BACKGROUND & AIMS: PURPOSE:Steroid sulfatase (STS) inhibitors that can decrease or prevent the biosynthesis of estrogenic steroids via the sulfatase route may play an important role in the treatment of breast cancer. We compare the in vivo efficacy of two potent STS inhibitors, STX64 and STX213, in a xenograft breast cancer model. EXPERIMENTAL DESIGN:MCF-7 cells stably expressing STS cDNA (MCF-7STS) were generated. Ovariectomized MF-1 female nude mice receiving s.c. injections of estradiol sulfate (E2S) and bearing both MCF-7STS and wild-type MCF-7 (MCF-7WT) tumors were orally treated with STX64 and STX213. Treatment was given for 49 days followed by a recovery period of 35 days in which animals received only E2S. Mice were weighed, and tumor measurements were taken weekly. RESULTS:STX64 and STX213 exhibited potent STS inhibition in vivo. However, STX213 showed a greater duration of activity. In vehicle-treated nude mice receiving E2S, tumor volumes increased 5.5-fold for MCF-7WT and 3.8-fold for MCF-7STS after 49 days compared with day 0. MCF-7WT tumor growth was reduced by 56% by STX213 over the dosing period, and subsequent growth was retarded during the recovery period. All treatments fully inhibited growth of MCF-7STS tumors, and recovery of these tumors was significantly retarded (P<0.01). All compounds completely inhibited liver and tumor STS activity. Additionally, STS mRNA expression in the MCF-7STS tumors directly correlated with the corresponding STS enzyme activity. CONCLUSIONS:This study indicates that STS inhibitors attenuate hormone-dependent human breast cancer growth and therefore offer a potentially novel treatment for this condition.

背景与目标：

BACKGROUND & AIMS: :Aldosterone is synthesized in the zona glomerulosa of the adrenal cortex under primary regulation by the renin-angiotensin system. Angiotensin II (A-II) acts through the angiotensin types 1 and 2 receptors (AT1R and AT2R). A-II is metabolized in different tissues by various enzymes to generate two heptapeptides A-III and angiotensin 1-7, which can then be catabolized into smaller peptides. A-II was more potent than A-III in stimulating aldosterone secretion in the adrenocortical cell line HAC15, and A-II, but not A-III, stimulated cortisol secretion. A-II stimulated mRNA expression of steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2, whereas A-III stimulated 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2 but decreased the expression of CYP17A1 required for cortisol synthesis. The stimulation of aldosterone secretion by A-II and A-III was blocked by the AT1R receptor blocker, losartan, but not by an AT2R blocker. A-II was rapidly metabolized by the HAC15 cells to mainly to angiotensin 1-7, but not to A-III, and disappeared from the supernatant within 6 h. A-III was metabolized rapidly and disappeared within 1 h. In conclusion, A-II was not converted to A-III in the HAC15 cell and is the more potent stimulator of aldosterone secretion and cortisol of the two. A-III stimulated aldosterone secretion but not cortisol secretion.

背景与目标： : 醛固酮在肾素-血管紧张素系统的主要调节下，在肾上腺皮质的肾小球中合成。血管紧张素II (A-II) 通过血管紧张素1型和2型受体 (AT1R和AT2R) 起作用。A-II在不同组织中被各种酶代谢，生成两个七肽A-III和血管紧张素1-7，然后可以分解为较小的肽。在刺激肾上腺皮质细胞系HAC15中，A-II比A-III更有效，而A-II (而不是A-III) 刺激皮质醇分泌。A-ii刺激类固醇生成急性调节蛋白，3β-羟基类固醇脱氢酶，CYP11B1和CYP11B2的mRNA表达，而a-iii刺激3β-羟基类固醇脱氢酶，CYP11B1和CYP11B2，但降低了皮质醇合成所需的CYP17A1的表达。AT1R受体阻滞剂氯沙坦阻断了A-II和A-III对醛固酮分泌的刺激，而AT2R阻滞剂则没有。A-II被HAC15细胞迅速代谢，主要代谢为血管紧张素1-7，但不代谢为A-III，并在6小时内从上清液中消失。A-III代谢迅速，并在1小时内消失。总之，A-II在HAC15细胞中未转化为A-III，并且是两者中醛固酮分泌和皮质醇的更有效刺激因子。A-III刺激醛固酮分泌，但不刺激皮质醇分泌。

