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1.
J Oral Rehabil ; 51(3): 574-580, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37964441

RESUMO

BACKGROUND: There is no clear objective indicator for selecting soft foods that are required for food bolus formation in older people with impaired oral function. OBJECTIVE: This study aimed to investigate the relationship between maximal isometric tongue pressure (MITP) and the mechanical properties of gels that can be crushed by the tongue. METHODS: This study included 65 healthy participants aged 22-96 (young group; 15 males, 15 females; older dentate group; 7 males, 8 females; older edentulous group; 10 males, 10 females). MITP was measured by the balloon-probe device. Agar gel with 10 different kinds of fracture force from 10N to 100N was used. The limit of fracture force of gels (LFFG) that were crushed by the tongue was measured by the up-and-down method. In the older edentulous group, two items were measured with and without dentures. Spearman's rank correlation coefficient was used to evaluate the relationship between MITP and LFFG in each group (p < .05). RESULTS: There were positive correlations between MITP and LFFG in all groups (overall groups: rs = .66, young group: rs = .46, older dentate group: rs = .61, older edentulous group with dentures: rs = .60, older edentulous group without dentures: rs = .47). CONCLUSION: MITP and LFFG were positively correlated in young, older dentate and older edentulous groups, suggesting that MITP has the potential to be an objective indicator of the range of mechanical properties of soft food that can be crushed by the tongue.


Assuntos
Boca Edêntula , Língua , Masculino , Feminino , Humanos , Idoso , Pressão , Géis
2.
J Clin Periodontol ; 50(2): 265-275, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36330666

RESUMO

AIM: To investigate the association between periodontal disease and atherosclerosis and to examine whether the association is modified by hypertension status. MATERIALS AND METHODS: In this cross-sectional study, 1472 Japanese individuals aged 50-79 years who underwent a medical check-up, dental examination, and carotid ultrasonography were studied. Carotid atherosclerosis was expressed as the maximum and mean carotid intima-media thickness (max-IMT, mean-IMT) and the presence of stenosis (≥75%). Periodontal status was examined by the Community Periodontal Index (CPI, codes 0-4). The participants were divided into three groups according to the periodontal status (CPI0-2, CPI3, CPI4). RESULTS: A positive correlation was found between mean-IMT and periodontal disease after adjustment for cardiovascular risk factors in the entire cohort (mean-IMT in hypertensives: CPI0-2: 0.848 mm, CPI3: 0.857 mm, CPI4: 0.877 mm; normotensives: 0.782, 0.802, 0.826). In the entire cohort, the multivariable-adjusted odds ratio of stenosis based on mean-IMT significantly increased according to periodontal status in normotensives (odds ratio; CPI0-2: 1, CPI3: 1.39, CPI4: 2.53; p-value for trend = .004) but showed only marginal significant increase in hypertensives (1, 1.15, 1.55; p-value for trend = .063). No significant relationships were observed for max-IMT in all analyses. CONCLUSION: We observed an association between periodontal disease and atherosclerosis in normotensive and hypertensive participants.


Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Hipertensão , Doenças Periodontais , Humanos , Espessura Intima-Media Carotídea , Artérias Carótidas , Constrição Patológica/complicações , População Urbana , Estudos Transversais , População do Leste Asiático , Hipertensão/complicações , Hipertensão/epidemiologia , Aterosclerose/complicações , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia , Fatores de Risco
3.
Surg Today ; 53(1): 98-108, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35913634

RESUMO

PURPOSE: Anticancer drugs for double cancers are selected based on their therapeutic effects on the target cancer, but there are insufficient data on the effects of anticancer drugs on comorbid cancer. We investigated the effect of chemotherapy on comorbid cancer in patients with simultaneous double cancers. METHODS: The subjects of this retrospective study were 51 patients with simultaneous double cancers at the time of receiving systemic chemotherapy. We evaluated the types of anticancer drugs used for double cancers, the therapeutic effects on targeted and comorbid cancers, and prognoses. RESULTS: Disease control was achieved for 90.9% of the target cancers and 90.7% of the comorbid cancers. The prognosis was significantly better when the disease was controlled, not only in the target cancer but also in the comorbid cancer. CONCLUSION: Physicians treating double cancers should develop treatment strategies focusing not only on the treatment for advanced cancer, but also on the course of comorbidities and the therapeutic effects of anticancer drugs. This study is important because it presents new possibilities to expand the indications for anticancer drugs, while allowing unnecessary clinical research to be avoided.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Estudos Retrospectivos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Antineoplásicos/efeitos adversos , Prognóstico
4.
Ann Surg Oncol ; 29(11): 7149-7162, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35644860

