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Biomedical subjects

F Imazeki

Publications and source records attributed to F Imazeki.

At least 55 records · Page 3Linked to original sources
PubMed1996

High incidence of ADH2*1/ALDH2*1 genes among Japanese alcohol dependents and patients with alcoholic liver disease.

In an attempt to clarify the genetic factors in alcoholism among the Japanese, polymorphism of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes has been investigated. Genetic polymorphism of ADH2/ALDH2 in 66 cases of normal subjects, 90 cases of alcohol dependent, and 31 patients with alcoholic liver disease among Japanese has been analyzed using a polymerase chain reaction assay followed by a direct sequencing method, because ethanol is mainly catabolized by ADH and ALDH and less by cytochrome P450IIE1 and catalase. The incidence of both ADH2*1/*1 and ALDH2*1/*1 was significantly higher in patients with alcohol dependence and in patients with alcoholic liver disease when compared with that in control subjects. In addition, the incidence of ALDH2*1/*2 and ALDH2*2/*2 was significantly reduced in alcoholics compared with control subjects. Genetic polymorphism of ADH2/ALDH2 in patients with alcoholic liver disease was not different from that of alcohol dependents. According to these results, not only ALDH2 gene, often claimed to be responsible for alcohol dependence among Japanese, but also ADH2 gene polymorphism, which modulates the metabolism of ethanol, play important roles in habitual alcohol intake behavior in Japanese patients and in some patients leads to alcoholic liver diseases.

Adult↗
PubMed1996

Point mutation in precore region of hepatitis B virus: sequential changes from 'wild' to 'mutant'.

One point mutation to make a stop codon in the precore (pre-C) region of the hepatitis B virus DNA in anti-HBe-positive patients has been reported recently. This mutation disturbs the formation of the pre-C protein that is processed to make HBeAg. The relationship between the point mutation and HBe antigen antibody status was investigated in B-viral liver diseases. The pre-C region was amplified by a polymerase chain reaction (PCR) method and the nucleotide sequences were determined by a direct sequencing method. In seven cases who were persistently HBeAg-positive, the wild type (no mutation in pre-C region) was detected in all. In 20 cases who were anti-HBeAg-positive at diagnosis, the mutant type (point mutation at nucleotide 1896 in pre-C region, which makes a stop codon) was detected in 16 cases and the wild type in two cases. In HBe seroconversion (SC) cases, the types of virus were investigated in serial blood samples. No mutant type was detected in initial sera during the HBeAg-positive period. In two 'natural' SC cases, the mutant type appeared before anti-HBe formation. However, in three anti-viral 'drug-induced' SC cases, the mutant type appeared after the formation of anti-HBe. In two 'reversed' seroconversion cases only the wild type was detected throughout the follow-up period. These data suggest that the appearance of a pre-C mutant may help to predict seroconversion from HBeAg to anti-HBe and may help distinguish 'natural' and 'drug-induced' seroconversion of HBeAg.

Adult↗
PubMed1995

Efficacy of longterm interferon treatment in chronic liver disease evaluated by sensitive polymerase chain reaction assay for hepatitis C virus RNA.

Effects of interferon treatment on hepatitis C virus were examined by investigating the presence of hepatitis C virus ribonucleic acid and anti-hepatitis C virus antibody in 70 patients with non-A, non-B chronic liver diseases. Twenty one patients were treated with three million units of interferon alfa 2a three times a week for 52 weeks, 24 patients were treated similarly for eight weeks, and 25 patients were given a placebo for eight weeks and served as control. Sixty six of 70 patients (94%) were positive for both hepatitis C virus RNA and second generation anti-hepatitis C virus antibody. Fourteen of 21 (67%) receiving the longterm treatment had a normalised alanine aminotransferase (ALT) activity, and in 12 of these hepatitis C virus ribonucleic acid became undetectable by the end of treatment and remained so during the three year follow up after the treatment. Anti-hepatitis C virus antibody determined by first generation assay became negative in one case at the end of the 52 week treatment, and in four cases at the end of the one year follow up. In contrast, only one of 24 (4%) who received the eight week treatment and only one of 25 (4%) who received the placebo had normalised ALT activities. Hepatitis C virus ribonucleic acid became negative in two patients undergoing short-term treatment and in none receiving the placebo. Thus, longterm interferon treatment seems effective in clearing hepatitis C virus from serum of patients with chronic liver disease.

