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Hiromitsu Saisho

Publications and source records attributed to Hiromitsu Saisho.

At least 55 records · Page 3Linked to original sources
PubMed2005

A role for c-fos/activator protein 1 in B lymphocyte terminal differentiation.

Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is essential for promoting B cell differentiation into plasma cells. However, a critical transcription factor for Blimp-1 expression in activated B cells is unclear. When splenic B cells were stimulated with CD40 ligand (CD40L) and IL-4, terminal differentiation was induced in the B cells from c-fos transgenic (H2-c-fos) mice but barely in those from control littermates and from c-fos-deficient mice. AP-1 family and Blimp-1 mRNAs were transiently induced in the control B cells, and overexpression of c-Fos induced a sufficient amount of Blimp-1 for terminal differentiation in the H2-c-fos B cells. When normal and c-fos-deficient B cells were stimulated with LPS, a sufficient amount of Blimp-1 for terminal differentiation was induced in those B cells. However, expression of c-fos/AP-1 family mRNAs in LPS-stimulated normal B cells was similar to that of normal B cells stimulated with CD40L and IL-4. EMSA and chromatin immunoprecipitation assays using the AP-1-binding DNA sequence in the murine Blimp-1 promoter region demonstrated that AP-1-binding activity in nuclear protein of LPS-stimulated normal B cells was prolonged more than that in normal B cells stimulated with CD40L and IL-4. Furthermore, the percentage of CD138(+) B cells within germinal center B cells in the spleen and the number of Ab-forming cells in the bone marrow of H2-c-fos mice was larger than that of control mice 12 days after immunization. Thus, although c-Fos is not essential for Blimp-1 expression, c-Fos/AP-1 positively regulates Blimp-1 expression and terminal differentiation of activated B cells.

Adjuvants, Immunologic↗
PubMed2005

Effect of lamivudine in HBeAg-positive chronic hepatitis B: discordant effect on HBeAg and HBV DNA according to pretreatment ALT level.

AIM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9+/-0.4 mo. RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs 2, P = NS; groups 1 vs 3, P = 0.002; groups 1 vs 4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P = NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs 2, P = 0.02; groups 1 vs 3, P = NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.

Adult↗
PubMed2005

Amantadine inhibits hepatitis A virus internal ribosomal entry site-mediated translation in human hepatoma cells.

The effect of six drugs (amantadine, glycyrrhizin, ribavirin, ursodeoxycholic acid, alcohol, and IFN) on HAV RNA translation from the HAV internal ribosomal entry site (IRES) was investigated using a bicistronic reporter construct containing HAV IRES as intragenic spacer. Huh-7 cells and derivatives were transfected with in vitro transcripts, and the reporter gene activity was determined. IFN suppressed both cap-dependent and HAV IRES-dependent translation, while amantadine specifically inhibited HAV IRES-dependent translation. In contrast to IFN, by reporter assay, amantadine did not activate the interferon-stimulated response element (ISRE) or interferon gamma-activated sequence (GAS)-associated pathways. Immunoblot analysis revealed that amantadine had no effect on PKR and on IFN-regulatory factor-1 (IRF-1) expression. These findings demonstrated a novel antiviral effect of amantadine against HAV with or without HCV infection.

Amantadine↗
PubMed2005

Functional analysis of transcriptional repressor Otx3/Dmbx1.

Otx3/Dmbx1 is a member of paired class homeodomain transcription factors. In this study, we found that Otx3/Dmbx1 represses the Otx2-mediated transactivation by forming heterodimer with Otx2 on the P3C (TAATCCGATTA) sequence in vitro. The 156 amino acid region (residues 1-156) of Otx3/Dmbx1 is required for its repressor activity, and interacts directly with Otx2. Co-localization of Otx3/Dmbx1 and Otx2 in brain sections was confirmed by in situ hybridization. These data suggest that Otx3/Dmbx1 represses Otx2-mediated transcription in the developing brain. We also identified the consensus binding sequence [TAATCCGATTA and TAATCC(N2-4)TAATCC] of Otx3/Dmbx1.

Animals↗
PubMed2005

Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B.

AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in "clinically severe" exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with life-threatening severe exacerbation of chronic hepatitis B. METHODS: Twenty-two patients, 14 men and 8 women, were defined as "severe" exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ("early high-dose" group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ("non-early high-dose" group). RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT) level, total bilirubin level, positivity of HBeAg, mean IgM-HBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the "early high-dose" group survived, while only 2 of 11 patients of the "non-early high-dose" group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the "early high-dose" group. Both ALT levels and HBV DNA polymerase levels fell in both groups. CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with "clinically life-threatening" severe exacerbation of chronic hepatitis B, when used in the early stage of illness.

Acute Disease↗
PubMed2005

CD34+CD7+ leukemic progenitor cells may be involved in maintenance and clonal evolution of chronic myeloid leukemia.

PURPOSE: We analyzed CD34+ cells coexpressing CD7 in chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase (AP) to clarify their role in progression or regression of the disease during treatment. EXPERIMENTAL DESIGN: Enumeration of CD34+CD7+ cells was done on bone marrow nucleated cells from normal donors and CML patients. Fluorescence in situ hybridization analysis was done on sorted CD34+CD7+and CD34+CD7- cells to examine the occupancy rate of each fraction by BCR-ABL+ cells with or without additional cytogenetic abnormalities. RESULTS: The proportion of CD34+CD7+cells was significantly affected by the treatment outcome and/or the disease status as follows: 20.5 +/- 10.4% in normal donors (n = 22), 18.1 +/- 10.2% in CP with major cytogenetic response (n = 14), 53.0 +/- 12.9% in CP at diagnosis (n = 18), 55.0 +/- 15.8% in CP with minor or no cytogenetic response (n = 28), and 70.2 +/- 18.1% in AP (n = 6). The proportion of CD34+CD7+cells decreased in parallel with cytogenetic improvement in individual patients. In six untreated CP patients, the ratio of BCR-ABL+ cells was comparable between each fraction. In three patients with major cytogenetic response, the ratio of BCR-ABL+ cells was remarkably lower in CD34+CD7- cells than in CD34+CD7+cells. In three AP patients with additional cytogenetic abnormalities, extra signals were detected at a much higher rate in CD34+CD7+ cells than in CD34+CD7- cells. CONCLUSIONS: Our results suggest that CD34+CD7+ cells may be involved in maintenance and clonal evolution of BCR-ABL+ cells in CML.

Adolescent↗
PubMed2005

Identification and investigation of methylated genes in hepatoma.

Gene silencing due to aberrant DNA methylation plays an important role in carcinogenesis. Previous microarray analysis demonstrated that 14 genes, including hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI2/PB) gene, showed particularly high inductions after 5-aza-2'deoxycytidine (5Aza-dC) treatment in multiple hepatoma cell lines. In the present study, we studied all of these genes except for the HAI2/PB gene and examined DNA methylation status and levels of acetylated histones using bisulphite genomic sequencing and the chromatin immunoprecipitation (ChIP) assay, respectively. Aberrant methylation in primary hepatoma tissues was also examined using methylation-specific polymerase chain reaction (MSP). Genes for E-cadherin, collagen type I alpha 2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), connective tissue growth factor (CTGF) and fibronectin 1 exhibited aberrant methylation in several hepatoma cell lines. The ChIP assay showed that DNA methylation and deacetylation of histones generally coexist except for fibronectin 1. In further studies of 24 primary hepatoma tissues, methylation signals for COL1A2, IGFBP2, CTGF and fibronectin 1 were detected in 13, 18, 4 and 10 patients, respectively. In conclusion, aberrant methylation of COL1A2, IGFBP2, CTGF and fibronectin 1 genes were detected in hepatoma cell lines. We also demonstrated that the methylation of 5'CpG islands and histone deacetylation generally coexisted in the regulation of gene expression except for fibronectin 1. The results of MSP in hepatoma tissues suggested that some of these genes might be involved in the development or progression of hepatoma.

Adult↗
PubMed2005

Sonographic shift of hypervascular liver tumor on blood pool harmonic images with definity: time-related changes of contrast-enhanced appearance in rabbit VX2 tumor under extra-low acoustic power.