BACKGROUND & AIMS: :Rats treated neonatally or at four weeks of age with dexamethasone on a single occasion showed a considerable decrease in thymic glucocorticoid reception. It appears that hormonal imprinting can take place in the cells of the cytogenic organs not only perinatally, but also later, owing to the undifferentiated (differentiating) state of the forming cells.

背景与目标： : 一次用地塞米松对新生儿或四周龄的大鼠进行治疗的大鼠，胸腺糖皮质激素的接收明显减少。由于形成细胞的未分化 (分化) 状态，激素印迹似乎不仅可以在细胞形成器官的细胞中发生，而且可以在以后发生。

BACKGROUND & AIMS: :Recent field studies on the reproductive ecology of western diamond-backed rattlesnakes (Crotalus atrox) from populations in southern Arizona showed significant differences in the concentration of plasma sex steroids (testosterone, T; 5alpha-dihydrotestosterone, DHT; and 17beta-estradiol, E2) throughout the active season (March-October), and peak levels were coincident with the two mating periods (late summer and early spring). There is, however, no information on levels of sex steroids during winter. Similar to most snakes, hibernating individuals of C. atrox are typically inaccessible, but in southern Arizona, where environmental conditions are typically mild during winter, adult males frequently bask at or near the entrances of communal dens. Basking activity, therefore, offers a unique logistical opportunity to assess the complete annual profile of plasma sex steroid levels in males of a temperate reptile in nature. From November to February, we measured levels of plasma T, DHT, and E2 in adult male C. atrox that were located basking at communal dens. Additionally, cloacal, core body, and ambient air temperatures were obtained to investigate potential relationships between body temperatures and levels of sex steroids. Mean levels of T, DHT, and E2 were relatively high, and the concentration hierarchy was T>DHT>E2. Mean levels of T, DHT, and E2 showed no significant variation across the four months of sampling; however, E2 levels decreased progressively. In the annul cycle, sex steroid levels during winter were not basal when compared to values obtained during the active season. Mean cloacal temperatures of basking males were significantly higher than core body temperatures of non-basking males (inside dens) from November-December, and in February, which suggests that one function of winter basking is to elevate body temperatures. Steroid levels, nonetheless, were not significantly correlated with cloacal temperatures. We suggest that future field studies of male C. atrox should: (a) investigate sex steroid levels in non-basking individuals and (b) test whether elevated levels of sex steroids during winter facilitate the large increases that occur in early spring, which are coincident with the second mating season. Our findings on the reproductive biology of C. atrox and other viperids are discussed in the context of the associated-dissociated model of reproduction.

背景与目标： : 最近对来自亚利桑那州南部种群的西方钻石支持响尾蛇 (Crotalus atrox) 的生殖生态学进行的实地研究表明，血浆性类固醇 (睾丸激素，T; 5α-二氢睾丸激素，DHT; 和17β-雌二醇，E2) 在整个活动季节 (3月-10月)，峰值水平与两个交配期 (夏末和初春) 一致。但是，没有关于冬季性类固醇水平的信息。与大多数蛇相似，通常无法进入冬眠的C. atrox个体，但在亚利桑那州南部，冬季环境条件通常温和，成年雄性经常在公共窝点的入口或附近晒太阳。因此，晒太阳活动提供了一个独特的后勤机会，可以评估自然界中温带爬行动物男性的血浆性类固醇水平的完整年度概况。从11月到2月，我们测量了位于公共窝点的成年男性C. atrox的血浆T，DHT和E2水平。此外，还获得了泄殖腔，核心体和环境空气温度，以研究体温与性类固醇水平之间的潜在关系。T，DHT和E2的平均水平相对较高，浓度等级为T>DHT>E2。在四个月的采样中，T，DHT和E2的平均水平没有显着变化; 但是，E2水平逐渐降低。在annul周期中，与活动季节获得的值相比，冬季的性类固醇水平不是基础。在11月12月和2月中，晒太阳的男性的平均泄殖腔温度显着高于非晒太阳的男性 (窝点内) 的核心体温，这表明冬季晒太阳的功能之一是提高体温。尽管如此，类固醇水平与泄殖腔温度没有显着相关。我们建议将来对雄性C. atrox进行实地研究 :( a) 调查非晒太阳个体的性类固醇水平，以及 (b) 测试冬季性类固醇水平升高是否会促进早春发生的大幅增加，这与第二个交配季节同时发生。我们在相关分离的生殖模型的背景下讨论了我们对C. atrox和其他生物的生殖生物学的发现。

