完全型雄激素不敏感综合征2例临床特点及处理

雄激素不敏感综合征(androgen insensitivity syndrome,AIS)又称为睾丸女性化综合征(testicular feminization syndrome,TFS),是一种X连锁遗传病,是男性假两性畸形中较常见的类型,可分为完全型AIS和不完全型AIS,其原因主要是雄激素受体(androgen receptor,AR)基因的突变导致其对雄激素产生抵抗和不应答。本文回顾南京医科大学附属妇产医院2例CAIS患者的临床资料及诊疗过程,以期能进一步提高对该病的认知及诊治水平。     

4例SRY阳性的46,XX男性综合征患者临床及细胞分子遗传学研究

目的:探讨SRY阳性的46,XX男性综合征患者的临床及细胞分子遗传学特征。方法:分析4例SRY阳性的46,XX男性综合征患者的临床特点,并进行染色体核型分析、荧光原位杂交(FISH)、SRY基因检测、Y染色体微缺失等细胞和分子遗传学检测。结果:4例患者社会性别均为男性,身材低于正常男性均值。均因不育就诊,双侧睾丸体积小、质地软,精液检查均为无精子症。阴茎发育正常。性激素检查示高促性腺激素性性腺功能不全。染色体核型均为46,XX,Y染色体微缺失检测示AZFa,b,c区域均缺失。SRY基因均存在,FISH结果3例患者显示SRY基因易位于X染色体短臂。结论:SRY阳性的46,XX男性综合征患者常为男性表型,但睾丸发育不良,多伴有身材矮小和不育。患者的男性表型是由于基因组中存在SRY基因。无精子表型是由于缺失AZF。Y染色体长臂上可能存在与身高相关的基因。深入进行细胞、分子遗传学研究有助于揭示46,XX男性综合征基因型-表型的关系。     

2-甲基-7-亚甲基-1,4,6-三氧螺[4,4]壬烷与丙烯腈、丙烯酸甲酯的共聚合反应及竞聚率的测定

用高效液相色谱跟踪2-甲基-7-亚甲基-1,4,6-三氧螺[4,4]壬烷(MMTN)与丙烯腈(AN),丙烯酸甲酯(MA)的共聚合反应。根据Lowry-Meyer共聚积分方程式,采用插值法进行数据拟合测定单体的竞聚率。对于体系MMTN(M_1)-AN(M_2),r_1=0.048;r_2=0.213;MMTN(M_1)-MA(M_2)r_1=0.025,r_2=0.764。说明两组共聚体系均有较强的交替共聚趋势。     

SRY基因突变和性腺肿瘤发生的研究Ⅰ．家族性46，XY女性SRY基因检测

近年证明ＳＲＹ男性性基因是性别决定关键。ＳＲＹ突变能引起男性性异常。４６，ＸＹ性腺发育不全（或ＸＹ女性）系ＳＲＹ基因突变所致，并有高发性腺肿瘤特点。ＳＲＹ突变有多种类型；本研究检测一家庭集聚性ＸＹ女性高发肿瘤成员有个ＳＲＹ基因缺失。结合细胞遗传学和病理学检查结果，对ＸＹ女性性腺癌变机理提出了推测。     

弱精子症患者精子蛋白的初步研究

目的从蛋白质水平探讨弱精子症患者精子蛋白的改变,以期寻找精子活动力低下的原因。方法运用蛋白凝胶电泳技术分离90例特发性弱精子症患者和30例正常供精者精子标本的总蛋白质,结合免疫印迹技术鉴定差异蛋白,并对试验数据进行统计学分析。结果患者组与对照组精子蛋白表达量存在差异,且患者组中精子活力低下不同严重程度者的蛋白含量也存在差异(P<0.05),对于差异显著条带的Western Blotting分析显示差异蛋白为DDX4。结论精子活力与蛋白质差异表达有关,主要差异蛋白DDX4可作为评估精子活力的生物标志物。     

Feedback Stimulation of Somatodendritic Serotonin Release: A 5-HT3 Receptor-Mediated Effect in the Raphe Nuclei of the Rat

Slices from rat midbrain containing the raphe nuclei and from hippocampus were prepared, loaded with [³H]5-HT and superfused and the resting and the electrically stimulated [³H]5-HT release was measured. The 5-HT₃ receptor agonist 2-methyl-5-HT (1 to 10 μmol/l) increased the resting tritium outflow in superfused raphe nuclei slices, EC₅₀ 5.3 μmol/l. The 2-methyl-5-HT-induced increase of tritium outflow was an external Ca²⁺-independent process and was not altered by reserpine pretreatment but it was reversed by addition of the 5-HT uptake inhibitor fluoxetine (1 μmol/l). The 5-HT₃ receptor antagonists ondansetron and GYKI-46 903 (1 μmol/l) did not antagonize the stimulatory effect of 2-methyl-5-HT on resting tritium outflow. 2-Methyl-5-HT in lower concentration increased the electrically induced tritium overflow from raphe nuclei slices (EC₅₀ 0.56 μmol/l) and also from hippocampal slices preloaded with [³H]5-HT. These effects were reversed by 1 μmol/l of ondansetron and GYKI-46903. The 5-HT₃ receptor antagonists (1 μmol/l) were without effects on depolarization-evoked [³H]5-HT release at 2 Hz stimulation, when 10 Hz stimulation was used, ondansetron and GYKI-46 903 reduced the tritium overflow from raphe nuclei slices. These data indicate that 5-HT₃ receptors positively alter depolarization-induced somatodendritic 5-HT release in the raphe nuclei. They also show that 2-methyl-5-HT is able to evoke 5-HT release not only from vesicles but also from cytoplasmic stores via a transporter-dependent exchange process.     

