Hitoshi Togashi

Yamagata University, Yamagata-shi, Yamagata-ken, Japan

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Publications (48)176.21 Total impact

  • Article: A case of monocular blindness as the initial presentation of hepatocellular carcinoma with skull metastasis
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    ABSTRACT: A 52-year-old man suffering from monocular blindness, with light perception only, was admitted to our hospital. The symptom had begun as low vision and developed rapidly within 3weeks into monocular blindness in the right eye, with no other systemic manifestations. Imaging examinations revealed multiple hepatocellular carcinomas in the cirrhotic liver, and tumors at the skull base and vertebra. A pathological and immunochemical study of specimens obtained by endoscopic transnasal tumor biopsy and laminectomy revealed them to be metastatic hepatocellular carcinomas (HCCs). Although the patient underwent radiation therapy and chemotherapy, he died 5months after admission to our hospital. The cranial HCC, involving only the optic canal, may have disturbed the optic nerve in preference to the other cranial nerves. This is the first report of a HCC patient with monocular blindness as the initial presentation of the disease. KeywordsBlindness–Hepatocellular carcinoma–Metastasis
    Clinical Journal of Gastroenterology 04/2012; 4(4):273-277.
  • Article: (99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C.
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    ABSTRACT: We describe a 62-year-old woman with advanced chronic hepatitis C who showed no response to low-dose long-term interferon-beta monotherapy (3 MU, three times a week). The interferon monotherapy was continued for 2 years and 9 months. Despite this lack of response to interferon, the patient's clinical course was good and liver function assessed by (99m)Tc-galactosyl human serum albumin single photon emission computed tomography ((99m)Tc-GSA SPECT) analysis improved significantly. Improvement of the data obtained by (99m)Tc-GSA SPECT analysis justified continuation of the treatment. (99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C, despite a lack of reduction of the ALT level and HCV-RNA titer.
    Annals of Nuclear Medicine 04/2011; 25(7):520-3. · 1.50 Impact Factor
  • Article: Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.
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    ABSTRACT: The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.
    Stem cells and development 03/2011; 20(9):1503-10. · 4.15 Impact Factor
  • Article: Enhanced expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocyte lineage.
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    ABSTRACT: The transplantation of bone marrow cells (BMCs) has been applied in liver regenerative cell therapy. However, details of the interaction between the transplanted BMCs and hepatic stem cells have not been elucidated. The aim of the present study was to investigate the interaction of BMCs with hepatic stem-like cells (HSLCs) and to determine the BMC factor that steers HSLC differentiation into the hepatocyte lineage. Both BMCs and HSLCs were obtained from an adult Sprague-Dawley rat, and a co-culture system was established. Cell proliferation was analyzed by a proliferation assay, and the differentiation of HSLCs into the hepatocyte lineage was evaluated by the detection of cellular mRNA for liver-specific proteins. DNA microarray analysis was applied to BMCs co-cultured with HSLCs to determine the genes upregulated by their interaction. The proliferation of HSLCs co-cultured with BMCs was significantly higher than that of HSLCs cultured alone, and the expression of mRNAs for both albumin and tryptophan-2,3-dioxygenase was detectable in the co-cultured HSLCs. DNA microarray analysis showed the upregulated expression of fibroblast growth factor 2 (FGF2) mRNA in BMCs co-cultured with HSLCs, and the expression of mRNAs for both albumin and tyrosine aminotransferase became detectable in HSLCs cultured with FGF2. Thus, BMCs stimulate both the proliferation of HSLCs and their differentiation into the hepatocyte lineage. FGF2 is one of the factors that is produced by the interacting BMCs and that stimulates this differentiation.
    Cell and Tissue Research 02/2011; 343(2):371-8. · 3.11 Impact Factor
  • Article: A clockwork liver: Time for liver injury and repair.
    Hitoshi Togashi
    Hepatology Research 11/2010; 40(11):1060-2. · 2.20 Impact Factor
  • Article: Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C.
