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Biomedical subjects

Michio Sata

Publications and source records attributed to Michio Sata.

At least 127 records · Page 7Linked to original sources
PubMed2003

Balloon-occluded retrograde transvenous obliteration improves liver function in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (B-RTO) is a novel therapeutic method for the treatment of large gastric fundal varices with spontaneous splenorenal shunt (SRS). However, the effects of B-RTO on liver function remain unknown. METHODS: Fourteen patients with portal hypertension and gastric varices with SRS were studied, consisting of four patients with acute bleeding, five with high-risk varices, and five with refractory portosystemic encephalopathy. Hepatic venous catheterization was performed to evaluate hepatic blood flow and liver function using the continuous indocyanine green (ICG) infusion method. To assess the metabolic activity of the hepatocyte, the intrinsic clearance of ICG was calculated. In all patients, endoscopic study was performed before and 1 week and 1 month after the B-RTO, and followed every 6 months thereafter. After baseline measurements, B-RTO was performed. Four weeks after the B-RTO, the same catheter measurements were repeated. RESULTS: The B-RTO was successful in all patients. Contrast-enhanced computed tomography showed complete obliteration of the SRS prior to the follow-up measurements. Endoscopic eradication of the fundal varices was obtained 6 months after B-RTO in all patients and encephalopathy was improved within 1 week after B-RTO. Following the B-RTO, hepatic blood flow (441 +/- 214 vs 668 +/- 299 mL/min, P < 0.0001) and the intrinsic clearance of ICG (233 +/- 123 vs 285 +/- 148 mL/min, P < 0.05) were significantly increased. Furthermore, intrahepatic resistance decreased after the B-RTO (P < 0.005). CONCLUSION: From short-term assessment, B-RTO increases hepatic blood flow and improves the metabolic activity of the liver in patients with portal hypertension.

Aged↗
PubMed2003

Hydrogen peroxide overproduction in megamitochondria of troglitazone-treated human hepatocytes.

Troglitazone has been withdrawn from therapeutic options for diabetes mellitus because of its severe hepatocyte toxicity of unknown pathogenesis. The aim of the present study was to assess both morphologic and functional alterations in the mitochondria of troglitazone-treated hepatocytes. A polarized human hepatocyte cell line, OUMS-29, was used in this study. The mitochondrial volume and the mitochondrial transmembrane potential (DeltaPsi(m)) were examined using flow cytometry with nonylacridine orange (NAO) and rhodamine-123, respectively. An ultrastructural examination of the troglitazone-treated OUMS-29 cells was performed using transmission electron microscopy (TEM). Reactive oxygen species (ROS) production was assessed using flow cytometry with dihydroethidium and 2',7'-dichlorodihydrofluorescein diacetate. A significant increase in the mitochondrial volume of the troglitazone-treated cells was found by the NAO analysis, in comparison with pioglitazone-treated and ciglitazone-treated cells. The increase in volume was due to a marked enlargement in the mitochondria. The markedly enlarged mitochondria with intramitochondrial electron-dense deposits were confirmed on TEM, which showed myelin-like structures, indicating degraded membrane constituents. The troglitazone-treated cells showed a significant decline in the DeltaPsi(m) per unit mitochondrial volume but resulted in no clear cell death. ROS analysis revealed a significant production of hydrogen peroxide in the troglitazone-treated hepatocytes. This production was attenuated using an antioxidant, N-acetyl-L-cysteine. In conclusion, troglitazone caused overproduction of hydrogen peroxide, which deteriorated both mitochondrial membrane structures and mitochondrial function, leading to a possible priming for the severe hepatocyte toxicity.

Acetylcysteine↗
PubMed2003

Troglitazone induces p27Kip1-associated cell-cycle arrest through down-regulating Skp2 in human hepatoma cells.

