研究者詳細 - 福永　興壱

論文 - 福永　興壱

分割表示 217 件中 201 - 217 件目／全件表示 >>

Regulation of phosphatidylinositol 3-kinase by polyisoprenyl phosphates in neutrophil-mediated tissue injury

Bonnans, C., Fukunaga, K., Keledjian, R., Petasis, N. A. and Levy, B. D.

J Exp Med 203 （ 4 ） 857 - 63 2006年04月

ISSN 0022-1007

Neutrophils play a central role in host defense, inflammation, and tissue injury. Recent findings indicate a novel role for polyisoprenyl phosphates (PIPPs) as natural down-regulatory signals in neutrophils. The relationship between PIPPs and neutrophil early activating signals, such as phosphoinositides, has not been previously determined. Here, we establish presqualene diphosphate (PSDP) as an endogenous PIPP regulator of phosphatidylinositol 3-kinase (PI3K). In human neutrophils, leukotriene B4 (LTB4) triggered rapid decreases in PSDP and reciprocal increases in PI3K activity. In addition, PSDP was identified by gas chromatography/mass spectrometry in p110gamma-PI3K immunoprecipitates obtained 30 s after LTB4, indicating a physical interaction between PSDP and PI3K in activated neutrophils. Moreover, PSDP (0.4-800 pmol) directly inhibited recombinant human p110gamma-PI3K activity. During an experimental model of lung injury and inflammation, a reciprocal relationship was also present in vivo for lung PSDP and PI3K activity. To investigate its therapeutic potential, we developed a new PSDP structural mimetic that blocked human neutrophil activation and mouse lung PI3K activity and inflammation. Together, our findings indicate that PSDP is an endogenous PI3K inhibitor, and suggest that in inflammatory diseases characterized by excessive neutrophil activation, PIPPs can serve as structural templates in a novel antineutrophil therapeutic strategy to limit tissue injury.

Access to Document (DOI)

Identification and functional characterization of a presqualene diphosphate phosphatase

Fukunaga, K., Arita, M., Takahashi, M., Morris, A. J., Pfeffer, M. and Levy, B. D.

J Biol Chem 281 （ 14 ） 9490 - 7 2006年04月

ISSN 0021-9258

Presqualene diphosphate (PSDP) is a bioactive lipid that rapidly remodels to presqualene monophosphate (PSMP) upon cell activation (Levy, B. D., Petasis, N. A., and Serhan, C. N. (1997) Nature 389, 985-990). Here, we have identified and characterized a phosphatase that converts PSDP to PSMP. Unlike the related polyisoprenyl phosphate farnesyl diphosphate (FDP), PSDP was not a substrate for type 2 lipid phosphate phosphohydrolases. PSDP phosphatase activity was identified in activated human neutrophil (PMN) extracts and partially purified in the presence of Nonidet P-40 with gel filtration and anion exchange chromatography. Peptide sequencing of a candidate phosphatase was consistent with phosphatidic acid phosphatase domain containing 2 (PPAPDC2), an uncharacterized protein that contains a lipid phosphate phosphohydrolase consensus motif. Recombinant PPAPDC2 displayed diphosphate phosphatase activity with a substrate preference for PSDP > FDP > phosphatidic acid. PPAPDC2 activity was independent of Mg(2+) and optimal at pH 7.0 to 8.0. Incubation of [(14)C]FDP with recombinant human squalene synthase led to [(14)C]PSDP and [(14)C]squalene formation, and in the presence of PPAPDC2, [(14)C]PSMP was generated from [(14)C]PSDP. PPAPDC2 mRNA was detected in human PMN, and is widely expressed in human tissues. Together, these findings indicate that PPAPDC2 in human PMN is the first lipid phosphate phosphohydrolase identified for PSDP. Regulation of this activity of the enzyme may have important roles for PMN activation in innate immunity.

Access to Document (DOI)

Lipoxin A(4) regulates bronchial epithelial cell responses to acid injury

Bonnans, C., Fukunaga, K., Levy, M. A. and Levy, B. D.

