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1.
J Oral Rehabil ; 51(6): 1025-1033, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38475974

RESUMEN

BACKGROUND: Longitudinal intervention studies on treatment options in temporomandibular dysfunction (TMD) including self reports and salivary biomarkers of stress are rare and the exact therapeutic function of occlusal splints widely unknown. METHODS: We examined the therapeutic effects of a Michigan splint with occlusal relevance in patients with TMD using a placebo-controlled, delayed-start design. Two intervention groups received a Michigan splint, while one of them had a placebo palatine splint for the first 3 weeks. We collected pain intensities (at rest and after five occlusal movements), salivary measures associated with stress (cortisol and alpha-amylase) and self-reported psychological distress (stress, anxiety, catastrophizing) at baseline and 3 and 7 weeks after onset of intervention. RESULTS: At baseline, we observed increased pain intensity and psychological distress in TMD patients compared to 11 matched healthy controls. Baseline anxiety was linked to movement pain intensity through stress. Over therapy reductions in pain intensity and morning cortisol were more pronounced in those patients starting immediately with the Michigan splint, while psychological distress decreased similarly in both groups. CONCLUSION: Our results suggest that perceived stress plays a role for the association between anxiety and TMD pain and underlines the need for an interdisciplinary perspective on the pathogenesis and therapy of TMD in a setting where psychotherapeutic knowledge is still scarce or rarely applied.


Asunto(s)
Biomarcadores , Hidrocortisona , Ferulas Oclusales , Dimensión del Dolor , Saliva , Estrés Psicológico , Trastornos de la Articulación Temporomandibular , Humanos , Femenino , Trastornos de la Articulación Temporomandibular/psicología , Trastornos de la Articulación Temporomandibular/terapia , Trastornos de la Articulación Temporomandibular/fisiopatología , Trastornos de la Articulación Temporomandibular/metabolismo , Trastornos de la Articulación Temporomandibular/complicaciones , Adulto , Masculino , Saliva/química , Saliva/metabolismo , Biomarcadores/análisis , Biomarcadores/metabolismo , Estrés Psicológico/terapia , Estrés Psicológico/metabolismo , Hidrocortisona/metabolismo , Hidrocortisona/análisis , Resultado del Tratamiento , Dolor Facial/terapia , Dolor Facial/psicología , Dolor Facial/fisiopatología , Dolor Facial/metabolismo , Persona de Mediana Edad , Adulto Joven , alfa-Amilasas/metabolismo , alfa-Amilasas/análisis
2.
Neuropsychologia ; 147: 107561, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32712148

RESUMEN

Since Tulving's influential work on the distinction between familiarity and recollection-based retrieval, numerous studies have found evidence for differential contribution of these retrieval mechanisms on emotional episodic memory. Particularly, retrieval advantage for emotional, compared to neutral, information has been related to recollection-, but not familiarity-mediated processes. Neuroimaging studies suggest that this recollection-based retrieval for emotional information is related to stronger engagement of regions in the medial temporal lobe (MTL), posterior parietal cortex (PPC), and prefrontal cortex (PFC). In the present study, we investigated neural correlates related to long-term memory of neutral information that has been associated with emotional and neutral contexts, using functional magnetic resonance imaging (fMRI). During encoding, different neutral objects integrated with emotional or neutral scenes were presented. One week later, the encoded objects were intermixed with new ones and participants had to indicate whether the objects were previously seen or not, using the Remember/Know procedure (item memory). Furthermore, memory for the correct scene background category was also tested (contextual source memory). First, replicating previous findings, we observed a preference for recollection-dependent memory retrieval versus familiarity-dependent memory retrieval for those neutral objects encoded in emotional compared to neutral contexts. Second, consistent with these behavioral effects, objects encoded with emotional, compared to neutral, scenes produced larger memory-related activity in recollection-sensitive brain regions, including PPC and PFC regions. Third, correctly retrieved emotional compared to neutral contextual information was associated with increased activity in these brain areas. Together, these results suggest that memory for information encoded in emotional contexts is remarkably robust over time and mediated by recollection-based processes.


