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1.
Acta Neurochir (Wien) ; 165(9): 2533-2539, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37347295

RESUMO

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is based on clinical, radiological, and hydrodynamic data of cerebrospinal fluid (CSF) obtained by invasive methods such as lumbar infusion test, which is used to determine the resistance to CSF outflow (Rout). However, Rout has limitations, and its value as predictor of valve response is questioned. Other variables can be obtained by lumbar infusion test, such as the time to reach the plateau (TRP) and the slope until reaching the plateau (SRP). The objectives were to determine if SRP could be a predictor of response to ventriculoperitoneal shunt (VPS) and what variable (Rout versus SRP) would have greater predictive value. METHOD: Patients with probable iNPH who underwent a lumbar infusion test and were indicated for a VPS were retrospectively studied. Two groups were established, responders and non-responders. Rout, TRP (period between the start of infusion until reaching the plateau measured in seconds) and SRP ((plateau pressure-opening pressure)/TRP) were obtained. For Rout and SRP, the receiver operating curves (ROC) with its areas under the curve (AUC) were calculated. RESULTS: One hundred ten patients were included, being 86 responders (78.20%). Shunt responders had a significantly greater Rout (17.02 (14.45-20.23) versus 13.34 (12.10-16.28) mmHg/ml/min, p = 0.002) and SRP (0.049 (0.043-0.054) versus 0.031 (0.026-0.036) mmHg/sec, p < 0.001) and smaller TRP (641.28 (584.83-697.73) versus 777.65 (654.03-901.27) sec, p = 0.028) than non-responders. The AUC for SRP was greater than the AUC for Rout (0.763 (95 % CI 0.655-0.871, p < 0.001) versus 0.673 (95 % CI 0.595-0.801, p = 0.008), respectively), but the differences were not significant (p = 0.180). CONCLUSIONS: SRP could be considered predictor of response to VPS, and its accuracy tends to be better than Rout. So, this variable may be a useful tool to select shunt candidates among patients with probable iNPH.


Assuntos
Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Estudos Retrospectivos , Derivações do Líquido Cefalorraquidiano/métodos , Próteses e Implantes , Catéteres
2.
Opt Express ; 24(22): 25565-25581, 2016 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-27828494

RESUMO

A spatio-temporal analysis of non-degenerate two-wave mixing in a saturable absorber, such as bacteriorhodopsin (bR) film, is performed. To do this, a theoretical model describing the temporal variation of the intensities is developed by taking into account the dielectric constant as a function of bR population. A good agreement between theory and experimental measurements is obtained. Thus, the dependence of the optical gain and the main dielectric constant parameters are studied at different intensities and frequencies. As a result, the best intensity-frequency zones where higher coupling is reached are proposed, and it is also demonstrated that non-uniform patterns, which evolve over time as a function of frequency difference, can be observed.


Assuntos
Bacteriorodopsinas , Luz , Modelos Teóricos , Análise Espaço-Temporal
3.
Opt Express ; 23(16): 20529-39, 2015 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-26367905

RESUMO

We analyze particle dynamics in an optical force field generated by helical tractor beams obtained by the interference of a cylindrical beam with a topological charge and a co-propagating temporally de-phased plane wave. We show that, for standard experimental conditions, it is possible to obtain analytical solutions for the trajectories of particles in such force field by using of some approximations. These solutions show that, in contrast to other tractor beams described before, the intensity becomes a key parameter for the control of particle trajectories. Therefore, by tuning the intensity value the particle can describe helical trajectories upstream and downstream, a circular trajectory in a fixed plane, or a linear displacement in the propagation direction. The approximated analytical solutions show good agreement to the corresponding numerical solutions of the exact dynamical differential equations.

4.
Opt Express ; 22(3): 3284-95, 2014 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-24663619

RESUMO

We theoretically study the three-dimensional behavior of nanoparticles in an active optical conveyor. To do this, we solved the Langevin equation when the forces are generated by a focusing system at the near field. Analytical expressions for the optical forces generated by the optical conveyor were obtained by solving the Richards and Wolf vectorial diffraction integrals in an approximated form when a mask of two annular pupils is illuminated by a radially polarized Hermite-Gauss beam. Trajectories, in both the transverse plane and the longitudinal direction, are analyzed showing that the behavior of the optical conveyor can be optimized by conveniently choosing the configuration of the mask of the two annular pupils (inner and outer radius of the two rings) in order to trap and transport all particles at the focal plane.


