The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Shigeru Kohno - One of the best experts on this subject based on the ideXlab platform.
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efficacy of long term macrolide antibiotic therapy in patients with Diffuse Panbronchiolitis comparison between hla b54 positive and negative cases
International Journal of Antimicrobial Agents, 2004Co-Authors: Junichi Kadota, Shigeru Kohno, Hiroshi Mukae, Kazunori Tomono, Masaru NasuAbstract:Abstract This study compared the clinical characteristics and the effects of long-term macrolide antibiotic therapy of HLA-B54-positive and -negative cases in patients with Diffuse Panbronchiolitis (DPB). Thirty-two Japanese patients were enrolled who had the clinical criteria for DPB. All patients received long-term macrolide therapy, and therapeutic results were compared according to the presence or the absence of HLA-B54 antigen. Clinical, laboratory, radiological and bacterial features were strikingly similar in both groups before macrolide therapy. Long-term treatment with macrolides improved clinical symptoms, PaO 2 , and forced expiratory volume in 1 s (FEV 1 ) equally in both groups. This study indicates that genetic susceptibility may not explain the pathogenesis of DPB, and that low-dose macrolide therapy can achieve clinical improvement irrespective of genetic predisposition in DPB.
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clinical similarities and differences between human t cell lymphotropic virus type 1 associated bronchiolitis and Diffuse Panbronchiolitis
Chest, 2004Co-Authors: Junichi Kadota, Takeshi Fujii, Hiroshi Mukae, Kazunori Tomono, Masafumi Seki, Shigeru KohnoAbstract:Study objectives Human T-cell lymphotropic virus type 1 (HTLV-1)-associated bronchiolitis and Diffuse Panbronchiolitis might overlap. We examined whether these conditions can be differentiated by comparing their clinical features and the effect of long-term macrolide treatment. Patients and methods Fifty-eight Japanese patients, including 15 with HTLV-1–associated bronchiolitis and 43 with Diffuse Panbronchiolitis. Both conditions were clinically compared using the clinical criteria for Diffuse Panbronchiolitis, including findings from CT scans and BAL fluid testing. Pulmonary function, blood gas levels, and cold hemagglutinin (CHA) levels were assessed before and after long-term treatment with macrolides. Interleukin-2 receptor (IL-2R) expression in T cells obtained from the BAL fluid of patients with HTLV-1–associated bronchiolitis or Diffuse Panbronchiolitis was analyzed by flow cytometry. Results Clinical, laboratory, radiologic, and bacterial features were strikingly similar in both groups, except for the fact that patients with HTLV-1–associated bronchiolitis had a higher ratio of IL-2R–positive cells in the BAL fluid. The histopathologic features were also similar. Long-term treatment with macrolides improved Pa o 2 , FEV 1 , and CHA in patients with HTLV-1–associated bronchiolitis to a lesser extent than in those with Diffuse Panbronchiolitis, and Pa o 2 and FEV 1 in the group of patients with HTLV-1–associated bronchiolitis who had high IL-2R levels did not respond after therapy. Conclusions These findings showed that the clinicopathologic features of the two conditions are quite similar, suggesting that Diffuse Panbronchiolitis is a chronic pulmonary manifestation of HTLV-1 infection. However, HTLV-1–associated bronchiolitis might be associated with conditions that are distinct from those of Diffuse Panbronchiolitis based on the different responses to macrolide treatment and the difference in the number of activated T cells bearing IL-2R in the lungs.
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clarithromycin inhibits overproduction of muc5ac core protein in murine model of Diffuse Panbronchiolitis
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Yukihiro Kaneko, Junichi Kadota, Katsunori Yanagihara, Yoshitsugu Miyazaki, Yoichi Hirakata, Hiroshi Mukae, Kazunori Tomono, Masafumi Seki, Misuzu Kuroki, Shigeru KohnoAbstract:Long-term treatment of macrolide antibiotics is considered an effective treatment for Diffuse Panbronchiolitis (DPB). Although hypersecretion is a common feature of this disease, and it is known th...
