伴玻璃样间质的透明细胞癌二例

例1男,76岁。因双下肢浮肿2个月余,声嘶1周于2000年3月12日入院。体检:一般情况差,左颈部触及肿大淋巴结约2cm×2cm大小,血生化检查提示肾功能及呼吸功能衰竭,后因呼吸困难作气管插管时舌根部见一菜花状肿瘤约3.0cm×2.5cm大小,行颈淋巴结及舌根部肿瘤活检术。术后1个月患者死于慢性肾炎所致肾功能及呼吸功能衰竭。病理检查:切除淋巴结大小2cm×2cm,切面灰白色,质硬。舌根部肿瘤大小3.0cm×2.5cm,表面呈菜花状,切面灰白色,质硬。镜下观察:舌根部肿瘤细胞形态较一致,排列呈互相吻合的小梁状、岛状或片状。巢间有大量玻璃样变的纤维性间质。瘤…     

CT模拟定位三维适形放射治疗食管癌的临床研究

目的探讨CT模拟定位三维适形放射治疗食管癌的疗效。方法1997年4月～2002年7月,经病理证实的食管鳞状细胞癌87例患者，其中男性56例，女性31例，年龄42～75岁，平均年龄62.5岁，随机分为2组，两组患者一般情况、性别、年龄及病变部位构成经统计学检验无统计学意义，一组为采用CT模拟定位进行三维适形放射治疗，另一组为常规模拟定位放射治疗，两组的剂量都为64～66Gy／32.33次／6.4～6.6周。结果采用Kaplan—Meier法计算生存率，并用Log—Rank检验其差异性。治疗计划各指标分析采用kolmogorowSmirnov法行正态分布检验，继而行t检验，以P〈0.05为差异有统计学意义。CT模拟定位三维适形放射治疗组和常规模拟定位放射治疗组1、2、3、4年生存率分别为70.1％、55.6％、40.4％、36.3％和65.4％、50.6％、30.6％、20.9％（p〉0.05）。但是对Ⅰ～Ⅱ期患者，CT模拟定位三维适形放射治疗组和常规模拟定位放射治疗组的生存率分别为81.2％、75.5％、67.3％、61.5％和80.1％、65.7％、54.9％、29.7％（P〈0，05），局部控制率分别为75.6％、71.7％、65.5％、59.0％和65.4％、50.6％、33.3％、25.6％（P〈0.05）。而对于Ⅲ～Ⅳ期的患者，两组之间的生存率和局部控制率差异无统计学意义。结论CT模拟定位三维适形放射治疗的疗效明显好于常规模拟定位放射治疗组。特别对Ⅰ-Ⅱ期早期食管癌患者两组之间差异有统计学意义，而对晚期患者差异无统计学意义。     

参杞合剂对小鼠腹水型肝癌细胞株H22细胞周期及凋亡的影响

目的：观察参杞合剂(SQ)在体内、外对小鼠腹水型肝癌细胞株(HcaF16A3)细胞周期及凋亡的影响。方法：用SQ对荷瘤小鼠连续胃饲治疗10d，观察其NK细胞／Mφ的杀伤活性及细胞周期的改变。用流式细胞仪检测SQ对HcaF16A3细胞增殖的抑制作用与诱导凋亡的作用。结果：SQ的抑瘤率为65．68％。流式细胞仪检测发现，SQ可使肿瘤细胞的细胞周期阻滞到S期，并在体外诱导其凋亡。结论：SQ在体内、外均有抑瘤作用，其机制与细胞周期阻滞继而诱发凋亡有关。     

