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BACKGROUND: Abdominoperineal resection (APR) is today the standard treatment for improving survival in case of mesorectal failure without anal canal recurrence after chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCC). The aim of this study was to assess if a sphincter-saving surgery is a safe alternative to classical salvage APR in these patients. METHODS: A retrospective study was conducted on all patients who had total mesorectal excision (TME) with sphincter-saving surgery either with coloanal or low colorectal anastomosis, for mesorectal failure after CRT for SCC between 2012 and 2020 at our institution. The main endpoint of our study was oncological results at the end of follow-up. Postoperative morbidity and mortality were secondary endpoints. RESULTS: There were 10 patients, (8 women, median age 55 years [range 45-61 years]). On TME specimens, R0 resections were noted in five (50%), R1 resection in four (40%) and R2 resection in one (10%). After a median follow-up of 42 months (4-74 months), five patients were alive, and four (40%) were alive at 5-year follow-up. During follow-up, locoregional failure after TME was noted in two patients (20%), distant relapse in three patients (30%) and both locoregional plus distant failure in two patients (20%). Only two patients (20%) had anal recurrence, one in the anal canal, the other in the peri-anastomotic area. Long- term local control was achieved in 2 of the 5 patients (40%) who underwent R0 resection versus only 1/4 patients (25%) with R1 resection. CONCLUSIONS: Our preliminary study suggested that sphincter-saving surgery could be proposed in selected patients with SCC presenting mesorectal failure after CRT, providing a feasible R0 resection.
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Neoplasias do Ânus , Carcinoma de Células Escamosas , Neoplasias Retais , Humanos , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , Canal Anal/cirurgia , Canal Anal/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Neoplasias do Ânus/cirurgia , Neoplasias Retais/cirurgia , Quimiorradioterapia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologiaRESUMO
Using first-principles calculations, we show that the origin of the intrinsic a1g(â¼3z2 - r2)-b1g(â¼x2 - y2) splitting, Δint, in tetragonal transition-metal complexes and the variations of the cubic field splitting, 10Dq, with the metal-ligand distance, R, are much more subtle than commonly thought. As a main novelty, the key role played by covalent bonding with deep valence ligand levels and thus the inadequacy of too simple models often used for the present goal is stressed. Taking as a guide the isolated D4h CuF64- complex, it is proved that Δint essentially arises from bonding with deep 2s(F) orbitals despite them lying â¼23 eV below 2p(F) orbitals. This conclusion, although surprising, is also supported by results on octahedral fluoride complexes where the contribution to 10Dq splitting from bonding with 2s(F) orbitals is behind its strong R dependence, stressing that explanations based on the crystal-field approach are simply meaningless.
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This work attempts to unveil the similarities and differences between Jahn-Teller (JT) and non-JT systems involving CuF64- units. For achieving this goal, we firstly explore Na2CuF4 and NaF:Cu2+ systems through first principles calculations and pay particular attention to the links between JT and non-JT systems looking at the electronic density of the hole. The results on Na2CuF4 in the monoclinic P21/c space group and also in the parent Pbam structure reveal that the local geometry can be understood as an initial tetragonally compressed CuF64- unit, followed by an additional orthorhombic instability that excludes the JT effect as the origin. Although the present results on NaF:Cu2+ underpin an elongated equilibrium geometry such as that measured for Cu2+ ions in the cubic perovskite KZnF3, the force constant for NaF:Cu2+ is half that for KZnF3:Cu2+. This crucial fact is direct proof of the elastic decoupling of CuF64- from the NaF lattice leading to a JT energy, EJT, which is twice that found for KZnF3:Cu2+. However, both systems have practically the same linear electron-vibration coupling constant, V1e, a relevant fact whose origin is discussed. The final aim of this work concerns the influence of tetragonal and orthorhombic distortions as well as the internal electric field on the A1g-B1g energy gap, Δ, of a variety of systems with CuF64- complexes. Interestingly, it is shown that compounds with orthorhombic instability and an internal electric field can have a Δ value comparable to the JT system NaF:Cu2+. Accordingly, explanations for optical spectra of transition metal compounds based on simple parameterized models can be meaningless. The present study shows that properties displayed by d9 compounds in low symmetry lattices can hardly stem from a static JT effect.
