121 results on '"Naohiro Yamamoto"'
Search Results
2. Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases
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Tomoyuki Akiyama, Ichiro Kuki, Kiyohiro Kim, Naohiro Yamamoto, Yumi Yamada, Kazuya Igarashi, Tomohiko Ishihara, Yuya Hatano, and Katsuhiro Kobayashi
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5‐formyltetrahydrofolic acid ,cerebral folate deficiency ,folate receptor 1 ,folinic acid ,Kearns‐Sayre syndrome ,methylenetetrahydrofolate reductase deficiency ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 ,Genetics ,QH426-470 - Abstract
Abstract Objective The use of folic acid (FA) has been discouraged in cerebral folate deficiency (CFD) because, theoretically, it could inhibit the transport of 5‐methyltetrahydrofolic acid (5MTHF) across the blood–cerebrospinal fluid (CSF) barrier. We present the clinical biochemical data of two cases with CFD to support this hypothesis. Methods We measured CSF and serum 5MTHF concentrations in a patient with Kearns‐Sayre syndrome (KSS) and a patient homozygous for MTHFR C677T polymorphism before and during folate supplementation therapy. To evaluate these 5MTHF concentrations, we also analyzed CSF and serum samples in pediatric patients without folate supplementation. Results Both patients had low CSF 5MTHF before treatment and high‐dose FA therapy did not normalize CSF 5MTHF. There was a dissociation between serum total folate and 5MTHF concentrations during FA therapy, which was considered to be due to the appearance of unmetabolized FA. The addition of folinic acid did not improve low CSF 5MTHF in the KSS patient and the cessation of FA resulted in the normalization of CSF 5MTHF. In the patient homozygous for MTHFR C677T, minimization of the FA dosage resulted in the normalization of CSF 5MTHF and an increased CSF‐to‐serum 5MTHF ratio. Conclusions Our data suggest that excess supplementation of FA impaired 5MTHF transport across the blood–CSF barrier. In the treatment of CFD, supplementation of folinic acid or 5MTHF (in cases of impaired 5MTHF synthesis) is preferred over the use of FA. The reference values of CSF 5MTHF concentration based on 600 pediatric cases were also provided.
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- 2022
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3. Optimal control input for discrete‐time networked control systems with data dropout
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Tadanao Zanma, Naohiro Yamamoto, Kenta Koiwa, and Kang‐Zhi Liu
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Computer engineering. Computer hardware ,TK7885-7895 ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Abstract These days, networked control systems (NCSs) in which data is transmitted via communication have been actively studied for many potential applications. In an NCS, data dropout degrades control performance depending on network conditions. For an NCS with data dropout, the authors propose a model‐predictive‐control‐based input optimisation, representing data dropout as both a Bernoulli model and a finite‐order Markov chain. Using the proposed NCS data dropout model, the authors derive an optimal input that provides the estimated error between the expected state of the plant and a given reference. The proposed control problem is formulated as its equivalent quadratic programming, as executed at each online sampling. The authors also demonstrate simulations and experiments to show the effectiveness of the proposed method.
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- 2022
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4. Cytokine/chemokine overproduction in parechovirus type 3 encephalitis with bilateral hippocampal lesions: A pediatric case report
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Kohei Matsubara, Megumi Nukui, Naohiro Yamamoto, Shizuka Nagase, Takeshi Inoue, Ichiro Kuki, Shin Okazaki, Hisashi Kawawaki, Atsushi Ujiro, and Hiroshi Sakuma
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Convulsions ,Encephalitis ,Hippocampal lesions ,PeV-3 ,Status epilepticus ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Parechovirus type 3 (PeV-3) presents with sepsis-like syndrome in neonates and young infants. PeV-3 has neurotropism and occasionally causes encephalitis. We evaluated the cytokine/chemokine profile in the cerebrospinal fluid of a young infant with PeV-3 encephalitis. The patient was a 1-month-old boy who developed fever, loss of consciousness, and seizures. On admission (2nd day of illness), no abnormalities were found on MRI. Thereafter, head MRI on the 4th day revealed abnormal intensities in the white matter around the bilateral lateral ventricles, corpus callosum, and bilateral hippocampus and amygdala. Although intravenous thiopental failed to stop the seizures, ketamine and phenobarbital were effective. Bilateral hippocampal lesions were unusual in HPeV-3 encephalitis and considered to be caused by super-refractory status epilepticus, indicating the strength of the disease. PeV-3 was detected in the blood, cerebrospinal fluid, nasal discharge, and fecal samples upon admission. The cytokine and chemokine levels in the cerebrospinal fluid were significantly elevated. Characteristically, neopterin levels in the cerebrospinal fluid increased as the white matter lesions appeared. These results suggested that cytokine/chemokine overproduction may be deeply involved in the pathology of the PeV-3 encephalitis. Although super-refractory status epilepticus and cytokine/chemokine overproduction indicated the strength of the disease, our patient was discharged without neurological sequelae and the combination of immunotherapy as well as seizure control may have contributed to the good outcome.
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- 2023
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5. Impact of the COVID-19 pandemic and multiplex polymerase chain reaction test on outpatient antibiotic prescriptions for pediatric respiratory infection.
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Daisuke Kitagawa, Taito Kitano, Madoka Furumori, Soma Suzuki, Yui Shintani, Hiroki Nishikawa, Rika Suzuki, Naohiro Yamamoto, Masayuki Onaka, Atsuko Nishiyama, Takehito Kasamatsu, Naoyuki Shiraishi, Yuki Suzuki, Akiyo Nakano, Ryuichi Nakano, Hisakazu Yano, Koichi Maeda, Sayaka Yoshida, and Fumihiko Nakamura
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Medicine ,Science - Abstract
This study aimed to evaluate the impact of the prolonged COVID-19 pandemic on outpatient antibiotic prescriptions for pediatric respiratory infections at an acute care hospital in Japan in order to direct future pediatric outpatient antibiotic stewardship. The impact of the COVID-19 pandemic and the FilmArray Respiratory Panel (RP) on outpatient antibiotic prescriptions was assessed from January 2019 to December 2021 using an interrupted time series analysis of children
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- 2023
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6. Characteristic features of electroencephalogram in a pediatric patient with GRIN1 encephalopathy
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Naohiro Yamamoto, Masataka Fukuoka, Ichiro Kuki, Naomi Tsuchida, Naomichi Matsumoto, and Shin Okazaki
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GRIN1 ,Electroencephalogram ,Paroxysmal fast activity ,N-methyl-D-aspartate receptor ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: The number of reports on GRIN1 variants associated with neurodevelopmental phenotypes has increased in recent years. However, there are only two detailed reports on electroencephalography findings. Case study: We had a case with severe global developmental delay, and exome sequencing revealed a novel de novo heterozygous variant of GRIN1. The patient's electroencephalography showed unique findings: paroxysmal fast activity—20–30 Hz beta waves, independently in the bilateral occipital regions, sometimes in a continuous manner—and prolonged alpha activity in the bilateral frontal regions, observed mainly during sleep, those findings were observed persistently. Discussion: The electroencephalography findings of our case have not been reported in the past. Receptor hypofunction due to the GRIN1 variant and imbalance in excitatory/inhibitory transmission owing to the dysfunction of the N-methyl-D-aspartate receptors may be the mechanism for the global developmental delay, stereotyped movements, and development of paroxysmal fast activity in our case. Accumulation of additional case reports is needed to confirm the reproducibility of the electroencephalography findings for disease specificity.
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- 2022
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7. HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts
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Gen Kuroyanagi, Go Sakai, Takanobu Otsuka, Naohiro Yamamoto, Kazuhiko Fujita, Tetsu Kawabata, Rie Matsushima-Nishiwaki, Osamu Kozawa, and Haruhiko Tokuda
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HSP22 ,PGF2α ,IL-6 ,VEGF ,Osteoblast ,Orthopedic surgery ,RD701-811 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. Methods MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. Conclusions Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.
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- 2021
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8. Freezing of cell sheets using a 3D freezer produces high cell viability after thawing
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Koji Ueno, Soichi Ike, Naohiro Yamamoto, Yutaro Matsuno, Hiroshi Kurazumi, Ryo Suzuki, Shunsaku Katsura, Bungo Shirasawa, and Kimikazu Hamano
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Cell sheet ,Freezing ,3D freezer ,Survival ,Regenerative medicine ,Temperature ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
In cell therapy, transplanting an appropriate number of cells to the target site is crucial. One way to achieve this is to transplant cell sheets. Transplantation of cell sheets has already been utilized for various diseases in clinical practice. However, reducing the cost of cell sheet utilization is essential so as to facilitate the spread of regenerative medicine. Several ways to reduce costs are available, one of which is the use of allogenic cells. Another alternative is the use of cell sheets, which necessitates the development of methods for freezing cell sheets. This is the first study to report the use of a 3D Freezer for freezing cells. 3D Freezers have been used in the field of food processing and technology for a long time. The 3D Freezer freezes objects using cold air at a uniform temperature from all directions. In this study, we analyzed the cooling speed of human fibroblast sheets in 11 cell preservation solutions using a 3D Freezer and a Program Freezer. The cooling speed was −2 °C per min in the 3D Freezer. Supercooling in 10 cell preservation solutions was lower in the 3D Freezer than in the Program Freezer. Cell viability after freeze–thaw of the cell sheets using 3D Freezer was more than 70% in five cell preservation solutions. The levels of hepatocyte growth factor and transforming growth factor-β1 were the same not only in the fibroblast sheets frozen using the five cell preservation solutions but also in the non-frozen fibroblast sheets. These results suggest that the 3D Freezer can freeze implantable cell sheets immediately after thawing.
