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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 325 records · Page 18Linked to original sources
PubMed1996

Inhibition of leukotriene synthesis by azelastine.

BACKGROUND: Azelastine, oxatomide, and ketotifen are used for patients with allergic diseases. These drugs inhibit the release of chemical mediators including the leukotrienes; however, the mechanism involved is unclear. OBJECTIVE: To clarify the mechanism of inhibition, we investigated the effects of three drugs on the function of phospholipase A2, 5-lipoxygenase, leukotriene C4 synthase, and leukotriene A4 hydrolase, which are all catabolic enzymes involved in synthesizing leukotriene C4 and leukotriene B4 in rat basophilic leukemia (RBL)-1 cells. METHODS AND RESULTS: The production of leukotriene C4 and leukotriene B4 was measured by high performance liquid chromatography (HPLC). All three drugs inhibited the production of leukotriene C4 and leukotriene B4 when cells were stimulated with A23187. All three drugs also inhibited the A23187-stimulated release of 3H-arachidonic acid from membrane phospholipids. Azelastine inhibited the production of leukotriene C4, but not leukotriene B4, when either arachidonic acid or leukotriene A4 free acid was used as the substrate in our cell free system. Oxatomide and ketotifen did not inhibit the synthesis of either leukotriene C4 or leukotriene B4 in the same cell free study. CONCLUSION: Results indicated that oxatomide and ketotifen inhibit the production of leukotriene C4 and leukotriene B4 by inhibiting phospholipase A2 activity, whereas, azelastine inhibits the leukotriene C4 production by inhibiting phospholipase A2 and leukotriene C4 synthase.

Animals↗
PubMed1996

Modification of beta 2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum.

beta 2microglobulin (beta 2m) isolated from the amyloid deposits in patients with dialysis-related amyloidosis (DRA) has been demonstrated to be modified with advanced glycation end products (AGEs). We demonstrated that AGE was localized to amyloid deposits in patients with DRA by immunohistochemistry using a monoclonal anti-AGE antibody. To clarify the mechanism of AGE modification of beta 2m-amyloid, we studied the effects of 3-deoxyglucosone (3-DG), a potent protein crosslinking the intermediate of the Maillard reaction, on the AGE modification of beta 2m, and quantified the serum levels of 3-DG in patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), and undialyzed patients. The serum levels of 3-DG were markedly increased in the dialyzed and undialyzed uremic patients. Although the serum level of 3-DG decreased after HD with a mean reduction rate of 67%, it was still significantly higher than in normal serum. Incubation of beta 2m with 3-DG at 37 degrees C emitted fluorescence characteristic for AGE, and caused AGE modification and dimer formation of beta 2m as demonstrated by Western blotting using the same monoclonal anti-AGE antibody used for immunohistochemical demonstration of AGE in DRA. The AGE-modified dimer of beta 2m could be extracted from the amyloid tissue of a patient with DRA. 3-DG showed more intense and faster reactivity with beta 2m to form AGE and dimer as compared with glucose, and aminoguanidine suppressed the AGE and dimer formation of beta 2m by 3-DG. In conclusion, 3-DG accumulating in uremic serum may be involved in the AGE modification of beta 2m-amyloid.

Amyloidosis↗
PubMed1996

Umbilical vein endothelial cells are an important source of c-kit and stem cell factor which regulate the proliferation of haemopoietic progenitor cells.

The expression and production of c-kit and its ligand, stem cell factor (SCF), in cord blood and neonates were studied. Serum SCF levels were significantly higher in cord blood, neonates aged 1-30 d, and in 4-month-old infants than in the maternal serum (P < 0.01). SCF levels decreased in children from 7 months to 15 years of age (P < 0.01). The serum soluble c-kit levels were significantly higher in cord (P < 0.01) and neonatal blood (P < 0.05) than in the maternal blood. SCF and c-kit levels in placental tissue homogenates and the culture media of decidual cells and trophoblasts were low. To determine the sites of high SCF and c-kit production in cord blood and in early neonates. SCF and c-kit mRNA expression was analysed in various tissues by polymerase chain reaction. High SCF mRNA expression was observed in human umbilical vein endothelial cells (HUVEC). Moderate c-kit mRNA expression was detected in HUVEC, the bone marrow, and cord blood. These findings suggest that endothelial cells mainly produce the SCF in cord blood and in early neonates. To confirm the role of endothelial cells in haemopoiesis, colony-forming assays were performed in the presence of HUVEC culture media, which induced the formation of high numbers of granulocyte and erythroid colonies in cord blood. IL-3, IL-6 and SCF levels were elevated in the media. Our findings suggest that endothelial cells have an important role in the maintenance and proliferation of progenitor cells in neonatal blood via the interaction of c-kit and SCF with other factors. The ex vivo expansion of cord progenitor cells in the presence of endothelial cells needs to be investigated further.

