Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side.

2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men.

3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.     

Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt-Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.     

Differences in the abilities of human tau isoforms to promote microtubule assembly.

Three isoforms of human tau protein were compared for their abilities to induce microtubule assembly. The three isoforms, tau 3 (tau containing three microtubule-binding domains), tau 4 (tau containing four microtubule-binding domains) and tau 4L (tau containing four microtubule binding domains plus a 58-amino-acid insert near the N-terminus) were expressed in E. coli and purified using ammonium sulfate precipitation, ion exchange, and size exclusion chromatography. All three isoforms induced microtubule assembly at micromolar concentrations and showed similar critical concentrations for assembly of 0.4-0.45 microM. However, tau 4 induced microtubule formation at a rate five- to tenfold faster than either tau 3 or tau 4L. The rate of microtubule elongation seen with tau 4 was twofold greater than with tau 3 or tau 4L, suggesting that the faster rate of microtubule assembly seen with tau 4 was due, at least in part, to faster elongation. Tau 4 induced a greater number of microtubules to form at steady state than did tau 3 or tau 4L. The microtubules generated with each tau isoform had similar steady-state length distributions and were equally susceptible to cold-induced disassembly. These results indicate that the additional microtubule-binding domain in tau 4 enhances microtubule assembly, while the 58-amino-acid insert negates the stimulatory effect of the fourth microtubule-binding domain.     

Progress toward re‐engineering non‐ribosomal peptide synthetase proteins: a potential new source of pharmacological agents

Many important pharmaceutical agents, including vancomycin, bleomycin, cyclosporin, and several antibiotics, are produced by non‐ribosomal peptide synthetase (NRPS) enzymes in microorganisms. The NRPS pathway produces an extensive library of products using multienzyme complexes acting in an assembly‐line fashion. Engineering an NRPS system to produce an even greater variety of products, some of which may also have beneficial therapeutic value, would be an enormous advantage. Several approaches have been successful in generating novel NRPS products: mutational biosynthesis during which nonnatural substrates are fed to an organism; domain and module swapping between different species to generate hybrid enzymes; and rational site‐directed mutagenesis, based either on phylogeny or computational prediction, intended to switch substrate specificity and produce altered products. This review will highlight the progress in these areas and describe research in the future that will extend the capacity for re‐engineering NRPS systems. Drug Dev. Res. 66:9–18, 2006. © 2006 Wiley‐Liss, Inc.     

PGA指数和透明质酸在诊断慢性乙肝肝纤维化中的价值

目的：寻找一种简便实用的诊断慢性乙型肝炎纤维化的方法。方法：以78例经肝穿刺病理证实的慢性乙型肝炎为对象，测定并比较了由PT、GGT、ApoA1组成的PGA指数和HA、LN、PⅢP、C－IV与肝内纤维化程度(S)和炎症活动度（G）的关系。结果：（1）LN、PⅢP、C－IV在轻度慢性乙肝时无明显升高，在中度慢性乙肝时明显高于正常，但与轻度慢性乙肝无差异，而PGA指数和HA不仅在轻度慢性乙肝时显著升高，而且在轻中度间差异明显.因重度慢性乙肝和活动性肝硬化时，五项指标均显著增高。（2）在G2－4期，HA、LN、PⅢP、C－IV均明显高升，但在G1期，只有PGA指数高于正常，且各期间差异显著。（3）在S1－2期，只有PGA指数、HA、C－IV明显上升，但C－IV的上升幅度远低于PGA指数和HA。（4）加以PGA＞4．5或HA＞200μg／L作为判断临界值，则两者判断肝纤维化的敏感性均＞94％，精确性＞91％，特异性＞86％，如两者结合，则分别达到98．3％、95．2％和96．4％。结论：PGA指数和HA均是反映慢性乙型肝炎患者肝内纤维化程度的良好指标，两者联合检测则可达到最大的价值效益比。     

脐动脉血PCT、CRP检测在早产儿早期感染中的作用

目的:为进一步提高早产儿重症感染的早期诊断率探讨一种快速、可靠的方法。方法:用LUMITestPCT方法检测我院出生的有感染可能的早产儿的脐动脉血清降钙素原(PCT)。同时检测脐动脉血C反应蛋白(CRP);由新生儿专业的医师对其病情进行观察,在不知道PCT值时做出病情的临床诊断,52例病例分为:重症感染组(n=28)和对照组(n=24)。进行回顾性对比分析。结果:早期开始的早产儿感染与CRP、PCT浓度在出生时的增加相关,差异有极显著性(P<0.001);脐动脉血中,PCT浓度的增加与CRP水平变化呈正相关(r=0.88)。PCT的敏感性(96.4%)和特异性(95.8%)均高于CRP(敏感性75%,特异性91.6%)。结论:PCT可作为早产儿早期感染的早期、快速检测指标,与CRP相比,PCT敏感性、特异性均高。本研究方法对早产儿无创伤。     

Spindle-cell glioblastoma or gliosarcoma?

