Biomedical subjects

Y Kaneda

Publications and source records attributed to Y Kaneda.

At least 19 recordsLinked to original sources

PubMed2005

Inhibition of ets, an essential transcription factor for angiogenesis, to prevent the development of abdominal aortic aneurysm in a rat model.

The pathophysiology of abdominal aortic aneurysms (AAA) is considered to be complicated. As matrix degradation contributes to the progression of AAA, the destruction and degradation of elastin fibers caused by an increase in matrix metalloproteinases (MMPs) plays a pivotal role in the development of AAA. Although ets, an essential transcription factor for angiogenesis, regulates MMPs, the role of ets in the development of AAA has not yet been clarified. Thus, we evaluated the role of ets in a rat AAA model using a decoy strategy. Transfection of ODN into AAA was performed by transient aortic perfusion of elastase and by wrapping the AAA in a delivery sheet containing decoy ODN. The inhibitory effect of ets decoy ODN on ets binding activity was confirmed by gel mobility shift assay. MMPs expression was decreased in the aorta transfected with ets decoy ODN as compared to scrambled decoy ODN. Also, ultrasound study demonstrated that elastase-induced aneurismal dilation was significantly suppressed by transfection of ets decoy ODN at 4 weeks after treatment as compared to scrambled decoy ODN. Moreover, the destruction of elastin fibers was inhibited in the aorta transfected with ets decoy ODN, accompanied by a reduction of MMPs expression. An inhibitory effect of decoy ODN on MMP expression was confirmed by ex vivo experiments showing that transfection of decoy ODN into an organ culture of human aorta resulted in significant inhibition of the secretion of both MMP-1 and MMP-9. Here, we demonstrated that ets may play a pivotal role in the progression of AAA through the activation of MMPs in a rat model. Ets might be a potential target to develop pharmacotherapy/gene therapy to treat AAA through the inhibition of MMPs.

Animals↗

PubMed2005

Relation between estradiol and negative symptoms in men with schizophrenia.

The authors tested the hypothesis that estradiol would be associated with negative symptoms in 30 male schizophrenia inpatients. Medications were switched from typical to atypical antipsychotics. Estradiol concentrations were inversely correlated with negative symptoms significantly before the switch and at a trend level of significance after the switch. Changes in negative symptoms were positively correlated with those in estradiol concentrations at a trend level of significance. Estradiol could be a biological marker for negative symptoms even in male schizophrenia patients.

Adult↗

PubMed2005

[Simultaneous resection of pulmomary metastasis of colon cancer and primary lung cancer].

A 70-year-old woman was admitted with a complaint of weight loss and an abnormal shadow on the chest X-ray. On palpation, the unmobilized mass, measuring 5 cm, was located in the left lower abdomen. The barium-enema examination showed the filling defect of the sigmoid colon. Chest computed tomography (CT) showed a tumor, measuring 20 x 20 mm, located in the right upper lobe (S3) and a nodule, measuring 3 mm, located in the right lower lobe (S8). At first, we performed sigmoidectomy (D 3) for the colon cancer. Next, performed right upper lobectomy and a partial resection of the right lower lobe. Histopathologically, the one is a primary lung cancer, the other is a metastatic lung cancer. With an increase in colorectal and lung cancer, similar cases as ours seem to increase in number. When we treat multiple lung nodules with malignancy of other organs, we should consider 3 types of cases, 1) only primary, 2) primary and metastatic, 3) only metastatic.

Aged↗

PubMed2005

[Primary pulmonary meningioma; report of a case].

Primary pulmonary meningiomas are quite rare, and their occurrence has been reported only sporadically. A 49-year-old, asymptomatic female was hospitalized for the evaluation of a coin lesion in the left lung radiography. She has no history of previous neoplasm or symptom referable to the central nervous system. Chest computed tomography (CT) demonstrated a 9 x 14 mm, round, noncalcified, well-demarcated lesion in the left upper lobe of the lung (S(1+2)). For diagnostic purposes, enucleation of the tumor was performed. The resected specimen revealed histologically classical typical meningioma. Because postoperative magnetic resonance imaging (MRI) of the brain did not show any intracranial mass, this case was and diagnosed as a primary pulmonary meningioma. The patient was discharged with no complication, and alive without recurrence of disease 14 months after surgery.

