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Crystal lattices with tetragonal or hexagonal structure often exhibit structural transitions in response to external stimuli1. Similar behaviour is anticipated for the lattice forms of topological spin textures, such as lattices composed of merons and antimerons or skyrmions and antiskyrmions (types of vortex related to the distribution of electron spins in a magnetic field), but has yet to be verified experimentally2,3. Here we report real-space observations of spin textures in a thin plate of the chiral-lattice magnet Co8Zn9Mn3, which exhibits in-plane magnetic anisotropy. The observations demonstrate the emergence of a two-dimensional square lattice of merons and antimerons from a helical state, and its transformation into a hexagonal lattice of skyrmions in the presence of a magnetic field at room temperature. Sequential observations with decreasing temperature reveal that the topologically protected skyrmions remain robust to changes in temperature, whereas the square lattice of merons and antimerons relaxes to non-topological in-plane spin helices, highlighting the different topological stabilities of merons, antimerons and skyrmions. Our results demonstrate the rich variety of topological spin textures and their lattice forms, and should stimulate further investigation of emergent electromagnetic properties.
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Magnetic skyrmions are topologically stable swirling spin textures that appear as particle-like objects in two-dimensional (2D) systems. Here, utilizing scalar magnetic X-ray tomography under applied magnetic fields, we report the direct visualization of the three-dimensional (3D) shape of individual skyrmion strings in the room-temperature skyrmion-hosting non-centrosymmetric compound Mn1.4Pt0.9Pd0.1Sn. Through the tomographic reconstruction of the 3D distribution of the [001] magnetization component on the basis of transmission images taken at various angles, we identify a skyrmion string running through the entire thickness of the sample, as well as various defect structures, such as the interrupted and Y-shaped strings. The observed point defect may represent the Bloch point serving as an emergent magnetic monopole, as proposed theoretically. Our tomographic approach with a tunable magnetic field paves the way for direct visualization of the structural dynamics of individual skyrmion strings in 3D space, which will contribute to a better understanding of the creation, annihilation and transfer of these topological objects.
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OBJECTIVES: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress. STUDY DESIGN: This was a cross-sectional study. METHODS: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis. RESULTS: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: ß = 0.24, P = 0.197; severe burden: ß = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: ß = -3.29, P < 0.01). CONCLUSIONS: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.
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Cuidadores/psicologia , Relações Interpessoais , Angústia Psicológica , Características de Residência , Adaptação Psicológica , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Primary analysis of the phase III study WJTOG 3405 demonstrated superiority of progression-free survival (PFS) for gefitinib (G) in patients treated with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) gefitinib compared with cisplatin plus docetaxel (CD) as the first-line treatment of stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. This report presents final overall survival (OS) data. PATIENTS AND METHODS: Patients were randomized between G (250 mg/day orally) and cisplatin (80 mg/m2 intravenously) plus docetaxel (60 mg/m2 i.v.), administered every 21 days for three to six cycles. After the exclusion of 5 patients, 172 patients (86 in each group, modified intention-to-treat population) were included in the survival analysis. OS was re-evaluated using updated data (data cutoff, 30 September 2013; median follow-up time 59.1 months). The Kaplan-Meier method and the log-rank test were used for analysis, and hazard ratios (HRs) for death were calculated using the Cox proportional hazards model. RESULTS: OS events in the G group and CD group were 68 (79.1%) out of 86 and 59 (68.6%) out of 86, respectively. Median survival time for G and CD were 34.9 and 37.3 months, respectively, with an HR of 1.252 [95% confidence interval (CI): 0.883-1.775, P = 0.2070]. Multivariate analysis identified postoperative recurrence and stage IIIB/IV disease as independent