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1.
Appl. cancer res ; 40(4): [1-12], 01 june 2020. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1103878

RESUMO

Background: Next-generation sequencing (NGS) based assay for finding an actionable driver in non-small-cell lung cancer is a less used modality in clinical practice. With a long list of actionable targets, limited tissue, arduous single-gene assays, the alternative of NGS for broad testing in one experiment looks attractive. We report here our experience with NGS for biomarker testing in hundred advanced lung cancer patients. Methods: Predictive biomarker testing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel V2 (30 tumors) and Oncomine™ Solid Tumor DNA and Oncomine™ Solid Tumor Fusion Transcript kit (70 tumors) on IonTorrent sequencing platform. Results: One-seventeen distinct aberrations were detected across 29 genes in eighty-six tumors. The most commonly mutated genes were TP53 (43% cases), EGFR (23% cases) and KRAS (17% cases). Thirty-four patients presented an actionable genetic variant for which targeted therapy is presently available, and fifty-two cases harbored non-actionable variants with the possibility of recruitment in clinical trials. NGS results were validated by individual tests for detecting EGFR mutation, ALK1 rearrangement, ROS1 fusion, and c-MET amplification. Compared to single test, NGS exhibited good agreement for detecting EGFR mutations and ALK1 fusion (sensitivity- 88.89%, specificity- 100%, Kappa-score 0.92 and sensitivity- 80%, specificity- 100%, Kappa-score 0.88; respectively). Further, the response of patients harboring tyrosine kinase inhibitor (TKI) sensitizing EGFR mutations was assessed. The progression-free-survival of EGFR positive patients on TKI therapy, harboring a concomitant mutation in PIK3CAmTOR and/or RAS-RAF-MAPK pathway gene and/or TP53 gene was inferior to those with sole-sensitizing EGFR mutation (2 months vs. 9.5 months, P = 0.015). Conclusions: This is the first study from South Asia looking into the analytical validity of NGS and describing the mutational landscape of lung cancer patients to study the impact of co-mutations on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and making treatment decisions in advanced lung cancer


Assuntos
Humanos , Masculino , Feminino , Biomarcadores Tumorais , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Mutação
2.
Electron. j. biotechnol ; 44: 19-24, Mar. 2020. ilus, graf
Artigo em Inglês | LILACS | ID: biblio-1087631

RESUMO

BACKGROUND: Pyruvic acid (PA), a vital α-oxocarboxylic acid, plays an important role in energy and carbon metabolism. The oleaginous yeast Yarrowia lipolytica (Y. lipolytica) has considerable potential for the production of PA. An increased NaCl concentration reportedly increases the biomass and PA yield of Y. lipolytica. RESULTS: To increase the yield of PA, the NaCl-tolerant Y. lipolytica A4 mutant was produced using the atmospheric and room temperature plasma method of mutation. The A4 mutant showed growth on medium containing 160 g/L NaCl. The PA yield of the A4 mutant reached 97.2 g/L at 120 h (0.795 g/g glycerol) in a 20-L fermenter with glycerol as the sole carbon source, which was 28.9% higher than that of the parental strain. CONCLUSION: The PA yield from Y. lipolytica can be improved by increasing its NaCl tolerance.


Assuntos
Ácido Pirúvico/metabolismo , Yarrowia/genética , Yarrowia/metabolismo , Pressão Osmótica , Leveduras , Carbono/metabolismo , Cloreto de Sódio , Reatores Biológicos , Tolerância ao Sal/genética , Fermentação , Glicerol/metabolismo , Mutação
4.
Horiz. méd. (Impresa) ; 19(4): 74-83, Dic. 2019. ilus
Artigo em Espanhol | LILACS, LIPECS | ID: biblio-1048874

RESUMO

En los últimos años, el rápido desarrollo tecnológico y el mayor conocimiento de aspectos genéticos y moleculares en medicina han permitido un mejor enfoque en el entendimiento, diagnóstico y tratamiento de diversas enfermedades oncológicas. En relación con el carcinoma de pulmón, ha habido una significativa evolución desde sus primeras clasificaciones, puramente morfológicas, hasta la última del año 2015, en la que se integra información histológica, inmunofenotípica, genética molecular, clínica, y radiológica, lo que permite una mejor evaluación y manejo terapéutico de estos pacientes. En el presente artículo se hace un repaso desde las primeras clasificaciones del carcinoma de pulmón hasta la última, y se examinan los cambios más relevantes y la importancia de los hallazgos genéticos moleculares para un mejor enfoque clínico y terapéutico.