ADP-ribosyl Cyclase↗
PubMed1996

Purification and characterisation of chicken liver monomeric glutathione peroxidase.

1. A novel glutathione peroxidase, which is distinct from tetrameric glutathione peroxidase, was purified to homogeneity from a broiler chick liver cytosolic fraction using 5 different column chromatographic methods. 2. The enzyme in cytosol was separated from 'classic' tetrameric glutathione peroxidase and glutathione S-transferases by DEAE-Sephacel and Sephadex G-100 chromatographies and further purified by Mono Q hydroxylapatite and sulphobromophthalein-S-glutathione-agarose chromatographies. 3. The molecular weight of the purified enzyme determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis was 19,500 and that found by gel filtration chromatography was comparable. This indicates that the enzyme protein is a single polypeptide. The isoelectric point of the enzyme was determined as 7.0 by polyacrylamide gel isoelectric focusing. 4. The purified enzyme catalysed the reduction of hydrogen peroxide, cumene hydroperoxide, text-butyl hydroperoxide and linoleic acid hydroperoxide. Furthermore, it reduced phosphatidylcholine hydroperoxide in the absence of phospholipase A2. The optimum pH for the enzyme reaction was 7.0. The antiserum against the purified enzyme reacted with the 19.5 kDa polypeptide in the liver cytosol of duck and quail.

Animals↗
PubMed1996

Outbreak of acute glomerulonephritis in children: observed association with the T1 subtype of group A streptococcal infection in northern Kyushu, Japan.

Group A streptococcal infection is associated with the occurrence of acute glomerulonephritis (AGN) and rheumatic fever (RF). A surveillance study in the Saga area, in northern Kyushu, Japan, showed a small variation in the reported number of group A streptococcal infections in the period 1988-94. However, of the AGN cases reported in this period, more than half were observed in 1992. In order to examine whether some change had occurred in the serotype distribution of Streptococcus pyogenes during the period, patients in the Saga area diagnosed as having group A streptococcal infection and patients with AGN or RF were analyzed. Serological T-typing of S. pyogenes was carried out for patients with group A streptococcal infections, and the association between the occurrence of AGN or RF and the distribution of each different T subtype was analyzed. M-typing of S. pyogenes was also carried out and the correlation between T and M types was examined. From 1988 to 1994, the annual number of patients with group A streptococcal infections in the Saga area showed a small variation, range 65-100 patients/year. Of the 42 patients with AGN and three with RF observed in this period, 27 with AGN (64%) and one with RF (33.3%) were detected in 1992. Only the T1 subtype increased in 1992; the other T subtypes showed little variation in incidence. The number of patients with the T1 subtype was significantly correlated with the occurrence of AGN by regression analysis (P < 0.01). Of the 170 subjects tested for both T and M subtypes, 44 of the 45 T1-typed subjects had the M1 protein. Our epidemiological study suggested that the T1 subtype of streptococcal infection was associated with an outbreak of AGN in 1992 in the Saga area.

Acute Disease↗
PubMed1996

Extensive white matter involvement in hemorrhagic shock and encephalopathy syndrome.

Reported is a case of hemorrhagic shock and encephalopathy syndrome (HSE) with extensive white matter involvement. A three year old, previously healthy boy was presented with an acute onset of fever, loss of consciousness and convulsions. He had disseminated intravascular coagulation, metabolic acidosis, non-ketotic hypoglycemia and hepatorenal dysfunction. The computed tomography (CT) scan of his head on the second day of illness demonstrated symmetric, extensive low-density areas in the cerebral and cerebellar white matter. The child died on the 13th hospital day. A post-mortem histopathological examination of the liver revealed centrilobular necrosis and infiltration of fatty acid droplets. The concentrations of serum 2',5'-oligoadenylate synthetase and urinary neopterin were markedly elevated, indicating excessively activated cell-mediated immunity. This overproduction of inflammatory cytokines might play an important role in the pathogenesis of the brain lesion as well as in other clinical and laboratory manifestations. The patient had a decreased serum level of alpha l-antitrypsin, which may have been associated with the development of uncontrolled inflammation and coagulation disorder.

