85 results on '"Mitsuyo Maeda"'
Search Results
2. An Myh11 single lysine deletion causes aortic dissection by reducing aortic structural integrity and contractility
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Keita Negishi, Kenichi Aizawa, Takayuki Shindo, Toru Suzuki, Takayuki Sakurai, Yuichiro Saito, Takuya Miyakawa, Masaru Tanokura, Yosky Kataoka, Mitsuyo Maeda, Shota Tomida, Hiroyuki Morita, Norifumi Takeda, Issei Komuro, Kazuomi Kario, Ryozo Nagai, and Yasushi Imai
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Medicine ,Science - Abstract
Abstract Pathogenic variants in myosin heavy chain (Myh11) cause familial thoracic aortic aneurysms and dissections (FTAAD). However, the underlying pathological mechanisms remain unclear because of a lack of animal models. In this study, we established a mouse model with Myh11 K1256del, the pathogenic variant we found previously in two FTAAD families. The Myh11 ∆K/∆K aorta showed increased wall thickness and ultrastructural abnormalities, including weakened cell adhesion. Notably, the Myh11 ∆K/+ mice developed aortic dissections and intramural haematomas when stimulated with angiotensin II. Mechanistically, integrin subunit alpha2 (Itga2) was downregulated in the Myh11 ∆K/∆K aortas, and the smooth muscle cell lineage cells that differentiated from Myh11 ∆K/∆K induced pluripotent stem cells. The contractility of the Myh11 ∆K/∆K aortas in response to phenylephrine was also reduced. These results imply that the suboptimal cell adhesion indicated by Itga2 downregulation causes a defect in the contraction of the aorta. Consequently, the defective contraction may increase the haemodynamic stress underlying the aortic dissections.
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- 2022
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3. Increased RNA Transcription of Energy Source Transporters in Circulating White Blood Cells of Aged Mice
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Yukiko Takeuchi, Orie Saino, Yuka Okinaka, Yuko Ogawa, Rie Akamatsu, Akie Kikuchi-Taura, Yosky Kataoka, Mitsuyo Maeda, Sheraz Gul, Carsten Claussen, Johannes Boltze, and Akihiko Taguchi
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aging ,white blood cell ,RNA transcription ,energy source transporter ,metabolism related gene ,neurogenesis ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Circulating white blood cells (WBC) contribute toward maintenance of cerebral metabolism and brain function. Recently, we showed that during aging, transcription of metabolism related genes, including energy source transports, in the brain significantly decreased at the hippocampus resulting in impaired neurological functions. In this article, we investigated the changes in RNA transcription of metabolism related genes (glucose transporter 1 [Glut1], Glut3, monocarboxylate transporter 4 [MCT4], hypoxia inducible factor 1-α [Hif1-α], prolyl hydroxylase 3 [PHD3] and pyruvate dehydrogenase kinase 1 [PDK1]) in circulating WBC and correlated these with brain function in mice. Contrary to our expectations, most of these metabolism related genes in circulating WBC significantly increased in aged mice, and correlation between their increased RNA transcription and impaired neurological functions was observed. Bone marrow mononuclear transplantation into aged mice decreased metabolism related genes in WBC with accelerated neurogenesis in the hippocampus. In vitro analysis revealed that cell-cell interaction between WBC and endothelial cells via gap junction is impaired with aging, and blockade of the interaction increased their transcription in WBC. Our findings indicate that gross analysis of RNA transcription of metabolism related genes in circulating WBC has the potential to provide significant information relating to impaired cell-cell interaction between WBC and endothelial cells of aged mice. Additionally, this can serve as a tool to evaluate the change of the cell-cell interaction caused by various treatments or diseases.
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- 2022
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4. Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2
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Junpei Ohtsuka, Masaki Imai, Masayuki Fukumura, Mitsuyo Maeda, Asami Eguchi, Ryoichi Ono, Tadashi Maemura, Mutsumi Ito, Seiya Yamayoshi, Yosky Kataoka, Yoshihiro Kawaoka, and Tetsuya Nosaka
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Infection control in health technology ,Virology ,Science - Abstract
Summary: We developed an intranasal vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the replication-incompetent human parainfluenza virus type 2 (hPIV2) vector BC-PIV, which can deliver ectopic gene as stable RNA and ectopic protein on the envelope. BC-PIV expressing the full-length prefusion-stabilized spike gene (K986P/V987P) of SARS-CoV-2, S-2PM, possessed a corona-like viral envelope. Intranasal vaccination of mice with BC-PIV/S-2PM induced high levels of neutralizing immunoglobulin G (IgG) and mucosal IgA antibodies against the spike protein. Although BC-PIV showed hemagglutinating activity, BC-PIV/S-2PM lacked such activity, in accordance with the presence of the massive spike protein on the viral surface. Furthermore, single-dose intranasal vaccination of hamsters with BC-PIV/S-2PM completely protected the lungs from SARS-CoV-2 at 11-week post-immunization, and boost vaccination two weeks before the challenge conferred virtually complete protection of the nasal turbinates against SARS-CoV-2. Thus, this chimeric hPIV2/spike intranasal vaccine is a promising vaccine candidate for SARS-CoV-2 to curtail virus transmission.
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- 2021
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5. Age-related changes in NG2-expressing telocytes of rat stomach.
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Yasuhisa Tamura, Kumi Takata, Asami Eguchi, Mitsuyo Maeda, and Yosky Kataoka
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Medicine ,Science - Abstract
NG2 immunoreactive cells (NG2 cells) are found in the brain and peripheral tissues including the skin, intestinal tracts, and bladder. In a previous study, we observed the presence of NG2 cells in the stomach using bioluminescence imaging techniques in NG2-firefly luciferase (fLuc) transgenic (Tg) rats. Here, we aimed to identify and characterize NG2 cells in the adult rat stomach. Immunohistochemical studies showed that NG2 cells were mainly present in the lamina propria and most of the cells were gastric telocytes, co-expressing CD34, and platelet-derived growth factor receptor alpha (PDGFRα), with a small oval-shaped cell body and extremely long and thin cellular prolongations. In the rat stomach, NG2-expressing telocytes comprised two subpopulations: NG2+/CD34+/PDGFRα+ and NG2+/CD34+/PDGFRα-. Furthermore, we showed that the expression of NG2 gene in the aged rat stomach decreased relative to that of the young rat stomach and the decline of NG2 expression in aged rats was mainly observed in NG2+/CD34+/PDGFRα+ telocytes. These findings suggested age-related alterations in NG2+/CD34+/PDGFRα+ telocytes of rat stomach.
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- 2021
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6. Autophagy in the Central Nervous System and Effects of Chloroquine in Mucopolysaccharidosis Type II Mice
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Mitsuyo Maeda, Toshiyuki Seto, Chiho Kadono, Hideto Morimoto, Sachiho Kida, Mitsuo Suga, Motohiro Nakamura, Yosky Kataoka, Takashi Hamazaki, and Haruo Shintaku
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autophagy ,brain ,chloroquine ,intellectual disability ,mucopolysaccharidosis ,neuron ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Mucopolysaccharidosis type II (MPS II) is a rare lysosomal storage disease (LSD) involving a genetic error in iduronic acid-2-sulfatase (IDS) metabolism that leads to accumulation of glycosaminoglycans within intracellular lysosomes. The primary treatment for MPS II, enzyme replacement therapy, is not effective for central nervous system (CNS) symptoms, such as intellectual disability, because the drugs do not cross the blood–brain barrier. Recently, autophagy has been associated with LSDs. In this study, we examined the morphologic relationship between neuronal damage and autophagy in IDS knockout mice using antibodies against subunit c of mitochondrial adenosine triphosphate (ATP) synthetase and p62. Immunohistological changes suggesting autophagy, such as vacuolation, were observed in neurons, microglia, and pericytes throughout the CNS, and the numbers increased over postnatal development. Oral administration of chloroquine, which inhibits autophagy, did not suppress damage to microglia and pericytes, but greatly reduced neuronal vacuolation and eliminated neuronal cells with abnormal inclusions. Thus, decreasing autophagy appears to prevent neuronal degeneration. These results suggest that an autophagy modulator could be used in addition to conventional enzyme replacement therapy to preserve the CNS in patients with MPS II.
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- 2019
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7. Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-β signaling.
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Ji Hae Seo, Takakuni Maki, Mitsuyo Maeda, Nobukazu Miyamoto, Anna C Liang, Kazuhide Hayakawa, Loc-Duyen D Pham, Fumihiko Suwa, Akihiko Taguchi, Tomohiro Matsuyama, Masafumi Ihara, Kyu-Won Kim, Eng H Lo, and Ken Arai
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Medicine ,Science - Abstract
Trophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB) function. Here we report that oligodendrocyte precursor cells (OPCs) secrete soluble factor TGF-β1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-β-receptor-MEK/ERK signaling pathway. Secondly, our immuno-electron microscopic observation revealed that in neonatal mouse brains, OPCs attach to cerebral endothelial cells via basal lamina. And finally, we developed a novel transgenic mouse line that TGF-β1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-β1 deficient mice (OPC-specific TGF-β1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-β1 total KO mice: PdgfraCre/Tgfb1flox/flox mice) exhibited cerebral hemorrhage and loss of BBB function. Taken together, our current study demonstrates that OPCs increase BBB tightness by upregulating tight junction proteins via TGF-β signaling. Although astrocytes and pericytes are well-known regulators of BBB maturation and maintenance, these findings indicate that OPCs also play a pivotal role in promoting BBB integrity.
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- 2014
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8. Development of Semantic Web-based Imaging Database for Biological Morphome.
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Satoshi Kume, Hiroshi Masuya, Mitsuyo Maeda, Mitsuo Suga, Yosky Kataoka, and Norio Kobayashi
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- 2021
9. Development of Semantic Web-Based Imaging Database for Biological Morphome.
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Satoshi Kume, Hiroshi Masuya, Mitsuyo Maeda, Mitsuo Suga, Yosky Kataoka, and Norio Kobayashi
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- 2017
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10. Compact laboratory-based X-ray microscope enabling nondestructive 3D structure acquisition of mouse nephron with high speed and better user accessibility
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Naoki Kunishima, Yoshihiro Takeda, Raita Hirose, Satoshi Kume, Mitsuyo Maeda, Akiko Oguchi, Motoko Yanagita, Hirotoshi Shibuya, Masaru Tamura, Yosky Kataoka, Yasuhiro Murakawa, Koichiro Ito, and Kazuhiko Omote
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Mice ,Microscopy ,Structural Biology ,X-Rays ,Animals ,Kidney Diseases ,Radiology, Nuclear Medicine and imaging ,Instrumentation - Abstract
X-ray microscopes adopting computed tomography enable nondestructive 3D visualization of biological specimens at micron-level resolution without conventional 2D serial sectioning that is a destructive/laborious method and is routinely used for analyzing renal biopsy in clinical diagnosis of kidney diseases. Here we applied a compact commercial system of laboratory-based X-ray microscope to observe a resin-embedded osmium-stained 1-mm strip of a mouse kidney piece as a model of renal biopsy, toward a more efficient diagnosis of kidney diseases. A reconstructed computed tomography image from several hours of data collection using CCD detector allowed us to unambiguously segment a single nephron connected to a renal corpuscle, which was consistent with previous reports using serial sectioning. Histogram analysis on the segmented nephron confirmed that the proximal and distal tubules were distinguishable on the basis of their X-ray opacities. A 3D rendering model of the segmented nephron visualized a convoluted structure of renal tubules neighboring the renal corpuscle and a branched structure of efferent arterioles. Furthermore, another data collection using scientific complementary metal-oxide semiconductor detector with a much shorter data acquisition time of 15 min provided similar results from the same samples. These results suggest a potential application of the compact laboratory-based X-ray microscope to analyze mouse renal biopsy.
