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1.
J Cancer Res Clin Oncol ; 150(4): 172, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38565653

RESUMO

PURPOSE: Visualizing mitochondria in cancer cells from human pathological specimens may improve our understanding of cancer biology. However, using immunohistochemistry to evaluate mitochondria remains difficult because almost all cells contain mitochondria and the number of mitochondria per cell may have important effects on mitochondrial function. Herein, we established an objective system (Mito-score) for evaluating mitochondria using machine-based processing of hue, saturation, and value color spaces. METHODS: The Mito-score was defined as the number of COX4 (mitochondrial inner membrane) immunohistochemistry-positive pixels divided by the number of nuclei per cell. The system was validated using four lung cancer cell lines, normal tissues, and lung cancer tissues (199 cases). RESULTS: The Mito-score correlated with MitoTracker, a fluorescent dye used to selectively label and visualize mitochondria within cells under a microscope (R2 = 0.68) and with the number of mitochondria counted using electron microscopy (R2 = 0.79). Histologically, the Mito-score of small cell carcinoma (57.25) was significantly lower than that of adenocarcinoma (147.5, p < 0.0001), squamous cell carcinoma (120.6, p = 0.0004), and large cell neuroendocrine carcinoma (111.8, p = 0.002). CONCLUSION: The Mito-score method enables the analysis of the mitochondrial status of human formalin-fixed paraffin-embedded specimens and may provide insights into the metabolic status of cancer.


Assuntos
Formaldeído , Neoplasias Pulmonares , Humanos , Parafina , Inclusão em Parafina , Mitocôndrias , Coloração e Rotulagem
2.
J Med Chem ; 67(7): 5305-5314, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38517948

RESUMO

Squalene synthase is one of the most promising pharmaceutical targets to treat hyperlipidemia. Inhibition of the squalene synthase causes a decrease in the hepatic cholesterol concentration. We have already reported the design and synthesis of highly potent benzhydrol-type squalene inhibitors. Although these templates showed unique and potent cyclic active conformations via intramolecular hydrogen bonds, the in vivo cholesterol-lowering efficacy was insufficient. We attempted to improve their potential as an orally active medicine. In our medicinal chemistry effort, cyclized 11-membered ring templates were acquired. The novel series of compounds exhibited potent squalene synthase inhibitory activity, and one of the derivatives, isomer A-(1S, 3R)-14i, showed plasma lipid-lowering efficacy in hamster and marmoset repeated-dose studies. Our findings provide valuable insights into the design and development of novel and unique 11-membered ring-type highly potent squalene synthase inhibitors.


Assuntos
Anticolesterolemiantes , Cricetinae , Animais , Anticolesterolemiantes/química , Farnesil-Difosfato Farnesiltransferase , Inibidores Enzimáticos/química , Colesterol , Fígado
3.
Clin Nephrol Case Stud ; 11: 87-94, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37363300

RESUMO

We performed a kidney biopsy in a 36-year-old man to evaluate microscopic hematuria and proteinuria. Light microscopy showed increased mesangial matrix and partial swelling of the glomerular basement membrane (GBM), and immunofluorescence showed positive staining only for C3. Immunoelectron microscopy showed that gold particle-labeled C3 was localized in the electron-dense and moderately electron-dense deposits shown by electron microscopy in the mesangium, the thickened GBM near the paramesangium, and the thickened distal portion of the GBM but was not localized in the non-thickened GBM. Gold-labeled immunoglobulin G, κ, and λ were not seen. C3 glomerulonephritis was more evident in gold-labeled electron microscopy, which further clarified the localization of C3 deposition.

