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1.
Cell ; 147(2): 261-2, 2011 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-22000005

RESUMO

Opioids such as morphine numb pain but often concomitantly induce itch. Liu et al. (2011) now separate the sensation of itch from opioid-induced analgesia, showing that in a subset of spinal neurons, morphine directly induces itch by signaling through a heteromer of opioid- and itch-mediating G protein-coupled receptors.

2.
J Biol Chem ; 300(2): 105630, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199568

RESUMO

Sterile alpha and toll/interleukin receptor motif-containing 1 (SARM1) is a critical regulator of axon degeneration that acts through hydrolysis of NAD+ following injury. Recent work has defined the mechanisms underlying SARM1's catalytic activity and advanced our understanding of SARM1 function in axons, yet the role of SARM1 signaling in other compartments of neurons is still not well understood. Here, we show in cultured hippocampal neurons that endogenous SARM1 is present in axons, dendrites, and cell bodies and that direct activation of SARM1 by the neurotoxin Vacor causes not just axon degeneration, but degeneration of all neuronal compartments. In contrast to the axon degeneration pathway defined in dorsal root ganglia, SARM1-dependent hippocampal axon degeneration in vitro is not sensitive to inhibition of calpain proteases. Dendrite degeneration downstream of SARM1 in hippocampal neurons is dependent on calpain 2, a calpain protease isotype enriched in dendrites in this cell type. In summary, these data indicate SARM1 plays a critical role in neurodegeneration outside of axons and elucidates divergent pathways leading to degeneration in hippocampal axons and dendrites.


Assuntos
Proteínas do Domínio Armadillo , Proteínas do Citoesqueleto , Neurônios , Animais , Camundongos , Proteínas do Domínio Armadillo/genética , Proteínas do Domínio Armadillo/metabolismo , Axônios/metabolismo , Calpaína/metabolismo , Proteínas do Citoesqueleto/metabolismo , Dendritos/metabolismo , Neurônios/metabolismo , Transdução de Sinais
3.
Heart Vessels ; 37(12): 2093-2100, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35842560

RESUMO

In the transcatheter aortic valve implantation (TAVI) era, the indications for balloon aortic valvuloplasty (BAV) are increasing. Previously, the INOUE-BALLOON® (IB) was used only for antegrade BAV, but recently, it has also been used for retrograde BAV. However, the safety and feasibility of retrograde BAV using an IB are not fully understood. In this study, we investigated the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe aortic stenosis (AS). We compared 39 cases of retrograde BAV using an IB performed from June 2018 to September 2020 and 34 cases of antegrade BAV using an IB performed from August 2013 to May 2018. The total number of complications was lower in retrograde BAV than in antegrade BAV (p = 0.020). The procedure time was significantly shorter in retrograde BAV than in antegrade BAV (p < 0.001), and the maximum balloon size and number of balloon inflations were smaller in retrograde BAV than in antegrade BAV (p = 0.002 and p < 0.001, respectively). There was no significant difference in the degree of improvement in the aortic valve area or ejection fraction between retrograde and antegrade BAV. In conclusion, the present study showed the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe AS compared with antegrade BAV using an IB.


Assuntos
Estenose da Valva Aórtica , Valvuloplastia com Balão , Substituição da Valva Aórtica Transcateter , Humanos , Idoso , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Estudos de Viabilidade , Valvuloplastia com Balão/efeitos adversos , Resultado do Tratamento , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estudos Retrospectivos
4.
Circ J ; 85(4): 345-350, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33597321