Adult↗
PubMed1995

Clonality in hepatocellular carcinoma: analysis of methylation pattern of polymorphic X-chromosome-linked phosphoglycerate kinase gene in females.

Analysis of X-chromosome inactivation patterns in women has been used to assess the clonality of various tumors. In this report, we analyzed 27 liver tumors in women, including 18 samples obtained by the performance of ultrasonically guided thin-needle biopsies. By analysis of the heterogeneity of phosphoglycerate kinase gene, 11 of 27 (41%) cases were found to be heterozygous at the gene. Of these informative 11 cases with liver tumors, 7 cases were "large" tumors (> 25 mm in diameter) and 4 cases were "small" tumors (< 25 mm in diameter). All 7 large tumors showed monoclonal patterns by the phosphoglycerate kinase gene analysis. Of the 4 small tumors, 2 showed monoclonal, and 2 showed polyclonal patterns. The 2 with monoclonal patterns were pathologically diagnosed as hepatocellular carcinoma despite their small sizes (20 mm and 23 mm). Of the two with polyclonal patterns, the smallest one (15 mm) was diagnosed as benign adenomatous hyperplasia, and the other as hepatocellular carcinoma heavily infiltrated by lymphocytes. These data suggest that analysis of the methylation pattern of the phosphoglycerate kinase gene may be helpful on rare occasions in elucidating the nature of liver tumors but must in fact be used in conjunction with histological appearances to avoid errors secondary to inflammatory infiltrates.

Base Sequence↗
PubMed1995

Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients.

The incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included). Of the cases of chronic hepatitis B, 5 cases of HCC (3.9%) were detected; among the chronic hepatitis C cases, 13 cases (10.4%) were detected. Thus, although the mean follow-up periods were in the same range, the incidence of hepatocellular carcinoma was 2.7 times higher in hepatitis C than in hepatitis B (chi 2 = 3.116, P < .05). Using the Kaplan-Meier method, the incidence of HCC was significantly higher in chronic hepatitis C (P = .0194, generalized Wilcoxon test). In hepatitis C, the incubation period until HCC was detected was shorter when the liver disease was more advanced. Such a tendency was not observed in hepatitis B. In the 13 cases of HCC occurring in chronic hepatitis C, noncirrhotic liver was seen in only 1 case (7.7%), whereas 2 of the 5 cases of HCC (40%) in chronic hepatitis B were noncirrhotic. The prevalence of hepatitis C virus (HCV) genotypes II and III was the same in the total followed cases and HCC cases.

Adult↗
PubMed1994

Coinfection study of precore mutant and wild-type hepatitis B-like virus in ducklings.

The precore mutant hepatitis B virus often emerges from a mixed infection with combined wild-type and precore mutant viruses. Nevertheless, the precore mutant does not seem to be an evolutionarily favored strain. To investigate the interaction between wild-type and precore mutant hepadnaviruses in an animal model of perinatal transmission, we used an e antigen-defective mutant duck hepatitis B virus with mutations inside the stem-loop structure of precore messenger RNA for this coinfection study. Thirty 1-day-old ducklings were infected with wild-type duck hepatitis B virus, precore mutant virus or both viruses. The amounts of viremia and the distribution of viruses were analyzed by spot hybridization, polymerase chain reaction, restriction fragment length polymorphism, cloning and sequencing. We found that all the ducklings became chronic carriers of duck hepatitis B virus. The precore mutant replicate was less active than wild-type duck hepatitis B virus, and it could be overgrown by wild-type virus during the course of coinfection. These results demonstrated that wild-type duck hepatitis B virus might become the predominant species in a situation similar to the perinatal cotransmission in human beings. This might at least in part explain why the prototype virus could prevail for years.

Animals↗
PubMed1994

[Significance of total dose of IFN in the treatment of chronic hepatitis C].

Two hundred thirteen patients with chronic hepatitis C were treated with IFN for 4 to 52 weeks and complete response, in which ALT levels sustained within the normal value after more than 6 months following IFN treatment, was achieved in only 10% of the patients treated with less than 300 MU of IFN, whereas it was 42% in those treated with more than 500 MU, hence the total amount of IFN is important in the treatment of chronic hepatitis C. The duration of the treatment (4 to 52 weeks) made little difference in the response when more than 500 MU of IFN were administered.