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- 2022
11. Morphology of Schwann Cell Processes Supports Renal Sympathetic Nerve Terminals With Local Distribution of Adrenoceptors
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Seishi Maeda, Yusuke Minato, Sachi Kuwahara-Otani, Hiroki Yamanaka, Mitsuyo Maeda, Yosky Kataoka, and Hideshi Yagi
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Male ,Nerve Endings ,Integrins ,Norepinephrine ,Histology ,Sympathetic Nervous System ,Animals ,Articles ,Schwann Cells ,Anatomy ,Rats ,Receptors, Adrenergic - Abstract
Nerves in the renal parenchyma comprise sympathetic nerves that act on renal arteries and tubules to decrease blood flow and increase primary urine reabsorption, respectively. Synaptic vesicles release neurotransmitters that activate their effector tissues. However, the mechanisms by which neurotransmitters exert individual responses to renal effector cells remain unknown. Here, we investigated the spatial and molecular compositional associations of renal Schwann cells (SC) supporting the nerve terminals in male rats. The nerve terminals of vascular smooth muscle cells (SMCs) enclosed by renal SC processes were exposed through windows facing the effectors with presynaptic specializations. We found that the adrenergic receptors (ARs) α2A, α2C, and β2 were localized in the SMC and the basal side of the tubules, where the nerve terminals were attached, whereas the other subtypes of ARs were distributed in the glomerular and luminal side, where the norepinephrine released from nerve endings may have indirect access to ARs. In addition, integrins α4 and β1 were coexpressed in the nerve terminals. Thus, renal nerve terminals could contact their effectors via integrins and may have a structure, covered by SC processes, suitable for intensive and directional release of neurotransmitters into the blood, rather than specialized structures in the postsynaptic region.
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- 2022
12. Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2
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Mitsuyo Maeda, Yoshihiro Kawaoka, Mutsumi Ito, Ryoichi Ono, Masaki Imai, Seiya Yamayoshi, Junpei Ohtsuka, Yosky Kataoka, Tadashi Maemura, Tetsuya Nosaka, Asami Eguchi, and Masayuki Fukumura
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Multidisciplinary ,viruses ,Science ,RNA ,Infection control in health technology ,Biology ,Virology ,Immunoglobulin G ,Article ,Vaccination ,Viral envelope ,biology.protein ,Nasal administration ,Vector (molecular biology) ,Antibody ,Gene - Abstract
We developed an intranasal vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the replication-incompetent human parainfluenza virus type 2 (hPIV2) vector BC-PIV, which can deliver ectopic gene as stable RNA and ectopic protein on the envelope. BC-PIV expressing the full-length prefusion-stabilized spike gene (K986P/V987P) of SARS-CoV-2, S-2PM, possessed a corona-like viral envelope. Intranasal vaccination of mice with BC-PIV/S-2PM induced high levels of neutralizing immunoglobulin G (IgG) and mucosal IgA antibodies against the spike protein. Although BC-PIV showed hemagglutinating activity, BC-PIV/S-2PM lacked such activity, in accordance with the presence of the massive spike protein on the viral surface. Furthermore, single-dose intranasal vaccination of hamsters with BC-PIV/S-2PM completely protected the lungs from SARS-CoV-2 at 11-week post-immunization, and boost vaccination two weeks before the challenge conferred virtually complete protection of the nasal turbinates against SARS-CoV-2. Thus, this chimeric hPIV2/spike intranasal vaccine is a promising vaccine candidate for SARS-CoV-2 to curtail virus transmission., Graphical abstract, Infection control in health technology; Virology
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- 2021
13. A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector
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Masayuki Fukumura, Shujie Wang, Hiroko Miyamoto, Yosky Kataoka, Wakako Furuyama, Akira Mizoguchi, Nobuyuki Tsuda, Aika Kaito, Kenichiro Hara, Mitsuyo Maeda, Masato Tsurudome, Junpei Ohtsuka, Ayato Takada, and Tetsuya Nosaka
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0301 basic medicine ,Viral vectors ,030106 microbiology ,Genetic Vectors ,lcsh:Medicine ,Biology ,Recombinant virus ,medicine.disease_cause ,Antibodies, Viral ,Epitope ,Article ,law.invention ,03 medical and health sciences ,Epitopes ,Mice ,Antigen ,law ,Neutralization Tests ,T-Lymphocyte Subsets ,Chlorocebus aethiops ,Gene Order ,medicine ,Animals ,Humans ,Vector (molecular biology) ,lcsh:Science ,Vero Cells ,Vaccines ,Vaccines, Synthetic ,Multidisciplinary ,Ebola virus ,lcsh:R ,Virology ,Antibodies, Neutralizing ,Reverse genetics ,Tumor antigen ,Parainfluenza Virus 2, Human ,Vaccinology ,030104 developmental biology ,Recombinant DNA ,lcsh:Q ,Genetic Engineering - Abstract
Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.
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- 2019
14. Morphological characteristics of p75 neurotrophin receptor‐positive cells define a new type of glial cell in the rat dorsal root ganglia
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Hisao Yamada, Taro Koike, Yosky Kataoka, Yukie Hirahara, Mitsuo Suga, Mitsuyo Maeda, Susumu Tanaka, Souichi Oe, and Kiyoshi Kurokawa
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Male ,0301 basic medicine ,Cell type ,SOX10 ,Schwann cell ,Nerve Tissue Proteins ,Biology ,Cell morphology ,Stem cell marker ,03 medical and health sciences ,0302 clinical medicine ,Ganglia, Spinal ,medicine ,Animals ,Receptors, Growth Factor ,Rats, Wistar ,Glial fibrillary acidic protein ,Satellite glial cell ,General Neuroscience ,Nestin ,Rats ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,biology.protein ,sense organs ,Neuroglia ,030217 neurology & neurosurgery - Abstract
In the dorsal root ganglia (DRG), two types of glial cells (Schwann cells and satellite glial cells) have been identified based on cell morphology and expression of specific markers. In the present study, we observed unknown glial cells that were positive for p75 neurotrophin receptor (p75NTR), and therefore were immunohistochemically and ultrastructurally characterized for the first time. These cells exhibited stronger immunoreactivity against an anti-p75NTR antibody than the DRG neurons (hereafter referred to as p75NTR++ cells). Moreover, these cells covered the glial cells surrounding proximal process of the large-diameter DRG neurons. The proximal process is called "dendro-axon." The p75NTR++ cells were predominantly distributed where the first myelinating Schwann cells appear. The p75NTR++ cells were also positive for the pan-glial cell markers S100, nestin, and Sox10, but negative for fibroblast and macrophage markers. Moreover, they were negative for a satellite glial cell marker, inwardly rectifying potassium channel Kir4.1, as well as a nonmyelinating Schwann cell marker, glial fibrillary acidic protein. In addition, their morphological features were distinct from those of the myelinating Schwann cells. To investigate the three-dimensional ultrastructure of the p75NTR++ cells, we used array tomography combined with correlative light and electron microscopic observation. Three-dimensional ultrastructural observation revealed that the p75NTR++ cells loosely covered glial cells around the dendro-axons with highly ramified processes. Glial cells with these morphological features have not been reported before, indicating that the p75NTR++ glial cells are a new glial cell type in the DRG. Our results will give new insights into cell-cell relationships.
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- 2019
15. Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction
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Akira Nishiyama, Hiromi Tamada, Hiroyuki Konishi, Okiru Komine, Nobuyuki Udagawa, Tomohiko Tamura, Keiko Ozato, Takayuki Okamoto, Steffen Jung, Yosky Kataoka, Masaaki Kobayashi, Katsuaki Sato, Toshiyuki Takai, Hiroshi Kiyama, Tomoo Ogi, Makoto Tsuda, Fumika Osako, Mitsuyo Maeda, Koji Yamanaka, and Yuichiro Hara
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Central Nervous System ,Male ,Phagocytosis ,Central nervous system ,microglia ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,astrocyte ,0302 clinical medicine ,Gene expression ,medicine ,Animals ,Receptor ,Molecular Biology ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,General Immunology and Microbiology ,Microglia ,Mechanism (biology) ,General Neuroscience ,Brain ,phagocytosis ,Articles ,Cell biology ,Disease Models, Animal ,medicine.anatomical_structure ,Astrocytes ,Interferon Regulatory Factors ,RNA‐seq ,Female ,debris ,030217 neurology & neurosurgery ,Clear cell ,Neuroscience ,Astrocyte - Abstract
Microglia are the principal phagocytes that clear cell debris in the central nervous system (CNS). This raises the question, which cells remove cell debris when microglial phagocytic activity is impaired. We addressed this question using Siglech dtr mice, which enable highly specific ablation of microglia. Non‐microglial mononuclear phagocytes, such as CNS‐associated macrophages and circulating inflammatory monocytes, did not clear microglial debris. Instead, astrocytes were activated, exhibited a pro‐inflammatory gene expression profile, and extended their processes to engulf microglial debris. This astrocytic phagocytosis was also observed in Irf8‐deficient mice, in which microglia were present but dysfunctional. RNA‐seq demonstrated that even in a healthy CNS, astrocytes express TAM phagocytic receptors, which were the main astrocytic phagocytic receptors for cell debris in the above experiments, indicating that astrocytes stand by in case of microglial impairment. This compensatory mechanism may be important for the maintenance or prolongation of a healthy CNS., Clearance of brain cell debris in the absence of functional microglia is not taken over by canonical phagocytic cell types, but surprisingly by astrocytes expressing TAM phagocytic receptors.
