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1.
Chem Commun (Camb) ; 60(61): 7918-7921, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38980140

RESUMO

We demonstrate that organic-inorganic interfacial charge-transfer transitions enable favourable photovoltaic conversion with CO2-fixation products such as aromatic carboxylic acids, verifying a new possibility of CO2-fixation products in the development of optoelectronic conversion materials.

2.
Nat Commun ; 15(1): 5380, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918393

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax oncoprotein regulates viral gene expression and persistently activates NF-κB to maintain the viability of HTLV-1-infected T cells. Here, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR as an essential survival factor of HTLV-1-transformed cells. Inhibition of KDR specifically induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4 + T cells from HAM/TSP patients. Furthermore, inhibition of KDR triggers the autophagic degradation of Tax resulting in impaired NF-κB activation and diminished viral transmission in co-culture assays. Tax induces the expression of KDR, forms a complex with KDR, and is phosphorylated by KDR. These findings suggest that Tax stability is dependent on KDR activity which could be exploited as a strategy to target Tax in HTLV-1-associated diseases.


Assuntos
Sobrevivência Celular , Produtos do Gene tax , Vírus Linfotrópico T Tipo 1 Humano , NF-kappa B , Paraparesia Espástica Tropical , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Produtos do Gene tax/metabolismo , Produtos do Gene tax/genética , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , NF-kappa B/metabolismo , Paraparesia Espástica Tropical/virologia , Paraparesia Espástica Tropical/metabolismo , Apoptose , Infecções por HTLV-I/virologia , Infecções por HTLV-I/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T/metabolismo , Linfócitos T/virologia , Leucemia-Linfoma de Células T do Adulto/virologia , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Fosforilação , Células HEK293
3.
Int J Mol Sci ; 24(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37511462

RESUMO

Immune responses in humanized mice are generally inefficient without co-transplantation of human thymus or HLA transgenes. Previously, we generated humanized mice via the intra-bone marrow injection of CD133+ cord blood cells into irradiated adult immunodeficient mice (IBMI-huNSG mice), which could mount functional immune responses against HTLV-1, although the underlying mechanisms were still unknown. Here, we investigated thymocyte development in IBMI-huNSG mice, focusing on the roles of human and mouse MHC restriction. IBMI-huNSG mice had normal developmental profiles but aberrant thymic structures. Surprisingly, the thymic medulla-like regions expanded after immunization due to enhanced thymocyte expansion in association with the increase in HLA-DR+ cells, including CD205+ dendritic cells (DCs). The organ culture of thymus from immunized IBMI-huNSG mice with a neutralizing antibody to HLA-DR showed the HLA-DR-dependent expansion of CD4 single positive thymocytes. Mature peripheral T-cells exhibited alloreactive proliferation when co-cultured with human peripheral blood mononuclear cells. Live imaging of the thymus from immunized IBMI-huNSG mice revealed dynamic adhesive contacts of human-derived thymocytes and DCs accompanied by Rap1 activation. These findings demonstrate that an increase in HLA-DR+ cells by immunization promotes HLA-restricted thymocyte expansion in humanized mice, offering a unique opportunity to generate humanized mice with ease.


Assuntos
Leucócitos Mononucleares , Timócitos , Humanos , Camundongos , Animais , Células Apresentadoras de Antígenos , Timo , Antígenos HLA-DR , Imunização
4.
PLoS Pathog ; 19(2): e1011104, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36730466

