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Biomedical subjects

Michio Sata

Publications and source records attributed to Michio Sata.

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

Bifidogenic growth stimulator for the treatment of active ulcerative colitis: a pilot study.

OBJECTIVES: Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders. Bifidogenic growth stimulator (BGS) is a prebiotic preparation produced by Propionibacterium freudenreichii isolated from Swiss cheese. Previously BGS was shown to act in the colon as a growth stimulator of Bifidobacteria. This study investigated the efficacy and safety of BGS in the treatment of ulcerative colitis. METHODS: Twelve patients with mildly to moderately active ulcerative colitis received orally 4.5 g of BGS daily for 4 wk in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Concentrations of short-chain fatty acids and the composition of commensal bacteria, including Bifidobacteria, Enterobacteria and Bacteroides species, were studied in stool samples. RESULTS: Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 7.4 +/- 2.8 to 4.7 +/- 1.5 (mean +/- standard error of the mean, P < 0.01). The endoscopic index score decreased from 4.4 +/- 1.7 to 2.8 +/- 1.8 (P < 0.05) with treatment. Patients showed an increase in stool butyrate concentrations after BGS treatment (P < 0.05). There were no significant changes in stool levels of bacteria as a result of BGS treatment. No side effects related to BGS were observed. CONCLUSIONS: Oral BGS therapy may represent a non-toxic way to treat ulcerative colitis. However, controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Adolescent↗
PubMed2005

Mobilization of human lymphoid progenitors after treatment with granulocyte colony-stimulating factor.

Hemopoietic stem and progenitor cells ordinarily residing within bone marrow are released into the circulation following G-CSF administration. Such mobilization has a great clinical impact on hemopoietic stem cell transplantation. Underlying mechanisms are incompletely understood, but may involve G-CSF-induced modulation of chemokines, adhesion molecules, and proteolytic enzymes. We studied G-CSF-induced mobilization of CD34+ CD10+ CD19- Lin- and CD34+ CD10+ CD19+ Lin- cells (early B and pro-B cells, respectively). These mobilized lymphoid populations could differentiate only into B/NK cells or B cells equivalent to their marrow counterparts. Mobilized lymphoid progenitors expressed lymphoid- but not myeloid-related genes including the G-CSF receptor gene, and displayed the same pattern of Ig rearrangement status as their bone marrow counterparts. Decreased expression of VLA-4 and CXCR-4 on mobilized lymphoid progenitors as well as multipotent and myeloid progenitors indicated lineage-independent involvement of these molecules in G-CSF-induced mobilization. The results suggest that by acting through multiple trans-acting signals, G-CSF can mobilize not only myeloid-committed populations but a variety of resident marrow cell populations including lymphoid progenitors.

Animals↗
PubMed2005

Identification of hepatitis C virus 1b-derived peptides recognized by both cellular and humoral immune systems in HCV1b(+) HLA-A24(+) patients.

Despite scientific advances, the therapeutic options for hepatitis C virus (HCV) are limited by poor response rates. HCV1b is particularly resistant to standard interferon therapy. The inhibition of the progression of chronic hepatitis and liver cirrhosis and the prevention of the occurrence and recurrence of hepatocellular carcinoma (HCC) are important and thus, there is a need for new therapeutic modalities for HCV1b infection. We, therefore, investigated highly immunogenic peptides and report in this study three novel candidate peptides (at positions 711-720 in envelope 2 protein, 885-893 in non-structural protein 2 and 1716-1724 in non-structural protein 4B) among 35 peptides of conserved regions of HCV1b proteins containing HLA-A24 binding motifs tested. Namely, HCV(711-720), HCV(885-893) and HCV(1716-1724) induced HLA-A24-restricted and peptide-specific cytotoxic T lymphocytes (CTLs) activity in peripheral blood mononuclear cells (PBMCs) from 7, 6 and 5 of 12 patients and also were recognized by plasma of 8, 5 and 7 of 12 HCV1b(+) patients, respectively. These results may provide new insight into the development of a peptide-based specific immunotherapy for HCV1b(+) HLA-A24(+) patients.

Journal Article↗
PubMed2005

Keratin-containing inclusions affect cell morphology and distribution of cytosolic cellular components.

