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2.
J Am Chem Soc ; 145(9): 5029-5040, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36812067

RESUMO

Atom trapping leads to catalysts with atomically dispersed Ru1O5 sites on (100) facets of ceria, as identified by spectroscopy and DFT calculations. This is a new class of ceria-based materials with Ru properties drastically different from the known M/ceria materials. They show excellent activity in catalytic NO oxidation, a critical step that requires use of large loadings of expensive noble metals in diesel aftertreatment systems. Ru1/CeO2 is stable during continuous cycling, ramping, and cooling as well as the presence of moisture. Furthermore, Ru1/CeO2 shows very high NOx storage properties due to formation of stable Ru-NO complexes as well as a high spill-over rate of NOx onto CeO2. Only ∼0.05 wt % of Ru is required for excellent NOx storage. Ru1O5 sites exhibit much higher stability during calcination in air/steam up to 750 °C in contrast to RuO2 nanoparticles. We clarify the location of Ru(II) ions on the ceria surface and experimentally identify the mechanism of NO storage and oxidation using DFT calculations and in situ DRIFTS/mass spectroscopy. Moreover, we show excellent reactivity of Ru1/CeO2 for NO reduction by CO at low temperatures: only 0.1-0.5 wt % of Ru is sufficient to achieve high activity. Modulation-excitation in situ infrared and XPS measurements reveal the individual elementary steps of NO reduction by CO on an atomically dispersed Ru ceria catalyst, highlighting unique properties of Ru1/CeO2 and its propensity to form oxygen vacancies/Ce+3 sites that are critical for NO reduction, even at low Ru loadings. Our study highlights the applicability of novel ceria-based single-atom catalysts to NO and CO abatement.

3.
Nature ; 611(7935): 284-288, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36289341

RESUMO

Single-atom catalysts1 make exceptionally efficient use of expensive noble metals and can bring out unique properties1-3. However, applications are usually compromised by limited catalyst stability, which is due to sintering3,4. Although sintering can be suppressed by anchoring the metal atoms to oxide supports1,5,6, strong metal-oxygen interactions often leave too few metal sites available for reactant binding and catalysis6,7, and when exposed to reducing conditions at sufficiently high temperatures, even oxide-anchored single-atom catalysts eventually sinter4,8,9. Here we show that the beneficial effects of anchoring can be enhanced by confining the atomically dispersed metal atoms on oxide nanoclusters or 'nanoglues', which themselves are dispersed and immobilized on a robust, high-surface-area support. We demonstrate the strategy by grafting isolated and defective CeOx nanoglue islands onto high-surface-area SiO2; the nanoglue islands then each host on average one Pt atom. We find that the Pt atoms remain dispersed under both oxidizing and reducing environments at high temperatures, and that the activated catalyst exhibits markedly increased activity for CO oxidation. We attribute the improved stability under reducing conditions to the support structure and the much stronger affinity of Pt atoms for CeOx than for SiO2, which ensures the Pt atoms can move but remain confined to their respective nanoglue islands. The strategy of using functional nanoglues to confine atomically dispersed metals and simultaneously enhance their reactivity is general, and we anticipate that it will take single-atom catalysts a step closer to practical applications.

4.
Angew Chem Int Ed Engl ; 60(50): 26054-26062, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34346155

RESUMO

A single-atom Pt1 /CeO2 catalyst formed by atom trapping (AT, 800 °C in air) shows excellent thermal stability but is inactive for CO oxidation at low temperatures owing to over-stabilization of Pt2+ in a highly symmetric square-planar Pt1 O4 coordination environment. Reductive activation to form Pt nanoparticles (NPs) results in enhanced activity; however, the NPs are easily oxidized, leading to drastic activity loss. Herein we show that tailoring the local environment of isolated Pt2+ by thermal-shock (TS) synthesis leads to a highly active and thermally stable Pt1 /CeO2 catalyst. Ultrafast shockwaves (>1200 °C) in an inert atmosphere induced surface reconstruction of CeO2 to generate Pt single atoms in an asymmetric Pt1 O4 configuration. Owing to this unique coordination, Pt1 δ+ in a partially reduced state dynamically evolves during CO oxidation, resulting in exceptional low-temperature performance. CO oxidation reactivity on the Pt1 /CeO2 _TS catalyst was retained under oxidizing conditions.

