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1.
J Pharmacol Sci ; 154(4): 264-273, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485344

RESUMO

The monosynaptic connection from the lateral parabrachial nucleus (LPB) to the central amygdala (CeA) serves as a fundamental pathway for transmitting nociceptive signals to the brain. The LPB receives nociceptive information from the dorsal horn and spinal trigeminal nucleus and sends it to the "nociceptive" CeA, which modulates pain-associated emotions and nociceptive sensitivity. To elucidate the role of densely expressed mu-opioid receptors (MORs) within this pathway, we investigated the effects of exogenously applied opioids on LPB-CeA synaptic transmission, employing optogenetics in mice expressing channelrhodopsin-2 in LPB neurons with calcitonin gene-related peptide (CGRP). A MOR agonist ([D-Ala2,N-Me-Phe4,Glycinol5]-enkephalin, DAMGO) significantly reduced the amplitude of light-evoked excitatory postsynaptic currents (leEPSCs), in a manner negatively correlated with an increase in the paired-pulse ratio. An antagonist of MORs significantly attenuated these effects. Notably, this antagonist significantly increased leEPSC amplitude when applied alone, an effect further amplified in mice subjected to lipopolysaccharide injection 2 h before brain isolation, yet not observed at the 24-h mark. We conclude that opioids could shut off the ascending nociceptive signal at the LPB-CeA synapse through presynaptic mechanisms. Moreover, this gating process might be modulated by endogenous opioids, and the innate immune system influences this modulation.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Núcleo Central da Amígdala , Camundongos , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Núcleo Central da Amígdala/metabolismo , Transmissão Sináptica , Neurônios , Sinapses/fisiologia , Receptores Opioides mu/metabolismo , Analgésicos Opioides/farmacologia
2.
Neuroendocrinology ; 113(1): 48-63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35785764

RESUMO

INTRODUCTION: Despite its recent reputation as prosocial neurohormone, the most important physiological role of oxytocin (OT) is stimulating uterine contractions. Though it is well known that plasma OT concentrations change drastically during delivery, it remains unexplored whether and how OT receptors in the maternal brain are activated. We examined whether the responses of cells in the central amygdala (CeA), an OT receptor-rich limbic site involved in pain and fear memory regulation, to exogenously applied OT analogue, Thr-Gly-OT (TGOT), vary depending on delivery. METHODS: Intracellular Ca2+ dynamics of the CeA cells were visualized in brain slices from female rats at virgin (VG), during pregnancy term (PT) days 16-21, within 24 h after delivery (G0), and within 1-3 days after delivery (G3). The Ca2+ responses to 1 µM TGOT, 20 mM KCl (high K), and 300 µM ADP were compared. RESULTS: We found that fraction of cells responding to TGOT, high K, and ADP differed significantly between the four delivery-associated terms. In particular, the fraction of cells responding to TGOT (TGOT responders) significantly increased from VG and PT at G0 and G3. Furthermore, the significant positive correlation between TGOT and high K response in TGOT and high K responders was reduced at G0, while that between TGOT and ADP responses in TGOT and ADP responders was increased at G0. CONCLUSION: These results indicate that the responses of CeA cells to an OT receptor agonist markedly change around delivery, which might play a role in controlling the labor-related pain and post-delivery emotional complications.


Assuntos
Núcleo Central da Amígdala , Ocitocina , Período Periparto , Receptores de Ocitocina , Animais , Feminino , Gravidez/metabolismo , Gravidez/psicologia , Ratos , Cálcio/metabolismo , Núcleo Central da Amígdala/metabolismo , Medo/fisiologia , Medo/psicologia , Ocitocina/análogos & derivados , Ocitocina/farmacologia , Dor/metabolismo , Dor/psicologia , Período Periparto/metabolismo , Período Periparto/psicologia , Receptores de Ocitocina/metabolismo
3.
Behav Sleep Med ; : 1-11, 2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37545146

