胞株MCF-7与MCF-7/ADR的 Notch1 表达、成球能力、干细胞池比例及干细胞内Notch1的表达,探讨Notch1 在逆转乳腺癌化疗耐药中的意义.方法 实时荧光定量逆转录-聚合酶链反应(RT-qPCR)及Western blot 法检测乳腺癌细胞株MCF-7、MCF-7/ADR 及表型为ALDH1+/CD44+/CD24- 乳腺癌干细胞中Notch1 的表达;无血清培养检测MCF-7及MCF-7/ADR 的成球能力;流式细胞仪检测MCF-7与MCF-7/ADR的干细胞比例并分选干细胞.结果 MCF-7/ADR的Notch1 的表达明显高于MCF-7(0.0748±0.0043比0.0461±0.0022,P＜0.05),微球体形成能力也明显高于MCF-7 (P＜0.05);流式细胞仪检测干细胞比例,MCF-7/ADR高于MCF-7(11.40％比1.89％);分选出的干细胞Notch1 的表达明显高于非干细胞(0.3096±0.0324比0.0428±0.0061,P ＜0.05).结论 Notch1 在乳腺癌及乳腺癌干细胞中高表达,干预Notch1 可能可以逆转乳腺癌治疗的耐药.     

Surgical management of symptomatic os odontoideum with posterior screw fixation performed using the magerl and harms techniques with intraoperative 3-dimensional fluoroscopy-based navigation

STUDY DESIGN.: Retrospective case series. OBJECTIVE.: To evaluate the accuracy of screw fixation using intraoperative three-dimensional fluoroscopy-based navigation (ITFN) and to assess the clinical outcomes of this treatment regimen. SUMMARY OF BACKGROUND DATA.: The surgical management of symptomatic os odontoideum poses considerable difficulties due to the highly variable anatomy of the upper cervical spine and surrounding neurovascular structures. Various methods have been described for the treatment of symptomatic os odontoideum, all of which have limitations. METHODS.: Nineteen patients with symptomatic os odontoideum were investigated. Pain scores were assessed using the visual analogue scale. Myelopathy was assessed using the Nurick scale and Odom's criteria. Radiological imaging was carried out in all patients for diagnosis and to assess the atlantodens interval, space available for cord, and presence of intramedullary hyperintensity signals on T2-weighted images at the C1-C2 level. Posterior stabilization was performed for all patients by using ITFN. RESULTS.: The mean Nurick score improved from 2.3 before surgery to 0.7 at the time of follow-up. The mean follow-up period was 34.7 months (range, 12-65 mo). According to Odom's criteria, outcomes were as follows: excellent, 47%; good, 37%; fair, 11%; and poor, 5%. All patients with preoperative neck pain had symptom relief or improvement, with all of these patients having more than 83.7% improvement in visual analogue scale scores. The mean preoperative space available for cord value of 9.3 mm improved to 17.7 mm. Solid fusion and reduction of atlantoaxial dislocation were achieved in every patient without screw failure. Sixty screws were placed in 19 patients. Two C2 polyaxial screws in 2 patients and 1 transarticular screw in 1 patient slightly penetrated the transverse foramen with no vascular injury and clinical sequelae. CONCLUSION.: ITFN is a safe, accurate, and effective tool for screw placement in patients with symptomatic os odontoideum.     

Direct killing of xenograft cells by CD8+ T cells of discordant xenograft recipients

BACKGROUND: Long-term pig xenografts in monkeys demonstrated the infiltration of CD8 T cells into pig cartilage xenografts, transplanted into monkeys. The objective of the present study was to determine in an experimental animal model whether CD8 T cells in pig xenograft recipients exert any direct cytotoxic effect on pig cells. METHODS: The killing of xenograft cells by CD8 T cells, obtained from xenograft recipients, was studied in alpha1,3galactosyltransferase knockout mice that were repeatedly injected intraperitoneally with pig kidney membranes. The pig kidney cell line PK15, which shares many antigens with pig kidney membranes, served as a model for xenograft target cells in cytotoxicity assays. Cell lines from other species were also studied as target cells. RESULTS: Lymphocytes obtained freshly from spleens of mice immunized with pig kidney membranes failed to display significant cytotoxic activity against pig cells. However, incubation of these lymphocytes with irradiated PK15 cells and addition of recombinant interleukin (IL)-2 (100 U/mL), on the third day of incubation, resulted in extensive proliferation and expansion of CD8 cytotoxic T lymphocytes (CTL). These CTL, obtained after 12 days of incubation, killed nonspecifically pig, human, and mouse normal and malignant cells. These CTL were not generated in cultures in the absence of stimulatory pig cells or in the absence of IL-2. These CTL could not be generated in cultures of lymphocytes from naive mice that were incubated with PK15 cells and IL-2. CONCLUSIONS: The data obtained imply that CD8 T cells from xenograft recipients can be stimulated in vitro by xenoantigens and IL-2 to differentiate into highly reactive nonspecific CTL that are capable of killing a large variety of xenogeneic and syngeneic cells. Similar in vivo microenvironmental conditions within the xenograft may induce the local differentiation of infiltrating CD8 T cells into CTL that can destroy nonspecifically adjacent xenograft cells. Such cells may not be active outside the xenograft because of the absence of IL-2 in sufficiently high concentrations.     

