肿瘤坏死因子受体-1在甲状腺癌中的表达及其意义

目的:研究肿瘤坏死因子受体-1(tumor nercosis factor receptors-1,TNFR1)在甲状腺癌组织中的表达及其与临床及病理因素的关系.方法:应用免疫组织化学SP法和显微图像分析技术检测41例甲状腺癌中TNFR1的表达,并与9例甲状腺腺瘤及7例腺瘤旁形态学正常的甲状腺组织作对照.结果:①甲状腺癌组织中TNFR1的表达水平显著高于腺瘤组及正常甲状腺组(P＜0.001),而在甲状腺腺瘤和正常甲状腺组织中的表达水平无显著性差异(P＞0.05).②在甲状腺癌各临床病理参数中,TNFR1的表达只与病理类型有关,在乳头状癌组中的表达水平高于滤泡状癌组(P＜0.05);而与年龄、性别、肿瘤大小、浸润程度及淋巴结转移等因素无关(P＞0.05).结论:TNFR1参与了甲状腺癌的发生发展过程,可以作为甲状腺癌诊断与鉴别诊断的病理学指标之一,但不能作为评估甲状腺癌生物学行为和预后的有关指标.     

肿瘤坏死因子受体p55和p75在甲状腺癌组织中的表达及其意义

目的:研究肿瘤坏死因子受体(tumor necrosis factor receptor,TNFR)p55和p75在甲状腺癌组织中的表达及其与临床病理因素之间的关系,从而探索两型受体在甲状腺癌组织中的作用及意义.方法:应用免疫组织化学SP法检测41例甲状腺癌中TNFRp55和TNFRp75的表达情况,并以9例甲状腺腺瘤及7例腺瘤旁形态学正常的甲状腺组织作为对照.结果:①甲状腺癌组织中TNFRp55和TNFRp75的表达水平显著高于甲状腺腺瘤组及正常甲状腺组(P＜0.001),而它们在甲状腺腺瘤和正常甲状腺组织中的表达水平无显著性差异(P＞0.05).②两型受体的表达与甲状腺癌的组织学类型密切相关,在乳头状癌组织中的表达水平高于滤泡状癌组织(TNFRp55,P＜0.05;TNFRp75,P＜0.001);而与甲状腺癌患者的年龄、性别、肿瘤大小、包膜是否受侵、淋巴结有无转移等临床病理因素无关.③在甲状腺癌组织中两型受体的表达呈正相关(r=0.77,P＜0.001).结论:TNFRp55和TNFRp75在甲状腺癌中协同高表达,参与了甲状腺癌的发生、发展过程.它们可以作为甲状腺癌诊断与鉴别诊断的病理学指标之一,但不能用来评估甲状腺癌的生物学行为及预后.     

肿瘤坏死因子受体p55和p75在甲状腺癌组织中的表达及其意义

目的:研究肿瘤坏死因子受体(tumor necrosis factor receptor,TNFR)p55和p75在甲状腺癌组织中的表达及其与临床病理因素之间的关系,从而探索两型受体在甲状腺癌组织中的作用及意义.方法:应用免疫组织化学SP法检测41例甲状腺癌中TNFRp55和TNFRp75的表达情况,并以9例甲状腺腺瘤及7例腺瘤旁形态学正常的甲状腺组织作为对照.结果:①甲状腺癌组织中TNFRp55和TNFRp75的表达水平显著高于甲状腺腺瘤组及正常甲状腺组(P＜0.001),而它们在甲状腺腺瘤和正常甲状腺组织中的表达水平无显著性差异(P＞0.05).②两型受体的表达与甲状腺癌的组织学类型密切相关,在乳头状癌组织中的表达水平高于滤泡状癌组织(TNFRp55,P＜0.05;TNFRp75,P＜0.001);而与甲状腺癌患者的年龄、性别、肿瘤大小、包膜是否受侵、淋巴结有无转移等临床病理因素无关.③在甲状腺癌组织中两型受体的表达呈正相关(r=0.77,P＜0.001).结论:TNFRp55和TNFRp75在甲状腺癌中协同高表达,参与了甲状腺癌的发生、发展过程.它们可以作为甲状腺癌诊断与鉴别诊断的病理学指标之一,但不能用来评估甲状腺癌的生物学行为及预后.     