RESUMO

BACKGROUND: Fibroblast growth factor receptor (FGFR)-signaling in lung squamous cell carcinoma (LSCC) is associated with cancer aggressiveness and poor prognosis. Small GTPase RAB11A regulates the recycling of membrane proteins such as FGFR. This study evaluated the potential of RAB11A as a new therapeutic target for LSCC through its regulation of FGFR-signaling. METHODS: Immunohistochemical analysis of 84 LSCC samples was performed to determine the correlation between RAB11A expression, clinicopathologic features, and prognosis. Alterations in FGFR-signaling were assessed in RAB11A-suppressed and RAB11A-overexpressed LSCC cells both in vitro and in vivo. RESULTS: The study identified RAB11A as a strong predictor of poor prognosis in the LSCC cohort. Cell proliferation and invasion were promoted and inhibited respectively in RAB11A-overexpressed and RAB11A -suppressed LSCC cells. In RAB11A-overexpressed and RAB11A-suppressed LSCC cells, FGFR-signaling was respectively up- and downregulated. The viability of the cells treated with nintedanib and lenvatinib was greater in RAB11A-overexpressing cells than in control cells. The in vivo tumor growth and micro-vessel density of RAB11A-overexpressing tumors were significantly higher than in the control cells. CONCLUSION: As a potentially valuable prognostic marker, RAB11A is a promising therapeutic target for LSCC. Evaluation of RAB11A may be useful for identification of LSCC in patients whose cancer is refractory to FGFR inhibitors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Laríngeas , Neoplasias Pulmonares , Proteínas Monoméricas de Ligação ao GTP , Proteínas rab de Ligação ao GTP , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/patologia , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Monoméricas de Ligação ao GTP/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/uso terapêutico
5.
J Clin Periodontol ; 48(9): 1208-1215, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34189741

RESUMO

AIM: We aimed to clarify the association between deterioration of periodontal status and masticatory performance in a longitudinal follow-up study of a general urban population. MATERIALS AND METHODS: This study investigated 663 participants in the Suita study with no changes in the number of functional teeth or occlusal support areas during a 5-year follow-up period. Participants were classified into three groups according to changes in periodontal status during the survey period: a recovered group; a stable group; and a deteriorated group. Rate of masticatory performance change was calculated by subtracting the value at baseline from the value at follow-up and dividing the resulting value by the baseline value. RESULTS: Median rates of masticatory performance change were -11.7% in the recovered group, -19.2% in the stable group, and -30.8% in the deteriorated group, and these values were significantly different (p < .001). Multiple regression analysis revealed periodontal status group (recovered group: reference; stable group: p = .029; deteriorated group: p = .006) as an independent variable was significantly associated with the rate of masticatory performance change. CONCLUSION: The present results suggest that deterioration of periodontal status increases the risk of age-related declines in masticatory performance.


Assuntos
Mastigação , Seguimentos , Humanos , População Urbana
6.
J Oral Rehabil ; 48(5): 575-581, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33432636

RESUMO

Dentists often encounter patients suffering from psychological and social stress due to declines in masticatory performance, making this a critical issue to manage. We aimed to clarify the relationships between salivary stress markers as objective indices of chronic stress and objective masticatory performance in a general urban Japanese population. Data from 880 participants (mean age, 65.8 years) in the Suita study were used. Salivary interleukin (IL)-6 and cortisol concentrations were measured by enzyme-linked immunosorbent assay. Objective masticatory performance was determined by measuring the increase in surface area test gummy jelly after 30 times chewing. Participants were divided into two groups based on masticatory performance: a decreased group (lowest quartile) and a non-decreased group (second to fourth quartiles). Odds ratios (ORs) of higher salivary levels of stress markers (highest quartile) according to masticatory performance were estimated using logistic regression analysis adjusting for age, sex, periodontal status, salivary flow rate and smoking habit. Salivary IL-6 level was significantly higher in the decreased group than in the non-decreased group. Logistic regression analysis showed the adjusted OR for higher salivary IL-6 was significantly higher in the decreased group than in the non-decreased group (OR = 1.92; 95% confidence interval = 1.33-2.76; P < .001). No significant associations were found between salivary cortisol and decreased masticatory performance in any analyses. Declines in objective masticatory performance may correlate with higher salivary IL-6 level as an objective index of chronic stress.


