BACKGROUND & AIMS: PURPOSE:To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the trabecular meshwork (TM). METHODS:Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human TM tissue and explant cultures of TM endothelial cells. Cultures of TM cells were treated with vehicle control or latanoprost acid for 24 hours. Real-time RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS:The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 and of TIMP-1 to -4 was present in TM tissue and cultures of TM cells. MMP-9 was not found. In control TM endothelial cells, the relative expression of MMP mRNA were MMP-2 and -14 > MMP-16, -19, and -24 > MMP-15 > MMP-11 and -17 > MMP-1 and -3 > MMP-12. The relative expressions of TIMP mRNA were TIMP-1 > TIMP-2 and -3 > TIMP-4. Latanoprost increased MMP-1 (in four of five cultures), MMP-3 (in four of five cultures), MMP-17 (in three of five cultures), MMP-24 (in all five cultures), TIMP-2, -3, and -4 expression (in three of five cultures); MMP-11 and -15 were downregulated. CONCLUSIONS:Contrary to the expected result, latanoprost seems to have a significant effect on TM cells. The transcription of the genes for MMP-1, -3, -17, and -24 is increased by latanoprost treatment. TIMP-2, -3, and -4 are also upregulated. The upregulation of these TIMPs may compensate for the increase of those MMPs. The absence of MMP-9 and concurrent upregulation of a greater number of TIMPs may explain the limited effect of latanoprost on TM outflow.

背景与目标： 目的：确定拉坦前列素对小梁网（TM）中人基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）表达的影响。
方法：分离总RNA，进行定性RT-PCR检测人TM组织和TM内皮细胞外植体培养物中MMP和TIMP的mRNA。用媒介物对照或拉坦前列素酸处理TM细胞的培养物24小时。对来自五个不同供体的细胞培养物进行了实时RT-PCR，以确定表达的相对变化。 GAPDH用作内源性对照。
结果：MMP-1，-2，-3，-11，-12，-14，-15，-16，-17，-19和-24和TIMP-1至-4的mRNA均存在于TM组织和TM细胞培养物。找不到MMP-9。在对照TM内皮细胞中，MMP mRNA的相对表达为MMP-2和-14> MMP-16，-19和-24> MMP-15> MMP-11和-17> MMP-1和-3> MMP -12。 TIMP mRNA的相对表达为TIMP-1> TIMP-2和-3> TIMP-4。拉坦前列素可提高MMP-1（在五种文化中的四种），MMP-3（在五种文化中的四种），MMP-17（在五种文化中的三种），MMP-24（在五种文化中），TIMP-2，- 3和-4表达（在五种文化中的三种）； MMP-11和-15下调。
结论：与预期结果相反，拉坦前列素似乎对TM细胞有显着影响。拉坦前列素处理可增加MMP-1，-3，-17和-24基因的转录。 TIMP-2，-3和-4也被上调。这些TIMP的上调可以补偿那些MMP的增加。 MMP-9的缺乏和大量TIMP的同时上调可能解释了拉坦前列素对TM外流的作用有限。

BACKGROUND & AIMS: Activation of helper T cells results in coordinate expression of a number of cytokines involved in differentiation, proliferation and activation of the haematopoietic system. Granulocyte-macrophage colony stimulating factor (GM-CSF) is one such cytokine, whose increased expression results mostly from increases in transcription. Cis-acting elements with NFkappaB, AP1 and ETS-like binding motifs have been identified in the promoter region of the GM-CSF gene, and are important or essential for transcriptional activity following T cell activation. ETS1 is a transcription factor of the ETS family that is expressed in T cells. We have previously shown that ETS1 can transactivate GM-CSF in Jurkat T cells, but only after the cells have been stimulated by treatment with PMA and ionomycin, agents that mimic T cell activation. Thus we proposed that ETS1, which is expressed constitutively in Jurkat cells, may act in concert with PMA/ionomycin inducible factors. Here we show that ETS1 can transactivate a GM-CSF reporter construct in unstimulated Jurkat cells, providing that either NFkappaB or AP1 transcription factors are supplied by co-transfection. We confirm that binding of endogenous NFkappaB and AP1 is induced following PMA/ionomycin treatment of T cells. Transactivation by ETS1, NFkappaB and AP1 is synergistic, and mutation of the individual binding sites reveals that the transcriptional activities of these factors are interdependent. Our results suggest that constitutive ETS1, and inducible NFkappaB and AP1, cooperate as part of a higher order transcriptional complex in activated T cells.

