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1.
Proc Natl Acad Sci U S A ; 116(6): 1929-1933, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30670652

RESUMO

Photoexcitation in solids brings about transitions of electrons/holes between different electronic bands. If the solid lacks an inversion symmetry, these electronic transitions support spontaneous photocurrent due to the geometric phase of the constituting electronic bands: the Berry connection. This photocurrent, termed shift current, is expected to emerge on the timescale of primary photoexcitation process. We observe ultrafast evolution of the shift current in a prototypical ferroelectric semiconductor antimony sulfur iodide (SbSI) by detecting emitted terahertz electromagnetic waves. By sweeping the excitation photon energy across the bandgap, ultrafast electron dynamics as a source of terahertz emission abruptly changes its nature, reflecting a contribution of Berry connection on interband optical transition. The shift excitation carries a net charge flow and is followed by a swing over of the electron cloud on a subpicosecond timescale. Understanding these substantive characters of the shift current with the help of first-principles calculation will pave the way for its application to ultrafast sensors and solar cells.

2.
Nano Lett ; 20(10): 7476-7481, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32897724

RESUMO

Magnetic Weyl semimetals attract considerable interest not only for their topological quantum phenomena but also as an emerging materials class for realizing quantum anomalous Hall effect in the two-dimensional limit. A shandite compound Co3Sn2S2 with layered kagome-lattices is one such material, where vigorous efforts have been devoted to synthesize the two-dimensional crystal. Here, we report a synthesis of Co3Sn2S2 thin flakes with a thickness of 250 nm by chemical vapor transport method. We find that this facile bottom-up approach allows the formation of large-sized Co3Sn2S2 thin flakes of high-quality, where we identify the largest electron mobility (∼2600 cm2 V-1 s-1) among magnetic topological semimetals, as well as the large anomalous Hall conductivity (∼1400 Ω-1 cm-1) and anomalous Hall angle (∼32%) arising from the Berry curvature. Our study provides a viable platform for studying high-quality thin flakes of magnetic Weyl semimetal and stimulate further research on unexplored topological phenomena in the two-dimensional limit.

3.
Scand J Rheumatol ; 48(3): 218-224, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30394816

RESUMO

OBJECTIVE: We aimed to describe the clinical characteristics and treatment course of hypertrophic pachymeningitis (HPM) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We retrospectively analysed 15 patients (11 men and four women). HPM was diagnosed based on thickening and enhancing of the brain and/or spinal dura mater on gadolinium-enhanced magnetic resonance imaging (MRI) T1 sequence. RESULTS: The median age at HPM onset was 60 years. Headache and cranial nerve impairment were observed in 14 and 10 patients, respectively. Otitis media and/or mastoiditis were found as complications of AAV in 11 patients. Fourteen patients were classified as having granulomatosis with polyangiitis (GPA). Single-positive myeloperoxidase-ANCA, single-positive proteinase 3-ANCA, and double-positive ANCA were identified in seven patients, five patients, and one patient, respectively. With MRI, thickening of the dura mater in the cranial fossa and tentorium cerebelli was found in 10 and eight patients, respectively. For remission induction, all patients were treated with corticosteroids, and immunosuppressants were added in 10 patients. Dura mater thickening partially improved in all patients, and cranial neuropathy completely remitted in eight patients. In a median follow-up of 43 months, four patients had HPM relapse and underwent reinduction therapy. All six patients treated with cyclophosphamide at initial therapy did not relapse. CONCLUSIONS: HPM was mostly associated with patients with GPA with otitis media and/or mastoiditis having either type of ANCA serology. Treatment with corticosteroids with or without immunosuppressants was effective. However, HPM relapse occasionally occurred, especially when cyclophosphamide was not used in initial treatment.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Encéfalo/diagnóstico por imagem , Dura-Máter , Granulomatose com Poliangiite , Imunossupressores/uso terapêutico , Meningite , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Doenças dos Nervos Cranianos/diagnóstico , Doenças dos Nervos Cranianos/etiologia , Dura-Máter/diagnóstico por imagem , Dura-Máter/patologia , Feminino , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Humanos , Hipertrofia , Japão , Imageamento por Ressonância Magnética/métodos , Masculino , Meningite/diagnóstico , Meningite/tratamento farmacológico , Meningite/imunologia , Meningite/fisiopatologia , Pessoa de Meia-Idade , Indução de Remissão
4.
Phys Rev Lett ; 120(3): 037203, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29400522

RESUMO

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.

