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1.
Immunity ; 43(1): 80-91, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26200012

RESUMO

The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming.


Assuntos
Cisteína Endopeptidases/biossíntese , Inflamação/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Macrófagos/metabolismo , Receptores de Estrogênio/genética , Receptor 4 Toll-Like/imunologia , Acetilação , Animais , Cálcio/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Cisteína Endopeptidases/genética , Ativação Enzimática/genética , Glicólise/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipopolissacarídeos , Macrófagos/imunologia , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/metabolismo , NAD/metabolismo , Fosforilação Oxidativa , Regiões Promotoras Genéticas/genética , Regiões Promotoras Genéticas/imunologia , Choque Séptico/imunologia , Transdução de Sinais , Sirtuína 1/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Transcrição RelA/metabolismo , Transcrição Gênica/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Ubiquitinação , Receptor ERRalfa Relacionado ao Estrogênio
2.
Nat Immunol ; 12(8): 742-51, 2011 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-21725320

RESUMO

The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxin-induced sepsis. SHP had dual regulatory functions in a canonical transcription factor NF-κB signaling pathway, acting as both a repressor of transactivation of the NF-κB subunit p65 and an inhibitor of polyubiquitination of the adaptor TRAF6. SHP-mediated inhibition of signaling via the TLR was mimicked by macrophage-stimulating protein (MSP), a strong inducer of SHP expression, via an AMP-activated protein kinase-dependent signaling pathway. Our data identify a previously unrecognized role for SHP in the regulation of TLR signaling.


Assuntos
NF-kappa B/imunologia , Receptores Citoplasmáticos e Nucleares/imunologia , Sepse/imunologia , Receptores Toll-Like/imunologia , Proteínas Quinases Ativadas por AMP/imunologia , Animais , Imunoprecipitação da Cromatina , Feminino , Immunoblotting , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/imunologia , Ubiquitinação/imunologia
3.
Fish Shellfish Immunol ; 120: 15-22, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34774731

RESUMO

Spawning in marine bivalves is a great energy-demanding process, and it often results in lethal and sublethal stresses during the post-spawning period, including depressed immune capacity. The blood cockle Tegillarca granosa (Linnaeus, 1758) distributes widely in silty-mud tidal flats on the south coast of Korea, and they spawn in late summer. To understand the impacts of spawning on immune parameters, we analyzed the total hemocyte count (THC), hemocyte mortality, phagocytosis capacity, and reactive oxygen species (ROS) production of T. granosa in pre-, and post-spawning condition using a flow cytometer. Histology indicated that the blood cockles occurring on the south coast of Korea ripe and ready to spawn in July, and they spawned in August and September. The THC in the blood cockle hemolymph declined from pre-spawning (1.2 × 108 cell mL-1) to post-spawning (0.9 × 108 cell mL-1), possibly due to the spawning stress and the massive infiltration of hemocytes in the gonad to phagocytose and resorb the residual gametes during the post-spawning period. The hemocyte mortality increased linearly from August (4.1%) to November (9.1%), as the histology revealed that the blood cockle completed spawning, and they resorbed the relict gametes. The granulocyte phagocytosis capacity declined dramatically from July (12.7%) to September (6.0%), when the cockles were engaged in active spawning. The flow cytometry revealed that the production of reactive oxygen species (ROS) from the granulocytes and the erythrocytes type II increased linearly from August (0.8-0.9 × 105 A U.) to December (2.1-2.8 × 105 A U.), which may cause stresses at a cellular level during this period. As the data indicated, spawning is a stressful activity inducing depressed immunological capacities in the blood cockles.