4.
Neurol Med Chir (Tokyo) ; 63(2): 73-79, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36599429

RESUMO

Mechanical thrombectomy (MT) is the standard treatment for acute large occlusion of the cerebral artery. Evidence for the success of this procedure was based on the treatment of patients with internal carotid artery and middle cerebral artery thrombi. There are a few reports on thrombi extending to the common carotid artery (CCA). We document our endovascular procedure and the clinical outcome in seven consecutive patients who underwent MT for CCA thrombi between September 2016 and April 2021. Their mean National Institutes of Health Stroke Scale score was 20.0 (range, 9-30), and the mean diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score on magnetic resonance images was 8.7 (range, 7-10). In six patients, MT of the CCA occlusion was successful, and the mean puncture-to-reperfusion time was 84 minutes (range, 39-211 minutes). In five patients, successful reperfusion was obtained. The mean total pass number was 4.1 (range, 2-7). Due to large thrombi, we performed balloon guide catheter (BGC) occlusion in three patients. Sheath occlusion occurred in two, and thrombus migration into the femoral artery around the sheath was observed in two patients. The mean modified Rankin Scale score 3 months post-stroke was 3.6 (range, 2-5). When the removal of a large CCA thrombus is attempted in a single step, catheter and sheath occlusion may occur, and this increases the risk for critical systemic artery occlusion. Therefore, we suggest that MT be combined with the BGC technique and propose the use of a large aspiration catheter to decrease the volume of the thrombus.


Assuntos
Arteriopatias Oclusivas , Isquemia Encefálica , Doenças das Artérias Carótidas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Trombose , Humanos , Trombectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/cirurgia , Procedimentos Endovasculares/métodos , Stents , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/cirurgia
5.
ACS Med Chem Lett ; 13(12): 1885-1891, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36518702

RESUMO

Internal tandem duplication (ITD) in the gene encoding FMS-like tyrosine kinase 3 (FLT3) (FLT3-ITD) is the most frequently observed mutation in acute myeloid leukemia (AML). Currently approved FLT3 kinase inhibitors have high efficacy, but drug resistance caused by reactivation of FLT3 kinase activity is often clinically observed. In this study, we developed novel FLT3 degraders by introducing gilteritinib, an FDA-approved FLT3 inhibitor, into targeted protein degradation technology. The most active compound, CRBN(FLT3)-8, potently degraded FLT3-ITD via the ubiquitin-proteasome system and inhibited the proliferation of FLT3-ITD mutant AML cells more effectively than gilteritinib. These findings provide a new lead compound for degradation-based drugs targeting FLT3-ITD-positive cancers.

6.
New Phytol ; 235(3): 993-1004, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35590479

RESUMO

In forest ecosystems, understanding the relationship between the vertical distribution of fine roots and residual soil nitrogen is essential for clarifying the diversity-productivity-water purification relationship. Vertical distributions of fine-root biomass (FRB) and concentrations of nitrate-nitrogen (NO3 -N) in soil water were investigated in a conifer plantation with three thinning intensities (Control, Weak and Intensive), in which hardwood abundance and diversity were low, moderate and high, respectively. Intensive thinning led to the lowest NO3 -N concentration in soil water at all depths (0-100 cm) and highest FRB at shallow depths (0-50 cm). The NO3 -N concentration at a given depth was negatively correlated with total FRB from the surface to the depth at which NO3 -N concentration was measured, especially at shallow depths, indicating that more abundant fine roots led to lower levels of downward NO3 -N leaching. FRB contributed positively to nitrogen content of hardwood leaves. These findings demonstrate that a hardwood mixture in conifer plantations resulted in sufficient uptake of NO3 -N from soil by well developed fine-root systems, and translocation to canopy foliage. This study suggests that productivity and water purification can be achieved through a hardwood mixture in conifer plantations.