5.
Lupus ; 27(3): 484-493, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29050536

RESUMO

Objectives The objective of this study was to test the correlation of urinary podocyte number (U-Pod) and urinary podocalyxin levels (U-PCX) with histology of lupus nephritis. Methods This was an observational, cross-sectional study. Sixty-four patients were enrolled: 40 with lupus nephritis and 24 without lupus nephritis (12 lupus nephritis patients in complete remission and 12 systemic lupus erythematosus patients without lupus nephritis). Urine samples were collected before initiating treatment. U-Pod was determined by counting podocalyxin-positive cells, and U-PCX was measured by sandwich ELISA, normalized to urinary creatinine levels (U-Pod/Cr, U-PCX/Cr). Results Lupus nephritis patients showed significantly higher U-Pod/Cr and U-PCX/Cr compared with patients without lupus nephritis. U-Pod/Cr was high in proliferative lupus nephritis (class III±V/IV±V), especially in pure class IV (4.57 (2.02-16.75)), but low in pure class V (0.30 (0.00-0.71)). U-Pod/Cr showed a positive correlation with activity index ( r=0.50, P=0.0012) and was independently associated with cellular crescent formation. In contrast, U-PCX/Cr was high in both proliferative and membranous lupus nephritis. Receiver operating characteristic analysis revealed significant correlation of U-Pod/Cr with pure class IV, class IV±V and cellular crescent formation, and the combined values of U-Pod/Cr and U-PCX/Cr were shown to be associated with pure class V. Conclusions U-Pod/Cr and U-PCX/Cr correlate with histological features of lupus nephritis.


Assuntos
Nefrite Lúpica/patologia , Nefrite Lúpica/urina , Podócitos/patologia , Sialoglicoproteínas/urina , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Creatinina/urina , Estudos Transversais , Feminino , Humanos , Japão , Modelos Lineares , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Curva ROC
6.
Lupus ; 26(6): 656-660, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27831538

RESUMO

Objectives The selectivity index has been proposed in predicting the response to immunosuppressive therapy in nephrotic syndrome and other primary kidney disorders. The aim of this study was to elucidate the predictive value of the selectivity index for the treatment response and renal outcome in patients with lupus nephritis. Methods Forty-four patients with lupus nephritis with selectivity index available at the time of renal biopsy were divided into two groups according to the cut-off value of the selectivity index determined by a receiver operating characteristics curve to differentiate treatment responders from non-responders. The baseline characteristics, overall response rate and renal functional outcome were studied retrospectively, and compared between the two groups. Prognostic factors for achieving remission were identified. Results The cut-off value of the selectivity index was 0.167. The low selectivity index (<0.167) and the high selectivity index (≥0.167) group included 24 and 20 patients, respectively. The overall response rate was significantly higher (88% vs. 50%, P = 0.007) and the rate of progression to end-stage renal disease was lower in the low selectivity index group (0% vs. 15%, P = 0.049). More patients in the high selectivity index group had chronic lesions on renal biopsy ( P = 0.002). The selectivity index was the prognostic factor for achieving overall response based on a multivariate analysis ( P = 0.020). Conclusions A selectivity index ≥0.167 was a strong predictor for a poor treatment response and the presence of chronic lesions on renal biopsy. Further exploration with a larger cohort and longer follow-up period is warranted.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Proteinúria/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
7.
Clin Radiol ; 72(10): 905.e1-905.e5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28629605