Assuntos
Hidrocortisona , Mastigação , Idoso , Biomarcadores , Humanos , Razão de Chances , Saliva , População Urbana
7.
Surg Today ; 50(9): 1099-1106, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32052182

RESUMO

PURPOSE: Exosomes and their cargo microRNAs play a significant role in various biological processes in cancer. We hypothesized that microRNAs in exosomes secreted by gefitinib-resistant lung cancer cells might induce resistant phenotypes in otherwise gefitinib-sensitive lung cancer cells. METHODS: We isolated exosomes generated by the gefitinib-resistant human lung adenocarcinoma cell line PS-9/ZD. PC-9, which is a gefitinib-sensitive cell line, was treated with the PC-9/ZD exosomes, and these PC-9 cells were analyzed for cell proliferation after treatment with gefitinib. miRNA arrays were analyzed in PC-9 and PC-9/ZD cells, and we isolated microRNAs that were expressed at elevated levels in PC-9/ZD cells. Furthermore, we transfected these microRNAs into PC-9 cells and analyzed the effects on the cells' sensitivity to gefitinib. RESULTS: Exosomes isolated from PC-9/ZD cells significantly increased the proliferation of PC-9 cells during gefitinib treatment. A microRNA array analysis showed that miR-564, miR-658, miR-3652, miR-3126-5p, miR-3682-3p and miR-6810-5p were significantly upregulated in PC-9/ZD cells. PC-9 cells transfected with miR-564 or miR-658 showed chemo-resistant phenotypes. CONCLUSION: Exosomal miR-564 and miR-658 derived from gefitinib-resistant lung cancer cells induce drug resistance in sensitive cells. Cell-to-cell interaction via exosomal microRNAs may be a novel mechanism and therapeutic target of resistance against gefitinib.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Comunicação Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/genética , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MicroRNAs , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Humanos , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , MicroRNAs/fisiologia , Terapia de Alvo Molecular , Regulação para Cima
8.
Odontology ; 108(4): 715-722, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32140950

RESUMO

Masticatory performance of subjects from a general urban population was examined by measurement at baseline and again at follow-up, to clarify whether periodical utilization of dental services (PUDS) is effective in maintaining masticatory performance. Subjects comprised 1010 people (414 males, 596 females; mean age at baseline, 65.7 ± 7.8 years) who participated in the Suita study with dental checkups at both baseline and follow-up (mean follow-up, 5.2 ± 1.5 years). Number of functional teeth, occlusal support, periodontal status, masticatory performance, maximum bite force, and salivary flow rate were surveyed. Subjects were divided into a with-PUDS group (n = 430), who responded at both baseline and follow-up that they regularly utilized dental services, and a without-PUDS group (n = 580), who responded otherwise. To evaluate longitudinal changes in masticatory performance over the study period, the rate of masticatory performance change was calculated by dividing the difference in masticatory performance between follow-up and baseline by the masticatory performance at baseline. The relationship between the presence of PUDS and the rate of masticatory performance change was investigated by multiple linear regression analysis. Analysis was performed using a model with number of functional teeth as an independent variable (number of functional teeth model), and a model with occlusal support as an independent variable (occlusal support model). Multiple linear regression analysis identified PUDS as significantly associated with the rate of masticatory performance change in both the number of functional teeth model and the occlusal support model. PUDS is likely to prove effective in ameliorating reductions in masticatory performance over time.


