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Sökning: WFRF:(Mäkinen K.)

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1.
  • Lepäntalo, M., et al. (författare)
  • PTFE bypass or thrupass for superficial femoral artery occlusion? : A randomised controlled trial
  • 2009
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 37:5, s. 578-584
  • Tidskriftsartikel (refereegranskat)abstract
    • Early results of a thrupass endograft in the treatment of femoral lesions are promising. Less morbidity and better cost-effectiveness are suggested to be achieved in the treatment of chronic lower limb ischaemia with endovascular treatment compared to surgical treatment. PATIENTS AND METHODS: This randomised multicentre trial aimed to enroll a group of 60+60 patients for the treatment of 5-25-cm occlusions of superficial femoral artery (SFA) to be followed up for 3 years. Patients were treated either with endoluminal PTFE thrupass (WL Gore & Ass) or with surgical polytetrafluoroethylene (PTFE) bypass to proximal popliteal artery. Primary patency at 3 years was scheduled to be the primary end-point and secondary patency, functional success, costs and quality of life the secondary end-points. RESULTS: A sample of 100 consecutive SFA occlusions in one of the centres revealed that only 4% of the lesions were amenable for the study. The trial was prematurely terminated due to the results of an interim analysis at the time when 44 patients were recruited: the 1-year primary patency (excluding technical failures) was 48% for thrupass and 95% for bypass (p=0.02). The patency difference in favour of surgical bypass over endovascular thrupass was also sustained after completion of 1-year follow-up, the primary patencies being 46% and 84% at 1 year with grossly equilinear life-table curves thereafter (p=0.18), respectively. The corresponding secondary patencies were 63% and 100% (p=0.05) when excluding technical failures and 58% and 100% (p=0.02) according to intention-to-treat analysis. Secondary outcomes were thus not analysed. CONCLUSION: Treatment of SFA occlusions (TASC IIB and C or Imelda Ia and II) should be done by PTFE bypass rather than by PTFE thrupass, as thrupass is connected with worse early outcome. These results represent only a small category of femoral disease.
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  • Mäkinen, Taija, et al. (författare)
  • Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3.
  • 2001
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The lymphatic vasculature transports extravasated tissue fluid, macromolecules and cells back into the blood circulation. Recent reports have focused on the molecular mechanisms regulating the lymphatic vessels. Vascular endothelial growth factor (VEGF)-C and VEGF-D have been shown to stimulate lymphangiogenesis and their receptor, VEGFR-3, has been linked to human hereditary lymphedema. Here we show that a soluble form of VEGFR-3 is a potent inhibitor of VEGF-C/VEGF-D signaling, and when expressed in the skin of transgenic mice, it inhibits fetal lymphangiogenesis and induces a regression of already formed lymphatic vessels, though the blood vasculature remains normal. Transgenic mice develop a lymphedema-like phenotype characterized by swelling of feet, edema and dermal fibrosis. They survive the neonatal period in spite of a virtually complete lack of lymphatic vessels in several tissues, and later show regeneration of the lymphatic vasculature, indicating that induction of lymphatic regeneration may also be possible in humans.
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5.
  • Achen, M G, et al. (författare)
  • Monoclonal antibodies to vascular endothelial growth factor-D block its interactions with both VEGF receptor-2 and VEGF receptor-3.
  • 2000
  • Ingår i: European Journal of Biochemistry. - 0014-2956 .- 1432-1033. ; 267:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor-D (VEGF-D), the most recently discovered mammalian member of the VEGF family, is an angiogenic protein that activates VEGF receptor-2 (VEGFR-2/Flk1/KDR) and VEGFR-3 (Flt4). These receptor tyrosine kinases, localized on vascular and lymphatic endothelial cells, signal for angiogenesis and lymphangiogenesis. VEGF-D consists of a central receptor-binding VEGF homology domain (VHD) and N-terminal and C-terminal propeptides that are cleaved from the VHD to generate a mature, bioactive form consisting of dimers of the VHD. Here we report characterization of mAbs raised to the VHD of human VEGF-D in order to generate VEGF-D antagonists. The mAbs bind the fully processed VHD with high affinity and also bind unprocessed VEGF-D. We demonstrate, using bioassays for the binding and cross-linking of VEGFR-2 and VEGFR-3 and biosensor analysis with immobilized receptors, that one of the mAbs, designated VD1, is able to compete potently with mature VEGF-D for binding to both VEGFR-2 and VEGFR-3 for binding to mature VEGF-D. This indicates that the binding epitopes on VEGF-D for these two receptors may be in close proximity. Furthermore, VD1 blocks the mitogenic response of human microvascular endothelial cells to VEGF-D. The anti-(VEGF-D) mAbs raised to the bioactive region of this growth factor will be powerful tools for analysis of the biological functions of VEGF-D.
