Skp2和PTEN在人脑星形细胞瘤中的表达及临床意义

目的探讨Skp2和PTEN在人脑星形细胞瘤中的表达及与病理分级的关系。方法免疫组化S-P法检测70例Ⅰ～Ⅳ级脑星形细胞瘤和8例正常脑组织标本中Skp2和PTEN的表达。结果(1)Skp2、PTEN在人脑星形细胞瘤组中阳性表达率分别为47.1%和50.0%,而在正常脑组织组中阳性表达率分别为0%和100%。从星形细胞瘤I、II级组,III级组到IV级组,Skp2的阳性表达率呈增高趋势,分别为9.1%、45.5%、80.8%,而PTEN的阳性表达率呈降低趋势,分别为90.9%、50.0%、15.4%。(2)Spearman等级相关检验证实病理分级和Skp2标记指数呈正相关,和PTEN标记指数呈负相关。人脑星形细胞瘤中Skp2和PTEN的表达呈负相关。结论Skp2和PTEN蛋白的表达情况可作为人脑星形细胞瘤的诊断和恶性程度评估的参考资料,可能成为人脑星形细胞瘤治疗的新靶点。     

14-3-3β在人脑星形细胞瘤中的表达及意义

目的探讨14-3-3β在人脑星形细胞瘤中表达与肿瘤病理分级的关系。方法采用免疫组化法检测14-3-3β亚型在80例人脑星形细胞瘤和10例正常脑组织标本中的表达水平。结果在正常脑组织中，14-3-3蛋白6亚型只表达于神经元胞体和突起，在胶质细胞中未见表达。母亚型在人脑星形细胞瘤的表达阳性率及免疫反应评分（IRS）分别为60％、1．86±1．83。Ⅰ～Ⅳ级脑星形细胞瘤中β亚型表达阳性率分别为40％（8／20）、50％（10／20）、70％（14／20）和80％（16／20）。Ⅰ～Ⅳ级脑星形细胞瘤中β亚型IRS分别为0．88．4±0．27、1．15±0．28、2．19±0．37和3．23±0．47。不同恶性级别的脑星形细胞瘤中，14．3-3蛋白β亚型的阳性表达率无显著差异，但其IRS有显著差异（P〈0．05）。结论14-3-3β在人脑星形细胞瘤中高表达，且随着星形细胞瘤病理级别的增高而表达增强，14-3-3蛋白β亚型在脑星形细胞瘤的发生过程中具有重要作用。     

PCNA和GFAP在脑星形胶质细胞瘤中表达的双重染色研究

目的研究人脑星形胶质细胞瘤中增殖细胞核抗原（PCNA）和胶质纤维酸性蛋白（GFAP）的表达及其与肿瘤分级的关系。方法采用免疫组化双重染色法对41例人脑星形胶质细胞瘤进行PCNA和GFAP两重标记检测。结果脑星形胶质细胞瘤中PCNA与GFAP表达率均为100％，PCNA表达水平与肿瘤分级呈正相关（r=-0．627，P〈0．01），GFAP表达水平与肿瘤分级呈负相关（r=-0．568，P〈0．01）；Ⅰ-Ⅱ级与Ⅲ-Ⅳ级胶质瘤间PCNA和GFAP表达均有显著性差异（P〈0．05）；GFAP表达和PCNA表达水平呈负相关（r=-0．332，P〈0．05）。结论PCNA与GFAP的表达有一定的相关性。PCNA与GFAP的双重表达与脑星形胶质细胞瘤的增殖活性和恶性程度有关。     

Skp2、P27kip1和PTEN在人脑胶质瘤中的表达及其相互关系的研究

目的探讨S期激酶相关蛋白2（skp2）、细胞周期素依赖性激酶抑制蛋白P27^kip1和抑癌基因蛋白PTEN表达与人脑胶质瘤发生、发展的关系。方法用免疫组化SP法检测52例人脑胶质瘤和8例正常脑组织标本中Skp2、P27^kip1和PTEN蛋白的表达。结果Skp2在8例正常脑组织中全部表达阴性。在52例胶质瘤标本中随着肿瘤恶性程度增高而表达增强。在低、高级别胶质瘤中的阳性率分别56％和81．5％，三者之间的表达水平差异有显著性意义（P〈0．001）。P27^kip1和PTEN在正常脑组织中表达均为强阳性，随着肿瘤恶性程度增高而表达减弱，P27^kip1和PTEN各自在低、高级别人脑胶质瘤中阳性率分别96％、77．8％和80％、55．6％。三者之间的表达水平差异有显著性意义（P〈0．01）。在52例胶质瘤标本中，Skp2表达与P27^kip1（r=-0．490，P〈0．01）和肿瘤抑制蛋白PTEN（r=-0．489，P〈0．01）表达呈负相关，PTEN表达与P27^kip1表达呈正相关（r=-0．802，P〈0．01）。结论人脑胶质瘤中Skp2蛋白过表达与P27^kip1降解及PTEN蛋白低表达有关，提示Skp2蛋白过表达可能是人脑胶质瘤发生和发展的一个重要原因。     