RESUMO

A small proportion of human T-cell leukemia virus type-1 (HTLV-1)-infected individuals develop adult T-cell leukemia/lymphoma, a chemotherapy-resistant lymphoproliferative disease with a poor prognosis. HTLV-1-specific cytotoxic T lymphocytes (CTLs), potential anti-tumor/virus effectors, are impaired in adult T-cell leukemia/lymphoma patients. Here, using Japanese monkeys naturally infected with simian T-cell leukemia/T-lymphotropic virus type-1 (STLV-1) as a model, we demonstrate that short-term-cultured autologous peripheral blood mononuclear cells (PBMCs) can serve as a therapeutic vaccine to activate such CTLs. In a screening test, STLV-1-specific CTL activity was detectable in 8/10 naturally STLV-1-infected monkeys. We conducted a vaccine study in the remaining two monkeys with impaired CTL responses. The short-term-cultured PBMCs of these monkeys spontaneously expressed viral antigens, in a similar way to PBMCs from human HTLV-1 carriers. The first monkey was subcutaneously inoculated with three-day-cultured and mitomycin C (MMC)-treated autologous PBMCs, and then boosted with MMC-treated autologous STLV-1-infected cell line cells. The second monkey was inoculated with autologous PBMC-vaccine alone twice. In addition, a third monkey that originally showed a weak STLV-1-specific CTL response was inoculated with similar autologous PBMC-vaccines. In all three vaccinated monkeys, marked activation of STLV-1-specific CTLs and a mild reduction in the STLV-1 proviral load were observed. Follow-up analyses on the two monkeys vaccinated with PBMCs alone indicated that STLV-1-specific CTL responses peaked at 3-4 months after vaccination, and then diminished but remained detectable for more than one year. The significant reduction in the proviral load and the control of viral expression were associated with CTL activation but also diminished 6 and 12 months after vaccination, respectively, suggesting the requirement for a booster. The vaccine-induced CTLs in these monkeys recognized epitopes in the STLV-1 Tax and/or Envelope proteins, and efficiently killed autologous STLV-1-infected cells in vitro. These findings indicated that the autologous PBMC-based vaccine could induce functional STLV-1-specific CTLs in vivo.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Vírus Linfotrópico T Tipo 1 de Símios , Linfócitos T Citotóxicos , Animais , Humanos , Leucócitos Mononucleares , Macaca fuscata , Provírus , Vacinação
5.
Nat Commun ; 13(1): 2405, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504920

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma (ATL), a cancer of infected CD4+ T-cells. There is both sense and antisense transcription from the integrated provirus. Sense transcription tends to be suppressed, but antisense transcription is constitutively active. Various efforts have been made to elucidate the regulatory mechanism of HTLV-1 provirus for several decades; however, it remains unknown how HTLV-1 antisense transcription is maintained. Here, using proviral DNA-capture sequencing, we found a previously unidentified viral enhancer in the middle of the HTLV-1 provirus. The transcription factors, SRF and ELK-1, play a pivotal role in the activity of this enhancer. Aberrant transcription of genes in the proximity of integration sites was observed in freshly isolated ATL cells. This finding resolves certain long-standing questions concerning HTLV-1 persistence and pathogenesis. We anticipate that the DNA-capture-seq approach can be applied to analyze the regulatory mechanisms of other oncogenic viruses integrated into the host cellular genome.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , DNA , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Provírus/genética , Sequências Reguladoras de Ácido Nucleico
6.
PLoS Pathog ; 17(11): e1010126, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34843591

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) infects target cells primarily through cell-to-cell routes. Here, we provide evidence that cellular protein M-Sec plays a critical role in this process. When purified and briefly cultured, CD4+ T cells of HTLV-1 carriers, but not of HTLV-1- individuals, expressed M-Sec. The viral protein Tax was revealed to mediate M-Sec induction. Knockdown or pharmacological inhibition of M-Sec reduced viral infection in multiple co-culture conditions. Furthermore, M-Sec knockdown reduced the number of proviral copies in the tissues of a mouse model of HTLV-1 infection. Phenotypically, M-Sec knockdown or inhibition reduced not only plasma membrane protrusions and migratory activity of cells, but also large clusters of Gag, a viral structural protein required for the formation of viral particles. Taken together, these results suggest that M-Sec induced by Tax mediates an efficient cell-to-cell viral infection, which is likely due to enhanced membrane protrusions, cell migration, and the clustering of Gag.


Assuntos
Membrana Celular/virologia , Modelos Animais de Doenças , Produtos do Gene tax/metabolismo , Infecções por HTLV-I/transmissão , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Fatores de Necrose Tumoral/metabolismo , Proteínas Estruturais Virais/metabolismo , Animais , Membrana Celular/metabolismo , Movimento Celular , Técnicas de Cocultura , Produtos do Gene tax/genética , Infecções por HTLV-I/metabolismo , Infecções por HTLV-I/virologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fatores de Necrose Tumoral/genética , Proteínas Estruturais Virais/genética
7.
J Phys Chem A ; 125(27): 5903-5910, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34212718