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6.
  • Achen, M G, et al. (författare)
  • Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4).
  • 1998
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 95:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We have identified a member of the VEGF family by computer-based homology searching and have designated it VEGF-D. VEGF-D is most closely related to VEGF-C by virtue of the presence of N- and C-terminal extensions that are not found in other VEGF family members. In adult human tissues, VEGF-D mRNA is most abundant in heart, lung, skeletal muscle, colon, and small intestine. Analyses of VEGF-D receptor specificity revealed that VEGF-D is a ligand for both VEGF receptors (VEGFRs) VEGFR-2 (Flk1) and VEGFR-3 (Flt4) and can activate these receptors. However. VEGF-D does not bind to VEGFR-1. Expression of a truncated derivative of VEGF-D demonstrated that the receptor-binding capacities reside in the portion of the molecule that is most closely related in primary structure to other VEGF family members and that corresponds to the mature form of VEGF-C. In addition, VEGF-D is a mitogen for endothelial cells. The structural and functional similarities between VEGF-D and VEGF-C define a subfamily of the VEGFs.
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7.
  • Brändström, B. U. E., et al. (författare)
  • Results from the intercalibration of optical low-light calibration sources 2011
  • 2012
  • Ingår i: Geoscientific Instrumentation, Methods and Data Systems. - : European Geosciences Union (EGU). - 2193-0856 .- 2193-0864. ; 1, s. 43-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the 38th Annual European Meeting on Atmospheric Studies by Optical Methods in Siuntio in Finland, an intercalibration workshop for optical low light calibration sources was held in Sodankylä, Finland. The main purpose of this workshop was to provide a comparable scale for absolute measurements of aurora and airglow. All sources brought to the intercalibration workshop were compared to the Fritz Peak reference source using the Lindau Calibration Photometer built by Wilhelm Barke and Hans Lauche in 1984. The results were compared to several earlier intercalibration workshops. It was found that most sources were fairly stable over time, with errors in the range of 5–25%. To further validate the results, two sources were also intercalibrated at UNIS, Longyearbyen, Svalbard. Preliminary analysis indicates agreement with the intercalibration in Sodankylä within about 15–25%.
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8.
  • Ihalainen, Johanna K., et al. (författare)
  • Strength Training Improves Metabolic Health Markers in Older Individual Regardless of Training Frequency
  • 2019
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10:FEB
  • Tidskriftsartikel (refereegranskat)abstract
    • The main purpose of the present study was to investigate the effect of frequency, thereby increasing training volume, of resistance training on body composition, inflammation markers, lipid and glycemic profile in healthy older individuals (age range 65-75 year). Ninety-two healthy participants were randomly assigned to one of four groups; performing strength training one- (EX1), two- (EX2), or three- (EX3) times-per-week and a non-training control (CON) group. Whole-body strength training was performed using 2-5 sets and 4-12 repetitions per exercise and 7-9 exercises per session. All training groups attended supervised resistance training for 6 months. Body composition was measured by dual X-ray absorptiometry and fasting blood samples were taken pre- and post-training. There were significant main effects of time for total fat mass (F = 28.12, P < 0.001) and abdominal fat mass (F = 20.72, P < 0.001). Pre- to post-study, statistically significant reductions in fat mass (Delta = -1.3 +/- 1.4 kg, P < 0.001, n = 26) were observed in EX3. Pre- to post-study reductions in low density lipoprotein (LDL) concentration (Delta = -0.38 +/- 0.44 mmol.L-1 , P = 0.003, n = 19) were observed only in EX3, whereas a significant pre- to post-study increases in high density lipoprotein (HDL) concentration (0.14-0.19 mmol.L-1) were observed in all training groups. Most variables at baseline demonstrated a significant (negative) relationship when correlating baseline values with their change during the study including: Interleukin-6 (IL-6) (r = -0.583, P < 0.001), high-sensitivity c-reactive protein (hs-CRP) (r = -0.471, P < 0.001, and systolic blood pressure (r = -0.402, P = 0.003). The present study suggests that having more than two resistance training sessions in a week could be of benefit in the management of body composition and lipid profile. Nevertheless, interestingly, and importantly, those individuals with a higher baseline in systolic blood pressure, IL-6 and hs-CRP derived greatest benefit from the resistance training intervention, regardless of how many times-a-week they trained. Finally, the present study found no evidence that higher training frequency would induce greater benefit regarding inflammation markers or glycemic profile in healthy older adults.