Current classification of lung carcinoma. Histological, immunophenotypic, molecular and clinical considerations ABSTRACT In recent years, the rapid technological development and the better knowledge of genetic and molecular aspects in medicine have allowed a better approach to understand, diagnose and treat various oncological diseases. Regarding lung carcinoma, there has been a remarkable evolution from the first classifications, which were purely morphological, to the last one issued in 2015. This last classification includes histological, immunophenotypic, molecular genetics, clinical and radiological information, which allows a better evaluation and therapeutic management of these patients. In the present article, the first classifications of lung carcinoma to the last one are reviewed, and the most relevant changes and the importance of the molecular genetics findings are examined for a better clinical and therapeutic approach.


Assuntos
Humanos , Carcinoma , Classificação , Pulmão , Mutação
5.
Arch. argent. pediatr ; 117(6): 684-687, dic. 2019. tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1051382

RESUMO

La xerocitosis hereditaria es un desorden poco frecuente causado por defectos en la permeabilidad eritrocitaria, que se caracteriza por anemia hemolítica de gravedad variable y sobrecarga de hierro. El diagnóstico suele ser tardío y confundirse con otras anemias hemolíticas, lo que puede llevar a indicaciones de procedimientos, como la esplenectomía, contraindicados en estos pacientes. Se reportan las características clínicas, hematológicas y moleculares de dos pacientes pediátricos no relacionados con diagnóstico de xerocitosis hereditaria. Ambos presentaban eritrocitos deshidratados con alta concentración de hemoglobina corpuscular media, frotis no patognomónico, marcadores de hemólisis y una curva de fragilidad osmótica resistente. El diagnóstico se confirmó por la secuenciación del gen PIEZO.Se resalta la importancia de reconocer la causa de la anemia hemolítica para dar un enfoque terapéutico preciso y dar adecuado consejo genético


Hereditary xerocytosis is a rare disorder caused by defects of red blood cell permeability that are characterized by hemolytic anemia of variable degree and iron overload. Diagnosis is usually late and confused with other hemolytic anemias, which can lead to procedural indications, such as splenectomy, contraindicated in these patients. We report the clinical, haematological, and molecular characteristics of two patients from two unrelated families affected by hereditary xerocytosis. Both patients had dehydrated erythrocytes with a high concentration of mean corpuscular hemoglobin, non-pathognomonic smears, markers of hemolysis and a resistant osmotic fragility curve. The diagnosis was confirmed by the sequencing of the PIEZO gene. We emphasize the importance of recognizing the cause of hemolytic anemia to give an accurate therapeutic approach and give adequate genetic counseling.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Hidropisia Fetal/diagnóstico , Anemia Hemolítica Congênita/diagnóstico , Mutação , Linhagem , Hemoglobinas/análise , Sobrecarga de Ferro , Índices de Eritrócitos , Anemia Hemolítica Congênita/complicações , Anemia Hemolítica Congênita/genética , Anemia Hemolítica Congênita/sangue , Icterícia Neonatal
6.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 37(4): 520-524, Oct.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1041362

RESUMO

ABSTRACT Objective: To describe the case of a patient with central congenital hypothyroidism (CCH) due to a recurrent mutation in the TSHB gene, as well as to conduct a genetic study of his family. Case description: It is presented a case report of a 5-month-old boy with a delayed diagnosis of isolated CCH in whom the molecular analysis was performed 12 years later and detected a recurrent mutation (c.373delT) in TSHB gene. The parents and sister were carriers of the mutant allele. Comments: The c.373delT mutation has previously been reported in patients from Brazil, Germany, Belgium, United States, Switzerland, Argentina, France, Portugal, United Kingdom and Ireland. In summary, our case and other ones reported in the literature support the theory that this mutation may be a common cause of isolated TSH deficiency. Isolated TSH deficiency is not detected by routine TSH-based neonatal screening, representing a clinical challenge. Therefore, when possible, molecular genetic study is indicated. Identification of affected and carriers allows the diagnosis, treatment and adequate genetic counseling.


