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41.
- Interactions between dopamine receptors and protein kinase C (PKC) have been proposed from biochemical studies. The aim of the present study was to investigate the hypothesis that there is an interaction between protein kinase C and inhibitory D2-dopamine receptors in the modulation of stimulation-induced (S-I) dopamine release from rat striatal slices incubated with [3H]-dopamine. Dopamine release can be modulated by protein kinase C and inhibitory presynaptic D2 receptors since phorbol dibutyrate (PDB) and (−)-sulpiride, respectively, elevated S-I dopamine release.
- The protein kinase C inhibitors polymyxin B (21 μM) and chelerythrine (3 μM) had no effect on stimulation-induced (S-I) dopamine release. However, when presynaptic dopamine D2 receptors were blocked by sulpiride (1 μM), an inhibitory effect of both PKC inhibitors on S-I dopamine release was revealed. Thus, sulpiride unmasks an endogenous PKC effect on dopamine release which suggests that presynaptic D2 receptors normally suppress endogenous PKC activity. This is supported by results in striatal slices which were pretreated with PDB to down-regulate PKC. In this case the facilitatory effect of sulpiride was completely abolished.
- The inhibitory effect of the dopamine D2/D3 agonist quinpirole on S-I dopamine release was partially attenuated by PKC down-regulation. Since the effect of sulpiride was completely abolished under the same conditions, this suggests that exogenous agonists may target a PKC-dependent as well as a PKC-independent pathway. The inhibitory effect of apomorphine was not affected by either polymyxin B or PKC down-regulation, suggesting that it operated exclusively through a PKC-independent mechanism.
- These results suggest that there are at least two pathways involved in the inhibition of dopamine release through dopamine receptors. One pathway involves dopamine receptor suppression of protein kinase C activity, perhaps through inhibition of phospholipase C activity and this is preferentially utilized by neuronally-released dopamine. The other pathway which seems to be utilized by exogenous agonists does not involve PKC.
42.
Silver S Turley C Smith C Laird J Majewski T Maguire B Orndorff J Rice L Vowels R 《Journal of allied health》1999,28(1):21-24
Two important goals in allied health education are to prepare future allied health professionals to function as members of interdisciplinary teams and to increase their awareness of issues related to the growing older adult population. The responsibility for achieving these goals rests on the faculty and administrators of allied health education programs, who may not themselves be proficient in either of these domains. A multidisciplinary team of health educators and administrators was brought together to produce six problem-based learning (PBL) cases related to older adults. Members of the team represented a variety of disciplines in health care, diverse philosophies of educational development, a variety of roles in allied health education, and differing levels of knowledge of issues related to older adults--parameters similar to those found in the members of an interdisciplinary healthcare team. The methods by which this multidisciplinary group functioned and the dynamics in attaining the goals of the project are presented. 相似文献
43.
H. Majewski L. Hedler A. Steppeler K. Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1982,319(2):125-129
Summary The outflow of noradrenaline, 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) from rabbit perfused hearts was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs and without nerve stimulation, the outflow of endogenous noradrenaline over a period of 108 min averaged 0.17 pmol×g–1×min–1 and the outflow of DOPEG 2.1 pmol×g–1×min–1. The outflow of DOMA was below the detection limit (<0.13 pmol×g–1×min–1). The effect of perfusion with (–)-noradrenaline 0.1, 1 or 10 mol/l for 18 min was then investigated. As the concentration of noradrenaline increased so did the outflow of DOPEG. Moreover, DOMA was found in the venous effluent during and after perfusion with noradrenaline 1 or 10 mol/l. The increase in the outflow of DOPEG and DOMA was almost abolished when cocaine 10 mol/l was present during the perfusion with noradrenaline 1 mol/l. The release of endogenous noradrenaline by sympathetic nerve stimulation or tyramine 10 mol/l, but not the release evoked by nicotine 30 mol/l, was accompanied by an increase in the outflow of DOPEG; an outflow of DOMA was not observed.It is concluded that, in the rabbit perfused heart, DOPEG is an important metabolite of endogenous noradrenaline. DOMA is at best a minor product, either when the neurones are at rest or when noradrenaline is released by sympathetic nerve stimulation, nicotine or tyramine. DOMA is formed in detectable amounts when the tissue is exposed to a high concentration of exogenous noradrenaline. Like DOPEG, it is formed intraneuronally. The results confirm and extend those obtained previously on guinea-pig incubated atria. They make it unlikely that, in these tissues at least, DOMA formation is one of the physiological pathways of noradrenaline catabolism. 相似文献
44.
Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice. 总被引:2,自引:0,他引:2
Marcin Makowski Tomasz Grzela Justyna Niderla Maciej ?Azarczyk Pawe? Mróz Maciej Kopeé Magdalena Legat Katarzyna Strusińska Katarzyna Koziak Dominika Nowis Piotr Mrówka Maria Wasik Marek Jakóbisiak Jakub Go?ab 《Clinical cancer research》2003,9(14):5417-5422
PURPOSE: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells. EXPERIMENTAL DESIGN: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors. RESULTS: PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals. CONCLUSIONS: COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination. 相似文献
45.
