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Michio Sata

Publications and source records attributed to Michio Sata.

At least 37 records · Page 2Linked to original sources
PubMed2006

Increased circulating concentrations of growth-related oncogene (GRO)-alpha in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory state associated with increased risk of intestinal cancers. The aim of this study is to examine serum concentrations of growth-related oncogene (GRO)-alpha, a cytokine with inflammatory and growth-regulatory properties, in patients with IBD. We measured serum concentrations of GRO-alpha in 60 patients with ulcerative colitis, 42 patients with Crohn's disease, 16 patients with other colitides, 12 patients with colorectal cancer, and 40 normal subjects using an enzyme-linked immunosorbent assay. We then analyzed how the cytokine was related to clinical and laboratory variables. Serum GRO-alpha concentrations in patients with active IBD were significantly higher than those in patients with quiescent disease, which in turn were higher than those in normal controls. Concentrations in patients with active ulcerative colitis were higher than in patients with active Crohn's disease. Analysis of paired serum samples showed a decrease in GRO-alpha after initiation of therapy. Furthermore, serum GRO-alpha correlated well with laboratory markers of IBD activity. We conclude that GRO-alpha may have an important role in development of IBD, and might itself be used as a marker of activity. Manipulation of GRO-alpha function might prove therapeutically useful.

Adolescent↗
PubMed2006

A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP.

It is known that there is a very high incidence of hepatocellular carcinoma (HCC) among patients with type C chronic hepatitis and cirrhosis, and alpha -fetoprotein (AFP) has been widely used as a diagnostic marker for HCC. However, there are some patients showing continuous high AFP values but no evidence of HCC, and some studies have defined such patients as a high-risk group for HCC. In vitro study has shown that interferon (IFN) inhibits cell proliferation and enhances apoptosis as well as specific cytotoxic T lymphocytes against HCC, resulting in direct anticancer actions. In this study, we investigated the effect of IFN on AFP changes in chronic hepatitis C patients. Of 40 patients with chronic hepatitis C in whom diagnostic imaging confirmed the absence of HCC, 24 patients showed high pretreatment AFP values (high AFP group: AFP level > 10 ng/dl; mean +/- SD, 46.3 +/- 41.5 ng/dl) and 16 showed low pretreatment AFP values (low AFP group: pretreatment AFP level < or = 10 ng/dl; mean +/- SD, 5.3 +/- 2.2 ng/dl). Pretreatment clinical parameters were statistically evaluated in relation to the AFP value. In the high AFP group, the platelet count, albumin level, and prothrombin (%) were significantly lower (P = 0.047, P = 0.0002, and P = 0.044, respectively), suggesting that AFP value increases with advancing liver disease. Subsequently 27 patients were administered IFN (IFN group), and the remaining 13 patients were administered Stronger Neo-minophagen C (SNMC), a glycyrrhizin preparation (SNMC group), as a control group receiving liver-protective therapy. Alanine aminotransferase was reduced in both the IFN and the SNMC group (mean, 132.56 to 60.07 mg/ml [P < 0001] and 147.85 to 56.23 mg/ml [P = 0.0240], respectively). AFP was significantly reduced in the IFN group (mean, 30.03 to 12.65 ng/ml; P = 0.0034), but there was no significant change in AFP in the SNMC group (mean, 29.70 to 39.17 ng/ml). AFP is useful for diagnosing HCC; however, some patients show a persistently high AFP level in the absence of HCC, and these patients have been described as a high-risk group for HCC. In this study, we found that IFN therapy but not SNMC universally reduced the AFP baseline. Since AFP is a significant predictor for HCC, therapeutic strategies for hepatitis C, e.g., long-term low-dose IFN treatment, may reduce hepatocarcinogenesis.

Aged↗
PubMed2006

Endothelial progenitor cell transplantation improves the survival following liver injury in mice.

