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Biomedical subjects

M Kikukawa

Publications and source records attributed to M Kikukawa.

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↗

[Infection in elderly leukemic patients].

Febrile episodes occurring in 29 elderly patients (mean age 75 years) with leukemia, from 1988 to 1993, were reviewed. A febrile episode was defined as a temperature of 38 degrees C or greater for at least 6 hours. The number of febrile episodes was 64. The average was 2.2 febrile episodes per patient. Seventy-two percent of febrile episodes occurred when the patients had neutropenia below 100/microliters, while 16% occurred with neutropenia of 101/microliters to 500/microliters. Causative microorganisms were identified in 48% of total febrile episodes. The most common infectious site was the urinary tract which accounted for 25% of total episodes. Pneumonia and septicemia accounted for 22% of total episodes, respectively. Gram-positive cocci were responsible for 66% of microbiologically documented febrile episodes, while 21% were caused by gram-negative bacilli. Gram-positive cocci, particularly staphylococcus aureus, coagulae-negative staphylococcus and enterococci increased compared with a decade ago in our department. Granulocyte colony-stimulating factor (G-CSF) was used 12 times for infection. No significant difference in fever amelioration was seen between G-CSF and non-G-CFS cases.

Aged↗

[An elderly patient with Ph1-positive chronic myelomonocytic leukemia].

An 80-year-old man with leukocytosis was admitted to our hospital on February 20, 1995. There were no blasts in the peripheral blood, but leukocytosis, associated with marked monocytosis, anemia, and thrombocytopenia was observed. The bone marrow was hyperplastic and there was a slight decrease in megakaryocytes. The myelogram showed 5.6% blasts + promyelocytes, and there was no basophilia. Mild dysplasia of third-line cells was observed. Chromosome analysis yielded 47, XY, +8, t (9;22) (q34;q11), and the Philadelphia (Ph1) chromosome and trisomy 8 were detected. Fluorescence in-situ hybridization revealed a large ber. Because the French-American-British (FAB) cooperative group diagnostic criteria for chronic myelomonocytic leukemia (CMMoL) were fulfilled and the Ph1 chromosome was detected, a diagnosis of Ph1-positive CMMoL was made. Hydroxyurea was given for cytoreduction and the patient has been followed with no evidence of acute transformation for about one year. CMMoL is classified as a myelodysplastic syndrome. However, it is rare to find the Ph1 chromosome in patients with these syndromes, and there have been very few reports of its detection in CMMoL. CMMoL may not be a single disease entity, and it may be useful to investigate more cases like the present one, to reassess this disease.

Aged↗

[Primary myelofibrosis with severe bone pain].

An 80-year-old man was admitted with bone pain, affecting both lower limbs and the dorsa of the feet, in September, 1991. Primary myelofibrosis was diagnosed. Bilateral x-ray films of the tibia, fibula, femur and vertebra revealed osteoporosis, but this was considered an unlikely source of the bone pain. The bone pain subsequently disappeared, but then became severe in both lower limbs and the dorsa of the feet and was accompanied by leukemic transformations in February, 1992. He died of aspiration pneumonia in July, 1992. Autopsy revealed microfractures with osteoporosis and infiltration of leukemic cells in the periosteum of the left tibia, which may have caused the bone pain. This case provides useful information to analyze the cause of bone pain in patients with myelofibrosis.

Aged↗

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↗

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↗

[Plasma concentration of cytosine arabinoside (Ara-C) in the elderly patients with hematological malignancy treated by Ara-C or cytarabine ocfosfate (SPAC)].