BACKGROUND & AIMS: OBJECTIVE:Cross-sectional data suggest that obesity, particularly central obesity, may be associated with decreased production of sex steroid hormones in men. However, longitudinal hormone data on men in relation to obesity status are limited. Previous studies have not consistently demonstrated whether sex steroids are associated specifically to body mass index or to measures of central obesity. Our objective was to examine the relation of obesity (body mass index > 30 kg/m2), and of central obesity (waist circumference > 100 cm or waist to hip ratio > 0.95) to longitudinal change in sex steroid hormones in men. DESIGN:Prospective follow-up of a population-based sample of men in Boston. PATIENTS:Nine hundred forty-two (942) men in the Massachusetts Male Ageing Study with complete anthropometry and hormone data at baseline (1987-1989, ages 40-70) and follow-up (1995-1997). MEASUREMENTS:Free and total testosterone (FT and TT), dehydroepiandrosterone sulphate (DHEAS), and sex hormone-binding globulin (SHBG) were assessed using standardized methods. Health behaviours and medical history were obtained by structured interview. Repeated measures regression was used to describe trends in steroid hormones and SHBG in relation to obesity status, adjusting for age, smoking, alcohol, comorbidities, and physical activity. RESULTS:Obesity was associated with decreased levels of total and free testosterone, and of SHBG at follow-up relative to baseline. For any given baseline concentration of TT, FT or SHBG, follow-up levels were lowest among men who remained obese or who became obese during follow-up. This was true for all three indices of obesity. Central adiposity was associated with lower DHEAS levels at follow-up, while elevated body mass index was not. CONCLUSIONS:Obesity may predict greater decline in testosterone and SHBG levels with age. Central adiposity may be a more important predictor of decline in DHEAS than is body mass index.

背景与目标：

BACKGROUND & AIMS: AIM:To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS:We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specific antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitative score based on their intensity, and the percentage of immunostained cells was measured. RESULTS:A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION:Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.

背景与目标：

BACKGROUND & AIMS: :Male pigs are routinely castrated at a young age to prevent the formation of androstenone, a 16-androstene testicular steroid that is a major component of boar taint. The practice of castration has been increasingly viewed as unfavorable, due to both economic considerations and animal welfare concerns. Other means of controlling boar taint, including reducing the synthesis of androstenone in the testes, would eliminate the need for castration. In this study, we determined the effects of transactivation of three nuclear receptors, the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and farnesoid X receptor (FXR), on gene expression and steroid hormone metabolism in primary porcine Leydig cells. Primary cells were isolated from mature boars, and transcript expression levels were assayed using real-time PCR. The transcripts of interest included porcine orthologs of common phase I and phase II metabolic enzymes, enzymes involved in steroidogenesis, and transcripts previously shown to be differentially expressed in boars with high androstenone and boar taint levels. Transactivation of CAR, PXR, or FXR increased the expression of several genes involved in steroidogenesis, including cytochrome B5A (CYB5A) and cytochrome B5 reductase 1 (CYB5R1), as well as hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4) and retinol dehydrogenase 12 (RDH12). Treatment with (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO), a CAR agonist, or rifampicin (RIF), a PXR agonist, resulted in significantly (p<0.05) decreased sex steroid production and significantly (p<0.05) increased production of 16-androstene steroids. Treatment with the FXR agonist chenodeoxycholic acid (CDCA) resulted in significantly (p<0.05) decreased sex steroid production. These results indicate that transactivation of these nuclear receptors may lead to increased levels of 16-androstene steroids, likely by altering the activity of CYP17A1 through CYB5A and CYB5R1 to the andien-β synthase reaction and away from the 17α-hydroxylase and C17, 20 lyase reactions.

