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Huntingtin processing in pathogenesis of Huntington disease

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Acta Pharmacologica Sinica 2004年第10期 3-9页

作者： Zheng-hong QIN, Zhen-lun GUdepartment of Pharmacology, soochow university School of Medicine, suzhou 215 007, china Laboratory of Cellular Neurobiology, department of Neurology, Massachusetts General hospital and Harvard Medical School, MA 02129, USA

Huntington's disease (HD) is caused by an expansion of the polyglutamine tract in the protein named huntingtin. The expansion of polyglutamine tract induces selective degeneration of striatal projection neurons and cortical pyramidal neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and cytoplasmic aggregates in association with other cellular proteins in vulnerable neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent. These pathological features are related to protein misfolding and impairments in protein processing and degradation in neurons. This review focused on the role of proteases in huntingtin cleavage and degradation and the contribution of altered processing of mutant huntingtin to HD pathogenesis.

关键词： Huntington disease huntingtin caspase calpain proteasome protein aggregation autophagy neurodegeneration

Caspase-1 inhibitor Ac-YVAD-CHO attenuates quinolinic acid-induced increases in p53 and apoptosis in rat striatum

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Acta Pharmacologica Sinica 2005年第2期26卷 150-154页

作者： Yi CAO Zhen-lun GU Fang LIN Rong HAN Zheng-hong QIN department of Pharmacology,soochow university School of Medicine,suzhou 215007,china department of Pharmacology Soochow University School of Medicine Suzhou 215007 China

Aim:To study the effects of the caspase-1 inhibitor Ac-YVAD-CHO on quinolinicacid(QA)-induced ***:Rats were pre-treated with intrastriatalinfusion of Ac-YVAD-CHO(2-8μg)before intrastriatal injection of QA(60 nmol).Striatal total proteins,genomic DNA,and nuclear proteins were *** of Ac-YVAD-CHO on QA-induced caspase-1 activity,internucleosomalDNA fragmentation, IκB-α degradation,NF-κB,and AP-1 activation,and increasesin p53 protein levels were measured with enzyme assays,agarose gel electro-phoresis,electrophoresis mobility shift assays,and Western blot ***:Pre-treatment with Ac-YVAD-CHO inhibited QA-induced internucleo-somal DNA ***-YVAD-CHO inhibited QA-induced increases incaspase-1 activity and p53 protein levels,but had no effect on QA-induced IκB-αdegradation,NF-κB or AP-1 ***:Caspase-1 is involved inQA-induced p53 upregulation but not IκB-α *** of caspase-1attenuates QA-induced apoptosis in rat striatum.

关键词： caspase 1 Ac-YVAD-CHO Huntington disease protein p53 NF-kappaB inhibitor alpha apoptosis NF-kappaB

CD4+CD25+ Regulatory T cells in Advanced Gastrointestinal Cancer Patients with Chemotherapy

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CD4+CD25+ Regulatory T cells in Advanced Gastrointestinal Ca...

第六届全国免疫学学术大会

作者： Hong Xu~(1.2,3,4) Yixiang Mao~(1,2,3,4) Yuedi Dai~2 Qincai Wang~2 XueGuang Zhang~(1,3,5) 1 Jiangsu Province Key Laboratory of Clinical Immunology,first affiliated hospital to suzhou university suzhou,china 2 department of oncology,first affiliated hospital to suzhou university,suzhou,china 3 department of Immunology,Institute of Biotechnology,suzhou university,suzhou,china 4 Hong Xu and Yixiang Mao contributed equally to this paper.

Background:Active suppression by CD4CD25 regulatory T cells(Tregs) plays an important role in the down-regulation of the response of T cells to foreign and self *** levels of Tregs have been reported in the peripheral...

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A migrated intravesical Copper-T intrauterine device with calculus formation was successfully treated using holmium:YAG laser under cystoscopy

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A migrated intravesical Copper-T intrauterine device with ca...