Assuntos
Arcidae , Sistema Imunitário , Animais , Arcidae/imunologia , Hemócitos , Sistema Imunitário/fisiologia , Espécies Reativas de Oxigênio , Reprodução , República da Coreia , Estações do Ano
4.
Dis Aquat Organ ; 152: 109-114, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36519682

RESUMO

A report on the new species Eomarteilia (=Marteilia) granula infecting Manila clam Ruditapes philippinarum from Japan in 2014 suggests the possibility of E. granula infecting other Manila clam populations in the Northwest Pacific region, including Korea. In this study, we report the first infections by E. granula in Manila clams off the south coast of Korea. Histology revealed Marteilia-like plasmodia in the digestive tubule epithelia. Tissue imprints demonstrated that each parasite sporangium enclosed 4 spores and transmission electron microscopy (TEM) revealed ultrastructure of primary cells enclosing secondary cells, which contained spores. Mature spores consisted of 3 sporoplasms: outermost, intermediate, and innermost. The outermost sporoplasm showed a peripheral electron-dense monolayer characteristic of E. granula. The 18S rDNA amplified from the Marteilia-like parasite yielded 1784-bp PCR amplicon sequences which were 99.8% similar to that of E. granula previously reported (as M. granula) from Japan. In the molecular phylogenetic analysis, the novel Marteilia-like organism formed a well-supported clade with E. granula. Accordingly, we concluded that the novel Marteilia-like parasite that we found infecting some Korean Manila clams is Eomarteilia granula. Field surveys revealed that the infection was limited to clams of the south coast of Korea, with the prevalence ranging from 3.3 to 5.0%.


Assuntos
Bivalves , Animais , Filogenia , Bivalves/parasitologia , DNA Ribossômico , Reação em Cadeia da Polimerase/veterinária , República da Coreia
5.
World J Surg ; 45(8): 2581-2590, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33881579

RESUMO

BACKGROUND: There has been increasing attention on the subjective recovery of patients undergoing cancer surgery. Total intravenous anesthesia (TIVA) and inhaled anesthesia with volatile anesthetics (INHA) are safe and common anesthetic techniques. Currently, TIVA and INHA have only been compared for less invasive and less complex surgeries. This prospective randomized trial aimed to compare the quality of recovery between TIVA and INHA in patients undergoing pancreatoduodenectomy (PD) or distal pancreatectomy (DP) using the Quality of Recovery (QOR)-40 questionnaire. METHODS: We enrolled 132 patients who were randomly assigned to either the desflurane (DES) (INHA, balanced anesthesia with DES and remifentanil infusion) or TIVA (effect-site target-controlled infusion of propofol and remifentanil) groups and completed the QOR-40 questionnaire postoperatively. RESULTS: The mean global QOR-40 score on postoperative day 3 was significantly higher in the TIVA group than in the DES group. In the PD group, the total QOR-40 score was significantly higher in the TIVA group than in the DES group. Moreover, the TIVA group had significantly higher scores in the physical comfort and psychological support QOR-40 dimensions than the DES group. CONCLUSION: TIVA provides better quality of recovery scores on POD 3 for patients undergoing curative pancreatectomy. CLINICAL TRIAL REGISTRATION NUMBER: NCT03447691.


Assuntos
Anestesia Intravenosa , Propofol , Período de Recuperação da Anestesia , Anestesia por Inalação , Anestésicos Intravenosos , Desflurano , Humanos , Pancreatectomia , Estudos Prospectivos , Inquéritos e Questionários
6.
World J Surg ; 45(6): 1860-1867, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33591427

RESUMO

BACKGROUND: Hypocapnia has been traditionally advocated during general anesthesia, even though it may induce deleterious physiological effects that result in unfavorable outcomes in patients. This study investigated the association between intraoperative end-tidal carbon dioxide (EtCO2) and length of hospital stay (LOS) in patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The medical records of 759 patients from 2006 to 2015 were reviewed. The patients were divided into two groups based on the mean EtCO2 value during general anesthesia: the hypocapnia group (< 35 mmHg) and the normocapnia group (≥ 35 mmHg). The primary outcome was LOS between the groups. Secondary outcomes included the length of intensive care unit (ICU) stay, postoperative 30-day, 1-year, and 2-year mortality, and perioperative factors associated with LOS. RESULTS: A total of 727 patients were finally analyzed. The median LOS of the hypocapnia group was significantly longer than that of the normocapnia group (22 days vs. 18 days, respectively; p < 0.001). Postoperative mortality did not differ between the groups. Cox regression analysis revealed that hypocapnia was an independent risk factor for longer LOS (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.37-1.89; p < 0.001). Age and postoperative pancreatic fistula were also risk factors for a longer LOS. CONCLUSIONS: It was concluded that low levels of intraoperative EtCO2 during general anesthesia were associated with an increased LOS for patients undergoing PPPD.


