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RB Penn JL Parent AN Pronin RA Panettieri JL Benovic 《Canadian Metallurgical Quarterly》1999,288(2):428-437
The use of pharmacological inhibitors of protein kinases represents a potentially powerful tool in dissecting the regulatory features of intracellular signaling pathways. However, although the in vitro potency, selectivity, and efficacy of numerous kinase inhibitors have been characterized, little is known regarding the usefulness of these compounds as inhibitors in intact cells. In attempting to characterize the role of protein kinase A (PKA) in regulating the beta-2 adrenergic receptor (AR) in human airway cells, we observed a seemingly profound capacity of the isoquinoline H-89, a potent and widely used PKA inhibitor, to attenuate agonist-mediated desensitization of the beta-2 AR. Although additional experiments identified H-89 as an effective inhibitor of intracellular PKA, extended analysis of the compound determined the principal effect of H-89 was via its action as a beta-2 AR antagonist. Pretreatment with or the acute addition of H-89 significantly attenuated isoproterenol-stimulated cAMP accumulation. In cells pretreated with H-89 and then washed extensively, the subsequent dose-dependent response to isoproterenol suggested beta-2 AR antagonism by retained H-89. Competition binding of [125I]iodopindolol established Ki values of approximately 180 nM and 350 nM for H-89 antagonism of beta-2 AR and beta-1 AR, respectively. Additional receptor binding studies suggest selectivity of H-89 for the beta-2 AR and beta-1 AR, although a weak antagonism (Ki values of approximately 10 microM or greater) of other G protein-coupled receptors was observed. Results from additional pharmacological and biochemical analyses of various protein kinase inhibitors further established the need for careful characterization of pharmacological inhibitors when used in intact cell models. 相似文献
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G Lucarelli RA Clift M Galimberti E Angelucci C Giardini D Baronciani P Polchi M Andreani D Gaziev B Erer A Ciaroni F D'Adamo F Albertini P Muretto 《Canadian Metallurgical Quarterly》1999,93(4):1164-1167
One hundred seven adult patients with thalassemia aged from 17 through 35 years and transplanted from HLA-identical siblings between November 1988 and September 1996 were evaluated on December 31, 1997. The outcome experience of 20 consecutive patients transplanted between November 13, 1988 and January 10, 1991 and reported in September 1992 is updated after 5 additional years. The experience on 87 patients transplanted between May 1991 and September 1996 is described and evaluated as of the end of December 1997. Of 107 patients, 69 survive between 1.5 and 9 years after transplantation. Sixty-six of these patients do not have thalassemia and are identified as ex-thalassemic after bone marrow transplantation. The youngest survivor is 20 years old, 6 are older than 30 years, and the oldest is 37 years of age. Patients with chronic active hepatitis at the time of transplant were significantly more likely to die than patients without (P =.05; relative risk, 2.05). Marrow transplantation is a valid treatment option for older patients with thalassemia who have suitable donors and show deterioration with conventional therapy. 相似文献
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Television images and adolescent girls' body image disturbance 总被引:4,自引:0,他引:4
RA Botta 《The Journal of communication》1999,49(2):22-41
The impact of media images on adolescents' body image and thin ideal endorsement has been consistently asserted in the body image literature, yet has remained inadequately tested. I used social comparison theory and critical viewing with a sample of 214 high school girls to predict adolescents' body-image disturbance and thin ideal endorsement. Media variables accounted fr 15% of the variance for drive for thinness, 17% for body dissatisfaction, 16% for bulimic behaviors, and 33% for thin ideal endorsement. Results suggest that body image processing is the boy to understanding how television images affect adolescent girls' body-image attitudes and behaviors. 相似文献
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RA Isoardi DW Townsend CS Carter A Herbster MA Dachille CC Meltzer 《Canadian Metallurgical Quarterly》1999,9(1):145-153
The success of the 15O-water PET technique to localize statistically significant changes in regional cerebral blood flow is dependent on factors such as the activity level injected and the magnitude of the flow change. Undetectable changes may occur if insufficient activity is injected leading to high levels of statistical noise or the task performed results in only small changes in blood flow. To explore the relationship between injected activity and statistical significance, we performed a series of studies with the ECAT EXACT HR+, a high resolution PET tomograph. A parametric verbal working memory task (the N-back task) was selected to examine the relationship between regional cerebral blood flow and working memory load across a range of injected doses of 15O-water. At each activity level the volunteers were required to perform four different levels of the N-back task, a task in which a letter displayed on a monitor is matched with the letter displayed N letters previously. With increasing N, this task places increased load on working memory. For this study, 5, 10, and 15 mCi of 15O-water were injected into nine normal volunteers. The complete sequence of four tasks (N = 0, 1, 2, and 3) at three activity levels was repeated twice, for a total of 24 injections of 15O-water. We show that the peak count rate performance for the HR+ is approached at injected activity levels of 15O-water around 15 mCi. For this particular choice of N-back task, robust activation maps can nevertheless be obtained with as little as 5 mCi injected dose. 相似文献
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EA Ratovitski MR Alam RA Quick A McMillan C Bao C Kozlovsky TA Hand RC Johnson RE Mains BA Eipper CJ Lowenstein 《Canadian Metallurgical Quarterly》1999,274(2):993-999
Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity. 相似文献
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This article reviews issues concerning the training and credentialing of vascular surgeons in the use of endovascular techniques in the peripheral vascular system. These guidelines update a prior document that was published in 1993. They have been rewritten to accommodate the rapid evolution that has occurred in the field and to provide the appropriate requirements that a vascular surgeon should fulfill to be competent in the basic skills needed to safely and effectively perform all presently accepted diagnostic and therapeutic endovascular procedures. 相似文献