Details of a Researcher - KURONUMA Kouji

Papers - KURONUMA Kouji

Division display 81 - 100 of about 129 ／ All the affair displays >>

Contribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in mcr-Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131-H30Rx and Non-x.

Toyotaka Sato, Tsukasa Shiraishi, Yoshiki Hiyama, Hiroyuki Honda, Masaaki Shinagawa, Masaru Usui, Koji Kuronuma, Naoya Masumori, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota

Antimicrobial agents and chemotherapy 62 ( 9 ) 2018.09 [International journal]

Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance (mcr) gene-negative colistin-resistant Escherichia coli clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-H30Rx (isolates SRE34 and SRE44; MIC for colistin = 16 mg/liter), non-x (SME296; MIC = 8 mg/liter), and O18-ST416 (SME222; MIC = 4 mg/liter). In this study, we investigated the colistin resistance mechanism and identified novel amino acid substitutions or deletions in the PmrAB two-component system that activates eptA (encoding a phosphoethanolamine transferase) and arnT (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferase) in all colistin-resistant isolates. SRE34 possessed deletion Δ27-45 (LISVFWLWHESTEQIQLFE) in PmrB, SRE44 possessed substitution L105P in PmrA, and both SME222 and SME296 included substitution G206D in PmrB. Matrix-assisted laser desorption ionization-time of flight mass spectrometry revealed that lipid A is modified with phosphoethanolamine in all four isolates. Deletion of pmrAB decreased colistin MICs to 0.5 mg/liter and lowered eptA and arnT expression. Chromosomal replacement of mutated pmrA or pmrB in colistin-susceptible O25b:H4-ST131 strain SME98 (colistin MIC = 0.5 mg/liter) increased the colistin MIC to that of the respective parent colistin-resistant isolate. In addition, SME98 mutants in which pmrAB was replaced with mutated pmrAB showed no significant differences in bacterial growth and competition culture from the parent strain, except for the mutant with L105P in PmrA, whose growth was significantly suppressed in the presence of the parent strain. In conclusion, some O25b:H4-ST131 strains appear to acquire colistin resistance via phosphoethanolamine modification of lipid A through amino acid changes in PmrAB, and the amino acid changes in PmrB do not influence bacterial growth.

DOI PubMed

Response to pneumococcal vaccine in interstitial lung disease patients: Influence of systemic immunosuppressive treatment.

Koji Kuronuma, Hiroyuki Honda, Tessei Mikami, Atsushi Saito, Kimiyuki Ikeda, Mitsuo Otsuka, Hirofumi Chiba, Gen Yamada, Toyotaka Sato, Shin-Ichi Yokota, Hiroki Takahashi

Vaccine 36 ( 33 ) 4968 - 4972 2018.08 [Refereed] [International journal]

BACKGROUND: Interstitial lung diseases (ILD) are severe respiratory diseases, and ILD patients are treated with corticosteroid and immunosuppressive agents. However, it is unclear whether these medications influence the response of pneumococcal vaccine. OBJECTIVES: We examined the immunogenicity of pneumococcal vaccines (PPSV23 and PCV13) in ILD patients undergoing immunosuppressive treatment. METHODS: ILD patients who were regularly followed at the outpatient clinic were enrolled. Sera were collected before and 4-8 weeks after vaccination. Serotype-specific immunoglobulin G (IgG) concentrations against pneumococcal serotype 19F were measured by ELISA. RESULTS: IgG concentrations to serotype 19F were increased in all groups in response to the vaccine. Both PCV13 and PPSV23 induced IgG concentrations in patients immunized for the first time. Response rates for the ILD group were comparable with those for the ILD group undergoing corticosteroid therapy. Only idiopathic pulmonary fibrosis patients undergoing immunosuppressive therapy had a significantly lower response.

DOI PubMed

Whole genome analysis of a multidrug-resistant Streptococcus pneumoniae isolate from a patient with invasive pneumococcal infection developing disseminated intravascular coagulation.