'Gliosarcomas' have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate 'gliosarcomas' from glioblastoma multiforme and suggests that 'gliosarcomas' should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as 'gliosarcomas' were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate 'gliosarcomas' from glioblastoma multiforme. Macroscopically, biopsies from 'gliosarcomas' ranged from firm, apparently well-circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which 'gliosarcomas' with large reticulin-rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP); S100 protein and alpha-smooth muscle actin (ASMA) showed that the majority of cells in reticulin-poor areas of 'gliosarcoma' and glioblastomas expressed S100 protein and GFAP; many expressed ASMA and some expressed both GFAP and ASMA. Spindle cells in reticulin-rich areas of 'gliosarcomas' and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and 'gliosarcoma' at different ends of the spectrum. It is suggested, therefore, that most, if not all, 'gliosarcomas' be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma.     

胃癌组织p16基因蛋白表达的意义

目的　检测 p1 6基因蛋白在胃癌组织、癌旁组织中的表达及其分布特点 ,分析其与胃癌临床病理学特征及预后的关系 .方法　采用 S- P免疫组织化学法对 53例胃癌组织及 35例癌旁组织进行 p1 6蛋白的定位观察 .结果　各病理类型胃癌组织、癌旁组织均有 p1 6基因蛋白表达 .阳性率分别为 62 .3% (33/53)和 88.6% (31 /35) ,阳性细胞的棕黄色颗粒主要位于细胞核 .胃癌 p1 6基因蛋白表达与性别、年龄、肿瘤部位在统计学上无差异 (P>0 .0 5) ;而与组织学类型、病理分级、淋巴结转移、临床病理分期在统计学上有差异 (P<0 .0 5) .p1 6蛋白阳性者 5年生存率 51 .0 %高于 p1 6蛋白阴性者 2 0 .0 % (P<0 .0 5) .结论　 p1 6基因缺失和表达水平的改变与胃癌发生、发展密切相关 ,检测 p1 6基因蛋白表达可作为辅助临床判断胃癌的生物学行为及推测预后的指标     

强直性脊柱炎患者外周血CD62P的表达

目的探讨剖宫产指征的变化情况，分析影响剖宫产率的因素。方法 回顾性分析1393例剖宫产患者的临床资料。结果2年的平均剖宫产率为66．7％，其中2004年的剖宫产率为59．9％，2005年的剖富产率为72．2％，差异有统计学意义（P〈0．05）。剖宫产率的主要影响因素依次为社会因素（29．43％）、胎儿宫内窘迫（25．13％）、胎位异常（9．62％）、巨大胎儿（7．25％）、中至重度妊娠高血压综合征（6．25％）。结论剖宫产率的上升不只是一个纯医学问题，社会因素使剖宫产指征相对扩大，只有合理掌握剖宫产指征，通过医患双方、社会的共同努力，才能更好地降低剖宫产率。     

胃癌组织中P16、Cyclin D1、Rb表达及其生物学行为的研究

目的研究P16、Cyclin、D1Rb基因在胃癌中的表达及其与胃癌生物学行为的关系.方法采用免疫组化方法检测10例正常胃黏膜、30例胃癌组织中P16、Cyclin D1、Rb蛋白的表达,并结合其临床资料进行分析.结果P16、Cyclin D1、Rb蛋白阳性表达,正常胃粘膜分别为90%、10%、90%;胃癌分别为36.67%、53.33%、50%,胃癌纽与正常对照组间差异均有显著性(P＜0.05),P16、Cyclin D1蛋白与胃癌分化程度、淋巴结转移与否、远处转移与否呈一定的相关性.结论P16、Cyclin D1、Rb基因与胃癌发生有关,P16、Cyclinp蛋白检测有助于胃癌预后的判断.