HIF-1α在甲状腺肿瘤中的表达及其临床意义

目的探讨HIF-1α蛋白在甲状腺肿瘤组织中的表达及其临床意义。方法应用免疫组织化学Envision法检测140例甲状腺癌组织、50例甲状腺腺瘤及30例正常甲状腺组织中HIF-1α蛋白的表达,分析HIF-1α蛋白的表达与甲状腺癌临床病理特征之间的关系。结果甲状腺癌中HIF-1α阳性表达明显高于正常甲状腺组织和甲状腺腺瘤,差异有统计学意义(P<0.05)。HIF-1α在140例甲状腺癌组织中的表达与是否有颈部淋巴结转移、浸润深度、分化程度以及AJCC分期密切相关(P<0.01)。结论 HIF-1α参与了甲状腺癌的形成过程,并与甲状腺癌的浸润、转移和预后密切相关,可作为辅助甲状腺癌早期鉴别诊断和预测其生物学行为的参考指标。     

肿瘤转移抑制基因KISS-1在甲状腺癌组织中表达和预后的研究

目的检测KISS-1蛋白、基质金属蛋白酶(MMP)-2、MMP-9及Ki67在甲状腺癌中的表达,探讨4者在甲状腺癌发生发展过程中的作用。方法采用免疫组织化学SP法检测10例正常甲状腺组织、12例结节性甲状腺肿,13例甲状腺腺瘤,68例甲状腺癌组织KISS-1蛋白、MMP-2、MMP-9及Ki-67的表达,分析4者在不同临床病理特征中表达的意义及它们之间的相关性。结果甲状腺癌组KISS-1蛋白阳性表达率(37%)明显低于正常甲状腺组织、结节性甲状腺肿和甲状腺腺瘤组(分别为100%、83%、62%,P<0.01),并且KISS-1蛋白低表达与甲状腺癌的临床分期和淋巴结转移有关(P<0.05),与甲状腺癌患者的年龄、病理类型无关(P>0.05)。甲状腺癌组和结节性甲状腺肿和甲状腺腺瘤组MMP-2阳性表达率(分别为78%,54%、67%)明显高于正常甲状腺组(10%,P<0.01),并且MMP-2高表达与甲状腺癌的临床分期和淋巴结转移有关(P<0.05),与甲状腺癌患者的年龄、病理学类型无关(P>0.05)。甲状腺癌组和结节性甲状腺肿和甲状腺腺瘤组MMP-9阳性表达率(分别为82%,69%、58%)明显高于正常甲状腺组(20%,P<0.01),并且MMP-9高表达与甲状腺癌的临床分期和淋巴结转移有关(P<0.05),与甲状腺癌患者的年龄、病理学类型无关(P>0.05)。甲状腺癌组Ki67阳性表达率(88%)明显高于正常甲状腺组和结节性甲状腺肿和甲状腺腺瘤组(10%、31%、42%;P<0.01),并且Ki67高表达与甲状腺癌的临床分期有关(P<0.05),与甲状腺癌患者的年龄、病理学类型和淋巴结转移无关(P>0.05)。结论 KISS-1蛋白、MMP-2、MMP-9及Ki-67与甲状腺癌的发生发展有关,联合检测4者的表达可能作为评估甲状腺癌预后和指导临床靶向治疗的重要指标。     

甲状腺肿瘤中CD15抗原的表达及临床意义

目的 研究甲状腺癌组织中CD15抗原的表达情况及其临床意义。方法 应用微波-LSAB免疫组织化学法,检测50例甲状腺癌、45例甲状腺腺瘤、20例癌旁甲状腺和10例正常甲状腺组织中CD15抗原的表达。结果 在甲状腺癌中CD15表达阳性率为68.0％,显著高于甲状腺腺瘤和癌旁甲状腺(42.0％和35.0％,P<0.05),10例正常甲状腺组织中2例呈CD15弱阳性反应。CD15表达与甲状腺癌组织类型无关,在淋巴结转移病例和病理分期Ⅲ～Ⅳ期病例,CD15表达阳性率显著高于相应的无淋巴结转移病例和病理分期Ⅰ～Ⅱ期病例(P<0.05)。CD15阳性的甲状腺癌复发及死亡率显著高于CD15阴性的甲状腺癌复发和死亡率(P<0.05)。结论 CD15表达对甲状腺癌恶性程度判断、生物学行为预测和预后评估是一种有意义的客观指标。     

