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<p><b>OBJECTIVE</b>To investigate the effect of immature dendritic cells (inDC) genetically modified to express sTNFR I on acute graft-versus-host disease (aGVHD) and the graft-versus-leukemia (GVL) effect ofter allogeneic bone marrow transplantation (allo-BMT) in leukemic mice and its mechanism.</p><p><b>METHODS</b>An EL4 leukemia allo-BMT model was established with the BALB/c (H-2d) donor mice (DM)and C57BL/6 (H-2b) recipient mice (RM). The RM received DM bone marrow (BM) cells at a 1:1 ratio with spleen cells intravenously via tail vein at 4 h after TBI. Fifty DM were separated randomly into five groups: (1) Group A: total body irradiation (TBI) group, (2) Group B: lymphoma cell leukemia group, (3) Group C: allo-BMT group, (4) Group D: pXZ9-DC group, (5) Group E: sTNFR I-DC group. Acute GVHD scores, incidence of leukemic cell infiltration, histopathological analysis, survival rate, and survival rate of the recipients were estimated after allo-BMT. Enzyme-linked immunosorbent assay (ELISA) method was used to detect cytokines (INF-gamma and IL-4 ) production. Flow cytometry (FCM) analysis was used to detect allogeneic chimerism.</p><p><b>RESULTS</b>(1) The mice in group A and group B all died of the BM failure and lymphoma cell leukemia, respectively. The mice in group C developed typical clinical signs of a GVHD after BMT with an average survival time(AST) of (11.50 +/- 3.50) d. The signs of aGVHD were less evident in the group D and E, and their AST (21.70 +/- 5.80 and 25.80 +/- 5.20 days, respectively) were all longer than that in group C (P < 0.05). AST of group E was the longest (P < 0.05). The mice in group B all died of leukemia within 18 days after engraftment of EL4 cells. There was was no significant difference in groups C, D and E in the incidence of leukemia (P > 0.05). (2) Serum IFN-gamma level reached peak value. At + 12 d, then decreased gradually in group C, D, and E, and then reached the nadir at +18 d post-BMT, with the lowest in group E (P < 0.05), and the level was significantly lower in group D than in group C (P < 0.05). After BMT, serum IL-4 level slightly decreased in group C, but gradually elevated in group D and E and reached their peak at +12 d, and even more significantly increased in group E (P < 0.05). There was no statistical significance in the pair wise comparison among three group (P < 0.05). (3) The average proportion of H-2d positive cells in RM was 95%-100% on day 30 post-BMT, with complete donor-type implantation.</p><p><b>CONCLUSION</b>Immature DC can induce immuno tolerance. Immature DC genetically modified to express sTNFR I has been shown to prevent acute GVHD in lethally irradiated mice reconstituted with allogeneic bone marrow grafts while maintaining the GVL response.</p>
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Animais , Feminino , Masculino , Camundongos , Transplante de Medula Óssea , Métodos , Células Dendríticas , Alergia e Imunologia , Doença Enxerto-Hospedeiro , Efeito Enxerto vs Leucemia , Tolerância Imunológica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores Tipo I de Fatores de Necrose Tumoral , Genética , Transplante HomólogoRESUMO
<p><b>OBJECTIVE</b>To study the specific amino acid variation in Nef that may be related to disease progression after infection with HIV-1 subtype B, a predominant strain circulating in China, and to determine whether changes in Nef secondary structure may influence different stages of AIDS development based on the concept that the Nef gene of HIV infection dramatically alter the severity of viral infection and virus replication and disease progression, and that long-term non-progressors (LTNP) of HIV infection are commonly associated with either a deletion of the Nef gene or the defective Nef alleles.</p><p><b>METHODS</b>The study subjects were divided into LTNP1(n=14), LTNP2 (n=16) and slow progressor (SP, n=19) groups for mutational analysis of the Nef sequence. The data were obtained by using Bioedit, MEGA, Anthewin and SAS software.</p><p><b>RESULTS</b>Residues in Nef TA(48/49) and K151 occurred more frequently in the LTNP group while AA(48/49) was more frequently observed in the SP group. Of the differences observed in the secondary structure comparison using Nef consensus sequences of these three groups, one was roughly corresponding to the Nef(48/49) mutation site.</p><p><b>CONCLUSION</b>TA(48/49), K(151), and AA(48/49) in the Nef gene might be associated with the different stages of HIV infection, and there may be a link between the Nef secondary structure and the progression of HIV-1 infection.</p>