5.
Antioxidants (Basel) ; 10(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803289

RESUMO

Dimethyl fumarate (DMF), an antioxidant/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. We hypothesized that DMF administration to simian immunodeficiency virus (SIV)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. Nine SIV-infected, CD8+-T-lymphocyte-depleted rhesus macaques were studied. Five received oral DMF prior to the SIV infection and through to the necropsy day. Protein expression was analyzed in 11 brain regions, as well as the thymus, liver, and spleen, using Western blot and immunohistochemistry for antioxidant, inflammatory, and neuronal proteins. Additionally, oxidative stress was determined in brain sections using immunohistochemistry (8-OHdG, 3NT) and optical redox imaging of oxidized flavoproteins containing flavin adenine dinucleotide (Fp) and reduced nicotinamide adenine dinucleotide (NADH). The DMF treatment was associated with no changes in virus replication; higher expressions of the antioxidant enzymes NQO1, GPX1, and HO-1 in the brain and PRDX1 and HO-2 in the spleen; lower levels of 8-OHdG and 3NT; a lower optical redox ratio. The DMF treatment was also associated with increased expressions of cell-adhesion molecules (VCAM-1, ICAM-1) and no changes in HLA-DR, CD68, GFAP, NFL, or synaptic proteins. The concordantly increased brain antioxidant enzyme expressions and reduced oxidative stress in DMF-treated SIV-infected macaques suggest that DMF could limit oxidative stress throughout the brain through effective induction of the endogenous antioxidant response. We propose that DMF could potentially induce neuroprotective brain responses in persons living with HIV.

7.
LGBT Health ; 7(4): 174-181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407149

RESUMO

Purpose: Sexual and gender minority persons in low-income countries have very limited access to routine health services. This study evaluated the feasibility of using a self-sampled human papillomavirus (HPV) test to increase access to screening for cervical cancer among transgender men in El Salvador. Methods: We partnered with a local advocacy organization for recruitment. A total of 24 transgender men (men assigned female at birth) ages 19-55 were enrolled and provided consent. Questionnaires assessed sociodemographics, health and sexual histories, and knowledge about HPV and cervical cancer. Screening was performed with a self-sampled HPV test. Participants with a positive test were offered colposcopy and cryotherapy treatment, if appropriate. Those with a negative test were advised to return in 5 years for rescreening. Results: Out of 24 consenting participants, 23 (95.83%) agreed to conduct HPV self-sampling, and 22/23 (95.65%) expressed willingness to self-sample in the future. Among self-sampled individuals, 3/23 (13%) tested positive and accepted colposcopy and biopsy. Analyses of biopsied tissue revealed one case of cervical intraepithelial neoplasia grade 1. Conclusion: HPV self-sampling and subsequent procedures were accepted by the majority of participants. This screening method may be a viable alternative to cytology among transgender men in El Salvador.


Assuntos
Detecção Precoce de Câncer , Programas de Rastreamento/métodos , Infecções por Papillomavirus/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde , Pessoas Transgênero , Transexualidade , Neoplasias do Colo do Útero/diagnóstico , Adulto , Alphapapillomavirus , Colposcopia , El Salvador , Feminino , Identidade de Gênero , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Prevalência , Autocuidado , Manejo de Espécimes , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Adulto Jovem
8.
Nat Commun ; 10(1): 1358, 2019 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-30911011

RESUMO

In this work, we compare the CO oxidation performance of Pt single atom catalysts (SACs) prepared via two methods: (1) conventional wet chemical synthesis (strong electrostatic adsorption-SEA) with calcination at 350 °C in air; and (2) high temperature vapor phase synthesis (atom trapping-AT) with calcination in air at 800 °C leading to ionic Pt being trapped on the CeO2 in a thermally stable form. As-synthesized, both SACs are inactive for low temperature (<150 °C) CO oxidation. After treatment in CO at 275 °C, both catalysts show enhanced reactivity. Despite similar Pt metal particle size, the AT catalyst is significantly more active, with onset of CO oxidation near room temperature. A combination of near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) and CO temperature-programmed reduction (CO-TPR) shows that the high reactivity at low temperatures can be related to the improved reducibility of lattice oxygen on the CeO2 support.

