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Hajime Fujimoto

Publications and source records attributed to Hajime Fujimoto.

15 recordsLinked to original sources
PubMed2006

Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse.

Tenascin C (TN-C) is an extracellular matrix glycoprotein whose expression is increased in several inflammatory diseases of the lung, including bronchial asthma. However, the exact function of TN-C in the pathogenesis of lung inflammation remains unclear. In the present study, we compared the degree of bronchial asthma in wild-type and TN-C-deficient (-/-) BALB/c mice. Bronchial asthma was induced by sensitization and challenge with ovalbumin. Littermates treated with saline were used as controls. Cytokines in bronchoalveolar lavage fluid and plasma were measured by enzyme immunoassays. The number of eosinophils in the lung was significantly increased in wild-type mice compared with TN-C-knockout mice. Airway hyperreactivity, NF-kappaB activation and concentrations of monocyte chemoattractant protein-1, IL-5, IL-13, metalloproteinase-9 and immunoglobulin-E in the bronchoalveolar lavage fluid were significantly decreased in ovalbumin-sensitized/challenged TN-C-knockout mice compared with their wild-type counterparts. In vitro experiments disclosed that TN-C significantly stimulates the secretion of IL-5, IL-13, IFN-gamma and immunoglobulin-E from spleen lymphocytes. These observations suggest that TN-C is involved in the pathogenesis of bronchial asthma.

Allergens↗
PubMed2006

Thrombin-activatable fibrinolysis inhibitor deficiency attenuates bleomycin-induced lung fibrosis.

Decreased fibrinolytic function favors the development of pulmonary fibrosis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a strong suppressor of fibrinolysis, but its role in lung fibrosis is unknown. Therefore, we compared bleomycin-induced lung fibrosis in TAFI-deficient, heterozygous, and wild-type mice. The animals were sacrificed 21 days after bleomycin administration, and markers of lung fibrosis and inflammation were measured. The bronchoalveolar lavage fluid levels of total protein, neutrophil proteases (elastase, myeloperoxidase), cytokines (tumor necrosis factor-alpha, interleukin-13), chemokine (monocyte chemoattractant protein-1), coagulation activation marker (thrombin-antithrombin complex), total soluble collagen, and growth factors (platelet-derived growth factor, transforming growth factor-beta1, granulocytic-macrophage growth factor) were significantly decreased in knockout mice compared to wild-type mice. Further, histological findings of fibrosis, fibrin deposition, and hydroxyproline and collagen content in the lung were significantly decreased in knockout mice compared to wild-type mice. Depletion of fibrinogen by ancrod treatment led to equalization in the amount of fibrosis and collagen deposition in the lungs of knockout and wild-type mice. No difference was detected in body temperature or arterial pressure between the different mouse phenotypes. These results suggest that the anti-fibrinolytic activity of TAFI promotes lung fibrosis by hindering the rate at which fibrin is degraded.

Animals↗
PubMed2006

[Definition and pathophysiology of acute coronary syndrome].

Acute coronary syndrome is a clinical state induced by the thrombosis following the rupture of unstable atherosclerotic plaque. Atherosclerotic plaque increases its vulnerability by the accumulation of foam cells, inflammation, oxidative stress, and apoptosis of vascular wall cells including macrophage. Inflammation and oxidative stress stimulates macrophages to produce matrix metalloproteinase (MMP), which degrades extracellular matric proteins and causes thinning of the fibrous cap. When the fibrous cap of the plaque tears, thrombogenic lipid core is exposed to blood, and platelets accumulate at the site, resulting in the significant reduction of coronary blood flow. Treatment of acute coronary syndrome patients should be focused on the stabilization of the plaque as well as vasodilatation, oxygen supply, or control of hemodynamics.

Angina, Unstable↗
PubMed2005

Sarcoidosis presenting as prepatellar bursitis.