Asunto(s)
Imagen por Resonancia Magnética , Memoria Episódica , Mapeo Encefálico , Emociones , Humanos , Recuerdo Mental , Reconocimiento en Psicología
3.
Behav Brain Res ; 380: 112417, 2020 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-31812503

RESUMEN

The term 'chill' refers to a short-term bodily event of high arousal, which marks an emotional peak experience when occurring in response to music. Chill responses arise in a clearly circumscribed time frame and can also be reliably elicited by unpleasant sounds. Previous research, however, mostly focused on individually selected stimuli and positive contexts, thus, limiting the scope of interpretation. Hence, we developed a standardized chill paradigm and used fMRI to test neural responses of 16 healthy volunteers to pleasant and unpleasant emotional sound material while collecting subjective reports of chill intensity and skin conductance response data. As predicted, we found chill-associated increases in autonomic arousal regardless of the valence of the sound material. Apart from activity in primary and higher auditory cortices, both pleasant and unpleasant chills were associated with anterior insula, thalamus and basal ganglia activity. In contrast, amygdala responses were observed only in association with chills elicited by unpleasant sounds. Thus, chills elicited by pleasant and unpleasant sounds share activity in a neural network that may be specifically involved in the arousal component of an emotional experience.


Asunto(s)
Amígdala del Cerebelo/fisiología , Percepción Auditiva/fisiología , Ganglios Basales/fisiología , Corteza Cerebral/fisiología , Emociones/fisiología , Respuesta Galvánica de la Piel/fisiología , Música , Tálamo/fisiología , Adolescente , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Nivel de Alerta/fisiología , Ganglios Basales/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Placer/fisiología , Tálamo/diagnóstico por imagen , Adulto Joven
4.
Sci Rep ; 9(1): 16976, 2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31740683

RESUMEN

High-fidelity single-shot readout of spin qubits requires distinguishing states much faster than the T1 time of the spin state. One approach to improving readout fidelity and bandwidth (BW) is cryogenic amplification, where the signal from the qubit is amplified before noise sources are introduced and room-temperature amplifiers can operate at lower gain and higher BW. We compare the performance of two cryogenic amplification circuits: a current-biased heterojunction bipolar transistor circuit (CB-HBT), and an AC-coupled HBT circuit (AC-HBT). Both circuits are mounted on the mixing-chamber stage of a dilution refrigerator and are connected to silicon metal oxide semiconductor (Si-MOS) quantum dot devices on a printed circuit board (PCB). The power dissipated by the CB-HBT ranges from 0.1 to 1 µW whereas the power of the AC-HBT ranges from 1 to 20 µW. Referred to the input, the noise spectral density is low for both circuits, in the 15 to 30 fA/[Formula: see text] range. The charge sensitivity for the CB-HBT and AC-HBT is 330 µe/[Formula: see text] and 400 µe/[Formula: see text], respectively. For the single-shot readout performed, less than 10 µs is required for both circuits to achieve bit error rates below 10-3, which is a putative threshold for quantum error correction.

5.
Rev Sci Instrum ; 88(12): 123301, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29289172

RESUMEN

We demonstrate a capability of deterministic doping at the single atom level using a combination of direct write focused ion beam and solid-state ion detectors. The focused ion beam system can position a single ion to within 35 nm of a targeted location and the detection system is sensitive to single low energy heavy ions. This platform can be used to deterministically fabricate single atom devices in materials where the nanostructure and ion detectors can be integrated, including donor-based qubits in Si and color centers in diamond.

