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BACKGROUND AND OBJECTIVES: The purpose of this study was to provide an effective RHD genotyping strategy for the East Asian blood donors. MATERIAL AND METHODS: RhD phenotyping, weak D testing and RhCE phenotyping were performed on 110 samples from members of the RhD-negative club, private organization composed of RhD-negative blood donors, in the GwangJu-Chonnam region of Korea. The RHD promoter, intron 4, and exons 7 and 10 were analysed by real-time PCR. Two nucleotide changes (c.1227 G>A, and c.1222 T>C) in exon 9 were analysed by sequencing. RESULTS: Of 110 RhD-negative club members, 79 (71·8%) showed complete deletion of the RHD gene, 10 (9·1%) showed results consistent with RHD-CE-D hybrid, and 21 (19·1%) showed amplification of RHD promoter, intron 4, and exons 7 and 10. Of the latter group, 16 (14·5%) were in the DEL blood group including c.1227 G>A (N = 14) and c.1222 T>C (N = 2), 2 (1·8%) were weak D, 1(0·9%) was partial D, and 2 (1·8%) were undetermined. The RhD-negative phenotype samples consisted of 58 C-E-c+e+, 19 C-E+c+e+, 3 C-E+c+e-, 21 C+E-c+e-, 6 C+E-c+e+ and 3 C+E-c-e + . Notably, all 58 samples with the C-E-c+e+ phenotype were revealed to have complete deletion of the RHD gene. The C-E-c+e+ phenotype showed 100% positive predictive value for detecting D-negative cases. CONCLUSIONS: RHD genotyping is not required in half of D-negative cases. We suggest here an effective RHD genotyping strategy for accurate detection of RhD variants in apparently RhD-negative blood donors in East Asia.
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Donantes de Sangre , Sistema del Grupo Sanguíneo Rh-Hr/genética , Pueblo Asiatico/genética , Frecuencia de los Genes , Genotipo , Humanos , Polimorfismo Genético , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Eliminación de SecuenciaRESUMEN
A novel A subgroup allele (c.538C>T p.Arg180Cys) showing weak A phenotype was found in a 30-year-old Korean woman with ABO discrepancy. Using 3D structural analysis, protein stability prediction and flow cytometric analysis of ABO antigen expression on HeLa cells transfected with plasmids containing the p.Arg180Cys mutant, we found that the Arg180 residue in the loop region of the A glycosyltransferases (GTA) structure plays significant role in stabilizing its closed conformation, which is required for substrate binding and catalysis study.
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N-Acetilgalactosaminiltransferasas/genética , Sistema del Grupo Sanguíneo ABO/genética , Adulto , Estabilidad de Enzimas , Femenino , Estudios de Asociación Genética , Células HeLa , Humanos , Mutación Missense , Fenotipo , Análisis de Secuencia de ADNRESUMEN
We observe D(0)-D(0) mixing in the decay D(0) â K+π- using a data sample of integrated luminosity 976 fb(-1) collected with the Belle detector at the KEKB e+e- asymmetric-energy collider. We measure the mixing parameters x'(2) = (0.09 ± 0.22) × 10(-3) and y'=(4.6 ± 3.4) × 10(-3) and the ratio of doubly Cabibbo-suppressed to Cabibbo-favored decay rates R(D) = (3.53 ± 0.13) × 10(-3), where the uncertainties are statistical and systematic combined. Our measurement excludes the no-mixing hypothesis at the 5.1 standard deviation level.
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The new allele A*02:07:02 shows a single nucleotide substitution compared with A*02:07:01 at codon 233 (ACC â ACT) without any amino acid change.
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Alelos , Pueblo Asiatico , Antígeno HLA-A2/genética , Secuencia de Bases , Codón , Dermatoglifia del ADN , Exones , Frecuencia de los Genes , Antígeno HLA-A2/inmunología , Humanos , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , República de Corea , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
We observe evidence for CP violation in the decay D+ â K(S)(0)π+ using a data sample with an integrated luminosity of 977 fb(-1) collected by the Belle detector at the KEKB e+ e- asymmetric-energy collider. The CP asymmetry in the decay is measured to be (-0.363±0.094±0.067)%, which is 3.2 standard deviations away from zero, and is consistent with the expected CP violation due to the neutral kaon in the final state.
