Repeated stimulation of pituitary cell cultures with GH-releasing hormone (GHRH) results in diminished responsiveness, a phenomenon referred to as homologous desensitization. One component of GHRH-induced desensitization is a reduction in GHRH-binding sites, which is reflected by the decreased ability of GHRH to stimulate a rise in intracellular cAMP. In the present study, we sought to determine if homologous down-regulation of GHRH receptor number is due to a decrease in GHRH receptor synthesis. To this end, we developed and validated a quantitative RT-PCR assay system that was capable of assessing differences in GHRH-R messenger RNA (mRNA) levels in total RNA samples obtained from rat pituitary cell cultures. Treatment of pituitary cells with GHRH, for as little as 4 h, resulted in a dose-dependent decrease in GHRH-R mRNA levels. The maximum effect was observed with 0.1 and 1 nM GHRH, which reduced GHRH-R mRNA levels to 49 +/- 4% (mean +/- SEM) and 54 +/- 11% of control values, respectively (n = three separate experiments; P < 0.05). Accompanying the decline in GHRH-R mRNA levels was a rise in GH release; reaching 320 +/- 31% of control values (P < 0.01). Because of the possibility that the rise in medium GH level is the primary regulator of GHRH-R mRNA, we pretreated pituitary cultures for 4 h with GH to achieve a concentration comparable with that induced by a maximal stimulation with GHRH (8 micrograms GH/ml medium). Following pretreatment, cultures were stimulated for 15 min with GHRH and intracellular cAMP accumulation was measured by RIA. GH pretreatment did not impair the ability of GHRH to induce a rise in cAMP concentrations. However, as anticipated, GHRH pretreatment (10 nM) significantly reduced subsequent GHRH-stimulated cAMP to 46% of untreated controls. These data suggest that GHRH, but not GH, directly reduces GHRH-R mRNA levels. To determine whether this effect was mediated through cAMP, cultures were treated with forskolin, a direct stimulator of adenylate cyclase. Forskolin (10 microM) significantly reduced GHRH-R mRNA concentrations (37 +/- 6% of control values) indicating that GHRH acts through the cAMP-second messenger system cascade to regulate GHRH-R mRNA. The somatostatin analogue, octreotide (10 nM), which has been previously reported to decrease adenylate cyclase activity, did not affect GHRH-R mRNA levels. Taken together, these results indicate that GHRH inhibits the production of its own receptor by a receptor-mediated, cAMP-dependent reduction of GHRH-R mRNA accumulation. 相似文献
In this paper, we report on our experience with the application of validated models to assess performance, reliability, and adaptability of a complex mission critical system that is being developed to dynamically monitor and control the position of an oil-drilling platform. We present real-time modeling results that show that all tasks are schedulable. We performed stochastic analysis of the distribution of task execution time as a function of the number of system interfaces. We report on the variability of task execution times for the expected system configurations. In addition, we have executed a system library for an important task inside the performance model simulator. We report on the measured algorithm convergence as a function of the number of vessel thrusters. We have also studied the system architecture adaptability by comparing the documented system architecture and the implemented source code. We report on the adaptability findings and the recommendations we were able to provide to the system’s architect. Finally, we have developed models of hardware and software reliability. We report on hardware and software reliability results based on the evaluation of the system architecture. 相似文献
Solar energy provides the reducing power within green leaves to convert CO2 and H2O into sugars. The CO2 is supplied by the atmosphere and enters the leaf by diffusion. Factors affecting the rate of photosynthesis must either change the CO2 diffusive resistances or the CO2 concentration gradient along the diffusion pathways. Therefore, these effects can be described in terms of diffusive control mechanisms.
Light affects CO2 diffusion by initiating photosynthesis, which removes CO2 at the chloroplast and establishes a diffusion gradient. Light also triggers stomatal opening, thereby sharply decreasing the diffusive resistance. However, intense radiation can cause desiccation of stomatal guard cells, a mechanism whereby the diffusive resistance increases.
During illumination, leaf cells have both a source (respiration) and sink (photosynthesis) for CO2. Respiration in some species appears to be greatly stimulated by light. This additional internal CO2 flux is a possible reason for a lower efficiency of energy utilization than in species whose respiration is not enhanced by light.
