Search PubMed⌕ Search

Biomedical subjects

Hirokazu Watanabe

Publications and source records attributed to Hirokazu Watanabe.

At least 19 recordsLinked to original sources
PubMed2006

Effect of the introduction of minimum lesion size on interobserver reproducibility using RECIST guidelines in non-small cell lung cancer patients.

We evaluated interobserver reproducibility for the response evaluation criteria in solid tumors (RECIST) guidelines and the influence of minimum lesion size (MLS) on reproducibility. The 110 consecutive patients with non-small cell lung cancer were treated with platinum-based chemotherapy. Five observers measured target lesions according to both the World Health Organization (WHO) criteria and RECIST. The percentage changes for unidimensional measurements (UD; RECIST type) and bidimensional measurements (BD; WHO type) were calculated for each patient. Interobserver reproducibility among five observers, that is 10 pairs, was expressed as the Spearman's correlation coefficient for the percentage changes, the proportion of agreement and the kappa statistics for response categories. The same analysis was carried out using MLS. BD was more reproducible than UD (Spearman rank correlation coefficient, 0.84 vs 0.81; proportion of agreement, 84.4% vs 82.5%; kappa value, 0.69 vs 0.61). When MLS was applied to UD, eligible cases decreased by 6.4% and the number of target lesions by 44.6%, whereas interobserver reproducibility for UD improved (Spearman rank correlation coefficient, 0.81-0.84; proportion of agreement, 82.5-84.2%; kappa value, 0.61-0.65). The introduction of MLS to UD could also improve intercriteria reproducibility between WHO and RECIST. It is important to apply the MLS when using RECIST for the comparable interobserver reproducibility attained with WHO.

Adult↗
PubMed2005

Oxygen-enhanced MR imaging: correlation with postsurgical lung function in patients with lung cancer.

PURPOSE: To prospectively determine if lung function as assessed with oxygen-enhanced magnetic resonance (MR) imaging correlates with postsurgical lung function in patients with lung cancer, as compared with quantitative and qualitative findings of computed tomography (CT) and scintigraphy. MATERIALS AND METHODS: Study received institutional review board approval, and informed patient consent was obtained. Thirty consecutive patients (16 men and 14 women, aged 44-81 years; mean age, 65 years) considered candidates for lung resection underwent oxygen-enhanced MR imaging, CT, perfusion scintigraphy, and measurement of forced expiratory volume in 1 second (FEV1). A respiratory-synchronized inversion-recovery half-Fourier single-shot turbo spin-echo MR sequence was used for data acquisition. Correlation of postsurgical lung function (postsurgical FEV1) as determined with oxygen-enhanced MR imaging (FEV1MR), quantitative assessment with CT (FEV1Quant), qualitative assessment with CT (FEV1Qual), and perfusion scintigraphy (FEV1PS) was conducted with actual postsurgical FEV1, and the limits of agreement of each were determined with Bland-Altman analysis. RESULTS: Correlation between postsurgical FEV1MR and actual postsurgical FEV1 values was excellent (r2= 0.81, P < .001); it was better than that of FEV1Qual (r2= 0.76) and FEV1PS (r2= 0.77) and similar to that of FEV1Quant (r2= 0.81) values. The limits of agreement of FEV1MR were between -9.9% and 10.9%. CONCLUSION: Oxygen-enhanced MR imaging can be used to predict posturgical lung function in patients with lung cancer, similar to quantitative CT.

Adult↗
PubMed2005

Thin-section multiplanar reformats from multidetector-row CT data: utility for assessment of regional tumor extent in non-small cell lung cancer.