9.
Adicciones ; 31(3): 221-232, 2019 Jul 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30059587

RESUMO

Alcohol dependence is associated with abnormalities in the processing of emotional signals and impulsive alcohol-seeking behaviours, and these alterations compromise the effectiveness of treatment approaches. However, there is a lack of studies linking the experience of emotions to everyday motivationally relevant stimuli in alcohol-dependent individuals using both autonomic and self-report measures. We analysed heart rate (HR), skin conductance (SC) and subjective emotional reactivity to everyday affective stimuli in alcohol-dependent individuals, and their associations with impulsivity and degree of alcohol consumption. SC and HR were continuously monitored in 28 alcohol-dependent individuals and in 31 non-alcohol healthy controls during passive viewing of pleasant, unpleasant, and neutral emotional pictures. Participants assessed the pictures for valence, arousal, and dominance and completed the Barratt Impulsiveness Scale. Alcohol-dependent individuals showed reduced HR and SC reactivity to both positive and negative emotional stimuli. In the case of SC, this blunted response was associated with impulsivity. Furthermore, alcohol-dependents displayed decoupled physiological and subjective responses, with blunted autonomic responses and normal subjective reports regarding emotional stimuli. Our findings indicate that alcohol-dependent individuals failed to use emotional autonomic feedback in response to natural, emotionally relevant stimuli, and provide initial evidence of the contribution of impulsivity to emotional processing deficits in this population. These results are in keeping with the proposed key role played by emotional experience and impulsivity in substance abuse.


La dependencia al alcohol está asociada con anormalidades en el procesamiento de las emociones y comportamientos impulsivos en la búsqueda de alcohol. Sin embargo, pocos estudios han analizado las respuestas emocionales hacia estímulos motivacionalmente relevantes en personas dependientes al alcohol usando medidas tanto autonómicas como subjetivas. En este estudio se analizó la tasa cardiaca (TC), la conductancia de la piel (CP) y las respuestas subjetivas a estímulos emocionales cotidianos en individuos dependientes al alcohol, y su asociación con la impulsividad y el consumo de alcohol. La TC y la CP fueron registradas en 28 participantes dependientes al alcohol y en 31 participantes sanos durante la visualización pasiva de imágenes emocionales placenteras, desagradables y neutras. Posteriormente, los participantes evaluaron valencia, activación y dominancia de las imágenes y completaron la Escala de Impulsividad de Barratt. Los participantes dependientes mostraron respuestas reducidas en TC y CP, tanto hacia las imágenes emocionales positivas como negativas. En el caso de la CP, estas respuestas se asociaron a la impulsividad. Los participantes dependientes al alcohol mostraron una disociación entre las respuestas fisiológicas y subjetivas, con unas respuestas autonómicas disminuidas y unas respuestas subjetivas normales. Estos resultados sugieren que los individuos dependientes al alcohol tienen problemas en utilizar el feedback fisiológico emocional al responder a estímulos emocionales relevantes, y proporcionan una evidencia inicial de la contribución de la impulsividad a los déficits de procesamiento emocional en esta población. Estos resultados son congruentes con el papel clave que juega la experiencia emocional y la impulsividad en el abuso de sustancias.


Assuntos
Alcoolismo , Nível de Alerta/fisiologia , Emoções , Frequência Cardíaca/fisiologia , Comportamento Impulsivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Adicciones (Palma de Mallorca) ; 31(3): 221-232, 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-185212