背景与目标： : 公猪通常在幼年时就被阉割，以防止雄烯酮的形成，雄烯酮是一种16-雄烯酮睾丸类固醇，是公猪污染的主要成分。由于经济考虑和动物福利方面的考虑，阉割的做法越来越被认为是不利的。其他控制公猪污染的方法，包括减少睾丸中雄烯酮的合成，将消除去势的需要。在这项研究中，我们确定了组成型雄激素受体 (CAR)，孕烷X受体 (PXR) 和法尼醇X受体 (FXR) 三种核受体的反式激活对原发性猪Leydig细胞的基因表达和类固醇激素代谢的影响。从成熟公猪中分离原代细胞，并使用实时PCR测定转录本表达水平。感兴趣的转录本包括常见的I期和II期代谢酶的猪直系同源物，与类固醇生成有关的酶以及先前显示在雄烯酮和公猪污染水平高的公猪中差异表达的转录本。CAR，PXR或FXR的反式激活增加了与类固醇生成有关的几个基因的表达，包括细胞色素B5A (CYB5A) 和细胞色素B5还原酶1 (CYB5R1) 以及羟基类固醇 (17-beta) 脱氢酶4 (HSD17B4) 和视黄醇脱氢酶12 (RDH12)。用 (6-(4-氯苯基) 咪唑并 [2,1-b][1,3) thiazole-5-carbaldehyde-O-(3,4-二氯苄基) 肟 (CITCO) (一种CAR激动剂) 或利福平 (RIF) (一种PXR激动剂) 治疗，导致性类固醇生成显著 (p<0.05) 减少，16-雄激素类固醇生成显著 (p<0.05) 增加。用FXR激动剂鹅去氧胆酸 (CDCA) 治疗导致性类固醇生成显著 (p<0.05) 减少。这些结果表明这些核受体的反式激活可能导致16-雄激素类固醇水平升高，可能通过将CYP17A1的活性通过CYB5A和CYB5R1改变为andien-β 合酶反应，并远离17α-羟化酶和C17，20裂解酶反应。

BACKGROUND & AIMS: Human endometrium undergoes sequential changes during the menstrual cycle and becomes receptive to implantation during a defined period in the secretory phase. We attempted to identify the genes expressed during this period by representational difference analysis (RDA). When the cDNAs of a proliferative endometrium were used as the driver and the cDNAs of a post-ovulatory day 5 endometrium were used as the tester, a number of bands were identified by RDA. DNA of the cloned RDA products revealed that the majority of the clones contained a fragment of a cDNA identical to that of a crystallin B chain. Northern blot analysis showed that the expression of the alpha crystallin B chain mRNA was absent during the proliferative phase. The expression of the mRNA of alpha crystallin B chain first appeared in the secretory phase, progressively increased during this phase and peaked in the late secretory endometria. The pattern of expression of alpha crystallin B chain mRNA in the endometrium of mature cycling baboons (Papio anubis) was similar to that seen in human endometrium. As revealed by Western blot analysis, the expression of the alpha crystallin B chain protein in human endometrium followed a pattern of expression similar to its mRNA. At the cellular level, the immunoreactive protein first appeared in the surface epithelial cells of human endometrium within the implantation window without significant immunoreactivity in the underlying glandular cells. During the mid- and late secretory phases, the intensity of staining in the epithelial cells was enhanced and an intense immunoreactivity was developed in the glandular epithelium, alpha crystallin B chain was virtually an epithelial product and no immunoreactivity for this protein was detectable in the stromal cells, endothelial cells or lymphoid cells. The expression of alpha crystallin B chain could be regulated, by medroxy progesterone acetate as well as by oestrogen withdrawal, in human endometrial carcinoma cells (EnCa-101), transplanted to nude mice. Based on the data presented here, the known function of alpha crystallin B chain and its distinct pattern of expression in human endometrium, we suggest that this protein is an important factor within the molecular repertoire that makes endometrium receptive to implantation.

