Publications by authors named "Ryo Shimada"

28 Publications

  • Page 1 of 1

Long-term viability and extensibility of an in situ regenerated canine aortic wall using hybrid warp-knitted fabric.

Interact Cardiovasc Thorac Surg 2021 Apr 21. Epub 2021 Apr 21.

Healthcare Business Development-Medical Device, Teijin Limited, Tokyo, Japan.

Objectives: Many surgical materials promoting tissue regeneration have been explored for use in paediatric cardiac surgery. The aim of this study is to evaluate the long-term viability and extensibility of the canine aortic wall regenerated using a novel synthetic hybrid fabric.

Methods: The sheet is a warp-knitted fabric of biodegradable (poly-l-lactic acid) and non-biodegradable (polyethylene terephthalate) yarns coated with cross-linked gelatine. This material was implanted as a patch to fill an oval-shaped defect created in the canine descending aorta. The tissue samples were explanted after 12, 24 or 36 months (N = 3, 2, 2, respectively) for histological examination and biomechanical testing.

Results: There was no shrinkage, rupture or aneurysmal change after 24 months. The regenerated wall showed prototypical vascular healing without material degeneration, chronic inflammation, calcification or abnormal intimal overgrowth. Bridging tissue across the patch was well-formed and had expanded over time. The biodegradable yarns had completely degraded at 24 months after implantation, as scheduled, but the regenerated aortic wall demonstrated satisfactory levels of mechanical strength and extensibility in tensile strength tests.

Conclusions: The sheet achieved good long-term viability and extensibility in the regenerated aortic wall. These findings suggest that it is a promising surgical material for repairing congenital heart defects. Further developments of the sheet are required, including clinical studies.
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http://dx.doi.org/10.1093/icvts/ivab064DOI Listing
April 2021

Drug Fever Due to Favipiravir Administration for the Treatment of a COVID-19 Patient.

Intern Med 2021 Apr 15;60(7):1115-1117. Epub 2021 Feb 15.

Department of General Medicine, Chiba University Hospital, Japan.

A 55-year-old Japanese man was hospitalized with the novel coronavirus disease 2019 (COVID-19). On the 14th day after the start of favipiravir administration, the patient developed a fever with a temperature of 38.1°C. His pulse rate also became elevated to 128 bpm, so relative bradycardia was not suspected. Since he was in good overall health and no concomitant symptoms and signs were apparent, we considered it to be drug fever due to favipiravir. After the completion of favipiravir treatment, the patient's temperature normalized within 24 hours. We herein report this case of drug fever caused by favipiravir.
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http://dx.doi.org/10.2169/internalmedicine.5813-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079902PMC
April 2021

Effects of Preexisting Diabetes Mellitus on the Severity of Traumatic Brain Injury.

J Neurotrauma 2021 Apr 18;38(7):886-902. Epub 2020 Nov 18.

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Falls and traffic accidents can cause traumatic brain injury (TBI). Assessment of the injury severity is essential to determine the prognosis or the cause of death. Diabetes mellitus (DM) is a common preexisting disease in elderly adults. We hypothesized that preexisting DM exacerbates TBI secondary to prolonged inflammation. In this study, we investigated TBI-induced changes in nerve function and inflammatory cell migration to the injury site, and the extent of brain contusion in KK-Ay (DM) and C57BL/6J (non-DM) mice. A controlled cortical impact device was used to induce TBI in each mouse. The brain contusion volume was measured using magnetic resonance imaging. Nerve function changes were assessed using the following animal behavior tasks: neurological severity score (NSS), Morris water maze, forced swim test, and beam walking. Immunohistochemical examinations of brain sections were performed to assess the infiltration of neutrophils, astrocytes, microglia, and macrophages, and to detect apoptosis. These experiments were performed on post-injury days 1-90 (over five experiments/time-points in each group). Compared with non-DM mice, DM mice showed significantly greater brain contusion volume, greater deterioration in the NSS, and a higher number of neutrophils, macrophages, and apoptotic cells in the brain tissue specimens. This study indicates that the prognosis of normal mice and DM mice differs, even if they acquire a TBI of the same severity. Therefore, it is important to evaluate patients with TBI for DM and other preexisting diseases in order to provide adequate treatment or to determine the correct cause of death.
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http://dx.doi.org/10.1089/neu.2020.7118DOI Listing
April 2021

Senescence-associated-β-galactosidase staining following traumatic brain injury in the mouse cerebrum.

PLoS One 2019 11;14(3):e0213673. Epub 2019 Mar 11.