RESUMO Objetivo: Descrever o caso de um paciente com hipotireoidismo congênito central (HCC) por conta de uma mutação recorrente no gene TSHB, bem como realizar um estudo genético de sua família. Descrição do caso: Relato de caso de um menino de 5 meses de idade com diagnóstico tardio de HCC isolado, em quem a análise molecular foi realizada 12 anos depois e detectou uma mutação recorrente (c.373delT) no gene TSHB. Os pais e a irmã eram portadores do alelo mutante. Comentários: A mutação c.373delT já foi relatada em pacientes do Brasil, da Alemanha, da Bélgica, dos Estados Uinidos, da Suíça, da Argentina, da França, de Portugal, do Reino Unido e da Irlanda. Em resumo, nosso caso e outros relatados na literatura reforçam a teoria de que essa mutação pode ser uma causa comum de deficiência isolada de TSH. A deficiência isolada de TSH não é detectada na triagem neonatal com base na dosagem de TSH, representando um desafio clínico. Portanto, quando possível, o estudo genético molecular é indicado. A identificação dos afetados e dos portadores permite o diagnóstico, o tratamento e o aconselhamento genético adequado.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Criança , Adulto , Triagem Neonatal , Hipotireoidismo Congênito/diagnóstico , Tireotropina Subunidade beta/genética , Diagnóstico Tardio , Mutação , Marcadores Genéticos , Hipotireoidismo Congênito/genética
7.
Rev. bras. cir. plást ; 34(4): 571-575, oct.-dec. 2019. ilus
Artigo em Inglês, Português | LILACS | ID: biblio-1047934

RESUMO

O presente estudo objetiva relatar a técnica do retalho toracoabdominal pós-mastectomia por tumor localmente avançado em paciente com mutação de BRCA1. Foi realizada a mastectomia com ressecção de quase todo o músculo peitoral maior à esquerda, com linfonodectomia axilar homolateral e reconstrução do grande defeito da parede torácica com retalho toracoabdominal fasciocutâneo, baseado nas artérias intercostais posteriores.


This case report describes the application of the thoracoabdominal flap technique after locally advanced tumor mastectomy in a patient with breast cancer 1 (BRCA1) mutation. The mastectomy included resection of nearly the entire left pectoralis major muscle, with homolateral axillary lymphadenectomy and reconstruction of the large chest wall defect with a fasciocutaneous thoracoabdominal flap based on the posterior intercostal arteries.


Assuntos
Humanos , Feminino , Adulto , História do Século XXI , Pacientes , Retalhos Cirúrgicos , Mama , Neoplasias da Mama , Procedimentos Cirúrgicos Reconstrutivos , Oncologia Cirúrgica , Mutação , Retalhos Cirúrgicos/transplante , Mama/cirurgia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Oncologia Cirúrgica/métodos , Mutação/ética
10.
An. bras. dermatol ; 94(6): 658-663, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1054887

RESUMO

Abstract Background: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. Objective: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. Methods: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. Results: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1). Study limitation: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. Conclusions: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Psoríase/genética , Interleucinas/genética , Mutação , Fenótipo , Psoríase/patologia , China , Análise de Sequência de DNA , Estatísticas não Paramétricas , Grupo com Ancestrais do Continente Asiático/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Estudos de Associação Genética , Dermatoses do Pé/genética , Dermatoses do Pé/patologia , Dermatoses da Mão/genética , Dermatoses da Mão/patologia , Heterozigoto
11.
J. bras. nefrol ; 41(3): 393-399, July-Sept. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1040251

RESUMO

Abstract Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.