RESUMO

La dependencia al alcohol está asociada con anormalidades en el procesamiento de las emociones y comportamientos impulsivos en la búsqueda de alcohol. Sin embargo, pocos estudios han analizado las respuestas emocionales hacia estímulos motivacionalmente relevantes en personas dependientes al alcohol usando medidas tanto autonómicas como subjetivas. En este estudio se analizó la tasa cardiaca (TC), la conductancia de la piel (CP) y las respuestas subjetivas a estímulos emocionales cotidianos en individuos dependientes al alcohol, y su asociación con la impulsividad y el consumo de alcohol. La TC y la CP fueron registradas en 28 participantes dependientes al alcohol y en 31 participantes sanos durante la visualización pasiva de imágenes emocionales placenteras, desagradables y neutras. Posteriormente, los participantes evaluaron valencia, activación y dominancia de las imágenes y completaron la Escala de Impulsividad de Barratt. Los participantes dependientes mostraron respuestas reducidas en TC y CP, tanto hacia las imágenes emocionales positivas como negativas. En el caso de la CP, estas respuestas se asociaron a la impulsividad. Los participantes dependientes al alcohol mostraron una disociación entre las respuestas fisiológicas y subjetivas, con unas respuestas autonómicas disminuidas y unas respuestas subjetivas normales. Estos resultados sugieren que los individuos dependientes al alcohol tienen problemas en utilizar el feedback fisiológico emocional al responder a estímulos emocionales relevantes, y proporcionan una evidencia inicial de la contribución de la impulsividad a los déficits de procesamiento emocional en esta población. Estos resultados son congruentes con el papel clave que juega la experiencia emocional y la impulsividad en el abuso de sustancias


Alcohol dependence is associated with abnormalities in the processing of emotional signals and impulsive alcohol-seeking behaviours, and these alterations compromise the effectiveness of treatment approaches. However, there is a lack of studies linking the experience of emotions to everyday motivationally relevant stimuli in alcohol-dependent individuals using both autonomic and selfreport measures. We analysed heart rate (HR), skin conductance (SC) and subjective emotional reactivity to everyday affective stimuli in alcohol-dependent individuals, and their associations with impulsivity and degree of alcohol consumption. SC and HR were continuously monitored in 28 alcohol-dependent individuals and in 31 non-alcohol healthy controls during passive viewing of pleasant, unpleasant, and neutral emotional pictures. Participants assessed the pictures for valence, arousal, and dominance and completed the Barratt Impulsiveness Scale. Alcohol-dependent individuals showed reduced HR and SC reactivity to both positive and negative emotional stimuli. In the case of SC, this blunted response was associated with impulsivity. Furthermore, alcohol-dependents displayed decoupled physiological and subjective responses, with blunted autonomic responses and normal subjective reports regarding emotional stimuli. Our findings indicate that alcohol-dependent individuals failed to use emotional autonomic feedback in response to natural, emotionally relevant stimuli, and provide initial evidence of the contribution of impulsivity to emotional processing deficits in this population. These results are in keeping with the proposed key role played by emotional experience and impulsivity in substance abuse


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Alcoolismo , Nível de Alerta/fisiologia , Emoções , Frequência Cardíaca/fisiologia , Comportamento Impulsivo
11.
Mucosal Immunol ; 11(6): 1716-1726, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30115994

RESUMO

Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born to untreated HIV-infected mothers become infected. This study assessed the protective capacity of natural HIV envelope-specific antibodies isolated from the milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. To mimic placental and milk maternal antibody transfer, infant RMs were i.v. infused and orally treated at the time of challenge with a single weakly neutralizing milk monoclonal antibody (mAb), a tri-mAb cocktail with weakly neutralizing and ADCC functionalities, or an anti-influenza control mAb. Of these groups, the fewest tri-mAb-treated infants had SHIV detectable in plasma or tissues (2/6, 5/6, and 7/8 animals infected in tri-mAb, single-mAb, and control-mAb groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer plasma transmitted/founder variants and reduced peripheral CD4+ T cell proviral loads at 8 weeks post-challenge compared to control mAb-treated infants. Abortive infection was observed as detectable CD4+ T cell provirus in non-viremic control mAb- and single mAb-, but not in tri-mAb-treated animals. These results suggest that polyfunctional milk antibodies contribute to the natural inefficiency of HIV-1 transmission through breastfeeding and infant vaccinations eliciting non-neutralizing antibody responses could reduce postnatal HIV transmission.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Macaca mulatta/imunologia , Leite Humano/virologia , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais/sangue , Modelos Animais de Doenças , Transmissão de Doença Infecciosa , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/transmissão , HIV-1/patogenicidade , Humanos , Imunização Passiva , Carga Viral
12.
Science ; 358(6369): 1419-1423, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29242344

