S Tsujita

Nara Medical University, Nara, Nara, Japan

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Publications (14)34.39 Total impact

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    ABSTRACT: An additional administration of high dose ethanol to chronic alcohol-fed rats led to a decrease in endotoxin clearance and an increase in endotoxin accumulation in the spleen accompanied by an elevation of tumour necrosis factor (TNF) levels in the portal vein. Endotoxin uptake and TNF production by Kupffer cells (KC) and splenic macrophages in the chronic ethanol load rats were significantly greater than those in the control rats. When these cells were precultured in the medium containing 10 to 100mmol/L ethanol, the endotoxin uptake and TNF production of KC were decreased. However, this did not affect the endotoxin uptake and TNF production of splenic macrophages.The hepatic production of endotoxin binding protein was increased when KC were preincubated in the medium containing ethanol and the resultant culture supernatant was added to the hepatocyte culture system. This endotoxin binding protein was proved to enhance the uptake of endotoxin and suppressed the production of TNF in the KC. When KC and hepatocytes were isolated from chronically alcohol-fed rats, further addition of ethanol to the culture medium of KC did not affect the hepatic production of endotoxin binding protein. The increase in hepatic production of endotoxin binding protein may serve as a defence mechanism against endotoxicity. There is a possibility that an impairment of this defence mechanism has a pivotal role in the development of endotoxaemia and endotoxicity in chronic alcoholics.
    Journal of Gastroenterology and Hepatology 06/2008; 10(S1):S31 - S34. · 3.33 Impact Factor
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    ABSTRACT: Endotoxin plays an important role in the initiation and aggravation of alcoholic liver disease. In this study, we evaluated plasma endotoxin levels and serum concentrations of cytokines and lipopolysaccharide binding protein (LBP) during the acute and recovery phase of patients with alcoholic hepatitis; we also explored the prognostic factors associated with a fatal outcome. Fourteen patients, consisting of eight patients with alcoholic hepatitis (AH), five cirrhotics with superimposed AH (LC+AH), and one patient with severe alcoholic hepatitis (SAH), were studied. Among these, two with LC+AH died of hepatic failure. Plasma endotoxin levels in the acute phase were higher in patients with AH (184.4 +/- 159.4 pg/ml) and LC+AH (206.9 +/- 174.9 pg/ml) than in healthy subjects (10.4 +/- 5.5 pg/ml, p < 0.001). In particular, in one patient with SAH and one of two nonsurvivors, plasma endotoxin levels were markedly high relative to the other cases. In most survivors, plasma endotoxin levels decreased in the recovery phase, whereas they further increased at the terminal stage in one of two nonsurvivors. Serum interleukin (IL)-6 and IL-8 levels in the acute phase were significantly higher in patients with AH and LC+AH as compared with healthy subjects. These levels were especially high in nonsurvivors and in one patient with SAH. IL-10 increased in two nonsurvivors, one patient with SAH, and one with LC+AH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in nonsurvivors, IL-6 remained high, and IL-8 and IL-10 further increased. Tumor necrosis factor-alpha levels were below the detection limit throughout the course in all patients. Serum lipopolysaccharide binding protein (LBP) generally was elevated in the acute phase and decreased in the recovery phase in all survivors, but in one of the nonsurvivors, LBP was elevated markedly at the terminal stage. In the acute phase, plasma endotoxin levels were correlated positively with white blood cell counts, neutrophil counts, and serum IL-8. IL-8 was correlated positively with neutrophil counts and negatively with serum cholinesterase, hepaplastin test, and serum albumin levels. IL-6 was correlated positively with white blood cell and neutrophil counts, C-reactive protein, and serum total bilirubin and negatively with hepaplastin test and serum total protein levels. Serum LBP was correlated positively with white blood cell and neutrophil counts. Endotoxemia and related elevation of IL-8 may play an important role in the activation and migration of neutrophils in patients with alcoholic hepatitis. Marked elevation of inflammatory cytokines, IL-6 and IL-8, are related to severity and poor prognosis of alcoholic hepatitis. Serum LBP may serve as an index of inflammatory reaction in alcoholics.
