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1.
Clin Radiol ; 79(5): e702-e714, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38402086

RESUMO

AIM: To evaluate the clinical utility of feature tracking (FT)-derived myocardial strain in patients with non-ischaemic dilated cardiomyopathy (NIDCM). MATERIALS AND METHODS: Electronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. Studies on NIDCM were divided into categories according to left ventricular ejection fraction (LVEF; <30%, 30-40%, >40%), and correlations between strains and prevalence of late gadolinium enhancement (LGE) were evaluated by weighted correlation coefficients. Global longitudinal strain (GLS) hazard ratios were also integrated for prediction of future adverse events. RESULTS: The present meta-analysis analysed data from 5,767 patients with NIDCM from 30 eligible studies. GLS and global circumferential strain significantly differed across the three LVEF categories (all p<0.05); however, global radial strain did not. Only GLS showed a strong correlation with the prevalence of LGE (Spearman's correlation coefficient = 0.61). The pooled HR of GLS for predicting adverse events was 1.15 (95% confidence interval [CI]: 1.07-1.23, p<0.001). CONCLUSION: In this meta-analysis, FT-derived GLS was strongly correlated with myocardial fibrosis and was an important predictor of future adverse events. These results suggest that FT-derived GLS may be useful in the pathological evaluation and risk stratification of NIDCM.


Assuntos
Cardiomiopatia Dilatada , Função Ventricular Esquerda , Humanos , Volume Sistólico , Prognóstico , Cardiomiopatia Dilatada/diagnóstico por imagem , Meios de Contraste , Imagem Cinética por Ressonância Magnética/métodos , Gadolínio , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes
2.
Acta Radiol ; 63(4): 458-466, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33709794

RESUMO

BACKGROUND: The low-tube-voltage scan generally needs a higher tube current than the conventional 120 kVp to maintain the image noise. In addition, the low-tube-voltage scan increases the photoelectric effect, which increases the radiation absorption in organs. PURPOSE: To compare the organ radiation dose caused by iodine contrast medium between low tube voltage with low contrast medium and that of conventional 120-kVp protocol with standard contrast medium. MATERIAL AND METHODS: After the propensity-matching analysis, 66 patients were enrolled including 33 patients with 120 kVp and 600 mgI/kg and 33 patients with 80 kVp and 300 mgI/kg (50% iodine reduction). The pre- and post-contrast phases were assessed in all patients. The Monte Carlo simulation tool was used to simulate the radiation dose. The computed tomography (CT) numbers for 10 organs and the organ doses were measured. The organ doses were normalized by the volume CT dose index, and the 120-kVp protocol was compared with the 80-kVp protocol. RESULTS: On contrast-enhanced CT, there were no significant differences in the mean CT numbers of the organs between 80-kVp and 120-kVp protocols except for the pancreas, kidneys, and small intestine. The normalized organ doses at 80 kVp were significantly lower than those of 120 kVp in all organs (e.g. liver, 1.6 vs. 1.9; pancreas, 1.5 vs. 1.8; spleen, 1.7 vs. 2.0) on contrast-enhanced CT. CONCLUSION: The low tube voltage with low-contrast-medium protocol significantly reduces organ doses at the same volume CT dose index setting compared with conventional 120-kVp protocol with standard contrast medium on contrast-enhanced CT.


Assuntos
Meios de Contraste , Doses de Radiação , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/instrumentação , Imagem Corporal Total/métodos , Adulto , Feminino , Humanos , Iodo , Masculino , Pessoa de Meia-Idade
3.
Int Endod J ; 53(10): 1387-1397, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32573791