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- 2020
16. Bone Marrow Mononuclear Cells Activate Angiogenesis via Gap Junction-Mediated Cell-Cell Interaction
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Takafumi Kimura, Sheraz Gul, Akie Kikuchi-Taura, Yuka Okinaka, Yuko Ogawa, Johannes Boltze, Mitsuyo Maeda, Carsten Claussen, Teruhito Yasui, Yukiko Takeuchi, Yosky Kataoka, and Akihiko Taguchi
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Male ,Angiogenesis ,Cell ,Neovascularization, Physiologic ,Bone Marrow Cells ,Cell Communication ,Cell therapy ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Cell–cell interaction ,Human Umbilical Vein Endothelial Cells ,Medicine ,Animals ,Humans ,030304 developmental biology ,Bone Marrow Transplantation ,Advanced and Specialized Nursing ,QM ,0303 health sciences ,business.industry ,QH ,Gap Junctions ,QP ,Cell biology ,Endothelial stem cell ,Vascular endothelial growth factor ,Mice, Inbred C57BL ,Stroke ,medicine.anatomical_structure ,chemistry ,Neurology (clinical) ,Bone marrow ,Stem cell ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Background and Purpose— Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. Activation of angiogenesis is believed to be one of major BM-MNC mode of actions, but the essential mechanism by which BM-MNCs activate angiogenesis have hitherto been elusive. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis. Methods— We have evaluated the effect of direct cell-cell interaction between BM-MNC and endothelial cell on uptake of VEGF (vascular endothelial growth factor) into endothelial cells in vitro. Cerebral ischemia model was used to evaluate the effects of direct cell-cell interaction with transplanted BM-MNC on endothelial cell at ischemic tissue. Results— The uptake of VEGF into endothelial cells was increased by BM-MNC, while being inhibited by blockading the gap junction. Low-molecular-weight substance was transferred from BM-MNC into endothelial cells via gap junctions in vivo, followed by increased expression of hypoxia-inducible factor-1α and suppression of autophagy in endothelial cells. The concentration of glucose in BM-MNC cytoplasm was significantly higher than in endothelial cells, and transfer of glucose homologue from BM-MNC to endothelial cells was observed. Conclusions— Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy. Visual Overview— An online visual overview is available for this article.
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- 2020
17. A Device for Ribbon Collection for Array Tomography with Scanning Electron Microscopy
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Taro Koike, Yosky Kataoka, Yuuki Yamaguchi, Mitsuyo Maeda, Yuji Hasebe, Hisao Yamada, Akira Saito, and Mitsuo Suga
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0301 basic medicine ,Histology ,Materials science ,Silicon ,Physiology ,Scanning electron microscope ,Analytical chemistry ,chemistry.chemical_element ,Substrate (printing) ,Biochemistry ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Ribbon ,post-embedding labeling ,array tomography ,serial ultrathin section ,business.industry ,three-dimensional observation ,fungi ,Scanning confocal electron microscopy ,Cell Biology ,body regions ,Technical Advancement ,030104 developmental biology ,chemistry ,Electron tomography ,Scanning ion-conductance microscopy ,Optoelectronics ,sense organs ,Tomography ,business ,scanning electron microscopy ,030217 neurology & neurosurgery - Abstract
“Array tomography” is a method used to observe the fine structure of cells and tissues in a three-dimensional view. In this method, serial ultrathin sections in the ribbon state (ribbons) are mounted on a solid substrate and observed by scanning electron microscopy (SEM). The method may also be used in conjunction with post-embedding immunocytochemistry. However, it is difficult to mount many serial ribbons on a substrate manually. We developed an inexpensive laboratory-made device that mounts ribbons by pulling a nylon fishing line and lifting the substrate up from the water in a knife boat. Using this device, we succeeded in mounting several ribbons consisting a mean of 205.6 (SD: 37.7) serial ultrathin sections on 1.25 (SD: 0.06) × 1.25 (SD: 0.06)-cm silicon substrates. Furthermore, it was confirmed that our method is suitable for ribbons derived from water-soluble resin blocks. We were also able to stain the specimens by post-embedding immunocytochemistry. Thus, our method is useful in mounting numerus sections on a substrate for array tomography with SEM.
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- 2017
18. Astrocytes Promote Oligodendrogenesis after White Matter Damage via Brain-Derived Neurotrophic Factor
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Evan K. Lo, Nobukazu Miyamoto, Takakuni Maki, Naohiro Egawa, Kanako Itoh, Masafumi Ihara, Mitsuyo Maeda, Ken Arai, Anna C. Liang, Josephine Lok, and Akihiro Shindo
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Male ,Morpholines ,Mice, Transgenic ,Brain Ischemia ,White matter ,Mice ,Leukoencephalopathies ,Neurotrophic factors ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Enzyme Inhibitors ,Cells, Cultured ,Myelin Sheath ,Brain-derived neurotrophic factor ,biology ,Glial fibrillary acidic protein ,Brain-Derived Neurotrophic Factor ,Stem Cells ,General Neuroscience ,Neurodegeneration ,Antimutagenic Agents ,Cell Differentiation ,Myelin Basic Protein ,Cobalt ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Oligodendrocyte ,Myelin basic protein ,Cell biology ,Mice, Inbred C57BL ,stomatognathic diseases ,Disease Models, Animal ,medicine.anatomical_structure ,Gene Expression Regulation ,Glutathione S-Transferase pi ,nervous system ,Chromones ,Astrocytes ,Culture Media, Conditioned ,Phosphopyruvate Hydratase ,biology.protein ,Brief Communications ,Neuroscience ,Astrocyte - Abstract
Oligodendrocyte precursor cells (OPCs) in the adult brain contribute to white matter homeostasis. After white matter damage, OPCs compensate for oligodendrocyte loss by differentiating into mature oligodendrocytes. However, the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that, during endogenous recovery from white matter ischemic injury, astrocytes support the maturation of OPCs by secreting brain-derived neurotrophic factor (BDNF). Forin vitroexperiments, cultured primary OPCs and astrocytes were prepared from postnatal day 2 rat cortex. When OPCs were subjected to chemical hypoxic stress by exposing them to sublethal CoCl2for 7 d,in vitroOPC differentiation into oligodendrocytes was significantly suppressed. Conditioned medium from astrocytes (astro-medium) restored the process of OPC maturation even under the stressed conditions. When astro-medium was filtered with TrkB-Fc to remove BDNF, the BDNF-deficient astro-medium no longer supported OPC maturation. Forin vivoexperiments, we analyzed a transgenic mouse line (GFAPcre/BDNFwt/fl) in which BDNF expression is downregulated specifically in GFAP+astrocytes. Both wild-type (GFAPwt/BDNFwt/flmice) and transgenic mice were subjected to prolonged cerebral hypoperfusion by bilateral common carotid artery stenosis. As expected, compared with wild-type mice, the transgenic mice exhibited a lower number of newly generated oligodendrocytes and larger white matter damage. Together, these findings demonstrate that, during endogenous recovery from white matter damage, astrocytes may promote oligodendrogenesis by secreting BDNF.SIGNIFICANCE STATEMENTThe repair of white matter after brain injury and neurodegeneration remains a tremendous hurdle for a wide spectrum of CNS disorders. One potentially important opportunity may reside in the response of residual oligodendrocyte precursor cells (OPCs). OPCs may serve as a back-up for generating mature oligodendrocytes in damaged white matter. However, the underlying mechanisms are still mostly unknown. Here, we use a combination of cell biology and an animal model to report a new pathway in which astrocyte-derived BDNF supports oligodendrogenesis and regeneration after white matter damage. These findings provide new mechanistic insight into white matter physiology and pathophysiology, which would be broadly and clinically applicable to CNS disease.
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- 2015
19. Autophagy in the Central Nervous System and Effects of Chloroquine in Mucopolysaccharidosis Type II Mice
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Chiho Kadono, Mitsuyo Maeda, Takashi Hamazaki, Sachiho Kida, Motohiro Nakamura, Haruo Shintaku, Yosky Kataoka, Toshiyuki Seto, Mitsuo Suga, and Hideto Morimoto
- Subjects
Male ,autophagy ,brain ,Mucopolysaccharidosis ,Central nervous system ,Iduronate Sulfatase ,Article ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,Mice ,Sequestosome-1 Protein ,Lysosomal storage disease ,medicine ,Animals ,Physical and Theoretical Chemistry ,Mucopolysaccharidosis type II ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Mucopolysaccharidosis II ,Neurons ,Microglia ,Chemistry ,Organic Chemistry ,Autophagy ,mucopolysaccharidosis ,Chloroquine ,General Medicine ,Enzyme replacement therapy ,Mitochondrial Proton-Translocating ATPases ,medicine.disease ,neuron ,Computer Science Applications ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,lcsh:Biology (General) ,lcsh:QD1-999 ,intellectual disability ,Knockout mouse - Abstract
Mucopolysaccharidosis type II (MPS II) is a rare lysosomal storage disease (LSD) involving a genetic error in iduronic acid-2-sulfatase (IDS) metabolism that leads to accumulation of glycosaminoglycans within intracellular lysosomes. The primary treatment for MPS II, enzyme replacement therapy, is not effective for central nervous system (CNS) symptoms, such as intellectual disability, because the drugs do not cross the blood&ndash, brain barrier. Recently, autophagy has been associated with LSDs. In this study, we examined the morphologic relationship between neuronal damage and autophagy in IDS knockout mice using antibodies against subunit c of mitochondrial adenosine triphosphate (ATP) synthetase and p62. Immunohistological changes suggesting autophagy, such as vacuolation, were observed in neurons, microglia, and pericytes throughout the CNS, and the numbers increased over postnatal development. Oral administration of chloroquine, which inhibits autophagy, did not suppress damage to microglia and pericytes, but greatly reduced neuronal vacuolation and eliminated neuronal cells with abnormal inclusions. Thus, decreasing autophagy appears to prevent neuronal degeneration. These results suggest that an autophagy modulator could be used in addition to conventional enzyme replacement therapy to preserve the CNS in patients with MPS II.
- Published
- 2019
20. Development of Semantic Web-Based Imaging Database for Biological Morphome
- Author
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Hiroshi Masuya, Norio Kobayashi, Yosky Kataoka, Satoshi Kume, Mitsuo Suga, and Mitsuyo Maeda
- Subjects
0301 basic medicine ,Gigabyte ,Database ,business.industry ,Computer science ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,computer.file_format ,Linked data ,computer.software_genre ,Morphome ,Metadata ,03 medical and health sciences ,030104 developmental biology ,RDF ,business ,computer ,Semantic Web ,Metadatabase ,Graphical user interface - Abstract
We introduce the RIKEN Microstructural Imaging Metadatabase, a semantic web-based imaging database in which image metadata are described using the Resource Description Framework (RDF) and detailed biological properties observed in the images can be represented as Linked Open Data. The metadata are used to develop a large-scale imaging viewer that provides a straightforward graphical user interface to visualise a large microstructural tiling image at the gigabyte level. We applied the database to accumulate comprehensive microstructural imaging data produced by automated scanning electron microscopy. As a result, we have successfully managed vast numbers of images and their metadata, including the interpretation of morphological phenotypes occurring in sub-cellular components and biosamples captured in the images. We also discuss advanced utilisation of morphological imaging data that can be promoted by this database.