背景与目标： 辅助T细胞的活化导致涉及造血系统分化，增殖和活化的多种细胞因子的协调表达。粒细胞-巨噬细胞集落刺激因子（GM-CSF）就是这样一种细胞因子，其表达增加主要是由于转录增加。具有NFkappaB，AP1和ETS样结合基序的顺式作用元件已经在GM-CSF基因的启动子区域被鉴定出来，并且对于T细胞活化后的转录活性是重要的或必不可少的。 ETS1是ETS家族的转录因子，在T细胞中表达。先前我们已经证明ETS1可以在Jurkat T细胞中激活GM-CSF，但是只有在用PMA和离子霉素处理后，这些细胞才可以模拟T细胞的激活。因此，我们提出在Jurkat细胞中组成性表达的ETS1可能与PMA /离子霉素诱导因子协同作用。在这里，我们证明ETS1可以在未刺激的Jurkat细胞中激活GM-CSF报告基因构建体，前提是NFkappaB或AP1转录因子是通过共转染提供的。我们确认内源性NFkappaB和AP1的结合在TMA的PMA /离子霉素处理后被诱导。 ETS1，NFkappaB和AP1的反式激活是协同的，单个结合位点的突变表明这些因子的转录活性是相互依赖的。我们的结果表明，组成型ETS1和诱导型NFkappaB和AP1在激活的T细胞中作为高阶转录复合物的一部分协同作用。

BACKGROUND & AIMS: :Elucidation of the cellular basis of arrhythmias in ion channelopathy disorders is complicated by the inherent difficulties in studying human cardiac tissue. Thus we used a computer modeling approach to study the mechanisms of cellular dysfunction induced by mutations in inward rectifier potassium channel (K(ir))2.1 that cause Andersen-Tawil syndrome (ATS). ATS is an autosomal dominant disorder associated with ventricular arrhythmias that uncommonly degenerate into the lethal arrhythmia torsade de pointes. We simulated the cellular and tissue effects of a potent disease-causing mutation D71V K(ir)2.1 with mathematical models of human ventricular myocytes and a bidomain model of transmural conduction. The D71V K(ir)2.1 mutation caused significant action potential duration prolongation in subendocardial, midmyocardial, and subepicardial myocytes but did not significantly increase transmural dispersion of repolarization. Simulations of the D71V mutation at shorter cycle lengths induced stable action potential alternans in midmyocardial, but not subendocardial or subepicardial cells. The action potential alternans was manifested as an abbreviated QRS complex in the transmural ECG, the result of action potential propagation failure in the midmyocardial tissue. In addition, our simulations of D71V mutation recapitulate several key ECG features of ATS, including QT prolongation, T-wave flattening, and QRS widening. Thus our modeling approach faithfully recapitulates several features of ATS and provides a mechanistic explanation for the low frequency of torsade de pointes arrhythmia in ATS.

背景与目标： ：由于研究人类心脏组织的固有困难，阐明离子性通道病疾病中的心律不齐的细胞基础变得复杂。因此，我们使用一种计算机建模方法来研究由引起Andersen-Tawil综合征（ATS）的内向整流钾通道（K（ir））2.1突变引起的细胞功能障碍的机制。 ATS是与室性心律失常相关的常染色体显性遗传疾病，通常退化为致命性心律失常扭转性尖端。我们用人心室肌细胞的数学模型和跨壁传导的双域模型模拟了强力致病突变D71V K（ir）2.1的细胞和组织作用。 D71V K（ir）2.1突变导致心内膜下，心肌中层和心外膜下心肌细胞的动作电位持续时间显着延长，但并未明显增加跨壁的复极分散。 D71V突变在更短的周期长度上的模拟在心肌中层而不是心内膜下或心外膜下的细胞中诱导了稳定的动作电位交替蛋白。动作电位交替素表现为跨壁ECG中的QRS缩略语，是动作电位在心肌中部组织中传播失败的结果。此外，我们对D71V突变的模拟概括了ATS的几个重要ECG功能，包括QT延长，T波展平和QRS展宽。因此，我们的建模方法忠实地概括了ATS的几个功能，并为ATS的扭转性点性心律失常的低频率提供了机械的解释。