BACKGROUND & AIMS: Neovascularization, which is vital to the healing of injured tissues, recently has been found to include both angiogenesis, which involves in mature endothelial cells, and vasculogenesis, involving endothelial progenitor cells. The aim of this study was to clarify the possible roles of endothelial progenitor cells during postnatal liver regeneration. METHODS: To determine how endothelial progenitor cells participate in liver regeneration, human or mouse endothelial progenitor cells were transplanted into the mice with carbon tetrachloride-induced acute liver injury. Survival rate of the mice in endothelial progenitor cell-transplanted and control groups was calculated. Separately, livers removed temporally from both groups were examined. RESULTS: At an early stage, transplanted human endothelial progenitor cells were seen mainly surrounding hepatic central veins where hepatocytes showed extensive necrosis; later, the transplanted cells formed tubular structures. More of these cells were observed along hepatic sinusoids. Transplantation of human or mouse endothelial progenitor cells improved survival of the mice following liver injury (from 28.6% to 85.7%, P < .0005 and from 33.3% to 80.0%, P < .001, respectively), accompanied by greater proliferation of hepatocytes. Human endothelial progenitor cells produced several growth factors, such as hepatocyte growth factor, transforming growth factor-alpha, heparin-binding epidermal growth factor-like growth factor, and vascular endothelial growth factor, and also elicited endogenous growth factors. CONCLUSIONS: Endogenous and exogenous growth factors and direct neovascularization after endothelial progenitor cell transplantation promoted liver regeneration, thus improving survival after liver injury. Transplantation of endothelial progenitor cells could represent a new therapeutic strategy for promoting liver regeneration.

Animals↗
PubMed2006

Gene transfer of kringle 1-5 suppresses tumor development and improves prognosis of mice with hepatocellular carcinoma.

BACKGROUND & AIMS: Recent studies indicate that kringle 1-5 has a potent and specific antiangiogenic activity. Here, we investigated the antitumor effect of kringle 1-5 gene transfer on hepatocellular carcinoma in mice. METHODS: The inhibitory effect of kringle 1-5 protein on proliferation of bovine capillary endothelial cells was evaluated by a tetrazolium-based assay. To study tumor growth, intrahepatic metastasis, and survival, liposome/kringle 1-5 complementary DNA complexes were injected intravenously in nude mice preimplanted with 1 of 3 hepatoma cell lines into the liver. Production of kringle 1-5 was tested by immunohistochemistry and Western blotting. Intratumoral vessel density was quantified. Expression of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in tumors was examined by Western blotting. Serum alanine aminotransferase and alpha-fetoprotein levels and body weights were measured. RESULTS: Proliferation of bovine capillary endothelial cells was inhibited by purified kringle 1-5 in a dose-dependent manner. Gene transfer of kringle 1-5 caused a significant reduction in vessel density with suppression of tumor growth of the 3 hepatoma cell lines and serum alpha-fetoprotein levels, prolonged the survival period, and reduced the number of intrahepatic metastases. Among the analyzed angiogenic factors, kringle 1-5 reduced angiopoietin-2 expression levels. Expression of kringle 1-5 protein was detected on hepatoma cells and hepatocytes in the liver. However, it did not alter serum alanine aminotransferase levels and body weights, suggesting kringle 1-5 lacks severe side effects. CONCLUSIONS: Antiangiogenic gene therapy with kringle 1-5 complementary DNA is a promising safe and effective strategy for suppression of growth of hepatocellular carcinoma.

Alanine Transaminase↗
PubMed2006

New epitope peptides derived from hepatitis C virus (HCV) 2a which have the capacity to induce cytotoxic T lymphocytes in HLA-A2+ HCV-infected patients.

Because cytotoxic T lymphocytes (CTLs) play an important role in the specific immunotherapy of hepatitis C virus (HCV) infection, a series of CTL epitopes has been defined from HCV genotype 1a or 1b protein. Here, we attempted to identify HCV2a-derived epitopes that are capable of inducing HLA-A2-restricted and peptide-specific CTLs. Peripheral blood mononuclear cells (PBMCs) of HLA-A2+ HCV2ainfected patients or healthy donors were stimulated in vitro with each of the HCV2a-derived peptides, which were prepared based on the HLA-A2-binding motif, and their peptide-specific and HLA-A2-restricted cytotoxicities were examined. The HCV2a 432-441, HCV2a 716-724, and HCV2a 2251-2260 peptides were found to efficiently induce peptide-specific CTLs from the PBMCs of HLA-A2+ HCV2ainfected patients. Cytotoxicity was mainly mediated by CD8+ T cells in a HLA class I-restricted manner. These results indicate that the HCV2a 432-441, HCV2a 716-724, and HCV2a 2251-2260 peptides might be applicable for peptide-based immunotherapy of HLA-A2+ HCV2a-infected patients.