Resumo A glomerulopatia por lipoproteínas (GLP) é uma patologia rara que causa síndrome nefrótica e/ou insuficiência renal. Na microscopia, a GLP é caracterizada pela presença de trombos de lipoproteínas em capilares glomerulares dilatados devido a diferentes mutações no gene da ApoE. O gene da ApoE está localizado no cromossomo 19q13.2 e pode ser identificado em quase todas as lipoproteínas séricas. A ApoE age como fator de proteção na arterioesclerose por conta de sua interação com a depuração de lipoproteínas mediada por receptores e com o receptor de colesterol. Dentre os polimorfismos mais comuns destacam-se ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3 e ApoE4/4. A GLP pode acometer indivíduos de todas as faixas etárias, com discreta predominância do sexo masculino. Pacientes afetados tipicamente apresentam dislipidemia, hiperlipoproteinemia tipo III e proteinúria. O tratamento da GLP é conduzido com fenofibrato, antilipêmicos, corticosteroides, LDL-aferese, troca de plasma, antiplaquetários, anticoagulantes, uroquinase e transplante renal. Recidiva no enxerto renal indica a existência de componentes patogênicos do complexo humoral extraglomerular resultante de metabolismo lipoproteico anômalo, possivelmente associado a ApoE.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Adulto , Pessoa de Meia-Idade , Nefropatias/patologia , Nefropatias/terapia , Apolipoproteínas E/genética , Fatores Sexuais , Transplante de Rim , Resultado do Tratamento , Nefropatias/complicações , Nefropatias/genética , Falência Renal Crônica/cirurgia , Falência Renal Crônica/etiologia , Mutação , Hipolipemiantes/uso terapêutico
12.
An. bras. dermatol ; 94(4): 458-460, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1038300

RESUMO

Abstract: Melanoma is widely known as the most lethal skin cancer. Specific tumor-related mortality can be significantly reduced if diagnosis and treatment are properly performed during initial phases of the disease. The current search for biomarkers in early-stage melanomas is a high-priority challenge for physicians and researchers. We aimed to assess the immunoexpression of BRAFV600E and KIT in a case series consisting of 44 early-stage melanomas. Formalin-fixed paraffin-embedded samples were systematically evaluated using a semi-quantitative method based on scores of percentage and intensity for immunostained tumor cells. We observed significant concordance between BRAFV600E and KIT immunoexpression in thin invasive melanomas. Our findings corroborate previous evidence showing abnormal expression of proteins associated with MAPK intracellular signaling pathway in early-stage melanomas.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Neoplasias Cutâneas/patologia , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas Proto-Oncogênicas B-raf/análise , Melanoma/patologia , Imuno-Histoquímica , Estudos Retrospectivos , Progressão da Doença , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Quinases Ativadas por Mitógeno/análise , Proteínas Proto-Oncogênicas B-raf/genética , Mutação , Estadiamento de Neoplasias
15.
Cambios rev. méd ; 18(1): 90-95, 28/06/2019. ilus; grafs
Artigo em Espanhol | LILACS | ID: biblio-1015167

RESUMO

INTRODUCCIÓN. La Agammaglobulinemia ligada al cromosoma X es un tipo de inmunodeficiencia primaria originada por una mutación en el gen que codifica a la proteína responsable del proceso madurativo de los linfocitos B, provocando la disminución o ausencia de inmunoglobulinas en sangre periférica y la predisposición a procesos infecciosos a repetición, sobre todo a nivel del tracto respiratorio y digestivo. La sospecha clínica orienta la solicitud de pruebas complementarias de forma secuencial. El tratamiento consiste en la administración sustitutiva de por vida de inmunoglobulina humana. CASO CLÍNICO. Se presentó el caso de un niño de 8 años de edad con infecciones respiratorias altas y bajas a repetición, con estudios radiográficos de tórax que revelaron una atelectasia persistente, en quien la sospecha clínica dio paso a los evaluativos inmunológico y genético. RESULTADOS. El diagnóstico fue realizado a los 6 años de edad con recuento sérico de inmunoglobulinas por debajo del rango para la edad, citometría de flujo con CD19+ del 0,08% y genética con mutación del gen BTK. Se instauró tratamiento con Inmunoglobulina humana a 400 mg/Kg cada 4 semanas, se monitorizó los niveles de IgG antes de cada infusión. DISCUSIÓN. La Agammaglobulinemia ligada al cromosoma X constituye una enfermedad poco prevalente e infradiagnosticada en la que la sospecha clínica representa la base del abordaje, lo que permitió el tratamiento sustitutivo apropiado. CONCLUSIÓN. El diagnóstico y tratamiento oportunos permitieron evitar el desarrollo de infecciones respiratorias graves, mejorar la calidad de vida del niño y el asesoramiento genético familiar.


