RESUMEN
An altered sense of the experience of time represents one of the nine dimensions that is conceived as characterizing a state of flow. While a number of other factors necessarily contribute to this overall experience of flow, subjective time perception is of particular quantitative interest and thus serves as the focus of the present meta-analysis. The extant body of relevant quantitative research was evaluated to identify data relating to both flow and change in the sense of time. Sixty-three (nâ¯=â¯63) articles were determined to qualify under the current specified inclusion criteria. These sixty-three studies yielded one thousand and ninety-four (nâ¯=â¯1094) effect sizes. All studies included in the meta-analysis were also coded for relevant moderator variables. Results indicated moderately positive correlations between affective, consciousness, and performance based aspects of flow (râ¯=â¯0.4, 0.21, 0.17 respectively), thus reinforcing the original conceptualization of their relationship for the generation and maintenance of the flow state. Additionally, variations in environmental conditions (both physical and social) were found to have differential effects on the overall level of experienced flow. The results of this meta-analysis also serve to inform the process of further model development that can more accurately quantify and predict temporal perception as one metric of flow.
Asunto(s)
Percepción del Tiempo , Afecto , Estado de Conciencia , Humanos , PensamientoRESUMEN
Extracellular nucleotides interact with specific cell surface receptors to mediate a variety of biological responses, including elevation of the cytosolic free Ca2+ concentration ([Ca2+]i) in a number of cell types. Although extracellular ATP has been shown to affect chondrocyte function, the underlying mechanisms are poorly understood. In the present study, we investigated whether Ca2+-mobilizing purinoceptors are present on sheep chondrocytes. Chondrocytes were isolated from the proximal tibial growth plate of day 120-130 sheep fetuses. Early passage cells were loaded with indo-1 or fluo-3, and [Ca2+]i was monitored by fluorescence spectrophotometry. ATP (0.3-100 microM) induced transient elevation of [Ca2+]i, lasting approximately 1 min. Half-maximal elevation of [Ca2+]i was observed at an ATP concentration of 5.0 +/- 0.2 microM. Responses were still observed in the absence of extracellular Ca2+, and were abolished by pretreatment with thapsigargin, consistent with the release of Ca2+ from intracellular stores. Several nucleotides were tested for their ability to elevate [Ca2+]i. In order of potency, these were UTP approximately ATP >> ADP approximately 2-methylthio-ATP. No responses were elicited by benzoylbenzoic-ATP, a P2Z-selective agonist; alpha,beta-methylene-ATP, an agonist selective for certain P2X purinoceptors; AMP; adenosine; or pyrophosphate (all at 100 microM), demonstrating specificity. Taken together, these data indicate that nucleotides elevate [Ca2+]i in chondrocytes through interaction with the P2U purinoceptor subtype. Although pretreatment with pertussis toxin virtually abolished the Ca2+ response to lysophosphatidic acid, the response to UTP was relatively insensitive, suggesting that P2U purinoceptors are not linked to a pertussis toxin-sensitive G protein in chondrocytes. In contrast, the Ca2+ response to UTP was markedly inhibited by the biologically active phorbol ester 12-O-tetradecanoyl-beta-phorbol 13-acetate, but not by the inactive control compound 4 alpha-phorbol 12,13-didecanoate, suggesting that a 12-O-tetradecanoyl-beta-phorbol 13-acetate-sensitive isoform of protein kinase C regulates P2U purinoceptor signaling in these cells. UTP (10 microM) enhanced the proliferative response to basic fibroblast growth factor. The response to basic fibroblast growth factor was also enhanced by ATP, but not by 2-methylthio-ATP, consistent with involvement of P2U purinoceptors. Nucleotides released during trauma, inflammation, or cell death may act through P2U purinoceptors to regulate chondrocyte function in an autocrine or paracrine manner.
Asunto(s)
Nucleótidos de Adenina/farmacología , Calcio/metabolismo , Cartílago Articular/citología , Cartílago Articular/fisiología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Receptores Purinérgicos P2/fisiología , Adenosina Trifosfato/farmacología , Animales , Bradiquinina/farmacología , Cartílago Articular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , ADN/biosíntesis , Sinergismo Farmacológico , Feto , Colorantes Fluorescentes , Placa de Crecimiento , Cinética , Lisofosfolípidos/farmacología , Toxina del Pertussis , Ovinos , Transducción de Señal/efectos de los fármacos , Suramina/farmacología , Tapsigargina/farmacología , Uridina Trifosfato/farmacología , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
Binding to PTH to its cell surface receptor activates both adenylyl cyclase and phospholipase-C, leading to elevation of cytosolic cAMP and free Ca2+. We have shown previously that extracellular nucleotides interact with P2U and P2Y subtypes of purinoceptor on osteoblastic cells, both linked to Ca2+ mobilization. In the present study, we investigated possible interactions between nucleotide and PTH signaling pathways in osteoblastic cells. The cytosolic free Ca2+ concentration ([Ca2+]i) of UMR-106 osteoblastic cells was monitored by fluorescence spectrophotometry. PTH (0.01-1 microM; bovine 1-84 or human 1-34) induced a small transient elevation of [Ca2+]i, lasting less than 1 min. A number of nucleotides, including ATP, UTP, and UDP, induced transient elevation of [Ca2+]i and potentiated the subsequent Ca2+ response to PTH. Of the nucleotides tested, UDP was the most effective at potentiating the PTH-induced Ca2+ transient. Treatment of cells with UDP (100 microM for 2.5 min), but not inorganic phosphate or uridine, reversibly potentiated the Ca2+ response to PTH (0.1 microM) by 11 +/- 2-fold (mean +/- SEM; n = 39). In contrast, UDP did not affect the cAMP response to PTH, indicating a selective action on Ca2+ signaling. Potentiation of the Ca2+ signal was still observed in the absence of extracellular Ca2+, establishing that nucleotides enhance PTH-induced release of Ca2+ from intracellular stores. Studies using selective purinoceptor agonists suggest that potentiation of PTH signaling is mediated by the P2U receptor subtype. In vivo, nucleotides released during trauma or inflammation may modulate PTH-induced Ca2+ signaling in osteoblasts.
