IL-6R distribution in normal human and cynomolgus monkey tissues

Interleukin-6 (IL-6) is a pleiotropic cytokine and a contributing factor in many diseases such as rheumatoid arthritis, Castleman’s disease, Crohn’s disease, and multiple myeloma. Since the blockade of the signaling pathway of the IL-6/interleukin-6 receptor (IL-6R)/gp130 complex is considered to have therapeutic value in such diseases, we developed an IL-6R humanized antibody (tocilizumab). In the current report, distribution of IL-6R in both normal human and cynomolgus monkey tissues was assessed as fundamental data to support preclinical and clinical studies of tocilizumab. Human and cynomolgus monkey tissue panels were stained with commercially available anti-human IL-6R and a species- and isotype-matched negative antibody, as well as assay control slides. The detection system applied used an Envision^® immunoperoxidase staining procedure with DAB reaction. Positive reactions were observed in the tissue elements of lymphatic, hematopoietic, digestive, reproductive, exocrine, endocrine, neural, muscular, epidermal, respiratory, and urinary systems of the human and cynomolgus monkey tissue panels. The current report is inclusive of a wide variety of tissues and shows the distribution of IL-6R to be similar for both human and monkey tissues. We consider this information fundamental for the support and interpretation of preclinical and clinical studies of anti-IL-6R antibody therapy.     

乳腺癌耐药蛋白在人体正常和肿瘤组织中的表达

目的研究乳腺癌耐药蛋白BCRP在人体正常和肿瘤组织中的表达及其意义. 方法采用半定量RT-PCR检测BCRP在人体正常组织和乳腺癌、胃癌组织中的表达水平. 结果研究发现BCRP mRNA在胎盘和肝脏组织中表达较高,在结肠、小肠、胃、乳腺和肾脏组织中表达较低,在胰腺、脾脏、外周血白细胞和卵巢组织中检测不到.20例乳腺癌中有5例(25%)BCRP阳性表达,而20例胃癌中BCRP均未表达.结论乳腺癌耐药蛋白BCRP在人体的一些正常组织和乳腺癌中具有表达,其作用可能与该组织的外排功能有关.     

bcl-2在大肠癌、大肠腺瘤及正常大肠黏膜中的表达及临床意义

目的:探讨抗凋亡基因bcl-2在正常大肠黏膜、大肠腺瘤和大肠癌中的表达变化及与大肠癌发生、发展和转移的关系.方法:采用免疫组化方法,分别检测20例正常大肠黏膜、22例大肠腺瘤和69例大肠癌中bcl-2蛋白表达情况.结果:bcl-2蛋白在正常大肠黏膜、大肠腺瘤和大肠癌中阳性表达率分别为20.00%、50.00%、52.17%.大肠腺瘤和大肠癌中bcl-2蛋白表达阳性率均显著高于正常大肠黏膜(P<0.05).在伴有淋巴结转移癌组织中bcl-2表达率为33.33%,无淋巴结转移者为62.22%,统计学分析差异有统计学意义(P=0.022 1<0.05);在高、中和低分化腺癌中Bcl-2表达率分别是100.00%(5/5)、82.35%(14/17)、36.17%(17/47),高分化、中分化与低分化腺癌相比,差异均有统计学意义(P值分别为0.023 2、0.0011);TNM IV期bcl-2表达率显著低于Ⅰ、Ⅱ、Ⅲ期,(P<0.05).大肠癌组织bcl-2表达与年龄、性别和肿瘤大体分型等临床病理参数无关(P>0.05).结论:bcl-2蛋白高表达对大肠癌的发生起重要作用.bcl-2蛋白参与了大肠癌的发生,其表达高低与肿瘤细胞的病理分级、TNM临床分期和淋巴结转移密切相关.     