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Humanos , Sequência de Aminoácidos , Sequência de Bases , Doadores de Sangue , Contagem de Linfócito CD4 , China , Epidemiologia , Progressão da Doença , Produtos do Gene nef , Genética , Infecções por HIV , Epidemiologia , Virologia , Sobreviventes de Longo Prazo ao HIV , HIV-1 , Classificação , Genética , Dados de Sequência Molecular , Mutação , Genética , Fatores de TempoRESUMO
<p><b>AIM</b>To investigate the pharmacokinetics of osthole in rabbits and obtain the main pharmacokinetic parameters.</p><p><b>METHODS</b>A simple high-performance liquid chromatography (HPLC) method was developed to study the pharmacokinetics of osthole in rabbits by joining an internal standard (paeonal). Methanol-water (80:20) was used as the mobile phase. According to the 3P87 pharmacokinetic program, the main parameters were calculated.</p><p><b>RESULTS</b>The osthole pharmacokinetics conforms to a two compartment open model after i.v. administration, T1/2 alpha = 5.81 min, T1/2 beta = 42.2 min, K21 = 0.036 0.min-1, K12 = 0.045 0.min-1, K10 = 0.054 0.min-1, AUC = 235 mg.min.L-1, CLs = 0.043 0 L.min-1.kg-1, Vc = 0.780 L.kg-1.</p><p><b>CONCLUSION</b>The pharmacokinetics of osthole after i.v. administration showed a rapid distribution and elimination process in rabbits.</p>
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Animais , Masculino , Coelhos , Área Sob a Curva , Bloqueadores dos Canais de Cálcio , Sangue , Farmacocinética , Cromatografia Líquida de Alta Pressão , Cnidium , Química , Cumarínicos , Sangue , Farmacocinética , Frutas , Química , Taxa de Depuração Metabólica , Plantas Medicinais , Química , Distribuição TecidualRESUMO
Objective To examine the concentrations of hepatocyte growth factor(HGF)and vascular endothelial growth factor (VEGF)in the patients with diabetic neovascular glaucoma(NVG),proliferative retinopathy without neovascularization of the iris(PDR) and idiopathic macular role(IMH),and to determine the relationship between HGF and VEGF.Design Prospective case series. Participants 14 patients(14 eyes)with NVG,22 patients(22 eyes)with non-NVI PDR,19 patients(19 eyes)with IMH.Methods The double-antibody sandwich enzyme-linked immunosorbent assay(ELISA)was used to measure the intravitreous level of HGF and VEGF.Main Outcome Measures The concentrations of HGF and VEGF in the same specimens.Results The concentrations of HGF (mean?SD)in vitreous of NVG group,PDR group and IMH group were(12908.42?2946.46)、(9770.86?3802.99)、(4160.54?2044.80)pg/ ml,respectively(Kruskal-Walls test,X~2=32.36,P=0.000).In addition,significant differences were observed between groups of the concentrations of HGF(P<0.01,respectively).The intravitreous concentrations of VEGF(mean?SD)in three groups were(823.50?718.58)、(821.82?786.27)、(22.73?3.20)pg/ml(X~2=28.30,P=0.O00),respectively(Kruskal-Walls test,X~2=32.36,P=0.000).There was no significant correlation between the concentrations of HGF and those of VEGF in the same specimens from each group(P>0.05, respectively).Conclusions The intravitreous concentrations of HGF in the patients with diabetic NVG are obviously higher than those with IMH and non-NVI PDR,suggesting that HGF appears to be associated with mediating the neovascularization of retina and iris in NVG.However,it is not found there is any relationship between the intravitreous levels of HGF and VEGF.
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Objective To investigate the characteristics of renal hemodynamic and the esoteric prostacyclin(PGI2),thromboxane A2(TXA2)level in children with early Henoch-Schonlein purpura(HSP),and study the function of TXB_2/6-Keto-prostaglandin F(6-Keto-PGF_(1?))(T/K)numerus in early changes of kidney injury.Methods Children involved in the experiment were dicided into 3 groups.Thirty-one patients with HSP,divided into 2 groups according to routine urianlysis:children with HSP without renal damage group(n=16)and Henoch-Schonlein purpura nephritis(HSPN)group(n=15).Control group with 16 healthy children,their age and sex match with the other 2 groups.The urine of all children,including the children in control group,was sampled in 24 hours.The urinary production of the samples were kept in the freezer at-20 ℃.The radioimmunoassay was applied to determine the 6-Keto-PGF_(1?),TXB_2 quantitatively,and calculate the number of T/K.In the early morning the children accept the Doppler arteria renalis sonography with an empty stomach to determine the Vmax of the period of contraction of the arteria renalis the Vmin of diastolic phase and the resistent index(RI).SPSS 13.0 software was used to analyze the data.Results 1.The renal hemodynamic indicated a change of high velocity and resistance,the masculine rate(83.9%)was ob-viously higher than that in routine urinalysis(48.4%)(?2=5.79 P0.05).The RI in the former group(0.798?0.165)was much higher than that in the other one(0.637?0.116)(t=4.02 P