Search PubMed⌕ Search

Biomedical subjects

Michio Sata

Publications and source records attributed to Michio Sata.

At least 109 records · Page 6Linked to original sources
PubMed2004

Germinated barley foodstuff prolongs remission in patients with ulcerative colitis.

Germinated barley foodstuff (GBF) is a prebiotic which increases luminal butyrate production by modulating the microfloral distribution. GBF has been shown to reduce both clinical activity and mucosal damage in active ulcerative colitis (UC) with mild to moderate activity. However, the efficacy of GBF in patients with UC during the remission stage is unknown. The aim of this study was to investigate the efficacy of GBF as a maintenance therapy in patients with UC while in remission. Fifty-nine patients with UC in remission according to Rachmilewitz's clinical activity index (CAI) score of </=4 were enrolled and divided into two groups, control (n=37) and GBF (n=22). Patients in the control group were given conventional treatment alone for 12 months, while patients in the GBF group received conventional therapy plus 20 g of GBF daily. The response to treatments was assessed by monitoring the CAI and endoscopic score according to Matts. Significantly better CAI values were seen in the GBF group at 3, 6, and 12 months compared with the values in the control group. The cumulative recurrence rate in the GBF group with steroid tapering treatment was significantly lower compared with the value in the control group. No side effects related to GBF were observed. GBF appeared to be effective and safe as a maintenance therapy to taper steroid dose and prolong remission in patients with UC.

Adult↗
PubMed2004

[Granulocyte-colony stimulating factor-producing myeloma with clinical manifestations mimicking chronic neutrophilic leukemia].

A 68-year-old man was diagnosed as having bronchial asthma in November 1996. He presented with leukocytosis in June 2002. The WBC count was 29,900/microliter with 82% mature neutrophils showing toxic granules. The neutrophil alkaline phosphatase score and serum level of vitamin B12 were elevated. Bone marrow demonstrated myeloid hyperplasia and plasmacytosis. Cytogenetic and molecular analyses were negative for Philadelphia chromosome and BCR/ABL fusion gene. Lambda-type Bence-Jones protein was detected on the serum and urinary immunoelectrophoresis. The coexistence of chronic neutrophilic leukemia and myeloma was suspected based on the clinical features. The serum level of granulocyte-colony stimulating factor (G-CSF) was elevated. Immunohistochemically, atypical plasma cells were positive for anti G-CSF antibody. Finally, we diagnosed this patient as having a G-CSF-producing myeloma. Treatment with melphalan and prednisolone was initiated without beneficial response. He was then admitted to our hospital for ROAD therapy (ranimustine, vincristine, melphalan, and dexamethasone). The neutrophil count decreased in parallel with the serum G-CSF level. These observations indicated that the neutrophilia in this case was probably caused by a reactive response to G-CSF secreted from the myeloma cells.

Aged↗
PubMed2003

The des-gamma-carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) has been reported to be an important prognostic factor in patients with hepatocellular carcinoma (HCC). Recently, a monoclonal antibody, 19B7, which recognizes the Gla domain of DCP, has been identified. The 19B7 antibody recognizes an epitope different from that recognized by MU-3, which is another antibody against DCP. In this study, the authors investigated the measurement of DCP using the antibodies MU-3 and 19B7, respectively, as a prognostic factor for patients with HCC who had solitary, small tumors and or Child Stage A HCC. METHODS: One hundred four patients with HCC who had solitary, small tumors or Child Stage A tumors were enrolled in the study between 1991 and 2001. All patients were treated and were followed for a mean of 3.2 years. The authors analyzed the correlation between the DCP Index (DCP measured by MU-3 and DCP measured by 19B7) and patient prognosis. The patients were classified into 3 groups based on their DCP Index: 1) DCP negative (DCP < 40 milli arbitrary unit (mAU)/mL)); 2) low DCP Index (DCP > or = 40 mAU/mL; MU-3:19B7 ratio, < 3.0; and 3) high DCP Index (DCP > or = 40 mAU/mL; MU-3:19B7 ratio, > or = 3.0). RESULTS: The survival rate for patients in the high DCP Index group was lower compared with the survival rate for patients in the DCP-negative group and was significantly lower compared with the survival rate for patients in the low DCP Index group. In a univariate Cox proportional hazards model, the positive factors were high DCP Index and low DCP Index. Among the positive predictive factors that were analyzed using a multivariate Cox proportional hazards model were age (hazard ratio, 3.27; P = 0.006), low DCP Index (hazard ratio, 2.87; P = 0.012), and high DCP Index (hazard ratio, 12.3; P < 0.0001). CONCLUSIONS: The prognosis of patients who had a high DCP Index score was poorer compared with patients who had a low DCP Index score and patients who were classified as DCP negative. The authors concluded that the DCP Index is a prognostic indicator for patients with HCC.