We elucidated the features of the time-related contrast-enhanced ultrasound appearance of hypervascular liver tumor using Definity, which has no accumulation activity in the liver. Ten rabbits with VX2 tumors broadcast into the liver were used. Changes in contrast-enhanced sonograms were evaluated by real-time observation (FR 15 Hz) of harmonic imaging under extra-low MI (MI 0.065) with Definity, and their intensity changes were analyzed. Hepatic angiography (4/10) and histopathological examination (10/10) were performed to investigate the tumor vascularity. VX2 tumors were hypervascular on angiogram (4/10) and histology (10/10). They showed time-related sonographic appearance changes from hyperechoic to hypoechoic, which were confirmed by quantitative intensity analysis. Hypervascular VX2 tumors showed characteristic time-related shift on contrast-enhanced sonograms in real-time and extra-low MI harmonic images with Definity. These findings may be useful for the ultrasound diagnosis of human hypervascular liver tumor like hepatocellular carcinoma with blood-pool contrast agent.

Acoustics↗
PubMed2005

Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation.

BACKGROUND/AIMS: To evaluate the therapeutic efficacy of percutaneous ethanol injection (PEI) for patients with < or = 3 lesions of small (< or = 3 cm diameter) hepatocellular carcinoma (HCC). METHODS: PEI was applied to 270 patients with small HCC as the first-line treatment option during a 20-year period. RESULTS: (1) There was no treatment-related deaths, and only 2.2% of severe complications; (2) PEI induced a complete response of all HCCs according to CT evaluation performed within one month after the procedure, and the local recurrence rate at 3 years was 10%; (3) the overall 3- and 5-year survival rates after treatment were 81.6 and 60.3%, respectively, but the rates were higher, 87.3 and 78.3%, in Child A patients with a solitary tumor < or = 2 cm in diameter; (4) factors significantly influencing survival were liver function (P = 0.0033) and serum alpha-fetoprotein level (P = 0.0014), and (5) the recurrence rate at remote sites in the liver was lower in patients with HCC < or = 2 cm (P = 0.0395) and in those with a solitary HCC (P < 0.0001) according to Cox's proportional hazard model. (6) Radiofrequency ablation would not have been performed in approximately 25% of these patients. CONCLUSIONS: PEI is considered a reliable treatment for small HCC in terms of safety and efficacy.

Adult↗
PubMed2005

Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.

BACKGROUND & AIMS: The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS: A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS: Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS: ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.

Adolescent↗
PubMed2005

Long-term follow-up of intraductal papillary mucinous neoplasm of the pancreas with ultrasonography.

BACKGROUND & AIMS: Most intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a favorable prognosis. This study was undertaken to clarify the clinical course of IPMNs and to set the criteria for surgical treatment on the basis of long-term follow-up by periodic transabdominal ultrasonography (US). METHODS: Eighty-one patients with IPMN were periodically subjected to US (>3 years); 27 were reviewed retrospectively (12 with benign neoplasms [adenoma, borderline] and 15 with malignant tumors [carcinoma in situ, invasive cancer]) and 54 prospectively. US examination was focused on the main pancreatic duct (MPD) diameter, cyst diameter, and presence or absence and height of the protruding lesion. Differences between the benign and malignant groups were examined to set the criteria for surgical treatment. Follow-up results of prospective patients were investigated. RESULTS: The increase of the MPD or the cyst diameter was significantly greater in the malignant group (P < .01). Maximum increases of the MPD diameter by 2.2 mm/year, the cyst diameter by 11.3 mm/year, and emergence or increase of the height of the protruding lesion by 3.3 mm/year were predominantly observed in the malignant group (accuracy, 90.9%, 81.3%, and 81.5%, respectively). The majority of the prospective patients showed no significant changes of these parameters; however, 2 patients (3.7%) were operated on, with the post-surgery histopathologic diagnosis of cancer. CONCLUSIONS: Periodic imaging follow-up is useful to detect a malignant IPMN. Changes in MPD diameter, cyst diameter, and/or size of the protruding lesion are the practical criteria for selecting surgery.

Aged↗
PubMed2005

Lamivudine treatment in a patient with hepatitis B virus reactivation after allogenic peripheral bone marrow transplantation.

