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Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Procedimientos Quirúrgicos Dermatologicos/educación , Neumonía Viral/complicaciones , Enfermedades de la Piel/cirugía , COVID-19 , Procedimientos Quirúrgicos Dermatologicos/métodos , Educación Médica/métodos , Humanos , Pandemias , SARS-CoV-2Asunto(s)
Eritema Nudoso/epidemiología , Lepra Lepromatosa/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Lepra Dimorfa/epidemiología , Masculino , México/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Mycetoma is recognized as a neglected tropical disease and there are still therapeutic challenges, especially in cases recalcitrant to standard therapy or with high risk of dissemination. Subcultures have been used previously to decrease the virulence of human pathogens. Previous reports have demonstrated that after carrying out 200 subcultures of Nocardia brasiliensis, a decrease in virulence was observed. AIM: To evaluate the effect of attenuated N. brasiliensis strains on the development of lesions in an established mycetoma infection. METHODS: Female 8-12-week-old BALB/c mice were injected with N. brasiliensis suspension to establish a mycetoma. Sixty mice were selected and divided into three groups: two of these groups were inoculated in the dorsum with N. brasiliensis subcultured 200 and 400 times, respectively, while the third group served as control. The thickness of each lesion was measured with calipers every week for 12 weeks. RESULTS: After 12 weeks, we observed that inoculation of 1 × 105 colony-forming units of attenuated N. brasiliensis strains was able to modify the natural history of the infection, with a decrease in the size of the lesions, particularly with P400, compared with the control group (P < 0.01). CONCLUSION: In this experimental evaluation of an immunomodulatory therapy with attenuated N. brasiliensis strains in a murine model, there was a greater stability in the size of the lesion over time in BALB/c mice inoculated with the P400 strain. This treatment could open the possibility of using the attenuated strain as immunomodulatory therapy in patients recalcitrant to standard therapy, with high risk of dissemination or who develop drug-related adverse effects.
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Inmunomodulación , Micetoma/terapia , Nocardia/patogenicidad , Animales , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Micetoma/inmunología , Micetoma/microbiología , VirulenciaAsunto(s)
Osteosarcoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Piel/patología , Adulto , Biopsia , Humanos , Masculino , Osteosarcoma/patología , Osteosarcoma/cirugía , Piel/diagnóstico por imagen , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Pared Torácica , Tomografía Computarizada por Rayos X , Resultado del TratamientoAsunto(s)
Leprostáticos/uso terapéutico , Lepra/diagnóstico , Mycobacterium leprae/aislamiento & purificación , Parestesia/etiología , Piel/patología , Anciano , Biopsia , Quimioterapia Combinada , Femenino , Humanos , Lepra/complicaciones , Lepra/tratamiento farmacológico , Lepra/microbiología , México , Parestesia/tratamiento farmacológico , Piel/microbiología , Texas , Resultado del TratamientoRESUMEN
RATIONALE: Mucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome is produced by the deficiency of the enzyme arylsulfatase B, responsible for the hydrolysis of N-acetyl-D-galactosamine, chondroitin sulfate, and dermatan sulfate. PATIENT CONCERNS: A 3-year-old male with Moroccan origins is the index case. He had healthy consanguineous parents and 4 healthy brothers and sisters. The patient showed a wide spectrum of symptoms including skeletal dysplasia and short stature with elevated glycosaminoglycans (GAGs) in urine. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: GAGs were quantified by spectrometry method with 1,9-dimethylen blue in 24-hour urine samples. The qualitative analysis of urine GAGs was obtained by thin-layer chromatography to determine the predominant presence of dermatan sulfate. The activities of both arylsulfatase B and beta-galactosidase as well as genetic studies were performed in dried blood spots. The genetic study was performed with deoxyribonucleic acid by massive sequencing a of lisosomal storage diseases. Results showed a new mutation c.263Aâ>âC with the severe phenotype in homozygous in the patient. The familiar study of ARSB and GLB1 genes presented some asymptomatic SNPs but with a discrete decrease in the activity of arylsulfatase B and beta-galactosidase. After an early detection by pediatricians, and both enzymatic and genetic confirmation, the patient had a good response to substitutive enzymatic treatment with galsulfase. LESSONS: Mucoplysaccharidosis type VI is an autosomal recessive rare disease characterized by a lysosomal storage disorder. Although a number of mutations have been already associated to the disease, we have found a new mutation located in the arylsulfatase B enzyme gene. We have described that this mutation is the ultimate cause of a severe presentation of the disease.
