RESUMEN
Psoriasis is one of the most common chronic immune-mediated skin diseases, having a strong genetic predisposition. Psoriasis is a T-cell-mediated disease with a mixed Th1/Th17 cytokines environment. IL-23/IL-17 axis hyperactivation is the primary pathogenesis. Psoriasis lesions have been known to exhibit high IFN-λ1 and IFN-stimulated genes (ISGs) expression, which appears to be driven by Th17 cells. However, the role and mechanism of IFN-λs in psoriasis disease remains unknown. The study aimed to investigate the relationship between IL-28B and IL-29 gene polymorphisms with psoriasis disease and clinical severity. We performed single-nucleotide polymorphisms (SNPs) of IL-28B rs12979860 (IL-28 C/T), rs8099917 (IL-28 T/G), and IL-29 rs30461 (IL-29 T/C) in 140 patients with psoriasis disease and 159 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequency distributions of the rs12979860 (IL-28 C/T) and rs30461 (IL-29 T/C) polymorphisms were similar in the patient and control groups and were not statistically significant. The TG genotype of rs8099917 was statistically significantly different in patients from both groups. The TG genotype increased the risk of disease1.9-fold. The G allele may be associated with the pathogenesis of psoriasis.
Asunto(s)
Interferones/genética , Interleucinas , Psoriasis , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Hepacivirus/genética , Humanos , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Psoriasis/genética , Interferón lambdaRESUMEN
During transformation, myelodysplastic syndromes (MDS) are characterized by reducing apoptosis of bone marrow (BM) precursors. Mouse models of high risk (HR)-MDS and acute myelogenous leukemia (AML) post-MDS using mutant NRAS and overexpression of human BCL-2, known to be poor prognostic indicators of the human diseases, were created. We have reported the efficacy of the BCL-2 inhibitor, ABT-737, on the AML post-MDS model; here, we report that this BCL-2 inhibitor also significantly extended survival of the HR-MDS mouse model, with reductions of BM blasts and lineage negative/Sca1+/KIT+ (LSK) cells. Secondary transplants showed increased survival in treated compared to untreated mice. Unlike the AML model, BCL-2 expression and RAS activity decreased following treatment and the RAS:BCL-2 complex remained in the plasma membrane. Exon-specific gene expression profiling (GEP) of HR-MDS mice showed 1952 differentially regulated genes upon treatment, including genes important for the regulation of stem cells, differentiation, proliferation, oxidative phosphorylation, mitochondrial function, and apoptosis; relevant in human disease. Spliceosome genes, found to be abnormal in MDS patients and downregulated in our HR-MDS model, such as Rsrc1 and Wbp4, were upregulated by the treatment, as were genes involved in epigenetic regulation, such as DNMT3A and B, upregulated upon disease progression and downregulated upon treatment.
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Compuestos de Bifenilo/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas de Unión al GTP Monoméricas/metabolismo , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/metabolismo , Nitrofenoles/administración & dosificación , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/efectos de los fármacos , Células Madre/metabolismo , Sulfonamidas/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Médula Ósea/metabolismo , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica/métodos , Estimación de Kaplan-Meier , Ratones , Ratones Transgénicos , Proteínas de Unión al GTP Monoméricas/genética , Síndromes Mielodisplásicos/mortalidad , Piperazinas/administración & dosificación , Proteínas Proto-Oncogénicas c-bcl-2/genética , Células Madre/efectos de los fármacos , Transcriptoma/efectos de los fármacosAsunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Proteínas con Dominio LIM/metabolismo , Linfoma de Células B Grandes Difuso , Tomografía Computarizada por Tomografía de Emisión de Positrones , Proteínas Proto-Oncogénicas/metabolismo , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Rituximab/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Psoriasis is a chronic inflammatory skin disorder, which is characterized by a heightened immunological response. Although the immunogenetics of this chronic inflammatory disorder is poorly understood, its expression is known to be dependent on proinflammatory cytokines. It is known that two distinct subtypes of chronic plaque psoriasis: Early-onset psoriasis (EOP) before the age of 40 years and late-onset psoriasis after the age of 40 years. Forkhead box class O3A (FOXO3A) is a transcription factor, which plays an important role in cell-cycle regulation, apoptosis, oxidative stress, and DNA repair. The silent information regulator (SIRT) is thought to have a role in skin disorders, including psoriasis, that are characterized by hyperproliferation and inflammation. AIM: The aim of this study was to investigate FOXO3A and SIRT1 gene polymorphisms in EOP. METHODS: The study group consisted of 142 EOP patients and 123 unrelated healthy controls. FOXO3A polymorphisms were determined using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. SIRT1 gene polymorphisms were determined by PCR-confronting two-pair primers methods. RESULTS: The FOXO3A rs4946936 and SIRT1 rs7069102 gene polymorphisms were positively correlated with EOP and disease severity. The GG genotype frequency of SIRT1 rs7069102 gene polymorphisms was increased in severe EOP. The CC frequency of FOXO3A rs4946936 was increased in EOP with nail disorders. CONCLUSION: The rs7069102 gene polymorphism of SIRT1 and rs4946936 polymorphism of FOXO3A are associated with early onset psoriasis; this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis and disease severity.