Aged↗
PubMed2003

Proteasome inhibition induces inclusion bodies associated with intermediate filaments and fragmentation of the Golgi apparatus.

The ubiquitin-proteasome system is involved in a variety of biological processes. Inclusion bodies associated with intermediate filaments (IFs) and ubiquitin are observed in various diseases; however, the precise mechanisms of formation and the pathological significance of inclusion bodies have not been fully understood. We examined the effect of proteasome inhibitors on the structure of IF using anti-cytokeratin antibodies or transfection of green fluorescent protein-fused cytokeratin 18 in a hepatoma cell line, Huh7. Intracellular organelles were visualized by immunofluorescent and electron microscopies. Proteasome inhibitors induced IF inclusions associated with ubiquitin. Electron microscopic examination revealed inclusion bodies surrounded by filamentous structures. Autophagic vacuoles and lysosomes were frequently observed, and the organization of the Golgi apparatus was disrupted in these cells. After the removal of the proteasome inhibitors, the IF network and organization of the Golgi apparatus were restored. The IF inclusions could be induced by inhibition of the proteasome function. IF inclusions induced fragmentation of the Golgi apparatus and might inhibit the function of this important station of membrane traffic. The IF inclusions disappeared by restoring proteasome function, and autophagy and lysosomal degradation might be, at least in part, associated with the elimination of inclusion bodies.

Autophagy↗
PubMed2003

Prognostic significance of the F-box protein Skp2 expression in diffuse large B-cell lymphoma.

The F-box protein Skp2 positively regulates the G1-S transition by promoting degradation of the cyclin-dependent kinase inhibitor p27(kip1) (p27). Recent evidence has suggested an oncogenic role of Skp2 in not only carcinogenesis but also lymphomagenesis. In this study, we performed immunohistochemical analysis on the cell-cycle-associated proteins, Skp2, p27, and Ki-67, in 27 patients with de novo diffuse large B-cell lymphoma (DLBCL), evaluating the correlation between the clinical characteristics and expression levels of these proteins. The patients were classified into two groups according to the positivity for Skp2 expression: a high Skp2 expression group (>60% positive for Skp2 in lymphoma cells) and a low Skp2 expression group (< or = 60%). A high level of Skp2 expression significantly correlated with advanced clinical stage (P = 0.029), although the increase did not correlate with age, gender, LDH levels, presence of extranodal disease, or performance status and resulted in no correlation with the International Prognostic Index-based risk grading. However, it was noteworthy that the high Skp2 expression group demonstrated a significantly worse prognosis than the low Skp2 expression group (P = 0.0007). The expression level of Skp2 correlated with that of Ki-67 but not necessarily with that of p27. The p27 expression level did not correlate patients' prognosis. Taken together, it was suggested that Skp2 was a valuable and independent marker predicting the outcome in DLBCL.

Adult↗
PubMed2003

Inhibition of proteasome-dependent degradation of Wee1 in G2-arrested Hep3B cells by TGF beta 1.

