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。     

脑脊液白蛋白和免疫球蛋白IgG检测在儿童病毒性脑炎诊治中的应用

目的：探讨病毒性脑炎患儿脑脊液白蛋白比值（QAlb)、IgG和IgG指数变化与疾病严重程度的相关性。方法研究对象分病毒性脑炎组和对照组,病毒性脑炎组按临床特点分为轻症病毒性脑炎组和重症病毒性脑炎组,采用免疫散射比浊法测定血清和脑脊液的白蛋白、IgG,计算QAlb和IgG指数,判断病毒性脑炎患儿血脑屏障功能状态及免疫球蛋白鞘内合成情况与临床严重程度的关系。结果病毒性脑炎组的QAlb高于对照组;重症病毒性脑炎组的QAlb较轻症病毒性脑炎组和对照组增高,差异有统计学意义（P<0.05）。重症病毒性脑炎组脑脊液IgG、IgG指数比轻症病毒性脑炎组和对照组增高,差异有统计学意义（P<0.05）。结论重症病毒性脑炎组患儿的血脑屏障功能损害程度、鞘内IgG合成情况与临床病情严重程度相关。检测脑脊液和血清中白蛋白、IgG,计算QAlb和IgG指数能反映病毒性脑炎患儿血脑屏障功能状态及IgG鞘内合成情况,为判断病毒性脑炎临床病情的严重程度提供相关依据。     

腹腔镜肾上腺手术中转开放手术及合并症分析

目的　分析腹腔镜肾上腺手术中转开放手术原因及合并症处理。　方法　对 19例腹腔镜肾上腺肿瘤切除术中 8例转开放手术的原因及合并症进行分析。　结果　 8例手术中转开放手术患者包括右肾上腺中静脉出血 1例 ,胰尾遮挡肾上腺肿瘤暴露困难 1例 ,左肾上腺囊肿被副脾遮挡1例 ,手术过程中气腹不满意 2例 ,未找到病灶 2例 ,腹膜后镜手术穿刺时引起腰大肌出血 1例。术后高热 3例 ,其中腹膜后脓肿 1例 ,反应性胸膜炎 1例。　结论　腹腔镜和腹膜后镜手术需要一定经验和熟练的配合 ,初学者操作易出现合并症 ,导致手术失败。腹膜后镜手术治疗肾上腺疾病更简便     

膀胱癌术后腹壁切口种植转移的治疗与预后

目的　总结膀胱部分切除术后腹壁切口种植转移患者的诊治效果。　方法　 1985～1999年共收治膀胱癌术后腹壁切口种植转移患者 10例。男 9例 ,女 1例。年龄 39～ 6 8岁。移行细胞癌 6例 ,均为低分化G3 肿瘤 ;移行细胞癌合并鳞癌和腺癌各 1例 ,鳞癌和粘液腺癌各 1例。腹壁转移灶 1.0～ 6 .9cm× 1.4～ 11.5cm。　结果　采用膀胱全切加腹壁转移灶切除 2例 ,经尿道膀胱肿瘤电切术 (TURBT)加腹壁转移灶切除 1例 ,尿流改道加放疗和 (或 )化疗 2例 ,腹壁转移灶切除加放疗和 (或 )化疗 3例 ,单纯放疗和 (或 )化疗 2例。 10例中死亡 7例 ,其中 6例生存 4～ 14个月 ,1例生存4 1个月 ;3例存活者随访 5～ 9个月 ,未见复发。　结论　膀胱癌术后腹壁切口种植转移癌一般分化差 ,或合并其他癌。膀胱全切加肿物切除 ,辅助放化疗虽然能延长患者生存期 ,但预后很差     

优克龙治疗输尿管结石(附60例报告)

目的　观察优克龙 (Urocalun )治疗输尿管结石的疗效和安全性。　方法　对 6 0例输尿管结石直径 <1cm的患者予口服优克龙治疗 ,4 5 0mg/次 ,3次 /d ,服药 5周。　结果　 6 0例患者中结石排出 4 5例 (75 % ) ;10例 (17% )结石位置下降 ;5例 (8% )位置无变化。 4例患者服药后有轻度胃部不适、恶心或口干。　结论　优克龙治疗输尿管结石效果良好。