弥漫性大B细胞淋巴瘤3q27染色体状态和不同亚型与预后的关系

目的 从蛋白和基因水平研究弥漫性大B细胞淋巴瘤(DLBCL)的3q27染色体状态和不同亚型与预后的关系.方法 应用免疫组织化学EnVision法对有随访资料的73例DLBCL进行CD3、CD10、CD20、bcl-6、MUM-1标记,根据Hans的分类方法分为生发中心B细胞型(GCB型)和非生发中心B细胞型(non-GCB型),其中54例应用荧光原位杂交(FISH)技术检测bcl-6基因所在的3q27染色体的断裂和扩增情况.结果 73例DLBCL患者GCB型16例(21.9%),non-GCB型57例(78.1%).54例DLBCL患者中3q27染色体断裂11例(20.4%),扩增14例(25.9%).5年总体生存率GCB型(78%)高于non-GCB型(40%),差异有统计学意义(P=0.011).bcl-6阳性表达较阴性者预后好(P=0.041);3q27断裂阳性组病例总体生存率低于3q27断裂阴性组.结论 DLBCL的GCB型比non-GCB型预后好.bcl-6蛋白表达有助于DLBCL的预后判断,3q27染色体断裂阳性病例总体生存率低于3q27断裂阴性组.目前仍有必要区分DLBCL的B细胞的起源.     

上海地区弥漫性大B细胞淋巴瘤的生发中心B细胞样型显著偏低

目的 探讨中国上海地区弥漫性大B细胞淋巴瘤(DLBCL)的生发中心B细胞(GCB)样型与非GCB样型的分布以及可能影响因素.方法 应用免疫组织化学EnVision法分析124例来自该院的原发DLBCL中CD10、bcl-6、MUMl、GCET1和FOXP15种蛋白的表达,采用Hans和Choi两种免疫表型分型法进行分型.其中118例应用荧光原位杂交技术检测t(14;18)和bcl-6基因重排情况.结果 使用Hans法对124例DLBCL进行分型,27例(22%)为GCB样型,97例(78%)为非GCB样型.使用Choi法进行分型显示34例(27%)为GCB样型,90例(73%)为非GCB样型(即ABe样型).GCB样型显著低于非GCB样型(P=0.0001).t(14;18)易位仅4例(3%),3例发生于GCB样型中.bcl-6基因重排阳性的病例为46例(39%),高发于GCB样型中.bcl-6基因重排与bcl-6蛋白表达没有明显相关性.结论 中国上海地区DLBCL的GCB样型显著低于非GCB样型,可能与其DLBCL的t(14;18)低水平发生有关.     

弥漫大B细胞淋巴瘤中C-MYC、BCL-2和BCL-6基因异常与临床病理意义

目的 探讨弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中C-MYC、BCL-2、BCL-6基因异常和蛋白表达及其临床意义。方法 收集205例DLBCL标本及临床资料,采用免疫组化EnVision法染色和FISH法检测DLBCL中C-MYC、BCL-2和BCL-6蛋白表达和基因易位情况,分析其与DLBCL临床病理特征的关系。结果 205例DLBCL中男性106例,女性99例,中位年龄60岁,C-MYC/BCL-2双表达44.4%(91/205)。按照Hans分型分类,GCB型占37.1%,non-GCB占62.9%;CMYC、BCL-2和BCL-6基因易位阳性率分别为9.3%、8.8%、30.1%。C-MYC与BCL-2基因异位在双表达组较高,与Hans分型、性别、年龄等无关;BLC-6基因易位在各组间差异均无统计学意义。双重打击淋巴瘤2例,三重打击淋巴瘤3例,占2.44%(5/205)。171例患者获得随访,34例失访,随访时间8～107个月,死亡48例,病死率为28.1%;患者生存时间与Hans分型及年龄有关,而C-MYC与BCL-2双表达组与双重打击及三重打击组总预后比普通组差。结论 C-MYC/BCL-2双表达对基因易位有提示作用,明确诊断可依靠免疫组化和FISH检测;C-MYC、BCL-2及BCL-6基因易位可作为DLBCL患者预后的指标。     

