Cloning and expression of SLC1OA4,a putative organic anion transport protein

AIM:To determine if novel bile acid transporters may be expressed in human tissues.METHODS:SLC10A1 (NTCP) was used as a probe to search the NCBI database for homology to previously uncharacterized ESTs. The homology search identified an EST (termed SLC10A4) that shares sequence identity with SLC10A1 and SLC10A2 (ASBT). We performed Northern blot analysis and RT-PCR to determine the tissue distribution of SLC10A4. SLC10A4 was cloned in frame with an epitope tag and overexpressed in CHO cells to determine cellular localization and functional analysis of bile acid uptake.RESULTS:Northern analysis revealed that SLC 10A4 mRNA is ubiquitously expressed fn human tissues with the highest levels of mRNA expression in brain,placenta, and liver. In SLC10A4-transfected CHO cells,immunoblotting analysis and immunofluorescence staining demonstrated a 49-kDa protein that is expressed at the plasma membrane and intracellular compartments.Functional analysis of SLC10A4 showed no significant taurocholate uptake in the presence of sodium when compared to untransfected CHO cells.CONCLUSION:To date, we have shown that this protein has no capacity to transport taurocholate relative to SLC1041; however, given its ubiquitous tissue distribution, it may play a more active role in transporting other endogenous organic anions.     

Primary peritoneal carcinoma in a UK cancer center: comparison with advanced ovarian carcinoma over a 5-year period

Abstract.   Jaaback KS, Ludeman L, Clayton NL, Hirschowitz L. Primary peritoneal carcinoma in a UK cancer center: comparison with advanced ovarian carcinoma over a 5-year period. Int J Gynecol Cancer 2006; 16(Suppl. 1): 123–128.
The relative incidence of primary peritoneal carcinoma (PPCa) and advanced (FIGO stage III or IV) ovarian serous carcinoma (AOSCa) was assessed over 5 years at a UK cancer center, and the sociodemographic, clinical, and survival data were compared. There were 23 women with PPCa and 55 with AOSCa. The ratio of PPCa:AOSCa was higher than previously reported. No statistical difference was found between the two groups with regard to age (mean 64.43 vs 64.07 years, P = 0.9), parity (1.6 vs 1.8, P = 1.0), personal/family history of another malignancy (although five patients with AOSCa but none with PPCa had personal histories of breast cancer), or serum CA125, CA19.9, and carcinoembryonic antigen (CEA) levels. Similar numbers in both groups had malignant ascites, although 5.8% of patients with AOSCa but none with PPCa had negative cytology. Tumor grade, stage, treatment, and survival were similar (median 586 vs 641 days, P = 0.66). This analysis of the largest published UK series of patients with PPCa does not support previous reports that patients with PPCa are older than those with AOSCa and have a worse prognosis; it suggests that both groups have similar sociodemographic characteristics, clinical profiles, and survival.     

欧芹素乙和异欧芹素乙对小鼠腹腔巨噬细胞体外释放肿瘤坏死因子的抑制作用

研究了欧芹素乙（Ｉｍｐｅｒａｔｏｒｉｎ，Ｉｍｐ）和异欧芹素乙（Ｉｓｏ－ｉｍｐｅｒａｔｏｒｉｎ，Ｉｓｉ）及对照药物维拉帕米（Ｖｅｒａｐａｍｉｌ，Ｖｅｒ）对小鼠腹腔巨噬细胞体外释放肿瘤坏死因子（Ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ，ＴＮＦ）的影响。结果表明：Ｉｍｐ、Ｉｓｉ及Ｖｅｒ对小鼠腹腔巨噬细胞体外释放ＴＮＦ具有显著的抑制作用。药物浓度在１０－６～１０－４ｍｏｌ／Ｌ范围内，该抑制作用呈剂量依赖性：药物浓度达１０－４ｍｏｌ／Ｌ时，则可完全抑制ＴＮＦ的释放。     

骨搬移法对下肢缺血疾病疗效的基础研究

目的　观察应用胫骨横向骨搬移法对犬下肢缺血性疾病动物模型的血管再生效果。方法　将 2 0只犬制成下肢缺血性疾病动物模型 ,建模后 1周对犬的后肢施行胫骨横向骨搬移术 ,即在胫骨内侧嵴开一个 5cm× 1cm骨窗 ,以特制的支架每天 1mm速度向外牵拉。分别于不同时期处死动物 ,通过皮温测定 ,光镜下测量血管密度 ,血管造影等方法来观察血管再生情况。结果　在不同时相点观察到伴随着骨的搬移 ,有明显的毛细血管再生现象 (以第 7～ 2 1天为著 )。结论　应用胫骨横向骨搬移法可对犬下肢缺血性疾病动物模型产生明显的血管再生 ,有明显的治疗效果     

介导感觉生理功能的瞬时受体电位通道蛋白(TRP)家族研究进展

瞬时受体电位通道蛋白(TRP)家族由一类特殊的阳离子通道蛋白组成,在神经细胞及其他非兴奋细胞中有重要作用,其中在介导多种感觉生理功能方面的作用尤其显著.TRP结构与功能的深入研究为阐明感觉生理功能的分子机制提供了重要线索.本文综述TRP家族在温度感受、机械刺激感受、光感受和化学信号感受等方面的研究进展.     

