RESUMEN
PURPOSE: Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid diseases. Current knowledge of HT genetics is limited, and not a single genome-wide association study (GWAS) focusing exclusively on HT has been performed to date. In order to decipher genetic determinants of HT, we performed the first GWAS followed by replication in a total of 1443 individuals from Croatia. METHODS: We performed association analysis in a discovery cohort comprising 405 cases and 433 controls. We followed up 13 independent signals (P < 10-5) in 303 cases and 302 controls from two replication cohorts and then meta-analyzed results across discovery and replication datasets. RESULTS: We identified three variants suggestively associated with HT: rs12944194 located 206 kb from SDK2 (P = 1.8 × 10-6), rs75201096 inside GNA14 (P = 2.41 × 10-5) and rs791903 inside IP6K3 (P = 3.16 × 10-5). Genetic risk score (GRS), calculated using risk alleles of these loci, accounted for 4.82% of the total HT variance, and individuals from the top GRS quartile had 2.76 times higher odds for HT than individuals from the lowest GRS quartile. CONCLUSIONS: Although discovered loci are implicated with susceptibility to HT for the first time, genomic regions harboring these loci exhibit good biological candidacy due to involvement in the regulation of the thyroid function and autoimmunity. Additionally, we observe genetic overlap between HT and several related traits, such as hypothyroidism, Graves' disease and TPOAb. Our study adds a new knowledge of underlying HT genetics and sets a firm basis for further research.
Asunto(s)
Biomarcadores/análisis , Estudio de Asociación del Genoma Completo , Enfermedad de Hashimoto/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Enfermedad de Hashimoto/patología , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Spinal lesions with marked destruction are common site of morbidity in patients with multiple myeloma causing serious clinical symptoms. The aim of the study was to evaluate the therapeutic benefit of percutaneous vertebroplasty (PVP) in treating vertebral body lesions in patients suffering from multiple myeloma. MATERIALS AND METHODS: Twenty nine patients (55 vertebral bodies) were treated after complete diagnostic evaluation, preparation and obtaining informed consent. Needle position and acrylic material injection was performed under fluoroscopic guidance. RESULTS: Average visual analogue score dropped from 7.8 before to 2.3 after the intervention. Soft tissue leak was present at 9 treated levels, small epidural cement collection at 5, venous leak at 4 and intradiscal leak at 3 levels without any clinically manifest complications. The effects of PVP were stable in all of the patients at 12 months follow-up. Subjective outcome scores collected through follow-up showed improvement of +1.45 in pain, + 1.15 in ambulation and + 1.23 in medication use. There were recurrence of back pain in 9 patients at non-treated levels due to the new lesions. CONCLUSION: In our series, PVP of painful lesions caused by multiple myeloma provides immediate and long-term pain relief. The procedure is safe and, despite of the present leakage of cement, may be performed on outpatients basis.
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Dolor de Espalda/terapia , Cementos para Huesos/uso terapéutico , Mieloma Múltiple/complicaciones , Polimetil Metacrilato/uso terapéutico , Enfermedades de la Columna Vertebral/terapia , Vertebroplastia , Anciano , Dolor de Espalda/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Radiografía Intervencional , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Enfermedades de la Columna Vertebral/etiologíaRESUMEN
Scorpinone (1), 3-methyl-6,8-methoxy-2-aza-9,10-anthraquinone, has been isolated from the mycelium of a cultured sterile fungus of Caribbean origin. The structure was elucidated by X-ray crystallography, and 2D NMR spectral data have been assigned. The compound is one of very few known fungal azaanthraquinones.
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Antraquinonas/aislamiento & purificación , Ascomicetos/química , Compuestos Aza/aislamiento & purificación , Antraquinonas/química , Compuestos Aza/química , Cafeína/química , Cafeína/aislamiento & purificación , Cromatografía en Capa Delgada , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Estructura MolecularRESUMEN
The first report of the biological production of bromo ochratoxin B by Aspergillus ochraceus Wilh. is presented as well as a study of the influence of potassium bromide, potassium iodide, potassium fluoride, and potassium chloride on the production of ochratoxin A and ochratoxin B. Potassium fluoride and potassium iodide inhibited the growth of the fungus, whereas potassium chloride substantially stimulated the production of ochratoxin A in shaken solid substrate fermentation on whole wheat or shredded wheat, generally giving a high yield of ochratoxins. Increasing levels of potassium bromide led to a decline in ochratoxin A production and an increase in bromo-ochratoxin B, ochratoxin B, and 4-hydroxy ochratoxin B. Nevertheless, A. ochraceus was much less versatile in the bromo analogues than other fungi, which produce metabolites containing chlorine. Analysis included aminopropyl solid-phase extraction column cleanup followed by quantitative analysis on reversed-phase HPLC using fluorescence detection and employing N-(5-chloro-2-hydroxybenzoyl)phenylalanine as an internal standard.
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Aspergillus ochraceus/efectos de los fármacos , Halógenos/farmacología , Ocratoxinas/biosíntesis , Aspergillus ochraceus/metabolismo , Halógenos/química , Sales (Química)Asunto(s)
Nefropatía de los Balcanes/metabolismo , Debrisoquina/metabolismo , Animales , Nefropatía de los Balcanes/etiología , Cruzamientos Genéticos , Dieta/efectos adversos , Modelos Animales de Enfermedad , Femenino , Microbiología de Alimentos , Humanos , Hidroxilación , Masculino , Penicillium/patogenicidad , Ratas , Ratas Sprague-DawleyRESUMEN
Leukaemic blasts isolated from peripheral blood of two patients with non-T, non-B ALL were cultivated for 10-13 days and cell markers were assayed on day 0 and during culture period. Using a panel of cell markers it was demonstrated that the populations of ALL blasts of both patients were composed of T10+Ia+ and "null" blasts. These blasts in the culture differentiated into three cell lines: T and B lymphocytes and myelomonocytic cells. The results thus obtained suggested that within the population of ALL blasts of these two patients there are progenitors of lymphoid and myelomonocytic cells ("null" blasts) and common precursors of T and B lymphocytes (T10+Ia+ blasts). In vitro differentiation of ALL blasts was not affected by LPS and CTPE.