- Published
- 2017
21. Three Dimensional Structure Analysis of Cell Nuclei in Mice Cerebellar Cortex Using Array Tomography
- Author
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Kohki Konishi, Mitsuo Suga, H. Nisioka, Keisuke Ohta, Mitsuyo Maeda, S. Kume, K. Suzuki, Motohiro Nakamura, T. Nonaka, and Yosky Kataoka
- Subjects
0301 basic medicine ,Structure analysis ,Chemistry ,Cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Nuclear magnetic resonance ,medicine.anatomical_structure ,Cerebellar cortex ,medicine ,Tomography ,Instrumentation ,030217 neurology & neurosurgery - Published
- 2018
22. Induction of Perivascular Neural Stem Cells and Possible Contribution to Neurogenesis Following Transient Brain Ischemia/Reperfusion Injury
- Author
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Akiko Nakano-Doi, Masayo Nakata, Yoshihiro Momota, Takayuki Nakagomi, Tomohiro Matsuyama, and Mitsuyo Maeda
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Neurogenesis ,Ischemia ,Brain Ischemia ,Brain ischemia ,Nestin ,Receptor, Platelet-Derived Growth Factor beta ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neural Stem Cells ,medicine ,Animals ,cardiovascular diseases ,Neurons ,biology ,Cell Death ,business.industry ,General Neuroscience ,Brain ,Endothelial Cells ,medicine.disease ,Neural stem cell ,Doublecortin ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Anesthesia ,Astrocytes ,Reperfusion Injury ,biology.protein ,Neurology (clinical) ,Pericyte ,Cardiology and Cardiovascular Medicine ,business ,Pericytes ,Reperfusion injury ,030217 neurology & neurosurgery - Abstract
Recent therapeutic advances have increased the likelihood of recanalizing the obstructed brain arteries in patients with stroke. Therefore, it is important to understand the fate of neural cells under transient ischemia/reperfusion injury. Accumulating evidence shows that neurogenesis occurs in perivascular regions following brain injury, although the precise mechanism and origin of these newborn neurons under transient ischemia/reperfusion injury remain unclear. Using a mouse model of transient brain ischemia/reperfusion injury, we found that neural stem cells (NSCs) develop within injured areas. This induction of NSCs following ischemia/reperfusion injury was observed even in response to nonlethal ischemia, although massive numbers of NSCs were induced by lethal ischemia. Immunohistochemical and immunoelectron microscopic studies indicated that platelet-derived growth factor receptor beta-positive (PDGFRβ+) pericytes within injured areas following nonlethal ischemia began to express the NSC marker nestin as early as 3 days after transient ischemia/reperfusion. Some PDGFRβ+ pericytes expressed the immature neuronal marker doublecortin at day 7. These findings indicate that brain pericytes are a potential source of the perivascular NSCs that generate neuronal cells under lethal and nonlethal ischemic conditions following transient ischemia/reperfusion. Thus, brain pericytes might be a target for neurogenesis mediation in patients with nonlethal and lethal ischemia following transient ischemia/reperfusion injury.
- Published
- 2016
23. New Approaches for high lateral resolution Array Tomography analysis
- Author
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Shunsuke Asahina, Tomohiro Haruta, Yukari Moriya, Yosky Kataoka, Yuuki Yamaguchi, Mitsuyo Maeda, Chikako Nakayama, Natasha Erdman, and Mitsuo Suga
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Materials science ,Optics ,business.industry ,02 engineering and technology ,Lateral resolution ,Tomography ,021001 nanoscience & nanotechnology ,0210 nano-technology ,business ,Instrumentation - Published
- 2017
24. Expression of Pancreatitis Associated Proteins in Urothelium and Urinary Afferent Neurons Following Cyclophosphamide Induced Cystitis
- Author
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Hidenori Kawashima, Yuki Takahara, Akinobu Suzuki, Hiroshi Kiyama, Tatsuya Nakatani, and Mitsuyo Maeda
- Subjects
Pathology ,medicine.medical_specialty ,Cyclophosphamide ,Urology ,Urinary system ,Population ,Pancreatitis-Associated Proteins ,Rats, Sprague-Dawley ,Antigens, Neoplasm ,Ganglia, Spinal ,Cystitis ,Biomarkers, Tumor ,medicine ,Animals ,Lectins, C-Type ,Neurons, Afferent ,Urothelium ,education ,Noxae ,education.field_of_study ,Urinary bladder ,business.industry ,Gene Expression Profiling ,Chronic Cystitis ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Female ,Neuron ,business ,medicine.drug - Abstract
We examined the expression profile of the members of the pancreatitis associated proteins/regenerating gene family in the bladder and in the primary afferent neurons of dorsal root ganglia using an animal model of cystitis.We examined the expression of pancreatitis-associated protein-I and pancreatitis-associated protein-III in the bladder and the dorsal root ganglia of female rats 4 hours, 48 hours or 10 days after cyclophosphamide (Sigma) injection using immunohistochemistry and reverse transcriptase-polymerase chain reaction.No pancreatitis-associated protein-III immunoreactivity was identified in control bladders but prominent expression was observed in the urothelium of animals with chronic cystitis. Cells expressing pancreatitis-associated protein-I were seen in the dorsal root ganglia but not in the bladder. In normal dorsal root ganglia pancreatitis-associated protein-I was expressed in a minor population of small diameter neurons (2.4%) that were also positive for isolectin-B4. However, by 10 days following the onset of cystitis the number of pancreatitis-associated protein-I positive neurons was increased (7.6%) and pancreatitis-associated protein-I immunoreactivity was further observed in a slightly larger group of neurons and tyrosine kinase A positive small neurons.The current results suggest that pancreatitis-associated protein-III is associated with bladder inflammation and they implicate pancreatitis-associated protein-I in the abnormal sensation in cystitis.
- Published
- 2008
25. Experimental pseudocyst model resembling human ganglion
- Author
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Hisashi Motomura, Masamitsu Ishii, Teruichi Harada, Mitsuyo Maeda, Toshiko Taniguchi, and Norihiro Ohba
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Sodium hyaluronate ,Lumen (anatomy) ,Antineoplastic Agents ,Dermatology ,Injections, Intralesional ,Picibanil ,chemistry.chemical_compound ,Animal model ,In vivo ,medicine ,Animals ,Cyst ,Rats, Wistar ,Ganglion Cysts ,business.industry ,General Medicine ,Anatomy ,medicine.disease ,Rats ,Ganglion ,Ganglion cyst ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,business ,Subcutaneous tissue - Abstract
There is no animal model of ganglion. We describe a simple and reproducible animal model of pseudocystic diseases. First, we experimented to establish a pseudocystic model. We used cylindrical glass implants (6 mm diameter, 30 mm long) to create fibrous capsules in rats. The implants were inserted in the subcutaneous tissue in the dorsum of rats. Sixty implants were carried out (two implants per rat). Twelve weeks after implantation, the glass implants were removed and 0.5 mL sodium hyaluronate solution was injected into each cavity. Next, we tested the model by histological examination after OK-432 administration. Microscopic examination revealed that the wall was composed of a layer of collagenous fibers similar to those noted in ganglia; the lumen was retained for 3 weeks. Histopathological changes after OK-432 administration showed nonspecific inflammatory response induced by OK-432, resulting in in vivo activation of many inflammatory cells and then fast and reliable closure of cavities. No harmful reactions to OK-432 were observed histopathologically. These data suggest that our experimental cyst is a suitable model for studying pseudocystic diseases. This model can be used for research evaluating safe drug doses, conducting therapeutic comparison of several agents, and histopathological time course studies of the affected tissues. OK-432 administration on this model showed the potential of one of the ideal agents to treat pseudocystic lesions like ganglion.
- Published
- 2008
26. New potential therapy for orthotopic bladder carcinoma by combining HVJ envelope with doxorubicin
- Author
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Akito Maeda, Mitsuyo Maeda, Shintaro Komaba, Yoshimitsu Kimura, Tsugiko Yamasaki, Hirokazu Kawano, and Yasufumi Kaneda
- Subjects
Cancer Research ,Combination therapy ,Cell Survival ,medicine.medical_treatment ,Tetrazolium Salts ,Biology ,Toxicology ,Sendai virus ,Mice ,Viral Envelope Proteins ,Cell Line, Tumor ,medicine ,Carcinoma ,Animals ,Pharmacology (medical) ,Doxorubicin ,Survival rate ,Cell Proliferation ,Pharmacology ,Carcinoma, Transitional Cell ,Chemotherapy ,Antibiotics, Antineoplastic ,Bladder cancer ,Cancer ,medicine.disease ,Survival Analysis ,Mice, Inbred C57BL ,Urinary Bladder Neoplasms ,Oncology ,Immunology ,Cancer research ,Doxorubicin Hydrochloride ,Female ,Neoplasm Transplantation ,medicine.drug - Abstract
To establish a new therapeutic method to treat bladder carcinoma, we investigated the therapeutic potential of doxorubicin hydrochloride (DXR) combined with hemagglutinating virus of Japan-envelope vector (HVJ-E) in an orthotropic mouse bladder cancer model.DXR and/or HVJ-E were instilled into the bladder after implantation of MB49 cells. Antitumor effects of combination therapy were evaluated by histological analysis of the bladder on day 14 after tumor implantation. The survival rate of MB49-disseminated mice was examined for 60 days after single or double administration of DXR alone or DXR/HVJ-E. The surviving mice were re-challenged with intravesical injection of MB49 cells, and the bladder was observed after 3 weeks.Combined intravesical instillation of HVJ-E and DXR resulted in a significantly higher rate of tumor-free mice (11/21) compared with mice treated using DXR alone (3/19, P0.05). Median survival was60 days for intravesical instillation of HVJ-E and DXR, compared with the 29 days for DXR instillation alone (P0.05). After combination therapy, surviving mice formed no tumors in the bladder following intravesical re-instillation of MB49.HVJ-E increased antitumor effects in combination with chemotherapeutic agent (DXR). Antitumor immunity appeared to be enhanced using HVJ-E.
- Published
- 2007
27. Erythropoietin contributes to implantation: Ectopic hemoglobin synthesis in decidual cells of mice
- Author
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Tadao Atsumi, Hiroyoshi Fujita, Megumi Yasuda, Tohru Sasaki, Yoshiko Yasuda, Mitsuyo Maeda, Yoshihiko Fujita, and Masanori Takagawa
- Subjects
Embryology ,medicine.medical_specialty ,Apoptosis ,Biology ,Hemoglobins ,Mice ,Pregnancy ,hemic and lymphatic diseases ,Internal medicine ,Decidua ,Receptors, Erythropoietin ,medicine ,Animals ,Decidual cells ,Embryo Implantation ,RNA, Messenger ,Globin ,Receptor ,Erythropoietin ,Cells, Cultured ,Hemoglobin E ,Uterus ,Hemoglobin A ,General Medicine ,Embryo, Mammalian ,Embryonic stem cell ,Erythropoietin receptor ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Female ,Hemoglobin ,5-Aminolevulinate Synthetase ,Signal Transduction ,Developmental Biology ,medicine.drug - Abstract
Erythropoietin, by binding to its receptor, stimulates definitive erythroblasts to accumulate hemoglobin (Hb) by up-regulating erythroid-specific genes and causes differentiation of erythroblasts into erythrocytes. In mouse decidua we have found the expression of transcripts for the erythropoietin receptor, the function of which has not yet been elucidated. Erythropoietin signaling was inhibited by the injection of a soluble form of the erythropoietin receptor capable of binding with erythropoietin into the mouse uterine cavity on day 4 of gestation, and pale and defective decidual bodies appeared three days later. These pale decidual bodies contained defective embryos without extension to the ectoplacental region, while normal reddish decidual bodies contained normal developing embryos and expressed embryonic and adult Hb with characteristic location of the respective hemoglobins in which an epsilon- or beta-globin signal was confirmed. Furthermore, blocking of erythropoietin signaling destroyed Hb-containing cells and resulted in apoptosis that caused embryonic death. Thus, erythropoietin-mediated Hb synthesis is essential for the survival of decidual cells. In addition, although no transcripts for GATA-1 and erythroid heme enzymes could be detected, genes for beta-globin, as well as non-specific delta-aminolevulinate synthase, were expressed and regulated in an erythropoietin-dependent manner. This is the first evidence that ectopic Hb synthesis exists and that erythropoietin coregulates erythroid (globin) and nonerythroid (delta-aminolevulinate synthase) genes.