Assuntos
Solo , Traqueófitas , Ecossistema , Nitrogênio/análise , Raízes de Plantas/química , Água
7.
Cancer Sci ; 113(8): 2828-2838, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35579105

RESUMO

BRAF mutations are frequently observed in melanoma and hairy-cell leukemia. Currently approved rapidly accelerated fibrosarcoma (RAF) kinase inhibitors targeting oncogenic BRAF V600 mutations have shown remarkable efficacy in the clinic, but their therapeutic benefits are occasionally hampered by acquired resistance due to RAF dimerization-dependent reactivation of the downstream MAPK pathway, which is known as paradoxical activation. There is also a concern that paradoxical activation of the MAPK pathway may trigger secondary cancer progression. In this study, we developed chimeric compounds, proteolysis targeting chimeras (PROTACs), that target BRAFV600E protein for degradation. CRBN(BRAF)-24, the most effective chimera, potently degraded BRAFV600E in a ubiquitin-proteasome system (UPS)-dependent manner and inhibited the proliferation of BRAFV600E -driven cancer cells. In BRAF wild-type cells, CRBN(BRAF)-24 induced neither BRAFWT degradation nor paradoxical activation of the MAPK pathway. Biochemical analysis revealed that CRBN(BRAF)-24 showed more potent and sustained suppression of MAPK signaling than a BRAFV600E inhibitor, PLX-8394, in BRAFV600E -driven cancer cells. Targeted degradation of BRAFV600E by CRBN(BRAF)-24 could be a promising strategy to evade paradoxical activation of the RAF-MAPK pathway.


Assuntos
Melanoma , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas B-raf , Linhagem Celular Tumoral , Humanos , Sistema de Sinalização das MAP Quinases , Melanoma/tratamento farmacológico , Melanoma/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo
8.
Int J Mol Sci ; 21(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971779

RESUMO

Steelmaking slags are a promising resource as artificial seaweed beds for the reconstitution of marine environments. To grow seaweed well, the formation of biofilms is an essential process in biofouling. This study focused on the formation of initial biofilms on steelmaking slag samples and analyzed the resulting bacterial communities using the next-generation sequencing technique. Three types of steelmaking slag were submerged in an area of Ise Bay in Mie Prefecture, Japan, for 3 and 7 days in the summer and winter seasons to allow the formation of biofilms. The bacterial communities of these biofilms were richer in sulfur-oxidizing bacteria compared to the biofilms formed on polyurethane sponges. It was found that Helicobacteraceae dominantly grew on the biofilms formed on the slag samples. This shows that steelmaking slags have potential to be used as artificial seaweed beds and marine water purifiers.


Assuntos
Bactérias/crescimento & desenvolvimento , Fenômenos Fisiológicos Bacterianos , Biofilmes/crescimento & desenvolvimento , Estações do Ano , Aço , Microbiologia da Água , Água , Japão , Metalurgia
9.
J Stroke Cerebrovasc Dis ; 29(10): 105121, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912506

RESUMO

INTRODUCTION: We aimed to identify the risk factors for surgical treatment of unruptured intracranial aneurysms (UIAs) in individuals aged >60 years, particularly focusing on white matter lesions (WMLs). MATERIAL AND METHODS: We investigated a total of 214 patients with UIAs. The patient group comprised 53 males and 151 females with an average age of 68.2 years. UIA size ranged from 2.7 to 26 (mean: 7.3) mm. The primary endpoint of the study was patient prognosis evaluated at the time of discharge using the modified Rankin Scale. We examined the risk factors for poor outcome and WMLs using magnetic resonance imaging. RESULTS: Poor outcome was observed in 23 (10.7%) patients. Significant correlations were observed between poor outcome and UIA size (P < 0.0001), UIAs located posteriorly (P = 0.0204), UIA thrombosis (P = 0.0002), and presence of WMLs (P < 0.0001) in univariate regression analysis. However, no significant correlations were noted between poor outcome and age (P = 0.1438). Multivariate logistic regression analyses showed significant correlations between poor outcome and UIA size (P < 0.0001), presence of WMLs (P = 0.001). Severe WMLs based on the Fazekas classification was correlated to age (P < 0.0001) and atherosclerosis (P = 0.0001). Severe WMLs were associated with ischemia (P < 0.001) and epilepsy (P = 0.0502) as well as length of hospitalization (P < 0.0001). CONCLUSION: Severe WMLs are risk factors for surgical treatment of UIAs in the elderly. Surgical indications must be considered and caution should be taken when managing patients with severe WMLs.