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overproduction of muc5ac core protein in patients with Diffuse Panbronchiolitis
Respiration, 2003Co-Authors: Yukihiro Kaneko, Junichi Kadota, Katsunori Yanagihara, Yoshitsugu Miyazaki, Yoichi Hirakata, Hiroshi Mukae, Kazunori Tomono, Yoshio Okada, Shigeru KohnoAbstract:Background: The genetic identities of mucins secreted in the airways of patients with Diffuse Panbronchiolitis (DPB) have not been previously investigated, although hypersecretion i
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characterization of cd44 expressed on alveolar macrophages in patients with Diffuse Panbronchiolitis
Clinical and Experimental Immunology, 2001Co-Authors: S Katoh, Junichi Kadota, Hiroshi Mukae, Shigeru Matsukura, Kiyoyasu Fukushima, Y Matsubara, Hirokazu Taniguchi, Shigeru KohnoAbstract:Interleukin (IL)-8 may play an important role in neutrophil infiltration in the airways of patients with Diffuse Panbronchiolitis (DPB). Furthermore, alveolar macrophages could produce IL-8 subsequent to CD44-hyaluronic acid (HA) interaction. The purpose of this study was to evaluate the contribution of CD44 expressed on alveolar macrophages to the pathogenesis of DPB. We examined the concentration of soluble CD44 (sCD44) in bronchoalveolar lavage fluid (BALF) and CD44 expression on macrophages in BALF from patients with DPB before and after low-dose, long-term macrolide therapy. We also assessed the HA-binding ability of alveolar macrophages as a functional analysis of the CD44 molecule. The sCD44 concentration in BALF was significantly lower in patients with DPB than in healthy volunteers. Percentages of alveolar macrophages expressing low CD44 (CD44 low+) and HA-nonbinding alveolar macrophages were higher in patients with DPB compared with healthy volunteers. Furthermore, macrolide therapy normalized CD44 expression and HA-binding ability of macrophages in BALF from DPB patients. Our findings suggest that alveolar macrophage dysfunction could result from abnormalities of CD44 expression in patients with DPB and that these events could contribute to the pathogenesis of DPB.
Junichi Kadota - One of the best experts on this subject based on the ideXlab platform.
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the development of Diffuse Panbronchiolitis during the treatment with long term low dose clarithromycin for chronic sinusitis
Journal of Infection and Chemotherapy, 2019Co-Authors: Masaru Ando, Tomoko Ono, Yuko Usagawa, Hiroki Yoshikawa, Takashi Hirano, Issei Tokimatsu, Junichi KadotaAbstract:Diffuse Panbronchiolitis (DPB) is a progressive inflammatory airway disease characterized by a chronic cough, copious sputum expectation, dyspnea, and chronic sinusitis. Owing to the long-term treatment of low-dose macrolides, the prognosis has been remarkably improved. However, in some cases, patients are refractory to macrolides, and the subsequent treatment strategies are controversial. We herein present a patient with the onset of DPB during treatment with long-term, low-dose clarithromycin (CAM) for chronic sinusitis who was successfully treated by switching to long-term treatment with normal-dose CAM. We should recognize that DPB may develop in patients with chronic sinusitis despite treatment with a long-term, low-dose macrolide. We also propose that increasing the dose of macrolide may be a useful strategy for treating refractory patients.
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efficacy of long term macrolide antibiotic therapy in patients with Diffuse Panbronchiolitis comparison between hla b54 positive and negative cases
International Journal of Antimicrobial Agents, 2004Co-Authors: Junichi Kadota, Shigeru Kohno, Hiroshi Mukae, Kazunori Tomono, Masaru NasuAbstract:Abstract This study compared the clinical characteristics and the effects of long-term macrolide antibiotic therapy of HLA-B54-positive and -negative cases in patients with Diffuse Panbronchiolitis (DPB). Thirty-two Japanese patients were enrolled who had the clinical criteria for DPB. All patients received long-term macrolide therapy, and therapeutic results were compared according to the presence or the absence of HLA-B54 antigen. Clinical, laboratory, radiological and bacterial features were strikingly similar in both groups before macrolide therapy. Long-term treatment with macrolides improved clinical symptoms, PaO 2 , and forced expiratory volume in 1 s (FEV 1 ) equally in both groups. This study indicates that genetic susceptibility may not explain the pathogenesis of DPB, and that low-dose macrolide therapy can achieve clinical improvement irrespective of genetic predisposition in DPB.