RESUMEN
Acute myeloid leukemia (AML) is induced by the cooperative action of deregulated genes that perturb self-renewal, proliferation, and differentiation. Internal tandem duplications (ITDs) in the FLT3 receptor tyrosine kinase are common mutations in AML, confer poor prognosis, and stimulate myeloproliferation. AML patient samples with FLT3-ITD express high levels of RUNX1, a transcription factor with known tumor-suppressor function. In this study, to understand this paradox, we investigated the impact of RUNX1 and FLT3-ITD coexpression. FLT3-ITD directly impacts on RUNX1 activity, whereby up-regulated and phosphorylated RUNX1 cooperates with FLT3-ITD to induce AML. Inactivating RUNX1 in tumors releases the differentiation block and down-regulates genes controlling ribosome biogenesis. We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression in FLT3-ITD AMLs. HHEX could replace RUNX1 in cooperating with FLT3-ITD to induce AML. These results establish and elucidate the unanticipated oncogenic function of RUNX1 in AML. We predict that blocking RUNX1 activity will greatly enhance current therapeutic approaches using FLT3 inhibitors.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal/fisiología , Leucemia Mieloide Aguda/etiología , Tirosina Quinasa 3 Similar a fms/fisiología , Animales , Células Cultivadas , Subunidad alfa 2 del Factor de Unión al Sitio Principal/antagonistas & inhibidores , Proteínas de Homeodominio/genética , Humanos , Ratones , Procesamiento Proteico-Postraduccional , Factores de Transcripción/genéticaRESUMEN
Severe human adenovirus (HAdV) infections are an increasing threat for immunosuppressed individuals, particularly those who have received stem cell transplants. It has been previously hypothesized that severe infections might be due to reactivation of a persistent infection, but this hypothesis has been difficult to test owing to the lack of a permissive in vivo model of HAdV infection. Here we established a humanized mouse model that reproduces features of acute and persistent HAdV infection. In this model, acute infection correlated with high mortality, weight loss, liver pathology, and expression of viral proteins in several organs. In contrast, persistent infection was asymptomatic and led to establishment of HAdV-specific adaptive immunity and expression of early viral genes exclusively in the bone marrow. These findings validate the use of humanized mice to study acute and persistent HAdV infection and strongly suggest the presence of cellular reservoirs in the bone marrow.