Amino Acid Sequence↗
PubMed2006

Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C.

BACKGROUND AND AIM: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. METHODS: A total of 7,715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2,515 (32.6%) patients. Of these 2,515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. RESULTS: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4-9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow-up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P=0.002). CONCLUSIONS: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.

Adult↗
PubMed2006

Value of fusing PET plus CT images in hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma patients with extrahepatic metastases: preliminary findings.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). METHODS: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. RESULTS: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. CONCLUSIONS: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

Adult↗
PubMed2006

Clinical features of hepatitis C virus-related hepatocellular carcinoma and their association with alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II.

PURPOSE: We investigated the differences in clinical features between alpha-fetoprotein (AFP)-predominant hepatocellular carcinoma (HCC) and protein induced by vitamin K absence or antagonist-II (PIVKA-II)-predominant HCC, especially regarding host factors thought to contribute to hepatocarcinogenesis in chronic hepatitis C virus (HCV) infection. METHODS: HCV-related HCC patients (n=306) were divided into four groups according to median AFP (48.1 ng/ml) and PIVKA-II (60 mAU/ml). Host factors, tumor factors, survival, and risk factors affecting survival were compared. RESULTS: Aspartate aminotransferase (AST; IU/L), alanine aminotransferase (ALT; IU/L), and platelet count (x 10(4)/ml) were, respectively, 81, 67, and 8.2 in AFP-predominant HCC (group A; n=66) vs. 50, 42, and 11.4 in PIVKA-II-predominant HCC (group P; n=52). Tumor sizes (mm) in groups A and P were 20 and 37, respectively. Significant differences were evident. Survival was identical between the two groups. Factors affecting survival were total bilirubin, portal tumor thrombus and number of nodule in group A, and albumin and tumor distribution in group P. CONCLUSIONS: PIVKA-II-predominant HCC had a milder hepatitis and a better-preserved platelet count compared with AFP-predominant HCC. Considering the strong relation between hepatocarcinogenesis and hepatic inflammation with chronic HCV infection, these differences indicate that hepatocarcinogenic mechanisms in PIVKA-II-predominant HCC may differ from those in AFP-predominant HCC.

Aged↗
PubMed2006

Simultaneous hepatic relapse of non-Hodgkin's lymphoma and hepatocellular carcinoma in a patient with hepatitis C virus-related cirrhosis.

We report a 66-year-old man with hepatitis C virus (HCV)-related cirrhosis and simultaneous hepatic relapse of non-Hodgkin's lymphoma (NHL) and of hepatocellular carcinoma (HCC). Although the liver is frequently involved by NHL, hepatic colocalization of NHL and HCC is rarely detected by imaging techniques. HCV has been suggested to be lymphotrophic as well as hepatotrophic, and therefore has attracted speculation about a causative role in some cases of lymphoma. The patient had a past history of cutaneous diffuse large B cell lymphoma (DLBCL) in concurrence with HCC 32 months previously. Complete remission (CR) had been maintained for both diseases until February 2004, when ultrasonography and computed tomography (CT) showed multiple liver tumors. Two of these, appearing hyperattenuating in the arterial phase of contrast-enhanced CT, were diagnosed histopathologically as HCC, and treated with radiofrequency ablation. The other tumors, hypoattenuating in the portal phase CT, were diagnosed histopathologically as DLBCL, and treated with cyclophosphamide, tetrahydropyranyl-Adriamycin, vincristine and prednisolone (THP-COP) in combination with rituximab. CR was achieved for both DLBCL and HCC. Given the previously demonstrated immune system tropism and perturbation by HCV, the virus might have contributed to the occurrence of the NHL as well as the HCC.

Aged↗
PubMed2006

Appearance-specific satiety increases appetite and quality of life in patients with metastatic liver tumor: a case report.