Assuntos
Dióxido de Carbono , Pancreaticoduodenectomia , Humanos , Tempo de Internação , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Piloro/cirurgia
7.
Anesth Analg ; 133(1): 168-175, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33181557

RESUMO

BACKGROUND: Extensive efforts have been made toward reducing postoperative opioid use in children. In this study, we assessed whether propacetamol, or a nonsteroidal anti-inflammatory drug (NSAID), or their combination could effectively reduce opioid use in children after laparoscopic inguinal hernia repair. METHODS: This randomized, double-blind clinical trial included 159 children aged 6 months to 6 years. Children were allocated into 1 of the following 3 groups: group I was treated with 10 mg·kg-1 ibuprofen, group P was treated with 30 mg·kg-1 propacetamol, and group I + P was treated with both drugs in their respective concentrations. If the face-legs-activity-crying-consolability (FLACC) score was ≥4 during the postanesthesia care unit stay, 1.0 µg·kg-1 fentanyl was administered as a rescue analgesic. The number of patients who received rescue fentanyl in the postanesthesia care unit was defined as the primary outcome; this was analyzed using the χ2 test. The secondary outcomes included the FLACC and the parents' postoperative pain measure (PPPM) scores until the 24-hour postoperative period. RESULTS: Among the 144 enrolled patients, 28.6% in group I, 66.7% in group P, and 12.8% in group I + P received rescue fentanyl in the postanesthesia care unit (P < .001). The highest FLACC score was lower in group I + P than in either group I or P (P = .007 and P < .001, respectively). Group I + P presented significantly lower PPPM scores than group P at 4 and 12 hours postoperative (P = .03 and .01, respectively). CONCLUSIONS: The use of ibuprofen plus propacetamol immediately following laparoscopic hernia repair surgery in children resulted in the reduced use of an opioid drug compared with the use of propacetamol alone.


Assuntos
Acetaminofen/análogos & derivados , Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Herniorrafia/efeitos adversos , Ibuprofeno/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Acetaminofen/administração & dosagem , Administração Intravenosa , Criança , Pré-Escolar , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Herniorrafia/tendências , Humanos , Lactente , Laparoscopia/efeitos adversos , Laparoscopia/tendências , Masculino , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Estudos Prospectivos
8.
Eur J Pediatr ; 180(5): 1413-1422, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33386997

RESUMO

This study aimed to identify the types and frequencies of adverse events, as well as the risk factors for respiratory complications related to pediatric sedation. This single-center, prospective, observational study was conducted in a radiology suite at a tertiary university hospital for 2 years. Patients aged under 18 years, who underwent sedation solely by anesthesiologists for computed tomography or magnetic resonance imaging scans, were eligible for inclusion. Univariate and multivariate logistic regression analyses were carried out to identify the risk factors of adverse events, including respiratory complications, related to the propofol-based sedation. We further performed a sensitivity test with 1-to-5 propensity score matching analysis to assess the robustness of our findings. Among 2569 children, 3.9% experienced respiratory problems related to the sedation. After 1-to-5 propensity matching analysis, cardiac and neurologic comorbidities, crying before sedation, a history of snoring or upper respiratory infection, and prolonged duration of sedation were independently associated with the occurrence of adverse respiratory events.Conclusions: Our protocol for pediatric sedation demonstrates a high success rate and low likelihood of fatal complications, but proactive management prior to propofol-based sedation is critical to prevent adverse respiratory events in children. What is Known: • Propofol-based pediatric sedation is associated with adverse events necessarily even though performed by professional anesthesiologists solely. What is New: • Cardiac and neurologic comorbidities, crying before sedation, a history of snoring or upper respiratory infection, and prolonged duration of sedation were independently associated with the occurrence of respiratory adverse events. • Proactive management prior to sedation is critical to preventing adverse respiratory events for pediatrics.