Assuntos
Iluminação/instrumentação , Micromanipulação/instrumentação , Modelos Teóricos , Pinças Ópticas , Refratometria/instrumentação , Simulação por Computador , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Iluminação/métodos , Espalhamento de Radiação , Estresse Mecânico
5.
Opt Express ; 22(10): 11600-9, 2014 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-24921281

RESUMO

Time-delay of transmitted pulses with respect to the incident pulse in bacteriorhodopsin films has been studied without the use of a pump beam. Based on a modified saturable absorber model, analytical expressions of the transmitted pulse have been obtained. As a result, time delay, distortion and fractional delay have been analyzed for sinusoidal pulses with a low background. A good agreement between theory and experiences has been observed.


Assuntos
Bacteriorodopsinas/metabolismo , Biofísica/instrumentação , Transferência de Energia , Modelos Estatísticos , Fotoquímica/métodos , Espalhamento de Radiação , Desenho de Equipamento , Luz , Teste de Materiais , Propriedades de Superfície , Temperatura
6.
J Opt Soc Am A Opt Image Sci Vis ; 30(4): 733-40, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23595335

RESUMO

We present a complete electromagnetic study, which includes electric, magnetic, and Poynting vector fields of diffracted convergent spherical waves under all possible polarization states compatible with Maxwell's equations. Exit pupil boundary conditions for these polarizations were obtained by means of Hertz potentials. Using these boundary conditions, two-dimensional Luneburg diffraction integrals for the three components of electric and magnetic fields were formulated, and after some approximations, we showed that the complete electromagnetic description of the inhomogeneous polarization states of spherical waves is reduced to the knowledge of seven one-dimensional integrals. The consistency of the method was tested by comparison with other previously reported methods for linearly polarized (LP), TE, and TM polarizations, while the versatility of the method was showed with the study of nonstandard polarization states, for example, that resulting from the superposition of TE and TM dephased spherical waves, which shows a helicoidal behavior of the Poynting vector at the focalization region, or the inhomogeneous LP state that exhibits a ring structure for the Poynting vector at the focal plane.

7.
Neurocirugia (Astur : Engl Ed) ; 34(5): 238-246, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-36931931

RESUMO

BACKGROUND AND OBJECTIVE: Intraoperative neurophysiological monitoring allows us to predict the functional status of the facial nerve after vestibular schwannoma surgery. Due to the great variability of the neurophysiological protocols used for it, the goal of this study is to determine the prognostic ability of our neurophysiological protocol. MATERIAL AND METHODS: We have performed a statistical analysis of the neurophysiological monitoring data collected from patients operated between March 2009 and July 2021 at the Neurosurgery Service of Salamanca according to their functional status, both in the immediate post-surgical period and one year after surgery. RESULTS: A number of 51 patients between 46 and 63 years old (median: 54) were analyzed. We have found significant differences studying the threshold value of the stimulation intensity of the facial nerve and the variation of the Cortico-bulbar Evoked Motor Potentials (P=0.043 and P=0.011, respectively) between the patients with good and bad clinical situation after surgery. The most discriminating intensity threshold value was 0.35mA (Sensitivity: 85%; Specificity: 48%). No statistical relationship was found in the study group one year after surgery. CONCLUSIONS: Our intraoperative monitoring protocol allows us to predict the clinical situation of patients in the immediate postoperative period and improve information for the patient and her relatives after surgery. We cannot, however, use these parameters to predict the functional situation one year after surgery and make clinical decisions in this regard.


Assuntos
Traumatismos do Nervo Facial , Paralisia Facial , Monitorização Neurofisiológica Intraoperatória , Neuroma Acústico , Feminino , Humanos , Pessoa de Meia-Idade , Paralisia Facial/diagnóstico , Paralisia Facial/etiologia , Monitorização Neurofisiológica Intraoperatória/métodos , Prognóstico , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Período Pós-Operatório
8.
J Biol Chem ; 286(21): 19065-75, 2011 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-21474444