RESUMO

Interfacial charge-transfer transitions (ICTTs) between organic compounds and inorganic semiconductors have recently attracted much attention due to the unique features of a wide range of visible light absorption with colorless organic molecules and direct interfacial charge separation for their potential applications in photoenergy conversions and chemical sensing. As the research on ICTT has almost been limited to titanium oxide semiconductors such as TiO2, the exploration of ICTT in other inorganic semiconductors is a high-priority issue. Recently, we demonstrated that ICTT is strongly induced by chemisorption of aromatic thiols on ZnO nanoparticles via the sulfur atom. Here, we report on ICTT in ZnO nanoparticles adsorbed with benzoic acid derivatives and the linkage dependence of ICTT in ZnO. We observed ICTT bands in the visible region upon adsorption of 4-(dimethylamino)benzoic acid (4-DMABA) and 3,4-dimethoxybenzoic acid (3,4-DMOBA) on ZnO nanoparticles via the carboxylate group. Notably, the ICTT absorption intensities are about 1 order of magnitude lower than those in the ZnO surface complexes with aromatic thiol compounds. Time-dependence density functional theory (TD-DFT) calculations well reproduce the linkage dependence of ICTT. This characteristic linkage dependence of ICTT in ZnO is attributed to the difference in the valence orbital of bridging atoms. The sulfur bridging atom with the larger 3p valence orbitals gives rise to strong electronic couplings between ZnO and adsorbates for ICTT, in contrast to very weak electronic couplings via the smaller 2p valence orbitals of the oxygen bridging atoms in the carboxylate linkage. Our research reveals the important linkage dependence of ICTT in ZnO and elucidates the mechanism.

8.
PLoS Pathog ; 17(5): e1009577, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34019588

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes an aggressive T-cell malignancy and a variety of inflammatory conditions. The integrated provirus includes a single binding site for the epigenomic insulator, CCCTC-binding protein (CTCF), but its function remains unclear. In the current study, a mutant virus was examined that eliminates the CTCF-binding site. The mutation did not disrupt the kinetics and levels of virus gene expression, or establishment of or reactivation from latency. However, the mutation disrupted the epigenetic barrier function, resulting in enhanced DNA CpG methylation downstream of the CTCF binding site on both strands of the integrated provirus and H3K4Me3, H3K36Me3, and H3K27Me3 chromatin modifications both up- and downstream of the site. A majority of clonal cell lines infected with wild type HTLV-1 exhibited increased plus strand gene expression with CTCF knockdown, while expression in mutant HTLV-1 clonal lines was unaffected. These findings indicate that CTCF binding regulates HTLV-1 gene expression, DNA and histone methylation in an integration site dependent fashion.


Assuntos
Epigênese Genética , Genoma Viral/genética , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Leucemia de Células T/virologia , Sítios de Ligação , Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Linhagem Celular , Cromatina/genética , Metilação de DNA , Epigenômica , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Mutação , Integração Viral , Latência Viral/genética
9.
Cell Tissue Res ; 385(1): 127-148, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33864500

RESUMO

The effect of the extracellular matrix substrates on the formation of epithelial cell sheets was studied using MDCK cells in which the α-catenin gene was disrupted. Although the mutant cells did not form an epithelial cell sheet in conventional cell culture, the cells formed an epithelial cell sheet when they were cultured on or in a collagen gel; the same results were not observed when cells were cultured on collagen-coated cover glasses or culture dishes. Moreover, the cells cultured on the cell culture inserts coated with fibronectin, Matrigel, or vitronectin formed epithelial cell sheets, whereas the cells cultured on cover glasses coated with these proteins did not form the structure, implying that the physical and chemical features of the substrates exert a profound effect on the formation of epithelial cell sheets. MDCK cells lacking the expression of E- and K-cadherins displayed similar properties. When the mutant MDCK cells were cultured in the presence of blebbistatin, they formed epithelial cell sheets, suggesting that myosin II was involved in the formation of these sheets. These cell sheets showed intimate cell-cell adhesion, and electron microscopy confirmed the formation of cell junctions. We propose that specific ECM substrates organize the formation of basic epithelial cell sheets, whereas classical cadherins stabilize cell-cell contacts and promote the formation of structures.


