A5105463008- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Pulmonary Hypertension Research and Treatments
- Structural Load-Bearing Analysis
- Fatigue and fracture mechanics
- Blood Coagulation and Thrombosis Mechanisms
- Structural Behavior of Reinforced Concrete
- Fire effects on concrete materials
- Protease and Inhibitor Mechanisms
- Cerebrospinal fluid and hydrocephalus
- Neuroscience and Neural Engineering
- Complement system in diseases
- Numerical methods in engineering
- Photoreceptor and optogenetics research
- Spinal Dysraphism and Malformations
- Ion Channels and Receptors
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Neuroendocrine regulation and behavior
- Fetal and Pediatric Neurological Disorders
- Nicotinic Acetylcholine Receptors Study
- Nitric Oxide and Endothelin Effects
- Neuroscience of respiration and sleep
- Engineering Structural Analysis Methods
- Welding Techniques and Residual Stresses
Kochi Prefectural Education Center
2023
Stanford University
2008-2022
VA Palo Alto Health Care System
2006-2022
Takenaka (Japan)
2004-2020
Central Institute for Experimental Animals
2012-2017
Eli Lilly (United States)
2014
Bruker (United States)
2014
Stanford Medicine
2000-2013
Tokyo University of Science
2004-2013
Research & Development Institute
2013
We developed an in vitro model system where induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional human hepatic organoids (HOs) through stages that resemble liver during its embryonic development. The HOs consist of hepatocytes, and cholangiocytes, which are organized epithelia surround the lumina bile duct-like structures. provide a potentially new for regenerative processes, were used to characterize effect different JAG1 mutations cause: (a) Alagille syndrome (ALGS),...
Although the mechanisms responsible for alveolar liquid clearance have been studied in several species, there has not any information regarding effect of ion transport agonists or antagonists on human lung. Therefore, we recently resected lung from patients who underwent surgery cancer. A test solution 40 ml isosmolar albumin was instilled into one segment a lobe within 10 min resection. Because protein leaves air spaces very slowly, concentration over 4 h used to quantify clearance. Basal...
Pulmonary vascular injury by toxins can induce neointimal formation, pulmonary arterial hypertension (PAH), right ventricular failure, and death. We showed previously that simvastatin attenuates smooth muscle proliferation in pneumonectomized rats injected with the alkaloid toxin monocrotaline. The present study was undertaken to investigate efficacy of its mechanism reversing established occlusion hypertension.Pneumonectomized monocrotaline at 4 weeks demonstrated severe PAH 11 (mean artery...
The latent plasma carboxypeptidase thrombin-activable fibrinolysis inhibitor (TAFI) is activated by thrombin/thrombomodulin on the endothelial cell surface, and functions in dampening fibrinolysis. In this study, we examined effect of TAFI (TAFIa) modulating proinflammatory bradykinin, complement C5a, thrombin-cleaved osteopontin. Hydrolysis bradykinin C5a osteopontin peptides TAFIa was as efficient that plasmin-cleaved fibrin peptides, indicating these are also good substrates for TAFIa....
Hypertensive pulmonary vascular disease is characterized by abnormal proliferation of endothelial and smooth muscle cells, leading to occlusion arterioles, hypertension, right ventricular failure, death. Compounds with antiproliferative effects on such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, may prevent the development experimental hypertensive disease. Pneumonectomized rats injected monocrotaline at 7 days develop severe neointimal formation. Rats were...
Pulmonary endothelial injury triggers a reparative program, which in susceptible individuals is characterized by neointima formation, vascular narrowing, and the development of pulmonary arterial hypertension. The neointimal cells human pathological plexiform lesions frequently coexpress smooth muscle α-actin von Willebrand antigen, creating question about their cellular lineage origin.Experimental hypertension with formation develops C57Bl/6 mice subjected to left pneumonectomy followed 1...