原发胃肠道弥漫性大B细胞淋巴瘤的免疫分型及其与预后的关系

目的 了解原发胃肠道弥漫性大B细胞淋巴瘤的免疫分型,并比较Choi、Tally和Hans 分型及其与预后的关系.方法 复习90例原发胃肠道弥漫性大B细胞淋巴瘤患者的临床及病理资料并进行随访,应用Kaplan-Meier法、Log-rank检验和Cox比例风险回归模型对临床资料、实验室检测结果 进行生存分析及单因素和多因素预后分析.免疫表型检测采用EnVision和EliVision法,选用的抗体有CD20、CD3ε、CDl0、bcl-6、MUM-1、CD5、bcl-2、GCET1、FOXP1、LMO2、BLIMP1和Ki-67等.结果 (1)年龄为27～83岁,中位年龄58岁,男女比为1.31:1;胃肿瘤58例,占64.4%(58/90);肠肿瘤32例,占35.6%(32/90).(2)肿瘤细胞均表达CD20抗原,均不表达CD3ε和CD5;CD10、bcl-6、MUM-1(30%/80%阈值)的表达率分别为17.8%(16/90)、75.6%(68/90)、52.2%(47/90)/43.3%(39/90),GCET1、FOXP1、LMO2的表达率分别为50.0%(45/90)、45.6%(41/90)、23.3%(21/90),bcl-2、BLIMP1的表达率分别为42.2%(38/90)、8.9%(8/90),Ki-67阳性指数20%～95%,中位数为80%.Hans分型:51.1%为生发中心B细胞型(GCB型),48.9%为非GCB型;Choi分型:55.6%为GCB型,44.4%为活化B细胞(ABC)型;Tally分型:34.4%为GCB型,65.6%为非GCB型.(3)67.8%(61/90)的患者接受化疗,68.9%(62/90)的患者接受手术.患者的2、3和5年总体生存率分别为58.5%、52.8%和49.8%,CHOP方案(环磷酰胺+多柔比星+长春新碱+泼尼松)治疗组的2、3和5年总体生存率分别为68.5%、61.2%和52.9%.结论 Hans和Choi分型各亚型比例差别不大,Tally分型中非GCB型较GCB型比例增高.三种分型的各亚型均存在GCB型优于非GCB/ABC型的趋势.Log-rank检验单因素分析提示乳酸脱氢酶(LDH)水平、国际预后指数(IPI)、化疗、手术、B症状、病变数量、临床分期对预后有影响.Cox比例风险回归模型多因素分析提示Hans分型、Choi分型、化疗、手术、LDH和Lugano分期是独立的预后因素.

Abstract：

Objective To study the immunophenotype and prognostic significance of primary gastrointestinal diffuse large B-cell Iymphoma, with reference to Hans, Choi and Tally algorithms. Methods The clinicopathologic features and follow-up data in 90 cases of primary gastrointestinal diffuse large B-cell lymphoma were analyzed by Kaplan-Meier method, Log-rank test and Cox regression model.Immunohistochemistry was carried out using EliVision and EnVision methods for CD20, CD3ε, CD10,bcl-6, MUM-1, CDS, bcl-2, GCET1, FOXP1, LMO2,BLIMP1 and Ki-67. Results The age of patients studied, 64. 4% (58/90) involved the stomach and 35.6% (32/90) involved the intestine. The immunohistochemical findings were as follows: 100% positivity for CD20, 0% for CD3ε and CD5, 17.8% (16/90) for CD10, 75.6% (68/90) for bcl-6, 52. 2% (47/90) for MUM-1 (cut off was 30%), 43.3%(39/90) for MUM-1 (cut off was 80%), 50.0% (45/90) for GCET1, 45.6% (41/90) for FOXP1,23.3%(21/90) for LMO2, 42.2% (38/90) for bcl-2 and 8.9% (8/90) for BLIMP1. The Ki-67 index ranged from 20% to95% (median =80%). According to Hans algorithm, 51.1% of the cases belonged to germinal center B-cell (GCB) subtype and 48.9% belonged to non-GCB subtype. In contrast, Choi algorithm classified 55.6% cases as GCB subtype and 44. 4% as activated B-cell (ABC) subtype.According to Tally algorithm, 34. 4% were of GCB subtype and 65.6% of non-GCB subtype. Most of the patients (67. 8% ,61/90) received chemotherapy and 68.9% (62/90) underwent surgical resection. The overall 2, 3 and 5-year survival rates were 58. 5%, 52. 8% and 49. 8%, respectively. The overall 2, 3 and 5-year survival rates in the CHOP therapy group were 68.5%, 61.2% and 52. 9%, respectively.Conclusions There is no significant difference in ratio between the GCB and non-GCB/ABC subtypes by Hans and Choi algorithms. The non-GCB subtype seems to be more prevalent according to Tally algorithm.Although there is no significant difference in survival between GCB and non-GCB/ABC subtypes by the 3algorithms, GCB subtype tends to show a better survival. In univariate analysis, LDH level, international prognostic index, chemotherapy, surgical resection, B symptoms, number of involved sites and clinical stage are found to have prognostic significance. In multivariate analysis, Choi algorithm, Tally algorithm,chemotherapy, surgical resection, LDH level and clinical stage are independent prognostic factors.     