BACKGROUND & AIMS: BACKGROUND:This study was undertaken to obtain differentially expressed genes related to human glioma by cDNA microarray and the characterization of a novel full-length gene. METHODS:Total RNA was extracted form human glioma and normal brain tissue, and mRNA was used as a probe. The results of hybridization procedure were scanned with the computer system. The gene named 507E08 cone was subsequently analyzed by northern blot, bioinformatic approach, and protein expression. RESULTS:Fifteen differentially expressed genes were obtained from human glioma by hybridization and scanning for four times. Northern blot analysis confirmed that the 507E08 clone was low expressed in human brain tissue and over expressed in human glioma tissues. The analysis of BLASTn and BLASTx showed that the 507E08 clone was a novel full-length gene, which codes 203 amino acid of protein and is called human ribosomal protein 14.22 gene. The nucleotide sequence had been submitted to the GenBank with the accession number of AF329277. After expression in E. coli., protein yielded a major band of apparent molecular mass 22 kDa on an SDS-PAGE gel. CONCLUSIONS:cDNA microarray technology can be successfully used to identify differentially expressed genes. The novel full-length gene of human ribosomal protein 13.22 may be correlated with the development of human glioma.

背景与目标： 背景：本研究旨在通过cDNA微阵列技术获得与人神经胶质瘤相关的差异表达基因，并鉴定一个新的全长基因。
方法：从人脑胶质瘤和正常脑组织中提取总RNA，并以mRNA为探针。杂交程序的结果用计算机系统扫描。随后通过Northern印迹，生物信息学方法和蛋白质表达来分析名为507E08视锥细胞的基因。
结果：通过杂交和扫描4次，从人脑胶质瘤中获得了15个差异表达基因。 Northern印迹分析证实507E08克隆在人脑组织中低表达而在人脑胶质瘤组织中高表达。对BLASTn和BLASTx的分析表明，507E08克隆是一个新颖的全长基因，其编码蛋白质的203个氨基酸，被称为人核糖体蛋白质14.22基因。该核苷酸序列已提交给GenBank，登录号为AF329277。在大肠杆菌中表达后，蛋白质在SDS-PAGE凝胶上产生一条表观分子量为22 kDa的主带。
结论：cDNA微阵列技术可成功用于鉴定差异表达的基因。人核糖体蛋白13.22的新的全长基因可能与人脑胶质瘤的发展有关。

BACKGROUND & AIMS: :The extracellular calcium-sensing receptor (CaR) is usually associated with systemic Ca(2+) homeostasis, but the CaR is also expressed in many other tissues, including pancreatic islets of Langerhans. In the present study, we have used human islets and an insulin-secreting cell line (MIN6) to investigate the effects of CaR activation using the calcimimetic R-568, a CaR agonist that activates the CaR at physiological concentrations of extracellular Ca(2+). CaR activation initiated a marked but transient insulin secretory response from both human islets and MIN6 cells at a sub-stimulatory concentration of glucose, and further enhanced glucose-induced insulin secretion. CaR-induced insulin secretion was reduced by inhibitors of phospholipase C or calcium-calmodulin-dependent kinases, but not by a protein kinase C inhibitor. CaR activation was also associated with an activation of p42/44 mitogen-activated protein kinases (MAPK), and CaR-induced insulin secretion was reduced by an inhibitor of p42/44 MAPK activation. We suggest that the beta-cell CaR is activated by divalent cations co-released with insulin, and that this may be an important mechanism of intra-islet communication between beta-cells.

