Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

猪尾导管连接化疗药盒实现肝脏肿瘤多重化疗的可行性研究

目的 探讨使用猪尾造影导管与单一化疗药盒连接实现肝脏肿瘤多重化疗的可行性及初步疗效。资料与方法 对30例晚期肝脏恶性肿瘤患者采用经股动脉穿刺、腹腔动脉内植入猪尾导管与皮下埋置药盒并序贯化疗，统计手术成功率、并发症及临床疗效。结果 30例手术全部成功，发生切口延迟愈合1例。术后随访28例，经影像学复查对比，病变缩小7例，稳定12例，进展9例。随访期间12例患者死亡，术后生存期42d-10个月，中位生存期6个月。另外16例患者至今存活，已达术后2-16个月。结论 采用猪尾造影导管置于腹腔动脉并与化疗药盒相连接，能够对晚期肝脏恶性肿瘤实现多重化疗，技术上简单可行，并发症少，初步疗效令人满意。     

Occurrence of thyroid autoimmunity in relapsing remitting multiple sclerosis patients undergoing interferon-β treatment

We analyzed the titer of antithyroid autoantibodies Abs) and thyroid function in 17 multiple sclerosis (MS) patients undergoing interferon-β (IFN-β) treatment and in 40 MS control patients. Basal evaluation revealed normal thyroid function in all patients. Abs were detected in 5 IFN-β-treated patients (29%) and in 4 MS control patients (10%). Our results indicate that IFN-β treatment may lead to thyroid autoimmunity. We therefore recommend periodic evaluations of antithyroid Abs and thyroid functionality in IFN-β-treated MS patients.     

Intracranial plasmacytoma: a case report

Multiple myeloma may have extraosseous manifestations in the cranial region. It may be a solitary intracranial tumour without any other signs of multiple myeloma, or intracranial disease may be a part of generalised disease, as in the present case. Our patient had received chemotherapy for multiple myeloma for 9 months, with good response. However, her condition suddenly deteriorated, with signs of increased intracranial pressure and a 5-cm-diameter tumour infiltrating the meninges and brain was found in the left temporal fossa. The radiological diagnosis, based on contrast-enhanced CT and angiography, was not straightforward or specific for plasmacytoma, as chemotherapy for the extracranial disease had been successful. Diseases such as meningioma, metastasis, lymphoma, chondrosarcoma or haemangioma had to be considered. Received: 1 November 1994 Accepted: 31 August 1995     

High resolution nuclear magnetic resonance imaging of the spinal cord in experimental demyelinating disease

Summary Chronic recurrent experimental allergic encephalomyelitis was induced in a strain 13 guinea pig by inoculation of isologous spinal cord homogenate. The spinal cord was obtained after perfusion with 4% paraformaldehyde and examined with nuclear magnetic resonance (NMR) imaging. Proton NMR spin echo images (repetition time: 3 s; echo times: 20 and 60 ms) were obtained from intact, isolated spinal cord in a 4.7 Tesla, 50 mm bore magnet. The slice thickness of the images was 380 m and the inplane resolution was 40×40 m. The images showed superficial areas of low signal intensity in the lateroventral regions of the white matter, in some instances with a seam of higher signal intensity. Neuropathologically, these abnormalities corresponded exactly to areas of demyelination. Control images did not show these abnormalities. The present high resolution imaging allowed a correlation between demyelination and abnormal NMR signals in a small laboratory animal with an inflammatory demyelinating disease.Supported by the Belgian Foundation of Medical Scientific Research (FGWO, grant 3.0096.86 and grant 3.0019.86), by the Institute for the promotion of Scientific Research in Industry and Agriculture (IWONL) and by the Scientic Research Planning Office of the Belgian Government (DPWB), contract no. 87/92-120     

产科多器官功能障碍综合征临床分析

目的探讨产科多器功能障碍综合征（MODS）的诱因、临床诊断及处理。方法对16例MODS的临床资料进行回顾性分析。结果导致MODS的主要因素为妊娠期高血压疾病及产后出血,器官功能障碍以肾功能衰竭为最多见。结论及时处理MODS的诱发因素,积极治疗妊娠期高血压疾病及产后出血,早期诊断及治疗肾功能衰竭及凝血功能障碍,是减少产科MODS患者死亡的关键。     

The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system white matter. The association of the disease with MHC genes, the inflammatory white matter infiltrates, similarities with animal models, and the observation that MS can be treated with immunomodulatory and immunosuppressive therapies support the hypothesis that autoimmunity plays a major role in the disease pathology. Evidence supports activated CD4⁺ myelin-reactive T cells as major mediators of the disease. In addition, a renewed interest in the possible contribution of B cells to MS immunopathology has been sparked by nonhuman primate and MS pathological studies. This review focuses on the immunopathology of MS, outlining the hypothetical steps of tolerance breakdown and the molecules that play a role in the migration of autoreactive cells to the CNS. Particular focus is given to autoreactive T cells and cytokines as well as B cells and autoantibodies and their role in CNS pathogenesis in MS.     

Fine-needle aspiration biopsy of multiple myeloma in a patient with renal-cell carcinoma: A case report

A case of multiple myeloma diagnosed by fine-needle aspiration (FNA) biopsy and confirmed by laboratory studies in a patient with a history of renal-cell carcinoma is presented. The patient was diagnosed with renal-cell carcinoma of the right kidney and a radical nephrectomy was performed. Eighteen months after this diagnosis was made, the patient developed chest wall pain and was found to have osteolytic bone lesions of the ribs and vertebral bodies. FNA of an osteolytic rib lesion disclosed multiple myeloma. Additional laboratory studies confirmed the diagnosis of multiple myeloma. This case report demonstrates the value of FNA as a diagnostic tool for the follow-up of cancer patients, the subsequent discrimination between metatastic lesions and a second primary malignancy, and the cytology of multiple myeloma.     

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.     

Peak Identification in Visual Evoked Potentials

Waveform patterns evoked by 4 intensities of flash in normal subjects were studied in relation to intersubject variability. Time-frequency distribution curves of all peaks occurring between 11 and 280 msec after flash onset and meeting minimal criteria were obtained from 46 males. These distributions closely corresponded to similar data reported by others for single intensity stimulation. An algorithm was developed which identified in 67 to 100% of instances a single “peak event’ within the time ranges of each of 6 peak distributions. Many peak events appeared and disappeared within the 4 intensity sets of individuals. Latencies were obtained for these peak events. Application of the algorithm to a replicate sample of 29 Ss, which included 8 females, indicated generalizability. Test-retest data on 15 Ss showed its reliability. The data suggest that methodology significantly contributes to the variability of peak identification among subjects. This may be reduced by employing multiple intensities of stimulation.