Assuntos
Caderinas/metabolismo , Adesão Celular/imunologia , Colágeno/metabolismo , Células Epiteliais/metabolismo , Fibronectinas/metabolismo , Células Madin Darby de Rim Canino/metabolismo , alfa Catenina/metabolismo , Animais , Cães , Humanos
10.
RSC Adv ; 11(34): 20725-20729, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35479337

RESUMO

Interfacial charge-transfer transitions (ICTTs) between organic compounds and inorganic semiconductors have recently attracted increasing attention for their potential applications in solar energy conversions and chemical sensing due to the unique functions of visible-light absorption with colourless organic molecules and direct charge separation. However, inorganic semiconductors available for ICTT are quite limited to a few kinds of metal-oxide semiconductors (TiO2, ZnO, etc.). Particularly, the exploration of ICTT in inorganic semiconductors with a lower-energy conduction band such as SnO2 is an important issue for realizing a wide range of visible-light absorption for organic adsorbates with the deep highest occupied molecular orbital (HOMO) such as benzoic acid derivatives. Here, we report the first observation of ICTT in SnO2. SnO2 nanoparticles show a broad absorption band in the visible region by chemisorption of 4-dimethylaminobenzoic acid (4-DMABA) and 4-aminobenzoic acid (4-ABA)) via the carboxylate group. The wavelength range of the ICTT band significantly changes depending on the kind of substituent group. The ionization potential measurement and density functional theory (DFT) analysis reveal that the absorption band is attributed to ICTT from the HOMO of the adsorbed benzoic acid derivatives to the conduction band of SnO2. In addition, we clarify the mechanism of ICTT in SnO2 computationally. Our research opens up a way to the fundamental research on ICTT in SnO2 and applications in solar energy conversions and chemical sensing.

11.
Inorg Chem ; 59(24): 17945-17957, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33169615

RESUMO

Chemical modification of insulating material surfaces is an important methodology to improve the performance of organic field-effect transistors (OFETs). However, few redox-active self-assembled monolayers (SAMs) have been constructed on gate insulator film surfaces, in contrast to the numerous SAMs formed on many types of conducting electrodes. In this study, we report a new approach to introduce a π-conjugated organic fragment in close proximity to an insulating material surface via a transition metal center acting as a one-atom anchor. On the basis of the reported coordination chemistry of a catecholato complex of Pt(II) in solution, we demonstrate that ligand exchange can occur on an insulating material surface, affording SAMs on the SiO2 surface derived from a newly synthesized Pt(II) complex containing a benzothienobenzothiophene (BTBT) framework in the catecholato ligand. The resultant SAMs were characterized in detail by water contact angle measurements, X-ray photoelectron spectroscopy, atomic force microscopy, and cyclic voltammetry. The SAMs served as good scaffolds of π-conjugated pillars for forming thin films of a well-known organic semiconductor C8-BTBT (2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene), accompanied by the engagements of the C8-BTBT molecules with the SAMs containing the common BTBT framework at the first layer on SiO2. OFETs containing the SAMs displayed improved performance in terms of hole mobility and onset voltage, presumably because of the unique interfacial structure between the organic semiconducting and inorganic insulating layers. These findings provide important insight into creating new elaborate interfaces through installing coordination chemistry in solution to solid surfaces, as well as OFET design by considering the compatibility between SAMs and organic semiconductors.

12.
Tohoku J Exp Med ; 251(1): 9-18, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32404541

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic articular and bone manifestations and its pathogenesis is driven by a complex network of proinflammatory cytokines, including tumor necrosis factor and interleukin (IL)-6. Treatment of rheumatoid arthritis (RA) has been standardized by the introduction of a treat-to-target approach. Subcutaneous tocilizumab (TCZ-SC) is a humanized anti-IL-6 receptor monoclonal antibody, and is widely used for refractory RA patients in the clinical settings. However, it remains unknown whether TCZ-SC shows effectiveness for elderly onset RA. The study was aimed to assess the effectiveness and safety of TCZ-SC in elderly-onset rheumatoid arthritis (EORA) patients in daily practice. Fifty-five RA patients were divided into two age groups upon TCZ-SC administration: young (Y) group (< 65 years old, n = 30) and elderly-onset (EO) group (> 65 years old, n = 25). Disease activity score-28 (DAS28) upon TCZ-SC administration (4.84 in EO group vs. 4.41 in Y group) was significantly decreased to 1.94 vs. 1.93 at 3 months and 1.61 vs. 1.75 at 12 months after administration. The clinical remission (DAS28 < 2.6) rate was 75% in EO group vs. 83% in Y group at 3 months and 90% vs. 85% at 12 months. The retention rate at 12 months was 88% in EO group and 92% in Y group without significant difference. The cessation cases of adverse events were two in each group. In conclusion, TCZ-SC showed good clinical effectiveness and safety in EORA patients. TCZ-SC is a useful agent for patients with EORA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Adulto , Idade de Início , Idoso , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Resistência a Medicamentos , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Autoadministração , Resultado do Tratamento
13.
J Neurovirol ; 26(3): 404-414, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32285300