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clinical similarities and differences between human t cell lymphotropic virus type 1 associated bronchiolitis and Diffuse Panbronchiolitis
Chest, 2004Co-Authors: Junichi Kadota, Takeshi Fujii, Hiroshi Mukae, Kazunori Tomono, Masafumi Seki, Shigeru KohnoAbstract:Study objectives Human T-cell lymphotropic virus type 1 (HTLV-1)-associated bronchiolitis and Diffuse Panbronchiolitis might overlap. We examined whether these conditions can be differentiated by comparing their clinical features and the effect of long-term macrolide treatment. Patients and methods Fifty-eight Japanese patients, including 15 with HTLV-1–associated bronchiolitis and 43 with Diffuse Panbronchiolitis. Both conditions were clinically compared using the clinical criteria for Diffuse Panbronchiolitis, including findings from CT scans and BAL fluid testing. Pulmonary function, blood gas levels, and cold hemagglutinin (CHA) levels were assessed before and after long-term treatment with macrolides. Interleukin-2 receptor (IL-2R) expression in T cells obtained from the BAL fluid of patients with HTLV-1–associated bronchiolitis or Diffuse Panbronchiolitis was analyzed by flow cytometry. Results Clinical, laboratory, radiologic, and bacterial features were strikingly similar in both groups, except for the fact that patients with HTLV-1–associated bronchiolitis had a higher ratio of IL-2R–positive cells in the BAL fluid. The histopathologic features were also similar. Long-term treatment with macrolides improved Pa o 2 , FEV 1 , and CHA in patients with HTLV-1–associated bronchiolitis to a lesser extent than in those with Diffuse Panbronchiolitis, and Pa o 2 and FEV 1 in the group of patients with HTLV-1–associated bronchiolitis who had high IL-2R levels did not respond after therapy. Conclusions These findings showed that the clinicopathologic features of the two conditions are quite similar, suggesting that Diffuse Panbronchiolitis is a chronic pulmonary manifestation of HTLV-1 infection. However, HTLV-1–associated bronchiolitis might be associated with conditions that are distinct from those of Diffuse Panbronchiolitis based on the different responses to macrolide treatment and the difference in the number of activated T cells bearing IL-2R in the lungs.
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clarithromycin inhibits overproduction of muc5ac core protein in murine model of Diffuse Panbronchiolitis
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Yukihiro Kaneko, Junichi Kadota, Katsunori Yanagihara, Yoshitsugu Miyazaki, Yoichi Hirakata, Hiroshi Mukae, Kazunori Tomono, Masafumi Seki, Misuzu Kuroki, Shigeru KohnoAbstract:Long-term treatment of macrolide antibiotics is considered an effective treatment for Diffuse Panbronchiolitis (DPB). Although hypersecretion is a common feature of this disease, and it is known th...
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overproduction of muc5ac core protein in patients with Diffuse Panbronchiolitis
Respiration, 2003Co-Authors: Yukihiro Kaneko, Junichi Kadota, Katsunori Yanagihara, Yoshitsugu Miyazaki, Yoichi Hirakata, Hiroshi Mukae, Kazunori Tomono, Yoshio Okada, Shigeru KohnoAbstract:Background: The genetic identities of mucins secreted in the airways of patients with Diffuse Panbronchiolitis (DPB) have not been previously investigated, although hypersecretion i
Hiroshi Mukae - One of the best experts on this subject based on the ideXlab platform.
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an autopsy case report of adult t cell leukemia accompanied by rheumatoid arthritis mimicking Diffuse Panbronchiolitis
Journal of UOEH, 2017Co-Authors: Tomoko Shiraishi, Hiroshi Ishimoto, Kazuhiro Yatera, Toshinori Kawanami, Kentaro Akata, Hiroshi MukaeAbstract:A 50-year-old female with a history of chronic sinusitis and rheumatoid arthritis visited our department with repetitive lower respiratory tract infections of Pseudomonas aeruginosa. Her chest CT showed Diffuse Panbronchiolitis-like pulmonary lesions, her blood examination revealed atypical lymphocytes, and she was serologically positive for anti-human T-lymphotrophic virus type 1 (HTLV-1) antibody. Her rheumatoid arthritis had been well-controlled after biological agent treatment followed by anti-inflammatory analgesic treatment. She received long-term low-dose macrolide therapy for four years. The Pseudomonas aeruginosa gradually became multi-antibiotic-resistant. Her lower respiratory infection gradually became uncontrollable, and her adult T cell leukemia (ATL) developed to the acute phase. Due to repetitive lower respiratory tract infections and respiratory failure, however, she could not receive any treatment for ATL, and she eventually died due to the progression of the disease. An autopsy revealed an invasion of abnormal lymphocytes in multiple organs, including the lungs, which indicated that the HTLV-1 infection and the progression of ATL were the dominant factors in this patient's clinical course. There have been no Diffuse Panbronchiolitis-like cases accompanied by rheumatoid arthritis and HTLV-1 infection so far. Because these diseases show similar clinical features, it is difficult to discriminate between them. There are presently no appropriate criteria for the proper time of treatment of patients with pulmonary lesion-associated ATL, but further research is expected to elucidate this matter.
