Use of Fmoc-N-(2-hydroxy-4-methoxybenzyl) amino acids in peptide synthesis

The use of N, O-bisFmoc-N-(2-hydroxy-4-methoxybenzyl) amino acid derivatives in the synthesis of peptides with difficult sequences has already been described. With these amino acid derivatives the reversible protecting group 2-hydroxy-4-methoxybenzyl (Hmb) for the backbone amide bonds of peptide chains is introduced, and thus the aggregation due to hydrogen-bond interchain association is inhibited. This paper describes the synthesis and use of Fmoc-N-(2-hydroxy-4-methoxybenzyl)amino acid derivatives as an alternative means of introducing Hmb backbone protection. These new monoFmoc derivatives were obtained in higher yield than the bisFmoc derivatives. Coupling yields to the amino peptide resin were the same as those obtained with bisFmoc derivatives, under the TBTU/HOBt/DIEA conditions. We also compared different syntheses of a difficult peptide with the Fmoc approach [triple coupling, capping, use of chaotropic agents, backbone protection using monoFmoc (Hmb)Ala] and with optimized Boc chemistry. Both the backbone protection and optimized Boc chemistry approaches gave the desired product in excellent yield and purity. © Munksgaard 1997.     

A comparative study of acute and chronic diseases induced by two subgroups of Theiler’s murine encephalomyelitis virus

Theiler’s murine encephalomyelitis viruses (TMEV) are divided into two subgroups on the basis of their different biological activities. The GDVII strain produces acute polioencephalomyelitis in mice, whereas the DA strain produces demyelination with virus persistence in the spinal cord. A comparative study of GDVII and DA strains suggested that low host immune responses are responsible for the development of acute GDVII infection and that the persistence of infected macrophages plays a crucial role in the development of chronic white matter lesions in DA infection. All 78 mice infected with GDVII died or became moribund by day 13, while none of 54 mice infected with DA died. In the acute stage, the distribution of viral antigens in the central nervous system (CNS) tissue was similar in both GDVII and DA infections, although the virus titer was higher in GDVII infection. In DA infection, a substantial number of T cells were recruited to the CNS on day 6 when they were virtually absent in GDVII infection. The titer of neutralizing antibody was already high on day 6 in DA infection but was negligible in GDVII infection. Development of chronic paralytic disease from day 35 of the DA infection was accompanied by focal accumulation of viral antigen-positive macrophages in the spinal white matter. In addition, white matter lesions comparable to those in chronic DA infection were induced in the spinal cord within 7 days after intracerebral injection of DA-infected murine macrophages. Received: 26 June 1995 / Revised, accepted: 27 December 1995     

Effect of hepatitis C antibody screening in blood donors on post-transfusion hepatitis in Taiwan

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.     

Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan. © 1993 Wiley-Liss, Inc.     

HCV的检测方法

从发现丙型肝炎病毒以来 ,丙肝的检测技术发展迅速 ,灵敏度和特异性都有明显的提高 ,方法学在不断改进完善。笔者就近年来丙型肝炎的实验室检测方法作简要的综述     

HBV-M定量检测与HBV-DNA含量水平关系的初步探讨

目的 研究乙型肝炎病毒标志物定量检测结果与其HBV-DNA含量的临床关系。方法 采用时间分辨免疫定量和荧光定量-PCR技术，对HBV-DNA和HBV-DNA含量进行检测。结果 在HBsAg/HBeAg/HBcAb,HBsAg/HBcAb/HBcAb,HBeAg/IC及单纯HBcAb阳性的四个组别中，HBV-DNA阳性率分别是97.17%、30.56%、100%和25%；在HBsAg,HBeAg,HBeAb,HBcAb定量检测高，低值两组HBV-DNA含量对比中，HBV-DNA阳性率分别为76.92%、58.14%；100%、97.26%；20.00%、11.42%；64.62%、27.63%。结论 HBV-DNV比HBV-M更能及时准确反映乙型肝炎病毒感染者的病程情况。     

LightCycler实时监测PCR定量分析血清HBV DNA

目的 检验LightCycler实时监测PCR（real-time detection PCR,RTD-PCR)对血清中HBV DNA定量检测的灵敏性和可重复性，探讨HBV血清标志物与HBV DNA定量的关系。方法 HBV定量按深圳匹基公司乙肝PCR荧光检测试剂盒使用说明，对乙肝标志物已明确的773例血清中HBV DNA定量结果进行统计分析。结果 实时监测PCR对血清中HBV DNA定量检测的灵敏性高，可检测低至1000拷贝／ml血清；可重复性好，批间误差＜20％；各种标志物类型的血清HBV DNA含量分布情况表明，HBV血清标志物中HBeAg与HBV DNA含量有明显的关系，一般HBeAg阳性血清HBV DNA含量较高，但也有相当一部分例外。结论 LightCycler实时监测PCR对血清中HBV DNA定量检测灵敏性高可重复性好；仅根据HBV血清标志物往往不能确定乙肝患者HBV DNA复制水平的高低，HBV DNA定量检测具有十分重要的临床意义。     

Spinal MRI in vacuolar myelopathy, and correlation with histopathological findings

We correlated MRI features with histopathological findings in an HIV-positive patient with vacuolar myelopathy. On MRI symmetrical nonenhancing high-signal areas in the posterior columns on T2-weighted images result from extensive vacuolation visible on histological sections. Received: 18 November 1997 Accepted: 23 March 1997     

新生儿先天性畸形与孕妇乙型肝炎病毒感染关系的研究

为探讨孕妇乙型肝炎病毒(HBV)感染和某些因素对先天性畸形的致病作用,本文进行了96对新生儿先天畸形的配对(1:1)病例对照研究,报道先天畸形的频率和构成,单因素和多因素的条件Logistic回归分析,表明孕妇HBsAg阳性等6个因素对先天畸形呈阴性结果,而与接触农药和孕周的因素有明显联系,值得进一步探讨。