Survivin、Bcl-2和PTEN在人脑星形细胞瘤中的表达及相关性研究

目的 研究人脑星形细胞瘤中survivin、bcl-2和PTEN的表达情况及相关性，探讨其与星形细胞瘤的发展、临床病理参数之间的关系。方法 应用免疫组织化学Elivision二步法检测实验组与正常对照组标本中survivin、bcl-2和PTEN的表达。结果 survivin、bcl-2和PTEN在不同级别星形细胞瘤中的阳性表达率有显著性差异（P〈0．01）。随着星形细胞瘤病理分级的增加，survivin和bcl-2表达的阳性率及表达强度渐增（P〈0．01），PTEN表达的阳性率及表达强度渐减（P〈0．01）。survivin和bcl-2的表达之间存在正相关关系（P〈0．01）；survivin、bcl-2与PTEN的表达均存在负相关关系（P〈0．01）。结论 在人脑星形细胞瘤中，survivin、bcl-2高表达和PTEN相对低表达，说明三者可能参与人脑星形细胞瘤的病理发展。     

ING4和HIF-1α在人脑不同级别星形细胞瘤中表达的研究

目的 研究ING4及HIF-1α在星形细胞瘤中的表达,探讨它们在星形细胞瘤发生和发展中的作用.方法 采用免疫组化法检测45例星形细胞瘤标本及11例正常脑组织中ING4和HIF-1α的表达.结果 ING4在正常脑组织和星形细胞瘤中的阳性表达率分别为100%、42.4%;Ⅰ～Ⅱ级和Ⅲ～Ⅳ级星形细胞瘤中的阳性表达率分别为58.3%、23.8%,差异均有统计学意义(P<0.05).HIF-1α在正常脑组织和星形细胞瘤中的阳性表达率分别为0、71.1%;在Ⅰ～Ⅱ级和Ⅲ～Ⅳ级星形细胞瘤中的阳性表达率分别为54.2%、90.5%,差异均有统计学意义(P<0.05).结论 ING4和HIF-1α基因的表达与星形细胞瘤分级有密切关系,在其发生和发展过程中起重要作用.     

血管内皮生长因子VEGF及其受体Flt-1在人脑星形细胞瘤中的表达

目的 检测血管内皮细胞生长因子VEGF及其受体Flt-1在人脑星形细胞瘤中和正常脑组织的表达,分析二者表达程度与脑星形细胞瘤病理分级的关系。方法采用免疫组织化学的方法,对33例脑星形细胞瘤组织和7例正常脑组织VEGF和Flt-1的表达情况进行了观察。结果VEGF在Ⅰ型、Ⅱ型、Ⅲ型和Ⅳ型脑星形细胞瘤之中阳性率分别为11％、50％、75％和75％,而正常成人脑组织无VEGF表达.脑星形细胞瘤与正常成人脑组织VEGF、表达有显著性差异(P<0.01)。7例正常成人脑组织未见Flt-1表达,脑星形细胞瘤Flt-1表达率分别为0、17％、50％和100％,限于肿瘤血管的内皮细胞表达。肿瘤细胞VEGF表达与Flt-1表达呈正相关(r:0.7376,p<0.001),无论VEGF还是Flt-1在坏死区周围表达都明显增强。结论 VEGF及其受体Flt-1在人脑星形细胞瘤和正常脑组织的表达有显著性差异,与脑星形细胞瘤病理分级有关。     

MMP-2及PTEN在人脑星形细胞瘤中的表达及意义

目的探讨基质金属蛋白酶2(MMP-2)及抑癌基因PTEN在人脑星形瘤中的表达及二者与人脑星形细胞瘤侵袭性的关系。方法用免疫组织化学SABC法检测50例人脑星形细胞瘤组织和10例正常人脑组织中的MMP-2和PTEN蛋白的表达,并且分析二者与人脑星形细胞瘤临床病理分级的关系。结果 MMP-2和PTEN在低度恶性星形细胞瘤和高度恶性星形细胞瘤组织中表达差别有统计学意义(p<0.05)。随着星形细胞瘤恶性度增高,MMP-2的表达强度呈上升趋势而PTEN表达强度逐渐下降;Spearman等级相关分析表明人脑星形细胞瘤中MMP-2和PTEN之间呈负相关(Rs=-0.518,P<0.01)。结论 MMP-2和PTEN是人脑星形细胞瘤分化程度和转移的潜在生物学指标,联合检测MMP-2和PTEN更有利于判断星形细胞瘤生物学行为和病理分级。     

Moesin在人脑星形细胞瘤的表达及意义

目的探讨膜结构伸展刺突蛋白（Moesin）在人脑星形细胞瘤中的表达及意义。方法应用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结法（SP法）,检测56例人脑星形细胞瘤和10例正常脑组织中Moesin和磷酸化Moesin的表达,并结合临床随访资料分析表达水平与星形细胞瘤临床预后的相关性。结果Moesin的阳性表达率在人脑星形细胞瘤组96．4％（54／56）和正常脑组织对照组0％（0／10）之间有统计学差异（P〈0．01）。Ⅲ～Ⅳ级星形细胞瘤Moesin的强阳性表达高于Ⅰ～Ⅱ级,两者相比有统计学差异（χ^3=27．50,P〈0．01）,磷酸化Moesin的表达结果与Moesin的结果基本一致。Moesin强阳性表达组患者比弱阳性＋阴性表达组患者的术后无瘤生存时间短,其差异有统计学意义（χ^2=29．85,P=0．000）。结论Moesin的表达水平与人脑星形细胞瘤的恶性程度密切相关,Moesin的过度表达对星形细胞瘤发展和预后起重要作用,提示Moesin可以作为反映星形细胞瘤预后的一种有价值的分子标志物。     