We report the case of a 52-year-old woman with hepatitis B virus (HBV) reactivation during treatment for chronic graft vs. host disease (GVHD) after peripheral bone marrow transplantation (PBSCT) to treat chronic myelocytic leukemia. She was given cyclosporine and prednisolone orally to treat chronic GVHD after PBSCT. Liver dysfunction first developed 25 months after transplantation with the appearance of hepatitis B s antigen (HBsAg), hepatitis B e antigen (HBeAg), and elevation of HBV-DNA up to 4.5 log copies/ml. Retrospective examination of her serum before PBSCT proved negative for HBsAg and HBeAg, and positive for anti-HBsAg, anti-HBeAg, anti-hepatitis B core antigen, and HBV-DNA (2.7 log copies/ml), showing that she was in a state of occult HBV infection. Nucleotide sequences of the HBV genome obtained from her serum showed no core promoter mutations at nt 1762 and 1764 and no pre-core mutation at nt 1896. Polymerase chain reaction-restriction fragment length polymorphism showed that she was infected with HBV genotype B. The administration of lamivudine, a nucleoside analog, improved her liver function and reduced HBV-DNA replication. We conclude that antiviral agents, such as lamivudine, are effective for treating hepatitis B reactivation during immunosuppressive treatment, such as for GVHD. The administration of a nucleoside analog before transplantation should also be considered in the light of HBV genotypes and mutations, even if HBsAg was negative and the viral load was low before transplantation.

Antigens, Viral↗
PubMed2005

Enhanced sensitivity of human hepatoma cells to 5-fluorouracil by small interfering RNA targeting Bcl-2.

This study was designed to reveal whether the apoptosis induced in human hepatocellular carcinoma (HCC) cell lines by 5-fluorouracil (5-FU) could be enhanced by transfecting Bcl-2 small interfering RNA (siRNA). Bcl-2 siRNA and control siRNA were transfected into cells following treatment with or without 5-FU. Suppression of Bcl-2 expression was confirmed by Western blotting; cell viability was evaluated by MTS assay, and the occurrence of apoptosis in cells was evaluated by apoptosis assay. Expression of Bcl-2 protein after transfection of 20 nM Bcl-2 siRNA was significantly lower than that of control. Incubation of all cell lines with Bcl-2 siRNA reduced cell viability 96 h after 5-FU treatment compared with all other controls: Huh-7 (P < 0.01), Huh-7 with hepatitis C replicon (P < 0.01), HepG2 (P < 0.01), HLE (P < 0.05). Moreover, the proportion of apoptosis in control siRNA, Bcl-2 siRNA, control siRNA prior to 5-FU treatment, and Bcl-2 siRNA prior to 5-FU treatment groups were (4.6 +/- 2.3)%, (7.5 +/- 0.5)%, (6.0 +/- 2.1)%, and (19.5 +/- 0.86)%, respectively. The Bcl-2 siRNA prior to 5-FU treatment group showed the strongest effect of inducing apoptosis. In conclusion, the combination Bcl-2 siRNA and 5-FU might represent a new therapeutic option for HCC.

Antimetabolites, Antineoplastic↗
PubMed2005

Usefulness of plasma vascular endothelial growth factor in the diagnosis of pancreatic carcinoma: differential diagnosis, tumor progression, and patient survival.

OBJECTIVES: This study aimed to examine the usefulness of plasma vascular endothelial growth factor (p-VEGF) in patients with pancreatic carcinoma (PC) as a tumor marker for PC in comparison with chronic pancreatitis (CP) and to clarify the relationship between p-VEGF and the clinicopathological features of PC. METHODS: The subjects were 69 patients with PC, 35 with CP, and 26 healthy volunteers (control group). The p-VEGF levels were measured by enzyme-linked immunoassay. RESULTS: p-VEGF levels were significantly higher in the PC group compared with the CP and control groups (P < 0.0001). A cut-off level of 149.5 pg/mL, discriminating between PC and CP, was determined based on a receiver operating characteristic curve. Using this cut-off level, the sensitivity was 60%, specificity was 96%, and accuracy was 73%. Patients with PC with distant metastases exhibited a significantly higher level of p-VEGF compared with those without metastasis (P = 0.0113). Multivariate analysis indicated that a high level of p-VEGF was an independent prognostic factor, and a significant association was observed between p-VEGF and median survival time (P = 0.0092). CONCLUSIONS: p-VEGF proved useful in differentiating between PC and CP, and in patients with PC, a high level of p-VEGF may be a predictor of distant metastases and poor prognosis.