Assuntos
Pediatria , Propofol , Radiologia , Adolescente , Anestesiologistas , Criança , Sedação Consciente/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Propofol/efeitos adversos , Estudos Prospectivos , Fatores de Risco
9.
Int J Med Sci ; 17(2): 207-213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32038104

RESUMO

Background: The incidence of postoperative nausea and vomiting (PONV) remains high. The effects of sufentanil for PONV is not firmly confirmed. The aim of this study was to compare the effect of sufentanil- and fentanyl-based intravenous patient-controlled analgesia (IV-PCA) on the incidence of PONV after laparoscopic nephrectomy. Methods: Eighty-six patients were randomly allocated to receive either the sufentanil (n =43) or fentanyl (n =43). IV-PCA was prepared using either sufentanil 3 µg/kg or fentanyl 20 µg/kg, ramosetron 0.3 mg, and ketorolac 120 mg. The primary outcome of was the incidence of PONV during 24 h after post anesthesia care unit (PACU) discharge. The secondary outcomes were the modified Rhodes index and patient satisfaction scores at 24 h after PACU discharge, need for rescue antiemetics, pain score, need for additional analgesics, and cumulative consumption of IV-PCA Results: The incidence of PONV was comparable between the sufentanil and fentanyl groups (64.3% vs. 65%, p = 0.946; respectively). The number of patients who required antiemetics (p = 0.946) and the modified Rhodes index at 24 h after post-anesthesia care unit discharge (p = 0.668) were also comparable in both groups. No significant differences were found in the secondary outcomes, including the analgesic profiles and adverse events between the groups. Conclusions: In conclusion, sufentanil- and fentanyl-based IV-PCA showed similar incidence of PONV with comparable analgesic effects after laparoscopic nephrectomy. Based on these results, we suggest that sufentanil and fentanyl may provide comparable effects for IV-PCA after laparoscopic nephrectomy.


Assuntos
Analgesia Controlada pelo Paciente/métodos , Fentanila/uso terapêutico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Sufentanil/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Humanos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Estudos Prospectivos , Adulto Jovem
10.
J Immunol ; 198(8): 3283-3295, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28275133

RESUMO

The role of peroxisome proliferator-activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M. bovis bacillus Calmette-Guérin. PPAR-α agonists regulated multiple genes involved in autophagy and lysosomal biogenesis, including Lamp2, Rab7, and Tfeb in bone marrow-derived macrophages. Silencing of TFEB reduced phagosomal maturation and antimicrobial responses, but increased macrophage inflammatory responses during mycobacterial infection. Moreover, PPAR-α activation promoted lipid catabolism and fatty acid ß-oxidation in macrophages during mycobacterial infection. Taken together, our data indicate that PPAR-α mediates antimicrobial responses to mycobacterial infection by inducing TFEB and lipid catabolism.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/imunologia , Imunidade Inata/imunologia , Metabolismo dos Lipídeos/imunologia , Infecções por Mycobacterium/imunologia , PPAR alfa/imunologia , Animais , Autofagia/fisiologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imunofluorescência , Immunoblotting , Imuno-Histoquímica , Gotículas Lipídicas/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium , PPAR alfa/metabolismo , Reação em Cadeia da Polimerase
11.
J Invertebr Pathol ; 163: 86-93, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30905857