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a case of good syndrome with pulmonary lesions similar to Diffuse Panbronchiolitis
Internal Medicine, 2012Co-Authors: Takaaki Ogoshi, Hiroshi Ishimoto, Kazuhiro Yatera, Keishi Oda, Kentarou Akata, Kei Yamasaki, Takashi Kido, Toshinori Kawanami, Chiharu Yoshii, Hiroshi MukaeAbstract:We herein present a case of Good syndrome complicated by Diffuse pulmonary lesions similar to Diffuse Panbronchiolitis (DPB). A 45-year-old Japanese man was referred to our department due to recurrent lower respiratory tract infections that had started and ameliorated nine months after thymectomy for pure red cell aplasia and myasthenia gravis. Diffuse centrilobular opacities on chest computed tomography and positivity for HLA-B54 were consistent with DPB. Additionally, hypogammaglobulinemia and a marked decrease of B-lymphocytes were observed, and therefore Good syndrome was considered. Combination therapy with azithromycin and clarithromycin alleviated the patient's respiratory symptoms and reduced the exacerbation of chronic bronchitis.
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efficacy of long term macrolide antibiotic therapy in patients with Diffuse Panbronchiolitis comparison between hla b54 positive and negative cases
International Journal of Antimicrobial Agents, 2004Co-Authors: Junichi Kadota, Shigeru Kohno, Hiroshi Mukae, Kazunori Tomono, Masaru NasuAbstract:Abstract This study compared the clinical characteristics and the effects of long-term macrolide antibiotic therapy of HLA-B54-positive and -negative cases in patients with Diffuse Panbronchiolitis (DPB). Thirty-two Japanese patients were enrolled who had the clinical criteria for DPB. All patients received long-term macrolide therapy, and therapeutic results were compared according to the presence or the absence of HLA-B54 antigen. Clinical, laboratory, radiological and bacterial features were strikingly similar in both groups before macrolide therapy. Long-term treatment with macrolides improved clinical symptoms, PaO 2 , and forced expiratory volume in 1 s (FEV 1 ) equally in both groups. This study indicates that genetic susceptibility may not explain the pathogenesis of DPB, and that low-dose macrolide therapy can achieve clinical improvement irrespective of genetic predisposition in DPB.
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clinical similarities and differences between human t cell lymphotropic virus type 1 associated bronchiolitis and Diffuse Panbronchiolitis
Chest, 2004Co-Authors: Junichi Kadota, Takeshi Fujii, Hiroshi Mukae, Kazunori Tomono, Masafumi Seki, Shigeru KohnoAbstract:Study objectives Human T-cell lymphotropic virus type 1 (HTLV-1)-associated bronchiolitis and Diffuse Panbronchiolitis might overlap. We examined whether these conditions can be differentiated by comparing their clinical features and the effect of long-term macrolide treatment. Patients and methods Fifty-eight Japanese patients, including 15 with HTLV-1–associated bronchiolitis and 43 with Diffuse Panbronchiolitis. Both conditions were clinically compared using the clinical criteria for Diffuse Panbronchiolitis, including findings from CT scans and BAL fluid testing. Pulmonary function, blood gas levels, and cold hemagglutinin (CHA) levels were assessed before and after long-term treatment with macrolides. Interleukin-2 receptor (IL-2R) expression in T cells obtained from the BAL fluid of patients with HTLV-1–associated bronchiolitis or Diffuse Panbronchiolitis was analyzed by flow cytometry. Results Clinical, laboratory, radiologic, and bacterial features were strikingly similar in both groups, except for the fact that patients with HTLV-1–associated bronchiolitis had a higher ratio of IL-2R–positive cells in the BAL fluid. The histopathologic features were also similar. Long-term treatment with macrolides improved Pa o 2 , FEV 1 , and CHA in patients with HTLV-1–associated bronchiolitis to a lesser extent than in those with Diffuse Panbronchiolitis, and Pa o 2 and FEV 1 in the group of patients with HTLV-1–associated bronchiolitis who had high IL-2R levels did not respond after therapy. Conclusions These findings showed that the clinicopathologic features of the two conditions are quite similar, suggesting that Diffuse Panbronchiolitis is a chronic pulmonary manifestation of HTLV-1 infection. However, HTLV-1–associated bronchiolitis might be associated with conditions that are distinct from those of Diffuse Panbronchiolitis based on the different responses to macrolide treatment and the difference in the number of activated T cells bearing IL-2R in the lungs.