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Terapia de Reemplazo Enzimático/métodos , Mucopolisacaridosis IV/tratamiento farmacológico , N-Acetilgalactosamina-4-Sulfatasa/uso terapéutico , Preescolar , Glicosaminoglicanos/orina , Homocigoto , Humanos , Masculino , Mucopolisacaridosis IV/genética , Mucopolisacaridosis IV/orina , N-Acetilgalactosamina-4-Sulfatasa/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Proteínas Recombinantes/uso terapéutico , beta-Galactosidasa/genéticaRESUMEN
Ring 21 is an unstable structural abnormality of chromosome 21 that can lead to RUNX1 gene amplification. We present a unique case with a carrier patient of a constitutional ring chromosome 21 (partial monosomy and trisomy 21) with dysmorphic features and congenital malformations phenotype, who developed acute myeloid leukaemia with myelodysplasia-related changes and two ring 21 chromosomes with RUNX1 amplification. The patient's constitutional ring 21 chromosome showed alterations in tumour suppressor genes, and oncogenes, but not in RUNX1. RUNX1 gene expression at acute myeloid leukaemia diagnosis, showed no upregulation, so other genes may also be the genetic amplification targets in this patient. Copyright © 2016 John Wiley & Sons, Ltd.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicos/genética , Preescolar , Cromosomas Humanos Par 21/genética , Femenino , Amplificación de Genes , Humanos , Cromosomas en AnilloRESUMEN
The expression of activation-induced cytidine deaminase, B-aggressive lymphoma, cyclin D1 and serine/threonine kinase 15 genes, among others, is increased in B cells from patients with chronic hepatitis C virus (HCV) infection. It is unknown whether the level of expression of these genes in B cells is increased in patients with hepatitis C who have achieved a sustained virological response (SVR) but who have persistent, detectable HCV RNA, so-called occult infection. Eighty-three patients who achieved and SVR, 27 with detectable HCV and 56 without detectable HCV RNA, 28 chronic hepatitis C patients and 32 healthy controls were studied. RNA was extracted from B cells, and gene expression levels were measured by RT-PCR. Patients with chronic HCV and those who achieved an SVR (with and without persistent low-level HCV RNA) showed a statistically significant higher expression compared to healthy controls, of activation-induced cytidine deaminase (P = 0.004, P < 0.001 and P = 0.002, respectively), B-aggressive lymphoma (P < 0.001, P = 0.001 and P = 0.006) and cyclin D1 (P = 0.026, P = 0.001; P = 0.038). For activation-induced cytidine deaminase patients with an SVR and 'occult infection' had a statistically significantly higher expression level than patients with and SVR without 'occult infection' (P = 0.014). The higher expression levels found for activation-induced cytidine deaminase, together with other genes indicates that these B lymphomagenesis-related genes are upregulated following HCV therapy and this is more marked when HCV can be detected in PBMCs.
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Linfocitos B/patología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/patología , ARN Viral/sangre , Respuesta Virológica Sostenida , Transcriptoma , Adulto , Anciano , Carcinogénesis , Femenino , Perfilación de la Expresión Génica , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Linfoma/fisiopatología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVES: Genetic background has been identified to be a major predictor of post-clopidogrel platelet inhibition in patients undergoing coronary stenting. However, there is a lack of data on clopidogrel response regarding genotype in patients undergoing carotid artery stenting (CAS). The influence of the most common allelic variants of CYP2C19 phenotypes and genotypes on response to baseline clopidogrel and on the pharmacodynamic effect of dose adjustment (high or standard dose of clopidogrel) in patients with high on-treatment reactivity after CAS was investigated. METHODS: Platelet reactivity was assessed before and 30 days after carotid stenting using the VerifyNow P2Y12 assay to obtain P2Y12 reactivity unit (PRU) values. RESULTS: A total of 209 patients (79.4% male, 44.1% currents smokers) were treated by CAS. Smokers improved responsiveness to clopidogrel (p = .034). With respect to CYP2C19 enzymatic function, 61 subjects (29.1%) were ultra-rapid metabolizers, 95 patients (45.5%) were extensive metabolizers, 51 (24.4%) were intermediate metabolizers, and two (0.96%) were poor metabolizers. Baseline PRU was significantly higher among intermediate-poor metabolizers compared with ultra-rapid (p = .001) or extensive metabolizers (p = .005). At 30 days follow up, in non-responding patients with the intermediate-poor metabolizer phenotype, the PRU value and inhibition percentage were significantly reduced with standard dose (p = .008; p = .0029) and high dose of clopidogrel (p = .00 0; p = .000). However, high dose clopidogrel did not achieve a more intense pharmacodynamic effect at 30 days (p = .994) compared with standard dose. CONCLUSIONS: In patients undergoing carotid stenting, those with the CYP2C19*2 allele had increased basal PRU values and in fact clopidogrel non-responders increased significantly among intermediate-poor metabolizers. Although high dose and standard dose clopidogrel therapy was effective in lowering the 30 day PRU values in patients with high on-treatment reactivity who are intermediate-poor metabolizers, the use of high dose clopidogrel did not result in statistically significantly greater reductions in reactivity compared with the standard dose.