6.
Br J Dermatol ; 174(6): 1308-17, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26800492

RESUMEN

BACKGROUND: Risk of melanoma is determined by genetic and exogenous factors. Only a few studies have included both characteristics in a comprehensive multivariable analysis. OBJECTIVES: To find determinants of patients at high risk of melanoma in Austria, including phenotype, genotype and lifestyle characteristics in comprehensive analyses. METHODS: In total, 1668 patients with melanoma from the M3 case-control study were studied. Overall, 567 participants were sequenced for CDKN2A, 232 for CDK4, 123 for MITF encoding the variant E318K and 964 for MC1R. RESULTS: Patients with melanoma with a positive family history (n = 190, 11·6%), multiple primary melanomas (n = 261, 15·7%) and younger age (< 50 years, n = 675, 40·5%) were defined as being at high risk. All other patients with melanoma were defined as the reference group. We found significant differences between those two groups and between the high-risk subgroups (positive family history, multiple primary melanomas and younger age). Pigmentation phenotype was associated with the high-risk group in general (childhood freckling, odds ratio 1·46, P = 0·007; blond/reddish hair colour, odds ratio 1·43, P = 0·011). Patients with a positive family history and patients with early-onset disease were similar regarding both their phenotypic characteristics and external factors. Established high-risk mutations in CDKN2A were found in cases with a positive family history (n = 12) or multiple melanomas (n = 2). Moreover, we found three patients carrying the MITF p.E318K variant, two with a CDK4 variant and seven with nonsynonymous MC1R variants with undescribed biological significance, of which four were predicted as damaging. CONCLUSIONS: Austrian patients could represent a reservoir for novel genetic variants. Further investigation of populations in Central and Eastern Europe might reveal more novel and disease-relevant variants.


Asunto(s)
Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Austria/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Genotipo , Humanos , Lactante , Masculino , Melanoma/genética , Persona de Mediana Edad , Mutación/genética , Proteínas de Neoplasias/genética , Linaje , Factores de Riesgo , Neoplasias Cutáneas/genética , Pigmentación de la Piel , Luz Solar/efectos adversos , Adulto Joven
7.
Nanotechnology ; 26(20): 205703, 2015 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-25927489

RESUMEN

We present transport measurements of silicon MOS split gate structures with and without Sb implants. We observe classical point contact (PC) behavior that is free of any pronounced unintentional resonances at liquid He temperatures. The implanted device has resonances superposed on the PC transport indicative of transport through the Sb donors. We fit the differential conductance to a rectangular tunnel barrier model with a linear barrier height dependence on source-drain voltage and non-linear dependence on gate bias. Effects such as Fowler-Nordheim (FN) tunneling and image charge barrier lowering (ICBL) are considered. Barrier heights and widths are estimated for the entire range of relevant biases. The barrier heights at the locations of some of the resonances for the implanted tunnel barrier are between 15-20 meV, which are consistent with transport through shallow partially hybridized Sb donors. The dependence of width and barrier height on gate voltage is found to be linear over a wide range of gate bias in the split gate geometry but deviates considerably when the barrier becomes large and is not described completely by standard 1D models such as FN or ICBL effects.

8.
Am J Transplant ; 14(11): 2633-9, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25250717

RESUMEN

We describe two cases of donor-derived methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that developed after transplantation of organs from a common donor who died from acute MRSA endocarditis. Both recipients developed recurrent MRSA infection despite appropriate antibiotic therapy, and required prolonged hospitalization and hospital readmission. Comparison of S. aureus whole genome sequence of DNA extracted from fixed donor tissue and recipients' isolates confirmed donor-derived transmission. Current guidelines emphasize the risk posed by donors with bacteremia from multidrug-resistant organisms. This investigation suggests that, particularly in the setting of donor endocarditis, even a standard course of prophylactic antibiotics may not be sufficient to prevent donor-derived infection.


Asunto(s)
Genoma Bacteriano , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Trasplante de Órganos/efectos adversos , Análisis de Secuencia de ADN , Infecciones Estafilocócicas/transmisión , Donantes de Tejidos , ADN Bacteriano/genética , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Polimorfismo de Nucleótido Simple , Infecciones Estafilocócicas/microbiología
9.
Behav Brain Res ; 272: 25-31, 2014 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-24983659