RESUMO

AIM: To investigate the relationship between apical periodontitis and atherosclerosis in rats by lipid profile and carotid artery intima tunic measurement, and histological and histometric evaluation of periapical lesions. METHODOLOGY: Forty male Wistar rats were allocated into four groups: control (C), with apical periodontitis (AP), with atherosclerosis (AT) and with AP and AT (AP + AT). Atherosclerosis was induced using a high-lipid diet associated with a surgical ligature in the carotid artery and a super dosage of vitamin D3 . AP was induced via pulp exposure to the oral environment. At 45 and 75 days, serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. The maxillary and mandibular jaws and carotid artery were collected and processed for histological analysis. The Kruskal-Wallis or Mann-Whitney test was performed for nonparametric data, and the Tukey's or Student's t-test was performed for parametric data (P < 0.05). RESULTS: In nonatherosclerotic animals, the induction of apical periodontitis increased TG levels significantly, from 63.1 ± 11.4 mg dL-1 in group C to 88.2 ± 7.9 mg dL-1 in the AP group (P < 0.05). The induction of AP was associated with a trend for higher TC and LDL-C levels in atherosclerotic animals (P > 0.05); however, it only significantly increased TG levels, from 93.2 ± 18.0 mg dL-1 in AT group to 121.9 ± 14.5 mg dL-1 in the AP + AT group (P < 0.05). Animals in the AP + AT group had a 36.5% increase in the thickness of the carotid intima tunic when compared with the AT group (P < 0.05). The intensity of the inflammatory infiltrate was significantly larger in the AP + AT group when compared with AP group (P < 0.05). The AP + AT group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 206.4 ± 56.3 × 104 µm2 , compared with 151.4 ± 49.1 × 104 µm2 in the AP group (P < 0.05). CONCLUSION: Apical periodontitis influenced triglyceride levels, increasing them even in the absence of atherosclerosis, and influenced the increase in the thickness of the carotid artery intima tunic in the presence of atherosclerosis. Atherosclerosis intensified the inflammatory reaction and increased bone resorption in periapical lesions.


Assuntos
Aterosclerose , Periodontite Periapical , Animais , Aterosclerose/etiologia , Humanos , Inflamação , Lipídeos , Masculino , Ratos , Ratos Wistar
4.
Int Endod J ; 53(5): 660-670, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31808951

RESUMO

AIM: To evaluate the morphology and impact of root canal preparation in maxillary incisors with palatogingival grooves (PGG). METHODOLOGY: Twenty extracted human maxillary incisors with PGG were subjected to macroscopic analysis and scanning electron microscopy analysis (SEM). The following characteristics of the PGG were evaluated: depth, point of origin in the cingulum, extension and position on the lingual surface. Furthermore, the presence of calculus, communications between the root canal system and the PGG, and root resorptions were investigated. The root canals were subsequently instrumented with K-files of three consecutive sizes. The teeth were sectioned, and the axial plane of each tooth section was imaged using SEM before and after instrumentation. The distance between the root canal walls and the PGG was calculated according to the location. Additionally, the distance between canal walls and cementum was measured at three different sites, to verify if instrumentation influenced dentine removal on a specific wall in teeth with PGG. Statistical analysis was performed using the Mann-Whitney or Student's t-test (P < 0.05). RESULTS: Macroscopic analysis revealed that a deep groove was most frequently observed (75%), followed by a depression/shallow groove (25%) (P < 0.05). PGG typically originated in the distal margin ridge of the cingulum (65%) (P < 0.05), extending only to the middle (45%) or up to the apical (50%) third of the root (P < 0.05). Additionally, PGGs were typically located on the distal aspect of the lingual surface (70%) (P < 0.05). Calculus was concentrated on the surface of the crown and cementum-enamel junction (P < 0.05). Communication between the root canal and PGG was present in 35% of teeth, and root resorptions were noted in 50% of teeth. The distance between the external root surface and the pulp cavity was significantly narrower after instrumentation (P < 0.05); however, root canal preparation did not influence dentine removal on the specific wall associated with the groove (P > 0.05). CONCLUSIONS: Palatogingival grooves were characteristically deep and originated from the distal margin of the cingulum. Although it has been associated with a thinner root wall, root canal preparation did not influence the thickness of the specific wall in the maxillary incisors with PGG.


Assuntos
Cavidade Pulpar , Camada de Esfregaço , Cemento Dentário , Dentina , Humanos , Incisivo , Irrigantes do Canal Radicular , Preparo de Canal Radicular , Tratamento do Canal Radicular
5.
AJNR Am J Neuroradiol ; 41(1): 106-110, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31857323