- Published
- 2007
28. Potential interactions between pericytes and oligodendrocyte precursor cells in perivascular regions of cerebral white matter
- Author
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Takakuni Maki, Tomohiro Matsuyama, Yoon Kyung Choi, Ryosuke Takahashi, Anna C. Liang, Maiko T. Uemura, Akihiro Shindo, Masafumi Ihara, Mitsuyo Maeda, Evan K. Lo, Ken Arai, Akihiko Taguchi, and Yasukazu Terasaki
- Subjects
Male ,Cell type ,Cell signaling ,Pathology ,medicine.medical_specialty ,Cell Communication ,Biology ,Article ,Corpus Callosum ,White matter ,Rats, Sprague-Dawley ,Species Specificity ,medicine ,Animals ,Humans ,Cells, Cultured ,Aged ,Cell Proliferation ,Cerebral Cortex ,General Neuroscience ,Stem Cells ,Middle Aged ,White Matter ,Mice, Inbred C57BL ,stomatognathic diseases ,Oligodendroglia ,medicine.anatomical_structure ,nervous system ,Cerebral cortex ,Basal lamina ,Female ,Pericyte ,Stem cell ,Pericytes ,Immunostaining - Abstract
Pericytes are embedded within basal lamina and play multiple roles in the perivascular niche in brain. Recently, oligodendrocyte precursor cells (OPCs) have also been reported to associate with cerebral endothelium. Is it possible that within this gliovascular locus, there may also exist potential spatial and functional interactions between pericytes and OPCs? Here, we demonstrated that in the perivascular region of cerebral white matter, pericytes and OPCs may attach and support each other. Immunostaining showed that pericytes and OPCs are localized in close contact with each other in mouse white matter at postnatal days 0, 60 and 240. Electron microscopic analysis confirmed that pericytes attached to OPCs via basal lamina in the perivascular region. The close proximity between these two cell types was also observed in postmortem human brains. Functional interaction between pericytes and OPCs was assessed by in vitro media transfer experiments. When OPC cultures were treated with pericyte-conditioned media, OPC number increased. Similarly, pericyte number increased when pericytes were maintained in OPC-conditioned media. Taken together, our data suggest a potential anatomical and functional interaction between pericytes and OPCs in cerebral white matter.
- Published
- 2015
29. Usefulness of FDG-microPET for early evaluation of therapeutic effects on VX2 rabbit carcinoma
- Author
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Takuhito Tada, Satoko Kondo, Yoshie Takada, Yasuhiro Wada, Kentaro Ishii, Yuichi Inoue, Mitsuyo Maeda, Yasuyoshi Watanabe, Terue Okamura, and Masako Hosono
- Subjects
Hyperthermia ,medicine.medical_treatment ,Tumor response ,Sensitivity and Specificity ,Fluorodeoxyglucose F18 ,Degree Celsius ,Carcinoma ,Animals ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiotherapy ,business.industry ,Therapeutic effect ,Reproducibility of Results ,Hyperthermia, Induced ,Neoplasms, Experimental ,General Medicine ,Prognosis ,Inflammatory cell infiltration ,medicine.disease ,Radiation therapy ,Treatment Outcome ,Positron-Emission Tomography ,Rabbits ,Radiopharmaceuticals ,business ,Nuclear medicine ,Progressive disease - Abstract
Purpose: The aim of this study was to determine the potential use of high-resolution FDGmicroPET for predicting the primary effects of radiotherapy and/or hyperthermia on tumor-bearing rabbits. Methods: Twenty-eight VX2 xenografts in the thighs of rabbits were divided into the following 5 treatment groups: radiotherapy at a single dose of 10, 20 or 30 Gy, hyperthermia (43 degrees Celsius, 1 hour), and the combination of radiotherapy and hyperthermia (10 Gy + 43 degrees Celsius, 1 hour). FDG-microPET images were obtained by using a microPET P4 system at pretreatment and at 24 hours and 7 days after treatment. For the evaluation by FDG-microPET, tumor/muscle (T/M) ratios, retention index [RI = (T/M ratio at 120 min − T/M ratio at 60 min) / T/M ratio at 60 min], and time activity curve (TAC) were acquired. Results: We divided the xenografts into a responder group (partial response + stable disease, n = 14) and a non-responder group (progressive disease, n = 14). The T/M ratio at 24 hours after the treatment in the responder group was decreased remarkably with that at pre-treatment (p < 0.05), while in the non-responder group it showed no significant change between the time points. The RI and TAC patterns were comparable to T/M ratios in each treatment group. T/M ratios, RI, and TAC indicated marked changes at the time point of 24 hours in the responder group, although the tumors did not show any significant change in volume at that time. Photomicrographs of sections showed that the number of viable tumor cells in the responder group decreased at 24 hours after treatment and that inflammatory cell infiltration was marked and almost all viable tumor cells had disappeared by day 7 after treatment. Conclusion: These results suggest that early evaluation by FDG-microPET, especially 24 hours after treatment, is useful to predict the primary effects of the treatment. Histological analysis showed that inflammatory cell infiltration at 7 days after treatment was considered to be a cause of accumulation of FDG in the tumors that showed a significant decrease in tumor cell number. This false-positive should be noted when predicting tumor response by FDG accumulation.
- Published
- 2006
30. Expression of damage-induced neuronal endopeptidase (DINE) mRNA in peri-infarct cortical and thalamic neurons following middle cerebral artery occlusion
- Author
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Masamitsu Ishii, Michinari Muraoka, Norihiro Ohba, Hiroshi Kiyama, Mitsuyo Maeda, and Sumiko Kiryu-Seo
- Subjects
Male ,medicine.medical_specialty ,Thalamus ,In situ hybridization ,Biology ,Biochemistry ,Neuroprotection ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Internal medicine ,Gene expression ,In Situ Nick-End Labeling ,medicine ,Animals ,RNA, Messenger ,Cerebral Cortex ,Neurons ,Activating Transcription Factor 3 ,Metalloendopeptidases ,Infarction, Middle Cerebral Artery ,Cerebral Infarction ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Cerebral cortex ,Peripheral nerve injury ,Disease Progression ,biology.protein ,Neuron ,NeuN ,Neuroscience ,Transcription Factors - Abstract
Damage-induced neuronal endopeptidase (DINE) is a unique nerve-injury associated molecule, which was recently identified in a peripheral nerve injury model. The aim of this study was to determine the expression profiles and distribution of DINE in adult rats after middle cerebral artery (MCA) occlusion. Focal cerebral ischemia induced late-onset and prolonged expression of DINE mRNA in the peri-infarct cortex and specific nuclei of thalamus. Double labeling using immunohistochemistry and in situ hybridization revealed that DINE mRNA was exclusively expressed in cells that were positive to a neuronal marker NeuN. Previously established knowledge on neuroanatomical fiber connection suggests that DINE mRNA was expressed in areas projecting their axons to or through the core region of the infarction. This unique expression profile was similar to that of activating transcription factor-3 (ATF-3), which is a marker of nerve-injured neuron. More than 98% of ATF-3 immunoreactive neurons simultaneously expressed DINE mRNA, suggesting that DINE expression is observed in injured neurons of CNS as well as PNS. Since DINE expression promotes antioxidant activity, our results suggest that DINE may act as a neuroprotective molecule in neurons under ischemic insult.
- Published
- 2004
31. mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells
- Author
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Mirei Murakami, Hiroshi Kiyama, Frank Edenhofer, Tomoko Ichisaka, Noriko Oshiro, Mitsuyo Maeda, Shinya Yamanaka, Kazuyoshi Yonezawa, and Kenta Hara
- Subjects
Heterozygote ,Time Factors ,Genotype ,Cell division ,Biology ,Mice ,Mammalian Genetic Models with Minimal or Complex Phenotypes ,Animals ,Inner cell mass ,Tissue Distribution ,Kinase activity ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Mice, Knockout ,Recombination, Genetic ,Sirolimus ,Models, Genetic ,Cell growth ,Ribosomal Protein S6 Kinases ,Stem Cells ,TOR Serine-Threonine Kinases ,Cell Cycle ,Cell Biology ,Cell cycle ,Embryo, Mammalian ,Flow Cytometry ,Embryonic stem cell ,Molecular biology ,Protein Structure, Tertiary ,Cell biology ,Blotting, Southern ,Blastocyst ,Mutation ,Protein Kinases ,Cell Division ,Gene Deletion - Abstract
TOR is a serine-threonine kinase that was originally identified as a target of rapamycin in Saccharomyces cerevisiae and then found to be highly conserved among eukaryotes. In Drosophila melanogaster, inactivation of TOR or its substrate, S6 kinase, results in reduced cell size and embryonic lethality, indicating a critical role for the TOR pathway in cell growth control. However, the in vivo functions of mammalian TOR (mTOR) remain unclear. In this study, we disrupted the kinase domain of mouse mTOR by homologous recombination. While heterozygous mutant mice were normal and fertile, homozygous mutant embryos died shortly after implantation due to impaired cell proliferation in both embryonic and extraembryonic compartments. Homozygous blastocysts looked normal, but their inner cell mass and trophoblast failed to proliferate in vitro. Deletion of the C-terminal six amino acids of mTOR, which are essential for kinase activity, resulted in reduced cell size and proliferation arrest in embryonic stem cells. These data show that mTOR controls both cell size and proliferation in early mouse embryos and embryonic stem cells.