Efficiency of work performance and contraction velocity in isotonic tetani of frog sartorius

Mechanical work, ATP, ADP, PC, free creatine and lactate concentrations were determined on IAA poisoned frog sartorii tetanically stimulated in humidified N, at 10°C in isotonic conditions (0.25 or 0.45 P₀). Tetanus duration was 0.35 s, number of tetani was varied from 0 (rest) to 25 (exhaustion). The mechanical work performed per mole ATP+PC split (W _P ^* ) amounted on the average to 16.7 kJ/mol. It was observed, however, that w _p ^* increased from about 13 to about 24 kJ/mol with decreasing ATP concentration from about 2 (resting value) to about 1 mol/g and that this decrease in ATP was associated with a decrease of the shortening (and relaxation) speed of the muscle to about 30% of the values observed on the first tetanus. It is concluded that the thermodynamic efficiency of muscle contraction, calculated from the ratio of w _P ^* (measured) to the thermodynamic affinity (free energy change) of ATP hydrolysis (estimated) increases from about 0.3 to about 0.5 with decreasing ATP concentration and shortening speed.This work was supported by the Fonds National Suisse de la Recherche Scientifique, Grants 3.332.78 and 3.364.0.82     

Measles virus-induced down-regulation of CD46 is associated with enhanced sensitivity to complement-mediated lysis of infected cells

CD46, the major component of the measles virus (MV) receptor complex and a member of the regulators of complement activity (RCA) gene cluster, is down-regulated in MV-infected cells. We investigated whether the reduction of surface CD46 correlates with enhanced sensitivity of lymphoid and monocytic cells to lysis by activated complement. On human U937 cells, acutely or persistently infected with MV-Edmonston (ED) vaccine strain, infection-dependent down-regulation of CD46 confers sensitivity to activated complement, regardless of the pathway of activation and the specificity of the activating antibodies. Interestingly, down-regulation of CD46 alone is sufficient to confer susceptibility of cells to complement lysis despite the continued surface expression of other RCA proteins such as CD35 and CD55. In primary cultures, both peripheral blood lymphocytes and macrophages are efficiently lysed in the presence of complement activated via the alternative pathway after MV infection. In contrast to the MV-ED infection, infection of cells with the lymphotropic MV wild-type strain WTF does not down-regulate CD46. Cells infected with MV-WTF do not exhibit enhanced susceptibility to complement lysis. These data suggest that MV strains similar to WTF that do not down-regulate CD46 may have an enhanced potential for replication and dissemination within the human host, whereas complement-mediated elimination of cells infected with CD46-down-regulating strains of MV, such as ED, may limit the spread of MV infection, and could thus represent an attenuating factor for MV.     

Study of carrier frequency of Warsaw breakage syndrome in the Ashkenazi Jewish population and presentation of two cases

Warsaw breakage syndrome (WABS), caused by bi‐allelic variants in the DDX11 gene, is a rare cohesinopathy characterized by pre‐ and postnatal growth retardation, microcephaly, intellectual disability, facial dysmorphia, and sensorineural hearing loss due to cochlear hypoplasia. The DDX11 gene codes for an iron–sulfur DNA helicase in the Superfamily 2 helicases and plays an important role in genomic stability and maintenance. Fourteen individuals with WABS have been previously reported in the medical literature. Affected individuals have been of various ethnic backgrounds with different pathogenic variants. We report two unrelated individuals of Ashkenazi Jewish descent affected with WABS, who are homozygous for the c.1763‐1G>C variant in the DDX11 gene. Their phenotype is consistent with previously reported individuals. RNA studies showed that this variant causes an alternative splice acceptor site leading to a frameshift in the open reading frame. Carrier screening of the c.1763‐1G>C variant in the Jewish population revealed a high carrier frequency of 1 in 68 in the Ashkenazi Jewish population. Due to the high carrier frequency and the low number of affected individuals, we hypothesize a high rate of miscarriage of homozygous fetuses and/or subfertility for carrier couples. If the carrier frequency is reproducible in additional Ashkenazi Jewish populations, we suggest including DDX11 to Ashkenazi Jewish carrier screening panels.