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Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/fisiología , Infecciones Asintomáticas , Modelos Animales de Enfermedad , Enfermedad Aguda , Inmunidad Adaptativa , Infecciones por Adenovirus Humanos/inmunología , Adenovirus Humanos/genética , Adenovirus Humanos/inmunología , Animales , Médula Ósea/virología , ADN Viral/genética , Humanos , Huésped Inmunocomprometido , Hígado/patología , Hígado/virología , Ratones , Ratones Transgénicos , Carga Viral , ViremiaRESUMEN
Addressing the global burden of cancer, understanding its diverse biology, and promoting appropriate prevention and treatment strategies around the world has become a priority for the United Nations and International Atomic Energy Agency (IAEA), the WHO, and International Agency for Research on Cancer (IARC). The IAEA sponsored an international prospective cohort study to better understand biology, treatment response, and outcomes of diffuse large B-cell lymphoma (DLBCL) in low and middle-income countries across five UN-defined geographical regions. We report an analysis of biological variation in DLBCL across seven ethnic and environmentally diverse populations. In this cohort of 136 patients treated to a common protocol, we demonstrate significant biological differences between countries, characterized by a validated prognostic gene expression score (p < .0001), but International Prognostic Index (IPI)-adjusted survivals in all participating countries were similar. We conclude that DLBCL treatment outcomes in these populations can be benchmarked to international standards, despite biological heterogeneity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/epidemiología , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Biomarcadores de Tumor , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Salud Global , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Prednisona/uso terapéutico , Pronóstico , Rituximab , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
Alkaline proteases have biotechnological importance due to their activity and stability at alkaline pH. 56 bacteria, capable of growing under alkaline conditions were isolated and their alkaline protease activities were carried out at different parameters to determine their optimum alkaline protease production conditions. Seven isolates were showed higher alkaline protease production capacity than the reference strains. The highest alkaline protease producing isolates (103125 U/g), E114 and C265, were identified as Bacillus licheniformis with 99.4% and Bacillus mojavensis 99.8% based on 16S rRNA gene sequence similarities, respectively. Interestingly, the isolates identified as Bacillus safensis were also found to be high alkaline protease producing strains. Genotypic characterizations of the isolates were also determined by using a wide range of molecular techniques (ARDRA, ITS-PCR, (GTG)5-PCR, BOX-PCR). These different techniques allowed us to differentiate the alkaliphilic isolates and the results were in concurrence with phylogenetic analyses of the 16S rRNA genes. While ITS-PCR provided the highest correlation with 16S rRNA groups, (GTG)5-PCR showed the highest differentiation at species and intra-species level. In this study, each of the biotechnologically valuable alkaline protease producing isolates was grouped into their taxonomic positions with multi-genotypic analyses.
Asunto(s)
Bacillus/clasificación , Bacillus/enzimología , Proteínas Bacterianas/metabolismo , Endopeptidasas/metabolismo , Regulación Bacteriana de la Expresión Génica/fisiología , Regulación Enzimológica de la Expresión Génica/fisiología , Bacillus/genética , Proteínas Bacterianas/genética , Endopeptidasas/genética , FilogeniaRESUMEN
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p<0.01) but not with event free survival (EFS, p=0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p<0.05), whereas those with low IPI scores show a trend not reaching significance (p=0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.
Asunto(s)
Biomarcadores de Tumor/genética , Fijadores/química , Formaldehído/química , Perfilación de la Expresión Génica/métodos , Linfoma de Células B Grandes Difuso/genética , Adhesión en Parafina , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fijación del Tejido/métodos , Transcriptoma , Anciano , Asia , Biopsia , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Perfilación de la Expresión Génica/normas , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , América del Sur , Factores de TiempoRESUMEN
Disrupting mutations of the RUNX1 gene are found in 10% of patients with myelodysplasia (MDS) and 30% of patients with acute myeloid leukemia (AML). Previous studies have revealed an increase in hematopoietic stem cells (HSCs) and multipotent progenitor (MPP) cells in conditional Runx1-knockout (KO) mice, but the molecular mechanism is unresolved. We investigated the myeloid progenitor (MP) compartment in KO mice, arguing that disruptions at the HSC/MPP level may be amplified in downstream cells. We demonstrate that the MP compartment is increased by more than fivefold in Runx1 KO mice, with a prominent skewing toward megakaryocyte (Meg) progenitors. Runx1-deficient granulocyte-macrophage progenitors are characterized by increased cloning capacity, impaired development into mature cells, and HSC and Meg transcription signatures. An HSC/MPP subpopulation expressing Meg markers was also increased in Runx1-deficient mice. Rescue experiments coupled with transcriptome analysis and Runx1 DNA-binding assays demonstrated that granulocytic/monocytic (G/M) commitment is marked by Runx1 suppression of genes encoding adherence and motility proteins (Tek, Jam3, Plxnc1, Pcdh7, and Selp) that support HSC-Meg interactions with the BM niche. In vitro assays confirmed that enforced Tek expression in HSCs/MPPs increases Meg output. Interestingly, besides this key repressor function of Runx1 to control lineage decisions and cell numbers in progenitors, our study also revealed a critical activating function in erythroblast differentiation, in addition to its known importance in Meg and G/M maturation. Thus both repressor and activator functions of Runx1 at multiple hematopoietic stages and lineages likely contribute to the tumor suppressor activity in MDS and AML.