RESUMO

BACKGROUND: When an internal iliac artery (IIA) has to be embolized during endovascular aneurysm repair (EVAR), buttock claudication sometimes poses problems. However, there is no established method to evaluate intraoperative blood flow to the gluteal muscles.Methods and Results:Gluteal regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy (NIRS) during surgery, and changes in rSO2were compared with treatment results. Twenty-seven patients who underwent EVAR and IIA embolization at our institution between April 2019 and May 2020 were included in this study. The association between intraoperative changes in rSO2and postoperative incidence of buttock claudication was analyzed. Furthermore, the presence or absence of communication between the superior and inferior gluteal arteries and the intraoperative changes in rSO2were compared to ascertain whether rSO2reflects blood flow change. Postoperative buttock claudication occurred in 4 of 19 patients (21%) with unilateral occlusion of IIA and in 4 of 8 patients (50%) with bilateral occlusion of IIAs. rSO2was found to decrease significantly further in patients with buttock claudication than in patients without buttock claudication (-15±12% vs. -4±16%, P<0.05). In addition, rSO2was predominantly lower in patients without the communication between the superior and inferior gluteal arteries than in those with the communication. CONCLUSIONS: Gluteal rSO2is useful as an indicator of intraoperative gluteal blood flow.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Nádegas/irrigação sanguínea , Procedimentos Endovasculares , Aneurisma Ilíaco , Aneurisma da Aorta Abdominal/cirurgia , Humanos , Aneurisma Ilíaco/cirurgia , Artéria Ilíaca/cirurgia , Claudicação Intermitente/terapia , Saturação de Oxigênio , Estudos Retrospectivos , Resultado do Tratamento
5.
J Bone Miner Metab ; 38(5): 710-717, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409847

RESUMO

INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe the changes in bone microarchitecture over time in vivo. In this study, the process of fracture healing was analyzed using HR-pQCT in patients with distal radius fracture who underwent osteosynthesis. MATERIALS AND METHODS: A total of 10 fracture sites identified from four patients with a distal radius fracture who underwent internal fixation with a volar locking plate (mean age 68.8 years, all women) were investigated. HR-pQCT was performed within a week (baseline) 4, 12, and 24 weeks after fracture. Rectangular region of interest (ROI) was established in the fracture site, inner callus, and external callus area, and the changes in bone mineral density (BMD) in each region were analyzed. RESULTS: From baseline to 24 weeks post-fracture, the BMD changed from 105.5 (95% CI 98.6-113) to 428.0 (331-554) mgHA/ccm at the fracture site, from 111.0 (104-119) to 375.3 (290-486) mgHA/ccm at the inner callus area, and from 98.5 (91.6-106) to 171.6 (132-222) mgHA/ccm at the external callus area. The BMD increased at the fracture site and inner callus area, but increased only slightly at the external callus area. At 24 weeks post-fracture, the BMD at the fracture site and inner callus area was significantly higher than the external callus area. CONCLUSION: In the healing process of postoperative distal radius fractures, increased BMD at the inner surface of the fracture site was confirmed in all fractures. Bone formation on the endosteal side may be a necessary condition for bone union of distal radius fractures.


Assuntos
Consolidação da Fratura , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/patologia , Tomografia Computadorizada por Raios X , Absorciometria de Fóton , Idoso , Densidade Óssea , Feminino , Humanos , Imageamento Tridimensional , Pessoa de Meia-Idade , Fatores de Tempo
6.
J Bone Miner Metab ; 38(1): 78-85, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31414282

RESUMO

The RDT population, initially at 215 patients, exceeded 300,000 in 2011, with a total of 329,609 patients at the end of December 2016. In our Institute, the number of patients with destructive spondylosis is increasing with the increase in the number of dialysis patients in Japan. We had 14 Cases in the 1990s, and then 82 cases in the 2000s and have already had 131 cases in the 2010s. The purpose of this study was to investigate the incidence of dialysis-related amyloidosis (DRA) such as destructive spondyloarthropathy (DSA), dialysis amyloid arthropathy (DAA), and carpal tunnel syndrome (CTS). In addition, another purpose was to examine the risk factors of the DRA. DAA made its own assessment on radiographs based on stage. Survey items were patient's basic data, laboratory data and X-ray view. Patient's basic data included such as sex, age, height, and weight and RDT-related factors such as kidney disease that led to RDT, age at start of RDT, RDT history, medical history (past and present), and history of surgery. The frequency of DRA was examined by medical history and radiological examination in 199 dialysis patients who obtained informed consent. The patients were divided into two groups according to the presence or absence of DRA, and risk factors of DRA were investigated from the medical history, basic data of patients, and blood tests. Of the 199 patients on regular dialysis therapy, 41 (20.6%) showed DRA. Based on the X-ray images, 21 patients (10.6%) showed DSA, while 22 patients (11.1%) showed DAA. Sixteen patients (8.0%) had CTS, determined through a history of surgery. Regarding overlap of conditions, 14 had both DSA and DAA, 3 had both DSA and CTS, and 2 had both DAA and CTS. There were statistically significant differences between the two groups in the cause of disease in Chronic glomerulonephritis and Diabetic Nephropathy, age at the start of RDT, period of RDT, body weight, blood platelet count, and blood Ca level. When multivariate analysis was performed on these items, statistical differences were recognized only during the dialysis period. In conclusion, long dialysis period was a risk factor for DRA.