miR-155、miR-34a和miR-30a在弥漫大B细胞淋巴瘤中的表达及意义

目的 分析miR-155、miR-34a和miR-30a在弥漫大B细胞淋巴瘤(diffuse large B-celllymphoma,DLBCL)中的表达水平,并探讨其与DLBCL临床病理特征的关系以及在DLBCL发生发展中扮演的角色.方法 应用RT-PCR方法检测46例DLBCL中miR-155、miR-34a及miR-30a的表达水平,用间期荧光原位杂交技术分析患者MYC和p53基因的异常情况,用免疫组织化学技术(Envision法)对DLBCL进行CD3、CD10、CD20、BCL-6、MUM-1标记.根据Hans的分类方法分为生发中心B细胞型(GCB型)和非生发中心B细胞型(non-GCB型).结果 与正常对照组相比,miR-155在DLBCL中显著高表达.miR-155在non-GCB型的表达明显高于GCB型.miR-155在MYC基因重排组表达降低.miR-34a在p53基因丢失组的表达较p53基因正常组显著降低.与BCL-6蛋白阴性表达组相比,miR-30a在BCL-6蛋白阳性组明显低表达.结论 miR-155在正常人群与DLBCL以及DLBCL的不同亚型之间表达不同,对DLBCL的诊断分型有一定参考价值.miR-34a对疾病预后判断有一定指导意义.miR-155、miR-34a和miR-30a可能是DLBCL潜在的治疗靶点.     

弥漫大B细胞淋巴瘤中CyclinD2的表达及其临床意义

目的探讨弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中Cyclin D2的表达及其与临床病理分型及预后的关系。方法收集79例确诊为DLBCL,每例分成两组:(1)石蜡标本制成组织芯片,应用光镜观察、免疫组化En Vision两步法检测CD3、CD20、CD10、BCL-6、MUM1、Ki-67、Cyclin D2蛋白,根据Hans分型法分型。(2)新鲜冷冻标本应用实时定量PCR(real-time quantitative PCR,qRT-PCR)法观察Cyclin D2 mRNA在不同亚型DLBCL中的相对表达量。应用Kaplan-Meier法分析Cyclin D2 mRNA相对表达量及各临床病理特征与生存期的关系。结果 79例DLBCL中,生发中心B细胞样(germinal center B-cell-like,GCB)型26例(32.9%),非生发中心B细胞样(non-germinal center B-cell-like,non-GCB)型53例(67.1%)。13例(16.5%)表达Cyclin D2蛋白,其中2例为GCB型(15.4%),11例为non-GCB型(84.6%),差异有统计学意义(P0.05)。Cyclin D2 mRNA的相对表达量在non-GCB型组显著高于GCB型组,差异有统计学意义(P0.05)。生存分析显示高临床分期及Cyclin D2 mRNA高表达组预后差。结论检测Cyclin D2蛋白及基因表达有助于提高DLBCL临床病理分型的准确性,并可能成为提示预后的重要指标。     

BCL-6、MYC和p53基因异常与弥漫性大B细胞淋巴瘤免疫学亚型及预后的关系

目的 探讨弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者BCL-6、MYC和p53基因的异常情况,用并分析它们与免疫学亚型及预后的关系.方法 应用间期荧光原位杂交技术分析46例DLBCL患者BCL-6、MYC和p53基因的异常情况,用免疫组织化学技术(Envision法)对DLBCL进行CD3、CD10、CD20、BCL-6、MUM-1、BCL-2和Ki-67标记,根据Hans的分类方法将其分为生发中心B细胞型(germinal center B cell,GCB型)和非生发中心B细胞型(non-germinal center B cell,non-GCB型).结果 46例患者中,BCL-6基因重排10例,BCL-6重排与BCL-6蛋白的表达两者之间差异无统计学意义(P=0.245).BCL-6基因重排与DLBCL患者的总生存时间(P=0.138)和无进展生存时间(P=0.095)无统计学相关性.MYC重排4例,全部见于GCB型.p53基因缺失14例,p53基因缺失组与p53基因正常组相比,生存时间差异有统计学意义(总生存时间:P=0.046;无进展生存时间::P=0.043).结论 间期荧光原位杂交技术可以快速、准确、灵敏的检测BCL-6、MYC和p53基因的异常.BCL-6基因重排与BCL-6蛋白的表达之间无统计学相关性.MYC重排多见于GCB亚型组,p53基因缺失的患者预后较差.p53基因可以作为判断DLBCL预后的参考指标.     