过氧化物酶体增生物激活受体在人体不同癌组织中的定量表达

目的通过检测过氧化物酶体增生物激活受体在人体不同器官癌组织中的表达,探讨PPARγ在癌组织中的意义。方法采用免疫组化法检测11例膀胱癌,8例胃癌,11例宫颈癌,12例甲状腺癌和9例肝癌组织中的PPARγ表达,并通过彩色医学图文分析系统检测PPARγ平均吸光度值。结果PPARγ在膀胱癌、胃癌、宫颈癌、甲状腺癌及肝癌中组织细胞的细胞核及细胞浆均有表达,细胞核的表达高于细胞浆的表达,但均无统计学差异。结论PPARγ表达与癌组织有关,PPARγ在癌症中的作用有待于进一步研究。     

高脂饮食诱导的胰岛素抵抗大鼠血清Apelin水平及其脂肪组织Apelin mRNA的表达

目的研究高脂饮食诱导的胰岛素抵抗大鼠血清Apelin水平及其脂肪组织Apelin mRNA表达,探讨Apelin与高胰岛素血症、体脂、糖脂代谢等的相关性。方法 Wistar雄性大鼠30只,随机分为正常对照组（NC组）和高脂饮食组（HF组）,每组15只。行高胰岛素-正葡萄糖钳夹实验确认胰岛素抵抗大鼠造模成功后,测定血清Apelin-36、空腹胰岛素（Fins）、空腹血糖（FBG）、三酰甘油（TG）、总胆固醇（TC）等指标。采用半定量RT-PCR技术测定脂肪组织Apelin mRNA表达。结果 HF组血清中Apelin-36、脂肪组织Apelin mRNA表达相对含量均高于NC组（P〈0.05或〈0.01）。血清Apelin与Fins、腹内脂、FBG（r=0.612,r=0.564,r=0.487,P均〈0.01）呈正相关,与TG、TC、体重正相关（r=0.444,r=0.375,r=0.367,P〈0.05）;多元逐步回归分析,表明血清胰岛素水平是Apelin的独立相关因素。结论血清Apelin水平及脂肪组织Apelin mRNA表达在胰岛素抵抗大鼠中增高,血清Apelin与高胰岛素血症、体脂、糖、脂代谢相关,血清胰岛素水平是其独立相关因素,推测Apelin可能参与了胰岛素抵抗的发生。     

CD43在人肺结核组织中的表达

目的 探讨CD43在人体组织内的表达情况,分析其所标记巨噬细胞在肺结核组与对照组中的数量变化及分布规律,并说明其意义.方法 应用免疫组织化学两步法检测64例肺结核患者组及35例非结核对照组肺组织中的巨噬细胞标志物CD43及CD68的表达,对阳性细胞数进行形态定量比较及相关分析.结果 肺结核患者组织中CD43标记的巨噬细胞全部阳性表达,计数结果为(39±34)个/HP.对照组中巨噬细胞计数为(20±10)个/HP ,两组比较差异有显著性.结论 CD43可表达于人体结核病变组织中,CD43的研究可作为反映机体免疫状态的指标之一,并可为结核病的诊断、治疗及预后研究提供更详细的参数.     

肝癌及癌周组织核转录因子-kB表达的免疫组织化学分析

目的:研究核转录因子(NF)-κB在肝癌和癌周组织中的表达及其临床病理学关系。方法:以自身配对法分别收集经手术切除患者的肝癌及其癌周组织各35份,以免疫组化染色法检测肝癌及其癌周组织NF-κB表达、胞内分布,以及病理学特征。结果:NF-κB阳性表达物呈棕黄色颗粒状染色,癌组织中NF-κB点灶状表达,定位于胞浆和细胞核;而癌周组织NF-κB阳性表达主要定位于胞浆,未见细胞核阳性。定性观察肝癌组织中NF-κB表达强度明显高于癌周组织,癌组织NF-κB表达阳性率为100%,癌周组织为68.6%,二者比较差异有非常显著性(χ2=13.1,P<0.01)。肝癌组织中NF-κB的表达强度与分化程度、肿瘤数目、HBsAg和肿瘤直径无关。结论:肝癌组织中NF-κB过表达,与肝癌的发生、发展密切相关。     