Yasuo Ohkoshi, Toyotaka Sato, Takayuki Wada, Yukari Fukushima, Hiromi Murabayashi, Yasunari Takakuwa, Kaoru Nishiyama, Hiroyuki Honda, Tsukasa Shiraishi, Koji Kuronuma, Hiroki Takahashi, Chie Nakajima, Yasuhiko Suzuki, Shin-Ichi Yokota

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 24 ( 8 ) 674 - 681 2018.08 [International journal]

Multidrug-resistant Streptococcus pneumoniae strains were isolated from blood and sputum of a patient with disseminated intravascular coagulation in Sapporo city, Japan. These antibiograms were only susceptible to vancomycin, linezolid, daptomycin, some carbapenems, and some fluoroquinolones. Identical antibiograms, serotypes (19F), and sequence types (ST10017) suggested a shared origin of these isolates. Only one ST10017 strain has been isolated in the same city in Japan previously (2014), and the 2014 isolate is still susceptible to macrolides. The whole genome of the blood-derived isolate was sequenced. The strain harbored resistance mutations in parC, gyrA, pbp1a, pbp2a, pbp2b, and pbp2x, and harbored the resistance genes, ermB and tetM. The nucleotide sequences of parC and pbp2x genes of strain MDRSPN001 were clearly different from those of other S. pneumoniae strains and were similar to those of oral streptococci strains. These findings suggest that strain MDRSPN001 has been rapidly and drastically evolving multidrug resistance by gene replacement and accumulation of genes originating from other strains, such as oral streptococci, Streptococcus mitis.

DOI PubMed

侵襲性肺炎球菌感染症患者から分離された多剤耐性肺炎球菌の解析

本田宏幸, 佐藤豊孝, 大越康雄, 村林広美, 小林智史, 齋藤充史, 錦織博貴, 黒沼幸治, 高橋弘毅, 横田伸一

日本化学療法学会雑誌 ( (公社)日本化学療法学会 ) 66 ( Suppl.A ) 289 - 289 2018.04

肺MAC症患者におけるL-Ficolinの役割の検討

小林智史, 齋藤充史, 本田宏幸, 錦織博貴, 黒沼幸治, 高橋弘毅

日本化学療法学会雑誌 ( (公社)日本化学療法学会 ) 66 ( Suppl.A ) 347 - 347 2018.04

結核感染を合併したStreptococcus salivariusおよびStreptococcus mitis/oralisによる肺膿瘍の1例

小林智史, 本田宏幸, 斎藤充史, 錦織博貴, 黒沼幸治, 高橋弘毅

感染症学雑誌 ( (一社)日本感染症学会 ) 92 ( 2 ) 229 - 230 2018.03

EGFR遺伝子変異陽性肺腺癌患者における予後予測因子としてのSP-Dの有用性

梅田泰淳, 長谷川喜弘, 大塚満雄, 黒沼幸治, 高橋素子, 高橋弘毅

日本内科学会雑誌 ( (一社)日本内科学会 ) 107 ( Suppl. ) 176 - 176 2018.02

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis.

Takahashi Y, Saito A, Chiba H, Kuronuma K, Ikeda K, Kobayashi T, Ariki S, Takahashi M, Sasaki Y, Takahashi H

Respiratory research 19 ( 1 ) 34 2018.02 [Refereed]

DOI PubMed

Poorer Prognosis of Idiopathic Pleuroparenchymal Fibroelastosis Compared with Idiopathic Pulmonary Fibrosis in Advanced Stage

Makoto Shioya, Mitsuo Otsuka, Gen Yamada, Yasuaki Umeda, Kimiyuki Ikeda, Hirotaka Nishikiori, Koji Kuronuma, Hirofumi Chiba, Hiroki Takahashi

Canadian Respiratory Journal ( Hindawi Limited ) 2018 2018

Objective. Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disease characterized by predominant upper lobe pulmonary fibrosis of unknown etiology. However, the prognosis of IPPFE has not been discussed. We investigated the clinical characteristics and prognostic factors of IPPFE and idiopathic pulmonary fibrosis (IPF). Methods. We performed a retrospective cohort study on 375 consecutive idiopathic interstitial pneumonia patients between April 2004 and December 2014. Among them, we diagnosed IPPFE and IPF patients using high-resolution computed tomography radiological criteria. Results. Twenty-nine IPPFE patients (9 males, 20 females) and 67 IPF patients (54 males, 13 females) were enrolled. IPPFE patients were significantly more likely to be females and nonsmokers and had lower body mass index, lower values of predicted percentage of forced vital capacity (%FVC), and a higher residual volume-to-total lung capacity ratio than IPF patients. Survival analysis revealed that they had significantly poorer prognosis than IPF patients in GAP (gender, age, and physiology) stages II + III. %FVC and GAP index independently predict mortality in patients with IPPFE. Conclusions. Patients with IPPFE showed poorer prognosis in the advanced stage than patients with IPF. %FVC and GAP index are independent predictors of survival in patients with IPPFE.