prognostic factors, with an HR of 0.459 (95% CI: 0.312-0.673, P < 0.001). Median survival time (postoperative recurrence versus stage IIIB/IV disease) were 44.5 and 27.5 months in the G group and 45.5 and 32.8 months in the CD group, respectively. CONCLUSION: G did not show OS benefits over CD as the first-line treatment. OS of patients with postoperative recurrence was better than that of stage IIIB/IV disease, even though both groups had metastatic disease.This study was registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Gefitinibe/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Docetaxel/efeitos adversos , Receptores ErbB/genética , Feminino , Gefitinibe/efeitos adversos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do TratamentoRESUMO
As a generic property, all substances transfer heat through microscopic collisions of constituent particles 1 . A solid conducts heat through both transverse and longitudinal acoustic phonons, but a liquid employs only longitudinal vibrations2,3. As a result, a solid is usually thermally more conductive than a liquid. In canonical viewpoints, such a difference also serves as the dynamic signature distinguishing a solid from a liquid. Here, we report liquid-like thermal conduction observed in the crystalline AgCrSe2. The transverse acoustic phonons are completely suppressed by the ultrafast dynamic disorder while the longitudinal acoustic phonons are strongly scattered but survive, and are thus responsible for the intrinsically ultralow thermal conductivity. This scenario is applicable to a wide variety of layered compounds with heavy intercalants in the van der Waals gaps, manifesting a broad implication on suppressing thermal conduction. These microscopic insights might reshape the fundamental understanding on thermal transport properties of matter and open up a general opportunity to optimize performances of thermoelectrics.
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The real-space spin texture and the relevant magnetic parameters were investigated for an easy-axis noncentrosymmetric ferromagnet Cr_{11}Ge_{19} with Nowotny chimney ladder structure. Using Lorentz transmission electron microscopy, we report the formation of bi-Skyrmions, i.e., pairs of spin vortices with opposite magnetic helicities. The quantitative evaluation of the magnetocrystalline anisotropy and Dzyaloshinskii-Moriya interaction (DMI) proves that the magnetic dipolar interaction plays a more important role than the DMI on the observed bi-Skyrmion formation. Notably, the critical magnetic field value required for the formation of bi-Skyrmions turned out to be extremely small in this system, which is ascribed to strong easy-axis anisotropy associated with the characteristic helix crystal structure. The family of Nowotny chimney ladder compounds may offer a unique material platform where two distinctive Skyrmion formation mechanisms favoring different topological spin textures can become simultaneously active.
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Differential scanning calorimetry, X-ray diffraction, and quasi-elastic neutron scattering (QENS) measurements of aqueous glycine solutions confined in mesoporous silica (MCM-41) were performed at different glycine concentrations, pH, and loading ratio (=mass of glycine solution/mass of dry MCM-41) in the temperature range from 305 to 180 K to discuss the confinement effect on the thermal behavior, the structure, and the dynamic properties of the solutions. The freezing points of the confined glycine solutions decreased, compared with those of the bulk solutions. The corresponding exothermic peak due to ice formation became broader with an increase in the glycine concentration. By subtracting X-ray diffraction patterns of dry MCM-41 from those of glycine solution-loaded MCM-41, information about the structure of the confined glycine solutions was obtained. The radial distribution functions of the confined glycine solutions showed that the peaks assigned to the interaction between glycine molecules and the surface silanol (Si-OH) groups of MCM-41 at pH = 5 were observed, in contrast to the case at pH = 2. The QENS data on H/D substituted aqueous glycine solutions gave the translational diffusion coefficients and the residence time of glycine and water molecules confined in MCM-41 individually. The activation energy of the diffusion coefficient of a glycine molecule at pH = 5 was larger than that at pH = 2. These results imply that glycine molecules locate near the pore surface of MCM-41 due to the formation of hydrogen bonding between glycine molecules and the silanol group of the MCM-41 wall at pH = 5.
