Akira Ito

Asahikawa medical university, Parasitology, Emeritus

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Eszter Krasznai Kovacs

University of Cambridge

David Seamon

Kansas State University

Remo Caponi

University of Cologne

Asli Odman

Mimar Sinan Fine Arts University

Armando Marques-Guedes

UNL - New University of Lisbon

Dorota Biczel

Barnard College

LUIS M A N U E L B R Á S BERNARDINO

Universidade Autónoma de Lisboa

Franco Barchiesi

Ohio State University

Andrea Purdekova

University of Bath

Dipesh Karmarkar

Smt. CHM College, Ulhasnagar, Thane

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Papers by Akira Ito

Skeletal muscle tissue engineering using functional magnetite nanoparticles

2009 International Symposium on Micro-NanoMechatronics and Human Science, 2009

ABSTRACT Skeletal muscular tissues were constructed using magnetic force-based tissue engineering... more ABSTRACT Skeletal muscular tissues were constructed using magnetic force-based tissue engineering (Mag-TE) techniques. Mouse myoblast C2C12 cells labeled with magnetite cationic liposomes (MCLs) were seeded into a well of 24-well ultra-low cell attachment culture plates. When a magnet was positioned underneath the well, cells accumulated evenly onto the culture surface and formed a multilayered cell sheet. Furthermore, because an angiogenic potential of transplants is considered to be important for the long-term maintenance of cell survival and tissue functions, a vascular endothelial growth factor (VEGF) gene-modified C2C12 (C2C12/VEGF) cell sheets were also fabricated by the Mag-TE technique. The secretion level of C2C12/VEGF sheets was 3.0 ng/day, indicating that VEGF gene-expressing cell sheets were successfully fabricated. Since the shape of artificial tissue constructs can be controlled by magnetic force, a cellular string-like assembly was formed by placing a linear-shaped magnetic field concentrator with a magnet. These cellular sheets and strings shrank and did not maintain their shapes for an additional in vitro culture period during myogenic differentiation. On the other hand, when a silicone plug was positioned at the center of well during the fabrication of cell sheets, the cell sheets shrank and formed a ring-like assembly around the plug. After 6-d cultivation of cell rings in differentiation medium, the C2C12 cells differentiated to form multinucleated myotubes. Thus, these procedures can provide a novel strategy for skeletal muscular tissue engineering.

Regional comparisons of porcine menisci

Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2014

The purpose of this study was to analyze histologic, biochemical, and biomechanical differences b... more The purpose of this study was to analyze histologic, biochemical, and biomechanical differences between zonal, regional, and anatomic locations of porcine menisci. We evaluated six menisci removed from pigs. Medial and lateral menisci were divided into three regions: anterior, middle, and posterior. In each portion, the central zone (CZ) and peripheral zone (PZ) were examined histologically (hematoxylin & eosin, safranin O/Fast green, and picrosiriusred staining), using scanning electron microscopy, biochemically (hydroxyproline assay for collagen content and dimethylmethylene blue assay for glycosaminoglycan [GAG] content), and biomechanically (compression testing). Collagen content in the CZ was lower than that in the PZ. GAG content in the CZ was higher than that in the PZ. GAG content in the PZ of the posterior portion was significantly higher than that in the anterior and middle portions. Compression strength in the CZ was higher than that in the PZ. The differences in cellular...

Graded Collector for Inductive Loads

Enhanced post-ischemic angiogenesis in mice lacking RNF213; a susceptibility gene for moyamoya disease

Brain research, Jan 12, 2015

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology that ... more Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology that is characterized by the development of abnormal vascular networks at the base of the brain. Recent genome-wide studies identified RNF213 as an important MMD susceptibility gene. However, the exact mechanism by which the RNF213 abnormality leads to MMD remains unknown. Thus, we sought to clarify the role of RNF213 in angiogenesis under ischemic conditions using conventional RNF213 knockout mice. We assessed the infarction volume, cerebral edema, and vascular density in the ischemic brain after transient middle cerebral artery occlusion (tMCAO). To further evaluate systemic angiogenesis following chronic ischemia, we investigated blood flow recovery using laser speckle flowmetry, the severity of ambulatory impairments, and vascular density in the hind-limb after permanent femoral artery ligation. Results were compared between homozygous RNF213 knockout mice (RNF213 -/-) and wild-type litte...

