Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord

Previously we have shown that leukaemia inhibitory factor (LIF) potentiates the development of murine spinal cord neurons in vitro , suggesting that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and show here that the generation of neurons in cultures of embryonic day 10 spinal cord cells is inhibited by antibodies to the β subunit of the LIF receptor. Since there are more undifferentiated precursors in antibody-treated cultures than in control and LIF-treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival. In addition, the failure of LIF to support neuronal survival in the period immediately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inability to express class I major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an intermediary cell. LIF also appears to be involved in regulating the differentiation of astrocytes, since it increases the number of glial fibrillary protein (GFAP)-positive cells present in the cultures and since the spontaneous production of GFAP-positive cells is blocked by antibodies to the LIF β receptor. These findings suggest that LIF or related factors promote the differentiation of neural precursors in the spinal cord, but that they are not involved in preferentially promoting precursors down a specific differentiation pathway.     

几种脊椎动物心肌细胞的超微结构观察

①目的进一步了解动物心肌细胞的种属特性。②方法应用电子显微镜对鲤、蟾蜍、鳖和家鸽等几种脊椎动物心肌细胞进行了观察。③结果这几种动物心肌细胞的侧面连接较多见。除家鸽外，心肌细胞的肌原纤维的排列比较松散。所观察各种属动物的心肌细胞均含有单位膜包绕的特殊颗粒，以心房肌细胞为多，但这几种动物心肌细胞的特殊颗粒在大小、形态、分布等方面均有明显差异。家鸽心肌细胞的特殊颗粒小，常成群分布于肌膜下方，并可见颗粒外排迹象。其它种属的特殊颗粒大小不等，多位于核周区。横小管系统以家鸽心室肌最易辨认，其它均少见。家鸽心肌细胞中的肌原纤维较其它动物密集，且排列整齐。④结论脊椎动物心肌细胞的超微结构有种属特性。     

Impaired Glucose Tolerance in Pregnancy - Is It of Consequence?

Summary: This study was done to determine if impaired glucose tolerance in pregnancy was associated with increased maternal and neonatal morbidity and if so, whether the increased morbidity was due to the confounding factors of increased maternal age and maternal obesity. It was a retrospective analysis to compare 944 women with impaired glucose tolerance (IGT) in pregnancy with 10,065 women without abnormal glucose tolerance. The incidence of impaired glucose tolerance in pregnancy was 8.6% in this study. Even when maternal age and obesity were excluded, the IGT group had significantly higher risks of labour induction (relative risk, RR, 1.15); Caesarean section (RR: overall 1.43, elective 1.72, emergency 1.31); Caesarean section for dystocia/no progress (RR 1.60); macrosomia (RR 1.69,1.76,1.61 for birth-weight =97th, 95th, 90th percentiles respectively) and shoulder dystocia (RR 2.84) when compared to the nondiabetics (NDM). The risks of hypertensive disease (RR 1.22) and Caesarean section for fetal distress/thick meconium-stained liquor (RR 1.53) were also higher in the IGT group but these increases were not statistically significant when maternal age and obesity were excluded. There was no significant difference in the rates of low Apgar scores at 1 and 5 minutes between the 2 groups.     

Surgical resections in parous patients with distal ileal and colonic Crohn's disease.

The surgical resection rates among parous women with distal ileal and colonic Crohn's disease have been compared with resection rates among distal ileal (n = 197) and colonic (n = 332) Crohn's disease patients. Thirty of 44 parous women with distal ileal Crohn's disease and 28 of 44 with colonic Crohn's disease had achieved their first pregnancy on average 8 years and 6.2 years respectively before the diagnosis of Crohn's disease was established. Resections for each patient were negatively correlated with parity in both groups. (Distal ileal disease (p = 0.034, rs = 0.3207), colonic disease (p = 0.051, rs = -0.2960)). Patients with distal ileal Crohn's disease and a history of pregnancy at diagnosis (n = 30, mean follow up = 15 years) had fewer resections/patient when compared with the published resection group: mean (SD); 1.17 (0.65) v 1.57 (1.05), p = 0.006. Patients with colonic Crohn's disease and a history of pregnancy at diagnosis (n = 28, mean follow up = 16.5 years) had fewer resections/patient when compared with the published resection group: mean (SD); 0.68 (0.77) v 1.05 (0.77), p = 0.019. In summary, patients with distal ileal and colonic Crohn's disease, who had been pregnant in the past subsequently need fewer surgical resections. Pregnancy could influence the natural history of Crohn's disease either by decreasing immune responsiveness or by retarding fibrous stricture formation, which is the commonest indication for surgical intervention.     

