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Biomedical subjects

Hiroshi Sakugawa

Publications and source records attributed to Hiroshi Sakugawa.

At least 19 recordsLinked to original sources
PubMed2006

A case-control study of response to lamivudine therapy for 2 years in Japanese and Chinese patients chronically infected with hepatitis B virus of genotypes Bj, Ba and C.

BACKGROUND/AIMS: In eastern Asian countries, hepatitis B virus (HBV) genotype Ba (HBV/Ba), HBV/Bj and HBV/C are prevalent. The aim was to investigate the response or resistance to lamivudine therapy among patients with different HBV genotypes. METHODS: Of 67 Japanese and Chinese patients with chronic hepatitis B, 18 patients with HBV/Bj, 15 with HBV/Ba and 34 with HBV/C were selected for a case-control study matched according to gender and age. All the patients were treated with lamivudine for 2 years and evaluated the response or emergence of the YMDD mutation at year 2 during the treatment. HBV genotypes were detected by the restriction fragment length polymorphism. The YMDD mutation was detected by the direct sequencing after amplification by PCR. RESULTS: At year 2 during therapy, 44.8% of the patients showed normalization of ALT and undetectable HBV DNA (favorable response), 35.8% developed the YMDD mutation. There was no significant difference of response to the therapy among the three genotype groups. The emergence of the YMDD mutation was associated with HBV/C. By the multiple logistic regression analysis, however, the significant factor of a favorable response was a higher pretreatment ALT level and negative HBeAg status and the significant factor of the emergence of the YMDD mutation was HBV/C. CONCLUSIONS: Higher pretreatment ALT level, HBeAg status or HBV genotype may affect the response or resistance to lamivudine therapy.

Journal Article↗
PubMed2006

Seasonal changes in needle water content and needle ABA concentration of Japanese red pine, Pinus densiflora, in declining forests on Mt. Gokurakuji, Hiroshima prefecture, Japan.

To evaluate the effects of air pollution on the decline of Pinus densiflora forests, various research has been conducted around Mt. Gokurakuji (34 degrees 23'N, 132 degrees 19'E, 693 m a.s.l.) north of the Seto Inland Sea, west Japan. To investigate the mechanisms responsible for decreases in photosynthesis (Pn) and stomatal conductance (gl), delta13C of needles and seasonal changes in the water content (WC) and abscisic acid concentration (ABA) of needles were measured in various stands. The delta13C values were less negative in declining stands and younger needles. ABA and WC were not correlated with each other. WC decreased consistently with needle age while the ABA showed a minimum in August and a smaller content in older needles. Monthly precipitation and the daily maximum vapor pressure were not correlated with ABA and WC. In declining stands, WC and ABA tended to be higher and lower, respectively, than in nondeclining stands. These results suggest that the trees in declining stands received less water stress than those in nondeclining stands and the differences in gl and delta13C are not caused by the difference in water stress. The possibilities of the effects of air pollution and the infection of pine-wood nematode on the physiological decline on the pine needles are discussed.

Abscisic Acid↗
PubMed2006

Hepatitis E virus infection in wild mongooses of Okinawa, Japan: Demonstration of anti-HEV antibodies and a full-genome nucleotide sequence.

Hepatitis E virus (HEV), a single-strand RNA virus, has been recovered not only from human beings but also from various species of animals. Here we report our results suggesting that mongoose should be added to the list of reservoir animals of HEV. Of 100 mongooses we examined in Okinawa, Japan, 21 were thought to be positive for anti-HEV antibodies, among which one was definitely positive for HEV RNA. Full-genome sequencing of the HEV isolate revealed that it segregates to a unique subgroup within genotype III. Interestingly, this mongoose strain was closely related to a swine isolate previously reported from Okinawa, implicating the possibility of interspecies transmission between these animals.

Journal Article↗
PubMed2006

Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection.

The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 +/- 16.3 vs. 36.0 +/- 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection.

Acute Disease↗
PubMed2006

Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 3.

