BACKGROUND & AIMS: We tested the hypothesis that enhanced intravascular coagulation in pregnancy could produce clinical symptoms similar to those of preeclampsia, such as hypertension, proteinuria, and edema. Having confirmed this, we then examined whether the pathological changes caused by intravascular coagulation could be suppressed by administration of antithrombin III (AT III), an endogenous inhibitor active to thrombin and factor X a. Intravascular coagulation was induced in Wistar rats on day 16-20 of pregnancy by 1-h arterial infusion of tissue thromboplastin (TP) through the left ventricle of the heart. One hour after the end of the infusion period, organ blood flows were measured by the radioactive ((57)Co-labeled) microsphere method, and fibrin deposition in organs was measured by radiolabeling with [(125)I] fibrinogen injected before TP infusion. Infusion of TP produced fibrin deposition in the kidney, lung, and liver, but not in the myometrium and placenta, as well as an 80% decrease in renal blood flow (RBF), with oliguria and proteinuria. TP also caused an increase in blood pressure (BP) accompanied by an increase in plasma renin activity (PRA), both of which were suppressed by bilateral nephrectomy before TP infusion. The prophylactic administration of AT III concentrates (60 or 300 U/kg intravenously (i.v.), followed by infusion of 30 or 150 U/kg/2 h, respectively) prevented all pathological changes in a dose-dependent manner. AT III increased placental blood flow regardless of the state of coagulation. These findings suggest that intravascular coagulation plays a significant part in the pathophysiology of preeclampsia and that AT III concentrates may have therapeutic potential in the treatment of this condition.

背景与目标： 我们检验了以下假设: 妊娠期血管内凝血增强可产生与先兆子痫相似的临床症状，例如高血压，蛋白尿和水肿。证实了这一点，我们随后检查了抗凝血酶III (AT III) 是否可以抑制由血管内凝血引起的病理变化，在怀孕的第16-20天，通过心脏左心室1小时动脉输注组织凝血活酶 (TP)，在Wistar大鼠中诱导了对凝血酶和因子X a有活性的内源性抑制剂。输注期结束后1小时，通过放射性 ((57) 共标记) 微球法测量器官血流量，并通过在TP输注前注射 [(125)I] 纤维蛋白原的放射性标记来测量器官中的纤维蛋白沉积。TP的输注在肾脏，肺和肝脏中产生纤维蛋白沉积，但在子宫肌层和胎盘中不产生纤维蛋白沉积，以及少尿和蛋白尿引起的肾血流量 (RBF) 80% 减少。TP还引起血压 (BP) 升高，并伴有血浆肾素活性 (PRA) 升高，这两者均在TP输注前被双侧肾切除术抑制。预防性施用AT III浓缩物 (静脉内) 60或300 U/kg，随后分别输注30或150 U/kg/2 h) 以剂量依赖性方式防止了所有病理变化。AT III不管凝血状态如何，胎盘血流量都会增加。这些发现表明，血管内凝血在先兆子痫的病理生理中起着重要作用，而AT III浓缩物可能在治疗这种疾病方面具有治疗潜力。

BACKGROUND & AIMS: :Despite their potential to impact diagnosis and treatment of cancer, few protein biomarkers are in clinical use. Biomarker discovery is plagued with difficulties ranging from technological (inability to globally interrogate proteomes) to biological (genetic and environmental differences among patients and their tumors). We urgently need paradigms for biomarker discovery. To minimize biological variation and facilitate testing of proteomic approaches, we employed a mouse model of breast cancer. Specifically, we performed LC-MS/MS of tumor and normal mammary tissue from a conditional HER2/Neu-driven mouse model of breast cancer, identifying 6758 peptides representing >700 proteins. We developed a novel statistical approach (SASPECT) for prioritizing proteins differentially represented in LC-MS/MS datasets and identified proteins over- or under-represented in tumors. Using a combination of antibody-based approaches and multiple reaction monitoring-mass spectrometry (MRM-MS), we confirmed the overproduction of multiple proteins at the tissue level, identified fibulin-2 as a plasma biomarker, and extensively characterized osteopontin as a plasma biomarker capable of early disease detection in the mouse. Our results show that a staged pipeline employing shotgun-based comparative proteomics for biomarker discovery and multiple reaction monitoring for confirmation of biomarker candidates is capable of finding novel tissue and plasma biomarkers in a mouse model of breast cancer. Furthermore, the approach can be extended to find biomarkers relevant to human disease.