Many neurodegenerative diseases are characterized by the presence of protein aggregates bundled with intermediate filaments (IFs) and similar structures, known as Mallory bodies (MBs), are observed in various liver diseases. IFs are anchored at desmosomes and hemidesmosomes, however, interactions with other intercellular junctions have not been determined. We investigated the effect of IF inclusions on junction-associated and cytosolic proteins in various cultured cells. We performed gene transfection of the green fluorescent protein (GFP)-tagged cytokeratin (CK) 18 mutant arg89cys (GFP-CK18 R89C) in cultured cells and observed CK aggregations as well as loss of IF networks. Among various junction-associated proteins, zonula occludens-1 and beta-catenin were colocalized with CK aggregates on immunofluorescent analyses. Similar results were obtained on immunostaining for cytosolic proteins, 14-3-3 zeta protein, glucose-6-phosphate dehydrogenase and DsRed. E-cadherin, a basolateral membrane protein in polarized epithelia, was present on both the apical and basolateral domains in GFP-CK18 R89C-transfected cells. Furthermore, cells containing CK aggregates were significantly larger than GFP-tagged wild type CK18 (GFP-WT CK18)-transfected or non-transfected cells (P < 0.01) and sometimes their morphology was significantly altered. Our data indicate that CK aggregates affect not only cell morphology but also the localization of various cytosolic components, which may affect the cellular function.

14-3-3 Proteins↗
PubMed2005

Distinct geographic distributions of hepatitis B virus genotypes in patients with acute infection in Japan.

Genotypes of hepatitis B virus (HBV) were determined in 145 patients with acute hepatitis B from various districts in Japan to establish their geographic distribution and evaluating the influence on the clinical illness and outcome. Genotypes were A in 27 (19%) patients, B in 8 (5%), C in 109 (75%) and mixed with B and C in the remaining one (1%). Genotype A was more frequent in metropolitan than the other areas (21/69 (30%) vs. 6/76 (8%), P < 0.001). On phylogenetic analysis, seven of the nine (78%) HBV/A isolates selected at random clustered with those from Europe and the United States, while the remaining two with those of subgroup A' prevalent in Asia and Africa. Maximum ALT levels were lower (2069 +/- 1075 vs. 2889 +/- 1867 IU/L, P = 0.03) and baseline HBV DNA titers were higher (5.90 +/- 1.45 vs. 5.13 +/- 1.36 log genome equivalents (LGE)/ml, P = 0.002) in patients infected with genotype A than C. Hepatitis B surface antigen persisted longer in patients infected with genotype A than C (1.95 +/- 1.09 vs. 1.28 +/- 1.42 months, P = 0.02). HBV infection became chronic in one (4%) patient with genotype A and one (1%) with genotype C infection. Fulminant hepatic failure developed in none of the patients with genotype A, one (13%) with genotype B and five (5%) with genotype C. The point mutation in the precore region (A1896) or the double mutations in the basic core promoter (BCP) region (T1762/A1764) were detected in none of the patients with genotype A, two (25%) with genotype B and 27 (26%) with genotype C. In conclusion, genotype A is frequent in patients with acute hepatitis B in metropolitan areas of Japan, probably reflecting particular transmission routes, and associated with longer and milder clinical course than genotype C.

Adult↗
PubMed2005

Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon.

BACKGROUND: Interferon (IFN) is expected to prevent the progression of hepatitis C virus infection to cirrhosis and the development of hepatocellular carcinoma (HCC), but there have been several reports of the development of HCC after a sustained response to IFN. Our aim was to elucidate the incidence and clinical features of, and risk factors for, HCC in sustained responders to IFN, taken for the treatment of chronic hepatitis C. METHODS: We designed a retrospective cohort study conducted at 16 major Hospitals. The subjects were a total of 1056 patients showing sustained responses, 29 of whom developed HCC. RESULTS: The incidence of HCC per 100 person-years was 0.56 (95% confidence interval, 0.35-0.76) in sustained responders. By the Cox proportional hazard model, we found that older age, higher serum aspartate aminotransferase level, and lower platelet count before IFN therapy were independent risk factors associated with the development of HCC. A risk index of HCC development, based on the coefficients of these risk factors, was used to classify patients into three groups, with low, intermediate, and high risk. The incidence rates of HCC for these three groups were 0.11, 0.44, and 1.98 per 100 person-years, respectively. The median period to the development of HCC was 4.6 years (range, 1.4-9.0 years), and there were no other specific clinical features of the HCC that developed in these patients. CONCLUSIONS: This study suggests that the risk of development of HCC is not completely eliminated in sustained responders to IFN. These findings may be useful in determining a follow-up strategy after a sustained response to IFN.