背景与目标： ：细胞外钙敏感受体（CaR）通常与全身性Ca（2）稳态相关，但该CaR在许多其他组织中也表达，包括Langerhans的胰岛。在本研究中，我们已经使用人类胰岛和胰岛素分泌细胞系（MIN6）来研究使用拟钙剂R-568（CaR激动剂在生理浓度的细胞外Ca（2）激活CaR的CaR激活）的作用。 。 CaR激活在葡萄糖的亚刺激浓度下启动了来自人胰岛和MIN6细胞的显着但短暂的胰岛素分泌反应，并进一步增强了葡萄糖诱导的胰岛素分泌。 CaR诱导的胰岛素分泌通过磷脂酶C或钙钙调蛋白依赖性激酶的抑制剂降低，但不通过蛋白激酶C抑制剂降低。 CaR激活还与p42 / 44丝裂原激活的蛋白激酶（MAPK）激活相关，并且CaR诱导的胰岛素分泌被p42 / 44 MAPK激活的抑制剂减少。我们建议β细胞CaR被与胰岛素共释放的二价阳离子激活，这可能是β细胞之间胰岛内通讯的重要机制。

BACKGROUND & AIMS: CONTEXT:In animal models, estrogen inhibits atherogenesis by inhibiting many of the early steps of atherosclerotic plaque formation. However, the lack of cardioprotective effect by postmenopausal hormone replacement therapy and possible increase in cardiovascular events observed during the first year after the initiation of hormone replacement therapy may suggest that once the plaque is formed, estrogen may have additional effects that may counteract its beneficial outcomes. Indeed, the effect of estrogen on plaque stability has not been identified. OBJECTIVE:We hypothesized that 17beta-estradiol (E2) may cause increased apoptosis in human coronary artery endothelial cells (HCAECs). This effect would explain an adverse effect on plaque stability in vivo. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S):The effect of E2 on apoptosis, cell proliferation, and expression of proapoptotic molecules Fas and Fas ligand (FasL) in cultured HCAECs was evaluated. RESULTS:HCAECs in culture treated with E2 showed an increase in DNA strand breaks and nuclear fragmentation indicative of apoptosis. E2 treatment also induced a significant concentration-dependent increase in Fas mRNA and protein expressions in HCAECs. Moreover, the expression of FasL mRNA and secretion of FasL protein by HCAECs were enhanced in response to E2 treatments. CONCLUSIONS:E2 increases the apoptosis in cultured HCAECs. Enhanced Fas and FasL expressions in response to E2 suggest that activation of the Fas/FasL pathway may be a mediator of the proapoptotic effects of E2 in these cells.

背景与目标： 背景：在动物模型中，雌激素通过抑制动脉粥样硬化斑块形成的许多早期步骤来抑制动脉粥样硬化。但是，绝经后激素替代疗法缺乏心脏保护作用，并且在开始激素替代疗法后的第一年内观察到的心血管事件可能增加，这表明一旦形成斑块，雌激素可能会产生额外的作用，从而抵消其有益结果。实际上，尚未确定雌激素对斑块稳定性的作用。
目的：我们假设17β-雌二醇（E2）可能导致人冠状动脉内皮细胞（HCAEC）凋亡增加。该作用将解释对体内斑块稳定性的不利影响。
干预和主要观察指标：评估了E2对培养的HCAEC中细胞凋亡，细胞增殖以及促凋亡分子Fas和FasL配体（FasL）表达的影响。
结果：用E2处理的培养物中的HCAECs显示DNA链断裂的增加和核碎裂指示凋亡。 E2处理还诱导了HCAECs Fas mRNA和蛋白表达的浓度依赖性显着增加。而且，响应于E2处理，HCAECs的FasL mRNA的表达和FasL蛋白的分泌得到增强。
结论：E2增加了培养的HCAECs的细胞凋亡。响应E2增强的Fas和FasL表达表明Fas / FasL途径的激活可能是这些细胞中E2促凋亡作用的介质。

BACKGROUND & AIMS: INTRODUCTION:Ethics committees are a necessary resource to guarantee ethical integrity in human research; they must apply international standards in their ethical evaluation of research projects involving human subjects. OBJECTIVE:The ethics committees for human research of Colombia were characterized, and recommendations for strengthening them were formulated. MATERIALS AND METHODS:In 2003, 280 groups with research projects involving human subjects were selected from a list of research groups which form part of the science and technology network of Colciencias. (Colciencias is the Colombian national agency that promotes and funds science and technology.) Eighty percent (224) of the projects were associated with 40 institutions, consisting of universities, hospitals, and public or private research centers. Thirty of these institutions had at least one ethics committee for evaluating use of human subjects. A questionnaire was mailed to each of these Committees, requesting information concerning its their compostition, regulations, multidisciplinarity, plurality, representativity and independence. The World Health Organization's Operational Guidelines for Ethic Committees that Evaluate Biomedical Research (TDR/PRD/ETHICS/2000) was used as reference for the analysis. In 5 of the cities, supplemental information was obtained by direct discussions with members of the ethics committees. RESULTS:Twenty-six committees responded to the questionnaire. The results indicated that 47% of the committee members were physicians, but only 23% of the committees had representatives from the community. In 60% of the Committees, members were not independent from the organization in which it was based. Seventy percent had established operating procedures. Lack of national regulations and limited education in research ethics were mentioned as the main drawbacks in providing effective guidance. CONCLUSIONS:These observations led to the conclusion that national guidelines must be established for ethics committees that correspond to international standards. Committee members must be trained before accepting committee responsibilities. Finally, new committees must be created along with the improvement of the currently existing committees for reinforcing and promoting the importance of ethical integrity in research.