背景与目标： : 尽管它们有可能影响癌症的诊断和治疗，但很少有蛋白质生物标志物在临床上使用。生物标志物的发现一直困扰着各种困难，从技术 (无法对蛋白质组进行全球询问) 到生物学 (患者及其肿瘤之间的遗传和环境差异)。我们迫切需要生物标志物发现的范例。为了最大程度地减少生物学变异并促进蛋白质组学方法的测试，我们采用了乳腺癌小鼠模型。具体地，我们从条件HER2/Neu驱动的乳腺癌小鼠模型中进行肿瘤和正常乳腺组织的lc-ms/MS，鉴定出代表> 700蛋白的6758肽。我们开发了一种新颖的统计方法 (SASPECT)，用于对lc-ms/MS数据集中差异表示的蛋白质进行优先级排序，并确定了肿瘤中过多或不足表示的蛋白质。使用基于抗体的方法和多反应监测-质谱 (mrm-ms) 的组合，我们证实了组织水平上多种蛋白质的过量生产，将fibulin-2鉴定为血浆生物标志物，并广泛表征骨桥蛋白作为能够在小鼠中早期疾病检测的血浆生物标志物。我们的结果表明，采用基于shot弹枪的比较蛋白质组学进行生物标志物发现和多反应监测以确认生物标志物候选物的分阶段管道能够在乳腺癌小鼠模型中发现新的组织和血浆生物标志物。此外，该方法可以扩展到寻找与人类疾病相关的生物标志物。

BACKGROUND & AIMS: :Ovarian primary carcinoid tumors of pure histological type can pose a significant diagnostic challenge in its separation from metastatic carcinoids from the gastrointestinal tract. Yet, their clinical management and prognosis are drastically different. At the molecular level, ovarian primary carcinoid tumors are thought to be of germ cell origin, frequently after the first meiotic division. We report a 21.5-cm ovarian insular carcinoid tumor in a 50-year-old woman who had no evidence of extraovarian tumor. The absence of teratomatous components and the presence of lymphovascular invasion prompted additional studies to rule out a metastatic tumor. The nature of this primary ovarian tumor was eventually confirmed by demonstration of its germ cell origin through DNA genotyping.

背景与目标： : 纯组织学类型的卵巢原发性类癌在从胃肠道与转移性类癌的分离中可能构成重大的诊断挑战。然而，他们的临床管理和预后截然不同。在分子水平上，卵巢原发性类癌被认为是生殖细胞起源的，通常是在第一次减数分裂之后。我们报告了一名50岁女性的21.5厘米卵巢岛状类癌，该女性没有卵巢外肿瘤的证据。畸胎瘤成分的缺乏和淋巴血管浸润的存在促使其他研究排除了转移性肿瘤。通过DNA基因分型证明其生殖细胞起源，最终证实了这种原发性卵巢肿瘤的性质。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to evaluate a 3D tumor segmentation method for fluorodeoxyglucose positron emission tomography (FDG-PET) in the context of noninvasive estimation of tumor metabolic length (Lm), as it correlates with surgical pathology and phantom results. METHODS:Thirty-four patients (7 women, 27 men) with esophageal cancer were retrospectively evaluated. All patients underwent FDG-PET-computed tomography (CT) imaging following endoscopic ultrasound (EUS). Seventeen patients had esophagectomy after PET/CT, without prior neoadjuvant therapy. Tumor length was assessed by EUS (Le, n=31) and histopathology (Lp, n=17). Images were evaluated quantitatively with a 3D threshold-based region-growing program (Medical Image Processing Analysis and Visualization). Lm, total metabolic volume (Vm), maximum standardized uptake value (SUVmax), and average SUV (SUVa) over the entire tumor were obtained for several threshold values (mean activity in the liver plus 0-, 1-, 2-, 3-, and 4-SD of the activity in the liver). RESULTS:Lm showed a good correlation with Lp for all thresholds (best correlation for Lm(2-SD), r=0.74, P<0.001). A positive nonsignificant correlation was observed between Lp and Le (r=0.30, P=0.29). Lm(2-SD) correlated well with Le (r=0.71, P<0.001). Good correlations were also observed between Lm(2-SD) and Vm(2-SD) (r=0.89, P<0.001) and SUVa(2-SD) (r=0.38, P<0.05). Vm(2-SD) also had a significant correlation with Lp (r=0.61, P<0.05) and Le (r=0.57, P<0.001). CONCLUSIONS:FDG-PET-derived tumor metabolic length of untreated esophageal carcinomas correlates well with surgical pathology results, and provides preliminary evidence that noninvasive delineation of the superior and inferior extent of viable tumor involvement might be feasible using computer-generated metabolic length measurements.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:In vitro and in vivo resistance of Plasmodium falciparum to atovaquone or atovaquone-proguanil hydrochloride combination has been associated to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and Tyr268Asn). However, little is known about the prevalence of codon-268 mutations in natural populations of P. falciparum without previous exposure to the drug in Africa. METHODS:The prevalence of codon-268 mutations in the cytb gene of African P. falciparum isolates from Nigeria, Malawi and Senegal, where atovaquone-proguanil has not been introduced for treatment of malaria was assessed. Genotyping of the cytb gene in isolates of P. falciparum was performed by PCR-restriction fragment length polymorphism and confirmed by sequencing. RESULTS:295 samples from Nigeria (111), Malawi (91) and Senegal (93) were successfully analyzed for detection of either mutant Tyr268Ser or Tyr268Asn. No case of Ser268 or Asn268 was detected in cytb gene of parasites from Malawi or Senegal. However, Asn268 was detected in five out of 111 (4.5%) unexposed P. falciparum isolates from Nigeria. In addition, one out of these five mutant Asn268 isolates showed an additional cytb mutation leading to a Pro266Thr substitution inside the ubiquinone reduction site. CONCLUSION:No Tyr268Ser mutation is found in cytb of P. falciparum isolates from Nigeria, Malawi or Senegal. This study reports for the first time cytb Tyr268Asn mutation in unexposed P. falciparum isolates from Nigeria. The emergence in Africa of P. falciparum isolates with cytb Tyr268Asn mutation is a matter of serious concern. Continuous monitoring of atovaquone-proguanil resistant P. falciparum in Africa is warranted for the rational use of this new antimalarial drug, especially in non-immune travelers.