BACKGROUND: Interferon regulatory factor (IRF)-3 plays an important role in initiating cellular interferon-stimulated gene-mediated antiviral responses. In the present study, we evaluated the effects of IRF-3 expression and activation on intracellular hepatitis C virus (HCV) replication using an HCV replicon system. METHODS: An HCV replicon was constructed that expressed a neomycin-selectable chimeric firefly luciferase reporter protein. A small interfering (si) RNA oligonucleotide directed against IRF-3 mRNA was designed and synthesized. A eukaryote expression plasmid vector was constructed that expressed IRF-3 mRNA under control of the cytomegalovirus early promoter/enhancer. To evaluate transcriptional activity of the interferon-stimulated genes, a reporter vector was used that expressed firefly luciferase under control of the interferon-stimulated response element (ISRE). RESULTS: The baseline expression of IRF-3 did not significantly differ between cells with and without expression of the replicon. Transfection of an IRF-3 expression plasmid into the cells raised the ISRE-luciferase activities. The increase of ISRE activity was significantly more potent in the replicon-expressing cells than in cells without replicon expression. Concomitantly, the overexpression of IRF-3 suppressed HCV replication levels. In contrast, siRNA knockdown of IRF-3 suppressed ISRE activity by 38% +/- 2%. Interestingly, the suppression of IRF-3 resulted in a significant increase of HCV replication, by up to twofold, depending on the IRF-3 suppression levels. CONCLUSIONS: IRF-3 negatively regulated intracellular HCV replication, and was partially activated in cells that expressed the HCV replicon. Thus, IRF-3 is a key molecule controlling HCV replication through modulation of host interferon gene responses.

Blotting, Western↗
PubMed2006

Molecular tracing of Japan-indigenous hepatitis E viruses.

The ancestor(s) of apparently Japan-indigenous strains of Hepatitis E virus (HEV) was probably of foreign origin, but it remains unclear when and from where it made inroads. In this study, 24 genotype 3 and 24 genotype 4 HEV strains recovered in Japan each showed a significant cluster, clearly distinct from those of foreign strains, in the phylogenetic tree constructed from an 821 nt RNA polymerase gene fragment. The evolutionary rate, approximately 0.8 x 10(-3) nucleotide substitutions per site per year, enabled tracing of the demographic history of HEV and suggested that the ancestors of Japan-indigenous HEV had made inroads around 1900, when several kinds of Yorkshire pig were imported from the UK to Japan. Interestingly, the evolutionary growth of genotype 3 in Japan has been slow since the 1920s, whereas genotype 4 has spread rapidly since the 1980s. In conclusion, these data suggest that the indigenization and spread of HEV in Japan were associated with the popularization of eating pork.

Animals↗
PubMed2006

Rapid and highly sensitive determination of low-molecular-weight carbonyl compounds in drinking water and natural water by preconcentration HPLC with 2,4-dinitrophenylhydrazine.

The aim of this research was to develop a simple procedure for a highly sensitive determination of low-molecular-weight (LMW) carbonyl compounds in drinking water and natural water. We employed a preconcentration HPLC system with 2,4-dinitrophenylhydrazine (DNPH) for the determination of LMW carbonyl compounds. A C-18 reverse-phase preconcentration column was used instead of a sample loop at the sample injection valve. A 0.1 - 5.0 mL portion of the derivatized sample solution was injected with a gas-tight syringe, and a 15% acetonitrile aqueous solution was pushed through the preconcentration column to remove the unreacted excess DNPH, which caused serious interference in the determination of formaldehyde. The detection limits were 1 - 3 nM with a relative standard deviation of 2 - 5% for 20 nM standard solutions (n = 5). The calibration curves were essentially unaffected by coexisting sea salts. Applications to commercial mineral water, tap water, river water, pond water and seawater are presented.

Aldehydes↗
PubMed2006

Impairment of host immune response against strongyloides stercoralis by human T cell lymphotropic virus type 1 infection.

A large-scale study was undertaken to clarify the prevalence rate of strongyloidiasis in Okinawa, Japan and to evaluate the relationship between strongyloidiasis and infection with human T cell lymphotropic virus type 1 (HTLV-1). The prevalence rate of Strongyloides stercoralis and HTLV-1 infection were 6.3% and 14.0%, respectively. Among 2,185 patients more than 50 years of age, the rate of S. stercoralis infection was significantly higher in patients with HTLV-1 infection compared with patients without HTLV-1 infection. In 252 patients treated with ivermectin, serum IgE levels and peripheral eosinophil counts were significantly lower in HTLV-1 co-infected patients compared with patients without HTLV-1 infection. In addition, the anthelmintic effect was significantly lower in patients with HTLV-1 infection compared with patients without HTLV-1 infection. Our prospective study demonstrated a prevalence rate for strongyloidiasis and HTLV-1 infections, and clearly demonstrated that co-infection with HTLV-1 impaired the immune response against S. stercoralis.