RESUMO

AIM: To assess detailed computed tomography (CT) findings in patients with the recently described thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome, in order to contribute to imaging interpretation in the challenging diagnosis of this disease. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived the need for informed consent. Eleven patients (six men, five women; mean age, 52.5 years) with confirmed TAFRO syndrome were included in this study. Chest-to-pelvis CT images were analysed for the presence of anasarca, organomegaly, bone lesions, and lung lesions. RESULTS: Anasarca was present in all patients and involved multiple cavities and tissues; pleural effusion and ascites were found in 100% of patients; pericardial effusion in 64%; periportal collar in 91%; gallbladder wall oedema in 78%; subcutaneous oedema in 91%; retroperitoneal oedema in 100%; and mesenteric oedema in 100%. Organomegaly involved multiple organs: hepatomegaly in 73%, splenomegaly in 82%, lymphadenopathy in 100%, and enlarged anterior mediastinum in 64% (solitary, well-circumscribed mass, 0%; infiltrative mass, 0%; non-mass-forming infiltrative lesion, 64%). Bone lesions were present in 91% patients and all bone lesions had ground-glass density with diffuse distribution. None of the patients had any lesions in their lungs. CONCLUSION: The present study revealed that the findings of anasarca, organomegaly, and diffuse bony ground-glass appearance were observed in detail on CT in patients with TAFRO syndrome. A "matted" appearance of the enlarged anterior mediastinum is the characteristic CT finding of TAFRO syndrome, and it is possible to diagnose TAFRO syndrome from the combination of several CT findings.


Assuntos
Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Edema/diagnóstico por imagem , Trombocitopenia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Hiperplasia do Linfonodo Gigante/patologia , Edema/complicações , Edema/patologia , Feminino , Febre/complicações , Febre/patologia , Fibrose/complicações , Fibrose/diagnóstico por imagem , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Reticulina , Estudos Retrospectivos , Síndrome , Trombocitopenia/complicações , Trombocitopenia/patologia
8.
Pharmazie ; 72(2): 95-97, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29441860

RESUMO

In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enrolled a total of 10 Japanese adult patients with RA who were treated with infliximab concomitantly with methotrexate or azathioprine. Serum concentrations of infliximab and ATI of these patients were measured. The mean serum infliximab concentrations was 1.6±1.3 µg/ml in patients with methotrexate and 1.0±0.5 µg/ml in patients with azathioprine. Serum ATI concentrations were below the limit of quantitation in 4 of 5 patients in each group. The results from the present study suggest that azathioprine suppresses ATI production.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Azatioprina/farmacologia , Infliximab/imunologia , Metotrexato/farmacologia , Adulto , Anticorpos/sangue , Anticorpos/imunologia , Azatioprina/administração & dosagem , Quimioterapia Combinada , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Infliximab/administração & dosagem , Metotrexato/administração & dosagem
9.
Pharmazie ; 72(1): 22-28, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29441893

RESUMO

Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) patients with low thiopurine (S)-methyltransferase (TPMT) activity tend to respond well to AZA therapy. In a previous study of Japanese SLE patients under low-dose AZA therapy, the group with the 94C>A mutation in inosine triphosphatase (ITPA) showed greater improvement in their disease activity index. However, it is not yet clear how genotypes relate to responsiveness to RA treatment. The genotypes ITPA 94C>A, TPMT*3C, NUDT15 595C>T, GST-M1, GST-T1 and MRP4/ABCC4 2269G>A of Japanese patients with RA were determined. The relationship between these genotypes and response to AZA therapy was evaluated using the Disease Activity Score 28 (DAS28) and various medical data. Of the 22 patients 15 had the ITPA 94C/C genotype, 7 had the ITPA 94C/A genotype, none had the TPMT*3C mutation, 4 had the NUDT15 595C>T mutation, 8 had the GST-M1 and T1 null genotypes and 9 had the MRP4/ABCC4 2269G>A mutation. Changes in DAS28 at 6 months after baseline were similar in both ITPA genotype groups. However, the maintenance dose of AZA was significantly lower in the C/A group than in the C/C group (0.85±0.30 mg/kg/day vs. 1.2±0.46 mg/kg/day, respectively; p = 0.043). The ITPA 94C/A group showed the same response to RA treatment as the C/C group, but at a lower dose. This demonstrates that RA patients with the ITPA 94C>A mutation are more responsive to AZA.