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- 2021
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9. Distinct dual cortico-cortical networks successfully identified between supplemental and primary motor areas during intracranial EEG for drug-resistant frontal lobe epilepsy
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Takeshi Inoue, Takehiro Uda, Ichiro Kuki, Naohiro Yamamoto, Shizuka Nagase, Megumi Nukui, Shin Okazaki, Toshiyuki Kawashima, Yoko Nakanishi, Noritsugu Kunihiro, Yasuhiro Matsuzaka, Hisashi Kawawaki, and Hiroshi Otsubo
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Epilepsy surgery ,High-frequency oscillation ,Cortico-cortical evoked potential ,Supplementary motor area ,Primary motor area ,Neurology. Diseases of the nervous system ,RC346-429 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
We present a case of drug-resistant focal motor seizures in which separate cortico-cortical epileptic networks within the supplementary motor area (SMA) proper and primary motor area (PMA) were proven by ictal high-frequency oscillation (HFO) and cortico-cortical evoked potential (CCEP). A 12-year-old girl presented with two types seizures: type A, tonic extension and subsequent clonic movements of the right arm; and type B, tonic and clonic movements of the right leg. MRI was normal and karyotype genetic analysis revealed 46,X,t(X;14)(q13;p12). She underwent placement of chronic subdural electrodes over the left hemisphere. We recorded a total of nine seizures during 10 days of epilepsy monitoring. Type A seizures started from the lower part of the left SMA proper and early spread to the hand motor area of the PMA. Type B seizures started from the upper part of the SMA proper and early spread to the leg motor area of the PMA. CCEPs of both SMA proper and PMA activated two identical routes for evoked potentials correlating with separate pathways. Corticectomy of the left SMA proper and PMA achieved seizure-free without hemiparesis. Within a small homunculus of the SMA proper, separate epileptic networks were proven and validated by seizure semiology, ictal HFO, and CCEP.
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- 2021
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10. Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts
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Gen Kuroyanagi, Takanobu Otsuka, Naohiro Yamamoto, Rie Matsushima-Nishiwaki, Akira Nakakami, Jun Mizutani, Osamu Kozawa, and Haruhiko Tokuda
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resveratrol ,fibroblast growth factor (FGF-2) ,osteoprotegerin ,osteoblast ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2) on osteoprotegerin (OPG) synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP) kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation.
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- 2014
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11. HSP90 inhibitors potentiate PGF2α-induced IL-6 synthesis via p38 MAP kinase in osteoblasts.
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Kazuhiko Fujita, Haruhiko Tokuda, Gen Kuroyanagi, Naohiro Yamamoto, Shingo Kainuma, Tetsu Kawabata, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, and Takanobu Otsuka
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Medicine ,Science - Abstract
Heat shock protein 90 (HSP90) that is ubiquitously expressed in various tissues, is recognized to be a major molecular chaperone. We have previously reported that prostaglandin F2α (PGF2α), a potent bone remodeling mediator, stimulates the synthesis of interleukin-6 (IL-6) through p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells, and that Rho-kinase acts at a point upstream of p38 MAP kinase. In the present study, we investigated the involvement of HSP90 in the PGF2α-stimulated IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. Geldanamycin, an inhibitor of HSP90, significantly amplified both the PGF2α-stimulated IL-6 release and the mRNA expression levels. In addition, other HSP90 inhibitors, 17-allylamino-17demethoxy-geldanamycin (17-AAG) and 17-dimethylamino-ethylamino-17-demethoxy-geldanamycin (17-DMAG) and onalespib, enhanced the PGF2α-stimulated IL-6 release. Geldanamycin, 17-AAG and onalespib markedly strengthened the PGF2α-induced phosphorylation of p38 MAP kinase. Geldanamycin and 17-AAG did not affect the PGF2α-induced phosphorylation of p44/p42 MAP kinase and myosin phosphatase targeting subunit (MYPT-1), a substrate of Rho-kinase, and the protein levels of RhoA and Rho-kinase. In addition, HSP90-siRNA enhanced the PGF2α-induced phosphorylation of p38 MAP kinase. Furthermore, SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by geldanamycin, 17-AAG or 17-DMAG of the PGF2α-stimulated IL-6 release. Our results strongly suggest that HSP90 negatively regulates the PGF2α-stimulated IL-6 synthesis in osteoblasts, and that the effect of HSP90 is exerted through regulating p38 MAP kinase activation.
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- 2017
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12. A Case of Childhood-onset Adolescent and Young Adult Refractory Frontal Lobe Epilepsy Treated by Semi-urgent Epilepsy Surgery: Unique Praxis-induced Supplementary Motor Area Seizures and Multidisciplinary Collaboration
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Naohiro Yamamoto, Takeshi Inoue, Takehiro Uda, Ichiro Kuki, Megumi Nukui, Atsushi Sunohara, Ryoko Umaba, Noritsugu Kunihiro, Ryohei Tatara, Daisuke Furutsuka, and Shin Okazaki
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Neurology ,Neurology (clinical) - Published
- 2023
13. A pediatric case of autoimmune glial fibrillary acidic protein astrocytopathy with unique brain imaging patterns and increased cytokines/chemokines
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Naohiro Yamamoto, Takeshi Inoue, Ichiro Kuki, Kohei Matsubara, Naoki Yamada, Shizuka Nagase-Oikawa, Keisuke Oki, Megumi Nukui, Shin Okazaki, Hiroshi Sakuma, Akio Kimura, Takayoshi Shimohata, and Hisashi Kawawaki
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Developmental Neuroscience ,Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,General Medicine - Published
- 2022
14. Late relapse of anti-N-methyl-d-aspartate receptor encephalitis with amusia and transiently reduced uptake in 123I-iomazenil single-photon emission computed tomography
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Naoki Yamada, Ichiro Kuki, Taeka Hattori, Naohiro Yamamoto, Shizuka Nagase, Megumi Nukui, Takeshi Inoue, Shin Okazaki, Hisashi Kawawaki, Asako Horino, and Hiroshi Sakuma
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Developmental Neuroscience ,Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,General Medicine - Published
- 2022
15. Laparoscopic-assisted thoracoscopic repair of latent traumatic diaphragmatic hernia: A case report.
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Sota Yoshimine, Toshiki Tanaka, Junichi Murakami, Naohiro Yamamoto, Hiroshi Kurazumi, Eijiro Harada, and Kimikazu Hamano
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DIAPHRAGMATIC hernia ,BLUNT trauma ,ABDOMEN ,THORACOSCOPY ,CHEST endoscopic surgery ,HERNIA - Abstract
Surgical approaches for traumatic diaphragmatic hernia include transabdominal, transthoracic, and thoracoabdominal. Selection of the optimal approach depends on the timing and organ damage, often minimally invasive approaches with laparoscopy or thoracoscopy are performed. A 47-year-old man with blunt chest trauma was diagnosed with left traumatic diaphragmatic hernia 1 month after the trauma. The prolapsed omentum was detached from the chest wall and around the hernia orifice and returned to the abdominal cavity by coordinated thoracoscopic and laparoscopic manipulations. The 4 x 2 cm herniation in the diaphragm was sutured closed from the thoracic side while preventing re-prolapse of the omentum and abdominal organs from the abdominal side. A combined thoracoscopic and laparoscopic approach can be effective in confirming organ damage, repositioning of prolapsed organs, and safe repair of the diaphragm in latent traumatic diaphragmatic hernia. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Availability of the direct current component of a finger plethysmograph as a measure for the concealed information test
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Naohiro Yamamoto
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General Psychology - Published
- 2022
17. Chemotherapy-induced autoimmune-mediated encephalitis during germinoma treatment
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Naoki Yamada, Hiroshi Sakuma, Naohiro Yamamoto, Ichiro Kuki, Junichi Hara, and Kai Yamasaki
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Chemotherapy ,Germinoma ,business.industry ,medicine.medical_treatment ,Autoantibody ,Induction chemotherapy ,Neopterin ,General Medicine ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Developmental Neuroscience ,chemistry ,Pediatrics, Perinatology and Child Health ,Acute disseminated encephalomyelitis ,Immunology ,medicine ,Infectious encephalitis ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Encephalitis - Abstract
Background Autoimmune mediated encephalitis (AME), which includes autoantibody-associated encephalitis and acute disseminated encephalomyelitis, is a common cause of encephalitis as well as infectious encephalitis in children. AME may be triggered by autoimmune responses to paraneoplastic syndromes and infections. Infectious encephalitis associated with an immunocompromised status caused by anti-cancer chemotherapy is well recognized; however, there have been few reports on the relationship between AME and chemotherapy. Case report A ten-year-old previously healthy, developmentally normal girl was diagnosed with a pure germinoma in the suprasellar region. Following 30 days of induction chemotherapy, she developed a depressed level of consciousness with accompanying right hemiplegia, aphasia, and unexplained fever. Cerebrospinal fluid (CSF) analysis revealed positive oligoclonal bands and elevated neopterin levels. Neither atypical cells suggesting tumor exacerbation nor pathogens known to cause encephalitis were identified in the CSF. She was administrated immunosuppressive therapy and her symptoms rapidly improved. No known autoantibodies associated with autoantibody-associated encephalitis were identified in blood or CSF. However, the presence of oligoclonal bands and elevated neopterin levels in the CSF, and the favorable response to immunosuppressive therapy were consistent with an AME diagnosis. Thirteen days after the third course of chemotherapy, the patient developed a depressed level of consciousness again. Due to the recurrence of encephalitis, re-administration of immunosuppressive therapy was performed, which led to improvement in her symptoms. Recurrence of encephalitis has not occurred for 1 year after completion of chemotherapy. Conclusion The chemotherapy-induced abnormal immune response might have triggered the AME.
