Biography:

In the past Akira Takada has collaborated on articles with Nobuyuki Enomoto and Mikihiro Tsutsumi. One of their most recent publications is There are two major types of hepatitis C virus in Japan. Which was published in journal Biochemical and Biophysical Research Communications.

More information about Akira Takada research including statistics on their citations can be found on their Copernicus Academic profile page.

Akira Takada's Articles: (15)

There are two major types of hepatitis C virus in Japan

AbstractThe 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.

There are two major types of hepatitis C virus in Japan

AbstractThe 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.

Genetic polymorphisms of cytochrome P4502E1 related to the development of alcoholic liver disease

AbstractBackground/Aims: Because heavy drinkers do not always develop alcoholic liver disease (ALD), genetic factors may be involved. Cytochrome P4502E1 is the main enzyme that oxidizes ethanol in the non-alcohol dehydrogenase pathway. Recently, the presence of genetic polymorphisms of this enzyme was confirmed. In the present study, the genotypes of P4502E1 were analyzed in patients with or without ALD. Methods: After extraction of DNA from white blood cells, genotypes of P4502E1 were determined by restriction fragment length polymorphisms using two endonucleases. The genotypes were separated into three types: type A, type C (homozygous for the c1 or c2 gene), and type B (heterozygous for both genes). Results: In 50 patients with ALD, the prevalence of type A was 16% and that of the c2 gene was 84%. The genotypes in 10 heavy drinkers without ALD were all type A. In 34 patients with non-alcoholic liver disease and in 88 patients without hepatobiliary disease, the prevalence of type A was 65% and 71%, respectively, indicating a significantly higher prevalence of the c2 gene in ALD. In healthy nonalcoholics, the prevalence of type A was 62%–68%. Conclusions: These results suggest that polymorphisms of P4502E1 may be related to the development of ALD.

Research paperChanges in liver and spleen volumes in alcoholic liver disease

AbstractLiver and spleen volumes were determined using computed tomography in 57 subjects with alcoholic liver disease and 76 subjects with nonalcoholic liver disease, in order to clarify the clinical characteristics and pathogenetic mechanisms of portal hypertension in alcoholic liver disease. The liver volumes in alcoholic liver disease were significantly larger than those in nonalcoholic liver disease, except in cases of decompensated liver cirrhosis. The increase in liver volume in alcoholic liver disease showed a significant correlation with the degree of hepatocytic ballooning. Overlapping of values for liver volume between alcoholic and nonalcoholic liver disease was quite small, suggesting that determination of liver volumes could be helpful for making etiological diagnoses in chronic liver disease. Spleen volumes were increased in the advanced cases of both alcoholic and nonalcoholic liver disease. The correlations between liver and spleen volumes were quite different between alcoholic and nonalcoholic liver disease. In nonalcoholic liver disease, a negative correlation was obtained, while, on the other hand, it was significantly positive in alcoholic liver disease. This appears to sugsest that the pathogenetic mechanism of portal hypertension may differ between the diseases. After abstinence from alcohol, the decrease in liver and spleen volumes showed a statistically significant correlation, suggesting that ballooning of the hepatocytes may play a role in the augmentation of portal hypertension in alcoholic liver disease.

Comparison of ballooned hepatocytes in alcoholic and non-alcoholic liver injury in rats

AbstractBallooned hepatocytes are commonly observed in alcoholic and sometimes in non-alcoholic liver diseases. To clarify whether pathogenesis of this change is different in alcoholic and non-alcoholic liver diseases, changes of the livers in rats fed alcohol with pyrazole for 12 weeks were compared with those of CCl4 treated rats. Both groups of rats showed marked ballooning of the hepatocytes in the centrolobular area. Immunohistochemically, the ballooned hepatocytes in alcohol-pyrazole treated rats reacted strongly with transferrin and albumin staining. However, staining reaction of the ballooned hepatocytes in the CCl4 treated rats was slight. In alcohol-pyrazole treated rats, hepatic microtubules were significantly decreased. Retention of transferrin and albumin were found only in the ballooned hepatocytes of alcohol-pyrazole treated rats. However, in the CCl4 treated rats, neither microtubular alteration nor retention of the exportable proteins was observed. These findings indicate that the pathogenesis of ballooning of hepatocytes is different in alcoholic and non-alcoholic liver injuries. In alcoholic liver injury, microtubular alteration may lead to retention of protein and ballooning of hepatocytes by interfering with the hepatic secretion of proteins.