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We report the first observation of the doubly Cabibbo-suppressed decays D(+)âK(+)η((')) using a 791 fb(-1) data sample collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The ratio of the branching fractions of doubly Cabibbo-suppressed relative to singly Cabibbo-suppressed D(+)âπ(+)η((')) decays are B(D(+)âK(+)η)/B(D(+)âπ(+)η)=(3.06±0.43±0.14)% and B(D(+)âK(+)η')/B(D(+)âπ(+)η')=(3.77±0.39±0.10)%. From these, we find that the relative final-state phase difference between the tree and annihilation amplitudes in D(+) decays, δ(TA), is (72±9)° or (288±9)°. We also report the most precise measurements of CP asymmetries to date: A(CP)(D(+)âπ(+)η)=(+1.74±1.13±0.19)% and A(CP)(D(+)âπ(+)η')=(-0.12±1.12±0.17)%.
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We have searched for CP violation in the decays D(0)âK(S)(0)P(0) where P(0) denotes a neutral pseudoscalar meson that is either a π(0), η, or η' using KEKB asymmetric-energy e(+)e(-) collision data corresponding to an integrated luminosity of 791 fb(-1) collected with the Belle detector. No evidence of significant CP violation is observed. We report the most precise CP asymmetry measurement in the decay D(0)âK(S)(0)π(0) to date: A(CP)(D(0)âK(S)(0)π(0))=(-0.28±0.19±0.10)%. We also report the first measurements of CP asymmetries in the decays D(0)âK(S)(0)η and D(0)âK(S)(0)η': A(CP)(D(0)âK(S)(0)η)=(+0.54±0.51±0.16)% and A(CP)(D(0)âK(S)(0)η')=(+0.98±0.67±0.14)%, respectively.
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Modelos Teóricos , Fenómenos Físicos , IncertidumbreRESUMEN
AIMS: Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. METHODS AND RESULTS: CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.
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Antibacterianos/farmacología , Poloxámero , Esteroides/farmacología , Tensoactivos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/química , Biopelículas/efectos de los fármacos , Ácido Cólico/química , Fibrosis Quística/microbiología , Hemólisis/efectos de los fármacos , Humanos , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Esteroides/administración & dosificación , Esteroides/uso terapéuticoRESUMEN
We have searched for CP violation in the charmed meson decays D((s))(+) --> K(S)(0)pi(+) and D((s))(+) --> K(S)(0)K(+) using 673 fb(-1) of data collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. No evidence for CP violation is observed. We report the most sensitive CP asymmetry measurements to date for these decays: A(CP)(D(+)-->K(S)(0)pi(+)) = (-0.71 +/- 0.19 +/- 0.20)%, A(CP)(D(s)(+) --> K(S)(0)pi(+)) = (+5.45 +/- 2.50 +/- 0.33)%, A(CP)(D(+) --> K(S)(0)K(+)) = (-0.16 +/- 0.58 +/- 0.25)%, and A(CP)(D(s)(+) --> K(S)(0)K(+)) = (+0.12 +/- 0.36 +/- 0.22)%, where the first uncertainties are statistical and the second are systematic.
