| 1. |
- Krettek, Alexandra, 1968-, et al.
(författare)
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Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGF-beta
- 2001
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 156:2, s. 267-275
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Tidskriftsartikel (refereegranskat)abstract
- In the early atherosclerotic lesion, monocytes accumulate at sites of inflammation and endothelial injury. Platelet-derived growth factor (PDGF), produced for example by macrophages, is a chemoattractant for smooth muscle cells and possibly also for macrophages. During early differentiation into macrophages, human monocytes (early hMDM) showed lower expression of PDGF alpha-receptor (PDGF-Ralpha) than beta-receptor (PDGF-Rbeta) mRNA. Early hMDM showed increased random motility (chemokinesis) in the presence of PDGF of the long (BB(L)) but not short (BB(S)) B-chain homodimer. Neither PDGF-AA(S) nor PDGF-AA(L) affected early hMDM motility. Since increased cytokine levels accompany inflammation, the influence of interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) on PDGF-R expression and migratory response were studied. Only PDGF-Ralpha mRNA was highly upregulated by IFN-gamma. TGF-beta only had minor effects on receptor mRNAs. Upregulation of PDGF-Ralpha levels by IFN-gamma was accompanied by significantly increased migration (chemotaxis) towards PDGF-AA(L) only. Consequently, IFN-gamma modulates PDGF-Rs expression in early hMDM and, subsequently, the chemotactic activity of PDGF-AA(L) on IFN-gamma-stimulated early hMDM. This suggests that PDGF-AA(L) may be involved in attracting activated monocytes to sites of inflammation and injury.
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| 2. |
- Krettek, Alexandra, 1968-, et al.
(författare)
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Quantitation of platelet-derived growth factor receptors in human arterial smooth muscle cells in vitro
- 1997
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 17:11, s. 2395-2404
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) is suggested to play an important role in the development of atherosclerosis as a migratory and mitogenic stimulus to arterial smooth muscle cells (ASMCs). Stimulated and unstimulated ASMCs were studied with respect to PDGF receptor (PDGF-R) mRNA and protein expression. Quantitative RT-PCR was developed for simultaneous evaluation of both PDGF-R alpha and -R beta mRNA expression and a quantitative ELISA for estimation of corresponding PDGF-R subunits. On the mRNA level, the overall PDGF-R beta expression was approximately 100 times lower than that of PDGF-R alpha. Furthermore, although PDGF-R alpha mRNA levels were high irrespective of hASMC phenotype, PDGF-R beta mRNA was influenced by serum stimulation with lower copy numbers in proliferating and confluent cells compared with quiescent cells. On the protein level, quiescent hASMCs expressed 10 times more PDGF-R beta than PDGF-R alpha. Serum stimulation decreased cell surface PDGF-Rs, with most prominent loss of PDGF-R alpha (ELISA and immunohistochemistry). Our results suggest a differential regulatory pattern for PDGF-R alpha and -R beta and are compatible with the usage of alternative promoters for regulation of -R alpha expression. Further, it seems that the number of available receptor subunits is not the only determinant of variations in cell stimulation with different PDGF isoforms.
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| 3. |
- Dota, Corina-Dana, et al.
(författare)
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PC-Based ECG waveform recognition-validation of novel software against a reference ECG database
- 2009
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Ingår i: Ann Noninvasive Electrocardiol. - 1542-474X. ; 14 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: PC-based ECG measurements must cope with normal as well as pathological ECGs in a reliable manner. EClysis, a software for ECG measurements was tested against reference values from the Common Standards for Quantitative Electrocardiography (CSE) database. METHODS: Digital ECGs (12 leads, 500 Hz) were recorded by the CSE project. Data Set 3 contains reference values for 125 ECGs (33 normal and 92 pathological). Median values of measurements by 11 computer programs and by five cardiologists, respectively, refer to the earliest P and QRS onsets and to the latest P, QRS, and T offsets in any lead of a selected (index) beat. EClysis automatically measured all ECGs, without user interference. RESULTS: The PQRST points were correctly detected but in two ECGs with AV block II-III. The software was not designed to detect atrial activity in atrial fibrillation (n = 9) and flutter (n = 1). In one case of atrial fibrillation, atrial activity interfered with positioning of QRS and T offsets. Regression coefficients between EClysis and CSE (software-generated and human) were above 0.95 (P < 0.0001). The confidence intervals were 95% for the slope and the intercept of the regression lines. CONCLUSIONS: The PC-based detection and analysis of PQRST points showed a high level of agreement with the CSE database reference values.
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| 4. |
- Gavell, Marcus, 1981, et al.
(författare)
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A third order analogue pre-distorter MMIC for E-band PA linearisation
- 2022
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Ingår i: 2022 17th European Microwave Integrated Circuits Conference, EuMIC 2022. ; , s. 189-192
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Konferensbidrag (refereegranskat)abstract
- In this paper we present the design, characterisation and non-linear control of an analogue pre-distortion (APD) MMIC at E-band. With non-linear behaviour models of the APD MMIC, we demonstrate the capability of controlling the quadrature gain and quadrature third order term. Finally, the APD is combined with a 1 W E-band PA, where we by cascading their measured responses show overall more linear behaviour towards saturated output power compared with the non-linearised 1 W PA. Simulated with 256 QAM modulated signals, the average output power of the linearised PA was 22.2 dBm in comparison to 18.7 dBm.