Assuntos
Amiloidose/epidemiologia , Amiloidose/etiologia , Síndrome do Túnel Carpal/epidemiologia , Síndrome do Túnel Carpal/etiologia , Diálise Renal/efeitos adversos , Espondiloartropatias/epidemiologia , Espondiloartropatias/etiologia , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico por imagem , Síndrome do Túnel Carpal/diagnóstico por imagem , Análise Fatorial , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Espondiloartropatias/diagnóstico por imagem , Adulto Jovem
7.
Circ J ; 84(10): 1862-1865, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32814725

RESUMO

BACKGROUND: There is insufficient evidence regarding the optimal treatment method for distal deep vein thrombosis (DVT), including indications for anticoagulation therapy. Treatment results of patients with distal DVT were evaluated to clarify the risk factors that result in extension of distal DVT to the proximal vein and indications for anticoagulation therapy.Methods and Results:Among 430 patients with DVT between January 2018 and December 2019, 253 were diagnosed with distal DVT; 41 patients who had already started anticoagulation therapy were excluded, and the remaining 212 were included as study subjects. Anticoagulation therapy was not started immediately; conservative treatment with compression stockings was performed. Ultrasonography after 2 weeks revealed thrombus disappearance in 39 patients (21%), and thrombus reduction in 38 patients (20%). In contrast, extension of thrombus to the proximal vein was noted in 12 patients (6.3%) and anticoagulation therapy was commenced. After 3 months, the thrombus had disappeared in 75 patients (52%). No patient developed pulmonary thromboembolism during follow-up. With respect to the risk factors for extension to proximal vein during conservative treatment, active cancer (P=0.03), prolonged bed rest (P<0.01), and D-dimer level >8µg/mL (P=0.01) were identified. CONCLUSIONS: It is reasonable to consider anticoagulation therapy in distal DVT patients with active cancer, prolonged bed rest or high D-dimer level.


Assuntos
Anticoagulantes/uso terapêutico , Tratamento Conservador/métodos , Progressão da Doença , Neoplasias/complicações , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Seguimentos , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar , Estudos Retrospectivos , Fatores de Risco , Comportamento Sedentário , Meias de Compressão , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagem
8.
Nature ; 509(7502): 622-6, 2014 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-24717433