RESUMO

To improve fuel efficiency, advanced combustion engines are being designed to minimize the amount of heat wasted in the exhaust. Hence, future generations of catalysts must perform at temperatures that are 100°C lower than current exhaust-treatment catalysts. Achieving low-temperature activity, while surviving the harsh conditions encountered at high engine loads, remains a formidable challenge. In this study, we demonstrate how atomically dispersed ionic platinum (Pt2+) on ceria (CeO2), which is already thermally stable, can be activated via steam treatment (at 750°C) to simultaneously achieve the goals of low-temperature carbon monoxide (CO) oxidation activity while providing outstanding hydrothermal stability. A new type of active site is created on CeO2 in the vicinity of Pt2+, which provides the improved reactivity. These active sites are stable up to 800°C in oxidizing environments.

13.
Science ; 353(6295): 150-4, 2016 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-27387946

RESUMO

Catalysts based on single atoms of scarce precious metals can lead to more efficient use through enhanced reactivity and selectivity. However, single atoms on catalyst supports can be mobile and aggregate into nanoparticles when heated at elevated temperatures. High temperatures are detrimental to catalyst performance unless these mobile atoms can be trapped. We used ceria powders having similar surface areas but different exposed surface facets. When mixed with a platinum/aluminum oxide catalyst and aged in air at 800°C, the platinum transferred to the ceria and was trapped. Polyhedral ceria and nanorods were more effective than ceria cubes at anchoring the platinum. Performing synthesis at high temperatures ensures that only the most stable binding sites are occupied, yielding a sinter-resistant, atomically dispersed catalyst.

14.
J Virol ; 89(20): 10156-75, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26223646

RESUMO

UNLABELLED: Deletion of Gly-720 and Tyr-721 from a highly conserved GYxxØ trafficking signal in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed ΔGY, leads to a striking perturbation in pathogenesis in rhesus macaques (Macaca mulatta). Infected macaques develop immune activation and progress to AIDS, but with only limited and transient infection of intestinal CD4(+) T cells and an absence of microbial translocation. Here we evaluated ΔGY in pig-tailed macaques (Macaca nemestrina), a species in which SIVmac239 infection typically leads to increased immune activation and more rapid progression to AIDS than in rhesus macaques. In pig-tailed macaques, ΔGY also replicated acutely to high peak plasma RNA levels identical to those for SIVmac239 and caused only transient infection of CD4(+) T cells in the gut lamina propria and no microbial translocation. However, in marked contrast to rhesus macaques, 19 of 21 pig-tailed macaques controlled ΔGY replication with plasma viral loads of <15 to 50 RNA copies/ml. CD4(+) T cells were preserved in blood and gut for up to 100 weeks with no immune activation or disease progression. Robust antiviral CD4(+) T cell responses were seen, particularly in the gut. Anti-CD8 antibody depletion demonstrated CD8(+) cellular control of viral replication. Two pig-tailed macaques progressed to disease with persisting viremia and possible compensatory mutations in the cytoplasmic tail. These studies demonstrate a marked perturbation in pathogenesis caused by ΔGY's ablation of the GYxxØ trafficking motif and reveal, paradoxically, that viral control is enhanced in a macaque species typically predisposed to more pathogenic manifestations of simian immunodeficiency virus (SIV) infection. IMPORTANCE: The pathogenesis of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) reflects a balance between viral replication, host innate and adaptive antiviral immune responses, and sustained immune activation that in humans and Asian macaques is associated with persistent viremia, immune escape, and AIDS. Among nonhuman primates, pig-tailed macaques following SIV infection are predisposed to more rapid disease progression than are rhesus macaques. Here, we show that disruption of a conserved tyrosine-based cellular trafficking motif in the viral transmembrane envelope glycoprotein cytoplasmic tail leads in pig-tailed macaques to a unique phenotype in which high levels of acute viral replication are followed by elite control, robust cellular responses in mucosal tissues, and no disease. Paradoxically, control of this virus in rhesus macaques is only partial, and progression to AIDS occurs. This novel model should provide a powerful tool to help identify host-specific determinants for viral control with potential relevance for vaccine development.


