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Dive into the research topics where Yoshiya Ito is active.

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Featured researches published by Yoshiya Ito.


Hepatology | 2004

Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice.

Robert S. McCuskey; Yoshiya Ito; Graham R. Robertson; Margaret K. McCuskey; M. A. Perry; Geoffrey C. Farrell

In alcoholic steatohepatitis, hepatic microvascular changes have pathogenic significance for hepatocellular function, perisinusoidal fibrosis, and portal hypertension. It is unclear whether similar changes occur in other forms of steatohepatitis. We therefore examined whether hepatic microvascular dysfunction occurs in fibrosing steatohepatitis induced by feeding mice a high‐fat methionine‐ and choline‐deficient (MCD) diet. Using in vivo microscopic—as well as histological and electron microscopic—methods, together with measurements of alanine aminotransferase (ALT), lipid content, and oxidative stress, hepatic microvascular structure and function were studied in relation to inflammatory and fibrotic changes during evolution of steatohepatitis. At 3 weeks of MCD diet intake, serum ALT was elevated and hepatic steatosis was pronounced. By 5 weeks, necroinflammatory change was noteworthy, and by 8 weeks perisinusoidal fibrosis was established. Compared with mice receiving the high‐fat diet supplemented with methionine and choline (controls), levels of hepatic lipid and lipoperoxides were elevated at 3 weeks and beyond. The numbers of perfused sinusoids were significantly reduced at each time point. Enlarged, fat‐laden hepatocytes together with perivascular fibrosis narrowed sinusoidal lumens, making vessels tortuous and impairing sinusoidal perfusion. At 3 and 5 weeks, MCD diet caused significant increases in phagocytic activity of macrophages in centrilobular regions. By 8 weeks, macrophage activity was less striking, but the number of leukocytes adherent to the sinusoidal lining had increased 5‐fold compared with controls. In conclusion, these results are consistent with a dysfunctional hepatic microvasculature. Thus, microvascular changes may contribute to progressive liver injury in metabolic and toxic forms of steatohepatitis. (HEPATOLOGY 2004;40:386–393.)


Microcirculation | 2003

Early hepatic microvascular injury in response to acetaminophen toxicity.

Yoshiya Ito; Nancy W. Bethea; Edward R. Abril; Robert S. McCuskey

Objective: The hepatic toxic response to acetaminophen (APAP) is characterized by centrilobular (CL) necrosis preceded by hepatic microvascular injury and congestion. The present study was conducted to examine changes in liver microcirculation after APAP dosing.


Experimental Gerontology | 2007

Age-related changes in the hepatic microcirculation in mice.

Yoshiya Ito; Karen Kristine Sørensen; Nancy W. Bethea; Dmitri Svistounov; Margaret K. McCuskey; Bård Smedsrød; Robert S. McCuskey

Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged), and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a fivefold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a threefold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers.


Pediatric Research | 2007

Intestinal Microcirculatory Dysfunction During the Development of Experimental Necrotizing Enterocolitis

Yoshiya Ito; Sarah M. Doelle; Jessica A. Clark; Melissa D. Halpern; Robert S. McCuskey; Bohuslav Dvorak

The aim of this study was to evaluate changes in intestinal microcirculation during necrotizing enterocolitis (NEC) and to examine the effect of endothelin (ET)-1 on the intestinal microcirculation. Prematurely born rats were either hand-fed formula (NEC) or dam fed (DF) and were exposed to asphyxia and cold stress twice daily to induce disease. At 0, 2, 3, and 4 d after the birth, the microcirculation in the ileum was examined using in vivo microscopic methods. The nutritive microvascular perfusion in the NEC group was progressively compromised from d 3 to d 4 (35% and 50% decrease, respectively) when compared with DF rats. Concomitantly, intestinal blood flow assessed by laser Doppler flowmetry was significantly reduced at d 2, 3, and 4 (by 31%, 36%, and 73%, respectively). Levels of ET-1 mRNA in the ileum were increased 3.7-fold. Microvascular responses to topically applied ET-1 were significantly increased in the NEC group, which was associated with decreased expression of ETB receptor. These results suggest that microcirculatory dysfunction in the distal ileum of neonatal rats with NEC contributes to disease progression and that enhanced microvascular responsiveness to ET-1 may participate in these microcirculatory disturbances.