甲状腺肿瘤微淋巴管生成因子-C CXCR4的表达与微淋巴管密度研究

目的探讨甲状腺肿瘤中微淋巴管生成因子(VEGF)-C、CXCR4的表达和微淋巴管密度(MLVD)及其意义。方法采用免疫组强化学检测100例甲状腺癌以及20例甲状腺腺瘤中VEGF-C、CXCR4的表达及D2-40标记的MLVD。结果甲状腺癌组VEGF-C和CXCR4的表达高于甲状腺腺瘤组;甲状腺癌淋巴结转移组VEGF-C和CXCR4的表达高于无淋巴结转移组;不同病理类型、不同分期的甲状腺癌中VEGF-C和CXCR4的表达不同;生存期不同的甲状腺癌中CXCR4的表达率不同;甲状腺癌伴淋巴结转移、无淋巴结转移及甲状腺腺瘤中MLVD不同,以上差异均有统计学意义(P<0.05);VEGF-C与MLVD正相关(P<0.05);。结论VEGF-C、CXCR4及MLVD在甲状腺良恶性肿瘤的鉴别诊断、甲状腺癌淋巴结转移及预后判断中有重要价值。     

良恶性甲状腺肿瘤组织中层粘连蛋白的表达及意义

目的比较层粘连蛋白（LN）在良恶性甲状腺肿瘤的表达及其意义。方法采用免疫组化方法检测12例甲状腺正常组织和38例甲状腺腺瘤、20例甲状腺癌组织中LN的表达，对LN表达率作两两比较。结果LN在甲状腺腺瘤与甲状腺癌组织中阳性表达率差异有显著意义（P〈0．05）；在甲状腺癌组织中与甲状腺正常组织中的阳性表达率差异有非常显著意义（P〈0．01）。LN在甲状腺癌细胞及出现于甲状腺滤泡性腺瘤组织中的乳头状腺瘤细胞胞浆中有表达。结论LN参与了肿瘤的发生发展，可作为甲状腺良恶性肿瘤的鉴别诊断指标之一。LN免疫反应物出现于肿瘤细胞胞浆很可能是良性肿瘤转化为癌的标志。     

Survivin血管内皮生长因子在甲状腺癌中的表达及其与预后的关系

目的探讨Survivin、血管内皮生长因子(VEGF)在甲状腺癌中的表达及其与预后的关系。方法采用免疫化学EliVison两步法检测70例甲状腺癌、14例甲状腺瘤及14例正常甲状腺组织中Survivin、VEGF的表达,并对甲状腺癌组织学分型、临床病理分期、病理类型及淋巴结转移等进行对比分析。结果70例甲状腺癌中Survivin、VEGF的阳性率分别为64%、66%,和正常甲状腺组织、腺瘤比较差异有统计学意义(P<0.05)。甲状腺癌中Survivin、VEGF的表达在不同组织学分型、病理类型、临床病理分期、淋巴结转移状态差异有统计学意义(P<0.05)。Survivin与VEGF的表达呈正相关(r=0.503,P<0.01);甲状腺癌中Survivin、VEGF表达阳性组和阴性组生存率差异有统计学意义(P<0.05),表达阳性组预后差。结论Survivin、VEGF在甲状腺癌的发生、发展中起着重要作用,二者联合检测可为甲状腺癌恶性程度和预后的判断提供有效证据。     

VEGF在甲状腺肿瘤中的表达及与肿瘤血管生成的关系

目的探讨VEGF在甲状腺肿瘤组织中的表达及其与肿瘤血管生成的关系。方法应用免疫组织化学Envision法检测140例甲状腺癌组织、50例甲状腺腺瘤及30例正常甲状腺组织中VEGF的表达,并检测肿瘤微血管计数(MVD),分析VEGF蛋白的表达与肿瘤血管生成的关系。结果甲状腺癌组织中VEGF阳性表达和MVD计数均明显高于正常甲状腺和甲状腺腺瘤组织(P0.05)。在甲状腺癌组织中有颈部淋巴结转移、AJCC分期Ⅲ～Ⅳ及浸润达包膜或包膜外者的VEGF表达及MVD计数明显高于无颈部淋巴结转移、AJCC分期I～Ⅱ及未突破包膜者(P0.05)。甲状腺癌组织中VEGF表达及MVD值之间呈显著正相关(r=0.564,P0.05)。结论 VEGF和MVD计数可作为辅助甲状腺肿瘤早期鉴别诊断和预测甲状腺癌浸润、转移和预后的参考指标。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.