PURPOSE: To determine the clinical utility of thin-section multiplanar reformats (MPRs) from multidetector-row CT (MDCT) data sets for assessing the extent of regional tumors in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Sixty consecutive NSCLC patients, who were considered candidates for surgical treatment, underwent contrast-enhanced MDCT examinations, surgical resection and pathological examinations. All MDCT examinations were performed with a 4-detector row computed tomography (CT). From each raw CT data set, 5mm section thickness CT images (routine CT), 1.25 mm section thickness CT images (thin-section CT) and 1.25 mm section thickness sagittal (thin-section sagittal MPR) and coronal images (thin-section coronal MPR) were reconstructed. A 4-point visual score was used to assess mediastinal, interlobar and chest wall invasions on each image set. For assessment of utility in routine clinical practice, mean reading times for each image set were compared by means of Fisher's protected least significant difference (PLSD) test. A receiver operator characteristic (ROC) analysis was performed to determine the diagnostic capability of each of the image data sets. Finally, sensitivity, specificity and accuracy of the reconstructed images were compared by McNemar test. RESULTS: Mean reading times for thin-section sagittal and coronal MPRs were significantly shorter than those for routine CT and thin-section CT (p<0.05). Areas under the curve (Azs) showing interlobar invasion on thin-section sagittal and coronal MPRs were significantly larger than that on routine CT (p=0.03), and the Az on thin-section sagittal MPR was also significantly larger than that on routine CT (p=0.02). Accuracy of chest wall invasion by thin-section sagittal MPR was significantly higher than that by routine CT (p=0.04). CONCLUSION: Thin-section multiplanar reformats from multidetector-row CT data sets are useful for assessing the extent of regional tumors in non-small cell lung cancer patients.

Adult↗
PubMed2005

Tissue regeneration using macrophage migration inhibitory factor-impregnated gelatin microbeads in cutaneous wounds.

Migration inhibitory factor (MIF) responds to tissue damage and regulates inflammatory and immunological processes. To elucidate the function of MIF in cutaneous wound healing, we analyzed MIF knockout (KO) mice. After the excision of wounds from the dorsal skin of MIF KO and wild-type (WT) mice, healing was significantly delayed in MIF KO mice compared to WT mice. Lipopolysaccharide treatment significantly increased [(3)H]thymidine uptake in WT mouse fibroblasts compared to MIF KO mouse fibroblasts. Furthermore, there was a significant reduction in fibroblast and keratinocyte migration observed in MIF KO mice after 1-oleoyl-2-lysophosphatidic acid treatment. We subsequently examined whether MIF-impregnated gelatin slow-release microbeads could accelerate skin wound healing. Injection of more than 1.5 microg/500 microl of MIF-impregnated gelatin microbeads around a wound edge accelerated wound healing compared to a single MIF injection without the use of microbeads. MIF-impregnated gelatin microbeads also accelerated skin wound healing in C57BL/6 mice and diabetic db/db mice. Furthermore, incorporating MIF-impregnated gelatin microbeads into an artificial dermis implanted into MIF KO mice accelerated procollagen production and capillary formation. These findings suggest that MIF is crucial in accelerating cutaneous wound healing and that MIF-impregnated gelatin microbeads represent a promising treatment to facilitate skin wound healing.

Animals↗
PubMed2005

Expression of macrophage migration inhibitory factor in rat skin during embryonic development.

We have previously shown that human epidermal keratinocytes express macrophage migration inhibitory factor (MIF) mRNA, and immunohistochemical studies showed that MIF is expressed in human epidermis. To explore the possible pathophysiological roles of MIF in skin during rat fetal development, we examined the expression patterns of MIF during rat epidermal development using Northern blot analysis and in situ hybridization. Expression of MIF mRNA was first detected by in situ hybridization in the developing epidermis and hair germ cells from embryonic day (ED) 16. From ED 19, moderate levels of MIF expression were detected in the epidermis and epithelial sheath cells of growing hair follicles. In postnatal rat skin, higher MIF expression was detected in the epidermis and hair follicles on postnatal day 3. These observations were also confirmed by Northern blot analysis. Immunohistochemical analysis with an anti-MIF antibody showed a similar distribution to that of the mRNA. Our results suggest that MIF is associated with epidermal and hair follicle development.

Animals↗
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

Quantitative assessment of regional pulmonary perfusion in the entire lung using three-dimensional ultrafast dynamic contrast-enhanced magnetic resonance imaging: Preliminary experience in 40 subjects.

