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Biomedical subjects

Y Azuma

Publications and source records attributed to Y Azuma.

At least 19 recordsLinked to original sources

Endocrine-disrupting effects of styrene oligomers that migrated from polystyrene containers into food.

The endocrine-disrupting effects of styrene dimers (SD: NSD-01, -08 and -09) and styrene trimers (ST: NST -01, -03 and -12), which migrated from polystyrene (PS) containers into instant food, were investigated together with styrene monomer (SM) using in vitro and in vivo assays. In the estrogen (ER) and androgen receptor (AR) binding assay, SM, SD and ST showed no binding activity at concentration of 10(-10)-10(-5) mol/l. In order to evaluate the estrogenic activity in vivo, the uterotrophic assay was conducted. When prepubertal and ovariectomized adult rats were dosed with SM, SD and ST for 3 days by subcutaneous injection, these compounds did not induce significant increase in uterine weight. Additionally, to evaluate anti-androgen activity in vivo, the Hershberger assay for anti-androgenic activity in the presence of testosterone treatment was conducted. When castrated, testosterone-treated immature male rats were dosed SM, SD and ST for 7 days by oral gavage, these compounds did not induce a decrease in the seminal vesicle, ventral prostate and levator ani plus bulbocavernosus muscle weights. To evaluate the effects on hormones other than sex hormones, the thyroid hormone receptor (TR) binding assay and rat serum prolactin (PRL) was conducted. In the TR binding assay, SM, SD and ST showed no binding activity at a concentration of 10(-5) mol/l. When ovariectomized rats were dosed with SM, SD and ST for 3 days by sc injection, the results showed there was no change in rat serum PRL. From the above these results, we concluded that SM, SD and ST exhibit no apparent estrogenic, androgenic, anti-androgenic and thyroid activity.

Animals↗

Inhibitory effect of mandarin juice rich in beta-cryptoxanthin and hesperidin on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary tumorigenesis in mice.

Previously we reported that a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ), MJ2 and MJ5, especially MJ5, effectively suppressed chemically-induced rat colon carcinogenesis (Int. J. Cancer 88 (2000) 146). MJ2 and MJ5 prepared from MJ have higher amounts of beta-cryptoxanthin and hesperidin than MJ, suggesting that principle chemopreventive factors in MJs may be beta-cryptoxanthin and hesperidin. Present study was conducted to test whether these MJs could modify carcinogenesis in other organ, lung initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in male A/J mice. Mice were given an intraperitoneal injection of NNK (10 micromol in saline/mouse) to induce pulmonary neoplasms. They also received MJ, MJ2 or MJ5 as a drinking water at night for 21 weeks, starting 1 week after the NNK injection. Treatments with MJ, MJ2, and MJ5 reduced the incidence of lung tumors and the inhibition by MJ5 (29% reduction) was statistically significant (P<0.05). MJs treatment lowered the multiplicity of lung neoplasms without statistical significance. Immunohistochemically, MJs, especially MJ5, reduced proliferating cell nuclear antigen (PCNA)-positive index in the lung tumors without affecting PCNA index in hyperplastic alveolar cell lesions. These findings might suggest that MJ5, which contain 3.9 mg beta-cryptoxanthin and 100 mg hesperidin in 100 g sample), has chemopreventive ability against NNK-induced mouse lung tumorigenesis.

Animals↗

Heterogeneous expression of Toll-like receptor 4 and downregulation of Toll-like receptor 4 expression on human gingival fibroblasts by Porphyromonas gingivalis lipopolysaccharide.

Porphyromonas gingivalis (P. gingivalis) is implicated in the initiation and progression of periodontitis. Human gingival fibroblasts (HGFs) are the major constituent of gingival connective tissue. P. gingivalis or its components such as lipopolysaccharide (LPS) upregulate the production of various inflammatory cytokines including interleukin (IL)-1 and IL-6 in HGFs. Recently, we demonstrated that the binding of P. gingivalis LPS to Toll-like receptor 4 (TLR4) on HGFs activates various second messenger systems (Biochem. Biophys. Res. Commun. 273, 1161-1167, 2000). In the present study, we examined the level of TLR4 expression on HGFs by flow cytometric analysis (FACS), and studied the levels of IL-1 and IL-6 in the culture medium upon LPS stimulation of HGFs by enzyme-linked immunosorbent assay (ELISA). Upon stimulation by P. gingivalis LPS for 24 h, HGFs that expressed a high level of TLR4 secreted significantly higher levels of IL-1 and IL-6 than HGFs that expressed a low level of TLR4. On the other hand, after stimulation with P. gingivalis LPS for 24 h, the level of TLR4 on the surface of HGFs decreased. These results suggest that the level of TLR4 expression on HGFs reflects the extent of inflammation in the gingival tissue, and that P. gingivalis LPS downregulates TLR4 expression on HGFs. These findings may be used to control inflammatory and immune responses in periodontal disease.