Brain↗
PubMed1996

Continuous subcutaneous insulin injection for self-care of young patients with insulin-dependent diabetes mellitus.

Continuous subcutaneous insulin injection was used for the self-care of five patients aged 10-18 years with insulin-dependent diabetes mellitus. After an introduction to the concept and procedures for continuous subcutaneous injection, the patients soon became familiar with self-care using an insulin pump at home and at school. Three months later, the control of blood glucose improved with smaller doses of insulin in four cases and milder hypoglycemia was observed compared to when using multiple injections. Significantly decreased variations and lowered means of early morning blood glucose values were observed and seemed to explain the reason for better glycemic control. Buffered regular insulin continuously injected by pumps brought a more stable nocturnal blood glucose level compared to isophane insulin injected at bedtime, the absorption of which seemed to vary considerably. On the contrary, unbuffered regular insulin injected by pumps brought frequent nocturnal hypoglycemia, sudden worsening of glycemic control and skin infections and thus, was deemed inadequate for continuous subcutaneous injection.

Adolescent↗
PubMed1996

[Prevention of infections in a case with myelodysplastic syndrome by an intermittent subcutaneous administration of G-CSF].

An 83-year-old male was admitted to our hospital because of pancytopenia and low grade fever on April 19, 1993. On admission, hematological data were as follows: WBC 1,000/microliters with 19% neutrophils, RBC 367 x 10(4)/microliters, Hb 9.5 g/dl and platelets 6.7 x 10(4)/microliters. Bone marrow examination revealed 6.6% myeloblasts and 33.5% erythroblasts. Morphological abnormalities included hypersegmentation, degranulation and pseudo-Pelger's nuclear anomaly in neutrophils. Based on these findings the diagnosis of refractory anemia with excess of blasts (RAEB) of the myelodysplastic syndrome (MDS) was made and therapy with low dose Cytarabine (Ara-C) was initiated in April 1993. The patient had two episodes of severe pneumonia in June and July. Therefore, 75 micrograms/day of G-CSF was given in addition to antibiotic therapy for the second episode of infection in July. Thereafter the severe infection subsided, and G-CSF administration was switched to an intermittent schedule (75 micrograms twice a week) since September. Cytarabine ocfosfate (100 mg/day) was added for 10-14 days at interval 1-2 months from October,1993. He has been well with no episode of infection for more than two year. One major concern regarding the clinical application of G-CSF in MDS patients is related to the possible stimulation of leukemic cell proliferation. Frequent hematological monitoring is necessary in patients with RAEB who are prone to develop acute myeloid leukemia. However, we administered G-CSF at a relatively low dose twice a week for over two year and could successfully prevent infections without inducing the leukemic changes.

Aged↗
PubMed1996

Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin.

Several previous investigators have reported that long-term administration of certain macrolides is efficacious in patients with persistent pulmonary Pseudomonas aeruginosa infections, even though the clinically achievable concentrations of these medications are far below their MICs. In the present study, we examined how sub-MICs of macrolide antibiotics affect the viability of and protein synthesis in several strains of P. aeruginosa. We report that 48 h, but not 12 or 24 h, of growth on agar containing a clinically achievable concentration of azithromycin (0.5 microgram/ml, 1/128 the MIC) significantly reduces the viability of strain PAO-1. Similar effects were seen with erythromycin and clarithromycin at 2 micrograms/ml (1/128 and 1/64 the respective MICs), whereas josamycin, oleandomycin, ceftazidime, tobramycin, minocycline, and ofloxacin had no effect on viability, even following 48 h of incubation with concentrations representing relatively high fractions of their MICs. The bactericidal activity of azithromycin seen following 48 h of incubation was not limited to strain PAO-1 but was also seen against 13 of 14 clinical isolates, including both mucoid and nonmucoid strains. Although viability was not decreased prior to 48 h, we found that 4 micrograms of azithromycin per ml inhibits protein synthesis after as little as 12 h and that protein synthesis continues to decrease in a time-dependent manner. We likewise found that P. aeruginosa accumulates azithromycin intracellulary over the period from 12 to 36 h. These results suggested that sub-MICs of certain macrolides are bactericidal to P. aeruginosa when the bacteria are exposed to these antibiotics for longer periods. Exposure-dependent intracellular accumulation of the antibiotic and inhibition of protein synthesis may partially account for the antipseudomonal activity of macrolides over relatively prolonged incubation periods.

