乳腺浸润性导管癌中ER、PR、Her-2、Ki-67表达与病理特征及预后的相关性

目的 探究Ki-67、ER、PR、Her-2等基因在乳腺浸润性导管癌（IDC）组织中的表达,分析其与患者临床病理特征及预后的相关性。方法 收集2013年1月~2014年12月广东医科大学附属医院病理科乳腺包埋石蜡块IDC组织74例。采用免疫组织化学法检测ER、PR、Her-2、Ki-67在IDC组织中的表达,分析其与患者年龄、组织学分级、TNM分期、淋巴结转移及预后的相关性。结果 ①不同年龄、组织学分级、淋巴结转移及TNM分期的IDC患者ER、PR表达情况比较,差异均无统计学意义（P＞0.05）;未发生淋巴结转移的IDC患者Her-2表达低于转移患者,差异有统计学意义（P＜0.05）;不同年龄、组织学分级、TNM分期的IDC患者Her-2表达比较,差异无统计学意义（P＞0.05）;不同TNM分期的IDC患者Ki-67表达情况比较,差异有统计学意义（P＜0.05）,不同年龄、组织学分级、淋巴结转移的IDC患者Ki-67表达比较,差异均无统计学意义（P＞0.05）。 ②Spearman相关性分析显示,ER与PR正相关,ER与Her-2、PR与Her-2负相关,ER、Ki-67和PR、Ki-67负相关,Her-2与Ki-67正相关。③Ki-67阳性表达的IDC患者病死率高于Ki-67阴性表达的患者,差异有统计学意义（P＜0.05）;不同ER、PR、Her-2表达情况的IDC患者病死率比较,差异无统计学意义（P＞0.05）;Ki-67阴性表达患者的总生存时间（OS）高于阳性表达患者,COX多因素分析显示,Ki-67阳性表达是影响IDC患者OS的独立因素（95%CI:0.212~0.865,P=0.018）。结论 Ki-67可作为乳腺浸润性导管癌危险评估的分子标志物,其阳性表达可影响乳腺癌患者的预后。ER、PR、Her-2的表达对乳腺浸润性导管癌患者的预后没有明显影响。     

乳腺浸润性导管癌神经侵犯的临床病理分析

目的探讨乳腺浸润性导管癌神经侵犯的相关临床病理影响因素。方法收集544例未经新辅助化疗的乳腺浸润性导管癌患者的临床病理资料,分析神经侵犯与乳腺癌临床病理特征的关系。结果544例乳腺浸润性导管癌中,神经侵犯阳性125例、阴性419例。单因素分析结果显示,乳腺浸润性导管癌神经侵犯与淋巴结转移数目、Ki-67增殖指数、ER及HER-2表达有关;与患者年龄、肿瘤直径、腋下淋巴结是否转移、TNM分期、脉管侵犯、分子分型、组织学分级和PR水平均无关。乳腺浸润性导管癌神经侵犯个数与患者年龄、腋下淋巴结是否转移、淋巴结转移个数及ER水平有关;与肿瘤直径、TNM分期、脉管侵犯、分子分型、组织学分级、Ki-67、PR及HER-2表达无关。多因素Logistic回归分析表明,淋巴结转移数目、ER、HER-2和Ki-67为乳腺浸润性导管癌神经侵犯的危险因素。结论乳腺浸润性导管癌患者神经侵犯与淋巴结转移数目、Ki-67增殖指数、ER及HER-2表达有关,且神经侵犯个数与患者年龄、腋下淋巴结是否转移、淋巴结转移个数及ER水平有关。     