RESUMO

How we sense touch remains fundamentally unknown. The Merkel cell-neurite complex is a gentle touch receptor in the skin that mediates slowly adapting responses of Aß sensory fibres to encode fine details of objects. This mechanoreceptor complex was recognized to have an essential role in sensing gentle touch nearly 50 years ago. However, whether Merkel cells or afferent fibres themselves sense mechanical force is still debated, and the molecular mechanism of mechanotransduction is unknown. Synapse-like junctions are observed between Merkel cells and associated afferents, and yet it is unclear whether Merkel cells are inherently mechanosensitive or whether they can rapidly transmit such information to the neighbouring nerve. Here we show that Merkel cells produce touch-sensitive currents in vitro. Piezo2, a mechanically activated cation channel, is expressed in Merkel cells. We engineered mice deficient in Piezo2 in the skin, but not in sensory neurons, and show that Merkel-cell mechanosensitivity completely depends on Piezo2. In these mice, slowly adapting responses in vivo mediated by the Merkel cell-neurite complex show reduced static firing rates, and moreover, the mice display moderately decreased behavioural responses to gentle touch. Our results indicate that Piezo2 is the Merkel-cell mechanotransduction channel and provide the first line of evidence that Piezo channels have a physiological role in mechanosensation in mammals. Furthermore, our data present evidence for a two-receptor-site model, in which both Merkel cells and innervating afferents act together as mechanosensors. The two-receptor system could provide this mechanoreceptor complex with a tuning mechanism to achieve highly sophisticated responses to a given mechanical stimulus.


Assuntos
Canais Iônicos/metabolismo , Mecanotransdução Celular , Células de Merkel/metabolismo , Tato/fisiologia , Potenciais de Ação , Animais , Condutividade Elétrica , Feminino , Técnicas In Vitro , Canais Iônicos/deficiência , Canais Iônicos/genética , Masculino , Mecanotransdução Celular/genética , Camundongos , Camundongos Knockout , Neuritos/metabolismo , Neurônios Aferentes/metabolismo , Pele/citologia , Pele/inervação , Tato/genética
9.
Heart Vessels ; 35(1): 46-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31278424

RESUMO

Our prospective study was therefore designed to determine which part of the systemic inflammatory response after cardiac operations resulted from Cardiopulmonary bypass (CPB) in neonates and infants. After approval by the human ethical committee of the Gunma Children's Medical Center (GCMC) and informed consent of the parents, 40 consecutive term congenital heart disease patients aged until 1 year who underwent long CPB time (> 3 h) at surgery were included in the prospective study between January 2012 and December 2014. C1 esterase inhibitor (C1-inh) drug (@Berinert) was generously provided by CSL Behring (King of Prussia, PA). The C1-inh (20 IU/kg) was given intravenously 60 min after CPB. Blood samples for complement factors were obtained before and 48 h after administration of C1-inh. Six patients did not survive and their data were not included. Of 34 patients included, median age was 6.5 months, median body weight was 6050 g, and 16 (47%) were female. According to the Mann-Whitney U test, there were no differences between the two groups concerning demographic and intraoperative data, postoperative chemical data. C1q concentration was only significant lower in patients with C1-inh non-treated group than in patients with C1-inh treated group. But, the consumption of C1q, C3, C4, CH50, and C1-inh in patients with C1-inhibitor non-treated group was observed early postoperatively. There is a significant difference in the values before and after C1-inh treatment between the two groups. The lower value in the C1-inh-treated group is explained by the activation of the classical pathway through the replenishment of complements by C1-inh treatment. This study proposes the administration of C1-inh is an effective therapy to reduce the activation and improve the clinical capillary leak syndrome.


Assuntos
Síndrome de Vazamento Capilar/prevenção & controle , Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Ativação do Complemento/efeitos dos fármacos , Proteína Inibidora do Complemento C1/administração & dosagem , Inativadores do Complemento/administração & dosagem , Cardiopatias Congênitas/cirurgia , Síndrome de Resposta Inflamatória Sistêmica/prevenção & controle , Administração Intravenosa , Síndrome de Vazamento Capilar/sangue , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/imunologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Proteína Inibidora do Complemento C1/efeitos adversos , Inativadores do Complemento/efeitos adversos , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/imunologia , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Estudos Prospectivos , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Fatores de Tempo , Resultado do Tratamento
10.
Int Heart J ; 61(5): 979-983, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921662