Transforming growth factor beta1 (TGF beta 1)-induced G2 arrest was observed when a proliferation inhibitory function of the retinoblastoma protein (Rb) was compromised, but the mechanism underlying the G2 arrest was poorly characterized compared with that of G1 arrest. In the present study, we characterized G2 arrest induced by TGF beta1 (1 ng/mL) in the Rb-negative hepatoma cell line (Hep3B) and compared with G1 arrest in the Rb-positive hepatoma cell line (Huh7). Activities of cyclin-dependent kinases (CDK) 2 and cell division cycle (CDC) 2 were markedly decreased at 24 h, the time when cell-cycle arrest became apparent in both cell lines. However, considerable amounts of inactive CDC2-cyclinB1 complexes were present in the nucleus of G2-arrested Hep3B but were not present in G1-arrested Huh7. The inhibitory phosphorylation of CDC2 on Tyr-15 was significantly elevated at 12-24 h, and its levels gradually declined during G2 arrest in Hep3B. In particular, augmentation of CDK inhibitors p21cip1 and p27kip1 and Wee1 kinase and diminution of CDC25C phosphatase coincided with induced Tyr-15 phosphorylation and inhibition of CDC2. Wee1 in Hep3B was unstable and was degraded in a proteasome-dependent manner, but it became substantially stabilized within 6 h of TGF beta 1 treatment. Moreover, a Wee1 inhibitor, PD0166285, abrogated the TGF beta 1-induced G2 arrest in Hep3B. These findings suggest that TGF beta 1 induced G2 arrest in Hep3B at least in part through stabilization of Wee1 and subsequent increase in Tyr-15 phosphorylation and inhibition of CDC2.

Base Sequence↗
PubMed2003

Germinated barley foodstuff, a prebiotic product, ameliorates inflammation of colitis through modulation of the enteric environment.

BACKGROUND: Germinated barley foodstuff (GBF), which contains glutamine-rich protein and hemicellulose-rich fiber, exhibits therapeutic effects in ulcerative colitis; however, its mechanism is still under investigation. The aim of this study was to evaluate the anti-inflammatory effects of GBF on colitis in terms of the epithelial inflammatory response. METHODS: Mice with dextran sulfate sodium-induced colitis were used. The effects of GBF on the colitis were evaluated by measuring the body weight; disease activity; mucosal damage (histology, mucosal inflammatory parameters, nuclear factor kappa B [NFkB] activation, and signal transducer and activator of transcription 3 [STAT3]); serum interleukin 6 (IL-6) level; cecal short-chain fatty acids (SCFAs); and bile acid contents. RESULTS: GBF significantly prevented disease activity and body weight loss after induction of colitis. Serum IL-6 level and mucosal STAT3 expression were also significantly attenuated, with a conspicuous reduction of mucosal damage; NFkB activity showed the same tendency. Cecal butyrate content was significantly higher and, interestingly, GBF mice had lower bile acid concentrations than the control group. CONCLUSIONS: GBF has the potential to reduce the epithelial inflammatory response by depressing STAT-3 expression and inhibiting NFkB binding activity. These effects may be brought about by an increase of butyrate production and adsorption of bile acids.

Animals↗
PubMed2003

Long-term survival following treatment with antineoplastons for colon cancer with unresectable multiple liver metastases: report of a case.

We report a case of survival for nearly 8 years after treatment of unresectable multiple liver metastases from colon cancer, using microwave ablation and the nontoxic antitumor agent, the antineoplastons. A 72-year-old man diagnosed with adenocarcinoma of the ascending colon and 14 bilateral liver metastases underwent a right hemicolectomy combined with microwave ablation of six metastatic liver tumors. We also decided to give antineoplastons to inhibit metastatic tumor growth and recurrence. Antineoplaston A10 was given intravenously, followed by oral antineoplaston AS2-1. Computed tomography scans done 1 and 4 years after the initial diagnosis showed recurrent tumors in S(4) and S(7), respectively. The patient underwent a second and a third microwave ablation of the recurrent tumors, and has survived for nearly 8 years without suffering any serious adverse effects. He is currently free from cancer. This case report demonstrates the potential effectiveness of the nontoxic antitumor agent, the antineoplastons, for controlling liver metastases from colon cancer.

Adenocarcinoma↗
PubMed2003

Unusual hyperbilirubinemia associated with bacterial pneumonia and acute myeloid leukemia.