RESUMO

BACKGROUND AND PURPOSE: Because it can be difficult to discriminate between a Rathke cleft cyst and cystic craniopharyngioma by conventional MR imaging alone, we investigated whether contrast-enhanced 3D T2-FLAIR MR imaging at 3T helps to distinguish a Rathke cleft cyst from a cystic craniopharyngioma. MATERIALS AND METHODS: We evaluated pre- and postcontrast T1-weighted and 3D T2-FLAIR images of 17 patients with pathologically confirmed Rathke cleft cyst (n = 10) or cystic craniopharyngioma (n = 7). All underwent 3T MR imaging studies before surgery. Two neuroradiologists independently recorded the enhancement grade of the lesion wall as grade 2 (most of the wall enhanced), grade 1 (some of the wall enhanced), and grade 0 (none of the wall enhanced). One neuroradiologist performed a blinded reading study of conventional MR images with/without 3D T2-FLAIR images. Interobserver agreement was determined by calculating the κ coefficient. Statistical analyses, including receiver operating characteristic curve analysis were performed. RESULTS: Interobserver agreement for postcontrast T1WI and 3D T2-FLAIR images was excellent (κ = 0.824 and κ = 0.867, respectively). Although the difference in the mean enhancement grade of Rathke cleft cysts and cystic craniopharyngiomas was not significant on postcontrast T1WIs, it was significant on postcontrast 3D T2-FLAIR images (P = .0011). The area under the receiver operating characteristic curve of the conventional MR alone and conventional MR with 3D T2-FLAIR readings was 0.879 and 1.0, respectively, though there was no significant difference in the area under the curve between the 2 readings. CONCLUSIONS: Contrast-enhanced 3D T2-FLAIR imaging at 3T helps to distinguish a Rathke cleft cyst from cystic craniopharyngioma.


Assuntos
Cistos do Sistema Nervoso Central/diagnóstico por imagem , Craniofaringioma/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Curva ROC , Estudos Retrospectivos
6.
AJNR Am J Neuroradiol ; 41(2): 310-317, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31879331

RESUMO

BACKGROUND AND PURPOSE: Intraplaque hemorrhage in the carotid artery is related to an increased risk of cerebrovascular ischemic events. We aimed to investigate whether quantitative susceptibility mapping can characterize carotid artery plaque components and quantify the severity of intraplaque hemorrhage. MATERIALS AND METHODS: For this ex vivo quantitative susceptibility mapping study, 9 carotid endarterectomy specimens were imaged on a 3T MR imaging scanner using a 3D multi-echo gradient-echo sequence and a microscopy coil. The samples were examined histologically using immunostains, including glycophorin A and Prussian blue. The areas of erythrocytes, iron deposits, calcification, and fibrous matrices observed on stained sections were compared with quantitative susceptibility mapping findings and their mean susceptibility values. RESULTS: Intraplaque hemorrhage and iron deposits were observed only in areas hyperintense on quantitative susceptibility mapping; calcifications and fibrous matrices were prevalent in hypointense areas. The mean susceptibility values for necrotic cores with intraplaque hemorrhage but no iron deposits, cores with iron deposits but no intraplaque hemorrhage, cores without either intraplaque hemorrhage or iron deposits, and cores with calcification were 188 ± 51, 129 ± 49, -11 ± 17, and -158 ± 78 parts per billion, respectively. There was a significant difference in the mean susceptibility values among the 4 histologic components (P < .01). The mean susceptibility values of the whole plaque positively correlated with the percentage area positive for glycophorin A (r = 0.65, P < .001) and Prussian blue (r = 0.47, P < .001). CONCLUSIONS: Our findings suggest that quantitative susceptibility mapping can characterize the composition of carotid plaques and quantify the degree of intraplaque hemorrhage and iron deposits.


Assuntos
Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Imageamento por Ressonância Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Clin Radiol ; 74(11): 898.e7-898.e13, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31439285

RESUMO

AIM: To determine the usefulness of three-dimensional reversed fast imaging with steady-state precession diffusion-weighted imaging (3D-PSIF DWI) for the detection of middle ear cholesteatoma. MATERIALS AND METHODS: The study population consisted of 81 patients who underwent 3D-PSIF-DWI at 3 T. They included cholesteatoma in 73 cases, otitis media in five, and cholesterol granuloma in three. Two observers independently performed qualitative evaluations for the detection of cholesteatoma and measured apparent diffusion coefficient (ADC) values and ADC ratios of the lesions. Kappa (κ) statistics, the intraclass correlation coefficient (ICC), the independent t-test, and receiver operating characteristic (ROC) analysis were used for statistical analysis. Pair-wise comparison of the ROC curves was performed using the area under the ROC curve (AUC). RESULTS: Interobserver agreement and ICC for the qualitative and quantitative evaluations were excellent (κ=0.92 and ICC=0.90-0.92, respectively). The ADC value and the ADC ratio were significantly lower for cholesteatoma than non-cholesteatoma lesions (p<0.0001). In <5 mm cholesteatoma group, the diagnostic performance of the ADC value (AUC=0.97) and the ADC ratio (AUC=1) was significantly superior to qualitative 3D-PSIF-DWI (AUC=0.76; p=0.0001 and <0.0001, respectively). For ≥5 mm cholesteatoma group, there were no significant differences in diagnostic performance among the three parameters. CONCLUSION: 3D-PSIF-DWI sequence is useful for the detection of middle ear cholesteatomas, especially <5 mm lesions.