RESUMO

OBJECTIVES: To develop the Parenting Behavior Checklist to Promote Preschoolers' sleep (PCPP), quantify sleep-promoting parenting behaviors for children, and examine the scale's reliability and validity. METHODS: The PCPP was developed based on the recommendations of the ABCs of SLEEPING for children's sleep, which is strongly supported by research evidence. Its validity and reliability were evaluated using data from 140 participants. Structural validity was estimated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and internal consistency was evaluated by Cronbach's α. Hypothesis testing was evaluated by analyzing the correlations between each factor of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P) and the PCPP. RESULTS: Regarding structural validity, EFA was conducted because CFA showed a poor model fit. The PCPP comprised one factor and six items. The JSQ-P subfactors of insomnia or circadian rhythm sleep-wake disorders, undesirable morning symptoms and behaviors, and insufficient sleep were moderately negatively correlated with the PCPP; the subfactor of undesirable daytime behaviors related to sleep problems was weakly negatively correlated with the PCPP. Thus, the sleep-promoting parenting behaviors listed in the PCPP were associated with better sleep in children. CONCLUSIONS: The PCPP showed sufficient reliability and validity. Future studies should use the scale to examine more effective interventions regarding sleep-promoting parental behaviors for children.

4.
J Immunol ; 204(12): 3077-3085, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32358018

RESUMO

Extracellular ATP released from stimulated and/or damaged cells modulates physiological responses via stimulation of various purinoceptors. We previously showed that ATP potentiated the Ag-induced mast cell (MC) degranulation via purinoceptors pharmacologically similar to the ionotropic P2X4 receptor. In this study, we investigated the role of P2X4 receptor in MC degranulation induced by stimulation of IgE-FcεRI complex with Ag, using bone marrow-derived MCs (BMMCs) prepared from wild type and P2X4 receptor-deficient (P2rx4-/- ) mice. ATP significantly increased Ag-induced degranulation in BMMCs prepared from wild type mice. This effect of ATP was reduced in BMMCs prepared from P2rx4-/- mice. The potentiating effect of ATP was restored by expressing P2X4 receptor in P2rx4-/- BMMCs. The P2X4 receptor-mediated effects were maintained even after differentiating into the connective tissue-type MCs. P2X4 receptor stimulation did not affect the Ag-induced Ca2+ response but enhanced Ag-induced early signals, such as tyrosine phosphorylation of Syk and phospholipase C-γ. Interestingly, these effects of ATP on Syk phosphorylation were not impaired by pretreatment with Cu2+, an inhibitor of the P2X4 receptor channel, or removal of external Ca2+, suggesting that a mechanisms other than Ca2+ influx through ion channel activity may be involved. In vivo experiments revealed that systemic and intradermal passive anaphylaxis responses were significantly alleviated in P2rx4-/- mice. Taken together, the present data suggest that the P2X4 receptor plays an essential role in ATP-induced upregulation of MC degranulation in response to Ag, and also contributes to the Ag-induced allergic response in vivo.


Assuntos
Trifosfato de Adenosina/metabolismo , Antígenos/metabolismo , Degranulação Celular/fisiologia , Hipersensibilidade/metabolismo , Mastócitos/metabolismo , Receptores Purinérgicos P2X4/metabolismo , Anafilaxia/metabolismo , Animais , Células da Medula Óssea/metabolismo , Cálcio/metabolismo , Imunoglobulina E/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores de IgE/metabolismo , Transdução de Sinais/fisiologia
5.
Endocr J ; 69(2): 199-207, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34588397

RESUMO

We investigated whether growth hormone (GH) treatment could accelerate the onset of puberty in patients with isolated GH deficiency (GHD). Of the 135 boys and 89 girls who started GH treatment before the onset of puberty and were followed up at Tanaka Growth Clinic, 83 boys and 51 girls who started GH treatment sufficiently earlier than the average age at onset of puberty of GHD patients (<10 years vs. 11.7 years for boys; <9.5 years vs. 11.4 years for girls) were analyzed. Age at onset of puberty significantly positively correlated to age at the start of GH treatment (boys: r = 0.427, p < 0.0001; girls: r = 0.302, p < 0.05). When the subjects were divided into two groups each: for boys, Groups A (n = 45) and B (n = 39), treatment was started at age <8 and 8 to <10 years, respectively; for girls, Groups A (n = 26) and B (n = 21), treatment was started at age <7 and 7 to <9.5 years, respectively, age at the onset of puberty was significantly lower in Groups A than in Groups B by the Mann-Whitney U test (boys: p < 0.01; girls: p < 0.05) and Kaplan-Meier log-rank test (boys: p < 0.01; girls: p < 0.05). These results indicate that GH treatment accelerates the delayed onset of puberty in patients with GHD. Heights at the onset of puberty in Groups A and B were not significantly different, suggesting that early treatment does not increase adult height.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Adulto , Estatura , Criança , Nanismo Hipofisário/tratamento farmacológico , Feminino , Hormônio do Crescimento , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Puberdade
6.
Tohoku J Exp Med ; 256(3): 225-234, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35314530

