脑尔康对Alzheimer病小鼠脑细胞凋亡相关基因表达的影响

目的　观察复方中药脑尔康对 Alzheimer病 (AD)模型小鼠 ,学习记忆障碍的改善作用及对凋亡相关基因的调控作用。方法　用跳台法测试各组小鼠学习记忆功能 ,用 SP免疫组化法检测 Fas、Bcl- 2阳性细胞计数。结果　模型组与空白对照组比较 ,触电时间延长 ,潜伏期缩短 ,错误次数增多 ;Fas、Bcl- 2表达升高 (均 P<0 .0 1 )。各用药组与模型组比较触电时间缩短 ,潜伏期延长 (均 P<0 .0 5) ,Fas、Bcl- 2表达下调 (P<0 .0 5或 P<0 .0 1 )。各参数中药中、小剂量组优于西药组。结论　脑尔康能改善 AD小鼠学习记忆障碍具有促智作用 ,可通过调控凋亡相关基因表达 ,抗脑细胞凋亡 ,减少神经元丢失 ,而发挥抗痴呆作用     

B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo

Highly regulated activation of B cells is required for the production of specific antibodies necessary to provide protection from pathogen infection. This process is initiated by specific recognition of antigen through the B cell receptor (BCR), leading to early intracellular signaling followed by the late recruitment of T cell help. In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo. This mechanism is effective over a wide range of antigen affinities but depends on exceeding a tightly regulated avidity threshold necessary for BCR-mediated internalization and CD1d-dependent presentation of particulate antigenic lipid. Subsequently, iNKT cells provide the help required for stimulating B cell proliferation and differentiation. iNKT-stimulated B cells develop within extrafollicular foci and mediate the production of high titers of specific IgM and early class-switched antibodies. Thus, we have demonstrated that in response to particulate antigenic lipids iNKT cells are recruited for the assistance of B cell activation, resulting in the enhancement of specific antibody responses. We propose that such a mechanism may operate to potentiate adaptive immune responses against pathogens in vivo.     

SPA免疫便潜血试验和直肠粘液T抗原试验互补普查大肠癌及其随访

本文联合采用人血红蛋白抗血清包被的含A蛋白葡萄球菌(SPA)进行免疫便潜血试验(SPA试验)和直肠粘液T抗原检测(T抗原试验)用于大肠癌普查初筛并对筛检人群进行随访。结果表明,在4843例无症状人群中,SPA和T抗原试验阳性者分别为472例(9.75％)和297例(6.13％).共769例阳性者行纤维结肠镜检查,检出大肠癌4例,腺瘤48例(>1.0cm者17例,占35.4％)。其中,SPA试验中仅3例癌,29例腺瘤阳性,T抗原试验中2例癌,27例腺瘤阳性,提示联合这两种初筛试验可提高大肠癌及其腺瘤的检出率。为验证普查后减少大肠肿瘤发生的效果,2年后对这些人群采用同样的普查方案随访,结果在受检的3641例人群中,共477例阳性者行纤维结肠镜检查,未发现大肠癌病例,腺瘤18例(>1.0cm者仅4例,占22.2％)。将两次检出的腺瘤进行不典型增生程度的比较,第二次检出的腺瘤轻度不典型增生病变占88.89％(16例),中重度不典型增生病变仅占11.11％(2例),而第一次检出腺瘤、中重度不典型增生病变占25％(12例)。上述结果表明利用这两种初筛试验进行互补性普查。可提高大肠癌及癌前病变的检出率,随访结果提示在无症状人群普查,不仅可使大肠癌及腺瘤的再检出率明显减少,且可使中重度不典型增生病变的发病机会明显减少。     

A gamma-detecting probe for radioimmune detection of CEA-producing tumors

The detection of tumors with radiolabeled antibodies against CEA is possible; however, current nuclear medicine scanning cameras rarely detect tumors smaller than 2 cm in diameter. One of the limitations to tumor detection is the inability to place a detecting camera near a deeply seated intra-abdominal tumor. A hand-held gamma-detecting probe, suitable for intraoperative use, was designed to locate radioactive tumors. Experimental work with CEA-producing colon tumor xenografts in nude mice suggests this probe is more sensitive than external scanners in detecting small tumors. A case report documents the clinical use of this new intraoperative probe. Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, June 5–9, 1983. Supported by PHs Grant No. CA 18016 awarded by the National Cancer Institute, DHHS.     