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The properties of MF2 (M = Cr, Cu) model compounds are usually interpreted assuming a Jahn-Teller effect leading to elongated MF64- units. By means of the analysis of experimental data and first-principles calculations on both the monoclinic P21/c structure and the parent rutile structure (tetragonal P42/mnm space group), we prove that such an assumption is not correct. It is shown that in MF2 compounds, the MF64- complexes are actually compressed in the parent phase but along a different direction, a situation that is however hidden by an additional orthorhombic instability due to a negative force constant of b2g and b3g modes of the cell. This distortion plays a key role in understanding the high experimental value of the lowest d-d transition energy, E1 = 1.23 and 0.93 eV for CrF2 and CuF2, respectively, when compared to the value E1 = 0.40 eV derived for the Jahn-Teller system of KZnF3:Cu2+. Aside from reproducing reasonably the experimental values of spin allowed d-d transitions of both compounds, our first-principles calculations show the existence of an accidental degeneracy involving the yz and xy levels in the final P21/c structure. Moreover, the internal electric field of CrF2 and CuF2 is found to be much less anisotropic than in layered compounds like K2CuF4 and thus it has little influence on the d-d transition energy. The influence of the (3z2 - r2) - (x2 - y2) hybridization, caused by the orthorhombic distortion, on the electronic density and the magnetic coupling between layers is also briefly discussed. The present results stress that the interpretation of experimental data using simple parameterized models can lead to wrong conclusions.
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The delicate balance between cooperative and local contributions in the ferroelectric distortions of BaTiO3 is explored by means of ab initio calculations. As a salient feature, it is found that a single Ti(4+) ion in BaTiO3 is not allowed to move off-center at ambient pressure, while this is no longer true if the lattice is expanded by only â¼5%, stressing the high sensitivity of the local contribution to chemical and hydrostatic pressures. In order to further understand the effect of local contributions on the phase transition mechanism of ferroelectrics, we have investigated the surprising C3v â C4v â Oh local transformations occurring in the 10-50 K temperature range for the MnCl6(5-) complex formed in KCl:Mn(+) that mimic the behavior of BaTiO3. From Boltzmann analysis of the vibronic levels derived from ab initio calculations and considering decoherence introduced by random strains, the present calculations reproduce the experimental phase sequence and transition temperatures. Furthermore, our calculations show that the off-center instability in KCl:Mn(+) would be suppressed by reducing by only 1% the lattice parameter, a situation that then becomes comparable to that found for BaTiO3 at ambient pressure. The present results thus stress the deep link between the structural phase transitions of ferroelectric materials and local phase transitions displayed by transition-metal impurities in insulators.
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This work is aimed at understanding the different behavior of optical sharp lines (corresponding to 10Dq-independent transitions) of Mn(2+) and Cr(3+) in normal and inverted perovskites that cannot be explained within the usual Tanabe-Sugano approach. In particular, we want to clarify why on passing from KMgF3:M to LiBaF3:M (M = Mn(2+), Cr(3+)) the energy, E((6)A1 â (4)A1), for Mn(2+) decreases by Δ = 1100 cm(-1), while Δ < 100 cm(-1) for the energy E((2)E â( 4)A2) corresponding to Cr(3+). The origin of this surprising difference in these model systems is clarified by writing the transition energies of MF6 complexes through the ten Coulomb and exchange integrals consistent with the cubic symmetry and not considered in the usual Tanabe-Sugano approach. It is shown that E((6)A1 â (4)A1) depends on exchange integrals K(3z(2) - r(2), xy) and K(x(2) - y(2), xy), while E((2)E â (4)A2) depends on K(xz, yz) where the two involved electrons display a π character. These exchange integrals have been calculated just considering a MF6 unit subject to the internal electric field due to the rest of the lattice ions. In addition to a reasonably reproduction of the main trends observed experimentally for the model systems, the present calculations prove that the exchange integrals are not related in a simple way to the covalency of involved orbitals. Particular attention is also paid to explain why the transitions, which are 10Dq-independent are less sensitive to the host lattice change than those which do depend on 10Dq. The present work shows that K(xz, yz) for Cr(3+) is particularly insensitive to the host lattice change and thus sheds light on the origin of the near independence of E((2)E â (4)A2) along the series of oxides doped with such an impurity .