RESUMEN

Functional imaging studies on responders and non-responders to therapeutic interventions in obese children are rare. We applied fMRI before and after a one-year sports therapy in 14 obese or overweight children aged 7-16 years. During scanning, participants observed a set of standardized pictures from food categories, sports, and pleasant and neutral images. We were interested in alterations of the cerebral activation to food images in association with changes in the BMI-standard deviation score (BMI-SDS) after therapy and therefore separated the observation group into two outcome subgroups. One with reduction of BMI-SDS >0.2 (responder group) and one without (non-responder group). Before therapy fMRI-activation between groups did not differ. After therapy we found the following results: in response to food images, obese children of the responder group showed increased activation in the left putamen when compared with the non-responder group. Pleasant images evoked increased insula activation in the responder group. Only the responder group showed enhanced activity within areas known to store trained motor patterns in response to sports images. Both the putamen and the insula are involved in the processing of emotional valence and were only active for the therapy responders during the observation of food or pleasant stimuli. Elevated activity in these regions might possibly be seen in the context of an increase of dopaminergic response to emotional positive stimuli during intervention. In addition, sport images activated motor representations only in those subjects who profited from the sports therapy. Overall, an altered response to rewarding and pleasant images and an increased recruitment of motor engrams during observations of sports pictures indicates a more normal cerebral processing in response to these stimuli after successful sports therapy in obese children.


Asunto(s)
Encéfalo/fisiopatología , Terapia por Ejercicio , Obesidad/fisiopatología , Obesidad/terapia , Adolescente , Índice de Masa Corporal , Mapeo Encefálico , Niño , Femenino , Alimentos , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Deportes , Resultado del Tratamiento , Percepción Visual/fisiología
10.
Br J Dermatol ; 171(3): 622-30, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24665948

RESUMEN

BACKGROUND: Only recently, site-dependent associations of actinic damage with melanoma were identified in our study population. OBJECTIVES: To elucidate the diverse aetiologies for actinic damage at different body sites. METHODS: We performed multivariate logistic regression analyses to identify independent risk factors for actinic damage on the face, hands and the back in 2112 participants of central European origin. RESULTS: For actinic damage on the face, age was the only risk factor that remained consistently significant in a multivariate analysis, whereas actinic damage on the back was predominantly associated with number of sunburns, freckles in childhood, holiday weeks and male sex. Moreover, we identified a particular significance of MC1R variants and dorsal actinic skin damage. CONCLUSIONS: The particular effect of MC1R variants and sun exposure during recreational time on dorsal actinic damage indicates that actinic damage on the back is more informative regarding susceptibility to sunlight and past sun exposure associated with melanoma risk.


Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Trastornos por Fotosensibilidad/etiología , Receptor de Melanocortina Tipo 1/genética , Luz Solar/efectos adversos , Adulto , Distribución por Edad , Dorso , Dermatosis Facial/etiología , Femenino , Dermatosis de la Mano/etiología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Distribución por Sexo
11.
Nat Commun ; 4: 2882, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24287692

RESUMEN

The interaction between cavity modes and optical transitions leads to new coupled light-matter states in which the energy is periodically exchanged between the matter states and the optical mode. Here we present experimental evidence of optical strong coupling between modes of individual sub-wavelength metamaterial nanocavities and engineered optical transitions in semiconductor heterostructures. We show that this behaviour is generic by extending the results from the mid-infrared (~10 µm) to the near-infrared (~1.5 µm). Using mid-infrared structures, we demonstrate that the light-matter coupling occurs at the single resonator level and with extremely small interaction volumes. We calculate a mode volume of 4.9 × 10(-4) (λ/n)(3) from which we infer that only ~2,400 electrons per resonator participate in this energy exchange process.

12.
Opt Express ; 21(4): 5198-208, 2013 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-23482053

RESUMEN

An optical phased array of nanoantenna fabricated in a CMOS compatible silicon photonics process is presented. The optical phased array is fed by low loss silicon waveguides with integrated ohmic thermo-optic phase shifters capable of 2π phase shift with ∼ 15 mW of applied electrical power. By controlling the electrical power to the individual integrated phase shifters fixed wavelength steering of the beam emitted normal to the surface of the wafer of 8° is demonstrated for 1 × 8 phased arrays with periods of both 6 and 9 µm.


