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Shoji Kudoh

Publications and source records attributed to Shoji Kudoh.

At least 19 recordsLinked to original sources
PubMed2003

Proteomic analysis of intestinal epithelial cells expressing stabilized beta-catenin.

Aberrant accumulation of beta-catenin protein because of mutation of either the beta-catenin or adenomatous polyposis coli gene plays an essential role in the development of colorectal carcinoma. We established previously a stable clone of the rat small intestinal epithelial cell line IEC6, which is capable of inducing stabilized beta-catenin protein lacking NH(2)-terminal glycogen synthase kinase-3beta phosphorylation site under a strict control of the tetracycline-regulatory system. This clone, IEC6-TetOFF-beta-catenin DeltaN89, shows in vitro polypoid growth on the removal of doxycycline and seems to be an appropriate model for analyzing the molecular mechanisms of early intestinal carcinogenesis. Of >2000 protein spots displayed by newly developed two-dimensional difference gel electrophoresis, 22 were found to be up- or down-regulated on the induction of stabilized beta-catenin. The majority of these proteins fell into two categories: (a) redox-status regulatory proteins and (b) cytoskeleton-associated proteins. Representatively, a key redox-status regulatory protein, manganese superoxide dismutase, up-regulated in IEC6 cells expressing stabilized beta-catenin protein, was overexpressed in adenoma and adenocarcinoma cells of familial adenomatous polyposis patients in parallel with the accumulation of beta-catenin. These results suggest that aberrant accumulation of beta-catenin might contribute to colorectal carcinogenesis by affecting redox status in the mitochondria of intestinal epithelial cells.

Adenocarcinoma↗
PubMed2003

Diesel exhaust particles upregulate eotaxin gene expression in human bronchial epithelial cells via nuclear factor-kappa B-dependent pathway.

Fine particles derived from diesel engines, diesel exhaust particles (DEP), have been shown to augment gene expression of several inflammatory cytokines in human airway epithelial cells in vitro. However, it remains unclear whether or not DEP have any effect on the expression and production of eotaxin, an important chemokine involved in eosinophil recruitment into the airways. We studied the effects of DEP by using a conventional suspended DEP and by a recently established in vitro cell exposure system to diesel exhaust (Abe S, Takizawa H, Sugawara I, and Kudoh S, Am J Respir Cell Mol Biol 22: 296-303, 2000). DEP showed a dose-dependent stimulatory effect on eotaxin production by normal human peripheral airway epithelial cells as well as by bronchial epithelial cell line BET-1A as assessed by specific ELISA. mRNA levels increased by DEP were shown by RT-PCR. DEP showed an additive effect on IL-13-stimulated eotaxin expression. DEP induced NF-kappaB activation by EMSA as previously reported but did not induce signal transducer and activator of transcription (STAT) 6 activation according to Western blot analysis. Finally, antioxidant agents (N-acetyl cysteine and pyrrolidine dithiocarbamate), which inhibited NF-kappaB activation but failed to affect STAT6 activation, almost completely attenuated DEP-induced eotaxin production, whereas these agents failed to attenuate IL-13-induced eotaxin production. These findings suggested that DEP stimulated eotaxin gene expression via NF-kappaB-dependent, but STAT6-independent, pathways.

Acetylcysteine↗
PubMed2003

Increased expression of the LGALS3 (galectin 3) gene in human non-small-cell lung cancer.

