DNA diagnosis of FRAXA and FRAXE in Chinese children with neurodevelopmental disorders and fragile X syndrome

Fragile X (FraX) syndrome is the most common cause of inherited mental retardation. To see whether FRAXA or FRAXE can account for the etiology of some unexplained neurodevelopmental disorders in children, we screened for trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and their mothers seen in 1995 (group 1) referred for developmental assessment due to developmental delay, language delay, attention deficit hyperactivity disorder, autistic spectrum disorder, mental retardation and/or learning disability. We also screened DNA samples of all five previously diagnosed cytogenetically-positive FraX boys, their mothers and sisters (group 2). A control group of unrelated teenagers and adults were recruited from the community (group 3). In group 1, 3 families (2 mothers and a mother and her son) were found to carry a small premutation allele at FRAXA (premutation frequency = 2%, 3/153 independent X chromosomes), but none had any expansion at FRAXE. In group 2, all 5 FraX boys had full mutation at FRAXA and normal repeat length at FRAXE. In group 3, 1 male has a premutation allele out of 18 males and 59 females tested (premutation frequency of control = 0.7%, 1 out of 136 X chromosomes). For FRAXE screening in group 3, 2 females were carriers (1.5%, 2 out of 136 X chromosomes). Thus, FRAXA and FRAXE cannot account for the etiology of neurodevelopmental disorders in our cohort of Chinese children, and the prevalence of FRAXE mutation in normal Chinese population appears to be higher than reported in the Caucasians.     

中国香港与西方儿童分泌性中耳炎发病率的比较

目的 调查中国香港儿童分泌性中耳炎发病率,并且进一步与西方的研究结果做比较。方法 1995-1998年,在中国香港特别行政区随机抽取小学、幼稚园(4-5岁)及幼儿园(2-3岁),对6872名2-7岁儿童进行检查,在校内接受由耳鼻咽喉科专家施行的耳镜检查及由听力学家执行的鼓室导抗测试。为了与西方研究结果作出标准化的比较,根据他们所采用的诊断标准重新计算。结果 在划分为2-3岁、4-5岁及6-7岁的研究对象中,若以耳镜临床诊断作标准,本研究分泌性中耳炎发病率为5.2％-21.6％;若以鼓室导抗图作诊断标准,发病率为7.3％-30.7％。同一组数据,发病率计算结果是会因为采用不同的鼓室导抗图诊断定义而有偏差,但无论是用哪种方法,结果都与西方同龄研究的发病率差异无显著性,而且发病率随年龄增加而下降。结论 香港2-3岁、4-5岁,及6-7岁中国儿童的分泌性中耳炎发病率与西方文献报告没有显著性差异。     

伊贝辛的分离和鉴定

从吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)鳞茎中分离出两种介藜芦胺类生物碱Ⅰ和Ⅱ。碱Ⅱ是一个新的甾体生物碱,定名为伊贝辛(yibeissine),结构为22,26-imino-17,23-oxidojerv-12-en-6-oxo-3β,11α-diol,碱Ⅰ是一个已知化合物,结构为11-deoxo-6-oxo-5α,6-dihydrojervine。     

Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function

Adult mammalian CNS neurons do not normally regenerate their severed axons. This failure has been attributed to scar tissue and inhibitory molecules at the injury site that block the regenerating axons, a lack of trophic support for the axotomized neurons, and intrinsic neuronal changes that follow axotomy, including cell atrophy and death. We studied whether transplants of fibroblasts genetically engineered to produce brain-derived neurotrophic factor (BDNF) would promote rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were modified by retroviral-mediated transfer of a DNA construct encoding the human BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and neomycin resistance genes. The modified fibroblasts produce biologically active BDNF in vitro. These cells were grafted into a partial cervical hemisection cavity that completely interrupted one RST. One and two months after lesion and transplantation, RST regeneration was demonstrated with retrograde and anterograde tracing techniques. Retrograde tracing with fluorogold showed that approximately 7% of RST neurons regenerated axons at least three to four segments caudal to the transplants. Anterograde tracing with biotinylated dextran amine revealed that the RST axons regenerated through and around the transplants, grew for long distances within white matter caudal to the transplant, and terminated in spinal cord gray matter regions that are the normal targets of RST axons. Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit regeneration. Behavioral tests demonstrated that recipients of BDNF-producing fibroblasts showed significant recovery of forelimb usage, which was abolished by a second lesion that transected the regenerated axons.     

Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism

To evaluate the response of circulating intact parathyroid hormone (iPTH) on myocardial hypertrophy in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), echocardiographic and neurohormonal assessments were performed over a 15-week period in 15 HD patients with SHPT before and after calcitriol treatment and 10 HD control patients with SHPT not receiving calcitriol therapy. We prospectively studied a group of 15 patients with significantly elevated iPTH levels (iPTH >450 pg/mL) receiving calcitriol (2 microg after dialysis twice weekly). Clinical assessment, medication status, and biochemical and hematological measurements were performed once a month. Throughout the study, calcium carbonate levels were modified to maintain serum phosphate levels at less than 6 mg/dL, but body weight, antihypertensive medication, and ultrafiltration dose remained constant. In patients treated with calcitriol, an adequate reduction of iPTH levels was found (1,112 +/- 694 v 741 +/- 644 pg/mL; P < 0.05) without changes in values of serum ionized calcium (iCa++), phosphate, or hematocrit. Blood pressure (BP), cardiac output (CO), and total peripheral resistance (TPR) did not significantly change. After 15 weeks of treatment with calcitriol, M-mode echocardiograms showed pronounced reductions in interventricular wall thickness (13.9 +/- 3.6 v 12.8 +/- 3.10 mm; P = 0.01), left ventricular posterior wall thickness (12.5 +/- 2.4 v 11.3 +/- 1.8 mm; P < 0.05), and left ventricle mass index (LVMi; 178 +/- 73 v 155 +/- 61 g/m2; P < 0.01). However, in control patients, these changes were not found after the treatment period. In addition, sequential measurements of neurohormonal mediator levels in patients receiving calcitriol showed that plasma renin (18.5 +/- 12.7 v 12.3 +/- 11.0 pg/mL; P = 0.007), angiotensin II (AT II; 79.7 +/- 48.6 v 47.2 +/- 45.7 pg/mL; P = 0.001), and atrial natriuretic peptide (ANP; 16.6 +/- 9.7 v 12.2 +/- 4.4 pg/mL; P = 0.03) levels significantly decreased, whereas antidiuretic hormone (ADH), epinephrine, and norepinephrine levels did not change significantly. The percent change in LVMi associated with calcitriol therapy had a strong correlation with the percent change in iPTH (r = 0.52; P < 0.05) and AT II (r = 0.47; P < 0.05) levels. We conclude that the partial correction of SHPT with intravenous calcitriol causes a regression in myocardial hypertrophy without biochemical or hemodynamic changes, such as heart rate, BP, and TPR. The changes in plasma levels of iPTH and, secondarily, plasma levels of neurohormones (especially AT II) after calcitriol therapy may have a key role in attenuating ventricular hypertrophy in SHPT.     

Morphologies of Binary AB/AC Diblock Copolymer Blends

The self‐assembled structures of the mixtures of AB and AC diblock copolymers were investigated using transmission electron microscopy (TEM). For this purpose, two kinds of asymmetric polystyrene‐block‐polyisoprene (SI30 and SI87) and one symmetric polystyrene‐block‐poly(2‐vinylpyridine) (SVP) were anionically polymerized. Both macro‐ and microphase separations occur in all binary mixtures examined in this work, yielding various morphologies. The morphologies of the phase‐separated macrodomains are found to be the same as those of pure diblock copolymers. However, at the phase boundary where two diblock copolymers with different microphase‐separated structures are in contact with each other, the morphological transition is observed due to the preferential location of the common polystyrene (PS) blocks in two copolymers at the interface. From TEM observations and random phase approximation (RPA)‐based prediction, it is identified that the macrophase transition takes place prior to the microphase transition, leading to the interface‐induced ordering.

TEM micrographs of SI87/SVP 60/40 binary blend taken at different magnifications. The phase boundary between SI87 and SVP macrodomains and SVP‐rich macrodomains are shown, respectively.     

免疫功能紊乱与再生障碍性贫血

免疫功能紊乱与再生障碍性贫血的发病密切相关。它不便宜接参与造血于细胞的损伤,促进造血于细胞的凋亡,而且可引发骨髓造血微环境的缺陷。本文综述了近年来这一方面的研究进展,并提出应用免疫调节剂治疗再障的重要性。