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1.
Blood ; 138(15): 1345-1358, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34010414

RESUMO

The blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of crucial transcription factors. One of the key master regulators in the hematopoietic systems is PU.1. Reduced levels of PU.1 are characteristic for human acute myeloid leukemia (AML) and are known to induce AML in mouse models. Here, we show that transcriptional downregulation of PU.1 is an active process involving an alternative promoter in intron 3 that is induced by RUNX transcription factors driving noncoding antisense transcription. Core-binding factor (CBF) fusions RUNX1-ETO and CBFß-MYH11 in t(8;21) and inv(16) AML, respectively, activate the PU.1 antisense promoter that results in a shift from sense toward antisense transcription and myeloid differentiation blockade. In patients with CBF-AML, we found that an elevated antisense/sense transcript and promoter accessibility ratio represents a hallmark compared with normal karyotype AML or healthy CD34+ cells. Competitive interaction of an enhancer with the proximal or the antisense promoter forms a binary on/off switch for either myeloid or T-cell development. Leukemic CBF fusions thus use a physiological mechanism used by T cells to decrease sense transcription. Our study is the first example of a sense/antisense promoter competition as a crucial functional switch for gene expression perturbation by oncogenes. Hence, this disease mechanism reveals a previously unknown Achilles heel for future precise therapeutic targeting of oncogene-induced chromatin remodeling.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade beta de Fator de Ligação ao Core/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Elementos Antissenso (Genética)/genética , Linhagem Celular Tumoral , Fusão Gênica , Humanos , Proteínas de Fusão Oncogênica/genética , Regiões Promotoras Genéticas , Proteína 1 Parceira de Translocação de RUNX1/genética , Células Tumorais Cultivadas
2.
Phys Rev Lett ; 131(17): 171901, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37955487

RESUMO

The first observation and study of two new baryonic structures in the final state Ξ_{b}^{0}π^{+}π^{-} and the confirmation of the Ξ_{b}(6100)^{-} state in the Ξ_{b}^{-}π^{+}π^{-} decay mode are reported using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9 fb^{-1}. In addition, the properties of the known Ξ_{b}^{*0}, Ξ_{b}^{'-} and Ξ_{b}^{*-} resonances are measured with improved precision. The new decay mode of the Ξ_{b}^{0} baryon to the Ξ_{c}^{+} π^{-} π^{+} π^{-} final state is observed and exploited for the first time in these measurements.

3.
Orthod Craniofac Res ; 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29927056

RESUMO

OBJECTIVES: To identify the genetic basis of severe tooth agenesis in a family of three affected sisters. PATIENTS AND METHODS: A family of three sisters with severe tooth agenesis was recruited for whole-exome sequencing to identify potential genetic variation responsible for this penetrant phenotype. The unaffected father was tested for specific mutations using Sanger sequencing. Gene discovery was supplemented with in situ hybridization to localize gene expression during human tooth development. RESULTS: We report a nonsense heterozygous mutation in exon 2 of WNT10A c.321C>A[p.Cys107*] likely to be responsible for the severe tooth agenesis identified in this family through the creation of a premature stop codon, resulting in truncation of the amino acid sequence and therefore loss of protein function. In situ hybridization showed expression of WNT10A in odontogenic epithelium during the early and late stages of human primary tooth development. CONCLUSIONS: WNT10A has previously been associated with both syndromic and non-syndromic forms of tooth agenesis, and this report further expands our knowledge of genetic variation underlying non-syndromic forms of this condition. We also demonstrate expression of WNT10A in the epithelial compartment of human tooth germs during development.