背景与目标： 人子宫内膜在月经周期中经历顺序变化，并在分泌期的特定时期接受植入。我们试图通过代表性差异分析 (RDA) 来鉴定在此期间表达的基因。当将增生性子宫内膜的cdna用作驱动程序，并将排卵后第5天子宫内膜的cdna用作测试仪时，RDA鉴定出许多条带。克隆的RDA产物的DNA显示，大多数克隆包含与晶体蛋白B链相同的cDNA片段。Northern印迹分析表明，在增殖期不存在 α 晶体蛋白B链mRNA的表达。Α 晶体蛋白B链mRNA的表达首先出现在分泌期，在此期逐渐增加，并在分泌期晚期子宫内膜达到峰值。成熟循环狒狒 (Papio anubis) 子宫内膜中 α 晶体蛋白B链mRNA的表达模式与人子宫内膜中相似。如Western印迹分析所示，人子宫内膜中 α 晶体蛋白B链蛋白的表达遵循与其mRNA相似的表达模式。在细胞水平上，免疫反应蛋白首先出现在植入窗口内的人子宫内膜表面上皮细胞中，而在下层腺体细胞中没有显着的免疫反应性。在分泌期中期和晚期，上皮细胞的染色强度增强，腺上皮细胞产生了强烈的免疫反应性，α 晶体蛋白B链实际上是上皮产物，在基质细胞，内皮细胞或淋巴样细胞中没有检测到该蛋白的免疫反应性。在移植到裸鼠的人子宫内膜癌细胞 (EnCa-101) 中，醋酸甲羟孕酮和雌激素戒断可以调节 α 晶体蛋白B链的表达。根据此处提供的数据，已知的 α 晶体蛋白B链的功能及其在人子宫内膜中的独特表达模式，我们建议该蛋白是使子宫内膜易于植入的分子库中的重要因素。

BACKGROUND & AIMS: :Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.

背景与目标： 急性移植物抗宿主病 (aGvHD) 降低异基因造血干细胞移植 (allo-HSCT) 的效率和安全性。近年来，人们尝试移植来自健康供体的粪便微生物群来治疗肠道GvHD。这项研究介绍了两例接受allo-HSCT的患者，这些患者后来被选为粪便微生物群移植 (FMT)。在第一例患者中，FMT导致症状完全缓解，而在第二例患者中未达到治疗效果。FMT消除了耐药病原体，即非常耐药的肠球菌属，但没有多药耐药的鲍曼不动杆菌或念珠菌属。需要进一步的研究，尤其是关于FMT在肠道类固醇耐药GvHD患者中的安全性以及移植菌群对allo-HSCT结局的远距离影响。FMT对于类固醇耐药GvHD患者的治疗似乎很有希望。

BACKGROUND & AIMS: :Neurosteroids are powerful modulators of brain function and behavior, yet their dynamics in the brain have remained elusive. Using in vivo microdialysis in male zebra finches, we found that local estradiol levels increased rapidly in the forebrain during social interactions with females. Furthermore, when males were exposed to other males' songs, local estradiol levels also increased and testosterone levels dropped in a cortical/pallial auditory region that is analogous to mammalian auditory cortex. We also found that local estradiol and testosterone levels were differentially regulated in this same region by the conventional neurotransmitters glutamate and GABA, respectively. This study provides direct evidence that forebrain steroid levels are acutely and differentially regulated during social behavior in a region-specific manner and in a rapid time course similar to that of traditional neuromodulators.