Female↗

PubMed2004

Inhibition of neointimal hyperplasia after balloon injury by cis-element 'decoy' of early growth response gene-1 in hypercholesterolemic rabbits.

Early growth response factor-1 (Egr-1) is a transcription factor that is rapidly activated after vascular injury and thus might contribute to vascular proliferation and inflammation. We hypothesized that Egr-1 might therefore be a therapeutic target against restenosis. Hypercholesterolemic rabbits were intraluminally administered synthetic DNA as a 'decoy' against Egr-1 immediately after carotid artery balloon injury. Efficient transfection was confirmed by the delivery of a fluorescence-labeled decoy. Gel mobility-shift assay showed increased Egr-1 activity after balloon injury and its prevention by Egr-1 decoy transfection in vivo. Egr-1 decoy transfection attenuated early inflammation and proliferation and later neointimal hyperplasia. In addition, Egr-1 decoy transfection reduced gene expression and protein production of Egr-1-dependent genes such as platelet-derived growth factor-B, transforming growth factor-beta1, and monocyte chemoattractant protein-1. The Egr-1 pathway has an essential role in the pathogenesis of neointimal hyperplasia after balloon injury in hypercholesterolemic rabbits. This decoy strategy is a potential practical form of therapy for human restenosis.

Angioplasty, Balloon↗

PubMed2004

Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma.

Systemic sclerosis (SSc) is a connective tissue disorder with an unknown etiology. There are currently no effective therapies for SSc. (In this study, working with a bleomycin(BLM)-induced scleroderma model mice, we performed two transfections of human hepatocyte growth factor (HGF) cDNA into the skeletal muscle and showed that this treatment not only helped to prevent the dermal sclerosis simultaneously injected BLM but also improved the symptoms of dermal sclerosis induced by BLM 4 weeks previously.) RT-PCR, ELISA and an immunohistochemical analysis revealed that both mRNA and protein of human HGF as well as murine HGF were enhanced in the skin, lung, muscle and the serum after two transfections of human HGF cDNA. These analyses also revealed that this treatment significantly reduced both the expression of the TGF-beta1 mRNA and the production of TGF-beta1 on macrophage-like cells that infiltrated the dermis and the fibroblastic cells in BLM-induced scleroderma. Furthermore, HGF-gene transfection both prevented and ameliorated the symptoms of not only dermal sclerosis but also of lung fibrosis induced by a subcutaneous BLM injection. These results indicated that gene therapy by the transfection of the human HGF cDNA may thus be a useful therapy for SSc and lung fibrosis involved with SSc.

Animals↗

PubMed2004

Transcription factor decoy for AP-1 reduces mesangial cell proliferation and extracellular matrix production in vitro and in vivo.

Diabetic nephropathy is characterized by an expansion of glomerular mesangium, caused by mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins, which eventually leads to glomerulosclerosis and renal failure. Activator protein-1 (AP-1), a transcription factor, is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation and ECM production. This investigation was undertaken to test the hypothesis that AP-1 plays an important role in ECM gene expression, and to develop a molecular therapeutic strategy based on decoy oligodeoxynucleotides (ODN). In this report, we show that transfection with AP-1 decoy ODN strongly inhibits high glucose- and angiotensin II-induced cell proliferation and expression of ECM genes in cultured mesangial cells in vitro. Administration of AP-1 decoy ODN into streptozotocin-induced diabetic rat kidney in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually abolished TGF-beta1 and plasminogen activator inhibitor-1 expression. Our results collectively indicate that AP-1 activation is crucial for mesangial cell proliferation and ECM production in response to high glucose and angiotensin II. Moreover, use of stable AP-1 decoy ODN combined with the highly effective HVJ-liposome method provides a novel potential molecular therapeutic strategy for the prevention of diabetic nephropathy.

