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Biomedical subjects

E Kikuchi

Publications and source records attributed to E Kikuchi.

At least 37 records · Page 2Linked to original sources

Role of albumin and high-density lipoprotein as endotoxin-binding proteins in rats with acute and chronic alcohol loading.

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.

Alcoholic Intoxication↗

Protective mechanism of high-density lipoprotein against endotoxemia in chronic alcohol ingestion.

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↗

An experimental study on an evaluation method for occupational therapy--the effectiveness of a newly developed computerized measurement system of finger function.

We developed a new computerized measurement system of finger function as a movement test. This type of measurement system is very novel in the field of occupational therapy. Eighty-seven healthy individuals and 101 patients participated in this study to investigate the effectiveness of the new system. The subjects were asked to test their eye-hand coordination by operating a joy-stick lever. The following findings were obtained. 1) A computerized measurement system of finger function was developed and effectiveness was improved. 2) Correlation between their age and finger function in the healthy group was 0.409, and 0.407 in the patient group. 3) The relationship between the time of testing and performance was stable in the healthy group throughout the measurements, while in the patient group, deviations from the value in the initial 5 seconds grew larger with the time of testing (p < .01). 4) In the hemiplegia patients, the performance level of the left hemiplegia group was lower than that of the right hemiplegia group (p < .01). By means of a computer analysis, it was confirmed that characteristics of individual finger function can be clarified in greater detail. The possibility of general application of this system in evaluation of the effects of occupational therapy were suggested.

Computer Systems↗

Interaction of Kupffer cells to splenic macrophages and hepatocytes in endotoxin clearance: effect of alcohol.

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.

Animals↗

Endotoxin inactivating action of plasma in patients with liver cirrhosis.

The endotoxin inactivating action of plasma was evaluated in 62 patients with cirrhosis and 10 healthy subjects. Endotoxin from E. coli 0111:B4 was added to each plasma sample to a final concentration of 250 pg/ml and the percentage loss of endotoxin activity by incubation (37 degrees C for 1 h) was calculated as the endotoxin inactivating rate. The plasma endotoxin inactivating rate in cirrhotics was significantly greater than that in healthy subjects, although patients with Child C cirrhosis and marked hyperbilirubinemia had a significantly lower endotoxin inactivating rate than other cirrhotics. The plasma endotoxin inactivating rate was positively correlated to serum HDL-cholesterol levels. In patients with Child A and Child B cirrhosis, the endotoxin inactivating rate was positively correlated to the endotoxin binding capacity of plasma albumin. The present results support the assumption that the plasma of cirrhotics has a high endotoxin inactivating capacity. Its decrease may augment endotoxicity in patients with advanced liver cirrhosis.

Albumins↗

[Involvement of substance P in gastric mucosal lesions of patients with rheumatoid arthritis].

We investigated the relation between gastric mucosal lesions and substance P (SP) in 64 patients with rheumatoid arthritis (RA) taking nonsteroidal antiinflammatory drugs (NSAIDs). In these patients, the incidence of gastric mucosal lesions was as high as 53.1%. Serum SP levels were significantly higher in patients with gastric mucosal lesions than in those without gastric lesions. Erythrocyte sedimentation rate, serum C-reactive protein and rheumatoid factor (RF) levels were also higher in patients with gastric mucosal lesions. A positive correlation between serum SP and RF levels was found in patients with RA. Experimental gastric mucosal lesions induced by an oral administration of indomethacin in rats were significantly enhanced by an additional intraperitoneal injection of SP. From these observations, it is suggested that, in addition to the effect of NSAIDs, SP elevation in blood has a role in the development of gastric mucosal lesion in patients with RA.

Animals↗

Effectiveness of daily living abilities (DLA) as a tool for evaluating vocational competencies: study of non-disabled workers aged 45 and over.

A questionnaire survey was conducted on 28-55 items of daily living abilities (DLA) linked to 13 basic vocational competencies such as memory, learning, planning, judgement, muscular power and concentration covering a total of 505 non-disabled blue collar male workers aged 45 and over. Results of the survey were as follows, (1) The 457 subjects were grouped into five groups ranging from normal to unsound groups according to the degree of DLA; (2) The reduction of DLA has directionality to two factors, memory and muscular power; (3) DLA provide clues for aging; (4) Among basic vocational competencies, muscular power showed the highest performance with a small standard deviation, while concentration scored low points with a large standard deviation (p < .05); (5) No age difference was found in planning ability, coordination, muscular power, physical tolerance, manual dexterity, and sense of equilibrium, while subjects aged 65 or over showed significantly low figures for learning ability, agility and concentration (p < .05); Since the findings showed various characteristics of vocational competencies and the aging process precisely in blue collar workers aged 45 and over, we assumed that the DLA survey is one of the alternatives for evaluating workers vocational competencies.

Activities of Daily Living↗

Effect of prostaglandin E1 on experimental acute hepatic failure in rabbits: prostaglandin E1 prevents the development of multiple-organ failure.

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)

Alprostadil↗

Effect of alcohol on the endotoxin binding protein produced in the liver.

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.

Animals↗

Dibutyryl cyclic AMP enhances the down-regulation of RB protein during G1 phase in the proliferating primary rat hepatocytes, but inhibits their entries into S phase and RB's phosphorylation.