RESUMO

Potassium channels encoded by the human ether-à-go-go-related gene (hERG) contribute to cardiac repolarization as a result of their characteristic gating properties. The hERG channel N terminus acts as a crucial determinant in gating. It is also known that the S4-S5 linker couples the voltage-sensing machinery to the channel gate. Moreover, this linker has been repeatedly proposed as an interaction site for the distal portion of the N terminus controlling channel gating, but direct evidence for such an interaction is still lacking. In this study, we used disulfide bond formation between pairs of engineered cysteines to demonstrate the close proximity between the beginning of the N terminus and the S4-S5 linker. Currents from channels with introduced cysteines were rapidly and strongly attenuated by an oxidizing agent, this effect being maximal for cysteine pairs located around amino acids 3 and 542 of the hERG sequence. The state-dependent modification of the double-mutant channels, but not the single-cysteine mutants, and the ability to readily reverse modification with the reducing agent dithiothreitol indicate that a disulfide bond is formed under oxidizing conditions, locking the channels in a non-conducting state. We conclude that physical interactions between the N-terminal-most segment of the N terminus and the S4-S5 linker constitute an essential component of the hERG gating machinery, thus providing a molecular basis for previous data and indicating an important contribution of these cytoplasmic domains in controlling its unusual gating and hence determining its physiological role in setting the electrical behavior of cardiac and other cell types.


Assuntos
Canais de Potássio Éter-A-Go-Go/metabolismo , Ativação do Canal Iônico/fisiologia , Substituição de Aminoácidos , Animais , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go/genética , Humanos , Mutação de Sentido Incorreto , Estrutura Terciária de Proteína , Xenopus laevis
9.
Pflugers Arch ; 463(5): 685-702, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22415214

RESUMO

While the thyrotropin-releasing hormone (TRH) effect of raising intracellular Ca(2+) levels has been shown to rely on G(q/11) and PLC activation, the molecular mechanisms involved in the regulation of ERG K(+) channels by TRH are still partially unknown. We have analysed the effects of ßγ scavengers, Akt/PKB inactivation, and TRH receptor (TRH-R) overexpression on such regulation in native and heterologous expression cell systems. In native rat pituitary GH(3) cells ß-ARK/CT, Gα(t), and phosducin significantly reduced TRH inhibition of rERG currents, whereas in HEK-H36/T1 cells permanently expressing TRH-R and hERG, neither of the ßγ scavengers affected the TRH-induced shift in V (1/2). Use of specific siRNAs to knock Akt/PKB expression down abolished the TRH effect on HEK-H36/T1 cell hERG, but not on rERG from GH(3) cells. Indeed, wortmannin or long insulin pretreatment also blocked TRH regulation of ERG currents in HEK-H36/T1 but not in GH(3) cells. To determine whether these differences could be related to the amount of TRH-Rs in the cell, we studied the TRH concentration dependence of the Ca(2+) and ERG responses in GH(3) cells overexpressing the receptors. The data indicated that independent of the receptor number additional cellular factor(s) contribute differently to couple the TRH-R to hERG channel modulation in HEK-H36/T1 cells. We conclude that regulation of ERG currents by TRH and its receptor is transduced in GH(3) and HEK-H36/T1 cell systems through common and different elements, and hence that the cell type influences the signalling pathways involved in the TRH-evoked responses.


Assuntos
Cálcio/metabolismo , Canais de Potássio Éter-A-Go-Go/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Animais , Sítios de Ligação , Células Cultivadas , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Subunidades beta da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Humanos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Transdução de Sinais
10.
Opt Express ; 20(23): 25497-512, 2012 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-23187367

RESUMO

The propagation of sinusoidal pulses in bacteriorhodopsin films has been theoretically analyzed using a complete study of the photoinduced processes that take into account all the physical parameters, the coupling of rate equations with the energy transfer equation and the temperature change during the experiment. The theoretical approach was compared to experimental data and a good concordance was observed. This theoretical treatment, can be widely applied, i.e when arbitrary pump and/or signal is used or in the case of the pump and signal beams have different wavelengths. Due to we have performed a rigorous analysis, from this treatment the corresponding two level approximation has also been analyzed for these systems.


Assuntos
Bacteriorodopsinas/metabolismo , Biofísica/métodos , Transferência de Energia , Desenho de Equipamento , Luz , Teste de Materiais , Matemática , Modelos Estatísticos , Conformação Molecular , Fotoquímica/métodos , Espalhamento de Radiação , Propriedades de Superfície , Temperatura , Fatores de Tempo
11.
Micromachines (Basel) ; 13(2)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35208403

RESUMO

We theoretically analyze the methodology for obtaining vectorial three-dimensional bullets, concretely Airy-Gauss bullets. To do this, binary micro zonal plates (BZP) were designed in order to obtain different Airy-Gauss bullets with sub-diffraction main lobe width. Following the vectorial diffraction theory, among the electrical field, we extend the theory to the magnetic field, and thus we analyze several properties such as the Poynting vector and the energy of Airy-Gauss vectorial bullets generated by illuminating the designed BZP with a temporal Gaussian circular polarized pulses.