Angiotensin II↗

PubMed2004

Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound.

Although gene therapy might become a promising approach for central nervous system diseases, the safety issue is a serious consideration in human gene therapy. To overcome this problem, we developed an efficient gene transfer method into the adult rat brain based on plasmid DNA using a microbubble-enhanced ultrasound method, since microbubble-enhanced ultrasound has shown promise for transfecting genes into other tissues such as blood vessels. Using the microbubble-enhanced ultrasound method, luciferase expression was increased approximately 10-fold as compared to injection of naked plasmid DNA alone. Interestingly, the site of gene expression was limited to the site of insonation with intracisternal injection, in contrast to previous studies using viruses. Expression of the reporter gene, Venus, was readily detected in the central nervous system. The transfected cells were mainly detected in meningeal cells with intracisternal injection, and in glial cells with intrastriatal injection. There was no obvious evidence of tissue damage by microbubble-enhanced ultrasound. Overall, the present study demonstrated the feasibility of efficient plasmid DNA transfer into the central nervous system, providing a new option for treating various diseases such as tumors.

Animals↗

PubMed2004

In vivo transfection of a cis element 'decoy' against signal transducers and activators of transcription 6 (STAT6)-binding site ameliorates IgE-mediated late-phase reaction in an atopic dermatitis mouse model.

Signal transducers and activators of transcription 6 (STAT6) play a crucial role in the transactivation of IL-4 and IL-13, which might be involved in the pathogenesis of atopic dermatitis (AD). We herein reported that the IgE-mediated late-phase reaction significantly decreased in STAT6-deficient (STAT6(-/-)) mice in AD model mice induced by intravenous injection of monoclonal anti-dinitrophenyl (DNP)-IgE antibody and subsequent skin testing with dinitrofluorobenzene. We therefore hypothesized that synthetic double-stranded DNA with a high affinity for STAT6 could be introduced in vivo as decoy cis elements to bind the transcriptional factor and block the gene activation contributing to the onset and progression of AD, thus providing effective therapy for AD. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODNs), but not scramble decoy ODN after sensitization by anti-DNP-IgE antibody, had a significant inhibitory effect on not only STAT6 binding to nuclei but also on the late-phase response. A histological analysis revealed that both edema and the infiltration of neutrophils and eosinophils significantly decreased in STAT6 decoy ODN-transfected mice. To examine the mechanism of the in vivo effect of STAT6 decoy ODN, we employed an in vitro mast cells culture system. After IgE receptor engagement, mast cells transfected by STAT6 decoy ODN exhibited normal histamine release, but their cytokine release (TNF-alpha, IL-6) markedly decreased. We herein report the first successful in vivo transfer of STAT6 decoy ODN to reduce the late-phase reaction, thereby providing a new therapeutic strategy for AD.

Animals↗

PubMed2004

In vivo transfection of a cis element 'decoy' against signal transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity.

We herein demonstrate that STAT6 plays an important role in the induction of not only acute contact hypersensitivity (CHS), but also chronic CHS in a mouse model using STAT6-deficient (STAT6(-/-)) mice. We, therefore, determine whether synthetic double-stranded DNA with a high affinity for STAT6 can be introduced in vivo as a decoy cis element to bind the transcriptional factor and block the induction of not only acute CHS but also chronic CHS. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODN), after the induction of 2,4,6-trinitrochlorobenzene or other haptens had a significant inhibitory effect on the induction of both acute CHS and chronic CHS. We thus examined the mechanism of the in vivo effect of the transfection of STAT6 decoy ODN in both acute and chronic CHS. In the histological analysis, the infiltration of eosinophils and degranulated mast cells, and the production of IL-4, IL-6 and eotaxin, but not IFN-gamma in the extracts from challenged skin significantly decreased by the transfection of STAT6 decoy ODN. We herein report the first successful in vivo transfer of STAT6 decoy ODN to inhibit acute and chronic CHS, thus providing a new therapeutic strategy not only for the treatment of CHS but also for atopic dermatitis.