Anti-Bacterial Agents↗
PubMed1996

Lipopolysaccharide-induced lethality and cytokine production in aged mice.

This study was designed to define the lipopolysaccharide (LPS) sensitivity of aged mice in terms of lethality and cytokine production and to determine down-regulating responses of corticosterone and interleukin 10 (IL-10). The 50% lethal doses of LPS in young (6- to 7-week-old) and aged (98- to 102-week-old) mice were 601 and 93 microg per mouse (25.6 and 1.6 mg per kg of body weight), respectively. Aged mice were approximately 6.5-fold more sensitive to the lethal toxicity of LPS in micrograms per mouse (16-fold more sensitive in milligrams per kilogram) than young mice. Levels in sera of tumor necrosis factor-alpha (TNF-alpha) IL-1alpha, and IL-6 after intraperitoneal injection of 100 microg of LPS peaked at 1.5, 3, and 3 h, respectively, and declined thereafter in both groups of mice. However, the peak values of these cytokines were significantly higher in aged than in young mice (P < 0.05). Gamma interferon (IFN-gamma) was detectable at 3 h, and sustained high levels were still detected after 12 h in both age groups. Although there were no significant differences in levels of IFN-gamma in sera from both groups, aged mice showed higher IFN-gamma levels throughout the 3- to 12-h study period. Administration of increasing doses of LPS revealed that aged mice had a lower threshold to IL-1alpha production than young mice. In addition, aged mice were approximately 4-fold more sensitive to the lethal toxicity of exogenous TNF in units per mouse (10-fold more sensitive in units per kilogram) than young mice. With regard to down-regulating factors, corticosterone amounts were similar at basal levels and no differences in kinetics after the LPS challenge were observed, whereas IL-10 levels in sera were significantly higher in aged mice at 1.5 and 3 h than in young mice (P < 0.01). These results indicate that aged mice are more sensitive to the lethal toxicities of LPS and TNF than young mice. We conclude that a relatively activated, or primed, state for LPS-induced cytokine production, in spite of full down-regulating responses by corticosterone and IL- 10, may explain at least in part LPS sensitivity in aged mice.

Aging↗
PubMed1996

Inhibition of leukotriene synthesis by honokiol in rat basophilic leukemia cells.

The effects of honokiol, a diphenyl compound extracted from a Chinese herbal medicine, on leukotriene (LT) synthesis were evaluated in rat basophilic leukemia (RBL) cells. The production of LTC4 and LTB4 stimulated by the Ca2+ ionophore A23187 was measured in RBL-1 cells by high-performance liquid chromatography. Honokiol inhibited the production of LTC4 and LTB4 stimulated by A23187 in RBL-1 cells. Honokiol did not inhibit either phospholipase A2 activity, measured by the release of 3H-arachidonic acid (AA), or LTC4 synthase and LTA4 hydrolase activities, measured with LTA4-free acid as substrate. The synthesis of LTC4 and LTB4 from AA in RBL-1 cell lysates in the presence of Ca2+ was inhibited by honokiol. These results indicate that honokiol blocks LT synthesis by inhibiting 5-lipoxygenase activity. Honokiol also inhibited immunoglobulin E-mediated production of these LTs in RBL-2H3 cells, which was measured by a specific radioimmunoassay (RIA). These results suggest that honokiol may exhibit antiallergic actions by inhibiting LT synthesis in immediate-type hyperreactivity.

Animals↗
PubMed1996

[The transport of enoxacin in cultured kidney epithelial cells LLC-PK1].

In this study, the transport of enoxacin (ENX) was investigated in a LLC-PK1 kidney epithelial cell line. The uptake of ENX by LLC-PK1 monolayers cultured in plastic dishes was shown to be temperature-dependent and concentration-dependent. Cimetidine and guanidine inhibited the uptake of ENX, whereas TEA and NMN did not. The basolateral to apical flux of ENX across LLC-PK1 monolayers cultured on permeable supports was about two times larger than the apical to basolateral flux. The basolateral to apical flux of ENX was remarkably inhibited by guanidine, whereas it was not inhibited by TEA, NMN and cimetidine. The apical to basolateral flux of ENX was inhibited by cimetidine and guanidine, whereas it was not inhibited by TEA and NMN.