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  • Mäkinen, Taija, et al. (författare)
  • Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1.
  • 1999
  • Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 274:30
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor B (VEGF-B) is expressed in various tissues, especially strongly in the heart, and binds selectively to one of the VEGF receptors, VEGFR-1. The two splice isoforms, VEGF-B(167) and VEGF-B(186), have identical NH(2)-terminal cystine knot growth factor domains but differ in their COOH-terminal domains which give these forms their distinct biochemical properties. In this study, we show that both splice isoforms of VEGF-B bind specifically to Neuropilin-1 (NRP1), a receptor for collapsins/semaphorins and for the VEGF(165) isoform. The NRP1 binding of VEGF-B could be competed by an excess of VEGF(165). The binding of VEGF-B(167) was mediated by the heparin binding domain, whereas the binding of VEGF-B(186) to NRP1 was regulated by exposure of a short COOH-terminal proline-rich peptide upon its proteolytic processing. In immunohistochemistry, NRP1 distribution was found to be overlapping or adjacent to known sites of VEGF-B expression in several tissues, in particular in the developing heart, suggesting the involvement of VEGF-B in NRP1-mediated signaling.
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11.
  • Mäkinen, Taija, et al. (författare)
  • Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3.
  • 2001
  • Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 20:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor receptor-3 (VEGFR-3/Flt4) binds two known members of the VEGF ligand family, VEGF-C and VEGF-D, and has a critical function in the remodelling of the primary capillary vasculature of midgestation embryos. Later during development, VEGFR-3 regulates the growth and maintenance of the lymphatic vessels. In the present study, we have isolated and cultured stable lineages of blood vascular and lymphatic endothelial cells from human primary microvascular endothelium by using antibodies against the extracellular domain of VEGFR-3. We show that VEGFR-3 stimulation alone protects the lymphatic endothelial cells from serum deprivation-induced apoptosis and induces their growth and migration. At least some of these signals are transduced via a protein kinase C-dependent activation of the p42/p44 MAPK signalling cascade and via a wortmannin-sensitive induction of Akt phosphorylation. These results define the critical role of VEGF-C/VEGFR-3 signalling in the growth and survival of lymphatic endothelial cells. The culture of isolated lymphatic endothelial cells should now allow further studies of the molecular properties of these cells.
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12.
  • Mäkinen, Taija, et al. (författare)
  • Molecular mechanisms of lymphangiogenesis.
  • 2002
  • Ingår i: Cold Spring Harbor Symposia on Quantitative Biology. - 0091-7451 .- 1943-4456. ; 67
  • Tidskriftsartikel (refereegranskat)
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  • Partanen, T A, et al. (författare)
  • Endothelial growth factor receptors in human fetal heart.