160例女性不孕症的四种病原体检测及意义

本文报告了对１６０例女性不孕症患者宫颈分泌物中解脲脲原体（Ｕｕ）、人型支原体（Ｍｈ）、沙眼衣原体（Ｃｔ）和淋病奈氏球菌（Ｎｇ）的测定，结果总体检出率７０％（１２０／１６０），明显高于对照组（同期早孕妇女），Ｐ＜０．０１。其中输卵管阻塞组阳性率８４．７８％（３９／４６），明显高于输卵管通畅组６３．４６％（３３／５２）及欠通畅组６４．５２％（４０／６２），Ｐ＜０．０５。且针对性治疗收到一定效果，提示妇女下生殖道Ｕｕ、Ｃｔ、Ｎｇ感染是输卵管阻塞性不孕的主要原因之一。对该类患者行三项检测，对不孕症的病因诊断及治疗有好处。     

鞍区肿瘤术后中枢性低钠血症的诊断和治疗

目的:探讨鞍区肿瘤术后中枢性低钠血症的诊断及处理方法。方法:对我科近四年鞍区肿瘤术后并发中枢性低钠血症的58例患者进行回顾性分析,术前、手术当日及术后每日定时检测血钠,观察尿量变化,测定中心静脉压,确定低钠血症的类型并给予相应的处理。结果:56例恢复正常,1例死于严重肺部感染,1例自动出院。结论:鞍区肿瘤易出现抗利尿激素分泌不当综合症和脑性耗盐综合症两种类型。前者需限水治疗,后者应予以充分补钠、补水,根据水、钠检测水平治疗。     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

脑卒中患者日常生活能力的评定

采用Ｂａｒｔｈｅｌ指数对１２０例脑卒中住院患者在发病后５￣６周进行日常生活活动（ＡＤＬ）能力的证实。因脑卒中遗留的功能不全，ＡＤＬ的受损率达６６．７％，肢体的Ｂｒｕｎｎｓｔｒｏｍ功能分级与ＡＤＬ积分高度相关，相关性下肢高于上肢；多元逐步回归分析显示，躯体（偏瘫）和心理（认知障碍和抑郁因素）影响ＡＤＬ的能力。认为ＡＤＬ能力的提高，不仅依赖于肢体功能障碍的改善，提高认知功能，改善情感状况，对于脑卒中患     

Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site

The structural requirements for ligand binding to the benzodiazepine receptor (BzR) inverse agonist site were probed through the synthesis and in vitro evaluation of 3-substituted beta-carbolines 6, 7, 11, 12, gamma-carboline 13, and diindoles 18-21, 23-25, 27, 28, and 34. On the basis of the apparent binding affinities of these and other analogues, a hydrogen bond acceptor site (A2) on the receptor is proposed to interact with the N(9) hydrogen atom of the beta-carbolines or the N(7) hydrogen nuclei of the diindoles. Likewise, a proposed hydrogen bond donating site (H1) interacts with the N(2) nitrogen atom of the beta-carbolines or the N(5) nitrogen atom of the diindoles. It appears that interaction with both sites is a prerequisite for high affinity since analogues which have either one or both of these positions blocked exhibit substantial reduction in affinity. Moreover, H1 appears to be capable of engaging in a three-centered hydrogen bond with appropriately functionalized ligands, which explains the increase in potency observed in the following series of 3-substituted beta-carbolines: the n-butyl (12, IC50 = 245 nM), n-propoxy (9, IC50 = 11 nM), and propyl ketone (11, IC50 = 2.8 nM) congeners. In addition to H1 and A2, there appears to be a relatively narrow hydrophobic pocket in the binding cleft that can accommodate substituents at the 3-position of the beta-carbolines which have chain lengths less than or equal to C5. There is a 1 order of magnitude decrease in affinity between n-propoxy analogue 9 (IC50 = 11 nM, chain length = 4) and n-butoxy derivative 7 (IC50 = 98 nM, chain length = 5). Furthermore, alpha- and gamma-branching [e.g. ethoxycarbonyl (2), IC50 = 5 nM and tert-butoxycarbonyl (31) IC50 = 10 nM] but not beta- and delta-branching [e.g. isopropoxy (6), IC50 = 500 nM and (neopentyloxy) carbonyl (48), IC50 = 750 nM] at position 3 are tolerated. Occupation of this hydrophobic pocket is clearly important for high affinity as evidenced by the relatively low affinity of 30, a beta-carboline which possesses a hydrogen atom at the 3-position. This same hydrophobic pocket is partially filled by the D and E rings of the diindoles, which accounts for the high affinity of several members of this series. An excluded volume analysis using selected 3-substituted beta-carbolines and ring-E substituted pyridodiindoles is consistent with the presence of this hydrophobic pocket (see Figure 1).(ABSTRACT TRUNCATED AT 400 WORDS)