1
The effects of 5‐hydroxytryptamine (5‐HT) in rat cardiac preparations were studied. 5‐HT up to 10 μM failed to affect contractility in papillary muscles. However, in electrically driven (1 Hz) left ...atria 5‐HT exerted a positive inotropic effect that started at 1 μM and attained its maximum at 10 μM (312±50% of predrug value, n=8).
2
5‐HT 10 μM stimulated the content of inositol‐1,4,5‐trisphosphate but not of cyclic AMP in rat left atria.
3
Plasma and serum levels of 5‐HT amounted to about 0.3 μM and 15 μM, respectively.
4
The selective 5‐HT4 receptor antagonists GR 125487 (10 nM and 1 μM) and SB 203186 (1 μM) did not attenuate the positive inotropic effect of 5‐HT in rat left atria. In contrast, the 5‐HT2 receptor antagonist ketanserin (5 nM, 50 nM, 1 μM) resulted in a concentration‐dependent diminution of the positive inotropic effect of 5‐HT in rat left atria.
5
Reverse transcriptase polymerase chain reaction with specific primers detected mRNA of the 5‐HT2A receptor in rat atria and ventricles, while expression of the 5‐HT4 receptor was confined to atria.
6
It is suggested that the positive inotropic effect of 5‐HT in electrically driven rat left atria is mediated by ketanserin‐sensitive 5‐HT2A receptors and not through 5‐HT4 receptors.
British Journal of Pharmacology (1998) 123, 1182–1188; doi:10.1038/sj.bjp.0701702
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
1 Institut für Pharmakologie und Toxikologie,
Westfälische Wilhelms-Universität Münster,
D-48129 Münster, Germany; and 2 Department of
Laboratories, Denver Health Medical Center, Denver, Colorado
...80204-4507
We studied the effects of the protein phosphatase
(PP) inhibitor cantharidin (Cant) on time parameters and force of
contraction (FOC) in isometrically contracting electrically driven
guinea pig papillary muscles. We correlated the mechanical parameters of contractility with phosphorylation of the inhibitory subunit of
troponin (TnI-P) and with the site-specific phosphorylation of
phospholamban (PLB) at serine-16 (PLB-Ser-16) and threonine-17 (PLB-Thr-17). Cant (after 30 min) started to increase FOC (112 ± 4% of control, n = 10) and TnI-P and PLB-Thr-17
(120 ± 5 and 128 ± 7% of control) without any alteration
of relaxation time. Cant (10 µM) started to increase PLB-Ser-16, but
the relaxation was shortened at only 100 µM (from 140 ± 9 to
116 ± 12 ms, n = 9). Moreover, 100 µM Cant, 3 min after application, started to increase PLB-Thr-17, TnI-P, and FOC.
Cant (100 µM) began to increase PLB-Ser-16 after 20 min. This was
accompanied by shortening of relaxation time. Differences in protein
kinase activation or different substrate specificities of PP may
explain the difference in Cant-induced site-specific phosphorylation of
PLB in isometrically contracting papillary muscles. Moreover,
PLB-Thr-17 may be important for inotropy, whereas PLB-Ser-16 could be a
major determinant of relaxation time.
cantharidin; protein phosphatase inhibitors; protein
phosphorylation; phospholamban; inhibitory subunit of troponin
In end-stage failing human hearts and in rat hearts after prolonged in vivo beta-adrenergic treatment, several proteins involved in the cAMP-dependent signal transduction are altered on the protein, ...mRNA, or transcriptional level, eg, beta-adrenoceptors, G-proteins, or proteins of Ca2+ homeostasis. In many tissues, cAMP-dependent transcriptional regulation occurs through the cAMP response element binding protein (CREB) and related transcription factors binding as dimers to cAMP response elements (CREs) in the promoter regions of regulated genes.
To investigate a possible role of CREB in the human heart, nuclear protein of explanted failing and nonfailing human hearts was used to test for CRE specific binding properties in gel mobility shift assays. CRE specific binding was found in competition studies, and CREB and its phosphorylated form were immunologically identified in supershift experiments. The alternatively spliced CREB isoforms CREB327 and CREB341 were found to be expressed on the mRNA level by the reverse transcriptase-polymerase chain reaction.
We conclude that in the failing and nonfailing human heart, CREB is expressed on the protein and mRNA levels and that CREB is phosphorylated and able to bind to CREs, indicating a functional role of CREB in the human heart.
In this paper, we explore the complex process of how ideas evolve in organizations that are engaged in developing and using information technology (IT)-based systems. We put forward a framework ...emphasizing the interconnection between creativity and institutionalization. We argue that ideas are embedded in existing institutionalized technologies in organizations and that emerging technologies introduce neoteric ideas to them. Furthermore, we argue that, when attempting to introduce technology-based ideas, human actors will focus their attention on ideas embedded in existing institutionalized technologies while informally evaluating and making sense of these ideas. Moreover, we suggest that conflicts between competing frames of reference during this evaluation may result in the rejection, adoption, or multiplication of new technology ideas. Drawing on information systems (IS)-based theories of creativity, Scandinavian institutionalism, and empirical data from two Danish organizations, we investigate the interplay between creativity, technology, and human sensemaking in the process of translating and transforming technology ideas into full-fledged technological innovations.
Abstract only
The transcription factor CREM plays an important role in cAMP mediated gene expression. Here we want to clarify the role of CREM in vasculature particularly with regard to the ...regulation of VSMCs proliferation, using CREM (CKO) and CREM isoform ICER (IKO) deficient mice.