4.
Int Endod J ; 51(11): 1271-1278, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29637579

RESUMO

AIM: To evaluate the presence and propagation of defects and their effects on surfaces of nickel-titanium (NiTi) instruments using noncontact, three-dimensional optical profilometry, and to assess the accuracy of this method of investigation. METHODOLOGY: The flute surface areas of instruments from two commercial instrumentation systems, namely Reciproc R25 (n = 5) and WaveOne Primary (n = 5), were assessed and compared before and after performing two instrumentation cycles in simulated root canals in clear resin blocks. All the analyses were conducted on areas measuring 211 × 211 µm, located 3 mm from the tips of the instruments. A quantitative analysis was conducted before and after the first and second instrumentation cycles, using the Sa (average roughness over the measurement field), Sq (root mean square roughness) and Sz (average height over the measurement field) amplitude parameters. All the data were submitted to statistical analysis at a 5% level of significance. RESULTS: There was a significant increase (P = 0.007) in wear in both groups, especially between baseline and the second instrumentation cycle, with significantly higher wear values being observed on WaveOne instruments (Sz median values = 33.68 and 2.89 µm, respectively, for WO and RP groups). A significant increase in surface roughness (P = 0.016 and P = 0.008, respectively, for Sa and Sq) was observed in both groups from the first to the second instrumentation cycle, mostly in WaveOne specimens. Qualitative analysis revealed a greater number of defects on the flute topography of all the instruments after use. CONCLUSIONS: More defects were identified in WaveOne Primary instruments compared to Reciproc R25, irrespective of the evaluation stage. The investigation method provided an accurate, repeatable and reproducible assessment of NiTi instruments at different time-points.


Assuntos
Níquel/química , Preparo de Canal Radicular/instrumentação , Tratamento do Canal Radicular/instrumentação , Titânio/química , Ligas Dentárias/química , Instrumentos Odontológicos , Cavidade Pulpar , Endodontia/instrumentação , Desenho de Equipamento , Falha de Equipamento , Humanos , Imageamento Tridimensional/métodos , Teste de Materiais , Reprodutibilidade dos Testes , Rotação , Propriedades de Superfície , Fatores de Tempo
5.
Int Endod J ; 50(2): 143-152, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26825427

RESUMO

The aim of this review was to provide a detailed analysis of the literature concerning the correlation between different movement kinematics and the cyclic fatigue resistance of NiTi rotary endodontic instruments. From June 2014 to August 2015, four independent reviewers comprehensively and systematically searched the Medline (PubMed), EMBASE, Web of Science, Scopus and Google Scholar databases for works published since January 2005, using the following search terms: endodontics; nickel-titanium rotary files; continuous rotation; reciprocating motion; cyclic fatigue. In addition to the electronic searches, manual searches were performed to include articles listed in the reference sections of high-impact published articles that were not indexed in the databases. Laboratory studies in English language were considered for this review. The electronic and manual searches resulted in identification of 75 articles. Based on the inclusion criteria, 32 articles were selected for analysis of full-text copies. Specific analysis was then made of 20 articles that described the effects of reciprocating and continuous movements on cyclic fatigue of the instruments. A wide range of testing conditions and methodologies have been used to compare the cyclic fatigue resistance of rotary endodontic instruments. Most studies report that reciprocating motion improves the fatigue resistance of endodontic instruments, compared to continuous rotation, independent of other variables such as the speed of rotation, the angle or radius of curvature of simulated canals, geometry and taper, or the surface characteristics of the NiTi instruments.


Assuntos
Ligas , Endodontia/instrumentação , Movimento , Rotação
6.
Int Endod J ; 50(9): 902-909, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27696455

RESUMO

AIM: To describe a new method for the assessment of nanoscale alterations in the surface topography of nickel-titanium endodontic instruments using a high-resolution optical method and to verify the accuracy of the technique. METHODOLOGY: Noncontact three-dimensional optical profilometry was used to evaluate defects on a size 25, .08 taper reciprocating instrument (WaveOne® ), which was subjected to a cyclic fatigue test in a simulated root canal in a clear resin block. For the investigation, an original procedure was established for the analysis of similar areas located 3 mm from the tip of the instrument before and after canal preparation to enable the repeatability and reproducibility of the measurements with precision. All observations and analysis were taken in areas measuring 210 × 210 µm provided by the software of the equipment. RESULTS: The three-dimensional high-resolution image analysis showed clear alterations in the surface topography of the examined cutting blade and flute of the instrument, before and after use, with the presence of surface irregularities such as deformations, debris, grooves, cracks, steps and microcavities. CONCLUSIONS: Optical profilometry provided accurate qualitative nanoscale evaluation of similar surfaces before and after the fatigue test. The stability and repeatability of the technique enables a more comprehensive understanding of the effects of wear on the surface of endodontic instruments.