Assuntos
Colesteatoma da Orelha Média/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colesteatoma da Orelha Média/cirurgia , Protocolos Clínicos , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Recidiva , Estudos Retrospectivos , Adulto Jovem
8.
Eur Rev Med Pharmacol Sci ; 23(2): 857-876, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30720195

RESUMO

OBJECTIVE: High-fat diet (HFD) feeding stimulates fat accumulation in mammals and Drosophila. In the present study, we examined whether simultaneous feeding of familiar anti-obesity drugs, quercetin glycosides (QG) and epigallocatechin gallate (EGCG), to Drosophila has the same suppressive effect on fat accumulation as previously reported in rats and mice. To understand the underlying molecular mechanisms of HFD diet-induced obesity and the suppression effect of the drugs, we performed transcriptome analyses. MATERIALS AND METHODS: We induced extra fat accumulation by feeding Drosophila fly food containing 20% coconut oil and quantified the triglyceride accumulated in flies. The effects of anti-obesity drugs were also evaluated. We isolated total RNA from each sample and performed RNA-seq analyses and quantitive Real Time-Polymerase Chain Reaction (qRT-PCR) to investigate altered gene expression. RESULTS: The mRNA levels of several genes involved in lipid metabolism, glycolysis/gluconeogenesis, and anti-oxidative stress changed in HFD-fed adults. Moreover, the levels altered in those fed an HFD with QG or EGCG. The qRT-PCR further confirmed the RNA-seq data, suggesting that the expression of five essential genes for lipid metabolism changed in HFD-fed flies and altered in the flies treated with anti-obesity drugs. The most remarkable alteration was observed in the dHSL gene encoding a lipase involved in lipid-storage after HFD feeding and HFD with QG or EGCG. These alterations are consistent with HFD-induced fat accumulation as well as the anti-obesity effects of the drugs in mammals, suggesting that the genes play an important role in anti-obesity effects. CONCLUSIONS: These are the first reports to date of entire profiles of altered gene expression under the conditions of diet-induced obesity and its suppression by anti-obesity drugs in Drosophila.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Catequina/análogos & derivados , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/metabolismo , Quercetina/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Catequina/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Drosophila , Avaliação Pré-Clínica de Medicamentos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/administração & dosagem , Humanos , Masculino , Metabolômica/métodos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA-Seq , Especificidade da Espécie
9.
Ann Oncol ; 30(2): 250-258, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566590

RESUMO

BACKGROUND: Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. PATIENTS AND METHODS: Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. RESULTS: Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. CONCLUSION: Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. CLINICALTRIALS.GOV ID: NCT02746796.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica/efeitos dos fármacos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Combinação de Medicamentos , Junção Esofagogástrica/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Nivolumabe/administração & dosagem , Oxaliplatina/administração & dosagem , Ácido Oxônico/administração & dosagem , Prognóstico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Tegafur/administração & dosagem
10.
Phys Rev B ; 100(13)2019.
Artigo em Inglês | MEDLINE | ID: mdl-33644522

RESUMO

An inelastic neutron scattering study has been performed in an S = 3/2 bilayer honeycomb lattice compound Bi3Mn4O12(NO3) at ambient and high magnetic fields. Relatively broad and monotonically dispersive magnetic excitations were observed at ambient field, where no long-range magnetic order exists. In the magnetic-field-induced long-range ordered state at 10 T, the magnetic dispersions become slightly more intense, albeit still broad as in the disordered state, and two excitation gaps, probably originating from an easy-plane magnetic anisotropy and intrabilayer interactions, develop. Analyzing the magnetic dispersions using the linear spin-wave theory, we estimated the intraplane and intrabilayer magnetic interactions, which are almost consistent with those determined by ab initio density functional theory calculations [M. Alaei et al., Phys. Rev. B 96, 140404(R) (2017)], except the third and fourth neighbor intrabilayer interactions. Most importantly, as predicted by the theory, there is no significant frustration in the honeycomb plane but frustrating intrabilayer interactions probably give rise to the disordered ground state.

