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Biomedical subjects

Y Azuma

Publications and source records attributed to Y Azuma.

At least 37 records · Page 2Linked to original sources
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by acting on the various cellular reactions in the fracture callus.

Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1-8; Ph-2, days 9-16; Ph-3, days 17-24; throughout [T], days 1-24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (muCT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) muCT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling.

Animals↗
PubMed2001

Targeted disruption of cadherin-11 leads to a reduction in bone density in calvaria and long bone metaphyses.

The migration and adhesion of osteoblasts requires several classical cadherins. Cadherin-11, one of the classical cadherins, was expressed in mouse osteoblasts in skull bone and femur, revealed by immunohistochemistry. To elucidate the function of cadherin-11 in osteoblastogenesis, cadherin-11 null mutant mice were investigated. Although apparently normal at birth, Alizarin red staining of null mutant mice showed a reduced calcified area at the frontal suture that caused a round-shaped calvaria with increasing animal age to 3 months. Consequently, there was a reduction in bone density at the femoral metaphyses and the diploë of calvaria in null mutant mice. In the in vitro culture of newborn calvarial cells, the calcified area of mutant cells was smaller than those derived from wild-type littermates. These results show that absence of cadherin-11 leads to reduced bone density in some parts of skeletons including calvaria and long bone metaphyses, and thus suggest that cadherin-11 plays roles in the regulation of osteoblast differentiation and in the mineralization of the osteoid matrix.

Animals↗
PubMed2001

Tumor necrosis factor alpha-induced osteoclastogenesis requires tumor necrosis factor receptor-associated factor 6.

Although tumor necrosis factor receptor-associated factor 6 (TRAF6) is required in receptor activator of NF-kappaB-receptor activator of NF-kappaB ligand (RANK-RANKL) signaling for osteoclastogenesis, it has remained unclear whether TRAF6 is crucial in tumor necrosis factor alpha (TNF-alpha)-induced osteoclastogenesis. We examined TRAF6 function in the TNF-alpha-induced osteoclastogenesis by using osteoclast progenitor cells from TRAF6-deficient mice. The results indicated that TNF-alpha did not effectively induce osteoclast differentiation from osteoclast progenitor cells derived from these mice into mature multinucleated osteoclasts, although c-jun N-terminal kinase (JNK) and TNF-alpha activation was observed in osteoclast progenitor cells. Thus, we have provided the first evidence showing that TRAF6 is involved in TNF-alpha-induced osteoclastogenesis.

Animals↗
PubMed2001

Low-intensity pulsed ultrasound initiates bone healing in rat nonunion fracture model.

Low-intensity pulsed ultrasound exposure has been shown clinically to shorten the fracture repair process and to induce healing of nonunions in humans, but its mechanism of action remains unclear. In this study we investigated the effect and mechanism of low-intensity pulsed ultrasound on nonunion fracture healing in rat tibias. A consistently reproducible nonunion was produced in rat tibias by muscle interposition without osteotomy. This model was produced by creating a closed tibial fracture with only the distal end of the tibialis anterior muscle interposed into the fracture site. One limb was noninvasively exposed to low-intensity pulsed ultrasound (a 200-millisecond burst of sine waves of 1.5 MHz, repeating at 1.0 kHz) for 20 minutes daily. The incident intensity was approximately 30 mW/cm2. Rats were killed at intervals between 2 and 6 weeks. The events were assessed by radiographs, microfocus X-ray computed tomograms, and histologic examination. After 6 weeks of exposure, 7 of 14 nonunion fractures showed healing on radiologic assessment. The results of three-dimensional microfocus X-ray computed tomographic reconstruction and histologic examination also supported this finding. On the other hand, all control tibias remained in a state of nonunion during the same period. These results indicate that low-intensity pulsed ultrasound promotes healing in the rat nonunion fracture model.

Animals↗
PubMed2001

Effect of Actinobacillus actinomycetemcomitans protease on the proliferation of gingival epithelial cells.

OBJECTIVE: Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) has been implicated as an important pathogen in periodontal disease. The aim of this report is to examine the effect of in vitro application of A. actinomycetemcomitans protease on the cell growth, DNA synthesis, and fibronectin level of human gingival epithelial cells. MATERIALS AND METHODS: A. actinomycetemcomitans protease was isolated from the culture supernatant of A. actinomycetemcomitans. Human gingival epithelial cells were incubated in the presence or absence of A. actinomycetemcomitans protease (0.01, 0.1, or I U) for 48 h. The proliferation of cells were tested with the MTT assay and the BrdU assay. The fibronectin level was examined by flow cytometric analysis. RESULTS: The cell growth rate, DNA synthesis rate, and fibronectin level of the gingival epithelial cells that had been incubated with protease, were lower than the respective values in the untreated gingival epithelial cells; as the dose of A. actinomycetemcomitans protease increased, the cell growth rate, DNA synthesis rate, and fibronectin level of the gingival epithelial cells decreased. A. actinomycetemcomitans protease may inhibit the proliferation of human gingival epithelial cells. CONCLUSIONS: This protease may play a key role as a major virulence factor in the development of periodontal disease.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

Immunomodulation of the neutrophil respiratory burst by endomorphins 1 and 2.