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Regulación de la Expresión Génica , Células Madre Hematopoyéticas/metabolismo , Megacariocitos/metabolismo , Transcripción Genética , Proteínas Supresoras de Tumor/metabolismo , Animales , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Células Madre Hematopoyéticas/patología , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Megacariocitos/patología , Ratones , Ratones Noqueados , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Proteínas Supresoras de Tumor/genéticaRESUMEN
We have previously shown that a specific promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) DNA vaccine combined with all-trans retinoic acid (ATRA) increases the number of long term survivors with enhanced immune responses in a mouse model of acute promyelocytic leukemia (APL). This study reports the efficacy of a non-specific DNA vaccine, pVAX14Flipper (pVAX14), in both APL and high risk myelodysplastic syndrome (HR-MDS) models. PVAX14 is comprised of novel immunogenic DNA sequences inserted into the pVAX1 therapeutic plasmid. APL mice treated with pVAX14 combined with ATRA had increased survival comparable to that obtained with a specific PML-RARA vaccine. Moreover, the survival advantage correlated with decreased PML-RARA transcript levels and increase in anti-RARA antibody production. In HR-MDS mice, pVAX14 significantly improved survival and reduced biomarkers of leukemic transformation such as phosphorylated mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1. In both preclinical models, pVAX14 vaccine significantly increased interferon gamma (IFNγ) production, memory T-cells (memT), reduced the number of colony forming units (CFU) and increased expression of the adapter molecule signalling to NF-κB, MyD88. These results demonstrate the adjuvant properties of pVAX14 providing thus new approaches to improve clinical outcome in two different models of myeloid malignancies, which may have potential for a broader applicability in other cancers.
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Adyuvantes Inmunológicos/farmacología , Vacunas contra el Cáncer/farmacología , Leucemia Promielocítica Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Neoplasias Experimentales/tratamiento farmacológico , Tretinoina/farmacología , Vacunas de ADN/farmacología , Animales , Anticuerpos/sangre , Secuencia de Bases , Vacunas contra el Cáncer/inmunología , Regulación Neoplásica de la Expresión Génica , Genes ras , Memoria Inmunológica/efectos de los fármacos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/inmunología , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones Transgénicos , Datos de Secuencia Molecular , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Neoplasias Experimentales/genética , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Transducción de Señal/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Factores de Tiempo , Carga Tumoral/efectos de los fármacos , Vacunación , Vacunas de ADN/inmunologíaRESUMEN
Vitiligo is an acquired epidermal pigment loss of the skin. Oxidative stress is one of the major theories in the pathophysiology of vitiligo. FOXO3A is the forkhead members of the class O (FOXO) transcription factors, and plays an important role in cell cycle regulation, apoptosis, oxidative stress, and DNA repair. The aim of our study was to investigate FOXO3A gene polymorphisms and FOXO3A protein levels, activities of superoxide dismutase (SOD) and catalase antioxidant enzymes in vitiligo patients and healthy controls. Moreover, the level of plasma advanced oxidation protein products (AOPP) in subjects was evaluated to understand the possible role of protein oxidation in disease etiology. Study groups included 82 vitiligo patients and 81 unrelated healthy controls. FOXO3A polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism method. FOXO3A levels and catalase activity were measured by ELISA whereas AOPP levels and SOD activity was measured by spectrophotometric analysis. We found a significant relationship between rs4946936 polymorphism of FOXO3A gene and vitiligo/active vitiligo patients (p=0.017; p=0.019 respectively), but not for rs2253310 (p>0.05). SOD activity and AOPP levels of vitiligo patient were increased compared with control group, whereas FOXO3A levels and catalase enzyme activity of vitiligo patient were decreased compared with control group (p<0.05). Our study indicates that rs4946936 of FOXO3A gene may associate susceptibility of vitiligo, especially active vitiligo. Moreover, our results confirm that oxidative stress may play a role in the pathophysiology of vitiligo. Further studies with larger samples are required to elucidate the role of FOXO3A in vitiligo.
