K Honda

Akita University Hospital, Akita, Akita, Japan

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Publications (20)77.7 Total impact

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    ABSTRACT: Linezolid exhibits a broad spectrum of activity against Gram-positive cocci, including Methicillin-resistant Staphylococcus aureus (mRSA) and vancomycin-resistant enterococci (VRe). However, recent studies have already reported the emergence of linezolid-resistant mRSA or VRe. the purpose of this study is to evaluate not only the efficacy of linezolid for the treatment of nosocomial mRSA infections but also the effect of a notification policy of linezolid use. the charts of inpatients who had been treated with linezolid were reviewed for clinical outcome. After introduction of the notification policy of linezolid use, the clinical success rate was 73.3%, and the rate of appropriate linezolid use was 80%, whereas the success rate was 14.2% and the appropriate use rate was 14.3% before the policy. in conclusion, appropriate use controlled by a notification policy of antibiotics use is essential for prevention of the emergence and spread of linezolid-resistant bacteria, and for proper demonstration of its antibacterial ability.
    Journal of chemotherapy (Florence, Italy) 03/2009; 21(1):52-7. · 0.83 Impact Factor
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    ABSTRACT: Reactive oxygen species (ROS) from eosinophils are known to cause tissue damage in allergic inflammation. CC chemokines, especially eotaxin and regulated on activation, normal T-cell expressed and secreted (RANTES), are involved not only in chemotaxis but also in eosinophil activation, such as ROS production. It has been shown that eosinophils from allergic patients are not functionally equivalent to those from normal subjects. In the present study, the characteristics of chemokine-primed ROS production in eosinophils from allergic patients and normal controls were compared. After pretreatment with chemokines, eosinophils were stimulated with calcium ionophore A23187. ROS production by eosinophils was measured using luminol-dependent chemiluminescence. Both RANTES and eotaxin exhibited a priming effect on calcium ionophore-induced ROS production from eosinophils. Despite there being no difference in expression of CC chemokine receptor 3, the priming effect of RANTES and eotaxin was significantly enhanced in eosinophils from the patients. Interleukin-5 further enhanced the priming effect of chemokines in eosinophils from normal subjects, but not those from allergic subjects. The present results suggest an upregulated response to chemokines in eosinophils from allergic patients, and that interleukin-5 can induce a similar phenotype to that found in vivo in allergic patients.
    European Respiratory Journal 07/2003; 21(6):925-31. · 6.36 Impact Factor
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    ABSTRACT: Adhesion molecules and C-C chemokines play an important role in the accumulation of eosinophils in allergic inflammation. In the present study, the expression and function of adhesion molecules on eosinophils from asthmatic patients and involvement of RANTES and eotaxin were examined. Eosinophils isolated by the CD16 negative selection method were stimulated with or without RANTES or eotaxin. Expression of b integrins on eosinophils and the functional adherence to recombinant soluble intercellular adhesion molecule-1 (r-sICAM-1)-coated plates were examined. Compared with normal subjects, eosinophils from asthmatic patients showed increased expression of b2 integrins and functional adherence to r-sICAM-1-coated plates. RANTES and eotaxin augmented the functional adherence of eosinophils without a significant upregulation of b2 integrins. Anti-b2 integrin antibody inhibited the augmentative effect on eosinophil adherence of RANTES and eotaxin. Pertussis toxin, wortmannin, and genistein inhibited chemokine-induced adherence. RANTES and eotaxin are closely related to eosinophil accumulation not only as chemotactic agents but also as augmentative agents for eosinophil adherence through involvement in functional eosinophil adherence to ICAM-1 by a possible qualitative change of b2 integrins. Pertussis toxin-sensitive G proteins, PI3 kinase, and tyrosine kinase are involved in signal transduction leading to activation of b2 integrins on eosinophil following stimulation with RANTES and eotaxin.