Am J Pathol 168 （ 4 ） 1064 - 72 2006年04月

ISSN 0002-9440

Aspiration of gastric acid commonly injures airway epithelium and, if severe, can lead to respiratory failure from acute respiratory distress syndrome. Recently, we identified cyclooxygenase-2 (COX-2)-derived prostaglandin E(2) (PGE(2)) and lipoxin A(4) (LXA(4)) as pivotal mediators in vivo for resolution of acid-initiated acute lung injury. To examine protective mechanisms for these mediators in the airway, we developed an in vitro model of acid injury by transiently exposing well-differentiated normal human bronchial epithelial cells to hydrochloric acid. Transmission electron microscopy revealed selective injury to superficial epithelial cells with disruption of cell attachments and cell shedding. The morphological features of injury were substantially resolved within 6 hours. Acid triggered and early marked increases in COX-2 expression and PGE(2) production, and acid-induced PGE(2) significantly increased epithelial LXA(4) receptor (ALX) expression. LXA(4) is generated in vivo during acute lung injury, and we observed that nanomolar quantities increased basal epithelial cell proliferation and potently blocked acid-triggered interleukin-6 release and neutrophil transmigration across well-differentiated normal human bronchial epithelial cells. Expression of recombinant human ALX in A549 airway epithelial cells uncovered ALX-dependent inhibition of cytokine release by LXA(4). Together, these findings indicate that injured bronchial epithelial cells up-regulate ALX in a COX-2-dependent manner to promote LXA(4)-mediated resolution of airway inflammation.

Access to Document (DOI)

Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury

Fukunaga, K., Kohli, P., Bonnans, C., Fredenburgh, L. E. and Levy, B. D.

J Immunol 174 （ 8 ） 5033 - 9 2005年04月

ISSN 0022-1767

Acute lung injury (ALI) is a severe illness with excess mortality and no specific therapy. In its early exudative phase, neutrophil activation and accumulation in the lung lead to hypoxemia, widespread tissue damage, and respiratory failure. In clinical trials, inhibition of proinflammatory mediators has not proven effective. In this study, we pursued a new investigative strategy that emphasizes mediators promoting resolution from lung injury. A new spontaneously resolving experimental murine model of ALI from acid aspiration was developed to identify endogenous proresolving mechanisms. ALI increased cyclooxygenase 2 (COX-2) expression in murine lung. Selective pharmacologic inhibition or gene disruption of COX-2 blocked resolution of ALI. COX-2-derived products increased levels of the proresolving lipid mediators lipoxin A4 (LXA4) and, in the presence of aspirin, 15-epi-LXA4. Both LXA4 and 15-epi-LXA4 interact with the LXA4 receptor (ALX) to mediate anti-inflammatory actions. ALX expression was markedly induced by acid injury and transgenic mice with increased ALX expression displayed dramatic protection from ALI. Together, these findings indicate a protective role in ALI for COX-2-derived mediators, in part via enhanced lipoxin signaling, and carry potential therapeutic implications for this devastating clinical disorder.

Human bronchial smooth muscle cell proliferation via thromboxane A2 receptor

Suzuki, Y., Asano, K., Shiraishi, Y., Oguma, T., Shiomi, T., Fukunaga, K., Nakajima, T., Niimi, K., Yamaguchi, K. and Ishizaka, A.

Prostaglandins Leukot Essent Fatty Acids 71 （ 6 ） 375 - 82 2004年12月

ISSN 0952-3278

Thromboxane A2 receptor (TP) mediates bronchial smooth muscle cell (BSMC) contraction, airway hyperresponsiveness, and airway inflammation in patients with asthma. In the present study, a pathogenic role of TP activation in airway remodeling was examined using primary cultures of human BSMC. A TP agonist, I-BOP, concentration-dependently enhanced not only bromodeoxyuridine (BrdU) uptake but also cell proliferation of BSMC. A TP-selective antagonist, AA-2414, blocked the effects of I-BOP on both BrdU uptake and cell proliferation. I-BOP-induced BrdU uptake was significantly blocked by two non-selective tyrosine kinase inhibitors, genistein and herbimycin A, or a Src family tyrosine kinase inhibitor, PP2, but not by an inhibitor of epidermal growth factor (EGF) receptor-associated tyrosine kinase, AG1478. In conclusion, TP receptor activation causes DNA synthesis and cell proliferation of human BSMC by activating tyrosine kinases including Src, but not by EGF receptor transactivation.