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    ABSTRACT: The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups (P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy.
    Journal of Medical Virology 08/2010; 82(8):1364-70. · 2.82 Impact Factor
  • Article: Relationship between alcohol consumption and serum adiponectin levels: the Takahata study--a cross-sectional study of a healthy Japanese population.
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    ABSTRACT: The relationship between alcohol consumption and serum adiponectin levels has not been fully explored in an Asian population. Our goal was to determine whether alcohol consumption is associated with a change in adiponectin levels in a healthy Japanese population. This was a cross-sectional study. Subjects were recruited from participants in a health check-up program. This study included 2932 subjects (1306 men and 1626 women). The effects of total weekly or daily volume of ethanol intake on serum adiponectin levels were evaluated. In addition, the correlation of clinical traits with serum adiponectin levels was examined. A multivariate regression model was used to control for possible confounding factors. Alcohol consumption was weakly correlated with decreased serum adiponectin levels in men [Spearman's ordered correlation coefficient (rs=-0.141; P<0.001]; an even weaker correlation was seen in women (rs=-0.055; P=0.025). Multivariate analysis demonstrated that alcohol consumption was independently associated with hypoadiponectinemia. In contrast to reports from the United States and Europe among White and Black subjects, our study demonstrated an inverse association between alcohol intake and serum adiponectin levels in Asian subjects, suggesting ethnic differences in the effects of alcohol consumption on serum adiponectin levels.
    The Journal of clinical endocrinology and metabolism 05/2010; 95(8):3828-35. · 6.50 Impact Factor
  • Article: Expression of the RNA-binding protein Musashi1 in adult liver stem-like cells.
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    ABSTRACT: Aim: Musashi1 is an RNA-binding protein that regulates the Notch signaling pathway in stem cells. Our previous study revealed that Musashi1 is expressed in early hepatocytes during liver development in the mouse. However, whether this unique protein is expressed with Notch signaling markers in adult liver stem-like cells remains unknown. Methods: Established hepatic stem-like cells (HSLC), which were derived from adult Sprague-Dawley rats, were used for experiments in vitro. HSLC were differentiated into mature cells in terms of producing albumin when co-cultured with epidermal growth factor (EGF). The mRNA expression of Musashi1, Notch family (Notch1 and Notch2), Jagged1 and Hes1 was examined in HSLC before and after cell differentiation using polymerase chain reaction-based techniques. Protein expression of Musashi1 was examined in the HSLC and normal mature hepatocytes by immunofluorescence staining. Results: The mRNA expression of Musashi1, Notch1, Jagged1 and Hes1 was detected in the original HSLC before culturing with EGF but not in primary cultured mature hepatocytes. The mRNA expression of Musashi1 and Hes1 was found to be downregulated in differentiated HSLC that produce albumin. Protein expression of Musashi1 was detectable in the original HSLC but not in both differentiated HSLC and mature hepatocytes. Conclusion: These findings demonstrate that the RNA-binding protein Musashi1 is expressed with Notch signaling markers in adult liver stem-like cells.
    Hepatology Research 04/2010; 40(4):432-7. · 2.20 Impact Factor
  • Article: Association study between the -1021C/T polymorphism of the dopamine-beta-hydroxylase gene promoter and personality traits in healthy subjects.
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    ABSTRACT: Dopamine and norepinephrine are implicated in the characterization of personality traits. Dopamine-beta-hydroxylase (DBH) is the enzyme responsible for conversion of dopamine to norepinephrine, and thus plays an important role in controlling dispositions of these neurotransmitters. Previous studies have shown that the -1021C/T polymorphism of the DBH gene promoter influences plasma DBH activity. Therefore, we examined the association between the -1021C/T DBH polymorphism and personality traits in 627 Japanese healthy volunteers. The DBH genotypes were identified by a PCR-RFLP method, and personality traits were assessed by the Temperament and Character Inventory (TCI). In the two-factor analysis of covariance with the DBH genotype and sex as factors and with age as a covariate, there was no main effect of the DBH genotype on any TCI score, while the interaction between the factors was significant in harm avoidance. In the post hoc analysis, the group with the T allele predictive of lower DBH activity had higher scores of harm avoidance than that without the T allele in females (p=0.006), but not in males. The present study suggests that the -1021C/T DBH polymorphism affects the personality trait of harm avoidance in healthy females.