Pneumonectomized rats develop pulmonary hypertension (PH) and vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley were injected with MCT (60 mg/kg) on Day 7 left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/kg/d, by gavage): Group PMR5–35 from 5 to 35, PMR5–14 14, PMR15–35 15 35. By that vehicle had higher mean arterial pressures (Ppa 41 ± 3 mm Hg) (p < 0.001), right ventricular systolic (Prv,s 45 2...
The immune and coagulation systems are both implicated in the pathogenesis of rheumatoid arthritis (RA). Plasma carboxypeptidase B (CPB), which is activated by thrombin/thrombomodulin complex, plays a procoagulant role during fibrin clot formation. However, an antiinflammatory for CPB suggested recent observation that can cleave proinflammatory mediators, such as C5a, bradykinin, osteopontin. Here, we show central downregulating C5a-mediated inflammatory responses autoimmune arthritis....
Interspecies differences in drug metabolism have made it difficult to use preclinical animal testing data predict the metabolites or potential drug-drug interactions (DDIs) that will occur humans. Although chimeric mice with humanized livers can produce known human for test substrates, we do not know whether be used prospectively a possible DDI. Therefore, investigated they could provide more predictive assessment clemizole, clinical development treatment of hepatitis C virus (HCV)...
Due to the substantial interspecies differences in drug metabolism and disposition, drug-induced liver injury (DILI) humans is often not predicted by studies performed animal species. For example, a (bosentan) used treat pulmonary artery hypertension caused unexpected cholestatic toxicity humans, which was preclinical toxicology multiple In this study, we demonstrate that NOG mice expressing thymidine kinase transgene (TK-NOG) with humanized livers have profile of biliary excretion test...
This paper reports the effect of triptolide (a diterpenoid triepoxide) on development monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague– Dawley rats were injected with MCT (60 mg/kg) Day 7 after left pneumonectomy. Rats received therapy from 5 to 35 (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml ethanol/cremophor 10). By 35, triptolide-treated demonstrated lower mean arterial pressure (mPAP) than vehicle-treated (mPAP 21 ±...
We investigated whether human pharmacogenetic factors could be characterized using chimeric NOG mice expressing a thymidine kinase transgene (TK-NOG) with 'humanized' livers.The rate of human-specific metabolism two drugs was measured in reconstituted hepatocytes different CYP2C19 and CYP2C9 genotypes.The generation human-predominant drug metabolites for S-mephenytoin diclofenac the correlated (n=9 donors, P=0.0005) or (n=7 P=0.0394) genotype, respectively, transplanted hepatocytes.This...
1. Voltage‐clamp recordings were made from neurones in rabbit vesical pelvic ganglia by using single microelectrodes filled with 2 M‐caesium chloride. Neurones superfused Krebs solution containing 300 nM‐tetrodotoxin and 50 mM‐tetraethylammonium. 2. Depolarizing voltage jumps activated inward currents followed slowly decaying tail at ‐30 to +30 mV, which accompanied a large increase membrane conductance. Both the current blocked cobalt (2 mM) or zero calcium 12 mM‐magnesium. 3. Substitution...
Objective— To determine whether procarboxypeptidase B (pCPB) −/− mice are susceptible to accelerated abdominal aortic aneurysm (AAA) development secondary unregulated OPN-mediated mural inflammation in the absence of CPB inhibition. Methods and Results— Thrombin/thrombomodulin cleaves thrombin-activatable pCPB or fibrinolysis inhibitor, activating CPB, which inhibits generation plasmin inactivates proinflammatory mediators (complement C5a thrombin-cleaved osteopontin [OPN]). Apolipoprotein E...
We developed a novel method for differentiating adipocyte-derived stem cells (ASCs) into hepatocyte-like (iHeps). ASCs are cultured as spherical cellular aggregates and then induced by culture in chemically defined media short time period to differentiate iHeps (SCi-Heps). SCi-Heps have many of the vitro functional properties mature hepatocytes, they can stably reconstitute functioning human liver vivo murine model system. Implantation studies demonstrate that very low malignant potential....