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Hirokazu Watanabe

Publications and source records attributed to Hirokazu Watanabe.

13 recordsLinked to original sources
PubMed2004

Macrophage migration inhibitory factor is induced by thrombin and factor Xa in endothelial cells.

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, has been shown to play a role in wound-healing processes. In this study, we investigated whether protease-activated receptor (PAR)-1 and PAR-2 mediated MIF expression in human endothelial cells. Thrombin, factor Xa (FXa), and trypsin induced MIF expression in human dermal microvascular endothelial cells and human umbilical vein endothelial cells, but other proteases, including kallikrein and urokinase, failed to do so. Thrombin-induced MIF mRNA expression was significantly reduced by the thrombin-specific inhibitor hirudin. Thrombin receptor activation peptide-6, a synthetic PAR-1 peptide, induced MIF mRNA expression, suggesting that PAR-1 mediates MIF expression in response to thrombin. The effects of FXa were blocked by antithrombin III, but not by hirudin, indicating that FXa might enhance MIF production directly rather than via thrombin stimulation. The synthetic PAR-2 peptide SLIGRL-NH(2) induced MIF mRNA expression, showing that PAR-2 mediated MIF expression in response to FXa. Concerning the signal transduction, a mitogen-activated protein kinase kinase inhibitor (PD98089) and a nuclear factor (NF)-kappaB inhibitor (SN50) suppressed the up-regulation of MIF mRNA in response to thrombin, FXa, and PAR-2 agonist stimulation, whereas a p38 inhibitor (SB203580) had little effect. These facts indicate that up-regulation of MIF by thrombin or FXa is regulated by p44/p42 mitogen-activated protein kinase-dependent pathways and NF-kappaB-dependent pathways. Moreover, we found that PAR-1 and PAR-2 mRNA expression in endothelial cells was enhanced by MIF. Furthermore, we examined the inflammatory response induced by PAR-1 and PAR-2 agonists injected into the mouse footpad. As shown by footpad thickness, an indicator of inflammation, MIF-deficient mice (C57BL/6) were much less sensitive to either PAR-1 or PAR-2 agonists than wild-type mice. Taken together, these results suggest that MIF contributes to the inflammatory phase of the wound healing process in concert with thrombin and FXa via PAR-1 and PAR-2.

Animals↗
PubMed2004

Dynamic perfusion MRI versus perfusion scintigraphy: prediction of postoperative lung function in patients with lung cancer.

OBJECTIVE: The purpose of this study was to determine the capability of dynamic perfusion MRI as an alternative to pulmonary perfusion scintigraphy for prediction of postoperative lung function in patients with lung cancer. SUBJECTS AND METHODS. Sixty patients with lung cancer (35 men, 25 women) underwent dynamic perfusion MRI, perfusion scintigraphy, and preoperative and postoperative pulmonary function tests (forced expiratory volume in 1 sec [FEV(1)]). Perfusion MRIs were obtained with a 3D turbo field-echo sequence (TR/TE, 2.7/0.6; flip angle, 40 degrees; matrix, 128 x 96) using a 1.5-T scanner. Regional blood flow was calculated from the signal intensity-time curves after bolus injection of contrast medium on MRI (Q(MRI)) and uptake ratios of radioisotope on perfusion scintigraphy (Q(PS)). Postoperative lung functions predicted by MRI (FEV(1,MRI)) and perfusion scintigraphy (FEV(1,PS)) were calculated from preoperative FEV(1) and regional Qs. To determine the capability of MRI as an alternative to scintigraphy, we evaluated correlations and the limits of agreement between predicted FEV(1,MRI) and postoperative FEV(1) and between predicted FEV(1,PS) and postoperative FEV(1). RESULTS: The correlation coefficient of postoperative FEV(1) with FEV(1,MRI) (r = 0.93, p < 0.0001) was better than that with FEV(1,PS) (r = 0.89, p < 0.0001). The limits of agreement between postoperative FEV(1) and predicted FEV(1,MRI) (0.9% +/- 10.4%) were smaller than those between postoperative FEV(1) and predicted FEV(1,PS) (2.1% +/- 13.2%). CONCLUSION: Dynamic perfusion MRI is a feasible alternative to pulmonary perfusion scintigraphy for predicting postoperative lung function in patients with lung cancer.