Assuntos
Fragilidade/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Leucoencefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Idoso Fragilizado , Nível de Saúde , Humanos , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco
10.
J Nippon Med Sch ; 87(3): 162-165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655093

RESUMO

BACKGROUND: Aneurysmal subarachnoid hemorrhage is a rare but important cause of maternal death during pregnancy. CASE DESCRIPTION: A 34-year-old primigravida (31 weeks of pregnancy) with acute headache but no neurological deficits or neck stiffness was prescribed medication and returned home. Four weeks later she presented with severe headache and consciousness disturbance. She was admitted to our hospital, where she fell into a deep coma. Brain CT and three-dimensional CT angiography showed subarachnoid hemorrhage and a 5-mm right internal carotid-posterior communicating artery aneurysm. Fetal heart rate was 60 beats per minute. Emergent cesarean section and surgical clipping were performed. Intraoperative examination revealed that the aneurysm originated at the right posterior communicating artery. There were no postoperative neurological focal deficits. On postoperative day 13 she developed delayed cerebral ischemia of the right temporo-parieto-occipital lobe. She was discharged home 36 days after surgery with left hemianopsia. The infant was free of complications and was discharged at age 17 days. CONCLUSIONS: A pregnant woman with severe headache should undergo brain CT or magnetic resonance imaging to rule out subarachnoid hemorrhage.


Assuntos
Cefaleia/etiologia , Complicações na Gravidez , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Doença Aguda , Adulto , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Artérias Carótidas , Angiografia por Tomografia Computadorizada , Transtornos da Consciência/etiologia , Feminino , Humanos , Imageamento Tridimensional , Gravidez , Complicações na Gravidez/etiologia , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos
11.
World Neurosurg ; 139: 401-404, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360920

RESUMO

BACKGROUND: We present a patient who underwent left superior temporal artery (STA)-to-right middle cerebral artery (MCA) bypass using a radial artery (RA) graft with resection of a giant right cervical common carotid artery (CCA) pseudoaneurysm after carotid artery stenting (CAS) and discuss the treatment strategy and surgical procedure in detail. CASE DESCRIPTION: An 86-year-old male presented with sudden onset of altered consciousness and complete left hemiparesis. Magnetic resonance angiography and catheter angiography of the brain revealed occlusion of the right cervical ICA. Endovascular thrombectomy and stenting of the cervical segment of the ICA were performed. Thirty-two days after CAS, the patient developed a high fever and rapid swelling of the neck. Catheter angiography showed a giant right CCA pseudoaneurysm that had a fistula just proximal to the carotid stent, and the aneurysm extended to the neck entirely. Because of the expanding neck infection, stent placement long lesion, and lack of distal collateral flow on angiography, we performed aneurysm and stent removal and left STA-to-right MCA bypass using an RA graft. The harvested RA graft was anastomosed side to end to both the M2 segment of the right MCA and the left STA. Bypass patency was confirmed before neck exposure. The pseudoaneurysm and proximal portion area of the stent were resected. The patient recovered well postoperatively, and follow-up catheter angiography showed patency of the bypass. CONCLUSIONS: Left STA-RA-right MCA bypass with aneurysm resection is a good treatment option for giant CCA pseudoaneurysms that occur after CAS.


