神经生长因子对局灶性脑缺血神经干细胞巢蛋白表达及细胞类型的影响

目的:实验于2006-02/07在锦州医学院科学实验中心完成。将72只健康SD大鼠按随机数字表法分为假手术组、模型组、神经生长因子治疗组,每组24只。采用Logna等改良法复制大脑中动脉血栓模型,动物清醒2h后进行功能评价,动物神经功能达到2级的纳入实验。假手术组除不进行大脑中动脉线栓外,其余同模型组。神经生长因子治疗组于缺血后立即腹腔注射神经生长因子1000μg/kg,1次/d。于缺血后1,3,7,14d处死动物,运用免疫组化和免疫荧光双标的方法观察神经生长因子对脑缺血后神经干细胞巢蛋白的表达及其细胞类型的影响。结果:72只大鼠均进入结果分析。①神经生长因子治疗组和模型组大脑皮质均可见巢蛋白阳性细胞,细胞呈圆形或椭圆形。与模型组相比,除缺血后1d外,神经生长因子治疗组其他时间点的巢蛋白阳性细胞数均明显高于模型组,两组缺血后各时间点的巢蛋白阳性细胞数均高于假手术组[模型组:(3.47±0.51),(5.13±1.14),(13.95±3.56),(8.97±2.08)个;神经生长因子治疗组:(3.81±0.66),(9.88±2.08),(19.87±3.86),(26.17±2.90)个,假手术组:0,P<0.05,P<0.01]。②模型组和神经生长因子治疗组3d时缺血皮质巢蛋白阳性突起主要与胶质纤维酸性蛋白共存,14d时巢蛋白与神经元特异性烯醇化酶共存明显增多。结论:神经生长因子能增加局灶性脑缺血后巢蛋白的阳性细胞的数目,并促进其分化为神经元和神经胶质细胞。     

Splenectomy in the treatment of severe forms of myasthenia

Translated from Zhurnal Nevropatologii i Psikhiatrii imeni S. S. Korsakova, Vol. 90, No. 9, pp. 6–9, September, 1990.     

OXIDATIVE STRESS AND DIABETIC NEUROPATHY: PATHOPHYSIOLOGICAL MECHANISMS AND TREATMENT PERSPECTIVES

Increased oxidative stress is a mechanism that probably plays a major role in the development of diabetic complications, including peripheral neuropathy. This review summarises recent data from in vitro and in vivo studies that have been performed both to understand this aspect of the pathophysiology of diabetic neuropathy and to develop therapeutic modalities for its prevention or treatment. Extensive animal studies have demonstrated that oxidative stress may be a final common pathway in the development of diabetic neuropathy, and that antioxidants can prevent or reverse hyperglycaemia-induced nerve dysfunction. Most probably, the effects of antioxidants are mediated by correction of nutritive blood flow, although direct effects on endoneurial oxidative state are not excluded. In a limited number of clinical studies, antioxidant drugs including alpha-lipoic acid and vitamin E were found to reduce neuropathic symptoms or to correct nerve conduction velocity. These data are promising, and additional larger studies with alpha-lipoic acid are currently being performed.     

Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation

Eight patients with cutaneous T cell lymphomas (CTCL) and five with various other T cell malignancies were treated with mouse monoclonal antibody (MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour period and resulted in one complete remission (convoluted T cell lymphoma) and one partial remission (CTCL). Remission duration was 6 weeks and 3 months, respectively. Frequent toxicities were pruritus, hives, flushing, and shortness of breath. Supraventricular arrhythmias and blood pressure instability were also observed. Complete targeting of peripheral blood T cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less than 10,000/microL), and free, bioavailable antibody was present at the next (10-mg) dose level. Even higher doses resulted in substantial antibody excess that persisted for as long as 6 weeks. Serum concentrations of MoAb decreased with increasing number of peripheral blood T cells, and 25 to 35 mg of T101 were required for induction of antibody excess in leukemic patients. Excess antibody induced antigenic modulation, which was of consequence only if MoAb excess persisted to the next treatment. In the original treatment, the rapidly administered MoAb was able to target and remove peripheral blood T cells before the development of antigenic modulation. Antimouse antibodies developed in three patients. Their presence rendered further therapy ineffective and was associated with an anaphylactic reaction in one patient. Development of these antibodies could not be predicted by lymphoproliferative assays. In these assays, however, the T101 protein strongly stimulated the mononuclear cells of the patient who reached the only complete remission of this trial. Immunologic stimulation by the MoAb thus might have played a role in this patient's antitumor response. In summary, therapy with MoAb T101 was specific but only modestly efficacious. Rapid infusion of nonmodulating doses of antibody provided excellent targeting and removal of peripheral blood T cells and might be a valid approach in future trials with immunoconjugated T101.     

Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B- cell precursors

Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen- activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using two-dimensional gel electrophoresis, we have compared the expression levels of two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD; isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or non-c-ALL patients. Compared with normal BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as in non- c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27 (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean level compared with normal BCPs and precursors from c-ALL at diagnosis), which might represent a differential enzymatic activity, this was not distinguishable from that of non-c-ALL patients. Therefore, our studies suggest constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and their relatively low- expressing, immunophenotypically normal bone marrow counterparts. In light of the occasional and possibly transient increase of hsp27 expression during nonleukemic BCP differentiation and the possible role of hsp27 in signal transduction to microfilaments, these differences might be of considerable biologic interest and of importance in future studies of regulated normal or dysregulated leukemic hematopoietic cellular differentiation.