Katarzyna Miekus Marta Pawlowska Ma?gorzata Seku?a Grazyna Drabik Zbigniew Madeja Dariusz Adamek Marcin Majka 《Oncotarget》2015,6(12):10086-10101
Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype.Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma. 相似文献
46.
This article proposes an indirect measurement method based on a dimensional and shape analysis of forgings for the evaluation of the manufacture and the proper operation of the key elements of the crank press, in which after modernization, a quick tool assembly based on SMED (Single Minute Exchange of Die) was implemented. As a result of the introduced changes aiming at improving the forging aggregate and increasing the production efficiency, errors were observed on the manufactured products-forgings in the form of twists and joggles. In order to solve the problem, a lot of advanced methods was used, including: dynamic system of deformation analysis, numerical modeling and as well as dimensional and shape analysis by 3d scanning. Despite the above, this approach (classic way) did not solve the problem. A proprietary method with the use of 3D reverse scanning was proposed, which allows to solve the problem of forgings errors. Based on the measurement results and analyses for a few variants of production cycles, the necessary changes were obtained, making it possible to minimize the errors and obtain proper products in respect of geometry and quality. 相似文献
47.
Tomasz Jazwiec Marcin Malinowski Haley Ferguson Jeremy Wodarek Nathan Quay Jared Bush Matthew Goehler Jessica Parker Manuel Rausch Tomasz A. Timek 《The Journal of thoracic and cardiovascular surgery》2021,161(4):e277-e286
ObjectiveTo investigate the effect of variable tricuspid annular reduction (TAR) on functional tricuspid regurgitation (FTR) and right ventricular (RV) dynamics in ovine tachycardia-induced cardiomyopathy.MethodsNine adult sheep underwent implantation of a pacemaker with an epicardial lead and were paced at 200 to 240 bpm until the development of biventricular dysfunction and functional TR was noted. During reoperation on cardiopulmonary bypass, 6 sonomicrometry crystals were placed around the tricuspid annulus (TA) and 14 were placed on the RV epicardium. Annuloplasty suture was placed around the TA and externalized to an epicardial tourniquet. After weaning from cardiopulmonary bypass, echocardiographic, hemodynamic, and sonomicrometry data were acquired at baseline and during 5 progressive TARs achieved with suture cinching. TA area and RV free wall strains and function were calculated from crystal coordinates.ResultsAfter pacing, changes in left ventricular (LV) ejection fraction and RV fractional area decreased significantly. Mean TA diameter increased from 25.1 ± 2.9 mm to 31.5 ± 3.3 mm (P = .005), and median TR (range, 0-3+) increased from 0 (0) to 3 (2) (P = .004). Progressive suture cinching reduced the TA area by 18 ± 6%, 38 ± 11%, 56 ± 10%, 67 ± 9%, and 76 ± 8%. Only aggressive annular reductions (67% and 76%) decreased TR significantly, but these were associated with deterioration of RV function and strain. A moderate annular reduction of 56% led to a substantial reduction of TR with little deleterious effect on regional RV function.ConclusionsA moderate TAR of approximately 50% may be most advantageous for correction of functional TR and simultaneous maintenance of regional RV performance. Additional subvalvular interventions may be needed to achieve complete valvular competence. 相似文献
48.
Jan Marcin Węsławski Lucyna Kryla-Straszewska Jan Warzocha Jacek Urbański Maria Włodarska-Kowalczuk Lech Kotwicki 《Oceanological and hydrobiological studies.》2013,42(3):289-295
Extensive sampling (450 grabs) was performed all over the inner part of Puck Bay (105 km2 area) in summers of 2007–2009. The GIS-based analysis of samples was performed to assess in detail the distribution of 32 benthic species. The minimum area of occurrence was less than 1 km2 for Lekanosphaera rugicauda and the maximum was 83 km2 for Cerastoderma glaucum. The material reveals that species with the pelagic larval stage were most widespread, with the least distance between individuals and the highest average density (e.g. Cerastoderma glaucum, Hydrobia ventrosa). The most isolated and the least dense species within the studied area were discretely mobile, non-larval crustaceans (e.g. Gammarus oceanicus and Lekanosphaera rugicauda), present at single sites with the largest distance from each other. We conclude that analysis of species distribution helps in understanding the threats to populations of marine invertebrates and marine spatial planning, through locating the isolated species and populations. 相似文献
49.
Marcin Markowski Adam Kaliński Joanna Skwarska Jarosław Wawrzyniak Mirosława Bańbura Janusz Markowski Piotr Zieliński Jerzy Bańbura 《Bulletin of environmental contamination and toxicology》2013,91(3):302-305
The aim of this study was to determine the possibility of using feathers of blue tit nestlings to assess the level of endogenous accumulation of lead. For this purpose we conducted an experiment with lead application to randomly chosen nestlings from eight randomly drawn broods. Five days after the exposure, feathers of lead-treated nestlings had significantly higher lead concentrations than control nestlings. This result suggests that feathers can be used as reliable non-destructive bioindicators to assess the level of heavy metals originating from contaminated food, which is of great significance for comparative studies on ecological consequences of pollution. 相似文献