Patients with lung cancer have a poor prognosis because of the high metastatic potential of the neoplasm. Therefore, identifying new molecular targets for anti-metastatic therapy is very important. To identify novel key factors of tumor metastasis in lung cancer, we established the gene expression profiles of two adenocarcinoma cell line variants, PC9/f9 and PC9/f14, by use of genome-wide human cDNA microarray analysis and comparing these profiles with that of the parental cell line, PC9. The PC9/f9 and PC9/f14 cell lines were selected for analysis because of their high metastatic potential. We identified five genes in the highly metastatic cell lines that showed a significantly enhanced or reduced expression and that had not been reported to be involved in metastasis of lung cancer. One of the overexpressed genes that was identified encoded the beta-galactoside-binding protein LGALS3 (Galectin 3). LGALS3 has been reported to be overexpressed in a variety of human cancers, but not in lung cancer, and to be involved in tumor metastasis. We examined the expression of LGALS3 by use of real-time quantitative reverse transcription-polymerase chain reaction in 38 lung cancer cell lines and in tumor tissue obtained by thoracoscopic biopsy. A population (10/30) of the non-small-cell lung cancers examined was found to overexpress the LGALS3 gene at levels three times higher than those of normal epithelial cells. In contrast, all small-cell lung cancers either failed to express the gene or expressed it at a very low level. The mean of the relative expression of the LGALS3 gene in non-small-cell lung cancer (3.065 +/- 3.976) was significantly higher than those of small-cell lung cancer (0.02 +/- 0.03) (P < 0.025). This is the first report of alterations of LGALS3 gene expression in lung cancer. These results, together with the previous reports on Galectin 3 function, suggest that Galectin 3 may play a role in the process of metastasis in non-small-cell lung cancer that overexpresses Galectin 3, but not in small-cell cancer. Accordingly, LGALS3 may be a phenotypic marker that excludes small-cell lung cancer and may represent a novel target molecule in non-small-cell lung cancer therapy.

Adenocarcinoma↗
PubMed2003

Influence of the rheological properties of airway mucus on cough sound generation.

OBJECTIVES: There have been several reports regarding the role of airway mucus in cough sound generation, but the properties of the mucus that influence cough sound generation remain unclear. The aim of this study was to elucidate the influence of the rheological properties of airway mucus on cough sound generation. METHODOLOGY: The acoustic properties of voluntary cough sounds from 15 patients with chronic productive cough and nine controls with dry cough were analyzed by dividing the energy envelope of the sounds into three phases and computing the root mean square values and the duration of each phase as a proportion of the total cough duration. The rheological properties of the airway mucus (yield value, ciliary transportability and spinability) were also measured. Differences between productive and dry cough sounds, and correlations between the acoustic properties of cough sounds and the rheological properties of the airway mucus, were analyzed. RESULTS: The acoustic properties of productive and dry cough sounds differed significantly (P < 0.05). The acoustic properties of second phase cough sounds correlated significantly with the yield value and ciliary transportability of the airway mucus (P < 0.05). CONCLUSIONS: The rheological properties of the airway mucus influenced cough sound generation.

Adult↗
PubMed2003

Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease.

OBJECTIVES: The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases. METHODS: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo. Sputum smears were also prepared to count sputum neutrophils. Patients' symptoms were assessed by a questionnaire that used a visual analogue scale. RESULTS: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 +/- 1.8 to 24.4 +/- 2.5 (P = 0.0103). CONCLUSIONS: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases.

Adult↗
PubMed2003

Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. The incidence of IPF increases with age. Aging contributes to lifestyle-related diseases, including diabetes mellitus (DM); therefore, it is possible that lifestyle-related diseases may affect either the initiation or progression of IPF. DESIGN: Case-control study. SETTING: Nippon Medical School and Omiya City Clinic. PATIENTS AND PARTICIPANTS: Sixty-five consecutive patients with IPF who were admitted to Nippon Medical School Hospital from 1995 to 2000, and 184 control subjects selected from 15,798 subjects who were admitted to Omiya City Clinic for routine medical examination between September 1999 and August 2000. MEASUREMENTS: Age, sex, smoking history, and results of physical examinations, blood examinations, and lung function testing were extracted from medical records and were compared with the diagnostic criteria for lifestyle-related diseases. RESULTS: The adjusted odds ratios for cigarette smoking were 5.40 (95% confidence interval [CI], 2.30 to 12.66) and 4.06 (95% CI, 1.80 to 9.15) for diabetes. There were no differences in clinical characteristics of patients with IPF that could be related to the presence of DM. CONCLUSION: DM may be a risk factor for IPF.

Aged↗
PubMed2003

A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line.