Increasing evidence has confirmed that ligands for peroxisome proliferator-activated receptor gamma (PPARgamma) exhibit antitumoral effects through inhibition of cell proliferation and induction of cell differentiation in several malignant neoplasms. Recently, we have documented the accumulation of a cyclin-dependent kinase inhibitor, p27(Kip1), as well as an unexpected accumulation in cyclin E in G1-arrested human hepatoma cells treated with the PPARgamma ligand troglitazone. Simultaneous accumulations in both p27(Kip1) and cyclin E are known to be characteristic phenotypes in cells derived from mice lacking Skp2, an F-box protein component of the SCF ubiquitin-ligase complex. Thus, the aim of the present study was to assess whether Skp2 might be involved in the down-regulation of p27(Kip1) in troglitazone-treated human hepatoma cells. A striking decrease in Skp2 expression and a reciprocal increase in p27(Kip1) expression were found in troglitazone-treated hepatoma cells but not in those cells treated with other PPARgamma ligands such as pioglitazone and ciglitazone. Quantitative real-time RT-PCR analysis showed that troglitazone down-regulated Skp2 at the mRNA levels. Consistently, ectopic overexpression in Skp2 brought resistance to troglitazone, resulting in a decreased population of arrested cells at the G1 phase compared with that in the mock-transfected cells. In surgically resected hepatocellular carcinoma (HCC) tissue, an increased expression in Skp2 was found in both the moderately differentiated HCCs and the poorly differentiated HCCs. In conclusion, troglitazone attenuated Skp2 expression, thereby promoting p27(Kip1) accumulation in human hepatoma cells. This therapeutic potential of the ligand may lead to new cell-cycle-based antitumor strategies for advanced HCCs.

Antineoplastic Agents↗
PubMed2003

Recent progress in the diagnosis and therapy for veno-occlusive disease of the liver.

Veno-occlusive disease (VOD) is one of the severe complications of the liver, which may occur after hematopoietic stem cell transplantation (HSCT). Although an early diagnosis is important to initiate antithrombotic therapy before serious organ failure, the widely used clinical criteria only become clinically fulfilled at an advanced stage of disease. Liver biopsy provides useful findings for the diagnosis of VOD, however, in the later or less severe stages of VOD liver biopsy may provide false-negative sampling error because the biopsy sample may be too small to evaluate the whole liver. In addition it may be difficult to follow the clinical course with repeat biopsy in individual cases. Imaging diagnosis of VOD including gray-scale US, Doppler US, and MRI have been reported as convenient and useful. Color-Doppler US is superior because of its specificity and sensitivity. Blood sampling tests including factor VII, protein C, N-terminal propeptide for type III procollagen (P-III-P) and hyarulonic acid have predictive value, and their measurement may simply be another way to evaluate early hepatic impairment. Since no optimal treatment for VOD has been established as yet, the prophylaxis of VOD or early initiation of treatment is important. These new diagnostic approaches for VOD may provide a direction to resolve the clinical problems of VOD such as the time of initiation of therapy, the therapeutic regimen of choice, and the cessation of therapy.

Anticoagulants↗
PubMed2003

Diagnostic clues for recurrent hepatocellular carcinoma: comparison of tumour markers and imaging studies.

OBJECTIVE: To elucidate the usefulness of monitoring Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin detected with a revised kit (DCP-R) as clues to the diagnosis of recurrent hepatocellular carcinoma (HCC). METHODS: A total of 57 patients with HCC were enrolled in the study. They were classified into two groups: group A comprised 27 patients in whom the diagnostic clue to recurrent HCC appeared before November 1997; these patients were monitored by ultrasonography, computed tomography (CT), AFP and des-gamma-carboxy prothrombin detected with a conventional kit (DCP-C). Group B comprised 30 patients in whom the diagnostic clue to recurrent HCC was detected after November 1997; these patients were monitored by ultrasound, CT, AFP, AFP-L3 and DCP-R. RESULTS: In group A, 22 and five HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. In group B, 17 and 13 HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. The number of patients in whom tumour markers were the first clue to the diagnosis of recurrent HCC was significantly higher in group B than in group A. CONCLUSIONS: Periodic examination of AFP-L3 and DCP-R may be useful for the early detection of recurrent HCC.

Aged↗
PubMed2003

Severe alcoholic hepatitis successfully treated by leukocytapheresis: a case report.