Adolescent↗
PubMed2005

Classifying genotype F of hepatitis B virus into F1 and F2 subtypes.

AIM: To explore the propriety of providing hepatitis B virus (HBV) genotypes F and H with two distinct genotypes. METHODS: Eleven HBV isolates of genotype F (HBV/F) were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported. RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by > 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of > 8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged. CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).

Amino Acid Sequence↗
PubMed2005

Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease.

AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease. However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type VI collagen 7S domain and hyaluronic acid. METHODS: One hundred and twelve patients with histologically proven NAFLD were studied. RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type VI collagen 7S domain > or =5.0 ng/mL, hyaluronic acid > or =43 ng/mL. Both markers had a high positive predictive value: type VI collagen 7S domain, 86% and hyaluronic acid, 92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type VI collagen 7S domain (> or =5.0 ng/mL), 84% and hyaluronic acid (> or =50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis. CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.

Adult↗
PubMed2005

Differences of hepatocellular carcinoma patients with hepatitis B virus genotypes of Ba, Bj or C in Japan.

Hepatitis B virus (HBV) genotypes B (HBV/B) and C (HBV/C) are prevalent in Asia. Recently HBV/B has been classified into two subtypes, HBV/Ba which is ubiquitously found in Asia, and HBV/Bj which is specific in Japan. In addition, the frequency of positive HBeAg has been reported to be higher in patients with HBV/Ba than those with HBV/Bj. However, little is known about the differences between patients with various genotypes who developed hepatocellular carcinoma (HCC). In 296 serum samples of HCC patients collected from all over Japan, HBV genotypes were determined with the restriction fragment length polymorphism. HBV/A was detected in 1.0%, HBV/Ba in 4.4%, HBV/Bj in 7.4%, and HBV/C in 86.5%. In the Tohoku district and Okinawa, HBV/Ba, HBV/Bj and HBV/C were found in 6.7, 40.0 and 48.9%, compared to 4.0, 1.6 and 93.2% in the other districts in Japan. HBV/Bj patients were more frequently found in the group older than 65 years while HBV/Ba patients were found in all age groups. The frequency of positive HBeAg in HBV/Bj patients was significantly low compared to that in the other patients. More than 60% of the patients with HCC had cirrhosis as the underlying liver diseases. However, in HBV/Ba patients aged 50 years or younger, 80% of them had chronic hepatitis, while 87.5% of those aged older than 50 years had cirrhosis. These data suggest that great differences exist among patients with HCC infected with different genotypes.

Adult↗
PubMed2004

Two subtypes of genotype B (Ba and Bj) of hepatitis B virus in Japan.

We have previously reported 2 subtypes of hepatitis B virus (HBV) genotype B, one of which has the recombination with genotype C over the precore region plus core gene (Ba) and the other of which does not (Bj). A restriction fragment-length polymorphism method with 2 endonucleases was newly developed for distinguishing between subtypes Ba and Bj and was applied to 313 carriers of HBV genotype B in Japan. Subtype Ba was detected in 38 (12%) and subtype Bj in 275 (88%) of the carriers of HBV genotype B. Hepatitis B e antigen in serum was found more frequently in patients with chronic infection with subtype Ba than in those with chronic infection with subtype Bj (8 [32%] of 25 vs. 25 [9%] of 273; P<.01). The new method for distinguishing between Ba and Bj by restriction fragment-length polymorphism would be useful in examining the distribution of these 2 subtypes in situations in which HBV genotype B is prevalent.

Acute Disease↗
PubMed2004

Metabolic syndrome is directly associated with gamma glutamyl transpeptidase elevation in Japanese women.