Loss of appetite is frequently seen and is a main factor affecting quality of life (QOL) in patients with advanced cancer. The etiology for loss of appetite in patients with cancer is multifactorial. The sensory properties of food are factors regulating appetite. Changes in taste, smell and texture of foods influence food intake. The appearance of the food is also a notable factor in sensory-specific satiety. We described a 46-year-old Japanese woman with multiple metastatic liver tumors. Although there was no obvious factor for loss of appetite, she suffered from a loss of appetite and subsequent malnutrition. In order to improve the appearance of food, we reduced the diet to 1,000 kcal/day from 1,500 kcal/day. On the new diet, the patient's appetite significantly increased and patient's nutritional status was improved. Eating whole diet was an important achievement and increased in mental aspects of QOL. Arrangement for the appearance of food may be a simple and nontoxic therapeutic strategy for patients with cancer suffering a loss of appetite.

Appetite↗
PubMed2006

Pro-inflammatory signaling by Jun-N-terminal kinase in inflammatory bowel disease.

Since Jun-N-terminal kinase participates in intracellular signaling cascades resulting in inflammatory responses, inhibiting this pathway may represent a new treatment for inflammatory bowel disease including ulcerative colitis and Crohn's disease. However, the functional significance of the activation of this kinase in inflammatory bowel disease remains unclear. We investigated whether Jun-N-terminal kinase activation is increased in inflammatory bowel disease and analyzed the effects of SP600125, which decreases inflammatory cytokine synthesis by inhibiting the phosphorylation of this kinase. Phosphorylation of the kinase was examined in affected human colon using an enzyme-linked immunosorbent assay and immunohistochemistry. The effect of SP600125 on cytokine production was examined in cultures of patients' leukocytes and colonic tissue. Finally, rats received injection of SP600125 (30 mg/kg, s.c.) or vehicle twice daily 2 h before the induction of colitis with dextran sulfate sodium. SP600125 effects were determined observationally and histologically. Colonic tissue contained increased phosphorylated kinase in patients with inflammatory bowel disease with expression localized to the nucleus of epithelial and lamina propria mononuclear cells in lesions. Culturing mononuclear cells or colonic tissue with SP600125 down-regulated inflammatory cytokine production. Prophylactic treatment with SP600125 significantly reduced clinical and pathological scores in dextran sulfate sodium-treated rats. This first demonstration of the pathogenetic role of Jun-N-terminal kinase in the development of intestinal inflammation suggests that inhibiting its phosphorylation could benefit patients with inflammatory bowel disease.

Animals↗
PubMed2006

Antibody to hepatitis B core antigen is associated with the development of hepatocellular carcinoma in hepatitis C virus-infected persons: a 12-year prospective study.

Several studies have reported that antibody to hepatitis B core antigen (anti-HBc) positivity may influence the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients, but the evidence is still not conclusive. In this study, we examined whether the presence of anti-HBc positive was associated with the development of HCC in hepatitis C virus (HCV)-infected subjects among the residents in an HCV hyperepidemic area who were followed up for 12 years. In an HCV hyperendemic area (positive rate of anti-HCV: 23.4%), 509 residents were examined by health screening in 1990. After 12 years of follow-up, we evaluated the risk factors for HCC. The incidence of HCC was compared between anti-HBc positive and anti-HBc negative subjects after 12 years of prospective observation. Univariate and multivariate analyses were conducted to determine risk factors for the development of HCC. The incidence of HCC was significantly higher in the anti-HBc positive group (13 subjects) than in the anti-HBc negative group (0 subjects) (P=0.012). Multivariate analysis identified positivity for anti-HBc and HCV RNA, history of icterus, and female gender as independent determinants of the development of HCC. Our findings provide clear evidence in a prospective study that presence of anti-HBc, that is, past hepatitis B virus (HBV) infection, is a risk factor for the development of HCC in HCV-infected people.

Aged↗
PubMed2006

[Bezafibrate alone is an effective first-line therapy for primary sclerosing cholangitis: a case report].

The patient was a 58-year-old female. Though she had been in good health, increased hepatobiliary enzymes were detected in a health examination. She visited our hospital for close examination. The serum IgG4 level was normal, but ERCP and MRCP showed band-like stricture and beaded appearance of the bile ducts. A diagnosis of primary sclerosing cholangitis (PSC) was made. Since hyperlipidemia was also observed, oral administration of bezafibrate (400mg/day) alone was performed as the initial treatment, and transaminase, ALP, and GGT rapidly decreased. These results suggested that the initial administration of bezafibrate alone is effective against PSC.

