Dural ectasia in individuals with Marfan‐like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2

Sheikhzadeh S, Rybczynski M, Habermann CR, Bernhardt AMJ, Arslan‐Kirchner M, Keyser B, Kaemmerer H, Mir TS, Staebler A, Oezdal N, Robinson PN, Berger J, Meinertz T, von Kodolitsch Y. Dural ectasia in individuals with Marfan‐like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2. Mutations in the genes FBN1, TGFBR1, and TGFBR2 can result in heritable connective tissue disorders comprising the Marfan syndrome and the Loeys‐Dietz syndrome. Dural ectasia is a characteristic manifestation of both syndromes. However, dural ectasia has not yet been investigated in connective tissue disorders that are unrelated to mutations in the FBN1, TGFBR1 or TGFBR2 genes. Here, we assessed dural ectasia in 33 individuals both with typical manifestations of heritable connective tissue disease and in whom mutations in all three genes had been excluded. We identified 19 individuals with dural ectasia (58%), who exhibited major skeletal manifestations of the Marfan syndrome more frequently than the remaining 14 persons without dural ectasia (p = 0.06). Moreover, only persons with dural ectasia fulfilled clinical criteria of the Marfan syndrome (p = 0.01). Conversely, aortic aneurysm (12 patients; p = 0.8), aortic dissection (five patients; p = 0.1), spontaneous dissection of the carotid arteries (five patients; p = 1), and mitral valve prolapse (13 patients; p = 0.4) were similarly frequent irrespective of dural ectasia. We conclude that dural ectasia is a marker for connective tissue disease which coincides with skeletal rather than with cardiovascular manifestations, and which may involve currently uncharacterized pathogenetic mechanisms and syndromes.     

自体外周血干细胞经冠状动脉移植治疗急性心肌梗死：近期疗效随访

目的:观察经皮经腔冠状动脉内移植外周血干细胞治疗急性心肌梗死的可行性与近期临床疗效。方法:①实验对象:选取2003-11/2005-01辽宁省人民医院收治的急性心肌梗死患者70例,男56例,女14例,年龄(60±10)岁,体质量(73±11)kg,急性心肌梗死病程(5±2)d,均对本实验知情同意,实验方案经辽宁省人民医院伦理委员会批准。70例患者随机数字表法分为细胞移植组、常规治疗组,35例/组。两组基线资料基本相似。②实验方法:常规治疗组单纯给予药物治疗 冠状动脉造影术或支架植入术。细胞移植组在常规治疗的基础上应用粒细胞集落刺激因子皮下注射动员自体骨髓干细胞,连续5d,第6天经血细胞分离机分离采集外周血干细胞悬液57mL,经over the wire球囊导管中心腔注入梗死相关动脉,注入CD34细胞数量为(7.25±7.33)×107个。③实验评估:在外周血干细胞动员、采集及经冠状动脉回输过程中观察患者不良反应。于术前及术后6个月检查两组患者左室形态、心功能、室壁节段性运动积分的改变。结果:术后6个月,细胞移植组全部完成随访,常规治疗组23例完成随访。①手术前后超声心动图参数值的变化:与术前比较,术后6个月细胞移植组左室收缩末容积、室壁节段性运动积分指数均明显下降(P<0.05),左室射血分数显著升高(P<0.05)。术后6个月与常规治疗组比较,细胞移植组左室射血分数明显升高,室壁节段性运动积分指数显著降低,差异有显著性意义(P<0.05)。②安全性评估:外周血干细胞动员时不良反应占37.1%,分离和采集过程不良反应占15.3%,经冠状动脉内回输过程不良反应占20.0%。结论:经皮经腔冠状动脉移植自体外周血干细胞治疗急性心肌梗死,可在近期有效地减少心肌梗死缺血面积,减轻左室重构,改善心功能。     

Decreased levels of p26-Bcl-2, but not p30 phosphorylated Bcl-2, precede TGFbeta1-induced apoptosis in colorectal adenoma cells

Bcl-2 expression is confined to the base of the colonic crypt, whereas transforming growth factor beta (TGFbeta) is expressed in the upper crypt, as are the apoptotic death promoters, Bak and Bax. In colonic adenoma cells, TGFbeta induces a growth arrest. In some adenoma cell lines, this is accompanied by apoptosis and in others it is not. In this study, we used two human colonic adenoma cell lines: RG/C2, in which TGFbeta induces a G1 arrest without apoptosis, and BH/C1, in which TGFbeta induces both a G1 arrest and apoptosis. TGFbeta does not induce apoptosis in RG/C2 cells even if hydrocortisone and insulin are removed from the culture medium. In BH/C1 cells, TGFbeta induces apoptosis in the presence of insulin and hydrocortisone. Apoptosis induced by TGFbeta is preceded by a reduction in p26-Bcl-2 protein levels. There was no change in the levels of the p30 phosphorylated form of Bcl-2 or in levels of the proapoptotic proteins Bax or Bak. RG/C2 cells did not show decreased Bcl-2 levels in response to TGFbeta- induced growth inhibition. Therefore, TGFbeta regulates Bcl-2 expression in colonic adenoma cells which undergo apoptosis in response to TGFbeta, but not in those which are growth inhibited, but resistant to TGFbeta-induced apoptosis. TGFbeta may play an important role in the colonic epithelium, not only in the inhibition of cell proliferation, but also in the regulation of apoptosis.      