背景与目标： 简介：伦理委员会是确保人类研究伦理完整的必要资源。他们必须在对涉及人类受试者的研究项目进行道德评估时采用国际标准。
目的：对哥伦比亚人类研究伦理委员会进行了描述，并提出了加强伦理委员会的建议。
材料与方法：2003年，从构成Colciencias科学技术网络一部分的研究组列表中选择了280个研究项目涉及人类主题的研究组。 （Colciencias是促进和资助科学技术的哥伦比亚国家机构。）80％的项目（224个）与40个机构相关，这些机构包括大学，医院以及公共或私人研究中心。这些机构中有30个设有至少一个道德委员会来评估人类受试者的使用情况。向每个委员会邮寄了一份调查表，要求提供有关其组成，法规，多学科性，多元化，代表性和独立性的信息。分析使用了世界卫生组织《评估生物医学研究的伦理委员会操作指南》（TDR / PRD / ETHICS / 2000）。在五个城市中，通过与道德委员会成员的直接讨论获得了补充信息。
结果：26个委员会对此问卷进行了答复。结果表明，委员会成员中有47％是医师，但是只有23％的委员会中有社区代表。在60％的委员会中，成员并非独立于其所在的组织。 70％的人已经建立了操作程序。提到缺乏国家法规和研究伦理学方面的教育有限，是提供有效指导的主要弊端。
结论：这些观察得出的结论是，必须为与国际标准相对应的伦理委员会建立国家准则。在接受委员会职责之前，必须对委员会成员进行培训。最后，必须建立新的委员会，并完善现有的委员会，以加强和促进研究中道德操守的重要性。

BACKGROUND & AIMS: :The signaling pathways mediating lysophosphatidic acid (LPA)-stimulated PKD(2) activation and the potential contribution of PKD(2) in regulating LPA-induced interleukin 8 (IL-8) secretion in nontransformed, human colonic epithelial NCM460 cells were examined. Treatment of serum-deprived NCM460 cells with LPA led to a rapid and striking activation of PKD(2), as measured by in vitro kinase assay and phosphorylation at the activation loop (Ser706/710) and autophosphorylation site (Ser876). PKD(2) activation induced by LPA was abrogated by preincubation with selective PKC inhibitors GF-I and Ro-31-8220 in a dose-dependent manner. These inhibitors did not have any direct inhibitory effect on PKD(2) activity. LPA induced a striking increase in IL-8 production and stimulated NF-kappaB activation, as measured by NF-kappaB-DNA binding, NF-kappaB-driven luciferase reporter activity, and IkappaBalpha phosphorylation. PKD(2) gene silencing utilizing small interfering RNAs targeting distinct PKD(2) sequences dramatically reduced LPA-stimulated NF-kappaB promoter activity and IL-8 production. PKD(2) activation is a novel early event in the biological action of LPA and mediates LPA-stimulated IL-8 secretion in NCM460 cells through a NF-kappaB-dependent pathway. Our results demonstrate, for the first time, the involvement of a member of the PKD family in the production of IL-8, a potent proinflammatory chemokine, by epithelial cells.