Expression of Na+/HCO3− co‐transporter proteins (NBCs) in rat and human skeletal muscle

Aim: Sodium/bicarbonate co‐transport (NBC) has been suggested to have a role in muscle pH regulation. We investigated the presence of NBC proteins in rat and human muscle samples and the fibre type distribution of the identified NBCs. Methods and results: Western blotting of muscle homogenates and sarcolemmal membranes (sarcolemmal giant vesicles) were used to screen for the presence of NBCs. Immunohistochemistry was used for the subcellular localization. The functional test revealed that approximately half of the pH recovery in sarcolemmal vesicles produced from rat muscle is mediated by bicarbonate‐dependent transport. This indicates that the NBCs are preserved in the vesicles. The western blotting experiments demonstrated the existence of at least two NBC proteins in skeletal muscle. One NBC protein (approximately 150 kDa) seems to be related to the kidney/pancreas/heart isoform NBC1, whereas the other protein (approximately 200 kDa) is related to the NBC4 isoform. The two NBC proteins represent the electrogenic isoforms named NBCe1 and NBCe2. Membrane fractionation and immunofluorescence techniques confirmed that the two NBCs are located in the sarcolemmal membrane as well as in some internal membranes, probably the T‐tubules. The two NBCs localized in muscle have distinct fibre type distributions. Conclusions: Skeletal muscle possesses two variants of the sodium/bicarbonate co‐transporter (NBC) isoforms, which have been called NBCe1 and NBCe2.     

肾衰合剂对维持性腹膜透析患者残余肾功能的影响

目的：观察肾衰舍剂对连续不卧床腹膜透析（CAPD）患者残余肾功能的影响，探讨中药治疗对CAPD患者残余肾功能的保护作用及其机制。方法：将56例脾肾气（阳）虚型的CAPD患者随机分为常规腹膜透析对照组，及加服中药肾衰合剂治疗组。治疗6个月，比较残余肾KT／V、残余肾CCr的变化及下降速率。结果：在维持总体透析效能的前提下，治疗组残余肾KT／V、残余肾CCr下降速度较对照组明显缓慢。结论：肾衰合荆能有效延缓PD患者的RRF的下降。     

运动对大鼠腓肠肌一氧化氮含量和铁转运蛋白表达的影响

目的观察游泳运动后大鼠腓肠肌一氧化氮(NO)含量及铁转运相关蛋白表达的变化,探讨运动对骨骼肌铁代谢的调节机制。方法20只雌性SD大鼠随机分为对照组和运动组(每天游泳1.5小时,6次/周),每组10只。实验10周后分别采用试剂盒测定两组大鼠腓肠肌和血清一氧化氮合酶(NOS)活性及NO含量,免疫组织化学方法测定腓肠肌二价金属离子转运体1(DMT1)、膜铁转运蛋白1(FP1)和转铁蛋白受体1(TfR1)的表达,分析其平均光密度变化。结果(1)运动组大鼠血清和腓肠肌NO含量和NOS活性均显著高于对照组(P<0.05);(2)运动组大鼠腓肠肌DMT1(IRE)和TfR1表达较对照组显著增加,FP1表达显著减少(P<0.05),而DMT1(non-IRE)表达无明显变化。结果提示运动可能通过增加NOS活性刺激NO合成增加,进而调节腓肠肌铁转运蛋白的表达,提高腓肠肌摄铁能力,以满足运动中机体对铁的需求。     

不同骨延长器治疗肢体畸形并大段骨缺损

[目的]利用Ilizarov支架、Orthofix肢体重建系统（Orthofix LRS）及Hybrid固定系统（Hybrid Fixation System）与Orthofix LRS的组合，对不同的肢体畸形并大段骨缺损进行矫形及骨延长治疗，同时观察其疗效。[方法]自2000年8月-2004年3月分别用Ilizarov支架、Orthofix LRS及Hybrid支架与Orthofix LRS的组合进行骨痂牵开／骨段滑移治疗合并肢体畸形的大段骨缺损。畸形处采用线形／楔形截骨。畸形愈合并骨短缩者楔形截骨后进行骨痂牵开骨延长术，骨不连并畸形及短缩者接合点加压与截骨矫形骨段滑移延长同时进行。[结果]矫正股骨短缩畸形7cm1例，胫骨6例，内翻畸形2例，后成角畸形2例，混合畸形2例。平均延长5．3cm（4．5—7cm），平均延长时间3．5个月，平均延长后外固定时间7个月，无神经血管损伤，膝踝关节活动未受影响。[结论]Ilizarov支架、Orthofix LRS、Hybrid固定系统与Orthofix LRS的组合用于骨痂牵开／骨段滑移治疗合并肢体畸形的大段骨缺损均能达到矫形及骨延长的治疗目的。Orthofix LRS及Hybrid固定系统与Orthofix LRS的组合较Ilizarov支架操作简便，安全可靠，患者乐于接受。     

Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.