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Biomedical subjects

Takeshi Tsuda

Publications and source records attributed to Takeshi Tsuda.

8 recordsLinked to original sources

An ultrasound imaging method for in vivo tracheal bulk and Young's moduli of elasticity.

Alterations in neonatal airway mechanical properties resulting from ventilatory therapies such as mechanical ventilation have been implicated in airway collapse and chronic disease. Advances in ultrasound (US) technology allow for real-time imaging and accurate measurement of tracheal dimensions in vivo; thus, changes in mechanical properties can be tracked longitudinally. In this report we introduce an adaptation of engineering concepts using US imaging data to study airway mechanics in vivo. In this protocol, tracheal segments are isolated in a spontaneously breathing newborn lamb model and the segments are exposed to time-cycled, pressure-limited mechanical ventilation. Serially, tracheal segments are filled with saline and pressure-volume relationships are recorded with stepwise volume infusions. US dimensional measurements of the segments are made while static (no distending pressure) and at pressure limits during dynamic ventilator cycling. US measurements are used to normalize pressure-volume data for resting volume, calculation of bulk modulus, stress-strain relationships and the adapted Young's modulus associated with tangential wall stress. Temporal changes in bulk and Young's moduli demonstrate the time dependence of alterations in conducting airway mechanical properties in vivo during the course of mechanical ventilation. This methodology will provide a means to evaluate respiratory therapies with respect to airway mechanics.

Animals↗

Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs.

Platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP), has been reported to possess angiogenic activity and to inhibit apoptosis. This study was performed to determine whether PD-ECGF/TP can be used to ameliorate chronic myocardial ischemia. Myocardial ischemia was created in 40 mongrel dogs by placement of an ameroid constrictor on the proximal left anterior descending coronary artery (LAD). Plasmid vector encoding human PD-ECGF/TP cDNA (pCIhTP group; n = 12), empty vector pCI (pCI group; n = 12), or saline (Saline group; n = 12) was directly injected into the LAD territory 3 wk after ameroid constrictor implantation. Myocardial blood flow was detected using PET at baseline, 3 wk after ameroid constrictor implantation, and 2 wk after therapeutic treatment. At the end of the experiment, the hearts were isolated for biological and histological analysis. In the pCIhTP group, the transfected heart strongly expressed PD-ECGF/TP. The size of the infarct was smaller in the pCIhTP group than in the pCI or Saline group. The number of apoptotic myocardial cells was decreased in the pCIhTP group compared with the control groups based on triple immunohistochemical staining for von Willebrand factor, alpha-actin smooth muscle cells, and single-strand DNA. The level of proapoptotic protein Bax markedly decreased in the pCIhTP group compared with the other groups. Double immunohistochemical staining for von Willebrand factor and alpha-actin smooth muscle cells demonstrated that angiogenesis and arteriogenesis occurred, and paralleled the changes in myocardial blood flow and myocardial function in the pCIhTP group. We conclude that genetic approaches using PD-ECGF/TP to target the myocardium are effective for alleviating chronic myocardial ischemia.

Animals↗

Fibulins in development and heritable disease.

Fibulins are a family of five extracellular glycoproteins found in a variety of tissues in association with diverse supramolecular structures, including elastic fibers, basement membrane networks, fibronectin microfibrils, and proteoglycan aggregates. Studies of the developmental expression patterns have indicated that several fibulins are prominently expressed at sites of epithelial-mesenchymal transformations during embryogenesis; among these sites, the cardiovascular system has been analyzed in more detail. Gene targeting of fibulins in mice has provided important insights into their biological roles, and has led to the identification of gene mutations in a congenital disorder of humans, cutis laxa. Genetic linkage and molecular studies have also associated several fibulin genes with various human heritable disorders that affect a wide range of organs, including limb, eye, blood, and arteries. In this review, we discuss the role of fibulins in development, with an emphasis on the cardiovascular system, and their involvement in human genetic disease.

Amino Acid Sequence↗

Zinc finger protein Zac1 is expressed in chondrogenic sites of the mouse.