RESUMO

Paramyxean parasites in the genus Marteilia deteriorate digestive tissues of the host organisms, resulting in mortality of oysters, cockles, and mussels. Most reports of infection by Marteilia spp. are from Europe, while a new species of Marteilia was identified recently in Japan. Here, we report a previously unidentified species in the genus Marteilia from digestive diverticula of Manila clam Ruditapes philippinarum from the south coast of Korea. Prevalence of the parasite was low, 0.5-3.3% in the study sites. We characterized this species using light and transmission electron microscopy (TEM), and analyzed the 18S rDNA sequence. Light microscopy revealed the sporulation process from uninucleated stage to spore in the epithelial tissues of the digestive gland. TEM revealed that the parasites produced four secondary cells containing four tri-cellular spores. An electron-dense haplosporosome-like structure and striated inclusions were evident in the spore and the primary cells, respectively, while refringent granules were rarely observed in the secondary cells. Phylogenetic analyses of the 18S rDNA sequence placed this isolate in the genus Marteilia, although it is not identical to other known species in the genus. Based on morphological and molecular characters, we describe this species as Marteilia tapetis sp. nov., the second Marteilia species reported parasitizing Manila clams in Asian waters.


Assuntos
Bivalves/parasitologia , Cercozoários , Animais , Cercozoários/classificação , Cercozoários/genética , Cercozoários/isolamento & purificação , Cercozoários/ultraestrutura , DNA de Protozoário , Sistema Digestório/microbiologia , Filogenia , Infecções por Protozoários/diagnóstico , Infecções por Protozoários/parasitologia , RNA Ribossômico 18S/genética
12.
J Pediatr Nurs ; 38: e47-e52, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29137839

RESUMO

PURPOSE: The current study investigates predictors of intention of reporting child abuse among emergency nurses in Korea. DESIGN AND METHODS: A descriptive cross-sectional design was used. Data were collected from 200 emergency nurses in eight general hospitals in Korea through a questionnaire that asked about their general characteristics, knowledge about child abuse, perceived behavioral control, experiences of child abuse cases and reporting, and attitude toward child abuse. RESULTS: Multiple regression analysis indicated that attitude toward child abuse was the most influential predictor of the intention of reporting child abuse among Korea's emergency nurses. Knowledge about child abuse, and perceived behavioral control were also significant influencing predictors of reporting intention. These variables explained 22.1% of the variances in the intention of reporting child abuse among emergency nurses. CONCLUSIONS: Reporting child abuse has not yet been established as a professional responsibility among Korea's emergency nurses. Increasing the level of awareness of the characteristics of child abuse and encouraging communication among nurses about the responsibility to report suspected child abuse will increase nurses' confidence to report. PRACTICE IMPLICATIONS: Training for reporting child abuse should be implemented in the near future to improve emergency nurses' understanding of child abuse. A support program is also needed to help emergency nurses build confidence in reporting child abuse as a professional responsibility.


Assuntos
Atitude do Pessoal de Saúde , Maus-Tratos Infantis/diagnóstico , Maus-Tratos Infantis/estatística & dados numéricos , Enfermagem em Emergência/métodos , Notificação de Abuso/ética , Pré-Escolar , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Intenção , Masculino , Projetos Piloto , Valor Preditivo dos Testes , República da Coreia
13.
Int J Mol Sci ; 19(9)2018 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-30200536

RESUMO

An in depth study of PSEN1 mutation p.Thr116Ile (c.335C>T) is presented from two Korean families with autosomal dominant inheritance. Clinical manifestation of our patients included memory loss, attention deficits, visuospatial dysfunction, agnosia, aphasia, apraxia, and personality changes, which occurred in their 30s. PSEN1 Thr116Ile was initially discovered in an Italian patient and two French families with early onset Alzheimer's disease (EOAD) with similar age of onset. To verify the possible pathogenic mechanisms of mutation, in silico predictions and 3D modeling were performed. Structure predictions revealed significant aberrations in first hydrophilic loop (HL-I loop). The hydrophobic isoleucine could alter the loop orientation through increased hydrophobic contacts with the surrounding amino acids. Mutation could destroy a possible hydrogen bond between tyrosine 115 and threonine 116, which may affect the loop conformation. HL-I was confirmed as a conservative region of PSEN1, which may be critical in PSEN1 functions. An additional pathogenic mutation, PSEN1 Thr116Asn, was also found for the same residue, where the patient presented young onset AD (YOND). Other mutations in HL-I loop, such as Tyr115His and Glu120Asp, were described in patients with YOND, supporting the critical role of HL-I loop in PSEN1 activity.