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice

Background

Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease.

Comparison of clinical outcomes in diabetic and non-diabetic burns patients in a national burns referral centre in southeast Asia: A 3-year retrospective review

Objective

Diabetic burns patients may be at risk of worse clinical outcomes. This study aims to further investigate the impact of diabetes mellitus on clinical outcomes in burns patients in Singapore.

Unexplained Pain Post Total Knee Arthroplasty With an Oxford Knee Score ≥20 at 6 Months Predicts Good 2-Year Outcome

Background

Total knee arthroplasty (TKA) is an effective procedure for end-stage osteoarthritis of the knee. Some patients experience persistent unexplained pain post-TKA despite normal investigations. The purpose of this study is to identify which of these patients are likely to improve without any surgical intervention. We hypothesize that patients with unexplained persistent pain and a poor 6-month Oxford knee score (OKS) post-TKA can improve at 2 years.

小脑扁桃体软膜下切除术与硬膜扩大修补术治疗ChiariⅠ型畸形并脊髓空洞的疗效观察

目的 :观察小脑扁桃体软膜下切除术与硬膜扩大修补术治疗ChiariⅠ型畸形合并脊髓空洞的手术效果及预后,为临床治疗提供决策。方法:回顾性分析2013年11月~2016年11月在我院接受治疗的115例ChiariⅠ畸形患者的临床资料,男34例,女81例;年龄16~60岁(42.3±11.3岁)。患者有脊髓空洞症表现49例次,枕大孔区神经刺激症状58例次,延颈髓受压症状9例次,后组颅神经及小脑功能障碍25例次,高颅压症状24例次。脊髓空洞26例累及颈段,85例累及胸段,4例累及腰段,3例合并有脑积水,2例合并有胸段脊柱侧凸。其中78例采用后颅窝减压+下疝的小脑扁桃体切除+四脑室流出道的膜性结构切除术(A组),37例采用枕骨大孔区减压+硬脑膜成形术(B组)。记录患者的住院时间,术中出血量,术后并发症,术前、术后6个月影像学特征,Klekamp神经评分,临床症状变化情况。结果:A组手术时间为159.32±40.06min,高于B组(134.10±30.76min)(P0.05);术后A、B组分别有11例、8例发热,3例、1例皮下积液,3例、2例切口感染,A组术后头晕头痛发生率(25.6%,20/78)高于B组(8.1%,3/37)(P0.05),总体并发症发生率两组无明显差异(P0.05)。术后疼痛、感觉障碍、共济失调、运动障碍的Klekamp神经评分较前有改善(P0.05);术后A组症状改善69例(88.4%),B组31例(83.8%);两组神经评分改变、临床表现改善情况差异无统计学意义(P0.05);术后空洞闭合或缩小例数分别为54例、29例,无变化例数分别为22例、7例,扩大例数为2例、1例,两组术后空洞变化差异无统计学意义(P0.05)。结论:小脑扁桃体软膜下切除术治疗ChiariⅠ型畸形并脊髓空洞手术效果与硬膜扩大修补术无明显差异,但手术时间长,术后头晕头痛发生率较高。     

胎盘生长因子的病理学作用

肿瘤的血管生成是肿瘤发生、发展、转移过程中的重要环节,受多种因子调节.胎盘生长因子是血管内皮生长因子家族中的一员,氨基酸序列和VEGF-A有高度的同源性,以VEGFR-1为受体.胎盘生长因子(placenta srowth factor,PLGF)在生理条件下,在成年人、成熟组织中表达弱,但在病理条件下,如缺氧、外伤、肿瘤等,是一种重要的病理性血管生成因子,在病理性妊娠、特别是多种肿瘤组织中有高表达,而且和肿瘤的病理程度相关,对其研究具有重要的临床价值.     

MRI三维重建在聚丙烯酰胺水凝胶注射隆乳术后诊断中的应用

目的 探讨聚丙烯酰胺水凝胶注射隆乳术后分布的有效诊断方法.方法 对聚丙烯酰胺水凝胶注射隆乳术后的患者进行双侧乳房MRI薄层扫描(层厚1 mm,t2_ps3d_cor序列),在计算机上运用Amira电脑软件模块对扫描信息分别进行体积重建和表面重建,观察水凝胶的分布范围和部位,并计算其体积.结果 自2007年3月以来,于临床应用23例(46只乳房),其中5例(10只)水凝胶位于乳房后间隙,包膜完整,分布均匀,无移位;6例(12只)注射的水凝胶包膜不完整,形态不规则,边缘不整,呈多处散在的团块分布;11例(22只)水凝胶浸及胸大肌内、胸大肌后方、乳腺组织内和皮下,1例(2只)外院双侧取除水凝胶术后复查发现仍有少量残留,散在分布于乳腺及变性肌肉组织中.初次就诊的22例(44只)注射水凝胶的总体积为220.309～372.371 ml,平均306.328ml.结论 MRI三维重建能清晰显示注射物的体积和分布范围,可以有效地指导水凝胶的手术取除.