Acute Disease↗

PubMed2004

[Negative pleural cytology after intrapleural perfusion hyperthermo-chemotherapy for malignant pleural effusion].

We gave intrapleural perfusion hyperthermo-chemotherapy to a 72-year-old woman in whom malignant pleural effusion developed after surgery for primary cancer. This procedure involved irrigating the pleural space for 2 hours with a water solution at 42-43 degrees containing 240 mg cisplatin using specially devised extracorporeal circuits. Thoracoscopy was used to examine the intrapleural cavity and to place the catheters for perfusion. The patient had an uneventful postoperative course and was discharged for hospital on the second postoperative day. Thereafter, she experienced good quality of life with negative pleural cytology. Unfortunately, the patient died 3 months after the therapy, but the cause of death was unknown and there was no cancer recurrence. This technique may be safe and feasible for controlling malignant effusion to preserve quality of life, although the survival benefit has not yet been clarified.

Aged↗

PubMed2004

[Thoracoscopic lung biopsy in the diagnosis of diffuse lung disease].

The diagnosis of diffuse lung disease can only be made accurately by performing a thoracoscopic lung biopsy. We evaluated the safety and efficacy of thoracoscopic lung biopsy in diffuse lung disease. Between May 1999 and April 2003, 34 patients were referred to us for thoracoscopic lung biopsy. We compared the clinical characteristics, number of biopsies, operation times, postoperative course, complications, and mortality in 19 patients with dyspnea and 15 patients who were asymptomatic. Although the number of biopsies, operation times, duration of chest drainage, and postoperative stay did not differ significantly between the 2 groups, postoperative oxygen support was needed for significantly longer in the dyspnea group (p =0.038). A pathological diagnosis was established in all patients. Postoperative complications developed in 4 patients. A prolonged air leak in 1 patient and a wound infection in another resolved conservatively, but 2 patients died of acute exacerbation. Thus, we conclude that the indications for surgery must be carefully considered in dyspneic patients with diffuse lung to prevent acute exacerbation.

Biopsy↗

PubMed2003

TNF combined with IFN-alpha accelerates NF-kappaB-mediated apoptosis through enhancement of Fas expression in colon cancer cells.

Immunostaining and EMSA revealed that NF-kappaB was activated strongly by TNF/IFN-alpha compared to TNF alone in a human colon adenocarcinoma cell line, RPMI4788. Although inhibition of activated NF-kappaB, by using an NF-kappaB decoy, reduced cell viability after treatment with TNF only, NF-kappaB decoy resulted in recovery of cell viability after TNF/IFN-alpha treatment. Caspase-3 activity was increased in cells induced by TNF/IFN-alpha, while suppression of caspase-3 activity was observed in cells transfected with NF-kappaB decoy and then treated by TNF/IFN-alpha. On the other hand, Fas expression was strongly enhanced by TNF/IFN-alpha, and inhibition of TNF/IFN-alpha-induced NF-kappaB activation, by using NF-kappaB decoy, decreased Fas expression. Cell viability and caspase-3 activity decreased in cells treated with TNF/IFN-alpha and anti-FasL antibody. Taken together, our findings suggest that activated NF-kappaB induced by the crosstalk between TNF and IFN-alpha is a novel pro-apoptotic signal acting via enhancement of Fas expression.

Antibodies↗

PubMed2003

Inhibition of NFkappaB activation using cis-element 'decoy' of NFkappaB binding site reduces neointimal formation in porcine balloon-injured coronary artery model.