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Primary and secondary traumatic brain injury (TBI) can cause tissue damage by inducing cell death pathways including apoptosis, necroptosis, and autophagy. However, similar pathways can also lead to senescence. Senescent cells secrete senescence-associated secretory phenotype proteins following persistent DNA damage response signaling, leading to cell disorders. TBI initially activates the cell cycle followed by the subsequent triggering of senescence. This study aims to clarify how the mRNA and protein expression of different markers of cell cycle and senescence are modulated and switched over time after TBI. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, immunohistochemical analysis, and real-time PCR to examine the time-dependent changes in expression levels of proteins and mRNA, related to cell cycle and cellular senescence markers, in the cerebrum during the initial 14 days after TBI using a mouse model of controlled cortical impact (CCI). Within the area adjacent to the cerebral contusion after TBI, the protein and/or mRNA expression levels of cell cycle markers were increased significantly until 4 days after injury and senescence markers were significantly increased at 4, 7, and 14 days after injury. Our findings suggested that TBI initially activated the cell cycle in neurons, astrocytes, and microglia within the area adjacent to the hemicerebrum contusion in TBI, whereas after 4 days, such cells could undergo senescence in a cell-type-dependent manner.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411151PMC
December 2019

Senescence-associated-β-galactosidase staining following traumatic brain injury in the mouse cerebrum.

PLoS One 2019 11;14(3):e0213673. Epub 2019 Mar 11.

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Primary and secondary traumatic brain injury (TBI) can cause tissue damage by inducing cell death pathways including apoptosis, necroptosis, and autophagy. However, similar pathways can also lead to senescence. Senescent cells secrete senescence-associated secretory phenotype proteins following persistent DNA damage response signaling, leading to cell disorders. TBI initially activates the cell cycle followed by the subsequent triggering of senescence. This study aims to clarify how the mRNA and protein expression of different markers of cell cycle and senescence are modulated and switched over time after TBI. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, immunohistochemical analysis, and real-time PCR to examine the time-dependent changes in expression levels of proteins and mRNA, related to cell cycle and cellular senescence markers, in the cerebrum during the initial 14 days after TBI using a mouse model of controlled cortical impact (CCI). Within the area adjacent to the cerebral contusion after TBI, the protein and/or mRNA expression levels of cell cycle markers were increased significantly until 4 days after injury and senescence markers were significantly increased at 4, 7, and 14 days after injury. Our findings suggested that TBI initially activated the cell cycle in neurons, astrocytes, and microglia within the area adjacent to the hemicerebrum contusion in TBI, whereas after 4 days, such cells could undergo senescence in a cell-type-dependent manner.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411151PMC
December 2019

Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect.

Biochem Biophys Rep 2018 Dec 11;16:62-68. Epub 2018 Oct 11.

Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.

Herbal medicine is mainly prepared from boiling herbal water extracts. Many epoch-making immunosuppressant drugs, such as glycyrrhizic acid (old example) and FTY720 (current example), were developed from herbal secondary metabolites in the boiling water extract by partition with organic solvents. However, few immunostimulants have been discovered by this method. Instead of the usual method, we aimed to find a novel immunostimulant component by two unique methods in the research of herbal medicine: ultracentrifugation and electron microscopy. The immunostimulant was not a secondary metabolite, as expected, but the structure was a nanoparticle formed by a polysaccharide. In addition, we clarified the immune effect of the nanoparticle. Intake of the nanoparticle by phagocytosis resulted in immunostimulant effects by increasing the genes and proteins of inflammatory cytokines in macrophage cells. The immunostimulant effects were inhibited by a phagocytosis inhibitor, cytochalasin D. To the best of our knowledge, this study is the first to describe the discovery of a nanoparticle in boiling herbal water extracts and its immunostimulant properties. This study will provide additional understanding of the efficacy of herbal medicine, in that the immunostimulant nanoparticle universally exists in boiling herbal water extracts. Thus, traditional herbal medicine may be an oldest known nanomedicine. Furthermore, this study suggests that the immunostimulant nanoparticle simply can be obtained from herbal medicine only by ultracentrifugation. We hope that this simple strategy will substantially contribute to drug development, including vaccine adjuvant, in the future.
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http://dx.doi.org/10.1016/j.bbrep.2018.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186954PMC
December 2018

Correction to: Development of a simple device enabling percutaneous flow regulation for a small vascular graft for a Blalock-Taussig shunt capable of flow regulation: complete translation of an original article originally published in Pediatric Cardiology and Cardiac Surgery (154-159, 2016: vol. 32).

Gen Thorac Cardiovasc Surg 2018 09;66(9):556

Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.

In the original publication of the article, the title was incorrectly published.
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http://dx.doi.org/10.1007/s11748-018-0958-2DOI Listing
September 2018

In situ tissue regeneration using a warp-knitted fabric in the canine aorta and inferior vena cava.