Assuntos
Motivos de Aminoácidos , Linfócitos T CD4-Positivos/imunologia , Imunidade nas Mucosas , Macaca nemestrina/virologia , Deleção de Sequência , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Linfócitos T CD4-Positivos/virologia , Progressão da Doença , Feminino , Expressão Gênica , Intestinos/imunologia , Intestinos/virologia , Macaca mulatta/virologia , Masculino , Dados de Sequência Molecular , Mucosa/imunologia , Mucosa/virologia , Sinais Direcionadores de Proteínas , Estrutura Terciária de Proteína , Transporte Proteico , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Especificidade da Espécie , Proteínas do Envelope Viral/deficiência , Proteínas do Envelope Viral/genética , Carga Viral/genética , Carga Viral/imunologia , Viremia/imunologia , Viremia/patologia , Replicação Viral/genética , Replicação Viral/imunologia
15.
J Virol ; 87(19): 10874-83, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23903838

RESUMO

Feline leukemia virus (FeLV) is a naturally transmitted gammaretrovirus that infects domestic cats. FeLV-945, the predominant isolate associated with non-T-cell disease in a natural cohort, is a member of FeLV subgroup A but differs in sequence from the FeLV-A prototype, FeLV-A/61E, in the surface glycoprotein (SU) and long terminal repeat (LTR). Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in pathogenesis indistinguishable from that of FeLV-A/61E, namely, thymic lymphoma of T-cell origin. In contrast, substitution of both FeLV-945 LTR and SU into FeLV-A/61E resulted in multicentric lymphoma of non-T-cell origin. These results implicated the FeLV-945 SU as a determinant of pathogenic spectrum. The present study was undertaken to test the hypothesis that FeLV-945 SU can act in the absence of other unique sequence elements of FeLV-945 to determine the disease spectrum. Substitution of FeLV-A/61E SU with that of FeLV-945 altered the clinical presentation and resulted in tumors that demonstrated expression of CD45R in the presence or absence of CD3. Despite the evident expression of CD45R, a typical B-cell marker, T-cell receptor beta (TCRß) gene rearrangement indicated a T-cell origin. Tumor cells were detectable in bone marrow and blood at earlier times during the disease process, and the predominant SU genes from proviruses integrated in tumor DNA carried markers of genetic recombination. The findings demonstrate that FeLV-945 SU alters pathogenesis, although incompletely, in the absence of FeLV-945 LTR. Evidence demonstrates that FeLV-945 SU and LTR are required together to fully recapitulate the distinctive non-T-cell disease outcome seen in the natural cohort.


Assuntos
Vírus da Leucemia Felina/patogenicidade , Linfoma/patologia , Glicoproteínas de Membrana/metabolismo , Infecções por Retroviridae/virologia , Sequências Repetidas Terminais/genética , Neoplasias do Timo/patologia , Infecções Tumorais por Vírus/virologia , Sequência de Aminoácidos , Animais , Southern Blotting , Gatos , DNA Viral/genética , Progressão da Doença , Feminino , Técnicas Imunoenzimáticas , Vírus da Leucemia Felina/fisiologia , Linfoma/genética , Linfoma/virologia , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Infecções por Retroviridae/metabolismo , Infecções por Retroviridae/patologia , Homologia de Sequência de Aminoácidos , Taxa de Sobrevida , Neoplasias do Timo/genética , Neoplasias do Timo/virologia , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/patologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
16.
Springer Semin Immunopathol ; 27(1): 87-104, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15711953

RESUMO

Human telomerase reverse transcriptase, a ribonucleoprotein intimately connected with the process of cell immortalization, is overexpressed in the vast majority of cancer cells, irrespective of their histological origin. Telomerase is currently viewed as the first antigen with the characteristics of common tumor antigen in humans, and it constitutes a potentially valuable target for attempts to control tumors through CD8 T cell immunity. Telomerase is a self antigen, making it possible that self tolerance imposes severe restrictions on our ability to generate effective anti-tumor immune responses in humans. In this article we review current studies on the antigenic and immunogenic properties of the human telomerase reverse transcriptase, placing them in the context of self tolerance and the size of the available CD8 T cell repertoire restricted by the HLA A2 molecule.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Citotoxicidade Imunológica , Proteínas de Ligação a DNA/imunologia , Neoplasias/imunologia , Telomerase/imunologia , Antígenos de Neoplasias/imunologia , Autoimunidade , Ensaios Clínicos como Assunto , Técnicas de Química Combinatória , Humanos , Neoplasias/terapia , Tolerância a Antígenos Próprios , Linfócitos T Citotóxicos/imunologia
17.
J Inorg Biochem ; 98(6): 1129-34, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15149824