RESUMO

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic myelopathy characterized by slowly progressive spastic paraparesis and urinary dysfunction. A few biomarkers in the cerebrospinal fluid are known to be related to disease activity, but no biomarker has been reported in peripheral blood. This study aims to explore the expression level of the adhesion molecule during the expression level of the adhesion molecule among HAM/TSP disease activity. In lymphocyte function-associated antigen 1 and DNAX accessory molecule 1, no variation in expression levels specific to HTLV-1 infection was observed in CD4-positive T cells; however, TSLC1 expression was higher in HAM patients than in asymptomatic carriers and non-infected persons. TSLC1 tended to be higher in patients whose symptoms were worsening. On the contrary, the expression level of TSLC1 in CD8-positive T cells was lower in HAM patients than in asymptomatic carriers, and this tendency was stronger in patients whose symptoms had deteriorated. No significant correlation was found between TSLC1 and either of the transcription factors Tax or HBZ in any T cell group. Therefore, TSLC1 expression in CD4-positive T cells might be a useful biomarker of HAM/TSP disease activity.


Assuntos
Linfócitos T CD4-Positivos/virologia , Molécula 1 de Adesão Celular/genética , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/genética , Adulto , Antígenos de Diferenciação de Linfócitos T/genética , Antígenos de Diferenciação de Linfócitos T/imunologia , Doenças Assintomáticas , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/imunologia , Biomarcadores/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Portador Sadio , Estudos de Casos e Controles , Molécula 1 de Adesão Celular/sangue , Molécula 1 de Adesão Celular/imunologia , Feminino , Regulação da Expressão Gênica , Produtos do Gene tax/genética , Produtos do Gene tax/imunologia , Infecções por HTLV-I/sangue , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Vírus Linfotrópico T Tipo 1 Humano/crescimento & desenvolvimento , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Antígeno-1 Associado à Função Linfocitária/genética , Antígeno-1 Associado à Função Linfocitária/imunologia , Masculino , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologia , Proteínas dos Retroviridae/genética , Proteínas dos Retroviridae/imunologia , Índice de Gravidade de Doença
14.
Chem Commun (Camb) ; 56(29): 4090-4093, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32162647

RESUMO

Interfacial charge-transfer transitions (ICTTs) between organic compounds and inorganic semiconductors have recently gained increasing interest as a new visible light absorption mechanism for optical biosensing via direct visualization, surface enhanced Raman scattering (SERS), and circular dichroism (CD) and also as a direct charge separation mechanism for photoenergy conversions such as photocatalytic reactions. So far, ICTTs have been observed with various organic compounds, while inorganic materials are almost limited to titanium oxides such as TiO2. Although SERS via ICTTs has been reported with several kinds of inorganic semiconductors, their ICTT bands have not been observed directly except for TiO2. From these viewpoints, the direct observation of ICTT bands in inorganic semiconductors other than TiO2 is an important issue. In this study, we demonstrate ICTTs in ZnO induced by the adsorption of aromatic thiols. ICTTs take place from the HOMO of the adsorbed thiol compounds to the conduction band of ZnO via a Ti-S linkage. Notably, ZnO selectively shows ICTTs with aromatic thiols, but almost no ICTT with oxygen-linkage-type organic compounds such as phenol. In addition, the wide-range control of ICTTs was achieved by the chemical modification of aromatic thiols. Our research not only opens up a new way for the research of ICTTs but also supports the reported ICTT-based SERS in ZnO.

