糖稳态调节细胞定向分化的基因改造方案探讨

目的:探索糖稳态调节细胞定向分化的基因改造方案思路.方法:①研究构建的解除干细胞分化抑制状态的信号传导与转录激活因子-3(STAT-3)基因载体,检测其介导目的基因感染ARIP等细胞基因表达;②研究构建的活化配体DL诱导N信号、在"旁侧抑制"过程中扮演重要角色的Kuzbanian(KUZ)基因载体在转基因小鼠表达后糖稳态调节细胞的分化.结果:在完成的STAT-3腺病毒基因载体生产了腺病毒,用带有目的基因的腺病毒对ARIP靶细胞进行感染,3 d后,荧光显微镜观察时,活细胞、固定液固定细胞均看到了构建基因中绿色荧光蛋白成功、高效的阳性表达报告.在完成的Kuzbanian(KUZ)基因载体构建、转基因、动物模型、小鼠品系鉴定后,用非放射性原位杂交实验对胰腺靶细胞的mRNA进行检测,获得了预期的阳性结果.结论:通过用某些分化抑制性基因的显性失活形式(DN)竞争性预先解除干细胞分化的抑制状态,然后再定向分化诱导使之朝向期望的目标细胞方向分化,可能是糖稳态细胞定向分化的可行途径之一.     

Hyperbilirubinemia, hypocarbia and periventricular leukomalacia in preterm infants: relationship to cerebral palsy

This study comprised 103 preterm infants with a gestational age less than 33 weeks who were born in Tampere University Hospital and who were followed up to two years of age. Sixty-four perinatal variables were compared to ultrasound findings in the neonatal period and neurologic handicap at the age of two years. Duration of hypocarbia (PCO2 < or = 30 mmHg) during the first 72 h and hyperbilirubinemia (the mean level of serum total bilirubin) at three days of age were independently and significantly related to periventricular leukomalacia, but not directly to cerebral palsy. The only perinatal variables related independently and significantly to cerebral palsy at two years of age were periventricular leukomalacia and ventriculomegaly. According to these results, periventricular leukomalacia was the main predictor of cerebral palsy in preterm infants. In addition to hypocarbia, hyperbilirubinemia may also be involved in the pathogenesis of extensive (severe cystic) periventricular leukomalacia.     

Qualitative assessment of maternal uterine and fetal umbilical artery blood flow and resistance in laboring patients by Doppler velocimetry

The purpose of this study is to evaluate the effect of uterine contractions during labor on both the uterine and the umbilical circulations. Twenty-seven patients in active labor were studied by continuous-wave Doppler velocimetry. Umbilical, left uterine, and right uterine arterial waveforms were obtained before, during, and after peak uterine contractions, and the ratio of maximum systolic and minimum diastolic velocities was calculated. Fifteen patients showed absent flow in end diastole on the uterine artery waveform and had significantly higher intra-amniotic pressures (64.5 +/- 3.5 mm Hg) during the peak amplitude of the uterine contraction compared with the 12 patients with maintained end diastolic flow (46.5 +/- 2.6 mm Hg; p less than 0.05). During the peak amplitude of the uterine contractions the 12 patients maintaining end-diastolic flow had significantly higher systolic/diastolic ratios in the uterine artery (6.5 +/- 1.5) compared with either before or after a contraction (2.1 +/- 0.15 and 2.0 +/- 0.2, respectively; p less than 0.05). Also, these 12 patients showed a linear relationship between the systolic/diastolic ratio and the intrauterine pressure. However, no differences were observed in the umbilical artery systolic/diastolic ratios before, during, or after a contraction in the intensity range studied. On the contrary, during contractions an increase in uterine artery resistance occurs with decreased or absent end-diastolic flow, which bears an inverse linear relationship to the intensity of the contraction. This suggests that during uterine contractions the human fetus continues to have uninterrupted fetoplacental blood flow, whereas the degree of interruption or reduction in uteroplacental blood flow is dependent on the intensity of uterine contraction.     

Physiological anticoagulants and activated protein C resistance in childhood stroke

Immunological and functional protein S, protein C and antithrombin III levels and anticoagulant responses to activated protein C were measured in 24 patients with stroke in childhood. No hereditary deficiencies were found. The protein S levels in healthy controls of younger age did not differ from the adult levels. For optimal screening of protein S deficiency, measurements using functional as well as immunological assays are recommended. Appropriate criteria for the diagnosis of the deficiencies must be carefully applied if unnecessary anxiety and inappropriate treatment of children are to be avoided.