The matrix metalloproteinases (MMPs) are likely to contribute to tumor cell invasion, metastasis and angiogenesis. Several MMP inhibitors have been developed, recently and their anti-tumor efficacy is being evaluated in clinical trials. FYK-1388 is a novel broad MMP inhibitor which blocks the activity of MMP-1, -2, -3, -7, -9, -13 and -14 (MT-MMP-1). It is especially effective against MMP-2 and -9 more so than other MMP inhibitors such as Marimastat, Ro 32-3555 and D-2163. Here, we investigated the anti-tumor efficacy of FYK-1388 using the human fibrosarcoma cell line HT-1080. These cells produced MMP-2 and -9, which FYK-1388 inhibited at a dose of 10(-8) M. FYK-1388 at 0.2 mg/mouse/day significantly suppressed tumor growth when given by s.c. injection for 22 days, experimental lung metastasis after 5 days s.c. injection and also suppressed tumor-induced angiogenesis in the dorsal air sac assay after 7 days s.c. injection. In the MTT assay, FYK-1388 had no effect on the in vitro growth of HT-1080 cells. These results suggest that FYK-1388 possesses anti-tumor efficacy as a result of inhibiting angiogenesis through the suppression of MMP-2 and -9 activity.

Angiogenesis Inhibitors↗
PubMed2003

[Macrolide].

Explore the source record for details and available documents.

Animals↗
PubMed2003

Familial clustering of dendriform pulmonary ossification.

Dendriform pulmonary ossification is an extremely rare disease, which is usually found and analysed postmortem. Pathogenesis of pulmonary ossification is therefore still unknown. We describe two males in the same family (a 29 year-old patients and his 58 year-old father) with pulmonary ossification. The young male was symptomatic pneumothorax but his father had been asymptomatic since youth. Familial clustering of pulmonary ossifications strongly suggests a genetic predisposition for the pathogenesis. This is the first report of two cases of dendriform pulmonary ossification in the same family.

Adult↗
PubMed2003

[Iressa (gefitinib)].

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor that is reported to be well tolerated and active in patients with chemotherapy-resistant non small cell lung cancer. On the other hand, gefitinib was also reported to produce a severe adverse event, interstitial lung disease, in less than 2% of treated patients. Given these circumstances, it is important to evaluate this drug and to establish its use clinically. We do not have sufficient data to evaluate gefitinib at this time. Phase III study of second/third line or maintenance therapy using gefitinib is required for such an evaluation. The development of individualized therapy with gefitinib might be also be required.

Antineoplastic Agents↗
PubMed2002

Differential secretion of cytokines and adhesion molecules by HUVEC stimulated with low concentrations of bleomycin.

Bleomycin (BLM) is known to induce lung inflammation and subsequent fibrosis. Endothelial cells have been reported to play an important role, producing cytokines and adhesion molecules during the inflammatory process in pulmonary fibrosis. To examine the effects of BLM on endothelial cells, we investigated the expression profiles of various cytokines and adhesion molecules produced by endothelial cells stimulated with BLM. Increased expressions of interleukin-8 and monocyte chemoattractant protein-1 measured as protein as well as mRNA by human umbilical vein endothelial cells (HUVECs) were detected after exposure to BLM. Similarly, increased expressions of E-selectin and intercellular adhesion molecule-3 were detected both at the protein and mRNA levels. Under these conditions, a small but significant decrease of [3H]thymidine uptake was detected. These findings indicate that HUVEC were stimulated to secrete cytokines and express adhesion molecules in the presence of low concentrations of BLM which have a mildly inhibitory effect on cellular proliferation.

Bleomycin↗
PubMed2002

The promoter region of the human BUBR1 gene and its expression analysis in lung cancer.