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| 5. |
- Krettek, Alexandra, 1968-, et al.
(författare)
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Effect of phenotype on the transcription of the genes for platelet-derived growth factor (PDGF) isoforms in human smooth muscle cells, monocyte-derived macrophages, and endothelial cells in vitro
- 1997
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 17:11, s. 2897-2903
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation of arterial smooth muscle cells (ASMCs) contributes considerably to enlargement of the arterial wall during atherosclerosis. The platelet-derived growth factor (PDGF) is a well-known mitogen and chemoattractant for ASMCs. Quantitative reverse transcription-polymerase chain reaction showed that cells appearing in atherosclerotic lesions, such as ASMCs, endothelial cells, and monocytes/macrophages, expressed mRNAs for both PDGF A and B chains in vitro, with the highest expression in endothelial cells. On proliferation, ASMCs and endothelial cells upregulated PDGF A mRNA. Differentiation of macrophages increased the amount of both mRNAs. Thus, the regulation of PDGF A- and B-chain expression depends on cell types and phenotypic states of the cells, which have also been found in vivo in human atherosclerotic lesions. PDGF A can be produced as short and long isoforms. The latter binds with high affinity to glycosaminoglycans. Irrespective of phenotype, only the minor part of total PDGF A mRNA consisted of the long variant in ASMCs, while endothelial cells produced 40% of total PDGF A as the long form. The differentiation of macrophages increased the production of the long PDGF A mRNA from 10% to 40%. Thus, increasing numbers of stimulated cells in the atherosclerotic lesion may increase the transcription of PDGF isoforms, and particularly of the long PDGF A isoform. Together with increasing amounts of ASMC-derived proteoglycans in developing lesions, this may contribute to accumulation of PDGF in the arterial wall matrix, resulting in prolonged stimulation of ASMCs.
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| 8. |
- Lustig, Florentina, 1948, et al.
(författare)
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Alternative splicing determines the binding of platelet-derived growth factor (PDGF-AA) to glycosaminoglycans.
- 1996
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 35:37, s. 12077-85
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Tidskriftsartikel (refereegranskat)abstract
- We have shown previously that the platelet-derived growth factor (PDGF) and a synthetic oligopeptide, corresponding to the basic carboxyl-terminal amino acid extension of the long PDGF-A isoform, bind to heparin. Here, we have expressed the long (rA125) and the short (rA109) variants of PDGF A-chains in Escherichia coli and produced the functional homodimers. Surface plasmon resonance analyses showed that while the dimeric rA125 bound with high affinity to low molecular weight heparin, the rA109, lacking the basic extension, did not. This strongly indicated that high affinity binding is due to the carboxyl-terminal extension. Investigations of kinetics and thermodynamics suggested an allosteric binding mechanism. Thus, dimeric rA125 contains two equivalent binding sites. Following low affinity binding of heparin to one binding site, the dimer undergoes a conformational change, increasing the affinity for heparin about 40 times. This positive cooperativity requires the basic amino acid extension in both monomers of the dimeric PDGF molecule. Thermodynamics of the reaction, showing an entropy-driven endothermic process, suggest the involvement of hydrophobic interactions in this rearrangement. Three amino acids in the basic carboxyl-terminal extension were essential for the interaction: the basic residues Arg111 and Lys116, and the polar Thr125. We also found that other glycosaminoglycan species, corresponding to those produced by human arterial smooth muscle cells, bound to dimeric rA125 and that heparan sulfate showed the highest affinity.
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| 9. |
- Lustig, Florentina, 1948, et al.
(författare)
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Processing of PDGF gene products determines interactions with glycosaminoglycans.
- 1999
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Ingår i: Journal of molecular recognition : JMR. - 0952-3499. ; 12:2, s. 112-20
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Tidskriftsartikel (refereegranskat)abstract
- The platelet derived growth factor (PDGF), a mitogen for mesenchymal cells, may be bound to and inhibited by heparin and other glycosaminoglycans. PDGF is a homo- or heterodimer of A- and B-chains. They occur as short (A109 and B110) and long (A125 and B160) isoforms. The latter contain basic carboxyl-terminal extensions. Dimeric A125 binds to heparin through its basic extension in a two-step reaction. The mechanism involves a conformational change and is consistent with a Monod-Wyman-Changeux allosteric model. Previous indirect experiments suggested that three critical amino acids (basic R111, K116 and polar T125) might be involved. Here, direct binding experiments using dimeric full-length mutants in surface plasmon resonanse analysis showed that all three critical amino acids in an R(X)4K(X)8T-motif contributed in a concerted manner to the high affinity binding. Mutations of these amino acids to alanine resulted in large thermodynamic changes, loss of the allosteric mechanism and order(s) of magnitude lower binding affinity. The binding mechanism and affinity of long dimeric rB were similar to the mutants. Short dimeric rA109 and rB110 showed 100 times lower binding affinity than rA125. Consequently, interactions with glycosaminoglycans in tissues varies between PDGF isoforms and may influence their local accumulation and activity.
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| 10. |
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