Adolescent↗
PubMed2005

Clinical course of patients with chronic hepatitis B with viral breakthrough during long-term lamivudine treatment.

BACKGROUND: We evaluated the clinical course of patients with chronic hepatitis B who showed viral breakthrough during long-term lamivudine therapy. METHODS: We initially studied 141 patients treated with lamivudine for 1 year or more, and 49 patients who showed viral breakthrough were the subjects of this study. Their mean lamivudine administration period was 2.3 +/- 0.9 years. RESULTS: After viral breakthrough, breakthrough hepatitis occurred in 47 patients (95.9%), but did not occur in the other 2 (4.1%). Four of the 47 patients with breakthrough hepatitis were observed without further treatment, and the alanine transferase (ALT) level was normalized in 2 of them but fluctuated in the other 2. Breakthrough hepatitis was treated by injection of glycyrrhizin or ursodeoxycholic acid administration in 36 of the remaining 43 patients, and by antiviral drug administration in the other 7 (entecavir in 2 patients, adefovir in 2, and interferon in 3). The ALT level was normalized in 5 of the 36 patients treated with glycyrrhizin or ursodeoxycholic acid, but persistently fluctuated in the other 31. In those with normalized ALT after the occurrence of breakthrough hepatitis, the peak ALT level at that point was significantly lower (86 +/- 47 IU/l) than that in the patients without normalization (206 +/- 167 IU/l). CONCLUSIONS: These results showed that there were a few patients who did not develop breakthrough hepatitis after showing viral breakthrough, and some who showed normalization of the ALT level after the occurrence of breakthrough hepatitis, but in many patients, ALT continuously fluctuated.

Administration, Oral↗
PubMed2005

A human T-cell lymphotropic virus type-1 (HTLV-1) carrier complicated with various autoimmune diseases including primary biliary cirrhosis.

A 47-year-old woman with primary biliary cirrhosis and scleroderma was examined at our hospital for a 1-week history of non-resolving fever, arthralgia, myalgia, muscle weakness and fatigue. A diagnosis of systemic lupus erythematosus was made based on arthralgia, low leukocyte count, low lymphocyte count, low serum concentration of complements, positive anti-nuclear antibody and positive anti-double-strand-DNA antibody. She was negative for anti-U1RNP antibody, but positive for anti-Jo1 antibody, and her initial serum concentration of creatine phosphokinase was elevated. We diagnosed her as having overlap syndrome with scleroderma, systemic lupus erythematosus and possible polymyositis associated with primary biliary cirrhosis. Prednisolone rapidly improved her symptoms. Lobulated leukocytes were observed in her peripheral blood specimen. She was positive for anti-HTLV-1 antibody, but Southern blot hybridization did not confirm monoclonal integration of HTLV-I proviral DNA in her peripheral blood. This suggests the possibility of a relationship between HTLV-1 infection and various autoimmune disorders including primary biliary cirrhosis.

Journal Article↗
PubMed2005

Impact of daily high-dose IFNalpha-2b plus ribavirin combination therapy on reduction of ALT levels in patients with chronic hepatitis C with genotype 1 and high HCV RNA levels.

The possibility of delaying progression to hepatocellular carcinoma in chronic hepatitis C patients with genotype 1 and high viral titers with baseline ALT levels of >/=50IU/L was examined by administration of IFN plus ribavirin combination therapy using ALT normalization as index and IFN monotherapy as control. The rate of sustained ALT normalization (ALT normal at 24 weeks after the end of treatment) was 28.1% with combination therapy and 10.5% with IFN monotherapy (P=0.001). Furthermore, the number of patients with sustained viral response (SVR) and with sustained ALT normalization in non-SVR patients was also significantly higher in the combination therapy versus monotherapy group. Mean ALT values during treatment and for 6 months after the end of treatment were significantly lower with combination therapy versus monotherapy even in virological nonresponders, as well as significantly lower during the post-treatment observation period in patients who relapsed after the end of treatment. Since increase in the rate of sustained ALT normalization and SVR were successfully achieved, inhibition of progression to hepatocellular carcinoma should be studied with long-term IFN and ribavirin combination therapy.

Journal Article↗
PubMed2005

Molecular evolutionary analyses implicate injection treatment for schistosomiasis in the initial hepatitis C epidemics in Japan.

