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Biomedical subjects

Takeshi Matsuda

Publications and source records attributed to Takeshi Matsuda.

9 recordsLinked to original sources

Induced angiogenesis under cerebral ischemia by cyclooxygenase 2 and hypoxia-inducible factor naked DNA in a rat indirect-bypass model.

We recently reported that hypoxic stress induces the expression of HIF-1alpha, HIF-2alpha, cyclooxygenases-2 (COX-2) and VEGF in vivo. In this study, we investigated whether HIF-1alpha, HIF-2alpha, or COX-2 naked DNA induced angiogenesis in a cerebral ischemic model in vivo. We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated naked DNA into the brain surface. We analyzed whether DNA induced angiogenic factors and neovascularization. New blood vessel formation was detected by anti-Factor VIII staining. A histological section treated with HIF-2alpha or COX-2 DNA showed an increased expression of VEGF with angiogenesis, in comparison to the control DNA. The HIF-1alpha, HIF-2alpha, and COX-2 are able to promote significant angiogenesis development. These results suggest the feasibility of a novel approach for therapeutic angiogenesis of cerebral ischemia in which neovascularization may be indirectly achieved using a transcriptional and cytokine's regulatory strategy.

Animals↗

Multiple beta 1 integrins mediate enhancement of human airway smooth muscle cytokine secretion by fibronectin and type I collagen.

Altered airway smooth muscle (ASM) function and enrichment of the extracellular matrix (ECM) with interstitial collagen and fibronectin are major pathological features of airway remodeling in asthma. We have previously shown that these ECM components confer enhanced ASM proliferation in vitro, but their action on its newly characterized secretory function is unknown. Here, we examined the effects of fibronectin and collagen types I, III, and V on IL-1beta-dependent secretory responses of human ASM cells, and characterized the involvement of specific integrins. Cytokine production (eotaxin, RANTES, and GM-CSF) was evaluated by ELISA, RT-PCR, and flow cytometry. Function-blocking integrin mAbs and RGD (Arg-Gly-Asp)-blocking peptides were used to identify integrin involvement. IL-1beta-dependent release of eotaxin, RANTES, and GM-CSF was enhanced by fibronectin and by fibrillar and monomeric type I collagen, with similar changes in mRNA abundance. Collagen types III and V had no effect on eotaxin or RANTES release but did modulate GM-CSF. Analogous changes in intracellular cytokine accumulation were found, but in <25% of the total ASM cell population. Function-blocking Ab and RGD peptide studies revealed that alpha2beta1, alpha5beta1, alphavbeta1, and alphavbeta3 integrins were required for up-regulation of IL-1beta-dependent ASM secretory responses by fibronectin, while alpha2beta1 was an important transducer for type I collagen. Thus, fibronectin and type I collagen enhance IL-1beta-dependent ASM secretory responses through a beta1 integrin-dependent mechanism. Enhancement of cytokine release from ASM by these ECM components may contribute to airway wall inflammation and remodeling in asthma.

Adjuvants, Immunologic↗

Hypoxia-inducible factor-1alpha DNA induced angiogenesis in a rat cerebral ischemia model.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a constitutively expressed subunit, HIF-1beta. In this study, we investigated HIF-1alpha naked DNA-induced angiogenesis in a cerebral ischemic model in vivo. METHODS: We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated HIF-1alpha DNA into the brain surface or the temporal muscle. We analysed whether HIF-1alpha induced angiogenic factors and collateral circulation. RESULTS: A histological section treated with HIF-1alpha DNA showed an increased expression of HIF1 a and VEGF with collateral circulation, in comparison with control DNA (p < 0.01). The HIF-1alpha transcription factor is able to promote significant angiogenesis development. CONCLUSION: These results suggest the feasibility of a novel approach for therapeutic collateral circulation of cerebral ischemia in which neovascularization may be achieved indirectly using a transcriptional regulatory strategy.

Animals↗

Comparative study between DNA copy number aberrations determined by quantitative microsatellite analysis and clinical outcome in patients with stomach cancer.