Assuntos
Antirreumáticos/metabolismo , Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Azatioprina/metabolismo , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Povo Asiático , Azatioprina/uso terapêutico , Feminino , Deleção de Genes , Frequência do Gene , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo Genético , Estudos Retrospectivos
10.
Scand J Rheumatol ; 45(1): 36-40, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26312949

RESUMO

OBJECTIVES: To clarify the prevalence of anti-signal recognition particle (anti-SRP) antibody in connective tissue diseases (CTDs) and investigate the clinical characteristics of patients without inflammatory myopathy. METHOD: Sera from 6180 patients with CTD were examined by immunoprecipitation (IPP) assays, and the records of patients positive for anti-SRP antibody were reviewed retrospectively. The antibody against the 54-kDa protein of SRP (SRP54) was quantified by enzyme-linked immunosorbent assay (ELISA) in patients with anti-SRP antibody. RESULTS: Of the 28 patients positive for anti-SRP antibody, nine (32.1%) did not have inflammatory myopathy. The clinical diagnoses and characteristics of those patients varied considerably. In patients with inflammatory myopathy, the index of anti-SRP54 was much higher than in those without myopathy (1.15 vs. 0.46; p = 0.036). CONCLUSIONS: The prevalence of anti-SRP antibody was 0.5% in a cohort of Japanese patients with CTD, and one-third of them did not have inflammatory myopathy. Sera from patients with inflammatory myopathy recognized SRP54 more strongly than in those without myopathy.

11.
Br J Cancer ; 112(6): 1121-33, 2015 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25688735

RESUMO

BACKGROUND: Bilateral Wilms tumours (BWTs) occur by germline mutation of various predisposing genes; one of which is WT1 whose abnormality was reported in 17-38% of BWTs in Caucasians, whereas no such studies have been conducted in East-Asians. Carriers with WT1 mutations are increasing because of improved survival. METHODS: Statuses of WT1 and IGF2 were examined in 45 BWTs from 31 patients with WT1 sequencing and SNP array-based genomic analyses. The penetrance rates were estimated in WT1-mutant familial Wilms tumours collected from the present and previous studies. RESULTS: We detected WT1 abnormalities in 25 (81%) of 31 patients and two families, which were included in the penetrance rate analysis of familial Wilms tumour. Of 35 BWTs from the 25 patients, 31 had small homozygous WT1 mutations and uniparental disomy of IGF2, while 4 had large 11p13 deletions with the retention of 11p heterozygosity. The penetrance rate was 100% if children inherited small WT1 mutations from their fathers, and 67% if inherited the mutations from their mothers, or inherited or had de novo 11p13 deletions irrespective of parental origin (P=0.057). CONCLUSIONS: The high incidence of WT1 abnormalities in Japanese BWTs sharply contrasts with the lower incidence in Caucasian counterparts, and the penetrance rates should be clarified for genetic counselling of survivors with WT1 mutations.


Assuntos
Mutação em Linhagem Germinativa , Neoplasias Renais/genética , Proteínas WT1/genética , Tumor de Wilms/genética , Povo Asiático/genética , Pré-Escolar , Feminino , Heterozigoto , Homozigoto , Humanos , Incidência , Lactente , Fator de Crescimento Insulin-Like II/genética , Masculino , Penetrância , Polimorfismo de Nucleotídeo Único
12.
Tissue Antigens ; 86(6): 431-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26593752