Adult↗
PubMed2003

Ultraviolet A-induced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor (MIF) in human dermal fibroblasts.

Matrix metalloproteinases (MMPs) are thought to be responsible for dermal photoaging in human skin. In the present study, we evaluated the involvement of macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation in cultured human dermal fibroblasts. UVA (20 J/cm(2)) up-regulates MIF production, and UVA-induced MMP-1 mRNA production is inhibited by an anti-MIF antibody. MIF (100 ng/ml) was shown to induce MMP-1 in cultured human dermal fibroblasts. We found that MIF (100 ng/ml) enhanced MMP-1 activity in cultured fibroblasts assessed by zymography. Moreover, we observed that fibroblasts obtained from MIF-deficient mice were much less sensitive to UVA regarding MMP-13 expression than those from wild-type BALB/c mice. Furthermore, after UVA irradiation (10 J/cm(2)), dermal fibroblasts of MIF-deficient mice produced significantly decreased levels of MMP-13 compared with fibroblasts of wild-type mice. Next we investigated the signal transduction pathway of MIF. The up-regulation of MMP-1 mRNA by MIF stimulation was found to be inhibited by a PKC inhibitor (GF109203X), a Src-family tyrosine kinase inhibitor (herbimycin A), a tyrosine kinase inhibitor (genistein), a PKA inhibitor (H89), a MEK inhibitor (PD98089), and a JNK inhibitor (SP600125). In contrast, the p38 inhibitor (SB203580) was found to have little effect on expression of MMP-1 mRNA. We found that PKC-pan, PKC alpha/beta II, PKC delta (Thr505), PKC delta (Ser(643)), Raf, and MAPK were phosphorylated by MIF. Moreover, we demonstrated that phosphorylation of PKC alpha/beta II and MAPK in response to MIF was suppressed by genistein, and herbimycin A as well as by transfection of the plasmid of C-terminal Src kinase. The DNA binding activity of AP-1 was significantly up-regulated 2 h after MIF stimulation. Taken together, these results suggest that MIF is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts through PKC-, PKA-, Src family tyrosine kinase-, MAPK-, c-Jun-, and AP-1-dependent pathways.

Animals↗
PubMed2003

Impaired contact hypersensitivity in macrophage migration inhibitory factor-deficient mice.

To determine whether macrophage migration inhibitory factor (MIF) is required for contact hypersensitivity (CHS) response, MIF-deficient (MIF KO) and wild-type (WT) mice were sensitized with trinitrochlorobenzene (TNCB) or oxazolone on their abdominal skin and challenged on the dorsum skin of one ear 5 days later. Significant ear swelling was observed in the WT mice, but this response was inhibited in the MIF KO mice (p<0.01 for MIF KO vs. WT mice in 24 h). In addition, lymph node cells from hapten-sensitized MIF KO mice showed a decreased capacity for transferring the CHS response. A topical application of TNCB (200 microg) caused a significant decline in epidermal Langerhans cell (LC) density (20.3%; p<0.01 compared with vehicle) 4 h after application in WT mice, but it failed to provoke a significant epidermal LC migration in MIF KO mice (7.4%). By mixed lymphocyte reaction, the T cell proliferative response to alloantigen was significantly decreased in the MIF KO mice compared with WT mice (p<0.005). Taken together, these results indicate that MIF is pivotal in the regulation of cutaneous immune responses and plays a central role in LC migration and T cell proliferation for the CHS response.

Administration, Topical↗
PubMed2003

Time-resolved contrast-enhanced pulmonary MR angiography using sensitivity encoding (SENSE).