第十五届全国泌尿外科学术会议

作者： Gang Li, Yuhua Huang, Jinfeng Wu, Jianquan Hou, Jianwei Yang and Chunyin Yan department of Urology, first affiliated hospital, soochow university, suzhou, china 215006

We report the case of a woman in whom an IUD had been inserted 10 years before and who was diagnosed with the migration of the IUD into urinary bladder. A 30-year-old woman was admitted to our hospital with a chief co...

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Treatment of pituitary prolactinomas with bromocriptine

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Treatment of pituitary prolactinomas with bromocriptine

中国抗癌协会神经肿瘤专业委员会第八届学术会议

作者： Xiangdong Li, Guozhen Hui department of Neurosurgery, the first hospital affiliated to suzhou university, Su Zhou 215006, china

Objective: Clinical effects and mechanisms of bromocriptine treatment on pituitary prolactinomas were explored in this clinical and pathological study. Method: Twenty-six patients with prolactinomas were selected. Bromocriptine was administrated in 16 patients before operation, while 7 patients were not treated with bromocriptine before operation. Tumor specimens were resected during operation and examined under a light microscope and an electron microscope. Three cases of giant adenoma were only treated with bromocriptine, and changes in tumor volume were observed. Results: In 16 cases with bromocriptine treatment, the cell size decreased while karyoplasmic ratio increased. Observation under an electron microscope revealed that secretory granules, mitochondria, and rough endoplasmic reticulum were markedly reduced. When treated with bromocriptine for a long period, margination of the nuclear chromatin occurred. Some chromatin detached from the nuclear membrane and spread into the cytoplasm in a budding manner forming an apoptotic body. Some tumor cells exhibited vacuolar degeneration, necrosis, or autolysis. In patients who received only bromocriptine treatment, the tumor volume decreased by 98.52%. Conclusion: Bromocriptine could cure prolactinomas. The main underlying mechanism was that bromocriptine could induce apoptosis and secondary necrosis of tumor cells.

关键词： bromocriptine pituitary prolactinomas apoptosis

Inhibitory effect of quercetin on proliferation of human microvascular endothelial cells in vitro

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Acta Pharmacologica Sinica 2003年第12期24卷 57-60页

作者： FAN Pan-Sheng, GU Zhen-Lun SHENG Rui, LIANG Zhong-Qin, WANG Xiao-Xia, ZHU Yi department of Pharmacology, Institute of Chinese Materia Medica, soochow university, suzhou 215007, china department of Pharmacology Institute of Chinese Materia Medica Soochow University Suzhou 215007 China

AIM: To investigate the role of quercetin (Que) in the proliferation of cultured human skin microvascular endothelial cells (MVEC). METHODS: Cell count and [methyl-~3H]thymidine ([~3H]TdR) uptake assay were used to measure the effect of Que in the proliferation of cultured MVEC. Cytotoxicity of Que on MVEC was also evaluated by51Cr release assay. RESULTS: When MVEC were treated with Que, the proliferation was significantly inhibited in a time-course and dose-dependent manner. Que 5 μmol/L did not inhibit the proliferation of MVEC. When the concentration of Que increased to 20, 40, 80, and 160μmol/L, the cell numbers per well were decreased and the inhibition rate was 12.2％, 23.5％, 35.3％, and 54.1％ respectively with IC50of 138 μmol/L. The inhibitory rate of [~3H]-TdR uptake was 18.7％, 34.4％, 48.9％, and 62.5％ respectively (IC50=87.5 μmol/L).51Cr release assay showed that Que 160μmol/L incubated with MVEC from 1 to 16h had no clear cytotoxicity compared with control group. CONCL

关键词： quercetin vascular endothelium cell division cytotoxicity human

Generation and selection of immunized Fab phage display library against human B cell lymphoma

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Cell Research 2007年第07期17卷 650-660页