PURPOSE: We detected the relative DNA copy numbers (RCNs) at target loci in patients with stomach cancer with quantitative microsatellite analysis. We additionally clarified the relationship between DNA copy number aberrations and the clinical outcome of the patients. EXPERIMENTAL DESIGN: Fresh frozen samples were obtained from 30 patients who had undergone surgery for stomach cancer. Seven microsatellite loci in chromosomes 8q, 16q, and 20q and one gene-specific locus (ZNF217) were selected as the target loci. The DNA copy number was obtained relatively to a pooled reference consisting of six microsatellite primer sets selected from the regions where few aberrations have been reported in comparative genomic hybridization analysis. On the basis of the TaqMan PCR system, the internal probes used were carrying donor (6-carboxyfluorescein) and acceptor (6-carboxytetramethylrhodamine) fluorescent molecules complementary to CA repeats in the microsatellite markers and to one gene-specific oligomer in the gene-specific marker. RESULTS: Chromosome 8q gain, 20q gain, and 16q loss were detected in 18 (60.0%), 8 (26.7%), and 13 (43.3%) cases, respectively. Gains in the RCNs of D8S1801 and D8S1724 were most frequently found (36.7%). There was a significant correlation between the loss of D16S3026 and reduced survival duration (P = 0.0158), and the simultaneous aberrations of D8S1801 gain and D16S3026 loss (double marker positive) was significantly associated with reduced survival duration (P = 0.0008). According to Cox proportional hazards model, the double marker positive was a significant and independent factor indicating an unfavorable prognostic factor (relative risk, 17.176; 95% confidence interval, 2.782-106.026; P = 0.0022). CONCLUSION: RCN aberrations in tumor tissues determined by quantitative microsatellite analysis enable identification of the prognostic factors that correlate with clinical outcome of the patients with stomach cancer.

Aged↗

Increased circulating matrix metalloproteinase-2 in patients with hypertrophic cardiomyopathy with systolic dysfunction.

BACKGROUND: Some patients with hypertrophic cardiomyopathy (HCM) develop left ventricular (LV) wall thinning associated with LV dilatation and systolic dysfunction. Recently, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were reported to be involved in ventricular remodeling, however, little is known about MMPs and TIMPs in patients with HCM. METHODS AND RESULTS: Enzyme-linked immunoassays were used to measure the plasma concentrations of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in 11 patients with HCM accompanied by systolic dysfunction (fractional shortening (FS) <25%, group A), 17 patients with HCM who had preserved systolic function (FS> or =25%, group B), and 50 age-matched clinically healthy control subjects (mean age: 57 years). The concentration of MMP-2 in group A was significantly higher than in group B and the control subjects (1,124 +/- 84, 792 +/- 49, 809 +/- 26 ng/ml, respectively), whereas there was no significant difference between group B and the control subjects. MMP-2 concentrations significantly increased as the New York Heart Association functional class increased in patients with HCM. TIMP-2 was also significantly higher in group A patients than in group B and the control subjects (45.3 +/- 4.7, 34.6 +/- 2.2, 33.7 +/- 1.8 ng/ml, respectively), but there was no difference between group B and control subjects. TIMP-1 was significantly higher in HCM patients than in control subjects. MMP-3 and MMP-9 concentrations did not differ among the 3 groups. Both MMP-2 and TIMP-2 correlated significantly with FS and LV dimension, negatively and positively, respectively. CONCLUSIONS: These results suggest that changes in the release and activity of MMP-2 and TIMP-2 may be associated with the mechanisms responsible for cardiac remodeling in patients with HCM.

Cardiomyopathy, Hypertrophic↗

Signaling pathways regulating interleukin-13-stimulated chemokine release from airway smooth muscle.