12.
Neurocirugia (Astur : Engl Ed) ; 33(3): 120-129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34217635

RESUMO

BACKGROUND AND OBJECTIVE: To study the prognostic value of the resistance to the cerebrospinal fluid outflow (Rout) obtained in the lumbar infusion test in idiopathic normal pressure hydrocephalus (iNPH), as well as the pulse pressure amplitudes in the different periods of the test and other new variables extracted by Neuropicture® software. MATERIAL AND METHODS: Patients with 'probable iNPH' who underwent a lumbar infusion test were retrospectively revised. The positive predictive values (PPV) of the cutoff point of the best prognostic accuracy of the Rout, the basal pulse pressure amplitude (AMPo), the pulse pressure amplitude during the first 10 min (AMP10min), the plateau pulse pressure amplitude (AMPmes), the Rout pulse pressure amplitude (AMPRout), the time to reach the plateau (T), and the slope until reaching the plateau were determined. Patients were categorized either as responders or non-responders. RESULTS: The study included 64 responders patients and 16 non-responders patients. The PPV of Rout > 15 mmHg/mL/min was 91.7%; AMPo > 2.34 mmHg: 91.3%; AMP10 min > 4.34 mmHg: 83.3%; AMPmes > 12.44 mmHg: 84.6%; AMPRout > 6.34 mmHg: 85%; T < 634 s: 86.7%; p > 0.040 mmHg/s: 96.3%. CONCLUSIONS: Rout is a valid criterion to indicate a ventricular shunt. Pulse pressure amplitudes in the different periods of the lumbar infusion test, in addition to T and P, are other variables whose positivity is indicative of shunt response and should be considered in the diagnostic protocol of the iNPH.


Assuntos
Hidrocefalia de Pressão Normal , Monofosfato de Adenosina , Pressão Sanguínea , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Pressão Intracraniana/fisiologia , Prognóstico , Estudos Retrospectivos
13.
Struct Dyn ; 9(6): 064301, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36389279

RESUMO

In the present contribution, we use x-rays to monitor charge-induced chemical dynamics in the photoionized amino acid glycine with femtosecond time resolution. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x-ray pulses track the induced coherence through resonant x-ray absorption that induces Auger decay. Temporal modulation of the Auger electron signal correlated with specific ions is observed, which is governed by the initial electronic coherence and subsequent vibronic coupling to nuclear degrees of freedom. In the time-resolved x-ray absorption measurement, we monitor the time-frequency spectra of the resulting many-body quantum wave packets for a period of 175 fs along different reaction coordinates. Our experiment proves that by measuring specific fragments associated with the glycine dication as a function of the pump-probe delay, one can selectively probe electronic coherences at early times associated with a few distinguishable components of the broad electronic wave packet created initially by the pump pulse in the cation. The corresponding coherent superpositions formed by subsets of electronic eigenstates and evolving along parallel dynamical pathways show different phases and time periods in the range of ( - 0.3 ± 0.1 ) π ≤ ϕ ≤ ( 0.1 ± 0.2 ) π and 18.2 - 1.4 + 1.7 ≤ T ≤ 23.9 - 1.1 + 1.2 fs. Furthermore, for long delays, the data allow us to pinpoint the driving vibrational modes of chemical dynamics mediating charge-induced bond cleavage along different reaction coordinates.

14.
Opt Express ; 19(8): 7094-105, 2011 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-21503022

RESUMO

We present a holographic system that can be used to manipulate the group velocity of light pulses. The proposed structure is based on the multiplexing of two sequential holographic volume gratings, one in transmission and the other in reflection geometry, where one of the recording beams must be the same for both structures. As in other systems such as grating induced transparency (GIT) or coupled-resonator-induced transparency (CRIT), by using the coupled wave theory it is shown that this holographic structure represents a classical analogue of the electromagnetically induced transparency (EIT). Analytical expressions were obtained for the transmittance induced at the forbidden band (spectral hole) and conditions where the group velocity was slowed down were analyzed. Moreover, the propagation of Gaussian pulses is analyzed for this system by obtaining, after further approximations, analytical expressions for the distortion of the transmitted field. As a result, we demonstrate the conditions where the transmitted pulse is slowed down and its shape is only slightly distorted. Finally, by comparing with the exact solutions obtained, the range of validity of all the analytical formulae was verified, demonstrating that the error is very low.