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clarithromycin inhibits overproduction of muc5ac core protein in murine model of Diffuse Panbronchiolitis
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Yukihiro Kaneko, Junichi Kadota, Katsunori Yanagihara, Yoshitsugu Miyazaki, Yoichi Hirakata, Hiroshi Mukae, Kazunori Tomono, Masafumi Seki, Misuzu Kuroki, Shigeru KohnoAbstract:Long-term treatment of macrolide antibiotics is considered an effective treatment for Diffuse Panbronchiolitis (DPB). Although hypersecretion is a common feature of this disease, and it is known th...
Shoji Kudoh - One of the best experts on this subject based on the ideXlab platform.
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Diffuse Panbronchiolitis long term low dose macrolide therapy
2017Co-Authors: Mutsuo Yamaya, Arata Azuma, Shoji KudohAbstract:Diffuse Panbronchiolitis (DPB) is characterized by thickening and inflammation of the walls of respiratory bronchioles. Patients with DPB suffer from several severe symptoms, including dyspnea, wheezing, cough, and large amounts of purulent sputum; therefore, the development of precise therapy was required. Kudoh et al. first reported the clinical benefits of erythromycin therapy in a male patient with DPB in 1984, and they reported improved 5-year survival rates as a result of this intervention in 1998. Following the initial report by Kudoh et al., many studies confirmed the clinical benefits of long-term low-dose macrolide therapy for DPB and the effects that include the immunomodulatory and physiological properties of macrolides in addition to their antimicrobial effects. Here, we introduce the history of the development of long-term low-dose macrolide therapy for DPB, and the mechanisms by which this therapy exerts its clinical benefits.
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genetic analysis of two novel mucin like genes in the disease susceptibility locus for Diffuse Panbronchiolitis
European Respiratory Journal, 2011Co-Authors: Minako Hijikata, Ikumi Matsushita, Yoshio Taguchi, Sakae Homma, Shoji Kudoh, Arata Azuma, Jun Ohashi, Hideyuki Ito, Naoto KeichoAbstract:Background: Diffuse Panbronchiolitis (DPB), which is characterized by chronic inflammation in respiratory bronchioles and sinobronchial infection, is a complex genetic disease affecting East Asians. DPB is strongly associated with HLA-B54 in Japanese and HLA-A11 in Koreans. We hypothesized that a major susceptibility gene for DPB might be located between the HLA-A and HLA-B loci and recently cloned two novel mucin-like genes designated Panbronchiolitis related mucin-like 1 and 2 (PBMUCL1 and PBMUCL2) in the candidate region. We found disease-associated genetic polymorphisms in the new genes. Objectives: The aim of the study is to compare the genetic polymorphisms of the genes between Japanese and European descent, because genetic predisposition to DPB has been assumed only in Asians. Methods: We genotyped polymorphisms in 50 DNA samples of European descent and compared their frequency and haplotype structure with 108 Japanese DPB patients and 98 Japanese controls. Expression of PBMUCL1 transcript was investigated in primary-cultured human bronchial epithelial (HBE) cells. Results: The haplotypes were different between European descent and Japanese. The mRNA expression pattern of the HBE cells with Asian-specific haplotype was analyzed. Conclusions: Further analysis of newly identified mucin-like genes may provide insights into the pathogenesis of the disease.
