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Biomedical subjects

N Enomoto

Publications and source records attributed to N Enomoto.

At least 19 recordsLinked to original sources
PubMed1992

Clinical backgrounds of the patients having different types of hepatitis C virus genomes.

Hepatitis C virus (HCV) genomes were recently detected in biological materials, and variations of nucleotide sequences were reported. In the present study, typing of the HCV genomes was performed in 91 HCV-RNA-positive patients and the clinical features of patients with different types of HCV were compared. From the nucleotide sequences of the cDNA fragments, HCV can be divided into at least two types: HCV-K1-PT and HCV-K2. All cDNAs amplified from 91 patients were hybridized with cDNA probes of either HCV-K1-PT or HCV-K2. HCV-K1-PT was found in about 80% of the patients, and HCV-K2 was found in about 20% of the patients. These results indicate that types of HCV are limited to two types, i.e., K1-PT and K2, and the major type is HCV-K1-PT, at least in Japan. Detection rate of antibodies to C-100-3 protein were not different between the patients having HCV-K1-PT and HCV-K2, indicating that the antibodies may develop in HCV-related patients without relation to the types of the HCV genomes. Prevalence of the two types of HCV were nearly the same in various forms of NANB-related liver disease. However, the prevalence was somewhat different in alcoholic liver disease. HCV-K2 was found in patients younger than the patients with HCV-K1-PT. Frequency of a history of blood transfusion tended to be lower and the initial response to interferon treatment was clearly better in patients having HCV-K2 versus patients having HCV-K1-PT. These results suggest the possibility that clinical features due to HCV-K1 may be somewhat different from those due to HCV-K1-PT. However, the number of patients examined was too small to allow a definite conclusion, indicating a necessity for further study with a larger number of patients.

DNA, Viral↗
PubMed1991

Hepatitis C virus RNA genome in plasma of patients with non-A, non-B hepatitis.

Recently, the assay system of anti-hepatitis C virus antibody (HCV-Ab) was developed. However, there is no clinically useful method to detect hepatitis C virus (HCV) itself. The authors recently developed a method to detect the HCV-RNA genome in plasma using polymerase chain reaction (PCR). In the present study, the specificity of this assay in detecting HCV infection was investigated. Freshly obtained 1 ml plasma specimens from 100 patients with various liver diseases and from 11 control subjects were studied. In patients with non-A, non-B (NANB) hepatitis-related liver diseases, HCV-RNA was detected in 2 out of 7 cases of acute hepatitis, in 29 out of 31 cases of chronic hepatitis, in 17 out of 21 cases of cirrhosis and in 2 out of 6 cases of hepatocellular carcinoma. On the other hand, no HCV-RNA was detected in 15 cases of various types of alcoholic liver diseases, in 12 cases of hepatitis B related liver diseases, and in 11 controls. HCV-RNA was detected in 2 of 6 drinkers with chronic hepatitis. The prevalence of HCV-RNA was not closely related to a history of blood transfusions. These results suggest that our method for HCV-RNA is specific for HCV infection and HCV infection is the likely etiology of most chronic NANB hepatitis cases. The clinical usefulness of our method is illustrated by the fact that we were able to study 100 patients and needed only 1 ml plasma per HCV-RNA assay.

Electrophoresis, Polyacrylamide Gel↗
PubMed1991

Genotyping of the aldehyde dehydrogenase 2 (ALDH2) gene using the polymerase chain reaction: evidence for single point mutation in the ALDH2 gene of ALDH2-deficiency.