McAb-RIHA和McAb-Dot-ELISA检测尿中循环抗原诊断日本血吸虫病的研究

通过建立的冰冻—加热浓缩法,将尿样浓缩20倍。应用 McAb-RIHA 和 McAb-Dot-ELISA 平行对比检测了83份急性血吸虫病患者和110例慢性血吸虫病尿样。前者两法的阳性检出率分别为78.31%和65.06%。后者两法的阳性检出率分别为20%和10%。检测101份健康人尿样。两法的假阳性率分别为14.85%和0%。应用 McAb-RIHA 和 McAb-Dot-ELISA对比检查55份华枝睾吸虫病患者和49份钩虫病患者尿样,前者出现的交叉反应率分别为16.36%和14.28%。后者出现的交叉反应率均为0%。12例尿路感染病人中5例含有蛋白的尿样加热前 McAb-Dot-ELISA 检测均阳性,而经76℃2h 加热后均为阴性。     

Alloreactive CD4+ T lymphocytes can exert cytotoxicity to chronic myeloid leukaemia cells processing and presenting exogenous antigen

Existing evidence supports that CD4⁺ T lymphocytes play a role in the graft-versus-leukaemia (GVL) reaction after allogeneic bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML), not only as initiators of the immune response but also as effectors of GVL. In BMT between HLA-identical pairs this CD4-mediated GVL would require CML cells to process and present antigens through MHC class II molecules. To investigate whether CML cells are capable of processing and presenting antigens, and suitable targets for CD4⁺ T-cell-mediated cytotoxicity, we generated HLA-DR1-restricted CD4⁺ cytotoxic T-cell clones that specifically recognized tuberculous purified protein derivative (PPD). We have shown that CML cells and B lymphoblastoid cell line (B-LCL) cells but not PHA-blasts from patients with CML processed exogenous antigen, PPD, and induced proliferative and cytotoxic CD4⁺ T-cell responses. Antigen presentation was blocked by antibodies to HLA-DR but not to MHC class I and by treatment with chloroquine and brefeldin. This indicates that CML cells use a classic MHC class II antigen processing pathway to present PPD antigens to CD4⁺ T cells. Cytotoxicity to CML was shown by antibody blocking studies to be mediated mainly through fas antigen. These findings indicate that donor CD4⁺ T cells alone are sufficient to mediate GVL effects following allogeneic BMT for CML.     

毕赤酵母重组猪囊尾蚴抗原cC1的特征研究

目的 研究毕赤酵母重组猪囊尾蚴抗原cC1蛋白的特征变化。方法 对表达产物行SDS—PAGE,FPLC离子交换层析和分子筛，等电聚焦，脱磷酸反应，N端氨基酸测序，小鼠免疫接种。结果 毕赤酵母重组猪囊尾蚴抗原cC1蛋白的分子量较原核的大，易于纯化，等电点较理论值低，重组cC1已被磷酸化，N端携带了来自载体的4个氨基酸，免疫原性较原核的明显增强。结论 毕赤酵母重组猪囊尾蚴抗原cC1蛋白的特征较原核的有了明显变化，尤其是蛋白易于纯化及免疫原性的增强，表明毕赤酵母表达系统非常适合重组亚单位疫苗的生产制备。     

Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals

BACKGROUND/AIMS: Clearance of hepatitis B virus (HBV) is characterised by a strong cytotoxic T cell response. Persistence of HBV in chronic hepatitis B carriers may be related to failure of this response. The aim of this study was to determine whether HLA class I restricted cytotoxic T lymphocyte (CTL) responses persist in anti-hepatitis B e (HBe) positive / HBV DNA negative individuals, and to correlate the presence of viral CTL epitope mutation with clinical outcome. METHODS: An HLA/HBV dual transfectant model was used to demonstrate these CTL responses in individuals chronically infected with HBV. Subsequently, a known hepatitis B core (HBc) CTL epitope was sequenced in a family of five chronically infected individuals all sharing a HLA allele (HLA-A68.1). RESULTS: Low level HLA class I restricted cytotoxic T cell responses were detected in the peripheral blood of five of eight anti-HBe positive individuals. In the family of HLA-A68.1 positive chronically infected individuals, mutation of the HLA-A68.1 restricted hepatitis B core antigen (HBcAg) CTL epitope STLPETTVVRR was found in all four anti-HBe positive individuals but not in the sole hepatitis B e antigen (HBeAg) positive patient. CONCLUSION: These data are consistent with a continued immune selection pressure on HBV in anti-HBe positive chronically infected individuals with low replicating HBV infection and suggest that mutation of a CTL epitope may be a consequence of the immune response, as opposed to the cause of viral persistence.     

Assessment of the value of carcinoembryonic antigen reduction ratio as a prognosis factor in rectal cancer

Background

Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. This study aimed to investigate the role of CEA reduction ratio after preoperative chemoradiotherapy (CRT).

Methods

We enrolled 284 patients who underwent preoperative CRT followed by radical surgical resection. Patients were divided into 3 groups: serum CEA levels before CRT (pre-CRT CEA) less than 5 ng/mL (group 1); pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio of 50% or more (group 2); and pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio less than 50% (group 3).

Results

The 5-year disease-free survival (DFS) rate was not different between groups 1 (71.8%) and 2 (69.4%) but was signi?cantly lower in group 3 (49.5%). CEA group, lymph node status after CRT (ypN) stage, and histologic type were independent prognostic factors for DFS on multivariate analysis.

Conclusions

CEA reduction ratio might be an independent prognostic factor for DFS in rectal cancer patients treated with preoperative CRT and radical surgery.