Alanine Transaminase↗
PubMed1993

p53 gene mutations and 17p allelic deletions in hepatocellular carcinoma from Japan.

BACKGROUND: p53 gene mutations at codon 249 have been reported in hepatocellular carcinoma (HCC) from China and South Africa, a phenomenon shown to be closely associated with food contamination by aflatoxin. There have been few reports, however, in regard to p53 gene mutations in HCC from other geographic areas. METHODS: The authors analyzed 20 HCC from Japan for alteration of the p53 gene by restriction fragment length polymorphisms and for nucleic acid mutations by polymerase chain reaction with direct sequencing. RESULTS: Alterations associated with the p53 gene were found in 6 of 20 HCC (30%). Allelic loss of chromosome 17p occurred in 5 of 14 informative (heterozygous) cases (36%). Mutations in the p53 gene were detected in three cases (15%), at codons 176 (exon 5), 236 (exon 7), and 294 (exon 8). These cases were different from the HCC cases from China and South Africa, where point mutations in the p53 gene were reported at the same codon 249 in half of the cases and where aflatoxin food contamination and hepatitis B virus infection are recognized risk factors of HCC. No p53 gene alterations were found in smaller HCC (< 3 cm) or at earlier stages. CONCLUSIONS: In Japan, p53 gene alterations seem to be a late event in the progression of hepatocarcinogenesis, which is often associated with persistent infection by the hepatitis C or B virus, but not usually with exposure to aflatoxin.

Alleles↗
PubMed1993

Expression of hepatitis C virus core protein as a fusion protein with maltose binding protein. Detection of anti-hepatitis C core antibody by western blot.

Putative hepatitis C virus core sequence was amplified from a serum sample positive for anti-C-100-3 and expressed in Escherichia coli. Approximately 62 kDa fusion protein with maltose binding protein containing 20 kDa hepatitis C core protein was obtained. The antibody to this protein was detected in 53 of 54 (98%) sera from hepatitis C virus ribonucleic acid-positive patients including 40 sera positive for anti-C-100-3 and 13 sera negative for anti-C-100-3. The antibody was also detected in all of 12 patients with acute hepatitis C showing the earlier detectability of the antibody than anti-C-100-3. Thus, the protein expressed from the amplified hepatitis C core sequence by the polymerase chain reaction would be useful for the diagnosis of hepatitis C.

ATP-Binding Cassette Transporters↗
PubMed1993

Precore mutations and core clustering mutations in chronic hepatitis B virus infection.

BACKGROUND: Mutant hepatitis B virus is often associated with severe liver damage. The purpose of this study is to elucidate the relationship between mutations in hepatitis B precore/core gene and the severity of liver damage. METHODS: The hepatitis B precore/core gene from 20 patients with chronic hepatitis B virus infection was studied by polymerase chain reaction and direct sequencing. RESULTS: Missense mutations in the core gene were only found in patients with chronic active hepatitis. Three mutation clustering regions of core gene, codons 48-60, 84-101, and 147-155, had higher substitution rates than other regions. All patients with chronic active hepatitis had missense mutation(s) either in codons 84-101 or in codons 48-60. There was a trend of increasing substitutions in the precore/core gene from e antigen-positive asymptomatic carriers to e antibody-positive patients with chronic active hepatitis. CONCLUSIONS: These data suggest that (1) severe liver damage in chronic hepatitis B virus infection is related to the clustering missense mutations in codons 48-60 and 84-101 of core gene and that (2) the emergence of precore stop codon mutation and missense mutations around the carboxy-terminal processing site of precore/core protein (codons 147-155) may be the adaptive mechanisms of hepatitis B virus to decrease production and secretion of viral protein and retain the viral persistence.

Adult↗
PubMed1993

[Heterogeneity of delta virus RNA sequences in Japan].

Hepatitis delta virus RNA sequences were determined in isolates from two Japanese patients, M and S, by polymerase chain reaction and direct nucleotide sequencing and compared with three isolates from Italy, USA and Taiwan. The sequence obtained for hepatitis delta virus RNA from patient M was 92-96% identical to the sequences obtained for three other strains of hepatitis delta virus, whereas the sequence of hepatitis delta virus RNA obtained from patient S was approximately 80% identical to the other sequenced strains. This suggests that the delta agent in Japan has a heterogeneous origin and the delta virus RNA sequence from Japanese patient S is the most divergent delta virus isolate yet analyzed.

