Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor

Unlike Mycobacterium leprae, Mycobacterium tuberculosis is not found inside cells other than macrophages and polymorphonuclear cells in vivo, yet previous work has revealed that in vitro it readily enters all cell lines tested. Moreover, these cells are not killed by the intracellular mycobacteria. We report here that when fibroblasts take up live (but not killed) M. tuberculosis H37Rv, they develop greatly increased sensitivity to the toxic effects of tumor necrosis factor (TNF) whether the cell line is inherently sensitive to TNF or not. Ultrasonically disrupted M. tuberculosis also has this property. The increased sensitivity is seen in the absence of metabolic inhibitors, although addition of emetine, an inhibitor of protein synthesis, causes the effect to manifest itself earlier and at a lower concentration of TNF. In contrast, infection with Mycobacterium bovis bacillus Calmette-Guérin induces little or no increased sensitivity to TNF, whereas Mycobacterium avium and M. tuberculosis H37Ra have intermediate sensitivities. We discuss the possibility that virulent tuberculosis strains produce a factor which distorts the normal protective function of TNF, rendering it toxic to host tissues and leading to the classical immunopathology of tuberculous lesions.     

A comparison of dementia in Alzheimer's disease and multiple sclerosis

We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions.     

个体化下肢小腿假肢接受腔设计的生物力学评价技术研究

作为传递体重、固定假肢的部件 ,接受腔对于小腿假肢使用的舒适性和方便程度有决定性的作用。本研究建立了基于有限元应力分析的小腿假肢生物力学评价技术平台 ,实现了小腿残端 /接受腔 3D几何建模与信息交互、三维有限元自动建模及应力分析。 3D模型与信息交互的实现基于得到广泛支持的OpenGL技术 ,有限元模型的构建采用了专门针对小腿残端 /接受腔结构特点的自动建模方法 ,通过构建档案数据库系统作为整个系统的操作平台。该技术平台可与现有的CAD/CAM系统相结合 ,为接受腔的个体化设计提供生物力学定量化依据。其临床应用将改善传统的设计流程 ,提高设计效率。同时 ,它也是未来构建接受腔设计专家 /智能系统的基础。     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

碱离子水饮用后血小板聚集率的的变化(附30例报告)

目的:报告30例饮用豪斯牌碱离子水前、后血小板聚集率的变化。方法:饮用碱离子水前、后(2～3月,>3～6月)作比浊法血小板聚集试验,以1分钟、5分钟及5分钟内最大聚集率(Max％)为指标,同时检测部分血粘度指标及凝血因子,并用自动生化仪检测血糖、血脂、主要电解质及部分肝、肾功能。结果:饮碱离子水后,血小板聚集率明显下降,而以疾病组(Max>80％)下降尤为明显,P均<0.001。饮碱离子水后血小板聚集率的下降,部分可能与损伤的血管内皮得到修复有关。主要电解质及部分肝、肾功能无明显异常改变。结论:由于心、脑血管血栓性疾病患者血小板聚集率多明显升高,饮碱离子水后血小板聚集率明显下降,且长期饮用对主要电解质及部分肝、肾功能无明显异常改变,作者认为碱离子水使用方例、安全、有效、价廉,因而对心、脑血管血栓性疾病防治方面可能是一种积极的辅助方法,值得临床进一步探索。     

Dendritic cell based vaccination strategy: an evolving paradigm

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p?<?0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p?=?0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r?=?0.418 and p?=?0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.     

Geriatric Treatment Center: a contemporary model for collaboration between psychiatry and neurology

The diagnosis and treatment of individuals with problems involving both psychiatry and neurology have become more sophisticated in recent years, but these advances may be difficult to implement in the modern health care environment. For 16 years, an inpatient Geriatric Treatment Center within a state mental hospital has been used to diagnose and treat older persons with complex neuropsychiatric disorders. Eight illustrative cases are presented of patients with major behavioral dysfunction that could not be managed effectively in other health care facilities. After neuropsychiatric evaluation and behavioral neurology consultation, all had neurologic diagnoses established as the cause of their presentation. Seven improved with appropriate treatment, of whom one could return to independent living, and the eighth died and had an autopsy diagnosis of his disease at a nearby academic medical center. This series highlights the value of collaboration between psychiatry and neurology for evaluation and treatment of older patients with neuropsychiatric problems not easily accommodated by many existing health care settings.