Asunto(s)
Lentes , Nanopartículas del Metal/química , Refractometría/instrumentación , Semiconductores , Resonancia por Plasmón de Superficie/instrumentación , Campos Electromagnéticos , Diseño de Equipo , Análisis de Falla de Equipo , Nanopartículas del Metal/efectos de la radiación
13.
Opt Lett ; 35(19): 3201-3, 2010 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-20890333

RESUMEN

We demonstrate a two-dimensional (2D) polarization-independent resonant subwavelength grating (RSG) in a filter array. RSGs, also called guided mode resonant filters, are traditionally one-dimensional gratings; however, this leads to TE and TM resonances at different wavelengths and with different spectral shape. A 2D grating can remove the polarization dependence at normal incidence, while maintaining the desirable RSG properties of high reflectivity, narrow passband, and low sidebands without ripple. We designed and fabricated 2D gratings with near-identical responses for both polarizations at normal incidence in the telecommunication band. Ninety percent reflectivity is achieved at the resonant wavelengths.

14.
J Med Imaging Radiat Oncol ; 54(4): 375-82, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20718919

RESUMEN

INTRODUCTION: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). METHODS AND MATERIALS: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V(100) >or= 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V(100). RESULTS: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V(100) for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27-17.5). CONCLUSIONS: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Sistema Límbico/efectos de la radiación , Tomografía Computarizada Espiral/métodos , Encéfalo , Neoplasias Encefálicas/diagnóstico por imagen , Estudios de Factibilidad , Hipocampo/diagnóstico por imagen , Hipocampo/efectos de la radiación , Humanos , Sistema Límbico/diagnóstico por imagen , Órganos en Riesgo , Dosis de Radiación
15.
Oncogene ; 27(53): 6707-19, 2008 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-18806827

RESUMEN

P14(ARF) (p19(ARF) in the mouse) plays a central role in the regulation of cellular proliferation. Although the capacity of p14(ARF) to induce a cell cycle arrest in G1 phase depends on a functional p53/p21-signaling axis, the G2 arrest triggered by p14(ARF) is p53/p21-independent. Using isogeneic HCT116 cells either wild-type or homozygously deleted for p21, 14-3-3sigma or both, we further investigated the cooperative effect of p21 and 14-3-3sigma on cell cycle regulation and apoptosis induction by p14(ARF). In contrast to DNA damage, which induces mitotic catastrophe in 14-3-3sigma-deficient cells, we show here that the expression of p14(ARF) triggers apoptotic cell death, as evidenced by nuclear DNA fragmentation and induction of pan-caspase activities, irrespective of the presence or absence of 14-3-3sigma. The activation of the intrinsic mitochondrial apoptosis pathway by p14(ARF) was confirmed by cytochrome c release from mitochondria and induction of caspase-9- (LEHDase) and caspase-3/7-like (DEVDase) activities. Moreover, 14-3-3sigma/p21 double-deficient cells were exceedingly sensitive to apoptosis induction by p14(ARF) as compared to wild-type cells or cells lacking either gene alone. Notably, p14(ARF)-induced apoptosis was preceded by an arrest in the G2 phase of cell cycle, which coincided with downregulation of cdc2 (cdk1) protein expression and lack of its nuclear localization. This indicates that p14(ARF) impairs mitotic entry by targeting the distal DNA damage-signaling pathway and induces apoptotic cell death, rather than mitotic catastrophe, out of a transient G2 arrest. Furthermore, our data delineate that the disruption of G2/M cell cycle checkpoint control critically determines the sensitivity of the cell toward p14(ARF)-induced mitochondrial apoptosis.