Assuntos
Força de Mordida , Mastigação , Feminino , Masculino
9.
Ann Surg Oncol ; 26(6): 1744-1750, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30924018

RESUMO

BACKGROUND: Lung combined neuroendocrine carcinomas (NECs) comprise NEC and non-NEC components, such as adenocarcinoma and squamous cell carcinoma. Mutation of epidermal growth factor receptor (EGFR) often is observed in non-NEC but is very rare in sporadic NEC, which almost always has p53 mutation. Therefore, we hypothesized the following research concept: mutation analysis of EGFR and p53 in each component of combined NEC tissues can provide important information on whether such components originate from the same tumor cells or incidentally arise as collision cancers. METHODS: We compared the mutations of EGFR and p53 in laser-microdissected NEC and non-NEC from lungs of eight cases affected by combined NEC. We examined the expression of EGFR and NEC markers in the combined NECs by immunohistochemistry. RESULTS: Five of eight cases of combined NEC had the same mutations of EGFR and/or p53 in both non-NEC and NEC. One case had EGFR mutation in only the non-NEC component, and two cases did not have these mutations. Replacement transformation was observed in borderline areas between non-NEC and NEC. The signal of activated EGFR in non-NEC with the same EGFR mutation was more intense than that in NEC components. CONCLUSIONS: Our study suggests the mechanism behind the carcinogenesis of lung combined NEC, which is partially caused by the transformation from epithelial carcinoma of non-NEC to NEC.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Mutação , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Idoso , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Análise Mutacional de DNA , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética
10.
Environ Health Prev Med ; 24(1): 15, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30836943

RESUMO

Reductions in masticatory function as a result of tooth loss have a negative impact on nutrient intake, decreasing general health. In addition, studies have reported an association between lower socioeconomic status (SES) and both higher numbers of lost teeth and worse nutrient intake status. Nakamura et al. conducted a study to clarify the relationship between number of teeth and nutrient intake status in their paper "Having few remaining teeth is associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese individuals: Findings from the NIPPON DATA", evaluating not only data obtained from a household-based dietary survey but also serum albumin levels as a nutritional biomarker. Importantly, the present study also took into account the individual SES of subjects in the analysis of number of teeth and nutrient intake. The present results show that the trend for poorer nutrient intake with lower number of teeth is more marked among individuals with low SES. It is therefore essential that individual SES is taken into account in efforts to improve nutrient intake and thus contribute to general health through oral health.


Assuntos
Perda de Dente , Dieta , Ingestão de Energia , Humanos , Japão , Pessoa de Meia-Idade , Nutrientes
11.
World J Surg ; 42(4): 1161-1170, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28983707

RESUMO

OBJECTIVES: The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC. METHODS: Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions. RESULTS: All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%). CONCLUSIONS: The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Pleura/patologia , Prognóstico , Radiografia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
BMC Oral Health ; 18(1): 77, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728099

RESUMO

BACKGROUND: The association of periodontal bacteria with lipid profile alteration remains largely unknown, although it has been suggested that chronic periodontitis increases the atherosclerotic risk. This cross-sectional study investigated the relationship between the prevalence and total burden of periodontal bacteria and serum lipid profile. METHODS: Saliva from enrolled participants was collected to detect 4 major periodontal bacteria (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Prevotella intermedia) using Polymerase Chain Reaction method. High-density lipoprotein (HDL) cholesterol, triglycerides (TG), and low-density lipoprotein cholesterol were assessed using blood samples. We compared the averages of each lipid in association with the prevalence of each bacterial species, their burden (low, moderate, and high), and the combination of bacterial burden and periodontal status, defined as periodontitis, using the Community Periodontal Index, after adjustment for other potential confounding factors, by employing general linear models with least square means. RESULTS: A total of 385 Japanese individuals (176 men, 209 women; mean age 69.2 years) were enrolled. The number of bacterial species and their co-existence with periodontitis were significantly related to a decrease in HDL (p for trend < 0.01) and increase in TG (p for trend = 0.04). The adjusted mean HDL levels (mg/dL) in individuals with low, moderate, and high levels of bacterial species were 66.1, 63.0, and 58.9, respectively, and those in the 6 groups defined by combination of the two factors were 67.9, 64.6, 64.3, 65.4, 61.5, and 54.7, respectively. CONCLUSION: Periodontal bacterial burden is suggested to be independently involved in lowering serum HDL level. Our findings suggest that bacterial tests in a clinical setting could be a useful approach for predicting the risk of HDL metabolism dysregulation.


