OBJECTIVETo evaluate the associations of human leukocyte antigen (HLA) DQB1 gene with onset age and autoantibodies in type 1 diabetes mellitus(T1DM) in Chinese Han population in Sichuan area.

METHODSForty-six type 1 diabetic patients and 52 healthy control subjects were involved in this study. HLA-DQB1 typing was performed by polymerase chain reaction-sequence specific primer(PCR-SSP). Glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) were qualitatively analyzed by enzyme linked immunosorbent assay (ELISA).

RESULTSThe positive rate of DQB1*0201 was higher in T1DM than in controls (OR=18, P<0.005), but those of DQB1*0601, *0602 were higher in controls than in T1DM(OR=0.07, 0.31 respectively, both P<0.05).The positive rate of DQB1*0602 in type 1 diabetic patients with onset age>or=20 years was higher than that in the patients with onset age <20 years (P<0.05). GADA was more frequent in DQB1*0201(+) patients than in DQB1*0201 (-) patients (P<0.025).

CONCLUSIONThe findings show that DQB1*0201 is susceptible to T1DM, whereas DQB1*0601, *0602 are protective in Chinese Han population in Sichuan area. DQB1*0602 may delay the onset of T1DM. The positive rate of DQB1*0201 correlates positively with that of GADA.

Adolescent ; Adult ; Age of Onset ; Autoantibodies ; immunology ; Child ; Child, Preschool ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; epidemiology ; genetics ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Genetic Predisposition to Disease ; genetics ; Glutamate Decarboxylase ; immunology ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Middle Aged ; Polymerase Chain Reaction ; Young Adult

OBJECTIVETo investigate the effect of small hairpin interfering RNA (shRNA) in suppressing cytochrome P450 3A4 (CYP3A4) gene expression in CHL-3A4 cells.

METHODSThree shRNA expression vectors targeting CYP3A4 gene (CYP3A4 I, C YP3A4 II, and CYP3A4 III, respectively) were designed, synthesized and transfected into CHL-3A4 cells via liposomes. The inhibitory effect of shRNA on CYP 3A4 gene expression was detected by Western blotting and RT-PCR, and the effect of shRNA transfection in suppressing cyclophosphamide-induced cytotoxicity was measured using MTT assay.

RESULTSThe vector carrying CYP3A4 III shRNA significantly reduced the expression of CYP3A4 gene at both the mRNA (75%) and protein levels (80%) in CHL3A4 cells. The cytotoxicity of cyclophosphamide was markedly inhibited by CYP3A4 III-mediated suppression of CYP3A4 gene expression by 75% in CHL-3A4 cells.

CONCLUSIONThe vector-mediated RNA interference can suppress CYP3A4 gene expression in CHL-3A4 cells, and RNA interference technique provides a new means for studying cytochrome P450 gene function in mammalian cells.

Animals ; Cells, Cultured ; Cricetinae ; Cytochrome P-450 CYP3A ; genetics ; Fibroblasts ; cytology ; metabolism ; Humans ; Lung ; cytology ; RNA Interference ; RNA, Small Interfering ; genetics

OBJECTIVETo observe the base of the interference in correlated biotic active matter obtained multi-drug resistance induced by chemotherapy for different alkaloid, and to supervise the use in clinic to restrain the multi-drug resistant of chemotherapy, and thereby to improve the curative effect.

METHODAfter bestowing subter-dosage unite chemotherapeutant to ascites S180 mouse to set up the mouse models of multi-drug resistance of S180 tumour cell, and giving the mouse matrine, terandrine, oxymatrine and berberine hydrooh loride for 4 weeks, the P170, LRP, TOPOII, Fas and apoposis were determined by flow cytometry.

RESULTMatrine and terandrine could obviously reduce the express of P170, LRP and the activation of TOPOII, and increase the ratio of the express of Fas and the apoposis of drug resistant tumour cell. And at the same time it could obviously reduce the express of intercellular adhesion molecule(CD54).

CONCLUSIONMatrine and terandrine can interfere in MDR which results from chemotherapeutics by the adjustment of correlated biotic active matter, besides, the different degree of alkaloid effect with different configuration.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Alkaloids ; isolation & purification ; pharmacology ; Animals ; Apoptosis ; drug effects ; Benzylisoquinolines ; isolation & purification ; pharmacology ; Berberine Alkaloids ; isolation & purification ; pharmacology ; DNA Topoisomerases, Type II ; metabolism ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Male ; Mice ; Plants, Medicinal ; chemistry ; Quinolizines ; isolation & purification ; pharmacology ; Random Allocation ; Sarcoma 180 ; metabolism ; pathology ; Tumor Cells, Cultured ; Vault Ribonucleoprotein Particles ; metabolism ; fas Receptor ; metabolism

