The effects of tibial rotation on patellar position

The effects of external and internal tibial rotation on patellar motion were investigated using a magnetic 3Space^® tracker system (Polhemus, Colchester, VT 05446, USA). Seven fresh-frozen adult cadaver knees were used in this study. The muscle alignment of each quadriceps muscle was measured to determine the direction of loading forces. Three loading patterns were used to simulate the unresisted knee extension during sitting, standing from squatting and the stance phase of walking, with different weights applied to each quadriceps muscle at each knee flexion angle. The position of the patella, along with patellar shift, tilt and rotation was measured and compared to external or internal tibial rotation and neutral rotation. In the sitting and squatting simulations the patella showed at the terminal extension of the knee more lateral shift and a more lateral tilt with tibial external rotation than in a neutral position (P < 0.05). In walking simulation, the patella showed more external rotation with external rotation of the tibia than with a neutral one, at the 0, 72 and 90% of the stance phase of walking (P < 0.05). These results demonstrate the importance of external tibial rotation as a factor in the development of patellar dislocations or subluxations, especially in athletes.     

Antibodies to acetylcholine receptors in myasthenia gravis. In vitro synthesis by peripheral blood lymphocytes before and after thymectomy.

Pokeweed mitogen (PWM)-driven in vitro synthesis of antibodies to the acetylcholine receptor (PSA) was studied in non-thymoma patients with myasthenia gravis. In a group of 46 patients, the occurrence of PSA was related to the presence of the thymus or, in operated patients, the absence of a clinical effect of thymectomy. Sixteen patients were followed before and soon after thymectomy. PSA disappeared in all patients, at least temporarily, between 6 weeks and 1 year afterwards, independent of the clinical course and eventual clinical effect of the operation. A recurrence was found only in one of the five patients who derived no benefit from the operation. These findings support the hypothesis that the therapeutic effect of thymectomy can be explained by removal of a source of autoreactive lymphocytes. There was no correlation between the changes in serum levels of a-AChR and clinical improvement, suggesting a minor role of circulating peripheral blood lymphocytes (PBL) and the thymus in the total production of a-AChR.     

Detection of numerical alterations of chromosome 1 in cytopathological specimens of breast tumors by chromogen in situ hybridization

To investigate the effectiveness of chromogen in situ hybridization (CISH) in the diagnosis of breast tumors, numerical alterations of chromosome 1 were examined by CISH and fluorescence in situ hybridization (FISH) methods, and the presence of der(16)t(1;16) was also examined by FISH in imprinted cytology specimens from resected tissues of 14 carcinomas and five non-malignant lesions. The modal signal counts of chromosome 1 were compared between the specimens processed by CISH and FISH for each case. Aneusomies of the long arm of chromosome 1 were detected in 10 (71%) carcinomas as the major clones by both methods. In addition, one atypical papilloma demonstrated tetrasomy of 1q12 as a major clone by CISH, but such a clone was at first overlooked by FISH. Four other benign lesions showed disomic 1q12 signals as a major clone by both CISH and FISH. As additional information from FISH, eight cancers showed structural or numerical alterations of chromosome 16, and four showed der(16)t(1;16). In total, 10 carcinomas showed chromosome 16 alterations, and all of these overlapped with the carcinomas with 1q12 aneusomies. The CISH method provided almost the same results as the FISH method, and both methods were considered applicable in supportive diagnosis of cytological specimens of breast tumors. In addition, the CISH method was superior in the detection of numerical alterations in carcinoma cells by referring to the morphology of cells and in the detection of significant clones which might be missed under dark-field microscopy.     

Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes

Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs, on average one per 3 cM, spaced over the entire human genome. By fluorescence in situ hybridisation (FISH), we have performed a systematic search for YACs spanning translocation breakpoints. Patients with DBCRs and either syndromic or non-syndromic mental retardation (MR) were ascertained through the Mendelian Cytogenetics Network (MCN), a collaborative effort of, at present, 270 cytogenetic laboratories throughout the world. In this pilot study, we have characterised 10 different MR associated chromosome regions delineating candidate regions for MR. Five of these regions are narrowed to breakpoint spanning YACs, three of which are located on chromosomes 13q21, 13q22, and 13q32, respectively, one on chromosome 4p14, and one on 6q25. In two out of six DBCRs, we found cytogenetically cryptic deletions of 3-5 Mb on one or both translocation chromosomes. Thus, cryptic deletions may be an important cause of disease in seemingly balanced chromosome rearrangements that are associated with a disease phenotype. Our region specific FISH probes, which are available to MCN members, can be a powerful tool in clinical cytogenetics and positional cloning.     

Keratin proteins and carcinoembryonic antigen in synovial sarcomas: an immunohistochemical study of 24 cases

Twenty-four synovial sarcomas were examined for the presence of keratin proteins by an indirect immunoperoxidase method with paraffin-embedded tissues. Keratin proteins were identified in 16 of 24 cases (67 per cent). Both the pseudoglandular and spindle cell areas of all eight of the biphasic synovial sarcomas and the spindle cells of eight of the 16 monophasic synovial sarcomas contained keratin proteins. In spindle cell areas, staining was observed in single cells and small cords and clusters of cells in the absence of cleft formation or other evidence of a pseudoglandular component. The predominant cytologic staining pattern in all cases was peripheral, with localization of staining to the cell membrane or adjacent areas, but diffuse and focal cytoplasmic staining patterns were also observed. No staining for keratin proteins was seen in 101 control cases, including 52 sarcomas of various types. Carcinoembryonic antigen was also identified in four of the 24 synovial sarcomas by an indirect immunoperoxidase technique. The identification of keratin proteins may be helpful in the pathologic diagnosis of synovial sarcoma, particularly the spindle cell monophasic variant.     

Effect of atropine on the bronchial response of asthmatic subjects to the inhalation of ultrasonically nebulized distilled water

To determine whether atropine provides protection against the bronchoconstriction that develops in asthmatic subjects after inhalation of ultrasonically nebulized distilled water, we exposed six asthmatic patients to this stimulus with and without pretreatment with atropine (0.04 mg/kg). The mean FEV1 decreased from 3.32 to 2.39 L (-28%) without and from 3.49 to 3.18 L (-9%) with atropine. This protective effect was statistically significant (p less than 0.05), suggesting that cholinergic pathways are involved in the obstructive response to the inhalation of ultrasonically nebulized distilled water.     

Type-specific evolution of amyloid plaque and angiopathy in APPsw mice

To clarify how Aβ deposits start in the brain, we examined the early to late stages of senile plaques and amyloid angiopathy in APPsw mice. All types of human senile plaques were observed in the mouse brains. The premature forms of cored plaques appeared first in the cerebral cortex of mice at 7–8 months old. Then, amyloid angiopathy emerged, followed by diffuse plaques consisting of Aβ1–42. Modifications of the N-terminus of Aβ were late phase phenomena. The premature forms of cored plaques were composed of central Aβ1–40 amyloid cores, surrounding amorphous Aβ1–42 deposits, and accumulation of Aβ1–42 in some peripheral cells. These cells were incorporated in amyloid cores, and these plaques developed to large cored plaques composed of Aβ1–40 and Aβ1–42. The size and number of cored plaques were increased with age. These findings indicate different evolution paths for cored plaques and diffuse plaques, and suggest the presence of a pathway that initiates with the intracellular accumulation of Aβ1–42 and leads to the development of classic plaques in human brain tissues.     

