Association between smoking and dopamine receptor D2 polymorphisms in male patients with schizophrenia / 中国心理卫生杂志

Objective:To investigate the association between dopamine receptor D2(DRD2) polymorphisms and smoking in male patients with schizophrenia.Methods:Totally 773 patients with schizophrenia (567 smokers and 206 non-smokers) and 302 normal controls (168 smokers and 134 non-smokers) were recruited.The two single nucleotide polymorphisms (SNPs) (rs1800497 and rs1079597) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP).SHEsis genetic analysis platform was used to calculate linkage disequilibrium index and infer allele distribution and haplotype frequency.Results:There was no significant difference in two SNPs genotype and allele distributions between the patients and normal controls or between smokers and non-smokers in either patients or normal controls alone (Ps ＞ 0.05);the frequency estimations of haplotype C-A and T-G in patients with schizophrenia were higher than in normal controls (8.0％ vs.5.2％,10.2％ vs.4.1％,Ps ＜0.05),T-A (34.6％ vs.40.2％,P ＜0.05),whereas the frequency estimation of haplotype T-A in patients with schizophrenia was lower than in normal controls,and all the differences were statistically significant (34.6％ vs.40.2％,P ＜ 0.05).It was also observed that the frequency estimation of haplotype T-A in normal smokers was significantly lower than in normal non-smokers (2.5％ vs.6.1％,P ＜0.05).Conclusion:There may be a correlation between DRD2 polymorphisms and the susceptibility to schizophrenia,but not between DRD2 polymorphisms and smoking neither in patients with schizophrenia nor in normal controls.

Impaired prepulse inhibition of acoustic startle in Chinese patients with first-episode, medication-naïve schizophrenia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with schizophrenia have prominent abnormality in information processing that can be observed by measures of prepulse inhibition (PPI) of acoustic startle reflex and PPI deficits have been considered as a candidate endophenotypic marker of schizophrenia. However, there has been little information on PPI and related measures in Chinese patients with schizophrenia. The research was to explore the deficits of acoustic startle reflex that might exist in Chinese patients with schizophrenia.</p><p><b>METHODS</b>Startle response to acoustic stimuli, habituation, and PPI were examined in 31 Chinese patients with first-episode, medication-naïve schizophrenia and 30 age- and sex-matched healthy Chinese controls. At the same day of startle testing, psychopathological symptoms of the patients were assessed with the Positive and Negative Syndrome Scale (PANSS).</p><p><b>RESULTS</b>Compared with healthy controls, patients exhibited the significant reduction in startle response and PPI deficits at 60 milliseconds (ms) intervals (PPI60, P < 0.05) but not at 30 or 120 ms intervals. Furthermore, there was a relatively strong correlation between PPI60 (P < 0.05) and scores of positive scale of PANSS in patients with schizophrenia.</p><p><b>CONCLUSION</b>Our findings confirmed impaired PPI in Chinese patients with schizophrenia and suggested that a relationship between sensorimotor gating deficits and clinical symptoms of patients with schizophrenia might exist.</p>

The preparation of monoclonal antibodies against AAV2 and study on their characterizations / 病毒学报

7 strains of stable cell lines secreting monoclonal antibodies against AAV2 capsids were obtained by immunizing BALB/C mice with highly purified recombinant adeno-associated virus. Among them, the monoclonal antibodies B10 and G4 had neutralizing activity, and their subtypes were IgG1 and IgG2a, respectively. The binding characterizations of the two neutralizing antibodies were studied. Both B10 and G4 showed serotype specific binding activities to rAAV2 virus particles other than AAV1, AAV5, and AAV8, and the binding could not be blocked by heparin. After incubating with the two antibodies separately, rAAV2 viruses could still bind to sensitive cell line BHK-21, suggesting that the binding sites of the two antibodies to rAAV2 located at different positions on viral particle surface from the primary receptor binding sites of AAV2. Western blotting assay showed that B10 could bind to VP1, VP2 and VP3 of rAAV2. However, G4 bound none of them. The results suggested that B10 recognized a linear epitope of AAV2 capsid, whereas G4 probably recognized a conformational epitope on the surface of AAV2 virus particle. The two antibodies with different characteristics provided valuable tools for AAV2 virus particles detection and infection processes.

Preparation of rAAV2/hFIX and experimentally application to gene therapy for hemophilia B / 中华血液学杂志

<p><b>OBJECTIVE</b>To prepare the rAAV2/hFIX and evaluate the efficiency of the preparation on gene therapy of hemophilia B model mice.</p><p><b>METHODS</b>The rAAV-2/hFIX was prepared by "one helper virus-one vector cell line" strategy and transfected both BHK-21 and C2C12 cells in vitro. The hFIX antigen level in cell culture supernatant was assayed. The rAAV-2/hFIX was injected into muscles of hemophilia B model mice and assayed the serum hFIX levels, hFIX clotting activity, bleeding time, 5 min bleeding volume.</p><p><b>RESULTS</b>The hFIX antigen could be detected from 24 h till 120 h after BHK-21 and C2C12 cells were transfected with highest levels at 24 h reaching (51.0 +/- 6.5) ng/10(5) cells and (68.0 +/- 7.2) ng/10(5) cells, respectively. The rAAV2/hFIX injected mice could efficiently express hFIX and peaked at three weeks after injection, then slowly decreased but low level hFIX antigen was still detectable till 10 weeks after injection. There were significant differences between the high, middle and low dose groups of rAAV2/hFIX and the control group (P < 0.01), the plasma FIX clotting activities in the model mice were improved remarkably, bleeding time was greatly shortened and bleeding in 5 min was decreased. The hFIX expression level and FIX clotting activity of the high dose of rAAV2/hFIX group (1.6 x 10(13) v.g./kg) reached about (387.0 +/- 12.5) ng/ml plasma in contrast with the normal levels of (30.0 +/- 5.5)% at the third week after injection. No rAAV2 vector DNA was detected in the organs except for injected muscle tissue.</p><p><b>CONCLUSION</b>The rAAV2/hFIX transfected BHK-21 and C2C12 cells could efficiently express hFIX antigen and was of therapeutic effects for the hemophilia B model mice by intramuscularly injection.The results provide the basis for clinical trial of rAAV2 gene therapy for hemophilia B.</p>