    Alcoholism Clinical and Experimental Research 04/2000; 24(4 Suppl):48S-54S. · 3.42 Impact Factor
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    ABSTRACT: In the present study, we evaluated the role of high-density lipoprotein (HDL) as an endotoxin-binding protein in chronically alcohol-fed rats. Although the blood endotoxin level was significantly elevated in chronic ethanol-loaded rats, compared with control rats, serum tumor necrosis factor (TNF), ALT, and lactate dehydrogenase were not elevated. Serum HDL and its endotoxin-binding capacity were significantly increased in chronic ethanol-loaded rats. When Kupffer cells isolated from control and chronic ethanol-loaded rats were cultured in the medium containing 3 to 30 mg/dl HDL and endotoxin (500 ng/ml), endotoxin uptake and TNF production of Kupffer cells were decreased in proportion to the concentration of HDL in the medium. These results suggest that the increase in endotoxin-binding capacity of HDL may serve as a protective mechanism against endotoxin in chronic ethanol-loaded rats.
    Alcoholism Clinical and Experimental Research 01/1997; 20(9 Suppl):356A-359A. · 3.42 Impact Factor
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    ABSTRACT: In the present study, the role of albumin and high-density lipoprotein (HDL) as endotoxin (Et)-binding proteins in chronically alcohol-fed rats was studied. In acute ethanol-loaded rats, the Et clearance in the blood was slightly prolonged, and the amount of albumin and HDL- bound Et in the blood was markedly increased. In chronic ethanol-loaded rats, the Et clearance was significantly faster than that in the control, and HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5 g/kg body weight of ethanol load, the Et clearance was much prolonged, and blood tumor necrosis factor and ALT was elevated, when HDL-bound Et was not further increased. Et-binding capacity of total proteins, albumin, and HDL in the hepatocyte culture medium were increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. In the culture experiment in the chronic ethanol-loaded rats, such increases were not observed. These results suggest that the increase in Et-binding capacity of HDL and albumin may serve as a protective mechanism against Et in chronic ethanol-loaded rats. An addition of high-dose ethanol to these rats may lead to impaired Et binding and inactivation, which may finally result in increased endotoxicity.
    Alcoholism Clinical and Experimental Research 03/1996; 20(1 Suppl):73A-76A. · 3.42 Impact Factor
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    ABSTRACT: An additional administration of high dose ethanol to chronic alcohol-fed rats led to a decrease in endotoxin clearance and an increase in endotoxin accumulation in the spleen accompanied by an elevation of tumour necrosis factor (TNF) levels in the portal vein. Endotoxin uptake and TNF production by Kupffer cells (KC) and splenic macrophages in the chronic ethanol load rats were significantly greater than those in the control rats. When these cells were precultured in the medium containing 10 to 100 mmol/L ethanol, the endotoxin uptake and TNF production of KC were decreased. However, this did not affect the endotoxin uptake and TNF production of splenic macrophages. The hepatic production of endotoxin binding protein was increased when KC were preincubated in the medium containing ethanol and the resultant culture supernatant was added to the hepatocyte culture system. This endotoxin binding protein was proved to enhance the uptake of endotoxin and suppressed the production of TNF in the KC. When KC and hepatocytes were isolated from chronically alcohol-fed rats, further addition of ethanol to the culture medium of KC did not affect the hepatic production of endotoxin binding protein. The increase in hepatic production of endotoxin binding protein may serve as a defence mechanism against endotoxicity. There is a possibility that an impairment of this defence mechanism has a pivotal role in the development of endotoxaemia and endotoxicity in chronic alcoholics.
    Journal of Gastroenterology and Hepatology 02/1995; 10 Suppl 1:S31-4. · 3.33 Impact Factor
  • International Hepatology Communications - INT HEPTAOL COMM. 01/1995; 3.
  • International Hepatology Communications - INT HEPTAOL COMM. 01/1995; 3.
