982 resultados para 1995_07181630 TM-3 4900204


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Purpose: Persistent infection of cervical epithelium with high risk human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV 16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX(TM) adjuvant (HPV16 Immunotherapeutic) for patients with CIN. Experimental design: Patients with CIN (n = 3 1) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. Results: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. Conclusions : The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX(TM) adjuvant is safe and induces vaccine antigen specific cell mediated immunity. (C) 2004 Elsevier Ltd. All rights reserved.

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Human Papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are associated with cervical cancer development and progression and can therefore be used as target antigens for cancer immunotherapy. In this study we evaluated the immunogenicity in mice, of different vaccine formulations using recombinant HPV16 derived E6E7 or E7GST fusion proteins. When co-administered with ISCOMATRIX(TM) adjuvant, these E6E7 proteins consistently induced E7 specific CTL, in vivo tumor protection, antibody and DTH responses. ISCOMATRIX(TM) adjuvant has been developed for use in the formulation of novel human vaccines and has been evaluated for safety and toxicity in human trials. A formulation containing aluminum hydroxide (Al(OH)(3)) gave a lesser degree of E7 specific antibody, and no local E7 specific CTL response but similar DTH and tumor protection. These findings demonstrate the potential of ISCOMATRIX(TM) adjuvant to stimulate both cellular and humoral immune responses to endogenously processed target antigens, and hence is the preferred adjuvant when CTL responses are desirable. (C) 2004 Elsevier Ltd. All rights reserved.

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Background: The purpose of the present study was to compare the effectiveness of three burns dressings (TransCyte, a bio-engineered skin substitute; Biobrane; and Silvazine cream (silver sulphadiazine and 0.2% chlorhexidine)), in treating children with partial-thickness burns. The primary objective was to determine the days until greater than or equal to90% re-epithelialization. The secondary objectives were to evaluate the number of wounds requiring autografting and the number of dressing changes/local wound care required. Methods: Study wounds were identified on each patient and the patients were randomized to receive TransCyte or Biobrane or Silvazine. Assessment of study wound closure began at 2 days after treatment and continued at least every other day thereafter until the wounds re-epithelialized or were autografted. A laser Doppler imaging system was used as an adjunct to assessing the depth of the burn. Results: Thirty-three patients with 58 wound sites enrolled in the study (TransCyte, n = 20, Biobrane, n = 17; Silvazine, n = 21). Mean time to re-epithelialization was 7.5 days for TransCyte, 9.5 days for Biobrane, and 11.2 days for Silvazine. The number of wounds requiring autografting were 5/21 (24%) for Silvazine, 3/17 (17%) for Biobrane, and 1/20 (5%) for TransCyte. Conclusions: When used in partial-thickness burns in children, TransCyte promotes fastest re-epithelialization and required less overall dressings then Biobrane or Silvazine. Patients who received Silvazine or Biobrane require more autografting than those treated with TransCyte.

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In this paper we proposed a composite depth of penetration (DOP) approach to excluding bottom reflectance in mapping water quality parameters from Landsat thematic mapper (TM) data in the shallow coastal zone of Moreton Bay, Queensland, Australia. Three DOPs were calculated from TM1, TM2 and TM3, in conjunction with bathymetric data, at an accuracy ranging from +/-5% to +/-23%. These depths were used to segment the image into four DOP zones. Sixteen in situ water samples were collected concurrently with the recording of the satellite image. These samples were used to establish regression models for total suspended sediment (TSS) concentration and Secchi depth with respect to a particular DOP zone. Containing identical bands and their transformations for both parameters, the models are linear for TSS concentration, logarithmic for Secchi depth. Based on these models, TSS concentration and Secchi depth were mapped from the satellite image in respective DOP zones. Their mapped patterns are consistent with the in situ observed ones. Spatially, overestimation and underestimation of the parameters are restricted to localised areas but related to the absolute value of the parameters. The mapping was accomplished more accurately using multiple DOP zones than using a single zone in shallower areas. The composite DOP approach enables the mapping to be extended to areas as shallow as <3 m. (C) 2004 Elsevier Inc. All rights reserved.

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The VPAC(1) receptor belongs to family B of G protein-coupled receptors (GPCR-B) and is activated upon binding of the vasoactive intestinal peptide (VIP). Despite the recent determination of the structure of the N terminus of several members of this receptor family, little is known about the structure of the transmembrane (TM) region and about the molecular mechanisms leading to activation. In the present study, we designed a new structural model of the TM domain and combined it with experimental mutagenesis experiments to investigate the interaction network that governs ligand binding and receptor activation. Our results suggest that this network involves the cluster of residues Arg(188) in TM2, Gln(380) in TM7, and Asn(229) in TM3. This cluster is expected to be altered upon VIP binding, because Arg(188) has been shown previously to interact with Asp(3) of VIP. Several point mutations at positions 188, 229, and 380 were experimentally characterized and were shown to severely affect VIP binding and/or VIP-mediated cAMP production. Double mutants built from reciprocal residue exchanges exhibit strong cooperative or anticooperative effects, thereby indicating the spatial proximity of residues Arg(188), Gln(380), and Asn(229). Because these residues are highly conserved in the GPCR-B family, they can moreover be expected to have a general role in mediating function.