PAK5与乳腺癌分子分型及临床病理特征的相关性分析

目的探讨PAK5表达与乳腺癌分子分型及临床病理特征的相关性。方法采用免疫组化法检测乳腺癌组织中PAK5、ER、PR、HER2、Ki-67表达并评分,应用荧光原位杂交(fluorescence in situ hybridization, FISH)进一步检测免疫组化HER2 2+的乳腺癌组织中HER2基因扩增情况,分析PAK5表达与乳腺癌分子分型、TNM分期、肿块大小、淋巴结转移等的关系。结果根据HER2基因有无扩增分别纳入HER2阳性组和阴性组。与癌旁组织相比,PAK5在乳腺癌组织中的表达增加;PAK5高表达与患者肿块较大、淋巴结转移、TNM高分期等呈正相关(P0.05);PAK5高表达与患者生存率低相关(P0.05);PAK5表达与ER、PR表达呈负相关,与Ki-67表达呈正相关(P0.05);与非三阴型乳腺癌相比,PAK5在三阴型乳腺癌中的表达增加,差异有统计学意义(P0.05)。结论 PAK5在乳腺癌组织中的表达增加,且与乳腺癌分子分型、TNM分期及不良预后密切相关,PAK5有望成为临床治疗乳腺癌的新靶点。     

乳腺癌复发转移灶与原发灶中ER、PR、HER-2、p53、Ki-67的表达差异

目的 探讨ER、PR、HER-2、p53、Ki-67在乳腺癌复发转移灶与原发灶中的表达差异。方法 采用免疫组化En Vision两步法检测156例乳腺癌原发病灶及对应的复发或转移灶中ER、PR、HER-2、p53及Ki-67的表达,比较各指标的表达差异,并分析发生局部复发或远处转移的乳腺癌临床病理特征及与原发癌相比与各指标表达的一致性。结果 乳腺癌局部复发组和远处转移组与肿瘤分期(P=0.015)、肿瘤直径(P=0.005)差异有显著性;与患者年龄、组织学分级和腋窝淋巴结状态的差异无显著性(P0.05)。复发转移灶ER、PR阳性率比原发灶均有所下降,但差异无显著性;ER、PR表达不一致(分别为18.6%、19.2%),差异有显著性(P=0.024,P=0.043);原发灶与复发转移灶HER-2表达有较高的一致性,表达不一致占5.1%;原发灶与复发转移灶p53的阳性率差异不大,p53表达不一致占14.1%;复发转移灶Ki-67高表达者比原发灶多,Ki-67表达不一致占30.8%,差异有显著性(P0.001)。局部复发组和远处转移组各指标表达不一致的差异无显著性。结论 乳腺癌原发灶与复发转移灶ER、PR和Ki-67表达存在不一致性,HER-2表达有较高一致性。因此,检测乳腺癌复发转移灶中各指标表达对治疗方案选择和预后有重要意义。     

浸润性乳腺癌及转移淋巴结中RKIP和Ki-67的表达及意义

目的 探讨RKIP和Ki-67在浸润性乳腺癌及其淋巴结转移灶中的表达及意义.方法 应用免疫组化SP法检测RKIP和Ki-67在52例浸润性乳腺癌及其淋巴结转移灶中的表达情况.结果 乳腺癌淋巴结转移灶与原发灶相比,RKIP表达水平明显下降,两者之间有统计学差异(P<0.01).Ki-67指数在乳腺癌淋巴结转移灶明显高于原发灶(P<0.01);但RKIP与Ki-67之间,无论是原发灶,还是转移灶,都无相关关系(均P>0.05).结论 RKIP具有抑制浸润性乳腺癌转移的作用,属于转移抑制基因;Ki-67可反映乳腺癌的增殖活性及转移和预后,但RKIP的表达对乳腺癌细胞的增殖无明显影响.     