11.
J Dent Res ; 96(6): 685-693, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28199142

RESUMO

Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis ( n = 6-7/group) where Pasteurella pneumotropica ( Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis. DC-STAMP was expressed on the cell surface of mature multinuclear OCs, as well as immature mononuclear OCs, in primary cultures of RANKL-stimulated bone marrow cells. Anti-DC-STAMP-mAb suppressed the emergence of large, but not small, multinuclear OCs, suggesting that DC-STAMP is engaged in the late stage of cell fusion. Anti-DC-STAMP-mAb also inhibited pit formation caused by RANKL-stimulated bone marrow cells. Attachment of ligature to a second maxillary molar induced DC-STAMP messenger RNA and protein, along with elevated tartrate-resistant acid phosphatase-positive (TRAP+) OCs and alveolar bone loss. As we expected, systemic administration of anti-DC-STAMP-mAb downregulated the ligature-induced alveolar bone loss. Importantly, local injection of anti-DC-STAMP-mAb also suppressed alveolar bone loss and reduced the total number of multinucleated TRAP+ cells in mice that received ligature attachment. Attachment of ligature induced significantly elevated tumor necrosis factor-α, interleukin-1ß, and RANKL in the gingival tissue compared with the control site without ligature ( P < 0.05), which was unaffected by local injection with either anti-DC-STAMP-mAb or control-mAb. Neither in vivo anti- Pp IgG antibody nor in vitro anti- Pp T-cell response and resultant production of RANKL was affected by anti-DC-STAMP-mAb. This study illustrated the roles of DC-STAMP in promoting local OC cell fusion without affecting adaptive immune responses to oral bacteria. Therefore, it is plausible that a novel therapeutic regimen targeting DC-STAMP could suppress periodontal bone loss.


Assuntos
Proteínas de Membrana/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Osteoclastos/metabolismo , Periodontite/patologia , Animais , Anticorpos Monoclonais/farmacologia , Western Blotting , Reabsorção Óssea/patologia , Diferenciação Celular , Fusão Celular , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica , Masculino , Proteínas de Membrana/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/antagonistas & inibidores , Osteoclastos/efeitos dos fármacos , Ligante RANK/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
12.
Pharmacogenomics J ; 17(1): 36-41, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26503819

RESUMO

Estrogen has been shown not only to reduce the incidence of colorectal cancer but also gastric cancer (GC). Polymorphisms in estrogen receptor ß gene, ESR2, correlate with colorectal cancer survival. To better understand the role of ESR2 in GC, genomic DNA extracted from 169 Japanese patients and 172 patients from Los Angeles County (LAC) was analyzed for association of overall survival (OS) with three ESR2 polymorphisms, which are of biological significance using multivariable Cox proportional hazard regression. ESR2 rs1271572 (C>A) and rs3020443 (T>G) had univariate and multivariable associations with OS in the Japanese cohort, whereas the C allele of ESR2 rs2978381 (T>C) predicted favorable OS in the Japanese cohort but worse OS in the LAC cohort. The interaction term of the ESR2 rs2978381 and cohort group reached statistical significance. Our study provides evidence that genetic variations in ESR2 gene are significantly associated with survival in patients with locally advanced GC.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Receptor beta de Estrogênio/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Japão , Estimativa de Kaplan-Meier , Los Angeles , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Fenótipo , Regiões Promotoras Genéticas , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Fatores de Tempo , Resultado do Tratamento
13.
Pharmacogenomics J ; 17(6): 528-534, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27241062

RESUMO

Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set. The C allele of PDCD1 rs10204525 had univariate and multivariable associations with shorter OS in Japanese cohort (P=0.015, P=0.043, respectively). In US cohort the C allele predicted worse OS (P=0.007). Univariate and multivariable analyses revealed IDO1 rs9657182 associated with OS in the Japanese cohort; moreover, the association was confirmed in the US cohort. Genetic predisposition of the host in the immunomodulators may serve as a prognostic biomarker in patients with locoregional GC.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Imunomodulação/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Intervalo Livre de Doença , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Receptor de Morte Celular Programada 1/genética , Neoplasias Gástricas/terapia
14.
Mucosal Immunol ; 10(3): 650-660, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27731324