Access to Document (DOI)

Plasma eotaxin level and severity of asthma treated with corticosteroid

Tateno, H., Nakamura, H., Minematsu, N., Nakajima, T., Takahashi, S., Nakamura, M., Fukunaga, K., Asano, K., Lilly, C. M. and Yamaguchi, K.

Respir Med 98 （ 8 ） 782 - 90 2004年08月

ISSN 0954-6111

Our understanding of asthma severity was advanced by the identification of biomarkers which account for differences in lung function impairment. We tried to examine the effects of corticosteroid treatment on known correlates of asthma severity including peripheral eosinophil counts, total IgE, IL-5, and eotaxin Levels in plasma. We compared these biomarkers among groups of stable asthmatics categorized by the dose of corticosteroid (N: steroid-free, n = 25; L: low-dose inhaled, n = 27; MH: medium or high-dose inhaled, n= 19; O: inhaled plus oral, n= 8). Next we compared these markers and peak expiratory flow rate (PEFR) in unstable asthmatics before and after treatment with steroids (n = 22). Eotaxin levels in the O group were higher than those in the N and MH groups (P < 0.05). Logistic regression analysis demonstrated that plasma eotaxin level was correlated with the severity of asthma defined by treatment intensity (P = 0.01) and % FEV1 (P = 0.04) while the other markers were not. Eotaxin levels did not change after steroid treatment in unstable patients, whereas eosinophil counts decreased in parallel with PEFR. Among biomarkers of asthma severity studied, plasma eotaxin level was not significantly affected by corticosteroid treatment, and was associated with the severity even in the presence of steroid therapy.

PAF responsiveness in Japanese subjects with plasma PAF acetylhydrolase deficiency

Naoki, K., Asano, K., Satoh, N., Fukunaga, K., Oguma, T., Shiomi, T., Suzuki, Y., Nakajima, T., Niimi, K., Shiraishi, Y., Ishizaka, A. and Yamaguchi, K.

Biochem Biophys Res Commun 317 （ 1 ） 205 - 10 2004年04月

ISSN 0006-291X

Approximately 4% of the Japanese population genetically lack plasma platelet activating factor acetylhydrolase (PAF-AH) and show a higher prevalence of thromboembolic disease, but whether they are susceptible to another PAF-related disease, asthma, remains controversial. To determine the role of plasma PAF-AH in airway physiology, we performed PAF bronchoprovocation tests in 8 plasma PAF-AH-deficient subjects and 16 control subjects. Serial inhalation of PAF (1-1000 microg/ml) concentration-dependently induced acute bronchoconstriction, but there was no significant difference between PAF-AH-deficient and control subjects (11.7 +/- 4.6% vs. 9.6 +/- 2.8% decrease in forced expiratory volume in 1 s). Transient neutropenia after single inhalation of PAF (1000 microg/ml) showed no significant difference between the groups either in its magnitude (72 +/- 11% vs. 65 +/- 9% decrease) or duration (4.1 +/- 1.0 vs. 3.3 +/- 0.8 min). In conclusion, a lack of plasma PAF-AH activity alone does not augment physiological responses to PAF in the airway.

Access to Document (DOI)

[Effects of docetaxel dosage in combination chemotherapy with carboplatin against advanced non-small cell lung cancer]

Oyamada, Y., Watanabe, H., Fukunaga, K., Nakamura, H., Asano, K., Hasegawa, N. and Yamaguchi, K.

Gan To Kagaku Ryoho 30 （ 12 ） 1917 - 22 2003年11月

ISSN 0385-0684

We retrospectively analyzed the effects of dosages of docetaxel (DOC) in combination chemotherapy with carboplatin (CBDCA) against advanced non-small cell lung cancer (NSCLC). Twenty-three cases of previously untreated NSCLC (stage III and IV, performance status: 0-1) that were pathologically or cytologically confirmed were divided into 2 groups (DOC-60, DOC-70) based on their received DOC doses (60 and 70 mg/m2, respectively). Both groups had similar patient characteristics and received similar treatment except for their DOC doses. Although not statistically significant, the response rates after the completion of whole cycles of the treatment (mean: 4 cycles) were 18.2% in DOC-60 and 41.6% in DOC-70. Leukocytopenia, neutropenia and anemia were observed similarly in both groups. However, while thrombocytopenia was not observed in DOC-70, it was found in 36.4% of the cases in DOC-60. In combination chemotherapy with carboplatin against advanced NSCLC, the use of DOC at 70 mg/m2 was rather protective against thrombocytopenia, keeping the response equivalent or possibly superior to that obtained in the patients treated with DOC at 60 mg/m2.

Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT(1) antagonist, pranlukast, in Japanese patients with moderate asthma

Asano, K., Shiomi, T., Hasegawa, N., Nakamura, H., Kudo, H., Matsuzaki, T., Hakuno, H., Fukunaga, K., Suzuki, Y., Kanazawa, M. and Yamaguchi, K.

Pharmacogenetics 12 （ 7 ） 565 - 70 2002年10月

ISSN 0960-314X

CysLT(1) antagonists are effective for a subset of patients with asthma; however, there has been no good way to predict a given patient's response. We examined the interaction between the clinical response to a cysLT(1) antagonist, pranlukast, and DNA sequence variant A(-444)C in leukotriene C(4) synthase (LTC(4) S) gene in Japanese patients with moderate asthma. The frequency of LTC(4) S C(-444) allele was 21.6% in the Japanese general population (n = 171) and 19.4% in the asthmatic subjects ( n= 349). A 4-week prospective, open trial of pranlukast (225 mg twice daily) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid (beclomethasone 400-800 microg/day or fluticasone 200-400 microg/day). The C(-444) allele carriers (n = 16) responded better to pranlukast compared to the A(-444) allele homozygotes ( n= 31) [14.3 5.3% vs. 3.1 2.4% improvement of forced expiratory volume in one second (FEV(1) ), 0.01], while LTC(4) S genotype-stratified response to inhaled beta-agonist salbutamol (200 microg) was not observed (17.5 2.1% vs. 18.7 2.2% improvement of FEV(1) ). Univariate analysis demonstrated that the better response to pranlukast (more than 10% improvement of FEV(1) ) was correlated with LTC(4) S genotype (P < 0.01) and pretreatment airway reversibility to salbutamol (P < 0.01), but not with sex, age, atopic status, urinary leukotriene E(4) excretion rate, or daily dose of inhaled corticosteroid. Furthermore, multivariate regression analysis suggested that LTC(4) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast (P < 0.05). We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.

Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs

Oguma, T., Asano, K., Shiomi, T., Fukunaga, K., Suzuki, Y., Nakamura, M., Matsubara, H., Sheldon, H. K., Haley, K. J., Lilly, C. M., Drazen, J. M. and Yamaguchi, K.

Am J Respir Crit Care Med 165 （ 3 ） 382 - 6 2002年02月

ISSN 1073-449X

Prostaglandins and thromboxanes are important modulators of airway physiology. The synthesis of these mediators depends on two isoforms of cyclooxygenase (COX), constitutive COX-1 and inducible COX-2. COX-2 expression has been observed in various inflammatory diseases, but not all aspects of the expression and the role of COX-2 in conditions of allergic inflammation such as asthma are clear. In the present study, we examined the 72-h kinetics of the expression of COX-isoform mRNA in ovalbumin-sensitized and -challenged guinea-pig lungs. The sensitized animals showed a robust and transient induction of COX-2 mRNA expression within 1 h after ovalbumin challenge, whereas their COX-1 mRNA levels remained unchanged. Upregulation of the level and activity of COX-2 protein followed the induction of COX-2 mRNA. Lung slices harvested from ovalbumin-challenged animals released more prostaglandin D(2) and prostaglandin E(2) spontaneously or in response to A23187 (10 microM) ex vivo than did those from unchallenged animals. This response was significantly blocked by the COX-2 selective inhibitors, NS-398 and JTE-522. In vivo administration of NS-398 significantly inhibited the accumulation of eosinophils and neutrophils in the lungs. In conclusion, de novo COX-2 expression during allergic inflammation modifies prostanoid synthesis in the lung and airway pathophysiology.

Access to Document (DOI)

Differential expression of CCR3 ligand mRNA in guinea pig lungs during allergen-induced inflammation

Asano, K., Nakamura, M., Oguma, T., Fukunaga, K., Matsubara, H., Shiomi, T., Ishizaka, A., Yamaguchi, K. and Kanazawa, M.