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- 2021
18. Impact of the COVID-19 pandemic and multiplex polymerase chain reaction test on outpatient antibiotic prescriptions for pediatric respiratory infection
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Daisuke Kitagawa, Taito Kitano, Madoka Furumori, Soma Suzuki, Yui Shintani, Hiroki Nishikawa, Rika Suzuki, Naohiro Yamamoto, Masayuki Onaka, Atsuko Nishiyama, Takehito Kasamatsu, Naoyuki Shiraishi, Yuki Suzuki, Akiyo Nakano, Ryuichi Nakano, Hisakazu Yano, Koichi Maeda, Sayaka Yoshida, and Fumihiko Nakamura
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Multidisciplinary - Abstract
This study aimed to evaluate the impact of the prolonged COVID-19 pandemic on outpatient antibiotic prescriptions for pediatric respiratory infections at an acute care hospital in Japan in order to direct future pediatric outpatient antibiotic stewardship.The impact of the COVID-19 pandemic and FilmArray Respiratory Panel (RP) on outpatient antibiotic prescriptions was assessed from January 2019 to December 2021 using an interrupted time series analysis of children The COVID-19 pandemic was not significantly related to the antibiotic prescription rate, suggesting that it did not impact physicians’ behavior toward antibiotic prescriptions. Replacing rapid antigen tests with the FilmArray RP introduced on December 1, 2020, did not affect the magnitude of the reduction in antibiotic prescription rate for pediatric respiratory infections.
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- 2022
19. Optimal control for networked control systems with stochastic data dropout.
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Naohiro Yamamoto, Tadanao Zanma, and Kang-Zhi Liu 0001
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- 2013
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20. Thoracoscopic left S3 segmentectomy for lung cancer with left B1+2 displaced anomalous bronchus: A case report
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Kimikazu Hamano, Junichi Murakami, Takayuki Kawachi, Sota Yoshimine, Toshiki Tanaka, and Naohiro Yamamoto
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Bronchus ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,medicine ,Radiology ,Lung cancer ,medicine.disease ,business - Published
- 2021
21. A case of infantile Tay-Sachs disease with late onset spasms
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Yasuko Furuichi, Shin Okazaki, Eiji Nanba, Naohiro Yamamoto, Megumi Nukui, Hisashi Kawawaki, Ichiro Kuki, Takeshi Inoue, Shizuka Nagase, Kaori Adachi, and Norio Sakai
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In vivo magnetic resonance spectroscopy ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Late onset ,Magnetic resonance imaging ,General Medicine ,Grey matter ,medicine.disease ,03 medical and health sciences ,Epilepsy ,Epileptic spasms ,0302 clinical medicine ,medicine.anatomical_structure ,Developmental Neuroscience ,Pediatrics, Perinatology and Child Health ,medicine ,Ictal ,Neurology (clinical) ,medicine.symptom ,business ,Myoclonus ,030217 neurology & neurosurgery - Abstract
Background Epilepsy is known to be associated with Tay-Sachs disease (TSD); however, no detailed reports are available. This case report aimed to present the clinical features of late onset spasms (LOS) in a patient with infantile TSD, and to elucidate the pathophysiology leading to LOS, using proton magnetic resonance spectroscopy (MRS). Case presentation At 11 months old, our patient had an afebrile seizure. At 14 months, he showed developmental stagnation and an increase in the frequency of epileptic seizures. Magnetic resonance imaging (T2-weighted images) showed high signal intensities in the thalamus bilaterally, and in the head of the caudate nucleus. Serum β-hexosaminidase enzyme activity was reduced, and he was diagnosed with TSD with a homozygous pathogenic variant of the HEXA gene (c. 571–1 G > T [IVS5, −1 G > T]), confirmed using direct sequence analysis. At 20 months, epileptic spasms in series around times of drowsiness and waking were observed on long-term video-electroencephalogram monitoring, in which ictal findings were different from those of startle seizures and non-epileptic myoclonus. Therefore, the epilepsy was classified as LOS. Epileptic spasms stopped following adrenocorticotropic hormone therapy, after which his vitality and consciousness improved. Serial MRS results showed a progressive decline in N-acetyl aspartate, and an increase in myoinositol in the grey matter over time. Discussion and conclusion Our patient’s MRS results suggested that cortical and subcortical axonal and neuronal degeneration with widespread gliosis in the cerebrum might lead to the development of LOS, and that LOS might be underestimated in patients with TSD.
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- 2021
22. Thyroid crisis mimicking clinically mild encephalitis/encephalopathy with a reversible splenial lesion: A pediatric case report
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Hisashi Kawawaki, Ichiro Kuki, Takeshi Inoue, Megumi Nukui, Shin Okazaki, Kohei Matsubara, Yuki Yamada, Naohiro Yamamoto, and Shizuka Nagase
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endocrine system ,Pathology ,medicine.medical_specialty ,Genu of the corpus callosum ,business.industry ,Thyroid ,Encephalopathy ,Thyroid Crisis ,Splenium ,General Medicine ,medicine.disease ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Developmental Neuroscience ,Pediatrics, Perinatology and Child Health ,medicine ,Neurology (clinical) ,medicine.symptom ,Thyroid function ,business ,Splenial ,030217 neurology & neurosurgery - Abstract
Background Reversible lesions in the splenium of the corpus callosum (SCC) with viral infections are associated mainly with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We report a pediatric patient in thyroid crisis with reversible SCC lesions. Case description We diagnosed a 9-year-old girl with thyroid crisis. She had presented with fever, tachycardia, and impaired consciousness. Magnetic resonance imaging revealed hyperintense signals in the splenium and genu of the corpus callosum and a white matter lesion of the left hemisphere in diffusion-weighted imaging. The initial, tentative diagnosis was clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We initiated intravenous methylprednisolone pulse therapy; thereafter, her level of consciousness rapidly improved. On admission, thyroid function studies revealed elevation of free thyroxine and a low level of thyroid stimulating hormone with thyroid-related autoantibodies. She was begun on thiamazole and was discharged without neurological sequelae. Conclusion Thyroid crisis is similar to acute encephalitis or encephalopathy associated with viral infection, especially with MERS, because the clinical and radiological features resemble those of thyroid crisis; therefore, thyroid diseases should be considered as a possible cause of reversible lesions in the splenium of the corpus callosum.
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- 2021
23. Possible critical region associated with late-onset spasms in 17p13.1-p13.2 microdeletion syndrome: a report of two new cases and review of the literature
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Naohiro, Yamamoto, Shin, Okazaki, Ichiro, Kuki, Naoki, Yamada, Shizuka, Nagase, Megumi, Nukui, Takeshi, Inoue, Rie, Kawakita, Tohru, Yorifuji, Takao, Hoshina, Toshiyuki, Seto, Toshiyuki, Yamamoto, and Hisashi, Kawawaki
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Spasm ,Epilepsy ,Seizures ,Humans ,Abnormalities, Multiple ,Electroencephalography ,Chromosome Deletion ,Spasms, Infantile ,Ubiquitin Thiolesterase - Abstract
17p13.1-2 microdeletion syndrome is a congenital anomaly syndrome with characteristic facial features and multiple malformations. The prevalence of epilepsy with 17p13.1-2 microdeletion is low, with only one case reported for late-onset spasms. Late-onset spasms is one of the rare epilepsy syndromes and one of the developmental epileptic encephalopathies requiring urgent treatment. We experienced two cases of 17p13.1-2 microdeletion syndrome, one of which presented with epileptic spasms in cluster at 18 months of age. EEG showed symmetrical hypsarrhythmia during interictal periods and a paroxysmal fast wave superimposed on widespread slow waves during seizures, leading to the diagnosis of late-onset spasms. Another case had no epilepsy. Comparing the extent of deletion in the two cases with that of previous reports, the involvement of the USP6 gene was suspected. However, the accumulation of additional case reports is needed to confirm the genetic involvement in late-onset spasms.
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- 2022
24. A case of empyema due to injury of diaphragm and transverse colon caused by rib fracture
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Kimikazu Hamano, Sota Yoshimine, Toshiki Tanaka, Naohiro Yamamoto, Junichi Murakami, and Fumiho Sano
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business.industry ,medicine ,Fracture (geology) ,Transverse colon ,Anatomy ,medicine.disease ,business ,Empyema ,Diaphragm (structural system) - Published
- 2020
25. Development of time interval-sliding method applicable to respiratory measures used in concealed information tests
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Naohiro Yamamoto
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business.industry ,Statistics ,Interval (graph theory) ,Medicine ,Respiratory system ,business - Published
- 2020
26. Freezing of cell sheets using a 3D freezer produces high cell viability after thawing
- Author
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Bungo Shirasawa, Soichi Ike, Yutaro Matsuno, Shunsaku Katsura, Ryo Suzuki, Koji Ueno, Hiroshi Kurazumi, Naohiro Yamamoto, and Kimikazu Hamano
- Subjects
Materials science ,Survival ,QH301-705.5 ,VEGF, Vascular endothelial growth factor ,Biophysics ,Cooling speed ,QD415-436 ,Biochemistry ,PAD, Peripheral arterial disease ,Freezing ,Preservation solutions ,Biology (General) ,Cell sheet ,3D freezer ,Temperature ,Cold air ,IND, Investigational new drug ,High cell ,HGF, Hepatocyte growth factor ,TGF, Transforming growth factor ,Clinical Practice ,Transplantation ,ELISA, Enzyme-linked immunosorbent assay ,Target site ,CLI, Critical limb ischemia ,Regenerative medicine ,Biomedical engineering ,Research Article - Abstract
In cell therapy, transplanting an appropriate number of cells to the target site is crucial. One way to achieve this is to transplant cell sheets. Transplantation of cell sheets has already been utilized for various diseases in clinical practice. However, reducing the cost of cell sheet utilization is essential so as to facilitate the spread of regenerative medicine. Several ways to reduce costs are available, one of which is the use of allogenic cells. Another alternative is the use of cell sheets, which necessitates the development of methods for freezing cell sheets. This is the first study to report the use of a 3D Freezer for freezing cells. 3D Freezers have been used in the field of food processing and technology for a long time. The 3D Freezer freezes objects using cold air at a uniform temperature from all directions. In this study, we analyzed the cooling speed of human fibroblast sheets in 11 cell preservation solutions using a 3D Freezer and a Program Freezer. The cooling speed was −2 °C per min in the 3D Freezer. Supercooling in 10 cell preservation solutions was lower in the 3D Freezer than in the Program Freezer. Cell viability after freeze–thaw of the cell sheets using 3D Freezer was more than 70% in five cell preservation solutions. The levels of hepatocyte growth factor and transforming growth factor-β1 were the same not only in the fibroblast sheets frozen using the five cell preservation solutions but also in the non-frozen fibroblast sheets. These results suggest that the 3D Freezer can freeze implantable cell sheets immediately after thawing., Highlights • 3D Freezer operates using cold air with uniform temperature directed at an object from all directions. • 3D Freezer was trialed for freezing 3D cell sheets for the first time. • 3D Freezer can generate high cell viability after freezing and thawing for cell therapy.