RESUMO

The PD-1/B7-H1 pathway regulates immune responses and maintains homeostasis. Here, we identified a unique expression of B7 homolog 1 (B7-H1) on masticatory mucosae in the oral cavity. B7-H1 was physiologically expressed on the dorsal surface of the tongue, gingiva, and hard palate. Other squamous epithelia and other structures of the epithelia did not express B7-H1 in the steady state. Physiological B7-H1 expression on masticatory mucosae was limited on prickle cells, and its expression on basal keratinocytes (KCs) was strictly regulated. B7-H1 on prickle cells was upregulated by external topical stimuli, but B7-H1 on basal KCs was induced only by internal stimuli via infiltrating cells. The blocking of KC-associated B7-H1 or the lack of programmed cell death-1 (PD-1) on tissue effector CD4+ T cells in mice lacking B7-H1 on immune cells drastically exacerbated the tissue inflammation induced by topical OVA painting as an exogenous antigen, indicating direct interaction with KCs and CD4+ T cells. Trans-coinhibitory signals by KCs may modulate local T-cell/dendritic cell activation, resulting in inhibition of T-cell responses in both peripheral and secondary lymphoid tissues. Careful control of B7-H1 induction in KCs may play a crucial role in the protection from CD4+ T cell-mediated tissue inflammation by exogenous antigens delivered from the mucosal surface.


Assuntos
Antígeno B7-H1/metabolismo , Linfócitos T CD4-Positivos/imunologia , Inflamação/imunologia , Queratinócitos/imunologia , Mucosa Bucal/imunologia , Boca/imunologia , Sistema Estomatognático/imunologia , Animais , Antígeno B7-H1/genética , Células Cultivadas , Feminino , Homeostase , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo
15.
AJNR Am J Neuroradiol ; 37(5): 782-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26822728

RESUMO

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping is useful for assessing iron deposition in the substantia nigra of patients with Parkinson disease. We aimed to determine whether quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference in iron deposits in the substantia nigra of patients with Parkinson disease. MATERIALS AND METHODS: Our study population comprised 24 patients with Parkinson disease and 24 age- and sex-matched healthy controls. They underwent 3T MR imaging by using a 3D multiecho gradient-echo sequence. On reconstructed quantitative susceptibility mapping, we measured the susceptibility values in the anterior, middle, and posterior parts of the substantia nigra, the whole substantia nigra, and other deep gray matter structures in both hemibrains. To identify the more and less affected hemibrains in patients with Parkinson disease, we assessed the severity of movement symptoms for each hemibrain by using the Unified Parkinson's Disease Rating Scale. RESULTS: In the posterior substantia nigra of patients with Parkinson disease, the mean susceptibility value was significantly higher in the more than the less affected hemibrain substantia nigra (P < .05). This value was significantly higher in both the more and less affected hemibrains of patients with Parkinson disease than in controls (P < .05). Asymmetry of the mean susceptibility values was significantly greater for patients than controls (P < .05). Receiver operating characteristic analysis showed that quantitative susceptibility mapping of the posterior substantia nigra in the more affected hemibrain provided the highest power for discriminating patients with Parkinson disease from the controls. CONCLUSIONS: Quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference of iron deposition in the substantia nigra of patients with Parkinson disease.


Assuntos
Imageamento Tridimensional/métodos , Ferro/análise , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Curva ROC , Substância Negra/química
16.
AJNR Am J Neuroradiol ; 36(9): 1669-74, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26066629

RESUMO

BACKGROUND AND PURPOSE: The precise identification and measurement of the medial geniculate nucleus and lateral geniculate nucleus on MR imaging remain technically challenging because the thalamic nuclei are small structures. We compared the visualization of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging with 3D high-resolution phase imaging, 2D-T2WI, STIR, proton attenuation-weighted imaging, and DTI acquired at 3T. We also measured the volume and height of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging. MATERIALS AND METHODS: Phase difference enhanced, 2D-T2-weighted, STIR, proton attenuation-weighted, and DTI were acquired on a 3T MR imaging unit in 10 healthy volunteers. Two neuroradiologists recorded the qualitative visualization scores of the medial geniculate nucleus and lateral geniculate nucleus, specifically the identification of their boundaries, for all images. Measurement differences were assessed with the Wilcoxon signed rank test. The volume and height of the medial geniculate nucleus and lateral geniculate nucleus were measured on phase difference enhanced imaging and compared with previously reported values. RESULTS: The qualitative visualization scores of the lateral geniculate nucleus and medial geniculate nucleus were significantly higher on phase difference enhanced images than on T2-weighted, proton attenuation-weighted, STIR, or DTI (P < .05). On phase difference enhanced imaging, the medial geniculate nucleus and lateral geniculate nucleus were bordered by low-intensity structures: the cerebral peduncle, the origin of the optic radiation, and the superior and inferior quadrigeminal brachia. The volume of the medial geniculate nucleus and lateral geniculate nucleus varied from 74.0 to 183.75 mm(3) (mean, 129.0 ± 34.7 mm(3)) and from 96.5 to 173.75 mm(3) (mean, 135.2 ± 28.0 mm(3)), respectively. CONCLUSIONS: For the depiction of the medial geniculate nucleus and lateral geniculate nucleus on 3T MR imaging, phase difference enhanced imaging is superior to conventional MR imaging. The medial geniculate nucleus and lateral geniculate nucleus volumes vary among individuals.