RESUMO

Major histocompatibility complex (MHC) genes encode proteins that play a critical role in vertebrate immune system and are highly polymorphic. To further understand the molecular evolution of the MHC genes, we compared MHC class II DRB genes between the Japanese weasel (Mustela itatsi), a species endemic to Japan, and the Siberian weasel (Mustela sibirica), a closely related species on the continent. We sequenced a 242-bp region of DRB exon 2, which encodes antigen-binding sites (ABS), and found 24 alleles from 31 M. itatsi individuals and 17 alleles from 21 M. sibirica individuals, including broadly distributed, species-specific and/or geographically restricted alleles. Our results suggest that pathogen-driven balancing selection have acted to maintain the diversity in the DRB genes. For predicted ABS, nonsynonymous substitutions exceeded synonymous substitutions, also indicating positive selection, which was not seen at non-ABS. In a Bayesian phylogenetic tree, two M. sibirica DRB alleles were basal to the rest of the sequences from mustelid species and may represent ancestral alleles. Trans-species polymorphism was evident between many mustelid DRB alleles, especially between M. itatsi and M. sibirica. These two Mustela species divided about 1.7 million years ago, but still share many MHC alleles, indicative of their close phylogenetic relationship.


Assuntos
Genes MHC da Classe II , Mustelidae/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Éxons/genética , Frequência do Gene , Variação Genética , Dados de Sequência Molecular , Mustelidae/imunologia , Filogenia , Pseudogenes/genética , Seleção Genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência , Especificidade da Espécie
13.
Phys Rev Lett ; 115(26): 266601, 2015 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-26765011

RESUMO

The longitudinal spin Seebeck effect has been investigated for a uniaxial antiferromagnetic insulator Cr(2)O(3), characterized by a spin-flop transition under magnetic field along the c axis. We have found that a temperature gradient applied normal to the Cr(2)O(3)/Pt interface induces inverse spin Hall voltage of spin-current origin in Pt, whose magnitude turns out to be always proportional to magnetization in Cr(2)O(3). The possible contribution of the anomalous Nernst effect is confirmed to be negligibly small. The above results establish that an antiferromagnetic spin wave can be an effective carrier of spin current.

14.
Mol Psychiatry ; 19(1): 55-62, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23183491

RESUMO

Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.


Assuntos
Analgésicos Opioides/administração & dosagem , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 2/genética , Metilases de Modificação do DNA/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/etiologia , Escalas de Graduação Psiquiátrica , Procedimentos de Cirurgia Plástica/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/genética , Adulto Jovem
15.
Anim Genet ; 46(2): 209-12, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25662601

RESUMO

East Balkan Swine (EBS) Sus scrofa is the only aboriginal domesticated pig breed in Bulgaria and is distributed on the western coast of the Black Sea in Bulgaria. To reveal the breed's genetic characteristics, we analysed mitochondrial DNA (mtDNA) and Y chromosomal DNA sequences of EBS in Bulgaria. Nucleotide diversity (πn ) of the mtDNA control region, including two newly found haplotypes, in 54 EBS was higher (0.014 ± 0.007) compared with that of European (0.005 ± 0.003) and Asian (0.006 ± 0.003) domestic pigs and wild boar. The median-joining network based on the mtDNA control region showed that the EBS and wild boar in Bulgaria comprised mainly two major mtDNA clades, European clade E1 (61.3%) and Asian clade A (38.7%). The coexistence of two mtDNA clades in EBS in Bulgaria may be the relict of historical pig translocation. Among the Bulgarian EBS colonies, the geographical differences in distribution of two mtDNA clades (E1 and A) could be attributed to the source pig populations and/or historical crossbreeding with imported pigs. In addition, analysis of the Y chromosomal DNA sequences for the EBS revealed that all of the EBS had haplotype HY1, which is dominant in European domestic pigs.


Assuntos
DNA Mitocondrial/genética , Variação Genética , Sus scrofa/genética , Cromossomo Y/genética , Animais , Bulgária , Haplótipos , Análise de Sequência de DNA
16.
Reprod Domest Anim ; 50(4): 696-703, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26095590