PURPOSE: To evaluate the relationship between gadolinium concentration and signal-to-noise ratio (SNR) on sensitivity encoding (SENSE) images, and determine the appropriate bolus injection protocol for visualizing pulmonary circulation. MATERIALS AND METHODS: Eighteen different gadolinium concentration phantoms (0, 0.01, 0.05, 0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.5, 2.0, 5.0, 10.0, 20.0, 30.0, 50.0, and 100.0 mmol/L) were analyzed to determine the relationship between gadolinium concentration and SNR on SENSE images in a phantom study. In an in vivo study, 3 mL (protocol A) or 6 mL (protocol B) of Gd-DTPA BMA at 3 mL/second, and 5 mL of Gd-DTPA BMA at 5 mL/second (protocol C) were administered to eight normal volunteers for contrast-enhanced (CE) pulmonary MR angiography (MRA) with SENSE. The peak SNRs of pulmonary parenchyma and the difference in SNR between pulmonary artery (PA) and pulmonary vein (PV) at peak SNR in the PA were statistically evaluated. RESULTS: For each flip angle at each gadolinium concentration, the SNRs and contrast-to-noise ratios (CNRs) of the SENSE images were significantly lower than those acquired with a nonparallel imaging technique (P < 0.05). The peak SNR of the pulmonary parenchyma, and differences in SNR between the PA and PV at the peak SNR of the PA obtained with a 5-mL/second bolus injection protocol were found to be significantly higher than those obtained with other protocols (P < 0.05). CONCLUSION: 3D-CE-MRA using SENSE demonstrated linearity between gadolinium concentration and SNR, and resulted in MRA with high spatial and temporal resolution with the aid of a sharp bolus injection protocol.

Adult↗
PubMed2003

Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand.

The pathogeneses of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), both severe blistering diseases usually associated with drug intake, are not fully elucidated. Histologically, both TEN and SJS are characterized by extensive keratinocyte apoptosis. Previous studies have shown that keratinocyte apoptosis in TEN and SJS was induced by a suicidal interaction between Fas and Fas ligand (FasL), which are both expressed by keratinocytes. However, our preliminary examinations demonstrated that FasL is hardly detected on keratinocytes. We hypothesized that soluble FasL (sFasL) is secreted by peripheral blood mononuclear cells (PBMCs), and this interacts with the Fas expressed on keratinocytes in TEN and SJS. To justify this hypothesis, we investigated whether sFasL secreted by PBMCs could induce the keratinocyte apoptosis in TEN and SJS. Enzyme-linked immunosorbent assay analysis demonstrated that there was no significant sFasL increase in any samples of healthy controls (<40 pg/ml, n = 14) and patients with an ordinary erythema multiforme-type drug eruption (41.5 +/- 3.1 pg/ml, n = 14), whereas high concentrations are detected in all samples of TEN and SJS patients (TEN: 131.5 +/- 57.4 pg/ml, n = 8; SJS: 119.1 +/- 41.0 pg/ml, n = 14) (P < 0.0001). In vitro analysis using cultured keratinocytes revealed that the sera of TEN and SJS patients induced abundant keratinocyte apoptosis compared to erythema multiforme-type drug eruption sera. Furthermore, on stimulation with the causal drug, PBMCs obtained from TEN and SJS patients secreted high levels of sFasL. Taken together, these results indicate that sFasL secreted by PBMCs, not keratinocytes, plays a crucial role in the apoptosis and pathomechanism of TEN and SJS, and that the serum sFasL level may be a good indicator for the early diagnosis of TEN and SJS.

Adult↗
PubMed2003

Tumor response to chemotherapy: the validity and reproducibility of RECIST guidelines in NSCLC patients.

We investigated the validity and inter-criteria reproducibility between RECIST (Response Evaluation Criteria in Solid Tumors) guidelines and WHO (World Health Organization) criteria, considering the decrease in patient numbers resulting from inclusion of the minimum lesion size criterion introduced in RECIST guidelines. RECIST guidelines are based on unidimensional measurement and exclusion of small lesions from measurement. The aims of the study were to examine: (1) the effect of the minimum lesion size criterion, (2) the validity of unidimensional and bidimensional measurements, i.e., their relationship with tumor volume, (3) the inter-criteria reproducibility between current RECIST guidelines and previous WHO criteria. One hundred and twenty patients with non-small cell lung cancer (NSCLC) in clinical trials were evaluated. By applying the minimum lesion size criterion, six cases became ineligible without any influence on precision of tumor volume measurement. In the validity study, actual tumor volume was regarded as the gold standard. Although the unidimensional measurement had a lower correlation with tumor volume value than the bidimensional measurement, both the unidimensional measurement and bidimensional measurement correlated sufficiently well with tumor volume changes and the assessed tumor volume response. In the inter-criteria reproducibility study between RECIST guidelines and WHO criteria, the response rate assessed by RECIST guidelines (19.3%) was almost the same as that assessed by WHO criteria (20.0%). In conclusion, RECIST guidelines are adequate for evaluating tumor response to chemotherapy in terms of both validity in relation to tumor volume and inter-criteria reproducibility with the WHO criteria.

