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Biomedical subjects

Michio Sata

Publications and source records attributed to Michio Sata.

At least 163 records · Page 9Linked to original sources
PubMed2002

Bronchiolitis obliterans organizing pneumonia in a patient with primary biliary cirrhosis and rheumatoid arthritis treated with prednisolone.

A 62-year-old woman with primary biliary cirrhosis (PBC) and rheumatoid arthritis (RA) was examined at our hospital for a 2-week history of non-resolving fever, cough and malaise. Her chest radiograph revealed left lower lobe opacity. Various kinds of antibiotics were not effective and transbronchial biopsy revealed non-specific inflammatory alveolar lesions. Chest radiograph at 14 days after admission revealed migration of the pulmonary opacity, suggesting bronchiolitis obliterans organizing pneumonia (BOOP), which responded well clinically and radiologically to oral corticosteroid therapy. BOOP may be one of the possible non-hepatic complications of PBC especially in patients associated with other connective tissue diseases.

Journal Article↗
PubMed2002

Expression of uncoupling protein-2 in biliary epithelial cells in primary biliary cirrhosis.

BACKGROUND/AIMS: Uncoupling proteins are thought to protect cells from oxidative stresses. Because uncoupling protein-2 is expressed in liver and reactive oxygen species are involved in pathogenesis of various liver diseases, this protein may protect liver cells from disease-associated oxidative stress. However, uncoupling protein-2 expression in human liver has not been examined. METHODS: We investigated hepatic uncoupling protein-2 distribution in various liver diseases including primary biliary cirrhosis, autoimmune hepatitis, chronic viral hepatitis, and histologically normal liver by immunohistochemistry. RESULTS: Uncoupling protein-2 was expressed in some hepatocytes, however, the degree of hepatocytic uncoupling protein-2 expression did not differ significantly among liver diseases and normal liver. Uncoupling protein-2 was abundant in biliary epithelial cells in primary biliary cirrhosis but not in other liver specimens. Enhanced uncoupling protein-2 expression in biliary epithelial cells was specific for primary biliary cirrhosis and did not result simply from cholestasis. The percentage of uncoupling protein-2 positive bile ducts in primary biliary cirrhosis patients treated with ursodeoxycholic acid was significantly lower than in untreated patients. CONCLUSIONS: These results suggest that uncoupling protein-2 is involved in the pathogenesis of primary biliary cirrhosis.

Bile Ducts↗
PubMed2002

Interferon therapy prolonged life expectancy among chronic hepatitis C patients.

BACKGROUND & AIMS: The effects of interferon therapy in chronic hepatitis C patients on survival are unclear. Our objective was to analyze survival among a large cohort of chronic hepatitis C patients. METHODS: We used a retrospective cohort study design in the setting of 7 university hospitals and 1 regional core hospital in Japan. Our study included 2889 patients with histological-proven chronic hepatitis C: 2430 patients received interferon therapy, and 459 patients were untreated. For intervention, the median dose and duration of interferon administration was 480 million units and 137 days, respectively. For measurements, survival status was confirmed by medical records or direct questionnaires. The effect of interferon therapy on survival was assessed by standardized mortality ratio (SMR) based on published mortality among the Japanese general population and by risk ratio calculated by proportional hazards regression. RESULTS: Thirty of 459 untreated patients, 7 of 817 virologic sustained responders, and 49 of 1613 nonresponders died in 5.4-years follow-up. Fifty-eight (67%) of 86 patient deaths were due to liver diseases (39 to hepatocellular carcinoma). Compared with the general population, overall mortality was high among untreated patients (SMR: 1.9; CI: 1.3-2.8) but not among interferon-treated patients (SMR: 0.9; CI: 0.7-1.1). The risk of death was reduced, compared with untreated patients, among interferon-treated patients (risk ratio for overall death: 0.367; CI: 0.236-0.596; for liver-related death: 0.284; CI: 0.164-0.494) and among sustained responders (risk ratios: 0.148; CI: 0.064-0.343 and 0.050; CI: 0.012-0.216). The risk of liver-unrelated deaths remained unchanged. CONCLUSIONS: Interferon therapy improved survival of chronic hepatitis C patients by preventing liver-related deaths.

Adult↗
PubMed2002

Alpha-fetoprotein- and des-gamma-carboxy prothrombin-producing advanced gastric cancer.

A case of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) producing gastric cancer with multiple liver metastasis is reported. The simultaneous presence of Borrmann I gastric cancer and IIa aggregating type gastric cancer was noted. Borrmann I gastric cancer was a poorly differentiated adenocarcinoma, while IIa aggregating type gastric cancer was a moderately differentiated adenocarcinoma. Plasma levels of AFP and DCP were 247,000 ng/ml and 320,000 mAU/ml, respectively. Immunohistochemical staining confirmed the production of these two proteins in Borrmann I gastric cancer.