RESUMO

A 14-month-old Japanese Black heifer was evaluated on Day 0 (D 0) for enlargement of the right ovary (RO). Transrectal ultrasonography (TRUS) revealed that the RO was markedly enlarged and multicystic, while the left ovary (LO) was small and inactive. The presumptive diagnosis was granulosa-theca cell tumour (GTCT), which was confirmed by markedly elevated plasma anti-Müllerian hormone (AMH) of 4.42 ng/ml. Therefore, ovariectomy of the RO was the treatment of choice. The heifer was checked by TRUS and blood sampling on D 42, D 63 and immediately before ovariectomy on D 85. On D 42, TRUS did not show marked changes in either ovary in comparison with D 0. However, on D 63, the RO had transformed into a single cyst, and on D 85, the LO had resumed cyclic activity. The RO was extracted on D 85 by hand-assisted laparoscopic ovariectomy to allow better control. Unexpectedly, histopathology revealed the lesion to be a fluid-filled cystic structure, with no neoplastic proliferation of follicular epithelium that would indicate GTCT. The wall of the cystic structure consisted of collagen fibres and a few degenerated granulosa cells. The retrospective hormonal analysis revealed that the AMH concentrations had markedly dropped on D 63 and 85, which coincided with resumption of cyclicity in the LO. These findings suggest that the GTCT had self-cured and transformed into a cyst-like structure. The heifer then received an oestrous synchronization regime on D 105, was artificially inseminated on D 115 and became pregnant.


Assuntos
Doenças dos Bovinos/patologia , Tumor de Células da Granulosa/veterinária , Neoplasias Ovarianas/veterinária , Tumor da Célula Tecal/veterinária , Animais , Hormônio Antimülleriano/sangue , Bovinos , Doenças dos Bovinos/cirurgia , Feminino , Tumor de Células da Granulosa/patologia , Tumor de Células da Granulosa/cirurgia , Laparoscopia Assistida com a Mão/veterinária , Hormônios/sangue , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovariectomia/veterinária , Gravidez , Remissão Espontânea , Estudos Retrospectivos , Tumor da Célula Tecal/patologia , Tumor da Célula Tecal/cirurgia
17.
Clin Exp Allergy ; 44(11): 1327-34, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25251750

RESUMO

BACKGROUND: It is increasingly clear that asthma is not a single disease, but a disorder with vast heterogeneity in pathogenesis, severity, and treatment response. To date, 30 genomewide association studies (GWASs) of asthma have been performed, including by our group. However, most gene variants identified so far confer relatively small increments in risk and explain only a small proportion of familial clustering. OBJECTIVE: To identify additional genetic determinants of susceptibility to asthma using a selected Japanese population with reduced tobacco smoking exposure. METHODS: We performed a GWAS by genotyping a total of 480 098 single-nucleotide polymorphisms (SNPs) for a Japanese cohort consisting of 734 healthy controls and 240 patients with asthma who had smoked for no more than 10 pack-years. The SNP with the strongest association was genotyped in two other independent Japanese cohorts consisting of a total of 531 healthy controls and 418 patients with asthma who had smoked for no more than 10 pack-years. For the hyaluronan synthase 2 (HAS2) gene, we investigated SNP-gene associations using an expression quantitative trait loci (eQTL) database and also analysed its gene expression profiles in 13 different normal tissues. RESULTS: In the discovery GWAS, a SNP located upstream of HAS2, rs7846389, showed the strongest statistical significance (P = 1.43 × 10(-7) ). In the two independent replication cohorts, rs7846389 was consistently associated with asthma (nominal P = 0.0152 and 0.0478 in the first and second replication cohorts, respectively). In the meta-analysis, association of rs7846389 with susceptibility to asthma reached the level of genomewide significance (P = 7.92 × 10(-9) ). This variant was strongly correlated with HAS2 mRNA expression. The strongest expression of the gene was detected in the lung. CONCLUSIONS: Our study identified HAS2 as a novel candidate gene for susceptibility to adult asthma.