Assuntos
Doença de Alzheimer/genética , Substituição de Aminoácidos , Presenilina-1/química , Presenilina-1/genética , Adulto , Idade de Início , Feminino , Predisposição Genética para Doença , Humanos , Ligação de Hidrogênio , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Linhagem , Estrutura Secundária de Proteína , República da Coreia , Análise de Sequência de DNA , Homologia Estrutural de Proteína , Treonina/genética
14.
Ann Neurol ; 80(2): 247-58, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27323247

RESUMO

OBJECTIVE: To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image-based tau staging in the Alzheimer disease (AD) spectrum. METHODS: We included 195 participants (53 AD, 52 amnestic mild cognitive impairment [MCI], 23 nonamnestic MCI, and 67 healthy controls) who underwent 2 PET scans ((18) F-florbetaben for amyloid-ß and (18) F-AV-1451 for tau). We assumed that regions with earlier appearances of pathology may show increased binding in a greater number of participants and acquired spreading order of tau accumulation by sorting the regional frequencies of involvement. We classified each participant into image-based tau stage based on the Z score of the composite region for each stage. RESULTS: Tau accumulation was most frequently observed in the medial temporal regions and spread stepwise to the basal and lateral temporal, inferior parietal, posterior cingulate, and other association cortices, and then ultimately to the primary cortical regions. In contrast, amyloid accumulation was found with similar frequency in the diffuse neocortical areas and then finally spread to the medial temporal regions. The image-based tau stage correlated with the general cognitive status, whereas cortical thinning was found only in the advanced tau stages: medial temporal region in stage V and widespread cortex in stage VI. INTERPRETATION: Our PET study replicated postmortem spreading patterns of tau and amyloid-ß pathologies. Unlike the diffuse accumulation of amyloid throughout the neocortex, tau spreading occurred in a stepwise fashion through the networks. Image-based tau staging may be useful for the objective assessment of AD progression. Ann Neurol 2016;80:247-258.


Assuntos
Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Córtex Cerebral/metabolismo , Disfunção Cognitiva/metabolismo , Proteínas tau/metabolismo , Idoso , Doença de Alzheimer/patologia , Amnésia/complicações , Amnésia/metabolismo , Amnésia/patologia , Atrofia/patologia , Córtex Cerebral/patologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
15.
Mol Cell Biochem ; 428(1-2): 57-66, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28063003

RESUMO

Biological effect of poly-L-arginine (PLR), the linear homopolymer comprised of L-arginine, was investigated to determine the activity of suppressing prions. PLR decreased the level of scrapie prion protein (PrPSc) in cultured cells permanently infected with prions in a concentration-dependent manner. The PrPSc inhibition efficacy of PLR was greater than that of another prion-suppressant poly-L-lysine (PLK) in a molecular mass-dependent fashion. The effective concentration of PLR to inhibit prions was achieved safely below the cytotoxic concentrations, and overall cytotoxicity of PLR was similar to that of PLK. PLR did not alter the cellular prion protein (PrPC) level and was unable to change the states of preformed recombinant PrP aggregates and PrPSc from prion-infected cells. These data eliminate the possibility that the action mechanism of PLR is through removal of PrPC and pre-existing PrPSc. However, PLR formed complexes with plasminogen that stimulates prion propagation via conversion of PrPC to the misfolded isoform, PrPSc. The plasminogen-PLR complex demonstrated the greater positive surface charge values than the similar complex with PLK, raising the possibility that PLR interferes with the role of cofactor for PrPSc generation better than PLK.