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Diffuse Panbronchiolitis in east asia
Respirology, 2006Co-Authors: Arata Azuma, Shoji KudohAbstract:Abstract: Diffuse Panbronchiolitis is characterized by chronic sinobronchial infection and Diffuse bilateral centrilobular lesions consisting of peribronchial infiltration of inflammatory cells. At present, it is known that Diffuse Panbronchiolitis is relatively restricted to East Asia. This uneven distribution is suspected to be highly associated with genetic predisposition located between human leucocyte antigen-A and -B loci. Low-dose, long-term macrolide therapy for the disease was suggested from a detailed observation of a single case that significantly improved by erythromycin therapy. Otherwise simple bactericidal activity of macrolides has been assumed as a candidate because of their clinical effect on the pathogenesis. In the last 10 years, the possible mechanism underlying the effectiveness of macrolide therapy has been dynamically investigated. To understand the pathological features and potential targets for macrolides in Diffuse Panbronchiolitis, the authors introduce the incidence of Diffuse Panbronchiolitis in East Asia, the profile of the disease and then trace the history of macrolide therapy in this review. The proposed mechanism of action includes the inhibition of excessive mucus and water secretion from the airway, the inhibition of neutrophil, and sometimes of lymphocyte and macrophage accumulating in the airway, the inhibition of transcription factors expressing several cytokines and the attenuation of bacterial virulence. Intracellular mechanisms of the action of macrolide are a hot topic of interest in research. The anti-inflammatory activity of macrolides is independent of their bactericidal effect, and a new anti-inflammatory analogue without antimicrobial activity should be developed to minimize the emergence of macrolide-resistant microorganisms and to maintain the safety of this treatment.
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applying lessons learned in the treatment of Diffuse Panbronchiolitis to other chronic inflammatory diseases
American Journal of Medicine Supplement, 2004Co-Authors: Shoji KudohAbstract:In addition to having antibacterial effects, macrolides modulate inflammatory responses. Their effectiveness in treating chronic inflammatory airway disease is well documented in patients with Diffuse Panbronchiolitis (DPB), a chronic condition characterized by inflammation of the airways that, if left untreated, progressively leads to respiratory failure and death. Long-term treatment with certain macrolides has dramatically improved the survival of patients with DPB. The mechanisms of action for the anti-inflammatory properties of macrolides are still being studied. The effects of macrolides on inflammation include decreasing chemotaxis of neutrophils to the respiratory tract and inhibiting the expression of adhesion molecules, with decreased infiltration of neutrophils into the respiratory epithelium. Macrolides also inhibit expression of transcription factors and formation of proinflammatory cytokines, and directly and indirectly block mucus secretion. Even with long-term use, macrolides are safe and well tolerated. The effectiveness of macrolides for treating DPB has led to interest in their use in treating other chronic inflammatory airway diseases. As discussed in this article, because of the similarities between the clinical presentation of cystic fibrosis and chronic bronchitis and DPB, the effects of macrolides in patients with these diseases are currently being studied with particular interest.
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Diffuse Panbronchiolitis: role of macrolides in therapy.
American journal of respiratory medicine : drugs devices and other interventions, 2002Co-Authors: Naoto Keicho, Shoji KudohAbstract:Diffuse Panbronchiolitis (DPB) is characterized by chronic sinobronchial infection and Diffuse bilateral micronodular pulmonary lesions consisting of inflammatory cells. Studies on disease etiology point to a genetic predisposition unique to Asians. Early therapy for DPB was largely symptomatic. The advent of macrolide antibiotics, including erythromycin, roxithromycin and clarithromycin, has strikingly changed disease prognosis. Low-dose, long-term macrolide therapy for DPB originated from detailed observations of response to therapy in a single patient. The bactericidal activity of macrolides, particularly erythromycin, is not a significant factor for their clinical efficacy in DPB. Firstly, irrespective of bacterial clearance, clinical improvement is observed in patients treated with erythromycin. Secondly, even in cases with bacterial superinfection with Pseudomonas aeruginosa resistant to macrolides, treatment has proved effective. Thirdly, the recommended dosage of macrolides produces peak levels in tissue that are below the minimum inhibitory concentrations for major pathogenic bacteria that colonize the airway. In the last two decades, the possible mechanism underlying the effectiveness of macrolide therapy has been extensively studied. The proposed mechanism of action includes inhibition of excessive mucus and water secretion from the airway epithelium, inhibition of neutrophil accumulation in the large airway, inhibition of lymphocyte and macrophage accumulation around the small airway, and modulation of bacterial virulence. The great success of macrolide therapy in Diffuse Panbronchiolitis may extend its application to the treatment of other chronic inflammatory disorders. If the anti-inflammatory activity of macrolides is independent of their bactericidal effect, new anti-inflammatory macrolides without antimicrobial activity should be developed to minimize emergence of macrolide-resistant micro-organisms.