To elucidate the cAMP's bi-directional dual effect on hepatic regeneration with a special reference to RB protein, we studied the serial change of RB protein in the proliferating primary rat hepatocytes and the effect of dibutyryl cAMP (DBcAMP) on it. RB protein in the hepatocytes was down-regulated during the G1 phase, and the highly phosphorylated/the underphosphorylated ratio of RB protein increased at the S phase. DBcAMP (1 mM) addition, inhibitory on the DNA synthesis, enhanced this down-regulation, but did not increase the phosphorylated form of RB protein at the S phase. High dose of cAMP at the late G1-G1/S phase could block some essential events for G1/S transition including phosphorylation of RB protein.

Animals↗

Prostaglandin E2 and rat liver regeneration.

BACKGROUND: Prostaglandin (PG) is reported to be involved in hepatic regeneration. However, little is known about the detailed relation in PG-induced stimulation of the proliferation. The present study was attempted to elucidate the relation. METHODS: The serial change of PGE2 level released from the regenerating rat liver and the effect of PGE2 on the proliferation of rat hepatocytes were studied, with special reference to PGE2 binding and cyclic AMP (cAMP). RESULTS: The PGE2 level increased 3 hours and 10 hours after partial hepatectomy. Timings of these increases seemed to coincide with those of the first and second increase of cAMP in the liver before the initiation of DNA synthesis. DNA synthesis of hepatocytes in primary culture between 24 and 36 hours, 36 and 48 hours, and 48 and 60 hours of culture were significantly enhanced by addition of PGE2 between 4 and 24 hours of culture at concentrations of 2 nmol/L to 1 mumol/L, 2 nmol/L to 200 nmol/L, and 5 mumol/L to 10 mumol/L, and 2 nmol/L and 10 mumol/L, respectively. Enhancement of DNA synthesis with PGE2 at concentrations less than 1 mumol/L seemed to be associated with the high-affinity binding and that at high concentrations with the low-affinity binding. Intracellular cAMP level in the hepatocytes increased during culture, and its increase was enhanced by PGE2 addition. CONCLUSIONS: It is suggested that PGE2 production in the liver increases biphasically during hepatic regeneration and that PGE2 enhances the proliferation of hepatocytes by a specific receptor-mediated process, which is largely associated with cAMP-dependent process.

Animals↗

Metabolic fate of endotoxin and blood tumour necrosis factor levels in rats with acute and chronic alcohol loading.

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.

Alcoholic Intoxication↗

Effect of alcohol on the functions of Kupffer cells and splenic macrophages in rats.

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.

Alcoholism↗

Exacerbation of ulcerative colitis during alpha-interferon therapy for chronic hepatitis C.

We report a 34-year-old man with chronic hepatitis C who showed exacerbation of ulcerative colitis during alpha-interferon (IFN alpha) therapy. Discontinuance of the IFN alpha therapy improved his symptoms, suggesting that IFN alpha administration might worsen ulcerative colitis. The administration of sulfasalazine allowed the patient to receive IFN alpha again without flare-up of ulcerative colitis. This case suggests the possible efficacy of sulfasalazine therapy in patients with ulcerative colitis complicated by some other diseases requiring IFN alpha administration.

Adult↗

D-galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes.

Specific bindings of [3H]prostaglandin E1 ([3H]PGE1), 125I-glucagon and [3H]norepinephrine to D-galactosamine (GalN)-treated rat hepatocytes in primary culture were investigated. After a two hour-treatment with GalN (1 and 10mg/ml), hepatocytes showed an enhanced specific binding to [3H]PGE1, whereas 125I-glucagon binding was little affected and [3H]norepinephrine binding was strongly diminished. Scatchard plot analysis indicated an increase of binding sites of [3H]PGE1. This unusual manner of [3H]PGE1 binding is suggested to indicate a special property of PGE1 receptor and may be associated with the cytoprotective effect of prostaglandins.

Alprostadil↗

A novel oral adjuvant for hepatitis B virus (HBV) vaccines.

A plasma-derived HBV vaccine was administered to 86 healthy men ranging in age from 40-56 years. A relatively high rate of nonresponders was found among the men who received the HBV vaccine alone. There was a significantly higher HBs antibody response rate among the vaccinees who received an oral adjuvant (taurine) compared to those not receiving the adjuvant. In the vaccinees who received the oral adjuvant, an in vitro polyclonal antibody response to taurine was detected in 17 (58.6%) of the 29 HBs responders, but in none of the HBs nonresponders. The development of oral adjuvants other than aluminum may be a valuable approach to the study of HBV vaccination.

Adjuvants, Pharmaceutic↗

Effects of acetate on the immune system of mice.

The effects of acetate on antibody production and cell-mediated immunity in mice were investigated. Polyclonal antibody responses could be enhanced in vivo by single intraperitoneal administration of acetate (5 mg/mouse) in C57BL/6 mice but not in DBA/2 mice. No enhancement of antibody production by acetate was also induced in athymic C57BL/6 nude mice and carrageenan-pretreated, macrophage-depleted mice. The inoculation of acetate-nonresponder BDF1 mice with T-cells and peritoneal adherent cells derived from acetate-treated C57BL/6 mice resulted in an enhanced antibody response. These results suggest that acetate increases polyclonal antibody responses in vivo by activating indirectly T-cells and macrophages. Acetate administration increased delayed hypersensitivity to pircryl chloride in C57BL/6 mice but not in DBA/2 mice. Allogeneic mixed lymphocyte reaction (MLR) of T-lymphocytes derived from the spleen of acetate-treated C57BL/6 mice was also enhanced. The natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) were also increased in C57BL/6 mice that were administered acetate. The possible mechanism of the immunopotentiating effect of this chemical is discussed.

Acetates↗