About half of all Japanese lack the activity of aldehyde dehydrogenase 2 (ALDH2), and suffer a flush after alcohol intake due to the marked elevation of blood acetaldehyde concentration. The cause of ALDH2 deficiency is thought to be a single point mutation in codon 487 of the ALDH2 gene. However, this mutant ALDH2 gene has not yet been cloned and sequenced. We amplified and cloned the exon 12 of the ALDH2 gene using polymerase chain reaction (PCR), and revealed that normal GAA coding glutamic acid is replaced for AAA coding lysine in codon 487 of the mutant ALDH2 gene. Based on this finding, we performed the genotyping of the ALDH2 gene using PCR and allele-specific oligonucleotide probes. The genotypes of 13 subjects with ALDH2-active phenotype were all homozygous for the normal ALDH2 gene (ALDH2(1)), while in 9 subjects with ALDH2-deficient phenotype 2 subjects were homozygous for the mutant ALDH2 gene (ALDH2(2)) and the other 7 subjects were heterozygous for both genes, indicating that the mutant ALDH2 gene is dominant. In 20 normal control subjects, the prevalence of ALDH2(1)/ALDH2(1), ALDH2(1)/ALDH2(2) and ALDH2(2)/ALDH2(2) was 45%, 45% and 10% respectively. On the other hand, in 36 alcoholic liver disease patients, the prevalence of the genotypes was 83%, 17% and 0%. These results confirmed the previous observation that the incidence of ALDH2 deficiency is much lower in alcoholic liver disease patients than in the general population, and suggested that most of the ALDH2 deficient patients with alcoholic liver disease are heterozygous for the normal and mutant ALDH2 genes.

Aldehyde Dehydrogenase↗
PubMed1991

Typing of hepatitis C virus genomes by restriction fragment length polymorphism.

Recently, we reported that hepatitis C virus (HCV) can be classified genetically into two types, HCV-K1 and HCV-K2, which show 67% and 71% identity at the nucleotide and amino acid sequence levels in a 340 bp region which encodes the NS5 gene Gly-Asp-Asp motif. To develop a rapid method to classify the genomes of HCV isolates, we identified restriction fragment length polymorphisms (RFLPs) in reverse transcriptase-polymerase chain reaction products encoding a portion of the NS5 gene. AluI and AccII enabled HCV to be classified into the K1 and K2 types, and Sau96I enabled classification into the K1 type, and the K2a and K2b subtypes. These RFLPs also generally allow Japanese isolates to be distinguished from the prototype (PT, an isolate from the U.S.A.), which is a K1 type. Sequence analysis of the 5'-untranslated regions of Japanese isolates revealed near identity between the K1 type and PT, and 93 to 94% identity between the K1 and K2 types, indicating that there are type K1- and K2-specific RFLPs in this region. Our results suggest that the nucleotide sequences of the K1 and K2 types are different throughout the HCV genome. The incidence of HCV types K1, K2a and K2b, and PT in 50 samples was 74%, 16%, 8% and 2%, respectively.

Base Sequence↗
PubMed1991

Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes.

In order to clarify the relationships between acetaldehyde (Ac-CHO) metabolism and low Km (mitochondrial) aldehyde dehydrogenase (ALDH2) genotypes, hepatic ALDH2 activity was determined and serial changes of blood Ac-CHO levels after ethanol administration were analyzed in the individuals homozygous for the normal ALDH2 genes, heterozygous for the normal and mutant ALDH2 genes, and homozygous for the mutant ALDH2 genes. Genomic DNA was extracted from white blood cells and genotyping of ALDH2 was performed using the polymerase chain reaction technique and slot blot hybridization with synthesized oligonucleotide probes specific to the normal and mutant ALDH2 genes. ALDH2 activity was not detectable in the liver in two cases of the mutant homozygote. In four out of eight cases of the heterozygote, hepatic ALDH2 activity was measurable, although the activity was lower compared with that in the normal homozygote. Blood ethanol levels after alcohol administration were not different among the three different ALDH2 genotypes. Blood Ac-CHO levels after drinking of alcohol were significantly higher in the heterozygotes and the mutant homozygotes than in the normal homozygotes. The levels after a moderate amount of ethanol (0.8 g/kg of body weight) in a case of the mutant homozygote were not different from those of the heterozygotes. However, the levels after a small amount of ethanol (0.1 g/kg of body weight) were significantly higher in the mutant homozygotes than in the heterozygotes. These results indicate that hepatic ALDH2 activity is lacking completely, and metabolism of Ac-CHO in the liver is severely impaired in the homozygotes of the mutant ALDH2 genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1991

Cholesterol-lowering effect of Agemaki, a kind of shellfish, in mice.