Mitotic checkpoint impairment is present in human lung cancers with chromosomal instability (CIN). Spindle-checkpoint genes have been reported to be mutated in several human cancers, but these mutations are infrequent. Recent reports suggest that the hBUBR1 gene may play an important role in mitotic checkpoint control and in mitotic checkpoint impairment in human cancers. We analyzed the expression of hBUBR1 in lung cancer cell lines using real time quantitative RT-PCR. The expression of BUBR1 was found to be up-regulated in all of these cell lines. In addition, we cloned and characterized the promotor region of hBUBR1 and determined its genomic structure, which includes 23 exons. The open reading frame (ORF) of the hBUBR1 gene comprises exons 1 through 23. There are GC-rich regions located at the flanking region and about 150 bp upstream from exon 1. The promoter region (424 bp upstream from exon 1) showed promoter activity and includes multiple transcription factor consensus binding motifs, including those for Sp1, Nkx-2, CdxA, SRY, MyoD, Ik-2, HNF-3b, Staf, Oct-1, Nkx-2, v-Myb, and AML 1a. Multiple pathways leading to activation of those binding factors may contribute to hBUBR1 gene transcription. Knowledge of the genomic structure and the promoter region of the hBUBR1 gene will facilitate investigation of its role in mitotic checkpoint control and tumor progression in human cancers.

Cell Cycle Proteins↗
PubMed2002

[Patient assessment for zanamivir therapy (second report) -- a survey of patients with influenza who were prescribed zanamivir during the 2001/2002 season in Japan].

Patients diagnosed as influenza who were prescribed zanamivir were surveyed from December 2001 to April 2002 in Japan as the same 2000/2001 influenza season. A total of 751 survey questionnaires were returned. We analyzed the efficacy of zanamivir against 367 patients who were diagnosed as influenza by rapid diagnosed kit and took zanamivir within 48 hours after onset of symptoms. Following the first zanamivir treatment, symptom relief was reported by 24.0% of the patients within 12 hours, 52.6% within 24 hours and 79.6% within 48 hours. The patients reported that the severest influenza symptom was fever, 28.4% of the patients started to feel reduction of fever within 12 hours, 62.2% within 24 hours. All of the 751 patients, 98.8% reported that the Diskhaler could be used as instructed by the doctor or pharmacist and 91.3% found the device easy or very easy to use. These results showed that the effect of zanamivir started very fast and the diskhaer was well accepted. This was the same as the previous results.

Adolescent↗
PubMed2002

Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis.

The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.

Actinomycetales Infections↗
PubMed2002

[Attenuated mRNA induction of molecules associated with neutrophil migration by 14-membered ring macrolides inhibits bleomycin induced acute lung injury in mice].

BACKGROUND: Although the pathogeneses of interstitial pneumonia are not well understood, it has been reported that inflammatory cells, especially neutrophils, and their injurious substances play important roles in the progression of interstitial pneumonia. Erythromycin and other 14-membered ring macrolides (14-MRMLs) have been reported to inhibit chronic airway inflammation by mechanisms of anti-neutrophil and several other anti-inflammatory activities. The present study was undertaken to investigate the effects and mechanisms of 14-MRMLs (erythromycin: EM; clarithromycin: CAM; roxithromycin: RXM) on an experimental model of bleomycin (BLM) -induced acute lung injury in mice. METHODS: BLM was administered intravenously to ICR mice. For the evaluation of early-phase inflammation, cell populations in broncho-alveolar lavage fluid (BALF) and induction of mRNA of adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1) and TNF-alpha tested by RT-PCR in lung tissues were examined at 0 to 13 days after BLM. These parameters were also compared with those of the control (NS alone), 14-MRMLs-untreated (BLM alone) and-pre-treated (BLM+pre 14-MRMLs) groups. RESULTS: The number of neutrophils, macrophages, and lymphocytes significantly increased in BAL. Neutrophils especially increased with two peaks after BLM administration. 14-MRMLs significantly inhibited both peaks of neutrophil. The increase in number of macrophages in BALF was significantly attenuated by EM and RXM, and slightly attenuated by CAM. Number of lymphocytes in BALF was significantly attenuated by EM and CAM, and slightly attenuated by RXM. Changes in mRNA expression of E-selectin, P-selectin, ICAM-1, VCAM-1, and TNF-alpha were associated with the number of neutrophils migrating into the airspace. 14-MRMLs clearly inhibited the induction of VCAM-1 mRNA, and tended to attenuate the induction of ICAM-1 and TNF-alpha mRNA, but did not inhibit the induction of E-selectin and P-selectin mRNA. DISCUSSION: These findings show that 14-MRMLs clearly attenuated the expression of VCAM-1mRNA, and tended to attenuate the induction of ICAM-1 and TNF-alpha mRNA, and subsequently inhibited leucocyte, especially neutrophil migration into the airspace during the early phase of BLM-induced lung injury and finally inhibited lung fibrosis. This might be one potent mechanism of the anti-inflammatory effects of 14-MRMLs in BLM-induced acute lung injury. The findings suggest that prophylactic administration of 14-MRMLs may be clinically efficacious in preventing acute exacerbation of interstitial pneumonia and acute lung injury.

