T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

p53 immunoreactivity in hepatocellular adenoma, focal nodular hyperplasia, cirrhosis and hepatocellular carcinoma

The prolonged half-life of mutant p53 makes feasible its immunocytochemical detection. In order to assess the pathogenetic role of mutant p53 in regenerative and neoplastc liver disease we studied its immunohistochemical expression in cases of hepatic cirrhosis, hepatocellular carcinoma (HCC), cirrhosis with areas of HCC, hepatocellular adenoma and focal nodular hyperplasia. The study included needle and wedge biopsies of 50 cirrhotic livers, 59 HCCs (36 of them with associated cirrhosis), six adenomas and two focal nodular hyperplasias. Sixty-five HCC fineneedle cytology specimens were also included in the study. There was no immunohistochemical evidence of mutant p53 expression in any of the cases of cirrhotic liver (except for one instance associated with HCC) adenoma or focal nodular hyperplasia. In contrast p53 was detected in 8.5% of HCC cases in the biopsy series and 24% of HCC cases in the fine needle aspiration series. In addition, mutant p53 expression in HCC was positively correlated with tumour grade. According to grade, the distribution of p53 positive immunoreactivity among HCCs was as follows: Grade I-II, 0% of cases in the biopsy series and 9% in the fine needle aspirates; Grade III, 18% in the biopsy series and 55% in the fine needle aspirates; and Grade IV, 40% in the biopsy series. Therefore, mutant p53 expression does not seem to be associated with benign liver lesions but seems to correlate with the progression of HCC through various grades of increasing malignancy.     

电离辐射对放射工作者职业健康的影响

目的 分析放射工作者外周血象、淋巴细胞微核及染色体畸变情况,为放射工作者职业防护和健康监测提供依据。方法 对2015年、2017年和2019年连续3次接受健康检查的127名放射工作者进行淋巴细胞微核、染色体及血象分析,将其设为放射组。另外选取133名无射线接触史的医务人员设为对照组;结果 放射组中淋巴细胞微核率和染色体畸变率高于对照组,白细胞和血小板计数低于对照组,均具有统计学意义（P < 0.05）。127名放射工作者外周血白细胞总数随着接触电离辐射时间的增长逐渐降低,染色体畸变率逐渐增加,均具有统计学意义（P < 0.05）。损害工龄大于20年的放射工作者染色体畸变率高于低工龄组,不同损害工龄之间比较无统计学意义（P > 0.05）。核医学与介入治疗工种染色体畸变率高于其他工种,具有统计学意义（P < 0.05）。结论 长时间接触低剂量电离辐射可使放射工作者白细胞总数降低和淋巴细胞染色体畸变率增加,应加强放射工作者防护措施以备降低电离辐射损伤程度,特别要加强核医学和介入治疗放射工作人员的职业防护。     

肝脏移植术后移植物抗宿主病的诊断和治疗

【目的】 探讨肝脏移植术后移植物抗宿主病（GVHD）的诊断和治疗。【方法】 分析我院2003年10月至2009年6月完成的772例肝脏移植的临床资料,总结肝脏移植术后GVHD的诊断和治疗经验。【结果】 772例肝脏移植术后5例病人发生GVHD,发病率为0.65%（5/772）,5例患者均在肝脏移植后2～5周出现发热、皮疹、腹泻和全血细胞减少,肝功能均接近正常,经皮肤活检和骨髓穿刺检查证实,并排除巨细胞病毒（CMV）和EB病毒感染。经过调整免疫抑制剂,加用IL-2受体单克隆抗体,积极抗感染和支持对症治疗,2例患者痊愈,3例患者死于严重感染、消化道出血和多器官功能衰竭。【结论】 肝脏移植术后GVHD死亡率高,早期诊断,及时调整免疫抑制剂方案,积极抗感染和营养支持是治疗的关键。     

Cyclic neutropenia (CN): a clue to the control of granulopoiesis

A simple quantitative feedback model of granulopoiesis is presented and discussed within the framework of existing data on granulopoiesis in both normals and patients with cyclic neutropenia (CN). The model assumes that the controlled compartment is the bone marrow pool of mature neutrophils (PMNs), which sends a negative feedback signal to the mitotic pool of early granulocyte precursors (i.e., CFU-C, myeloblasts, etc.) thus controlling the granulocyte production rate. Three parameters are found to play important roles in determining the response of the system to perturbations. These are: TM, the granulocyte maturation time; a, a parameter reflecting the strength of the negative feedback exerted by mature PMNs on the granulocyte production rate; and b, a parameter describing the leakiness of the bone marrow for PMN egress. It is shown that depending on the relative magnitudes of a and b, the system will either respond to perturbations with a damped oscillation (a less than b: the normal state) or with a sustained oscillation (a greater than b: the CN state). In both cases, the oscillation period is found to approximately equal 2TM. Deductions of the values of a, b, and TM from experimental data are consistent with the predictions of the model and show an increased value of a in CN relative to the normal state. This suggests an overly active feedback mechanism as the pathophysiologic basis of CN. In addition, the model can explain how various therapeutic agent correct CN and also provides insight into why other hematologic cell lines and CSA oscillate in CN.     