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Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Proteínas de Neoplasias/genética , Testes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Antieméticos/farmacocinética , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Feminino , Genótipo , Granisetron/farmacocinética , Granisetron/uso terapêutico , Humanos , Isoquinolinas/farmacocinética , Isoquinolinas/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Palonossetrom , Quinuclidinas/farmacocinética , Quinuclidinas/uso terapêuticoRESUMO
The internal and lattice structures of magnetic Skyrmions in B20-type FeGe are investigated using off-axis electron holography. The temperature, magnetic field, and angular dependence of the magnetic moments of individual Skyrmions are analyzed. The internal Skyrmion shape is found to vary with applied magnetic field. In contrast, the inter-Skyrmion distance remains almost unchanged in the lattice phase over the studied range of applied field. The amplitude of the local magnetic moment is found to vary with temperature, while the Skyrmion shape does not change significantly. Deviations from a circular to a hexagonal Skyrmion structure are observed in the lattice phase, in agreement with the results of micromagnetic simulations.
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J-PARC, Japan Proton Accelerator Research Complex provides short pulse proton beam at a repetition rate 25Hz and the maximum power is expected to be 1MW. Materials and Life Science Experimental Facility (MLF) has 23 neutron beam ports and 21 instruments have already been operated or under construction/commissioning. There are 6 inelastic/quasi-elastic neutron scattering spectrometers and the complementary use of these spectrometers will open new insight for life science. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.
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Elasticidade , Difração de Nêutrons/instrumentação , Análise Espectral/instrumentação , DNA/química , Japão , Bicamadas Lipídicas/química , Fônons , Prótons , Água/químicaRESUMO
Ionic liquids (ILs) are potential candidates for new antimicrobials due to their tunable antibacterial and antifungal properties that are required to keep pace with the growing challenge of bacterial resistance. To a great extent their antimicrobial actions are related to the interactions of ILs with cell membranes. Here, we report the effects of ILs on the nanoscopic dynamics and phase behaviour of a dimyristoylphosphatidylcholine (DMPC) membrane, a model cell membrane, as studied using neutron scattering techniques. Two prototypical imidazolium-based ILs 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM[BF4]) and 1-decyl-3-methylimidazolium tetrafluoroborate (DMIM[BF4]), which differ only in terms of the alkyl chain length of cations, have been used for the present study. Fixed Elastic Window Scan (FEWS) shows that the incorporation of ILs affects the phase behaviour of the phospholipid membrane significantly and the transition from a solid gel to a fluid phase shifts to lower temperature. This is found to be consistent with our differential scanning calorimetry measurements. DMIM[BF4], which has a longer alkyl chain cation, affects the phase behaviour more strongly in comparison to BMIM[BF4]. The pressure-area isotherms of the DMPC monolayer measured at the air-water interface show that in the presence of ILs, isotherms shift towards higher area-per lipid molecule. DMIM[BF4] is found to shift the isotherm to a greater extent compared to BMIM[BF4]. Quasielastic neutron scattering (QENS) data show that both ILs act as a plasticizer, which enhances the fluidity of the membrane. DMIM[BF4] is found to be a stronger plasticizing agent in comparison to BMIM[BF4] that has a cation with a shorter alkyl chain. The incorporation of DMIM[BF4] enhances not only the long range lateral motion but also the localised internal motion of the lipids. On the other hand, BMIM[BF4] acts weakly in comparison to DMIM[BF4] and mainly alters the localised internal motion of the lipids. Any subtle change in the dynamical properties of the membrane can profoundly affect the stability of the cell. Hence, the dominant effect of the IL with the longer chain length on the dynamics of the phospholipid membrane might be correlated with its cytotoxic activity. QENS data analysis has provided a quantitative description of the effects of the two imidazolium-based ILs on the dynamical and phase behaviour of the model cell membrane, which is essential for a detailed understanding of their action mechanism.