Assuntos
Peptídeos/farmacologia , Plasminogênio/metabolismo , Proteínas PrPSc/antagonistas & inibidores , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Camundongos , Polilisina/farmacologia , Proteínas PrPC/metabolismo , Isoformas de Proteínas/metabolismo
16.
Proc Natl Acad Sci U S A ; 109(20): 7729-34, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22547814

RESUMO

The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis. Enhanced intracellular survival (Eis) protein, secreted by Mtb, enhances survival of Mycobacterium smegmatis (Msm) in macrophages. Mtb Eis was shown to suppress host immune defenses by negatively modulating autophagy, inflammation, and cell death through JNK-dependent inhibition of reactive oxygen species (ROS) generation. Mtb Eis was recently demonstrated to contribute to drug resistance by acetylating multiple amines of aminoglycosides. However, the mechanism of enhanced intracellular survival by Mtb Eis remains unanswered. Therefore, we have characterized both Mtb and Msm Eis proteins biochemically and structurally. We have discovered that Mtb Eis is an efficient N(ε)-acetyltransferase, rapidly acetylating Lys55 of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase. In contrast, Msm Eis is more efficient as an N(α)-acetyltransferase. We also show that Msm Eis acetylates aminoglycosides as readily as Mtb Eis. Furthermore, Mtb Eis, but not Msm Eis, inhibits LPS-induced JNK phosphorylation. This functional difference against DUSP16/MKP-7 can be understood by comparing the structures of two Eis proteins. The active site of Mtb Eis with a narrow channel seems more suitable for sequence-specific recognition of the protein substrate than the pocket-shaped active site of Msm Eis. We propose that Mtb Eis initiates the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation by acetylating DUSP16/MKP-7. Our work thus provides insight into the mechanism of suppressing host immune responses and enhancing mycobacterial survival within macrophages by Mtb Eis.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Modelos Moleculares , Mycobacterium smegmatis/metabolismo , Conformação Proteica , Acetilação , Acetiltransferases , Animais , Sequência de Bases , Western Blotting , Clonagem Molecular , Cristalização , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Humanos , Cinética , Macrófagos , Camundongos , Dados de Sequência Molecular , Mycobacterium smegmatis/genética , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Difração de Raios X
17.
Can J Neurol Sci ; 41(5): 597-602, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25373810

RESUMO

BACKGROUND: Cognitive impairments are common in Parkinson's disease (PD). Despite its clinical importance, the development of dementia is still difficult to predict. In this study, we investigated the possible associations between non-motor symptoms and the risk of developing dementia within a 2-year observation period in PD. METHODS: A total of 80 patients with PD participated in this study. Nonmotor symptoms (the Nonmotor Symptoms Questionnaire), PD status (Unified Parkinson's Disease Rating Scale), depression (Geriatric d Depression Scale or Montgomery-Asberg Depression Scale), stereopsis and severity of nonmotor symptoms (Non-motor symptoms scale) were assessed. Global cognitive function (Mini-Mental State Examination) were evaluated at baseline and 2 years later. RESULTS: Presence of depression, vivid dreaming, REM sleep behavior disorders, hyposmia, abnormal stereopsis, non-smoking and postural instability/ gait disturbance phenotype were associated with a significantly more rapid decline of Mini-Mental State Examination. Logistic regression analyses demonstrated that depression (odds ratio=13.895), abnormal stereopsis (odds ratio=10.729), vivid dreaming (odds ratio=4.16), REM sleep behavior disorders (odds ratio=5.353) and hyposmia (odds ratio=4.911) were significant independent predictors of dementia risk within 2 years. Postural instability/ gait disturbance phenotype and age >62 years were also independent predictors of dementia risk (odd ratio=38.333, odds ratio=10.625). CONCLUSIONS: We suggest that depression, vivid dreaming, REM sleep behavior disorders, hyposmia and abnormal stereopsis are closely associated with cognitive decline, and that presence of these nonmotor symptoms predict the subsequent development of Parkinson's disease dementia.