Asunto(s)
Apoptosis/fisiología , Biomarcadores de Tumor/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Exonucleasas/metabolismo , Fase G1/fisiología , Fase G2/fisiología , Proteínas de Neoplasias/metabolismo , Proteína p14ARF Supresora de Tumor/metabolismo , Proteínas 14-3-3 , Animales , Biomarcadores de Tumor/genética , Proteína Quinasa CDC2 , Caspasas/genética , Caspasas/metabolismo , Línea Celular Tumoral , Ciclina B/genética , Ciclina B/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Quinasas Ciclina-Dependientes , Citocromos c/genética , Citocromos c/metabolismo , Daño del ADN/fisiología , Fragmentación del ADN , Exonucleasas/genética , Exorribonucleasas , Humanos , Ratones , Mitocondrias/genética , Mitocondrias/metabolismo , Proteínas de Neoplasias/genética , Proteína p14ARF Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
16.
Oncogene ; 25(50): 6582-94, 2006 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-16847458

RESUMEN

In contrast to the initial notion that the biological activity of p14(ARF) strictly depends on a functional mdm-2/p53 signaling axis, we recently demonstrated that p14(ARF) mediates apoptosis in a p53/Bax-independent manner. Here, we show that p14(ARF) induces breakdown of the mitochondrial membrane potential and cytochrome c release before triggering caspase-9- and caspase-3/7-like activities in p53/Bax-deficient DU145 prostate cancer cells expressing wild-type Bak. Re-expression of Bax in these cells failed to further enhance p14(ARF)-induced apoptosis, suggesting that p14(ARF)-induced apoptosis primarily depends on Bak but not Bax in these cells. To further define the role of Bak and Bax in p14(ARF)-induced mitochondrial apoptosis, we employed short interference RNA for the knockdown of bak in isogeneic, p53 wild-type HCT116 colon cancer cells either proficient or deficient for Bax. There, combined loss of Bax and Bak attenuated p14(ARF)-induced apoptosis whereas single loss of Bax or Bak was only marginally effective, as in the case of DU145. Notably, HCT116 cells deficient for Bax and Bak failed to release cytochrome c and showed attenuated activation of caspase-9 (LEHDase) and caspase-3/caspase-7 (DEVDase) upon p14(ARF) expression. These data indicate that p14(ARF) triggers apoptosis via a Bax/Bak-dependent pathway in p53-proficient HCT116, whereas Bax is dispensable in p53-deficient DU145 cells. Nevertheless, a substantial proportion of p14(ARF)-induced cell death proceeds in a Bax/Bak-independent manner. This is also the case for inhibition of clonogenic growth that occurs, at least in part, through an entirely Bax/Bak-independent mechanism.


Asunto(s)
Mitocondrias/fisiología , Proteína p14ARF Supresora de Tumor/metabolismo , Proteína Destructora del Antagonista Homólogo bcl-2/fisiología , Proteína X Asociada a bcl-2/genética , Apoptosis/fisiología , Factor Inductor de la Apoptosis/metabolismo , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Caspasa 9/metabolismo , Caspasas/metabolismo , Supervivencia Celular , Genes p53/fisiología , Células HCT116 , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Modelos Biológicos , Células Tumorales Cultivadas
17.
Oncogene ; 25(7): 972-80, 2006 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-16331277

RESUMEN

There is an ongoing controversy regarding the relevance of apoptosis induction by ionizing irradiation as compared with other end points including transient or permanent cell cycle arrest of damaged cells. Here, we show that such permanent cell cycle arrest and apoptosis represent two sides of the same coin. MCF-7 cells fail to express procaspase-3, which results in resistance to apoptosis induced by anticancer drugs. Conversely, restoration of procaspase-3 sensitizes MCF-7 cells to chemotherapeutics including epirubicine, etoposide and taxol. In contrast, irradiation does not trigger apoptotic cell death but results in prolonged arrest in the G2 phase of the cell division cycle regardless of procaspase-3 expression. This suggested that the propensity of MCF-7 cells to arrest at the G2 checkpoint results in resistance to apoptosis upon gamma-irradiation. This G2 arrest was associated with upregulation of p21CIP/WAF-1. Inhibition of DNA-damage-induced stress kinases and p21CIP/WAF-1 expression by caffeine abrogated G2 arrest and induced apoptosis of the irradiated cells in a caspase-3-dependent manner. Inhibition of cell cycle progression by adenoviral expression of the cyclin dependent kinase inhibitor p21CIP/WAF-1 prevented apoptosis upon caffeine treatment indicating that cell cycle progression, that is, G2-release, is required for induction of apoptosis. Likewise, cells homozygously deleted for p21CIP/WAF-1 (HCT116 p21-/-) display enhanced irradiation-induced apoptosis via a caspase-3-dependent mechanism. These data indicate that the disruption of G2 checkpoint control overcomes cell cycle arrest and resistance to gamma-irradiation-induced cell death. Thus, DNA damage may trigger a permanent G2 arrest as an initial inactivation step of tumor cells where the phenomenon of apoptosis is hidden unless cell cycle arrest is overcome. The efficient induction of apoptosis upon G2 release thereby depends on the propensity to activate the key executioner caspase-3. This finding is of crucial importance for the understanding of molecular steps underlying the efficacy of ionizing radiation to delete tumor cells.