Naoto Keicho - One of the best experts on this subject based on the ideXlab platform.
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genetic analysis of two novel mucin like genes in the disease susceptibility locus for Diffuse Panbronchiolitis
European Respiratory Journal, 2011Co-Authors: Minako Hijikata, Ikumi Matsushita, Yoshio Taguchi, Sakae Homma, Shoji Kudoh, Arata Azuma, Jun Ohashi, Hideyuki Ito, Naoto KeichoAbstract:Background: Diffuse Panbronchiolitis (DPB), which is characterized by chronic inflammation in respiratory bronchioles and sinobronchial infection, is a complex genetic disease affecting East Asians. DPB is strongly associated with HLA-B54 in Japanese and HLA-A11 in Koreans. We hypothesized that a major susceptibility gene for DPB might be located between the HLA-A and HLA-B loci and recently cloned two novel mucin-like genes designated Panbronchiolitis related mucin-like 1 and 2 (PBMUCL1 and PBMUCL2) in the candidate region. We found disease-associated genetic polymorphisms in the new genes. Objectives: The aim of the study is to compare the genetic polymorphisms of the genes between Japanese and European descent, because genetic predisposition to DPB has been assumed only in Asians. Methods: We genotyped polymorphisms in 50 DNA samples of European descent and compared their frequency and haplotype structure with 108 Japanese DPB patients and 98 Japanese controls. Expression of PBMUCL1 transcript was investigated in primary-cultured human bronchial epithelial (HBE) cells. Results: The haplotypes were different between European descent and Japanese. The mRNA expression pattern of the HBE cells with Asian-specific haplotype was analyzed. Conclusions: Further analysis of newly identified mucin-like genes may provide insights into the pathogenesis of the disease.
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genetic predisposition to Diffuse Panbronchiolitis
Respirology, 2011Co-Authors: Naoto Keicho, Minako HijikataAbstract:Diffuse Panbronchiolitis is characterized by chronic inflammation in respiratory bronchioles and sinobronchial infection. The pathophysiology accompanying the persistent bacterial infection is noteworthy for the accumulation of lymphocytes and foamy macrophages around the small airways, for mucus hypersecretion, and for the number of neutrophils in the large airways. Until the establishment of long-term macrolide therapy, the prognosis was generally poor. Case studies of Diffuse Panbronchiolitis in East Asians, including Japanese, Koreans and Chinese, have frequently been reported, and genetic predisposition to the disease has been assumed in Asians. Immunogenetic studies revealed a strong association with human leukocyte antigen (HLA)-B54 in Japanese, whereas an association with HLA-A11 was reported in Koreans. These findings imply that a major susceptibility gene may be located between the HLA-A and HLA-B loci on the short arm of human chromosome 6. We have recently cloned novel mucin-like genes in this candidate region. In addition to accumulated knowledge of classical HLA genes and mucin genes, further analysis of newly identified genes may provide insights into the pathogenesis of the disease.
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Diffuse Panbronchiolitis: role of macrolides in therapy.