Assuntos
Lesões das Artérias Carótidas/cirurgia , Artéria Carótida Primitiva/cirurgia , Revascularização Cerebral/métodos , Artéria Radial/transplante , Idoso de 80 Anos ou mais , Lesões das Artérias Carótidas/etiologia , Artéria Carótida Primitiva/patologia , Artéria Carótida Interna/patologia , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Procedimentos Endovasculares/efeitos adversos , Humanos , Masculino , Stents , Trombectomia/efeitos adversos
12.
J Stroke Cerebrovasc Dis ; 29(6): 104795, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32222416

RESUMO

OBJECTIVE: Japan has the largest elderly population in the world. As data on the clinical outcomes in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH), including those older than 80 years, are lacking, we analyzed the characteristics of 54,805 aSAH patients and recorded their treatments and clinical outcomes using a Japanese nationwide inpatient database. METHODS: Using the Japanese Diagnostic Procedure Combination database, we identified aSAH patients aged 18 years or older who were hospitalized between July 1, 2010 and March 31, 2016. They were categorized as less than or equal to 60-, 61-70-, 71-80-, 81-90-, and greater than or equal to 91 years of age. The primary outcome was the modified Rankin Scale (mRS) score at discharge. Multivariable logistic regression analysis was performed to examine factors affecting the mRS score at discharge. RESULTS: Of 54,805 patients, 37.5% were aged less than or equal to 60 years; 24.8% were 61-70-, 21.8% were 71-80-, 13.9% were 81-90-, and 2.0% were greater than or equal to 91 years old at the time of the insult. Among 46,107 patients younger than 81 years, 58.9% underwent surgical clipping (SC), 22.9% endovascular coiling (EC), and 18.2% were treated conservatively. There were 8,698 patients aged 81 years or older, 32.4% underwent SC, 23.2% EC, and 44.4% were treated conservatively. A poor mRS score (3-6) at discharge was recorded in 87.2% of patients older than 80 years. Multivariable logistic regression was used to compare their estimated odds ratio (OR) for a poor mRS score at discharge with that of patients aged less than or equal to 60 years. The OR increased by 87% in patients between 61 and 70 years of age (P < .001; OR, 1.87; 95% confidence interval (CI), 1.77-1.98), by 358% in patients aged from 71 to 80 years (P < .001; OR, 4.58; 95%CI, 4.29-4.89), by 1,035% in patients between 81 and 90 years (P < .001; OR, 11.35; 95%CI, 10.32-12.49), and by 1,710% in patients aged more than or equal to 91 years (P < .001; OR, 18.10; 95%CI, 13.96-23.46). CONCLUSIONS: As the treatment outcomes in elderly aSAH patients, especially those 80 years old or older, were poor, the appropriate therapy decisions must be made on a case-by-case basis.


Assuntos
Tratamento Conservador , Procedimentos Endovasculares , Procedimentos Neurocirúrgicos , Hemorragia Subaracnóidea/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Tratamento Conservador/efeitos adversos , Tratamento Conservador/mortalidade , Bases de Dados Factuais , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Nível de Saúde , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/mortalidade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/mortalidade , Fatores de Tempo , Resultado do Tratamento
13.
J Infect Chemother ; 26(3): 285-288, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31680037

RESUMO

Ceftriaxone (CTRX) is a third-generation cephalosporin commonly used to treat infections such as community-acquired pneumonia and urinary tract infections caused by mainly Gram-negative bacteria and some Gram-positive bacteria. Here, we report a case of a patient on hemodialysis who had chorea-like symptoms with high blood concentration of CTRX. A 74-year-old Japanese woman receiving hemodialysis was admitted with obstructive cholangitis and was started on CTRX therapy at a dose of 2 g every 24 hours. On the 6th day after starting administration of CTRX, chorea-like symptoms appeared. We suspected that her symptoms were caused by a high blood concentration of CTRX. We performed a series of blood sampling to determine the concentration of CTRX at different time points before and after discontinuing CTRX administration. CTRX concentrations were higher than those expected in healthy adults, and her chorea-like symptoms had disappeared from the second day of discontinuation of CTRX. The association between CTRX blood concentration and chorea-like symptoms is unclear. However, measuring a series of plasma or serum concentrations from symptom onset to disappearance suggested that chorea-like symptoms appeared when the concentration exceeded approximately 450 µg/mL. Care should be taken when administering CTRX to patients with cholestasis undergoing hemodialysis, as blood CTRX levels may rise unexpectedly and result in complications.