Eur J Cardiothorac Surg 2018 08;54(2):318-327

Healthcare Business Development, Teijin Limited, Hino, Tokyo, Japan.

Objectives: Materials used in paediatric cardiac surgery have drawbacks of deterioration, calcification and pseudointimal proliferation resulting in haemodynamic disturbance. The aim of this study was to investigate whether these drawbacks can be overcome by in situ tissue regeneration using a newly developed synthetic hybrid fabric (SHF).

Methods: The SHF is an expandable, warp-knitted fabric composed of a combination of biodegradable [poly-l-lactic acid (PLLA)] and non-biodegradable (polyethylene terephthalate) yarns. The fabric is coated with cross-linked gelatin. Mechanical properties of the SHF were compared with those of 2 commercial products: expanded polytetrafluoroethylene sheet and glutaraldehyde-treated bovine pericardium. An oval-shaped defect created in the canine descending aorta or inferior vena cava was filled with the SHF patch. After 2 weeks and 1, 3, 6 and 12 (or 24 in the inferior vena cava) months, the patch was removed for histological examination and evaluation of the remaining PLLA.

Results: The SHF exhibited satisfactory tensile and suture retention strength for surgical implantation similar to or better than the 2 commercial products. Tissue regeneration was induced with multilayered smooth muscle cells and collagen fibres on both sides of the patch, along with a mature endothelial layer and tissue connections containing vasa vasorum across the patch in the aorta and inferior vena cava. Inflammatory reactions were minimal, and no calcium deposition occurred. The molecular weight of PLLA was reduced to half at 12 months after implantation.

Conclusions: The SHF may solve the drawbacks of the existing products. Further studies of the expandability of the SHF patch after degradation of PLLA are warranted.
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http://dx.doi.org/10.1093/ejcts/ezy045DOI Listing
August 2018

Pseudoaneurysm of the external iliac artery is a rare late complication after total hip arthroplasty.

J Vasc Surg Cases Innov Tech 2017 Sep 18;3(3):149-151. Epub 2017 Jul 18.

Department of Thoracic and Cardiovascular Surgery, Osaka Medical College Hospital, Osaka, Japan.

Vascular injury as a delayed complication of total hip arthroplasty (THA) is rare. We present a case of pseudoaneurysm of the external iliac artery due to chronic irritation from a prominent bone spicule occurring 2 years after revision THA. We successfully managed the patient with open repair, and there has been no sign of recurrence in the 2 years since the previous surgery. This report suggests that patients who have undergone THA should be followed up carefully and assessed for vascular injuries even after a substantial time.
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http://dx.doi.org/10.1016/j.jvscit.2017.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764856PMC
September 2017

Development of a new surgical sheet containing both silk fibroin and thermoplastic polyurethane for cardiovascular surgery.

Surg Today 2018 May 18;48(5):486-494. Epub 2017 Dec 18.

Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, 2-7 Daigaku-Machi, Takatsuki, Osaka, 569-8686, Japan.

Purpose: The surgical sheets that are currently used for congenital cardiovascular surgery have several drawbacks, including material deterioration, calcification, and pseudo-intimal proliferation resulting in hemodynamic disturbance. The aim of this study was to evaluate a newly developed sheet made from a combination of silk fibroin (SF) and a synthetic polymer, thermoplastic polyurethane (TPU), for surgical use.

Methods: The hybrid SF/TPU sheet was a non-woven fabric with nanofibers that was made using the electrospinning method. The mechanical properties of the SF/TPU sheet were characterized. To determine its biocompatibility, part of the wall of the canine descending aorta was replaced with a SF/TPU sheet as a patch. The patches were removed after 3 months and a histological examination was performed.

Results: The flexibility, water permeability, and suture retention strength of the SF/TPU sheet were excellent and equivalent to those of existing sheets. The SF/TPU sheet had excellent handling properties and fit well into the vascular wall without needle hole bleeding. The histological examination revealed that the intimal tissue was restored well over the intraluminal surface of the explanted SF/TPU sheet, the absence of calcium deposition, and minimal inflammatory reaction, without signs of degradation.

Conclusion: The SF/TPU sheet had excellent mechanical properties and tissue biocompatibility. These favorable features and possible biodegradability of the SF portion warrant a long-term follow-up study.
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http://dx.doi.org/10.1007/s00595-017-1615-6DOI Listing
May 2018

Development of a simple device enabling percutaneous flow regulation for a small vascular graft for a Blalock–Taussig shunt capable of flow regulation: complete translation of an original article originally published in Pediatric Cardiology and Cardiac Surgery (154–159, 2016: vol. 32).

Gen Thorac Cardiovasc Surg 2018 03 9;66(3):145-149. Epub 2017 Nov 9.

Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.

Objectives: The Blalock-Taussig shunt (BTS) operation is a cornerstone as initial palliative surgery for congenital heart disease with severely reduced pulmonary blood flow (PBF). The ideal PBF provided by BTS is crucial for an uneventful postoperative course, since excess PBF results in acute distress of the systemic circulation and insufficient PBF requires another BTS surgery. Therefore, the goal of this study was to develop a simple device to control the shunt graft flow percutaneously using a constrictor balloon connected to a subcutaneous port.

Methods: The device consists of a cylindrical balloon and an anti-bending structure extension connected to the balloon center. A PTFE vascular graft wrapped by the device was connected to a simulated closed circuit to measure the relationship between pressure and blood flow while changing the inner volume of the balloon. In a beagle model of replacement of the right carotid artery, blood flow velocity was measured in the carotid artery after saline injection into the balloon. The blood flow velocity before and after balloon inflation was compared immediately after implantation of the device and at 3 months after implantation.

Results: The device provided good flow control by inflating and deflating the balloon ex vivo and in vivo for up to 3 months in a canine model with a small graft wrapped with the device.

Conclusions: The simple device developed in this study may enable regulation of PBF through a small vascular graft and help to prevent severe morbidity and mortality in the clinical setting of BTS.
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http://dx.doi.org/10.1007/s11748-017-0860-3DOI Listing
March 2018

Dose-dependent mortality involving convulsions due to subarachnoid Urografin® injection in rats.

Leg Med (Tokyo) 2017 Nov 30;29:29-33. Epub 2017 Sep 30.

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

An ionically hypertonic contrast medium Urografin® was inadvertently administered into the subarachnoid space of an individual and this resulted in convulsions and acute respiratory failure. We examined the effects of subarachnoid Urografin® injections on the rat central nervous system. The onset and frequency of the convulsions, as well as fatality, were dependent on the amount of Urografin® administered. No convulsions were observed in rats receiving injections of hypertonic NaCl solution or saline. The results confirmed that subarachnoid injections of Urografin® cause convulsions and death, as previously reported in human cases, and our study ascertained the causal relationship between the above malpractice and fatal outcomes.
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http://dx.doi.org/10.1016/j.legalmed.2017.09.004DOI Listing
November 2017

[Three Surgical Cases of Quadricuspid Aortic Valve].

Kyobu Geka 2017 Sep;70(10):811-815

Department of Cardiovascular Surgery, Osaka Medical College, Takatsuki, Japan.

Quadricuspid aortic valve is a rare congenital disease. We experienced 3 surgical cases of quadricuspid aortic valve. Patient 1 was a 72-year-old man who was noted to have a quadricuspid aortic valve associated with aortic regurgitation and an ascending aortic aneurysm(51 mm in diameter). He underwent replacement of the aortic valve and the ascending aorta. Patient 2 was a 71-year-old man with severe aortic stenosis, regurgitation, and coronary triple vessel disease. He underwent aortic valve replacement and coronary artery bypass grafting. Preoperative echocardiography revealed no abnormalities in the number of valve leaflets, but quadricuspid aortic valve was identified during surgery. Patient 3 was a 79-year-old man with severe aortic regurgitation, who underwent aortic valve replacement. In all patients, the 4 valve cusps were approximately of the same size. Multi-detector computed tomography is useful for evaluation of valve morphology. Indication of prophylactic ascending aorta replacement in patients with aortic dilatation requires further study.
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September 2017

Hippocampal neuronal degeneration in the traumatic brain injury mouse: non-trivial effect of scalp incision.

Neurol Res 2016 Nov 10;38(11):994-1002. Epub 2016 Sep 10.

a Department of Legal Medicine , School of Medicine, Tokyo Women's Medical University , Tokyo , Japan.

Objectives: In experimental models of traumatic brain injury (TBI), posttraumatic hippocampal neuronal degeneration in the cornu ammonis 1 (CA1), and/or the cornu ammonis 3 (CA3) regions are regarded as the most notable phenotypic appearances relating to the pathophysiology of human post-concussion syndrome. However, these morphological changes are often also seen in subjects without TBI, namely 'sham' groups. The frequencies and reasons of appearance of hippocampal neuronal degeneration in mice with TBI and/or sham are not clear.

Methods: We compared the frequencies of hippocampal neuronal degeneration among three groups: TBI (mice with external force impact performed by Marmarou's weight drop model after scalp incision), sham (mice with scalp incision alone), and control (mice with neither external force impact nor scalp incision), using hematoxylin and eosin stain in day 6 (n = 5 in each group.) Isoflurane was used for anesthesia in all mice.