RESUMO

The Tohoku University Hospital has been a clinical and research facility for all the related departments of Tohoku University. Medical-dental and interprofessional collaboration has resulted in special treatment teams, made up of members of departments such as the center for head and neck cancer, the center for dysphagia, and the cleft lip and palate center. Those treatment teams held conferences, case study meetings, reading sessions, and in-hospital seminars. The purpose of this study was to evaluate the outcomes of various medical-dental and the interprofessional collaboration at Tohoku University Hospital and training program to equip hospital dentists in higher medical institutions. The attainment targets are the acquisition of basic medical skills and knowledge under the guidance of supervising doctors. As a result, the hospital dentists could acquire their own specialized knowledge and skills certificated by each academic society. The smooth team treatment has been achieved, and the number of cases discussed by cancer boards and center for dysphagia has increased year by year due to the efficiency of their clinical pathways. On the dental care side as well, the wearing rates of maxillofacial prosthetic devices such as maxillofacial prostheses and palatal augmentation prostheses (PAP) have improved, which have contributed to improving patient's stomatognathic function. Tohoku University Hospital has been practicing collaboration between medical and dental professionals and it has produced mutual benefits. Our interprofessional training system based on the medical-dental collaboration could develop professionals who have acquired cross-disciplinary knowledge and skills from experienced doctors.


Assuntos
Fenda Labial , Fissura Palatina , Hospitais Universitários , Humanos , Relações Interprofissionais
7.
Gerodontology ; 39(1): 10-16, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34726288

RESUMO

OBJECTIVE: This study aimed to verify the compatibility of masticatory performance tests using different two types of gummy jellies. BACKGROUND DATA DISCUSSING THE PRESENT STATUS OF THE FIELD: Compatibility between the glucose concentration measuring method (GC) and 10-steps visual scoring method (VS), which are masticatory performance tests for diagnosing decreased masticatory function (DMF) in oral hypofunction and the use of different types of gummy jelly, has yet to be confirmed. MATERIALS AND METHODS: The participants consisted of 134 Japanese older people (51 men and 83 women). GC, VS and the increased surface area measuring method (ISA), as an alternative analysis method for VS, were conducted to evaluate masticatory performance. Cohen's Kappa coefficient was used to verify the consistency for detecting DMF between GC and VS. Pearson's correlation coefficient was used to analyse the relationship between GC and ISA. Each masticatory performance was compared among three different groups for the number of residual teeth. Cut-off values of VS and ISA for DMF that were consistent with GC were identified. RESULTS: Glucose concentration measuring method and VS showed an excellent consistency (Kappa coefficient = 0.86). There was a high positive correlation between GC and ISA (r = .70). However, the change in masticatory performance according to the number of teeth was different between GC and VS/ISA. The cut-off values of VS and ISA were a Score of 2 and 1687 mm2 , respectively. CONCLUSION: Glucose concentration measuring method and VS/ISA remained fairly consistent for detecting DMF, which might be useful information to interconnect the various studies on masticatory performance.


Assuntos
Alimentos , Mastigação , Idoso , Feminino , Géis , Humanos , Masculino
8.
BMC Womens Health ; 21(1): 171, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882923

