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.      

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

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.     

虾青素对去卵巢糖尿病大鼠骨质流失的防治作用

目的探讨虾青素能否防治去卵巢糖尿病大鼠的骨质流失以及可能的机制。方法 3月龄雌性SD大鼠分为3组(每组6只):对照组CON(假手术),模型组OVX/T1DM(去卵巢糖尿病大鼠),药物组OVX/T1DM-ASX(去卵巢糖尿病大鼠,给予虾青素100 mg/(kg·d)。结果连续治疗60 d后,与OVX/T1DM组相比,OVX/T1DM-ASX组骨密度(BMD)明显升高(P0.01),血清I型胶原蛋白(CTX-1)、骨钙素、I型前胶原蛋白n端前肽(PINP)、抗酒石酸磷酸酶5b(TRACP 5b)水平均显著升高(P0.01)。虾青素治疗能抑制去卵巢糖尿病大鼠骨组织形态学的改变,减少骨髓脂肪细胞增加,提高OPG/RANKL的比值。结论虾青素对绝经后糖尿病骨质流失有保护作用,这种作用与调控OPG/RANKL轴有关。     

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。     

彩色多普勒超声心动图诊断肺心病的临床价值

目的：阐述彩色多普勒超声心动图（CDE）诊断肺心病的临床价值。方法：通过CDE对临床上拟诊的肺心病患者进行肺动脉高压（PH）定性、定量的诊断、并观测由PH继发引起心脏在CDE上的异常改变。结果：CDE测定PH44例（88％）,其肺动脉收缩压（SPAP）＞36mmHg,6例（32mmHg≤SPAP＜36mmHg,确诊CPM的临床符合率665（50／76）。结论作为无创性诊技术,CDE估测PH或诊断CPM准确简便,重复性强,对于指导临床治疗意义重大。     

不良妊娠TORCH感染分析

目的　为了了解不良妊娠中TORCH感染的影响。方法　应用酶联免疫吸附试验 (ELISA)对 31例不良妊娠及 43例正常妊娠的孕妇进行TORCH感染监测。结果　两组感染率最高均为CMV ,其次为HSVⅠ 。两组相比CMV有极显著性差异 (P <0 .0 0 5 ) ;HSVⅠ 有显著差异 (P <0 .0 5 )。两组IgG检出率最高均为CMV ,分别为 96 .77%及 6 9.77% ,最低均为TOXO ,分别为 2 .9%、9.3% ;两组的IgM检出率最高均为CMV ,分别为 35 .48%、16 .2 8%。两组易感染率最高均为TOXO。结论　CMV、HSVⅠ 是本地区TORCH感染中对妊娠影响最大的病原体 ,二者均为性传播疾病 ,对其危害不容忽视     

共刺激分子B7在肾细胞癌的表达及意义

目的：检测Ｂ７基因在肾细胞癌的表达及其与肾细胞癌分级、分期及预后的关系。方法：本文应用ＲＴＰＣＲ和免疫组织化学技术检测了２２例肾细胞癌组织Ｂ７的表达。结果：ＲＴＰＣＲ５例阳性,免疫组化４例阳性,Ｂ７ｍＲＮＡ表达与肾癌病理分级、分期无关系;病理切片ＨＥ染色显示,Ｂ７阳性肿瘤组织内淋巴细胞浸润明显增多。结论：表达Ｂ７的肿瘤组织局部抗肿瘤免疫反应增强,提示Ｂ７表达可能与肿瘤预后有关。大部分泌尿系肿瘤不表达Ｂ７,为转Ｂ７基因治疗泌尿系肿瘤提供了理论依据。     

蒙药忠论-5胶囊总生物碱测定及其体外溶出度研究

目的 考察蒙药忠伦-5胶囊中总生物碱含量及其体外溶出情况。方法 以苦参碱为对照品，利用酸性染料比色法测定总生物碱；以水为介质，用转篮法考察其体外溶出度。结果 含量测定方法精密度为RSD＝1．89％，平均回收率为100．89％，RSD＝3．49％。；苦参总生物碱相对累积溶出度与溶出时间相关显著(P＜0．01)，T50＝24min，Td＝31min，m＝1．32。结论 用上法测定总生物碱含量及体外溶出度，对评估忠伦-5胶囊质量有实用价值。