- Published
- 2004
32. Transgenic mouse overexpressing the Akt reduced the volume of infarct area after middle cerebral artery occlusion
- Author
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Mitsuyo Maeda, Michinari Muraoka, Sumiko Kiryu-Seo, Hiroshi Kiyama, Masamitsu Ishii, and Norihiro Ohba
- Subjects
Genetically modified mouse ,medicine.medical_specialty ,Ratón ,Transgene ,Ischemia ,Mice, Transgenic ,Protein Serine-Threonine Kinases ,Biology ,Severity of Illness Index ,Neuroprotection ,Mice ,In vivo ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Animals ,Protein kinase B ,General Neuroscience ,Infarction, Middle Cerebral Artery ,Cerebral Infarction ,Genetic Therapy ,medicine.disease ,Recombinant Proteins ,Genetic Enhancement ,Treatment Outcome ,Endocrinology ,Feasibility Studies ,Endothelin receptor ,Proto-Oncogene Proteins c-akt - Abstract
Transgenic mouse lines expressing the active form Akt gene under the control of the damage-induced neuronal endopeptidase (DINE) promoter were made from three different founder mice, and its neuroprotective potential against ischemic brain damage was investigated. Twenty-four hours after middle cerebral artery occlusion, two DINE-Akt-transgenic mouse lines displayed reductions of the infarcted area by 35% compared to the wild-type littermate. RT-PCR assays showed a high level of transgene in response to ischemic brain damage in these lines. These results suggest that the DINE promoter is a useful promoter, which responds to neuronal insults and that the Akt-induced neuroprotective effect against ischemic damage is potent in vivo.
- Published
- 2004
33. Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils
- Author
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Satoshi Fujikawa, Makoto Inoue, Mamoru Hasegawa, K Washizawa, Kazuhiko Watabe, Mitsuyo Maeda, Yasuhiro Yoshikawa, S Komaba, and Masayuki Shirakura
- Subjects
Programmed cell death ,viruses ,Ischemia ,Pharmacology ,Hippocampus ,Sendai virus ,Brain Ischemia ,Brain ischemia ,chemistry.chemical_compound ,Neurotrophic factors ,Nerve Growth Factor ,Genetics ,Glial cell line-derived neurotrophic factor ,medicine ,Animals ,Glial Cell Line-Derived Neurotrophic Factor ,Nerve Growth Factors ,Molecular Biology ,Neurons ,Cell Death ,biology ,Gene Transfer Techniques ,virus diseases ,Genetic Therapy ,respiratory system ,medicine.disease ,biology.organism_classification ,Vascular endothelial growth factor ,Nerve growth factor ,nervous system ,chemistry ,Immunology ,biology.protein ,Molecular Medicine ,Gerbillinae - Abstract
Sendai virus (SeV) vector-mediated gene delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) prevented the delayed neuronal death induced by transient global ischemia in gerbils, even when the vector was administered several hours after ischemia. Intraventricular administration of SeV vector directed high-level expression of the vector-encoded neurotrophic factor genes, which are potent candidates for the treatment of neurodegenerative diseases. After occlusion of the bilateral carotid arteries of gerbils, SeV vector carrying GDNF (SeV/GDNF), NGF (SeV/NGF), brain-derived neurotrophic factor (SeV/BDNF), insulin-like growth factor-1 (SeV/IGF-1) or vascular endothelial growth factor (SeV/VEGF) was injected into the lateral ventricle. Administration of SeV/GDNF, SeV/NGF or SeV/BDNF 30 min after the ischemic insult effectively prevented the delayed neuronal death of the hippocampal CA1 pyramidal neurons. Furthermore, the administration of SeV/GDNF or SeV/NGF as late as 4 or 6 h after the ischemic insult also prevented the death of these neurons. These results indicate that SeV vector-mediated gene transfer of neurotrophic factors has high therapeutic potency for preventing the delayed neuronal death induced by transient global ischemia, and provides an approach for gene therapy of stroke.
- Published
- 2004
34. Expression and involvement of gicerin, a cell adhesion molecule, in the development of chick optic tectum
- Author
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Keiko Kohama, Yasuhiro Tsukamoto, Mitsuyo Maeda, Eiichi Taira, Hiroshi Kiyama, and Naomasa Miki
- Subjects
Retina ,Neurite ,Cell adhesion molecule ,Cell migration ,Biology ,Biochemistry ,Retinal ganglion ,Cell aggregation ,Cell biology ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Laminin ,biology.protein ,medicine ,Immunoglobulin superfamily ,sense organs ,Neuroscience - Abstract
Gicerin is a cell adhesion molecule belonging to the immunoglobulin superfamily. It has both a homophilic binding activity and a heterophilic binding activity to neurite outgrowth factor (NOF) a molecule belonging to the laminin family. We have reported many studies on the heterophilic activity of gicerin and NOF, but the function of its homophilic binding activity in vivo had been unclear. In the retina, gicerin is expressed in retinal ganglion cells only when they extend neurites to the optic tectum. In this report we have found that gicerin is also transiently expressed in the optic tectum during this time. First, cell aggregation assays were used to show that gicerin expressed in the optic tectum displays homophilic binding activity. Then, explant cultures of embryonic day 6 chick optic tectum on gicerin-Fc chimeric protein-coated dishes and NOF-coated dishes were carried out. It was found that gicerin-gicerin homophilic interactions promoted cell migration, whereas heterophilic interactions with NOF induced neurite formation. Furthermore, when anti-gicerin antibodies were injected in order to examine the effect of gicerin protein in the formation of the tectal layer in ovo, cell migration was strongly inhibited. These data suggest that homophilic interaction of gicerin participates in the migration of neural cells during the layer formation and plays a crucial role in the organization of the optic tectum.
- Published
- 2003
35. Attenuation of ganglioside GM1 accumulation in the brain of GM1 gangliosidosis mice by neonatal intravenous gene transfer
- Author
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T Yagi, A Oshima, Akemi Tanaka, Eiji Nanba, N Takaura, Mitsuyo Maeda, T. Yamano, and Yoshiyuki Suzuki
- Subjects
medicine.medical_specialty ,Ratón ,Genetic enhancement ,Genetic Vectors ,Central nervous system ,G(M1) Ganglioside ,Gene delivery ,Biology ,Adenoviridae ,law.invention ,Mice ,Transduction, Genetic ,law ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Gangliosidosis, GM1 ,Lung ,Ganglioside ,Histocytochemistry ,Cerebrum ,Brain ,Genetic Therapy ,Molecular biology ,Mice, Mutant Strains ,medicine.anatomical_structure ,Endocrinology ,Animals, Newborn ,Models, Animal ,Recombinant DNA ,Molecular Medicine - Abstract
A single intravenous injection with 4 x 10(7) PFU of recombinant adenovirus encoding mouse beta-galactosidase cDNA to newborn mice provided widespread increases of beta-galactosidase activity, and attenuated the development of the disease including the brain at least for 60 days. The beta-galactosidase activity showed 2-4 times as high a normal activity in the liver and lung, and 50 times in the heart. In the brain, while the activity was only 10-20% of normal, the efficacy of the treatment was distinct. At the 30th day after the injection, significant attenuation of ganglioside GM1 accumulation in the cerebrum was shown in three out of seven mice. At the 60th day after the injection, the amount of ganglioside GM1 was above the normal range in all treated mice, which was speculated to be the result of reaccumulation. However, the values were still definitely lower in most of the treated mice than those in untreated mice. In the histopathological study, X-gal-positive cells, which showed the expression of exogenous beta-galactosidase gene, were observed in the brain. It is noteworthy that neonatal administration via blood vessels provided access to the central nervous system because of the incompletely formed blood-brain barrier.
- Published
- 2003
36. Biphasic expression of activating transcription factor-3 in neurons after cerebral infarction
- Author
-
Saya Nakagomi, Norihiro Ohba, Mitsuyo Maeda, Michinari Muraoka, and Hiroshi Kiyama
- Subjects
Male ,Time Factors ,Proto-Oncogene Proteins c-jun ,viruses ,genetic processes ,Thalamus ,Ischemia ,Activating transcription factor ,Nerve Tissue Proteins ,environment and public health ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,medicine.artery ,Glial Fibrillary Acidic Protein ,Gene expression ,In Situ Nick-End Labeling ,medicine ,Animals ,RNA, Messenger ,Cyclic AMP Response Element-Binding Protein ,Molecular Biology ,In Situ Hybridization ,Neurons ,Activating Transcription Factor 3 ,Activating Transcription Factor 2 ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Cerebral infarction ,fungi ,Brain ,Infarction, Middle Cerebral Artery ,Cerebral Infarction ,medicine.disease ,Immunohistochemistry ,Activating transcription factor 2 ,Rats ,Cell biology ,Disease Models, Animal ,Gene Expression Regulation ,Middle cerebral artery ,biology.protein ,Neuroscience ,Immediate early gene ,Transcription Factors - Abstract
It has been demonstrated that some of immediate early genes such as c-Jun are induced immediately and transiently following focal cerebral ischemia. Here we newly characterize the activating transcription factor (ATF)-3 as a focal ischemia associated immediate early gene. Using in situ hybridization and immunohistochemistry, we compared the expression profile of ATF-3 with those of ATF-2 and c-Jun after middle cerebral artery (MCA) occlusion. Focal cerebral ischemia induced two temporal and spatial patterns of ATF-3 expression. Early and transient induction of ATF-3 mRNA was observed in the core and margins of the cortex immediately after MCA occlusion. Late-onset and prolonged expression of ATF-3 mRNA and its protein were specifically identified in the peri-infarct cortex and thalamus where neurons survive at least 1 month. The expression profiles of ATF-3 and c-Jun were virtually similar, but c-Jun expression was also observed in other regions of the brain in control rats. Expression of ATF-2 was ubiquitously seen in neuronal cells throughout the brain in normal rats, but was suppressed in ischemic regions. Double immunohistochemical labeling revealed concurrent expression of ATF-3 and phospho-c-Jun in neurons. We conclude that the transcription factor ATF-3 is a suitable marker of neurons subjected to ischemic insult directly and indirectly, and that cooperative works of ATF-3 and c-Jun may be crucial triggers of various transcriptional responses to the ischemic insult.
- Published
- 2003
37. Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-β signaling
- Author
-
Mitsuyo Maeda, Loc-Duyen D. Pham, Fumihiko Suwa, Takakuni Maki, Kyu-Won Kim, Eng H. Lo, Ji Hae Seo, Ken Arai, Tomohiro Matsuyama, Kazuhide Hayakawa, Anna C. Liang, Nobukazu Miyamoto, Masafumi Ihara, and Akihiko Taguchi
- Subjects
Genetically modified mouse ,Endothelium ,Central nervous system ,lcsh:Medicine ,Biology ,Blood–brain barrier ,Rats, Sprague-Dawley ,Neural Stem Cells ,Developmental Neuroscience ,Transforming Growth Factor beta ,medicine ,Animals ,lcsh:Science ,Multidisciplinary ,Tight junction ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Cell biology ,Rats ,Oligodendroglia ,stomatognathic diseases ,medicine.anatomical_structure ,nervous system ,Blood-Brain Barrier ,Cellular Neuroscience ,Immunology ,Basal lamina ,lcsh:Q ,Signal transduction ,Transforming growth factor ,Signal Transduction ,Research Article ,Neuroscience - Abstract
Trophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB) function. Here we report that oligodendrocyte precursor cells (OPCs) secrete soluble factor TGF-β1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-β-receptor-MEK/ERK signaling pathway. Secondly, our immuno-electron microscopic observation revealed that in neonatal mouse brains, OPCs attach to cerebral endothelial cells via basal lamina. And finally, we developed a novel transgenic mouse line that TGF-β1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-β1 deficient mice (OPC-specific TGF-β1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-β1 total KO mice: PdgfraCre/Tgfb1flox/flox mice) exhibited cerebral hemorrhage and loss of BBB function. Taken together, our current study demonstrates that OPCs increase BBB tightness by upregulating tight junction proteins via TGF-β signaling. Although astrocytes and pericytes are well-known regulators of BBB maturation and maintenance, these findings indicate that OPCs also play a pivotal role in promoting BBB integrity.