DOI PubMed

Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients

Y. Umeda, Y. Hasegawa, M. Otsuka, S. Ariki, R. Takamiya, A. Saito, Y. Uehara, H. Saijo, K. Kuronuma, H. Chiba, H. Ohnishi, Y. Sakuma, H. Takahashi, Y. Kuroki, M. Takahashi

Oncogene 36 ( 46 ) 6432 - 6445 2017.11

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. We herein demonstrate that SFTPD downregulates ligand-independent signaling in cells harboring EGFR mutations such as TKI-sensitive exon 19 deletion (Ex19del) and L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing cellular growth and motility. Lectin blotting and ligand blotting in lung cancer cell lines suggested that EGFR mutants express oligomannose-type N-glycans and interact with SFTPD directly. Cross-linking assay indicated that SFTPD inhibits ligand-independent dimerization of EGFR mutants. We also demonstrated that SFTPD reduced dimerization-independent phosphorylation of Ex19del and T790M EGFR mutants using point mutations that disrupted the asymmetric dimer interface. It was confirmed that SFTPD augmented the viability-suppressing effects of EGFR-TKIs. Furthermore, retrospective analysis of 121 patients with lung adenocarcinoma to examine associations between serum SFTPD levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, including Ex19del or L858R, high serum SFTPD levels correlated with a lower number of distant metastases and prolonged overall survival and progression-free survival. These findings suggest that SFTPD downregulates both TKI-sensitive and -resistant EGFR mutant signaling, and SFTPD level is correlated with clinical outcome. These findings illustrate the use of serum SFTPD level as a potential marker to estimate the efficacy of EGFR-TKIs.

DOI PubMed

Surfactant protein A down-regulates epidermal growth factor receptor by mechanisms different from those of surfactant protein D.

Yoshihiro Hasegawa, Motoko Takahashi, Shigeru Ariki, Atsushi Saito, Yasuaki Uehara, Rina Takamiya, Koji Kuronuma, Hirofumi Chiba, Yuji Sakuma, Hiroki Takahashi, Yoshio Kuroki

The Journal of biological chemistry 292 ( 45 ) 18565 - 18576 2017.11 [International journal]

We recently reported that the lectin surfactant protein D (SP-D) suppresses epidermal growth factor receptor (EGFR) signaling by interfering with ligand binding to EGFR through an interaction between the carbohydrate-recognition domain (CRD) of SP-D and N-glycans of EGFR. Here, we report that surfactant protein A (SP-A) also suppresses EGF signaling in A549 human lung adenocarcinoma cells and in CHOK1 cells stably expressing human EGFR and that SP-A inhibits the proliferation and motility of the A549 cells. Results with 125I-EGF indicated that SP-A interferes with EGF binding to EGFR, and a ligand blot analysis suggested that SP-A binds EGFR in A549 cells. We also found that SP-A directly binds the recombinant extracellular domain of EGFR (soluble EGFR or sEGFR), and this binding, unlike that of SP-D, was not blocked by EDTA, excess mannose, or peptide:N-glycosidase F treatment. We prepared a collagenase-resistant fragment (CRF) of SP-A, consisting of CRD plus the neck domain of SP-A, and observed that CRF directly binds sEGFR but does not suppress EGF-induced phosphorylation of EGFR in or proliferation of A549 cells. These results indicated that SP-A binds EGFR and down-regulates EGF signaling by inhibiting ligand binding to EGFR as well as SP-D. However, unlike for SP-D, SP-A lectin activity and EGFR N-glycans were not involved in the interaction between SP-A and EGFR. Furthermore, our results suggested that oligomerization of SP-A is necessary to suppress the effects of SP-A on EGF signaling.

DOI PubMed

Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone

Kimiyuki Ikeda, Masanori Shiratori, Hirofumi Chiba, Hirotaka Nishikiori, Keiki Yokoo, Atsushi Saito, Yoshihiro Hasegawa, Koji Kuronuma, Mitsuo Otsuka, Gen Yamada, Hiroki Takahashi

RESPIRATORY MEDICINE ( W B SAUNDERS CO LTD ) 131 184 - 191 2017.10 [Refereed]

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone. Methods: We retrospectively investigated patients with IPF who started treatment with pirfenidone between December 2008 and November 2014 at the Sapporo Medical University Hospital. Patients treated with pirfenidone for >6 months were enrolled in this study and were observed until November 2015. We investigated the association of clinical characteristics, pulmonary function test results, and blood examination results at the start of pirfenidone with the outcome of patients. Results: Sixty patients were included in this study. In multivariate logistic regression analysis, % predicted FVC and serum surfactant protein (SP)-D levels were predictors of a >10% decline in FVC in the initial 12 months. In the Cox proportional hazards model, these two factors predicted progression-free survival. Pack-years, % predicted diffusing capacity for carbon monoxide, and SP-D levels predicted overall survival. Conclusions: The serum SP-D level was a predictor of disease progression and prognosis in patients with IPF treated with pirfenidone. In addition, this analysis describes the relative usefulness of other clinical parameters at baseline in estimating the prognosis of patients with IPF who are candidates for pirfenidone therapy. (C) 2017 Elsevier Ltd. All rights reserved.