Objective To analyze the clinical value of minimal residual disease(MRD) of acute myeloblastic leukemia(AML) with AML 1-ETO by using the real-time quantitative reverse transcriptase polymerase chain reaction(RQ-RT-PCR).Methods From Jan.2001 to Jan.2007,the MRD of 32 AML1-ETO-positive AML patients were analyzed by using PQ-RT-PCR.The detection of the AML1-ETO was taken after the induced chemotherapy every 1.5-2.0 months during the consolidation therapy.The survival of different stages in children with AML was analyzed by SPSS 10.0 software and calculated by using Kaplan-Meier analysis.Results Thirty-two patients received the induced chemotherapy and 29 patients with complete remission morphologically,3 patients had no complete remission morphologically and then gave up.Patients with molecular remission were associated with a high probability of survival(P=0.001 8).Patients with high transcript levels at diagnosis had no difference in event free survival with patients with low transcript levels.The quality of molecular response after induction,6 months in the chemotherapy as well as consolidation period,has significant impact on the event free survival(P=0.023,0.000 1,0.004 9).Conclusion The current study demonstrate that quantitative evaluation of AML1-ETO transcript levels is important and may be helpful for therapeutic decisions in future.

Objective To summarize the experience of long-term survival in patients after simulta- neous kidney-pancreas transplantation(SKPT)with modified enteric drainage(ED).Methods From October 2001 to July 2004,6 patients with end-stage renal disease due to Type 1 diabetes underwent SKPT with modified ED,ie,side-to-side anastomosis between the duodenum of donors and jejunum of recipients. The medication regimen included:mycophenolic acid 500 mg and tacrolimus 2 mg before operation;methyl- prednisolone(MP)1.0 during operation;and 2-dose anti-IL-2 receptor monoclonal antibody(2 cases)or antihuman thymocyte globulin(ATG)(4 cases)for immune induction therapy;MP was used on the first 3 d after transplantation,triple immunosuppressive therapy(tacrotimus,mycophenolic acid and prednisone)was used on the second d after transplantation.Anticoagulants such as low molecular heparin or alprostadil were used for 7-10 d to prevent thrombosis in pancreas graft.Somatostatin was used as prophylaxis for graft pan- creatitis.Ganciclovir was used to prevent cytomegalovirus infection when renal graft gradually recovered 3 to 5 d after transplantation.The follow-up was from 1 year and 3 months to 4 years and 1 month.Results Transplantation was successful in all 6 cases.The blood sugar levels were 6-16 mmol/L.Low-dose insulin was used for 5-10 d,then the blood sugar levels returned to normal range.One of 6 patients experienced nephrotoxicity because of high tacrolimus blood concentration at 7 d after operation;after 3 dialyses and re- duction of tacrolimus dose,the renal allograft regained normal function.Three cases experienced alimentary tract hemorrhage at 14,20 and 22 d,respectively,after operation;the bleeding was stopped after treatment. There were no complications such as pancreatic fistula,intestinal fistula and thrombosis early after operation. All the patients are now alive,specifically,1 survived over 4 years,3 over 3 years,1 over 2 years,and 1 over 1 year.All had normal blood sugar free of insulin use.Five cases had normal renal graft function,with normal sCr,and 1 had sCr＞400?mol/L. Two cases were admitted to hospital due to upper respiratory infection and furuncles in the skin of head 6 months and 2 years,respectively,after operation.They were both cured.No complications such as urinary infection,metabolic acidosis and dehydration occurred.Conclusions SKPT is effective for the treatment of end-stage renal disease due to Type 1 diabetes.SKPT with modified ED are relatively simple with physiological compatibility and fewer complications.High quality of donated organs, HLA matching,pancreatic drainage pattern,rational periopcrative medications and infection late after trans- plantation are important factors affecting the long-term survival of the patients.

Objective To study the biological characteristics of natural reservoirs of Yesinia ( Y.) pestis in China.Methods Species and genera of natural reservoirs of E pestis in China and their faunal distribution were characterized with modem taxonomic techniques.The ecological roles of natural reservoirs of Y.pestis in the natural plague foci were determined according to the animal ecological experiments.Results There were 86 species of natural reservoirs of Y.pestis including 14 major reservoirs and 72 kinds of the secondary or occasional reservoirs.Conclusion The biological characteristics of major reservoirs of Y.pestis and their roles in natural plague foci were defined.