PURPOSE: To assess regional differences in quantitative pulmonary perfusion parameters, i.e., pulmonary blood flow (PBF), mean transit time (MTT), and pulmonary blood volume (PBV) in the entire lung on a pixel-by-pixel basis in normal volunteers and pulmonary hypertension patients. MATERIALS AND METHODS: Three-dimensional ultrafast dynamic contrast-enhanced MR imaging was performed in 15 normal volunteers and 25 patients with pulmonary hypertension. From the signal intensity-time course curves, PBF, MTT and PBV maps were generated using deconvolution analysis, indicator dilution theories, and the central volume principle, on a pixel-by-pixel basis. From pulmonary perfusion parameter maps of normal volunteers and pulmonary hypertension patients, regional PBF, MTT, and PBV were statistically evaluated. RESULTS: Regional PBF, MTT, and PBV showed significant differences in the gravitational and isogravitational directions (P < 0.05). The quantitative pulmonary perfusion parameter maps demonstrated significant differences between normal volunteers and pulmonary hypertension patients (P < 0.05). CONCLUSION: Three-dimensional ultrafast dynamic contrast-enhanced MR imaging is feasible for the assessment of regional quantitative pulmonary perfusion parameters in the entire lung on a pixel-by-pixel basis in normal volunteers and pulmonary hypertension patients.

Adult↗
PubMed2004

Centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo sequence: improvement of the image quality of oxygen-enhanced MRI.

PURPOSE: The purpose of the study presented here was to determine the improvement in image quality of oxygen-enhanced magnetic resonance (MR) subtraction imaging obtained with a centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo (c-IR-HASTE) sequence compared with that obtained with a conventional sequentially reordered inversion recovery single-shot HASTE (s-IR-HASTE) sequence for pulmonary imaging. MATERIALS AND METHODS: Oxygen-enhanced MR imaging using a 1.5 T whole body scanner was performed on 12 healthy, non-smoking volunteers. Oxygen-enhanced MR images were obtained with the coronal two-dimensional (2D) c-IR-HASTE sequence and 2D s-IR-HASTE sequence combined with respiratory triggering. For a 256x256 matrix, 132 phase-encoding steps were acquired including four steps for phase correction. Inter-echo spacing for each sequence was 4.0 ms. The effective echo time (TE) for c-IR-HASTE was 4.0 ms, and 16 ms for s-IR-HASTE. The inversion time (TI) was 900 ms. To determine the improvement in oxygen-enhanced MR subtraction imaging by c-IR-HASTE, CNRs of subtraction image, overall image quality, and image degradation of the c-IR-HASTE and s-IR-HASTE techniques were statistically compared. RESULTS: CNR, overall image quality, and image degradation of c-IR-HASTE images showed significant improvement compared to those s-IR-HASTE images (P<0.05). CONCLUSION: Centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo (c-IR-HASTE) sequence enhanced the signal from the lung and improved the image quality of oxygen-enhanced MR subtraction imaging.

Adult↗
PubMed2004

Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo.

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. In this study, we have investigated both the in vitro and in vivo growth characteristics of human malignant melanoma G361 cell lines, stably transfected to overexpress human PEDF. Expression levels of PEDF proteins in melanoma cell lines G361 and A375 were comparable with that of human cultured melanocytes, whereas vascular endothelial growth factor levels in two tumor cell lines were much stronger than that in normal melanocytes. Overexpression of PEDF was found to significantly inhibit tumor growth and vessel formation in G361 nude mice xenografts. Furthermore, in vitro proliferation rates of G361 cells were decreased in PEDF-transfected cells. PEDF proteins showed dose-dependent induced growth retardation and apoptotic cell death in nontransfected G361 cells, which were completely prevented by treatment with antibodies against the Fas ligand. Our present study highlights two beneficial effects of PEDF treatment on melanoma growth and expansion; one is the suppression of tumor angiogenesis, and the other is induction of Fas ligand-dependent apoptosis in tumor cells. PEDF therefore might be a promising novel therapeutic agent for treatment of patients with melanoma.

Animals↗
PubMed2004

Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions.

Advanced glycation end products (AGE), nonenzymatically glycated protein derivatives, have been implicated in the development and progression of diabetic angiopathies, including skin dermopathy. Nevertheless, the involvement of AGE in the development and progression of melanoma has not been fully elucidated. In this study we investigated the expression levels of their receptor for AGE (RAGE) in human melanoma and subsequently studied the effects of AGE on melanoma growth and migration. First, RAGE was detected in the cytoplasm of human melanoma cells (G361 and A375). Among the different types of AGE, glyceraldehyde- and glycolaldehyde-derived AGE significantly stimulated the growth and migration of human melanoma cells. Furthermore, tumor formation of melanoma cell xenografts in athymic mice was prevented by treatment with anti-RAGE neutralizing antibodies. In tumor-bearing mice, survival rates were prolonged, and spontaneous pulmonary metastases were inhibited by treatment using anti-RAGE neutralizing antibodies. In addition, all AGE were present in beds of human melanoma tumor, whereas they were barely detected in normal skin. These results suggest that AGE might be involved in the growth and invasion of melanoma through interactions with RAGE and represent promising candidates for assessing the future therapeutic potential of this therapy in treating patients with melanoma.

