人脑胶质瘤组织中骨形成蛋白-2的表达及其临床病理学意义

目的:探讨骨形成蛋白-2(BMP-2)在人脑胶质瘤中的表达和临床意义.方法:随机选取脑胶质瘤患者88例, 采用SABC免疫组化方法和RT-PCR技术, 检测脑胶质瘤组织和正常脑组织中BMP-2蛋白及其mRNA的表达.并分析其与脑胶质瘤组织临床分级之间的关系.结果:BMP-2蛋白在脑胶质瘤组织中的阳性表达率为78.40% (69/88), 明显高于(P<0.01)其在正常脑组织中的阳性表达率[3% (6/20)].BMP-2蛋白与mRNA 在脑胶质瘤高级别组(Ⅲ～Ⅳ级) 中的表达均明显高于低级别组(Ⅰ～Ⅱ级), 说明随着肿瘤级别的升高BMP-2表达也增强.结论:BMP-2蛋白及其mRNA的异常表达可能与脑胶质瘤的恶性程度有关, 可以作为一个肿瘤标志物在临床中应用.     

脑胶质瘤中膜联蛋白A2的表达及意义

目的:研究膜联蛋白A2在人脑胶质瘤中的表达及其与病理分级的相关性,探讨其成为胶质瘤诊断标志物的可能性。方法:分别使用RT-PCR和免疫组化法检测胶质瘤和瘤周组织中膜联蛋白A2的mRNA及蛋白表达水平。结果:RT-PCR法显示胶质瘤中膜联蛋白A2mRNA的表达率和表达量远远高于瘤旁脑组织(P0.05),免疫组化的结果也显示胶质瘤中膜联蛋白A2的表达高于瘤旁组织(P0.05)。结论:胶质瘤中膜联蛋白A2表达明显高于瘤周脑组织,且和胶质瘤病理分级呈正相关,可作为胶质瘤诊断辅助指标之一。     

胸腺素β4在人脑胶质瘤组织中表达及意义的研究

目的探讨人脑胶质瘤组织中胸腺素β4基因和蛋白的表达及其临床意义。方法收集40例人脑胶质瘤患者手术肿瘤组织切除标本及2例癫痫病人手术后切除脑组织对照标本,采用逆转录聚合酶链反应法和免疫组织法检测所有标本中胸腺素β4基因和蛋白的表达。结果人脑胶质瘤组织中胸腺素β4m RNA和蛋白在各个级别胶质瘤组织中均有表达,而在正常脑组织表达缺失,不同病理级别胶质瘤之间胸腺素β4的m RNA和蛋白表达水平随着胶质瘤病理级别的增加而增加,表达水平均为I级II级III级IV级。结论胸腺素β4基因和蛋白在人脑胶质瘤组织过表达,可能与其发生发展相关,可作为早期诊断的标志物。     

ClC-3在人胶质瘤中的表达及分布

目的：探讨ClC-3在人脑胶质瘤中的表达及其生物学意义。 方法： 应用免疫组织化学染色技术检测24例人胶质瘤以及4例脑转移癌手术标本中ClC-3蛋白的表达；RT-PCR检测ClC-3蛋白表达阳性的手术标本中其mRNA表达。 结果： 4例正常脑组织ClC-3蛋白的表达为阴性；而蛋白表达阳性的19例胶质瘤及4例脑转移癌中，ClC-3主要位于瘤细胞和微血管内皮细胞的胞浆或胞膜上。蛋白表达阳性的手术标本中16例胶质瘤和4例脑转移癌检测到ClC-3 mRNA的表达。少突胶质细胞瘤Ⅲ级中ClC-3的mRNA和蛋白表达明显高于其Ⅱ级。 结论： ClC-3在人胶质瘤及脑转移癌组织中普遍表达，并且可能与少突胶质细胞瘤病理分级相关。     

ClC-3在人胶质瘤中的表达及分布

目的探讨ClC-3在人脑胶质瘤中的表达及其生物学意义。方法应用免疫组织化学染色技术检测24例人胶质瘤以及4例脑转移癌手术标本中ClC-3蛋白的表达;RT-PCR检测ClC-3蛋白表达阳性的手术标本中其mRNA表达。结果4例正常脑组织ClC-3蛋白的表达为阴性;而蛋白表达阳性的19例胶质瘤及4例脑转移癌中,ClC-3主要位于瘤细胞和微血管内皮细胞的胞浆或胞膜上。蛋白表达阳性的手术标本中16例胶质瘤和4例脑转移癌检测到ClC-3mRNA的表达。少突胶质细胞瘤Ⅲ级中ClC-3的mRNA和蛋白表达明显高于其Ⅱ级。结论ClC-3在人胶质瘤及脑转移癌组织中普遍表达,并且可能与少突胶质细胞瘤病理分级相关。     

