脂蛋白对实验变态反应性脑脊髓炎的阻断研究

腹腔注射脂蛋白（ＰＬＰ）进行免疫耐受诱导，可保护小鼠既不发生ＰＬＰ引起的主动性实验变态反应性脑脊髓炎（ＥＡＥ）又不发生ＰＬＰ特异性淋巴细胞引起的被动性ＥＡＥ。提示在ＥＡＥ发病过程中，ＰＬＰ较髓鞘硷性蛋白（ＭＢＰ）更具作用。免疫耐受的机理可能为非胸腺依赖性且与非特异性免疫有一定关系。     

Subsets of lymphoid cells in blood and thymus in myasthenia gravis : Monoclonal Antibody Analysis

Lymphoid cell subpopulations in peripheral blood and thymus were analyzed in patients with myasthenia gravis (MG) using monoclonal antibodies. The proportion of lymphocytes of T lineage (OKT 3 +, OKT 4 +, OKT 8 + cells) in peripheral blood of 11 MG patients, was significantly decreased in comparison with controls, but the ratio of OKT 4+/OKT 8+ cells was not different. Thymus cells were studied in 9 patients. The percentage of OKIa 1 + cells was significantly higher in MG thymus than in control thymus (P < 0.0005). There were no significant differences in the proportions of T lymphocyte subsets between MG and control thymuses.     

Humoral immune responses to myelin basic protein, cerebroside and ganglioside in chronic relapsing experimental allergic encephalomyelitis of the guinea pig

Titers of serum antibodies to myelin basic protein, cerebroside and ganglioside were determined in chronic relapsing experimental allergic encephalomyelitis in strain 13 guinea pigs at various intervals after inoculation with whole central nervous system (CNS) tissue. Levels of antibodies to cerebroside and ganglioside were higher in the animals with paralysis than those without paralysis during the early chronic stage. In the late chronic stage, these antibodies were still at high levels, but none of the levels correlated with clinical activity. Levels of antibody to cerebroside were significantly related to the amount of demyelination. The humoral response to the CNS antigens was monophasic, although the clinical course was polyphasic. Another factor seems to be required for clinical relapses in this animal model.     

Activation of effector cells of experimental allergic encephalomyelitis in Lewis rats: comparison of T-cell lines with primary cultured lymph node cells

We studied the mechanism of activation of effector cells in experimental allergic encephalomyelitis (EAE) by using T-cell lines (EAE/TL) reactive against guinea pig myelin basic protein generated from in vivo primed lymph node cells (LNC) of Lewis rats. EAE-effector cells are activated in the presence of a specific antigen and antigen-presenting cells (APC) with a compatible Ia antigen. The antigen presentation occurs during the first 18 h. EAE-effector cells cannot be activated by allogeneic stimulator cells, but a nonspecific T-cell mitogen, concanavalin A, can activate the effector cells in the presence of syngeneic as well as allogeneic APC.     

The prognostic significance of cell cycle markers in esophageal cancer after neoadjuvant chemotherapy

Proliferating cell nuclear antigen (PCNA), p27 and cyclin A were analyzed by immunohistochemistry in 89 patients (untreated control n = 40, neoadjuvant chemotherapy n = 49) with esophageal cancer invading the submucosal lesion. The mitotic index (MI) was calculated as the percentage of mitotic cells. In control subjects, the mean PCNA, p27, cyclin A and MI were, respectively, 60.4%, 18.0%, 19.9% and 1.7%; in the chemotherapy group, these values were 46.8%, 15.1%, 18.0% and 1.2% respectively. Neoadjuvant chemotherapy decreased PCNA and the MI significantly. As prognostic indicators, PCNA and the MI were significant in control subjects and p27 and cyclin A were significant in the chemotherapy group. Using multivariate analysis, p27 was a prognostic factor in both groups and cyclin A was prognostic only in the chemotherapy group. Although PCNA and the MI were useful growth and prognostic markers in untreated control subjects, their significance was lost after neoadjuvant chemotherapy. p27 and cyclin A were determined to be significant markers in the neoadjuvant chemotherapy group, especially p27, which was independent in both groups.     

Sendai virus vector-mediated brain-derived neurotrophic factor expression ameliorates memory deficits and synaptic degeneration in a transgenic mouse model of Alzheimer's disease

Growing evidence suggests that decreased brain-derived neurotrophic factor (BDNF) levels are associated with Alzheimer's disease (AD) pathogenesis. Therefore, BDNF gene therapy is considered to be a promising therapeutic strategy for treating AD. Sendai virus (SeV) is a type I parainfluenza virus that does not interact with host chromosomes because of its strict cytoplasmic life cycle. Although SeV is nonpathogenic in primates, including humans, its infectivity for neurons is strong. Here we demonstrate that SeV vectors effectively infected neurons, even though they were injected into subcortical white matter. Moreover, SeV vectors significantly induced BDNF expression, ameliorating synaptic degeneration and memory deficits in a transgenic mouse model of AD (Tg2576). This is the first study to demonstrate that viral vector administration in white matter is sufficient to restore cognitive function in vivo. These results also support the feasibility of using SeV vectors for gene therapy targeting the brain.