Adenocarcinoma↗
PubMed2002

Elevation of serum MAGE-4 protein levels and prediction of hepatocellular carcinogenesis in patients with liver cirrhosis.

Early detection of hepatocellular carcinoma (HCC) is clinically important because advanced HCC limits treatment modalities for the cancer. We have previously reported that serum levels of MAGE-4 protein are strongly associated with the development of HCC. The present study was designed to determine whether elevated serum MAGE-4 protein levels can predict hepatocellular carcinogenesis in patients with liver cirrhosis before clinical diagnosis. Among 62 cirrhotic patients, 28 patients were diagnosed with HCC during the follow-up period. The levels of MAGE-4 protein and alpha-fetoprotein (AFP) were significantly elevated in cirrhotic patients with HCC. Univariate and multivariate analyses suggest that elevated serum MAGE-4 protein is more significant than AFP. Importantly, retrospective analysis of prefrozen sera of cirrhotic patients revealed a transient or continuous elevation of serum MAGE-4 protein levels in 14 of 28 cirrhotic patients with HCC (50%) before clinical diagnosis. In contrast, elevated serum MAGE-4 protein levels were observed in 3 of 33 cirrhotic patients without HCC (9%), and in 2 of 34 hepatitic patients (6%). These results indicate that elevated serum MAGE-4 protein levels can be a predictive marker of hepatocellular carcinogenesis in cirrhotic patients, thereby enabling us to treat patients at an earlier stage.

Aged↗
PubMed2002

Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan.

OBJECTIVE: We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg(+)]. METHODS: Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(-)/anti-HCV(-) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB). RESULTS: There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(-)/anti-HCV(-) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(-)/anti-HCV(-) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum alpha-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.

Aged↗
PubMed2002

Efficacy of vascular endothelial growth factor in the treatment of experimental gastric injury.

BACKGROUND/AIMS: Studies indicate that angiogenesis is important in tissue healing. However, the role of vascular endothelial growth factor (VEGF) in tissue healing has not been established. The aim of the study is to determine whether VEGF has a gastroprotective role in experimental gastric injury. METHODS: Acute gastric injury was induced in Sprague-Dawley rats by intragastric administration of 100% ethanol. Expression of gastric VEGF was determined in tissue homogenates by enzyme-linked immunosorbent assay and in paraffin-embedded sections by immunohistochemistry. The effect of systemic administration of anti-VEGF antibodies and recombinant VEGF on injury severity was assessed macroscopically and microscopically. RESULTS: Gastric VEGF concentrations peaked at 6 h and again 3 days after acute injury. The presence of VEGF was demonstrated in epithelial cells and in mononuclear cells. Blocking endogenous VEGF effects with anti-VEGF antibodies exacerbated mucosal injury. Administration of recombinant VEGF after the onset of injury reduced the severity of mucosal injury, irrespective of the timing of initial treatment with VEGF. Immunohistochemical detection of vascular endothelial cells revealed that the VEGF-induced mucosal repair is closely related to the degree of angiogenesis. CONCLUSION: The results provide strong evidence for the role of VEGF in the repair of tissue damage induced by ethanol. The results also show how VEGF may be used in a clinical setting to treat some acute gastric lesions.

Animals↗
PubMed2002

Confocal laser microscopy of chondrocytes that received gene transfer using in vitro electroporation.

To develop a gene therapy for osteopathies, this study was conducted to establish a method of transferring the BMP gene, a bone formation factor, to cells and administering the cells with BMP expression to patients with osteopathies. Although virus vectors are frequently used for gene transfer, there has been reported a death case of gene therapy using the adenovirus vector. Therefore, various efforts have been made to prevent such complications. In the present study, we used electroporation by which gene transfer can be efficiently performed without inducing severe complications after electric perforation of the cell membrane. Human bone tissues were initially collected intraoperatively, and BMP-2 and Smad4 genes were cloned and integrated into GFP and DsRed plasmid vectors. Using in vitro electroporation, these plasmid vectors were transferred to the cultured chondrocytes (KTN-1) derived from human herniated intervertebral disk. Confocal laser microscopy revealed that the BMP gene was successfully transferred to the nucleus of chondrocytes in the presence of Smad. Since electroporation facilitated human gene transfer to the target cells, gene therapy using electroporation may facilitate individualized treatment for patients.