RESUMO

The Fontan procedure is a palliative surgery performed for patients with complex congenital heart disease who exhibit functional single ventricular physiology. Although clinical outcomes of the Fontan procedure have improved in recent years and most patients who undergo the procedure reach adulthood, Fontan-associated liver disease (FALD) is a noncardiovascular complication that has become increasingly common; its risk factors remain unknown.A total of 95 patients who underwent the Fontan procedure and who were followed up for at least three years at Gunma Children's Medical Center and Kitasato University Hospital between 1996 and 2015 were retrospectively enrolled in this study.The mean age of the patients at the time of Fontan procedure was 2.3 ± 1.4 years. Overall, 21 patients (23.1%) experienced FALD. All Fontan procedures were performed with extracardiac total cavopulmonary connection using 16-mm expanded polytetrafluoroethylene grafts. The presence of systemic right ventricle, requirement of pulmonary vasodilator, application of a non-fenestrated Fontan procedure, and absence of fenestration flow at the time of follow-up catheter examination were identified as predictors of FALD using univariate analysis. All these factors, except the requirement of pulmonary vasodilator, remained significant predictors of FALD in multivariate logistic regression analysis.Patients with a systemic right ventricle who undergo the Fontan procedure are at a high risk of FALD in the mid-term. Creating fenestration at the time of Fontan and maintaining the fenestration flow may reduce the mid-term risk of FALD.


Assuntos
Técnica de Fontan/métodos , Cardiopatias Congênitas/cirurgia , Hepatopatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Vasodilatadores/uso terapêutico , Adolescente , Alanina Transaminase/sangue , Anastomose Cirúrgica/métodos , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Pressão Venosa Central/fisiologia , Criança , Pré-Escolar , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Lactente , Hepatopatias/sangue , Modelos Logísticos , Masculino , Análise Multivariada , Complicações Pós-Operatórias/sangue , Estudos Retrospectivos , Fatores de Risco , Resistência Vascular
11.
Blood Purif ; 47 Suppl 2: 19-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943515

RESUMO

BACKGROUND/AIM: In this study, we compared the dialysis efficiency, oxidative stress, and nutritional conditions between predilution on-line hemodiafiltration (pre-OL-HDF) and conventional hemodialysis (HD) using a super-flux dialyzer (CHD). METHOD: This was a crossover study of 38 maintenance HD patients. All patients were treated with CHD for the first 4 months (1st CHD period), then were switched to pre-OL-HDF for 4 months (pre-OL-HDF period), and were returned to CHD for the next 4 months (2nd CHD period). RESULTS: We found no significant difference in the removal ratio of small uremic substances or the indices of inflammation or nutritional states between the pre-OL-HDF and CHD periods. However, we found higher removal of ß2 micro-globulin in the pre-OL-HDF period, and the human mercapto-albumin (Alb)/human serum Alb ratio was significantly higher in the pre-OL-HDF period. CONCLUSION: Treatment with pre-OL-HDF enabled enhanced removal of middle molecule uremic toxins and better Alb redox than did CHD.


Assuntos
Hemodiafiltração/métodos , Estresse Oxidativo , Albumina Sérica Humana/isolamento & purificação , Compostos de Sulfidrila/isolamento & purificação , Toxinas Biológicas/isolamento & purificação , Idoso , Estudos Cross-Over , Feminino , Hemodiafiltração/economia , Hemodiafiltração/instrumentação , Humanos , Inflamação/sangue , Nefropatias/sangue , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Oxirredução , Albumina Sérica Humana/análise , Compostos de Sulfidrila/análise , Toxinas Biológicas/sangue
13.
Surg Today ; 48(8): 748-755, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29549520

RESUMO

PURPOSE: To evaluate the safety and efficacy of our new delayed sternal closure (DSC) method, involving sternal semi-closure using a bioresorbable osteosynthesis device and complete skin closure. METHODS: Between 2013 and 2017, 36 patients underwent DCS at our hospital. The patients were divided into two groups based on the method used for DSC. The later conventional DSC group consisted of 18 patients undergoing late complete sternal closure following fixation of pulmonary and hemodynamic instability, and the new DSC group consisted of 18 patients undergoing early sternal semi-closure a few days after surgery. In the new DSC group, the sternum was fixed with Super Fixsorb MX40, followed by complete skin closure. RESULTS: Respiratory and hemodynamic conditions, such as systolic blood pressure, cardiac index, tidal volume, and regional oxygen saturation, were significantly more stable in the new DCS group than in the conventional DSC group. The hospital stay was also significantly shorter in the new DSC group. Although there were no serious complications, one patient from the new DCS group suffered deformity of the sternum, which was managed successfully. CONCLUSION: The sternal semi-closure method decreases pulmonary and cardiac instability during DSC, making early DSC possible.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais , Implantes Absorvíveis , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas/cirurgia , Esterno/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Esternotomia/métodos
14.
J Biol Chem ; 291(4): 1719-1734, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26589795