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    ABSTRACT: Acute hepatic failure was induced in 50 male rabbits by D-galactosamine HCl (1 g per kg bw), and the effects of prostaglandin E1 on this model were investigated. Twelve hours after the administration of D-galactosamine HCl, a continuous infusion of prostaglandin E1 (2 micrograms.kg-1.h-1 or 20 micrograms.kg-1.h-1) was started. Ten animals in each group were observed until the time of death and mean survival times were compared between the groups. Five animals in each group were used for the determination of regional blood flows and brain water content. After the injections of D-galactosamine HCl, serum aspartate transaminase and alanine transaminase activity rose markedly and prothrombin time was prolonged. The administration of prostaglandin E1 did not affect these levels. However, the survival time in the prostaglandin E1 20 micrograms.kg-1.h-1 group (48.2 +/- 10.4 h) was significantly longer (p < 0.005, p < 0.01) than those in the untreated group (24.9 +/- 5.0 h) and the prostaglandin E1 2 micrograms.kg-1.h-1 group (28.1 +/- 5.8 h). Prostaglandin E1 20 micrograms.kg-1.h-1 inhibited elevations of blood urea nitrogen and creatinine and significantly inhibited the decrease of urine volume and urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Hepatology 04/1994; 20(4):478-82. · 9.86 Impact Factor
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    ABSTRACT: The Kupffer cell-hepatocyte interaction in the process of endotoxin clearance and the effect of alcohol on it were investigated in a newly developed rat Kupffer cell-hepatocyte culture system. The hepatic production of endotoxin binding protein was increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. The amount of endotoxin binding protein produced by the hepatocytes was increased as the ethanol concentration in the culture medium of Kupffer cells was increased. This endotoxin binding protein was proved to enhance the uptake of endotoxin and suppressed the production of tumor necrosis factor in the Kupffer cells. When Kupffer cells and hepatocytes were isolated from chronically alcohol-fed rats, further addition of ethanol to the culture medium of Kupffer cells did not affect the hepatic production of endotoxin binding protein. The increase in hepatic production of endotoxin binding protein may serve as a defence mechanism against endotoxicity. There is a possibility that an impairment of the defence mechanism has a pivotal role in the development of endotoxemia and endotoxicity in chronic alcoholics.
    Alcohol and alcoholism (Oxford, Oxfordshire). Supplement 02/1994; 29(1):87-91.
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    ABSTRACT: Plasma endotoxin levels in 12 cirrhotics with bleeding from oesophageal varices and 50 cirrhotics without bleeding were measured by the chromogenic assay after the pretreatment of sample by perchloric acid (HClO4) and triethylamine. Endotoxin in cirrhotics with bleeding from varices was significantly higher than those without bleeding. In patients with bleeding, endotoxin increased for 3 days after the bleeding, first in the supernatant fraction and then in the precipitate fraction by HClO4 treatment. Peak plasma alpha 1-acid glycoprotein and haptoglobin were observed 3 days after the bleeding. Alpha 1-antitrypsin gradually increased for 14 days. Transferrin did not markedly change. The endotoxin-binding capacity of transferrin and alpha 1-acid glycoprotein increased immediately after bleeding and thereafter decreased, but that of alpha 1-antitrypsin tended to increase in the recovery period. In summary, the plasma endotoxin concentration and endotoxin-binding capacity of alpha 1-acid glycoprotein and transferrin were shown to have increased after bleeding from varices by this new method. There may be a close relationship between endotoxaemia and acute phase reaction in this situation.
    Journal of Gastroenterology and Hepatology 01/1994; 9(6):582-6. · 3.33 Impact Factor
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    ABSTRACT: We report a case of double male syndrome, a type of Klinefelter's syndrome with 48,XXYY chromosome, associated with acromegaloidism. Although the patient presented acromegalic appearance, he did not show hypersecretion of growth hormone (GH). GH provocation tests revealed a rather low GH responses or no responses. After testosterone therapy, the GH responses were normalized except to Insulin tolerance test (ITT). On the other hand, the plasma corticotropin (ACTH) and cortisol levels were decreased paradoxically after hypoglycemia. Testosterone therapy did not restore this ACTH response. It was speculated that these abnormal GH and ACTH responses to hypoglycemia might indicate another congenital anomaly.