15.
Sci Rep ; 11(1): 8073, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850198

RESUMO

Focusing systems with high numerical aperture can be used to convert spin angular momentum into orbital angular momentum with efficiencies of 50%, while for low numerical apertures this conversion vanishes. In this paper, based on the properties of binary Fresnel zone plates, we propose a structure that is achieved by making an accurate selection of the width and the depth of the rings. This allows us to obtain a large increase in the spin to orbital angular momentum conversion of the resulting focusing fields, and it also has the special characteristic that the obtained conversion is higher for low numerical aperture structures, where standard focusing systems do not work. The ability of the system to perform this extraordinary conversion is demonstrated by FDTD methods and an analytical model developed using a combination of guided mode theory for the structure and Stratton-Chu diffraction theory.

16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33875381

RESUMO

BACKGROUND AND OBJECTIVE: To study the prognostic value of the resistance to the cerebrospinal fluid outflow (Rout) obtained in the lumbar infusion test in idiopathic normal pressure hydrocephalus (iNPH), as well as the pulse pressure amplitudes in the different periods of the test and other new variables extracted by Neuropicture® software. MATERIAL AND METHODS: Patients with ́probable iNPH́ who underwent a lumbar infusion test were retrospectively revised. The positive predictive values (PPV) of the cutoff point of the best prognostic accuracy of the Rout, the basal pulse pressure amplitude (AMP0), the pulse pressure amplitude during the first 10minutes (AMP10min), the plateau pulse pressure amplitude (AMPmes), the Rout pulse pressure amplitude (AMPRout), the time to reach the plateau (T), and the slope until reaching the plateau were determined. Patients were categorized either as responders or non-responders. RESULTS: The study included 64 responders patients and 16 non-responders patients. The PPV of Rout> 15mmHg/ml/min was 91.7%; AMP0> 2.34mmHg: 91.3%; AMP10min>4.34mmHg: 83.3%; AMPmes>12.44mmHg: 84.6%; AMPRout>6.34mmHg: 85%; T <634seconds: 86.7%; P>0.040mmHg/sec: 96.3%. CONCLUSIONS: Rout is a valid criterion to indicate a ventricular shunt. Pulse pressure amplitudes in the different periods of the lumbar infusion test, in addition to T and P, are other variables whose positivity is indicative of shunt response and should be considered in the diagnostic protocol of the iNPH.

17.
Neurocirugia (Astur : Engl Ed) ; 32(2): 69-77, 2021.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32430242

RESUMO

Since the first report in 1954, abdominal pseudocysts have been recognized as a particularly uncommon complication of ventriculoperitoneal shunts of CSF, so their etiology, diagnosis, and therapeutic management remain very controversial. Our objective is to offer a critical and updated systematic review of those controversial points, using a thorough search and review of the most relevant literature available. The clinical presentation of pseudocysts is normally through non-specific abdominal symptoms. The most validated etiology consists on the existence of a concomitant infection of the CSF shunt system, and so, treatment needs of antibiotherapy and total or partial substitution of the system. However, the pseudocyst itself doesn't need an active treatment, except for some specific cases. This management, algorithmically presented in the present work, achieves a lower recurrence rate than other options, but this one is still important, and is also associated with other complications of those shunts related with several other factors which need to be taken in account.


Assuntos
Cistos , Hidrocefalia , Abdome , Cistos/etiologia , Cistos/cirurgia , Humanos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Recidiva Local de Neoplasia , Próteses e Implantes , Derivação Ventriculoperitoneal/efeitos adversos
18.
Brain Pathol ; 31(2): 365-380, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33314398