RESUMO

BACKGROUNDCXS: Early detection of breast cancer is effective for prolonging survival, but the participation rate in breast cancer screening among target Japanese women remains low. This study examined the relationships between tendencies in decision-making under conditions of uncertainty, health behaviors, demographics, and breast cancer screening participation in Japanese women. METHODS: Secondary analysis was performed using data from the 2017 Keio Household Panel Survey (KHPS). The study population consisted of 2945 households. Data were obtained from the KHPS for women aged 40 years or older. Breast cancer screening participation in the past year, risk aversion, time preference, health behaviors (e.g., smoking, alcohol consumption, and medical treatment received in the past year), and demographic variables were analyzed. RESULTS: Data from 708 women were analyzed. Among the respondents, 28.8% had attended breast cancer screening in the past year. Factors found to significantly contribute to breast cancer screening participation included higher risk aversion (odds ratio [OR], 2.34; 95% confidence interval [CI] = 1.03-5.32; p = 0.043), medical treatment received in the past year (OR, 1.56; 95% CI = 1.06-2.30; p = 0.026), higher self-rated health (OR, 1.47; 95% CI = 1.18-1.83; p = 0.001), living above the poverty line (OR, 2.31; 95% CI = 1.13-4.72; p = 0.022), and having children (OR, 1.57; 95% CI = 1.02-2.42; p = 0.042). Factors significantly associated with non-participation in breast cancer screening were smoking (OR, 0.20; 95% CI = 0.10-0.42; p < 0.000), alcohol consumption (OR, 0.56; 95% CI = 0.37-0.86; p = 0.007), being self-employed (OR, 0.22; 95% CI = 0.10-0.46; p < 0.000), and being unemployed (OR, 0.48; 95% CI = 0.26-0.90; p = 0.022). No significant relationship was observed between time preference and screening participation. CONCLUSIONS: The results indicate that women who recognize the actual risk of developing breast cancer or have high awareness of breast cancer prevention tend to participate in breast cancer screening. Barriers to screening participation are not working for an organization that encourages screening and low income.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Neoplasias da Mama/diagnóstico , Criança , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Mamografia , Programas de Rastreamento , Incerteza
9.
J Stroke Cerebrovasc Dis ; 30(4): 105637, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33508727

RESUMO

Immune thrombocytopenic purpura (ITP) can increase the risk of not only hemorrhagic incidents but also thrombotic events. Although several patients with ITP who developed cerebral infarction have been reported, concurrence of spinal cord infarction and ITP has not been reported. We report the case of a female patient who developed spinal cord infarction during the exacerbation of her ITP. This case suggests a possible association between spinal cord infarction and ITP, which can cause paradoxical thrombosis.


Assuntos
Infarto/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Medula Espinal/irrigação sanguínea , Trombose/etiologia , Idoso , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Infarto/diagnóstico por imagem , Infarto/reabilitação , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Trombose/diagnóstico por imagem , Resultado do Tratamento
10.
J Prosthet Dent ; 124(1): 123-127, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31810617

RESUMO

STATEMENT OF PROBLEM: Although closed hollow obturator prostheses provide the benefit of minimized weight, they also pose challenges. They are complex to fabricate, and contaminated water can easily enter the hollow section through the joined part, making them unsanitary and leading to malodor and increased weight. PURPOSE: The purpose of this in vitro study was to investigate the hermeticity and durability of a hollow obturator model fabricated by using computer-aided design (CAD) and rapid prototyping (RP) techniques and to evaluate the possibility of its clinical use. MATERIAL AND METHODS: Leak testing was used to evaluate the hermeticity and durability of hollow spherical obturator specimens with an outer diameter of 30 mm and 2 different wall thicknesses (1.5 and 2.0 mm). Six specimens were fabricated for each of the wall thicknesses by using CAD and RP techniques. The accumulation of fluids in the hollow obturator specimens was evaluated every day by using megascopic observation with photoirradiation from the base of the specimens. The amount of water absorption and the rate of increase in the weight of the 2 specimens were calculated and compared. Statistical analysis was performed by using the Mann-Whitney U test (α=.05). RESULTS: The application of CAD and RP techniques made it possible to fabricate a hollow obturator model specimen with completely unified parts. The 1.5-mm specimen showed an absorption rate (2.61%) that significantly exceeded that of the 2.0-mm specimen (2.53%) on day 130 (P=.006). By the end of the observation period, the 1.5-mm specimen exhibited large amounts of water absorption and destruction. The 1.5-mm-thick wall had reduced hermeticity than the 2.0-mm-thick wall. CONCLUSIONS: A fully unified hollow obturator model with 2.0-mm-thick walls was fabricated by using CAD and RP techniques. The absence of any joints prevented fluid accumulation, making this method suitable for the fabrication of hollow prostheses.