乳腺癌中EPCR的表达及其预后意义

目的观察EPCR在乳腺癌中的表达,并分析其预后意义。方法采用免疫组化Eli Vision法检测99例非特殊型浸润性乳腺癌组织中EPCR蛋白的表达,并复习相关文献。结果 EPCR在乳腺癌组织中的阳性率为36.4%,其表达与组织学分级、淋巴结转移、HER-2及Ki-67表达呈正相关,与ER、PR表达呈负相关,并在管腔A型中呈低表达,差异有统计学意义(P0.05);Kaplan-Meier单因素生存分析显示,EPCR阳性组的无瘤生存期(disease free survival,DFS)明显低于EPCR阴性组(P=0.011,Log-rank test=6.391),多因素Cox回归分析结果显示,EPCR在pN1组的乳腺癌中是独立的预后因素(hazard ratio=6.063,P=0.032)。结论 EPCR在乳腺癌中的表达与组织学高分级、淋巴结转移、HER-2阳性、高Ki-67、低ER/PR及更短的DFS相关,提示乳腺癌的不良预后。     

AR在ER阳性和阴性乳腺癌中的表达及临床意义

目的 探讨雄激素受体(androgen receptor, AR)在ER阳性和阴性乳腺癌中的表达及其与临床病理特征、预后的关系。方法 收集270例浸润性乳腺癌患者的临床病理资料，将ER分成阳性组与阴性组。分析两组AR表达与乳腺癌临床病理特征及多种蛋白标志物的关系，并复习相关文献。使用Kaplan-Meier Plotter数据库对AR在乳腺癌患者的预后价值进行分析。结果 270例浸润性乳腺癌患者AR阳性率为78.5%。AR与ER、PR、HER-2、CK5/6、组织学分级、Ki-67增殖指数、神经侵犯及脉管侵犯有关(P<0.05)。ER阳性组中AR阳性率(88.1%)高于ER阴性组(60.2%)。进一步分析发现ER阳性组中AR与组织学分级及CK5/6阳性有关(P<0.05);ER阴性组中AR与HER-2、CK5/6、组织学分级、神经侵犯、脉管侵犯、淋巴结转移及pTNM分期有关(P<0.05)。Kaplan-Meier Plotter预后分析发现，ER阳性组中AR高表达者总生存期显著高于低表达者，而ER阴性组中AR高表达者总生存期低于低表达者(P<0.05)。结论 ...     

hRad17在浸润性乳腺癌中表达及其与细胞增殖、凋亡的关系

目的 探讨乳腺癌组织中hRad17表达及其与细胞增殖、凋亡之间的关系.方法 采用免疫组化SP法检测90例乳腺浸润性癌、8例乳腺原位癌及20例乳腺良性病变组织中hRad17表达.测定90例乳腺浸润性癌组织中Ki-67、微小染色体维持蛋白7(minichromosome maintenance proteins,MCM7)、Bcl-2、p53、ER、PR、c-erbB-2的表达.结果 hRad17蛋白在乳腺浸润性癌、乳腺原位癌和乳腺良性病变三组病例中表达差异有统计学意义(P<0.05).90例乳腺浸润性癌中,hRad17阳性表达56例(62.2%).乳腺浸润性癌的hRad17的阳性表达与乳腺癌的临床分期、组织学分级、淋巴结转移及Ki-67、MCM7、Bcl-2表达密切相关,与患者生存期呈负相关(P<0.05).hRad17的表达与患者年龄、肿块大小、组织学类型和p53、ER、PR、c-erbB-2表达均无关(P>0.05).结论 hRad17在乳腺癌中表达上调,提示在乳腺癌发生、发展中起重要作用.hRad17可成为判断乳腺癌预后新的分子标记物.     