    Neuroscience Letters 07/2009; 462(1):54-7. · 2.11 Impact Factor
  • Article: Impact of metabolic syndrome on elevated serum alanine aminotransferase levels in the Japanese population.
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    ABSTRACT: Measurement of the serum alanine aminotransferase (ALT) level is used as an initial test for detection of liver diseases, and recent studies have also highlighted its potential value as a measure of overall health and survival as a marker of an increased risk of metabolic disorder. This study was designed to clarify the prevalence of elevated ALT levels in the Japanese population and to assess factors associated with ALT elevation. The subjects were 2165 individuals aged 40 to 85 years who participated in a Japanese community-based study referred to as the Takahata Study. Serum ALT levels and factors associated with ALT elevation were investigated. Among 2087 subjects who were negative for hepatitis B and C, the rates of elevated ALT greater than 30 U/L in men and greater than 25 U/L in women were 217 (22.7%) of 957 and 239 (21.2%) of 1130, respectively. These ALT cutoff levels had a specificity of more than 80% for exclusion of subjects with none or 1 of 3 metabolic risk factors: hypertension, lipid metabolism abnormality, and hyperglycemia. Multivariate analysis revealed 5 factors with a significant association with ALT elevation in men (n = 957): high gamma-glutamyltranspeptidase, low adiponectin, high low-density lipoprotein cholesterol, high body mass index, and high homeostasis model assessment insulin resistance index. Similarly, 4 factors were significantly associated with ALT elevation in women (n = 1130): high gamma-glutamyltranspeptidase, low adiponectin, high body mass index, and high homeostasis model assessment insulin resistance index. These results suggest that elevated ALT levels in the Japanese population older than 40 years have a strong association with metabolic syndrome-related features including obesity and insulin resistance.
    Metabolism: clinical and experimental 06/2009; 58(8):1067-75. · 2.59 Impact Factor
  • Article: [Case of chronic type C hepatitis complicated with idiopathic thrombocytopenic purpura that was successfully treated by interferon therapy].
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    ABSTRACT: We report a case of chronic hepatitis C complicated with idiopathic thrombocytopenic purpura (ITP), successfully treated with interferon (IFN) beta. A 65-year-old woman was admitted to our hospital for the treatment of chronic hepatitis C with IFN beta. ITP was also diagnosed because of the presence of platelet associated IgG and the findings of bone marrow examination. We started IFN therapy, which resulted in normalization of transaminases, complete HCV eradication, and increased number of platelet.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 04/2009; 106(3):405-10.
  • Article: Effect of month of birth on personality traits of healthy Japanese.
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    ABSTRACT: The effect of month of birth on personality traits was investigated in 595 healthy Japanese. Personality traits were evaluated by the Temperament and Character Inventory (TCI). Statistical analyses were conducted in two steps. Firstly, months of the year were divided according to ambient temperature or photoperiod, and TCI scores were compared between month groups by analysis of covariance (ANCOVA) with age as a covariate. Secondly, multiple regression analysis was performed with TCI scores as dependent variables and ambient temperature and photoperiod at birth month and age as independent variables. Both analyses showed that higher ambient temperature at birth month was related to higher scores of self-directedness and persistence in females. Also, higher ambient temperature at birth month was related to lower body mass index (BMI) in females. These results suggest that month of birth affects self-directedness and persistence in healthy Japanese females, and these effects may be mediated by BMI changes associated with ambient temperature at birth month.