Results: The frequencies were 80, 100, and 20% in CA1, and 20, 40, and 60% in CA3, for TBI, sham, and control, respectively. In CA1, a significant difference of the frequency was observed between sham and control (p = 0.048), but not, between TBI and sham (p = 1.000) in Fisher's exact test. In CA3, no significant difference in the frequency was observed between the three groups.

Conclusion: Scalp incision, rather than external impact force, might affect the CA1 hippocampal neuronal degeneration in mice with TBI. In addition, factor(s) other than external impact force or scalp incision may also cause hippocampal neuronal degeneration in both CA1 and CA3. Careful interpretation is needed concerning hippocampal neuronal degeneration induced by a weight drop device observed in mice with TBI.
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http://dx.doi.org/10.1080/01616412.2016.1228746DOI Listing
November 2016

Investigation of single nucleotide polymorphism loci susceptible to degradation by ultraviolet light.

J Forensic Leg Med 2016 Oct 12;43:120-125. Epub 2016 Aug 12.

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address:

DNA in biological fluids is often degraded by environmental factors. Given that single nucleotide polymorphism (SNP) analyses require shorter amplicons than short tandem repeat (STR) analyses do, their use in human identification using degraded samples has recently attracted attention. Although various SNP loci are used to analyze degraded samples, it is unclear which ones are more appropriate. To characterize and identify SNP loci that are susceptible or resistant to degradation, we artificially degraded DNA, obtained from buccal swabs from 11 volunteers, by exposure to ultraviolet (UV) light for different durations (254 nm for 5, 15, 30, 60, or 120 min) and analyzed the resulting SNP loci. DNA degradation was assessed using gel electrophoresis, STR, and SNP profiling. DNA fragmentation occurred within 5 min of UV irradiation, and successful STR and SNP profiling decreased with increasing duration. However, 73% of SNP loci were still detected correctly in DNA samples irradiated for 120 min, a dose that rendered STR loci undetectable. The unsuccessful SNP typing and the base call failure of nucleotides neighboring the SNPs were traced to rs1031825, and we found that this SNP was susceptible to UV light. When comparing the detection efficiencies of STR and SNP loci, SNP typing was more successful than STR typing, making it effective when using degraded DNA. However, it is important to use rs1031825 with caution when interpreting SNP analyses of degraded DNA.
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http://dx.doi.org/10.1016/j.jflm.2016.08.002DOI Listing
October 2016

Traumatic brain injury decreases serotonin transporter expression in the rat cerebrum.

Neurol Res 2016 Apr 15;38(4):358-63. Epub 2016 Apr 15.

b Department of Legal Medicine , School of Medicine, Tokyo Women's Medical University , Tokyo , Japan.

Objectives: An association has been postulated between traumatic brain injury (TBI) and depression. The serotonin transporter (SERT) regulates the concentration of serotonin in the synaptic cleft and represents a molecular target for antidepressants. We hypothesized that SERT expression in the brain changes following TBI.

Methods: We performed immunohistochemistry, real-time polymerase chain reaction analysis for mRNA and western blot analysis for protein to examine the time-dependent changes in SERT expression in the cerebrum during the first 14 days after TBI, using a controlled cortical impact model in rats.

Results: SERT immunoreactivity in neuronal fibres within the area adjacent to the cortical contusion decreased 1 to 14 days after injury. Significantly decreased SERT mRNA and protein expression were noted in the area adjacent to the cortical contusion 7 days after injury. There were no significant changes in SERT expression in the cingulum of the injured brain.

Discussion: The findings of this study indicate that TBI decreases SERT expression in the cerebral cortex. The decreased levels of SERT expression after TBI may result in decreased serotonin neurotransmission in the brain and indicate a possible relationship with depression following TBI.
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http://dx.doi.org/10.1080/01616412.2015.1110402DOI Listing
April 2016

Surgical treatment of a mycotic pseudoaneurysm of the transverse arch using a rifampicin-impregnated dacron patch in an infant.

J Card Surg 2015 Mar 11;30(3):281-3. Epub 2014 Dec 11.

Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Osaka, Japan.

We describe a case of successful treatment of mycotic pseudoaneurysm of the transverse aortic arch in a male infant. The aneurysm was resected and the defect was repaired using a patch made from a rifampicin-impregnated Dacron graft.
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http://dx.doi.org/10.1111/jocs.12492DOI Listing
March 2015

Changes in dopamine transporter expression in the midbrain following traumatic brain injury: an immunohistochemical and in situ hybridization study in a mouse model.