Interleukin (IL)-13 receptor activation on airway smooth muscle cells induces eotaxin release and activates multiple signaling pathways including mitogen-activated protein kinases, and signal transducer and activator of transcription 6 (STAT6). To examine a requirement for STAT6 in mediating IL-13-stimulated eotaxin release we used antisense oligodeoxynucleotides (ODNs) to downregulate endogenous STAT6 protein. STAT6 antisense ODNs were taken up by about 85% of cells. Selective downregulation of STAT6 protein occurred with antisense ODNs, but not with sense or scrambled ODNs. Eotaxin release induced by IL-13 or IL-4 (10 ng/ml) was reduced by 81 +/- 4 and 75 +/- 7%, respectively, in cells transfected with antisense ODNs (p < 0.001), but not with a sense ODN or a scrambled ODN. Eotaxin release induced by IL-1beta was unaffected by STAT6 antisense ODN (p > 0.05). Finally, IL-13- or IL-4-dependent eotaxin release was abolished when inhibitors of both p42/p44 ERK (U0126, 10 microM) and p38 (SB202190, 10 microM) mitogen-activated protein kinase pathways were combined in STAT6 antisense ODN-transfected cells. In contrast, about 25% of the response remained when each inhibitor was examined alone in STAT6 antisense ODN-treated cells. These data support roles for both STAT6- and mitogen-activated protein kinase-dependent pathways in mediating eotaxin release from airway smooth muscle by IL-13 or IL-4.

Adult↗

Measles outbreak in a suburb of Tokyo, Japan, in 1998-1999.

A 1998-1999 outbreak of measles in Kawasaki City was studied to provide an up-to-date epidemiological understanding of the disease in Japan. 21 of the 69 total patients (30.4%) seen at the hospital were under 1 y of age. None of the 69 patients had received measles vaccine. 43 out of 50 nasopharyngeal swabs subjected to polymerase chain reaction assay (86%) were positive for the hemagglutinin (H) gene. The measles strain isolated from patients was classified as a D3 genotype. Such outbreaks are important epidemiologically, and these findings shed light on vaccination and immunity patterns in this urban population.

Adolescent↗

[A case of multiple mycotic intracranial aneurysms presenting with subdural hematoma].

A patient with subdural hematoma associated with multiple mycotic intracranial aneurysms is reported. A 22-year-old woman presented with headache and disturbance of consciousness. A CT showed subdural hematoma at the tentrium and the left cerebral convexity. Conservative treatment and was used and she was discharged 10 days later. However, follow-up CT demonstrated a parenchymal hematoma in the right posterior temporal lobe. Cerebral angiography demonstrated a large right posterior cerebral aneurysm and multiple right middle cerebral aneurysms. A cardiac ultrasonography showed a verruca at the mitral valve. The posterior cerebral aneurysms increased in size and one new middle cerebral aneurysm appeared at follow-up angiography one week later. Endovascular treatment with coils was applied for the right posterior cerebral aneurysm, and others were treated with antibiotic therapy under serial observation, using MR angiography. She was discharged without any symptoms two months after embolization. Follow-up angiography at one year after embolization showed disappearance of the aneurysms. The possibility of mycotic aneurysm should be considered in the differential diagnosis of non-traumatic acute subdural hematoma.

Adult↗

Effect of temporal subtraction technique on the diagnosis of primary lung cancer with chest radiography.

PURPOSE: The purpose of this study was to assess the diagnostic accuracy of the temporal subtraction technique in the detection of primary lung cancers by readers with different levels of experience. METHODS: Previous and current chest radiographs from 40 patients with histologically proven lung cancer and 40 controls were studied. Temporal subtraction images were produced using an automated digital subtraction technique. We evaluated the effect of temporal subtraction images in the diagnosis of lung cancer with chest radiographs via an observer performance study with the use of receiver operating characteristic analysis. Six experienced radiologists and six residents participated as observers. RESULTS: Observer performance for all observers was superior when temporal subtraction images were used (mean Az value increased from 0.764 to 0.836, p=0.0006). Although the average Az value for residents increased significantly, from 0.707 to 0.795 (p=0.0038), the average Az value for experienced radiologists increased only from 0.821 to 0.878 (n.s.). CONCLUSION: In conclusion, the temporal subtraction technique clearly improves diagnostic accuracy for the detection of primary lung cancer. The results indicated that the use of temporal subtraction images was more beneficial for the residents than for the experienced radiologists. This method would compensate to some extent for experience-dependent diagnostic accuracy in the detection of lung cancer.

Adenocarcinoma↗