Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by inter-facial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatial implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamne frr at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-β-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.     

CD44v7/8基因表达与宫颈癌关系的探讨

目的探讨宫颈癌组织中CD44v7/8基因的异常表达及临床意义。方法1986～2000年沈阳医学院附属中心医院采用免疫组化的方法随机测定59例宫颈癌、18例尖锐湿疣和18例慢性宫颈炎组织中CD44v7/8基因的表达情况。结果宫颈癌、尖锐湿疣及慢性宫颈炎3种疾病中CD44v7/8表达阳性率分别为76.27%、11.11%和11.11%,宫颈癌组的CD44v7/8表达分别高于慢性宫颈炎组及尖锐湿疣组,且差异非常显著(P<0.01)。慢性宫颈炎组及尖锐湿疣组比较差异无显著性(P>0.05)。结论CD44v7/8蛋白的表达增强与宫颈癌的发生、发展及和局部浸润转移有关。     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

Open, Double-Blind and Long-Term Study of Vigabatrin in Chronic Epilepsy

We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

益肾调督针法对实验大鼠脑梗死恢复期TNF-α、IL-6和IL-8的影响

目的 观察益肾调督针法对脑梗死恢复期治疗及预防再梗的作用机制。方法 将实验大鼠随机分为对照组、模型组、益肾调督针法组、常规针法组和非穴针刺组各10例，用血栓栓塞法制备局灶性脑梗死模型，观察治疗前后大鼠神经功能改变，应用双抗体夹心ELISA法分别测定各组大鼠血清中TNF-α、IL-6和IL-8的含量。结果 治疗前后大鼠神经功能评分以益。肾调督针法组及常规针法组有效，差异具有显著性（P〈0．01）；模型组大鼠血清中TNF．仅、IL-6和IL．8含量较对照组明显升高（P〈0．01），施予针刺治疗后各针法组含量均有不同程度的下降。结论 益肾调督针法可以有效地抑制TNF-α、IL-6和IL-8的表达．从而在脑梗死恢复期治疗及预防再梗方面发挥作用。     

卡维地洛对不稳定型心绞痛患者血浆炎症因子的影响

目的观察卡维地洛对不稳定型心绞痛（UAP）患者高敏C反应蛋白（hs-CRP）、白介素-6（IL-6）及细胞间可溶性黏附分子1（sICAM-1）水平的影响。方法UAP患者62例采用完全随机化方法分成对照组（n=30）和治疗组（n=32）,在常规抗血小板、扩血管治疗基础上,对照组予美托洛尔（12.5mg,2次/d×3d）口服,治疗组服卡维地洛（6.25mg,2次/d×3d）,在治疗前后分别测定hs-CRP、IL-6、sICAM-1值。结果对照组和治疗组在治疗前hs-CRP、IL-6、sICAM-1均无显著性差异;用药后两组3指标均较用药前显著降低（P<0.05）;治疗组在用药后IL-6、sI-CAM-1显著低于对照组（P<0.05）。同时,用药后两组患者的心率、血压、心肌耗氧量均较用药前显著降低（P<0.05）,治疗组的心肌耗氧量显著低于对照组（P<0.05）。结论卡维地洛可显著降低UAP患者的炎症因子IL-6、sICMA-1水平。     

CD80mAb协同imDC诱导同种异体大鼠胰十二指肠移植免疫耐受

目的 观察共刺激分子阻断剂CD80单克隆抗体（CD80mAb）在协同未成熟树突细胞（imDC）诱导同种异体大鼠胰十二指肠移植免疫耐受中的作用。方法 建立糖尿病大鼠胰十二指肠移植动物模型；4E5杂交瘤细胞株BABIMC小鼠腹腔注射，抽取腹水，分离纯化后获得CD80mAb；分离供体大鼠骨髓来源DC细胞前体，经GM—CSF、IL-4体外刺激后。再加入IL-10共培养，鉴定为imDC；移植前7d，将2×10^6imDC经静脉途径注射至受体体内，同时分别给予生理盐水1ml、CD80mAb5mg连续14d。结果 四组受体大鼠移植后中位生存时间分别为12．7d、32．4d、50．2d、92．0d，实验组存活时间明显延长；组织学观察发现移植后7dCD80mAb＋imDC组移植物形态尚完整，淋巴细胞浸润减少；混合淋巴细胞反应证实移植后7dCD80mAb＋imDC组供受体间呈低反应性。结论 共刺激分子阻断剂CD80mAb能够协同imDC诱导受体T细胞对移植物的免疫耐受，降低宿主对移植物的急、慢性排斥反应，延长移植物的存活时间。     

CD44分子与乳腺癌

CD44分子属于黏附分子家族中的一员，其CD44的异常表达与乳腺癌的发生、发展和转移密切相关。近年来研究表明乳腺癌干细胞表面高度表达CD44分子，针对CD44分子与乳腺癌干细胞关系的研究，将为乳腺癌的临床治疗提供新的靶点。     

胃肠道癌肿患者外周血CD4^＋CD25^＋FOXP3^＋调节性T细胞的表达及临床意义

目的：研究胃肠道癌肿患者外周血CD4^＋CD25^＋FOXP3^＋调节性T（Treg）细胞的表达，并探讨其临床意义。方法：通过免疫荧光术及流式细胞仪检测20例胃癌患者及20例结肠癌患者外周血CD4^＋CD25^＋FOXP3^＋Treg细胞、CD4^＋CD25^＋high Treg细胞、CD4^＋T细胞及CD4^＋ CTLA-4^＋T细胞。结果：胃癌组、结肠癌组与健康献血者比较外周血CD4^＋CD25^＋FOXP3^＋ Treg细胞、CD4^＋CD25^＋high Treg细胞及CD4^＋CTLA-4^＋T细胞显著增多，CD4^＋T细胞显著减少；胃癌、结肠癌患者之间其外周血中CD4^＋CD25^＋FOXP3^＋Treg细胞、CD4^＋CD25^＋high Treg细胞、CD4^＋T细胞及CD4^＋CTLA-4^＋T细胞无显著差异。结论：胃肠道癌肿患者外周血CD4^＋CD25^＋FOXP3^＋Treg细胞显著高于健康献血者，这可能与胃肠道癌肿患者的免疫抑制和肿瘤的进展相关。