Opioid peptides were found to be released from cells of the immune system during inflammation and stress, and were associated with altered immune responses. Production of superoxide anions by PMA-stimulated neutrophils was markedly inhibited in a concentration-dependent manner by preincubation for 15 min with 10(-18) - 10(-6) M of the endogenous opioid peptides endomorphin 1 or 2. Inhibition was prevented by prior treatment with the micro-opioid receptor-selective antagonist beta-funaltrexamine at 10(-12) - 10(-8) M, but not the delta-opioid receptor-selective antagonist naltrindole. In contrast, endomorphins 1 and 2 caused significant potentiation of superoxide anion production in unstimulated neutrophils. These results suggest that the endogenous opioid peptides endomorphins 1 and 2 may modulate the production of superoxide anions in neutrophils via mu-opioid receptors.

Animals↗
PubMed2000

Suppression of azoxymethane-induced colon carcinogenesis in male F344 rats by mandarin juices rich in beta-cryptoxanthin and hesperidin.

We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes. In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of 69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5 administration significantly reduced the frequency of colonic carcinoma [MJ: 35% (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15% (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47% reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5: 0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These findings might suggest effective chemopreventive ability of MJs, especially MJ5, in colon tumorigenesis.

Adenocarcinoma↗
PubMed2000

Toll-like receptor 4-mediated signal pathway induced by Porphyromonas gingivalis lipopolysaccharide in human gingival fibroblasts.

The lipopolysaccharide (LPS) secreted by Porphyromonas gingivalis is implicated in the initiation and progression of periodontitis. Human gingival fibroblasts (HGFs) are the major constituent of gingival connective tissue. In this study, we examined the expression of Toll-like receptor 4 (TLR4) on HGFs by flow cytometric analysis, and studied the signal transduction induced by LPS stimulation of HGFs by enzyme-linked immunosorbent assay, Western blotting, and immunoprecipitation. We show that LPS binds to HGFs, and that HGFs express TLR4 and myeloid differentiation primary response gene 88 (MyD88). P. gingivalis LPS-induced interleukin (IL)-1 production in HGFs was inhibited by anti-TLR4 antibody. P. gingivalis LPS treatment of HGFs activated several intracellular proteins including protein tyrosine kinases, and upregulated the expression of IL-1 receptor-associated kinase (IRAK), nuclear factor-kappaB (NF-kappaB), and activating protein-1 (AP-1), and these events were suppressed by anti-TLR4 monoclonal antibody. Our findings suggest that the binding of P. gingivalis LPS to TLR4 on HGFs activates various second messenger systems.

Antibodies, Monoclonal↗
PubMed2000

Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts.

Osteoclast progenitors differentiate into mature osteoclasts in the presence of receptor activator of NF-kappaB (RANK) ligand on stromal or osteoblastic cells and monocyte macrophage colony-stimulating factor (M-CSF). The soluble RANK ligand induces the same differentiation in vitro without stromal cells. Tumor necrosis factor-alpha (TNF-alpha), a potent cytokine involved in the regulation of osteoclast activity, promotes bone resorption via a primary effect on osteoblasts; however, it remains unclear whether TNF-alpha can also directly induce the differentiation of osteoclast progenitors into mature osteoclasts. This study revealed that TNF-alpha directly induced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), which produced resorption pits on bone in vitro in the presence of M-CSF. The bone resorption activity of TNF-alpha-induced MNCs was lower than that of soluble RANK ligand-induced MNCs; however, interleukin-1beta stimulated this activity of TNF-alpha-induced MNCs without an increase in the number of MNCs. In this case, interleukin-1beta did not induce TRAP-positive MNC formation. The osteoclast progenitors expressed TNF receptors, p55 and p75; and the induction of TRAP-positive MNCs by TNF-alpha was inhibited completely by an anti-p55 antibody and partially by an anti-p75 antibody. Our findings presented here are the first to indicate that TNF-alpha is a crucial differentiation factor for osteoclasts. Our results suggest that TNF-alpha and M-CSF play an important role in local osteolysis in chronic inflammatory diseases.

Animals↗
PubMed2000

Anabolic response of mouse bone-marrow-derived stromal cell clone ST2 cells to low-intensity pulsed ultrasound.

The effects of 20-min exposure to low-intensity, pulsed ultrasound were investigated in ST2 cells of bone marrow stromal origin. They responded to ultrasound with elevated levels of IGF mRNAs, osteocalcin, and bone sialoprotein mRNAs. The upregulated expression of these messages appeared in a biphasic manner, with the first peak resistant to the protein synthesis inhibitor cycloheximide, and a second peak that was eliminated by NS398, an inhibitor of the inducive prostaglandin G/H synthase (cyclooxygenase-2). A cumulative effect of mechanical loading called the memory effect, which has been observed in vivo, can be explained from such a biphasic anabolic reaction mediated by prostaglandins. The upregulation of IGF or osteocalcin mRNAs can be observed even at 24 h after the initiation of the 20-min exposure to ultrasound. Our results suggest that this low-intensity, pulsed ultrasound, which has been clinically used to accelerate the healing processes of fractured bone, induces a direct anabolic reaction of osteogenic cells, leading to bone matrix formation.

Animals↗