Assuntos
Ligas , Instrumentos Odontológicos , Teste de Materiais/métodos , Endodontia/instrumentação , Imageamento Tridimensional , Propriedades de Superfície
7.
Int Endod J ; 48(8): 801-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25186632

RESUMO

AIM: Compare the displacement resistance of AH Plus, Ad Seal and Real Seal on dentine discs (DDs) treated with 10% citric acid, 17% EDTA or 2.5% NaOCl, through a new push-out test method. METHODOLOGY: From the middle third of the roots of 15 maxillary central incisors, three dentine discs 1 ± 0.1 mm thick were obtained. On the axial surface of each dentine disc, three 1.2-mm-wide holes were drilled. In the third dentine disc from the same root, each hole was treated with one of three irrigating solutions for 30 s, rinsed with distilled water and dried. Each hole of the same dentine disc was filled with sealer, and the discs were maintained at 37 °C for 7 days. The dentine discs were fixed on a testing machine to test the shear strength. Data were compared using the univariate anova test with a 5% significance level. The Tukey test was used for multiple comparisons. RESULTS: The irrigating solutions did not affect the adhesion of the sealers (P > 0.05). There was no significant difference between the Ad Seal and AHPlus (P > 0.05); however, Real Seal had a significantly lower shear bond strength (P < 0.05). CONCLUSION: The use of different irrigating solutions did not affect resistance to the displacement of resin sealers. Real Seal sealer was less resistant than Ad Seal and AHPlus.


Assuntos
Resinas Compostas/química , Colagem Dentária/métodos , Resinas Epóxi/química , Materiais Restauradores do Canal Radicular/química , Análise do Estresse Dentário , Humanos , Técnicas In Vitro , Incisivo , Teste de Materiais , Irrigantes do Canal Radicular/química , Resistência ao Cisalhamento
8.
Environ Geochem Health ; 36(2): 209-23, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23990124

RESUMO

In order to study the pollution of an aquatic ecosystem, it is necessary to analyze not only the levels of chemical pollutants in water, but also those accumulated in the sediment matrix, as well as to assess its ecotoxicological status. The Alqueva reservoir, the largest artificial lake in Europe, was chosen as case study as it constitutes the most important water supply source in southern Portugal. It is located in the Guadiana River Basin, in a semi-arid region with high levels of water scarcity and where agriculture is one of the main activities. The evaluation of sediments comprised: (1) physical and chemical analysis (grain size, pH, organic matter, nitrogen, phosphorus); (2) potentially toxic trace elements (Cu, As, Pb, Cr, Cd, Zn and Ni); and (3) ecotoxicological evaluation with Vibrio fischeri, Thamnocephalus platyurus, Daphnia magna, and Heterocypris incongruens. Total trace element concentrations indicated that As, Cd, and Pb surpassed the Canadian levels for the protection of aquatic life, in most of Alqueva's sites. The results of the toxicity assessment showed that some locations induced acute and chronic toxicity in the species used. Further, the H. incongruens was the most sensitive species as far as the contamination found in the sediment is concerned, followed by the bacteria V. fischeri. This integrative approach, together with the water column quality assessment, allowed a comprehensive evaluation of the environmental quality of this strongly modified water body and will allow the implementation of remediation strategies to obtain a good ecological potential as proposed in the Water Framework Directive.


Assuntos
Ecotoxicologia/métodos , Água Doce , Sedimentos Geológicos/análise , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Aliivibrio fischeri/efeitos dos fármacos , Animais , Crustáceos/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Monitoramento Ambiental/métodos , Concentração de Íons de Hidrogênio , Metais/análise , Nitrogênio/análise , Fósforo/análise , Portugal , Testes de Toxicidade Crônica
9.
Osteoporos Int ; 24(10): 2707-12, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23632825