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OBJECTIVES: To clarify the functional status of the articularis genus muscle (AGM) in individuals with knee osteoarthritis (OA) and to analyze the muscle's relationship with knee OA. METHODS: Fifty-two individuals with knee OA (mean age, 73.4 years), 50 elderly individuals without knee OA changes (mean age, 71.2 years) and 75 young individuals (mean age, 20.2 years) were observed the AGM using ultrasonography. The thickness of the AGM, the anteroposterior distance of the suprapatellar bursa, and moving distance of the muscle insertion were measured both at rest and during isometric contraction, and values during contraction were expressed as percentages of the values at rest (%Muscle-Increase, %Bursa-Increase). RESULTS: Muscle thickness at rest, %Muscle-Increase, %Bursa-Increase, and moving distance of the muscle insertion were significantly lower and anteroposterior distance of the suprapatellar bursa was significantly higher in the OA group than in the controls (p<0.001, all). In the OA group, these values for the AGM were significantly correlated with knee range of motion, knee pain, and Kellgren and Lawrence grade. CONCLUSIONS: Individuals with knee OA exhibited atrophic changes and dysfunctions of the AGM, and these were associated with symptoms. Atrophic changes and dysfunctions of the AGM may be specific changes associated with knee OA.
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Osteoartrite do Joelho/fisiopatologia , Músculo Quadríceps/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/patologia , Amplitude de Movimento Articular/fisiologia , UltrassonografiaRESUMO
BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E). METHODS: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours. RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis revealed that performance status, residual tumor, metastatic sites, no debulking surgery, and non-S/E tumours were independent poor prognostic factors. For patients with non-S/E tumours, prognosis was more favourable for single-organ metastasis, except for liver or distant lymph nodes, no residual tumor, and resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively). CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a significantly poorer prognosis and higher rates of early mortality compared to S/E tumours. Therefore, careful management and development of new strategies are required.
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Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Carcinoma Endometrioide/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Carcinoma Epitelial do Ovário , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
Here, we describe an human leukocyte antigen (HLA)-A*24:02-restricted cytotoxic T-lymphocyte (CTL) clone, 1G3, established from naïve CD8(+) T-lymphocytes obtained from a healthy donor stimulated with HLA-modified TOV21G, an ovarian cancer cell line. The 1G3 clone responds not only to ovarian cancer cells in the context of HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive T-cell receptor recognition. Expression screening using a complementary DNA library constructed from TOV21G messenger RNA revealed that this alloreactivity was mediated through the nine-mer peptide VRTPYTMSY, derived from RNA-binding motif protein 4. To our knowledge, this study presents the first example of the allorecognition of an HLA-Cw molecule by HLA-A-restricted T-cells, thereby revealing a naturally processed epitope peptide. These findings provide the structural bases for the allorecognition of human T-cells. In addition, this study suggests that unexpected alloresponses occur in certain HLA combinations, and further study is needed to understand the mechanisms of alloreactivity for better prediction of alloresponses in clinical settings.
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Reações Cruzadas/imunologia , Antígeno HLA-A24/imunologia , Antígenos HLA-C/imunologia , Neoplasias Ovarianas/imunologia , Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional , Linfócitos T Citotóxicos/imunologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Linhagem Celular Tumoral , Células Clonais , DNA Complementar/genética , Epitopos/imunologia , Feminino , Células HEK293 , Humanos , Dados de Sequência Molecular , Neoplasias Ovarianas/patologia , Peptídeos/química , Ligação Proteica , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismoRESUMO
OBJECTIVE: Roles of aging or immune responses mediated by Toll-like receptors and natural killer cell in the onset or progression of human candidiasis remain unclear. This study was designed to elucidate the roles using peripheral blood mononuclear cells from healthy donors and patients with oral candidiasis. SUBJECTS AND METHODS: Subjects tested were healthy volunteers and patients who visited Dental Clinical Division of Hokkaido University Hospital. The patients with oral candidiasis included 39 individuals (25-89 years of age) with major complaints on pain in oral mucosa and/or dysgeusia. Healthy volunteers include students (25-35 years of age) and teaching staffs (50-65 years of age) of Hokkaido University Graduate School of Dental Medicine. RESULTS: Functions of Toll-like receptors 2 and 4 were downregulated significantly and the natural killer activity was slightly, but not significantly downregulated in aged healthy volunteers compared with healthy young volunteers. Functions of Toll-like receptors 2 and 4 and the natural killer activity were significantly downregulated in patients with oral candidiasis compared with healthy volunteers. CONCLUSION: Downregulation of functions of Toll-like receptors 2 and 4 as well as natural killer activity is suggested to be associated with the onset or progression of oral candidiasis in human.