Assuntos
Lipídeos/sangue , Periodonto/microbiologia , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Porphyromonas gingivalis , Prevotella intermedia , Saliva/microbiologia , Tannerella forsythia , Treponema denticola , Triglicerídeos/sangue
13.
Angew Chem Int Ed Engl ; 57(36): 11629-11633, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-29978938

RESUMO

Exon 20 insertion (Ex20Ins) mutations are the third most prevalent epidermal growth factor receptor (EGFR) activating mutation and the most prevalent HER2 mutation in non-small cell lung cancer (NSCLC). Novel therapeutics for the patients with Ex20Ins mutations are urgently needed, due to their poor responses to the currently approved EGFR and HER2 inhibitors. Here we report the discovery of highly potent and broadly effective EGFR and HER2 Ex20Ins mutant inhibitors. The co-crystal structure of compound 1 b in complex with wild type EGFR clearly revealed an additional hydrophobic interaction of 4-fluorobenzene ring within a deep hydrophobic pocket, which has not been widely exploited in the development of EGFR and HER2 inhibitors. As compared with afatinib, compound 1 a exhibited superior inhibition of proliferation and signaling pathways in Ba/F3 cells harboring either EGFR or HER2 Ex20Ins mutations, and in the EGFR P772_H773insPNP patient-derived lung cancer cell line DFCI127. Our study identifies promising strategies for development of EGFR and HER2 Ex20Ins mutant inhibitors.


Assuntos
Fluorbenzenos/química , Fluorbenzenos/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/química , Receptores ErbB/genética , Éxons , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Simulação de Acoplamento Molecular , Mutação , Receptor ErbB-2/química , Receptor ErbB-2/genética
14.
Acta Neuropathol ; 134(4): 605-617, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28478503

RESUMO

Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid beta (Aß) deposits and causes cerebral hemorrhage and dementia. The exact molecules that co-accumulate with cerebrovascular Aß deposits are still not fully known. In our study here, we performed proteomic analyses with microdissected leptomeningeal arteries and cerebral neocortical arterioles from 8 cases with severe CAA, 12 cases with mild CAA, and 10 control cases without CAA, and we determined the levels of highly expressed proteins in cerebral blood vessels in CAA. We focused on sushi repeat-containing protein 1 (SRPX1), which is specifically expressed in CAA-affected cerebral blood vessels. Because SRPX1, which is known as a tumor suppressor gene, reportedly induced apoptosis in tumor cells, we hypothesized that SRPX1 may play an important role in Aß-induced apoptosis in CAA. Immunohistochemical studies revealed that SRPX1 co-accumulated with Aß deposits in cerebral blood vessels of all autopsied cases with severe CAA. In contrast, no SRPX1 co-accumulated with Aß deposits in senile plaques. Furthermore, we demonstrated that both Aß40 and Aß42 bound to SRPX1 in vitro and enhanced SRPX1 expression in primary cultures of cerebrovascular smooth muscle cells. SRPX1 enhanced caspase activity induced by Aß40. Knockdown of SRPX1, in contrast, reduced the formation of Aß40 accumulations and the activity of caspase in cultured cerebrovascular smooth muscle cells. SRPX1 may thus be a novel molecule that is up-regulated in cerebrovascular Aß deposits and that may increase Aß-induced cerebrovascular degeneration in CAA.


Assuntos
Encéfalo/metabolismo , Angiopatia Amiloide Cerebral/metabolismo , Proteínas de Membrana/metabolismo , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Animais , Apolipoproteínas E/genética , Encéfalo/patologia , Células Cultivadas , Angiopatia Amiloide Cerebral/genética , Angiopatia Amiloide Cerebral/patologia , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Proteoma , RNA Interferente Pequeno
15.
Cancer Sci ; 107(7): 1055-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27420474