BACKGROUND/AIMS: The mortality due to hepatocellular carcinoma (HCC) has ranged widely in various areas of Japan since 30 years ago and the incidence was particularly high in once Schistosoma japonicum (Sj)-endemic areas. Our aim was to estimate the spread time of hepatitis C virus (HCV) infection in the past with possible relevance to a higher incidence of HCC in once Sj-endemic than Sj-nonendemic areas. METHODS: During 2001, 131 strains of HCV-1b were obtained from patients in three previously Sj-endemic areas, as well as Sj-nonendemic areas in Japan and a cross-sectional study was conducted on them with molecular evolutionary analyses. RESULTS: A phylogenetic tree reconstructed on HCV-1b sequences in the NS5B region disclosed 2 independent clusters for Sj-positive and -negative groups with a high bootstrap value. The estimated effective number of HCV-infections indicated a transition from quiescence to rapid exponential growth in the 1920s among patients with schistosomiasis, which is 20 years earlier than that among patients without schistosomiasis. CONCLUSIONS: The estimated spread time in previously Sj-endemic areas in Japan coincides with injection treatment for Sj since 1921. A high incidence of HCC there would be attributed to a long duration of HCV infection since 1920s.

Aged↗
PubMed2005

The Wilson disease protein ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 protein.

Wilson disease is a genetic disorder characterized by the accumulation of copper in the body due to a defect of biliary copper excretion. Although the Wilson disease gene has been cloned, the cellular localization of the gene product (ATP7B) has not been fully clarified. Therefore, the precise physiological action of ATP7B is still unknown. We examined the distribution of ATP7B using an anti-ATP7B antibody, green fluorescent protein (GFP)-ATP7B (GFP-ATP7B) and ATP7B-DsRed in various cultured cells. Intracellular organelles were visualized by fluorescence microscopy. The distribution of ATP7B was compared with that of Rab7 and Niemann-Pick C1 (NPC1), proteins that localize in the late endosomes. U18666A, which induces the NPC phenotype, was used to modulate the intracellular vesicle traffic. GFP-ATP7B colocalized with various late endosome markers including Rab7 and NPC1 but not with Golgi or lysosome markers. U18666A induced the formation of late endosome-lysosome hybrid organelles, with GFP-ATP7B localized with NPC1 in these structures. We have confirmed that ATP7B is a late endosome-associated membrane protein. ATP7B appears to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes. Thus, defective copper ATPase activity of ATP7B in the late endosomes appears to be the main defect of Wilson disease.

Adenosine Triphosphatases↗
PubMed2005

Comparison of liver histology between patients with non-alcoholic steatohepatitis and patients with alcoholic steatohepatitis in Japan.

BACKGROUND: This study compared the liver histology of patients with NASH and patients with ASH. METHODS: Subjects consisted of 79 patients (41 in the NASH group and 38 in the ASH group). We performed physical and laboratory examinations as well as liver biopsy in all subjects, and we evaluated the differences between the NASH and ASH groups. In addition, we compared the liver histology of patients with obesity, diabetes or hyperlipidemia within the NASH group. RESULTS AND CONCLUSIONS: BMI was significantly higher in the NASH group than in the ASH group. Steatosis and nuclear vacuoles were more prevalent in the NASH group than in the ASH group. On the other hand, ballooning hepatocytes, lipogranuloma, focal necrosis, acidophilic bodies and fibrosis were more remarkable in the ASH group than in the NASH group. The degrees of steatosis and lipogranuloma gradually decreased as the stage of liver fibrosis progressed. Necro-inflammation and fibrosis tended to be more remarkable in the ASH group than in the NASH group. In the NASH group, ballooning hepatocytes and acidophilic bodies were significantly higher in the group with diabetes than in that without diabetes. Perivenular fibrosis, pericellular fibrosis and portal fibrosis were also higher in the NASH group with diabetes than in the NASH group without diabetes. These findings suggested that diabetes is deeply involved in the development and progression of NASH.

Adult↗
PubMed2005

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

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

Adult↗
PubMed2005

Determination of thrombopoietin-derived peptides recognized by both cellular and humoral immunities in healthy donors and patients with thrombocytopenia.