Administration, Oral↗
PubMed2006

[A case of autoimmune pancreatitis complicated with immune thrombocytopenia].

A 80-year old man was referred to our hospital because of an elevation of serum amylase level. Diffuse enlargement of the pancreas was detected by abdominal computed tomography, and also diffuse narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. The serum level of IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet-associated IgG, antiplatelet antibody and antinuclear antibody in serum were positive. The levels of serum complements were low. From all these findings the patient was diagnosed as autoimmune pancreatitis complicated with immune thrombocytopenia. The treatment with prednisolone was started, which was effective on each disease. The medication was suspended a year ago, and so far there is no data suggesting the recurrence of autoimmune pancreatitis or immune thrombocytopenia.

Aged, 80 and over↗
PubMed2006

Role of vascular endothelial growth factor in protein loss of Ménétrier's disease.

Vascular endothelial growth factor (VEGF) promotes protein leakage from blood vessels and endothelial cell growth. The expression of transforming growth factor (TGF)-alpha and its receptor is increased in the gastric mucosa of patients with Ménétrier's disease. Since TGF-alpha stimulates the expression of VEGF mRNA in cultured keratinocytes, we hypothesized that VEGF may play an important role in the protein leakage of Ménétrier's disease. Immunohistochemistry was performed using specific antibodies against VEGF and CD31 in gastric tissue specimens from 7 patients with Ménétrier's disease and 10 controls. The effect of recombinant TGF-alpha on VEGF production by cultured lamina propria mononuclear cells (LPMCs) was assessed. VEGF expression was detected for LPMCs and occasional epithelial cells of the gastric mucosa of Ménétrier's patients. VEGF-positive LPMCs were increased in tissues from patients with Ménétrier's disease (P<0.001). Of the LPMCs, T-lymphocytes and macrophages were the major sources of VEGF. CD31-positive blood vessels were increased in Ménétrier's tissue. (P<0.05). Recombinant TGF-alpha induced the production of VEGF in cultured LPMCs (P<0.05). In conclusion, the increased expression of VEGF, as a result of overproduction of TGF-alpha, may play a key role in the pathophysiology of Ménétrier's disease.

Adult↗
PubMed2006

[Arterial infusion chemotherapy for patients with advanced pancreatic cancer].

Although various therapies have been tried to improve advanced nonresectable pancreatic cancer, a sufficient consensus has not yet been obtained about the treatment. We have performed arterial infusion chemotherapy for pancreatic cancer in order to maintain QOL. The response rate was 17.3%, the mean survival time 282.1+/-204.7 days, median survival time 243.0+/-84.7 days, and many patients were continuously treated on an outpatient basis. It is thus expected that survival time and maintenance of QOL can be extended by self-sustaining arterial infusion chemotherapy.

Ambulatory Care↗
PubMed2005

Timing of interferon therapy and sources of infection in patients with acute hepatitis C.

BACKGROUND/AIMS: Controversy over the selection of patients and optimum therapeutic method for acute hepatitis C has continued. The aims of this study were to investigate the source of infection, and to evaluate the timing of interferon (IFN) therapy in patients with acute hepatitis C in Japan. METHODS: The records of 102 patients from 12 facilities in Japan who developed acute hepatitis C after 1990 were investigated. In the patients treated with IFN, we performed multivariate analysis to investigate factors related to sustained virological response (SVR). RESULTS: Medical procedure was the most common source of infection, accounting for 32.4% in the 102 patients (33/102). Of 81 patients treated with IFN, 71 patients were followed after IFN therapy, and 57/71 (80.3%) had SVR. The SVR rate was significantly higher in patients treated with IFN within 24 weeks from onset of symptoms than the SVR rate in those treated after 25 weeks (P=0.0016). Multivariate analysis revealed that only the duration between onset of symptoms and initiation of IFN therapy (within 24 weeks) was related to SVR. CONCLUSIONS: Our multicenter cooperative survey revealed that medical procedure was the most frequent source of infection in acute hepatitis C. As concerns the therapy, interferon treatment should be initiated within 24 weeks after onset of symptoms.

Journal Article↗