Inflamm Res 50 （ 12 ） 625 - 30 2001年12月

ISSN 1023-3830

OBJECTIVE AND DESIGN: The gene expression profile of CCR3 ligands, eotaxin, RANTES, and monocyte chemoattractant protein-3 (MCP-3), was examined in normal and inflamed guinea pig lungs. MATERIAL: Male Hartley guinea pigs (n = 49). METHODS: Pulmonary mRNA was obtained from naive animals, animals treated with intravenous lipopolysaccharide administration, and animals repeatedly exposed to aerosolized allergen (ovalbumin). Northern analysis was performed to quantify pulmonary expression of eotaxin, RANTES, and MCP-3 mRNA. Pulmonary eosinophil peroxidase (EPO) activity was measured to quantify eosinophil accumulation. RESULTS: Eotaxin and RANTES mRNAs, but not MCP-3 mRNA, were constitutively expressed in guinea pig lungs. Lipopolysaccharide treatment increased MCP-3 mRNA expression, but not eotaxin or RANTES mRNA. In contrast, allergen exposure in sensitized animals caused an increase in eotaxin mRNA, which demonstrated good temporal and quantitative correlation with pulmonary EPO activity, but not in MCP-3 or RANTES mRNA. CONCLUSIONS: Guinea pig CCR3 ligands demonstrated different gene expression profiles in normal and inflamed airways, suggesting that they play different physiological and pathophysiological roles in the airway.

Access to Document (DOI)

Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation

Fukunaga, K., Ishii, S., Asano, K., Yokomizo, T., Shiomi, T., Shimizu, T. and Yamaguchi, K.

J Biol Chem 276 （ 46 ） 43025 - 30 2001年11月

ISSN 0021-9258

Various proinflammatory and vasoactive actions of platelet-activating factor (PAF) are mediated through a specific G-protein-coupled PAF receptor (PAFR). We identified a novel DNA variant in the human PAFR gene, which substitutes an aspartic acid for an alanine residue at position 224 (A224D) in the putative third cytoplasmic loop. This mutation was observed in a Japanese population at an allele frequency of 7.8%. To delineate the functional consequences of this structural alteration, Chinese hamster ovary cells were stably transfected with constructs encoding either wild-type or A224D mutated PAFR. No significant difference was observed in the expression level of the receptor or the affinity to PAF or to an antagonist, WEB2086, between the cells transfected with wild-type and mutant PAFR. Chinese hamster ovary cells expressing A224D mutant PAFR displayed partial but significant reduction of PAF-induced intracellular signals such as calcium mobilization, inositol phosphate production, inhibition of adenylyl cyclase, and chemotaxis. These findings suggest that this variant receptor produced by a naturally occurring mutation exhibits impaired coupling to G-proteins and may be a basis for interindividual variation in PAF-related physiological responses, disease predisposition or phenotypes, and drug responsiveness.

Access to Document (DOI)

Differential expression of CCR3 ligands mRNA in guinea pig lungs during allergen-induced inflammation

Asano Koichiro, Nakamura Morio, Oguma Tsuyoshi, Fukunaga Kouichi, Matsubara Hiroaki, Shiomi Tetuya, Ishizaka Akitoshi, Kanazawa Minoru, Yamaguchi Kazuhiro

Inflammation Research 50 （ 12 ） 625-630 2001年10月

研究論文（学術雑誌）, 共著

Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British asthmatics

Fukunaga, K., Asano, K., Mao, X. Q., Gao, P. S., Roberts, M. H., Oguma, T., Shiomi, T., Kanazawa, M., Adra, C. N., Shirakawa, T., Hopkin, J. M. and Yamaguchi, K.

Eur Respir J 17 （ 1 ） 59 - 63 2001年01月

ISSN 0903-1936

Whole genome scan analyses have revealed that chromosomal region 3p21-24, which contains a gene cluster of CC chemokine receptors such as CCR3, is possibly linked to asthma. Because CCR3 ligands play a pivotal role in the selective recruitment and activation of inflammatory cells in the asthmatic airway, the authors examined whether there is any association between asthma and the CCR3 gene polymorphisms. Three polymorphisms were identified using the single stranded conformational polymorphism method in Japanese (Asian) and British (Caucasian) subjects; one silent mutation T51C and two missense mutations G824A and T971C. These polymorphisms were examined in 391 Japanese subjects (210 asthmatics and 181 nonasthmatic controls) and 234 British subjects (142 asthmatics and 92 nonasthmatic controls). Asthma diagnosis was based on episodic symptoms, documented wheeze, and the presence of reversible airflow limitation. CCR3 T51C demonstrated a significant association with the diagnosis of asthma in the British population (odds ratio 2.35, p<0.01), but not in the Japanese population. Multiple logistic regression analysis also showed that CCR3 T51C was associated with asthma (odds ratio 2.83, p < 0.02), independent of atopic phenotypes such as high levels of total or house dust mite-specific immunoglobulin-E in serum. In conclusion, a significant association between asthma and CCR3 T51C polymorphism localized on chromosome 3p21 was found.