A 61-year-old woman complained of a subcutaneous mass in her right knee. MR images revealed a well-defined subcutaneous mass in the prepatellar region, containing some fluid and foci of short T2. The lesion showed some marginal contrast uptake after an administration of meglumine gadopentetate (Gd-DTPA), consistent with prepatellar bursitis. The pathological specimen, however, revealed subcutaneous sarcoidosis involving the bursa.

Bursitis↗
PubMed2005

Radiological and pathological correlation of lung malignant tumors treated with percutaneous radiofrequency ablation.

Radiological and histological correlation was evaluated in patients with malignant tumors of the lung that underwent radiofrequency ablation (RFA). One of the patients had a primary lung tumor and another patient had three metastatic lung tumors. RFA was performed under computed tomography (CT) fluoroscopic guidance. CT showed ground glass shadows around the tumoral lesions immediately after RFA, but one week later homogenous opacification without tumoral enhancement was noted. Two months after RFA, most lesions showed cystic changes without activity on FDG-PET. Histological evaluation showed massive coagulation necrosis throughout the tumor and some viable cells at the peripheral areas in all lesions. Although RFA is a promising therapeutic approach for malignant lung tumors, some viable cells may persist in peripheral areas of the tumor.

Aged↗
PubMed2004

Carbon monoxide protects against cardiac ischemia--reperfusion injury in vivo via MAPK and Akt--eNOS pathways.

BACKGROUND: Carbon monoxide (CO) is postulated to protect tissues against several types of injuries. We investigated the role of CO in amelioration of cardiac ischemia-reperfusion injury in vivo and the mechanisms involved in it. METHODS AND RESULTS: Rats inhaled CO (250 ppm, 500 ppm, or 1000 ppm) for 24 hours in a chamber after myocardial ischemia-reperfusion induced by occluding the left anterior descending coronary artery for 30 minutes. Pre-exposure to 1000 ppm of CO significantly reduced the ratio of infarct areas to risk areas and suppressed the migration of macrophages and monocytes into infarct areas, and the expression of tumor necrosis factor (TNF)-alpha in the heart; however, 250 ppm, 500 ppm of CO, or low barometric pressure hypoxia (0.5 atm) did not affect them. Exposure to 1000 ppm CO resulted in the activation of p38 mitogen-activated protein kinase (p38MAPK), protein kinase Balpha(Akt), endothelial nitric oxide synthase (eNOS), and cyclic guanosine monophosphate (cGMP) in the myocardium. Inhibition of p38MAPK, PI3kinase, NO, and soluble guanylate cyclase with SB203580, wortmannin, N(G)-nitro-L-arginine methyl ester (L-NAME), and methylene blue, respectively, attenuated the cytoprotection by CO. CONCLUSIONS: CO has beneficial effects on cardiac ischemia-reperfusion injury; this effect is mediated by p38MAPK pathway and Akt-eNOS pathway, including production of cGMP.

Animals↗
PubMed2004

Increased circulating levels of thrombin-activatable fibrinolysis inhibitor in lung cancer patients.

Impairment of fibrinolytic function plays an important role in the mechanism of thrombotic disorders in cancer patients. This study assessed the circulating level of thrombin-activatable fibrinolysis inhibitor in patients with lung cancer and its expression by several lung cancer cell lines. The plasma concentrations of thrombin-activatable fibrinolysis inhibitor were significantly increased in lung cancer patients compared to healthy subjects. The concentration of thrombin-activatable fibrinolysis inhibitor was particularly higher in patients with small cell carcinoma compared to those with adenocarcinoma or squamous cell carcinoma, and in cancer patients that responded to chemotherapy compared to non-responders. In vitro studies showed more expression of thrombin-activatable fibrinolysis inhibitor in small cell carcinoma than in adenocarcinoma cell lines and more expression in lung cancer cell lines sensitive to anti-cancer agents than in resistant cell lines. This study suggests that thrombin-activatable fibrinolysis inhibitor, in part secreted from lung cancer cells, may play a role in the pathogenesis of thrombotic disorders in lung cancer patients.