Antibodies, Monoclonal↗

Endomorphins 1 and 2 modulate chemotaxis, phagocytosis and superoxide anion production by microglia.

We evaluate the role of endomorphins 1 and 2 on microglial functions. Endomorphins 1 and 2 blocked phagocytosis of Escherichia coli. In addition, both markedly inhibited chemotaxis toward zymosan-activated serum. In contrast, when microglia was preincubated with these endomorphins, followed by incubation with LPS before stimulation with phorbol 12-myristate 13-acetate (PMA) at 200 nM, they potentiated superoxide anion production. Furthermore, when microglia was preincubated with these endomorphins together with PMA at 20 nM, followed by stimulation with PMA at 200 nM, superoxide anion production was potentiated. These results suggest that endomorphins 1 and 2 modulate phagocytosis, chemotaxis and superoxide anion production by microglia.

Animals↗

Differentiation by in vitro treatment of lidocaine-epinephrine and prilocaine-felypressine in neutrophils.

Neutrophils are often the first cells of the immune system to encounter an invader, such as bacteria and fungi. Lidocaine-epinephrine induced transient potentiation of the production of superoxide anion, while prilocaine-felypressine induced persistent inhibition of the production in neutrophils. Moreover, lidocaine-epinephrine inhibited the production of hydrogen peroxide in spite that it potentiated the production of superoxide anion, while prilocaine-felypressine inhibited the production of hydrogen peroxide as well as superoxide anion. By contrast, lidocaine-epinephrine and prilocaine-felypressine are both effective in significantly inhibiting adhesion and phagocytosis. Using flow cytometric analysis, both local anesthetics were found to be effective in inhibiting the expression of Mac-1 (CD11b/CD18) in neutrophils. These results suggest that lidocaine-epinephrine and prilocaine-felypressine differentially modulate the production of superoxide anion, and could similarly inhibit adhesion, phagocytosis, and the production of hydrogen peroxide by neutrophils.

Anesthetics, Local↗

Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus.

Pseudohypoparathyroidism type Ib (PHP-Ib) is a paternally imprinted disorder which maps to a region on chromosome 20q13.3 that comprises GNAS1 at its telomeric boundary. Exon A/B of this gene was recently shown to display a loss of methylation in several PHP-Ib patients. In nine unrelated PHP-Ib kindreds, in whom haplotype analysis and mode of inheritance provided no evidence against linkage to this chromosomal region, we confirmed lack of exon A/B methylation for affected individuals, while unaffected carriers showed no epigenetic abnormality at this locus. However, affected individuals in one kindred (Y2) displayed additional methylation defects involving exons NESP55, AS and XL, and unaffected carriers in this family showed an abnormal methylation at exon NESP55, but not at other exons. Taken together, current evidence thus suggests that distinct mutations within or close to GNAS1 can lead to PHP-Ib and the associated epigenetic changes. To further delineate the telomeric boundary of the PHP-Ib locus, the previously reported kindred F, in which patient F-V/51 is recombinant within GNAS1, was investigated with several new markers and direct nucleotide sequence analysis. These studies revealed that F-V/51 remains recombinant at a single nucleotide polymorphism (SNP) located 1.2 kb upstream of XL. No heterozygous mutation was identified between exon XL and an SNP approximately 8 kb upstream of NESP55, where this affected individual becomes linked, suggesting that the genetic defect responsible for parathyroid hormone resistance in kindred F, and probably other PHP-Ib patients, is located >or=56 kb centromeric of the abnormally methylated exon A/B. A region upstream of the known coding exons of GNAS1 is therefore predicted to exert, presumably through imprinting of exon A/B, long-range effects on G(s)alpha expression.

