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Association of polymorphisms in non-classic MHC genes with susceptibility to autoimmune hepatitis

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Hepatobiliary & Pancreatic diseases International 2012年第2期11卷 125-131页

作者： Jie Tang,Cheng Zhou,Zhi-Jun Zhang and Shu-Sen Zheng hangzhou,china Key Laboratory of Combined Multi-organ Trans- plantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery , and State Key Laboratory for Diagnosis and Treatment of infectious Disease, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china [a] Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery Hangzhou China [b] State Key Laboratory for Diagnosis and Treatment of infectious Disease First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Autoimmune hepatitis is a chronic,generally progressive inflammatory disorder of the liver,of which the cause is *** was demonstrated that genetic factors are involved in its *** studies showed that human leukocyte antigen in the major histocompatibility complex(MHC) is associated with susceptibility to autoimmune *** genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune *** article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune *** SOURCES:Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis,polymorphism,CTLA-4,Fas,TNF-α TGF-β1,TBX21 and VDR up to May *** papers were identified by a manual search of the references from key ***:According to the case-control studies on genetic polymorphisms,at least six genes(CTLA-4,Fas,TNF-α TGF-β1,TBX21 and VDR) are involved in autoimmune hepatitis besides *** far,there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still ***:Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms,but also provide new targets for therapy in the future.

关键词： autoimmune hepatitis polymorphism gene expression

Recent advances in heat shock protein-based cancer vaccines

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Hepatobiliary & Pancreatic diseases International 2006年第1期5卷 22-27页

作者： Hao-Hao Wang, Chen-Yu Mao, Li-Song Teng and Jiang Cao Department of Oncology Surgery, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china Clinical Research institute, Sir Run Run Shaw Hospital, zhejiang university, hangzhou 310016, china Department of Oncology Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: Active immunotherapy has been successful in preventing many infectious diseases, and is being explored for its anti-tumor use. Purified antigens, peptides, gene-based systems and antigens contained in whole cells or cell lysates are used in specific active immunotherapy for cancer, known as cancer vaccines. Cancer vaccines do not directly kill tumor cells, but prime a specific humoral and/or cellular immune response against the tumor. Up to date, many kinds of cancer vaccines have been tested in the world and have shown their own advantages. Heat shock protein (HSP)-based cancer vaccine is one of the outstanding representatives. In this paper, we review recent advances in HSP-based cancer vaccines. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on HSP, cancer vaccines and other related subjects. RESULTS: Several kinds of HSP-based cancer vaccines which have been explored worldwide, include tumor derived HSP-pepdde complex cancer vaccines, artificially reconstituted HSP-peptide complex cancer vaccines, HSPpeptide fusion protein cancer vaccines and HSP-based DNA cancer vaccines, etc. Many HSP-based cancer vaccines are being tested in clinical trials, and some are being tested in phase Ⅲ clinical trials at present. CONCLUSION: The available results in preclinical tests and clinical trials indicate that HSP-based cancer vaccines are promising in cancer therapy.

关键词： heat shock protein cancer vaccines immunotherapy active

DNA immune responses induced by codelivery of IL-12 expression vectors with hepatitis C structural antigens

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Hepatobiliary & Pancreatic diseases International 2002年第4期1卷 553-557页

作者： Mei-Mei Shan Ke-Zhou Liu Hai-Lin Fang Zhi Chen the institute of Infections diseases, zhejiang Univiersity school of medicine, hangzhou 310006, china institute of infectious diseases Zhejiang University School of Medicine Hangzhou 310006 China.

Objective: To demonstrate the utility of DNA vaccines for the tailored methods, the efficacy of enhanced immune responses, and the types of increased im- mune responses. Methods: Four recombinant plasmids constructed in- cluded the coding regions for the core protein (pC) and for the core, E_1 and E_2 together (pCE_1E_2), IL- 12 p35 and p40. These plasmids were transfected into mammalian cells to test their protein expression and were injected into the quadriceps muscles of BALB/ C mice for measurement of specific antibodies and cytotoxic T-lymphocyte (CTL) responses. Results: All the recombinant plasmids were shown to express specific antigens stably in mammalian cells. Codelivery of pIL-12 expression cassettes with pC and pCE_1E_2 in mice resulted in the enhancement of Ag-dependent CTL responses and the reduction of specific Ab response. The CTL activity was: pC= 18.65%±5.71%, pCE_1E_2=20.07%±11.11%, pC +pIL-12=60.11%±17.37%, pCE_1E_2+pIL-12= 67.48%±15.57%, respectively. The average A val- ues of anti-HCV were pC=0.415±0.127, pCE_1E_2= 0.358±0.096, pC+pIL-12=0.210±0.086, pCE_1E_2 +pIL-12=0.258±0.125. Conclusion: Codelivery of pIL-12 with plasmid DNA can enhance the efficacy of immune responses and shift the type of immune responses.