Assuntos
Antibacterianos , Ceftriaxona , Coreia/induzido quimicamente , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Ceftriaxona/efeitos adversos , Ceftriaxona/sangue , Ceftriaxona/farmacocinética , Ceftriaxona/uso terapêutico , Colangite/tratamento farmacológico , Coreia/fisiopatologia , Feminino , Humanos , Diálise Renal
14.
Circ J ; 84(1): 69-75, 2019 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-31801927

RESUMO

BACKGROUND: The impact of cold ambient temperature on out-of-hospital cardiac arrest (OHCA) in aged individuals caused by cardiovascular events in indoor environments has not been investigated sufficiently.Methods and Results:We conducted a case-crossover study. The relationship between OHCA caused by cardiovascular events and exposure to minimum temperature <0℃ was analyzed. Conditional logistic regression analysis was performed to estimate the odds ratios for the relationship between exposure to minimum temperature <0℃ and the risk of OHCA. Between January 1, 2011, and December 31, 2015, a total of 1,452 cases of OHCA were documented, and patients were screened for enrollment. A total of 458 individuals were enrolled in this analysis, and were divided into 2 groups of 110 (elderly group: 65-74 years old) and 348 (aged group: ≥75 years old). The aged individuals had a significant increased risk of OHCA after exposure to minimum temperature <0℃ (odds ratio [OR]: 1.528, 95% confidence interval [CI] 1.009-2.315, P=0.045). Cold ambient temperature was an especially significant increased risk for OHCA occurrence for males (OR: 1.997, 95% CI 1.036-3.773, P=0.039) and during winter (OR: 2.391, 95% CI 1.312-4.360, P=0.004) in the aged group. CONCLUSIONS: Cold ambient temperature significantly affected aged individuals (≥75 years old) experiencing an OHCA caused by cardiovascular events in indoor environments.


Assuntos
Temperatura Baixa/efeitos adversos , Parada Cardíaca Extra-Hospitalar/mortalidade , Estações do Ano , Idoso , Estudos de Casos e Controles , Estudos Cross-Over , Serviços Médicos de Emergência , Feminino , Humanos , Japão/epidemiologia , Masculino , Fatores de Risco
15.
Molecules ; 24(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561457

RESUMO

Porous glass was prepared by the hydrothermal reaction of sodium borosilicate glass, and oxygen-ion characterization was used to identify the hydroxyl groups in its surface area. A substantial amount of "water" was introduced into the ionic structure as either OH- groups or H2O molecules through the hydrothermal reaction. When the hydrothermally treated glass was reheated at normal pressures, a porous structure was formed due to the low-temperature foaming resulting from the evaporation of H2O molecules and softening of the glass. Although it was expected that the OH- groups would remain in the porous glass, their distribution required clarification. Oxygen K-edge X-ray absorption fine structure (XAFS) spectroscopy enables the bonding states of oxygen ions in the surface area and interior to be characterized using the electron yield (EY) and fluorescence yield (FY) mode, respectively. The presence of OH- groups was detected in the O K-edge XAFS spectrum of the porous glass prepared by hydrothermal reaction with a corresponding pre-edge peak energy of 533.1 eV. In addition, comparison of the XAFS spectra obtained in the EY and FY modes revealed that the OH- groups were mainly distributed in the surface area (depths of several tens of nanometers).