INTRODUCTION. X-linked Agammaglobulinemia is a type of primary immunodeficiency caused by a mutation in the gene that encodes the protein responsible for the maturation process of B lymphocytes, causing the decrease or absence of immunoglobulins in peripheral blood and the predisposition to repeated infectious processes, especially at the level of the respiratory and digestive tracts. Clinical suspicion guides the request for complementary tests sequentially. The treatment consists of lifelong substitute administration of human immunoglobulin. CASE REPORT. The case of an 8-year-old boy with repeated high and low respiratory infections was presented, with chest radiographic studies that revealed persistent atelectasis, in whom clinical suspicion gave way to immunological and genetic evaluations. RESULTS. The diagnosis was made at 6 years of age with serum immunoglobulin counts below the age range, flow cytometry with CD19 + of 0,08% and genetics with BTK gene mutation. Treatment with human Immunoglobulin at 400 mg / Kg every 4 weeks was initiated, IgG levels were monitored before each infusion. DISCUSSION. X- linked Agammaglobulinemia is a rare and underdiagnosed disease in which clinical suspicion represents the basis of the approach, which allowed for appropriate replacement. CONCLUSION. Timely diagnosis and treatment allowed to avoid the development of serious respiratory infections, improve de child ́s quality of life and family genetic couseling.


Assuntos
Humanos , Masculino , Criança , Infecções Bacterianas , Saúde da Criança , Mutação , Infecções Respiratórias , Cromossomo X , Linfócitos B , Agamaglobulinemia
16.
J. pediatr. (Rio J.) ; 95(3): 282-290, May-June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1012607

RESUMO

Abstract Objective: To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. Methods: A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. Results: After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. Conclusions: The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients.


Resumo Objetivo: Descrever os resultados obtidos em um programa de triagem neonatal após sua implementação e avaliar os perfis clínicos e moleculares de casos confirmados e suspeitos de hiperplasia adrenal congênita. Métodos: Foi feito um estudo transversal. Recém-nascidos com suspeita da doença devido aos altos níveis de 17-alfa-hidroxiprogesterona e ajustados pelo peso ao nascer foram selecionados. A hiperplasia adrenal congênita clássica (forma perdedora de sal e forma virilizante simples) foi diagnosticada por um aumento nos níveis de 17-alfa-hidroxiprogesterona confirmado no reteste, avaliação clínica e genótipo determinado com o uso do ensaio SNaPshot e amplificação multiplex de sondas dependente de ligação. Resultados: Após 24 meses, 15 casos clássicos de hiperplasia adrenal congênita foram diagnosticados em 217.965 recém-nascidos, com uma incidência estimada de 1:14.531. De 132 pacientes, sete não clássicos e 14 heterozigotos foram submetidos à triagem para mutações no gene CYP21A2 e 96 pacientes apresentaram resultados falso-positivos com CYP21A2 do tipo selvagem. No reteste, níveis aumentados de 17-alfa-hidroxiprogesterona foram encontrados em pacientes com hiperplasia adrenal congênita clássica e mostraram correlação significativa com HAC clássica relacionada ao genótipo. As mutações mais frequentes foram IVS2-13A/C>G, seguidas de deleção gênica ou eventos de rearranjo na forma clássica. Em casos de doenças não clássicas e heterozigose, a mutação p.Val282Leu foi a mais comum. Conclusões: Os resultados ressaltam a eficácia da triagem neonatal para a hiperplasia adrenal congênita no sistema público de saúde e indicam que a estratégia adotada foi adequada. A segunda coleta de amostras, juntamente com a genotipagem dos casos suspeitos, ajudou a diagnosticar adequadamente os casos graves e mais leves e diferenciá-los de pacientes com resultado falso-positivo.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Esteroide 21-Hidroxilase/sangue , Triagem Neonatal/métodos , Hiperplasia Suprarrenal Congênita/diagnóstico , 17-alfa-Hidroxiprogesterona/sangue , Fenótipo , Brasil/epidemiologia , Biomarcadores/sangue , Incidência , Estudos Transversais , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/epidemiologia , Genótipo , Mutação
17.
Int. j. morphol ; 37(2): 757-765, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002290