Plasma concentration of cytosine arabinoside (Ara-C) was determined in elderly patients with myelodysplastic syndromes or acute myelocytic leukemia who were treated with subcutaneous injection of Ara-C (Ara-C s.c.; 10 mg/m2/12 hr, 14-21 days), continuous drip infusion of Ara-C (Ara-C d.i.v.; 20 mg/m2/day, 24 hr 14 days) and/or oral administration of cytarabine ocfosfate (SPAC) (SPAC p.o.; 100 mg-300 mg/body/day, 14 days) by radioimmunoassay. In the Ara-C s.c. patients, the peak plasma level (Cmax) of Ara-C was 103 ng/ml and the time to reach Cmax was 15 min. The elimination half-like (t1/2) was 25 min and no accumulation was detected after 14 days of consecutive Ara-C s.c. administrations. In the SPAC p.o. patients, Cmax of Ara-C was 3-8 ng/ml and it took 3-5 days to reach Cmax. The plasma concentration level of Ara-C remains almost at the Cmax level during the SPAC p.o. administration and it remained higher than 0.32 ng/ml for as long as 15 days after the end of administration. In a Ara-C d.i.v. patient, plasma level of Ara-C was detected 4-7 ng/ml during the administration (day 7 through day 14). In all patients bone marrow suppression was observed after chemotherapy regardless of regimen, and there was no significant difference between nadir peripheral cell blood counts of Ara-C s.c. patients and SPAC p.o. patients.

Administration, Oral↗

[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↗

Multiple sclerosis presented acute hearing loss and vertigo.

A case of multiple sclerosis with acute deafness and dizziness as initial symptoms was reported. The pure-tone audiometry showed a high-frequency sensorineural hearing loss; in the auditory evoked brain stem response (ABR), the left side had a normal peak I with an absence of subsequent peaks. In the equilibrium test, Bruns' nystagmus was present, and the caloric test demonstrated CP on the left side. MRI disclosed a high-intensity lesion in the cerebellar peduncle (T2-weighted image). With steroid therapy, the deafness and dizziness improved within 10 days, although, after 20 days, the findings of the ABR and caloric test remained unchanged.

Adult↗

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↗

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↗

Stepping analysis in patients with spinocerebellar degeneration and Parkinson's disease.

POLGON (Polarized light goniometer) was used to evaluate ataxia during stepping movements in patients with spinocerebellar degeneration (SCD) and Parkinson's disease. The measurements included mean angular change of shoulders (M.A.C.S.) and its coefficient of variation (C.V.). In patients with SCD, the values of M.A.C.S. were significantly larger at 1.0 step/s than those at other stepping rhythms. This results suggests that the stepping rhythm of 1.0 step/s is useful for the detection of cerebellar ataxia. The values of C.V. correlated with the degree of advancement of SCD. In patients with Parkinson's disease, the values of M.A.C.S. tended to decrease because of the restricted elevation of the knee, while those of C.V. were increased. The results showed that the stepping test using the POLGON was useful for estimation of the characteristic disequilibrium of SCD and Parkinson's disease.

Adult↗

Relationship between movements of the head and the center of gravity of the body in Menière's disease.

The body sway of the patients with unilateral and bilateral Ménière's disease was recorded by using a cephalograph and a stabilometer, and analyzed with a microcomputer. The results show that the locus type, locus area and locus length traced by the head's center and the body's center of gravity are useful parameters of the body sway, representing the characteristics of peripheral vestibular disorders. The noteworthy characteristics are shown in the right-and-left type and forward-and-backward type in statokinesigram, in the significant differences of locus area and/or locus length between the head movement and the movement of the center of gravity, and the change of the averaged divisional frequencies of the body sway with eye-closing.

Dominance, Cerebral↗

Clinical significance of head movement while stepping.

Head movement of normal subjects and patients with peripheral vestibular disorders while stepping was recorded using three accelerometers, a multi-channel telemeter and a microcomputer. The head movement registered from normal subjects was stable at a stepping speed of 1.2 or 1.4 steps/sec. Patients with peripheral vestibular disorders (except for BPPV) showed significantly greater head movement values in all three directions and smaller ratios of anteroposterior component to lateral component in the head movement, as compared with those of normal subjects.

Adolescent↗

Pancreatic pleural effusion with a pancreaticopleural fistula diagnosed by magnetic resonance cholangiopancreatography and cured by somatostatin analogue treatment.

A 69-year-old man with chronic alcoholic pancreatitis developed a left-sided massive pleural effusion. Magnetic resonance cholangiopancreatography clearly demonstrated the pancreatic cyst and the fistula connecting the cyst with the left pleural cavity, resulting in the diagnosis of pancreatic pleural effusion with a pancreaticopleural fistula. Conservative somatostatin analogue treatment completely eradicated the pancreatic pleural effusion and closed the pancreaticopleural fistula.

Aged↗