    Beiträge zur Klinik der Tuberkulose 02/2002; 180(5):251-63. · 2.06 Impact Factor
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    ABSTRACT: The CC chemokine eotaxin not only attracts eosinophils to inflamed sites but also promotes adhesion, degranulation and reactive oxygen species production of eosinophils. Reactive oxygen species released from eosinophils are believed to injure epithelial cells at inflamed sites, resulting in airway hyperresponsiveness. Roxithromycin has been reported to have antiasthmatic effects, although its mechanism of action is not thoroughly understood. Therefore, the effect of roxithromycin on eotaxin-primed reactive oxygen species production from eosinophils was studied. Reactive oxygen species production by eosinophils cultured with or without roxithromycin was evaluated using luminol-dependent chemiluminescence. Roxithromycin inhibited the release of reactive oxygen species from eosinophils evoked with the calcium ionophore A23187, regardless of pretreatment with or without eotaxin. Roxithromycin may protect epithelial cells at inflamed sites, at least partly by inhibiting the release of reactive oxygen species from eosinophils.
    International Archives of Allergy and Immunology 02/2001; 125 Suppl 1:38-41. · 2.25 Impact Factor
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    ABSTRACT: It is assumed that the very late antigen-4 (VLA-4) plays a key role in selective migration and accumulation of eosinophils to the allergic inflammatory focus. The regulatory mechanism for VLA-4 expression is poorly understood, as is its relationship between other adhesion molecules. The aim of the study was to elucidate the relationship between VLA-4 expression and the activation of eosinophils. The surface expression of VLA-4, Mac-1, ICAM-1, CD4, CD25, CD69, CD89, IL-5 receptor and GM-CSF receptor on eosinophils isolated from the peripheral blood of 15 patients with eosinophilia and 16 healthy volunteers was measured. The surface expression of VLA-4 presented in mean fluorescent intensity by flow-cytometric analysis showed a significant decrease in the patients with eosinophilia (>700 eosinophils/microl) compared to that of the subjects without eosinophilia. On the other hand, the surface expression of Mac-1 was significantly increased in the patients with eosinophilia. There was an inverse correlation between the expression of VLA-4 and that of Mac-1 (r = -0.81) on the eosinophils obtained from the patients with eosinophilia. The changes on the surface expressions of Mac-1 and VLA-4 may be indicating the activation of eosinophils in the patients with eosinophilia and may contribute to their migration to the allergic inflammatory focus.
    International Archives of Allergy and Immunology 01/2001; 125 Suppl 1:33-7. · 2.25 Impact Factor
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    ABSTRACT: Recently, adhesion molecules have been suggested to play an important role in allergic inflammatory diseases such as bronchial asthma. It is unclear whether eosinophil activation and paracrine or autocrine synthesis of eosinophilopoietic growth cytokines is mediated through signaling by intercellular adhesion molecule-1 (ICAM-1) and the beta2 integrin family. We examined whether signaling by ICAM-1 and its ligands (beta2 integrins) could prolong eosinophil survival. Eosinophils were isolated from patients with hypereosinophilia by modified CD16 negative selection. After culture with or without recombinant soluble ICAM-1, eosinophil viability was measured by trypan blue dye exclusion. Eosinophil survival was prolonged in cultures with recombinant soluble ICAM-1 compared with cultures without it (P <.01 on days 2, 4, and 6); this effect was dose-dependent. Eosinophil survival in cultures with recombinant soluble ICAM-1 was significantly inhibited by antibodies against ICAM-1 (P <.01), complement receptor 3 (P <.01), and lymphocyte function-associated antigen-1beta (P <.01). Anti-IL-3 showed no effect on eosinophil survival, whereas anti-IL-5 caused partial inhibition of survival. Interestingly, anti-granulocyte/macrophage colony-stimulating factor caused the complete inhibition of eosinophil survival in cultures with recombinant soluble ICAM-1. These results suggested the importance of the beta2 integrins in eosinophil-mediated allergic inflammation.