儿童腹腔非霍奇金B细胞淋巴瘤的临床病理及免疫表型分析

目的 探讨儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理、免疫表型与EBER特征及其病理诊断和鉴别诊断.方法 按WHO(2008年)淋巴瘤分类标准分析74例儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理资料,制备组织芯片,进行免疫组织化学SP法染色,EBER原位杂交和c-myc基因荧光原位杂交,观察CD20、CD79a、CD3、CD10、bcl-6、MUM1、bcl-2、CD43、CD38和Ki-67蛋白的表达和EBER表达特征,并区分伯基特淋巴瘤(BL)、弥漫性大B细胞淋巴瘤(DLBCL)和介于BL和DLBCL之间的不能分类的B细胞淋巴瘤(DLBCL/BL)病理类型,在DLBCL中再区分其生发中心B细胞型(GCB)和非生发中心B细胞型(non-GCB)的分化特征.结果 儿童腹腔非霍奇金B细胞淋巴瘤中BL为65例(87.8%),DLBCL为4例(5.4%),DLBCL/BL为5例(6.8%).临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状.BL免疫组织化学表达CD20(65例)、CD79a(65例)、CD10(63例)、bcl-6(62例)、MUM1(15例)、CD43(46例)和CD38(63例);不表达CD3、bcl-2;27例(41.6%)EBER阳性;54例(93.0%)c-myc基因位点断裂.DLBCL免疫组织化学表达CD20(4例)、CD79a(4例)、CD10(3例)、bcl-6(2例)、MUM1(2例)、bcl-2(3例)、CD43(2例)、CD38(2例);不表达CD3;其中2例GCB,2例non-GCB;EBER阴性;1例c-myc基因位点断裂.DLBCL/BL免疫组织化学表达CD20(5例)、CD79a(5例)、CD10(5例)、bcl-6(4例)、MUM1(3例)、CD43(5例)、CD38(3例),不表达CD3和bcl-2;4例EBER阴性;3例c-myc基因位点断裂.结论 儿童腹腔非霍奇金B细胞淋巴瘤具有侵袭性生长的特点,以BL为主要病理类型.临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状,主要累及回盲部肠组织及周围系膜淋巴结,病理形态、免疫表型、EBER、c-myc基因的检测对BL、DLBC及DLBCL/BL淋巴瘤的诊断和鉴别诊断有重要作用.     

应用细胞芯片荧光原位杂交技术检测弥漫性大B细胞淋巴瘤3q27重排

目的 研究3q27染色体断裂及bcl-6基因扩增与弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma, DLBCL)与其分子分类及治疗效果、临床分期的关系.方法 用细胞芯片荧光原位杂交(fluorescence in situ hybridization,FISH)技术对60例DLBCL的标本进行3q27染色体断裂及bcl-6扩增检测;采用免疫组化S-P法在组织微阵列上同步观测CD20、CD10、bcl-6、MUM1的表达,进行生发中心样(germinat center Bcell-like,GCB)和非生发中心样(non-germinal center B-cell-like, non-GCB)分子分类;通过对临床病例的分析得出与治疗效果及临床分期的信息;统计分析以上各因素之间的关系.结果 在60例DLBCL中,GCB占48.3%(29/60),non-GCB占51.7%(31/60).FISH结果显示,3q27断裂阳性15例,bcl-6基因扩增阳性22例.存在3q27染色体断裂的15例中BCL-6蛋白表达阳性3例(20.0%),阴性12例(80.0%),与无3q27染色体断裂者相比其BCL-6蛋白表达率降低(P=0.017).在60例DLBCL中,bcl-6扩增22例,其中GCB 5例(22.7%),non-GCB 17例(77.3%),与无bcl-6扩增者相比差异有统计学意义(P=0.003).在36例经正规CHOP治疗的DLBCL中,bcl-6扩增15例,其治疗效果显效、部分有效、无效分别为4(26.7%)、4(26.7%)、7(46.7%),与无bcl-6扩增的病例比差异有统计学意义(P=0.016).bel-6扩增与BCL-6蛋白表达及I临床分期的关系差异无统计学.BCL-6蛋白表达阳性组、阴性组与治疗效果及临床分期关系差异无统计学意义.结论 存在bel-6基因断裂的病例,其BCL-6蛋白表达率低.存在bcl-6基因扩增的DLBCL多数为non-GCB,并且治疗效果差,临床分期较晚,可能与DLBCL晚期染色体呈多倍体增加的趋势有关.     