关键词： hepatitis C virus DNA immunization IL-12 expression vectors

Influence factors of serum fibrosis markers in liver fibrosis

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World Journal of Gastroenterology 2003年第11期9卷 2497-2500页

作者： Jun Tao Hui-Qin Peng Wei-Min Cai Feng-Qin Dong Hong-Lei Weng Rong-Hua Liu, institute of infectious diseases, First Affiliated Hospital, school of medicine, zhejiang university, hangzhou 310003 zhejiang Province, china institute of infectious diseases First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 Zhejiang Province China. taojun20001@***

AIM: To analyze the factors which influence the serum levels of hyaluronic acid (HA), type Ⅲ pro-collagen (PCIII), laminin (LN) and type Ⅳ collagen (C-Ⅳ) in liver ***: The serum specimens from 141 chronic hepatitis patients were assayed for fibrosis indexes including HA, PCIIT,LN and C-Ⅳ with radioimmunoassay (RIA) and liver function indexes by an automatic biochemistry analyzer. The patients were then divided into consistent group and inconsistent group. The patients'clinical manifestations were recorded,routine blood pictures were done by a blood counter and analyzer (AC-900). Liver biopsy specimens were examined path-morphologically. The inner diameters of portal vein,splenic vein and thickness of spleen were all measured by ***: Sixteen patients (14.16 %) had serum fibrosis indexes inconsistent with histological stage of their hepatic fibrosis. Their serum fibrosis indexes did not correlate with the stage of hepatic fibrosis (P>0.05), but were positively correlated with the grade of inflammation (X2=12.07, P0.05).CONCLUSION: Serum fibrosis indexes can be influenced by the grade of inflammation, some liver function indexes and clinical manifestations. Comprehensive analysis is necessary for its proper interpretation.

关键词：肝纤维化血清标志物放射免疫分析透明质酸胶质原

Diagnostic value of platelet derived growth factor-BB,transforming growth factor-131,matrix metalloproteinase-1,and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis

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World Journal of Gastroenterology 2003年第11期9卷 2490-2496页

作者： Bin-Bin Zhang Wei-Min Cai Hong-Lei Weng Zhong-Rong Hu Jun Lu Min Zheng Rong-Hua Liu, institute of infectious diseases, First Affiliated Hospital, school of medicine, zhejiang university, hangzhou 310003, zhejiang Province, china Bin-Bin Zhang Wei-Min Cai Hong-Lei Weng Zhong-Rong Hu Jun Lu Min Zheng Rong-Hua Liu Institute of Infectious Diseases First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 Zhejiang Province China

AIM: Noninvasive diagnosis of hepatic fibrosis has become the focus because of the limited biopsy, especially in the surveillance of treatment and in screening hepatic fibrosis. Recently, regulatory elements involved in liver fibrosis, such as platelet derived growth factor-BB (PDGF-BB), transforming growth factor-β1(TGF-β1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), have been studied extensively. To determine whether these factors or enzymes could be used as the indices for the diagnosis of hepatic fibrosis, we investigated them by means of receiver operating characteristic (ROC) curve. METHODS: Serum samples from sixty patients with chronic viral hepatitis B and twenty healthy blood donors were assayed to determine the level of PDGF-BB, TGF-β1, MMP-1, and TIMP-1 with ELISA, and HA, PCIII, C-IV, and LNlevel with RIA. The message RNA (mRNA) expression of TIMP-1 and MMP-1 in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR and Northern blot hybridization. Liver biopsy was performed in all patients. The biopsy samples were histopatholocjically examined. The trial was double-blind controlled. RESULTS: The serum level of PDGF-BB, TIMP-1, the ratio of TIMP-1 and MMP-1 (TIMP-1/MMP-1), mRNA expression of TIMP-1 (TIMP-lmRNA), and the ratio of TIMP-lmRNA and MMP-lmRNA (TIMP-lmRNA/MMP-lmRNA) in patients was significantly higher than those in the healthy blood donors (t=2.514-11.435, P=0.000-0.016). The serum level of PDGF-BB, TIMP-1, TIMP-1/MMP-1, and TIMP-lmRNA was positively correlated with fibrosis stage and inflammation grade (r=0.239-0.565, P=0.000-0.033), while the serum level of MMP-1 was negatively correlated with fibrosis stage and inflammation grade, and TIMP-lmRNA/MMP-lmRNA was positively correlated with inflammation grade. Through the analysis by ROC curve, serum PDGF-BB was the most valuable marker, and its sensitivity was the highest among the nine indices. The markers with the highest spe