Proliferation,apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade

AIMS: Abnormalities involving proliferation, apoptosis, and angiogenesis are important in tumorigenesis. The purpose of this study was to examine these three biological processes, and their relation with the clinical stage and cytological grade in multiple myeloma (MM). METHODS: Fifty four newly diagnosed patients with MM were studied by immunohistochemistry using bone marrow clot sections. Proliferation and apoptosis were evaluated for the proportion of MM cells (indicated by morphology and CD138 reactivity) positive for the Ki67 antigen and single stranded DNA (ssDNA), respectively. Angiogenesis was evaluated by measuring the intratumoral microvessel density (IMVD) and by assessing the immunoreactivity of vascular endothelial growth factor (VEGF). RESULTS: There were 30 men and 24 women (median age, 65 years; range, 37-84). At initial presentation, 15 (28%) were in Durie stage I, 15 (28%) in stage II, and 24 (44%) in stage III. Advanced clinical stage correlated with high cytological grade (p < 0.03). The medians for Ki67, ssDNA, and IMVD were 4.4% (range, 0-15%), 0.2% (range, 0-2.8%), and 15.5 (range, 0-63), respectively. Among these three continuous parameters, the only significant correlation was that between Ki67 and IMVD (p < 0.0001). Both Ki67 and IMVD also correlated with the clinical stage, cytological grade, and VEGF positivity (p <0.05). No correlation was found between ssDNA and all of the other parameters. CONCLUSIONS: These data suggest that proliferation is associated with angiogenesis in MM. Furthermore, proliferation and angiogenesis, but not apoptosis, may be important in disease progression. Lastly, increased production of VEGF may be one of the contributing factors to the increase in intratumoral vascularity seen in advanced MM.     

Ischemia/Reperfusion Injury in the Rat Colon

This study investigated metabolic and biochemical consequences of colonic ischemia/reperfusion (I/R) in the rat and evaluated whether antioxidants prevent I/R-induced functional damage in the rat colon. The surgical preparation involved a 10 cm segment of the colon and occlusion of the superior mesenteric artery (SMA) to induce I/R. Arterial blood from the aorta and venous blood from the superior mesenteric vein (SMV) was collected to measure blood gases, lactic acid (LA) and arachidonic acid (AA) metabolites. Tissue xanthine oxidase (XO) and thiobarbituric acid (TBA) derivatives were measured before and after reperfusion. In addition, vascular and mucosal permeability, and the effect of MDL 73404 (a water soluble vitamin E analog) and 5-aminosalicylic acid on LA, AA, XO and TBA was measured. After ischemia, the colon displayed a metabolic shift from aerobic to anaerobic course by increasing lactic acid production in the colon (183% increase in SMV lactate level compared 87% in the SMA; p < 0.03). After 10 minutes of reperfusion, circulating 6-keto-prostaglandin F₁ increased by 3.85 fold (p < 0.001) and thromboxane B₂ increased by 2 to 3 fold. An Ischemia time longer than 60 minutes was required to cause changes in tissue XO levels. Tissue TBA levels showed a good dose response corresponding with I/R time. I/R (60 minutes) caused a three and 16 fold increase (p < 0.01) in vascular and mucosal permeability, respectively. MDL 73404 and 5-aminosalicylic acid significantly inhibited the vascular permeability and decreased LA, AA, XO and TBA. These observations provide the first direct experimental evidence for I/R-induced damage in the colon and some of its effects can be reversed by conventional and novel antioxidants.     

中国胰岛素依赖性糖尿病病人（HLA－DR9）的HLA－DQB1基因顺序分析

用血清学方法研究显示中国人胰岛素依赖性糖尿病（ＩＤＤＭ）与ＨＬＡ－ＤＲ９相关。鉴于白种人中的研究显示ＩＤＤＭ与ＨＬＡ－ＤＱβ链第５７位氨基酸相关，Ａｓｐ－５７对ＩＤＤＭ呈抗性，ｎｏｎ－Ａｓｐ与ＩＤＤＭ易感性相关。我们用ＰＣＲ技术扩增了中国人中血清学ＤＲ９纯合的ＩＤＤＭ患者和正常对照的ＨＬＡ－ＤＱＢ１基因第二外显子并测定了核苷酸顺序，结果未发现ＩＤＤＭ特异ＨＬＡ－ＤＱＢ１等位基因，但发现ＩＤＤＭ病人ＨＬＡ－ＤＱＢ１５７位均为天冬氨酸。表明中国ＩＤＤＭ患者中的ＨＬＡ－ＤＱＢ１５７位天冬氨酸不一定具有保护个体抵抗ＩＤＤＭ的足够能力。ＩＤＤＭ易感性可能涉及多个基因位点的变化，另外还可能与其它遗传因素及环境因素有关。     

Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain

Pentoxifylline, a non-specific cytokine inhibitor, has shown to be beneficial in inflammatory pain in both experimental and clinical studies. The present study demonstrates for the first time, to our knowledge, the antihyperalgesic effect of pentoxifylline in the neuropathic pain using L5 spinal nerve transection rat model. In a preventive paradigm, pentoxifylline (12.5, 25, 50, or 100 mg/kg intraperitoneally) was administered systemically daily, beginning 1 h prior to nerve transection. Pentoxifylline (50, or 100 mg/kg i.p.) produced significant decrease in the mechanical and thermal hyperalgesia. However, pentoxifylline (100 mg/kg i.p.) did not influence the paw pressure thresholds and paw withdrawal latency in sham-operated rats. In order to understand the possible antinocicieptive effect of pentoxifylline in neuropathic pain, we examined the level of TNFα, IL-1β, IL-6 and IL-10 protein in the contralateral brain on day 7 post-transection. Pentoxifylline administration resulted in a dose-dependent reduction of the production of proinflammatory cytokines like TNFα, IL-1β and IL-6, and enhancement of IL-10. Furthermore, we investigated the activity of nuclear factor kappa B (NF-κB) in the contralateral brain on days 7 after surgery. In accordance with the change of proinflammatory cytokines, Pentoxifylline (50 or 100 mg/kg) significantly inhibited the activation of NF-κB in the brain. This research supports a growing body of literature emphasizing the importance of neuroinflammation and neuroimmune activation in the development of neuropathic pain states, and the potential preventive value of pentoxifylline in the treatment of neuropathic pain.     

Troponin C regulates the rate constant for the dissociation of force-generating myosin cross-bridges in cardiac muscle

It is well known that cardiac troponin C (cTnC) regulates the association of force-generating myosin cross-bridges. We report here evidence for an additional role for cTnC. This hypothesis states that Car²⁺ binds more strongly to cTnC when force-generating myosin cross-bridges are attached to actin and that removal of this bound Ca²⁺ accelerates the dissociation of force-generating myosin cross-bridges. Intact Fura-2-loaded rat papillary muscles and skinned (permeabilized) ventricular preparations were used. The preparations were mounted in the Guth Muscle Research System which is capable of measuring simultaneously fluorescence and force in response to length perturbations. All mechanical perturbations of muscle length (isotonic shortening, quick stretches and releases, and length vibrations) which cause dissociation of force-generating myosin cross-bridges during a twitch resulted in Ca²⁺ being released from troponin as judged from changes in the Ca²⁺ transients (Fura-2 (340/380) fluorescence ratio). Thus dissociation of force-generating myosin cross-bridges cause Ca²⁺ to be released from cTnC. Conversely, it would be expected that removal of strongly bound Ca²⁺ from cTnC would result in an increase in the rate of dissociation of force-generating myosin cross-bridges. To test this hypothesis actomyosin ATPase (NADH fluorescence change) and isometric force were measured in skinned cardiac preparations. The ratio of the ATPase/Force is proportional to the rate constant (g_app) for the dissociation of force-generating myosin cross-bridges. The data showed that decreasing the amount of Ca²⁺ bound to cTnC in skinned cardiac fibers caused an increase in the ratio of ATPase/Force, the rate of dissociation (g_app) of force-generating myosin cross-bridges.     

Genetic basis for individual variations in pain perception and the development of a chronic pain condition

Pain sensitivity varies substantially among humans. A significantpart of the human population develops chronic pain conditionsthat are characterized by heightened pain sensitivity. We identifiedthree genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase(COMT) that we designated as low pain sensitivity (LPS), averagepain sensitivity (APS) and high pain sensitivity (HPS). We showthat these haplotypes encompass 96% of the human population,and five combinations of these haplotypes are strongly associated(P=0.0004) with variation in the sensitivity to experimentalpain. The presence of even a single LPS haplotype diminishes,by as much as 2.3 times, the risk of developing myogenous temporomandibularjoint disorder (TMD), a common musculoskeletal pain condition.The LPS haplotype produces much higher levels of COMT enzymaticactivity when compared with the APS or HPS haplotypes. Inhibitionof COMT in the rat results in a profound increase in pain sensitivity.Thus, COMT activity substantially influences pain sensitivity,and the three major haplotypes determine COMT activity in humansthat inversely correlates with pain sensitivity and the riskof developing TMD.     

Application of capillary electrophoresis in clinical chemistry: the clinical value of urinary modified nucleosides

Urinary modified nucleosides were determined by capillary electrophoresis using a 300 mM SDS-25 mM sodium tetraborate-50 mM sodium dihydrogenphosphate buffer. The nucleosides were extracted from urine by phenylboronate affinity gel chromatography. In cancer patients the levels of the modified nucleosides are generally elevated. By an artificial neural network method breast cancer patients were differentiated from normal individuals, which indicates that the modified nucleosides could be of clinical value as tumor markers.