Neurol Res 2014 Mar;36(3):239-46

Objectives: An association has been suggested between trauma and neurological degenerative diseases. Magnetic resonance imaging has revealed that traumatic brain injury (TBI) can cause primary lesions in the midbrain including the substantia nigra (SN). Dopamine transporter (DAT) is mainly expressed in the SN, ventral tegmental area (VTA), and retrorubral field (RRF) of the ventral midbrain. Previous western blot studies have examined DAT levels in the rat frontal cortex and striatum after a controlled cortical impact (CCI); however, no study has comprehensively examined DAT expression in the midbrain following TBI in an animal model.

Methods: We used immunohistochemistry and in situ hybridization to examine the time-dependent changes in the expression of DAT in the midbrain during the first 14 days after TBI in a mouse CCI model.

Results: The expression of DAT protein in the RRF on the side ipsilateral to the site of injury decreased in 14 days after injury. Dopamine transporter mRNA expression in the RRF on the ipsilateral side decreased in 1, 7, and 14 days and increased in 4 days after injury.

Discussion: These findings indicated that TBI induced changes in DAT expression in the RRF. Because the DAT pumps dopamine (DA) out of the synapse back into the cytosol and maintains DA homeostasis, the decreased expression of DAT after TBI may result in decreased DA neurotransmission in the brain.
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http://dx.doi.org/10.1179/1743132813Y.0000000289DOI Listing
March 2014

Temporal and regional variations in accidental deaths of elderly people in Japan.

Med Sci Law 2013 Jul 28;53(3):172-6. Epub 2013 Jun 28.

Tokyo Women's Medical University, School of Medicine Tokyo, Japan.

To ascertain the characteristics of accidental deaths of elderly people in urban and rural areas, we analyzed the deaths of elderly people over the 10-year period from 2000 to 2009, in three geographic areas: nationwide, in the 23 wards of the metropolis of Tokyo, and in Saga prefecture. In addition, to assess the regional variation in accidental deaths of the elderly, we aggregated the numbers of accidental deaths of elderly people for each of Japan's prefectures in the year 2009 and categorized the deaths by accident type. The results showed that nationwide, deaths due to threats to breathing, falls, and drowning and submersion are increasing, while deaths due to transport accidents are decreasing, indicating a need for measures to prevent deaths from accidents other than transport accidents. In the urban areas of Tokyo's 23 wards, there is an increasing incidence of deaths due to falls, which is likely due to the high number of structures such as buildings and railway stations that elderly people need to negotiate. In urban areas, measures to reduce the incidence of accidental deaths need to focus on improving the physical environment to help prevent falls. In the rural locality of Saga prefecture, increasing numbers of elderly people are dying by drowning and submersion. The results of analysis of accidents in all prefectures of Japan by accident type show that the causes of accidental deaths of elderly people vary regionally, suggesting that accident prevention measures for elderly people need to consider the characteristics of the locality.
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http://dx.doi.org/10.1177/0025802412473596DOI Listing
July 2013

A rat model of changes in dural mast cells and brain histamine receptor H3 expression following traumatic brain injury.

J Clin Neurosci 2012 Mar 25;19(3):447-51. Epub 2012 Jan 25.

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Mast cells can secrete histamine in response to extrinsic stimuli. Histamine plays a role in the development of brain edema and can induce histamine receptor H3 (HRH3) expression in the brain to provide protective feedback effects against histamine neurotoxicity. We investigated time-dependent changes in dural mast cell numbers and HRH3 expression in the brain for one to 14 days after traumatic brain injury in a controlled cortical impact model in the rat. The number of tryptase-immunoreactive dural mast cells at the site of impact was significantly decreased one and four days after the injury. Furthermore, immunoreactivity and messenger RNA (mRNA) expression of HRH3 at the underlying cortical contusion site were significantly increased one and four days after the injury. These data suggest that histamine released from degranulated unstainable mast cells induces a transient increase in presynaptic autoinhibitory HRH3 immunoreactivity and mRNA expression as a mechanism to counteract histamine neurotoxicity.
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http://dx.doi.org/10.1016/j.jocn.2011.06.033DOI Listing
March 2012

Frequent detection of stomach contents in accidental drowning.

Med Sci Law 2011 Jul;51(3):161-3

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

We analysed forensic autopsies of 536 consecutive adults to determine the relationship between the presence of stomach contents and the manner of death. Stomach contents were identified in 27 (79.4%) of 34 accidental drownings and in 22 (43.1%) of 51 suicidal drownings (P < 0.01). Accidental drowning was the manner of death most frequently associated with the presence of stomach contents, and stomach contents were found significantly more often in this type of death than in suicidal drowning. These findings indicate that food intake is a factor possibly related to accidental drowning and suggest that fasting may be required before swimming or taking a bath to prevent accidental drowning.
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http://dx.doi.org/10.1258/msl.2011.010150DOI Listing
July 2011

Accidental deaths occurring in bed: review of cases and proposal of preventive strategies.