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Candidíase Bucal/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Receptores Toll-Like/biossíntese , Receptores Toll-Like/imunologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Candida albicans/isolamento & purificação , Candidíase Bucal/microbiologia , Progressão da Doença , Regulação para Baixo , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores Toll-Like/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is a major etiological agent in the development and progression of periodontal diseases. In this study, we isolated a cell growth inhibitor against P. gingivalis species from rice protein extract. MATERIAL AND METHODS: The cell growth inhibitor active against P. gingivalis was purified from polished rice extract using a six-step column chromatography process. Its antimicrobial properties were investigated through microscope analysis, spectrum of activity and general structure. RESULTS: The inhibitor was identified as AmyI-1, an α-amylase, and showed significant cell growth inhibitory activity against P. gingivalis species. Scanning electron microscopy micrograph analysis and bactericidal assay indicated an intriguing possibility that the inhibitor compromises the cell membrane structure of the bacterial cells and leads to cell death. Moreover, α-amylases from human saliva and porcine pancreas showed inhibitory activity similar to that of AmyI-1. CONCLUSIONS: This is the first study to report that α-amylases cause cell death of periodontal pathogenic bacteria. This finding highlights the potential importance and therapeutic potential of α-amylases in treating periodontal diseases.
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Antibacterianos/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , alfa-Amilases/farmacologia , Animais , Membrana Celular/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Oryza/enzimologia , alfa-Amilases Pancreáticas/farmacologia , Doenças Periodontais/microbiologia , Extratos Vegetais/farmacologia , Porphyromonas gingivalis/crescimento & desenvolvimento , Porphyromonas gingivalis/ultraestrutura , Saliva/enzimologia , Proteínas e Peptídeos Salivares/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Suínos , alfa-Amilases/isolamento & purificaçãoRESUMO
BACKGROUND: NY-ESO-1 antibodies are specifically observed in patients with NY-ESO-1-expressing tumours. We analysed whether the NY-ESO-1 humoral immune response is a useful tumour marker of gastric cancer. METHODS: Sera from 363 gastric cancer patients were screened by enzyme-linked immunosorbent assay (ELISA) to detect NY-ESO-1 antibodies. Serial serum samples were obtained from 25 NY-ESO-1 antibody-positive patients, including 16 patients with curative resection and 9 patients who received chemotherapy alone. RESULTS: NY-ESO-1 antibodies were detected in 3.4% of stage I, 4.4% of stage II, 25.3% of stage III, and 20.0% of stage IV patients. The frequency of antibody positivity increased with disease progression. When the NY-ESO-1 antibody was used in combination with carcinoembryonic antigen and CA19-9 to detect gastric cancer, information gains of 11.2% in stages III and IV, and 5.8% in all patients were observed. The NY-ESO-1 immune response levels of the patients without recurrence fell below the cutoff level after surgery. Two of the patients with recurrence displayed incomplete decreases. The nine patients who received chemotherapy alone continued to display NY-ESO-1 immune responses. CONCLUSION: When combined with conventional tumour markers, the NY-ESO-1 humoral immune response could be a useful tumour marker for detecting advanced gastric cancer and inferring the post-treatment tumour load in seropositive patients.