    European Psychiatry 01/2009; 24(2):86-90. · 2.77 Impact Factor
  • Article: Reply to comments on "What can be revealed by extending the sensitivity of HBsAg detection to below the present limit?"
    Hitoshi Togashi, Sumio Kawata
    Journal of Hepatology 11/2008; · 9.26 Impact Factor
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    Article: What can be revealed by extending the sensitivity of HBsAg detection to below the present limit?
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    ABSTRACT: We investigated what can be revealed by extending the sensitivity of HBsAg detection to below the present limit. We examined the sensitivity of this immunoassay in comparison with real-time PCR detection of HBV DNA using serially diluted sera from HBV carriers. Low HBsAg was measured in 210 healthy volunteers and 368 patients with non-B chronic liver diseases who were negative for HBsAg by a standard EIA method. The radical immunoassay was able to detect HBsAg at a concentration of 0.025 ng/ml. Low HBsAg was positive in 6 of 210 normal volunteers (2.86%), 5 of 65 non-B, non-C cirrhosis patients (7.69%), 6 of 62 non-B, non-C hepatocellular carcinoma patients (9.68%: p=0.04 vs. volunteers), 12 of 134 chronic hepatitis C patients (8.96%: p<0.02 vs. volunteers), and 11 of 107 hepatocellular carcinoma patients complicated by chronic hepatitis C (10.28%: p<0.008 vs. volunteers). Although no HBV DNA was positive in healthy volunteers, 9 patients with non-B chronic liver diseases were positive for HBV DNA by real-time PCR analysis. Increasing the sensitivity of HBsAg detection to below the present limit has revealed that infection with HBV, including occult HBV, is far more endemic than suspected previously.
    Journal of Hepatology 07/2008; 49(1):17-24. · 9.26 Impact Factor
  • Article: CASE REPORT: A patient who developed an amoebic liver abscess during treatment with interferon
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    ABSTRACT: A 65-year-old female received recombinant interferon (IFN) α-2b daily for the treatment of chronic hepatitis C. Fever (39°C or higher) developed 14 days after the start of administration. Abdominal computed tomography suggested multiple liver abscesses, which had not been detected before IFN administration. An autopsy revealed an amoebic liver abscess. A subclinical infection of Entamoeba histolytica in this case developed into amoebic liver abscess during IFN administration.
    Journal of Gastroenterology and Hepatology 06/2008; 13(10):1068 - 1071. · 2.87 Impact Factor
  • Article: [Two cases of pyogenic spondylitis with chronic hepatitis C during combination therapy of interferon alfa and ribavirin].
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    ABSTRACT: This report describes our experience with two cases of pyogenic spondylitis with chronic hepatitis C during combination therapy of interferon alfa and ribavirin. The first patient, a 59-year-old man, was treated conservatively and improved, but the second patient, a 69-year-old woman, was not improved by conservative therapy and reconstructive operation was performed. The combination therapy of interferon alfa and ribavirin has a high risk of severe infectious diseases as side effects. CT scan and MRI are recommended immediately to diagnose pyogenic spondylitis, when patients has pyrexia and lumbago with laboratory data suspected inflammation during interferon therapy.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 11/2007; 104(10):1519-25.
  • Article: Risk of hepatocellular carcinoma and secondary structure of hepatitis C virus (HCV) NS3 protein amino-terminus, in patients infected with HCV subtype 1b.
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    ABSTRACT: We conducted a retrospective study of 65 patients with chronic hepatitis C, to determine whether the secondary structure of the amino-terminal 120 residues of the hepatitis C virus (HCV) NS3 protein is associated with an increased risk of development of hepatocellular carcinoma (HCC). The cumulative incidence of HCC was highest among patients infected with group B HCV-1b, wherein the risk of HCC significantly increased compared with that among patients infected with group A (hazard ratio, 4.95 [95% CI, 1.43-17.11]) after adjustment for age and histological stage. This HCV-1b grouping may be a useful marker for detecting the risk of development of HCC.