背景与目标： ：审查了介导溶血磷脂酸（LPA）刺激的PKD（2）激活和PKD（2）在调节LPA诱导的非转化型人结肠上皮NCM460细胞中LPA诱导的白介素8（IL-8）分泌中的潜在作用。用体外LPA处理血清缺乏的NCM460细胞会导致PKD（2）迅速而惊人的活化，这是通过体外激酶测定和活化环（Ser706 / 710）和自磷酸化位点（Ser876）的磷酸化来测量的。通过与选择性PKC抑制剂GF-1和Ro-31-8220呈剂量依赖性方式进行预孵育，可以消除LPA诱导的PKD（2）激活。这些抑制剂对PKD（2）活性没有任何直接的抑制作用。如通过NF-κB-DNA结合，NF-κB驱动的萤光素酶报道分子活性和IkappaBalpha磷酸化所测量，LPA诱导IL-8产量显着增加并刺激NF-κB活化。 PKD（2）基因沉默利用针对不同的PKD（2）序列的小干扰RNA，大大降低了LPA刺激的NF-κB启动子活性和IL-8的产生。 PKD（2）激活是LPA的生物学作用中的一个新的早期事件，并通过NF-κB依赖性途径介导NCM460细胞中LPA刺激的IL-8分泌。我们的结果首次证明，上皮细胞参与了PKD家族成员参与IL-8（一种有效的促炎趋化因子）的生产。

BACKGROUND & AIMS: :This study was designed to evaluate the hypothesis that administration of a replication-deficient, recombinant adenovirus vector to the epithelial surface of the respiratory tract can be used to deliver a recombinant protein to the systemic circulation in sufficient quantities to evoke a systemic response appropriate to the recombinant protein. We administered AdCMV.TPO-an adenovirus vector containing an expression cassette coding for the human thrombopoietin (TPO) cDNA-to the respiratory epithelium of immunocompetent Balb/c mice. Over the following week, serum human TPO levels were elevated, platelet levels increased more than sixfold, and megakaryocytosis was evident in bone marrow. This strategy may be a useful approach to the nonparenteral administration of a variety of therapeutic recombinant proteins, such as those relevant to clotting, endocrine function, and bone-marrow function.

背景与目标： ：这项研究旨在评估以下假设：向呼吸道上皮表面施用复制缺陷型重组腺病毒载体可将重组蛋白以足够的量递送至全身循环，以引起适当的全身反应。重组蛋白。我们将AdCMV.TPO-一种含有编码人血小板生成素（TPO）cDNA的表达盒的腺病毒载体施用于具有免疫功能的Balb / c小鼠的呼吸道上皮。在接下来的一周中，人的血清TPO水平升高，血小板水平升高了六倍以上，并且在骨髓中发现了巨核细胞增多。该策略可能是非胃肠道给药多种治疗性重组蛋白（例如与凝血，内分泌功能和骨髓功能相关的蛋白）的有用途径。

BACKGROUND & AIMS: BACKGROUND:A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue. METHODS:Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies. RESULTS:(1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes. CONCLUSIONS:Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.

背景与目标： 背景：α-1肾上腺素受体亚型（高，低）的新型分类被应用于人类良性前列腺肥大（BPH）组织。
方法：使用3H-吡唑嗪通过放射性配体结合测定法检查人的BPH标本，并将这些数据与术前治疗进行比较。
结果：（1）Scatchard分析显示高亲和力位点（Kd：27.18 /-6.41 pM; Bmax：9.29 /-0.98 fM / mg蛋白;平均值/-SE）为alpha 1H，低亲和力位点（Kd ：prazosin：α1L亚型：4088.0 /-744.34 pM，Bmax：140.81 /-19.98 fM / mg蛋白）。 （2）在未经治疗的组（n = 5），α1受体阻滞剂组（n = 5）和抗雄激素组（n = 5）中，Kd和Bmax的差异无显着性，二者均为α1-高亲和力或α1-低亲和力亚型。 （3）以上两种肾上腺素受体亚型的苯氧基苯甲胺的pKi值不同。斯卡查德分析表明，在存在1 microM苯氧基苯扎明的情况下，α1高亲和力结合位点消失了，在存在1 microM苯氧基苯扎明的情况下，Kd和Bmax值几乎与两种亚型的α1低亲和力位点相同。 。
结论：根据对Prazosin的亲和力，人类BPH组织同时具有alpha 1H-和alpha 1L-肾上腺素受体亚型，只有一定浓度的苯氧基苯扎明才能完全抑制alpha 1H亚型。用α1受体阻滞剂治疗可能不会改变前列腺组织中α1肾上腺素能受体的状况。