RESUMO

SUMMARY: We investigated vitamin D status in Brazilian cities located at different latitudes. Insufficiency (<50 nmol/L) was common (17 %), even in those living in a tropical climate. Vitamin D insufficiency increased as a function of latitude. Mean 25-hydroxyvitamin D (25(OH)D) levels in each site and latitude correlation were very high (r = -0.88; p=0.02). [corrected]. INTRODUCTION: Inadequate vitamin D, determined by low levels of 25(OH)D, has become very common despite the availability of sunlight at some latitudes. National data from a country that spans a wide range of latitudes would help to determine to what extent latitude or other factors are responsible for vitamin D deficiency. We investigated vitamin D status in cities located at different latitudes in Brazil, a large continental country. METHODS: The source is the Brazilian database from the Generations Trial (1,933 osteopenic or osteoporotic postmenopausal women (60 to 85 years old) with 25(OH)D measurements). 25(OH)D below 25 nmol/L (10 ng/mL) was an exclusion criterion. Baseline values were between fall and winter. The sites included Recife, Salvador, Rio de Janeiro, São Paulo, Curitiba, and Porto Alegre. Mean and standard deviation of 25(OH)D, age, spine and femoral neck T-score, calcium, creatinine, and alkaline phosphatase were calculated for each city. Pearson correlation was used for 25(OH)D and latitude. RESULTS: Insufficiency (<50 or <20 ng/mL) was common (329 subjects, 17 %). Vitamin D insufficiency increased as a function of latitude, reaching 24.5 % in the southernmost city, Porto Alegre. The correlation between mean 25(OH)D levels in each site and latitude was very high (r = -0.88, p < 0.0001). CONCLUSION: There is a high percentage of individuals with vitamin D insufficiency in Brazil, even in cities near the equator, and this percentage progressively increases with more southern latitudes.


Assuntos
Pós-Menopausa/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Brasil/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Prevalência , Pigmentação da Pele , Luz Solar , Saúde da População Urbana/estatística & dados numéricos , Vitamina D/sangue , Deficiência de Vitamina D/sangue
10.
Appl Environ Microbiol ; 78(8): 2553-61, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22307282

RESUMO

The Bacillus cereus sensu lato complex has recently been divided into several phylogenetic groups with clear differences in growth temperature range. However, only a few studies have investigated the actual pathogenic potential of the psychrotolerant strains of the B. cereus group at low temperature, and little information is available concerning gene expression at low temperature. We found that vegetative cells of the psychrotolerant B. weihenstephanensis strain KBAB4 were pathogenic against the model insect Galleria mellonella at 15°C but not at 30°C. A similar temperature-dependent difference also was observed for the supernatant, which was cytotoxic to Vero epithelial cell lines and to murine macrophage J774 cells at 15°C but not at 30°C. We therefore determined the effect of low temperature on the production of various proteins putatively involved in virulence using two-dimensional protein gel electrophoresis, and we showed that the production of the Hbl enterotoxin and of two proteases, NprB and NprP2, was greater at a growth temperature of 15°C than at 30°C. The quantification of the mRNA levels for these virulence genes by real-time quantitative PCR at both temperatures showed that there was also more mRNA present at 15°C than at 30°C. We also found that at 15°C, hbl mRNA levels were maximal in the mid- to late exponential growth phase. In conclusion, we found that the higher virulence of the B. cereus KBAB4 strain at low temperature was accompanied by higher levels of the production of various known PlcR-controlled virulence factors and by a higher transcriptional activity of the corresponding genes.


Assuntos
Bacillus/fisiologia , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Transativadores/metabolismo , Fatores de Virulência/biossíntese , Animais , Bacillus/genética , Bacillus/metabolismo , Linhagem Celular , Chlorocebus aethiops , Eletroforese em Gel Bidimensional , Células Epiteliais/microbiologia , Perfilação da Expressão Gênica , Lepidópteros/microbiologia , Macrófagos/microbiologia , Camundongos , Proteoma/análise , Temperatura
11.
J Evol Biol ; 25(11): 2171-80, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22905893

RESUMO

Song learning has evolved within several avian groups. Although its evolutionary advantage is not clear, it has been proposed that song learning may be advantageous in allowing birds to adapt their songs to the local acoustic environment. To test this hypothesis, we analysed patterns of song adjustment to noisy environments and explored their possible link to song learning. Bird vocalizations can be masked by low-frequency noise, and birds respond to this by singing higher-pitched songs. Most reports of this strategy involve oscines, a group of birds with learning-based song variability, and it is doubtful whether species that lack song learning (e.g. suboscines) can adjust their songs to noisy environments. We address this question by comparing the degree of song adjustment to noise in a large sample of oscines (17 populations, 14 species) and suboscines (11 populations, 7 species), recorded in Brazil (Manaus, Brasilia and Curitiba) and Mexico City. We found a significantly stronger association between minimum song frequency and noise levels (effect size) in oscines than in suboscines, suggesting a tighter match in oscines between song transmission capacity and ambient acoustics. Suboscines may be more vulnerable to acoustic pollution than oscines and thus less capable of colonizing cities or acoustically novel habitats. Additionally, we found that species whose song frequency was more divergent between populations showed tighter noise-song frequency associations. Our results suggest that song learning and/or song plasticity allows adaptation to new habitats and that this selective advantage may be linked to the evolution of song learning and plasticity.