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The first and third extracellular loops (ECL) of G protein-coupled receptors (GPCRs) have been implicated in ligand binding and receptor function. This study describes the results of an alanine/leucine scan of ECLs 1 and 3 and loop-associated transmembrane (TM) domains of the secretin-like GPCR calcitonin receptor-like receptor which associates with receptor activity modifying protein 1 to form the CGRP receptor. Leu195Ala, Val198Ala and Ala199Leu at the top of TM2 all reduced aCGRP-mediated cAMP production and internalization; Leu195Ala and Ala199Leu also reduced aCGRP binding. These residues form a hydrophobic cluster within an area defined as the "minor groove" of rhodopsin-like GPCRs. Within ECL1, Ala203Leu and Ala206Leu influenced the ability of aCGRP to stimulate adenylate cyclase. In TM3, His219Ala, Leu220Ala and Leu222Ala have influences on aCGRP binding and cAMP production; they are likely to indirectly influence the binding site for aCGRP as well as having an involvement in signal transduction. On the exofacial surfaces of TMs 6 and 7, a number of residues were identified that reduced cell surface receptor expression, most noticeably Leu351Ala and Glu357Ala in TM6. The residues may contribute to the RAMP1 binding interface. Ile360Ala impaired aCGRP-mediated cAMP production. Ile360 is predicted to be located close to ECL2 and may facilitate receptor activation. Identification of several crucial functional loci gives further insight into the activation mechanism of this complex receptor system and may aid rational drug design.

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Multidrug resistance protein 1 (MRP1) confers drug resistance and also mediates cellular efflux of many organic anions. MRP1 also transports glutathione (GSH); furthermore, this tripeptide stimulates transport of several substrates, including estrone 3-sulfate. We have previously shown that mutations of Lys(332) in transmembrane helix (TM) 6 and Trp(1246) in TM17 cause different substrate-selective losses in MRP1 transport activity. Here we have extended our characterization of mutants K332L and W1246C to further define the different roles these two residues play in determining the substrate and inhibitor specificity of MRP1. Thus, we have shown that TM17-Trp(1246) is crucial for conferring drug resistance and for binding and transport of methotrexate, estradiol glucuronide, and estrone 3-sulfate, as well as for binding of the tricyclic isoxazole inhibitor N-[3-(9-chloro-3-methyl-4-oxo-4H-isoxazolo-[4,3-c]quinolin-5-yl)-cyclohexylmethyl]-benzamide (LY465803). In contrast, TM6-Lys(332) is important for enabling GSH and GSH-containing compounds to serve as substrates (e.g., leukotriene C(4)) or modulators (e.g., S-decyl-GSH, GSH disulfide) of MRP1 and, further, for enabling GSH (or S-methyl-GSH) to enhance the transport of estrone 3-sulfate and increase the inhibitory potency of LY465803. On the other hand, both mutants are as sensitive as wild-type MRP1 to the non-GSH-containing inhibitors (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK571), 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl]-ethanone (LY171883), and highly potent 6-[4'-carboxyphenylthio]-5[S]-hydroxy-7[E], 11[Z]14[Z]-eicosatetrenoic acid (BAY u9773). Finally, the differing abilities of the cysteinyl leukotriene derivatives leukotriene C(4), D(4), and F(4) to inhibit estradiol glucuronide transport by wild-type and K332L mutant MRP1 provide further evidence that TM6-Lys(332) is involved in the recognition of the gamma-Glu portion of substrates and modulators containing GSH or GSH-like moieties.

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Room temperature, tunable, external-cavity short-wavelength InAs/AlSb quantum cascade laser (QCL) is reported. Wavelength tuning of 85 nm for the spectral range between 3190 nm and 3275 nm has been achieved by rotating the diffraction grating forming the external cavity. To suppress lasing inside the QCL cavity, its ridge was tilted by 7° at the external cavity end. The optimal tilting angle of the laser ridge was chosen by careful consideration of the return losses of the TM-polarized waveguide mode from the diffraction grating in a quasi-Littrow configuration and the Fabry-Pérot feedback from the tilted laser facet. No antireflection coating was used. © 2013 American Institute of Physics.