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Many relevant properties (including superconductivity and colossal magnetoresistance) of layered materials containing Cu(2+), Ag(2+), or Mn(3+) ions are commonly related to the Jahn-Teller instability. Along this line, the properties of the CuF6(4-) complex in the K2ZnF4 layered perovskite have recently been analyzed using a parametrized Jahn-Teller model with an imposed strain [Reinen, D. Inorg. Chem.2012, 51, 4458]. Here, we present results of ab initio periodic supercell and cluster calculations on K2ZnF4:Cu(2+), showing unequivocally that the actual origin of the unusual compressed geometry of the CuF6(4-) complex along the crystal c axis in that tetragonal lattice is due to the presence of an electric field due to the crystal surrounding the impurity. Our calculations closely reproduce the experimental optical spectrum. The calculated values of the equilibrium equatorial and axial Cu(2+)-F(-) distances are, respectively, R(ax) = 193 pm and R(eq) = 204 pm, and so the calculated distortion R(ax) - R(eq) = 11 pm is three times smaller than the estimated through the parametrized Jahn-Teller model. As a salient feature, we find that if the CuF6(4-) complex would assume a perfect octahedral geometry (R(ax) = R(eq) = 203 pm) the antibonding a(1g)*(â¼3z(2) - r(2)) orbital is placed above b(1g)*(â¼x(2) - y(2)) with a transition energy E((2)A(1g) â (2)B(1g)) = 0.34 eV. This surprising fact stresses that about half the experimental value E((2)A(1g) â (2)B(1g)) = 0.70 eV is not due to the small shortening of the axial Cu(2+)-F(-) distance, but it comes from the electric field, E(R)(r), created by the rest of the lattice ions on the CuF6(4-) complex. This internal field, displaying tetragonal symmetry, is thus responsible for the compressed geometry in K2ZnF4:Cu(2+) and the lack of symmetry breaking behind the ligand relaxation. Moreover, we show that the electronic energy gain in this process comes from bonding orbitals and not from antibonding ones. The present results underline the key role played by ab initio calculations for unveiling all the complexity behind the properties of the model system K2ZnF4:Cu(2+), opening at the same time a window for improving our knowledge on d(9), d(7), or d(4) ions in other layered compounds.
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Despite its relevance, the microscopic origin of the energy barrier, B, between the compressed and elongated geometries of Jahn-Teller (JT) systems is not well understood yet because of a lack of quantitative data about its various contributions. Seeking to clear up this matter, we have carried out both periodic and cluster ab initio calculations on the model system NaCl:Ni(+). This system is particularly puzzling because, according to experimental data, its barrier is much smaller than that for other d(9) and d(7) ions in similar lattices. All calculations performed on the model system lead, in fact, to values |B| ≤ 160 cm(-1), which are certainly smaller than B = 500 cm(-1) derived for NaCl:M(2+) (M = Ag, Rh) or B = 1024 cm(-1) obtained for KCl:Ag(2+). As a salient feature, analysis of calculations carried out as a function of the Qθ (â¼3z(2) - r(2)) coordinate unveils the microscopic origin of the barrier. It is quantitatively proven that the elongated geometry observed for NaCl:Ni(+) is due to the 3d-4s vibronic admixture, which is slightly larger than the anharmonicity in the eg JT mode that favors a compressed geometry. The existence of these two competing mechanisms explains the low value of B for the model system, contrary to cases where the complex formed by d(9) or d(7) ions is elastically decoupled from the host lattice. Although the magnitude of B for NaCl:Ni(+) is particularly small, the tunneling splitting, 3Γ, is estimated to be below 9 cm(-1), thus explaining why the coherence is easily destroyed by random strains and thus a static JT effect is observed experimentally. As a main conclusion, the barrier in JT systems cannot be understood neglecting the tiny changes of the electronic density involved in small distortions. The present calculations reasonably explain the experimental g tensor of NaCl:Ni(+), pointing out that the d-d transitions in NiCl6(5-) are much smaller than those for CuCl6(4-) and the optical electronegativity of Ni(+) is only around 1.