Chromosome Mapping↗

15-Deoxy-delta(12,14)-prostaglandin J(2) inhibits IL-10 and IL-12 production by macrophages.

15-Deoxy-Delta(12,14)-prostaglandin J(2) (dPGJ(2)) is a metabolite of prostaglandin D(2), that binds to peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma and prostaglandin D(2) synthase, which is required for dPGJ(2) synthesis, are predominantly expressed in macrophages. In contrast, IL-10 and IL-12 produced by macrophages stimulate Th1 and Th2 immune response, respectively. This study investigated the effect of dPGJ(2) on IL-10 and IL-12 production by macrophages in response to lipopolysaccharide (LPS). Our data clearly demonstrated that dPGJ(2) inhibits LPS-induced IL-10 and IL-12 production by macrophages. A different agonist of PPARgamma, 13-hydroxyoctadecadienoic acid, similarly inhibited the production of IL-10 and IL-12 in response to LPS. Further, dPGJ(2) did not appear to act through the PGD(2) receptor. These results suggest that dPGJ(2) may inhibit LPS-induced IL-10 and IL-12 production by macrophages through PPARgamma.

Animals↗

Polarized XAFS study of high-temperature phases of NaNbO3.

Temperature dependence of the Nb displacement relative to the center of oxygen octahedron in NaNbO3 has been studied by polarized Nb K XAFS. Spectra were measured at two orientations of a single crystalline sample. Room temperature EXAFS data are in a good agreement with earlier X-ray diffraction data: Nb antiferroelectric displacements were found to be orthogonal to the b axis. Analysis of the temperature dependent EXAFS data didn't reveal any abrupt changes of Nb-O distances in the phase transition points. In all high-temperature paraelectric phases Nb appeared to be displaced to the off-center positions. Displacements, orthogonal to b axis, remained almost constant, while displacement along b axis gradually increased with temperature, so that in the cubic phase the displacements along all axes became equal. This shows, that disorder plays an important role in the high temperature phases. The above results are supported also by the analysis of the pre-edge structure, - the integral intensity of the pre-edge peak was temperature-independent when the polarization vector of the X-rays was orthogonal to b axis and gradually increased with temperature when the polarization was parallel to b.

Journal Article↗

Pore distribution effect of activated carbon in adsorbing organic micropollutants from natural water.

Adsorption isotherms of organic micropollutants in coexistence with natural organic matter (NOM) were analyzed to evaluate the impacts of pore size distribution of activated carbon (AC) on the competition effects of the NOM. Single solute adsorption experiments and simultaneous adsorption experiments with NOM contained in a coagulation-pretreated surface water were performed for four agricultural chemicals and three coal-based activated carbons (ACs) having different pore distributions. The results showed that, for all the carbons used, the adsorption capacity of the chemicals was reduced distinctly in the presence of NOM. Such a reduction was more apparent for AC with a larger portion of small pores suitable for the adsorption of small organic molecules and for the agricultural chemicals with a more hydrophilic nature. Ideal adsorbed solution theory (IAST) incorporated with the Freundlich isotherm expression (IAST-Freundlich model) could not interpret the impact of NOM on the adsorption capacity of the chemicals unless a pore blockage effect caused by the adsorption of NOM was also considered. By taking into account this effect, the adsorption isotherm of the chemicals in the presence of NOM was well described, and the capacity reduction caused by the NOM was quantitatively assessed from the viewpoints of the site competition and the pore blockage. Analytical results clearly indicated that pore blockage was an important competition mechanism that contributed to 10-99% of the total capacity reductions of the chemicals, the level depended greatly on the ACs, the chemicals and the equilibrium concentrations, and could possibly be alleviated by broadening the pore size distributions of the ACs to provide a large volume percentage for pores with sizes above 30 A.

Adsorption↗

Assessment of styrene oligomers eluted from polystyrene-made food containers for estrogenic effects in in vitro assays.