弥漫性大B细胞淋巴瘤中hENT1的表达及意义

目的 探讨hENT1在生发中心B细胞(germinal center B cell-like,GCB)型与非GCB(non-GCB)型弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及意义.方法 采用免疫组化PV 6000两步法检测CD10、BCL-6、MUM1蛋白在DLBCL的表达并对DLBCL进行亚型分类,同时检测hENT1蛋白的表达,探讨免疫组化染色结果和临床病理参数及预后的关系.结果 (1)hENT1蛋白在DLBCL的GCB及non-GCB亚型中表达差异有显著性(P=0.031,P<0.05).(2)hENT1的表达与患者性别、年龄、部位、LDH高低、Ann Arbor分期、有无B症状的差异均无统计学意义.(3)对76例DLBCL患者进行生存分析,中位随访时间21个月.Log-rank检验GCB/non-GCB组累计生存率差异有统计学意义(P=0.010).结论 DLBCL中non-GCB型患者比例较大,预后差.在治疗过程中,检测hENT1的表达为能否使用核苷类药物提供依据.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

Beta-endorphin and drug-induced reward and reinforcement

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. beta-Endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.     

PTEN与信号转导及肿瘤

ＴＥＮ[1] (ｐｈｏｓｐｈａｔａｓｅａｎｄｔｅｎｓｉｎｈｏｍｏｌｏｇｙｄｅｌｅｔｅｄｏｎｃｈｒｏｍｏｓｏｍｅｔｅｎ)又名ＭＭＡＣ1 [2 ] (ｍｕｔａｔｅｄｉｎｍｕｔｉｐｌｙａｄａｎｃｅｄｃａｎｃｅｒ 1 )和ＴＥＰ1 [3 ] (ＴＧＦ -βｒｅｇｕｌａｔｅｄａｎｄｅｐｉｔｈｅｌｉａｌｃｅｌｌ -ｒｉｃｈｅｄｐｈｏｓｐｈａｔａｓｅ 1 ) (以下均称为ＰＴＥＮ) ,是 1 997年由 3个研究小组先后发现的一个具有双特异磷酸酶活性的抑癌基因。ＰＴＥＮ基因异常广泛存在于人类多种恶性肿瘤 ,如恶性神经胶质瘤、前列腺癌、子宫内膜癌、黑色素瘤等…     

Tobacco and alcohol and the risk of head and neck cancer

Summary We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.     

Postinfectious immunodeficiency and autoimmunity: pathogenic and clinical values and implications

Autoimmunity is still a mystery of clinical immunology and medicine as a whole. The etiology and pathogenesis of autoimmune disorders remain unclear and, thus, are assessed as a balance between hereditary predisposition, triggering factors and the appearance of autoantibodies and/or self-reactive T cells. Among the immunological armamentarium, molecular mimicry, based on self-reactive T- and B-cell activation by cross-reactive epitopes of infectious agents, is of special value. Hypotheses regarding the possible involvement of molecular mimicry in the development of postinfectious autoimmunity are currently very intriguing. They provide new approaches for identifying etiological agents that are associated with postinfectious autoimmunity, paired microbial- and tissue-linked epitopes targeted for autoimmune reaction determination, postinfectious autoimmunity pathogenesis recognition and specific prevention, and therapy for autoimmune disorder development.     

类赖氨酰氧化酶2与肿瘤转移和发生

类赖氨酰氧化酶2(lysyl oxidase-like 2,LOXL2)是赖氨酰氧化酶(lysyl oxidase,LOX)基因家族的成员之一,其表达产物能促进胶原沉积.LOXL2的过表达能促进纤维化,并与肿瘤侵袭、转移及不良预后有关.目前大部分学者认为LOXL2是一种转移促进基因,也有实验支持其是一种肿瘤抑制基因.研究发现LOXL2可以通过激活Snail/Ecadherin通路或Src/FAK通路促进转移.LOXL2有望作为肿瘤生物标志物,用于预后判断,成为一个新的治疗靶点.     

Muscle strength and serum testosterone,cortisol and SHBG concentrations in middle-aged and elderly men and women

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age-related declines in the maximal voluntary neuromuscular performance capacity in aging people.