    Journal of Allergy and Clinical Immunology 08/2000; 106(1 Pt 2):S99-103. · 12.05 Impact Factor
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    ABSTRACT: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. The purpose of this study was to determine clinically useful markers of acute graft-versus-host disease. We measured the serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble c-kit, soluble Fas, soluble intercellular adhesion molecule-1, growth-related oncogene protein-alpha, thrombomodurin, and interleukin-16 in 13 patients at 1 to 7 weeks after allogenic bone marrow transplantation. The patients with acute graft-versus-host disease showed a significant increase of tumor necrosis factor, soluble tumor necrosis factor receptor 1, soluble Fas, soluble intercellular adhesion molecule-1, and growth-related oncogene protein-alpha, although there was a decrease of soluble c-kit. The increases of serum soluble tumor necrosis factor receptor 1, intercellular adhesion molecule-1, and growth-related oncogene protein-alpha were preceded by the elevation of soluble Fas. The patients with acute graft-versus-host disease had increased serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble Fas, and soluble intercellular adhesion molecule 1 and a decreased soluble c-kit level. Tumor necrosis factor-alpha and soluble c-kit were shown to be sensitive and specific parameters for graft-versus-host disease after bone marrow transplantation, and soluble Fas was shown to be a predictor of acute graft-versus-host disease after bone marrow transplantation.
    Journal of Allergy and Clinical Immunology 08/2000; 106(1 Pt 2):S40-4. · 12.05 Impact Factor
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    ABSTRACT: It is known that growth hormones such as insulin-like growth factor-I (IGF-I) and several kinds of cytokines are involved in the regeneration process of injured epithelial cells in chronic respiratory inflammatory diseases such as bronchial asthma. Repetitive degeneration/regeneration processes of the airway epithelial layer is supposed to be responsible for the remodeling and irreversible organic changes of the airway in bronchial asthma. The purpose of this study is to establish a simple and reliable in vitro method for studying airway epithelial cell growth and proliferation using IGF-I. By altering the number of cultured epithelial cells (strain NCI-H(292)), culture duration before stimulation with IGF-I, concentration of IGF-I, and duration of IGF-I stimulation, the optimum conditions for epithelial cell growth was determined. The epithelial cell growth was evaluated using [methyl-(3)H]thymidine uptake. Among various culture conditions, the epithelial cells cultured at 1 x 10(3) cells/well for 24 h followed by 24 h of stimulation by 10(-8) M of IGF-I showed the highest growth. The method for the evaluation of epithelial cell growth established in this study requires a small number of cells and has no complicated procedure. This simple model enables us to investigate the effect of various substances on bronchial epithelial cell growth in the presence of IGF-I.
    International Archives of Allergy and Immunology 06/2000; 122 Suppl 1:59-62. · 2.25 Impact Factor
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    K Honda, J Chihara
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    ABSTRACT: The CC chemokine eotaxin has been shown to possess selective chemotactic activity for eosinophils, the major effector cells in allergic inflammation. Reactive oxygen species (ROS) from eosinophils may damage cells or tissue, such as the mucosal epithelium. In this study, we examined the effect of eotaxin on ROS from eosinophils and compared its activity with RANTES and interleukin (IL)-5. Moreover, we examined the signal transduction of eotaxin and the effect of dexamethasone on ROS from eosinophils. Eosinophils were isolated by modified CD16-negative selection. ROS in luminol-dependent or lucigenin-dependent chemiluminescence reaction were examined. Calcium ionophore A23187 was added to the mixture of eosinophils with luminol or lucigenin, and then ROS were determined. Eotaxin primed the production of ROS in a dose-dependent manner. ROS from untreated eosinophils evoked with calcium ionophore A23187 in luminol-dependent chemiluminescence gave a maximal value of 4957+/-1035 intensity counts (IC) (mean+/-SE, n=7) and an integral value of 15.75+/-3.14 IC (x10(-4)), while eosinophils that were treated with eotaxin gave maximal values of 11 142+/-2300 IC (10 nM) and 29165+/-3718 IC (100 nM) and integral values of 41.07+5.44 IC (x10(-4)) (10 nM) and 152.90+/-22.38 IC (x10(-4))(100 nM). Moreover, eotaxin was less effective as a priming agent with lucigenin-sensitive pathways than luminol-sensitive pathways. Among several kinds of eosinophils activating cytokines and chemokines, the priming effect of eotaxin on RO5 was the most potent. Eotaxin-primed ROS were inhibited by pertussis toxin, which ADP-ribolysates G proteins; wortmannin, a phosphatidylinositol-3-kinase inhibitor; and genistein, a tyrosine kinase inhibitor, suggesting the involvement of pertussis toxin-sensitive G proteins, phosphatidylinositol-3-kinase, and tyrosine kinase in the signal transduction of eotaxin. Moreover, dexamethasone inhibited ROS from not only untreated eosinophils but also eosinophils treated with eotaxin. Eotaxin may play an important role in the pathogenesis of allergic inflammation through eosinophil activation by priming of eosinophil oxidative metabolism, as well as by involvement in selective eosinophil chemotaxis.