- Published
- 2014
38. Detection of the exogenous hGDNF in gerbils under the treatment with AxCAhGDNF adenoviral vector
- Author
-
Mitsuyo Maeda, Takashi Yagi, Akemi Tanaka, and Mitsuhiro Hara
- Subjects
Pathology ,medicine.medical_specialty ,Time Factors ,Ependymal Cell ,Genetic Vectors ,Nerve Tissue Proteins ,In situ hybridization ,Hippocampal formation ,Biology ,Hippocampus ,Adenoviridae ,Viral vector ,Neurotrophic factors ,In Situ Nick-End Labeling ,Glial cell line-derived neurotrophic factor ,medicine ,Animals ,Humans ,Glial Cell Line-Derived Neurotrophic Factor ,Nerve Growth Factors ,RNA, Messenger ,In Situ Hybridization ,TUNEL assay ,Pyramidal Cells ,General Neuroscience ,Gene Transfer Techniques ,beta-Galactosidase ,Molecular biology ,Neuroprotective Agents ,Ischemic Attack, Transient ,biology.protein ,Gerbillinae - Abstract
Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent neurotrophic factors and promotes survival in many populations of cells. We examined the neuroprotective effect of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the transient global ischemia [Brain Res. 885 (2000) 273–282]. Gerbils received AxCAhGDNF or an adenoviral vector encoding bacterial β-galactosidase gene (AxCALacZ) through administration into the lateral ventricle. Two days later, occlusion of the common carotid arteries for 5 min bilaterally using aneurysm clips produced transient global forebrain ischemia. Animals showed intense immunolabeling for GDNF in ependymal cells on 2, 4 and 7 days after the operation. The exogenous gene transducted by the adenovirus in the same cells was detected by in situ hybridization. The treatment with AxCAhGDNF significantly prevented the loss of hippocampal CA-1 pyramidal neurons 2 to 7 days after the operation, as compared to AxCALacZ treatment. Also terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) staining was markedly reduced in the case with AxCAhGDNF treatment at 7 days after the operation. In this paper, we describe in detail the techniques for the detection of the exogenous gene of hGDNF under the treatment with AxCAhGDNF.
- Published
- 2001
39. JDD1, a Novel Member of the DnaJ Family, Is Expressed in the Germinal Zone of the Rat Brain
- Author
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Yoshio Akagi, Hideshi Yagi, Keisaku Hase, Yoshihiro Takamura, Mitsuyo Maeda, Takunari Yoneda, and Makoto Sato
- Subjects
Aging ,Transcription, Genetic ,Molecular Sequence Data ,Biophysics ,Subventricular zone ,Gestational Age ,Biology ,Biochemistry ,Embryonic and Fetal Development ,Pregnancy ,Complementary DNA ,medicine ,Animals ,Humans ,Amino Acid Sequence ,RNA, Messenger ,Cloning, Molecular ,Rats, Wistar ,Molecular Biology ,Peptide sequence ,Heat-Shock Proteins ,In Situ Hybridization ,Zinc finger ,chemistry.chemical_classification ,Messenger RNA ,Sequence Homology, Amino Acid ,Neurogenesis ,Brain ,Gene Expression Regulation, Developmental ,Cell Biology ,HSP40 Heat-Shock Proteins ,Molecular biology ,Rats ,Amino acid ,Neuroepithelial cell ,medicine.anatomical_structure ,Animals, Newborn ,chemistry ,Female ,Sequence Alignment - Abstract
We identified a novel gene encoding a new member of the DnaJ family, JDD1 (J domain of DnaJ-like-protein 1), from the rat. The cloned JDD1 cDNA is 1689 bp in size and its deduced amino acid sequence consists of 259 amino acid residues. Immunoblot analysis revealed that JDD1 protein is approximately 30 kDa in size. JDD1 has a J domain that is unique to the DnaJ family but lacks the G/F region (a region that is rich in the amino acids glycine and phenylalanine) and the zinc finger region (also known as the cysteine-rich region)-both characteristic to the DnaJ. JDD1 mRNA is expressed heterogeneously in vivo. In the central nervous system, JDD1 mRNA expression is confined to the germinal (ventricular and subventricular) zone where, except for cells situated deepest in the ventricular zone, neurons and glias are generated and then differentiate during the embryonic period. Expression of JDD1 mRNA in the subventricular zone persists after birth. In addition to the brain, its robust expression is notable in the liver, lung, cortex of the kidney, and several other tissues in the embryo.
- Published
- 2001
40. Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector
- Author
-
Jin Kanzaki, T Kanamori, S Fujikawa, Koichiro Saito, Hiroyuki Fukuda, X Hou, C Kadono, T Yamamoto, S Komaba, Masayuki Fukumura, Mamoru Hasegawa, Yuko Sakai, Y Nagai, Mitsuyo Maeda, K Washizawa, Makoto Inoue, Akihiro Shiotani, and Kazuhiko Watabe
- Subjects
Male ,viruses ,medicine.medical_treatment ,Transgene ,Genetic Vectors ,Gene Expression ,Transfection ,Recombinant virus ,Injections, Intramuscular ,Respirovirus ,Muscle hypertrophy ,Rats, Sprague-Dawley ,Insulin-like growth factor ,Genetics ,medicine ,Animals ,Humans ,Regeneration ,Myocyte ,Transgenes ,Insulin-Like Growth Factor I ,Muscle, Skeletal ,Molecular Biology ,Cells, Cultured ,biology ,Genetic transfer ,virus diseases ,Skeletal muscle ,Genetic Therapy ,Neuromuscular Diseases ,respiratory system ,biology.organism_classification ,Virology ,Recombinant Proteins ,Sendai virus ,Hindlimb ,Rats ,Cell biology ,medicine.anatomical_structure ,Lac Operon ,Models, Animal ,Molecular Medicine - Abstract
We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene transfer into skeletal muscle. Seven days after the intramuscular injection of LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis muscle with/without bupivacaine treatment and the transgene expression persisted up to 1 month after injection. Recombinant hIGF-I was detected as a major protein species in culture supernatants of a neonatal rat myoblast cell line L6 and thus induced the cells to undergo myogenetic differentiation. The introduction of hIGF-I/SeV into the muscle showed a significant increase in regenerating and split myofibers which were indicative of hypertrophy, and also an increase in the total number of myofibers, in comparison to that seen in the LacZ/SeV-treated control muscle. These results demonstrate that SeV achieves high-level transgene expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may therefore have great potential in the treatment of neuromuscular disorders.
- Published
- 2001
41. Cloning of a lymphatic peptide/histidine transporter
- Author
-
Kazuko SAKATA, Toshihide YAMASHITA, Mitsuyo MAEDA, Yoshinori MORIYAMA, Shoichi SHIMADA, and Masaya TOHYAMA
- Subjects
Cell Biology ,Molecular Biology ,Biochemistry - Abstract
Although peptide transport across the plasma membrane has been characterized well in the kidney and the intestine, the functional relevance of this transport in other organs has not been addressed. Here we report the cloning of a cDNA for a novel peptide/histidine transporter found in the rat (rPHT2), whose mRNA is expressed mainly in the lymphatic system. rPHT2 encodes a protein of 582 amino acids and showed 49% identity with the brain PHT (PHT1) [Yamashita, Shimada, Guo, Sato, Kohmura, Hayakawa, Takagi and Tohyama (1997) J. Biol. Chem. 272, 10205–10211]. rPHT2 mRNA was abundant in lung, spleen and thymus, and detected faintly in brain, liver, adrenal gland and heart by Northern-blot analysis and reverse transcriptase PCR (RT-PCR). Intense signals for the gene were found in immunocytes using in situ hybridization. Ectopic expression of rPHT2 protein in HEK-293T cells and BHK cells was not found on the cell surface, but was found on the lysosomal membrane using light- and electron-microscopic analysis. Recombinant rPHT2 protein reconstituted into liposomes showed proton-dependent transport activity with histidine and histidyl-leucine. These findings suggest that rPHT2 is involved in the protein catabolic pathway in the lymphatic system.
- Published
- 2001
42. Pyrogenic cytokines injected into the rat cerebral ventricle induce cyclooxygenase-2 in brain endothelial cells and also upregulate their receptors
- Author
-
Noriyuki Shirakawa, Chunyu Cao, Shigeo Kobayashi, Ikuyo Jikihara, Kiyoshi Matsumura, Mitsuyo Maeda, and Yasuyoshi Watanabe
- Subjects
medicine.medical_specialty ,Endothelium ,biology ,General Neuroscience ,medicine.medical_treatment ,Interleukin ,medicine.anatomical_structure ,Endocrinology ,Interleukin 20 ,Cytokine ,Downregulation and upregulation ,Cerebral cortex ,Internal medicine ,medicine ,biology.protein ,Receptor ,Interleukin 6 - Abstract
Peripheral immunological insults induce interleukin (IL)-1 beta and IL-6 in the brain. To elucidate the mechanism(s) of fever evoked by these brain-derived cytokines, and possible interactions between them, we examined in rats: (i) whether cyclooxygenase-2 is responsible for fever evoked by central injection of these cytokines; (ii) if so, where in the brain cyclooxygenase-2 is induced; (iii) where the receptors for these cytokines are located; and (iv) how the expression of these receptors is influenced by the cytokines. Intracerebroventricular injection of these cytokines evoked fever that was suppressed by a cyclooxygenase-2 inhibitor. Brain endothelium was the site of cyclooxygenase-2 induction by these cytokines. IL-1 receptor (IL-1R) was constitutively expressed in brain endothelium, and its mRNA was further upregulated by either cytokine. IL-6R mRNA was constitutively expressed in the cerebral cortex, and was newly induced in as yet unidentified cells in brain blood vessels by either cytokine. Messenger RNAs for cyclooxygenase-2, IL-1R, and IL-6R were often observed in the same blood vessels. These results suggest that COX-2 induced in brain endothelium is, at least in part, involved in the fever evoked by these cytokines, and that one possible interaction between these two cytokines is mutual upregulation of their receptors in the endothelium or perivascular cells, resulting in augmentation of their actions.