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Angioplastia/instrumentación , Plaquetas/efectos de los fármacos , Enfermedades de las Arterias Carótidas/terapia , Citocromo P-450 CYP2C19/genética , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Polimorfismo Genético , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Stents , Ticlopidina/análogos & derivados , Anciano , Angioplastia/efectos adversos , Plaquetas/metabolismo , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico , Clopidogrel , Citocromo P-450 CYP2C19/metabolismo , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética , Fenotipo , Inhibidores de Agregación Plaquetaria/metabolismo , Antagonistas del Receptor Purinérgico P2Y/metabolismo , Receptores Purinérgicos P2Y12/sangre , Receptores Purinérgicos P2Y12/efectos de los fármacos , Ticlopidina/administración & dosificación , Ticlopidina/metabolismo , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Chromosomal rearrangements involving NUP98 gene have been associated with human leukemias such as de novo AML, therapy-related AML (t-AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Genetic fusion NUP98-HOXA9, caused by t(7;11)(p15;p15), is a recurrent cytogenetic alteration in de novo acute myeloid leukemia (AML) usually found in young Asian patients and its description in therapy-related myeloid neoplasms (t-MN) is rare. Only one Asian case with molecular demonstration of the NUP98-HOXA9 fusion has been reported in therapy-related leukemia. NUP98-HOXA9 leukemogenic mechanism is derived from the transcription factor activity of the chimeric protein, which enhances the expression of genes related to cellular differentiation arrest and proliferation. PATIENTS AND METHODS: We studied a Caucasian woman with a therapy-related acute myeloid leukemia after Ewing's sarcoma. Molecular demonstration of the genetic fusion NUP98-HOXA9 was performed by RT-PCR, and gene expression was analyzed by real-time PCR, including four AML patients with MLL rearrangements for comparative analysis. Cytologic and flow cytometric analysis was also carried out. RESULTS: After cytologic and flow cytometric analysis diagnostics was therapy-related myeloid neoplasm (t-MN). The major component of blasts in the acute leukemia was with neutrophilic differentiation, but 13% erythroid lineage blasts were also found. Cytogenetic and FISH analysis revealed t(7;11)(p15;p15) and NUP98-HOXA9 fusion gene was demonstrated. Gene expression analysis showed upregulation of EVI1 and MEIS1 in the index patient, both of them previously related to a worst outcome. CONCLUSION: In this work, we include a detailed molecular, clinical, cytological, and cytometric study of the second t-AML bearing NUP98-HOXA9 genetic fusion.
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Proteínas de Unión al ADN/genética , Expresión Génica , Proteínas de Homeodominio/genética , Leucemia Mieloide Aguda/etiología , Células Mieloides/metabolismo , Proteínas de Neoplasias/genética , Neoplasias Primarias Secundarias , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Fusión Oncogénica/genética , Proto-Oncogenes/genética , Factores de Transcripción/genética , Tirosina Quinasa 3 Similar a fms/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Manejo de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Proteína del Locus del Complejo MDS1 y EV11 , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide , Translocación GenéticaRESUMEN
The first nickel(ii) complex with the heteroscorpionate-like bridging ligand DIMMAL (2-di1H-2-imidazolylmethylmalonate), [Ni(DIMMAL)(H2O)3]n·3nH2O (1), is a one-dimensional coordination polymer whose structure shows regular Ni(ii) chains with H-bonding inter-chain interactions and a rare example of a Quadruple Imidazolyl Embrace (QIE). The Ni(ii) chain shows a weak antiferromagnetic interaction that can be modelled with a regular S = 1 chain model including a zero field splitting with g = 2.270, J = -1.5 cm(-1) and D = -2.26 cm(-1).
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OBJECTIVE: The aim of this study was to investigate the pattern of microRNA (miRNA) expression in CD19+ and CD4+ cells from asymptomatic patients with systemic lupus erythematosus (SLE). METHODS: A screening of the expression of 377 miRNAs was performed in human CD4+ and CD19+ cells isolated from the peripheral blood by using a TaqMan Human MicroRNA Array. Validation of differential expression pattern of those was performed using TaqMan assays in these cell populations obtained from a larger cohort of patients and controls. RESULTS: According to the screening assays, three miRNAs were differentially expressed (p value <0.1) in cell populations from both patients and controls: hsa-miR-143, hsa-miR-224 and hsa-miR-576-5p for CD4+ cells, and hsa-miR-10a, hsa-miR-31 and hsa-miR-345 for CD19+ cells. After validation, significant differences (p value <0.05) were confirmed only for hsa-miR-143 and hsa-miR-224 in CD4+ cells and for hsa-miR-10a and hsa-miR-345 in CD19+ cells. In all cases, the miRNAs were over expressed in SLE patients compared with healthy donors. CONCLUSIONS: Our results support a different pattern of miRNA expression in SLE patients.
