Gene therapy of malignant brain tumors: a rat glioma line bearing the herpes simplex virus type 1-thymidine kinase gene and wild type retrovirus kills other tumor cells.

Tumor cells infected with a retrovirus vector (VIK) containing the herpes simplex virus thymidine kinase (HSV-TK) gene can be selectively killed by treatment with nucleoside analogues, such as ganciclovir. To mediate delivery of the HSV-TK gene to "recipient" tumor cells, "donor" C6 rat glioma cells infected with the VIK vector (C6VIK) were superinfected with wild type Moloney murine leukemia virus (WT Mo-MLV). These modified donor cells (C6VIKWT) produced both wild type retrovirus and the VIK vector. In culture, C6VIKWT cells were 300-fold more sensitive to the toxicity of ganciclovir than were C6VIK cells, suggesting that the presence of wild type retrovirus contributed to the toxicity. Co-culture of C6VIKWT cells with the C6 subline, C6BAG, sensitized the latter to ganciclovir treatment. Nude mice inoculated subcutaneously with a mixture of C6VIKWT and C6BAG cells showed regression of subsequent tumors when treated with ganciclovir. The observations show that tumor cells modified in culture by infection with a retrovirus bearing the HSV-TK gene and wild type retrovirus are not only sensitive to ganciclovir, but can transfer this sensitivity to neighboring "naive" tumor cells in culture and in vivo.     

氧化苦参碱对胆碱酯酶影响的临床研究

目的　研究氧化苦参碱 (OM)治疗病毒性肝炎过程中 ,胆碱酯酶 (ChE)的动态变化及与同期白蛋白 (ALB)、凝血酶原活动度 (PTA)及其他肝功能的关系。方法　 98例病毒性肝炎患者分成 4组 ;A组 31例 (静脉注射OM) ,B组 30例 (口服OM) ,C组 7例 (肌内注射OM) ,D组 30例 (一般护肝药物 ,不用OM)。定期检测血清ChE、ALB、PTA、肝功能、肾功能、血常规、血清补体 1型受体 (sCR1)、红细胞黏附功能 (EIIAF)指标。结果　A、B、C 3组在治疗中ChE明显下降 ,治疗前中后比较 ,差异有显著意义 (P值分别为 <0 0 0 1、<0 0 0 1、0 0 2 3) ;同时在ChE数值及异常率与对照组比较 ,差异有显著意义(P <0 0 0 1)。A、B、C 3组在治疗前中后 ,ALB、PTA随病情而变化 (P值均 >0 0 5 )。4组治疗后病情均有明显好转 ,ChE的下降并不伴随肝功能的恶化。结论　OM制剂在治疗病毒性肝炎中ChE明显下降 ,但反映肝脏实质功能的ALB、PTA等指标无改变 ,ALT、AST、TBiL好转。在OM治疗结束后 ,ChE迅速恢复正常。所以 ,ChE的下降并不表明病情的恶化 ,其机理尚待探讨。     

Increased susceptibility to HIV-1 of peripheral blood lymphocytes in acute infection with Epstein-Barr virus

Epstein-Barr virus (EBV) is an important pathogen in human immunodeficiency virus (HIV)-infected individuals that causes lymphoma and other lymphoproliferative disorders upon disease progression; however, interaction between the two viruses during acute infection is not well known. Expression of CCR5, a major coreceptor for HIV, was enhanced on CD4+ T cells from patients with acute EBV infection. Furthermore, susceptibility of those cells to R5-HIV-1, but not X4-HIV-1, was increased. EBV effects on CCR5 expression on or susceptibility to R5-HIV-1 of CD4+ T cells did not require coinfection of the same cell with the two viruses, because CD4+ T cells from patients with acute EBV infection were not infected with EBV. Considering that both HIV and EBV are transmitted by intimate contact, such possible interaction between the two viruses may have implications for viral transmission and the pathogenesis of HIV disease.     

Restriction endonuclease analysis of varicella-zoster vaccine virus and wild-type DNAs

The DNA from several clinical isolates of varicella-zoster virus (VZV) were compared with the DNA from the vaccine strain VZV using three restriction endonucleases: BamHI, BgII, and HpaI. When electrophoresed through an agarose gel, the vaccine DNA digestion pattern was significantly different from the digestion patterns of the wild-type DNAs. Variations in the digestion pattern of the separate clinical isolates were also observed.     