背景与目标：

BACKGROUND & AIMS: The technique of drill biopsy of suspicious masses in the breast has been used in 135 patients, with 98.5% accuracy. It has permitted discrimination in the application of expensive scanning studies. Prior confirmation of the diagnosis of carcinoma reduces operating room and anesthesia time, and eliminates the need for two sets of instruments.

背景与目标： 乳腺可疑肿块的钻孔活检技术已用于135患者，准确性98.5%。它允许在昂贵的扫描研究应用中进行歧视。事先确认癌症的诊断可减少手术室和麻醉时间，并且无需使用两套仪器。

BACKGROUND & AIMS: :Partial resection of the urethra is sometimes necessary in the surgical treatment of locally advanced vulvar cancer. In this study, the frequency of urinary incontinence after partial urethral resection was compared with that of patients who were treated without partial resection of the urethra. Eighteen patients with vulvar cancer encroaching or infiltrating the urethra, treated by a radical vulvectomy and partial urethrectomy, were compared with 17 patients treated by vulvectomy without partial removal of the urethra. Data on urinary incontinence pre- and postoperatively from both groups were retrospectively collected from the patient files. A questionnaire on urinary incontinence was sent to a subset of patients from both groups in order to get information on the current micturation pattern. In four out of 18 patients (22%) with a partial urethrectomy, incontinence was reported, versus two out of 17 patients (12%) in the control group (P= 0.860). Eight patients in the study group and 12 in the control group are currently alive, and all responded to the questionnaire. Two (25%) in the study group and three (25%) in the control group reported to have current symptoms of urinary incontinence. This retrospective study shows that partial resection of 1-1.5 cm of the distal urethra in addition to a radical local excision for vulvar cancer does not result in a significant increase in the frequency of urinary incontinence, compared with vulvar cancer patients without partial urethrectomy.

背景与目标： : 在局部晚期外阴癌的手术治疗中，有时需要部分切除尿道。在这项研究中，将部分尿道切除术后的尿失禁频率与未部分尿道切除术的患者进行了比较。将通过根治性外阴切除术和部分尿道切除术治疗的18例外阴癌侵犯或浸润尿道的患者与17例未部分切除尿道的外阴切除术治疗的患者进行了比较。从患者档案中回顾性收集两组术前和术后尿失禁的数据。向两组患者的一部分发送了有关尿失禁的问卷，以获取有关当前排尿方式的信息。在接受部分输尿管切除术的18例患者中，有4例 (22% 例) 报告了尿失禁，而对照组的17例患者中有2例 (12% 例) 报告了尿失禁 (P = 0.860)。研究组的8名患者和对照组的12名患者目前还活着，并且都对问卷进行了答复。研究组中有两个 (25%) 和对照组中有三个 (25%) 报告有尿失禁的当前症状。这项回顾性研究表明，与没有部分尿道切除术的外阴癌患者相比，除了根治性局部切除外阴癌外，部分切除1-1.5厘米远端尿道不会导致尿失禁的频率显着增加。

BACKGROUND & AIMS: :Diffuse-type tenosynovial giant cell tumor can rarely present as an entirely extra-articular mass, which can be misdiagnosed as a sarcoma especially when giant cells are absent, dominated by large dendritic mononuclear cells, and desmin expression is extensive.