Pathogenesis, Treatment and Prognosis of Impending Myocardial Infarction and Early Post-Infarction Angina : Relation between ST-segment shift during myocardial ischemia and the pathogenesis : PATHOGENESIS AND MANAGEMENT OF IMPENDING MYOCARDIAL INFARCTION

Japanese Circulation Journal, Nov 20, 1992

We studied 141 patients to evaluate the pathogenesis and clinical picture of high-risk unstable a... more We studied 141 patients to evaluate the pathogenesis and clinical picture of high-risk unstable angina (UA), designated as impending myocardial infarction (IMI) in this study, or severe early post-infarction angina (PIA). IMI and PIA were diagnosed when chest pain appeared at rest and lasted 15 min or more despite extensive pharmacological therapy during hospital stay among consecutive 510 patients with UA. All patients underwent coronary angiography urgently within 72 h after chest pain, and were divided into 2 subgroups according to ST segment shifts during chest pain. In IMI, 42 patients with ST depression had higher incidences of prior myocardial infarction (MI), worsening UA, multivessel disease and complex lesions such as eccentric irregular lesion or ulceration. On the contrary, in 44 with ST elevation, new onset UA, single vessel disease and coronary thrombus (CT) were dominant. In PIA, 32 patients with ST elevation revealed higher incidences in Q wave MI, ST elevation at the MI onset, single vessel disease and CT, compared to 23 with ST depression who showed a high proportion of complex lesions. Thus, it was evident that there was a common link between the pathogenesis of IMI and PIA. The therapeutic options were also different in the groups according to ST segment shift. We conclude that ST segment shifts during chest pain may be useful for determining the pathogenesis and clinical features of high-risk UA.

Effects of type IV collagen on myogenic characteristics of IGF-I gene-engineered myoblasts

Journal of bioscience and bioengineering, Jan 21, 2014

Skeletal muscle regeneration requires migration, proliferation and fusion of myoblasts to form mu... more Skeletal muscle regeneration requires migration, proliferation and fusion of myoblasts to form multinucleated myotubes. In our previous study, we showed that insulin-like growth factor (IGF)-I gene delivery stimulates the proliferation and differentiation of mouse myoblast C2C12 cells and promotes the contractile force generated by tissue-engineered skeletal muscles. The aim of this study was to investigate the effects of the extracellular matrix on IGF-I gene-engineered C2C12 cells in vitro. Retroviral vectors for doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into C2C12 cells. When cultured on a type IV collagen-coated surface, we observed significant increases in the migration speed and number of IGF-I gene-engineered C2C12 cells with Dox addition, designated as C2C12/IGF (+) cells. Co-culture of C2C12/IGF (+) cells and parental C2C12 cells, which had been cultured in differentiation medium for 3 days, greatly enhanced myotube formation. Moreover, type I...

Analysis of Peripheral Blood Mononuclear Cells in Operational Tolerance After Pediatric Living Donor Liver Transplantation (LDLT)

Transplantation, 2004

Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment

Neuroscience letters, Jan 17, 2014

Hypofunction of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors may be involved in... more Hypofunction of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors may be involved in the pathophysiology of schizophrenia. Many studies have investigated peripheral NMDA receptor-related glutamatergic amino acid levels because of their potential as biological markers. Peripheral d-serine levels and the ratio of d-serine to total serine have been reported to be significantly lower in patients with schizophrenia than in controls. Peripheral d-serine levels and the d-/l-serine ratio have also been reported to significantly increase in patients with schizophrenia as their clinical symptoms improve from the time of admission to the time of discharge. In this study, we examined whether peripheral NMDA receptor-related glutamatergic amino acids levels were altered in patients with treatment-resistant schizophrenia compared to controls and whether these peripheral amino acids levels were altered by clozapine treatment. Twenty-two patients with treatment-resistant schizophrenia ...

Proton computed tomography applied to small biomedical samples

Biol Tr Elem Res, 1987

The computed tomography (CT) using the high-energy proton beam has the potential advantage of sup... more The computed tomography (CT) using the high-energy proton beam has the potential advantage of superior density resolution in the soft tissue analysis as compared to the conventional X-ray CT.We have developed the &quot;first generation&quot; type proton CT system using a 25-MeV proton beam to study the density distributions in small biomedical samples (&lt;6 mm ϕ).The specimens were fixed in a cylindrical sample holder that was immersed in a water bath. The sample holder was scanned in front of the external semimicro beam of protons with a width of 0.06 mm at full width of half maximum (FWHM). The residual energy of the penetrated proton beam was analyzed with a solid state detector (SSD). The obtained integral density projection views were reconstructed into the density image by the filtered back projection method using the Shepp-Logan filter function.The spatial resolution of 0.1 mm and the density resolution of 0.1% were obtained by our system.The technique was applied to the eyes of small animals to study the changes in the density distributions of lenses, which develop with lens opacification in cataracts.