- Published
- 2021
27. Subtotal hemispherotomy for late-onset spasms after anti-myelin oligodendrocyte glycoprotein antibody-positive acute haemorrhagic leukoencephalitis
- Author
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Hiroshi Sakuma, Naohiro Yamamoto, Takeshi Inoue, Megumi Nukui, Hisashi Kawawaki, Ichiro Kuki, Shin Okazaki, Noritsugu Kunihiro, Takehiro Uda, Shin-ichiro Hamano, Shizuka Nagase, Masataka Fukuoka, and Jun Kubota
- Subjects
Pathology ,medicine.medical_specialty ,Spasm ,biology ,Hemispherectomy ,business.industry ,Late onset ,General Medicine ,Acute haemorrhagic leukoencephalitis ,Myelin oligodendrocyte glycoprotein ,Leukoencephalitis, Acute Hemorrhagic ,Neurology ,medicine ,biology.protein ,Humans ,Myelin-Oligodendrocyte Glycoprotein ,Neurology (clinical) ,Antibody ,Age of Onset ,business ,Autoantibodies - Published
- 2021
28. Examining probability distribution of within a set judgment method for Concealed Information Test
- Author
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Naohiro Yamamoto
- Subjects
Set (abstract data type) ,Computer science ,Statistics ,Probability distribution ,Test (assessment) - Published
- 2019
29. Reply to the letter: 'A case of infantile Tay-Sachs disease with late onset spasms'
- Author
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Naohiro Yamamoto, Eiji Nanba, Shizuka Nagase, Shin Okazaki, Norio Sakai, Yasuko Furuichi, Kaori Adachi, Megumi Nukui, Takeshi Inoue, Hisashi Kawawaki, and Ichiro Kuki
- Subjects
Pediatrics ,medicine.medical_specialty ,Developmental Neuroscience ,business.industry ,Pediatrics, Perinatology and Child Health ,Tay-Sachs disease ,medicine ,Late onset ,Neurology (clinical) ,General Medicine ,medicine.disease ,business - Published
- 2021
30. HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts
- Author
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Takanobu Otsuka, Kazuhiko Fujita, Naohiro Yamamoto, Tetsu Kawabata, Osamu Kozawa, Go Sakai, Gen Kuroyanagi, Haruhiko Tokuda, and Rie Matsushima-Nishiwaki
- Subjects
0301 basic medicine ,lcsh:Diseases of the musculoskeletal system ,p38 mitogen-activated protein kinases ,Down-Regulation ,Dinoprost ,p38 Mitogen-Activated Protein Kinases ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,lcsh:Orthopedic surgery ,Downregulation and upregulation ,Heat shock protein ,Medicine ,Animals ,Orthopedics and Sports Medicine ,Phosphorylation ,Cells, Cultured ,Heat-Shock Proteins ,IL-6 ,Osteoblasts ,biology ,business.industry ,Kinase ,Interleukin-6 ,Vascular Endothelial Growth Factors ,Osteoblast ,Transfection ,VEGF ,Cell biology ,Vascular endothelial growth factor ,lcsh:RD701-811 ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,PGF2α ,030220 oncology & carcinogenesis ,Mitogen-activated protein kinase ,Gene Knockdown Techniques ,biology.protein ,HSP22 ,Surgery ,lcsh:RC925-935 ,Mitogen-Activated Protein Kinases ,business ,Research Article ,Molecular Chaperones - Abstract
Background Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. Methods MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. Conclusions Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.
- Published
- 2021
31. A new within set judgement method for concealed information test
- Author
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Naohiro Yamamoto
- Subjects
Set (abstract data type) ,business.industry ,Computer science ,Judgement ,Artificial intelligence ,business ,computer.software_genre ,computer ,Natural language processing ,Test (assessment) - Published
- 2018
32. Analysis of Initial Heart Rate Deceleration in the Concealed Information Test
- Author
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Naohiro Yamamoto
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Heart rate deceleration ,Cardiology ,medicine ,business ,Test (assessment) - Published
- 2018
33. Heat shock protein 27 (HSPB1) suppresses the PDGF-BB-induced migration of osteoblasts
- Author
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Kazuhiko Fujita, Rie Matsushima-Nishiwaki, Osamu Kozawa, Gen Kuroyanagi, Haruhiko Tokuda, Shingo Kainuma, Takanobu Otsuka, Tetsu Kawabata, Naohiro Yamamoto, and Go Sakai
- Subjects
0301 basic medicine ,endocrine system ,animal structures ,Pyridines ,heat shock protein 27 ,p38 mitogen-activated protein kinases ,Becaplermin ,HSP27 Heat-Shock Proteins ,heat shock protein ,Biology ,migration ,urologic and male genital diseases ,Cell Line ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Hsp27 ,Cell Movement ,platelet-derived growth factor-BB ,Heat shock protein ,Genetics ,Animals ,Protein kinase A ,Protein Kinase Inhibitors ,Anthracenes ,Flavonoids ,Sirolimus ,Osteoblasts ,phosphorylation ,Kinase ,Imidazoles ,Proto-Oncogene Proteins c-sis ,Articles ,General Medicine ,Molecular biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mitogen-activated protein kinase ,embryonic structures ,osteoblast ,biology.protein ,Phosphorylation ,Mitogen-Activated Protein Kinases ,Proto-Oncogene Proteins c-akt ,Platelet-derived growth factor receptor - Abstract
Heat shock protein 27 (HSP27/HSPB1), one of the small heat shock proteins, is constitutively expressed in various tissues. HSP27 and its phosphorylation state participate in the regulation of multiple physiological and pathophysiological cell functions. However, the exact roles of HSP27 in osteoblasts remain unclear. In the present study, we investigated the role of HSP27 in the platelet-derived growth factor-BB (PDGF-BB)-stimulated migration of osteoblast-like MC3T3-E1 cells. PDGF-BB by itself barely upregulated the expression of HSP27 protein, but stimulated the phosphorylation of HSP27 in these cells. The PDGF-BB-induced cell migration was significantly downregulated by HSP27 overexpression. The PDGF-BB-induced migrated cell numbers of the wild-type HSP27-overexpressing cells and the phospho-mimic HSP27-overexpressing (3D) cells were less than those of the unphosphorylatable HSP27-overexpressing (3A) cells. PD98059, an inhibitor of MEK1/2, SB203580, an inhibitor of p38 mitogen-activated protein kinase, and SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) reduced the PDGF-BB-induced migration of these cells, whereas Akt inhibitor or rapamycin, an inhibitor of upstream kinase of p70 S6 kinase (mTOR), barely affected the migration. However, the PDGF-BB-induced phosphorylation of p44/p42 MAPK, p38 MAPK and SAPK/JNK was not affected by HSP27 overexpression. There were no significant differences in the phosphorylation of p44/p42 MAPK, p38 MAP kinase or SAPK/JNK between the 3D cells and the 3A cells. These results strongly suggest that HSP27 functions as a negative regulator in the PDGF-BB-stimulated migration of osteoblasts, and the suppressive effect is amplified by the phosphorylation state of HSP27.