ArticleDetermination of aldehyde dehydrogenase isozyme activity in human liver

AbstractAs acetaldehyde (Ac-CHO) has been implicated as a cause of alcoholic liver injury, accurate knowledge concerning changes in the Ac-CHO oxidizing system in human liver is essential for the understanding of the pathogenesis. However, an assay system for aldehyde dehydrogenase (ALDH: EC 1.2, 1.3) isozymes in human biological material has not yet been established. In the present study, the assay systems for human liver ALDH isozyme activity were analyzed. In human red blood cells, in which only one type of ALDH isozyme, high Km ALDH, is present, a maximum activity was observed at a substrate concentration of over 300 μM. In human liver of the ususal type in which ALDH I (low Km isozyme) was not deficient, the activity reached a first plateau at 12 μM Ac-CHO after which the activity started to increase again at 20 μM Ac-CHO and continued to increase until 5.0 mM Ac-CHO. In the liver of the unusual type, which is deficient in low Km ALDH, activity was not detected at Ac-CHO concentrations lower than 10 μM. These results indicate that the optimum substrate concentrations for the determination of ALDH isozymes are 12 μM for low Km, 300 μM for high Km and over 1 mM for very high Km ALDH isozymes. The maximum activities of these three isozymes in the liver were obtained at a pH ranging between 9.0–9.5 and at an NAD concentration of over 500 μM. From these results, it is concluded that the assay system of Blair and Bodley is applicable for the determination of ALDH isozyme activity in human biological material with the exception of determining Km values.

Changes in blood acetaldehyde levels after ethanol administration in alcoholics

AbstractSerial changes in blood ethanol (Et-OH) and acetaldehyde (Ac-CHO) levels following a single oral administration of 0.8 g/kg of Et-OH were determined in order to clarify the metabolism of Ac-CHO in alcoholic liver disease (ALD). The Et-OH metabolic rate (EMR) in alcoholics either with or without liver disease was significantly higher than the rate in nonalcoholics. Peak values of blood Ac-CHO levels and the Ac-CHO/EMR ratios in ALD were significantly higher than those in subjects with nonALD or alcoholics and nonalcoholics without liver disease. In the type I aldehyde dehydrogenase isozyme deficient cases (unusual type), blood Ac-CHO levels and Ac-CHO/EMR ratios were very high and the levels remain at a plateau until 90 minutes after Et-OH administration and then decreased relatively quickly. Changes in blood Ac-CHO levels and Ac-CHO/EMR ratios in ALD were similar to those in cases of the unusual type. These results indicate that Ac-CHO metabolism in ALD is decreased relative to its production and that this decrease might be due to increased production of Ac-CHO in the nonalcohol dehydrogenase pathway located in the microsomes, in which degradation of Ac-CHO was slow.

Short communicationStudies on intra-familial transmission of hepatitis C virus: An evidence for transplacental vertical transmission from mother to baby

AbstractIn order to clarify the mode of transmission of hepatitis C virus (HCV) within the same family, HCV markers and HCV genotypes in family members of 44 patients with chronic HCV-related liver diseases and in four neonates borne by HCV marker-positive mothers, were studied. The detection rate of HCV markers in the same family was very high compared to non-familial blood donor controls, indicating intra-familial accumulation of HCV infection. The coincidence rate of the HCV genotypes was 75% in four couples, and 33.3% in three pairs of mothers and children. HCV markers were not always positive in children from the same mother. Within 2 days of delivery, HCV-RNA was positive in two neonates from the four HCV-RNA-positive mothers. HCV genotypes in two neonates were the same as that of their respective mothers. In one neonate, HCV-Ab disappeared from blood during a 1-year observation period; however, HCV-RNA was persistently positive. These results suggest that vertical transmission of HCV from mothers to neonates occurs transplacentally. However, the coincidence rate of HCV genotypes between mothers and their children was low, suggesting that vertical transmission of HCV may occur only in a limited number of families. The low coincidence rate of HCV genotypes between mothers and their children suggests that shared family life, including medical treatment by the same doctor, may be more important than direct transmission for intra-familial accumulation of HCV infection.