Asunto(s)
Apoptosis , Neoplasias de la Mama/radioterapia , Carcinoma/radioterapia , Caspasas/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Tolerancia a Radiación , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Cafeína/farmacología , Carcinoma/metabolismo , Caspasa 3 , Fase G2/efectos de los fármacos , Fase G2/efectos de la radiación , Rayos gamma , Humanos , Tolerancia a Radiación/efectos de los fármacos , Células Tumorales Cultivadas , Regulación hacia Arriba
18.
J Asthma ; 42(7): 583-6, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16169793

RESUMEN

To compare the deposition patterns of heliox-driven and air-driven radiolabeled bronchodilator aerosol, a prospective randomized study was undertaken at the Ben Taub Hospital in Houston, Texas. The working hypothesis was that nebulization with heliox would improve the peripheral deposition of a bronchodilator aerosol. Twelve mild-moderate known asthmatics were recruited for the study. They were asked to withhold medications for 8-24 hours prior to reporting for the study. Each subject was randomized to receive either heliox or oxygen for delivery of albuterol labeled with Tc-99m DTPA. Prior to the nebulization, baseline spirometry was performed. Following nebulization, the subjects were scanned for 1,000,000 counts on the ADAC Genesis Scanner. A postbronchodilator spirometry was then performed. Subjects returned about a week later, this time to have the same process repeated with the other gas. The normalized pixel counts were obtained, and the frequency distribution histograms were constructed for each of the deposition images. Skew and kurtosis were calculated. A lower skew and kurtosis value suggests a more peripheral distribution of the bronchodilator, whereas a higher pixel count corresponds with an increased area and uniformity of deposition. There were no statistically significant differences in baseline PFTs on the 2 days of the study. The pixel count was statistically higher after the heliox-driven nebulization than the air-driven nebulization. The skew and kurtosis values were lower after the heliox-driven nebulization than after the air-driven nebulization of radiolabeled aerosol. All patients had a good bronchodilator response with either driving gas. However, the degree of improvement was more with heliox-driven nebulization than with air-driven nebulization. We conclude that aerosol delivery with heliox results in more uniform and peripheral deposition. Thus, this mode of delivery can be used when uniform, peripheral deposition is desired as with drug delivery during an exacerbation or with aerosolized gene therapy.


Asunto(s)
Propelentes de Aerosoles , Albuterol/farmacocinética , Asma/tratamiento farmacológico , Broncodilatadores/farmacocinética , Helio , Oxígeno , Administración por Inhalación , Adulto , Albuterol/administración & dosificación , Asma/diagnóstico por imagen , Disponibilidad Biológica , Broncodilatadores/administración & dosificación , Femenino , Humanos , Recién Nacido , Pulmón/diagnóstico por imagen , Pulmón/efectos de los fármacos , Mediciones del Volumen Pulmonar , Masculino , Estudios Prospectivos , Cintigrafía , Espirometría , Pentetato de Tecnecio Tc 99m
19.
Ann Trop Med Parasitol ; 98(7): 703-14, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15509424