- Published
- 2017
34. (−)-Epigallocatechin gallate but not chlorogenic acid upregulates osteoprotegerin synthesis through regulation of bone morphogenetic protein-4 in osteoblasts
- Author
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Kazuhiko Fujita, Naohiro Yamamoto, Go Sakai, Takanobu Otsuka, Shingo Kainuma, Tetsu Kawabata, Gen Kuroyanagi, Haruhiko Tokuda, Reou Ohguchi, Osamu Kozawa, and Rie Matsushima‑Nishiwaki
- Subjects
musculoskeletal diseases ,0301 basic medicine ,MAPK/ERK pathway ,Cancer Research ,medicine.medical_specialty ,p38 mitogen-activated protein kinases ,Biology ,Epigallocatechin gallate ,complex mixtures ,03 medical and health sciences ,chemistry.chemical_compound ,Immunology and Microbiology (miscellaneous) ,Downregulation and upregulation ,Osteoprotegerin ,Internal medicine ,medicine ,heterocyclic compounds ,Protein kinase A ,food and beverages ,Osteoblast ,Articles ,General Medicine ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Bone morphogenetic protein 4 - Abstract
Chlorogenic acid (CGA) is a primary phenolic component of coffee and (−)-epigallocatechin gallate (EGCG) is a primary flavonoid component of green tea, both of which have been documented to possess beneficial health properties. A previous study by the present authors demonstrated that p38 mitogen-activated protein kinase (MAPK) may be associated with osteoprotegerin synthesis stimulated by bone morphogenetic protein-4 (BMP-4) in osteoblast-like MC3T3-E1 cells. In the present study, the effects of CGA and EGCG on BMP-4-stimulated osteoprotegerin synthesis in MC3T3-E1 cells were investigated. It was observed that CGA had no effect on osteoprotegerin release stimulated by BMP-4, whereas EGCG significantly enhanced BMP-4-stimulated osteoprotegerin release (P=0.003). Levels of osteoprotegerin mRNA expression induced by BMP-4 were also significantly increased by EGCG (P=0.03). By contrast, EGCG had no significant effect on phosphorylation of Smad1 or p38 MAPK induced by BMP-4. In addition, EGCG had little effect on BMP-induced phosphorylation of p70 S6 kinase; however rapamycin, as an inhibitor of p70 S6 kinase, significantly suppressed osteoprotegerin release (P=0.007). These data suggest that EGCG but not CGA may upregulate the synthesis of osteoprotegerin induced by BMP-4 in osteoblasts.
- Published
- 2017
35. Resveratrol suppresses thyroid hormone-induced osteocalcin synthesis in osteoblasts
- Author
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Atsushi Harada, Naohiro Yamamoto, Takanobu Otsuka, Rie Matsushima‑Nishiwaki, Kazuhiko Fujita, Osamu Kozawa, Haruhiko Tokuda, Gen Kuroyanagi, and Shingo Kainuma
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,endocrine system diseases ,p38 mitogen-activated protein kinases ,Osteocalcin ,Biology ,Resveratrol ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Antioxidants ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Transactivation ,SRT1720 ,Internal medicine ,Stilbenes ,Genetics ,medicine ,Animals ,Phosphorylation ,Molecular Biology ,Osteoblasts ,Activator (genetics) ,Sirtuin 1 ,Kinase ,Anti-Inflammatory Agents, Non-Steroidal ,food and beverages ,3T3 Cells ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Oncology ,chemistry ,Protein Biosynthesis ,biology.protein ,Triiodothyronine ,Molecular Medicine ,hormones, hormone substitutes, and hormone antagonists - Abstract
Resveratrol, a polyphenolic compound that is present in grape skins, berries and red wine, may be beneficial for human health through its anti‑inflammatory and anti‑oxidant effects. It has been previously demonstrated that resveratrol exerts its biological effects primarily via sirtuin 1 (SIRT1) activation. We previously reported that triiodothyronine (T3) induces osteocalcin synthesis in osteoblast‑like MC3T3‑E1 cells, and that p38 mitogen‑activated protein (MAP) kinase mediates the T3‑stimulated synthesis of osteocalcin. The present study investigated the effect of resveratrol on T3‑induced osteocalcin synthesis and its underlying mechanism in MC3T3‑E1 cells. Cultured cells were stimulated with T3, and osteocalcin release from MC3T3‑E1 cells was measured by ELISA and phosphorylation of p38 MAP kinase was analyzed by western blotting. Resveratrol significantly suppressed the release of osteocalcin stimulated by T3, and SRT1720, a SIRT1 activator, significantly reduced T3‑induced osteocalcin release. The expression level of osteocalcin mRNA stimulated by T3 was significantly attenuated by resveratrol and T3‑induced transactivation activity of the thyroid hormone‑responsive element was significantly diminished by resveratrol. However, only limited effects of resveratrol on the T3‑induced phosphorylation of p38 MAP kinase were observed. The results of the present study demonstrated that resveratrol suppresses T3‑stimulated osteocalcin synthesis at a point upstream of transcription in osteoblasts, and that the inhibitory effect of resveratrol is mediated, at least partially, through SIRT1 activation. These results indicate that there may be a novel role for the polyphenol in the modulation of bone metabolism.
- Published
- 2017
36. Attenuation of prostaglandin E1-induced osteoprotegerin synthesis in osteoblasts by normoxic HIF inducers
- Author
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Kazuhiko Fujita, Naohiro Yamamoto, Rie Matsushima‑Nishiwaki, Shingo Kainuma, Gen Kuroyanagi, Haruhiko Tokuda, Reou Ohguchi, Osamu Kozawa, and Takanobu Otsuka
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,MAP Kinase Kinase 4 ,p38 mitogen-activated protein kinases ,Prostaglandin ,Deferoxamine ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Osteoprotegerin ,Internal medicine ,Genetics ,medicine ,Animals ,Mimosine ,RNA, Messenger ,Alprostadil ,Phosphorylation ,Protein kinase A ,Molecular Biology ,Osteoblasts ,biology ,Interleukin-6 ,Kinase ,Fabaceae ,Molecular biology ,030104 developmental biology ,Endocrinology ,Oncology ,chemistry ,Protein Biosynthesis ,Mitogen-activated protein kinase ,biology.protein ,Molecular Medicine ,Hypoxia-Inducible Factor 1 - Abstract
Mimosine, which is a natural plant amino acid present in the Leucaena genus, is able to induce hypoxia‑inducible factors (HIFs). Previous evidence has indicated that HIF regulates angiogenesis‑osteogenesis coupling in bone metabolism, and it has previously been reported that mimosine inhibits prostaglandin (PG)F2α‑induced osteoprotegerin (OPG) synthesis without affecting interleukin‑6 (IL‑6) production in osteoblast‑like MC3T3‑E1 cells. In addition, PGE1 has been demonstrated to induce OPG synthesis via activation of p38 mitogen‑activated protein (MAP) kinase and stress‑activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) in these cells, and PGE1 stimulates IL‑6 production via the activation of protein kinase A. In the present study, the effects of mimosine on the PGE1‑stimulated synthesis of OPG and IL‑6 were investigated in osteoblast‑like MC3T3‑E1 cells. The concentrations of OPG and IL‑6 were measured using relevant ELISA kits. OPG mRNA was measured by semi‑quantitative reverse transcription polymerase chain reaction. The phosphorylation of p38 MAP kinase and SAPK/JNK was analyzed by western blotting. Mimosine significantly reduced PGE1‑induced release of OPG and OPG mRNA expression levels without affecting the release of IL‑6. In addition, deferoxamine, which is also a normoxic HIF inducer, significantly inhibited PGE1‑induced OPG release and OPG mRNA expression levels; however, it had little effect on IL‑6 release. Furthermore, mimosine and deferoxamine failed to affect PGE1‑stimulated phosphorylation of p38 MAP kinase or SAPK/JNK. These results strongly suggest that normoxic HIF inducers attenuate PGE1‑stimulated OPG synthesis without affecting IL‑6 production in osteoblasts.
- Published
- 2017
37. Heat shock protein 22 (HSPB8) limits TGF-β-stimulated migration of osteoblasts
- Author
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Kazuhiko Fujita, Osamu Kozawa, Haruhiko Tokuda, Rie Matsushima-Nishiwaki, Gen Kuroyanagi, Takanobu Otsuka, Naohiro Yamamoto, and Shingo Kainuma
- Subjects
0301 basic medicine ,TGF alpha ,Pyridines ,p38 mitogen-activated protein kinases ,HSP27 Heat-Shock Proteins ,Receptor, Transforming Growth Factor-beta Type I ,Muscle Proteins ,Smad Proteins ,Protein Serine-Threonine Kinases ,Biology ,Biochemistry ,Cell Line ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Cell Movement ,Transforming Growth Factor beta ,Heat shock protein ,Animals ,HSP20 Heat-Shock Proteins ,Pyrroles ,RNA, Messenger ,Phosphorylation ,RNA, Small Interfering ,Protein kinase A ,Protein Kinase Inhibitors ,Molecular Biology ,Heat-Shock Proteins ,R-SMAD ,Osteoblasts ,Receptor, Transforming Growth Factor-beta Type II ,Transforming growth factor beta ,TGF beta receptor 2 ,Endoglin ,Isoquinolines ,Molecular biology ,030104 developmental biology ,Animals, Newborn ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,biology.protein ,Receptors, Transforming Growth Factor beta ,Molecular Chaperones ,Protein Binding - Abstract
Heat shock proteins (HSPs) are induced in response to various physiological and environmental conditions such as chemical and heat stress, and recognized to function as molecular chaperones. HSP22 (HSPB8), a low-molecular weight HSP, is ubiquitously expressed in many cell types. However, the precise role of HSP22 in bone metabolism remains to be clarified. In the present study, we investigated whether HSP22 is implicated in the transforming growth factor-β (TGF-β)-stimulated migration of osteoblast-like MC3T3-E1 cells. Although protein levels of HSP22 were clearly detected in unstimulated MC3T3-E1 cells, TGF-β failed to induce the protein levels. The TGF-β-stimulated migration was significantly up-regulated by knockdown of HSP22 expression. The cell migration stimulated by platelet-derived growth factor-BB was also enhanced by HSP22 knockdown. SB203580, an inhibitor of p38 mitogen-activated protein kinase, PD98059, an inhibitor of MEK1/2, or SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase had no effects on the TGF-β-induced migration. SIS3, a specific inhibitor of TGF-β-dependent Smad3 phosphorylation, significantly reduced the migration with or without TGF-β stimulation. Smad2, Smad3, Smad4 or Smad7 was not coimmunoprecipitated with HSP22. On the other hand, the TGF-β-induced Smad2 phosphorylation was enhanced by HSP22 down-regulation. The protein levels of TGF-β type II receptor (TGF-β RII) but not TGF-β type I receptor (TGF-β RI) was significantly up-regulated in HSP22 knockdown cells compared with those in the control cells. However, the levels of TGF-β RII mRNA in HSP22 knockdown cells were little different from those of the control cells. Neither TGF-β RI nor TGF-β RII was coimmunoprecipitated with HSP22. SIS3 reduced the amplification by HSP22 knockdown of the TGF-β-stimulated cell migration almost to the basal level. Our results strongly suggest that HSP22 functions as a negative regulator in the TGF-β-stimulated migration of osteoblasts via suppression of the Smad-dependent pathway, resulting from modulating the protein levels of TGF-β RII.