Application of DNA technology to regulate the transcription of disease-related genes has important therapeutic potential. The transcription factor NFkappaB plays a pivotal role in the transactivation of inflammatory and adhesion molecule genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for NFkappaB may be introduced as 'decoy' cis elements to bind NFkappaB and block the activation of genes mediating inflammation, resulting in effective drugs for treating intimal hyperplasia. In this study, we tested the feasibility of NFkappaB decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model as a pre-clinical study. An angioplasty catheter was introduced into the left anterior descending coronary artery of the pig to cause vascular injury. First, we tested the feasibility of transfection of FITC-labeled NFkappaB decoy ODN using a hydrogel balloon catheter. Fluorescence due to NFkappaB decoy ODN could be detected throughout the medial layer. Therefore, we transfected NFkappaB decoy ODN into the balloon-injured LAD using a hydrogel catheter. Histological evaluation demonstrated that the neointimal area in the balloon-injured artery was significantly reduced by NFkappaB decoy ODN as compared to scrambled decoy ODN at 1 week after single transfection, accompanied by a significant reduction in PCNA-positive stained cells (P < 0.01). Interestingly, the reduction of ICAM-positive staining was observed, accompanied by the inhibition of migration of macrophages. Of importance, intravascular ultrasound (IVUS) confirmed that neointimal area in the balloon-injured artery was significantly reduced by NFkappaB decoy ODN at 4 weeks after transfection (P < 0.01). Interestingly, the inhibition of neointimal area was only limited to the lesion transfected with NFkappaB decoy ODN, while other lesions without NFkappaB decoy ODN demonstrated a marked increase in neointimal formation. Here, we report the successful in vivo transfer of NFkappaB decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery.

Angioplasty, Balloon, Coronary↗

PubMed2003

Transfection of NFkappaB-decoy oligodeoxynucleotides using efficient ultrasound-mediated gene transfer into donor kidneys prolonged survival of rat renal allografts.

Nuclear factor kappaB (NFkappaB) plays a pivotal role in the coordinated transactivation of a series of genes of cytokines and adhesion molecules that are highly involved in the onset of acute rejection in organ transplantation. We previously developed decoy cis-elements oligo deoxyribonucleic acid against NFkappaB (NFkappaB-decoy) that effectively inhibited the activation of major inflammatory mediators in vitro and in vivo. Accordingly, we hypothesized that transfection of NFkappaB-decoy into the donor kidney would prevent acute rejection and prolong graft survival, and thus provide effective therapy for renal acute rejection. To transfect NFkappaB-decoy, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison, and clearly demonstrated successful transfection of NFkappaB-decoy into renal tissue. The therapeutic effect of NFkappaB-decoy on renal allografts was then evaluated in a rat renal allograft model (Wistar-Lewis). In the control group, graft function significantly deteriorated with marked destruction of renal tissue, accompanied by increased production of major inflammatory mediators, and all animals died of renal failure by 9 days. In contrast, graft function (serum creatinine on day 2, NFkappaB-treated: 0.97+/-0.16 versus control: 1.84+/-0.23 mg/dl, P<0.01) and histological structure were well preserved with significantly decreased expression of NFkappaB-regulated cytokines and adhesion molecules, including IL-1, iNOS, MCP-1, TNF-alpha, and ICAM-1, in allografts transfected with NFkappaB-decoy. As a result, animal survival was significantly prolonged in this group as compared to controls (14.2+/-5.2 versus 7.1+/-1.2 days, P<0.01). Thus, we established a novel ultrasound-Optison-mediated gene transfection approach and demonstrated the significant prolongation of graft survival by the successful transfection of NFkappaB-decoy into the donor kidney in a rat renal allograft model.

Albumins↗

PubMed2003

[Use of the bipolar vessel sealing system in lung resection].