背景与目标： : 神经类固醇是大脑功能和行为的强大调节剂，但它们在大脑中的动态仍然难以捉摸。在雄性斑马雀中使用体内微透析，我们发现在与雌性的社交互动中，前脑中的局部雌二醇水平迅速增加。此外，当男性暴露于其他男性的歌曲时，类似于哺乳动物听觉皮层的皮质/苍白质听觉区域的局部雌二醇水平也会升高，睾丸激素水平也会下降。我们还发现，在同一区域，常规神经递质谷氨酸和GABA分别对局部雌二醇和睾丸激素水平进行了差异调节。这项研究提供了直接证据，表明前脑类固醇水平在社交行为中以特定区域的方式和与传统神经调节剂相似的快速时间过程受到急性和差异调节。

BACKGROUND & AIMS: :The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

背景与目标： : 血栓性血小板减少性紫癜 (TTP) 的治疗结果已通过血浆置换得到改善。但是，对于难治性血浆置换的病例，目前的治疗选择有限。已证明阻断ADAMTS13活性的自身抗体在TTP的发病机理中起作用; 因此，可以中和这些自身抗体的大剂量免疫球蛋白可能对难治性TTP有用。然而，韩国尚未报道大剂量免疫球蛋白对血浆置换和皮质类固醇难治性TTP的成功治疗。在本文中，我们描述了用高剂量免疫球蛋白成功治疗的难治性病例。一名29岁的男性被诊断为TTP，在血浆置换联合其他大剂量皮质类固醇治疗后未能改善。作为挽救性治疗，我们开始了为期7天的大剂量免疫球蛋白 (400 mg/kg) 输注方案，从而完全缓解，持续到最后一次随访18个月。大剂量免疫球蛋白可能被证明是难治性血浆置换患者的有用治疗方法; 它还可以促进恢复并减少对血浆置换的需求。

BACKGROUND & AIMS: :Uptake of organic solutes and xenobiotics by mammalian cells is mediated by ATP-independent transporters, and four families of transporters have now been identified. To search for novel organic solute transporters, a liver cDNA library from an evolutionarily primitive marine vertebrate, the little skate Raja erinacea, was screened for taurocholate transport activity by using Xenopus laevis oocytes. In contrast to the organic anion transporters identified to date, a transport activity was identified in this library that required the coexpression of two distinct gene products, termed organic solute transporter alpha and beta (Ostalpha, Ostbeta). Ostalpha cDNA encodes for a protein of 352 aa and seven putative transmembrane (TM) domains. Ostbeta contains 182 aa and has at least one and perhaps two TM domains. There is no significant sequence identity between Ostalpha and Ostbeta, and only low identity with sequences in the databases; however, Ostalpha bears a resemblance to some G protein-coupled receptors, and Ostbeta exhibits 22% amino acid identity with the C-terminal TM and intracellular domains of protocadherin-gamma, a cell surface glycoprotein. Xenopus oocytes injected with the cRNA for both Ostalpha and Ostbeta, but not each separately, were able to take up taurocholate, estrone sulfate, digoxin, and prostaglandin E(2), but not p-aminohippurate or S-dinitrophenyl glutathione. Transport was sodium-independent, saturable, and inhibited by organic anions and steroids, including the major skate bile salt, scymnol sulfate. These results identify an organic anion transporter composed of a putative seven-helix TM protein and an ancillary membrane polypeptide.