RESUMO

An 80-year-old man, who developed multiple lymph node and skin metastasis of malignant melanoma, received nivolumab monotherapy. Two weeks after the first dose, he experienced anorexia and fatigue, and suffered from progressive, severe dyspnea and muscle weakness. We diagnosed him with myocarditis, myositis, and myasthenic crisis induced by nivolumab. We commenced steroid therapy, immune absorption therapy, plasma exchange therapy, and i.v. immunoglobulin therapy, and succeeded in saving his life. Because his serum level of anti-acetylcholine receptor antibodies in a sample collected before nivolumab treatment were positive and were elevated significantly after nivolumab, we suspected that nivolumab triggered a severe autoimmune response, which progressed subclinical myasthenia gravis to myasthenic crisis. We carried out T cell receptor repertoire analysis using next-generation sequencing technologies and identified infiltration of clonally expanded T cell populations in the skeletal muscle after nivolumab treatment, implying a very strong T cell immune response against muscular cells. To avoid severe immune-related adverse events, the exclusion of patients with subclinical autoimmune disease is very important for treatment with immune checkpoint inhibitors.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Miastenia Gravis/induzido quimicamente , Polimiosite/induzido quimicamente , Idoso de 80 Anos ou mais , Humanos , Masculino , Miastenia Gravis/sangue , Miastenia Gravis/genética , Miastenia Gravis/imunologia , Miocardite/sangue , Miocardite/induzido quimicamente , Miocardite/genética , Miocardite/imunologia , Nivolumabe , Polimiosite/sangue , Polimiosite/genética , Polimiosite/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Transcriptoma
16.
J Surg Oncol ; 112(2): 231-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26180037

RESUMO

BACKGROUND: Despite advances in the development of various therapeutic agents, non-small cell lung cancer (NSCLC) is associated with a poor prognosis. To improve the prognosis of patients with NSCLC, new therapeutic targets for overcoming drug resistance are required. The process of autophagy is required to support the tumorigenesis and drug resistance of cancer cells. We investigated the clinical significance of SIRT6, a member of the NAD(+) -dependent deacetylase family, which regulates a variety of cancer-related processes, including autophagy. METHODS: Immunohistochemistry analysis of SIRT6 expression and localization in 98 NSCLC clinical specimens and in vitro analysis using SIRT6-knockout lung carcinoma cell lines were performed. RESULTS: Patients with high cytoplasmic expression and low nuclear expression of SIRT6 (n = 33) had more aggressive cancer, shorter overall survival, and shorter recurrence-free survival than did patients with different SIRT6 expression profiles (P < 0.05). In vitro analysis revealed that SIRT6 knockdown lung adenocarcinoma cell line improved paclitaxel sensitivity (P < 0.05) and reduced the expression levels of both nuclear factor kappaB and autophagy marker Beclin1. CONCLUSION: Our data demonstrated that SIRT6 expression in NSCLC could be a useful prognostic marker and that SIRT6 might represent a novel target gene for predicting sensitivity of chemotherapy in lung adenocarcinoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/química , Neoplasias Pulmonares/tratamento farmacológico , Sirtuínas/análise , Adenocarcinoma/química , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Adulto , Idoso , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Radioterapia Adjuvante
17.
Brain ; 137(Pt 2): 520-36, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24271323

RESUMO

The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting TH1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/líquido cefalorraquidiano , Hipertrofia/sangue , Hipertrofia/líquido cefalorraquidiano , Meningite/sangue , Meningite/líquido cefalorraquidiano , Peroxidase/sangue , Peroxidase/líquido cefalorraquidiano , Vasculite/enzimologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Hipertrofia/enzimologia , Masculino , Meningite/enzimologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Vasculite/sangue , Vasculite/líquido cefalorraquidiano
18.
J Clin Periodontol ; 41(5): 497-503, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24527750

RESUMO

AIM: In this study, we investigated the effect of differences in periodontal status in the masticatory performance of dentate subjects with the same occlusal supporting area. MATERIALS AND METHODS: The subjects of the analysis were classified into those of Eichner A1-3 (n = 1094) and Eichner B1-4 (n = 529). Subjects' periodontal status was evaluated on the basis of the Community Periodontal Index (CPI). The number of functional teeth and occlusal support were investigated, the latter on the basis of the Eichner Index. Furthermore, masticatory performance was investigated by means of test gummy jelly. For each group, periodontal status was classified in two different ways, either with/without moderate periodontitis (CPI Code ≤2/≥3) or with/without severe periodontitis (CPI Code ≤3/4), and masticatory performance was compared between the various groups. RESULTS: In subjects who were Eichner A1 and B3, masticatory performance was significantly lower in subjects with moderate periodontitis compared with those without, and in subjects with severe periodontitis compared with those without. CONCLUSION: Periodontal disease affects masticatory performance not only if occlusion is established by natural dentition with no tooth loss but also if occlusal support has decreased.