A case of poorly differentiated hilar lung adenocarcinoma of an unidentified histological type

Ogawa Satoshi, Fukunaga Kouichi, Hiraoka Rika, Kohda Eiichi, Yamaguchi Kazahiro, Ito Daisuke, Hata Junichi

The Keio Journal of Medicine 49 （ 4 ） 162-172 2000年03月

研究論文（学術雑誌）, 共著

Cellular source(s) of platelet-activating-factor acetylhydrolase activity in plasma

Asano, K., Okamoto, S., Fukunaga, K., Shiomi, T., Mori, T., Iwata, M., Ikeda, Y. and Yamaguchi, K.

Biochem Biophys Res Commun 261 （ 2 ） 511 - 4 1999年08月

ISSN 0006-291X

Platelet activating factor (PAF) is immediately degraded and inactivated in the bloodstream by plasma PAF acetylhydrolase (PAF-AH). Although plasma PAF-AH-like activity was secreted in vitro from various cell types such as macrophages and hepatocytes, the exact cellular source(s) of this enzyme activity in vivo remains unclear. There is a naturally-occurring missense mutation (V279F) in the plasma PAF-AH gene in the Japanese population which results in complete loss of the enzyme activity. We analyzed 52 Japanese who had received an allogeneic bone marrow transplant and maintained donor-derived hematopoiesis. Ten recipients had chimeric plasma PAF-AH genotypes between the donor-derived peripheral blood leukocytes and the recipient-derived epithelial cells of buccal mucosa. Multiple regression analysis demonstrated that PAF-AH activity in plasma depended on the donor's genotype (standardized regression coefficient = 0.68, P < 0.0001), but not on the recipient's genotype (p = 0.48). One recipient who was a V279F homozygote in leukocytes and wild type homozygote in buccal mucosa had undetectable PAF-AH activity in plasma. We conclude that most of the PAF-AH activity in human plasma originates from hematopoietic lineage cells.

Access to Document (DOI)

Plasma platelet-activating factor acetylhydrolase deficiency in Japanese patients with asthma

Satoh, N., Asano, K., Naoki, K., Fukunaga, K., Iwata, M., Kanazawa, M. and Yamaguchi, K.

Am J Respir Crit Care Med 159 （ 3 ） 974 - 9 1999年03月

ISSN 1073-449X

Platelet-activating factor (PAF), a phospholipid with a wide range of proinflammatory actions, is immediately degraded and inactivated in vivo by PAF acetylhydrolase (PAF-AH). Surprisingly, 4% of the Japanese population lacks the extracellular isoform of this enzyme, plasma PAF-AH, due to a genetic missense (V279F) mutation. We studied the association of this mutation with asthma prevalence and phenotypes in the Japanese adult population. The allele frequency of V279F mutation was 18.6% in 279 patients with asthma (28.7% heterozygotes and 4.3% homozygotes) and 21.7% in 217 healthy subjects (32.3% heterozygotes and 5.5% homozygotes). V279F mutant allele prevalence was consistent regardless of asthma type (16.3% in atopic [n = 156] and 21.6% in nonatopic [n = 123]), or the severity of disease (21.7% in patients with mild [n = 97], 17.5% in those with moderate [n = 131], and 15.8% in those with severe [n = 51] asthma). Plasma PAF-AH activity was inversely proportional to the number of mutant alleles, and did not correlate with asthma prevalence, type, or severity. We concluded that plasma PAF-AH deficiency due to V279F mutation is not essential to the pathophysiology of asthma in the Japanese adult population.

Access to Document (DOI)

　前のページ - 次のページ　

福永 興壱

論文 - 福永 興壱

福永　興壱

論文 - 福永　興壱