线粒体DNA与人宫颈细胞癌变的关系

目的探讨线粒体DNA与人宫颈细胞癌变的关系.方法采用PCR方法制备地高辛标记的3条人mtDNA探针,对一株人宫颈癌Hela细胞系、1例原代培养人皮肤成纤维细胞和24例子宫颈癌患者的活检癌组织及癌旁宫颈组织的染色体或间期细胞核进行了荧光原位杂交分析.结果 3条mtDNA探针在原代培养人皮肤成纤维细胞染色体或间期核中均未出现阳性杂交信号;而在人宫颈癌Hela细胞和24例肿瘤组织标本的部分染色体或间期细胞核中均出现了阳性杂交信号.而在癌旁组织的部分染色体或间期细胞核中虽也出现了阳性杂交信号.但与肿瘤组织标本相比有显著性差异.结论表明癌细胞核基因组中存在mtDNA的同源序列,这些同源片段的出现可能与细胞癌变有关.     

FAS and FAS-L expression by tumor cells and lymphocytes in breast carcinomas and their lymph node metastases

FAS receptor (FAS, CD95) and FAS ligand (FAS-L, CD95-L) are complementary members of a particular apoptotic pathway that plays a major role in immune regulation. The activation of FAS-L may trigger cytotoxic mechanisms leading to the death of FAS-expressing cells. Tumor cells and tumor-infiltrating lymphocytes (TIL) may express FAS and FAS-L in various proportions, and their interplay may affect tumor behavior. In the present study, we explored the expression of FAS and FAS-L in 28 mammary carcinomas (19 ductal and 9 lobular) and in their lymph node metastases. The expression of these mediators in immunostained sections was graded and evaluated comparatively between normal and neoplastic mammary epithelium, between tumor cells and TILs, and between mammary carcinoma cells and their lymph node metastases. We demonstrated the coexpression of FAS and FAS-L by breast carcinoma cells and TIL, with FAS expressed more strongly by normal epithelial cells and TIL than tumor cells. FAS-L was better stained on tumor cells than on TIL. There was equal or greater expression of FAS and FAS-L in the primary tumors and their TIL than in the metastatic counterparts. Comparing the expression of FAS with that of FAS-L, we recorded FAS equal or stronger than FAS-L in the primary mammary tumors and the reversal of their expression, FAS-L greater than FAS in the lymph node metastases. These results are consistent with reports of studies with other tumors, suggesting that the upregulated FAS-L indicates an increased ability of tumor cells to induce apoptosis in TIL and in the normal tissues invaded. However, it is understood that the FAS/FAS-L system, although essential for apoptosis, is only a contributing factor to the complex process of tumor invasion and antitumor defense.     

新型抗蝰蛇毒血清对不同喹蛇毒作用的实验研究

目的　探讨新型抗蝰蛇毒血清对国产圆斑蝰蛇毒及缅甸蝰蛇毒的作用 .方法　采用免疫电泳、SDS -聚丙烯酰胺电泳及动物实验等方法 .结果　国产圆斑蝰蛇毒的LD50 (腹腔注射 )为 0 .3 0 6± 0 .0 0 3mg/kg ,缅甸蝰蛇毒的LD50 (腹腔注射 )为 0 .2 90± 0 .0 0 3mg/kg .免疫电泳结果表明国产圆斑蝰蛇毒和缅甸蝰蛇毒均和新型抗蝰蛇毒血清产生明显的免疫沉淀线 .体外中和实验表明抗蝰蛇毒血清对国产圆斑蝰蛇毒的中和抗体效价为 2 75 0 μg/ml(约45 0LD50 ) ,对缅甸蝰蛇毒的中和抗体效价为 2 490 μg/ml(约 43 0LD50 ) .体内保护实验表明给予 0 .0 5ml抗蝰蛇毒血清可抵御 2 5 4μg(约41 5LD50 )国产圆斑蝰蛇毒或 116μg(约 2 0LD50 )缅甸蝰蛇毒的攻击 ,使小鼠全部存活 .结论　新型抗蝰蛇毒血清对国产圆斑蝰蛇毒及缅甸蝰蛇毒的中和抗体效价均较高 ,有较大的应用价值 .