Assuntos
Desenho Assistido por Computador
11.
Gan To Kagaku Ryoho ; 47(12): 1687-1690, 2020 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-33342984

RESUMO

We retrospectively investigated the use of oral hydromorphone for cancer pain. Nineteen patients treated for cancer pain with oral hydromorphone were reviewed in this study. Cancers had occurred in the gastrointestinal (n=4), lung(n=3), breast(n=2), bone and soft tissue(n=2), hematological(n=2), and others(n=6). The administered opioids before switching to hydromorphone were morphine, oxycodone, and tapentadol. The mean oral morphine equivalent daily dose (OMEDD)was 89.3 mg. The average dose of hydromorphone administered was 16.4 mg/day, and average NRS 10(numerical rating scale: 0-10)scores of cancer pain before and after switching were 4.1 and 3.8, respectively, showing no significant differences. In this study, switching from other opioids to oral hydromorphone was feasible with an approved conversion ratio, ie, an oral hydromorphone-to-oral morphine ratio of 1:5. No severe adverse effects were observed. The oral hydromorphone extended-release formulation was administered every 24 h, as a tiny tablet formulation that is preferable owing to easy administration and adherence.


Assuntos
Hidromorfona , Neoplasias , Analgésicos Opioides/efeitos adversos , Humanos , Hidromorfona/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Oxicodona/efeitos adversos , Estudos Retrospectivos
12.
Histopathology ; 74(6): 892-901, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30586197

RESUMO

AIMS: Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease of patients with cancer that causes progressive pulmonary hypertension (PH). Its pathology is characterised by fibrocellular intimal proliferation and thrombosis caused by tumour emboli in microscopic pulmonary arteries. However, such PTTM-like lesions often appear incidentally. We sought to identify features that distinguished PTTM from incidental pulmonary tumour emboli, and to gain an overall picture of PTTM morphology in terms of its pathogenesis. METHODS AND RESULTS: Twenty-five PTTM cases were classified into two groups: (i) a definite group (n = 14), clinically diagnosed with PH; and (ii) a suspicious group (n = 11) with respiratory symptoms but without a clinical evidence of PH. As a control group, autopsy cases with PTTM-like lesions lacking progressive respiratory symptoms were selected (n = 7). PTTM-like lesions in these groups were studied and a diagnostic guide for PTTM formulated as follows: PTTM-like lesions with >17 affected vessels observed in a 1-cm2 area of lung specimen, and the absence of pulmonary metastatic nodules. PTTM due to gastric cancers was shown to have a significantly shorter course and larger arterial involvement than cases with non-gastric cancers. Serial sections revealed a PTTM lesion to be a longitudinal obstruction that accumulated in microscopic pulmonary arteries and that showed a proximal extension via supernumerary arteries. CONCLUSION: We suggest novel pathological diagnostic characteristics for PTTM deduced from a study of 25 autopsy cases. This includes PTTM-like lesions with >17 affected vessels in a 1-cm2 area of lung specimen and the absence of pulmonary metastatic nodules.


Assuntos
Pneumopatias/diagnóstico , Pneumopatias/etiologia , Neoplasias/complicações , Células Neoplásicas Circulantes/patologia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Adenocarcinoma/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Hepatol Res ; 49(8): 950-956, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30861263

RESUMO

A 66-year-old man was admitted to our department due to cholestatic liver injury. He had received five cycles of pembrolizumab for small-cell lung cancer. Imaging showed the possibility of sclerosing cholangitis (SC) with hemobilia. Histologically, CD8+ T cells had infiltrated the biliary epithelium of the extrahepatic bile duct. We reached the diagnosis of secondary SC induced by pembrolizumab. Although we treated him with high-dose corticosteroids, laboratory data showed only a moderate response. Clinicians should recognize that immune checkpoint inhibitors can sometimes cause severe and irreversible SC.

14.
Biol Blood Marrow Transplant ; 24(1): 43-49, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28860001

RESUMO

Late graft failure (LGF) without evidence of residual recipient cells is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-SCT) and often requires stem cell infusion from the same donor when the patient fails to respond to conventional therapies. We screened the peripheral blood (PB) of 14 patients who developed donor-type LGF at 2 to 132 months after allo-SCT for the presence of the markers for immune-mediated bone marrow (BM) failure. Increased glycosylphosphatidyl inositol-anchored protein-deficient (GPI-AP-) leukocytes, which accounted for .009% to 0.147% of the total granulocytes, were detected in 5 patients (severe aplastic anemia, n = 2; follicular lymphoma, n = 1; acute lymphoblastic leukemia, n = 1; myelodysplastic syndromes; n = 1) and 4.7% to 81.2% HLA-allele-lacking leukocytes (HLA-LLs) were detected in 2 patients (acute myelogenous leukemia, n = 1; and myelodysplastic syndromes, n = 1). Three of the 5 patients with increased GPI-AP- leukocytes were treated with antithymocyte globulin (ATG), and 2 patients achieved transfusion independence. These results suggest that immune mechanisms that are similar to acquired aplastic anemia underlie condition of approximately one-half of the patients with donor-type LGF, and that in patients with increased GPI-AP- cells, donor-derived hematopoiesis may be restored by ATG therapy alone without donor stem cell infusion.