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Anticorpos Antineoplásicos/sangue , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/sangue , Proteínas de Membrana/imunologia , Neoplasias Gástricas/imunologia , Idoso , Antígenos Glicosídicos Associados a Tumores/análise , Antígeno Carcinoembrionário/análise , Progressão da Doença , Feminino , Humanos , Imunidade Humoral , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Carga TumoralRESUMO
BACKGROUND: Gestational trophoblastic diseases (GTDs) are related to trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well as normal placentas. However, the asparagine-linked sugar chains on hCG contain abnormal biantennary structures in invasive mole and choriocarcinoma, but not normal pregnancy or hydatidiform mole. N-acetylglucosaminyltransferase-IV (GnT-IV) catalyses ß1,4-N-acetylglucosamine branching on asparagine-linked oligosaccharides, which are consistent with the abnormal sugar chain structures on hCG. METHODS: We investigated GnT-IVa expression in GTDs and placentas by immunohistochemistry, western blot, and RT-PCR. We assessed the effects of GnT-IVa knockdown in choriocarcinoma cells in vitro and in vivo. RESULTS: The GnT-IVa was highly expressed in trophoblasts of invasive mole and choriocarcinoma, and moderately in extravillous trophoblasts during the first trimester, but not in hydatidiform mole or other normal trophoblasts. The GnT-IVa knockdown in choriocarcinoma cells significantly reduced migration and invasive capacities, and suppressed cellular adhesion to extracellular matrix proteins. The extent of ß1,4-N-acetylglucosamine branching on ß1 integrin was greatly reduced by GnT-IVa knockdown, although the expression of ß1 integrin was not changed. In vivo studies further demonstrated that GnT-IVa knockdown suppressed tumour engraftment and growth. CONCLUSION: These findings suggest that GnT-IVa is involved in regulating invasion of choriocarcinoma through modifications of the oligosaccharide chains of ß1 integrin.
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Biomarcadores Tumorais/metabolismo , Coriocarcinoma/enzimologia , Coriocarcinoma/patologia , Doença Trofoblástica Gestacional/enzimologia , Doença Trofoblástica Gestacional/patologia , N-Acetilglucosaminiltransferases/metabolismo , Neoplasias Uterinas/enzimologia , Neoplasias Uterinas/patologia , Adulto , Western Blotting , Movimento Celular , Proliferação de Células , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Mola Hidatiforme Invasiva/enzimologia , Mola Hidatiforme Invasiva/patologia , Imuno-Histoquímica , Integrina beta1/metabolismo , N-Acetilgalactosaminiltransferases/metabolismo , Invasividade Neoplásica , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
We have investigated terahertz (THz) photon-assisted tunneling in single self-assembled InAs quantum dots (QDs). Two types of photon-assisted tunneling processes have been observed in the THz range: ground state resonance and photon-induced excited state resonance, depending on the relative magnitude between the orbital quantization energy of the QDs and the THz photon energy. Furthermore, we could realize a very high coupling efficiency between THz waves and QDs and observed multiphoton absorption up to the fourth-order during the tunneling process, resulting in almost complete lifting of the Coulomb blockade.
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OBJECTIVES: Although the rotation of lower extremities has gained increasing recognition as a risk factor for anterior cruciate ligament (ACL) injury. This study clarified the influence of lower extremity rotation on the knee during single-leg landing. DESIGN AND SETTING: We recruited 30 students to perform single-leg landing from a height of 30 cm with their lower extremities in neutral, and externally and internally rotated. The knee abduction, flexion angles, and abduction angular velocity were measured. Furthermore, the abduction angle was analyzed at knee flexion angles of 15°, 20°, 25°, and 30° and compared among the three conditions using a repeated measures analysis of variance with Bonferroni post hoc tests. RESULTS: The maximum abduction angle was significantly greater when internally rotated than in the neutral. The maximum abduction angular velocity was significantly greater in the internally rotated compared to in the neutral. Finally, the abduction angle at a knee flexion angle of 30° was significantly greater when internally rotated compared to in the neutral. CONCLUSION: Rotation of the lower extremities affects knee kinematics, and landing on a knee that is internally rotated may increase the risk of ACL injury.