Animals↗
PubMed1996

Establishment of a series of alien monosomic addition lines of Japanese bunching onion (Allium fistulosum L.) with extra chromosomes from shallot (A. cepa L. aggregatum group).

Forty one plants of alien monosomic addition lines of Allium fistulosum L. with extra chromosomes from A. cepa L. Aggregatum group (FF + nA) were produced through the second backcross of amphidiploids between these two species to A. fistulosum. Identification of the extra chromosomes in the 16 plants by elaborate karyotype analyses indicate that a complete series (eight different types) of the alien monosomic addition lines was established in Allium for the first time in this study. Chromosomal locations of malate dehydrogenase (MDH) gene, triosephosphate isomerase (TPI) gene and 5S rDNA of A. cepa Aggregatum group were determined using the series; The gene locus Mdh-1 was located on 4A, Tpi-1 on 3A and a 5S rDNA locus on 7A. Our previous and present studies using the alien monosomic addition lines revealed 11 genetic markers (isozyme and 5S rDNA) assigned to all eight chromosomes of A. cepa Aggregatum group, and these markers reconfirmed the completion of the series. Extra chromosomes of 25 other plants were examined by means of simple analyses of the chromosome markers and karyotypes. Of the total 41 plants, frequencies of the alien monosomic addition lines with extra chromosomes 1A to 8A were as follows: 1A, 5 plants; 2A, 3; 3A, 5; 4A, 9; 5A, 4; 6A, 2; 7A, 11; and 8A, 2.

Chromosome Mapping↗
PubMed1996

Epidemiological survey of small rodents for spotted fever rickettsial antibody in Hokkaido, Japan.

The prevalence of antibody against spotted fever group rickettsia (SFGR) was investigated with Rickettsia japonica antigen in small rodents captured in an area in Hokkaido, where no human cases of SFGR infection had been reported. Antibody against SFGR was found in Apodemus speciosus and Clethrionomys rufocanus but not in Apodemus argenteus. None of these rodents had antibody against R. typhi. This is the first report of the antibody against SFGR in rodents in Hokkaido.

Animals↗
PubMed1996

[Familial amyotrophic lateral sclerosis showing variable clinical courses with (Leu84-->Val) mutation of Cu/Zn superoxide dismutase].

A family with autosomal-dominant amyotrophic lateral sclerosis with histopathological confirmation on autopsy was described. A 42-year-old female proband showed the signs and symptoms only in the lower limbs characteristic of lower motor neuron involvement at the onset. ALS had been diagnosed in other five members in three generations of her family. The mean +/- SD age of onset of the disease was 42.5 +/- 9.3 years with a range of 30 to 51 years. The mean +/- SD duration of the disease (n = 5, excluding the proband) was 56 +/- 70 months with a range of 7 to 180 months. Molecular genetic studies showed a T-to-G transversion that results in the substitution of valine for leucine84 in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene on chromosome 21 in a proband. This mutation is identical to that found in the Japanese family with autosomal-dominant ALS characterized by short duration of the disease, within 1.5 years, in all the affected family members. Therefore, the clinical phenotype, especially the duration of the disease seems to be highly variable even in the families with the identical mutation of the Cu/Zn SOD gene.

Adult↗
PubMed1996

Effects of an oral adsorbent on cisplatin-induced nephropathy in rats.

A 26-week experiment was designed to determine the effect of an oral adsorbent, AST-120 (Kremezin), in rats with cisplatin-induced interstitial nephropathy. We found that creatinine clearance during the 24th week of the experiment was significantly higher in the AST-120-treated rats (n = 11) than in the control animals (n = 11) (1.09 +/- 0.14, vs. 0.63 +/- 0.12 ml/min; p < 0.05). Furthermore, the kidneys, which were examined morphometrically using a computerized image scan, revealed that the AST-120-treated rats had a significantly lower ratio of the tubular cross-sectional area over the cortex and outer medulla cross-sectional area than the control group (0.26 +/- 0.03 vs. 0.38 +/- 0.02; p < 0.05). An additional experiment was conducted to see if the oral adsorbent affects absorption and excretion of intraperitoneally administered cisplatin. There was no difference between the control group (n = 12) and the AST-120-treated group (n = 12) in serum concentration or urinary excretion of cisplatin during a 72-hour period after the injection. The results of our experiments suggest that the oral absorbent, AST-120, blunts progressive deterioration of renal function and nephron architecture in cisplatin nephropathy.

Administration, Oral↗