RESUMO

The aim of this study was to estimate the values of morphological traits of myocardium in American minks. The study was conducted on 342 male mink hearts and 416 female mink hearts. Mink coat coloration resulting from mutation or crossbreeding of mutational variants with each other and sex were assumed as a source of variation. Carcass, lung and heart weights, heart height, width, depth and circumference, as well as left and right ventricular wall weights and thickness at two locations were determined. The values of 10 indices characterising the relative size of the heart were estimated. The results showed no normal distribution of the heart traits examined. The greatest average heart weight was characteristic of male mutational colour variant minks (17.40 ± 2.34 g). These hearts were heavier by more than 8 % than those of male standard colour variant minks. The hearts of male mutational colour variant minks were characterised by the greatest left and right ventricle weights (P≤0.01) compared to those of male standard colour variant minks, in which in turn the greatest left and right ventricle wall thickness was larger than that in standard colour variant minks. It was found that a greater difference calculated between mean left ventricle wall thickness and mean right ventricle wall thickness in standard colour variant minks may provide more evidence of its adaptation to a greater effort, referring thus to their evolutionary history than to the occurrence of signs of multistage myocardial hypertrophy.


El objetivo de este estudio fue estimar los valores de los rasgos morfológicos del miocardio en el visón americano. El estudio se realizó en 342 corazones de visón macho y 416 corazones de visón hembra. La coloración de la capa de visón resultante de la mutación o el cruce de variantes mutacionales entre sí, y el sexo se asumieron como una fuente de variación. Se determinaron los pesos de la canal, los pulmones y el corazón, la altura del corazón, el ancho, la profundidad y la circunferencia, así como los pesos y el grosor de las paredes de los ventrículos izquierdo y derecho en dos ubicaciones. Se estimaron los valores de 10 índices que caracterizan el tamaño relativo del corazón. Los resultados no mostraron una distribución normal de los rasgos de los corazones examinados. El mayor peso promedio del corazón fue característico de los visones de variante de color mutacional macho (17,40 ± 2,34 g). Estos corazones eran más pesados en más de un 8 % que los de los visones con variante de color estándar machos. Los corazones de los visones de variante de color mutacional macho se caracterizaron por los mayores pesos de los ventrículos izquierdo y derecho (P≤0,01) en comparación con los de los visones de color estándar machos, en los que a su vez el mayor grosor de las paredes de los ventrículos izquierdo y derecho fue mayor que el de las variantes de colores estándar. Se observó que una mayor diferencia entre los grosores medio de las paredes de los ventrículos izquierdo y derecho en las variantes de color estándar, puede proporcionar más pruebas de su adaptación a un mayor esfuerzo, refiriéndose así a su historial evolutivo, pese a la aparición de signos de hipertrofia miocárdica multietapa.