LIM结构域结合蛋白1在脑胶质瘤患者中的表达研究

目的 观察LIM结构域结合蛋白1(LIM-domain-binding 1,Ldb1)在脑胶质瘤患者中的表达.方法 采用Real-timePCR方法检测46例脑胶质瘤手术患者脑组织、18例正常对照和16例良性脑肿瘤对照脑组织标本中Ldb1 mRNA的表达水平;采用免疫组化EnVision二步法观察Ldb1在高级别胶质瘤中的蛋白表达定位.结果 脑胶质瘤患者脑组织Ldb1的mRNA表达高于正常对照组和良性脑肿瘤对照组.Ldb1在不同分级的胶质瘤中表达并不相同,在Ⅲ、ⅣV级中的相对表达量明显高于Ⅰ、Ⅱ级(P ＜0.001).在高级别胶质瘤中,Ldb1蛋白主要表达在肿瘤细胞核和胞浆内.结论 脑胶质瘤患者肿瘤组织中Ldb1表达增高,可能参与了胶质瘤的发生、发展过程.     

脑胶质瘤患者LMO-1和LMO-4基因表达水平的改变及其意义

目的探讨脑胶质瘤患者脑组织中LMO-1和LMO-4基因表达水平的改变及其意义。方法采用实时荧光定量聚合酶链反应（real-time PCR）检测46例脑胶质瘤手术患者脑组织及19例正常脑组织标本中LMO1和LMO4的表达水平,分析LMO1、LMO4与病理分级之间的关系。结果脑胶质瘤患者脑组织中LMO-1表达高于正常对照组（P〈0.05）;LMO1在不同分级的胶质瘤中表达并不相同,在Ⅲ、Ⅳ级中的相对表达量显著高于Ⅰ、Ⅱ级（P〈0.01）;LMO1表达水平与胶质瘤分级正相关,差异具有显著性意义（P〈0.05）。在多形性胶质母细胞瘤患者脑组织中,LMO-4的表达明显高于其它级别胶质瘤和正常对照组（P〈0.05）。结论脑胶质瘤患者肿瘤组织中LMO-1和LMO-4表达增高,可能参与了胶质瘤的发生、发展过程。     

趋化素样因子超家族成员6 在胶质瘤中的表达及临床意义

目的:探究趋化素样因子超家族成员6(CMTM6)在胶质瘤中的表达及临床意义。方法:采用免疫组化、免疫荧光、Western blot和qRT-PCR检测CMTM6在胶质瘤组织和细胞系中的表达。结果:CMTM6表达于神经胶质细胞的胞质和胞膜;在胶质瘤组织和胶质母细胞瘤细胞系(U87、U251)中CMTM6的表达均高于正常脑组织和人脑正常胶质细胞系(HEB);高级别组阳性表达率高于低级别组;CMTM6高表达患者的总生存期和无病生存期均比低表达患者明显缩短;年龄、病理分级和CMTM6的表达水平均是评判胶质瘤预后的独立危险因素。结论:CMTM6在胶质瘤中高表达,可作为胶质瘤患者预后评判的独立危险因子。     

NDR2 mRNA在肿瘤组织中的差异表达

检测NDR2基因在人类正常组织及相应肿瘤组织中的表达分布，为进一步研究该基因功能提供线索。提取人脑与胶质瘤、肺与肺癌、胃与胃癌、结肠与结肠与结肠癌组织总RNA，RT－PCR方法半定量分析NDR2基因在上述组织中的表达水平。在人脑和胶质瘤组织、肺与肺癌组织、胃与胃癌组织、结肠与结肠癌组织中均有NDR2mRNA表达，其表达水平以脑组织为最同。NDR2mRNA在正常脑和肺组织的表达水平分别显著高于胶质瘤与肺癌组织，而结肠与结肠癌组织，胃与胃癌组织NDR2mRNA表达水平则无显著差别。以上结果表明，NDR2基因可能广泛表达于人体正常组织内，而在胶质瘤与肺癌中的表达较相应正常组织减低，提示该基因可能与神经系统与呼吸系统肿瘤的发生发展有关。     

4-1BBL分子在脑胶质瘤组织中的表达及其临床意义

目的:探讨共刺激分子4-1BBL(CD137L)在胶质瘤组织中的表达及其临床意义。方法:免疫组化方法检测4-1BBL在82例脑胶质瘤组织中的表达,并分析其与病理分级、患者年龄、性别及生存时间的关系。结果:正常3例脑组织标本未见4-1BBL表达。82例胶质瘤标本31例4-1BBL阳性,阳性表达率为37.8%。统计学提示组织标本中4-1BBL表达与病理级别无明显相关性,与年龄有关(P0.05),4-1BBL阳性患者生存期更长(P0.05)。结论:4-1BBL在部分胶质瘤组织中有表达,其表达对判断胶质瘤患者的预后有一定的参考价值。     

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.