Recently, several substances from among the huge numbers of chemicals used by mankind have been implicated as instigators of disrupted endocrine function and related human health problems. Polystyrene (PS) is one of the most frequently used resins in the world, and the styrene oligomer dissolved out from PS has been designated as a potential trigger of estrogen-like activity in the Wingspread Declaration and the Japan Environment Agency's SPEED98 [JEA (Japan Environment Agency) Strategic Problem on Environmental Endocrine Disruptors '98 (SPEED) '98), http://www.env.go.jp/en/pol/speed98/sp98.html]. In order to assess the endocrine disrupting effect of styrene oligomers, we tested one styrene monomer (SM), three styrene dimers (SDs) and seven styrene trimers (STs), newly isolated from optical isomers, known to dissolve in small amounts from cup noodle containers made of polystyrene by the estrogen receptor binding assay, luciferase reporter gene assay, and human breast cancer cell MCF-7 proliferation assay. In all three tests, none of the SM, SDs and STs showed any significant activity. Accordingly, we concluded that these substances have no estrogenic activity.

Animals↗

Quinolones alter defense reactions mediated by macrophages.

The innate host defense system is regulated in part by the number and activation of the function of neutrophils and macrophages. The immunological effects of a variety of quinolones on host defense functions of macrophage are reported. Ofloxacin (OFLX), lomefloxacin (LFLX), tosufloxacin (TFLX), fleroxacin (FLRX), sparfloxacin (SPFX) and levofloxacin (LVFX) significantly inhibited phagocytosis of Escherichica coli by macrophages. Moreover, TFLX markedly potentiated the expression of the adhesion molecule Mac-1 by macrophages. No significant alteration was detected in the adherence and the expression of adhesion molecule Mac-1 in macrophages treated with the other quinolones. In contrast, OFLX, LFLX, TFLX, and LVFX were effective in significantly increasing the production of hydrogen peroxide, while the other agents did not. These results suggest that the quinolones at a therapeutic concentration differentially affect phagocytosis, adhesion, and the production of hydrogen peroxide by macrophages.

Animals↗

Comparison of the effect of lidocaine-epinephrine and prilocaine-felypressine to alter macrophage functions.

In vitro treatment of macrophages with lidocaine-epinephrine or prilocaine-felypressine resulted in inhibition of their adhesion, chemotaxis and phagocytosis. However, prilocaine-felypressine was a much more potent inhibitor of adhesion and phagocytosis than lidocaine-epinephrine. On the other hand, lidocaine-epinephrine induced transient potentiation of superoxide anion production by macrophages, while prilocaine-felypressine consistently inhibited this. Moreover, lidocaine-epinephrine and prilocaine-felypressine both inhibited the production of hydrogen peroxide. In contrast, epinephrine strongly potentiated superoxide anion production, while markedly inhibiting hydrogen peroxide production. This potentiation by epinephrine was not prevented by adrenergic antagonists. In addition, superoxide dismutase potentiated the production of hydrogen peroxide, which was in part prevented by epinephrine. These results suggest that lidocaine-epinephrine and prilocaine-felypressine inhibit adhesion, chemotaxis, phagocytosis, and the production of hydrogen peroxide by macrophages. In addition, lidocaine-epinephrine evidently differs from prilocaine-felypressine regarding the molecular mechanisms underlying the modulation of superoxide anion production by macrophages.

Adrenergic Agonists↗

Histamine inhibits chemotaxis, phagocytosis, superoxide anion production, and the production of TNFalpha and IL-12 by macrophages via H2-receptors.

Histamine is released from stimulated basophils and mast cells, and plays an important role in the pathogenesis of allergic inflammatory processes. In vitro treatment of macrophages with histamine resulted in inhibition of chemotaxis. Moreover, histamine at l0(-5) M markedly inhibited the production of superoxide anions by both opsonized zymosan-A and phorbol 12-myristate 13-acetate (PMA) stimulated macrophages and histamine at a concentration range of 10(-7) to 10(-5) M significantly inhibited phagocytosis of Escherichia coli by macrophages. In addition, H2-selective receptor agonist dimaprit resulted in inhibition of macrophage chemotaxis and markedly inhibited the production of superoxide anion by PMA-stimulated macrophages and phagocytosis of E. coli by macrophages. On the other hand, histamine and dimaprit both resulted in a concentration-dependent inhibition of lipopolysaccharide-induced production of TNFalpha and IL-12 by macrophages. These results suggest that histamine and dimaprit may inhibit chemotaxis, phagocytosis, superoxide anion production, and the production of TNFalpha and IL-12 by macrophages via H2-histamine receptors. reserved.