Assuntos
Corpos Geniculados , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Masculino
17.
Aust Dent J ; 60(3): 412-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25280059

RESUMO

This is a rare case report of a cerebellopontine angle (CPA) mass mimicking lingual nerve injury after a dental implant placement. Lingual nerve injury is a common complication following dental implant placement. CPA masses are likely to cause symptomatic trigeminal neuralgia, and thus can mimic and be easily confused with oral diseases. We experienced a case of CPA mass mimicking lingual nerve injury after dental implant placement. The patient was a 57-year-old Japanese female who complained of glossalgia. She underwent dental implant placement in the mandible before visiting our clinic. Panoramic x-ray radiography revealed no abnormalities; the salivary flow rate by gum test was 7.0 ml/10 min. She was diagnosed with lingual nerve injury and secondary burning mouth syndrome. Vitamin B12 and oral moisturizer did not provide relief; furthermore, numbness in the lower lip emerged. A Semmes Weinstein test demonstrated elevation of her sensitivity threshold. Finally, magnetic resonance imaging revealed a 20-mm diameter mass in the CPA. The patient is now being followed under conservative management. Our experience underscores the importance of including CPA mass in the differential diagnosis of dental diseases.


Assuntos
Doenças Cerebelares/diagnóstico , Ângulo Cerebelopontino/patologia , Implantes Dentários/efeitos adversos , Traumatismos do Nervo Lingual/diagnóstico , Síndrome da Ardência Bucal/diagnóstico , Diagnóstico Diferencial , Feminino , Seguimentos , Glossalgia/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Radiografia Panorâmica , Neuralgia do Trigêmeo/diagnóstico
18.
Ann Oncol ; 26(2): 332-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25411415

RESUMO

BACKGROUND: Nuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions. There have been few reports regarding association of the macrophage function-related genes with the clinical outcome in gastric cancer. We hypothesized that variants in genes encoding for NF-κB and CCL2/CCR2 axis may predict prognosis in gastric cancer and tested whether the functional single-nucleotide polymorphisms (SNPs) will be associated with clinical outcome in patients with gastric cancer across two independent groups. PATIENTS AND METHODS: This study enrolled two cohorts which consisted of 160 Japanese patients and 104 US patients with locoregional gastric cancer. Genomic DNA was analyzed for association of 11 SNPs in NFKB1, RELA, CCL2, and CCR2 with clinical outcome using PCR-based direct DNA sequencing. RESULTS: The univariable analysis showed four SNPs had significant association with clinical outcome in the Japanese cohort, NFKB1 rs230510 remained significant upon multivariable analysis. The patients with the A allele of the NFKB1 rs230510 had significantly longer overall survival (OS) compared with those with the T/T genotype in both the Japanese and US cohort in the univariable analysis. In contrast, genotypes with the T allele of CCL2 rs4586 were significantly associated with shorter OS compared with the C/C genotype in the US cohort [hazard ratio (HR) 2.43; P = 0.015] but longer OS in the Japanese cohort (HR 0.58; P = 0.021), resulting in the statistically significant opposite impact on OS (P = 0.001). CONCLUSIONS: Our study provides the first evidence that the NFKB1 rs230510 and CCL2 rs4586 are significantly associated with the clinical outcome in patients with locoregional gastric cancer. These results also suggest that the genetic predisposition of the host may dictate the immune-related component of the tumor for progression in gastric cancer.