    Allergy 01/2000; 54(12):1262-9. · 5.88 Impact Factor
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    ABSTRACT: Background: Recently, adhesion molecules have been suggested to play an important role in allergic inflammatory diseases such as bronchial asthma. It is unclear whether eosinophil activation and paracrine or autocrine synthesis of eosinophilopoietic growth cytokines is mediated through signaling by intercellular adhesion molecule-1 (ICAM-1) and the β2 integrin family. Objective: We examined whether signaling by ICAM-1 and its ligands (β2 integrins) could prolong eosinophil survival. Methods: Eosinophils were isolated from patients with hypereosinophilia by modified CD16 negative selection. After culture with or without recombinant soluble ICAM-1, eosinophil viability was measured by trypan blue dye exclusion. Results: Eosinophil survival was prolonged in cultures with recombinant soluble ICAM-1 compared with cultures without it (P
    Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2000; 106(1).
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    ABSTRACT: The early detection of retroperitoneal masses in children, such as neuroblastoma, Wilm's tumor, hydronephrosis and cystic renal diseases, has a great clinical importance for the improvement of their prognosis. The kidney is often affected in its size or position by these lesions, and occasionally allows clinicians to find a clue to reach the correct diagnosis before the patient become symptomatic. Since we had no clinically available nomogram on the position and the size of the kidney in Japanese children, we measured the size and position of the kidneys on plain abdominal x-rays in 347 Japanese children in preschool years with a special attention to their relationship with the spine. As a result, the nomogram showed age dependent growth of the kidneys keeping almost the same ratio with the spine, while the distance between the upper pole of the kidney and the spine remained less than 10 mm in all age groups. Our nomogram may be useful not only for picking up the malposition of the kidneys but also for the follow up of the patients with chronic renal diseases affecting the growth of the kidneys.
    The Tohoku Journal of Experimental Medicine 06/1999; 188(1):23-9. · 1.37 Impact Factor
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    ABSTRACT: RANTES and eotaxin are important chemokines involved in the activation and migration of eosinophils and are considered to play a major role in allergic inflammation. In this study, we used RT-PCR to investigate the kinds of cells that express mRNA for CCR3, a common receptor of these chemokines, and eotaxin, a ligand for CCR3. CCR3 mRNA was expressed in eosinophils, peripheral mononuclear cells, an eosinophilic cell line (EoL-1), a bronchial epithelial cell line (NCI-H(292)), human endothelial cells and nasal washings from patients with allergic rhinitis. These results suggest that the CCR3-eotaxin system plays an important role in generating inflammation, since these substances are expressed not only in cells implicated in activation or migration of eosinophils but also in various other cells involved in allergic inflammation.