Mini-reviewDiagnostic criteria for alcoholic liver disease

AbstractNew diagnostic criteria for alcoholic liver disease have been proposed. By these criteria, the etiological diagnosis of liver disease in alcoholics is classified into three groups: alcohol alone; combination of alcohol and virus; and others which may be caused by virus alone. In the alcohol alone group, virus markers were negative and serum ALT and AST levels decreased to less than 80 units during the first 4 weeks of abstinence. In patients whose ALT and AST levels were less than 100 units before abstinence, their levels decreased to less than 50 units. Serum gamma-glutamyl transpeptidase (GGT) levels during the first 4 weeks of abstinence also decreased either to less than 1.5 times their normal values or to less than 40% of their initial levels. In the combination group of alcohol and virus, virus markers were positive. Serum ALT and ASt levels decreased to less than 120 units during abstinence with the same decrease in GGT levels as seen in the alcohol alone group. Patients who did not exhibit this reduction were included in the other group. These criteria are applicable to liver disease in alcoholics in Japan.

Intermolecular interaction between the pendant chain of perfluorinated ionomer and methanol

AbstractA comparison between water and methanol on the interaction with a pendant chain model for perfluorosulfonic ionomers (PFI), CF3OCF2CF2SO3−, was made by using molecular orbital calculation. Intermolecular interaction energy (Eint) of the most stable complex for CF3OCF2CF2SO3− + CH3OH, where methanol associates with sulfonic acid group, is −10.38 kcal/mol at the MP2/aug-cc-pVDZ//B3LYP/6-31 + G* level, and it is almost the same with that of CF3OCF2CF2SO3− + H2O complex (−10.58 kcal/mol). Since an association of methanol to the sulfonic acid group is quite advantageous in energy, it is expected that, similarly to water, methanol would likely populate around the acidic site. On the contrary, according to a systematic Eint analysis for 500 random configurations, dissimilar distribution of Eint was observed for methanol compared with water. This is because methyl group substitution reduces oxygen surface area and causes more attractive dispersion energy with CF3OCF2CF2SO3− by about 1.0 kcal/mol on average compared with water. To see how the difference in the interaction energy affects the solvation structure of methanol and water to the PFI, molecular dynamics simulations of a CF3OCF2CF2SO3− molecule in methanol solutions have also been carried out at the methanol concentration of 10–90 mol%. Consequently, water probably associates with the sulfonic acid group-pushing methanol close to hydrophobic sites. It was also observed that methanol molecule tends to point its methyl group toward the solute at hydrophobic sites. These results demonstrated that methanol should locate in the vicinity of hydrophobic site compared with water due to methyl group substitution.

Residual entropy and structural disorder in glass: Fluctuation phenomena and time-dependent features as deduced from an Ising-type structural model

AbstractAs part of our study of configurational entropy in non-equilibrium systems, we have determined the time-dependent fluctuations in a simple system that undergoes structural transformations similar to those of an Ising model. First, we demonstrate that the calorimetric entropy does approximate the statistical thermodynamic entropy, and that the former reflects the spatial arrangements dealt with by the latter. We then show that neither the assumption of ergodicity nor the use of a canonical ensemble is required to account for non-equilibrium states. We use instead the concept of ‘spatial sampling’ with which enthalpy, entropy and volume can be defined for each structure at any time. In this way fluctuations of all variables can be calculated without any inconsistency. Finally, we point out that introduction of the new concepts of magnitude and phase factor into configurational entropy can not only explain the existence of residual entropy at 0 K for disordered materials but also allows one to discuss spatially related randomness and kinetically induced fluctuations on an equal footing.

Short CommunicationGenetic Organization and Diversity of the 3′ Noncoding Region of the Hepatitis C Virus Genome☆

AbstractThe 3′ noncoding region (3′ NCR) of the hepatitis C virus (HCV) genome contained in viral particles was analyzed by an RNA linker ligation followed by reverse transcription-polymerase chain reaction. Sequence analysis of the amplified fragment from four strains, including different genotypes 1b, 2b, 3a, and 3b indicated that the 3′ NCR is composed of between 200 and 235 nts. The sequence of the 3′ NCR consists of a type-specific region (immediately following the termination codon), a poly(U) stretch, a C(U)n-repeat, and highly conserved region termed the core element. The poly(U) stretch and C(U)n-repeat regions varied in length and in sequence among different genotypes. Core elements having putative secondary structure consisted of 98 or 100 nts and were highly conserved in all genotypes. Most of the nt changes found in different genotypes did not affect the secondary structure of the core elements, suggesting that this region may play an important role in replication, stabilization of the HCV RNA, and/or packaging of the genome. Most of the HCV-1b strains carried two U residues at the 3′ end of the core element, while the minor HCV-1b strains had no U residues, demonstrating that there are two variants in type 1b strains. Amplification of the core element using linker-primed cDNA was comparable with that using the 3′ proximal core element-primed cDNA, indicating that the 3′ end of HCV genome was terminated by an OH group.