Assuntos
Animais , Masculino , Feminino , Coração/anatomia & histologia , Vison/anatomia & histologia , Vison/genética , Tamanho do Órgão/genética , Caracteres Sexuais , Mutação
18.
Arch. argent. pediatr ; 117(2): 131-136, abr. 2019. tab
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1001168

RESUMO

Los moduladores cystic fibrosis transmembrane conductance regulator (CFTR) representan el presente y el futuro del manejo farmacológico para los pacientes con fibrosis quística. El objetivo de esta publicación es realizar una revisión de esta opción terapéutica. Se revisaron artículos científicos consultando las bases de datos MedLine, información disponible a través de la página oficial Cystic Fibrosis Foundation, desde 2009 hasta 2018, en el idioma inglés. Sin restricciones respecto al tipo de estudio, se seleccionaron 12 artículos que incluyeron información sobre el estado actual de la investigación sobre moduladores CFTR. Actualmente, están aprobados por la Food and Drug Administration tres moduladores: ivacaftor, lumacaftor + ivacaftor y tezacaftor + ivacaftor, y hay otros 11 en diferentes fases de estudio. La terapia con moduladores CFTR es una realidad en desarrollo que apunta al máximo objetivo de la medicina personalizada y que promete mejorar la calidad de vida de pacientes con fibrosis quística.


Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are the present and future of drug management for patients with cystic fibrosis. The objective of this article is to review this therapeutic option. Scientific articles were reviewed by searching the MedLine database, which is available through the Cystic Fibrosis Foundation's official website, from 2009 to 2018, in English. Twelve articles about the current status of research in CFTR modulators were selected without restrictions regarding the type of study. To date, the United States Food and Drug Administration has approved three modulators: ivacaftor, lumacaftor + ivacaftor, and tezacaftor + ivacaftor, while other 11 drugs are being studied in different investigation phases. CFTR modulator therapy is a developing reality aimed at the highest goal of personalized medicine and promises to improve the quality of life of cystic fibrosis patients.


Assuntos
Humanos , Criança , Adolescente , Terapêutica , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Mutação
19.
Vaccimonitor (La Habana, Print) ; 28(1)ene.-abr. 2019. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1094616

RESUMO

Con la finalidad de evaluar la patogenia en cepas de Salmonella Typhimurium con mutaciones en los genes invG/invE de la Isla de Patogenicidad de Salmonella 1 (SPI-1) y de los genes ssaJ/ssaK en la SPI-2, se evaluaron los modelos asa intestinal ligada de ratón asociado a la observación de los tejidos por microscopía electrónica de transmisión (MET) y la producción de salmonelosis sistémica en ratón. Para ello, se utilizaron seis cepas de Salmonella: S. Typhimurium SL-1344 (cepa control) y sus derivadas mutantes: ∆invEG S. Typhimurium SL-1344 (mutante en SPI-1) y ∆ssaJK S. Typhimurium SL-1344 (mutante en SPI-2), S. Typhimurium (cepa clínica) y sus derivadas mutantes: ∆invEG S. Typhimurium y ∆ssaJK S. Typhimurium. Los resultados de MET permitieron verificar las alteraciones morfológicas del epitelio intestinal en el ratón infectado con cepas de Salmonella cuyos genes de patogenicidad estaban intactos. Fue comprobada la pérdida del poder invasivo solo en las cepas mutadas en la SPI-1. A través del modelo de salmonelosis sistémica en ratón se pudo comprobar la pérdida de la capacidad de diseminación en ambas mutantes. En conclusión los modelos permitieron verificar la importancia que tienen los genes invG/invE de la SPI-1 y ssaJ/ssaK de la SPI-2 en la patogenia de la salmonelosis, utilizando como modelo experimental de infección ratones BALB/c. Se sugieren estos modelos in vivo para evaluar mutantes de genes implicados en la patogenia de Salmonella, ya que representan una herramienta importante para la comprensión de la interacción Salmonella-hospedero(AU)