RESUMO

Diverse lines of evidence suggest that amyloid-ß (Aß) peptides causally contribute to the pathogenesis of Alzheimer disease (AD), the most frequent neurodegenerative disorder. However, the mechanisms by which Aß impairs neuronal functions remain to be fully elucidated. Previous studies showed that soluble Aß oligomers interfere with synaptic functions by depleting NMDA-type glutamate receptors (NMDARs) from the neuronal surface and that overexpression of the receptor tyrosine kinase EphB2 can counteract this process. Through pharmacological treatments and biochemical analyses of primary neuronal cultures expressing wild-type or mutant forms of EphB2, we demonstrate that this protective effect of EphB2 depends on its PDZ-binding motif and the presence of neuronal activity but not on its kinase activity. We further present evidence that the protective effect of EphB2 may be mediated by the AMPA-type glutamate receptor subunit GluA2, which can become associated with the PDZ-binding motif of EphB2 through PDZ domain-containing proteins and can promote the retention of NMDARs in the membrane. In addition, we show that the Aß-induced depletion of surface NMDARs does not depend on several factors that have been implicated in the pathogenesis of Aß-induced neuronal dysfunction, including aberrant neuronal activity, tau, prion protein (PrP(C)), and EphB2 itself. Thus, although EphB2 does not appear to be directly involved in the Aß-induced depletion of NMDARs, increasing its expression may counteract this pathogenic process through a neuronal activity- and PDZ-dependent regulation of AMPA-type glutamate receptors.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Receptor EphB2/química , Receptor EphB2/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Doença de Alzheimer/genética , Motivos de Aminoácidos , Animais , Células Cultivadas , Feminino , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Neurônios/química , Domínios PDZ , Ligação Proteica , Receptor EphB2/genética , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/genética
15.
Cancer Sci ; 108(3): 488-496, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28075524

RESUMO

T-lymphokine-activated killer cell-originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA-mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC50 ; 0.4-42.6 nM) and led to their apoptotic cell death. TOPK inhibition caused cell morphologic changes in SCLC cells, elongation of intercellular bridges caused by cytokinesis defects or neuronal protrusions induced by neuronal differentiation in a subset of CSC-like SCLC cells. Treatment with OTS514 suppressed forkhead box protein M1 (FOXM1) activity, which was involved in stemness of CSC. Furthermore, OTS514 treatment reduced CD90-positive SCLC cells and showed higher cytotoxic effect against lung sphere-derived CSC-like SCLC cells. Collectively, our results suggest that targeting TOPK is a promising approach for SCLC therapy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinolonas/farmacologia , Carcinoma de Pequenas Células do Pulmão/patologia , Tiofenos/farmacologia , Proliferação de Células/genética , Proteína Forkhead Box M1/antagonistas & inibidores , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Células-Tronco Neoplásicas/patologia , Interferência de RNA , RNA Interferente Pequeno/genética , Esferoides Celulares/efeitos dos fármacos , Antígenos Thy-1/metabolismo , Células Tumorais Cultivadas
16.
Pathol Int ; 67(2): 99-104, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28093881