DOI PubMed

Deterioration of regulatory B cells and activation of follicular helper T cells in idiopathic interstitial pneumonias patients

Asai Yuichiro, Chiba Hirofumi, Kondoh Syun, Nishikiori Hirotaka, Takahashi Mamoru, Kuronuma Koji, Otsuka Mitsuo, Yamada Gen, Kamekura Ryuta, Ichimiya Shingo, Takahashi Hiroki

EUROPEAN RESPIRATORY JOURNAL 50 2017.09 [Refereed]

DOI

高周波スネアによる腫瘍切除術を施行した気管支発生の炎症性筋線維芽細胞腫瘍の1例

浅井悠一郎, 梅田泰淳, 黒沼幸治, 横山早織, 近藤瞬, 須藤悠太, 小林智史, 亀田優美, 錦織博貴, 千葉弘文, 山田玄, 高橋弘毅

気管支学 ( (NPO)日本呼吸器内視鏡学会 ) 39 ( 5 ) 386 - 391 2017.09

背景. 炎症性筋線維芽細胞腫瘍(inflammatory myofibroblastic tumor:IMT)は、炎症細胞浸潤を伴う筋線維芽細胞の増殖からなる稀な腫瘍である。今回、我々は気管支内腔にポリープ状に増殖したIMTに対して、気管支鏡下に高周波スネアによる切除を行った。症例. 56歳の男性。咳嗽、喘鳴、血痰を主訴に近医を受診した。胸部CTで右主気管支内腔に結節性病変を認めた。FDG-PETで同部位に一致した集積亢進を認め、悪性腫瘍が疑われたため、精査・治療を目的に当科に紹介となった。気管支鏡検査では右主気管支内腔に軟骨輪側に基部をもつポリープ状腫瘍を認めた。画像所見から基部は比較的小範囲に限局していると推定されたため、高周波スネアによる気管支鏡下腫瘍切除術を施行した。病理組織検査では、異型性に乏しい核を有する紡錘形細胞の束状増殖に加え、背景にはリンパ球と形質細胞を主体とした細胞浸潤を認めることから、IMTと診断した。さらに1ヵ月後に切除断端にargon plasma coagulationを追加した。切除後1年4ヵ月が経過したが再発を認めていない。結論. 気管支内腔にポリープ状に増殖したIMTに対する気管支鏡下腫瘍切除術は、有用な治療法の一つになりうると考えられた。(著者抄録)

Volatile Organic Compounds in Exhaled Breath of Idiopathic Pulmonary Fibrosis for Discrimination from Healthy Subjects

Yu-ichi Yamada, Gen Yamada, Mitsuo Otsuka, Hirotaka Nishikiori, Kimiyuki Ikeda, Yasuaki Umeda, Hirofumi Ohnishi, Koji Kuronuma, Hirofumi Chiba, Joerg Ingo Baumbach, Hiroki Takahashi

LUNG ( SPRINGER ) 195 ( 2 ) 247 - 254 2017.04 [Refereed]

Purpose Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =-0.393, p = 0.013), %VC (r =-0.569, p < 0.001), FVC (r = -0.440, p = 0.004), %FVC (r =-0.539, p < 0.001), DLco (r =-0.394, p = 0.018), and %DLco (r =-0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.

DOI PubMed

Surfactant protein A (SP-A) and SP-A-derived peptide attenuate chemotaxis of mast cells induced by human β-defensin 3.