15.
Mod Rheumatol ; 30(3): 495-501, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31116054

RESUMO

Objectives: To clarify changes in the incidence of cervical lesions in rheumatoid arthritis (RA) patients with advanced treatment and the impact of cervical lesions on the patients' quality of life (QOL).Methods: Incidence of radiographic cervical lesions in 1333 RA patients in 2015 was compared with that in our 1999 survey. The association between cervical lesions and QOL evaluated using three different patient-based questionnaires was also analyzed.Results: The incidence of atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS) in 2015 decreased by 50%, 75%, and 5%, respectively, compared to the 1999 survey. Although QOL, evaluated using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ; specific to myelopathy), deteriorated as the cervical lesion progressed, there was no association between cervical lesion progression and QOL evaluated using the Short Form-8™ (SF-8™; comprehensive health-related QOL). Cervical lesion progression was also associated with QOL deterioration evaluated using the Health Assessment Questionnaire Disability Index (HAQ-DI; specific to RA), but age and disease duration had stronger influences.Conclusion: The incidence of cervical lesions decreased in 2015 compared to 1999. Cervical lesion progression may be associated with QOL deterioration due to myelopathy. Age and disease duration have more impact on disease-specific QOL.


Assuntos
Artrite Reumatoide/complicações , Vértebras Cervicais/diagnóstico por imagem , Luxações Articulares/diagnóstico por imagem , Qualidade de Vida , Adulto , Idoso , Feminino , Humanos , Incidência , Luxações Articulares/epidemiologia , Luxações Articulares/etiologia , Masculino , Pessoa de Meia-Idade , Radiografia
16.
Chem Commun (Camb) ; 55(97): 14641-14644, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31746847

RESUMO

Molecular transport by use of light energy is a new photofunction for light powered molecular carriers and light induced nano-structure formation on a substrate. However, this research field has not been cultivated yet. In order to understand the basic mechanism and potentialities, experimental observations of photoactivated molecular migration and its functions in various systems are required. Here, we report visible light induced H-aggregation of cationic dyes (methylene blue and toluidine blue) on metal-oxide surfaces (TiO2 and ZnO) via photoactivated surface migration of these dyes. Our research widely expands the scope of photoinduced surface molecular migration to the conventional dyes and metal-oxide surfaces, and also demonstrates that the photoinduced molecular assembly provides a photochromic function. It is noteworthy that high aggregates, which are difficult to form in the dark, can be formed by the photoinduced surface migration of excited dyes.

17.
Cell Rep ; 29(3): 724-735.e4, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618639

RESUMO

The retrovirus human T-cell leukemia virus type 1 (HTLV-1) integrates into the host DNA, achieves persistent infection, and induces human diseases. Here, we demonstrate that viral DNA-capture sequencing (DNA-capture-seq) is useful to characterize HTLV-1 proviruses in naturally virus-infected individuals, providing comprehensive information about the proviral structure and the viral integration site. We analyzed peripheral blood from 98 naturally HTLV-1-infected individuals and found that defective proviruses were present not only in patients with leukemia, but also in those with other clinical entities. We further demonstrated that clones with defective-type proviruses exhibited a higher degree of clonal abundance than those with full-length proviruses. The frequency of defective-type proviruses in HTLV-1-infected humanized mice was lower than that in infected individuals, indicating that defective proviruses were rare at the initial phase of infection but preferentially selected during persistent infection. These results demonstrate the robustness of viral DNA-capture-seq for HTLV-1 infection and suggest potential applications for other virus-associated cancers in humans.


Assuntos
Genoma Viral , Infecções por HTLV-I/diagnóstico , Vírus Linfotrópico T Tipo 1 Humano/genética , Animais , Infecções por HTLV-I/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Células Jurkat , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/virologia , Camundongos , Modelos Animais , Análise de Sequência de DNA , Integração Viral
18.
Exp Ther Med ; 17(5): 3701-3708, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30988755

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL). Following viral infection with HTLV-1, certain infected cells exhibit clonal proliferation. Additional genetic and epigenetic changes in these clonally proliferating cells provide them with the selective advantage of growth, which eventually results in ATL. The precise mechanism, however, has yet to be completely elucidated. It has previously been established that APOBEC3 enzymes are potent host-antiviral restriction factors. Conversely, previous studies have reported that the A3B level is increased in tumor virus infections, such as those caused by HBV and HPV, suggesting that A3B exerts a function as a mutagen. Therefore, the present study analyzed the expression of APOBEC3 family members in various HTLV-1 infection states. No significant differences were observed in the expression between healthy donors and patients with HTLV-1-associated myelopathy. Although no significant changes in the expressions of A3C, A3D, A3F and A3G between uninfected and HTLV-1-infected mice were observed, an increased A3B expression was observed in a short-term humanized mouse model following HTLV-1 infection. In a long-term humanized mouse model following HTLV-1 infection, the gene expression array data exhibited an apparent increase in A3B and CADM1, which are indicators of ATL. Collectively, the results of the present study suggest that A3B is likely involved in the development of ATL in HTLV-1-infected humanized mice.