    International Archives of Allergy and Immunology 02/1999; 120 Suppl 1:45-7. · 2.25 Impact Factor
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    ABSTRACT: The CC chemokine eotaxin is a selective chemoattractant for eosinophils. Eosinophils have been considered to be the major effector cells in allergic inflammation, since not only eosinophil-specific granule proteins but also reactive oxygen species (ROS) from eosinophils may cause the damage to the cells or tissue of the mucosal epithelium. In this study, we examined the effect of eotaxin on ROS from an eosinophil cell line, YY-1. ROS in luminol-dependent reaction were examined. Calcium ionophore A23187 were added to the mixture of YY-1 cells with luminol, and then ROS were determined. Eotaxin primed the production of ROS from YY-1 cells. ROS from untreated YY-1 cells evoked with calcium ionophore A23187 in luminol-dependent chemiluminescence gave a maximal value of 1,928 +/- 223 intensity counts (IC; mean +/- SE, n = 4) and an integral value of 17.04 +/- 1. 51 IC (x10(-4)), while eosinophils that were treated with eotaxin gave a maximal value of 2,264 +/- 86 IC (10 nM), 2,691 +/- 124 IC (100 nM) and an integral value of 21.22 +/- 0.67 IC (x10(-4); 10 nM), 26.20 +/- 1.41 IC (x10(-4); 100 nM). Eotaxin might play important roles in the pathogenesis of allergic inflammation through eosinophil activation by priming of eosinophil oxidative metabolism as well as involvement in selective eosinophil chemotaxis.
    International Archives of Allergy and Immunology 02/1999; 120 Suppl 1:48-50. · 2.25 Impact Factor
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    ABSTRACT: Activation of eosinophils is closely associated with the pathology of allergic inflammatory disease, especially bronchial asthma. We recently investigated the activation of eosinophils by applying whole blood to a flow cytometer. We measured here beta1 and beta2 integrin on eosinophils stimulated by phorbol-12-myristate-13-acetate (PMA)/ionomycin to evaluate eosinophil activation in vitro using whole blood. Heparinized whole blood was diluted with the same volume of RPMI 1640, then cells were incubated in the presence or absence of PMA and ionomycin for 45 min at 37 degrees C. After hemolyzation with lysing solution, flow-cytometric findings for CR3, LFA1-alpha, LFA1-beta and VLA-4 expression on eosinophils were examined. Mean fluorescent intensity (MFI) of CR3 and LFA1-beta stimulated by PMA and ionomycin was significantly higher than that of the unstimulated control. MFI of LFA1-alpha showed no significant difference from the unstimulated control. On the other hand, MFI of VLA-4 tended to decrease. Our method to distinguish eosinophils from various cell groups in whole blood is simple and time-saving, similar to conditions in vivo and may allow intensive investigation of eosinophils in clinical laboratories as well as in research laboratories. We are currently investigating the influence of different kinds of stimulations, regulation factors or agents on eosinophils using this method.
    International Archives of Allergy and Immunology 02/1999; 120 Suppl 1:27-9. · 2.25 Impact Factor
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    ABSTRACT: RANTES has been shown to possess chemotactic activity for eosinophils, which have also been considered to play a role in allergic inflammation through reactive oxygen species. Thus, in this study, we examined the effect of RANTES on radical oxygen products from eosinophils. Purified eosinophils by CD16-negative selection or an eosinophilic cell line (EoL-1) were incubated with or without RANTES (2.5 x 10(-6) M). To the mixture of eosinophils and luminol, calcium ionophore (A23187) or opsonized zymosan (OZ) was added, and radical oxygen products were determined by luminol-dependent chemiluminescence for 600 s. Eosinophil-mediated radical oxygen products of untreated eosinophils produced with A23187 gave a peak value of 14.09 +/- 2.40 (mean +/- SE, n = 12) relative light units (RLU) and an integrated value of 3232.20 +/- 513.09 RLU. However, with treatment with RANTES, a peak value of 18.66 +/- 2.40 RLU and an integrated value of 5301.05 +/- 561.02 RLU were obtained. Eosinophil oxidative metabolism-induced A23187 or OZ was apparently augmented by the preincubation with RANTES. In addition, the radical oxygen products of EoL-1 showed similar results. Thus, we concluded that RANTES may play an important role in the pathogenesis of allergic inflammation through its involvement in eosinophil activation, as evidenced by oxygen products, as well as in selective eosinophil infiltration as selective eosinophil chemoattractant.