Base Sequence↗
PubMed2002

Effect of AGEs on human disc herniation: intervertebral disc hernia is also effected by AGEs.

Currently, extracellular matrix MMP has been discussed in relation to the extrusion and spontaneous regression of the herniated mass observed in lumbar disc herniation. However, the question remains as to whether degenerated protein is really the cause of this condition's pathogenesis. We confirmed immunologically by means of electron microscopy that extrusion is caused by the AGEs (advanced glycation end products)-induced cross-linking of collagen, and that spontaneous regression is due to AGE receptors on macrophages. Further, AGEs were found to be already exposed during histogenesis, suggesting a relation to apoptosis. In lumbar disc herniation and aging, glucose-derived AGEs cross-link proteins and cause vascular tissue damage.

Base Sequence↗
PubMed2002

Prebiotic treatment of experimental colitis with germinated barley foodstuff: a comparison with probiotic or antibiotic treatment.

There is increasing evidence that intestinal microflora play an important role in the pathogenesis of ulcerative colitis. Therefore, modification of the microflora by prebiotics, probiotics, and antibiotics may be a rational approach for controlling intestinal inflammation. Germinated barley food-stuff (GBF) is an insoluble mixture of glutamine-rich protein and hemicellulose-rich dietary fiber. GBF is utilized efficiently by Bifidobacterium, Lactobacillus, and Eubacterium and converted by them into lactate, acetate, and butyrate. These bacterial organic acids preserve a favorable intestinal condition. We have previously shown that GBF has attenuated intestinal inflammation in patients with ulcerative colitis and experimental colitis models through prebiotic actions. The aim of this study was to compare the effect of GBF with that of probiotics and antibiotics in an experimental colitis model. Colitis was induced by feeding male SD rats with a diet containing 3.0-3.5% dextran sodium sulfate (DSS). The therapeutic effect of oral administration of a prebiotic (GBF), probiotics (mixture of Lactobacillus and Clostridium butyricum), antibiotics (vancomycin, metronidazole), and the vehicle was determined by assessing clinical and pathological scores on day 6 after initiation of colitis. Butyrate concentrations in the cecal content were also determined. GBF treatment significantly reduced colonic inflammation as assessed by clinical scores with an increase in cecal butyrate levels. Probiotic treatment with a mixture of Lactobacillus and Clostridium butyricum did not show such an effect. Both antibiotic treatments significantly attenuated clinical and pathological scores. However, in contrast to GBF, this treatment led to a significant decrease in cecal butyrate levels. These data suggest that modification of the intestinal microflora by prebiotics, including GBF, may serve as a useful adjunct in the treatment of ulcerative colitis as well as antibiotic treatment.

Animal Feed↗
PubMed2002

Abnormal accumulation in lipopolysaccharide in biliary epithelial cells of rats with self-filling blind loop.

Primary sclerosing cholangitis (PSC) is known to be frequently associated with inflammatory bowel diseases. In a rat with self-filling blind loop (SFBL), a proposed animal model for PSC, hepatobiliary inflammation has previously been demonstrated. In this study, we assessed the involvement of lipopolysaccharide (LPS), a bacterial endotoxin, in the pathogenesis of hepatobiliary inflammation of the SFBL model. The hepatic localization of LPS was examined by immunohistochemistry using an anti-lipid A antibody. The portal blood concentration of LPS was measured by an endotoxin-specific chromogenic Limulus test (Endospecy test). LPS was localized in the biliary epithelial cells (BECs) of rats with SFBL, and the portal blood concentration of LPS was significantly higher than that of sham-operated rats. Development of hepatobiliary inflammation, peribiliary fibrosis, and injury to the intestinal mucosa were histologically confirmed. Constriction in the biliary trees was radiologically demonstrated. These findings suggested that abnormal accumulation of LPS, which may be derived from portal blood, in BECs was involved in the pathogenesis of hepatobiliary inflammation with intestinal injury.

Animals↗
PubMed2002

Additional benefit of lamivudine treatment as a preventive therapy for hepatic encephalopathy in patients with decompensated liver cirrhosis associated with hepatitis B.

Lamivudine has previously been found to be effective not only in patients with compensated liver disease due to hepatitis B virus (HBV) but also in those with hepatic decompensation. However, long-term follow-up of patients with hepatic encephalopathy (HE) has not been previously reported. We describe a patient with recurrent HE associated with decompensated liver cirrhosis due to hepatitis B. After the initiation of treatment with lamivudine, manifestation of HE has not been observed for about 2 years and liver function has improved as well. This experience suggests that improved liver function using lamivudine may contribute to prevention from recurrence of HE.

Antiviral Agents↗