RESUMO

Ciliated muconodular papillary tumor (CMPT) is a rare papillary tumor that arises in the peripheral lung fields and is associated with the proliferation of ciliate d and goblet cells and increased mucin production. We report a case of CMPT involving the rearrangement of the anaplastic lymphoma kinase (ALK) gene. The patient was an 84-year-old Japanese female who had exhibited a small nodular shadow on chest computed tomography during a regular checkup 10 years ago. She underwent a partial resection of segment S10 of the right lung. The cut surface of the surgical specimen revealed a well-circumscribed, jelly-like mass measuring 8 × 8 × 10 mm. Histologically, the tumor was composed of a mixture of ciliated, goblet, and basal cells arranged in a papillary pattern together with pools of mucin. A diagnosis of CMPT was made. The lung tumor cells were subjected to fluorescent in situ hybridization and highly sensitive immunohistochemical staining for the ALK protein, both of which produced positive results. CMPT usually follows a favorable course, but the exact nature of this tumor; i.e., whether it is benign or malignant, has not been established. This is the first reported case of an ALK-positive CMPT.


Assuntos
Carcinoma Papilar/patologia , Neoplasias Pulmonares/patologia , Receptores Proteína Tirosina Quinases/genética , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais , Carcinoma Papilar/genética , Feminino , Células Caliciformes/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/genética , Mucinas , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Neoplasias do Colo do Útero/patologia
17.
Biologicals ; 46: 68-73, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28162840

RESUMO

Aggregates of human plasma-derived intravenous immunoglobulins (IVIGs) carries a risk of severe adverse events after nonspecific complement activation induced in humans administrated. Therefore, the anti-complementary activity (ACA) test is legally required in every batch of IVIGs in Japan. However, due to the intrinsic nature of this bioassay, there might be large differences in the results of ACA tests from laboratories, even when the same batch of IVIGs was measured. Our six laboratories evaluated whether there were such differences and argued for establishment of a reference material (RM) for standardization of the ACA test. Our results revealed inter-laboratory differences in ACA values, indicating a need to establish an RM. Therefore, after ACA values in candidate RMs were measured collaboratively, one RM was selected from two candidates and unit value-assigned. The RM in fact normalized the ACA test values for samples measured in parallel at almost all the laboratories, when the values were calculated relative to the assigned unit value of the RM. Thus, we established a first RM to standardize the ACA test in Japan, which enabled each laboratory to normalize ACA values constantly for IVIGs. This indicates that the establishment of an RM can contribute to quality control of IVIGs.


Assuntos
Ativação do Complemento/efeitos dos fármacos , Inativadores do Complemento/farmacologia , Imunoglobulinas Intravenosas/farmacologia , Animais , Bioensaio/métodos , Bioensaio/normas , Calibragem , Inativadores do Complemento/normas , Comportamento Cooperativo , Cobaias , Humanos , Imunoglobulinas Intravenosas/normas , Japão , Laboratórios/normas , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Ovinos
18.
Pediatr Int ; 59(2): 141-144, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27378014

RESUMO

BACKGROUND: Electrical velocimetry correlates well with established methods of measuring cardiac output (CO) such as thermodilution and echocardiography. In this study, we compared the cardiac function of children with single right ventricle (SRV) and single left ventricle (SLV) on non-invasive postoperative measurement of hemodynamic parameters using AESCULON® mini. METHODS: Demographic, preoperative, and perioperative data were obtained from medical records. We retrospectively reviewed the AESCULON mini data of 21 patients with single ventricle who underwent Fontan operation. The patients were divided into two groups according to morphologic diagnosis: SRV (n = 9) and SLV (n = 12). The following hemodynamic parameters were analyzed: stroke volume (SV); CO; cardiac index (CI); stroke volume variation (SVV); and ventricular ejection time (VET). RESULTS: Hemodynamic parameters were as follows (SRV vs SLV): heart rate (HR), 140.5 beats/min versus 121 beats/min; SV, 14.5 mL vs 19.9 mL; CO, 2 L/min vs 2.3 L/min; CI, 4.3 L/min/m2 versus 4.4 L/min/m2 ; SVV, 15.5% versus 13.9%; and VET, 167.7 s versus 197.7 s. HR and VET were statistically different between the two groups. CONCLUSIONS: CI does not differ with laterality of the single ventricle. SRV VET, however, was significantly shorter than SLV VET in the acute postoperative period. Conversely, SRV HR was higher than SLV HR, which may mean that SRV compensates for lower VET by increasing HR.