OBJECTIVE: To explore the protective effect of amlodipine on the cytotoxicity induced by contrast media (meglumine diatrizoate) in human kidney cells (HKC). METHODS: An HKC line was used. The experiment was divided into 4 groups: a model group (diatrizoate 111g/L), a prevention group (diatrizoate 111g/L+amlodipine 10(-5)mol/L), an amlodipine control group (amlodipine 10(-5)mol/L), and a culture medium control group (simple none blood serum DMEM-F12 medium). Cytotoxicity induced by meglumine diatrizoate was analysed by methyl thiazolyl tetrazolium (MTT) test, lactate dehydrogenase (LDH) assay, Hochest33258 fluorescence stained cytospins, and flow cytometric DNA analysis. The protein expression of Bax was determined by Western blot, and caspase-3 activity was examined by fluorometric method. RESULTS: In the prevention group, the cell viability increased significantly (P<0.05), LDH levels decreased (P<0.05), and the apoptosis was lower than that of the model group (P<0.05) .Bax protein expression and caspase 3 activity decreased (P<0.05). CONCLUSION Amlodipine can inhibit the HKC apoptosis and protect the renal tubule cell from injury induced by meglumine diatrizoate.
Amlodipine ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line ; Contrast Media ; toxicity ; Diatrizoate Meglumine ; toxicity ; Epithelial Cells ; cytology ; drug effects ; Humans ; Kidney Tubules ; cytology ; drug effects ; Protective Agents ; pharmacology

OBJECTIVETo explore factors that affecting the outcome of systemic lupus erythematosus (SLE) therapy.

METHODSFactors on the results of therapy were analysed through a case-control study.

RESULTSThe common symptoms of SLE were fever, joint pain and skin eruption on face while the common provocation factors of SLE were infection and birth. Through multivariate logistic regression analyses, factors that influencing SLE result of treatment were tachycardia, diastolic pressure step-up, complement C(3) reduction, anti-ds-DNA antibody, SLE relapse and brain syndrome with the OR values as 2.28, 2.34, 2.42, 2.47, 1.98 and 5.56, respectively.

CONCLUSIONThe symptom and clinical characteristics of SLE were complicated. SLE treatment result could be influenced by tachycardia, diastolic pressure step-up, complement C(3) reduction, anti-ds-DNA antibody, SLE relapse and brain syndrome suggesting that the prognosis of SLE patients should be comprehensively considered.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Child ; China ; epidemiology ; Female ; Humans ; Lupus Erythematosus, Systemic ; epidemiology ; therapy ; Male ; Middle Aged ; Prognosis ; Regression Analysis

To investigate the molecular mechanisms of all-trans retinoic acid (ATRA)-induced rig-g gene expression and to better understand the signal transduction of ATRA during acute promyelocytic leukemia (APL) cell differentiation, the luciferase reporter assay, co-immunoprecipitation and chromatin immunoprecipitation were used to clarify the basic transcriptional factors, which directly initiated the expression of rig-g gene. The results showed that the expression of STAT2, IRF-9 and IRF-1 could be upregulated by ATRA with different kinetics in NB4 cells. IRF-9 was able to interact with STAT2 to form a complex, which could bind the rig-g gene promoter and trigger the rig-g expression. IRF-1 alone could also activate the reporter gene containing rig-g gene promoter, but C/EBPalpha could strongly inhibit this transcription activity of IRF-1. It is concluded that during ATRA-induced APL cell differentiation, IRF-1 is first upregulated by ATRA, and then IRF-1 increases the protein levels of IRF-9 and STAT2 with the downregulation of C/EBPalpha. The complex of IRF-9 and STAT2 is the primary transcriptional factor for rig-g gene induction. This study will be helpful for better understanding the signal transduction networks of ATRA during the course of APL cell differentiation.
CCAAT-Enhancer-Binding Protein-alpha ; metabolism ; Gene Expression Regulation, Leukemic ; drug effects ; Genes, Regulator ; drug effects ; Humans ; Interferon Regulatory Factor-1 ; metabolism ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; metabolism ; Intracellular Signaling Peptides and Proteins ; genetics ; Leukemia, Promyelocytic, Acute ; genetics ; STAT2 Transcription Factor ; metabolism ; Signal Transduction ; Tretinoin ; pharmacology ; Tumor Cells, Cultured

OBJECTIVETo study the regulatory role of interferon-stimulated response elements (ISREs) located on the retinoic acid-induced gene G (RIG-G) promoter in RIG-G expression.

METHODSBy using point mutation technique, the authors constructed the wide type and site mutant reporter gene plasmids according to the ISRE sequence on RIG-G promoter, and detected the functional activities by luciferase reporter assay.

RESULTSMutation in ISRE II alone had no obvious effect on the expression of the reporter gene, whereas mutation in ISRE I dramatically inhibited the transactivity of RIG-G promoter. Mutation in both ISRE I and ISRE II resulted in complete loss of its response to the transcription factors for the reporter gene.

CONCLUSIONBoth ISRE I and ISRE II on the RIG-G promoter are the binding sites for the complex of transcription factors. They are required for RIG-G expression, and ISRE I has a preferential role over ISRE II.

Cell Line, Tumor ; Humans ; Interferon Regulatory Factor-1 ; genetics ; metabolism ; Interferons ; genetics ; metabolism ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Promoter Regions, Genetic ; genetics ; Response Elements ; genetics ; STAT2 Transcription Factor ; genetics ; metabolism