Assuntos
Povo Asiático/genética , Asma/genética , Predisposição Genética para Doença , Glucuronosiltransferase/genética , Adulto , Idoso , Asma/diagnóstico , Estudos de Casos e Controles , Cromossomos Humanos Par 8 , Enganação , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hialuronan Sintases , Japão , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , RNA Mensageiro/genética , Fatores de Risco
18.
Clin Exp Rheumatol ; 32(2): 211-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24321457

RESUMO

OBJECTIVES: Recent genome-wide association studies disclosed that several single nucleotide polymorphisms (SNPs), including tumour necrosis factor (TNF) receptor-associated factor 1 (TRAF1) (+16860A/G), are associated with the pathophysiology of rheumatoid arthritis (RA). We assessed the usefulness of TRAF1 genotyping as a genetic predictor of the response to anti-TNF treatment in Japanese RA patients. METHODS: TRAF1 (+16860A/G) was genotyped using the TaqMan SNP genotyping assay in 101 Japanese RA patients treated with anti-TNF drugs for >24 weeks. We retrospectively analysed the association between SNP and the clinical response to treatment. TRAF1 mRNA and protein expression was also evaluated in CD4+, CD8+, CD14+, or CD19+ cells from 25 healthy subjects using quantitative polymerase chain reaction and intracellular staining flow cytometry, respectively. RESULTS: No statistical difference in DAS28-ESR at baseline was observed between the patient groups with the AA, AG, or GG genotype. The GG genotype was more frequent in non-responders than in good or moderate responders [odds ratio (OR) 7.4, 95% confidence interval (CI) 1.5-37.5]. The non-responders possessed the G allele more frequently than the good or moderate responders (OR 3.5, 95% CI 1.4-9.0). TRAF1 protein expression increased significantly in CD14+ monocytes from healthy subjects with the GG genotype compared with that in subjects with the AA or AG genotype. CONCLUSIONS: TRAF1 (+16860A/G) may be useful for predicting the clinical response to anti-TNF treatment and may contribute to resistance to treatment in RA patients with the GG genotype by increasing the TRAF1 expression in circulating inflammatory cells.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Artrite Reumatoide , Fator 1 Associado a Receptor de TNF/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Povo Asiático/genética , Feminino , Técnicas de Genotipagem , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodos , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
19.
Cell Tissue Res ; 353(3): 563-73, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23736379

RESUMO

Adhesion molecules are redistributed in rat uterine epithelial cells (UECs) during early pregnancy for endometrial receptivity and implantation. Intercellular adhesion molecule-2 (ICAM-2) is located as an oligomer on the basal plasma membrane of non-receptive UECs on day 1 of pregnancy and colocalizes with the lipid raft marker flotillin-2. At the time of implantation in rats and in ovariectomized rats primed with progesterone, ICAM-2 disappears from the basal plasma membrane and lipid rafts redistribute to the apical membrane. The loss of ICAM-2 might render UECs less adherent to the underlying basal lamina and more prone to apoptosis. Flotillin-2 in the apical plasma membrane at the time of implantation might provide an anchoring point for several adhesion molecules that are known to localize to this region at this time. We suggest that flotillin-2 is involved with adhesion between UECs and the implanting blastocyst, whereas ICAM-2 is associated with the ability for UECs to be removed at the time of implantation.


Assuntos
Moléculas de Adesão Celular/metabolismo , Implantação do Embrião/fisiologia , Células Epiteliais/metabolismo , Microdomínios da Membrana/metabolismo , Gravidez/metabolismo , Útero/metabolismo , Animais , Adesão Celular/fisiologia , Feminino , Proteínas de Membrana/metabolismo
20.
Phys Rev Lett ; 110(10): 107204, 2013 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-23521291

RESUMO

We investigate the two-dimensional highly spin-polarized electron accumulation layers commonly appearing near the surface of n-type polar semiconductors BiTeX (X=I, Br, and Cl) by angular-resolved photoemission spectroscopy. Because of the polarity and the strong spin-orbit interaction built in the bulk atomic configurations, the quantized conduction-band subbands show giant Rashba-type spin splitting. The characteristic 2D confinement effect is clearly observed also in the valence bands down to the binding energy of 4 eV. The X-dependent Rashba spin-orbit coupling is directly estimated from the observed spin-split subbands, which roughly scales with the inverse of the band-gap size in BiTeX.

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