Adult↗
PubMed2003

CT-guided transthoracic needle aspiration biopsy of small (< or = 20 mm) solitary pulmonary nodules.

OBJECTIVE: The purpose of our study was to determine the diagnostic accuracy and to analyze the factors influencing the diagnostic accuracy and incidences of pneumothorax and chest tube insertion rates for percutaneous CT-guided needle biopsy of small (< or = 20 mm) solitary pulmonary nodules. SUBJECTS AND METHODS: One hundred sixty-two patients with 162 small solitary pulmonary nodules underwent CT-guided transthoracic needle aspiration biopsy. The overall diagnostic accuracy, pneumothorax rate, and chest tube insertion rate were calculated. Factors influencing the diagnostic accuracy and pneumothorax rate were statistically evaluated. Influencing factors, diagnostic accuracies, pneumothorax rates, and chest tube insertion rates were statistically compared. RESULTS: Overall diagnostic accuracy, pneumothorax rate, and chest tube insertion rate were 77.2%, 28.4%, and 2.5%, respectively. Diagnostic accuracy was significantly affected by length of needle path and lesion size (p < 0.05). The pneumothorax rate was significantly affected by the percentage of predicted forced expiratory volume in 1 sec, the number of punctures, and the needle path length (p < 0.05). The chest tube insertion rate was significantly affected by the number of punctures (p < 0.05). For diagnostic accuracy, needle path lengths of 40 mm or less and lesion sizes greater than 10 mm were significantly more accurate than other factors (p < 0.05). For pneumothorax rates, a percentage of predicted forced expiratory volume in 1 sec of greater than 70%, a single puncture, and a needle path length of 40 mm or less were significantly lower than other factors (p < 0.05). CONCLUSION: CT-guided transthoracic needle aspiration biopsy is a useful diagnostic tool for small solitary pulmonary nodules smaller than 20 mm in diameter. The diagnostic accuracy is significantly improved for large (> 10 mm) lesion size and short (< or = 40 mm) needle path length.

Adult↗
PubMed2002

Histochemical analysis of macrophage migration inhibitory factor in psoriasis vulgaris.

Psoriasis is a persistent cutaneous disease characterized by skin inflammation and infiltration of immunocytes such as lymphocytes and monocytes/macrophages, concomitant with abnormal epidermal hyperproliferation. We previously showed that the serum level of macrophage migration inhibitory factor (MIF) and its production by peripheral blood mononuclear cells of patients with psoriasis were closely correlated with the severity of clinical symptoms; however, the precise role of MIF in psoriatic epidermis remains to be clarified. The current study was carried out to elucidate the possible involvement of MIF in psoriasis, using immunohistochemistry and in situ hybridization. In contrast to elevated serum MIF in psoriasis, MIF-positive staining in the lesional psoriatic epidermis was significantly decreased, as demonstrated by immunohistochemical analysis using an anti-MIF antibody. Consistent with this finding, we found, by in situ hybridization, that MIF mRNA concomitantly decreased in the psoriatic lesions. Although the reason for the different MIF levels in the psoriatic epidermis and in the circulation remains unknown, it is hypothesized that MIF, a potential growth factor, might be decreased in psoriatic lesions to counterregulate the abnormal epidermal proliferation caused by dysregulation of cytokines and growth factors.

Adult↗
PubMed2002

[Carboplatin].

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Antineoplastic Combined Chemotherapy Protocols↗