BACKGROUND: The prognosis of severe alcoholic hepatitis is poor, and there is no established method for a cure. METHODS: A 34-year-old man was admitted to Kurume University Hospital because of severe liver dysfunction due to excess alcohol intake. He was treated with prednisolone and two sessions of granulocyte and monocyte adsorption apheresis (GCAP) using an Adacolumn, which removes leukocytes--especially granulocytes and monocytes--from the peripheral blood. We evaluated the changes in the serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule-1, as well as the conventional liver tests and peripheral white blood cell count. RESULTS: Prednisolone was effective in the short term but resulted in an increase in C-reactive protein (CRP), peripheral leukocytes, and serum total bilirubin. GCAP performed on the 34th and 41st hospital days produced decreases in the white blood cell count, total bilirubin, and intercellular adhesion molecule-1. The patient survived, despite the expected poor prognosis on admission. CONCLUSIONS: GCAP is recommended as a potential therapeutic option for severe alcoholic hepatitis.

Actuarial Analysis↗
PubMed2003

A real-time quantitative polymerase chain reaction method for hepatitis B virus in patients with chronic hepatitis B treated with lamivudine.

OBJECTIVES: During treatment of chronic hepatitis B with lamivudine, changes in the level of hepatitis B virus (HBV) DNA were investigated using a real-time polymerase chain reaction (PCR) method with a detection limit of 1.7 log copies/ml (50 copies/ml) to clarify its clinical significance, particularly the association between HBV DNA levels and the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants. METHODS: Twenty-four patients who had received lamivudine therapy for >1 yr were studied. HBV DNA levels were determined using transcription-mediated amplification for sera with >3.7 log genome equivalents/ml, the Roche Monitor kit for sera with >/=2.6 log copies/ml, and real-time PCR for sera with < 2.6 log copies/ml (the detection limit was 1.7 log copies/ml). Patients were classified into three groups according to the minimal HBV DNA level attained during lamivudine therapy: the <1.7 log copies/ml group (eight patients), the 1.7-2.5 log copies/ml group (five patients), and the >/=2.6 log copies/ml group (11 patients). RESULTS: Pretreatment HBV DNA levels were significantly lower in the <1.7 copies/ml group than in the other two groups (p < 0.05). Neither the emergence of YMDD mutants nor a virological breakthrough of serum HBV DNA was observed in any of the eight patients in the <1.7 copies/ml group. In contrast, in the 1.7-2.5 copies/ml and >/=2.6 copies/ml groups, virological breakthroughs resulting from the emergence of YMDD mutants were observed in two of five patients and in all 11 patients, respectively (p < 0.001). Virological breakthroughs were observed at a mean of 49.6 +/- 18.4 wk in 11 the patients in the >/=2.6 copies/ml group and at wk 107 and 115 in two patients in the 1.7-2.5 copies/ml group. CONCLUSIONS: The real-time PCR method is useful for predicting the emergence of YMDD mutants and the estimated time of their emergence.

Adult↗
PubMed2003

Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudine.

Breakthroughs during lamivudine therapy were assessed according to hepatitis flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients. Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean duration of 29 months on lamivudine. The virological breakthrough occurred 14.5 months after the start of lamivudine treatment, and all the patients with it developed breakthrough hepatitis 3 months later. The clinical course of breakthrough hepatitis was self-limited except in one patient who had already developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum ALT, albumin, prothrombin time and platelet counts were maintained well on conventional treatments without resorting to interferon. Major HBV mutants during breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom mutations at nucleotide 529 occurred including the 2 who later developed hepatocellular carcinoma. There was no clear relationship between distinct mutational patterns and clinical courses. Further studies are needed for making out the effects of lamivudine-resistant mutants on clinical outcomes, taking into considerations genotypes of HBV.

Antiviral Agents↗
PubMed2003

Interventional radiology for advanced hepatocellular carcinoma: comparison of hepatic artery infusion chemotherapy and transcatheter arterial lipiodol chemoembolization.