DERMAL NEUROVASCULAR DYSFUNCTION IN TYPE 2 DIABETES

The present article summarizes recent observations obtained in our laboratory which clearly indicate that sex steroids exert relevant effects on the peripheral nervous system. In particular, the following important points have emerged: (1) Steroids exert stimulatory actions on the synthesis of the proteins proper of the peripheral myelin (e.g., glycoprotein Po and peripheral myelin protein 22) in vivo and on the Schwann cells in culture; (2) in many cases the actions of hormonal steroids are not due to their native molecular forms but rather to their metabolites (e.g., dihydroprogesterone and tetrahydroprogesterone in the case of progesterone; dihydrotestosterone and 5 alpha-androstane-3 alpha,17 beta -diol in the case of testosterone); (3) the mechanism of action of the various steroidal molecules may involve both classical (progesterone and androgen receptors) and nonclassical steroid receptors (GABA, receptor); and finally, (4) the stimulatory action of steroid hormones on the proteins of the peripheral myelin might have clinical significance in cases in which the rebuilding of myelin is needed (e.g., aging, peripheral injury, demyelinating diseases, and diabetic neuropathy).     

Antenatal platelet antibody testing by flow cytometry—results of a pilot study

BACKGROUND: Maternal platelet antibodies can cause fetomaternal alloimmune thrombocytopenia (FMAT), which has significant mortality and morbidity even in a first pregnancy. Prenatal diagnosis of FMAT has not previously been possible in the first affected pregnancy. STUDY DESIGN AND METHODS: Using flow cytometry, a sensitive, inexpensive test for the detection of platelet antibodies has been developed. It was adapted for use as a possible antenatal screening test, and 600 pregnant women were tested in a pilot study. RESULTS: In the study group, two women tested positive for platelet-specific IgG antibodies, one for anti-HPA- 1a and the other for anti-HPA-1a with anti-HLA. In each case, the fetus was found to be affected in utero, and treatment was initiated before successful delivery. Another woman was shown to have a platelet- reactive autoantibody without IgG specificity, and her infant was unaffected. A total of 95 (15.8%) of the women tested had HLA antibodies alone, and the majority demonstrated IgG specificity. On follow-up of 62 infants born to these women, none had thrombocytopenia; thus HLA antibodies were not shown to lead to FMAT in this study. CONCLUSION: The flow cytometry-based test for platelet antibodies can detect clinically significant maternal antibodies, and it may be that early diagnosis and treatment in utero can enhance outcome in FMAT. A population screening program is planned to determine the predictive power of this test, in addition to its sensitivity, specificity, and efficiency.     

吡啶及其衍生物的流动注射荧光分析

本文利用吡啶及其衍生物与过氧化氢的加热反应,建立了流动注射荧光分析法。吡啶及其衍生物在5～100ng范围内具有良好的线性关系(r=0.999).异烟肼、乙酰异烟肼和异烟酸在进样25ng时的相对标准偏差(n=10)平均为1.2%。异烟肼、乙酰异烟肼的检出限(S/N=3)为0.5ng,异烟酸的检出限为0.25ng.分析速度为30样/h。     

Sex differences in salicylic acid metabolism in streptozotocin induced diabetes in rats

The metabolism of salicylic acid was studied in male and female streptozotocin-induced diabetic Wistar rats. Results obtained showed that in both sexes there was a significant increase in urinary excretion of salicyluric acid in diabetic rats when compared to controls (P less than or equal to 0.001). Within the diabetic groups, there was a significant increase in the urinary excretion of salicyluric acid in the female in comparison to the male rats (P less than or equal to 0.01). A statistically significant increase was observed in urinary excretion of salicyl-glucuronic acid in diabetic female compared to control female rats (P less than or equal to 0.01) while comparison of diabetic male to control male showed a significant decrease in urinary excretion of salicyl-glucuronic acid (P less than or equal to 0.01). Comparison of the diabetic female and male groups showed a high statistically significant difference in urinary excretion of salicyl-glucuronic acid. The diabetic ration, ie diabetic/control was significantly higher in female than in male rats with respect to salicyl-glucuronic acid (P less than or equal to 0.001) and total urinary excretion (P less than or equal to 0.01). The diabetic ratio may likely reflect the true significance of the roles played by the two metabolic pathways. The results suggest sex differences in the metabolism of salicylic acid; this may also be the case in other disease states.     

Cyclic endometrial changes: US assessment with histologic correlation

The ultrasonographic (US) appearance of the endometrium was evaluated in 80 patients, and the US diagnosis of endometrial stage was compared with that from same-day endometrial biopsy specimens. The US signs of proliferative endometrium included triple-line sign, hypoechoic function layer, and minimal or absent posterior acoustic enhancement. The signs of secretory endometrium included absent triple-line sign, hyperechoic functional layer, and strong posterior acoustic enhancement. When all of these US signs were clearly depicted in combination, the accuracy of diagnosis was 93% (30 patients). The accuracy of diagnosis for all patients in the study was 76% (73 patients). The relative distributions of each US sign in proliferative and secretory endometrium were compared. Despite complicating extrinsic factors such as uterine leiomyomas and intrinsic factors such as the transition period between endometrial phases, US staging of the endometrium is a useful diagnostic technique that allows serial examinations of the endometrium.