Structures of Flavamine and Flavadine from Aconitum flavum

Two new diterpenoid alkaloids, flavamine ( 1) and flavadine ( 2), were isolated from the roots of ACONITUM FLAVUM Hand-Mazz. The structures were established on the bases of spectral analyses and chemical correlations with napelline ( 3) and lucidusculine ( 4), respectively.     

宫颈粘液过氧化物酶在月经周期中的变化规律

本文对29例月经周期正常妇女的宫颈粘液过氧化物酶进行了30个周期的研究。在月经周期不同时间测定宫颈粘液过氧化物酶(CMPx)活性及血清促黄体生成素(LH)、雌二醇(E_2)和孕酮(P)。结果表明:在排卵前三天酶活性明显下降,至排卵后一天开始上升。卵泡期,酶活性与E_2呈负相关(r=-0.67);黄体期,酶活性与P呈正相关(r=0.79)。本研究提示:1.CMPx在排卵周期具有特定的变化规律,其变化受体内激素水平影响,可作为预告排卵的指标。2.如简化测定方法,可为自然避孕提供新途径。     

"Schnyder's rule" of heritability of skin tumors and its extension to cases of segmental presentation

"Schnyder's rule" states that multiple tumours of the skin are dominantly inherited, whereas solitary tumours of the same histological type are noninherited. This rule may be extended to cover segmental cases representing somatic mutations.     

Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.     

Calcineurin B1 is essential for positive but not negative selection during thymocyte development

During development, discrete cell fates often result from variation in the intensity of a particular signal. The mechanisms underlying these seemingly analog-to-digital switches are not understood. In developing T lymphocytes, low-intensity signals through the antigen receptor result in positive selection while more intense signals give rise to negative selection. By deleting the genetic locus encoding the regulatory B1 subunit of calcineurin specifically in thymocytes, we found an absolute requirement for calcineurin in positive selection. In contrast, calcineurin activity was dispensable in several models of negative selection. Unexpectedly, we found that removal of calcineurin activity from thymocytes results in inefficient ERK activation at the double-positive stage of thymocyte development, when selection occurs. These studies clarify the mechanism by which graded signals are converted to discrete outcomes in T cell development and further indicate that the developmental roles of calcineurin likely contribute to immunosuppression by calcineurin inhibitors.     

Unusual cardiac papillary fibroelastoma in the right ventricular outflow tract.

Cardiac papillary fibroelastoma (CPF) is the second most common benign neoplasm of the heart. This study describes the case of an 81-year-old man who was admitted to the hospital for severe vertigo and in whom a tumor at the right ventricular outflow tract (RVOT) was identified incidentally during echocardiography. The CPF was excised smoothly following the confirmation of its position by computed tomography. The comprehensive pathologic findings of CPF were reviewed. Detailed immunohistochemical analyses of CD34 and factor VIII-related antigen were performed on the covering endocardial cells. The unique chondroid metaplasia of fibrous tissue in this CPF has never been reported. This work is the first to present an unusual CPF at the RVOT with reactive process of fibrous connective tissue.     

CYP17A1基因新突变致17α-羟化酶/17,20-裂解酶部分性缺陷症

目的研究1例17α-羟化酶/17,20-裂解酶部分性联合缺陷症患者CYP17A1基因突变特点,并结合患者的临床表现与基因突变类型初步探讨P450C17酶蛋白的结构与功能的关系。方法收集1例17α-羟化酶/17,20-裂解酶部分性联合缺陷症患者的临床资料及其亲属血标本,提取基因组DNA,设计7对引物扩增CYP17A1基因的8个外显子及外显子与内含子的连接区域,琼脂糖凝胶电泳鉴定PCR产物,产物胶回收后直接做为DNA双链模板测序。DNA双链模板不一致的PCR产物经克隆后测序。测序结果在核苷酸序列数据库进行比较分析。结果患者CYP17A1基因突变检测结果为5994-5995delAT/7541C>T复合杂合子。这两种突变均未见报道。推测5994-5995delAT导致I259H,274X,突变形成的截短蛋白质缺少血红素结合区域,因此是没有功能的;而通过人类P450C17酶计算机模型分析显示7541C>T导致的A398V远离酶的活性中心,推测突变可能使酶的活性减弱,而不是完全地丧失。患者临床表现为有自发不规则月经及轻度高血压、低血钾,结合激素测定结果提示肾上腺和性腺保留部分功能。因而患者的基因型与其临床表型是一致的。结论应进行突变P450C17酶的功能学研究来进一步明确结构改变对功能的影响。     

Morphine prevents glutamate-induced death of primary rat neonatal astrocytes through modulation of intracellular redox

This study is designed to investigate the effect of morphine on glutamate-induced toxicity of primary rat neonatal astrocytes. Glutamate decreases the intracellular GSH level, and thereby induces cytolysis of astrocytes and C6 glial cells accompanied by apoptotic features. Glutamate-induced cytotoxicity is protected by morphine and antioxidants such as GSH and NAC, whereas MK-801, an antagonist of glutamate receptor NMDA does not protect astrocytes against glutamate toxicity. Also, morphine antagonist, naloxone, as well as selective ligands for opioid receptor subtypes, including DAMGO, DPDPE, and U69593, do not inhibit the protective effect of morphine on glutamate-induced cytotoxicity. Morphine significantly prevents the depletion of GSH by glutamate and thereby inhibits the generation of H2O2 in a dose-dependent manner. Furthermore, morphine prevents the change of mitochondrial permeability transition by glutamate. Taken together, we suggest that morphine protects the primary rat neonatal astrocytes from glutamate toxicity via modulation of intracellular redox status.     

Effect of anti-inflammatory medication on monocyte response to titanium particles

Cytokines produced by macrophages in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. The present study characterizes the response of human peripheral blood monocytes to titanium particles. Monocytes were obtained from donated blood and were cultured in the presence of different-sized titanium particles. Exposure to titanium-aluminum-vanadium particles significantly changed the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 (IL-1), whereas there was no significant effect on the release of prostaglandin E(2) (PGE(2)). When monocytes were cultured with particles, the titanium alloy particles induced significantly more release of TNF-alpha and less IL-1 secretion. Ciprofloxacin inhibited production of TNF-alpha, IL-6, IL-1, and PGE(2) in human monocytes exposed to titanium particles. In contrast to ciprofloxacin, indomethacin was not a potent inhibitor of TNF-alpha production but potentiated IL-6 production in titanium-stimulated monocytes. Indomethacin had no effect on the production of IL-1 and was a potent inhibitor of PGE(2) production in titanium-stimulated monocytes. Pentoxifylline had an inhibitor effect on TNF-alpha production in titanium-stimulated monocytes. Pentoxifylline potentiated IL-6 and IL-1 production in monocytes exposed to titanium particles and had a biphasic effect on the PGE(2) production. The results of this study support our hypothesis that human monocytes release bone resorption mediators after in vitro exposure to TiAlV alloy particles. The results also demonstrate the differences of bone-resorbing mediators in response to different wear particle size. The pharmacologic agents (ciprofloxacin, pentoxifylline, and indomethacin) that can modulate the release of bone resorbing mediators such as PGE(2), TNF-alpha, IL-1, and IL-6 release from human monocytes. The results help to elucidate the differences in cellular response to wear particles but may not be directly transposed to the human situation.