OBJECTIVE: The prognosis of advanced hepatocellular carcinoma remains poor. The aim of this study was to compare the efficacy of hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization for treatment of advanced tumor. SUBJECTS AND METHODS. Thirty-seven patients with hepatocellular carcinoma and unresectable tumors were enrolled. In the hepatic artery infusion chemotherapy group (n = 16), cisplatin (10 mg/person, on days 1-5) and subsequent 5-fluorouracil (250 mg/person, on days 1-5) were administered for four serial courses. In the transcatheter arterial Lipiodol chemoembolization group (n = 21), an emulsion of Epirubicin (20-30 mg/person) and Lipiodol was administered every 3-4 weeks. RESULTS: The tumor response rates (complete response plus partial response for all cases) of the hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization groups were 56.3% and 23.8%, respectively, showing the significantly higher rate in the former than in the latter group. The cumulative survival rates between the two groups were not significantly different; whereas in those patients whose tumors were classified as TNM stage IV or as having the maximal tumor size of greater than 5 cm, patients tended to have higher survival rates in the hepatic artery infusion chemotherapy group than in the transcatheter arterial Lipiodol chemoembolization group. Univariate analysis identified the serum aspartate aminotransferase value as solely significant. Patients' adverse reactions were successfully managed by treatment of symptoms. Adverse events, such as obstructions of the catheter or hepatic artery or infection around the catheter, rarely occurred. CONCLUSION: Hepatic artery infusion chemotherapy had a better antitumor effect than transcatheter arterial Lipiodol chemoembolization and may be a useful therapeutic option for more advanced hepatocellular carcinoma.

Adult↗
PubMed2003

Markedly prolonged jaundice from simultaneous infection with hepatitis E virus and leptospira.

We treated a patient simultaneously infected with hepatitis E virus and Leptospira interrogans, both acquired in China. Severe hyperbilirubinemia required nearly 200 days to resolve, transminase elevation showed a fluctuating course, and liver biopsy specimens showed fibrosis unusual for hepatitis E. Leptospirosis appeared to have altered the course of hepatitis E virus infection in this patient, even though infection with Leptospira was cleared with antibiotics by 50 days after the onset of the hepatitis symptoms.

Hepatitis E↗
PubMed2003

B-Flow contrast US with Levovist in hepatic tumors: preliminary results.

Usefulness of Levovist contrast ultrasonography by the B-Flow method was evaluated in cases of hepatic tumor. Subjects included 14 patients with moderately differentiated hepatocellular carcinoma and 4 patients with hepatic hemangioma. Each patients had a single tumor mass. Images showed strong staining in 11 of the 14 nodes in the hepatocellular carcinomas and all 4 hemangiomas. Staining was seen only in lesions located within 4 cm of the probe. Thus B-Flow ultrasonography using Levovist was proved useful for evaluating vascularity of superficially located.

Adult↗
PubMed2003

Effective extracorporeal shock wave lithotripsy for pancreatic duct stone.

A 55-year-old man with alcoholic chronic pancreatitis was hospitalized for further treatment of intractable repeated upper abdominal pain. A laboratory data showed normal hepatobiliary enzymes and glucose tolerance test, but abnormal pancreatic enzymes including amylase, lipase, trypsin and elastase I. Pancreatic function diagnostant test was 71%. Abdominal ultrasound examination and computed tomography showed an approximately 4 mm main pancreatic duct stone and multiple small stones in the surrounding parenchyma, and the findings being compatible with chronic pancreatitis. Endoscopic retrograde cholangiopancreatrography revealed that there was a main pancreatic duct stone in the pancreas head, and that the caudal pancreatic duct could not be visualized due to the impacted stone. In addition, intrapancreatic bile duct showed no malignant irregularity, but pancreatitis-induced smooth narrowing. The patient underwent extracorporeal shock wave lithotripsy (ESWL) alone, because endoscopic manipulation for pancreatic stone removal was impossible due to tightly impacted stone with stenosis. Successful ESWL was achieved with the stone disappearance and without any complication.

Calculi↗
PubMed2003

A case report of primary hepatic squamous cell carcinoma that remarkably responded to low dose arterial injection of anti-cancer drugs.