Assuntos
Débito Cardíaco , Cardiografia de Impedância/instrumentação , Técnica de Fontan , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Monitorização Fisiológica/instrumentação , Cuidados Pós-Operatórios/instrumentação , Pré-Escolar , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Humanos , Lactente , Estudos Retrospectivos
19.
J Orthop Sci ; 22(5): 868-873, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28734667

RESUMO

INTRODUCTION: Osteoarthritis of the knee is generally evaluated by plain X-rays, which are incapable of detecting small cartilage damage. There are some patients who have small cartilage defects on MRI with no abnormal findings on plain X-rays. In this study, the prevalence and regional characteristics of cartilage defects detected by MRI were studied in cases with normal X-ray findings (Kellgren-Lawrence grade 0 and 1). Relationships between the cartilage defects and OA risk factors such as obesity and leg alignment were also investigated. METHODS: A total of 51 knees of Kellgren-Lawrence grade 0 or 1 without knee joint pain were included. Fat-suppressed spoiled-gradient recalled (SPGR) sagittal images were scanned by 3 T MRI, and the presence of cartilage damage was confirmed. Cartilage damage was visualized three-dimensionally, and its location and morphology were analyzed. On a full length standing radiograph of the lower extremities, leg alignment and other parameters were measured, and their associations with cartilage damage were analyzed. RESULTS: Cartilage defects were detected in 26% of women aged >50 years. Cartilage damage was located on the medial femoral condyle near the intercondylar notch, and was mostly elliptically shaped in the anteroposterior direction. Subjects with damaged cartilage were not obese and did not have abnormal leg alignment. CONCLUSION: It should be borne in mind that some elderly women may have damaged cartilage on the intercondylar notch side of the medial joint, even though plain X-rays appear normal, and this cannot be predicted by obesity or leg alignment.


Assuntos
Doenças das Cartilagens/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Osteoartrite do Joelho/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade
20.
Arch Orthop Trauma Surg ; 137(3): 303-310, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28132085

RESUMO

PURPOSE: Tibial condylar valgus osteotomy (TCVO) is a type of opening-wedge high tibial osteotomy for advanced medial knee osteoarthritis (OA) with subluxated lateral joint. We report the concept, the current surgical technique with a locking plate, and the short-term clinical and radiological results of this procedure. METHODS: 11 knees with medial OA and a widened lateral joint were treated by TCVO (KL stage III: 6, IV: 5). In this procedure, by the L-shaped osteotomy from the medial side of the proximal tibia to the intercondylar eminence and the valgus correction, lateralization of the mechanical axis and reduction of the subluxated lateral joint are obtained with early postoperative weight-bearing. Before, 6 months, 1, and 5 years after the operation, a visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), alignment of the lower extremity, and congruency and stability of the femorotibial joint were investigated. RESULTS: The VAS improved from an average of 73 mm to 13 mm, and the total WOMAC score from 52 to 14 before to 5 years after the operation, respectively. The mechanical axis changed from 1 to 60%, and the FTA changed from 186° to 171°. The joint line convergence angle (JLCA) changed from 6° to 1°, and the angle difference of JLCA between varus and valgus stress improved from 8° to 4° after the procedure. CONCLUSION: Improvements in pain and activities of daily living were observed by TCVO along with valgus correction of the lower extremity and stabilization of the femorotibial joint.


Assuntos
Placas Ósseas , Geno Valgo/cirurgia , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Tíbia/cirurgia , Atividades Cotidianas , Idoso , Deambulação Precoce , Feminino , Geno Valgo/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Ontário , Osteoartrite do Joelho/diagnóstico por imagem , Medição da Dor , Radiografia , Resultado do Tratamento , Suporte de Carga
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