A 77-year-old man with pneumonia associated with acute myeloid leukemia was introduced to the hepatology unit at our hospital for hyperbilirubinemia. He had been suffering from a high fever because of pneumonia. He was icteric and his serum concentrations of total and direct bilirubin were 13.1 and 7.9 mg/dl, respectively. However, the other standard biochemical examinations for hepatic function, such as serum concentrations of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase were normal except for lactate dehydrogenase. Lactate dehydrogenase isoenzyme analysis revealed that the high concentration was derived from leukemia cells. Ultrasonography of the abdomen revealed no abnormality in the liver or biliary tract. Administration of antibiotics for pneumonia decreased the serum bilirubin concentration, however, he died because of respiratory failure caused by the progression of pneumonia at 33 days after the admission. It was suggested that a disturbance in the bilirubin metabolism without hepatocyte necrosis or mechanical cholestasis might be involved in the pathogenesis of hyperbilirubinemia in patients with infectious diseases.

Journal Article↗
PubMed2003

Investigation of associating factors in exacerbation of liver damage after chemotherapy in patients with HBV-related HCC.

BACKGROUND/AIMS: Flare-up of hepatitis due to the reactivation of hepatitis B virus (HBV) is a well-known complication in patients with malignant disease who receive chemotherapy. Despite the widespread use of chemotherapy for patients with HBV-related hepatocellular carcinoma (HCC), there is little corresponding data on exacerbation of liver damage in these patients. In the present study, we investigated the associating factors in exacerbation of liver damage in patients with HBV-related HCC who were undergoing trans-hepatic arterial infusion chemotherapy (THAIC). PATIENTS AND METHODS: Thirty-three patients who received THAIC for HCC were investigated. All patients were hepatitis B surface antigen positive. Hepatitis e antigen and antibody were generally tested at baseline and within 1 month of final chemotherapy. Serum alanine aminotransferase, asparate aminotransferase, albumin, total bilirubin, and prothrombin time were estimated once a week or every 2 weeks. HBV-DNA levels were measured at baseline and once a month. Mutation in the regions of precore and core promoter in HBV DNA was generally estimated at baseline and within 1 month of final chemotherapy. RESULTS: Eight patients with hepatitis Be antigen positive and hepatitis Be antibody negative at baseline were found to have exacerbation of liver damage during or after chemotherapy. Of these, three patients died of progressive liver failure. There was no association between exacerbation of liver damage and age, sex, hepatic reserve function, HBV-DNA levels, precore and core promoter sequencing, therapeutic regimen, or tumor stage. The only associating factor was HBeAg positivity. CONCLUSIONS: These results suggest that hepatitis B e antigen positivity is a significant associating factor in exacerbation of liver damage during or after chemotherapy in patients with HBV-related HCC.

Journal Article↗
PubMed2003

Association of troglitazone-induced liver injury with mutation of the cytochrome P450 2C19 gene.

An anti-diabetic agent, troglitazone, was withdrawn from the market because of its association with liver injury. However, the mechanism of the injury has not been elucidated. We examined, retrospectively, the frequency of the polymorphisms of the cytochrome P450 (CYP) 2C19 and 2D6 genes in eight patients with type 2 diabetes who had troglitazone-induced liver injury and 31 subjects who tolerated troglitazone well. Polymorphisms of CYP 2C19 and 2D6 genes were analyzed by polymerase chain reaction using peripheral white blood cells. The incidence of mutations was compared with known population data for the Japanese. Homozygous or compound heterozygous mutations in CYP 2C19 alleles were found in four of the eight (50.0%) patients with troglitazone-induced liver injury. This rate was significantly higher than that in patients without liver injury (four of 31, 12.9%). The frequency of P450 2D6 mutations was the same in both groups. In conclusion, troglitazone-induced liver injury occurred more frequently in subjects with the CYP 2C19 mutations in Japanese patients.

Journal Article↗
PubMed2003

Clinical significance of antibody against hepatitis B virus core antigen in patients with hepatitis C virus-related hepatocellular carcinoma.