Yasuaki Uehara, Motoko Takahashi, Masaki Murata, Atsushi Saito, Rina Takamiya, Yoshihiro Hasegawa, Koji Kuronuma, Hirofumi Chiba, Jiro Hashimoto, Norimasa Sawada, Hiroki Takahashi, Yoshio Kuroki, Shigeru Ariki

Biochemical and biophysical research communications 485 ( 1 ) 107 - 112 2017.03 [International journal]

Human β-defensin 3 (hBD3) is known to be involved in mast cell activation. However, molecular mechanisms underlying the regulation of hBD3-induced mast cell activation have been poorly understood. We previously reported that SP-A and SP-A-derived peptide 01 (SAP01) regulate the function of hBD3. In this study, we focused on the effects of SP-A and SAP01 on the activation of mast cells induced by hBD3. SAP01 directly bound to hBD3. Mast cell-mediated vascular permeability and edema in hBD3 administered rat ears were decreased when injected with SP-A or SAP01. Compatible with the results in rat ear model, both SP-A and SAP01 inhibited hBD3-induced chemotaxis of mast cells in vitro. Direct interaction between SP-A or SAP01 and hBD3 seemed to be responsible for the inhibitory effects on chemotaxis. Furthermore, SAP01 attenuated hBD3-induced accumulation of mast cells and eosinophils in tracheas of the OVA-sensitized inflammatory model. SP-A might contribute to the regulation of inflammatory responses mediated by mast cells during infection.

DOI PubMed

非HIV患者におけるST合剤使用困難ニューモシスチス肺炎に対するアトバコンの使用経験

小林智史, 齊藤充史, 錦織博貴, 黒沼幸治, 高橋弘毅

感染症学雑誌 ( (一社)日本感染症学会 ) 91 ( 1 ) 93 - 93 2017.01

黒沼幸治, 本田宏幸

Medicina ( (株)医学書院 ) 54 ( 1 ) 106 - 108 2017.01

Congenital Pulmonary Vein Atresia in an Adult.

Koji Kuronuma, Tomofumi Kobayashi, Youhei Takahashi, Hiroki Takahashi

Internal medicine (Tokyo, Japan) 56 ( 7 ) 877 - 878 2017 [Domestic journal]

DOI PubMed

Treatment of pulmonary fibrosis with siRNA against a collagen-specific chaperone HSP47 in vitamin A-coupled liposomes

Mitsuo Otsuka, Masanori Shiratori, Hirofumi Chiba, Koji Kuronuma, Yasushi Sato, Yoshiro Niitsu, Hiroki Takahashi

EXPERIMENTAL LUNG RESEARCH ( TAYLOR & FRANCIS INC ) 43 ( 6-7 ) 271 - 282 2017 [Refereed]

Background: Pulmonary fibrosis is a life-threatening pathological state of progressive interstitial lung diseases, such as idiopathic pulmonary fibrosis. Myofibroblasts are known to play a critical role in the pathogenesis of pulmonary fibrosis. This study aimed to evaluate the inhibitory effect of a small interfering RNA (siRNA) on a collagen-specific chaperone heat shock protein 47 (HSP47). The siRNA was preferentially delivered to myofibroblasts in a bleomycin (BLM)-induced pulmonary fibrosis rat model using siRNA against HSP47, encapsulated in a vitamin A-coupled liposome (VA-lip-siRNA HSP47). Methods and Results: Male Sprague-Dawley rats were treated with an intratracheal injection of BLM or phosphate buffered saline followed by an intravenous injection of VA-lip-siRNA HSP47 three times per week under preventive administration schedules from day 1 to day 21 and therapeutic administration schedules from day 15 to day 35. The expression of HSP47 after the treatment was assessed by immunoblotting. The specific delivery of VA-lip-siRNA HSP47 conjugated with 6'-carboxyfluoresce into myofibroblasts was examined by immunofluorescence staining. The effect of VA-lip-siRNA HSP47 on fibrosis was analyzed by morphological and biochemical methods. Preferential delivery of VA-lip-siRNA HSP47 to myofibroblasts in fibrotic areas in BLM-treated rats was verified by immunofluorescence staining. Treatment of VA-lip-siRNA HSP47 clearly suppressed HSP47 expression and induced apoptosis of myofibroblasts in the lung of BLM-treated rats. Hydroxyproline levels and inflammatory cytokines in the lungs, and the number of inflammatory cells in the bronchial alveolar lavage of BLM-treated rats were significantly suppressed by the treatment. Morphological assessment showed that VA-lip-siRNA HSP47 also significantly improved the morphological pulmonary fibrosis of BLM-treated rats in both preventive and therapeutic schedules. Conclusions: These results suggest that VA-lip-siRNA HSP47 improves pulmonary fibrosis in not only preventive, but also therapeutic schedules, and thus, this drug delivery system should provide a novel therapy for refractory pulmonary fibrosis.

DOI PubMed

　 PREV - NEXT 　

<KURONUMA Kouji>

Papers - KURONUMA Kouji