- Published
- 2016
38. Neonatal gastric perforation enclosed by the lesser sac
- Author
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Hiroyuki Ichiba and Naohiro Yamamoto
- Subjects
medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Neonatal gastric perforation ,Pediatrics, Perinatology and Child Health ,Medicine ,business ,Lesser sac ,Surgery - Published
- 2019
39. Possible involvement of AMP-activated protein kinase in PGE1-induced synthesis of osteoprotegerin in osteoblasts
- Author
-
Naohiro Yamamoto, Gen Kuroyanagi, Shingo Kainuma, Takanobu Otsuka, Rie Matsushima-Nishiwaki, Haruhiko Tokuda, and Osamu Kozawa
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,biology ,MAP kinase kinase kinase ,p38 mitogen-activated protein kinases ,AMPK ,General Medicine ,Mitogen-activated protein kinase kinase ,MAP2K7 ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Immunology and Microbiology (miscellaneous) ,AMP-activated protein kinase ,Osteoprotegerin ,Internal medicine ,medicine ,biology.protein ,Protein kinase A - Abstract
AMP-activated protein kinase (AMPK) is firmly established as a central regulator of cellular energy homeostasis. We have previously reported that prostaglandin E1 (PGE1) stimulates the synthesis of osteoprotegerin through p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. The present study investigated the involvement of AMPK in PGE1-induced osteoprotegerin synthesis in MC3T3-E1 cells. The levels of osteoprotegerin were measured using an enzyme-linked immunosorbent assay, while the phosphorylation of AMPK, acetyl-CoA carboxylase, p38 MAP kinase and SAPK/JNK were analyzed by western blotting. In addition, the mRNA expression levels of osteoprotegerin were determined by a reverse transcription-quantitative polymerase chain reaction. It was revealed that PGE1 significantly induced the phosphorylation of the α and β subunits of AMPK in a time-dependent manner (P
- Published
- 2016
40. Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts
- Author
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Kazuhiko Fujita, Haruhiko Tokuda, Reou Ohguchi, Osamu Kozawa, Shingo Kainuma, Gen Kuroyanagi, Rie Matsushima-Nishiwaki, Naohiro Yamamoto, and Takanobu Otsuka
- Subjects
0301 basic medicine ,MAP Kinase Kinase 4 ,p38 mitogen-activated protein kinases ,Deferoxamine ,Dinoprost ,p38 Mitogen-Activated Protein Kinases ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Osteoprotegerin ,Genetics ,medicine ,Animals ,Mimosine ,Inducer ,RNA, Messenger ,Protein kinase A ,Osteoblasts ,biology ,Interleukin-6 ,Kinase ,Gene Expression Regulation, Developmental ,Cell Differentiation ,General Medicine ,Peptide Fragments ,Cell biology ,030104 developmental biology ,chemistry ,Mitogen-activated protein kinase ,Cancer research ,biology.protein ,Hypoxia-Inducible Factor 1 ,Tumor Suppressor Protein p53 ,Transcription Factors ,medicine.drug - Abstract
Mimosine, a plant amino acid, is known to act as a normoxic inducer of hypoxia-inducible factor (HIF). Previous research has suggested that HIF plays important roles in angiogenesis-osteogenesis coupling and bone metabolism. We previously reported that prostaglandin F2α (PGF2α) induced osteoprotegerin synthesis through p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. We have also demonstrated that PGF2α induced the synthesis of interleukin-6 (IL-6) via p38 MAP kinase and p44/p42 MAP kinase but not SAPK/JNK in these cells. In the present study, we investigated the effects of mimosine on the PGF2α-induced synthesis of osteoprotegerin or IL-6 in MC3T3-E1 cells. We found that deferoxamine, another inducer of HIF, as well as mimosine, upregulated the protein levels of HIF-1α. Both mimosine and deferoxamine significantly suppressed the PGF2α-induced release of osteoprotegerin, and the mRNA expression level, without markedly affecting PGF2α-induced IL-6 release. Both mimosine and deferoxamine, by themselves, induced the release of vascular endothelial growth factor. The phosphorylation of p38 MAP kinase, p44/p42 MAP kinase or SAPK/JNK induced by PGF2α was not markedly affected by either mimosine or deferoxamine. Thus, the results of the present study strongly suggest that mimosine, a normoxic inducer of HIF, inhibits the PGF2α‑induced osteoprotegerin synthesis without affecting the IL-6 synthesis in osteoblasts.
- Published
- 2016
41. Amplification by (-)-epigallocatechin gallate and chlorogenic acid of TNF-α-stimulated interleukin-6 synthesis in osteoblasts
- Author
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Takanobu Otsuka, Haruhiko Tokuda, Shingo Kainuma, Gen Kuroyanagi, Reou Ohguchi, Rie Matsushima-Nishiwaki, Osamu Kozawa, Kazuhiko Fujita, and Naohiro Yamamoto
- Subjects
endocrine system ,Blotting, Western ,Flavonoid ,Enzyme-Linked Immunosorbent Assay ,Biology ,Epigallocatechin gallate ,complex mixtures ,Catechin ,Cell Line ,Mice ,chemistry.chemical_compound ,Chlorogenic acid ,Genetics ,Animals ,heterocyclic compounds ,Phosphorylation ,Interleukin 6 ,chemistry.chemical_classification ,Osteoblasts ,Interleukin-6 ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor Necrosis Factor-alpha ,Ribosomal Protein S6 Kinases, 70-kDa ,food and beverages ,General Medicine ,Molecular biology ,Gene Expression Regulation ,chemistry ,Apoptosis ,biology.protein ,Tumor necrosis factor alpha ,sense organs ,Chlorogenic Acid - Abstract
Polyphenolic compounds in foods and beverages have beneficial effects on human health. (-)-Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), a major flavonoid in green tea and a major phenolic acid in coffee, respectively, have potent properties, including antioxidative effects. Our previous study demonstrated that p70 S6 kinase acts as a negative regulator in tumor necrosis factor-α (TNF-α)-stimulated interleukin-6 synthesis in osteoblast-like MC3T3-E1 cells. In the present study, the effects of EGCG and CGA on the TNF-α-stimulated interleukin‑6 synthesis were investigated in MC3T3‑E1 cells. EGCG and CGA significantly enhanced TNF-α-stimulated interleukin-6 release. In addition, the interleukin-6 mRNA expression levels induced by TNF‑α were supported by EGCG, as well as CGA. EGCG markedly attenuated the TNF-α-induced phosphorylation of p70 S6 kinase whereas CGA failed to affect the phosphorylation. These results strongly suggest that EGCG and CGA enhance the TNF-α-stimulated interleukin-6 synthesis in osteoblasts, and that the amplifying effect of EGCG, but not CGA, is exerted via inhibiting p70 S6 kinase.
- Published
- 2015
42. Unphosphorylated HSP27 (HSPB1) regulates the translation initiation process via a direct association with eIF4E in osteoblasts
- Author
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Naohiro Yamamoto, Rie Matsushima‑Nishiwaki, Gen Kuroyanagi, Takanobu Otsuka, Haruhiko Tokuda, and Osamu Kozawa
- Subjects
endocrine system ,animal structures ,Osteocalcin ,HSP27 Heat-Shock Proteins ,Biology ,Transfection ,urologic and male genital diseases ,environment and public health ,Cell Line ,Mice ,chemistry.chemical_compound ,Hsp27 ,Genetics ,Animals ,Humans ,RNA, Messenger ,Phosphorylation ,Peptide Chain Initiation, Translational ,Osteoblasts ,EIF4G ,EIF4E ,General Medicine ,Cell cycle ,Molecular biology ,Up-Regulation ,Eukaryotic Initiation Factor-4E ,chemistry ,Cell culture ,embryonic structures ,biology.protein - Abstract
Heat-shock protein 27 (HSP27/HSPB1) and its phosphorylation are implicated in multiple physiological and pathophysiological cell functions. Our previous study reported that unphosphorylated HSP27 has an inhibitory role in triiodothyronine (T(3))‑induced osteocalcin (OC) synthesis in osteoblasts. However, the mechanisms behind the HSP27‑mediated effects on osteoblasts remain to be clarified. In the present study, to investigate the exact mechanism of HSP27 and its phosphorylation in osteoblasts, the molecular targets of HSP27 were explored using osteoblast‑like MC3T3‑E1 cells. The levels of OC mRNA induced by T(3) in the HSP27‑overexpressing cells did not show any significant differences compared with those in the control empty vector‑transfected cells. Therefore, the interactions between HSP27 and translational molecules were focused on, including eukaryotic translation initiation factor 4E (eIF4E), eIF4G and 4E‑binding protein 1 (4E‑BP1). The HSP27 protein in the unstimulated cells co‑immunoprecipitated with eIF4E, but not eIF4G or 4E‑BP1. In addition, the association of eIF4E with 4E‑BP1 was observed in the HSP27‑overexpressing cells, as well as in the control cells. Under T(3) stimulation, the binding of eIF4E to eIF4G was markedly attenuated in the HSP27‑overexpressing cells compared with the control cells. In addition, the binding of HSP27 to eIF4E in the unstimulated cells was diminished by the phosphorylation of HSP27. In response to T(3) stimulation, the association of eIF4E with eIF4G in the unphosphorylatable HSP27‑overexpressing cells was markedly reduced compared with the phospho‑mimic HSP27‑overexpressing cells. Taken together, these findings strongly suggest that unphosphorylated HSP27 associates with eIF4E in osteoblasts and suppresses the translation initiation process.