  • 1999
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 100:6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Endothelial receptor tyrosine kinases include 3 members of the vascular endothelial growth factor receptor (VEGFR) family and 2 members of the angiopoietin receptor (Tie) family. In addition, the VEGF(165) isoform binds to neuropilin-1 (NP-1), a receptor for collapsins/semaphorins. The importance of these receptors for vasculogenesis and angiogenesis has been shown in gene-targeted mice, but so far, little is known about their exact expression patterns in the human vasculature.METHODS AND RESULTS: Frozen sections of human fetal heart were stained immunohistochemically with receptor-specific monoclonal (VEGFR, Tie) or polyclonal (NP-1) antibodies. The following patterns were observed: The endocardium was positive for VEGFR-1, VEGFR-2, NP-1, Tie-1, and Tie-2 but negative for VEGFR-3. The coronary vessels were positive for Tie-1, Tie-2, VEGFR-1, and NP-1 and negative for VEGFR-2 and VEGFR-3. Myocardial capillaries and epicardial blood vessels stained for VEGFR-1, VEGFR-2, NP-1, and Tie-1; myocardial capillaries and epicardial veins weakly for Tie-2; and epicardial lymphatic vessels for VEGFR-2 and VEGFR-3, weakly for Tie-1 and Tie-2, but not for VEGFR-1 or NP-1.CONCLUSIONS: The results demonstrate differential expression of the endothelial growth factor receptors in distinct types of vessels in the human heart. This information is useful for the understanding of their roles in physiological and pathological processes and for their diagnostic and therapeutic application in cardiovascular medicine.
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15.
  • Petrova, T V, et al. (författare)
  • Signaling via vascular endothelial growth factor receptors.
  • 1999
  • Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 253:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiogenesis, or development of blood vessels from preexisting vasculature, has important functions under both normal and pathophysiological conditions. Vascular endothelial growth factor receptors 1-3, also known as flt-1, KDR, and flt-4, are endothelial cell-specific receptor tyrosine kinases which serve as key mediators of the angiogenic responses. The review focuses on the signaling pathways that are initiated from these receptors and the recently identified VEGF coreceptor neuroplilin-1.
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  • Rajan-Sithamparanadarajah, R, et al. (författare)
  • Patterns of dermal exposure to hazardous substances in European union workplaces.
  • 2004
  • Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 48:3, s. 285-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other types) in five countries in Europe. In order to optimize data collection and to develop a representative picture of dermal exposure, scenarios (tasks made up of a series of activities) were grouped together into dermal exposure operation units (DEOs). The allocation of scenarios to relevant DEOs was achieved on the basis of similarities of exposure routes, tasks and professional judgement. Sampling and quantification procedures were based on the approaches recommended by the OECD protocol. The laboratories involved in the analysis of the samples participated in quality assurance programmes. This exercise resulted in 419 body measurements and 437 measurements on hands expressed in terms of formulation (product) in use. Exposures for a given scenario varied by several orders of magnitude. The extent and patterns of exposure were found to be dependent on various exposure determinants, including inter- and intra-scenario variations. Hands were found to be the most contaminated parts of the body. Exposure patterns for liquid and solid contaminants were different. On the basis of the analysis of the data presented here, the averaged results (median and 95th percentile) for a given DEO unit should not be used as a representative measure of dermal exposure for all scenarios within that DEO without taking the exposure determinants into account. However, the data could be used to develop an exposure matrix (indicative exposure distributions) for different types of scenario and workplace, using determinants of exposure and a Bayesian approach to integrating expert opinion.
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18.
  • Saari, Ulla A., et al. (författare)
  • Exploring factors influencing the acceptance of social robots among early adopters and mass market representatives
  • 2022
  • Ingår i: Robotics and Autonomous Systems. - : Elsevier. - 0921-8890 .- 1872-793X. ; 151
  • Tidskriftsartikel (refereegranskat)abstract
    • When designing social robots, it is crucial to understand the diverse expectations of different kinds of innovation adopters. Different factors influence early adopters of innovations and mass market representatives’ perceptions of the usefulness of social robots. The first aim of the study was to test how applicable the technology acceptance model 3 (TAM3) is in the context of social robots. Participants’ acceptance of social robotics in a workplace environment in the fuzzy front-end (FFE) innovation phase of a robot development project was examined. Based on the findings for the model, we developed a reduced version of the TAM3 that is more applicable for social robots. The second objective was to analyze how early adopters’ and mass market representatives’ acceptance of social robots differs. Quantitative research methods were used. For early adopters, result demonstrability has a significant influence on perceived usefulness of social robots, while for mass market representatives, perceived enjoyment has a more significant influence on perceived usefulness. The findings indicate that users’ innovation adoption style influences the factors that users consider important in the usefulness of social robots. Robot developers should take these into account during the FFE innovation phase.