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The task of expression undertaken by the performer falls largely on the right hand of guitarist. Aware of this fact, past and present masters have left their contributions to the development of right hand technique. It is clear, with rare exceptions, that educational and interpretative proposals, so far, have addressed the attack on the strings from the flexion of the fingers. This work, however, presents a technical resource called imalt, including in the attack action, the extension movement. Some techniques used in specific circumstances, such as the dedillo, the alzapúa, the tremulo and the rasgueado also use extension movements in the attack. They are put in perspective with the imalt providing a panoramic view of their individual characteristics. The use of imalt in the traditional guitar repertoire is exemplified in Villa Lobos, Ponce and Brouwer. Three pieces were composed for this work: Shravana, Alegoria and Vandana. Compositional techniques such as melodic contour applying and ostinato have been reviewed and used in the preparation of these compositions. A detailed record of compositional trajectory is presented. Therefore, the Model for the Compositional Process Accompaniment according Silva (2007) is used. Some events that have left the imalt in evidence are reported, as the launch and distribution of the Compact Disc (CD) Imalt, publishing scores and interviews. Finally is presented concluding comments, pointing possibilities opened up by this work.

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A literatura realça a importância do impacto do comportamento parental no desenvolvimento de ansiedade em crianças e adolescentes. Dado a pertinência do tema, o foco do presente estudo visa analisar o papel que a perceção dos adolescentes sobre os estilos educativos parentais tem sobre a manifestação de sintomatologia ansiosa. A amostra desta investigação envolveu 136 adolescentes do 3º ciclo do ensino básico, 48 rapazes e 88 raparigas com idades compreendidas entre os 12 e os 15 anos, com uma média de idades de 13,2 anos, recolhida no Colégio São Martinho em Coimbra. O protocolo de investigação incluiu os seguintes instrumentos de colheita de dados: Questionário Sociodemográfico, State-Trait Anxiety Inventory for Children (STAIC) e EMBU-A. Os resultados do estudo sugerem que os adolescentes mais velhos manifestam maior sintomatologia ansiosa, estatisticamente significativa ao nível da ansiedade-estado. No que respeita ao desempenho académico, são os adolescentes com elevado insucesso escolar que exteriorizam mais ansiedade-traço. Porém, não foram encontradas diferenças significativas na manifestação da ansiedade dos adolescentes em função das variáveis género, posição na fratria e habilitações literárias dos pais. Por seu lado, em relação aos estilos educativos parentais, os jovens que têm maior insucesso escolar percecionam níveis elevados de sobreproteção da mãe, e de rejeição do pai e da mãe. Os adolescentes que têm um pai com mais baixo nível de escolaridade percecionam maior rejeição materna, e são os filhos de mães com menos habilitações literárias que sentem maior sobreproteção da mãe e rejeição do pai. Verificou-se, em particular, uma associação significativa entre a rejeição paterna e níveis mais elevados de sintomatologia ansiosa. O modelo preditivo avançado no estudo confirma que a rejeição paterna, em conjunto com a idade do adolescente, são bons preditores da sintomatologia ansiosa. Especificamente, a rejeição paterna é evidenciada como o melhor preditor da sintomatologia ansiosa, sendo o principal responsável pela manifestação de ansiedade nos adolescentes. Os resultados sugerem que a rejeição do pai desencadeia níveis elevados de sintomatologia ansiosa. Assim, este estudo permite concluir que a rejeição paterna é o estilo educativo parental que exerce maior influência na manifestação de ansiedade nos adolescentes. / The literature highlights the importance of the impact of parental behavior on the development of anxiety in children and adolescents. Given the relevance of the topic, the focus of this study is to analyze the role that the adolescents’ perception about parental rearing styles have on the manifestation of anxiety symptoms. The sample of this research involved 136 adolescents from the 3rd cycle of basic education, 48 boys and 88 girls aged between 12 and 15 years, with a mean age of 13,2 years, gathered in Colégio São Martinho in Coimbra. The investigation protocol included the following data collection instruments: Sociodemographic Questionnaire, State-Trait Anxiety Inventory for Children (STAIC) and the EMBU-A. The results of the study suggest that older adolescents show greater anxiety symptoms, statistically significant at the level of state anxiety. With regard to academic performance, are adolescents with high failure rates that externalize more trait anxiety. However, there were significant differences in the manifestation of anxiety in adolescents function of the variables gender, sibling position and educational background of the parents. For its part, in relation to parental rearing styles, young people who have higher academic failure perceive high levels of overprotection of the mother, and rejection of father and mother. Adolescents who have a father with the lowest educational level perceive greater maternal rejection, and are the children of mothers with less qualification who feel greater overprotection of the mother and father's rejection. There was, in particular, a significant association between paternal rejection and higher levels of anxiety symptoms. The predictive model advanced in the study confirms that parental rejection, together with the adolescents’ age, are good predictors of anxiety symptoms. Specifically, parental rejection is evidenced as the best predictor of anxiety symptoms, being primarily responsible for the manifestation of anxiety in adolescents. The results suggest that the father rejection triggers high levels of anxiety symptoms. Thus, this study shows that rejection is the paternal parental rearing style that has more influence on the manifestation of anxiety in adolescents.