Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C

Background and Aim: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. Methods: A total of 7715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2515 (32.6%) patients. Of these 2515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. Results: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4–9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow‐up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P = 0.002). Conclusions: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.     

Detection of hepatocellular carcinoma after interferon therapy for chronic hepatitis C: Clinical study of 26 cases

The clinical findings in 26 patients in whom hepatocellular carcinoma (HCC) was detected after the start of interferon (IFN) therapy for chronic hepatitis C were analysed. Histological study before IFN therapy showed that 34.6% of patients were categorized as stage 3 (septal fibrosis with architectural distortion; the 0–4 scale) and 80.8% demonstrated at least some evidence of septal fibrosis or more advanced features. The AFP levels examined before IFN therapy were more than 20 ng/mL in 13 patients (84.6% of those studied). One of 26 patients had a complete response to IFN therapy, while six of 26 patients had only a partial response. HCC was detected within 1 year after the start of IFN therapy in 76.9% of patients. Thus, the possibility of the early occurrence of HCC or its existence at the time of therapy should be seriously considered when IFN therapy is contemplated. Patients with stage 3 or 3–4 histology may already have a small undetectable HCC before IFN therapy. Thus, for this reason, every patient treated with IFN should be examined at short regular intervals for the development of HCC during and after IFN therapy.     

Dynamic mutation loci: allele distributions in different populations

To assess the relative contributions of trans -acting factors (replication and repair functions) and cis -acting elements (repeat and flanking DNA composition) to the mechanism of trinucleotide repeat sequence mutation we have analysed the distribution of copy number polymorphisms at 12 loci associated with dynamic mutations in 15 populations of different ethnic origins. Genome wide instability of repeats in a particular population would be evidence of trans -acting factor instigation of the mutation process, whereas instability at a particular locus (perhaps even in several populations) would be evidence that the composition of the particular locus was the most significant factor contributing to mutation. The FRA16A locus is highly polymorphic in only the European population. Some other loci exhibit distinct distributions of alleles between different populations. Therefore sequences in the vicinity of the repeat - the cis component of a particular locus - appear(s) to be more important in the mutation mechanism than sporadic genome-wide instability induced by trans -acting factors such as the DNA mismatch repair enzymes.     

Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy

Hypertrophic cardiomyopathy and dilated cardiomyopathy are two major clinical phenotypes of “idiopathic” cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. A hypertrophic cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic cardiomyopathy and dilated cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.     

中药与日本汉方药原植物的差异比较及原因分析

依据 2000年版《中国药典》和第十四改《正日本药局方》收载植物类生药品种 ,列表比较了中药与日本汉方药原植物的差异 ,并对产生差异的现象和原因进行了分析和探讨。     

Aqueous fraction of Sauropus androgynus might be responsible for bronchiolitis obliterans

Background and objective: Bronchiolitis obliterans (BO) has been reported to develop following ingestion of Sauropus androgynus (SA), a leafy shrub distributed in Southeast Asia. Little is known about direct effects of SA on airway resident cells or haematopoietic cells in vitro. Identification of the SA component responsible for the development of BO would be an important key to elucidate its mechanism. We sought to elucidate the direct effects of SA on airway resident cells or haematopoietic cells and identify the SA element responsible for the pathogenesis of BO. Methods: SA dry powder was partitioned into fractions by solvent extraction. Human and murine monocytic cells, epithelial cells and endothelial cells were cultured with SA solution or fractions eluted from SA. We also investigated the effect of SA in vivo using a murine BO syndrome (BOS) model. Results: The aqueous fraction of SA induced significant increases of inflammatory cytokine and chemokine production from monocytic lineage cells. This fraction also induced significant apoptosis of endothelial cells and enhanced intraluminal obstructive fibrosis in allogeneic trachea allograft in the murine BOS model. We found individual differences in tumour necrosis factor α (TNF‐α) production from monocytes of healthy controls stimulated by this aqueous fraction of SA, whereas it induced high‐level TNF‐α production from monocytes of patients with SA‐induced BO. Conclusions: These results suggest that an aqueous fraction of SA may be responsible for the pathogenesis of BO.     

某城市交通区大气多环芳烃污染的时空分布特征

[目的]了解城市交通区不同地区和不同时间内颗粒物中多环芳烃的分布特征。[方法]对某城市某交通区不同地点颗粒物和多环芳烃的含量分别进行了监测，同时在1个地点进行了连续24h监测。[结果]不同地段颗粒物中多环芳烃的含量不同，总体趋势是：高架下大气中颗粒物多环芳烃的污染比高架上严重；城区比郊区污染严重；隧道内比隧道外污染严重。同时，同一地点颗粒物及其中多环芳烃连续24h的监测结果表明，在24h内，大气中颗粒物及其中的多环芳烃含量有规律的波动，在清晨、下午出现两个高峰。研究还发现在颗粒物和其中多环芳烃之间存在明显的相关性，相关系数为0．231，并得到了回归模型；对不同粒径的成分分析结果表明，PM2.5占PM10的30％～50％，是主要的多环芳烃携带颗粒物。[结论]交通因素以及周围环境因素是导致大气中颗粒物多环芳烃污染浓度改变的主要因素之一；PM2.5是主要的多环芳烃的携带者。     

Immunogenicity and reactogenicity of the component acellular pertussis vaccine produced by a combination of column purified pertussis toxin and filamentous haemagglutinin

This is the report on a prospective, single blind, comparative study of a component acellular pertussis vaccine produced by a combination of detoxified, column purified pertussis toxin (PT) and filamentous hemagglutinin (FHA) combined with diphtheria and tetanus toxoids (DTcaP) and the traditional acellular pertussis vaccine produced with essentially the same method as described by Sato with DT (DTaP) of the same manufacturer. A total of 616 infants and children received DTcaP and a total of 289 received DTaP. In all age groups for both vaccines values of serum antibodies to PT and FHA after two doses of the vaccines were comparable to those of convalescent sera. Incidences of systemic and local reactions were, in general, not greatly different between DTcaP and DTaP recipients. In Japan the use of traditional acellular vaccines replaced whole cell vaccines in 1981. Protective antigens of Bordetella pertussis have now been specified and thus component vaccines have become theoretically possible. This is the first component vaccine which has been developed in Japan. Several other component vaccines are now under investigation in the world.