With the aim of evaluate the pathogenesis in Salmonella Typhimurium strains with mutations in genes invG/invE of Salmonella Pathogenicity Island 1 (SPI-1) and genes ssaJ/ssaK in the SPI-2 models were evaluated ligated intestinal loop associated mouse tissues by observation by transmission electron microscopy (TEM) and the production of mouse systemic salmonellosis. For this, we used six Salmonella strains: S. Typhimurium SL-1344 (control strain) and its derived mutants: ΔinvEG S. Typhimurium SL-1344 (mutant in SPI-1) and ΔssaJK S. Typhimurium SL-1344 (mutant in SPI-2), S. Typhimurium (clinical isolate) and its derived mutants: ΔinvEG S.Typhimurium and ΔssaJK S. Typhimurium. TEM results allowed us to verify the morphological alterations of the intestinal epithelium in mice infected with Salmonella strains whose pathogenicity genes were intact. It was proven invasive power loss only in strains mutated in the SPI-1. Through systemic salmonellosis model mouse we noted the loss of the ability to spread in both mutants. In conclusion, the models allowed us to verify the importance of the invG/invE genes of SPI-1 and ssaJ/ssaK of SPI-2 in the pathogenesis of salmonellosis, using BALB/c mice as an experimental model of infection. These in vivo models are suggested to evaluate mutants of genes involved in the pathogenesis of Salmonella, since they represent an important tool for the understanding of the Salmonella-host interaction(AU)


Assuntos
Animais , Camundongos , Salmonella typhimurium/patogenicidade , Ilhas Genômicas/genética , Microscopia Eletrônica de Transmissão/métodos , Mutação/genética
20.
Rev. cuba. hematol. inmunol. hemoter ; 35(1): e911, ene.-mar. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1003885

RESUMO

Las neoplasias mieloproliferativas crónicas (NMPC) son enfermedades clonales caracterizadas por un aumento en el número de células maduras circulantes; estas incluyen: policitemia vera (PV), trombocitemia esencial (TE), mielofibrosis primaria (MFP), entre otras. Una de las principales características moleculares de estas tres entidades es la ausencia del gen de fusión BCR/ABL. La primera mutación relacionada directamente con estas neoplasias fue detectada en el gen JAK2; a partir de su descubrimiento, otras mutaciones en los genes del receptor de trombopoyetina (MPL) y calreticulina (CALR) han sido fuertemente relacionadas con la presentación de la enfermedad. La calreticulina es una proteína del retículo endoplásmico con diversas funciones a nivel celular como la homeostasis del calcio y la actividad de chaperona. Hasta la fecha se ha identificado un gran número de mutaciones en el gen CALR. La mayoría de ellas son inserciones y deleciones que generan cambios a nivel proteico con implicaciones importantes en el curso clínico y pronóstico de las neoplasias. Debido a su alta frecuencia y fuerte asociación con las NMPC, las mutaciones de CALR se incluyen como criterio mayor para el diagnóstico de estas entidades. Por este motivo, se han desarrollado varias técnicas encaminadas a la detección rápida, eficiente, sensible y especifica de esta mutación como: la secuenciación, el análisis de fragmentos y el análisis de fusión de alta resolución. El conocimiento e implementación de estas técnicas en los laboratorios clínicos constituye un avance importante para el diagnóstico y la evolución de los pacientes(AU)


Chronic myeloproliferative neoplasms (NMPC) are clonal diseases characterized by an increase in the number of mature circulating cells; these diseases include: polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (MFP) among others. One of the main molecular characteristics of these three entities is the absence of the BCR/ABL fusion gene. The first mutation related to this group of neoplasms was detected in the JAK2 gene; since its discovery, other mutations in thrombopoietin receptor (MPL) and calreticulin (CALR) genes have been strongly related with the presentation of the disease. Calreticulin is an endoplásmic reticulum protein with different functions in the cell such as calcium homeostasis and the chaperone activity. To date, a large number of mutations have been identified in CALR gene most of them are insertions and deletions that generate changes in the protein that generate important implications in the clinical course and prognosis of neoplasms. Due to its high frequency and strong association with NMPC, CALR mutations are included as a major criteria for the diagnosis of these entities. For this reason, several techniques have been developed aimed at the rapid, efficient, sensitive and specific detection of this mutation as: sequencing, fragment analysis and high resolution fusion analysis. The knowledge and implementation of these techniques in clinical laboratories is an important advance for the diagnosis and in the evolution of patients(AU)


Assuntos
Humanos , Masculino , Feminino , Calreticulina/síntese química , Técnicas de Diagnóstico Molecular , Mutação
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