CT引导经皮置钉治疗病理性骶髂关节疼痛

目的：探讨在CT引导下经皮微创技术置入空心拉力螺钉治疗病理性骶髂关节疼痛。方法：骶髂关节转移肿瘤患者8例，男4例，女4例；年龄12～83岁，平均53岁。单侧转移5例，双侧3例。肺癌2例，乳腺癌1例，卵巢癌1例，非霍奇金淋巴瘤1例，横纹肌肉瘤1例，骨髓瘤1例，前列腺癌1例。试行在CT引导下经皮微创技术置入空心拉力螺钉稳定病理性骶髂关节不稳。术前和术后通过Ennek—ing疼痛评分进行比较。结果：8例均获随访，随访时间4个月～29个月，平均18．2个月。均1周内疼痛缓解，无并发症发生，3例术后6个月内死亡，余5例疼痛明显减轻。结论：CT引导下经皮置入空心拉力螺钉能有效缓解病理性骶髂关节不稳所致的疼痛。     

不同途径前列腺切除术后发生性功能障碍的比较

目的:探讨耻骨上经膀胱前列腺切除术(SPP)、经尿道前列腺电切术(TURP)、经尿道前列腺电气化联合电切术(TUVP加TURP)治疗BPH对患者性功能的影响。方法:采用国际勃起功能问卷简化表(IIEF5)通过调查问卷方式,对104例接受上述手术的BPH患者术前、术后6个月勃起功能及逆行射精情况进行问卷评分。结果:SPP、TURP、TUVP加TURP三组患者术前IIEF5评分分别为17.4、17.9、18.1分,术后6个月IIEF5评分分别为11.7、13.2、10.2分,手术前后比较差别有统计学意义(P<0.05)。三组之间IIEF5评分降低程度比较TUVP加TURP>SPP>TURP,差别有统计学意义(P<0.05)。三组术后逆行射精的发生率分别为23.1%、32.5%、25.0%。结论:三组手术均可导致患者勃起功能障碍的发生,其中以TUVP加TURP发生率最高,逆行射精发生率以TURP最高。提高手术操作技巧,避免包膜损伤,作好解释工作,可减少术后患者勃起功能障碍的发生。     

284例泌尿系结石成分分析与代谢评价

目的 研究结石成分与代谢异常的关系。方法 分析284例泌尿系结石患者的结石成分及其中191例完整血生化及24h尿分析结果。结果 草酸钙结石195例（68．7％），感染性结石41例（14．4％），尿酸结石38例（13．4％），磷酸盐结石6例（2．1％），胱氨酸结石4例（1．4％）。191例有完整血生化及24h尿分析结果患者中代谢异常176例（92．1％），其中高钙尿症27例（14．1％），高尿酸尿症54例（28．3％），高草酸尿症41例（21．5％），高尿磷55例（28．8％），低枸橼酸尿症128例（67．0％），低尿镁症80例（41．9％），24h尿量〈2000ml者65例（34．0％），高胱氨酸尿症4例（2．1％）。94例随访10～58个月，平均22个月。无泌尿系结石复发52例，复发42例，无复发组代谢无异常12例，复发组2例（P〈0．01），无复发组和复发组4种异常者分别为2例和7例（P〈0．01）。结论　结石复发与多种代谢异常关系密切；确定结石成分及患者的代谢评价对泌尿系结石的成因、治疗和预防有重要的临床意义。     

多层螺旋CT联合纤维蛋白原或血清淀粉样蛋白A对直肠癌外科决策的随机对照研究

目的 探讨多学科协作模式 (MDT)下血清淀粉样蛋白A(SAA)或纤维蛋白原(FIB)和64排多层螺旋CT(MSCT)联合评估对于直肠癌手术方式选择的影响和意义.方法 前瞻性纳入2009年2～6月期间四川大学华西医院肛肠外科住院的直肠癌患者240例,随机均分为MSCT+SAA组(术前行MSCT和SAA联合评估)和MSCT+FIB组(术前行MSCT和FIB联合评估),将术前分期和预测手术方案分别与术后病理分期和实际手术方案比较,并分析手术方案选择与临床病理因素的关系.结果 本研究实际纳入病例234例, MSCT+SAA组118例,MSCT+FIB组116例,2组基线情况一致(P>0.05).MSCT+SAA组的术前T、N、M和TNM分期的准确度分别为72.9%、83.1%、100%和80.1%; MSCT+FIB组的术前T、N、M和TNM分期的准确度分别为68.1%、75.0%、100%和74.1%.2组术前各分期准确度差异均无统计学意义(P>0.05).2组手术方案的预测符合率分别为99.6%及96.6%,差异无统计学意义(P>0.05).分析直肠癌手术方案的选择与多种临床病理因素的关系发现,pT分期(P＜0.001)、pN分期(P＜0.001)、pTNM分期(P＜0.001)、术前血清SAA水平(P＜0.001)、术前血清FIB水平(P＜0.001)和肿瘤下缘距齿状线距离(P＜0.05)与直肠癌手术方案的选择相关.结论 MSCT联合FIB可以提高直肠癌术前分期和手术方案预测的准确度,但其临床价值可能并不优于MSCT联合SAA.