背景与目标： : 哺乳动物细胞对有机溶质和异种生物的吸收是由ATP非依赖性转运蛋白介导的，现在已经确定了四个转运蛋白家族。为了寻找新的有机溶质转运蛋白，使用非洲爪蟾卵母细胞筛选了来自进化原始海洋脊椎动物小溜冰鞋Raja erinacea的肝脏cDNA文库的牛磺胆酸盐转运活性。与迄今为止鉴定的有机阴离子转运蛋白相反，在该文库中鉴定出一种转运活性，该转运活性需要两种不同基因产物的共表达，称为有机溶质转运蛋白 α 和 β (Ostalpha，Ostbeta)。Ostalpha cDNA编码352 aa和七个推定的跨膜 (TM) 结构域的蛋白质。Ostbeta包含182 aa并且具有至少一个和可能两个TM结构域。Ostalpha和Ostbeta之间没有显着的序列同一性，仅与数据库中的序列低同一性; 但是，Ostalpha与某些g蛋白偶联受体相似，Ostalpha与原钙粘蛋白-γ 的C末端TM和细胞内结构域具有22% 的氨基酸同一性，一种细胞表面糖蛋白。注射了用于Ostalpha和Ostbeta的cRNA的非洲爪蟾卵母细胞 (但不是分别) 能够吸收牛磺胆酸盐，硫酸雌酮，地高辛和前列腺素E(2)，但不能吸收对氨基马尿酸盐或S-二硝基苯基谷胱甘肽。转运是钠非依赖性的，可饱和的，并受到有机阴离子和类固醇的抑制，包括主要的冰鞋胆盐，硫酸scymnol。这些结果确定了由推定的七螺旋TM蛋白和辅助膜多肽组成的有机阴离子转运蛋白。

BACKGROUND & AIMS: :The aim of this study was to investigate the effect of oxandrolone on body composition in boys with constitutional delay of growth and puberty. In 14 prepubertal boys, height, weight, triceps and subscapular skinfolds and upper arm circumference were measured. Body mass index, the ratio of subscapular to triceps skinfolds and the upper muscle area were also determined. The difference of the various measurements and indices, 3 to 6 months before and after commencement of oxandrolone treatment, were calculated, while the boys remained prepubertal. We observed a marked increase in body mass index, a decrease of triceps and subscapular skinfolds, an increase in the ratio of subscapular to triceps skinfolds and also an increase in upper muscle area after the onset of oxandrolone treatment. These results suggest that low dose oxandrolone administration in prepubertal boys with constitutional growth delay causes a disproportionate increase of weight to height which is largely due to increased body muscle.

背景与目标： : 这项研究的目的是研究奥沙洛尔酮对发育和青春期体质延迟的男孩身体成分的影响。在14个青春期前男孩中，测量了身高，体重，三头肌和肩胛下皮褶和上臂围。还确定了体重指数，肩cap下与肱三头肌皮褶的比率以及上肌面积。计算了开始奥沙酮治疗前后3至6个月的各种测量和指标的差异，而男孩仍处于青春期前。我们观察到在开始oxandrolone治疗后，体重指数显着增加，肱三头肌和肩胛下皮褶减少，肩胛下与肱三头肌皮褶的比例增加以及上肌面积增加。这些结果表明，在具有体质生长延迟的青春期前男孩中，低剂量的oxandrolone给药会导致体重与身高不成比例的增加，这在很大程度上是由于身体肌肉的增加。

BACKGROUND & AIMS: :The aim of the present study was to describe the normal cellular distribution of progesterone receptors in the canine ovary at different stages of the oestrous cycle. Samples of both ovaries were obtained from 75 healthy adult bitches of various breeds and ages, including five pregnant bitches and three bitches that had just delivered. The presence of progesterone receptors was visualized by immunohistochemistry on paraffin wax sections using a monoclonal antibody. Nuclear staining for progesterone receptors was observed in the surface epithelium, cortical tubules, rete ovarii, follicle cells, thecal cells, luteal cells, granulosa cell cords and ovarian stroma. The staining intensity for progesterone receptors in the follicle cells increased with the stage of follicle development, indicating an intrafollicular role of progesterone in the mechanism of ovulation and luteinization. The stronger staining intensities for progesterone receptors in thecal cells compared with follicle cells may be explained by the fact that thecal cells mediate some effects of steroid hormones on the follicle cells in secondary and tertiary follicles. Little correlation was found between the expression of progesterone receptors in follicle cells and oestradiol, progesterone or testosterone concentrations. This finding indicates a different regulating mechanism for progesterone receptors in canine ovarian follicles compared with other tissues of the genital tract. During pregnancy all groups of ovarian cells had lower staining intensity scores than during the oestrous cycle, although the sex steroid hormone concentrations in pregnant bitches were similar to those in non-pregnant bitches during the luteal phase of the oestrous cycle. The lower expression of progesterone receptors during pregnancy may be due to higher tissue concentrations of progesterone that are not reflected in the serum because of haemodilution and increased metabolism and clearance during pregnancy.