Assuntos
Aves/fisiologia , Aprendizagem , Ruído , Canto , Adaptação Psicológica , Animais , Evolução Biológica , Brasil , Ecossistema , Meio Ambiente , Modelos Lineares , México , Seleção Genética , Especificidade da Espécie
12.
Ecotoxicol Environ Saf ; 72(2): 344-50, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18547642

RESUMO

Endosulfan sulphate is the transformation product of endosulfan and it is the most frequent form of surface water contamination with endosulfan. The aim of this study was to evaluate the possible effects promoted by endosulfan sulphate in changes on the life cycle, embryo development and sex differentiation of Daphnia magna. The endpoints used were moulting frequency, fecundity, growth, developmentally abnormalities and sexual differentiation. The nominal concentrations of endosulfan sulphate tested ranged from 9.2 to 458.7 microg L(-1). Endosulfan sulphate promoted a significant decrease of the offspring number in all concentrations. Results showed a reduction of the size of females, together with a decrease in moulting frequency. Furthermore, an increase in embryo deformities was observed at all concentrations tested. Above a concentration of 91.7 microg L(-1) there was an increased production of males. The results suggest that endosulfan sulphate interferes with the life cycle and sex determination of the crustacean D. magna.


Assuntos
Daphnia/efeitos dos fármacos , Daphnia/fisiologia , Desenvolvimento Embrionário/efeitos dos fármacos , Endossulfano/toxicidade , Inseticidas/toxicidade , Diferenciação Sexual/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Daphnia/embriologia , Daphnia/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Desenvolvimento Embrionário/fisiologia , Feminino , Masculino , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Diferenciação Sexual/fisiologia , Razão de Masculinidade , Testes de Toxicidade Crônica
13.
Ecotoxicol Environ Saf ; 72(6): 1714-8, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19482356

RESUMO

Chlorpyrifos is a non-systemic organophosphorus insecticide leading to the inhibition of the enzyme cholinesterase. Nowadays, this insecticide is widely used on a variety of crops and is frequently detected in surface waters around the world. The main aims of this study were to evaluate the effects of this insecticide on the embryonic development of Daphnia magna, and to assess the sensitivity of this endpoint in comparison with the endpoint of the chronic 21-day test. The featured endpoints were the number of offspring per female and abnormalities of both offspring and embryos. Chlorpyrifos exhibited significant toxic effects on the embryonic development manifested in the appearance of abnormalities, including arrested eggs, in 20% of the embryos exposed to a concentration of 0.01 microgL(-1). Furthermore, chronic exposition to the insecticide yielded a proportion of offspring abnormalities in later stages of development of about 43% at 0.01 microgL(-1). In contrast, a significant reduction in the number of offspring produced per female was only observed above a concentration of 0.03 microgL(-1). Hence, these results suggest that developmental abnormality was a more sensitive endpoint than the number of offspring production per female.


Assuntos
Clorpirifos/toxicidade , Daphnia/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Inseticidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Daphnia/embriologia , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Feminino , Exposição Materna
14.
J Comp Pathol ; 162: 29-42, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30060840