AIM: This study aimed to determine whether metabolic syndrome is directly or indirectly, through fatty liver, associated with elevated gamma-glutamyl transpeptidase (GGT) levels in Japanese women. METHODS: From 4 366 women who received their annual health check-up, 4 211 women were selected for analysis. All 4 211 women were negative for both hepatitis B surface antigen and antibody to hepatitis C virus. Clinical and biochemical variables were examined by using univariate and multivariate analysis. RESULTS: A raised GGT level (>68 IU/L) was seen in 258 (6.1%) of the 4 211 women. In univariate analysis, all variables examined (age, body mass index, blood pressure, hemoglobin concentration, fasting blood glucose, glycosylated hemoglobin A1c, cholesterol, triglyceride, and uric acid) were associated with the elevated GGT level, whereas in multivariate analysis, four variables (age > or =50 yr, hemoglobin > or =14 g/dL, triglyceride > or =150 mg/dL, and presence of diabetes) were significantly and independently associated with raised GGT level. Clinical variables predicting the presence of ultrasonographic evidence of fatty liver were also examined by multivariate analysis; four variables were associated with the presence of fatty liver: BMI > or =25 kg/m(2), hemoglobin > or =14 g/dL, triglyceride > or =150 mg/dL, and uric acid > or =7 mg/dL. There was no significant association between the raised GGT level and the presence of fatty liver. Hypertriglyceridemia was significantly and independently associated with both the raised GGT level and the presence of fatty liver. CONCLUSION: Metabolic syndrome seemed to be directly, not indirectly through fatty liver, associated with the raised GGT level in Japanese women.

Adult↗
PubMed2004

Quantitation of the level of hepatitis delta virus RNA in serum, by real-time polymerase chain reaction--and its possible correlation with the clinical stage of liver disease.

Some hepatitis B virus (HBV) carriers with chronic hepatitis delta virus (HDV) superinfection show progressive chronic hepatitis, whereas others show no apparent signs of liver disease. In the present study, we established a sensitive method for the quantitation of the level of HDV RNA in serum on the basis of real-time reverse-transcription polymerase chain reaction (RT-PCR), to clarify the role that the level of HDV RNA in serum plays in the diverse natural course of clinical manifestation. In 48 subjects who were positive for hepatitis B surface antigen and for anti-hepatitis delta antibody, the levels of HDV RNA in serum were quantitated by RT-PCR. The levels of HBV DNA in serum were determined by a transcription-mediated amplification assay. The levels of HDV RNA in serum of subjects with chronic hepatitis and of subjects with liver cirrhosis were significantly higher than those in asymptomatic carrier subjects. The levels of HBV DNA in serum did not differ significantly among these 3 groups. In conclusion, HDV RNA quantification by real-time RT-PCR is possibly a useful tool for understanding the pathophysiology of HDV infection.

Adult↗
PubMed2004

Mobilization of arsenic from subsurface sediments by effect of bicarbonate ions in groundwater.

Arsenic leaching by bicarbonate ions has been investigated in this study. Subsurface sediment samples from Bangladesh were treated with different carbonate and bicarbonate ions and the results demonstrate that the arsenic leaching efficiency of the carbonate solutions decreased in the order of Na2CO3>NaHCO3>BaCO3>MnCO3. Sodium carbonate and bicarbonate ions extracted arsenic most efficiently; Na2CO3 leached maximum 118.12 microg/l of arsenic, and NaHCO3, 94.56 microg/l of arsenic from the Ganges delta sediments after six days of incubation. The arsenic concentrations extracted in the batch experiments correlated very well with the bicarbonate concentrations. The kinetics study of arsenic release indicates that arsenic-leaching rate increased with reaction time in bicarbonate solutions. Bicarbonate ions can extract arsenic from sediment samples in both oxic and anoxic conditions. A linear relationship found between arsenic contents in core samples and those in leachates suggests that dissolved arsenic concentration in groundwater is related to the amount of arsenic in aquifer sediments. In batch experiment, bicarbonate solutions effectively extracted arsenic from arsenic adsorbed iron oxyhydroxide, reflecting that bicarbonate solutions may mobilize arsenic from iron and manganese oxyhydroxide in sediments that are ubiquitous in subsurface core samples. Carbonate ion may form complexes on the surface sites of iron hydroxide and substitute arsenic from the surface of minerals and sediments resulting in release of arsenic to groundwater. Like in the batch experiment, arsenic and bicarbonate concentrations in groundwater of Bangladesh correlated very well. Therefore, bicarbonate leaching is presumed to be one important mechanism to mobilize arsenic in bicarbonate dominated reducing aquifer of Bangladesh and other parts of the world as well.

Arsenic↗