作者： Yongmei Shen1,2 Xiaochun Yang1 Ningzheng Dong3 Xiaofang Xie1,2 Xia Bai3 Yizhen Shi1,21 department of Radioimmunoassay2 department of Clinical Laboratory, Second affiliated hospital of soochow university, suzhou 215004, china3 Leukemia Research Unit, Jiangsu Institution of Hematology, first affiliated hospital of soochow university, Suzho 215006, china departmentofRadioimmunoassay Suzhou215004China departmentofClinicalLaboratory SecondAffiliatedHospitalofSoochowUniversitySuzhou215004China LeukemiaResearchUnit JiangsuInstitutionofHematologyFirstAffiliatedHospital

The approval of using monoclonal antibodies as a targeted therapy in the management of patients with B cell lym-phoma has led to new treatment options for this group of patients. Production of monoclonal antibodies by the traditionalhybridoma technology is costly, and the resulting murine antibodies often have the disadvantage of triggering humananti-mouse antibody （HAMA） response. Therefore recombinant Fab antibodies generated by the phage display technol-ogy can be a suitable alternative in managing B cell lymphoma. In this study, we extracted total RNA from spleen cellsof BALB/c mice immunized with human B lymphoma cells, and used RT-PCR to amplify cDNAs coding for the κ lightchains and Fd fragments of heavy chains. After appropriate restriction digests, these cDNA fragments were successivelyinserted into the phagemid vector pComb3H-SS to construct an immunized Fab phage display library. The diversity ofthe constructed library was approximately 1.94×10～7. Following five rounds of biopanning, soluble Fab antibodies wereproduced from positive clones identified by ELISA. From eight positive clones, FabC06, FabC21, FabC43 and FabC59were selected for sequence analysis. At the level of amino acid sequences, the variable heavy domains （VH） and variablelight domains （VL） were found to share 88-92% and 89-94% homology with sequences coded by the corresponding murinegermline genes respectively. Furthermore, reactivity with membrane proteins of the B cell lymphoma was demonstratedby immunohistochemistry and western blotting. These immunized Fab antibodies may provide a valuable tool for furtherstudy of B cell lymphoma and could also contribute to the improvement of disease therapy.

关键词： B cell lymphoma Fab phage display library pComb3H-SS vector

In vitro study of radio-sensitization by Aidi injection in SHG44 cell line from glioma

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In vitro study of radio-sensitization by Aidi injection in S...

中国抗癌协会神经肿瘤专业委员会第八届学术会议

作者： Yao Song,Juying Zhou*,Xiaoting Xu,Songbin Qin,Zhiying Yu,Qiong Wu,Qi Zhao Yuan Xu,Meiyu Yang(department of Radiation oncology,The first affiliated hospital of soochow university,suzhou 215006,china)

＜正＞The aim of this study was to explore the effect and possible mechanism in vitro of radio-sensitization by Aidi injection in SHG44 cell line from *** SHG44 cell line from glioma was chosen for the study to determ...

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健康教育对社区高尿酸血症患者的影响

苏州大学学报（医学版） 2008年第6期28卷 1015-1017页

作者：施俭苏州大学附属第一医院内科门诊江苏苏州215006

目的评价健康教育对社区高尿酸血症患者疾病了解、行为、饮食结构和生活质量的影响。方法对45例社区高尿酸血症患者通过问卷方式实施健康教育。结果高尿酸血症患者对疾病有关知识的了解及康复知识明显高于教育前,差异有统计学意义(P<0.0... 详细信息

目的评价健康教育对社区高尿酸血症患者疾病了解、行为、饮食结构和生活质量的影响。方法对45例社区高尿酸血症患者通过问卷方式实施健康教育。结果高尿酸血症患者对疾病有关知识的了解及康复知识明显高于教育前,差异有统计学意义(P<0.05或<0.001)。结论实施健康教育能帮助高尿酸血症患者获得更多的高尿酸血症知识,养成健康的生活习惯,提高自我保健意识和建立良好的遵医行为,提高生活质量。

关键词：健康教育社区高尿酸血症

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