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  • Tukiainen, T., et al. (författare)
  • Mild cognitive impairment associates with concurrent decreases in serum cholesterol and cholesterol-related lipoprotein subclasses
  • 2012
  • Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 16:7, s. 631-635
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: Accumulating evidence suggests that serum lipids are associated with cognitive decline and dementias. However, majority of the existing information concerns only serum total cholesterol (TC) and data at the level of lipoprotein fractions and subclasses is limited. The aim of this study was to explore the levels and trends of main cholesterol and triglyceride measures and eight lipoprotein subclasses during normal aging and the development of mild cognitive impairment by following a group of elderly for six years. Design: Longitudinal. Setting: City of Kuopio, Finland. Participants: 45 elderly individuals of which 20 developed mild cognitive impairment (MCI) during the follow-up. Measurement: On each visit participants underwent an extensive neuropsychological and clinical assessment. Lipoprotein levels were measured via 1H NMR from native serum samples. Results: Serum cholesterol and many primarily cholesterol-associated lipoprotein measures clearly decreased in MCI while the trends were increasing for those elderly people who maintained normal cognition. Conclusion: These findings suggest that a decreasing trend in serum cholesterol measures in elderly individuals may suffice as an indication for more detailed inspection for potential signs of cognitive decline.
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21.
  • Veikkola, T, et al. (författare)
  • Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice.
  • 2001
  • Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 20:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor receptor-3 (VEGFR-3) has an essential role in the development of embryonic blood vessels; however, after midgestation its expression becomes restricted mainly to the developing lymphatic vessels. The VEGFR-3 ligand VEGF-C stimulates lymphangiogenesis in transgenic mice and in chick chorioallantoic membrane. As VEGF-C also binds VEGFR-2, which is expressed in lymphatic endothelia, it is not clear which receptors are responsible for the lymphangiogenic effects of VEGF-C. VEGF-D, which binds to the same receptors, has been reported to induce angiogenesis, but its lymphangiogenic potential is not known. In order to define the lymphangiogenic signalling pathway we have created transgenic mice overexpressing a VEGFR-3-specific mutant of VEGF-C (VEGF-C156S) or VEGF-D in epidermal keratinocytes under the keratin 14 promoter. Both transgenes induced the growth of lymphatic vessels in the skin, whereas the blood vessel architecture was not affected. Evidence was also obtained that these growth factors act in a paracrine manner in vivo. These results demonstrate that stimulation of the VEGFR-3 signal transduction pathway is sufficient to induce specifically lymphangiogenesis in vivo.
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22.
  • Wise, L M, et al. (författare)
  • Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1.
  • 1999
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 96:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Orf virus, a member of the poxvirus family, produces a pustular dermatitis in sheep, goats, and humans. The lesions induced after infection with orf virus show extensive proliferation of vascular endothelial cells, dilation of blood vessels and dermal swelling. An explanation for the nature of these lesions may lie in the discovery that orf virus encodes an apparent homolog of the mammalian vascular endothelial growth factor (VEGF) family of molecules. These molecules mediate endothelial cell proliferation, vascular permeability, angiogenesis, and lymphangiogenesis via the endothelial cell receptors VEGFR-1 (Flt1), VEGFR-2 (KDR/Flk1), and VEGFR-3 (Flt4). The VEGF-like protein of orf virus strain NZ2 (ORFV2-VEGF) is most closely related in primary structure to VEGF. In this study we examined the biological activities and receptor specificity of the ORFV2-VEGF protein. ORFV2-VEGF was found to be a disulfide-linked homodimer with a subunit of approximately 25 kDa. ORFV2-VEGF showed mitogenic activity on bovine aortic and human microvascular endothelial cells and induced vascular permeability. ORFV2-VEGF was found to bind and induce autophosphorylation of VEGFR-2 and was unable to bind or activate VEGFR-1 and VEGFR-3, but bound the newly identified VEGF165 receptor neuropilin-1. These results indicate that, from a functional viewpoint, ORFV2-VEGF is indeed a member of the VEGF family of molecules, but is unique, however, in that it utilizes only VEGFR-2 and neuropilin-1.
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