关键词：外周血基质多发蛋白酶-1 单核细胞肝纤维化转化生长因子血小板衍化生长因子

Association of cytomegalovirus infection with human leukocyte antigen genotypes in recipients after allogeneic liver transplantation

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Hepatobiliary & Pancreatic diseases International 2006年第1期5卷 34-38页

作者： Jun Fan, Xue-Qin Meng, Mei-Fang Yang, Lin Zhou, Xiao-Ming Chen, Min-Jun Hu, Wei-Wei Fan, Wei-Hang Ma and Lan-Juan Li Key Laboratory of Viral infectious diseases, Ministry of Public Health, institute of infectious diseases Organ Transplantation Center First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003. china Key Laboratory of Viral infectious diseases Ministry of Public Health Institute of Infectious Diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China. fanjunyz@***

BACKGROUND: Cytomegalovirus (CMV) infection is the important cause affecting the survival rate and function of the transplanted organ after transplantation. The occurrence of CMV infection after liver transplantation (LT) is associated with many factors. Lots of studies suggest that genetic mutation between hosts and CMV may play a role in the occurrence and development of CMV infection. CMV exists in an incubative state, affect or destroy the expression of human leukocyte antigen (HLA) molecules in the host cell surface, and interfere antigen's submission. This mechanism is the key of CMV to avoid immune defense mechanism of the host. To detect HLA and CMV antibody (CMV-Ab), CMV antigen (CMV-Ag) of transplantation recipients, we evaluated the association of CMV infection and the particular HLA genotypes in recipients after LT. METHODS: 277 blood samples were collected from 39 LT recipients. CMV antibody and antigen were detected by ELISA or immunohistochemical methods. The HLA types of the recipients were determined by PCR. To analyze the association of HLA alleles and the occurrence of CMV antigenemia in the patients, relative risk degree (RR) was used as the parameter for the Chi-square test. RESULTS: The LT recipients were serum CMV IgG positive (100%), but none of them was CMV IgM positive (0%). Thirty-three LT recipients (84.6%) were CMV antigenic positive with 1-50 positive leukocytes per 50000 leukocytes in extent and 7.2±4.2 positive leukocytes per 50000 leukocytes on average. Thirteen patients developed CMV pneumonia, with CMV antigenic positive (100%) and 17.7±5.5 positive leukocytes per 50000 leukocytes on average. Some HIA alleles were associated with the occurrence and extent of CMV antigenemia. HLA-A2 was the higher frequency allele for patients with antigenemia (P<0.05), and 7 patients carrying HLA-DR11 allele developed antigenemia (P<0.05). In the lower antigenemia group, HLA-A11 was higher in frequency than others (P<0.05). Besides, none of the pat

关键词： cytomegalovirus human leukocyte antigen liver transplantation cytomegalovirus antigen

Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats

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Acta Pharmacologica Sinica 2004年第7期25卷 69-74页

作者： Hong-wei YAO2,3, Jun LI3,4, Ji-qiang CHEN2, Shu-yun XU3 2 zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of china, school of medicine, zhejiang university, hangzhou 310031 3institute of Clinical Pharmacology, Anhui Medical university, Hefei 230032, china zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of china School of Medicine Zhejiang University Hangzhou 310031 Chin

AIM: To study the effect of leflunomide on CCl4-induced hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by subcutaneous injection with 50 % CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-β1 (TGF-β1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-κB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxy- lin and eosin. RESULTS: Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-κB expression in liver tissue, and reduced elevated serum TGF-β1 and NO levels in rats of hepatic fibrosis. CONCLUSION: Leflunomide showed inhibitory action on hepatic fibrosis induced by CCl4 in rats.