RESUMO

Endomyocarditis is a commonly detected post-mortem finding in domestic cats presenting for sudden onset cardiovascular death, yet the aetiology remains unresolved. Cats are documented reservoir hosts for Bartonella henselae, the infectious cause of cat scratch disease in man. Various Bartonella spp. have been associated with culture-negative endocarditis, myocarditis and sudden death in man and animals. We hypothesized that Bartonella spp. DNA could be amplified more often from the hearts of cats with feline endomyocarditis-left ventricular endocardial fibrosis (FEMC-LVEF) complex compared with cats with hypertrophic cardiomyopathy (HCM) or cats with grossly and microscopically unremarkable hearts (designated non-cardiac disease controls). Formalin-fixed and paraffin wax-embedded, cardiac tissues from 60 domestic and purebred cats aged 3 months to 18 years were examined, and histological features were recorded. Cardiac tissue sections were tested for Bartonella DNA using multiple 16-23S intergenic transcribed spacer region polymerase chain reaction (PCR) primer sets, including two Bartonella genera, a Bartonella koehlerae species-specific and a Bartonella vinsonii subsp. berkhoffii-specific assay, followed by DNA sequence confirmation of the species or genotype. Special precautions were taken to avoid DNA cross-contamination between tissues. Bartonella spp. DNA was amplified by PCR and sequenced from 18 of 36 cats (50%) with FEMC-LVEF and 1/12 (8.3%) cats with HCM. Bartonella spp. DNA was not amplified from any non-cardiac disease control hearts. Based on PCR/DNA sequencing, one Bartonella spp. was amplified from 10 cats, while the remaining eight were coinfected with more than one Bartonella spp. To our knowledge, this study represents the first documentation of B. vinsonii subsp. berkhoffii genotype I infection in cats (n = 11). Fluorescence in-situ hybridization testing facilitated visualization of Bartonella bacteria within the myocardium of four of seven PCR-positive FEMC-LVEF hearts. Collectively, these findings support the hypothesis that Bartonella spp. may play a primary role or act as a cofactor in the pathogenesis of FEMC-LVEF. Studies involving cats from other geographical regions and definitive demonstration of Bartonella spp. within regions of inflammation are needed to confirm an association between Bartonella spp. and FEMC-LVEF induced morbidity and mortality in cats.


Assuntos
Infecções por Bartonella/veterinária , Doenças do Gato/microbiologia , Endocardite Bacteriana/veterinária , Miocardite/veterinária , Animais , Bartonella , Gatos , DNA Bacteriano/análise
15.
Aliment Pharmacol Ther ; 48(5): 507-522, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29873091

RESUMO

AIM: To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. METHODS: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. RESULTS: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P < 0.001). Anti-CT-P13 sera of patients with IBD (n = 32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naïve individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. CONCLUSIONS: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.


Assuntos
Anticorpos Monoclonais/imunologia , Epitopos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Infliximab/imunologia , Anticorpos Monoclonais/análise , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Estudos de Casos e Controles , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Humanos , Imunoglobulina G/análise , Imunoglobulina G/sangue , Imunoglobulina G/química , Infliximab/uso terapêutico , Biblioteca de Peptídeos
16.
Transplant Proc ; 49(4): 890-892, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28457419

RESUMO

Hematopoietic stem cell transplantation is a potentially curative therapy for a range of malignant and non-malignant hematological diseases. Analysis of chimerism following allogeneic stem cell transplantation has been a routine method for the assessment of engraftment and early detection of graft failure. Lineage-specific chimerism monitoring is progressively used to specifically detect chimerism in one or more cell subsets, which may be undetected in assessment of the whole leukocyte population. The chimerism study in different leukocyte subpopulations increases sensitivity and specificity in the monitoring after transplantation, especially the analysis of T lymphocytes. All peripheral blood samples were separated into mononuclear cells and granulocytes by Ficoll density gradient centrifugation and T, B, and CD34+ was separated by immunomagnetic automatic cell separator. After DNA extraction, chimerism monitoring was performed using short tandem repeat by multiplex polymerase chain reaction followed by capillary electrophoresis. Quantification of chimerism was performed by determining the ratio of peak areas from donor and recipient informative short tandem repeat. Donor-recipient chimerism analysis in patients after allogeneic stem cell transplantation is a practical, feasible, and useful tool that predicts clinical outcomes and provides a guide for suitable therapeutic interventions.


Assuntos
Quimerismo , Rejeição de Enxerto/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Complicações Pós-Operatórias/genética , Quimeras de Transplante/genética , Adulto , Linhagem da Célula , Eletroforese Capilar , Estudos de Viabilidade , Feminino , Rejeição de Enxerto/diagnóstico , Humanos , Contagem de Leucócitos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Complicações Pós-Operatórias/diagnóstico , Período Pós-Operatório , Recidiva , Sensibilidade e Especificidade , Linfócitos T
17.
Environ Sci Process Impacts ; 18(9): 1208-19, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27499386