- Published
- 2015
43. Resveratrol amplifies BMP-4-stimulated osteoprotegerin synthesis via p38 MAP kinase in osteoblasts
- Author
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Jun Mizutani, Haruhiko Tokuda, Naohiro Yamamoto, Rie Matsushima‑Nishiwaki, Takanobu Otsuka, Osamu Kozawa, and Gen Kuroyanagi
- Subjects
musculoskeletal diseases ,Cancer Research ,medicine.medical_specialty ,p38 mitogen-activated protein kinases ,Bone Morphogenetic Protein 4 ,Resveratrol ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Cell Line ,Mice ,chemistry.chemical_compound ,Downregulation and upregulation ,Osteoprotegerin ,Internal medicine ,Stilbenes ,Genetics ,medicine ,Animals ,Molecular Biology ,Osteoblasts ,Bone Density Conservation Agents ,biology ,Kinase ,food and beverages ,Cell biology ,Endocrinology ,Oncology ,chemistry ,Mitogen-activated protein kinase ,Osteocalcin ,biology.protein ,Molecular Medicine ,Phosphorylation - Abstract
Resveratrol is a naturally occurring polyphenol that possesses health‑related properties, and is predominantly found in grapes and berries. Bone morphogenetic protein‑4 (BMP‑4) stimulates osteocalcin synthesis via p38 mitogen‑activated protein (MAP) kinase in osteoblast‑like MC3T3‑E1 cells. The present study aimed to investigate the effects of resveratrol on BMP‑4‑induced osteoprotegerin (OPG) synthesis in MC3T3‑E1 cells. Resveratrol alone had no effect on OPG expression levels, but significantly enhanced BMP‑4‑induced OPG release. In addition, resveratrol markedly amplified the mRNA expression levels of BMP‑4‑induced OPG. SB203580 is an inhibitor of p38 MAP kinase, which was shown to suppress BMP‑4‑stimulated OPG release. BMP‑4‑induced phosphorylation of p38 MAP kinase was also enhanced by resveratrol. Furthermore, SB203580 significantly reduced the resveratrol‑induced amplification of BMP‑4‑stimulated OPG release. These results suggested that resveratrol was able to upregulate BMP‑4‑stimulated OPG synthesis via the amplification of p38 MAP kinase activity in osteoblasts.
- Published
- 2015
44. Rac limits TGF-β-induced VEGF synthesis in osteoblasts
- Author
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Rie Matsushima-Nishiwaki, Akira Kondo, Gen Kuroyanagi, Naohiro Yamamoto, Osamu Kozawa, Haruhiko Tokuda, and Takanobu Otsuka
- Subjects
Transcriptional Activation ,Vascular Endothelial Growth Factor A ,rac1 GTP-Binding Protein ,Mitogen-activated protein kinase kinase ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Cell Line ,Mice ,chemistry.chemical_compound ,Endocrinology ,Transforming Growth Factor beta ,Animals ,Phosphorylation ,Protein kinase A ,Molecular Biology ,MAPK14 ,Osteoblasts ,biology ,MAP kinase kinase kinase ,Chemistry ,Kinase ,Neuropeptides ,Cyclin-dependent kinase 2 ,Molecular biology ,Vascular endothelial growth factor ,Pyrimidines ,Mitogen-activated protein kinase ,Aminoquinolines ,biology.protein ,Protein Processing, Post-Translational - Abstract
We previously showed that transforming growth factor-β (TGF-β) stimulates vascular endothelial growth factor (VEGF) synthesis via p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of Rac, which is a member of the Rho family of small GTPases, in the TGF-β-stimulated VEGF synthesis in MC3T3-E1 cells. TGF-β markedly increased the levels of GTP-bound Rac. NSC23766, a selective inhibitor of Rac-guanine nucleotide exchange factor interaction, significantly increased both the release of VEGF and the mRNA expression levels induced by TGF-β. In addition, the release of VEGF stimulated by TGF-β was amplified in Rac-knock down cells. Meanwhile, SIS3, a specific inhibitor of TGF-β-dependent Smad3 phosphorylation, significantly reduced the TGF-β-stimulated VEGF release. However, the phosphorylation of Smad2 or Smad3 induced by TGF-β was hardly affected by NSC23766. On the other hand, NSC23766 enhanced the TGF-β-induced phosphorylation of p38 MAP kinase without affecting the phosphorylation of p44/p42 MAP kinase or SAPK/JNK. Furthermore, the phosphorylation of p38 MAP kinase induced by TGF-β was markedly upregulated in the Rac-knock down cells. These results strongly suggest that Rac negatively regulates the TGF-β-stimulated VEGF synthesis via the inhibition of p38 MAP kinase in osteoblasts.
- Published
- 2015
45. Resveratrol suppresses TGF-β-induced VEGF synthesis in osteoblasts: Inhibition of the p44/p42 MAPKs and SAPK/JNK pathways
- Author
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Takanobu Otsuka, Gen Kuroyanagi, Haruhiko Tokuda, Naohiro Yamamoto, Osamu Kozawa, and Rie Matsushima‑Nishiwaki
- Subjects
Cancer Research ,biology ,MAP kinase kinase kinase ,business.industry ,Sirtuin 1 ,p38 mitogen-activated protein kinases ,food and beverages ,Articles ,General Medicine ,Mitogen-activated protein kinase kinase ,Resveratrol ,Cell biology ,Vascular endothelial growth factor ,chemistry.chemical_compound ,Immunology and Microbiology (miscellaneous) ,chemistry ,Mitogen-activated protein kinase ,Immunology ,biology.protein ,Medicine ,Protein kinase A ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Resveratrol, which is found in grape and berry skins and red wine, is generally known to be beneficial for human health due to its anti-inflammation and antioxidant effects. We have recently reported that transforming growth factor-β (TGF-β) stimulates vascular endothelial growth factor (VEGF) synthesis through Smad-independent pathways, such as the p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathways, in osteoblast-like MC3T3-E1 cells. The aim of the present study was to investigate the effect of resveratrol on the TGF-β-induced VEGF synthesis and the mechanism in osteoblast-like MC3T3-E1 cells. Resveratrol significantly suppressed the TGF-β-stimulated release of VEGF and the VEGF mRNA expression levels. SRT1720, a synthetic sirtuin 1 (SIRT1) activator, also reduced the VEGF release and the mRNA levels. With regard to the intracellular signaling in the TGF-β-stimulated VEGF synthesis, resveratrol and SRT1720 significantly attenuated the phosphorylation of p44/p42 MAP kinase and SAPK/JNK stimulated by TGF-β; however, the TGF-β-induced phosphorylation of Smad2 and p38 MAP kinase was hardly affected by resveratrol or SRT1720. These results strongly suggest that the TGF-β-stimulated VEGF synthesis is suppressed by resveratrol through the inhibition of p44/p42 MAP kinase and SAPK/JNK in osteoblasts, and that the suppressive effect is mediated, at least in part, via SIRT1 activation.
- Published
- 2015
46. Rho-kinase regulates human platelet activation induced by thromboxane A2 independently of p38 MAP kinase
- Author
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Rie Matsushima-Nishiwaki, Kumiko Tanabe, Shinji Ogura, Gen Kuroyanagi, Masanori Tsujimoto, Toru Iwama, Takanobu Otsuka, Haruhiko Tokuda, Yuko Iida, Naohiro Yamamoto, Hiroki Iida, Tomoaki Doi, Osamu Kozawa, and Yukiko Enomoto
- Subjects
Blood Platelets ,Pyridines ,Thromboxane ,Clinical Biochemistry ,p38 Mitogen-Activated Protein Kinases ,Thromboxane receptor ,Thromboxane A2 ,chemistry.chemical_compound ,Humans ,Platelet activation ,Enzyme Inhibitors ,Phosphorylation ,Rho-associated protein kinase ,rho-Associated Kinases ,biology ,Chemistry ,Imidazoles ,Fasudil ,Cell Biology ,Cofilin ,Platelet Activation ,Amides ,Cell biology ,Actin Depolymerizing Factors ,15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ,biology.protein ,Cancer research ,Platelet-derived growth factor receptor ,Signal Transduction - Abstract
We have previously demonstrated that ristocetin, an activator of GPIb/IX/V, induces the release of soluble CD40 ligand (sCD40L) via thromboxane A2 production in human platelets. It has been shown that thromboxane A2 induces the activation of Rho-kinase, a downstream effector of Rho, in human platelets. In the present study, we investigated the exact roles of Rho-kinase in thromboxane A2-induced platelet activation. We found that U46619, a thromboxane receptor (TP) agonist, induced the phosphorylation of cofilin, a target of Rho-kinase signaling, and that the cofilin phosphorylation by U46619 was suppressed by Y27632 or fasudil, specific inhibitors of Rho-kinase. Y27632 and fasudil markedly decreased large platelet aggregate formation by U46619. The release of sCD40L and secretion of platelet-derived growth factor (PDGF)-AB stimulated by U46619 were inhibited by Y27632 and fasudil. SB203580, a specific inhibitor of p38 mitogen-activated protein (MAP) kinase, reduced the sCD40L release and PDGF-AB secretion. Y27632 and fasudil failed to affect the phosphorylation of p38 MAP kinase whereas SB203580 had little effect on the phosphorylation of cofilin induced by U46619. In conclusion, our results strongly suggest that Rho-kinase regulates thromboxane A2-induced human platelet activation independently of p38 MAP kinase.