Adult↗
PubMed1992

Detection of antibody to hepatitis C E2/NS1 protein in patients with type C hepatitis.

Putative E2/NS1 sequence of hepatitis C virus was expressed in E. coli as a fusion protein with maltose binding protein. Approximately 80 kDa protein was obtained containing 38 kDa E2/NS1 protein. The antibody to this protein was detectable in the same serum from which the sequence was amplified. It was also detectable in none of 7 acute hepatitis, in 2 of 12 chronic persistent hepatitis, in 3 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was detectable in none of 10 normal subjects. In 3 cases who were positive for the antibody before the interferon treatment, it became undetectable after the treatment. Thus, it seems that the antibody is not a neutralizing antibody and is related to active viral replication.

Base Sequence↗
PubMed1992

Effects of antiviral agents on chronic hepatitis B. Analysis using Cox proportional hazard model.

Two hundred fifteen courses of antiviral treatment including interferon with or without steroid withdrawal, adenine arabinoside with steroid withdrawal, and steroid withdrawal alone were given to 175 patients with HBe-antigen positive chronic hepatitis B. The effectiveness was judged on loss of HBe antigen and formation of anti-HBe, and was compared with 80 controls. According to cumulative HBe seronegative and seroconversion rates as analyzed by the Kaplan-Meier method, interferon with steroid withdrawal increased both the cumulative HBe seronegative and seroconversion rates significantly (P < 0.0001). Adenine arabinoside with steroid withdrawal and interferon alone increased the cumulative HBe seronegative rate only (P < 0.001). The Cox proportional hazard regression model was fitted to the data of 188 cases whose pretreatment liver biopsy specimens were obtained. Among treatment protocols, interferon with steroid withdrawal shortened both the HBeAg-positive period and the duration until anti-HBe becomes reactive significantly (P < 0.0001). Interferon without steroid withdrawal and adenine arabinoside with steroid withdrawal shortened the HBeAg positive interval only (P < 0.05). Among patients' characteristics, female and advanced liver histology were favorable factors. Effects of treatment protocols were analyzed after averaging each parameter of the patients' characteristics. Interferon and adenine arabinoside with steroid withdrawal shortened the HBeAg-positive interval significantly (P < 0.0001 and P < 0.05, respectively), and interferon alone showed a tendency to shorten the interval. In particular, interferon with steroid withdrawal increased the chance of losing HBeAg 7.3 times more than control. The effectiveness of antiviral treatment on chronic hepatitis B, especially the priority of interferon with steroid withdrawal, was thought to be established through this study.

Antiviral Agents↗
PubMed1992

p53 gene mutations in gastric and esophageal cancers.

The presence of point mutation of the p53 gene in exons 5, 6, 7, and 8 was examined in 10 cases of gastric adenocarcinoma and 5 cases of esophageal squamous cell carcinoma by polymerase chain reaction and direct nucleotide sequencing. Mutations of the p53 gene were found in 5 cases of gastric cancer and 4 cases of esophageal cancer. The mutations in the stomach cancers consisted of four missence mutations (exons 5 and 8) and one frame shift (exon 7). In the esophageal cancers, three missence mutations (exons 6, 7, and 8) and one point mutation within the splice donor site of intron 5 were found. Of the seven missence mutations in the two cancers, five showed the transition from G to A and two from G to T. All these changes occurred in the highly conserved region of the p53 protein. These results suggest that mutations of the p53 gene are genetic events in the pathogenesis of gastric adenocarcinoma and esophageal squamous cell carcinoma.

Adult↗
PubMed1991

Resolution of acute hepatitis C after therapy with natural beta interferon.

To test whether interferon can prevent acute non-A, non-B hepatitis from becoming chronic, a prospective controlled trial was conducted in 25 patients; 11 were treated for an average of 30 days with a mean of 52 megaunits of interferon and 14 acted as controls. 4 patients in the treatment group who continued to have raised serum aminotransferase concentrations after a year's follow-up were given a second course of interferon. Follow-up at 3 years has revealed that all but 1 of those treated showed normal serum aminotransferase, whereas only 3 controls showed such change (p less than 0.02). Serum hepatitis C virus RNA became undetectable in 10 of 11 treated and in only 1 of 12 control patients, which suggests that interferon prevents the progression of acute non-A, non-B hepatitis to chronicity by eradicating HCV.

Acute Disease↗