结缔组织生长因子在病理性瘢痕成纤维细胞中的表达

要目的探讨结缔组织生长因子(CTGF)人类增生性瘢痕成纤维细胞中的表达与瘢痕纤维化之摘在间的关系。方法应用半定量逆转录聚合酶链反应(RT-PCR)术,测了瘢痕组织原代培养的成纤维细技检胞中CTGFmRNA表达。结果CTGFmRNA在人类增生性瘢痕成纤维细胞中高度表达,与正常皮肤组织的成纤维细胞比较,有显著性差异(P<0.01)。结论CTGF在人类增生性瘢痕成纤维细胞中高度表达,提示其在增生性瘢痕的纤维化进程中起着重要的作用,这为临床上寻找安全、有效的治疗增生性瘢痕提供了新的思路。     

乳腺癌耐药蛋白BCRP在人体正常和肿瘤组织中的表达及其意义

目的 研究乳腺癌耐药蛋白BCRP在人体正常和肿瘤组织中的表达及其意义．方法 采用半定量RT-PCR检测BCRP在人体正常组织和乳腺癌、胃癌组织中的表达水平。结果 研究发现BCRP mRNA在胎盘和肝脏组织中表达较高．在结肠、小肠、胃、乳腺和肾脏组织中表达较低．在胰腺、脾脏、外周血白细胞和卵巢组织中检测不到。20例乳腺癌中有5例(25％)BCRP阳性表达，而20例胃癌中BCRP均未表达。结论 乳腺癌耐药蛋白BCRP在人体的一些正常组织和乳腺癌中具有表达，其作用可能与该组织的外排功能有关。     

RAGE在结肠癌和正常结肠组织的表达差异

目的研究晚期糖基化终末产物受体蛋白(RAGE)在结肠癌和正常结肠组织中的表达差异。方法采用实时荧光定量PCR法、Western blot法分别从mRNA水平、蛋白水平检测12例结肠癌患者新鲜手术切除标本中RAGE表达。另取60例结肠癌组织标本和10例正常结肠组织标本,采用免疫组织化学链霉素抗生物素蛋白-过氧化物酶(SP)法检测RAGE表达。分析表达差异及其与临床病理因素的关系。结果 RAGE定位于正常组织及癌组织的细胞质,在癌组织中的表达明显增多(P<0.05)。RAGE的表达与结肠癌的组织分化程度呈负相关,与TNM分期呈正相关。RAGE在低分化、Ⅲ和Ⅳ期结肠癌组织中阳性表达率增高。结论 RAGE在结肠癌中的表达与其侵袭能力存在相关性。     

病理性瘢痕组织中TGF-β1及MMP-1的表达

目的 研究人体病理性瘢痕组织（增殖性瘢痕及瘢痕疙瘩）中转化生长因子β1（TGF-β1）及基质金属蛋白酶1（MMP-1）的表达。方法取10例病理性瘢痕切片，SP法检测TGF-β1及MMP-1，并与正常皮肤组织对照。结果免疫组化法沉淀病理性瘢痕中TGF-β1、MMP-1表达较正常皮肤组显著增高（P〈0．05）。结论病理性瘢痕组织中TGF-β1及MMP-1均呈高表达，导致胶原沉积，瘢痕形成。     

Peroxisome proliferator-activated receptor isoform expression changes in human gestational tissues with labor at term