Primary hepatic squamous cell carcinoma is rare. In this case, a malignant lesion was detected in bilateral hepatic lobes by ultrasound sonography and computed tomography. The maximum tumor diameter was approximately 10 cm. Tumor tissue obtained by aspiration liver biopsy was diagnosed as poorly differentiated squamous cell carcinoma. In gallium radioisotope scanning, no focus was detected in any organs other than the liver. As therapy, anti-cancer drugs were administered via hepatic arterial infusion. The patient received 10 mg of cis-diaminedichloroplatinum (CDDP) and 250 mg of 5-fluorouracil (5-FU) for 5 days every week. The therapy was continued for 3 weeks, and the same doses of CDDP and 5-FU were given to the patient once per 2 weeks in the clinic. The intrahepatic tumor lesion began to decrease from the start of treatment, and had almost disappeared 8 months after. Recurrence of the liver tumor occurred at 12 months from the start of treatment. The patient was re-admitted and treated with the same anti-cancer drugs via hepatic arterial injection. However, the drugs showed remarkable effect no longer and she died in month 23. The treatment with chemotherapy via hepatic arterial injection for a patient with squamous cell carcinoma offered a favorable therapeutic effect.

Aged↗
PubMed2003

A patient with hyperlipidemia who had a gallbladder stone caused by administration of fenofibrate.

Fibrates are widely used for treatment of hyperlipidemia. It has been reported that gallbladder stones are formed by administration of clofibrate. It is thought that fenofibrate can cause the formation of gallbladder stone as a side effect. We encountered a patient with hyperlipidemia in whom a gallbladder stone was detected by computed tomographic scanning 3 months after the start of administration of fenofibrate during follow-up observation by blood biochemical examination and computed tomographic scanning. This case report will be of great value and importance.

Cholelithiasis↗
PubMed2003

Light and electron microscopic analyses of immediate and late tissue damage caused by radiofrequency ablation in porcine liver.

Radiofrequency ablation (RFA) is an effective procedure for localized hepatocellular carcinoma. Contrast-enhanced CT depicts the ablated area as a hypoattenuated area without hepatic blood flow; however, light microscopy does not show obvious necrosis in the ablated area. We evaluated liver tissue changes after RFA by light microscopy and electron microscopy. The normal livers of three anesthetized pigs were coagulated using RFA after laparotomy. The liver was examined immediately, and 1 week after operation by light and electron microscopy. After RFA, the liver parenchyma surrounding the needle electrode was brown in color and surrounded by a red marginal zone separate from the normal liver parenchyma. Hematoxylin-eosin staining of the central area did not show cell necrosis, and the structures of liver sinusoids, liver cell cord and the nuclei of hepatocytes were preserved. However, electron microscopic examination of tissue immediately after RFA showed destruction of mitochondria of hepatocytes and fixation of sinusoidal cells. One week later, there was a large quantity of debris in the enlarged sinusoids, in addition to irreversible destruction of hepatocyte organelles. RFA of the porcine liver causes hepatocyte damage. This damage was not evident by light microscopy but clearly identified by electron microscopy.

Animals↗
PubMed2003

Wilson disease protein ATP7B is localized in the late endosomes in a polarized human hepatocyte cell line.

Wilson disease is a genetic disorder characterized by the accumulation of copper in the body due to a defect of biliary copper excretion. The gene responsible for Wilson disease has been cloned, however, the precise localization of this gene product ATP7B, a copper-transporting ATPase, is still controversial. We examined the localization of ATP7B by expressing a chimeric protein, ATP7B-tagged with green fluorescent protein (GFP) (GFP-ATP7B), in HEK293, Hep3B and a highly polarized human hepatocyte line (OUMS29). Intracellular organelles were visualized by immunofluorescence microscopy. The effects of bathocuproine disulfonate, a copper chelator, and copper sulfate were examined. GFP-ATP7B colocalized with a late endosome marker, but not with endoplasmic reticulum, Golgi, or lysosome markers in a copper-depleting condition. Treatment with copper sulfate did not affect the localization of ATP7B. ATP7B is localized in the late endosomes in both copper-depleting and copper-loaded conditions. ATP7B seems to translocate copper from the cytosol into the late endosomes, and copper may be excreted to bile via lysosomes. We believe that the disturbed incorporation of copper into the late endosomes caused by mutated ATP7B is the main defect in Wilson disease.

Adenosine Triphosphatases↗