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Despite the importance of vacancies over the properties of insulating oxides its influence on neighboring transition metal ions is far from being understood. This work is devoted to find the origin of various up to now unexplained properties of chromium bounded either to a <100> or a <110> Mg(2+) vacancy in MgO. In these model systems particular attention is paid to understand, by means of ab initio calculations, why the cubic field splitting parameter, 10Dq, is surprisingly 1600 cm(-1) higher for a <100> than for a <110> vacancy, a fact behind the suppression of the sharp (2)E â (4)A2 luminescence in the latter case. Our calculations, which reproduce the main experimental facts, prove that the average Cr(3+)-O(2-) distance is the same within 0.8% for both systems, and thus, the low 10Dq value for a <110> vacancy is shown to be due mainly to the electrostatic potential from the missing Mg(2+) ion, which increases the energy of antibonding t(2g) (â¼xy, xz, yz) levels. By contrast, for a <100> Mg(2+) vacancy that potential provides a supplementary increase of the e(g) (â¼x(2) - y(2), 3z(2 )- r(2)) level energy and thus of 10Dq. The existence of the (2)E â (4)A2 luminescence for Cr(3+)-doped MgO under perfect cubic symmetry or with a <100> vacancy is shown to be greatly helped by the internal electric field created by the rest of the lattice ions on the CrO6(9-) unit, whose importance is usually ignored. The present results underline the role of ab initio calculations for unveiling the subtle effects induced by a close vacancy on the properties of transition metal ions in oxides. At the same time they stress the failure of the empirical superposition model for deriving the equilibrium geometry of C4v and C2v centers in MgO:Cr(3+).
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The complete genome of a severe isolate of Cucumber vein yellowing virus (CVYV) from Jordan was sequenced. Comparison with the genome of a Spanish CVYV isolate inducing very mild symptoms in cucumber cultivars revealed a nucleotide identity of 94% for the complete genome and an amino acid identity of 96% for the coding region. Comparison of synonymous and non-synonymous substitutions suggested a negative selection at amino acid and nucleotide levels with different degrees depending on the different coding regions. Finally, specific amino acid changes in the zinc finger domain of P1b and in the P1-P3 proteolytic site were found which could be involved in the virulence of CVYV.
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Cucumis sativus/virologia , Genoma Viral , Doenças das Plantas/virologia , Potyviridae/genética , Potyviridae/isolamento & purificação , Sequência de Bases , Jordânia , Dados de Sequência Molecular , Filogenia , Potyviridae/classificaçãoRESUMO
The origin of the spectrochemical series and the different dependence of crystal-field splitting (10Dq) and Racah parameters on the metal-ligand distance, R, is explored through ab initio calculations on Cr(3+)-doped K2NaScF6, Cs2NaYCl6, Cs2NaYBr6, and Cs2NaYI6 lattices. For this purpose both periodic and cluster calculations have been performed. An analysis of ab initio results proves that 10Dq values mostly come from the small admixture of deep nLs ligand orbitals present in the antibonding eg(â¼ x(2)-y(2),3z(2)-r(2)) level and not from the dominant covalency with valence nLp ligand orbitals, which is actually responsible for the reduction of Racah parameters. This study thus reveals the microscopic origin of the stronger dependence upon R of 10Dq when compared to that observed for Racah parameters, thus explaining why electronic transitions which are 10Dq-independent give rise to sharp optical bands. As a salient feature, while the covalency with nLp levels increases significantly on passing from CrF6(3-) to CrI6(3-), the nLs admixture in eg is found to be practically unmodified. This fact helps to understand the progressive decrease of 10Dq through the series of CrF6(3-), CrCl6(3-), CrBr6(3-), and CrI6(3-) complexes embedded in the corresponding host lattices when compared at the corresponding equilibrium distance at zero pressure. The growing importance of the nLs admixture is well-depicted using deformation density diagrams on passing from the ground state (4)A2(t2g(3)) to the (4)T2(t2g(2)eg) excited state depicted at several R values.