Adenocarcinoma↗
PubMed2004

Preoperative parameters expanding the indication of sphincter preserving surgery in patients with advanced low rectal cancer.

OBJECTIVE: To clarify the preoperative parameters of the required distal margin that can be applied to the criteria of sphincter-preserving surgery in rectal cancer. SUMMARY BACKGROUND DATA: Although aggressive sphincter-preserving surgery, including intersphincteric resection, is beginning to be applied to low rectal tumors, unexpected distal cancer spread might undermine local control in patients undergoing such a procedure. The 'two-centimeter rule' of distal clearance is predominant at present, whereas preoperative criteria to determine the individual required distal margin have not yet been established. METHODS: First, by reviewing 556 rectal cancers, promising risk parameters of intramural distal spread (IM) were selected and, subsequently, such parameters were examined in regard to whether they could be evaluated preoperatively. Furthermore, 80 patients with lower rectal cancers located above the anal canal who were undergoing abdominoperineal resection were reviewed as to whether IM risk factors could be used as criteria to identify the low rectal cancer with or without anal canal involvement. RESULTS: IM was observed in 10.6% (IM >or= 10 mm: 2.3%) of the patients examined, and the incidence was higher in tumors with certain unfavorable histologic characteristics, including tumor "budding," in their submucosal region at the distal edge (24.4%) than in those with no such histology (5.3%). Regarding such unfavorable histology as IM risk factor, together with 3/4 or more annularity and type 3 gross appearance, IM rates were 3.3% (IM >or= 10 mm: 0.5%) in the no-risk group, 9.1% (IM >or= 10 mm: 1.7%) in the one-risk group, and 29.1% (IM >or= 10mm: 7.8%) in the multiple-risks group. These results were reproduced well even if such risk factors were evaluated endoscopically or histologically on preoperative biopsy specimens. Furthermore, no anal canal involvement was observed in 32 tumors without IM risk; however, microscopic cancer spread down to the anal canal, including that into outside of the internal sphincter muscle, was observed in 9.1% of tumors with one IM risk and in 26.7% of multiple-risk tumors. CONCLUSIONS: The preoperative evaluation of particular parameters related to IM enabled the accurate selection of rectal cancer to which the one-centimeter rule of distal clearance can be applied. This could allow us to expand the indication of sphincter preservation for very low rectal cancer patients.

Adult↗
PubMed2004

Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse.

The expression of aquaporin-5, the major water channel expressed in alveolar, tracheal, and upper bronchial epithelium, is significantly down-regulated during acute lung injury. In the present study, the expression of aquaporin-5 in two different mouse models of lung fibrosis was evaluated. Lung fibrosis was induced by intratracheal and by subcutaneous infusion of bleomycin. The expression of aquaporin-5 was investigated by immunohistochemical studies and by polymerase chain reaction. There were many cells with loss of aquaporin-5 immunoreactivity in type I alveolar epithelial cells in the mouse models of lung fibrosis. Immunohistochemistry of lung tissue in aquaporin-5 knockout mice revealed a fibrotic phenotype with increased deposition of extracellular collagen type I in thickened alveolar walls. Semiquantitative analysis of aquaporin-5 mRNA expression showed more abundant content of aquaporin-5 in the lung of the normal mouse compared to the mouse with lung fibrosis. The results of this study showed, for the first time, that chronic lung injury and lung fibrosis is associated with decreased protein and mRNA expression of aquaporin-5 in the lung.

Animals↗
PubMed2003

Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice.