PTEN／MMAC1基因表达与星形细胞瘤细胞增殖的相关性研究

目的研究人脑星形细胞瘤中PTEN/MMAC1基因编码蛋白的表达和星形细胞瘤增殖的关系,探讨PTEN/MMAC1基因突变在人脑星形细胞瘤增殖中的作用。方法应用PCR-SSCP、SP免疫组织化学法检测了52例星形细胞瘤中PTEN/MMAC1基因突变及表达情况,和肿瘤细胞核增殖抗原(PCNA)增殖程度;并用SPSS10.0统计软件分析PTEN/MMAC1基因表达与PCNA的关系。结果52例人脑星形细胞瘤中,PTEN/MMAC1蛋白表达缺失率约40.4%(21/52)。PTEN/MMAC1表达与肿瘤病理分级有显著关系,其中Ⅰ-Ⅱ级阳性率约80.0%,Ⅲ级约55.0%、Ⅳ级为33.3%,各级别组PTEN/MMAC1表达的差异有显著性(P<0.01);PTEN/MMAC1表达程度与星形细胞瘤的增殖呈显著负相关(r=-0.846,P<0.01)。结论PTEN/MMAC1表达与星形细胞瘤的恶性程度有关系,恶性程度越高,病人预后越差,该蛋白水平越低,肿瘤细胞的恶性增殖越明显。     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Opiate and digitalis receptor assays distinguish between neuroexcitant and inactive organochlorines and between anesthetics and convulsants

Specific binding of [3H]naloxone to rat brain tissue in vitro was inhibited by the excitant organochlorinated insecticides (OCI), by ether (E) and octanol (OCT), and by the convulsant indoklon (IND) and its anesthetic isomer, isoindoklon (ISO). In the presence of 100 mM NaCl the inhibition of naloxone binding by E, OCT and ISO was greatly potentiated, whereas that by OCI and IND was attenuated. KCl (100 mM) was equally effective as NaCl on the action of anesthetics, but the effect of the excitant drugs was, in contrast to NaCl, unaffected by KCl. Specific binding of [3H]ouabain in the absence of Na, was depressed by anesthetics and enhanced by neuroexcitants. In the presence of NaCl, which by itself inhibits ouabain binding to brain, both anesthetics and excitants enhanced ouabain binding. DDE, a non-insecticidal analog of DDT, and the dimethyl derivative of the OCI, lindane, were inactive in the receptor assays. These observations point to a unique isolated system which responds consistently to anesthetic agents as a class and, in a different way, to neuroexcitant compounds.     

Learning and forgetting new names and objects in MCI and AD

We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.     

Satellite cells and myonuclei in young and elderly women and men

The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.     

Necdin蛋白与神经元的生长分化

在神经系统 ,Necdin只在成熟神经元的细胞核中表达 ,可能与成熟神经元分裂静止状态的保持有关。近年的研究表明 ,Necdin是一种生长抑制蛋白 ,能与多种因子如SV4 0大T抗原 ,腺病毒E1A ,转录因子E2F1以及肿瘤抑制蛋白p5 3等结合 ,在功能上类似于成视网膜瘤蛋白Rb。necdin基因缺陷时 ,会引起脑内 ,特别是下丘脑神经元分化障碍。人类necdin基因位于PWS综合征的基因缺失区 ,可能与PWS的一些症状有关。本文从Necdin蛋白的基本概况 ,生物功能以及Necdin与疾病三个方面进行了综述     

Necdin蛋白与神经元的生长分化

在神经系统,Necdin只在成熟神经元的细胞核中表达,可能与成熟神经元分裂静止状态的保持有关.近年的研究表明,Necdin是一种生长抑制蛋白,能与多种因子如SV40大T抗原,腺病毒E1A,转录因子E2F1以及肿瘤抑制蛋白p53等结合,在功能上类似于成视网膜瘤蛋白Rb.necdin基因缺陷时,会引起脑内,特别是下丘脑神经元分化障碍.人类necdin基因位于PWS综合征的基因缺失区,可能与PWS的一些症状有关.本文从Necdin蛋白的基本概况,生物功能以及Necdin与疾病三个方面进行了综述.     

Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics

We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V(1a), V(1b) and V(2) receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V(1b) receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V(1a) agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V(2) /V(1a) antagonist, conivaptan and the V(2) antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V(1a), V(1b) and V(2) antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences.     

Retrospective and prospective design and data

The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder - MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile.     

Cortisol levels and depression in men and women using heroin and cocaine

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.