J Forensic Nurs 2011 Sep;7(3):130-6

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

The bed is thought to be a safe place, but posses a number of risks that can cause deaths. To identify the causes of accidental death in bed and propose strategies for the prevention of further accidents, we surveyed and analyzed the literature on accidental deaths in bed from Japan and abroad, as well as legal cases related to accidental death in bed in Japan. A search of the medical literature in Japan (1983-2007), abroad (1976-2007), and Japan's legal cases (1989-2007) located 39 cases. The vast majority of accidental deaths in bed occur among infants and elderly individuals with neurologic disorders. The main causes of death within these two groups are head injuries caused by falls from a bed and asphyxia caused by pressure to the neck when wedged against a bed rail. It is necessary to focus on prevention of falls from bed and prevention of asphyxia caused by bed rails in the case of infants and elderly individuals with neurologic disorders. Infants should be placed to sleep in beds designed for their ages and placed on their back. Elderly individuals need to sleep in beds with properly fitting bed rails to reduce wedging.
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http://dx.doi.org/10.1111/j.1939-3938.2011.01109.xDOI Listing
September 2011

Analysis of pituitary lesions in fatal closed head injury.

Am J Forensic Med Pathol 2012 Sep;33(3):206-10

Department of Legal Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

We analyzed forensic autopsy findings of 66 consecutive patients with fatal closed head injury who survived up to 48 days after trauma to ascertain the causal factors and the time course of development of posttraumatic pituitary lesions. Pituitary lesions were identified in 27 patients. In patients with pituitary lesions, posterior lobe hemorrhage was observed in 21 patients, followed by anterior lobe hemorrhage in 10 patients and anterior lobe infarct in 7 patients. Comparisons between patients with and without pituitary lesions showed that falls and subdural hematoma were significantly frequent in patients with pituitary lesions. Immunohistochemistry of neurophysin showed increased immunoreactivity in the hypothalamus of patients with pituitary lesions and brain edema, providing morphologic evidence of pituitary dysfunction. Hemorrhage in the anterior or posterior lobe was identifiable in patients with short survival periods, whereas infarct in the anterior lobe appeared in patients surviving at least 14 hours. These data further our understanding of the mechanisms of pituitary dysfunctions and help in the estimation of the survival period after head trauma.
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http://dx.doi.org/10.1097/PAF.0b013e3181fe33e8DOI Listing
September 2012

Aggressive angiomyxoma mimicking inguinal hernia in a man.

Int J Clin Oncol 2009 Aug 25;14(4):365-8. Epub 2009 Aug 25.

Department of Urology, Azumino Red Cross Hospital, 5685 Toyoshina, Azumino, Nagano, Japan.

We report the case of a 37-year-old Japanese man who presented with a left lower abdominal mass that was initially interpreted clinically as an inguinal hernia. The patient reported a swelling in his left lower abdomen over the past 6 months. Magnetic resonance imaging revealed a left inguinal mass extending from the left spermatic cord to the left inguinal subcutaneous layer. Local excision was performed, with a preoperative diagnosis of benign soft tissue tumor. Histopathological diagnosis revealed aggressive angiomyxoma (AAM), and no recurrence was observed 6 months after surgery. AAM is a rare tumor which most commonly occurs in the pelvis or perineum of premenopausal women, with extremely rare cases in men. The findings from previously reported cases and our case suggest that AAM should be considered in patients with an inguinal or scrotal swelling with a suspicious soft tissue tumor.
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http://dx.doi.org/10.1007/s10147-008-0850-7DOI Listing
August 2009

A case of generalized hypoxic brain damage following traumatic brain damage.

Leg Med (Tokyo) 2005 Mar;7(2):117-21

Section of Forensic Medicine, Department of International Health Development, Division of Public Health, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.

In forensic autopsy cases, transient brain hypoxia can be induced by cardiac arrest, hypovolemic shock, and other conditions with severe circulatory failure. Although cortical laminar necrosis in watershed areas between territories of the major cerebral arteries is occasionally seen, cases with global hypoxic damage to the brain is rare, because patients with irreversible severe brain damage rarely survive for more than a few days. In this report we describe autopsy results for an injury victim who survived unconscious for approximately 4 weeks after admission. Macroscopic thinning of the gray matter and uniformly cheesecake-like cloudy changes in white matter were observed. Microscopically, cortical laminar necrosis was observed in all lobes of the cerebrum, and massive gliosis was diffused throughout the white matter. We speculate that traumatic brain damage, continuous hypoxemia, and many other factors induced these characteristic pathological changes during the long time interval from brain damage to death.
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http://dx.doi.org/10.1016/j.legalmed.2004.10.003DOI Listing
March 2005

Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of female Long-Evans Cinnamon rats, a model of Wilson disease.