Design and synthesis of mono and bicyclic tetrapeptides thioester as potent inhibitor of histone deacetylases

Amino Acids, 2014

Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that have a... more Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that have an effect on gene regulation. The naturally occurring cyclic depsipeptide FK228 containing disulfide and Largazole possessing thioester functionalities act as pro-drugs and share the same HDAC inhibition mechanism in cell. Inspired from these facts, we have reported bicyclic tetrapeptide disulfide HDAC inhibitors resembling FK228 with potent activity and enhanced selectivity. In the present study, we report the design and synthesis of several mono and bicyclic tetrapeptide thioester HDAC inhibitors that share the inhibition mechanism similar to Largazole. Most of the compounds showed HDAC1 and HDAC4 inhibition and p21 promoting activity in nanomolar ranges. Among these the monocyclic peptides 1, 2 and bicyclic peptide, 4 are notable demanding more advanced research to be promising anticancer drug candidates.

Induction of gastric tumor and intestinal metaplasia in rats exposed to localized X-irradiation of the gastric region

Japanese Journal of Cancer Research, 1987

The induction of gastric tumor and intestinal metaplasia was examined in 8-week-old male JCL/SD r... more The induction of gastric tumor and intestinal metaplasia was examined in 8-week-old male JCL/SD rats exposed to localized X-irradiation of the gastric region. The animals were each given two 20 Gy fractions of X-rays, with a one-week interval between fractions (total, 40 Gy). Nine atypical hyperplasias (20%) and 13 adenocarcinomas (28%) in the pyloric mucosa of the glandular stomach were found in 46 animals with X-irradiation. The incidence of intestinal metaplasia was 93% in the pyloric mucosa, 50% in the fundic mucosa and 96% in both the pyloric and fundic mucosa. Type B metaplasia (intestinal metaplasia without Paneth cells) was most common and type C (intestinal metaplasia with Paneth cells) was less frequent. No gastric tumor or intestinal metaplasia appeared in non-irradiated control rats. This study shows that local X-irradiation of the gastric region induced both gastric tumor and intestinal metaplasia independently.

Design and synthesis of CHAP31, trapoxin B and HC-toxin based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors

Bioorganic & medicinal chemistry, 2014

The naturally occurring cyclic depsipeptide, FK228 inhibits histone deacetylase (HDAC) enzymes af... more The naturally occurring cyclic depsipeptide, FK228 inhibits histone deacetylase (HDAC) enzymes after reductive cleavage of intra-molecular disulfide bond. One of the sulfhydryl groups produced in the reduction interacts with zinc atom that involved in the catalytic mechanism of type 1 and 2 HDACs such as HDAC1, HDAC4, and HDAC6. In the present study, we describe the development of CHAP31, trapoxin B and HC-toxin based cyclic tetrapeptides with intra-molecular disulfide bond as HDAC inhibitors. The bicyclic tetrapeptides disulfide showed potent HDAC1 and HDAC4 inhibition and p21 promoting activity.

Annihilation and formation of electron traps in hydrogen-implanted n-type silicon by light illumination

Materials Science Engineering B Solid State Materials For Advanced Technology, Feb 1, 2000

Annihilation and formation of electron traps by light illumination in 170-keV-hydrogen-implanted ... more Annihilation and formation of electron traps by light illumination in 170-keV-hydrogen-implanted n-type silicon with a dose of 2×10 10 cm − 2 has been studied with deep level transient spectroscopy for fabricated gold Schottky diodes. In addition to the well-known vacancy-related traps (A center, divacancy and E center), two hydrogen-related E(0.32) and E(0.49) traps are produced by hydrogen implantation. It is found in zero-biased diodes that the partial annihilation of vacancy-related traps and corresponding formation of hydrogen-related traps occurs with illumination of light with photon energy above the band-gap energy. No effects of light illumination are found in reverse-biased diodes. The partial annihilation of vacancy-related defects is caused by the complex formation with hydrogen which is liberated from shallow-level, hydrogen-containing defects other than the E(0.32) and E(0.49) traps. The hydrogen liberation is thought to occur through induced instability of hydrogen-containing defects by changing their charge states with electron capture. The hydrogen-related E(0.32) trap is ascribed to the complex of the A center and hydrogen.

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Identification of sumoylation inhibitors targeting a predicted pocket in Ubc9

Journal of chemical information and modeling, Jan 27, 2014

Sumoylation is a post-translational modification that plays an important role in a wide range of ... more Sumoylation is a post-translational modification that plays an important role in a wide range of cellular processes. Among the proteins involved in the sumoylation pathway, Ubc9 is the sole E2-conjugating enzyme required for sumoylation and plays a central role by interacting with almost all of the partners required for sumoylation. Ubc9 has been implicated in a variety of human malignancies. In order to exploit the therapeutic potential of Ubc9, we have identified the potential site to target for rational drug design using molecular modeling approaches. The structural information derived was then used to prioritize hits from a small-molecule library for biological assay using a virtual screening protocol that involves shape matching with a known inhibitor inhibitors and docking of a small-molecule library utilizing computational approaches that incorporate both ligand and protein flexibility. Nineteen compounds were acquired from different chemical vendors and were tested for Ubc9 ...