Agemaki (Sinonovacula constricta) is an edible and popular shellfish in the western part of Japan. The present study demonstrated the effects of feeding Agemaki on cholesterol and triglyceride concentrations in mice plasma and liver. Mice were fed a diet containing 0.1% cholesterol and 0.1% Na-cholate for 1 week, and then a cholesterol-free diet or a cholesterol-enriched one for 2 weeks. To both diets, freeze-dried Agemaki was added at a 5% level. There was no statistically significant effect on the body-weight gain, food intake, and liver weight by feeding Agemaki in both dietary regimens. However, Agemaki significantly lowered the concentrations of plasma and liver cholesterol and also of plasma triglyceride in mice feeding on the cholesterol-rich diet. A similar tendency was also observed for the mice feeding on the cholesterol-free diet. The analysis of freeze-dried Agemaki revealed a relatively larger proportion of n-3 polyunsaturated fatty acids and plant sterols, which may possibly decrease plasma lipids. So far as we know, this is the first report showing hypolipidemic effect of Agemaki.

Animals↗
PubMed1991

Different types of chronic hepatitis in alcoholic patients: does chronic hepatitis induced by alcohol exist?

To verify the existence of chronic hepatitis induced by alcohol, the clinicopathological features of chronic hepatitis in heavy drinkers were studied using various viral markers. Histological features of chronic active hepatitis were seen in 27 heavy drinkers. These patients were divided into four groups. The AL group (seven cases) consisted of alcoholics who were negative for both hepatitis C antibody and HBsAg; the HB group (four cases) was positive for HBsAg; the HC1 group (seven cases) was positive for hepatitis C antibody but negative for hepatitis C virus-RNA genome; and the HC2 group (nine cases) was positive both for hepatitis C antibody and hepatitis C virus-RNA genome. Serum AST and ALT activity declined during 4 wk of abstinence in most patients in the AL group and in the HC1 group. The response of serum AST and ALT to abstinence was poor in most patients in the HB group and the HC2 group. Serum desialo-transferrin and alcohol liver membrane antibodies were detected more frequently in the sera of patients in the AL group and HC1 group. A trend toward increased frequency of centrilobular ballooning existed in the AL group, but this did not reach statistical significance. These results suggest that chronic active hepatitis in patients in the AL group, in whom markers of HBV and hepatitis C virus were absent, may be caused by alcohol. Patients in the HC1 group who had hepatitis C antibody but not hepatitis C virus-RNA may represent cases where both alcohol and hepatitis C virus are involved.

Adult↗
PubMed1991

Alcoholic liver disease in heterozygotes of mutant and normal aldehyde dehydrogenase-2 genes.

To clarify the pathogenetic role of acetaldehyde in the development of alcoholic liver disease, genotyping of aldehyde dehydrogenase-2 genes was performed and the clinical features of the alcoholic liver disease patients with different genotypes were compared. Genotyping of aldehyde dehydrogenase-2 was performed in 47 patients with alcoholic liver disease using the polymerase chain reaction and slot-blot hybridization. Of the 47 patients with alcoholic liver disease, 40 were homozygous for the normal aldehyde dehydrogenase-2 gene and the remaining seven cases were heterozygous for the normal and mutant aldehyde dehydrogenase-2 genes. No homozygote was found for the mutant aldehyde dehydrogenase-2 genes. Daily alcohol intake was less than 100 gm in all heterozygotes without relation to the type of alcoholic liver disease. On the other hand, all but four patients homozygotic for the normal aldehyde dehydrogenase-2 gene drank more than 100 gm alcohol/day. The mean daily alcohol intake in the heterozygotes was significantly lower than that in the normal homozygotes. The incidence of alcoholic fibrosis tended to be lower in the heterozygotes than in the normal homozygotes (14.2% vs. 52.5%). On the other hand, the incidence of alcoholic hepatitis and/or cirrhosis tended to be higher in the heterozygotes than in the normal homozygotes. These results indicate that alcoholic liver disease develops even with moderate amounts of alcohol intake in heterozygotes of the aldehyde dehydrogenase-2 genes, in which acetaldehyde metabolism in the liver is impaired and liver damage in the heterozygotes is more severe than that in the normal homozygotes, suggesting that habitual drinkers who are heterozygotes of the aldehyde dehydrogenase-2 genes may be at high risk for alcoholic liver disease.

Alcohol Drinking↗
PubMed1990

There are two major types of hepatitis C virus in Japan.