CKO mice showed an increase of neointima formation associated with a higher proliferation rate of aortic VSMCs under platelet‐derived growth factor (PDGF) treatment. The PDGF alpha receptor (Pdgfra) promoter was inducible by cAMP and mRNA was upregulated in aortae and PDGF‐treated primary VSMCs of CKO mice. In untreated IKO‐VSMCs the proportion of proliferating cells was higher as compared to WT‐VSMCs, while no differences were observed under PDGF treatment. Induction of cAMP by forskolin reduced the proliferation rate of both IKO and WT‐VSMCs under PDGF treatment.
Accordingly, ICER was linked to the elevated proliferation of VSMCs under non‐stimulated conditions, however, other CREM isoforms than ICER inhibit PDGF‐mediated proliferation of VSMCs possibly by modulation of cAMP‐dependent
Pdgfra
gene regulation. (supported by DFG)
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose:
To determine if angioplasty of atherosclerotic renal artery stenosis, which reduces the activation of the renin-angiotensin-aldosterone system (RAAS), may lead to regression of left ...ventricular hypertrophy.
Methods:
The study included 102 patients (58 men; mean age 67 years, range 66–69) who underwent stent-supported percutaneous transluminal renal angioplasty (PTRA) and were included in a clinical follow-up program (mean 24±14 months, range 6–60). As a control group, 101 contemporaneous patients (68 men; mean age 68 years, range 66–70) with essential hypertension were investigated. The primary endpoint was the change in left ventricular mass index (LVMI) determined by echocardiography.
Results:
Mean follow-up intervals were 24±14 months (range 6–60) in the study group and 27±14 months (range 6–60) in the controls (p=0.09). LVMI decreased significantly by −10±26 g/m2 in the study group, while it increased significantly by 9±28 g/m2 in the control group (p=0.001 between groups). In the study group, mean arterial blood pressure was significantly reduced from 99±11 mmHg to 90±11 mmHg (p<0.0001) during follow-up despite a significant reduction in medication, whereas it increased significantly from 102±11 mmHg to 105±11 mmHg (p=0.008) in the control group, although medication was significantly increased. After adjustment for various factors and covariables, PTRA prevailed as an independent predictor for regression of LVMI (p=0.038).
Conclusion:
PTRA induces regression of LVMI that is independent of the reduction in blood pressure induced by this procedure. Reduced activity of the RAAS may account for this regression.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
In this paper we describe the hacker culture by analyzing 25 years of communication on one of the oldest and most renowned hacker Web sites. For this purpose, we utilize a previously documented text ...analysis technique 14 which provides an efficient and effective method of producing a quick overview of values underlying any written text. The technique allows for the creation of culture profiles of texts based on the competing values framework 2. The paper contributes to understanding an important but overlooked hotbed of creativity -- the hacker community. It provides examples of how hackers -- by playing with existing technologies -- help push technological progress. Furthermore, the paper demonstrates the usefulness of semi-automated text analyses for the purpose of understanding the values and assumptions that are expressed in documents. We highlight the value of the technique in analyzing large volumes of empirical data and assessing cultures of communities, organizations, or other units of analysis.
Abstract only
Transgenic mice with heart directed expression of transcription factor CREM‐IbΔC‐X (TG) develop atrial alterations including dilatation, impaired electrical conduction and impaired ...regulation of intracellular Ca
2+
preceding spontaneous‐onset atrial fibrillation. Here, we studied whether CREM‐IbΔC‐X is linked to proarrhythmic alterations in ventricular cardiomyocytes (CMs). Action potentials were prolonged in TG CMs along with reduced mRNA of the I
to
underlying channel subunit Kv4.2 as compared to wild‐type (WT) CMs. In TG vs. WT CMs Ca
2+
transient amplitude was unaltered under basal conditions but increased under stimulation with isoproterenol. Under both conditions Ca
2+
release was retarded but the Ca
2+
decay was accelerated in TG vs. WT CMs. The frequency of Ca
2+
sparks was enhanced while spark amplitude was reduced in TG vs. WT CMs. Stress stimulation protocols revealed an enhanced rate of spontaneous Ca
2+
releases in TG vs. WT CMs. Hence, human cardiac isoform CREM‐IbΔC‐X is linked to an increased susceptibility to arrhythmia possibly by regulating the transcription of genes modulating AP shape and duration and intracellular Ca
2+
cycling. Supported by IZKF Münster
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Transcription factors of the CREB/CREM/ATF1‐family (cAMP responsive‐element (CRE) binding protein and modulator and activating transcription factor 1) play an important role in the cAMP mediated gene ...control. To address the vascular role of CREM and ATF1 we studied mice with a global inactivation of CREM (CKO) or ATF1 (AKO).
CKO mice showed an increase in neointima formation after ligation of the carotid artery associated with an elevated proliferation rate of VSMCs in carotid media. Atherogenic high‐fat‐diet revealed a 20% increase of plaque area in CKOxApoE‐KO vs. control mice. In primary VSMC proliferation rate was increased 1.3 fold in CKO vs. controls after platelet derived growth factor (PDGF) stimulation associated with a 3 fold increased CRE‐mediated transcriptional activity.
In AKO VSMCs PDGF induced proliferation was blunted compared to controls. AKO VSMCs also revealed a 1.9‐fold higher proportion of apoptotic cells after H2O2 treatment. These results were not associated with differences in neointima‐ or plaque formation.
We conclude that ATF1 is in principle involved in the regulation of vascular proliferation and apoptosis but may play an inferior role under physiological conditions. Anti‐proliferative effects suggest CREM as an important factor for the pathogenesis of vascular proliferative disorders. (Supported by the IZKF Münster).
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