    The Journal of Infectious Diseases 11/2007; 196(7):1006-9. · 6.41 Impact Factor
  • Article: Characteristics of three cases of hepatocellular carcinoma showing enhanced technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin accumulation by single photon emission computed tomography analysis.
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    ABSTRACT: Background: The asialoglycoprotein receptor (ASGP-R) is abundantly expressed on the sinusoidal surfaces of hepatocytes. However, the majority of hepatocellular carcinomas (HCC) lack ASGP-R on their cell surface membranes. We describe three cases of HCC showing increased expression of ASGP-R in comparison with the surrounding liver tissue. Methods: We performed technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin ((99m)Tc-GSA) single photon emission computed tomography (SPECT) analysis on patients with HCC. Three cases of HCC showing enhanced accumulation of (99m)Tc-GSA were included in the present study. Histopathological and radiological examinations of the HCC were conducted. The three affected patients were all female and over 60 years old. Results: Computed tomography (CT) angiography or dynamic CT showed hypo-enhancement of the tumors during the hepatic arterial to portal phases. Patient 1 received percutaneous ethanol injection therapy and died 5 years later because of chronic renal failure. Patient 2 underwent surgeryand is currently healthy 5 years after the operation. Patient 3 underwent percutaneous ethanol injection therapy and died 4 years later because of a newly occurred HCC to another part of the liver. Histopathological examination showed well-differentiated HCC in all three cases. Immunohistochemical examination showed that the expression of ASGP-R was higher in the HCC than in the non-tumorous liver tissue. Conclusion: We have named the HCC of this type ASGP-Roma. ASGP-Roma is well-differentiated HCC, shows CT findings that are atypical of HCC, and is diagnosed by (99m)Tc-GSA SPECT analysis. We propose that ASGP-Roma be placed in a special category among well-differentiated HCC.
    Hepatology Research 09/2007; 37(8):628-36. · 2.20 Impact Factor
  • Article: Serum levels of stem cell factor and thrombopoietin are markedly decreased in fulminant hepatic failure patients with a poor prognosis.
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    ABSTRACT: Hematopoietic growth factors including stem cell factor (SCF), thrombopoietin (TPO) and granulocyte colony stimulating factor (G-CSF) have a potential role in inducing bone marrow hematopoietic stem cells to move into the circulation, and the association of these factors with liver regeneration has received a lot of attention recently. The aim of this study was to determine the serum levels of such factors in patients with acute liver injury. The subjects were 25 patients with acute hepatitis (AH) who had a favorable prognosis and 26 patients with fulminant hepatitis (FH), of whom 11 were alive and 15 had died. Sixty-six healthy subjects matched for age and sex served as controls. Serum samples were collected before treatment, and the levels of SCF, TPO and G-CSF were measured using enzyme-linked immunosorbant assays. The levels of SCF and TPO were significantly lower in FH patients than in AH patients and the controls, and were also significantly lower in the FH patients who died, compared to the surviving patients. The G-CSF levels did not differ among them. These results suggest that low serum levels of SCF and TPO may be linked to poor prognosis in patients with severe liver injury.
    Journal of Gastroenterology and Hepatology 09/2007; 22(8):1265-70. · 2.87 Impact Factor
  • Article: [Clonorchiasis complicated with duodenal papillary cancer in a visitor from China].
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    ABSTRACT: It is well known that long-term infection with Clonorchis sinensis often causes bile duct cancer, usually. It occurs in the intrahepatic bile duct. We encountered a rare case of clonorchiasis complicated with duodenal papillary cancer. The patient was a woman from China. Although clonorchiasis is rarely found in Japan, the promotion of international exchange may increase the number of visitors from endemic areas. Thus we must pay sufficient attention to this disease. Also, we reported that the microplate ELISA technique was useful in the diagnosis of clonorchiasis with high accuracy in this case.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 03/2007; 104(2):213-8.