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Factores de Transcripción Forkhead/sangre , Factores de Transcripción Forkhead/genética , Estrés Oxidativo/genética , Polimorfismo de Nucleótido Simple , Vitíligo/sangre , Vitíligo/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/metabolismo , Estudios de Casos y Controles , Femenino , Proteína Forkhead Box O3 , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Vitíligo/epidemiología , Adulto JovenRESUMEN
Two novel endospore-forming, aerobic bacilli, strains E173a(T) and E265(T), were isolated from soil and sediment samples from Kozakli and Altinsu hot springs, Nevsehir (Turkey). Their young cells in the exponential phase of growth were motile, Gram-stain-positive, straight rods, 0.6-1.1×3.0-8.0 µm in size, but they became strikingly long, approximately 0.6-1.2 by 9.0-35.0 µm, after the stationary phase of growth. Cells varied in tests for oxidase, and had a weakly positive reaction for catalase. Both strains could grow between 40 and 70 °C, with optimal growth at 60 °C (E173a(T)) and 55 °C (E265(T)). Growth occurred within the range pH 5.0-11.0 with optimal growth at pH 9.0 (E173a(T)) and pH 8.5 (E265(T)). Strain E173a(T) grew within a salinity range from 0 to1.5â% (w/v) NaCl with optimal growth at 0.5â%, while strain E265(T) grew within the range 0-5.0â% (w/v), with an optimum at 3.0â%. The new isolates differed from each other in some phenotypic and chemotaxonomic characters as well as repetitive extragenic palindromic element PCR (rep-PCR) fingerprints. 16S rRNA gene sequence similarities suggested distant relationships with other members of the family Bacillaceae (<95.8â%), although the two strains showed 97.5â% sequence similarity between them, and had 55â% relatedness by DNA-DNA hybridization. The DNA G+C contents were 44.8 (E173a(T)) and 43.5 mol% (E265(T)). Moreover, the chemotaxonomic data of E173a(T) and E265(T) [presence of low amounts of meso-diaminopimelic acid, A1γ to A1γ' cross-linkage types in peptidoglycan, fatty acids including iso-C15â:â0 (>60â%), iso-C17â:â0 and C16â:â0] supported the consideration of these isolates as members of a novel genus. Based upon phenotypic, phylogenetic and chemotaxonomic characteristics, it is proposed that new isolates represent a novel genus, Thermolongibacillus gen. nov., with two novel species: Thermolongibacillus altinsuensis sp. nov. (type strain E265(T)â=âDSM 24979(T)â=âNCIMB 14850(T)) and Thermolongibacillus kozakliensis sp. nov. (type strain E173a(T)â=âDSM 24978(T)â=âNCIMB 14849(T)).
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Bacillaceae/clasificación , Manantiales de Aguas Termales/microbiología , Filogenia , Bacillaceae/genética , Bacillaceae/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Peptidoglicano/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Salinidad , Análisis de Secuencia de ADN , Turquía , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Aim. Cavernous hemangioma-like Kaposi sarcoma is a rare morphologic type of Kaposi sarcoma. So far there are no cases in the literature defining the histological features of this morphologic spectrum in detail. In this study we presented two classical-type cutaneous Kaposi sarcoma cases with histologic findings resembling cavernous hemangioma in company with clinical and histopathological data. Cases. One hundred and eighty-five classical-type cutaneous Kaposi sarcoma lesions in 79 patients were assessed retrospectively in terms of histopathological features. Findings of two cases showing features of cavernous hemangioma-like Kaposi sarcoma whose clinical data could be accessed were presented in accompany with the literature data. Both cases were detected to have bluish-purple, protruded, irregularly bordered cutaneous lesions. Histopathological examination revealed a lesion formed by cavernous hemangioma-like vascular structures organized in a lobular pattern that became dilated and filled with blood. Typical histological findings of early-stage KS, consisting of mononuclear inflammation, extravasated erythrocytes, and a few immature vascular structures in superficial dermis, were observed. All cases were serologically HIV-1 negative. A positive reaction with HHV-8, CD31, CD34, and D2-40 monoclonal antibodies was identified at both cavernous hemangioma-like areas and in immature vascular structures. Results. Cavernous hemangioma-like Kaposi sarcoma is a rare Kaposi sarcoma variant presenting with diagnostic challenges, that may be confused with hemangioma. As characteristic morphological features may not be observed in every case, it is important for diagnostic purposes to show immunohistochemical HHV-8 positivity in this variant.