RESUMEN

In October 2000, to interrupt transmission of Wuchereria bancrofti, an intense health-education campaign followed by a mass drug administration (MDA) with diethylcarbamazine and albendazole was undertaken in Leogane, Haiti. Three months after the MDA, which was the first in the study area, a knowledge-attitude-practice (KAP) survey, with a cluster-sample design and probability sampling, was undertaken, to determine the existing knowledge of the local residents, their attitudes toward the MDA, and the possible reasons for non-compliance. Questionnaire-based interviews were used to explore the KAP of 304 subjects (one randomly chosen resident aged > 14 years from each selected household) in 33 communities. Most (93%) of the interviewees were aware of filariasis and 72% knew at least one clinical sign of the disease. Awareness of the MDA was high (91%). The most frequently mentioned sources of information were other people (56%) and radio announcements (33%). More than 80% of the respondents encouraged other people to take the drugs distributed in the MDA and 63% had been treated. The primary reasons given for failing to take the drugs were absenteeism during the distribution (17%), use of contraceptive drugs (12%) and pregnancy (11%). In a multivariate analysis, being male [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.5-7.4], knowing that a mosquito transmits the disease (OR = 2.6; CI = 1.2-5.4), and having learned about the MDA through posters and banners (OR = 2.9; CI = 1.2-7.5) were found to be positively associated with taking the drugs. Information from such post-treatment surveys should be useful in developing better health communication for subsequent MDA.


Asunto(s)
Filariasis Linfática/prevención & control , Filaricidas/administración & dosificación , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud/psicología , Adolescente , Adulto , Anciano , Filariasis Linfática/psicología , Filariasis Linfática/transmisión , Femenino , Haití , Educación en Salud/métodos , Promoción de la Salud , Investigación sobre Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Negativa del Paciente al Tratamiento
20.
Occup Environ Med ; 61(4): 295-304, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15031386

RESUMEN

BACKGROUND: Because of the high concentration of oil refining and petrochemical facilities, the industrial area of the lower Mississippi River of South Louisiana has been termed the Industrial Corridor and has frequently been referred to as the "Cancer Corridor". AIMS: To quantitatively assess the "Cancer Corridor" controversy based on mortality data available in the public domain, and to identify potential contributing factors to the observed differences in mortality. METHODS: Age adjusted mortality rates were calculated for white and non-white males and females in the Industrial Corridor, Louisiana, and the United States for the time periods 1970-79, 1980-89, and 1990-99. RESULTS: All-cause mortality and all cancer combined for white males in the Industrial Corridor were significantly lower than the corresponding Louisiana population while Louisiana had significantly higher rates than the US population for all three time periods. Cancer of the lung was consistently higher in the Industrial Corridor region relative to national rates but lower than or similar to Louisiana. Non-respiratory disease and cerebrovascular disease mortality for white males in the Industrial Corridor were consistently lower than either Louisiana or the USA. However, mortality due to diabetes and heart disease, particularly during the 1990s, was significantly higher in the Industrial Corridor and Louisiana when compared to the USA. Similar mortality patterns were observed for white females. The mortality for non-white males and females in the Industrial Corridor was generally similar to the corresponding populations in Louisiana. There were no consistent patterns for all cancer mortality combined. Stomach cancer was increased among non-whites in both the Industrial Corridor and Louisiana when compared to the corresponding US data. Mortality from diabetes and heart disease among non-whites was significantly higher in the Industrial Corridor and Louisiana than in the USA. CONCLUSIONS: Mortality rates in the Industrial Corridor area were generally similar to or lower than the State of Louisiana, which were increased compared to the United States. Contrary to prior public perceptions, mortality due to cancer in the Industrial Corridor does not exceed that for the State of Louisiana.


Asunto(s)
Mortalidad/tendencias , Adolescente , Adulto , Distribución por Edad , Anciano , Población Negra/estadística & datos numéricos , Causas de Muerte/tendencias , Niño , Preescolar , Femenino , Humanos , Industrias/estadística & datos numéricos , Lactante , Mortalidad Infantil/tendencias , Recién Nacido , Esperanza de Vida , Louisiana/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Distribución por Sexo , Factores Socioeconómicos , Población Blanca/estadística & datos numéricos
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