Assuntos
Escalas de Graduação Psiquiátrica Breve , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/psicologia , Demência/diagnóstico , Demência/epidemiologia , Demência/psicologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/psicologia , Doença de Parkinson/psicologia
18.
Can J Neurol Sci ; 41(2): 187-92, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24534029

RESUMO

BACKGROUND: few studies have addressed the association between the characteristics of ischemic lesions detected by diffusion-weighted imaging (dWi) and the clinical outcome in patients with hyperacute posterior circulation ischemic stroke. this study demonstrates a relationship between the findings assessed by dWi and the outcome in patients with hyperacute posterior circulation ischemic stroke. METHODS: We reviewed data from 118 patients who had posterior circulation ischemic stroke within six hours from the onset of their symptoms. the clinical outcome included early neurological deterioration (end) and a favorable outcome at three months after the onset of symptoms. using dWi, the lesion volume and the number and location of injured anatomical regions were analyzed to evaluate whether the results correlated with the clinical outcome measures. RESULTS: the number of injured anatomical regions assessed by dWi was associated with the initial and delayed neurological status. Both the total volume and the number of injured anatomical regions associated with end and a favorable outcome. analysis of the location of the injured regions determined that only a pontine lesion independently associated with end. interestingly, four out of five patients who underwent decompressive craniectomy exhibited a large infarction volume but minor symptoms. CONCLUSIONS: in patients with hyperacute posterior circulation ischemic strokes, the lesions assessed by dWi were associated with the clinical outcome, regardless of the initial neurological status. dWi is an effective initial imaging tool for assessing the extent of lesions and clinical outcomes in patients with hyperacute posterior circulation ischemic stroke.


Assuntos
Artéria Basilar , Ponte/patologia , Artéria Cerebral Posterior , Sistema de Registros , Acidente Vascular Cerebral/diagnóstico , Artéria Vertebral , Idoso , Estudos de Coortes , Craniectomia Descompressiva , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ponte/irrigação sanguínea , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/terapia , Tempo para o Tratamento
19.
J Korean Med Sci ; 29(12): 1604-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25469058

RESUMO

Misfolded isoform of prion protein (PrP), termed scrapie PrP (PrP(Sc)), tends to aggregate into various fibril forms. Previously, we reported various conditions that affect aggregation of recombinant PrP into amyloids. Because amyloidogenesis of PrP is closely associated with transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans, we investigated infectivity of recombinant PrP amyloids generated in vitro. Using cultured cell lines which overexpress cellular PrP of different species, we measured the level of de novo synthesized PrP(Sc) in cells inoculated with recombinant mouse PrP amyloids. While PrP-overexpressing cells were susceptible to mouse-adapted scrapie prions used as the positive control, demonstrating the species barrier effect, infection with amyloids made of truncated recombinant PrP (PrP[89-230]) failed to form and propagate PrP(Sc) even in the cells that express mouse cellular PrP. This suggests that infectivity of PrP amyloids generated in vitro is different from that of natural prions. Recombinant PrP (89-230) amyloids tested in the current study retain no or a minute level, if any, of prion infectivity.


Assuntos
Rim/metabolismo , Rim/patologia , Proteínas PrPSc/metabolismo , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Príons/metabolismo , Proteínas Recombinantes/metabolismo , Animais , Linhagem Celular , Camundongos , Coelhos , Regulação para Cima
20.
Arch Craniofac Surg ; 25(1): 48-50, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38461829

RESUMO

Identifying tumors or wounds on the scalp is difficult because hair blocks the vision during surgery and suturing. In the meantime, we have commonly used hairpins to hold the hair for a clearer view; however, we would like to suggest a new method, a "hair-fixing sheet," consisting of hook-like surface. We applied the two methods, hair-fixing sheets and hairpins, assuming several situations. In these situations, it was possible to fix a wider range or various shapes more conveniently using a hair-fixing sheet than using several hairpins at a similarly low cost. In addition, it was easy to change the hair to be fixed, remove it postoperatively, and prevent the hair from being pulled out, thereby preventing additional postoperative pain.

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