背景与目标： : 弥漫性腱膜巨细胞瘤很少以完全关节外肿块的形式存在，尤其是当没有巨细胞，以大的树突状单核细胞为主，并且结蛋白表达广泛时，可被误诊为肉瘤。

BACKGROUND & AIMS: BACKGROUND:Rhipicephalus microplus, an invasive tick species of Asian origin and the main vector of Babesia species, is considered one of the most widespread ectoparasites of livestock. The tick has spread from its native habitats on translocated livestock to large parts of the tropical world, where it has replaced some of the local populations of Rhipicephalus decoloratus ticks. Although the tick was reported in Uganda 70 years ago, it has not been found in any subsequent surveys. This study was carried out to update the national tick species distribution on livestock in Uganda as a basis for tick and tick-borne disease control, with particular reference to R. microplus. METHODS:The study was carried out in Kadungulu, Serere district, south-eastern Uganda, which is dominated by small scale livestock producers. All the ticks collected from 240 cattle from six villages were identified microscopically. Five R. microplus specimens were further processed for phylogenetic analysis and species confirmation. RESULTS:The predominant tick species found on cattle was Rhipicephalus appendiculatus (86.9 %; n = 16,509). Other species found were Amblyomma variegatum (7.2 %; n = 1377), Rhipicephalus evertsi (2.3 %; n = 434) and R. microplus (3.6 %; n = 687). Phylogenetic analysis of the 12S rRNA, 16S rRNA and ITS2 gene sequences of R. microplus confirmed the morphological identification. CONCLUSIONS:It is concluded that R. microplus has replaced R. decoloratus in the sampled villages in Kadungulu sub-county, since the latter was not any longer found in this area. There is currently no livestock movement policy in force in Uganda, which could possibly limit the further spread of R. microplus ticks. Future surveys, but also retrospective surveys of museum specimens, will reveal the extent of distribution of R. microplus in Uganda and also for how long this tick has been present on livestock without being noticed.

背景与目标：

BACKGROUND & AIMS: PURPOSE:To determine whether a modified non-contrast very low-dose computed tomography (VLD-CT) protocol is applicable for confirmation of known urolithiasis. METHODS AND MATERIALS:Consecutive adult patients with a CT scan showing urinary tract stone(s) between 6/2017-12/2018 were included. They were referred to a modified VLD-CT protocol if stone presence was equivocal or if stone location needed reassessment before an endourological interventional procedure. The scanned area was limited to the level of initial stone location caudally. Data on patients' demographics andbody mass index, were collected. The scanned length and radiation dose were calculated. Images were reviewed by two radiologists who assessed stone size and location. Follow-up reference standard included stone passage, surgical removal, and other imaging and clinical information. RESULTS:Sixty-three patients [63 stones, mean BMI 28.7 (range 19-41.9)] were included. VLD-CTs revealed 31 stones in 31 patients, with a mean stone length of 5.5 mm. Fifteen stones remained at the same location, and 16 had migrated, of which two appeared in the bladder. Thirty-two stones were not observed on VLD-CT. The mean span scanned on the VLD-CT was 274 mm (± 80). The average radiation exposure was 1.47 mGy (range 1.09-3.3), and the absorbed dose was 0.77 mSv (range 0.39-1.43), compared to 10.24 mGy (range 1.75-28.9) and 7.87 mSv (range 1.44-18.5) in the previous scan. The mean radiation dose reduction between scans was 89%. On follow-up, all VLD-CT findings were confirmed. CONCLUSION:A modified imaging protocol is applicable for confirmation of stone presence and location by utilizing very low-dose radiation exposure.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:DNA melting curve analysis using double-stranded DNA-specific dyes such as SYTO9 produce complex and reproducible melting profiles, resulting in the detection of multiple melting peaks from a single amplicon and allowing the discrimination of different species. We compare the melting curves of several Naegleria and Cryptosporidium amplicons generated in vitro with in silico DNA melting simulations using the programs POLAND and MELTSIM., then test the utility of these programs for assay design using a genetic marker for toxin production in cyanobacteria. RESULTS:The SYTO9 melting curve profiles of three species of Naegleria and two species of Cryptosporidium were similar to POLAND and MELTSIM melting simulations, excepting some differences in the relative peak heights and the absolute melting temperatures of these peaks. MELTSIM and POLAND were used to screen sequences from a putative toxin gene in two different species of cyanobacteria and identify regions exhibiting diagnostic melting profiles. For one of these diagnostic regions the POLAND and MELTSIM melting simulations were observed to be different, with POLAND more accurately predicting the melting curve generated in vitro. Upon further investigation of this region with MELTSIM, inconsistencies between the melting simulation for forward and reverse complement sequences were observed. The assay was used to accurately type twenty seven cyanobacterial DNA extracts in vitro. CONCLUSION:Whilst neither POLAND nor MELTSIM simulation programs were capable of exactly predicting DNA dissociation in the presence of an intercalating dye, the programs were successfully used as tools to identify regions where melting curve differences could be exploited for diagnostic melting curve assay design. Refinements in the simulation parameters would be required to account for the effect of the intercalating dye and salt concentrations used in real-time PCR. The agreement between the melting curve simulations for different species of Naegleria and Cryptosporidium and the complex melting profiles generated in vitro using SYTO9 verified that the complex melting profile of PCR amplicons was solely the result of DNA dissociation. Other data outputs from these simulations were also used to identify the melting domains that contributed to the observed melting peaks for each of the different PCR amplicons.