Assuntos
Vidro/química , Íons/química , Oxigênio/química , Silicatos/química , Espectroscopia por Absorção de Raios X , Porosidade , Temperatura , Água/química
16.
Mol Cell Biol ; 38(24)2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30224520

RESUMO

Hepatocyte nuclear factor 4α (HNF4α) is a critical factor for hepatocyte differentiation. HNF4α expression is decreased in hepatocellular carcinoma (HCC), which suggests a role in repression of hepatocyte dedifferentiation. In the present study, hepatic expression of HNF4γ was increased in liver-specific Hnf4a-null mice. The HNF4γ whose expression was increased contained two variants, a known short variant, designated HNF4γ1, and a novel long variant, designated HNF4γ2. HNF4G2 mRNA was highly expressed in small intestine, and the transactivation potential of HNF4γ2 was the strongest among these variants, but the potential of HNF4γ1 was the lowest. Cotransfection experiments revealed that HNF4γ1 repressed HNF4α- and HNF4γ2-dependent transactivation, while HNF4γ2 promoted HNF4α-dependent transactivation. HNF4γ1 and HNF4γ2 were able to bind to the HNF4α binding sites with an affinity similar to that of HNF4α. Furthermore, HNF4γ2, but not HNF4γ1, robustly induced the expression of typical HNF4α target genes to a greater degree than HNF4α. Additionally, HNF4γ2 suppressed proliferation of hepatoma cells as well as HNF4α and HNF4γ1 did, and HNF4γ2 induced critical hepatic functions, such as glucose and urea production, and cytochrome P450 1A2 activity more strongly than HNF4α and HNF4γ1 did. These results indicate that HNF4γ2 has potential for redifferentiation of HCC and thus may be explored as a target for HCC therapy.


Assuntos
Variação Genética/genética , Fator 4 Nuclear de Hepatócito/genética , Hepatócitos/metabolismo , Fígado/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Células CACO-2 , Carcinoma Hepatocelular/genética , Diferenciação Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Células HCT116 , Células HEK293 , Células HT29 , Células HeLa , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células PC-3 , RNA Mensageiro/genética , Alinhamento de Sequência
17.
World Neurosurg ; 114: 113-116, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29550600

RESUMO

OBJECTIVE: We describe the technique for surgical "transaneurysmal" embolectomy in a patient with subarachnoid hemorrhage and multiple cerebral aneurysms who manifested large-vessel occlusion during coil embolization. METHODS: An 84-year-old woman with subarachnoid hemorrhage and bilateral internal carotid artery (ICA)-posterior communicating artery and bilateral middle cerebral artery aneurysms (MCAs) was admitted to our institution. We performed clipping to the left ICA and MCAs; however, we could not find the rupture point of both aneurysms. We chose to treat 2 aneurysms on the other side by coil embolization. After complete coil embolization of a right ICA aneurysm, angiograms showed occlusion of the right MCA just proximal to an MCA aneurysm. Considering the risk of bleeding of an untreated MCA distal to the occlusion by endovascular thrombectomy, we performed open transaneurysmal embolectomy at the occlusion site and surgical clipping of the MCA. After cutting the aneurysmal wall, we inserted a suction tube into the cut surface of the aneurysm. The clot was gradually and completely pulled through the cut surface of the aneurysm. Finally, the aneurysm was completely clipped with titanium clips to preserve the M1 and M2 branches. DISCUSSION: Different from usual surgical thrombectomy, suturing the vessel wall is not required for transaneurysmal embolectomy and the area of brain ischemia is confined. Aneurysms with the fragile wall may rupture during clearance of tissue on the aneurysmal surface, and suction may increase vessel damage. CONCLUSION: Transaneurysmal thrombectomy may be useful and safe for large-vessel occlusion just distal to cerebral aneurysms.


