大鼠肝内移植肿瘤与肥大细胞关系的形态学研究

目的：研究大鼠肝内移植肿瘤与其周边肥大细胞的关系。方法：建立40只雄性Wistar大鼠肝内移植肿瘤模型，运用HE染色，肥大细胞（mast cell，MC）Alcian blue特殊染色，苦味酸-天狼猩红染色和电镜等技术，观察移植肿瘤肝组织的形态学改变，肿瘤周边浸润MC的数量以及MC与肿瘤组织的关系，8只正常大鼠为对照组。结果：肿瘤组织周边部分肝细胞形态学异常；肝组织内胶原纤维增生，主要为Ⅰ型和Ⅲ型胶原，并包绕肿瘤组织，肿瘤周边MC浸润，并沿胶原纤维分布，不同大鼠其肿瘤周边MC数量不一，有的差异明显。超微结构观察显示MC通过多个接触点与肿瘤细胞紧密相连，并释放胞质颗粒内容物，导致肿瘤细胞崩解。结论：MC与肿瘤组织有着非常密切的关系，MC可能通过多种途径直接和间接地发挥抗肿瘤作用。     

通痹灵对于IL-2及其受体α链影响的体内外研究

从体内体外两个方面 ,研究通痹灵对于CIA大鼠关节滑膜原代细胞分泌IL 2 ,以及通痹灵总碱对于IL 2受体α链CD2 5表达的影响。体内实验采用CIA大鼠动物模型。容积法测量足肿胀度 ,原代滑膜细胞培养、放免法检测培养液上清 ,观察通痹灵对滑膜内IL 2的影响 ;体外实验 ,分离大鼠淋巴细胞 ,佛波醇酯 (PDB )或刀豆蛋白 (ConA )体外刺激 ,双色免疫荧光标记 ,流式细胞仪检测 ,观察通痹灵总碱对CD3+CD2 5 +表达的影响。结果是体内实验 ,通痹灵高剂量可明显减轻CIA大鼠的足肿胀度 ,与MTX比较无显著性差异 (P >0 0 5 ) ,通痹灵高、低剂量可明显抑制CIA大鼠滑膜内IL 2的合成 (P <0 0 1) ;体外实验 ,通痹灵总碱显著抑制ConA刺激下的CD3+CD2 5 +的表达 ,而对PDB加ionomycin没有明显作用。提示通痹灵可以通过抑制IL 2合成及ConA激活的IL 2受体α链CD2 5信号转导通路 ,减轻局部关节的炎症 ,为其用于类风湿性关节炎的治疗提供了实验依据     

人成纤维细胞在裸鼠体内生长和胶原分泌的观察

目的观察人成纤维细胞注射移植后是否在裸鼠体内增殖并分泌胶原。方法将经原代培养的2×1010L-1人成纤维细胞1mL注射于BALB/CNU裸鼠真皮内,于1、2和3个月处死取材,行HE和Ⅰ、Ⅲ型胶原免疫组化染色。结果在1、2和3个月时可以观察到人成纤维细胞在裸鼠体内呈分裂象,随着时间的推移细胞外基质Ⅰ、Ⅲ型胶原分泌量呈增多趋势。结论人成纤维细胞注射移植裸鼠后,能够自行分裂、增殖并分泌人Ⅰ、Ⅲ型胶原,为自体成纤维细胞作为移植材料,发挥充填功能的持久性提供了理论依据。     

Vestibular and audiological findings in the Alport syndrome

Alport syndrome (AS) is caused by mutations in collagen IV, which is widespread in the basement membranes of many organs, including the kidneys, eyes, and ears. Whereas the effects of collagen IV changes in the cochlea are well known, no changes have been described in the posterior labyrinth. The aim of this study was to investigate both the auditory and the vestibular function of a group of individuals with AS. Seventeen patients, aged 9–52, underwent audiological tests including pure‐tone and speech audiometry, immittance test and otoacoustic emissions and vestibular tests including video head impulse test, rotatory test, and vestibular evoked myogenic potentials. Hearing loss affected 25% of the males and 27.3% of the females with X‐linked AS. It was sensorineural with a cochlear localization and a variable severity. 50% of the males and 45.4% of the females had a hearing impairment in the high‐frequency range. Otoacoustic emissions were absent in about one‐third of the individuals. A peripheral vestibular dysfunction was present in 75% of the males and 45.4% of the females, with no complaints of vertigo or dizziness. The vestibular impairment was compensated and the vestibulo‐ocular reflex asymmetry was more evident in rotatory tests carried out at lower than higher speeds; a vestibular hypofunction was present in all hearing impaired ears although it was also found in subjects with normal hearing. A posterior labyrinth injury should be hypothesized in AS even when the patient does not manifest hearing disorders or evident signs of renal failure.     

mTOR signaling contributes to chondrocyte differentiation.

The mammalian Target Of Rapamycin (mTOR) is a nutrient-sensing protein kinase that regulates numerous cellular processes. Fetal rat metatarsal explants were used as a physiological model to study the effect of mTOR inhibition on chondrogenesis. Insulin significantly enhanced their growth. Rapamycin significantly diminished this response to insulin through a selective effect on the hypertrophic zone. Cell proliferation (bromodeoxyuridine incorporation) was unaffected by rapamycin. Similar observations were made when rapamycin was injected to embryonic day (E) 19 fetal rats in situ. In the ATDC5 chondrogenic cell line, rapamycin inhibited proteoglycan accumulation and collagen X expression. Rapamycin decreased content of Indian Hedgehog (Ihh), a regulator of chondrocyte differentiation. Addition of Ihh to culture medium reversed the effect of rapamycin. We conclude that modulation of mTOR signaling contributes to chondrocyte differentiation, perhaps through its ability to regulate Ihh. Our findings support the hypothesis that nutrients, acting through mTOR, directly influence chondrocyte differentiation and long bone growth.     

Heritable dentin defects: Nosology,pathology, and treatment

Heritable dentin defects have been divided into 2 main categories: dentinogenesis imperfecta (DI) and dentin dysplasia (DD). Recent studies have shown that they share many features in common. Of the connective tissue diseases, only osteogenesis imperfecta (OI) has been linked to these disorders. So far, no definitive relation between the type of OI and the dental involvement can be established. Familial occurrence of DI with OI cannot be comprehensively explained by mutations in type I collagen genes. No information about the gene defects in DD is available. At the ultrastructural level, the organization of the normally cross-striated collagen fibers in the dentin matrix varies markedly in patients affected by DI.