背景与目标：

BACKGROUND & AIMS: :A simple, first stereoselective total synthesis of botryolide-E has been described. The synthesis started from propylene oxide employing Jacobsen's hydrolytic kinetic resolution (HKR), selective epoxide opening, sharpless asymmetric dihydroxylation, one pot acetonide deprotection and lactonization as key steps. Further, the synthesis confirms the absolute configuration of the natural product botryolide-E and we evaluated the biological behavior of natural product botryolide-E against a panel of bacteria and fungi. Botryolide-E exhibits significant potent activity against Staphylococcus aureus (MTCC 96) (6.25 μg/ml), good against Escherichia coli (MTCC 443) (12.5 μg/ml), Bacillus subtilis (MTCC 441) (25 μg/ml) and compound 1 exhibited good to moderate antifungal activity.

背景与目标： : 已经描述了一种简单的，首次立体选择性的botryoolide-E全合成。该合成从环氧丙烷开始，采用Jacobsen水解动力学拆分 (HKR)，选择性环氧开放，sharpless不对称二羟基化，一锅丙酮脱保护和内酯化作为关键步骤。此外，该合成证实了天然产物botryoolide-E的绝对构型，并且我们评估了天然产物botryoolide-E对一组细菌和真菌的生物学行为。葡萄糖醇内酯-E对金黄色葡萄球菌 (mtcc96) (6.25 μ g/ml) 表现出显著的有效活性，对大肠杆菌 (MTCC 443) (12.5 μ g/ml)，枯草芽孢杆菌 (MTCC 441) (25 μ g/ml) 表现出良好的抗真菌活性，化合物1表现出良好至中等的抗真菌活性。

BACKGROUND & AIMS: :Leptospirosis is considered an endemic disease in Buenos Aires province, Argentina, with human cases reported annually from rural and urban areas. The aim of the study was to describe the variables that influence the delay in the serological confirmation of leptospirosis in human cases (period 2006-2014) from Buenos Aires province. Sixty-four percent (64%) of cases could be confirmed by microscopic agglutination test (MAT) with the first sample. The time of confirmation of the human leptospirosis cases was on average 21 days from the onset of the first clinical signs, and varied depending on the distance of the different sanitary regions. The geographical distribution of the confirmed leptospirosis human cases, in addition to the high number of suspected cases and probable cases (which could not be confirmed by MAT), demonstrate that leptospirosis is endemic and underreported in Buenos Aires province, and that distance and lack of resources could be determinant factors of this situation.