RESUMO

Biomonitoring is an important tool for the assessment of the quality and functions of ecosystems, providing information about the pollutants present and the direct effects that they exert on organisms. Biomonitoring relies upon the quantification of variables that can be biochemical, genetic, morphological and physiological changes. Such variables are designated as biomarkers, and multiple biomarkers are usually determined simultaneously in order to have a more integrated analysis and information about sublethal early effects of contaminants. In this work, we quantified biomarkers, associated with oxidative stress (glutathione-S-transferases GSTs, and catalase CAT, activities; levels of peroxidative alterations, by the thiobarbituric acid reactive substances assay, TBARS) and neurotoxicity (acetylcholinesterase activity, AChE) in the polychaete Hediste diversicolor. Organisms were collected at three distinct estuaries, Ria de Aveiro (Laranjo and São Jacinto), Douro River (São Paio, Afurada, and Ribeira da Granja), both impacted by human activities, and Minho River (Seixas), which has been used as a reference site. Obtained data showed the occurrence of anti-oxidant responses, in most samples from contaminated sites, which was not followed however by the occurrence of oxidative damage in organisms from Ria de Aveiro. None of the analyzed organisms had significant impairment of cholinesterasic activity, suggesting the absence of a prior exposure to neurotoxic compounds. In fact, organisms collected at Ria de Aveiro had largely increased AChE activity, suggesting an uncommon paradoxical biological response that is further discussed.


Assuntos
Poliquetos/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Catalase/metabolismo , Monitoramento Ambiental/métodos , Estuários , Estresse Oxidativo/efeitos dos fármacos , Portugal , Poluentes Químicos da Água/análise
18.
Semergen ; 42(6): 380-7, 2016 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-26364135

RESUMO

OBJECTIVE: The aim of this work is to study the survival of lung cancer patients treated at a referral hospital in Zaragoza (Spain). MATERIAL AND METHOD: The Kaplan-Meier test was used to calculate observed survival. The automatic calculation of the Catalan Institute of Oncology was used to analyse relative survival. RESULTS: Mean survival time was 25.74 months. There was no difference when comparing age groups (P=.151), gender (P=.369), and histological type of tumour (P=.086). Survival by stage of the disease at diagnosis revealed statistically significant differences (P<.001). Relative survival 5 years after diagnosis for the group analysed was 14%. Survival was higher for men (15.5%), in patients under 60 (16.7%) and squamous tumours (18.7%). CONCLUSIONS: Survival by tumour stage was in line with the TNM Staging System for Lung Cancer. These results suggest that overall survival rate for lung cancer in Zaragoza remains very low in the long term, and this depends on the stage of the disease at diagnosis.


Assuntos
Carcinoma/mortalidade , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores Sexuais , Espanha/epidemiologia , Taxa de Sobrevida , Centros de Atenção Terciária
19.
Int J Parasitol ; 24(2): 255-8, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8026903

RESUMO

Sera from 60 horses held in breeding herd in Brazil were examined monthly by ELISA, immunofluorescence antibody test (IFAT) and Western blot. All foals had maternal antibodies detectable by ELISA and IFAT, and sero-conversion took place between the 2nd and 5th month of age. The 48 and 50 kDa antigens were recognized first in the course of infection. Of 79 sera taken after sero-conversion 78 reacted with the 48 kDa antigen, 76 with the 50 kDa, 50 with the 70 kDa, 54 with the 112 kDa, 72 with the 141 kDa antigen. In general, sera from horses older than 1 year reacted with all 5 diagnostic antigen bands, but sera from horses older than 3 years only weakly. The antigens of 48 and 50 kDa appear to be conserved among all strains of B. caballi examined so far and are consistently recognized by all infected horses. They are the target antigens for a serological test based on antigens produced by recombinant DNA techniques.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários , Babesia/imunologia , Babesiose/diagnóstico , Doenças dos Cavalos/diagnóstico , Animais , Antígenos de Protozoários/imunologia , Western Blotting , Brasil , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Cavalos , Soros Imunes/imunologia
20.
Bone Marrow Transplant ; 22 Suppl 1: S56, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9715889

RESUMO

We report a comparative study of the expression of multilineage and adhesion molecules on CD34+ cells isolated from human umbilical cord blood (CB) and G-CSF-mobilized peripheral blood progenitor cells (PBPC) from healthy volunteers. The major difference found between the two sources of CD34+ populations was the expression of CD54 molecule, which was higher in CB in comparison to PBPC.


Assuntos
Antígenos CD34/análise , Sangue Fetal/citologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Antígenos CD/análise , Biomarcadores , Sangue Fetal/química , Antígenos HLA-DR/análise , Humanos , Propriedades de Superfície
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