Thrombopoietin (TPO) is a cytokine that promotes megakaryocytopoiesis and thrombopoiesis and is considered a drug suitable for patients with thrombocytopenia. However, unexpected severe thrombocytopenia has developed in some healthy individuals participating in phase I clinical trials with a pegylated recombinant human megakaryocyte growth factor (PEG-rHuMGDF) that contained the first 163 amino acids of endogenous TPO, which resulted in hampering the further development of clinical trials. Autoimmune responses to PEG-rHuMGDF, which cross-reacted with endogenous TPO, were suggested to be involved in this rare but severe adverse event, although the immunogenic epitopes have not yet been determined. To better understand the molecular basis of such autoimmune reactions, we investigated the reactivity of 18 TPO-derived peptides with HLA-A2-binding motifs to plasma and T cells, both from patients with thrombocytopenia (n=24) and from healthy donors (HDs) (n=24). Four peptides, including those possessing amino acids in receptor-binding sites, were preferentially reactive to plasma from at least 20% of the patients, whereas one peptide at position 101-109 was equally reactive to those of the patients and the HDs. Each of the five peptides had the ability to induce peptide-specific cytotoxic T lymphocytes (CTLs) in both groups, albeit with less frequency among the patients. More important, each of these five peptides had the ability to induce HLA-A2-restricted and peptide-specific CTL activity reactive to cells that produce TPO. These results may provide new insights to gain a better understanding of autoimmune reactions to TPO.

Adult↗
PubMed2005

Atypical manifestations of pancreatitis with autoimmune phenomenon in an adolescent female.

We report a case of an adolescent girl with atypical manifestations of pancreatitis with autoimmune phenomenon presenting with epigastralgia and back pain. While no abnormalities were detected on computed tomography and magnetic resonance imaging, apart from the absence of peripancreatic spread, laboratory and serological findings, such as hypergammaglobulinemia, a high titer of immunoglobulin G, a high titer of immunoglobulin G4, slight positivity for antinuclear antibodies, and positivity for autoantibodies to lactoferrin, were suggestive of autoimmune pancreatitis (AIP). Magnetic resonance cholangiopancreatography imaging (MRCP) visualized only the main pancreatic duct (MPD) in the pancreas head region. Proteoclastic enzyme inhibitor treatment was ineffective but the patient responded well to oral prednisolone. The patient and her family did not consent to endoscopic retrograde pancreatography or biopsy/histopathological examination. The case could not be diagnosed as AIP due to lack of typical diagnostic criteria, and thus the final diagnosis was considered pancreatitis with autoimmune phenomenon. We considered that the MRCP finding of partly visible MPD was due to diffuse irregular narrowing of the MPD. This case suggests that while MRCP imaging of the MPD may be helpful in the diagnosis of pancreatitis with autoimmune phenomenon, a negative result does not preclude such diagnosis.

Adolescent↗
PubMed2005

A case of mediastinal pancreatic pseudocyst successfully treated with somatostatin analogue.

A 57-year-old man with a 3-year history of chronic pancreatitis was admitted to our hospital with upper abdominal pain. Based on examination findings, the patient was diagnosed as having pseudocysts in the pancreatic body and the mediastinum that were associated with acute aggravation of chronic pancreatitis. Because of the patient refused an operation, he was submitted to conservative management including intramuscular injection with somatostatin analogue of 100 microg/day. On the 14th day of the treatment, pleural effusion and pseudocyst in the pancreatic head were additionally diagnosed based on the findings of computed tomography, magnetic resonance imaging and other examinations, and the dose of somatostatin analogue was increased to 200 microg/day. As a result, on the 28th day of the treatment, pancreatitis was inactivated, and the pseudocysts in the mediastinum and the pancreas disappeared. The patient has been followed up for 15 months, and there has been no recurrence.

Humans↗
PubMed2005

Vascular endothelial growth factor is involved in angioedema associated with eosinophilia.

Angioedema associated with eosinophilia is a disorder characterized by angioedema and eosinophilia. However, the pathogenesis of this disorder has not been fully understood. We experienced 4 patients with angioedema associated with eosinophilia. All patients were young, 3 were female and 1 was male. All patients revealed edema of the limbs and eosinophilia. The symptom was rapidly improved after the initiation of low or medium dose of prednisolone. We evaluated the serum concentration of interleukin 5 (IL-5) and the plasma concentration of vascular endothelial growth factor (VEGF) in 1 patient. Both cytokines were markedly elevated before the treatment and decreased after the treatment. Angioedema associated with eosinophilia is not so rare, and IL-5 and VEGF are involved in the pathogenesis of this disease.

Adult↗