Animals↗
PubMed2002

Fourteen-membered ring macrolides inhibit vascular cell adhesion molecule 1 messenger RNA induction and leukocyte migration: role in preventing lung injury and fibrosis in bleomycin-challenged mice.

BACKGROUND AND OBJECTIVE: Although the pathogenesis of interstitial pneumonia and pulmonary fibrosis are not well understood, it has been reported that inflammatory cells, especially neutrophils, and the injurious substances produced by them play important roles in the progression of interstitial pneumonia and subsequent fibrosis. Erythromycin and other 14-membered ring macrolides (14-MRMLs) have been reported to improve the survival of patients with diffuse panbronchiolitis by antineutrophil and several other anti-inflammatory mechanisms. The present study was undertaken to investigate the effects of 14-MRMLs on an experimental model of bleomycin-induced acute lung injury and subsequent fibrosis in mice. METHODS: Bleomycin was administered IV to ICR mice. At 28 days after bleomycin injection, fibrotic foci were histologically observed in left lung tissues, and hydroxyproline content in right lung tissues was chemically analyzed. The inhibitory effects of 14-MRMLs were assessed by overall comparison between control (normal saline solution [NS] alone), untreated (bleomycin alone), and treated (bleomycin plus 14-MRMLs) groups. For evaluation of early-phase inflammation, cell populations in BAL fluid and induction of messenger RNA (mRNA) of adhesion molecules (E-selectin, P-selectin, intercellular adhesion molecule 1 [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1]) in lung tissues were examined at 0 to 13 days after bleomycin treatment. These parameters were also compared with those for the control (NS alone), 14-MRML untreated (bleomycin alone), and 14-MRML pretreated (bleomycin plus 14-MRML pretreated) groups. RESULTS: Bleomycin-induced pulmonary fibrosis was inhibited by erythromycin and other 14-MRMLs on day 28 after bleomycin injection in ICR mice, especially those pretreated with 14-MRMLs. Hydroxyproline content in lung tissues was also decreased in the 14-MRML-pretreated groups. The number of neutrophils in BAL fluid significantly increased, with two peaks at 1 day and 9 days (from 6 to 11 days) after bleomycin administration. 14-MRMLs significantly inhibited both peaks of neutrophil infiltration into the airspace. Changes in mRNA expression of adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1) were associated with leukocyte migration into the airspace. 14-MRMLs clearly inhibited the induction of VCAM-1 mRNA, and tended to attenuate that of ICAM-1 mRNA, but inhibited the induction of neither E-selectin mRNA nor P-selectin mRNA. CONCLUSION: These findings indicate that attenuation of inflammatory cell migration into the airspace by 14-MRMLs, especially of neutrophils and macrophages, resulted in inhibition of lung injury and subsequent fibrosis. 14-MRMLs clearly attenuated the expression of VCAM-1 mRNA during the early phase of bleomycin-induced lung injury, and this might be one mechanism of inhibition of neutrophil and macrophage migration into the airspace by 14-MRMLs. This may be one mechanism of the anti-inflammatory and antifibrotic effects of 14-MRMLs. These findings suggest that prophylactic administration of 14-MRMLs may be clinically efficacious in preventing acute exacerbation of interstitial pneumonia and acute lung injury.

Animals↗