Physiological growth responses or movements often occur that position leaves in the light. Plants lacking this capability are often excluded in ecological succession in nature. 相似文献
We provide a response to a commentary by Wiers and Stacy (see record 2009-24669-003) on our model of the alcohol–behavior link (see record 2009-09537-002). Whereas Wiers and Stacy generally supported our model, they took issue with our conceptualization of the alcohol expectancy construct. We address the major concerns of Wiers and Stacy by demonstrating that our own view is consistent with basic cognitive scientific conceptualizations of the nature of associative and propositional reasoning within a dual-systems framework. In clarifying these issues, we maintain that although the predictions presented by Wiers and Stacy are important and useful in this area, they are predictions that can be derived from our original formulation of the alcohol–behavior link. We conclude that this kind of useful debate can only aid the generation of conceptually consistent and testable models that will advance the understanding of the alcohol–behavior link. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
Within the medical domain there are clear expectations as to how a patient should respond to treatments administered. When these responses are not observed it can be challenging for clinicians to understand the anomalous responses. The work reported here describes a tool which can detect anomalous patient responses to treatment and further suggest hypotheses to explain the anomaly. In order to develop this tool, we have undertaken a study to determine how Intensive Care Unit (ICU) clinicians identify anomalous patient responses; we then asked further clinicians to provide potential explanations for such anomalies. The high level reasoning deployed by the clinicians has been captured and generalised to form the procedural component of the ontology-driven tool. An evaluation has shown that the tool successfully reproduced the clinician’s hypotheses in the majority of cases. Finally, the paper concludes by describing planned extensions to this work. 相似文献
Hierarchically structured poly(alkyl‐p‐xylylene) (alkyl‐PPX) nonwovens are prepared by specific parameter variation during the electrospinning process. The investigated parameters are changes in solutions properties and ambient humidity level, which lead to the formation of different fiber architectures and surface morphologies. The characterization of the nonwovens by scanning electron microscopy confirms the formation of hierarchically structured fibers, comprising bead‐on‐string architecture if spun from tetrahydrofuran (THF) solutions, and porous surfaces at relative humidity (RH) levels > 30% for both chloroform and THF solutions. The wetting properties of nonwovens spun from THF and chloroform solutions are analyzed by water contact angle (CA) measurements, roll‐angle determination, and high speed imaging. PPX‐heptyl and PPX‐butyl fiber mats spun from 2.5 wt% THF and PPX‐heptyl spun from 3 wt% chloroform solutions at RH > 75% show superhydrophobic and self‐cleaning properties with CA > 153° and roll‐off angles of 10–15°. The nonwovens maintain their fiber morphology and water‐repellent properties after thermal and mechanical stress.
PURPOSE: We determine the presence of an open bladder neck during video urodynamic studies and relate that finding to the presence of stress urinary incontinence. MATERIALS AND METHODS: Patients presenting with urinary incontinence, voiding dysfunction or pelvic floor prolapse underwent video urodynamics. With the patient upright and after 200 ml. contrast material had been instilled into the bladder the bladder neck was viewed to determine if it was open or closed. At that point the abdominal leak point pressure was measured. RESULTS: Of 102 women, average age 56.5 years (range 31 to 82), 13% had an open bladder neck and demonstrable stress incontinence on video urodynamics with an average abdominal leak point pressure of 45 cm. water (range 26 to 90). Of those with stress incontinence on urodynamics 23% had an open bladder neck. No continent patient had an open bladder neck. CONCLUSIONS: The presence of an open bladder neck with the bladder filled to 200 ml. correlates strongly with the presence of stress incontinence. 相似文献
Neuromuscular disease commonly affects the rearfoot as equinus, equinovarus, and equinovalgus deformity. Spastic hemiplegia caused by stroke, head injury, and cerebral palsy results in equinovarus deformity of the rearfoot. Spastic diplegia, most frequently caused by cerebral palsy, results in equinovalgus rearfoot deformity. Problems in ambulation, footwear, and bracing, as well as their orthopedic management, in patients with neuromuscular disease are discussed in a case-report format. 相似文献
Mal II, a 19-residue peptide derived from the second type 1 properdin-like repeat of the antiangiogenic protein thrombospondin-1 (TSP-1), was inactive in angiogenesis assays. Yet the substitution of any one of three L-amino acids by their D-enantiomers conferred on this peptide a potent antiangiogenic activity approaching that of the intact 450-kDa TSP-1. Substituted peptides inhibited the migration of capillary endothelial cells with an ED50 of 8.5 nM for the D-Ile-15 substitution, 10 nM for the D-Ser-4 substitution, and 0.75 nM for the D-Ser-5 substitution. A peptide with D-Ile at position 15 could be shortened to its last seven amino acids with little loss in activity. Like whole TSP-1, the Mal II D-Ile derivative inhibited a broad range of angiogenic inducers, was selective for endothelial cells, and required CD36 receptor binding for activity. A variety of end modifications further improved peptide potency. An ethylamide-capped heptapeptide was also active systemically in that when injected i.p. it rendered mice unable to mount a corneal angiogenic response, suggesting the potential usefulness of such peptides as antiangiogenic therapeutics. 相似文献