The polymerase chain reaction (PCR) was used to detect hepatitis C virus (HCV) in plasma from chronic non-A, non-B hepatitis patients. By choice of adequate primers, 19 of 24 samples (79%) were found positive. Sequence analysis of amplified 400 bp cDNA fragments encoding a portion of NS5 gene suggested that HCV can be classified into two types (named K1 and K2) in Japan. Slot blot hybridization of the fragments indicated that 13 were HCV-K1 and 6 were HCV-K2, which show 80% and 67% nucleotide sequence homology, respectively, with that of the prototype.

Amino Acid Sequence↗
PubMed1990

Formation of diastereoisomeric 3a-hydroxypyrroloindoles from a tryptophan residue analog mediated by iron (II)-EDTA and L-ascorbate.

Oxygenation of a tryptophan residue analog by ascorbate in the presence of catalytic amounts of iron(II) and ethylenediaminetetraacetic acid (EDTA) has been studied. Under physiological conditions, reaction of the tryptophan derivative (N-t-butoxycarbonyl-L-tryptophan) with Fe(II)-EDTA and ascorbate resulted mainly in the oxygenation of the indole moiety of the substrate. In this reaction, cis and trans diastereoisomeric alcohols 3a-hydroxy-1-t-butoxycarbonyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3- b]indoles have been successfully identified in the metal-catalyzed free radical oxidation of indole compounds. Hydroxylation at C-5 and C-6 and a ring opening reaction between C-2 and C-3 have also been confirmed. The reaction of Fe(II)-EDTA/ascorbate with the tryptophan derivative was apparently nonselective with regard to position and was significantly suppressed by the hydroxyl radical scavengers (mannitol and dimethylsulfoxide), suggesting the participation of the hydroxyl radical as the actual oxidizing species.

Ascorbic Acid↗
PubMed1990

Urinary polyamine excretion measured by a simple enzymatic method is clinically useful as an expression of hepatic regeneration in liver diseases.

Polyamines have been known to play an important role in hepatic regeneration. In the present study, we measured the amount of urinary polyamine excretion in various liver diseases using a simple enzymatic method. Urinary polyamine excretion was elevated above the normal range in 21 out of 47 cases with fulminant hepatic failure, acute hepatitis, chronic active hepatitis, and liver cirrhosis. No change, however, was observed in 11 patients with chronic inactive hepatitis. In fulminant hepatic failure, two patients with urinary polyamine concentrations above 100 mumoles/g.cr. recovered, while two patients with concentrations of 56.2 and 26.7 mumoles/g.cr., died. In acute hepatitis, urinary polyamine excretion was significantly less in the recovery stage compared with the acute stage. When insulin and glucagon infusion therapy was performed in patients with liver cirrhosis without ascites, urinary polyamine excretion was significantly elevated after three days. These results suggest that measuring the amount of polyamine in urine is clinically useful for monitoring hepatic regeneration.

Biogenic Polyamines↗
PubMed1989

Influence of risk factors on long-term survival following acute myocardial infarction: a follow-up study in central Japan.

The long-term survival rate following acute myocardial infarction (AMI) was studied in 358 patients in central Japan who were monitored for 8 to 20 years after discharge from hospital for AMI. Fifteen-year cardiac survival rates were 65% in males and 72% in females. In both sexes, the survival rate decreased with increasing age at the time of AMI. The survival rate was significantly lower in recurrent MI than in first MI patients. Those who had smoked cigarettes before AMI or had hyperlipidemia during hospitalization did not show any significant decrease in cardiac survival rate, which may be due to cessation of smoking or control of hyperlipidemia after AMI. The 15-year survival rate was significantly lower in patients with a past history of angina pectoris or hypertension. Patients with a large infarct had a lower survival rate, as did those with a large cardiothoracic ratio on chest x-ray, and those who received digitalis during hospitalization. On the other hand, patients who were administered anticoagulants during hospitalization had a higher survival rate. Multiple regression analysis gave similar results. In conclusion, factors that reduced long-term survival rate after AMI were older age at time of the first attack, reduced cardiac function, and a history of angina pectoris or hypertension. Anticoagulant therapy appeared to improve the long-term survival rate.

Age Factors↗