RESUMEN
Previous studies indicate that 25-45% of chronic urticaria patients have an autoimmune etiology. Autologous serum skin test (ASST) and autologous plasma skin test (APST) are simple tests for diagnosing chronic autoimmune urticaria (CAU). However, there are still some questions about the specificity of these tests. This study consisted of 50 patients with chronic spontaneous urticaria (CSU) and 50 sex- and age-matched healthy individuals aged 18 years, and older. A total of 31 (62%) patients and 5 (10%) control patients had positive ASST; 21 (42%) patients and 3 (6%) control patients had positive APST. Statistically significant differences were noted in ASST and APST positivity between the patient and control groups (ASST P < 0.001; APST P < 0.001). Thirteen (26%) patients and 5 (10%) control patients had antithyroglobulin antibodies or antithyroid peroxidase antibody positivity. No statistically significant differences were noted in thyroid autoantibodies between the patient and control groups (anti-TG P = 0.317; anti-TPO P = 0.269). We consider that the ASST and APST can both be used as in vivo tests for the assessment of autoimmunity in the etiology of CSU and that thyroid autoantibodies should be checked even when thyroid function tests reveal normal results in patients with CSU.
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BACKGROUND: In this study, the clinical and morphological features of vesiculobullous lesions observed in Kaposi sarcoma are analyzed, and the features of bullous Kaposi sarcoma cases are emphasized. METHODS: A total of 178 biopsy materials of 75 cases diagnosed as classic-type cutaneous Kaposi sarcoma were reviewed. Twenty-five cases showing vesiculobullous features were included in the study. Tumor, epidermis, dermis, and clinical data regarding these cases was evaluated. RESULTS: Vesicular changes were observed in 21 (12%) out of 178 lesions of the 75 cases, while bullous changes were present in only 4 (2%). In all cases where vesicular and bullous changes were detected, tumor, epidermis, and dermis changes were similar. All cases were nodular stage KS lesions, whereas hyperkeratosis and serum exudation in the epidermis, marked edema in the dermis, and enlarged lymphatic vessels and chronic inflammatory response were observed. CONCLUSIONS: Our findings suggest that changes in vascular resistance occurring during tumor progression are the most important factors comprising vesiculobullous morphology. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1646397188748474.
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Dermis/patología , Epidermis/patología , Sarcoma de Kaposi/patología , Enfermedades Cutáneas Vesiculoampollosas/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Vesícula/patología , Dermis/química , Progresión de la Enfermedad , Epidermis/química , Femenino , Humanos , Inmunohistoquímica , Vasos Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Sarcoma de Kaposi/química , Neoplasias Cutáneas/químicaRESUMEN
Previously isolated 115 endospore-forming bacilli were basically grouped according to their temperature requirements for growth: the thermophiles (74%), the facultative thermophiles (14%) and the mesophiles (12%). These isolates were taken into 16S rRNA gene sequence analyses, and they were clustered among the 7 genera: Anoxybacillus, Aeribacillus, Bacillus, Brevibacillus, Geobacillus, Paenibacillus, and Thermoactinomycetes. Of these bacilli, only the thirty two isolates belonging to genera Bacillus (16), Brevibacillus (13), Paenibacillus (1) and Thermoactinomycetes (2) were selected and presented in this paper. The comparative sequence analyses revealed that the similarity values were ranged as 91.4-100 %, 91.8- 99.2 %, 92.6- 99.8 % and 90.7 - 99.8 % between the isolates and the related type strains from these four genera, respectively. Twenty nine of them were found to be related with the validly published type strains. The most abundant species was B. thermoruber with 9 isolates followed by B. pumilus (6), B. lichenformis (3), B. subtilis (3), B. agri (3), B. smithii (2), T. vulgaris (2) and finally P. barengoltzii (1). In addition, isolates of A391a, B51a and D295 were proposed as novel species as their 16S rRNA gene sequences displayed similarities ¡Ü 97% to their closely related type strains. The AluI-, HaeIII- and TaqI-ARDRA results were in congruence with the 16S rRNA gene sequence analyses. The ARDRA results allowed us to differentiate these isolates, and their discriminative restriction fragments were able to be determined. Some of their phenotypic characters and their amylase, chitinase and protease production were also studied and biotechnologically valuable enzyme producing isolates were introduced in order to use in further studies.