Dynamics of HIV replication in lymphocytes and the efficacy of protease inhibitors

Using a system that allows transfection of resting peripheral blood lymphocytes (PBLs) two questions were addressed: the kinetics of HIV replication from the state of proviral latency, and the impact of different parameters on the efficacy of protease inhibitors to control HIV replication. PBLs were transfected with an infectious full length HIV-DNA harboring a luciferase reporter gene and activated thereafter. Ritonavir was added at different times at doses ranging from to 0.06 to 1 microM. Viral expression was assessed by quantifying luciferase activity in cell extracts and levels of p24 HIV antigen in culture supernatants. After transfection and cell activation, intracellular expression of HIV proteins, as assessed by luciferase detection, occurred within 2 hr. HIV-gag p24 antigen was detected in culture supernatants between 6 and 8 hr post-activation. Ritonavir was effective in blocking viral replication when given within 4 hr following HIV reactivation, but a delay in ritonavir administration or breaches in ritonavir levels after 6 hr from transfection resulted in viral escape. HIV reactivation from proviral latency in PBLs is an extremely rapid process, faster than estimated from previous models. These data stress the need for maintaining effective antiretroviral concentrations to block completely viral replication.     

临床诊断为非甲～戊型肝炎患者的病原学研究

目的探讨临床诊断为非甲-戊型肝炎患者的病原学。方法 采用巢式PCR（nPCR)检测HBV、TTV、B19、和SENV DNA；用逆转录巢式PCR（RT-nPCR)检测HGV和HCV RNA。结果 60例临床诊断为非甲-戊型肝炎患者中，单独HBVDNA阳性30例（阳性率为50.0%)，HBV和TTVDNA阳性10例（16.7%)，HBV和B19DNA阳性6例（10.0%)，HCVRNA、HBV和SENVDNA阳性1例（1.7%)，单独HCVRNA阳性1例（1.7%)，HCVRNA和B19DNA阳性1例（1.7%),HGVRNA无一例阳性，单独B19DNA阳性2例（3.3%)。单独TTVDNA阳性1例（1.7%)，另8例（13.3%)上述病毒核酸均为阴性。HBV合并感染TTV或B19对其血清学生化指标无影响。结论HBV是临床诊断为非甲-戊型肝炎的主要病原，HGV、TTV、B19和SENV与非甲-戊型肝炎无关。     

Evidence for Presence of Types A and B of Beet Necrotic Yellow Vein Virus (BNYVV) in Iran

Rhizomania a viral disease, caused by beet necrotic yellow vein benyvirus (BNYVV), is now widely spread, throughout the sugar beet growing areas of Iran. Genomes of BNYVV are composed of five RNA molecules with specific functions. In this study sequence analyses were conducted on the major coat protein gene (CP21), and parts of RNA3 and RNA4 of an Iranian strain of BNYVV from the Fars province. Sequence alignments of Iran Fars CP21 with other isolates showed closed similarities at nucleotide and amino acid levels with BNYVV pathotype A isolates; S from Japan, and YU2 from Yugoslavia. These results suggest that Iran-Fars isolate probably originated from Asia or neighboring European countries rather than from Germany or France.     

West Nile virus encephalitis with myositis and orchitis

This report documents the hospital course and autopsy findings of a 43-year-old man with a renal allograft who died of West Nile virus (WNV) encephalitis. Central nervous system (CNS) findings were those of severe necrotizing and hemorrhagic encephalitis affecting gray matter regions limited to the diencepahlon, rhombencephalon, spinal cord, and limbic system. The bilateral process exhibited preferential involvement of motor neurons. Brain imaging obtained 6 days before death demonstrated an unusual pattern of involvement corresponding with the autopsy findings, confirming that imaging may be a specific diagnostic guide in WNV encephalitis. Extra-CNS findings include myositis with T-lymphocyte infiltration of nerve fibers, suggesting that the virus may reach the CNS via peripheral nerves. Orchitis with dense T-lymphocyte infiltration and syncytial cell formation thought to be due to WNV were also noted.     

散发性戊型肝炎病毒感染的诊断

用基因工程重组的戊型肝炎病毒基因结构区第二码框架和第二读码框架具有免疫表位的嵌合抗原，建立了间接酶联免疫法，检测散发性急性肝炎病人血清中抗－ＨＥＶＩｇＧ和ＩｇＭ抗体。在４６例急性肝炎病人中出抗－ＨＥＶＩｇＧ抗体阳性７例，阳性率为１５．２２％，７例ＩｇＧ抗体阳性中，有５例ＩｇＭ抗体也阳性，占７１．４％。