UNLABELLED: Numerous methods exist to separate incomplete fissure and attain homeostasis in lung surgery. A new device was evaluated for dividing lung parenchyma and creating homeostasis in animal and lung cancer patients. METHODS: The LigaSure vessel sealing system was utilized in animal to divide lung parenchyma (1 cm, 3 cm, and 5 cm) and close 3 or 4 mm pulmonary arteries. This bipolar sealing instrument was also used in human to divide incomplete fissure and close small pulmonary arteries. RESULTS: No air leakage were seen when device was used in animal to divided less than 3 cm lung parenchyma, even if air way pressure was elevated to 30 cmH2O. No bleeding were seen when the devise applied to small pulmonary arteries in animal, even when pulmonary arterial pressure was elevated to 75/17 mmHg using 10 gamma dopamine. This devise was also useful in human to divide incomplete fissure without a significant air leakage and to close small pulmonary arteries. CONCLUSION: The LigaSure sealing system represents a significant advance in dividing the incomplete fissure less than 3 cm, and sufficient homeostasis in close pulmonary arteries smaller than 3 or 4 mm. Results of this evaluation indicate the LigaSure system is a variable alternative to autosure device or clips in pulmonary resection.

Animals↗

PubMed2003

[Intrathoracic bleeding during video-assisted thoracoscopic lobectomy and segmentectomy].

We have reviewed our experience from January 2001 through January 2003 in 33 video-assisted thoracoscopic lobectomy and segmentectomy (VATS) in patients with cT1N0M0 lung cancer to look at intraoperative bleeding from pulmonary vessels. Intraoperative bleeding occurred in 15 cases, 45.5% of 33 VATS procedures, and 2 cases, 6.1% of VATS procedures converted to an open procedure. Intraoperative bleeding occurred more frequently in VATS segmentectomy than VATS lobectomy. Most of bleeding from pulmonary arteries and veins can be controlled by compression, and they can be controlled thoracoscopically by tie or suture through the utility thoracotomy. But, significant bleeding from pulmonary arteries, which can not be controlled with a mounted swab, it should be converted to an open procedure.

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

HGF/NK4 inhibited VEGF-induced angiogenesis in in vitro cultured endothelial cells and in vivo rabbit model.

AIMS/HYPOTHESIS: As vascular endothelial growth factor (VEGF) plays a pivotal role in the development of diabetic retinopathy, inhibition of angiogenesis induced by VEGF is crucial to treat diabetic retinopathy. HGF (hepatocyte growth factor)/NK4, containing the N-terminal hairpin domain and the four subsequent kringle domains of HGF, is considered as a specific antagonist for HGF. Our aim was to explore the inhibitory effects of HGF/NK4 on angiogenesis induced by VEGF. METHODS: To analyze the in vivo angiogenesis, we used rabbit corneal micropocket assay. Proliferation and migration of human endothelial cells, expression of ets-1, an essential transcription factor for angiogenesis, and the phosphorylation of extracellular signal-regulated kinase (ERK) was examined with or without HGF/NK4. RESULTS: Using corneal micropocket assay, in vivo administration of HGF/NK4 inhibited angiogenesis induced by VEGF. HGF/NK4 inhibited proliferation and migration of human endothelial cells induced by VEGF in a dose-dependent manner. Interestingly, VEGF-mediated phosphorylation of ERK was significantly attenuated by HGF/NK4. Of importance, HGF/NK4 attenuated the increase in ets-1 protein stimulated by VEGF. Nevertheless, HGF/NK4 did not affect phosphorylation of VEGF receptor-2 [kinase domain region (KDR)/foetal liver kinase (Flk)-1]. Although tyrosine phosphatase inhibitor (Na(3)VO(4)), or okadaic acid, serine-threonin kinase inhibitor, did not prevent the inhibition of ERK phosphorylation by HGF/NK4, co-incubation of HGF/NK4 with VEGF significantly diminished mitogen-activated protein (MAP) ERK kinase (MEK) phosphorylation (p<0.01). CONCLUSIONS/INTERPRETATION: Overall, HGF/NK4 inhibited angiogenesis induced by VEGF through inhibition of phosphorylation of ERK and ets-1 expression in in vitro cultured endothelial cells and in vivo rabbit model.

Animals↗