Asunto(s)
Calcio/metabolismo , AMP Cíclico/metabolismo , Nucleótidos/farmacología , Osteoblastos/metabolismo , Hormona Paratiroidea/farmacología , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Animales , Bradiquinina/farmacología , Línea Celular , Citosol/metabolismo , Sinergismo Farmacológico , Cinética , Osteoblastos/efectos de los fármacos , Hormona Paratiroidea/administración & dosificación , Fragmentos de Péptidos/farmacología , Ratas , Receptores Purinérgicos P2/efectos de los fármacos , Receptores Purinérgicos P2/fisiología , Transducción de Señal , Tionucleótidos/farmacología , Uridina Difosfato/farmacología , Uridina Trifosfato/farmacologíaRESUMEN
PURPOSE: This study was designed to investigate an animal model of uveitis that resembles anterior uveitis in humans after immunization with iris-ciliary body antigen. METHODS: Male Lewis rats 6 to 8 weeks of age were immunized with the buffer- and detergent-insoluble bovine iris-ciliary body antigen mixed with complete Freund's adjuvant and pertussis toxin. Antigen was digested with various proteolytic enzymes and tested in different rodent strains for a uveitogenic response. RESULTS: Acute iridocyclitis developed in both eyes of the Lewis rat during the second week after immunization, and the pattern of inflammation was similar to acute anterior uveitis in humans, with sudden onset, localization to the anterior uvea, and spontaneous resolution. Among the strains tested, F344 rats were susceptible to experimental autoimmune anterior uveitis but Long-Evans rats were not. Experimental autoimmune anterior uveitis did not develop in any of the mice studied, nor was it induced by immunization with synthetic melanin, amelanotic bovine tissues, pigmented bovine skin, or pigmented rat and rabbit iris-ciliary body. A soluble fraction derived from bovine melanin-associated antigen (BMAA) after digestion with the proteolytic enzyme V8 protease resulted in a disease similar to that observed with intact BMAA. CONCLUSIONS: A model of anterior uveitis has been induced in the Lewis rat after immunization with bovine uveal antigen, and it resembles the acute iridocyclitis observed in humans. These results suggest that the pathogenic antigen is a melanin-associated protein(s) present within the iris-ciliary body.
Asunto(s)
Autoantígenos/inmunología , Cuerpo Ciliar/inmunología , Iris/inmunología , Melaninas/inmunología , Uveítis Anterior/inmunología , Animales , Cuerpo Ciliar/patología , Modelos Animales de Enfermedad , Endopeptidasas/farmacología , Inmunización , Iris/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Conejos , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Especificidad de la Especie , Uveítis Anterior/genética , Uveítis Anterior/patologíaRESUMEN
High-quality echocardiograms were performed on 146 normal individuals whose ages ranged from 3 to 73 years (mean 27 years). Normal values for mitral diastolic excursion and E-F slope, the chamber dimensions of the right ventricle, left atrium, and left ventricle, the aortic root dimension, and thickness of the interventricular septum and left ventricular posterior wall were determined. Each tracing was then read independently by two experienced echocardiographers. The extent of interobserver variability was calculated and expressed as a percent of the mean. The 95 per cent confidence limits for these estimates were calculated. Small but significant interobserver variability was found for all nine of these commonly measured echocardiographic parameters. Observer variability is a small but potentially important consideration in investigative echocardiography.
Asunto(s)
Ecocardiografía , Cardiopatías/diagnóstico , Adolescente , Adulto , Anciano , Niño , Preescolar , Competencia Clínica , Ecocardiografía/normas , Humanos , Persona de Mediana EdadRESUMEN
The prevalence of mitral valve prolapse has been established in selected groups of patients but not in the general population. The present study was designed to define the echocardiographic spectrum of mitral valve motion in a population of young individuals without clinical evidence of significant cardiac disease or hypertension. Echocardiograms were performed on 136 normal volunteers. Six subjects (4.4 per cent) had mitral valve prolapse. Eighteen subjects (13.2 per cent) had a lesser degree of posterior systolic motion of the mitral valve leaflets which was suggestive but not diagnostic of prolapse. Minor degrees of posterior systolic mitral valve motion may represent a variant of normal. Caution should be exercised in making the echocardiographic diagnosis of mitral prolapse until this question is settled.