Adult↗
PubMed2005

Large regenerative nodule perfused by the portal vein.

In a 42-year-old Japanese woman with esophageal varices, abdominal ultrasound (US) demonstrated a hyperechoic lesion 3 cm in diameter in segment 4 (S4). This nodular lesion had high intensity on T1-weighted magnetic resonance imaging (MRI), low intensity on T2, and very high intensity on superparamagnetic iron oxide (SPIO) enhanced MRI. Angiography showed sparse distribution of arterial branches and dense distribution of portal branches in S4. Meandering, thin arteries were seen in the peripheral area of the right lobe. The second branches of the portal vein were hardly visualized anywhere in the liver. Computed tomography arterioportography (CTAP) revealed portal blood flow dominance in this nodular lesion. There was no evidence of ischemic liver damage, such as thromboembolic episodes, laboratory data of liver damage, coagulation abnormalities etc. Therefore this abnormality was more likely to be caused by anomalous changes than thrombotic changes. Needle biopsy revealed no atypical cells. Two years later, the nodule size was reduced to 1.9 cm, showing its benign nature. Based on these findings, this lesion was classified as a new type of large regenerative nodule (LRN) associated with anomalies in the portal veins and arteries. This is the first report of an LRN of this size in which portal vein perfusion was dominant. Moreover, this lesion was difficult to differentiate from hepatocellular carcinoma (HCC) by imaging. Analysis of the images and pathological features of this case would contribute to a better understanding of the pathogenesis of nodular lesions of the liver.

Adult↗
PubMed2005

Lower incidence of hepatic failure than hepatocellular carcinoma in Japanese patients with chronic hepatitis C.

BACKGROUND: Previous studies have shown that the development of hepatic failure was found more frequently than that of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C in the United States and European countries. We investigated the status in Japan in a retrospective cohort study. METHODS: The incidences of HCC and hepatic failure were accessed in 459 patients with biopsy-proven C-viral chronic liver disease with a mean follow-up period of 8.9+/-3.2 years and the cause of death was also analyzed in the cohort. RESULTS: HCC developed in 63 patients, 46 of 355 interferon (IFN)-treated and 17 of 104 untreated patients. In contrast, the development of hepatic failure was found in 18 patients, 12 of 355 IFN-treated and six of 104 untreated patients. HCC developed in four of 116 with sustained virological response (SVR), and hepatic failure developed in one of them. Thirty-two of 63 patients developing HCC and eight of 18 patients developing hepatic failure died. CONCLUSIONS: Development of hepatic failure was less frequent than that of HCC in Japan. It is important for a favorable prognosis of patients with C viral chronic liver disease to achieve a higher SVR and thus inhibit the development of HCC in Japan.

Antiviral Agents↗
PubMed2005

Study of portal vein thrombosis in patients with idiopathic portal hypertension in Japan.

BACKGROUND/AIMS: The aim of this study was to elucidate the incidence and clinical manifestations of portal vein thrombosis (PVT) in patients with idiopathic portal hypertension (IPH) in Japan during long-term follow-up. PATIENTS AND METHODS: Twenty-two patients with IPH were examined for PVT by sonography during a follow-up of 12+/-6 years. Clinical manifestations and patient outcome related to PVT were studied. Seventy patients with liver cirrhosis were examined by sonography as an incidence control of thrombosis. RESULTS: Nine IPH patients had portal thrombosis (9/22, 41%), a higher incidence than in liver cirrhosis patients (7/70, 10%). Those with thrombosis showed ascites, marked hypersplenism, and low serum albumin. Four patients with thrombosis died. Patients without thrombosis showed less clinical problems after long-term follow-up. Plasma antithrombin III and protein C activity decreased in almost half of the patients. However, there were no differences in these parameters between patients with and without thrombosis. CONCLUSIONS: In Japan, IPH patients had a high incidence of portal thrombosis, a significant factor for poor prognosis. Whether the management of PVT contributes to an improvement of a clinical course of IPH or not should be clarified in further study.

Adult↗