Assuntos
Quimerismo , Rejeição de Enxerto/etiologia , Transplante Homólogo/efeitos adversos , Adulto , Soro Antilinfocitário/uso terapêutico , Feminino , Proteínas Ligadas por GPI/metabolismo , Rejeição de Enxerto/imunologia , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucócitos/química , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
15.
Genes Cells ; 22(2): 160-173, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28097745

RESUMO

The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1-191, Core191) but not by the mature Core (aa 1-177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane. In contrast, Core177 inhibits ERAD-M but not ERAD-L. In addition, requirement of an unfolded protein sensor in the ER lumen suggested that inhibition of ERAD-L is probably responsible for Core191-dependent UPR activation. These results implicate inadequate maturation of Core as a trigger for induction of ER stress and UPR.


Assuntos
Degradação Associada com o Retículo Endoplasmático/fisiologia , Hepacivirus/metabolismo , Saccharomyces cerevisiae/virologia , Resposta a Proteínas não Dobradas/fisiologia , Proteínas do Core Viral/metabolismo , Animais , Citosol/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Humanos , Proteínas de Membrana/metabolismo , Dobramento de Proteína , Saccharomyces cerevisiae/metabolismo
16.
J Neurooncol ; 136(2): 317-326, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29143277

RESUMO

It is sometimes difficult to distinguish gliomas from other tumors on routine imaging. In this study, we assessed whether 3-T magnetic resonance spectroscopy (MRS) with LCModel software might be useful for discriminating glioma from other brain tumors, such as primary central nervous system lymphomas (PCNSLs) and metastatic tumors. A total of 104 cases of brain tumor (66 gliomas, 20 PCNSLs, 6 metastatic tumors, 12 other tumors) were preoperatively investigated with short echo time (35 ms) single-voxel 3-T MRS. LCModel software was used to evaluate differences in the absolute concentrations of choline, N-acetylaspartate, N-acetylaspartylglutamate, glutamate + glutamine, myo-inositol (mIns), and lipid. mIns levels were significantly increased in high-grade glioma (HGG) compared with PCNSL (p < 0.001). In multivariate logistic regression analysis, mIns was the best marker for differentiating HGG from PCNSL (p < 0.0001, odds ratio 1.9927, 95% confidence interval 1.3628-3.2637). Conventional MRS detection of mIns resulted in a high diagnostic accuracy (sensitivity, 64%; specificity, 90%; area under the receiver operator curve, 0.80) for HGG. The expression of inositol 3-phosphate synthase (ISYNA1) was significantly higher in gliomas than in PCNSLs (p < 0.05), suggesting that the increased level of mIns in glioma is due to high expression of ISYNA1, the rate-limiting enzyme in the mIns-producing pathway. In conclusion, noninvasive analysis of mIns using single-voxel MRS may be useful in distinguishing gliomas from other brain tumors, particularly PCNSLs.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Glioma/diagnóstico por imagem , Glioma/metabolismo , Inositol/análise , Linfoma/diagnóstico por imagem , Linfoma/metabolismo , Espectroscopia de Ressonância Magnética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
17.
Clin Transplant ; 31(11)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28871665