背景与目标： : 钩端螺旋体病被认为是阿根廷布宜诺斯艾利斯省的一种地方病，每年从农村和城市地区报告人类病例。该研究的目的是描述影响布宜诺斯艾利斯省人类病例 (2006-2014年) 中钩端螺旋体病血清学确认延迟的变量。通过第一个样品的显微凝集试验 (MAT) 可以确认60 4% (64%) 的病例。人类钩端螺旋体病病例的确认时间平均为从首次临床体征开始的21天，并且根据不同卫生区域的距离而变化。确诊的钩端螺旋体病人类病例的地理分布，以及大量疑似病例和可能的病例 (MAT无法证实)，表明钩端螺旋体病在布宜诺斯艾利斯省是地方性的，报道不足，距离和缺乏资源可能是这种情况的决定因素。

BACKGROUND & AIMS: PURPOSE:For nonoperable stage I non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has emerged as a standard treatment option. We aimed to compare the clinical outcomes of lung SBRT between patients with versus without pathologic cancer diagnosis. METHODS AND MATERIALS:We included patients treated by SBRT for a single pulmonary lesion between July 2009 and July 2017. Patients in the clinical diagnosis group had a positron emission tomography/computed tomography scan showing hypermetabolism, growth of the mass on sequential computed tomography, and were not eligible for biopsy, refused biopsy, or had an inconclusive biopsy. For each of those patients, a matched pair in the pathologic diagnosis group was identified by matching for patient, treatment, and tumoral characteristics. We performed a power calculation to estimate the sample size required to detect a difference arising from a 5% or 15% rate of benign processes in the group without pathology. RESULTS:A total of 924 lung SBRT treatments were performed among 878 patients from 2009 to 2017. Within this population, 131 patients were treated based on clinical findings. They were matched with 131 patients with a pathologic diagnosis who received treatment. At 3 years, no significant differences were observed in overall survival (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.7-2.1), local control (HR, 0.9; 95% CI, 0.4-2), or regional (HR, 0.5; 95% CI, 0.2-1.4) or distant recurrence (HR, 0.6; 95% CI, 0.3-1.1). CONCLUSIONS:In our population, we found no clinically significant difference in patterns of recurrence or survival after lung SBRT for patients who had received clinical versus pathological diagnoses. There was, however, a trend toward more distant recurrences in the pathologic diagnosis group. Our power calculation suggests that data from multiple institutions would be required to rule out a difference in outcomes due to 5% to 15% of clinically diagnosed cases being treated for benign processes.

背景与目标：

BACKGROUND & AIMS: :The human androgen receptor (hAR) is an important regulatory protein particularly in male sexual differentiation. The investigation of hAR functionality has been hampered by the lack of AR specific monoclonal antibodies recognizing the functional domains of the receptor. Therefore production of high affinity mono-specific polyclonal (PAbs) and monoclonal antibodies (MAbs) directed to the hAR was initiated following the synthetic peptide (SP) strategy. Five hAR specific peptides were selected on the basis of their predicted antigenic properties avoiding homology with other steroid hormone receptors. Peptide specific polyclonal antisera were obtained following selected immunization protocols. Mono-specific polyclonal antibody responses were elicited to all peptides in mice and rabbits. Crossreactivity of the peptide specific antisera with the native hAR in various biochemical assays was observed with two out of five peptides. Peptide SP61 (hAR residues 301-320) was used for the generation site-directed MAbs specific for the hAR. Specificity for the hAR was established by immunoprecipitation, immune-complex density gradient centrifugation and immunohistochemistry on human prostate tissue sections. The multi-assay performance of the selected high affinity antibodies proved the usefulness of the straight forward peptide approach and opens a wide field of possible biochemical and physiological investigations into questions related to androgen action.

背景与目标： : 人类雄激素受体 (hAR) 是一种重要的调节蛋白，尤其是在男性性别分化中。缺乏识别受体功能域的AR特异性单克隆抗体，阻碍了对hAR功能的研究。因此，按照合成肽 (SP) 策略开始生产针对hAR的高亲和力单特异性多克隆 (PAbs) 和单克隆抗体 (mab)。根据其预测的抗原特性选择了五种hAR特异性肽，以避免与其他类固醇激素受体的同源性。按照选定预防接种方案获得了肽特异性多克隆抗血清。对小鼠和兔子的所有肽均产生单特异性多克隆抗体反应。在各种生化测定中，用五分之二的肽观察到肽特异性抗血清与天然hAR的交叉反应性。肽SP61 (hAR残基301-320) 用于hAR特异性的生成定点mab。通过免疫沉淀，免疫复合物密度梯度离心和免疫组织化学对人前列腺组织切片确定hAR的特异性。所选的高亲和力抗体的多测定性能证明了直接肽方法的有用性，并为与雄激素作用有关的问题开辟了可能的生化和生理研究的广阔领域。