V180I mutation of the prion protein gene associated with atypical PrP glycosylation

A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the two N-glycosylation sites of the cellular prion protein (PrP^C). Western blot analysis revealed accumulation in the brain of the pathogenic proteinase K-resistant PrP (PrP^Sc) isoform with the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrP^Sc was not due to the mutation at position 180. These results suggest that the diglycosylated form of the mutant PrP^180I prevents its conversion into the pathogenic mutant form PrP^Sc180I, supporting a central role of N-linked glycan chains in the PrP conversion process.     

What and where in human audition: selective deficits following focal hemispheric lesions

A sound that we hear in a natural setting allows us to identify the sound source and localize it in space. The two aspects can be disrupted independently as shown in a study of 15 patients with focal right-hemispheric lesions. Four patients were normal in sound recognition but severely impaired in sound localization, whereas three other patients had difficulties in recognizing sounds but localized them well. The lesions involved the inferior parietal and frontal cortices, and the superior temporal gyrus in patients with selective sound localization deficit; and the temporal pole and anterior part of the fusiform, inferior and middle temporal gyri in patients with selective recognition deficit. These results suggest separate cortical processing pathways for auditory recognition and localization. Electronic Publication     

Monosomy 9q and trisomy 16q in a case of congenital solitary infantile myofibromatosis

Although infantile myofibromatosis (IM) is the most common fibrous proliferation of infancy, many aspects of this benign lesion have not been explored. IM histogenesis is still poorly understood, despite immunohistochemical staining and ultrastructural features that suggest a myofibroblastic origin. IM diagnosis is often made difficult by the predominance of small primitive spindle cells over myofibrobasts and the presence of intravascular growth. Genetic information is scarce, with only one karyotyped case. Here we describe a case of solitary IM discovered at birth in an otherwise healthy girl. The tumor was well circumscribed, arranged in nodules and made up of ovoid cells without atypia, in a myxoid background. Immunohistochemical evaluation indicated a myofibroblastic differentiation. The cytogenetic and fluorescence in situ hybridization analyses revealed an abnormal chromosome 9, derived from an unbalanced whole-arm translocation between chromosomes 9 and 16. On both chromosomes, the breakpoints were located in the pericentric heterochromatic region. This clonal abnormality has not been reported in other tumors and is different from the chromosome 6q deletion reported in the single previous reported IM karyotype.     

CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding

Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled receptors characterized by a large, extracellular N-terminal domain comprising the glutamate-binding site. In the current study, we examined the pharmacological profile and site of action of the non-amino-acid antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt). CPCCOEt selectively inhibited glutamate-induced increases in intracellular calcium at human mGluR1b (hmGluR1b) with an apparent IC50 of 6.5 microM while having no agonist or antagonist activity at hmGluR2, -4a, -5a, -7b, and -8a up to 100 microM. Schild analysis indicated that CPCCOEt acts in a noncompetitive manner by decreasing the efficacy of glutamate-stimulated phosphoinositide hydrolysis without affecting the EC50 value or Hill coefficient of glutamate. Similarly, CPCCOEt did not displace [3H]glutamate binding to membranes prepared from mGluR1a-expressing cells. To elucidate the site of action, we systematically exchanged segments and single amino acids between hmGluR1b and the related subtype, hmGluR5a. Substitution of Thr815 and Ala818, located at the extracellular surface of transmembrane segment VII, with the homologous amino acids of hmGluR5a eliminated CPCCOEt inhibition of hmGluR1b. In contrast, introduction of Thr815 and Ala818 at the homologous positions of hmGluR5a conferred complete inhibition by CPCCOEt (IC50 = 6.6 microM), i.e., a gain of function. These data suggest that CPCCOEt represents a novel class of G protein-coupled receptor antagonists inhibiting receptor signaling without affecting ligand binding. We propose that the interaction of CPCCOEt with Thr815 and Ala818 of mGluR1 disrupts receptor activation by inhibiting an intramolecular interaction between the agonist-bound extracellular domain and the transmembrane domain.     

VEGF,PDGF和MVD在喉癌中的表达及临床意义

目的 探讨血管内皮生长因子(vascular endothelial growth factor,VEGF),血小板来源的内皮生长因子(platelet-derived endothelial growth factor,PDGF),Ⅷ因子测定的微血管密度(microvessel density,MVD)与喉癌微血管生成、临床分期和病理分级的关系。方法 应用免疫组织化学LASB法检测1998～1999年40例喉鳞状细胞癌和11例喉正常粘膜VEGF、PDGF、微血管密度的表达情况,结合临床相关因素进行统计分析。结果 喉鳞状细胞癌中VEGF表达在肿瘤T分级、临床分期、淋巴结转移和病理分级中有统计学意义(P<0.05)。PDGF计数标识指数与病人肿瘤T分级、临床分期中差异有统计学意义(P<0.05)。MVD测定均数在早、晚期分组中有统计学意义(P<0.05)。结论 喉癌的发展、侵袭需要持续的新生血管,本实验提示肿瘤增殖与理论相符,VEGF、PDGF和MVD可作为临床预测重要参考指标。     

眼镜蛇毒的化学成分研究进展

眼镜蛇毒具有广泛的生物学活性。文章综述了近年来眼镜蛇毒中研究较为深入的一些组分的分离提纯、理化性质及其生物活性等方面的研究进展。     

喉癌、下咽癌颈廓清组织中转移淋巴结的分布研究

对54侧经临床检查或／和CT扫描确诊为有淋巴结转移而行预廓清的标本进行病理学观察，发现：喉癌、下咽癌淋巴结转移有一定规律可循，即LevelⅡ、Ⅲ有较高的转移率，LevelⅣ、Ⅵ的发生率较低，而LevelⅠ、LevelⅤ很少发生转移。提示：喉癌、下咽癌病人的颈廓清的施术应在颈LevelⅡ～Ⅳ廓清的同时行同侧甲状腺侧叶的切除以将颈中器官周围淋巴结清扫彻底。对LevelⅠ，LevelⅤ的清扫应在临床触诊、CT检查的证实下或术中发现转移时方可进行．以减少颈廓清手术范围、手术时间和术后并发症的发生。     

自身免疫性感音神经性聋的内耳代谢与电生理研究

为探讨自身免疫性感音神经性聋（ＡＳＨＬ）的内耳病理生理学机制，采用听觉电生理技术和酶组织化学方法，观察ＡＳＨＬ模型动物的内耳生理功能与组织内主要酶活性的变化。结果示：听视经复合动作电位和耳蜗微音器电位阈值明显升高，内淋巴电位（包括负相）幅值均有不同程度的降低，并与血管纹和内淋巴囊局部组织内Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶和琥珀酸脱氢酶活性改变之间的相关性。表明自身免疫性内耳损伤，进而造成组织内相关酶代谢