关键词： leflunomide hepatic fibrosis nuclear factor-kappa B transforming growth factor-beta nitric oxide

The three-dimensional structure of infectious flacherie virus capsid determined by cryo-electron microscopy

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Science china(Life Sciences) 2009年第12期52卷 1186-1191页

作者： XIE Li1,4, ZHANG QinFen2·, LU XingMeng3, DAI XinHong2, LI KunPeng2, HONG Jian1,4· & ZHOU XuePing11 institute of Biotechnology, zhejiang university, hangzhou 310029, china 2 State Key Laboratory of Biocontrol, school of Life Sciences, Sun Yat-Sen university, Guangzhou 510275, china 3 College of Animal Sciences, zhejiang university, hangzhou 310029, china 4 Center of Analysis and Measurement, zhejiang university, hangzhou 310029, china institute of Biotechnology Zhejiang University Hangzhou 310029 China State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-Sen University Guangzhou 510275 China College of Animal Sciences Zhejiang University Hangzhou 310029 China Center of Analysis and Measurement Zhejiang University Hangzhou 310029 China

Cryo-electron microscopy and image reconstruction were used to determine the three-dimensional structure of infectious flacherie virus (IFV). 5047 particles were selected for the final reconstruction. The FSC curve showed that the resolution of this capsid structure was 18 ·. The structure is a psuedo T=3 (P=3) icosahedral capsid with a diameter of 302.4 · and a single shell thickness of 15 ·. The density map showed that IFV has a smooth surface without any prominent protrude or depression. Comparison of the IFV structure with those of the insect picorna-like virus-Cricket paralysis virus (CrPV)and human picornavirus-Human rhinovirus 14 (HRV 14) revealed that the IFV structure resembles the CrPV structure. The "Rossmann canyon" is absent in both IFV and CrPV particles. The polypeptide topology of IFV VP2, IFV VP3 was predicted and the subunit location at the capsid surface was further analyzed.

关键词： infectious flacherie virus cryo-electron microscopy three-dimensional structure polypeptide folding

Effect of primary iris and ciliary body cyst on anterior chamber angle in patients with shallow anterior chamber

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2012年第9期13卷 723-730页

作者： Bing-hong WANG Yu-feng YAO Department of Ophthalmology Sir Run Run Shaw Hospital School of MedicineZhejiang UniversityHangzhou 310016China Sir Run Run Shaw institute of Clinical medicine of zhejiang university Hangzhou 310016China

Objective:To evaluate the prevalence of primary iris and/or ciliary body cysts in eyes with shallow anterior chamber and their effect on the narrowing of the anterior chamber ***:Among the general physical check-up population,subjects with shallow anterior chambers,as judged by van Herick technique,were recruited for further *** biomicroscope(UBM) was used to detect and measure the cysts located in the iris and/or ciliary body,the anterior chamber depth(ACD),the angle opening distance at 500 μm(AOD500),and the trabecular-iris angle(TIA).A-scan ultrasonography was used to measure the ocular biometry,including lens thickness,axial length,lens/axial length factor(LAF),and relative lens position(RLP).The effect of the cyst on narrowing the corresponding anterior chamber angle and the entire angle was evaluated by the UBM images,ocular biometry,and gonioscopic *** eye with unilateral cyst was compared with the eye without the cyst for further ***:Among the 727 subjects with shallow anterior chamber,primary iris and ciliary body cysts were detected in 250(34.4%) patients;among them 96(38.4%) patients showed unilateral single cyst,21(8.4%) patients had unilateral double cysts,and 42(16.8%) patients manifested unilateral multiple and multi-quadrants *** iris configuration was found in 140 of 361(38.8%) eyes with *** mean size of total cysts was(0.6547±0.2319) *** evaluation of the effect of the cyst size and location on narrowing the corresponding angle to their position,the proportion of the cysts causing corresponding angle narrowing or closure among the cysts larger than 0.8 mm(113/121,93.4%) was found to be significantly higher than that of the cysts smaller than 0.8 mm(373/801,46.6%),and a significant higher proportion was also found in the cysts located at iridociliary sulcus(354/437,81.0%) than in that at the pars plicata(131/484,27.1%).In evaluating the effect of the cyst on the entire anterior ch

关键词： Iris and ciliary body cyst Ultrasound biomicroscope Shallow anterior chamber