Assuntos
Dentição , Mastigação/fisiologia , Índice Periodontal , Idoso , Estudos de Coortes , Coroas , Cálculos Dentários/classificação , Cálculos Dentários/fisiopatologia , Prótese Parcial Fixa , Feminino , Humanos , Japão , Arcada Parcialmente Edêntula/classificação , Arcada Parcialmente Edêntula/fisiopatologia , Estudos Longitudinais , Masculino , Periodontite/classificação , Periodontite/fisiopatologia , Estudos Prospectivos , Perda de Dente/fisiopatologia
19.
Geriatr Gerontol Int ; 24 Suppl 1: 327-333, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38114072

RESUMO

AIM: Awareness of difficulty chewing may limit the diversity of food intake in older adults. However, few studies have clarified which factors are related to subjective difficulty in chewing. The aim was to identify factors related to subjective difficulty in chewing in 70- and 80-year-old Japanese older adults. METHODS: A total of 1680 participants (792 men, 888 women) were surveyed. Difficulty in chewing was assessed with questionnaires regarding food intake, such as rice, apples, beef, and hard rice crackers. The participants were classified into two groups, the "with difficulty" group (participants who answered "cannot eat," "can eat with difficulty," and "can eat if small") and the "without difficulty" group (participants who answered "can eat without problems"), according to their answers to questionnaires for each food. A logistic regression analysis with subjective difficulty in chewing as the dependent variable was performed for each food. RESULTS: Subjective difficulty in chewing was associated with age, occlusal force, and depression for rice; age, number of remaining teeth, occlusal force, and depression for apples; number of remaining teeth, occlusal force, and depression for beef; and number of remaining teeth and occlusal force for hard rice crackers. CONCLUSIONS: Age, number of remaining teeth, and occlusal force, as well as depression, might be related to subjective evaluation of difficulty chewing in community-dwelling Japanese older adults. Geriatr Gerontol Int 2024; 24: 327-333.


Assuntos
Vida Independente , Mastigação , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Inquéritos e Questionários , Alimentos , Força de Mordida
20.
J Dent ; 145: 104991, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38608831

RESUMO

OBJECTIVES: This study aimed to investigate the association between the number of teeth, food intake, and cognitive function in Japanese community-dwelling older adults. METHODS: This 9-year longitudinal study included a total of 293 analyzable participants who participated in baseline and follow-up surveys. Dental status (number of teeth and periodontal pocket depth), dietary assessment using the brief-type self-administered diet history questionnaire, cognitive function, and the following confounding factors were evaluated: educational level, financial satisfaction, living situation, smoking and drinking habits, history of chronic diseases, apolipoprotein E-ε4 carrier, body mass index, handgrip strength, instrumental activities of daily living, and depressive symptomatology. The Japanese version of the Montreal Cognitive Assessment was used to evaluate cognitive function. A multinomial logistic regression analysis for the intake level of each food categorized into three groups (low, moderate, high), and a generalized estimating equation (GEE) for cognitive function over nine years were performed. RESULTS: After controlling for confounding factors, the number of teeth was shown to be associated with the intake of green-yellow vegetables and meat. Furthermore, the GEE indicated that the lowest quartile of intake of green-yellow vegetables significantly associated with lower cognitive function (unstandardized regression coefficient [B] = -0.96, 95 % confidence interval [CI]: -1.72 to -0.20), and the lowest quartile of intake of meat significantly associated with lower cognitive function (B = -1.42, 95 % CI: -2.27 to -0.58). CONCLUSIONS: The intake of green and yellow vegetables and meat, which is influenced by the number of teeth, was associated with cognitive function in Japanese community-dwelling older adults. CLINICAL SIGNIFICANCE: There are few studies that have examined the association between oral health, food intake, and cognitive function. This 9-year longitudinal study suggests that it is important to maintain natural teeth to enable the functional means to consume green-yellow vegetables and meat, and thereby help maintain cognitive function.


Assuntos
Cognição , Ingestão de Alimentos , Humanos , Estudos Longitudinais , Idoso , Masculino , Feminino , Cognição/fisiologia , Japão , Ingestão de Alimentos/fisiologia , Dieta , Verduras , Perda de Dente , Pessoa de Meia-Idade , Vida Independente , Idoso de 80 Anos ou mais , Comportamento Alimentar , Saúde Bucal , Inquéritos e Questionários , Carne , Atividades Cotidianas
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