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Ligantes , Metais/química , Algoritmos , Fenômenos Eletromagnéticos , Modelos Químicos , Teoria QuânticaRESUMO
This work is aimed at clarifying the changes on optical spectra of Cr(3+) impurities due to either a host lattice variation or a hydrostatic pressure, which can hardly be understood by means of the usual Tanabe-Sugano (TS) approach assuming that the Racah parameter, B, grows when covalency decreases. For achieving this goal, the optical properties of Cr(3+)-doped LiBaF(3) and KMgF(3) model systems have been explored by means of high level ab initio calculations on CrF(6)(3-) units subject to the electric field, E(R)(r), created by the rest of the lattice ions. These calculations, which reproduce available experimental data, indicate that the energy, E((2)E), of the (2)E(t(2g)(3)) â (4)A(2)(t(2g)(3)) emission transition is nearly independent of the host lattice. By contrast, the energy difference corresponding to (4)A(2)(t(2g)(3)) â (4)T(1)(t(2g)(2)e(g)(1)) and (4)A(2)(t(2g)(3)) â (4)T(2)(t(2g)(2)e(g)(1)) excitations, Δ((4)T(1); (4)T(2)), is shown to increase on passing from the normal to the inverted perovskite host lattice despite the increase in covalency, a fact which cannot be accounted for through the usual TS model. Similarly, when the Cr(3+)-F(-) distance, R, is reduced both Δ((4)T(1); (4)T(2)) and the covalency are found to increase. By analyzing the limitations of the usual model, we found surprising results that are shown to arise from the deformation of both 3d(Cr) and ligand orbitals in the antibonding e(g) orbital, which has a σ character and is more extended than the π t(2g) orbital. By contrast, because of the higher stiffness of the t(2g) orbital, the dependence of E((2)E) with R basically follows the corresponding variation of covalency in that level. Bearing in mind the similarities of the optical properties displayed by Cr(3+) impurities in oxides and fluorides, the present results can be useful for understanding experimental data on Cr(3+)-based gemstones where the local symmetry is lower than cubic.
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Cromo/química , Fluoretos/química , Óxidos/química , Teoria QuânticaRESUMO
INTRODUCTION: Athletes training is often associated with morphological changes in the heart. In this sense, the ventricular pressure-volume (PV) relation provides a complete characterization of cardiac pump performance. Regarding the arterial system (AS), arterial wall viscosity is a source of energy dissipation, that takes place during mechanical transduction. Left ventricular stroke work (SW) constitutes the useful fraction of ventricular energy that is delivered to the AS. OBJECTIVE: Left ventricular PV-loops were evaluated in terms of AS viscous property, by means of the interaction of two SW components (Stroke Work Damping Ratio, SWDR), both in untrained and trained subjects. MATERIAL AND METHODS: Fourteen healthy individuals (seven trained) were noninvasively evaluated in terms of echocardiographic and aortic pressure measurements. RESULTS: SWDR was observed to be increased in trained subjects. CONCLUSION: SWDR was evaluated in trained individuals, being increased in comparison with the non-trained group. This effect is a consequence of a significant increase of SWD, which could be related with the viscous mechanical property of AS.
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Acidente Vascular Cerebral , Função Ventricular Esquerda , Atletas , Ecocardiografia , Humanos , Volume SistólicoRESUMO
INTRODUCTION: Left ventricular (LV) interaction with the arterial system (arterial-ventricular coupling, AVC) is a central determinant of cardiovascular performance and cardiac energetics. Stress Echocardiography (SE) constitutes a valuable clinical tool in both diagnosis and risk stratification of patients with suspected and established coronary artery disease. Cluster Analysis (CA), an unsupervised Machine Learning technique, defines an exploratory statistical method which can be used to uncover natural groups within data. OBJECTIVE: To evaluate the capacity of CA to identify uncoupled groups with ischemic condition based on SE baseline information. MATERIAL AND METHODS: CA was applied to SE data acquired at baseline and peak exercise (PE) conditions. Obtained clusters were evaluated in terms of coupling conditions and LV wall motility alterations. RESULTS: Inter cluster significant AVC differences were obtained in terms of baseline data and changes in wall motility, confirmed by CA applied to PE data. CONCLUSION: AVC impairment was evidenced in both normal and ischemic subjects by applying CA.