非小细胞肺癌中Ki-67和BCL-2表达的临床意义及预后价值

目的 探讨细胞增殖核抗原Ki-67蛋白及凋亡调节因子BCL-2蛋白在非小细胞肺癌(non-small cell lung carcinoma,NSCLC)中表达.方法 采用组织芯片技术用Ki-67和BCL-2单克隆抗体对261例NSCLC标本进行免疫组化染色.结果 Ki-67增殖指数为61.3%,在8例正常对照组织中呈阴性;Ki-67蛋白表达在高分化组明显低于低分化组、淋巴结转移阳性组明显高于淋巴结转移阴性组,差异均有显著性(P＜0.01);Ki-67表达与患者年龄、性别、组织类型和T分期无关;Ki-67阳性组患者平均存活月数明显低于阴性组,差异有显著性(P<0.01).BCL-2蛋白阳性率为43.68%,对照组阴性;BCL-2在低分化组和淋巴结转移阳性组分别低于高分化组和淋巴结转移阴性组,差异均无显著性(P>0.05);BCL-2阳性组患者平均存活月数高于阴性组患者,差异无显著性(P>0.05);BCL-2蛋白表达与患者年龄、性别、组织学类型、T分期无关;114例BCL-2阳性患者中Ki-67阳性率仅26.88%,而101例Ki-67阴性患者中BCL-2阳性率为70.30%.结论 BCL-2表达与NSCLC临床病理因素无相关性,Ki-67与BCL-2表达呈明显负相关.Ki-67蛋白作为细胞增生标志与NSCLC淋巴结转移相关,Ki-67阳性者预后差,Ki-67可作为判断NSCLC预后的一个有价值的分子标志.     

乳腺癌中HIF-1α与Ki-67、Caspase-3和VEGF表达的意义

目的：分析乳腺浸润性导管癌中缺氧诱导因子-1α( hypoxia inducible factor-1α, HIF-1α)表达,探讨其表达与Ki-67、Caspase-3和VEGF表达的关系。方法收集105例乳腺癌手术切除标本,采用免疫组化SP法检测HIF-1α、Ki-67、Caspase-3和VEGF 的表达,分析 HIF-1α表达与 Ki-67、Caspase-3和VEGF表达的关系。结果 HIF-1α的阳性率在乳腺癌组织(68.6%)与淋巴结转移癌组织(77．1%)的差异无统计学意义(P >0．05),但均明显高于正常乳腺组织(17．7%, P <0．05)。同时乳腺癌组织中伴淋巴结转移(65．3%)与无淋巴结转移(71．4%)的 HIF-1α阳性率差异无统计学意义( P>0．05)。与HIF-1α阴性组相比, HIF-1α阳性组乳腺癌细胞的Ki-67增殖指数和VEGF表达明显增高,而Caspase-3表达明显降低( P<0．05)。结论乳腺癌中HIF-1α的表达与 Ki-67、Caspase-3和 VEGF表达密切相关,可能会通过促进肿瘤组织的血管生成,使肿瘤细胞的增殖加快和凋亡减少,为以HIF-1α靶点的临床治疗提供实验基础。     

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.     

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.     

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.     

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.     

Platelet-activating factor receptor and respiratory and metabolic responses to hypoxia and hypercapnia

Activation of the platelet-activating factor receptor (PAFR) regulates neural transmission. A PAFR blocker reduced the peak hypoxic (pHVR) but not hypercapnic ventilatory (HCVR) responses in rats [Am. J. Physiol. 275 (1998) R604]. To further examine the role of PAFR in respiratory control, genotype-verified PAFR -/- and PAFR +/+ adult male mice underwent hypoxic and hypercapnic challenges. HCVR was similar in the two groups (p-NS). However, pHVR was significantly reduced in PAFR -/- mice (38 +/- 13% baseline [S.D.]) compared to PAFR +/+ mice (78 +/- 16% baseline; P < 0.001, ANOVA), with reduced tidal volume recruitments during pHVR. In addition, hypoxic ventilatory depression was attenuated in PAFR -/- mice (P < 0.01), and was primarily due to attenuation of the time-dependent decreases in oxygen consumption during sustained hypoxia (P < 0.01). Thus, PAFR expression/function modulates components of the acute ventilatory and metabolic adaptations to hypoxia but not to hypercapnia. Imbalances in PAFR activity may lead to maladaptive regulation of the tightly controlled metabolic-ventilatory relationships during hypoxia.