RESUMO
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR], 3.06; corrected P [Pc] = .005), DRB3/4/5*blank (OR, 2.3; Pc = .007), DQA1*01:03 (OR, 2.25; Pc = .006), and DQB1*06:01 (OR,: 2.41; Pc = .003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs 6.0%; Pc < .001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR, 0.23; Pc = .076; and OR, 0.23, Pc = .034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in the Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and white individuals. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, bound to the shared ADAMTS13 peptide in an in silico prediction model.
Assuntos
Proteína ADAMTS13/fisiologia , Povo Asiático/genética , Antígenos HLA-DR/genética , Púrpura Trombocitopênica Trombótica/genética , Alelos , Motivos de Aminoácidos , Sequência de Aminoácidos , Simulação por Computador , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade , Humanos , Japão/epidemiologia , Masculino , Modelos Moleculares , Fragmentos de Peptídeos/metabolismo , Conformação Proteica , Mapeamento de Interação de Proteínas , Púrpura Trombocitopênica Trombótica/etnologia , Púrpura Trombocitopênica Trombótica/imunologiaRESUMO
Thermally-induced isomerization of spiropyran derivatives in aqueous media has been studied. The colorless spirocyclic (SP) forms of spiropyran derivatives are isomerized to colored merocyanine (MC) forms even in dark conditions at elevated temperature. Equilibrium, kinetic, and deuterium experiments reveal that the thermal SP â MC isomerization is due to the stabilization of MC form by a hydrogen bonding interaction with water molecules. This leads to the ground state energy of the MC form decreasing to lower than that of the SP form, resulting in SP â MC isomerization. The thermal isomerization property is applicable to a rough indication of solution temperature. The spiropyran derivatives, when dissolved in aqueous media under irradiation of visible light with an appropriate light intensity, demonstrate an increase in MC absorbance with a rise in temperature. The absorption response occurs reversibly regardless of the heating/cooling sequence. The spiropyran derivatives therefore have a potential for colorimetric temperature indication.
RESUMO
A spiropyran derivative (1) behaves as a selective and sensitive cyanide anion receptor in aqueous media under UV irradiation. The receptor can be reproduced just by irradiation with visible light.
Assuntos
Ânions/análise , Benzopiranos/química , Cianetos/análise , Monitoramento Ambiental/métodos , Indóis/química , Nitrocompostos/química , Cianetos/química , Processos Fotoquímicos , Raios UltravioletaRESUMO
Neurological topodiagnosis has some considerable difficulties because of the complex anatomy involved. One answer to this problem is making a computer system able to map the pathways responsible for the patients' symptoms and also able to pinpoint the causative lesions. We introduced a new computer system for such purpose. Human memory has its limits so it is in a way inevitable that computers will be used in neurological diagnosis.