- Published
- 2015
47. Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts
- Author
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Naohiro Yamamoto, Rie Matsushima-Nishiwaki, Takanobu Otsuka, Akira Nakakami, Gen Kuroyanagi, Haruhiko Tokuda, Osamu Kozawa, and Jun Mizutani
- Subjects
Pyridines ,Mitogen-Activated Protein Kinase 3 ,Basic fibroblast growth factor ,Resveratrol ,resveratrol ,p38 Mitogen-Activated Protein Kinases ,lcsh:Chemistry ,Mice ,chemistry.chemical_compound ,Stilbenes ,Phosphorylation ,lcsh:QH301-705.5 ,Spectroscopy ,Anthracenes ,Mitogen-Activated Protein Kinase 1 ,biology ,Anti-Inflammatory Agents, Non-Steroidal ,Imidazoles ,food and beverages ,3T3 Cells ,General Medicine ,Recombinant Proteins ,fibroblast growth factor (FGF-2) ,Computer Science Applications ,Mitogen-activated protein kinase ,osteoblast ,Fibroblast Growth Factor 2 ,musculoskeletal diseases ,medicine.medical_specialty ,p38 mitogen-activated protein kinases ,Down-Regulation ,Heterocyclic Compounds, 4 or More Rings ,Article ,Catalysis ,Inorganic Chemistry ,Internal medicine ,medicine ,Animals ,Physical and Theoretical Chemistry ,Protein kinase A ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Flavonoids ,Osteoblasts ,Organic Chemistry ,JNK Mitogen-Activated Protein Kinases ,Endocrinology ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,osteoprotegerin ,biology.protein ,Proto-Oncogene Proteins c-akt - Abstract
It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2) on osteoprotegerin (OPG) synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP) kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation.
- Published
- 2014
48. Association of HSP22 with mTOR in osteoblasts: regulation of TNF-α-stimulated IL-6 synthesis
- Author
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Takanobu Otsuka, Kazuhiko Fujita, Haruhiko Tokuda, Rie Matsushima-Nishiwaki, Osamu Kozawa, Tetsu Kawabata, Naohiro Yamamoto, and Go Sakai
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,MAP Kinase Signaling System ,Biophysics ,Muscle Proteins ,P70-S6 Kinase 1 ,Biochemistry ,Cell Line ,03 medical and health sciences ,Mice ,Structural Biology ,Heat shock protein ,Genetics ,medicine ,Animals ,HSP20 Heat-Shock Proteins ,Phosphorylation ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Heat-Shock Proteins ,Mitogen-Activated Protein Kinase 1 ,Gene knockdown ,Osteoblasts ,Chemistry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,TOR Serine-Threonine Kinases ,Interleukin ,Ribosomal Protein S6 Kinases, 70-kDa ,Osteoblast ,Cell Biology ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Tumor necrosis factor alpha ,Molecular Chaperones - Abstract
Heat shock protein 22 (HSP22) is ubiquitously expressed in various types of cells including in osteoblasts. We previously reported that tumor necrosis factor (TNF)-α stimulates interleukin (IL)-6 synthesis via p44/p42 MAPK in osteoblast-like MC3T3-E1 cells and that mTOR/p70 S6 kinase (p70 S6K) negatively regulates the IL-6 synthesis. In this study, we investigated the involvement of HSP22 in TNF-α-stimulated-IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. HSP22 knockdown reduces TNF-α-stimulated release of IL-6. In addition, HSP22 knockdown strengthens TNF-α-induced phosphorylation of p70 S6K but suppresses that of p44/p42 MAPK. HSP22 coimmunoprecipitates with mTOR. HSP22 knockdown increases the basal levels of phosphorylated mTOR. These results strongly suggest that HSP22 interacts with mTOR and regulates TNF-α-induced IL-6 synthesis in osteoblasts.
- Published
- 2017
49. Treatment of Lateral Tibial Condylar Fractures Using Bioactive, Bioresorbable Forged Composites of Raw Particulate Unsintered Hydroxyapatite/Poly-L-Lactide Screws
- Author
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Hiroyuki Yoshihara, Takanobu Otsuka, Yukio Yoshida, Naoya Takada, Gen Kuroyanagi, Kunio Yamada, Hiroyuki Suzuki, and Naohiro Yamamoto
- Subjects
musculoskeletal diseases ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Radiodensity ,Polyesters ,Bone Screws ,02 engineering and technology ,Bone healing ,medicine.disease_cause ,Condyle ,Weight-bearing ,03 medical and health sciences ,Fracture Fixation, Internal ,0302 clinical medicine ,Absorbable Implants ,medicine ,Internal fixation ,Humans ,Orthopedics and Sports Medicine ,Composite material ,Reduction (orthopedic surgery) ,Aged ,030222 orthopedics ,business.industry ,Middle Aged ,musculoskeletal system ,021001 nanoscience & nanotechnology ,Tibial Fractures ,Durapatite ,Treatment Outcome ,Orthopedic surgery ,Surgery ,Female ,0210 nano-technology ,business ,Range of motion ,Follow-Up Studies - Abstract
Forged composites of raw particulate unsintered hydroxyapatite/poly-L-lactide (F-u-HA/PLLA) devices possess high mechanical strength, bioactivity, and radio-opacity. The aim of this study was to assess the efficacy of F-u-HA/PLLA screws in the treatment of lateral tibial condylar fractures. From January 2005 to December 2010, a total of 7 patients with displaced closed lateral tibial condylar fractures (Schatzker type II) were treated using F-u-HA/PLLA screws. Open reduction and internal fixation was performed using 2 or 3 F-u-HA/PLLA screws. After surgery, weight bearing was not allowed for 6 weeks. Range of motion exercise was initiated after removal of the plaster splint. Radiographs were evaluated for fracture healing, joint depression, and the radioopacity of F-u-HA/PLLA screws. Clinical outcomes and postoperative complications were also assessed. Average follow-up was 44 months. All fractures were successfully healed. Average values for joint depression were 4.7 mm (range, 2–9 mm) preoperatively, 0.4 mm (range, 0–1 mm) postoperatively, and 0.4 mm (range, 0–1 mm) at final follow-up. Whole shadows of F-u-HA/PLLA screws were observed during the follow-up period. Breakage of screws, osteolysis, and a radiolucent zone around the screws were not observed at final follow-up. Average knee flexion and extension were 134° (range, 110° to 150°) and −1° (range, −10° to 0°), respectively. No patient had wound infection, late aseptic tissue response, or foreign body reaction postoperatively. None of the patients reported pain at final follow-up. These results suggest that F-u-HA/PLLA screws could be an alternative option for the treatment of lateral tibial condylar fractures. [ Orthopedics . 2018; 41(3):e365–e368.]
- Published
- 2017
50. Suppression by HSP90 inhibitors of BMP‑4‑stimulated osteoprotegerin synthesis in osteoblasts: Attenuation of p70 S6 kinase
- Author
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Go Sakai, Haruhiko Tokuda, Tetsu Kawabata, Osamu Kozawa, Kazuhiko Fujita, Rie Matsushima‑Nishiwaki, Takanobu Otsuka, Gen Kuroyanagi, Shingo Kainuma, and Naohiro Yamamoto
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Smad5 Protein ,Cancer Research ,Lactams, Macrocyclic ,Bone Morphogenetic Protein 4 ,Biology ,Bone morphogenetic protein ,Biochemistry ,Cell Line ,Smad1 Protein ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Mothers against decapentaplegic homolog 1 ,Osteoprotegerin ,Heat shock protein ,polycyclic compounds ,Genetics ,Benzoquinones ,Animals ,HSP90 Heat-Shock Proteins ,Phosphorylation ,Molecular Biology ,Osteoblasts ,Ribosomal Protein S6 Kinases, 70-kDa ,Cell cycle ,Geldanamycin ,Hsp90 ,030104 developmental biology ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Molecular Medicine - Abstract
Heat shock protein 90 (HSP90) is an ATP‑dependent ubiquitous molecular chaperon which is important in cell homeostasis. The authors previously demonstrated that bone morphogenetic protein (BMP)‑4 stimulates osteoprotegerin (OPG) production in osteoblast‑like MC3T3‑E1 cells, and that p70 S6 kinase positively regulates the OPG synthesis by BMP‑4. The present study investigated the involvement of HSP90 in the BMP‑4‑stimulated OPG synthesis and the mechanism in MC3T3‑E1 cells. HSP90 inhibitors, 17‑allylamino‑17demethoxy‑geldanamycin (17‑AAG), 17‑dimethylamino‑ethylamino‑17‑demethoxy‑geldanamycin (17‑DMAG) and geldanamycin significantly suppressed the BMP‑4‑stimulated OPG release. Geldanamycin markedly reduced the BMP‑4‑induced mRNA expression of OPG. 17‑AAG and 17‑DMAG significantly attenuated the phosphorylation of p70 S6 kinase induced by BMP‑4 without affecting the BMP‑4‑induced phosphorylation of mothers against decapentaplegic homolog 1/5. The results suggest that HSP90 inhibitors suppress the BMP‑4‑stimulated OPG synthesis in osteoblasts, and that their suppressive effects are exerted through downregulating p70 S6 kinase.
- Published
- 2017
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