Zac1 is a zinc finger transcription factor that elicits antiproliferative activity and is a potential tumor suppressor gene. Through a detailed spatiotemporal study by in situ hybridization of mouse embryos, we have found that Zac1 transcript is predominantly localized in developing chondrogenic tissue, in addition to the central nervous system as reported elsewhere. Zac1 is also expressed transiently in the myocardium, skeletal muscle, and basal aspect of the stratified embryonic epithelia. During cartilage development, the pattern of Zac1 expression is in close accordance with the distribution of type II collagen mRNA in mesenchymal condensation and prehypertrophic chondrocytes. In mouse ATDC5 cells undergoing in vitro chondrogenesis, the Zac1 mRNA is up-regulated in parallel with genes expressed in precartilage but the Zac1 expression is low when type II collagen mRNA is markedly increased in differentiated cells. Together, these results suggest that Zac1 is a potential regulatory gene involved in chondrogenic differentiation.

Animals↗

Post-ischemic myocardial fibrosis occurs independent of hemodynamic changes.

OBJECTIVES: Myocardial fibrosis is a major component of ventricular remodeling after large myocardial infarction (MI). The present study tests the hypothesis that post-ischemic myocardial fibrosis can occur independent of hemodynamic changes. METHODS: A mouse model of distal left coronary artery ligation was established to induce a small infarct (less than 15% of the left ventricle) in order to avoid significant mechanical overload after permanent myocardial ischemia. Left heart catheterization was performed to evaluate the post-infarct hemodynamics. Tissues from both ischemic and non-ischemic myocardium were examined for mRNA and protein expression at 24, 72 h and 7 days after ligation. RESULTS: Heart/body weight ratio after ligation was increased by approximately 10% over sham control although there is no statistically significant difference in hemodynamic parameters between the two groups. Non-ischemic myocardium distant from the infarct site showed molecular evidence of myocardial fibrosis 72 h and 7 days after ligation. There was marked up-regulation of mRNAs for extracellular matrix (ECM) proteins and their cross-linking enzyme, such as collagens type I, III and VI, and lysyl oxidase. Immunohistochemical study confirmed that the expression of these ECM proteins was significantly increased in the non-ischemic myocardium after 7 days. TGF-beta1 was up-regulated after 72 h in both ischemic and non-ischemic myocardium. CONCLUSIONS: Molecular and histopathological findings demonstrate that abnormal myocardial fibrosis can be induced by a small infarct independent of secondary hemodynamic changes.

Animals↗

Prominent expression of lysyl oxidase during mouse embryonic cardiovascular development.

By mRNA differential display in mouse hearts, lysyl oxidase (Lox), a key enzyme catalyzing cross-links in elastin and collagens, was found to be up-regulated between embryonic days 11 (E11) and 13 (E13). This was confirmed by semiquantitative RT-PCR. We analyzed its spatio-temporal expression pattern by in situ hybridization in regard to the development of myocardial cells, endocardial cushion tissue, aortic arch vessels, and epicardium.

Animals↗

Giant mediastinal bronchial artery aneurysm mimicking benign esophageal tumor: a case report and review of 26 cases from literature.

Mediastinal bronchial artery aneurysm is rare but potentially life-threatening, and requires prompt treatment to avert rupture with catastrophic results. A 78-year-old man was referred to our hospital with a benign esophageal tumor, which appeared as an extrinsic, extramucosal filling defect on an esophagogram. Chest computed tomography and selective bronchial arteriography led to a definitive diagnosis of mediastinal bronchial artery aneurysm. Aneurysmectomy and closure of the ostia of both the afferent and efferent bronchial arteries was performed via standard posterolateral thoracotomy. Postoperative course was uneventful, and the patient was discharged on the seventh postoperative day.

Aged↗

Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs.

We examined the role of matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs), and plasminogen activator (PA) in transmyocardial laser revascularization (TMLR)-induced angiogenesis. TMLR was accomplished with a carbon dioxide laser in seven dogs whose left anterior descending coronary artery (LAD) was ligated. Seven control dogs underwent only LAD ligation, and four dogs underwent a sham operation, consisting only of a left thoracotomy. Two weeks later, transmural myocardial samples were harvested from the distributions of the LAD and the left circumflex artery for substrate zymography, immunohistochemical staining, and in situ zymography. MMP-1, MMP-2, TIMP-1, TIMP-2, and urokinase-type PA levels in the distribution of the LAD were higher in the laser group than in the control or sham group. Counts of von Willebrand factor-positive microvessels and smooth muscle alpha-actin-positive arterioles demonstrated that the angiogenesis and ateriogenesis was promoted in the laser group and correlated directly with the number of MMP-stained microvessels. We conclude that TMLR induces the expression of MMPs, TIMPs, and urokinase-type PA and that these proteinases play an important role in angiogenesis after TMLR.

Animals↗