Assuntos
Aneurisma Roto/cirurgia , Embolectomia/métodos , Embolização Terapêutica/métodos , Aneurisma Intracraniano/cirurgia , Idoso de 80 Anos ou mais , Aneurisma Roto/diagnóstico por imagem , Feminino , Humanos , Doença Iatrogênica , Aneurisma Intracraniano/diagnóstico por imagem
18.
Heart Vessels ; 33(6): 615-622, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29204682

RESUMO

We evaluated the impact of pharmacist-led heart failure (HF) drug recommendations during hospitalization for hospitalized patients with HF. Hospitalized patients with HF were retrospectively reviewed. Patients were hospitalized before (n = 208, non-intervention group) or after (n = 170, intervention group) the launch of the HF multidisciplinary team (HFMDT) approach with pharmacist-led HF medication optimization. There were no significant group differences in patient background characteristics at admission. Patients with HF with reduced ejection fraction who were not on beta blockers or angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACE-I/ARB) at admission were significantly more likely to be on beta blockers at the time of discharge in the intervention group (73.3 vs 96.3%, P = 0.027) compared to those in non-intervention group; however, the change in ACE-I/ARB prescriptions was not significant (53.3 vs 63.3%, P = 0.601). The proportion of patients on any drug with recommendations against its use in patients with HF did not change from admission to discharge in the non-intervention group (21.2 vs. 20.2%, P = 0.855), but was significantly reduced in the intervention group (22.9 vs. 12.9%, P = 0.005). There were no group differences in the in-hospital all-cause mortality (non-intervention, 3.4%; intervention, 2.4%; P = 0.761) or length of hospital stay (median: non-intervention, 13 days; intervention, 14 days; P = 0.508). Pharmacist-led HF drug recommendations during hospitalization as part of a HFMDT approach for hospitalized patients with HF can increase beta blocker prescriptions and decrease non-preferred drug prescriptions.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/tendências , Equipe de Assistência ao Paciente , Farmacêuticos , Idoso , Fármacos Cardiovasculares/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
19.
Sci Rep ; 7(1): 11449, 2017 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-28904389

RESUMO

In March 2011, the Fukushima Daiichi Nuclear Power Plant accident caused nuclear fuel to melt and the release of high-volatility fission products into the environment. Caesium and iodine caused environmental contamination and public exposure. Certain fission-product behaviours remain unclear. We found experimentally that liquid CsI disperses extremely favourably toward solid UO2, exhibiting a contact angle approaching zero. We further observed the presence of CsI several tens of micrometres below the surface of the solid UO2 sample, which would be caused by the infiltration of pores network by liquid CsI. Thus, volatile fission products released from molten nuclear fuels with complex internal composition and external structure migrate or evaporate to varying extents, depending on the nature of the solid-liquid interface and the fuel material surface, which becomes the pathway for the released fission products. Introducing the concept of the wettability of liquid chemical species of fission products in contact with solid fuels enabled developing accurate behavioural assessments of volatile fission products released by nuclear fuel.

20.
BMC Gastroenterol ; 17(1): 94, 2017 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-28784105

RESUMO

BACKGROUND: We report a unique case of a superficial esophageal cancer arising in a single diverticulum, diagnosed with magnifying image-enhanced endoscopy and then successfully treated by endoscopic submucosal dissection (ESD). CASE PRESENTATION: A 66-year-old man with alcohol-related liver injury visited our hospital for endoscopy for investigation of varix. Esophagogastroduodenoscopy showed no varix but a large epiphrenic diverticulum with an area of fainted redness just above the esophagogastric junction. Narrow band imaging revealed a sharply demarcated brownish dotted area, and dilated intra-epithelial papillary capillary loops (IPCL) were subsequently seen after magnification. Chromoendoscopy with 1% Lugol's iodine solution demonstrated a well-demarcated unstained area, approximately 20 mm in diameter. Endoscopic biopsy revealed a squamous cell carcinoma (SCC). CONCLUSION: The tumor was completely resected by ESD without perforation. Histologically, it was an intraepithelial SCC without lympho-vascular invasion of cancer cells. No local recurrence or metastasis was detected at the last follow-up of 42 months.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Divertículo Esofágico/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Esofágicas/cirurgia , Idoso , Carcinoma de Células Escamosas/patologia , Divertículo Esofágico/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Humanos , Masculino
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