RESUMO

Evaluation methods, such as scoring systems for predicting complications in advance, are necessary for determining the adaptation of allogeneic hematopoietic cell transplantation (HCT) and selecting appropriate conditioning regimens. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), which is based on functions of main organs, is a useful tool for pre-transplant risk assessments and has been widely applied in determining treatment strategies for patients with hematological diseases. However, as allogeneic HCT is performed on patients with diverse backgrounds, another factor, which reinforces the HCT-CI, is required to evaluate pre-transplant risk assessments. The Glasgow Prognostic Score (GPS), which assesses the combined C-reactive protein and albumin, was reported to predict survival of patients with solid-organ malignancies independently of receiving chemo/radiotherapy and stages of cancer. In this study, we applied the GPS for pre-transplant risk assessments for allogeneic HCT. The GPS successfully stratified the patients into three risk groups of overall survival (OS) and non-relapse mortality (NRM). Moreover, the GPS could predict outcomes independently of the HCT-CI for OS and NRM in multivariate analysis. The GPS is considered to be a useful tool and reinforces the HCT-CI for determining adaptation of allogeneic HCT for patients with hematopoietic neoplasms.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/normas , Recidiva Local de Neoplasia/prevenção & controle , Cuidados Pré-Operatórios/normas , Adolescente , Adulto , Idoso , Comorbidade , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
19.
Pathol Int ; 66(3): 164-168, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26778729

RESUMO

A 19-year-old woman with a history of recurrent aphthous stomatitis and genital ulceration was diagnosed with Behçet disease. She was treated with steroids and immunosuppressive agents for more than 30 years, but multiple complications manifested including ileocecal ulcer, aortic valve regurgitation, renal failure, ischemic enterocolitis, and arteriosclerotic obliterans until her death at the age of 56 from pneumonia. An autopsy examination demonstrated an entirely calcified aorta and major aortic branches. The ascending aorta was dilatated 55 mm in diameter and branches were all stenosed. Microscopically, the aortic arch and its branches showed collagenous fibrosis of the outer media and adventitia, whereas coronary and abdominal aortic branches showed conventional atherosclerosis. Although the ante-mortem diagnosis was angio-Behçet disease, its pathophysiology along with her clinical history, morphology of the lead pipe-like aorta, predominant destruction of the outer arteries, and a human leukocyte antigen (HLA) haplotype of B39 were all suggestive of Takayasu arteritis. Thus, this case implies that HLA-B39 may be associated with the pathogenesis of arteritis like Takayasu arteritis, even if the primary disease is Behçet disease.


Assuntos
Síndrome de Behçet/diagnóstico , Antígeno HLA-B39/metabolismo , Arterite de Takayasu/etiologia , Aorta/patologia , Aorta Torácica/patologia , Insuficiência da Valva Aórtica , Autopsia , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/patologia , Evolução Fatal , Feminino , Fibrose/etiologia , Fibrose/patologia , Humanos , Pneumonia/complicações , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/patologia , Calcificação Vascular , Adulto Jovem
20.
Tohoku J Exp Med ; 238(3): 229-36, 2016 03.
Artigo em Inglês | MEDLINE | ID: mdl-26983794

RESUMO

The many women with breast cancer who underwent axillary lymph node dissection (ALND) suffer from the upper arm dysfunction. In this study, we investigated the effectiveness of a perioperative educational program for improving upper arm dysfunction in breast cancer patients following ALND. This study was a sub-analysis of a previous controlled trial with an educational program. The subjects of this analysis included 64 patients following ALND who completed measurements at 12 months. The perioperative educational program consisted of monitoring of arm dysfunction, exercises, massage, and lifestyle adjustments. The intervention group (37 patients) received this perioperative educational program over 12 months, while 27 patients in the control group received written information about shoulder exercise from on-site staff only before surgery. Primary outcomes were shoulder range of motion (ROM), arm girth, and grip strength. Secondary outcomes were evaluated with the Subjective Perception of Post-Operative Functional Impairment of the Arm (SPOFIA) scores, the Disabilities of the Arm, Shoulder and Hand (DASH) scores, and the Medical Outcome Study 36-Item Short-Form Health Survey v2 (SF-36v2). The SF-36v2 measures health-related quality of life (QOL). Primary and secondary outcomes were compared between groups at 1 week (after drainage tube removal) and 12 months after surgery, using the Mann-Whitney U test. The horizontal extension was significantly improved only in the intervention group. Moreover, the SPOFIA score was significantly improved in the intervention group, and other scores of the secondary outcomes were similar between the two groups. The perioperative educational program may improve postoperative upper arm dysfunction and symptoms.


Assuntos
Braço/fisiopatologia , Neoplasias da Mama , Movimento (Física) , Educação de Pacientes como Assunto , Assistência Perioperatória/educação , Adulto , Feminino , Seguimentos , Força da Mão , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estudos Prospectivos
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