PURPOSE: We investigated the unsettled issue of whether seropositivity for antibody to hepatitis B core antigen (anti-HBc) affects characteristics of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: Antibody status was determined by enzyme immunoassay in 243 patients with this cancer, and associations with clinicopathologic characteristics and outcome were analysed. Serum hepatitis B virus (HBV) DNA was determined by real-time polymerase chain reaction. RESULTS: Of 235 patients with unequivocal serologic status, 142 were seropositive and 93 were seronegative. Clinicopathologic characteristics and overall cumulative survival rates were comparable between the two groups. However, seropositivity tended to predict poor outcome for patients in Child class B or C (P=0.068), those in tumour-nodes-metastasis-based stage 3 or 4 (P=0.081), those with tumours exceeding 25 mm (P=0.068), and those with a past history of clinical liver disease (P=0.088). Multivariate analysis identified serum albumin, portal vein tumour thrombosis, and tumour size as independent determinants of survival. Serum HBV DNA was below 1.7 log copies/ml in all 40 patients tested. CONCLUSIONS: Overall, the clinical features of HCV-HCC were unaffected by seropositivity for anti-HBc. Seropositivity tended to worsen prognosis for subgroup with poor hepatic reserve or advanced tumours.

Adult↗
PubMed2003

Tumor necrosis factor-alpha and interferon-gamma directly impair epithelial barrier function in cultured mouse cholangiocytes.

BACKGROUND/AIMS: In primary biliary cirrhosis (PBC), cytokines from CD4+ T lymphocytes were suggested to contribute to the intralobular bile duct damage together with cellular immunity by CD8+ T lymphocytes. Recently, we reported that immunolocalization of 7H6--a tight junction (TJ)-associated protein--was significantly diminished in cholangiocytes in the PBC liver. In this study, we examined the direct effects of several cytokines--tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-2 and 4 (IL-2 and 4)--on TJ in immortalized mouse cholangiocytes. Moreover, we examined the inhibitory effect of ursodeoxycholic acid (UDCA) on cytokine-induced changes in paracellular permeability. METHODS: Barrier function of TJ was evaluated by measuring transepithelial electrical resistance (TER) and 3H-inulin flux. We also performed immunostaining and immunoblotting for TJ-associated proteins--claudin-1 and -3, occludin, zonula occluden-1 (ZO-1) and 7H6. RESULTS: TNF-alpha and IFN-gamma, but neither IL-2 nor IL-4, significantly decreased TER (P < 0.005). 3H-inulin flux studies confirmed IFN-alpha-induced increases in paracellular permeability of cholangiocytes (P < 0.001). In immunostaining and immunoblotting studies, TJ-associated proteins were well preserved in TNF-alpha- or IFN-gamma-treated cells. Ursodeoxycholic acid has been found to have no inhibitory effect on increased paracellular permeability induced by TNF-alpha or IFN-gamma. CONCLUSION: These findings show that TNF-alpha and IFN-gamma disrupt barrier function of TJ in cholangiocytes without major structural changes to TJ and suggest that disruption of TJ function and subsequent leakage of the bile constituents may influence the aggravation of cholestasis in PBC.

Animals↗
PubMed2003

Incidence of Sjögren's syndrome in Japanese patients with hepatitis C virus infection.

BACKGROUND AND AIM: Hepatitis viruses induce not only chronic liver diseases but also the impairment of other organs and tissues as extrahepatic manifestations. In particular, hepatitis C virus (HCV) is involved in various extrahepatic manifestations. The purpose of the present study was to evaluate Sjögren's syndrome (SS) and lichen planus (LP) involvement, which are various extrahepatic manifestations in patients with liver diseases related to hepatitis B virus (HBV) or HCV. METHODS: We examined a total of 110 Japanese patients with chronic liver disease: 29 with HBV infections and 81 HCV infections. RESULTS: The prevalence of SS according to European and Japanese criteria in patients with chronic HCV infection was significantly higher than in patients with chronic HBV infection (European criteria: 25.9 vs 3.4%; P < 0.05, Japanese criteria: 21.0 vs 3.4%; P = 0.05). Lichen planus was observed in one (3.4%) of 29 patients with chronic HBV infection, and in 11 (13.6%) of 81 patients with chronic HCV infection. Simultaneously combined LP and SS occurred in 8.6% (seven of 81) of patients with HCV infection, but in none with HBV infection. CONCLUSIONS: Clinicians should routinely follow the HCV-infected patients, paying sufficient attention to the presence of SS and LP, and they should also carefully monitor their prognosis.

Adult↗