Animals↗

15-Deoxy-delta(12,14)-prostaglandin J2 is a negative regulator of macrophage functions.

15-Deoxy-delta(12,14)-prostaglandin J2 (dPGJ2) is a bioactive metabolite of the J2 series that has been identified as a ligand for peroxisome proliferator-activated receptor gamma (PPARgamma). Because PPARgamma is highly expressed in macrophages obtained from stimulant-elicited peritonitis, but not in resident peritoneal macrophages, the effect of dPGJ2 was tested on innate functions of macrophages. dPGJ2 inhibited adhesion and phagocytosis of Escherichia coli. Inhibition of these functions by dPGJ2 was not mediated via the adhesion molecule Mac-1. In addition, dPGJ2 inhibited chemotaxis toward zymosan-activated serum and it also inhibited the production of superoxide anion when macrophages were stimulated with phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan (OPZ), but not lipopolysaccharide. Similarly, dPGJ2 inhibited the production of hydrogen peroxide when macrophages were stimulated with either PMA or OPZ. These studies suggest that dPGJ2 may be a negative regulator of macrophage functions.

Animals↗

The effect of alpha2,6-linked sialic acid on anti-IgM antibody-induced apoptosis in Ramos cells.

Apoptosis in B cells is induced through the B cell antigen receptor (BCR) and affects the sialic acid recognition molecules on B cells. We investigated the effects of alpha(1)-acid glycoprotein (AGP), which mainly contains alpha2,6-linked sialic acid, on anti-IgM antibody (Ab)-induced apoptosis in Ramos cells, which are derived from Burkitt's lymphoma. When Ramos cells were incubated with anti-IgM-Ab in plates coated with AGP, neuraminidase-digested AGP (asAGP) or alpha2,3-sialylated AGP (2,3AGP), apoptosis was suppressed only in those coated with AGP. We also studied the effects of CD22, which is expressed on the surface of mature B cells and binds to sugar chains containing alpha2,6-linked sialic acid, with anti-CD22 monoclonal antibody (mAb). Anti-CD22mAb enhanced anti-IgM Ab-induced apoptosis in Ramos cells. These contradictory results suggested that the recognition molecules for alpha2,6-linked sialic acid on AGP, which inhibits B-cell apoptosis, is distinct from CD22, or that different binding domains of CD22 between alpha2,6-linked sialic acid and anti-CD22 mAb exert opposite functions of suppression or enhancement to anti-IgM Ab-induced B cells.

Antibodies, Anti-Idiotypic↗

NTE-122, an acyl-coa:cholesterol acyltransferase inhibitor, prevents the progression of atherogenesis in cholesterol-fed rabbits.

The cholesterol-lowering and anti-atherosclerotic effects of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylaminophenyl)ureido]methyl]cyclohexane), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, were evaluated in 1% cholesterol diet-fed rabbits. NTE-122 (1, 3 and 10 mg/kg per day) lowered the total cholesterol levels in both plasma and liver dose-dependently (by 99% and 94% at 10 mg/kg per day, respectively). In the aortic wall of the rabbits given NTE-122, the atherosclerotic lesion area in both aortic arch and thoracic aorta were dose-dependently reduced (by 100% at 10 mg/kg per day), and the total cholesterol content in aortic arch was also lowered significantly at more than 3 mg/kg per day. These results suggest that NTE-122 is capable of exhibiting anti-atherosclerotic effects.

Acetyl-CoA C-Acetyltransferase↗

Lactobacillus casei NY1301 increases the adhesion of Lactobacillus gasseri NY0509 to human intestinal caco-2 cells.

In the presence of Lactobacillus casei NY1301, the adhesion of Lactobacillus gasseri NY0509 to cultured human intestinal Caco-2 cells was significantly increased (P<0.01). In contrast, L. gasseri NY0509 did not affect the adhesion of L. casei NY1301. A heat-stable cell component of L. casei NY1301 was involved in this increase of adhesion. These results suggest that a combination of these strains may have synergistic effects of adhesion to human intestinal mucosa.

Bacterial Adhesion↗