    Internal Medicine 03/1993; 32(2):160-5. · 0.97 Impact Factor
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    ABSTRACT: To investigate the metabolic fate of endotoxin in alcoholics and its possible relationship to cytokines and liver injury, we administered a low-dose radiolabelled endotoxin to rats given alcohol in various conditions and studied the organ distribution of endotoxin and measured plasma levels of tumour necrosis factor (TNF). In the chronic alcohol-fed rats (Lieber-DeCarli liquid diets for 6 weeks) 3H-endotoxin was rapidly cleared by the liver and excreted into faeces. However, the endotoxin clearance was decreased after an acute ethanol load to rats (5 mg/g body wt ethanol i.p.) or in the chronic ethanol-fed rats with an additional 5 mg/g body wt ethanol load. Plasma TNF was not elevated in the control or in the acute ethanol load rats, slightly elevated in the chronic ethanol-fed rats and markedly elevated in the chronic ethanol-fed rats with an additional high-dose ethanol load. Serum GPT was elevated only in the chronic ethanol-fed rats with an additional high-dose ethanol. In conclusion, an additional administration of a high dose ethanol to chronic alcohol-fed rats led to decrease of endotoxin clearance and elevation of plasma TNF, which may play an important role in the pathogenesis of alcoholic hepatitis.
    Alcohol and alcoholism (Oxford, Oxfordshire). Supplement 02/1993; 1A:65-70.
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    ABSTRACT: Uptake of endotoxin and production of tumor necrosis factor (TNF) by Kupffer cells and splenic macrophages were measured in chronically alcohol-fed rats. Twenty male Sprague-Dawley rats, weighing 200-250 g, were pair-fed by isocaloric control and ethanol-containing Lieber-DeCarli liquid diets for 6 weeks. Endotoxin uptake and TNF production of Kupffer cells and splenic macrophages in the chronic ethanol load-group were significantly (P < 0.001) greater than those in the control group. The increase in endotoxin uptake was more prominent in Kupffer cells and the increase in TNF production was more marked in splenic macrophages in the chronic ethanol group. When these cells were precultured in the medium containing 10-100 mM ethanol, the endotoxin uptake and TNF production of Kupffer cells isolated from control and chronic ethanol-fed rats were decreased in proportion to the concentration of ethanol in the culture medium. However, the addition of ethanol to the culture medium did not affect the endotoxin uptake and TNF production of splenic macrophages. These results support the hypothesis that the splenic macrophages are important for endotoxin uptake, and excessive production of TNF in rats given large amounts of alcohol.
    Alcohol and alcoholism (Oxford, Oxfordshire). Supplement 01/1993; 1B:53-7.
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    ABSTRACT: A recently developed chromogenic endotoxin assay with plasma Tween 80 pretreatment was compared with the conventional dilution and heating method. Plasma endotoxin was measured in patients with liver cirrhosis and upper gastrointestinal (GI) bleeding by these methods. Plasma endotoxin concentration was calculated from an individual internal standard curve by adding three different standard endotoxin solutions to each sample. By the conventional heating method, added standard endotoxin gave different OD values in each sample and the slope of the standard curve showed interindividual variations. When sample plasma from chronic alcoholics was pretreated with 1% Tween 80 and ultrasonification after heating, the slope of standard curves was somewhat increased and interindividual variation was minimized. Significantly higher plasma endotoxin levels in cirrhotics with upper GI bleeding compared with those without upper GI bleeding was detected by this Tween 80 method. There was a strongly positive correlation between the endotoxin levels determined by this method and those determined by the perchloric acid method and endotoxin-specific substrate in patients with upper GI bleeding. Endotoxin levels, which were elevated 1-2 days after the bleeding, tended to decrease as patients recovered. In summary, the recovery of endogenous and exogenous endotoxin from plasma sample was increased by adding Tween 80 before the chromogenic substrate assay. Transient elevation of plasma endotoxin was demonstrated by this Tween 80 method in patients with liver cirrhosis and upper GI bleeding.
    Journal of Gastroenterology and Hepatology 01/1993; 8(6):577-81. · 3.33 Impact Factor