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation. Three subtypes have been identified: PPAR-alpha, -delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the amnion, choriodecidua, and placenta, and its level of expression was unchanged with labor. To evaluate whether PPAR-alpha and -delta subtypes are present in intrauterine tissues, placentae were obtained from women at term after spontaneous vaginal delivery (TSL; n = 15) and elective caesarean section before labor (TNL; n = 15). Northern blot analyses were used to evaluate the mRNA for PPARs. Activities of PPARs were assessed using JEG3 choriocarcinoma cells transfected with a PPAR-response element reporter construct (pTK-PPREx3-luc) and treated with PPAR ligands. The PPAR-gamma-specific ligand rosiglitazone induced PPAR response element (PPRE)-mediated activity in a concentration-dependent manner, whereas the PPAR-gamma-specific irreversible inhibitor GW9662 fully inhibited this induction. However, GW9662 only partially inhibited 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2)-induced luciferase activity, suggesting that 15d-PGJ2 may also activate either of the other isoforms. PPAR-alpha and -delta are expressed in the amnion, choriodecidua, and placental villous tissues. In the amnion, although for PPAR-alpha no significant difference in expression was observed with labor, PPAR-delta expression increased significantly (p < 0.001). In the choriodecidua, expression of PPAR-alpha declined with labor (p < 0.01), whereas, as in the amnion, PPAR-delta expression increased (p < 0.05). In the placenta, both PPAR-alpha and -delta expression increased with labor (p < 0.005). The changes observed with labor suggest that regulation of PPAR expression and function may have roles to the mechanisms that maintain pregnancy or initiate labor.     

原癌基因Fra－1在人乳腺肿瘤组织中表达的初步研究

目的：探讨转录因子Fra－1在人乳腺良、恶性肿瘤组织中的表达及细胞内的定位。方法：采用免疫组织化学方法检测良、恶性乳腺肿瘤组织Fra－1表达及细胞定位;并分析恶性乳腺肿瘤组织Fra-1表达与乳腺癌预后指标ER、PR和HER－2表达的相关性。结果：61例良、恶性肿瘤组织都存在Fra－1的细胞核表达。在20例良性肿瘤组织中,17例（85．0％）Era－1主要定位于上皮细胞核内,3例（15．0％）可见Fra－1细胞核及细胞质共表达。而37例（90．2％）恶性肿瘤组织存在Fra－1细胞核和细胞质共表达,Fra－1在恶性肿瘤细胞质中的表达明显高于良性肿瘤（P=0．000）。恶性肿瘤Fra－1细胞质表达与ER、PR和HER－2的表达无明显相关性。结论：Fra－1蛋白的表达强度和方式与乳腺癌上皮细胞的癌变有关;它在乳腺癌细胞细胞席的滞留与乳腺癌的发生、发展具有一定的相关性。     

Study of the beta1 adrenergic receptor expression in human tissues: immunological approach

Questions exist regarding tissue distribution of the beta1 adrenergic receptor (beta1-AR). The aim of this study was to investigate relative distribution patterns of the beta1-AR at the protein level in a variety of human tissues by Western blot analysis. The specificity of anti-peptide antibodies was confirmed both by Western blot with recombinant beta1-AR expressed as a membrane protein in E. coli and by immunoprecipitation of membranes from Sf9 cells infected with baculovirus to express the human recombinant beta1-AR. beta1-AR was found in all tissues examined. The relative amount of protein varied significantly between the tissues, from highest in lung and testis to very low in liver. beta1-ARs were rather abundant in heart, kidney, placenta, spleen and thyroid. These results reveal unique distribution of beta1-AR protein that suggests its tissue specific role. Moreover, our data demonstrate a high sensitivity of immunological detection that allows direct comparison of beta1-AR subtype expression and could be used for receptor study in biopsies available in limited amounts, such as human heart biopsy.     

Lead in human tissues.

Tissues from 46 white males from the Cincinnati area have been analyzed for lead content. Tissue sections and procedures were standardized and detailed information was obtained in order to account for variables such as age, postmortem changes, type of death and pathological conditions. This report focuses on the lead concentrations found in 29 tissues from each person deceased, including their changes with age, and compares the results with those found in the literature. Although lead concentrations in calcified tissues increased with age, in several tissues the lead concentrations decreased. Some of these decreases were associated with aging and pathological changes. Dense bone lead content increased steadily with age, while spongy bone lead leveled off or decreased in later years. The apparent body burden of lead of this population sample was less than that reported by others. Many of these individuals (70% or more) seemed to be in lead balance with their environment.