Animals↗
PubMed2004

Metastases in mediastinal and hilar lymph nodes in patients with non-small cell lung cancer: quantitative and qualitative assessment with STIR turbo spin-echo MR imaging.

PURPOSE: To evaluate short inversion time inversion-recovery (STIR) turbo spin-echo (TSE) magnetic resonance (MR) imaging for detection of metastases in lymph nodes by using quantitative and qualitative analyses. MATERIALS AND METHODS: One hundred ten patients (68 men and 42 women) with non-small cell lung cancer who ranged in age from 36 to 82 years (mean age, 64 years) were examined with respiratory-triggered STIR TSE MR imaging. Ratios of signal intensity in a lymph node to that in a 0.9% saline phantom (lymph node-saline ratios [LSRs]) for all lymph nodes were classified into three groups according to nodal short-axis diameter. LSRs of each group were compared by using pathologic diagnosis as the standard of reference. For quantitative analysis, the LSR threshold value for a positive test was determined on a per-node basis and tested for ability to enable a correct diagnosis on a per-patient basis. For qualitative analysis, signal intensities of lymph nodes were assessed by using a five-point visual scoring system. Results of quantitative and qualitative analyses were compared on a per-patient basis with McNemar testing. RESULTS: In 110 patients, 92 of 802 lymph nodes were pathologically diagnosed as containing metastases, while 710 lymph nodes did not contain metastases. Mean LSR in the lymph node group with metastasis was higher than that in the group without metastasis (P <.05). When an LSR of 0.6 was used as the positive-test threshold at quantitative analysis, sensitivity was 93% (37 of 40 patients) and specificity was 87% (61 of 70 patients) on a per-patient basis. With a score of 4 as the positive-test threshold at qualitative analysis, sensitivity was 88% (35 of 40 patients) and specificity was 86% (60 of 70 patients) on a per-patient basis. There was no significant difference (P >.05) between results of quantitative and those of qualitative analysis. CONCLUSION: Quantitative and qualitative analyses of STIR TSE MR images enable differentiation of lymph nodes with metastasis from those without. Qualitative analysis can substitute for quantitative analysis of STIR TSE MR imaging data.

Adult↗
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

Study of paclitaxel and dose escalation of cisplatin in patients with advanced non-small cell lung cancer.

BACKGROUND: We conducted a dose-finding and feasibility study in which we administered a fixed dose 3-h infusion of paclitaxel and an escalating dose of cisplatin in Japanese patients with advanced non-small cell lung cancer. METHODS: Chemotherapy consisted of fixed dose (210 mg/m(2)) paclitaxel given over 3 h on day 1 and an escalating dose of cisplatin on day 2, every 3-4 weeks. The dose of cisplatin was 40 mg/m(2) at level 1, 60 mg/m(2) at level 2 and 80 mg/m(2) at level 3. RESULTS: Between October 1999 and February 2001, 24 patients were enrolled and 58 cycles were administered. The major hematological toxicities were leukopenia and neutropenia. Grade 4 neutropenia developed in 83.3%, 66.7% and 83.3% of patients at the dose levels of 1, 2 and 3, respectively. The major non-hematological toxicities consisted of alanine aminotransferase (ALT) elevation and peripheral neuropathy. Grade 3 ALT elevation was observed in two of the 12 patients at level 3, but both recovered within 3 days. The peripheral neuropathy was sensory-dominant and frequent, and it was almost tolerable. The maximum tolerated dose was not identified even at the highest dose of paclitaxel (210 mg/m(2)) and cisplatin (80 mg/m(2)) administered in the study. The recommended dose was determined to be paclitaxel 210 mg/m(2) on day 1 and cisplatin 80 mg/m(2) on day 2, every 3-4 weeks. Seven partial responses were observed in the 24 patients. CONCLUSIONS: The combination of paclitaxel 210 mg/m(2) and cisplatin 80 mg/m(2) was found to be a well-tolerated active regimen in Japanese patients with advanced non-small cell lung cancer.

Adult↗