19.
Eur Spine J ; 28(5): 976-982, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30850879

RESUMO

PURPOSE: To investigate the prevalence of and factors associated with dysfunctional low back pain (LBP) in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study included 1276 RA outpatients from two hospitals. The Roland-Morris Disability Questionnaire was used to address the functional-dysfunctional state criterion. Clinical variables, such as medical status, disease activity, bone mineral density, and spinopelvic alignment parameters, were compared between patients with and without dysfunctional LBP. RESULTS: Mean age and disease duration were 64.6 and 13.4 years, respectively; the prevalence of dysfunctional LBP was 32.8%. On univariate analysis, significant differences existed in many variables, except sex, body weight, C-reactive protein (CRP) level, and prevalence of biological agent users, between patients with and without dysfunctional LBP. Multivariate logistic regression analysis revealed body mass index (BMI; odds ratio [OR], 1.116; P < 0.001), onset age of RA (OR, 1.020; P = 0.020), disease duration of RA (OR, 1.043; P < 0.001), methotrexate (MTX) use (OR, 0.609; P = 0.007), vertebral fractures (OR, 2.189; P = 0.001), vertebral endplate and/or facet erosion (OR, 1.411; P = 0.043), disease activity score (DAS) in 28 joints-CRP (DAS-28CRP) (OR, 1.587; P = 0.001), pelvic tilt (PT; OR, 1.023; P = 0.019), and sagittal vertical axis (SVA; OR, 1.007; P = 0.043) as associated factors. CONCLUSION: The factors associated with dysfunctional LBP in patients with RA were more vertebral fractures, higher DAS-28CRP, vertebral endplate and/or facet erosion, higher BMI, longer disease duration, greater PT, older onset age, greater SVA, and less MTX use. Strictly controlling patients' body weight and disease activity with MTX and avoiding spinopelvic malalignment through vertebral fracture prevention are important. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Artrite Reumatoide/complicações , Dor Lombar/complicações , Idade de Início , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Índice de Massa Corporal , Proteína C-Reativa/análise , Estudos Transversais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Fraturas da Coluna Vertebral/complicações , Coluna Vertebral/diagnóstico por imagem
20.
J Shoulder Elbow Surg ; 28(5): 915-924, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30630713

RESUMO

BACKGROUND: Total elbow arthroplasty (TEA) is a treatment option for destructive and painful unstable elbows in rheumatoid arthritis (RA). We evaluated the clinical outcomes of unconstrained TEA (Niigata-Senami-Kyocera modular system). METHODS: Seventy-five unconstrained TEAs were performed in patients with RA (mean age, 64 years; age range, 41-79 years; follow-up rate, 97%). Outcome measures included the Japanese Orthopaedic Association (JOA) functional evaluation score for the elbow joint (JOA score), range of motion, and arc. Bone ingrowth of the humeral component, the incidence of stress shielding around the humeral component, the incidence of loosening of the ulnar component, complications, and the survival rate were investigated. RESULTS: The mean follow-up period was 5.2 years (range, 2-11.3 years). The JOA elbow score improved from 42 points preoperatively to 87 points postoperatively (P < .0001). Each specified item improved (P < .0001). Flexion improved from 109° to 134°; the flexion-plus-extension arc improved from 70° to 108° (P < .0001). Bone ingrowth of the humeral implant was achieved in all elbows. Stress shielding of the humeral component was detected in 11 elbows (14%); it was significantly higher in 10- and 9-mm-diameter humeral stems than in 8-mm-diameter humeral stems (P = .008). The ulnar component showed no loosening except in 1 elbow owing to infection. Complications were detected in 9 patients (9 elbows, 12%): periprosthetic infection (3), fracture (4), and dislocation (2). The survival rates were 97% at 5 years and 93% at 10 years postoperatively. DISCUSSION: The Niigata-Senami-Kyocera modular system for patients with RA showed good outcomes. Stress shielding can be avoided by using an 8-mm-diameter humeral stem.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia de Substituição do Cotovelo/instrumentação , Prótese de Cotovelo , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Artroplastia de Substituição do Cotovelo/efeitos adversos , Feminino , Seguimentos , Humanos , Luxações Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Resultado do Tratamento
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