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Previous evidence suggests that the serotonin transporter gene (SLC6A4) is associated with the structure of brain regions that are critically involved in dysfunctional limbic-cortical network activity associated with major depressive disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics were used to investigate changes in white matter integrity in patients with MDD compared with healthy controls. A possible association between structural alterations in white matter tracts and DNA methylation of the SLC6A4 promoter region was also assessed. Thirty-five medication-naive patients with MDD (mean age: 40.34, male/female: 10/25) and age, gender and education level matched 49 healthy controls (mean age: 41.12, male/female: 15/34) underwent DTI. SLC6A4 DNA methylation was also measured at five CpG sites of the promoter region, and the cell type used was whole-blood DNA. Patients with MDD had significantly lower fractional anisotropy (FA) values for the genu of the corpus callosum and body of the corpus callosum than that in healthy controls (family-wise error corrected, P<0.01). Significant inverse correlations were observed between SLC6A4 DNA methylation and FA (CpG3, Pearson's correlation: r=-0.493, P=0.003) and axial diffusivity (CpG3, Pearson's correlation: r=-0.478, P=0.004) values of the body of the corpus callosum in patients with MDD. These results contribute to evidence indicating an association between epigenetic gene regulation and structural brain alterations in depression. Moreover, we believe this is the first report of a correlation between DNA methylation of the SLC6A4 promoter region and white matter integrity in patients with MDD.
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Cuerpo Calloso/diagnóstico por imagen , Trastorno Depresivo Mayor/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Sustancia Blanca/diagnóstico por imagen , Adulto , Estudios de Casos y Controles , Metilación de ADN , Trastorno Depresivo Mayor/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: Anecdotal reports documented extended survival times for patients who developed infections at the site of resection of malignant gliomas. Hypothesized mechanisms for this phenomenon include immune responses triggered by lipopolysaccharide (LPS). This investigation assessed whether LPS could produce tumor regression in an in vivo model of malignant glioma. METHODS: Delayed brain tumor cells (2 x 10(6)) were injected subcutaneously into female BALB/c mice. LPS (300-500 microg) was injected intratumorally or subcutaneously at a contralateral site on Days 10, 17, and 24. Control animals received phosphate-buffered saline intratumorally or subcutaneously. Mice were killed on Day 28, and tumors were removed. Mean tumor masses for control animals and the two LPS-treated groups (intratumoral or contralateral subcutaneous treatment) were compared. Histological assessments of treated and control tumors were performed. RESULTS: Complete or nearly total tumor regression was achieved in all 20 mice with subcutaneous delayed brain tumor cell tumors treated intratumorally with 400 microg of LPS (mean tumor mass of 0.09 +/- 0.38 g versus 2.42 +/- 2.46 g for control animals, P < 0.0001). Intratumoral administration of 300 microg of LPS or subcutaneous injection of 300 or 400 microg of LPS at a contralateral site resulted in less consistent regression of subcutaneous tumors. Administration of 500 microg of LPS resulted in tumor regression similar to that observed with lower doses but was limited by treatment-related deaths in 40% of animals. Histological assessment revealed lymphocytic infiltration of LPS-treated tumors. CONCLUSION: Intratumoral injections of LPS caused dramatic regression of subcutaneously implanted delayed brain tumor cell mouse gliomas. Investigation of this antitumoral effect may improve treatment responses for patients with malignant gliomas.
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Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Lipopolisacáridos/administración & dosificación , Animales , Femenino , Inyecciones Intralesiones , Inyecciones Subcutáneas , Lipopolisacáridos/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Inducción de RemisiónRESUMEN
We report the first observation of the doubly Cabibbo-suppressed decay D_{s};{+}-->K;{+}K;{+}pi;{-} using 605 fb;{-1} of data collected with the Belle detector at the KEKB asymmetric-energy e;{+}e;{-} collider. The branching ratio with respect to its Cabibbo-favored counterpart B(D_{s};{+}-->K;{+}K;{+}pi;{-})/B(D_{s};{+}-->K;{+}K;{-}pi;{+}) is (0.229+/-0.028+/-0.012)%, where the first uncertainty is statistical and the second is systematic. We also report a significantly improved measurement of the doubly Cabibbo-suppressed decay D;{+}-->K;{+}pi;{+}pi;{-}, with a branching ratio B(D;{+}-->K;{+}pi;{+}pi;{-})/B(D;{+}-->K;{-}pi;{+}pi;{+})=(0.569+/-0.018+/-0.014)%.