Asunto(s)
Bacilos Grampositivos Formadores de Endosporas/genética , Bacilos Grampositivos Formadores de Endosporas/aislamiento & purificación , Enzimas Reparadoras del ADN , ARN , Microbiología AmbientalRESUMEN
Previously isolated 115 endospore-forming bacilli were basically grouped according to their temperature requirements for growth: the thermophiles (74%), the facultative thermophiles (14%) and the mesophiles (12%). These isolates were taken into 16S rRNA gene sequence analyses, and they were clustered among the 7 genera: Anoxybacillus, Aeribacillus, Bacillus, Brevibacillus, Geobacillus, Paenibacillus, and Thermoactinomycetes. Of these bacilli, only the thirty two isolates belonging to genera Bacillus (16), Brevibacillus (13), Paenibacillus (1) and Thermoactinomycetes (2) were selected and presented in this paper. The comparative sequence analyses revealed that the similarity values were ranged as 91.4-100 %, 91.8- 99.2 %, 92.6- 99.8 % and 90.7 - 99.8 % between the isolates and the related type strains from these four genera, respectively. Twenty nine of them were found to be related with the validly published type strains. The most abundant species was B. thermoruber with 9 isolates followed by B. pumilus (6), B. lichenformis (3), B. subtilis (3), B. agri (3), B. smithii (2), T. vulgaris (2) and finally P. barengoltzii (1). In addition, isolates of A391a, B51a and D295 were proposed as novel species as their 16S rRNA gene sequences displayed similarities ≤ 97% to their closely related type strains. The AluI-, HaeIII- and TaqI-ARDRA results were in congruence with the 16S rRNA gene sequence analyses. The ARDRA results allowed us to differentiate these isolates, and their discriminative restriction fragments were able to be determined. Some of their phenotypic characters and their amylase, chitinase and protease production were also studied and biotechnologically valuable enzyme producing isolates were introduced in order to use in further studies.
RESUMEN
Behçet's disease, a systemic vasculitis, can cause varying degrees of activity limitation, fatigue and quality of life impairment. To date, there have been no studies regarding sleep disturbance and its relationship with fatigue and life quality in Behçet's disease. We aimed to evaluate sleep disorders and polysomnographic parameters, and to determine their relationship with fatigue and quality of life in Behçet's disease. Fifty-one patients with Behçet's disease without any neurological involvement were interviewed regarding sleep disorders. Twenty-one subjects with no sleep complaints were included as the control group. Sleep-related complaints were evaluated in a face-to-face interview. Sleep quality, excessive daytime sleepiness, fatigue, depression, anxiety, disease activity/severity, and quality of life questionnaires and an overnight polysomnography were performed. Prevalences of restless legs syndrome (35.3%) and obstructive sleep apnea syndrome with/without other sleep disorders (32.5%) were higher than in the control group and the general population. Fatigue was higher in patients with restless legs syndrome and obstructive sleep apnea syndrome, and in those with lower minimum oxygen saturation; hence, only patients with restless legs syndrome had quality of life impairment. Sleep efficiency index and sleep continuity index were lower, and wake after sleep onset, respiratory disturbance index and apnea-hypopnea index were higher than in controls (P < 0.01). Neither sleep disorders nor polysomnographic parameters were related to disease activity and severity. In conclusion, it is important to question sleep disorder followed by a polysomnography, if necessary, in order to improve quality of life and fatigue in Behçet's disease.
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Síndrome de Behçet/complicaciones , Polisomnografía/métodos , Síndrome de las Piernas Inquietas/diagnóstico , Trastornos del Sueño-Vigilia/diagnóstico , Adulto , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/etiología , Fatiga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Calidad de Vida , Síndrome de las Piernas Inquietas/etiología , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/etiología , Trastornos del Sueño-Vigilia/etiología , Encuestas y CuestionariosRESUMEN
To analyze the effect of possible risk factors, including breastfeeding, on the development of childhood-onset psoriasis, a multicenter case-control study with prospective collection of data was performed. Using a standard questionnaire, personal and specific variables including family history of psoriasis, maternal and environmental tobacco smoke exposure, body mass index (BMI), exclusive and partial breastfeeding for at least 3 and 12 months, cow's milk intake before 1 year, birth delivery method, and stressful life events were collected during 2009 from 537 patients with psoriasis and 511 controls younger than 18. Overall, patients more frequently reported exposure to environmental tobacco smoke at home and stressful life events in the year preceding the diagnosis than controls. The odds ratios (OR) for smoking and stressful life events were 2.90 (95% confidence interval [CI]=2.27-3.78) and 2.94 (95% CI=2.28-3.79), respectively. In addition, children with psoriasis were more likely to have a higher BMI (>26) than controls (OR=2.52; 95% CI=1.42-4.49). High BMI, environmental tobacco smoke exposure at home, and stressful life events may influence the development of pediatric psoriasis.