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Artérias , Ventrículos do Coração , Análise por Conglomerados , Exercício Físico , Ventrículos do Coração/diagnóstico por imagem , HumanosRESUMO
The putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer (NK) cells have not been elucidated. We report here that the nuclear factor of activated T cells (NFATp), a cyclosporin A (CsA)-sensitive factor that regulates the transcription of several cytokines, mediates CD16-induced activation of cytokine genes in human NK cells. CD16 (Fc gamma RIIIA)-induced expression of cytokine mRNA in NK cells occurs via a CsA-sensitive and Ca(2+)-dependent mechanism. Stimulation of NK cells with CD16 ligands induces NFAT-like DNA binding activity in the nuclear extracts from these cells, as detected in electrophoretic mobility shift assays. This occurs with fast kinetics after stimulation, via a CsA-sensitive and Ca(2+)-dependent mechanism that does not require de novo protein synthesis. NK cell NFAT is present in the cytosol of nonstimulated cells, migrates to the nucleus upon stimulation, and can associate with AP-1. Two distinct molecules, NFATp and NFATc, have been reported to mediate NFAT activity. The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily, if not exclusively, NFATp, and Western blot analysis shows that this has the same electrophoretic mobility (approximately 120 kD) as that of T lymphocytes. NK cells do not express NFATc constitutively, but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands. However, supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester-stimulated cells at any time tested, up to 4 h. These results provide the first direct evidence that both CsA-sensitive transcription factors, NFATp and NFATc, are expressed in human NK cells, and that their activation and/or expression can be regulated in primary cells by a single stimulus, that, in the case of CD16 in NK cells, results in early activation of NFATp and subsequently induced expression of NFATc mRNA.
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Proteínas de Ligação a DNA/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Proteínas Nucleares , Receptores de IgG/fisiologia , Fatores de Transcrição/biossíntese , Animais , Anticorpos Monoclonais/farmacologia , Complexo Antígeno-Anticorpo/imunologia , Linfócitos B , Sequência de Bases , Linhagem Celular Transformada , Chlorocebus aethiops , Ciclosporina/farmacologia , Citocinas/biossíntese , Citocinas/genética , Proteínas de Ligação a DNA/genética , Humanos , Interleucina-12/farmacologia , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Leucemia-Linfoma de Células T do Adulto/patologia , Ligantes , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Dados de Sequência Molecular , Fatores de Transcrição NFATC , Fatores de Transcrição/genética , Células Tumorais CultivadasRESUMO
We have recently described a novel glycoprotein, Kp43, expressed on the surface of human natural killer (NK) cells that appears to regulate their functional activity. In this report, signaling mechanisms through the Kp43 surface antigen have been studied. Incubation of interleukin 2 (IL-2)-treated NK cells with anti-Kp43 monoclonal antibody F(ab')2 fragments resulted in the time- and dose-dependent stimulation of NK cell phospholipase D. Phospholipase D activation through the Kp43 surface antigen was found to take place in the absence of polyphosphoinositide turnover and appeared not to depend on the presence of Ca2+ in the extracellular medium. On the other hand, signaling mechanisms through the CD16 receptor (FcR-III) on NK cells were comparatively studied. Stimulation of IL-2-treated NK cells with anti-CD16 monoclonal antibody F(ab')2 fragment also resulted in time- and dose-dependent activation of phospholipase D. However, CD16-triggered phospholipase D activation took place concomitant to phospholipase C-mediated polyphosphoinositide breakdown and showed a strong dependence on extracellular Ca2+. These results provide, to our knowledge, the first evidence for the presence of activatable phospholipase D in NK cells, as well as the first indication that distinct receptor-modulated pathways exist for activation of phospholipase D within the same cell type. On the other hand, phosphatidic acid, the physiologic product of phospholipase D action on phospholipids, was found to mimic the effect of anti-Kp43 monoclonal antibody regarding tumor necrosis factor alpha (TNF-alpha) biosynthesis and secretion by NK cells. Addition of phosphatidic acid vesicles to IL-2-treated NK cell cultures stimulated a TNF-alpha production that was abolished when the cells were previously treated with actinomycin D. Other phospholipids, including lysophosphatidic acid, were ineffective. However, phosphatidic acid-induced TNF-alpha production was strongly inhibited by the presence of propranolol, an inhibitor of phosphatidic acid phosphohydrolase. Moreover, in cells responding to phorbol myristate acetate, a compound that triggers activation of phospholipase D, TNF-alpha synthesis was also inhibited by propranolol. Thus, these data suggest a second messenger role for phosphatidic acid-derived diradylglycerol in the induction of TNF-alpha gene expression.