Laboratory InvestigationIntrarenal vascular changes in experimental glomerulonephritis

Intrarenal vascular changes in experimental glomerulonephritis.The present study was undertaken to elucidate the serial vascular changes in glomerulonephritis during the progression from mild alterations to those associated with a contracted kidney.Changes of intrarenal vascular architecture were correlated with histopathological lesions in unilateral glomerulonephritis.Parallel microangiographic and histological examination was carried out in 20 diseased and 5 normal rabbits.In the diseased kidney, cortical vasculature was impaired as renal parenchymal lesions developed while the medullary vasculature remained relatively well preserved.Furthermore, the arteriolae rectae verae started to increase in number even in the presence of minor glomerular lesions, and they continued to increase as the renal parenchymal lesions progressed.There was a positive correlation between the increased number of arteriolae rectae and the severity of the glomerular lesions.In the diseased kidney arteriolae rectae verae arose from the interlobular artery as well as from the more proximal vessels.In the normal kidney they only arose proximal to the interlobular artery.As histological lesions of the renal parenchyma advanced, the vessels became progressively more spiralled.Spiralling of the interlobular artery was not found until a contracted kidney was noted.It is likely that interstitial fibrosis is the major cause of spiralling.Changements vasculaires intrarenaux au cours de la glomérulonéphrite experimentale.La présente étude a été entreprise afin d'élucider les changements vasculaires progressifs qui surviennent dans la glomérulonéphrite à partir des modifications minimes jusqu'au rein atrophique en établissant une corrélation 'entre les changements de l'architecture vasculaire intrarénale en regard des lésions histopathologiques au cours de la glomérulonéphrite unilatérale.Des examens microangiographiques et histologiques ont été faits en parallèle chez 20 lapins malades et 5 lapins normaux.Dans le rein malade, avec le développement de lésions parenchymateuses rénales, la vasculature corticale était atteinte tandis que la vasculature médullaire demeurait relativement bien conservée.De plus, les artérioles verae rectae commencèrent à augmenter en nombre même avec des lésions glomérulaires minimes et continuèrent à augmenter avec la progression des lésions rénales parenchymateuses.Il y avait une corrélation positive entre l'accroissement du nombre des artérioles rectae et la gravité des lésions glomérulaires.Dans le rein malade, les artérioles verae rectae prenaient naissance des artères interlobulaires aussi bien que des vaisseaux plus proximaux.Dans le rein normal, elles n'originaient que proximalement aux artères interlobulaires.Avec la progression des lésions histologiques du parenchyme rénal, une configuration en spirale des vaisseaux devenait de plus en plus évidente quoique cette configuration n'était retrouvée au niveau des artères interlobulaires que lorsque le rein était atrophié.Il semble que la fibrose interstitielle soit la principale cause de cette configuration en spirale.

Generating morality in directive sequences: Distinctive strategies for developing communicative competence in Japanese caregiver–child interactions

Highlights•Caregiver often modulates the intensity of directives to regulate child’s behavior.•The caregiver also effectively uses reported speech when issuing modified directives.•Reacting to directives the child often attempts to change the frame of conversation.•While pursuing this, the child often cites involvement in a pro-moral activity.•These strategies were induced by the structural requirements of conversation.

ArticleEffects of ethanol on the secretion of hepatic secretory protein in rat alcoholic liver injury

It has been pointed out that one of the pathogenetic causes of alcoholic liver injury is the hepatocytic accumulation of exportable proteins due to a decrease in hepatic microtubules caused by acetaldehyde. To confirm and extend this secretory protein accumulation in the hepatocytes, the effects of alcohol treatment on the intracellular transport of secretory protein in the hepatocyte was studied using radioisotope-labeled leucine and fucose. Acute ethanol administration to rats did not show any effects on intrahepatocytic transport and secretion of transferrin. In alcohol pyrazole hepatitis rats, the secretion of transferrin labeled with both radioactive leucine and fucose into the serum was significantly delayed. Delaying in the secretion of fucose-labeled transferrin was more prominent than in leucine-labeled transferrin. This secretory inhibition was accompanied by a corresponding increase in the hepatic retention of both leucine- and fucose-labeled transferrin. At the time of the maximum inhibition of secretion, radioisotope labeled transferrin mainly retained in the Golgi apparatus. These results indicated that movement of secretory proteins along the secretory pathway impaired in alcoholic liver injury and that accumulation of the secretory proteins might play an important role in the development of alcoholic liver injury.

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