RESUMO

Cellular Al accumulation has been shown to alter iron metabolism and induce peroxidative injury. Therefore antioxidants could potentially reduce or prevent peroxidative injury in Al-loaded cells. To test this hypothesis we assessed the effect of the antioxidants N-acetyl cysteine (NAC), catalase, superoxide dismutase (SOD), and tetramethylpiperidine 1-oxyl (TEMPO) in abrogating Al-associated cell toxicity and melonyldialdehyde (MDA) accumulation in mouse hepatocytes. Mouse hepatocytes (MH) were grown in media containing the minimum toxic concentration of Al (100 microg/L as Al-transferrin). All antioxidants protected MH from injury as assessed by cell growth and enzyme leakage into media. The antioxidants did not affect Al uptake by MH, protect MH from lipid peroxidation or decrease the reactive iron content of MH. Although antioxidants protected Al loaded MH from injury the mechanisms of this effect are unknown.


Assuntos
Alumínio/toxicidade , Antioxidantes/farmacologia , Hepatócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Proliferação de Células/efeitos dos fármacos , Hepatócitos/patologia , Ferro/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos
19.
Dermatol. venez ; 33(2): 99-103, 1995. ilus
Artigo em Espanhol | LILACS | ID: lil-185654

RESUMO

Un estudio simple, abierto, multicéntrico, se enrolaron 93 pacientes (43 varones y 48 mujeres) mayores de 18 años con tinea unguis de pies, quienes recibieron terbinafina (Lamisil), 250 mg diarios por 90 días. De ellos se aislaron 71 cepas de Trichophyton rubrum, 21 de Tr. mentagrophytes y 1 de Epidermophyton floccosum. Al término de la medicación (3 meses), se presentaron 67 pacientes, 65 de los cuales (96,5 por ciento) resultaron negativos al examen micológico. A los 3 meses de seguimiento, un paciente más resultó negativo. A los 6 meses de seguimiento, se registró recaída. Cuatro pacientes mostraron leves efectos secundarios adversos; dos de ellos se retiraron del estudio. En conclusión, pensamos que, bajo las condiciones del presente ensayo, la terbinafina (Lamisil) ha mostrado rápida e intensa actividad y alta tolerabilidad


Assuntos
Adulto , Humanos , Masculino , Feminino , Onicomicose/terapia , Venezuela
20.
Rev. invest. clín ; 34(2): 95-8, 1982.
Artigo em Inglês | LILACS | ID: lil-9828

RESUMO

La infiltracion del sistema nervioso central (SNC) por celulas leucemicas es una complicacion que se presenta cada vez con mayor frecuencia. El diagnostico de infiltracion leucemica se confirma por la observacion de celulas malignas en el liquido cefalorraquideo (LCR). No obstante, la evaluacion morfologica de las celulas resulta dificil, ya que estas pierden frecuentemente su morfologia debido a las caracteristicas fisicas del LCR y porque en ocasiones la celulas leucemicas se encuentran confinadas unicamente al parenquima cerebral. Para demonstrar la infiltracion leucemica del SNC se midieron los niveles de ferritina en el LCR mediante una tecnica inmunorradiometrica. Los pacientes con infiltracion del SNC tuvieron niveles mas altos de ferritina en el LCR (11.2 +/- 1.4 ug/l) que los enfermos con leucemia aguda que no presentaban esta complicacion (p = 0.001). Los niveles de ferritina en LCR en el grupo control y en los enfermos con leucemia aguda sin infiltracion leucemica fueron casi identicos 4.4 +/- 0.6 y 4.5 +/- 0.7 ug/l respectivamente.Estos hallazgos sugieren que la dosificacion de ferritina en el LCR puede ser de utilidad en el diagnostico de esta grave complicacion


Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Líquido Cefalorraquidiano , Ferritinas , Leucemia
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