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Antígenos de Diferenciação/fisiologia , Antígenos de Superfície/fisiologia , Células Matadoras Naturais/metabolismo , Fosfolipase D/fisiologia , Receptores Fc/fisiologia , Fator de Necrose Tumoral alfa/biossíntese , Cálcio/fisiologia , Células Cultivadas , Diglicerídeos/biossíntese , Ativação Enzimática , Humanos , Interleucina-2/farmacologia , Ácidos Fosfatídicos/biossíntese , Receptores de IgGRESUMO
The magnitude of tunneling splitting, 3Gamma, that governs decoherence in quantum systems under symmetric potentials, is frequently unknown. Using first-principles calculations, we have obtained 3Gamma for a number of E[symbol:see text]e Jahn-Teller impurities in solids. Calculated values span 6 orders of magnitude on passing from KCl:Ag{2+} to MgO:Cu{2+}. Values associated with Cu2+- and Ag2+-doped MgO are 2 orders of magnitude larger than those previously assumed and consistent with the existence of a dynamic Jahn-Teller effect. The origin and enhancement with pressure of these high 3Gamma values is discussed in detail.
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INTRODUCTION: Arterial-ventricular coupling (AVC) has been recognized as a key determinant of global cardiovascular performance. Diastolic dysfunction (DD) occurs when inadequate filling of the ventricles is related to an abnormal elevation of intracardiac filling pressures. In some cases, DD is evidenced during cardiac stress, provoked by exercise. OBJECTIVE: To evaluate AVC in individuals with stress evidenced DD, in relation to controls. MATERIALS AND METHODS: Stress echocardiography was applied to assess cardiac function during exercise. Arterial-ventricular coupling was evaluated, based on the assessment of left ventricular and arterial elastances. RESULTS: AVC showed a significant difference at peak exercise compared to controls, basically due to a loss of cardiac contractility. CONCLUSION: The manifestation of AVC coupling imbalance could act as a complementary parameter to support the diagnosis of DD.
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Artérias , Ventrículos do Coração , Exercício Físico , Humanos , Contração Miocárdica , Projetos PilotoRESUMO
The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.
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Calcineurina/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Imunossupressores/farmacologia , Proteínas Nucleares , Oligopeptídeos/farmacologia , Peptídeos/farmacologia , Linfócitos T/efeitos dos fármacos , Fatores de Transcrição/antagonistas & inibidores , Sequência de Aminoácidos , Sítios de Ligação , Inibidores de Calcineurina , Núcleo Celular/metabolismo , Ciclosporina/farmacologia , Citocinas/biossíntese , Citocinas/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células HeLa , Humanos , Imunossupressores/química , Imunossupressores/metabolismo , Células Jurkat , Dados de Sequência Molecular , Fatores de Transcrição NFATC , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Biblioteca de Peptídeos , Peptídeos/química , Peptídeos/metabolismo , Fosforilação , Proteínas Recombinantes de Fusão/metabolismo , Linfócitos T/imunologia , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , TransfecçãoRESUMO
In the recent study of Cu(2+)-doped BaF(2) Hoffmann et al. demonstrated using electron paramagnetic resonance spectroscopy that the Cu(2+) impurity experiences an off-center shift from the substitutional position and ascribe this distortion to the Jahn-Teller effect. In this comment, we propose that the off-center distortion observed for BaF(2):Cu(2+) is driven by pseudo-Jahn-Teller interactions which are qualitatively different and in competition with the usual Jahn-Teller effect. It is also stressed that off-center phenomena in a given host lattice are not necessarily enhanced by decreasing the ionic radius of the impurity.