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Antígenos CD19/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Lupus Eritematoso Sistémico/genética , MicroARNs/genética , Adulto , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos/métodosRESUMEN
BACKGROUND: Insulin resistance has been strongly associated with the attainment of sustained viral response (SVR) in hepatitis C patients. AIM: To determine, in a cohort of Spanish patients with chronic hepatitis C treated with peginterferon plus ribavirin (P+R), whether insulin resistance predicts SVR independently of interleukin-28B rs12979860 polymorphism. METHODS: Insulin resistance was measured as [HOMA-IR = Insulin (IU/mL)*glucose (mmol/L)/22.5]. Genotype, viral load and histological fibrosis using Scheuer score were also measured. Binary logistic regression analysis was used for statistical purposes. RESULTS: In a cohort of 240 patients [78% genotype 1, 24% showing advanced fibrosis, 71% high viral load (≥800 000 IU/mL), 31% IL28b genotype CC and 50% with HOMA >2] treated with P+R, 126 (53%) reached SVR. HOMA-IR index (HOMA <2: 63% vs. HOMA >2: 42%; P = 0.001 and IL28b (genotype CC: 68% vs. genotype CT/TT: 45%; P = 0.002) were significantly associated with SVR. In multivariable logistic regression analysis in the overall cohort, variables independently associated were: viral genotype OR: 0.29 (95% CI: 0.11-0.78), P = 0.01; fibrosis OR: 1.62 (95% CI: 1.22-2.16), P = 0.001; HOMA-IR OR: 1.22 (95% CI: 1.02-1.47), P = 0.03; and IL28B genotype OR: 2.43 (95% CI: 1.45-4.07), P = 0.001. The analyses also showed that degree of steatosis, HOMA-IR >2, mild fibrosis and IL28B CC genotype were significantly related to SVR in patients infected with HCV genotypes 1&4, but not in those with genotypes 2&3. No differences were seen in glucose, insulin level or HOMA-IR index segregated according to IL28B genotypes. CONCLUSION: Our results suggest that insulin resistance, fibrosis stage and IL28B polymorphisms were independent variables associated with sustained viral response.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Resistencia a la Insulina/genética , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Adulto , Glucemia/análisis , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Genotipo , Técnicas de Genotipaje , Hepatitis C Crónica/genética , Humanos , Insulina/sangre , Interferón-alfa/uso terapéutico , Interferones , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Análisis de Regresión , Ribavirina/uso terapéutico , Resultado del Tratamiento , Carga ViralRESUMEN
It is unknown whether hepatitis C virus (HCV)-specific cellular immune responses can develop in seronegative sexual partners of chronically HCV-infected patients and whether they have occult infection. Thirty-one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti-HCV seropositive patients, without viremia, were used as controls. Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124 (P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks (sexual, professional and familial altogether) than in those without risks. RNA was extracted from peripheral blood mononuclear cells (PBMC), and detection of HCV-RNA positive and replicative (negative) strands was performed by strand-specific real-time PCR. In four sexual partners, the presence of positive and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an HCV-specific cellular immune response as well as occult HCV infection in seronegative and aviremic sexual partners of chronically HCV-infected patients.
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Hepacivirus/inmunología , Hepatitis C Crónica/inmunología , Inmunidad Celular , Adulto , Anciano , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Antígenos Virales/inmunología , Linfocitos T CD4-Positivos/química , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/química , Linfocitos T CD8-positivos/inmunología , Femenino , Citometría de Flujo , Heterosexualidad , Humanos , Interferón gamma/biosíntesis , Interleucina-4/biosíntesis , Lectinas Tipo C/análisis , Masculino , Persona de Mediana EdadRESUMEN
Impaired innate inflammatory response has a key role in the Crohn's disease (CD) pathogenesis. The aim of this study was to investigate the possible role of the TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6 cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA quantification were performed using TaqMan assays. Nucleotide-binding oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci interaction was analyzed by logistic regression and multifactor-dimensionality reduction (MDR). Entropy-based analysis was used to interpret combination effects. One TLR10 haplotype (TLR10(GGGG)) was found associated with CD susceptibility in both cohorts, individuals with two copies had approximately twofold more risk of CD susceptibility than individuals having no copies (odds ratio=1.89, P-value=0.0002). No differences in the mRNA levels were observed among the genotypes. The strongest model for predicting CD risk according to the MDR analysis was a two-locus model including NOD2 mutations and TLR10(GGGG) haplotype (P(c)<0.0001). The interaction gain attributed to the combination of both genes was negative (IG=-2.36%), indicating redundancy or independent effects. Our results support association of the TLR10 gene with CD susceptibility. The effect of TLR10 would be independent of NOD2, suggesting different signaling pathways for both genes.