Microcirculation | 2006

Dietary steatotic liver attenuates acetaminophen hepatotoxicity in mice.

Yoshiya Ito; Edward R. Abril; Nancy W. Bethea; Margaret K. McCuskey; Robert S. McCuskey

Objective: To determine whether hepatic steatosis is susceptible to acetaminophen (APAP) hepatotoxicity.


Microcirculation | 2003

Hepatic Microcirculatory Dysfunction During Cholestatic Liver Injury in Rats

Yoshiya Ito; Nancy W. Bethea; Gregory L. Baker; Margaret K. McCuskey; Renate Urbaschek; Robert S. McCuskey

Objective: The present study was conducted to elucidate the sequential alterations in the hepatic microvascular inflammatory response to extrahepatic biliary obstruction.


Microcirculation | 2004

Ethanol Binging Enhances Hepatic Microvascular Responses to Acetaminophen in Mice

Yoshiya Ito; Edward R. Abril; Nancy W. Bethea; Robert S. McCuskey

Objective: Chronic alcoholism has been considered to be a risk for acetaminophen (APAP) hepatotoxicity, but little is known about the effect of binge alcohol drinking on APAP‐induced liver injury. The present study was conducted to examine the effect of ethanol binging on APAP‐induced hepatic microcirculatory dysfunction.


Hepatology Research | 2000

Late administration of dimethyl sulfoxide minimizes the hepatic microvascular inflammatory response to chloroform in rats.

Yoshiya Ito; Richard C. Lind; Carmen Begay; A. Jay Gandolfi; Margaret K. McCuskey; Robert S. McCuskey

Dimethyl sulfoxide (DMSO) protects against liver injury elicited by chloroform (CHCl(3)) in rats even when given 24 h after the toxicant. Aminobenzotriazole (ABT) is a cytochrome P-450 inhibitor as is DMSO. The present study was conducted to examine the effect of DMSO or ABT on the hepatic microvascular inflammatory response to CHCl(3) using in vivo microscopy. Rats received 0.75 ml/kg CHCl(3) by oral administration followed 24 h later by either 2.0 ml/kg DMSO, 30 mg/kg ABT, or saline injected intraperitoneally. Untreated animals served as controls. At 28 h after CHCl(3) administration, the number of leukocytes adhering to the sinusoidal wall was significantly increased associated with a reduction in the numbers of perfused sinusoids. DMSO, but not ABT, caused a restoration of perfused sinusoids to 85% of normal. At 32 h after, leukocyte adhesion and Kupffer cell phagocytic activity were significantly increased. The numbers of perfused sinusoids were decreased by 32% in periportal regions and 50% in centrilobular regions. Sinusoidal perfusion and Kupffer cell activity were modified significantly by either DMSO or ABT, while leukocyte adhesion was reduced by DMSO alone. The results suggest that attenuation of the hepatic microvascular response to CHCl(3) is a potential mechanism of post-treatment with DMSO.


Comparative Hepatology | 2004

Effects of acetaminophen on hepatic microcirculation in mice

Yoshiya Ito; Nancy W. Machen; Edward R. Abril; Robert S. McCuskey

Acetaminophen (APAP) intoxication from overdosing can result in severe hepatic damage, which is characterized by hemorrhagic centrilobular necrosis and by towering the levels of transaminase. The APAP-induced hepatic necrosis is preceded by centrilobular microvascular congestion thought to be due to collapse of the sinusoidal wall and the infiltration of blood elements into the space of Disse [1]. These findings suggest that, in addition to direct hepatocellular damage, sinusoidal endothelial cells (SECs) participate in liver injury elicited by APAP overdose. As a result, the present study was conducted to examine changes in hepatic microcirculation after APAP administration using in vivo microscopic methods.


Hepatology | 2003

Decreased hepatic nitric oxide production contributes to the development of rat sinusoidal obstruction syndrome

Laurie D. DeLeve; Xiangdong Wang; Gary Kanel; Yoshiya Ito; Nancy W. Bethea; Margaret K. McCuskey; Zoltán A. Tökés; Jeffrey Tsai; Robert S. McCuskey

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Laurie D. DeLeve

University of Southern California

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Xiangdong Wang

University of Southern California

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Geoffrey C. Farrell

Australian National University

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Anwar Farhood

University of Texas Health Science Center at Houston

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