    Allergy 01/1999; 53(12):1178-82. · 5.88 Impact Factor
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    ABSTRACT: Adhesion molecules are thought to play a key role in inflammatory processes in bronchial asthma. We previously observed an increased expression of the beta2-integrin family on an eosinophilic cell line (EoL-1) by platelet-activating factor (PAF). In the present study, we examined the effect of ibudilast (KC-404), a novel anti-asthma agent, on beta2 integrin expression induced by PAF. EoL-1 cells (1x10(6)/mL) were incubated in the presence or absence of 10(-6) M ibudilast (KC-404), then cells were cultured in the presence or absence of PAF (10(-7) M) for 45 minutes. Flow cytometric analysis for CD11a, CD11b, and CD18 expression was examined. Ibudilast had an inhibitory effect on beta2 integrin expression induced by PAF [CD11a: 84.8% versus 73.1% (preincubation with ibudilast), CD11b: 35.8% versus 26.2%, CD18 74.9% versus 65.6%]. Ibudilast (KC-404) has anti-inflammatory activities through its inhibitory effect on the expression of adhesion molecules on eosinophils.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/1998; 81(5 Pt 1):448-50. · 3.45 Impact Factor
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    ABSTRACT: RANTES (regulated on activation, normal T expressed and secreted) has been shown to possess chemotactic activity for eosinophils. Eosinophils have been considered to play a key role in the allergic inflammation through the release of inflammatory molecules such as radical oxygen products. Thus, in this study, we examined the effect of RANTES on radical oxygen products from eosinophils. Eosinophils were isolated from heparinized venous blood of patients with bronchial asthma by the modified CD16-negative depletion method. Radical oxygen products were examined in terms of lucigenin-dependent chemiluminescence. To a mixture of 50 microl of eosinophils (2x10(6)/ml) and 50 microl of lucigenin (5x10(-4)M), 50 microl of calcium ionophore A23187 (final concentration 10(-5)M) was added, and radical oxygen products were determined for 600 s. RANTES treatment resulted in the enhancement of peak value (0.64+/-0.23 RLU) and integrated value (119.08+/-20.52 RLU) as compared to untreated cells (0.15+/-0.03 RLU, 29.48+/-8.92 RLU, respectively). CONCLUSIONS We could conclude that RANTES might play an important role in the pathogenesis of allergic inflammation through involvement in selective eosinophil infiltration and eosinophil activation by augmentation of eosinophil oxidative metabolism.
    International Archives of Allergy and Immunology 10/1998; 117 Suppl 1:40-3. · 2.25 Impact Factor
  • Annals of Allergy Asthma & Immunology - ANN ALLERGY ASTHMA IMMUNOL. 01/1998; 81(5):448-450.
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    ABSTRACT: RANTES is considered to play an important role in various immune and allergic disorders since it is a potent chemoattractant for inflammatory cells such as eosinophils, memory T cells, and monocytes. To investigate the possible role of RANTES in the pathogenesis of bronchial asthma. The plasma level of RANTES was measured in 12 asthma patients and 15 normal controls by a sandwich enzyme-linked immunosorbent assay. In the patients with asthma, the plasma RANTES level was significantly elevated during acute attacks compared to that in the controls. In addition, it was higher than that during the asymptomatic state in the same patients. Plasma beta-thromboglobulin levels were also elevated in asthma patients during acute attacks and showed a correlation with the RANTES level. These findings suggest a role for RANTES in the pathogenesis of asthma and a possible role for platelets in RANTES release in asthma.
    Journal of Allergy and Clinical Immunology 01/1998; 100(6 Pt 2):S52-5. · 12.05 Impact Factor
  • Japanese Journal of Clinical Immunology 01/1998; 20(6):481-5.