PubMed Health⌕ Search

Biomedical subjects

Kengo Tomita

Publications and source records attributed to Kengo Tomita.

8 recordsLinked to original sources
PubMed2006

[Imaging of NASH].

Nonalcoholic steatohepatitis (NASH) is the most serious form of nonalcoholic fatty liver disease (NAFLD). Although imaging studies identify hepatic steatosis when the amount of fat in the liver is significant, differences between NASH and nonprogressive NAFLD were not apparent with any imaging modalities. Ultimately a liver biopsy is needed to diagnose NASH. Because NASH is a progressive fibrotic disease, patients with NASH and cirrhosis may progress to hepatocellular carcinoma(HCC). Regular screening based on tumor markers and imaging modalities is needed to detect HCC, in patients with NASH and cirrhosis.

Carcinoma, Hepatocellular↗
PubMed2006

[Drug therapy for non-alcoholic steatohepatitis].

Nonalcoholic steatohepatitis (NASH) once considered a benign process is now known to lead to progressive fibrosis and cirrhosis. NASH is frequently associated with the metabolic syndrome. Gradual weight reduction and increased physical activity are always recommended in overweight patients, but not always effective in reversing NASH. Promising pharmacological treatments have been demonstrated with antioxidants, insulin sensitizers, hepatoprotectants, lipid-lowering agents, and antihypertensive drugs. The similar histological features and natural histories of alcoholic steatohepatitis (ASH) and NASH suggest that common pathogenic mechanisms might be involved in these two conditions. Therapeutic strategies targeting the common mechanisms may also have promising potential. A larger randomized-controlled trial is needed to definitively determine the efficacy of pharmacological treatments for NASH.

Antihypertensive Agents↗
PubMed2006

Current situation of web-based chemical registration system in the University of Tokyo.

The web-based University of Tokyo Chemical Registration Information System with computational support has been introduced in all areas using chemicals owing to the unified management of the university and the management of chemicals in conformity with legal controls. This system enables chemical users to manage chemicals easily and reduces the burden inflicted by such management. In this report, we introduce the style of chemical management in the University of Tokyo, the functions of the web-based chemical registration system, the current situation of the system and future plans.

Chemical Phenomena↗
PubMed2005

AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats.

BACKGROUND: Previous work with metformin has shown that this antidiabetic agent improves nonalcoholic fatty liver in ob/ob mice. AMP-activated protein kinase (AMPK) is one of the major cellular regulators of lipid and glucose metabolism, and reportedly mediates the beneficial metabolic effects of metformin. In this study, we examined the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an AMPK activator, on an experimental model of ethanol-induced hepatic steatosis. METHODS: Rats were randomly divided into three groups: (A) rats fed ethanol-containing liquid diet for six weeks; (B) rats pair-fed ethanol-containing liquid diet for six weeks, during the last three weeks of which they were subcutaneously injected with 0.5 mg AICAR/g body weight per day; (C) rats pair-fed isocaloric liquid diet without ethanol for six weeks. At the end of the six-week period, the animals were sacrificed. Serum and liver specimens were analyzed using biochemical and histologic methods, as well as real-time PCR. RESULTS: Chronic ethanol feeding resulted in fatty liver both histologically and biochemically, whereas AICAR administration attenuated the degree of change in the liver. AICAR also decreased the hepatic sterol regulatory factor binding protein-1c (SREBP-1c) and reduced fatty acid synthase (FAS) expression; these changes led to reduced triglyceride synthesis in rat livers. Furthermore, detection of 4-hydroxy-2-nonenal (4-HNE)-protein adducts showed that the AICAR treatment also decreased the products of lipid peroxidation. CONCLUSION: In this preclinical rat model, AICAR, an AMPK activator, appears to protect the liver from fatty changes associated with chronic alcohol use. As such, AICAR may have a role in the treatment and prevention of alcohol-induced fatty liver.

AMP-Activated Protein Kinases↗
PubMed2004

Pioglitazone prevents alcohol-induced fatty liver in rats through up-regulation of c-Met.

