Thrombopoietin stimulates megakaryocytopoiesis, myelopoiesis, and expansion of CD34+ progenitor cells from single CD34+Thy-1+Lin- primitive progenitor cells

Thrombopoietin (TPO) or MpI ligand is known to stimulate megakaryocyte (MK) proliferation and differentiation. To identify the earliest human hematopoietic cells on which TPO acts, we cultured single CD34+Thy- 1+Lin- adult bone marrow cells in the presence of TPO alone, with TPO and interleukin-3 (IL-3), or with TPO and c-kit ligand (KL) in the presence of a murine stromal cell line (Sys1). Two distinct growth morphologies were observed: expansion of up to 200 blast cells with subsequent differentiation to large refractile CD41b+ MKs within 3 weeks or expansion to 200-10,000 blast cells, up to 25% of which expressed CD34. The latter blast cell expansions occurred over a 3- to 6-week period without obvious MK differentiation. Morphological staining, analysis of surface marker expression, and colony formation analysis revealed that these populations consisted predominantly of cells committed to the myelomonocytic lineage. The addition of IL-3 to TPO-containing cultures increased the extent of proliferation of single cells, whereas addition of KL increased the percentage of CD34+ cells among the expanding cell populations. Production of multiple colony- forming unit-MK from single CD34+Thy-1+Lin- cells in the presence of TPO was also demonstrated. In limiting dilution assays of CD34+Lin- cells, TPO was found to increase the size and frequency of cobblestone areas at 4 weeks in stromal cultures in the presence of leukemia inhibitory factor and IL-6. In stroma-free cultures, TPO activated a quiescent CD34+Lin-Rhodamine 123lo subset of primitive hematopoietic progenitor cells into cycle, without loss of CD34 expression. These data demonstrate that TPO acts directly on and supports division of cells more primitive than those committed to the MK lineage.     

多聚二磷酸腺苷核糖合成酶抑制剂对血管紧张素Ⅱ刺激培养心肌细胞异常基因表达的阻止作用

目的:观察多聚二磷酸腺苷(ADP)核糖合成酶(PARP)抑制剂对血管紧张素Ⅱ(AngⅡ)刺激的乳鼠心脏心肌重构的预防作用.方法:新生大鼠心肌细胞原代培养,传代,用PARP抑制剂3-AB预处理细胞,观察PARP抑制剂对AngⅡ诱导心肌细胞PARP激活、PARPl表达,细胞内ROS产生和c-fos,ANP,β/aMHC基因表达的影响.结果:AngⅡ显著诱导心肌细胞PARP激活,ROS产生增加,PARPl、c-los、β/a-MHC、ANP基因表达增加.给予3-AB预处理可显著抑制AngⅡ诱导的上述变化.结论:AngⅡ可以诱导培养的心肌细胞内PARP激活,PARPl蛋白表达增加,3-AB预处理可以明显降低AngⅡ诱导的心肌细胞内异常基因表达增加,提示PARPl参与了心室重构的发生发展过程.     

Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.      

A STD/HIV prevention trial among adolescents in managed care

OBJECTIVE: To determine if sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, risk assessment, and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors. DESIGN: A randomized intervention trial with 3- and 9-month follow-up. SETTING: Five staff-model managed care sites in Washington, DC (n = 19 pediatricians). PATIENTS: Consecutive 12- to 15-year-olds receiving a general health examination; 81% minority. Participation rate = 215/432 (50%). Nine-month follow-up rate = 197/215 (92%). INTERVENTION: Audiotaped STD risk assessment and education about staying safe (safer = condoms, safest = abstinence). MAIN OUTCOME MEASURES: Adolescent-reported sexual intercourse and condom use. RESULTS: More intervention adolescents reported pediatrician discussion on 11/13 sexual topics. Although more vaginal intercourse (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.04-5.84) was reported in the intervention group at 3 months, this was not true of overall sexual intercourse (OR = 1.55, 95% CI =.73-3.32). More sexually active adolescents reported condom use in the intervention group at 3 months (OR = 18.05, 95% CI = 1.27-256.03). At 9 months, there were no group differences in sexual behaviors; however, more signs of STD were reported by the control (7/103) than the intervention group (0/94). CONCLUSIONS: STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education. Any impact on sexual activity and condom use was short-lived. Further research is needed to develop brief, office-based sexual risk reduction for young adolescents.     

核辐射对机体的影响

机体受到一定剂量核辐射后会出现多个器官结构和功能的改变.本文综述了机体受到低剂量核辐射后出现的免疫细胞数量和功能变化,包括淋巴细胞总数和部分亚群数量、淋巴细胞转化率、血清免疫球蛋白含量以及单核细胞功能等变化.同时还综述了核辐射对内分泌及遗传的影响.