RESUMO

The distribution and role of tumor-infiltrating leucocytes in glioblastoma (GBM) remain largely unknown. Here, we investigated the cellular composition of 55 primary (adult) GBM samples by flow cytometry and correlated the tumor immune profile with patient features at diagnosis and outcome. GBM single-cell suspensions were stained at diagnosis (n = 44) and recurrence following radiotherapy and chemotherapy (n = 11) with a panel of 8-color monoclonal antibody combinations for the identification and enumeration of (GFAP+ CD45- ) tumor and normal astrocytic cells, infiltrating myeloid cells -i.e. microglial and blood-derived tumor-associated macrophages (TAM), M1-like, and M2-like TAM, neutrophils. and myeloid-derived suppressor cells (MDSC)- and tumor-infiltrating lymphocytes (TIL) -i.e. CD3+ T-cells and their TCD4+ , TCD8+ , TCD4- CD8- , and (CD25+ CD127lo ) regulatory (T-regs) subsets, (CD19+ CD20+ ) B-cells, and (CD16+ ) NK-cells-. Overall, GBM samples consisted of a major population (mean ± 1SD) of tumor and normal astrocytic cells (73% ± 16%) together with a significant but variable fraction of immune cells (24% ± 18%). Within myeloid cells, TAM predominated (13% ± 12%) including both microglial cells (10% ± 11%) and blood-derived macrophages (3% ± 5%), in addition to a smaller proportion of neutrophils (5% ± 9%) and MDSC (4% ± 8%). Lymphocytes were less represented and mostly included TCD4+ (0.5% ± 0.7%) and TCD8+ cells (0.6% ± 0.7%), together with lower numbers of TCD4- CD8- T-cells (0.2% ± 0.4%), T-regs (0.1% ± 0.2%), B-lymphocytes (0.1% ± 0.2%) and NK-cells (0.05% ± 0.05%). Overall, three distinct immune profiles were identified: cases with a minor fraction of leucocytes, tumors with a predominance of TAM and neutrophils, and cases with mixed infiltration by TAM, neutrophils, and T-lymphocytes. Untreated GBM patients with mixed myeloid and lymphoid immune infiltrates showed a significantly shorter patient overall survival versus the other two groups, in the absence of gains of the EGFR gene (p = 0.02). Here we show that immune cell infiltrates are systematically present in GBM, with highly variable levels and immune profiles. Patients with mixed myeloid and T-lymphoid infiltrates showed a worse outcome.


Assuntos
Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Neutrófilos/imunologia , Macrófagos Associados a Tumor/imunologia
19.
Chemphyschem ; 11(10): 2158-66, 2010 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-20533497

RESUMO

A new model is developed to describe the orientational order of dense molecular systems under an applied external electric field as a function of the n-particle distribution functions of a system under no external perturbation. From an approximation of this expression, the effects of several variables on this orientational order, such as the microscopic properties of the oriented molecules (the molecular geometry and multipole moments) and the solvent or matrix properties, are studied. The theoretical predictions show that, for a correct description of the orientational order, quadrupole and octupole moments must be included, as they play an important role in the orientational order achieved, depending on the molecular geometry. Furthermore, to verify the validity of the model, theoretical predictions are compared with experimental results, and show a good concordance.

20.
Biochim Biophys Acta ; 1783(10): 1681-99, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18634834

RESUMO

The intracellular N-terminus of human ether-a-go-go-related gene (HERG) potassium channels constitutes a key determinant of activation and deactivation characteristics and is necessary for hormone-induced modifications of gating properties. However, the general organization of the long amino and carboxy HERG terminals remains unknown. In this study we performed fluorescence resonance energy transfer (FRET) microscopy with a library of fluorescent HERG fusion proteins obtained combining site-directed and transposon-based random insertion of GFP variants into multiple sites of HERG. Determinations of FRET efficiencies with functional HERG channels labeled in different combinations localize the fluorophores, introduced in the amino and carboxy ends, in two quadratic planes of 7.8 and 8.6 nm lateral size, showing a vertical separation of nearly 8 nm without major angular torsion between the planes. Similar analysis using labels at positions 345 and 905 of the amino and carboxy terminals, located them slightly above the planes delimited by the amino and carboxy end labels, respectively. Our data also indicate an almost vertical arrangement of the fluorophores introduced in the NH(2) and COOH ends and at position 905, but a near 45 degrees angular rotation between the planes delimited by these labels and the 345-located fluorophores. Systematic triangulation using interfluorophore distances coming from multiply labeled channels provides an initial constraint on the overall in vivo arrangement of the HERG cytoplasmic domains, suggesting that the C-linker/CNBD region of HERG hangs centrally below the transmembrane core, with the initial portion of the amino terminus around its top and side surfaces directed towards the gating machinery.


Assuntos
Citoplasma/metabolismo , Canais de Potássio Éter-A-Go-Go/metabolismo , Animais , Linhagem Celular , Cricetinae , Canal de Potássio ERG1 , Eletrofisiologia , Canais de Potássio Éter-A-Go-Go/genética , Transferência Ressonante de Energia de Fluorescência , Expressão Gênica , Genes Reporter/genética , Humanos , Modelos Moleculares , Técnicas de Patch-Clamp , Estrutura Quaternária de Proteína , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
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