Assuntos
Quimiocina CCL2/genética , Macrófagos/imunologia , NF-kappa B/genética , Receptores CCR2/genética , Neoplasias Gástricas/genética , Fator de Transcrição RelA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade
19.
AJNR Am J Neuroradiol ; 35(10): 2013-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24948497

RESUMO

BACKGROUND AND PURPOSE: Systematic investigations of the distinguishing imaging features between spinal hyperplastic hematopoietic bone marrow and bone metastasis have not been reported, to our knowledge. The purpose of this study was to determine the distinguishing imaging features of the 2 entities. MATERIALS AND METHODS: We retrospectively reviewed the radiologic images of 8 consecutive male patients (age range, 52-78 years; mean, 64 years) with suspected spinal metastasis on MR imaging and FDG-PET, which was later confirmed as hyperplastic hematopoietic bone marrow. MR imaging, FDG-PET, CT, and bone scintigraphy images were qualitatively and/or quantitatively evaluated. Imaging findings in 24 patients with spinal metastasis were compared, and differences were statistically analyzed. RESULTS: All 8 vertebral hyperplastic hematopoietic bone marrow lesions were hypointense on T1- and T2-weighted images; lesions contiguous with the adjacent vertebra were significantly more often seen in hyperplastic hematopoietic bone marrow than in metastasis (P = .035). T2 signal intensity of the lesion was significantly different between the 2 entities (P = .033). FDG-PET showed slightly higher uptake in all hyperplastic hematopoietic bone marrow lesions; their maximum standard uptake value was significantly lower than that of metastatic lesions (P = .037). CT attenuation of hyperplastic hematopoietic bone marrow was equal to or slightly higher than that of adjacent normal-appearing vertebra; the CT appearances of hyperplastic hematopoietic bone marrow and metastasis were significantly different (P < .01). Bone scintigraphy showed normal uptake for all vertebrae with hyperplastic hematopoietic bone marrow; the uptake was significantly different from that of metastasis (P < .01). CONCLUSIONS: If a lesion was isointense to hyperintense to normal-appearing marrow on MR imaging or had a maximum standard uptake value of >3.6, the lesion was considered metastatic. A normal appearance on CT or bone scintigraphy excluded metastasis.


Assuntos
Doenças da Medula Óssea/diagnóstico , Medula Óssea/patologia , Neoplasias da Coluna Vertebral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Hiperplasia/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Cintilografia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
J Dent Res ; 93(3): 288-93, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24378366

RESUMO

Dendritic cell (DC) migration to regional lymph nodes (RLNs) is an essential step in adaptive immunity, and cell-surface antigens on migrating DCs greatly affect the quality and quantity of subsequent immune responses. Although MHC class II(+) DC-like cells exist in the dental pulp, the lineage and function of these cells remain unknown. Here, we identified migratory DCs from the dental pulp after cusp trimming and acid etching in KikGR mice, in which the photoconvertible fluorescent protein changed from green to red upon violet light exposure. Two major cell fractions from the dental pulp had migrated to the RLNs at 16 hrs after cusp treatment, which showed the following lineage markers in the main and second fractions: CD11c(high)CD11b(++)Ly6C(low) Ly6G(low) F4/80(+) and CD11c(med)CD11b(+++)Ly6C(++)Ly6G(+++)F4/80(-), respectively. These lineage markers indicate that the former cells were DCs that had migrated through afferent lymphoid vessels, and the latter were granulocytes recruited via blood circulation. Migratory dental pulp DCs were mature, expressing the highest levels of CD273 (B7-DC) and CD86 co-stimulators and MHC class II. Our results suggest that cariogenic-bacteria-exposed dental pulp DCs migrate to RLNs and there trigger adaptive immune responses.


Assuntos
Células Dendríticas/imunologia , Polpa Dentária/citologia , Linfonodos/imunologia , Condicionamento Ácido do Dente/métodos , Imunidade Adaptativa/imunologia , Animais , Antígenos de Diferenciação/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos Ly/análise , Antígeno B7-2/análise , Antígeno CD11b/análise , Antígeno CD11c/análise , Linhagem da Célula/imunologia , Movimento Celular/imunologia , Feminino , Corantes Fluorescentes , Técnicas de Introdução de Genes , Antígenos de Histocompatibilidade Classe II/análise , Glicoproteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos BALB C , Proteína 2 Ligante de Morte Celular Programada 1/análise , Preparo do Dente/métodos
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