BACKGROUND & AIMS: Treatment of steatosis is important in preventing development of fibrosis in alcoholic liver diseases. This study aimed to examine if pioglitazone, an antidiabetic reagent serving as a ligand of peroxisome proliferator-activated receptor gamma (PPAR gamma), could prevent alcoholic fatty liver. METHODS: Rats fed with an ethanol-containing liquid diet were given the reagent at 10 mg/kg per day intragastrically for 6 weeks. Hepatic genes involved in actions of the reagent were mined by transcriptome analyses, and their changes were confirmed by real-time polymerase chain reaction and Western blotting analyses. The direct effects of pioglitazone on primary-cultured hepatocytes were also assessed in vitro. RESULTS: Pioglitazone significantly attenuated steatosis and lipid peroxidation elicited by chronic ethanol exposure without altering insulin resistance. Mechanisms for improving effects of the reagent appeared to involve restoration of the ethanol-induced down-regulation of c-Met and up-regulation of stearoyl-CoA desaturase (SCD). Such effects of pioglitazone on the c-Met signaling pathway resulted from its tyrosine phosphorylation and resultant up-regulation of the apolipoprotein B (apoB)-mediated lipid mobilization from hepatocytes through very low-density lipoprotein (VLDL) as well as down-regulation of sterol regulatory element binding protein (SREBP) -1c and SCD levels and a decrease in triglyceride synthesis in the liver. CONCLUSIONS: Pioglitazone activates c-Met and VLDL-dependent lipid retrieval and suppresses triglyceride synthesis and thereby serves as a potentially useful stratagem to attenuate ethanol-induced hepatic steatosis.

Alcohol Drinking↗
PubMed2004

Leptin deficiency enhances sensitivity of rats to alcoholic steatohepatitis through suppression of metallothionein.

Oxidative stress is stated to be a central mechanism of hepatocellular injury in alcohol-induced liver injury. Recent reports have shown that Kupffer cell dysfunction in the leptin-deficient state contributes partly to the increased sensitivity to endotoxin liver injury. Here we report that leptin also plays a key role in the development of alcoholic liver injury and that leptin signaling in hepatocytes is involved in cellular mechanisms that mediate ethanol-induced oxidative stress. We found that chronic ethanol feeding in leptin receptor-deficient Zucker (fa/fa) rats for 6 wk resulted in a much more severe liver injury and augmented accumulation of hepatic lipid peroxidation compared with control littermates. The hepatic induction of stress-response and antioxidant proteins, such as metallothionein (MT)-1 and -2, was significantly suppressed in fa/fa rats after chronic ethanol feeding. Zinc concentration in liver was also decreased in fa/fa rats, compared with control littermates. In primary cultured hepatocytes from fa/fa rats, incubation with ethanol significantly suppressed MT-1 and -2 expressions. Addition of leptin to leptin-deficient ob/ob mouse primary hepatocytes led to an increase in MT-1 and -2 mRNA levels and a decrease in oxidative stress after incubation with ethanol. In conclusion, leptin deficiency enhances sensitivity of rats to alcohol-induced steatohepatitis through hepatocyte-specific interaction of MT-1 and -2 and resultant exaggeration of oxidative stress in hepatocytes. These findings suggest that leptin resistance in hepatocytes is an important mechanism of alcohol-induced liver injury.

Animals↗
PubMed2003

Regulation of mouse retinol dehydrogenases and retinal dehydrogenases in hepatocyte differentiation.

Retinoic acid (RA) is produced via two sequential reactions of retinol dehydrogenases (RDHs) and retinal dehydrogenases (RALDHs). We found that primary cultured mouse hepatocytes on a single collagen gel gradually lost hepatocyte specific morphology, and that another collagen gel overlay remarkably recovered it. The levels of albumin and liver-dominant expressed RDHs expression in hepatocytes paralleled their morphological change, decreased during single collagen gel culture, and were up-regulated by sequential collagen overlay. Quite similar to the expression changes, albumin and those RDHs' mRNA expression levels increased along with liver differentiation during pre- and postnatal liver development. Our data supports that all-trans and 9-cis RA, catalyzed by the RDHs, indeed play an important role in liver differentiation and regeneration.

Aldehyde Oxidoreductases↗