American journal of respiratory medicine : drugs devices and other interventions, 2002Co-Authors: Naoto Keicho, Shoji KudohAbstract:Diffuse Panbronchiolitis (DPB) is characterized by chronic sinobronchial infection and Diffuse bilateral micronodular pulmonary lesions consisting of inflammatory cells. Studies on disease etiology point to a genetic predisposition unique to Asians. Early therapy for DPB was largely symptomatic. The advent of macrolide antibiotics, including erythromycin, roxithromycin and clarithromycin, has strikingly changed disease prognosis. Low-dose, long-term macrolide therapy for DPB originated from detailed observations of response to therapy in a single patient. The bactericidal activity of macrolides, particularly erythromycin, is not a significant factor for their clinical efficacy in DPB. Firstly, irrespective of bacterial clearance, clinical improvement is observed in patients treated with erythromycin. Secondly, even in cases with bacterial superinfection with Pseudomonas aeruginosa resistant to macrolides, treatment has proved effective. Thirdly, the recommended dosage of macrolides produces peak levels in tissue that are below the minimum inhibitory concentrations for major pathogenic bacteria that colonize the airway. In the last two decades, the possible mechanism underlying the effectiveness of macrolide therapy has been extensively studied. The proposed mechanism of action includes inhibition of excessive mucus and water secretion from the airway epithelium, inhibition of neutrophil accumulation in the large airway, inhibition of lymphocyte and macrophage accumulation around the small airway, and modulation of bacterial virulence. The great success of macrolide therapy in Diffuse Panbronchiolitis may extend its application to the treatment of other chronic inflammatory disorders. If the anti-inflammatory activity of macrolides is independent of their bactericidal effect, new anti-inflammatory macrolides without antimicrobial activity should be developed to minimize emergence of macrolide-resistant micro-organisms.
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association of gc globulin variation with susceptibility to copd and Diffuse Panbronchiolitis
European Respiratory Journal, 2001Co-Authors: Takeo Ishii, Naoto Keicho, Arata Azuma, S Kudoh, Shinji Teramoto, Yoshinosuke Fukuchi, Yasuyoshi Ouchi, Takeshi MatsuseAbstract:Chronic obstructive pulmonary disease (COPD) and Diffuse Panbronchiolitis (DPB) are both characterized by chronic airflow limitation. Although the aetiology of these diseases is under investigation, it is commonly hypothesized that neutrophils have a major role in the disease pathogenesis. The variation of the genes related to chemotaxis of neutrophils may confer a risk for the development of both COPD and DPB. In the present report, the authors investigated the association between genetic variation that codes for the 416th and 420th amino acid of Gc-globulin, reported to be associated with chemotaxis of neutrophils, and susceptibility to COPD and DPB. Blood samples obtained from patients with COPD (n=63), DPB (n=82), and control subjects (n=82) were used for the genotyping assay. The proportion of GC*1F homozygotes was significantly higher in the COPD patients than the control subjects (COPD 36.5% versus control 20.7%), and the odds ratio for GC*1F homozygotes was 2.2 (95% confidence interval 1.1–4.6) for the COPD group. There was no difference on the distribution of the other genotypes (GC*1F-1S heterozygotes, GC*1S homozygotes, GC*2-1F heterozygotes, GC*2-1S heterozygotes and GC*2 homozygotes) or the allele frequencies among these groups. These findings suggest that the GC*1F gene polymorphism of Gc-globulin may be one of the risk factors for chronic obstructive pulmonary disease. However, no association between this polymorphism of Gc-globulin and susceptibility to Diffuse Panbronchiolitis was found.
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genetic variation of nadph nadh oxidase and susceptibility to Diffuse Panbronchiolitis dpb and chronic obstructive pulmonary disease copd
The journal of the Japanese Respiratory Society, 2001Co-Authors: Takeo Ishii, Naoto Keicho, Arata Azuma, S Kudoh, Shinji Teramoto, Yoshinosuke Fukuchi, Yasuyoshi Ouchi, Takeshi MatsuseAbstract:Diffuse Panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD) are both characterized by chronic airflow obstruction of unknown etiology. It is hypothesized that neutrophils play the major role in the pathogenesis of these diseases. Recent studies have suggested that genetic factors may be related to individual susceptibility to these diseases. We have investigated the association between the C 242 T polymorphism of p 22 phox, a critical subunit of superoxide-generating NADH/NADPH oxidase, and susceptibility to DPB and COPD. Blood samples obtained from both patients with DPB (n = 82), COPD (n = 53), and control subjects (n = 82) were used for this genotyping assay; and the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype the gene. The frequency of the C allele was 0.91, 0.92, 0.92 in the DPB, COPD, and control groups, respectively. There were no differences in the distribution of the genotype of p 22 phox among these groups, either. We concluded that there is no association between the C 242 T polymorphism of p 22 phox, and susceptibility to DPB and COPD.