Asthma is one of the most common diseases and is characterized by airway obstruction, airway inflammation, and increased airway responsiveness. Glucocorticoids are very effective in treatment, but their long-term use is associated with several side effects, so that new anti-inflammatory drugs are in development. Activated protein C (APC) is a serine protease with potent anti-inflammatory effects. This study evaluated the effect of inhaled APC on airway inflammation and hyperresponsiveness in a murine asthma model. Asthma was induced in BALB/c mice by exposure to chicken egg ovalbumin (OVA), and the effect of inhaled APC was assessed by administering prior to OVA exposure. Inhalation of APC significantly inhibited the expression of T helper 2 (Th2) cytokines, immunoglobulin E (IgE), eosinophilic inflammation, and hyperresponsiveness. APC also significantly suppressed the expression of Th2 cytokines and IgE from lymphocytes isolated from OVA-sensitized/challenged animals. In addition, binding of signal transducer and activator of transcription 6 (STAT6) and nuclear factor kappa B (NF-kappa B) oligonucleotides to lung nuclear proteins was significantly reduced in mice treated with inhaled APC. In brief, the exogenous supplementation of APC inhibits the immunologic and inflammatory responses induced by Th2 cytokines in a mouse model of asthma and may represent a novel anti-inflammatory treatment.

Animals↗
PubMed2003

Thrombin-activatable fibrinolysis inhibitor and protein C inhibitor in interstitial lung disease.

Intraalveolar activation of the coagulation system due to reduced fibrinolytic function plays a critical role in the pathogenesis of interstitial lung disease. Recently, a new potent inhibitor of fibrinolysis, thrombin-activatable fibrinolysis inhibitor, has been isolated and characterized from human plasma. This study evaluated the levels of thrombin-activatable fibrinolysis inhibitor and protein C inhibitor, another suppressor of fibrinolysis, in the bronchoalveolar lavage fluid from patients with interstitial lung disease. There were 82 patients with interstitial lung disease and 8 normal subjects. The bronchoalveolar lavage fluid levels of thrombin-activatable fibrinolysis inhibitor and protein C inhibitor were significantly higher in all patients with interstitial lung disease than in normal subjects. Both inhibitors of fibrinolysis were significantly and inversely correlated with fibrinolytic activity in all patients. The levels of thrombin-activatable fibrinolysis inhibitor were significantly correlated with those of protein C inhibitor, thrombin-antithrombin complex, and monocyte chemoattractant protein-1. Reverse transcriptase-polymerase chain reaction showed that alveolar macrophages isolated from patients with interstitial lung disease as well as immortalized lung epithelial cell lines express thrombin-activatable fibrinolysis inhibitor antigen. Overall, these findings suggest that thrombin-activatable fibrinolysis inhibitor and protein C inhibitor may play important roles in the mechanism of intraalveolar hypofibrinolysis associated with interstitial lung diseases.

Alveolitis, Extrinsic Allergic↗
PubMed2002

Sarcoidosis breaching the fascia and mimicking a sarcoma.

A 55-year-old woman complained of a subcutaneous mass in her left buttock. MR images revealed an ill-defined soft tissue mass that crossed the fascia of the gluteus maximus muscle. Some surrounding edema was noted. The lesion showed some contrast uptake after administration of Gd-DTPA. An excisional biopsy revealed sarcoidosis involving both the muscle and subcutaneous tissue across the fascia, mimicking a sarcoma.

Buttocks↗
PubMedDate not supplied

Diffusion-weighted imaging of prostate cancer.

OBJECTIVE: The purpose of this study was to assess whether T2-weighted (T2W) imaging with diffusion-weighted (DW) imaging could improve prostate cancer detection as compared with T2W imaging alone. METHODS: The subjects consisted of 37 patients with prostate cancer and 23 without cancer undergoing magnetic resonance (MR) imaging. Using a 1.5-T superconducting magnet, all patients underwent T2W and DW imaging with parallel imaging. Images were independently reviewed by 3 readers to determine the detectability of prostate cancer. The detectability of T2W imaging without and with DW imaging was assessed by means of receiver operating characteristic analysis. RESULTS: Mean areas under the receiver operating characteristic curve for T2W imaging alone and for T2W imaging with DW imaging were 0.87 and 0.93, respectively. The receiver operating characteristic analysis showed that the addition of DW imaging to conventional T2W imaging significantly improved tumor detection (P = 0.0468) compared with T2W imaging alone. CONCLUSIONS: The addition of DW imaging to conventional T2W imaging provides better detection of prostate cancer.

Artifacts↗