背景与目标： : 本研究的目的是描述在发情周期的不同阶段，犬卵巢中孕酮受体的正常细胞分布。两个卵巢的样本都是从75个不同品种和年龄的健康成年母狗中获得的，其中包括五个怀孕的母狗和三个刚分娩的母狗。使用单克隆抗体通过石蜡切片上的免疫组织化学观察孕酮受体的存在。在表面上皮，皮质小管，卵巢，卵泡细胞，鞘细胞，黄体细胞，颗粒细胞索和卵巢基质中观察到孕激素受体的核染色。卵泡细胞中孕激素受体的染色强度随着卵泡发育阶段的增加而增加，表明孕激素在排卵和黄体化机制中的卵泡内作用。与卵泡细胞相比，卵泡细胞中孕酮受体的染色强度更强，这可以解释为卵泡细胞介导了类固醇激素对次级和三级卵泡中卵泡细胞的某些作用。卵泡细胞中孕酮受体的表达与雌二醇，孕酮或睾丸激素浓度之间几乎没有相关性。这一发现表明，与生殖道其他组织相比，犬卵巢卵泡中孕酮受体的调节机制不同。在怀孕期间，所有卵巢细胞组的染色强度评分均低于发情周期，尽管在发情周期的黄体期，怀孕母狗中的性类固醇激素浓度与未怀孕母狗中的性类固醇激素浓度相似。孕酮受体在怀孕期间的表达较低，可能是由于孕酮的组织浓度较高，而由于血液稀释和妊娠期间的新陈代谢和清除率增加而未在血清中反映出来。

BACKGROUND & AIMS: BACKGROUND:Treatment of adults with steroid-dependent minimal change nephrotic syndrome (SD-MCNS) can be a significant challenge. Cyclophosphamide (CYC) and cyclosporin (CYA) are often effective steroid-sparing agents. Tacrolimus (TAC) may be another treatment option. METHODS:This open, prospective cohort study enrolled Chinese adults with SD-MCNS. At the start of the study, we administered TAC or intravenous CYC together with prednisone (0.5 mg/kg/day), the dose of which was tapered off throughout the study. The TAC cohort received oral TAC (target trough blood level of 4-8 ng/ml) for 24 weeks and the CYC cohort received intravenous CYC (750 mg/m(2) body surface) once every 4 weeks for 24 weeks. RESULTS:Twenty-six patients met the criteria for enrollment (14 patients in the CYC group and 12 patients in the TAC group). One patient from each group discontinued treatment because of a drug-related side effect. Complete remission (CR) after the 24-week therapeutic period was 76.9% (10/13) in the CYC group and 90.9% (10/11) in the TAC group. The mean time required for CR in the TAC group was significantly less than in the CYC group (P = 0.031). Eight of 13 (61.5%) patients in the CYC group and 8 of 11 (72.7%) patients in the TAC group successfully stopped steroids and changed their status from steroid dependence. Sixty percent (6/10) of the CYC patients and 50% (5/10) of the TAC patients who achieved CR maintained remission during the follow-up period of 23.0 +/- 10.1 months. Four (40%) CYC patients and five (50%) TAC patients experienced relapses, and two CYC patients experienced frequent relapses. CONCLUSION:A 24-week course of TAC is a favorable steroid-sparing agent for treatment of Chinese adults with SD-MCNS. Therapy with TAC accompanied by a tapering dose of prednisolone appears to yield quicker remission than treatment with CYC together with prednisone.

背景与目标：