- Published
- 2001
43. Diffusional Anisotropy in Cranial Nerves with Maturation: Quantitative Evaluation with Diffusion MR Imaging in Rats
- Author
-
Masaya Takahashi, Koushi Harada, David B. Hackney, Jiro Ono, and Mitsuyo Maeda
- Subjects
Sensitivity and Specificity ,law.invention ,Diffusion ,law ,medicine ,Animals ,Cranial nerve disease ,Radiology, Nuclear Medicine and imaging ,Trigeminal Nerve ,Rats, Wistar ,Diffusion (business) ,skin and connective tissue diseases ,Anisotropy ,Trigeminal nerve ,medicine.diagnostic_test ,Phantoms, Imaging ,business.industry ,Cranial nerves ,Cranial Nerves ,Optic Nerve ,Magnetic resonance imaging ,Anatomy ,Image Enhancement ,Magnetic Resonance Imaging ,Rats ,Microscopy, Electron ,Optic nerve ,sense organs ,Electron microscope ,medicine.symptom ,business - Abstract
PURPOSE: To investigate the correlation between diffusional anisotropy and developmental changes in anatomy, which include myelination, in central and peripheral nerves in an animal model by using quantitative diffusion magnetic resonance (MR) imaging and electron microscopy. MATERIALS AND METHODS: In vivo transverse and longitudinal apparent diffusion coefficients (ADCs) of the optic and trigeminal nerves in 2-10-week-old rats were measured with MR imaging. Then the animals were sacrificed at each time point, and transverse and longitudinal sections of optic and trigeminal nerves were studied with electron microscopy. RESULTS: In the optic nerve, the ADC parallel to the neurofibers increased with development and increased contemporaneously with myelination, while the ADC perpendicular to the nerve did not change. This resulted in a significant increase in diffusional anisotropy. There were no significant changes in ADCs in either direction in the trigeminal nerve. Longitudinal sections of optic nerve showed a marked change in the orientation of each fiber. As development proceeded, the axons, which initially followed tortuous courses, assumed straighter and more parallel orientations. Trigeminal nerves displayed straight parallel courses at 2 weeks that did not change over the study period. CONCLUSION: Changes in fiber anatomy in maturation from tortuous to straighter and more parallel orientation can account for changes in longitudinal ADC and in diffusional anisotropy.
- Published
- 2000
44. Single stranded DNA as an immunocytochemical marker for apoptotic change of ischemia in the gerbil hippocampus
- Author
-
Toshihiro Sugiyama, Hiroshi Takagi, Yasuhito Hayashi, Mitsuyo Maeda, Fumiharu Akai, and Ikuyo Jikihara
- Subjects
Male ,Programmed cell death ,Pathology ,medicine.medical_specialty ,Immunocytochemistry ,Ischemia ,DNA, Single-Stranded ,Hippocampus ,Apoptosis ,Biology ,Gerbil ,Brain Ischemia ,Brain ischemia ,medicine ,Animals ,General Neuroscience ,medicine.disease ,Immunohistochemistry ,Molecular biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Ribonucleoproteins ,nervous system ,Female ,Gerbillinae ,Nucleus ,Biomarkers - Abstract
The light and electron microscopic localizations of single stranded DNA (SSD) protein, a marker of apoptosis and programmed cell death, in the gerbil hippocampus were examined by immunocytochemistry after transient brain ischemia. SSD-immunoreactive (IR) cells appeared from post-operative day 1 (PO 1) to PO 7 after 5- or 10-min ischemia. Immunoreaction was recognized in the nucleus of the CA1 pyramidal neurons without remarkable morphological changes on PO 1. These findings suggest that SSD degradation can occur during delayed neuronal death in the CA1, preceding the appearance of double strand breaks, one of the characteristic features of apoptosis.
- Published
- 1998
45. Neuronal integrity and astrocytic reaction in cold injury: an immunohistochemical investigation
- Author
-
Mitsuyo Maeda, Fumiharu Akai, and Takehiko Yanagihara
- Subjects
Pathology ,medicine.medical_specialty ,Neutrophils ,Serum albumin ,Poison control ,Brain Edema ,Pathology and Forensic Medicine ,Cerebral edema ,Lesion ,Cellular and Molecular Neuroscience ,Glial Fibrillary Acidic Protein ,Neuropil ,medicine ,Animals ,Serum Albumin ,Neurons ,biology ,Glial fibrillary acidic protein ,business.industry ,Albumin ,medicine.disease ,Immunohistochemistry ,Extravasation ,Cold Temperature ,medicine.anatomical_structure ,nervous system ,Astrocytes ,Brain Injuries ,biology.protein ,Neurology (clinical) ,medicine.symptom ,Gerbillinae ,business ,Microtubule-Associated Proteins - Abstract
The relationship between extravasation of serum albumin and damage to the neuronal elements as well as the astrocytic reaction was investigated following cold injury, using immunohistochemistry for albumin, microtubule-associated protein I and II (MAPs) and glial fibrillary acidic protein (GFAP). After 30 min, spreading of albumin to the neuropil and uptake into nerve cell bodies and dendrites were clearly observed in the area surrounding the cold lesion. Extravasation of albumin was maximal at 24 h and extended to the ipsilateral hippocampus and thalamus as well as to the paramedian part of the contralateral cerebral hemisphere. Uptake of albumin was seen in neurons with and without loss or reduction of the reaction for MAPs, but the former was confined to the area surrounding the cold lesion. When extravasated albumin receded from the neuropil, the positive reaction for albumin also disappeared from the neuronal elements and those neurons recovered immunoreactivity for MAPs. Astrocytes immunopositive for albumin were observed at 24 h in the white matter, and reactive astrocytes became notable even in the gray matter surrounding the cold lesion. Although reactive astrocytes persisted even after resolution of cerebral edema, immunopositivity for albumin disappeared from astrocytes soon after the disappearance of the reaction from the neuropil. As to the mechanism, rapid endo- and exocytosis may take place in response to the amount of edema fluid in the surrounding extracellular space, where albumin may be eliminated through the transvascular route and/or via the cerebrospinal fluid space.
- Published
- 1997
46. Differentiation between dysmyelination and demyelination using magnetic resonance diffusional anisotropy
- Author
-
Bernhard Fritz-Zieroth, Norio Sakai, Tetsushi Kagawa, Mitsuyo Maeda, Shigeo Hashimoto, Toshisaburo Nagai, Jiro Ono, Masaya Takahashi, Shintaro Okada, Koushi Harada, Kosuke Sakurai, Kazuhiro Ikenaka, and Akio Nihei
- Subjects
Pathology ,medicine.medical_specialty ,law.invention ,Diagnosis, Differential ,Central nervous system disease ,Mice ,law ,medicine ,Animals ,Cranial nerve disease ,Trigeminal Nerve ,Molecular Biology ,Trigeminal nerve ,Mice, Inbred BALB C ,Mice, Jimpy ,medicine.diagnostic_test ,Chemistry ,General Neuroscience ,Pelizaeus–Merzbacher disease ,Optic Nerve ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Disease Models, Animal ,Optic nerve ,Krabbe disease ,Anisotropy ,Neurology (clinical) ,medicine.symptom ,Electron microscope ,Demyelinating Diseases ,Developmental Biology - Abstract
Using magnetic resonance (MR) diffusion-weighted method, we examined the optic and the trigeminal nerves of jimpy and twitcher mice, considered to be animal models of Pelizaeus-Merzbacher disease, hypomyelination disorder, and Krabbe disease, demyelination disorder, respectively. In jimpy mice, diffusional anisotropy of optic nerve did not show a significant difference compared to age-matched control mice, suggesting that diffusional anisotropy does exist in absence of multiple layers of myelin sheath. In twitcher mice, diffusional anisotropy was attenuated remarkably in the optic and trigeminal nerves. Loss of axonal straightness on longitudinal section confirmed by electron microscopy appeared to be the principal explanation for it. It is further suggested that this MR diffusion-weighted imaging method enables us to differentiate hypomyelination from demyelination in vivo.
- Published
- 1995
47. C4-P-05Fusion of plasma membrane between NG2-Expressing Progenitor Cells and Neurons in the Cerebral Cortex of Rats
- Author
-
Mitsuo Suga, Yuji Hasebe, Mitsuyo Maeda, Yosky Kataoka, Asami Eguchi, and Yasuhisa Tamura
- Subjects
Fusion ,Corticogenesis ,Membrane ,medicine.anatomical_structure ,Structural Biology ,Cerebral cortex ,Chemistry ,medicine ,Radiology, Nuclear Medicine and imaging ,Progenitor cell ,Instrumentation ,Cell biology - Published
- 2015
48. A case report of pineocytoma
- Author
-
Shigeo Hashimoto, Mitsuyo Maeda, Kurenai Tanji, Motohiro Imano, Shingo Hiruma, Fumiharu Akai, Koichi Fujii, and Takao Satou
- Subjects
medicine.medical_specialty ,business.industry ,Pineocytoma ,Medicine ,Radiology ,business ,medicine.disease - Published
- 1994
49. Endotoxin Clearance Through Whole Body Rinse Out in Relation to Histologic Integrity in the Rat
- Author
-
Tencho Voynikov, Irina Nikolova, Yasuko Yamanishi, Hideaki Higashino, Mitsuyo Maeda, and Aritomo Suzuki
- Subjects
Male ,Fluorocarbons ,Biomedical Engineering ,Biophysics ,Alanine Transaminase ,Bioengineering ,General Medicine ,Shock, Septic ,Rats ,Endotoxins ,Biomaterials ,Liver ,Blood Substitutes ,Intestine, Small ,Animals ,Aspartate Aminotransferases ,Rats, Wistar ,Lung ,Spleen - Abstract
The effects of normothermic whole body rinse out (NWBRO) with FC-43 perfluorocarbon emulsion on the course of endotoxic shock were examined in male Wistar rats. These animals, conscious and unrestrained, were infused over 10 min with 60 mg/kg of E. coli endotoxin (LD100) and observed for 6 hr. The rats developed hypotension, plasma extravasation, metabolic acidosis, increase in serum GPT and GOT, and extensive hemorrhages in the small intestine. Another group of rats was subjected to blood substitution with FC-43 emulsion (artificial blood) 30 min after endotoxin infusion, until the hematocrit dropped to less than 3%, after which 6-9 ml of donor blood was exchange transfused with the emulsion. NWBRO caused a transitory rise in the GOT level, but more importantly it resulted in 98% endotoxin clearance, improved blood alkaline reserves, trimmed elevated GPT and GOT levels, and attenuated hemorrhage and epithelial necrosis in the small intestine.
- Published
- 1993
50. A pediatric case of mesenteric cyst classified histologically as intraabdominal cystic lymphagnioma
- Author
-
Motohiro Imano, Takao Satou, Mitsuyo Maeda, Shigetoshi Uno, Shigeo Hashimoto, Harumasa Ohyanagi, Tadao Uesugi, and Akio Kubota
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,medicine ,Mesenteric cyst ,business ,medicine.disease - Published
- 1993
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