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Carcinogenicity of 1,2-dimethylhydrazine in colorectal tissue heteropically transplanted intothe glandular stomach of rats

Japanese Journal of Cancer Research, 1992

The present study was designed to examine the effect of the intestinal carcinogen 1,2-dimethylhyd... more The present study was designed to examine the effect of the intestinal carcinogen 1,2-dimethylhydrazine (DMH) on grafted colorectal mucosa implanted into the glandular stomach of rats. Four groups were studied: Group 1 received the operation and DMH, Group 2 received the operation alone, Group 3 received DMH alone and Group 4 (controls) received only a sham operation. For Groups 1 and 2, about 8-mm diameter segments of colorectal tissue obtained from various sites in the large intestine of 8-week-old male F344 rats were isologously implanted into the fundic region of the stomachs of age-matched rats. DMH was injected at a dose of 20 mg/kg body weight i.m. per week for 20 weeks beginning 4 weeks after the operation. The animals were then observed for 8 months after the initial DMH treatment. In Group 1, adenocarcinomas developed in 41 of 60 successful implants (68%). Furthermore, poorly differentiated type tumors were observed in the grafts obtained from the rectum. This finding was contrary to that for intrinsic rectal tumors, all of which were well differentiated. The histochemical staining of mucin in the tissues from different sites of the large intestine revealed that sulfomucin, which normally exists essentially only in the intrinsic descending colon or rectum, was present in the grafts from the proximal ascending or ascending colon. No gastric tumors were observed in the control rats, which received either DMH or sham operations alone. Tumors in the intrinsic large intestine were observed only in rats that received DMH. These results indicate that colorectal mucosa implanted into the glandular stomach, like the intrinsic large intestine, is still sensitive to tumorigenesis caused by DMH.

Multilayering of peritubular capillary is a specific diagnostic criterion for immunologic chronic rejection: does a humoral factor contribute to the pathogenesis of peritubular capillary lesions in chronic rejection?

Transplantation Proceedings, 2000

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Relation between SSTs and Predictability of Seasonal Mean Precipitation over the Western Tropical Pacific

Journal of the Meteorological Society of Japan, 2005

... Bull. Amer. Me-teor. Soc., 65, 114–125. Kobayashi, C., K. Takano, S. Kusunoki, M. Sugi,and A.... more

A unique mechanism of tolerance by perioperative intrathymic injection of bone marrow cells with a short course of ALS and FK506 in the rat cardiac allograft model

Transplantation Proceedings, 1997

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The carboxy-terminal 10 amino acid residues of cytochrome b5 are necessary for its targeting to the endoplasmic reticulum

The Embo Journal, Dec 1, 1992

Cytochrome b5 is an integral membrane protein located on the outer surface of the endoplasmic ret... more Cytochrome b5 is an integral membrane protein located on the outer surface of the endoplasmic reticulum (ER). This cytochrome is considered to be synthesized on free ribosomes and to be inserted post-translationally into the ER membrane, without participation of a signal recognition particle. To elucidate the signal responsible for targeting of cytochrome b5 to the ER membrane in vivo, DNAs encoding various derivatives of the cytochrome were constructed and introduced into cultured mammalian COS cells, and the subcellular distributions of the derivatives expressed in the cells were then analyzed. The deletion of more than 11 amino acid residues at the carboxy-terminal end of cytochrome b5 abolished the targeting and anchoring of the cytochrome to the ER membrane. Fusion proteins consisting of the carboxy-terminal 10 amino acid residues of cytochrome b5 and passenger proteins with the hydrophobic portion could be localized in the ER membrane. Thus, the last 10 amino acid residues of cytochrome b5 carry information necessary for the cytochrome to be targeted to the ER membrane.

Production of recombinant human erythropoietin/Fc fusion protein by genetically manipulated chickens

Transgenic Research, 2010

We previously reported the production of human erythropoietin (hEpo) using genetically manipulate... more We previously reported the production of human erythropoietin (hEpo) using genetically manipulated (GM) chickens. The recombinant hEpo was produced in the serum and egg white of the GM chickens, and the oligosaccharide chain structures of the serum-derived hEpo were more favorable than those of the egg white-derived hEpo. In the present study, a retroviral vector encoding an expression cassette for