J Nutr Biochem 2004 May;15(5):273-80

Department of Preventive Nutraceutical Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.

In the Long-Evans Cinnamon rat, copper accumulates in the liver because of a mutation in the copper-transporting ATPase gene, and peroxidative stresses are supposed to be augmented. We examined the effects of dietary fatty acids on hepatitis, hepatic gene expression, and survival. Rats were fed a conventional, low-fat diet (CE2), a CE2 diet supplemented with 10 wt% of lard (Lar), high-linoleic soybean oil (Soy), or a mixture of docosahexaenoic acid (DHA)-rich fish oil and soybean oil (DHA/Soy). Among female rats, the mean survival times of the DHA/Soy and the Soy groups were longer by 17 approximately 20% than in the Lar and the CE2 groups. Among male rats, the survival times were much longer than in the females, but no significant difference in survival was observed among the dietary groups. Serum ceruloplasmin levels in female and male rats of all of the dietary groups were similar. Serum transaminase levels of the DHA/Soy group tended to be lower than in the CE2 group. Histological examinations revealed a marked degeneration in hepatic tissue integrity in the Lar and CE2 groups but not in the DHA/Soy group. Hepatic levels of metal-related genes, transferrin and ceruloplasmin, as well as those related to bile acid synthesis were up-regulated, and an inflammation-related gene (cyclooxygenase [COX]-2) was down-regulated in the DHA/Soy group. Some proliferation-related genes were also affected by the dietary fatty acids. These results indicate that polyunsaturated fatty acids suppress the development of acute hepatitis and prolong survival in females, regardless of whether they are of the n-6 or n-3 type, which are associated with altered gene expressions.
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http://dx.doi.org/10.1016/j.jnutbio.2003.11.005DOI Listing
May 2004

Changes in blood flow and function of the liver after right portal vein embolization.

Arch Surg 2002 Dec;137(12):1384-8

First Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.

Hypothesis: Abrupt occlusion of hemihepatic portal vein induced by preoperative portal vein embolization (PVE) may result in drastic alterations in blood flow and functional mass of the liver.

Design: Prospective study investigating the outcome of an intervention (PVE).

Setting: University tertiary-care referral center.

Patients: Thirteen patients who underwent PVE before extended right hepatectomy.

Main Outcome Measures: The functional plasma flow and functional mass of the liver as well as the volumes of the left and right lobes were assessed before and after PVE. The functional plasma flow and functional mass of the liver were estimated by measuring the hepatic clearances of sorbitol (a high-extraction drug) and antipyrine (a low-extraction drug), respectively. The liver lobar volumes were measured by computed tomography.

Results: Hepatic plasma clearance of sorbitol (mean +/- SD; before PVE, 632.9 +/- 142.9 mL/min; day 14, 620.2 +/- 138.3 mL/min; not significant by 1-way repeated analysis of variance) and that of antipyrine (before PVE, 27.3 +/- 12.0 mL/min; day 14, 27.9 +/- 13.6 mL/min; P =.85, by paired t test) were stable after PVE. Fourteen days after PVE, the non-PVE-treated lobe was enlarged (mean +/- SD, 137% +/- 30%) and the PVE-treated lobe was atrophic (mean +/- SD, 87% +/- 15%); however, the total liver volume did not change significantly.

Conclusions: The functional mass and plasma flow of the entire liver were stable after PVE despite the drastic change in the lobar distribution of the portal blood flow, whereas the non-PVE-treated lobe increased significantly in size. Our findings suggest that PVE leads to an increase in both the volume and the functional capacity of the non-PVE-treated lobe.
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http://dx.doi.org/10.1001/archsurg.137.12.1384DOI Listing
December 2002

Securing a small-caliber pancreatic duct for longitudinal pancreatojejunostomy.

Hepatogastroenterology 2002 Jul-Aug;49(46):1139-40

First Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 3908621, Japan.

In patients with chronic pancreatitis, surgical therapy is indicated for intractable pain. There is no definite opinion about the diameter of the pancreatic duct when deciding the necessity for some forms of surgery. In some patients with a small-caliber duct, ductal decompression is also necessary for the relief of refractory pain. Ultrasound-guided needle puncture provides an easy approach for opening the dilated duct, but in the case of a small-caliber duct, needle puncture alone is insufficient. Insertion of a guide-wire into the duct can secure the ductal cavity, even if the duct is not markedly dilated. Using this technique, with or without intravenous administration of secretin, we have performed longitudinal ductal opening in some patients with chronic pancreatitis. We describe our reliable technique for opening of a small pancreatic duct, and the results we obtained in our series.
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February 2003