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  • 1
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background and Aims:  Recombinant erythropoietin upregulates the expression of the vascular endothelial growth factor (VEGF) receptors, Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), in endothelial cells. The integrity of the VEGF system seems to be crucial for the regulation of endothelial permeability and thus for the avoidance of renal protein leakage. As albuminuria/proteinuria is a hallmark of diabetic nephropathy, we examined cross-sectionally in 35 type 1 and 37 type 2 diabetic patients with various degrees of renal dysfunction and albuminuria whether there was an interrelationship between intrinsic erythropoietin (EPO) and VEGF/Flt-1.Methods and Results:  In patients with plasma creatinine values ≤1.5 (n = 53) or 〉1.5 mg/dL (n = 19), the mean serum EPO was 5.6 ± 4.4 and 10.2 ± 7.0 mU/mL (P = 0.02), respectively. In the two groups, urinary and serum VEGF165 concentrations were similarly distributed (mean 94.3 ± 91.8 vs 108 ± 72.2 ng/L and 91.7 ± 76.8 vs 91.9 ± 74.9 ng/L, respectively; both P = NS). The mean urinary Flt-1 for the two groups amounted to 0.14 ± 0.35 and 0.51 ± 0.93 ng/mL (P = 0.045), respectively. No correlation between VEGF or Flt-1 and EPO was apparent.Conclusion:  Our data suggest that in vivo EPO does not affect the functionality and/or production of components of the VEGF/Flt-1 system in diabetics with normal or reduced renal function.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 186 (1992), S. 251-257 
    ISSN: 1432-0568
    Keywords: Chorioallantoic membrane ; Angiogenesis ; Growth factors ; VEGF ; PDGF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo effects of two growth factors, VEGF165 and PDGF-BB, were studied in the chick chorioallantoic membrane (CAM). The factors were airdried on Thermanox discs and the inverted discs were placed on the day-13 CAM for a period of 3 days. The specimens were then fixed, examined under a stereomicroscope and processed for semi- and ultrathin sectioning. VEGF165 induces marked vascular growth. Many new blood vessels emerge from the precapillary arterioles, and a brush-like formation of vessels can be seen in this region. In the venous part of the vascular system, the formation of sinusoidal or lacunar vessels can be seen. Edema does not develop. PDGF-BB induces thickening of the CAM due to extracellular-matrix production and the proliferation or immigration of fibrocytes. These lie just beneath the ectodermal epithelium and are oriented parallel to it. Out of the four factors we have already studied (PDGF-BB, VEGF165, Angiogenin, bFGF), only VEGF165 specifically induces the growth of blood vessels.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] FIG. 1 VEGF mRNA is expressed in some astrocytoma cells but is significantly upregulated in a subset of glioblastoma cells in vivo. Frozen sections from low-grade and high-grade glioma hybridized in situ with VEGF cRNA. a-d (facing page), Low-power microphotographs from low-grade glioma ...
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0878
    Keywords: Chorioallantoic membrane ; Angiogenesis ; Vascular endothelial growth factor (VEGF) ; Basic fibroblast growth factor (bFGF) ; Heparin ; Domestic fowl (White Leghorn)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of vascular endothelial growth factor (VEGF165) on the chorioallantoic membrane (CAM) of 13-day-old chick embryos was studied. The factor was applied in doses of 0.5–4 μg for a period of up to 4 days. Macroscopical, histological and immunohistological studies were carried out. The localization of the factor was examined with an anti-VEGF antibody. The mitogenicity of VEGF165 and basic fibroblast growth factor (bFGF) were studied by means of the BrdU-anti-BrdU method. Furthermore, the effect of heparin alone and in combination with VEGF165 was investigated. VEGF165 specifically induces angiogenesis in doses of 0.5 μg and more. A brush-like formation of blood vessels can be seen in the region of the precapillary vessels. Angiogenesis also takes place in the region of the capillaries and the venules. Histologically we found indications of sprouting as well as of intussusceptive capillary growth. The presence of the factor in the application area could be demonstrated with the anti-VEGF antibody for a period of 3 days. The factor is located in the chorionic epithelium and the intraepithelial capillaries. The BrdU-studies show that VEGF165 induces strong endothelial cell proliferation, whereas bFGF elicits fibrocyte proliferation and minor endothelial cell proliferation. Heparin induces squamous metaplasia of the chorionic and allantoic epithelium in combination with an aggregation of fibrocytes. We could not detect any enhancement of VEGF165 by heparin.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Angiogenesis 3 (1999), S. 33-39 
    ISSN: 1573-7209
    Keywords: angiogenesis ; Flt-1 ; soluble receptors ; vascular endothelial growth factor ; VEGF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The three human VEGF receptors 1–3 mediate biological signals important for new blood vessel formation and lymphangiogenesis. Soluble VEGF receptors contain all the information necessary for high affinity ligand binding and have been used as experimental tools and regulators in several angiogenic in vitro and in vivo models. Recombinant receptor molecules can be used for specific inhibition of VEGF mediated signal transduction and for blocking tumor angiogenesis by limiting the amount of VEGF secreted from tumor cells or stroma cells. A naturally occurring soluble VEGFR-1 has been discovered in the supernatant from endothelial cells and at present appears to be the key regulator for the availability of VEGF secreted from different cells and tissues. The exact physiological role has not yet been demonstrated.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7209
    Keywords: Capillary ; heterodimer ; homodimer ; vascular ; endothelial growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to characterize the capillary density, progression and persistence of new capillaries induced by different isoforms of vascular endothelial growth factor (VEGF)-A. They were produced and purified using the same protocol and assessed in the same experimental model, the rabbit cornea assay. Monogenic homodimers for VEGF121 and VEGF165 together with the heterodimer VEGF121/165 were tested as slow release polymer pellets implanted into the avascular rabbit cornea and examined up to 18 days post-implantation. The implants consistently stimulated angiogenesis in the absence of inflammation. The VEGF121 isoform produced the strongest increase of new capillary vessels which rapidly and persistently progressed into the corneal stroma. VEGF165 promoted the growth of a smaller number of capillaries which ten-ded to regress over time. Heterodimers of VEGF121/165 produced intermediate in vivo activities between the two homodimers. In vitro endothelial cell proliferation, mobilization and adhesion were promoted by all VEGF isoforms under serum-free or serum-reduced conditions with the same order of potency. Anti-soluble KDR (sKDR) antibody completely inhibited the effects of all the isoforms. These results indicate that monogenic homodimer preparations of VEGF121 and VEGF165 can display distinct biological effects which are functionally retained after the heterodimeric assembly of VEGF121 and VEGF165. The observed different biological behavior of the VEGF isoforms reveals the possibility that in vivo the assembly of dimers derived from splicing of a single gene may yield molecules with either different matrix or receptor interaction, stability or diffusion rate according to specific needs.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 47 (1991), S. 158-164 
    ISSN: 0730-2312
    Keywords: bFGF ; capillary endothelial cells ; transcriptional regulation ; autoinduction ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The growth of capillary endothelial cells (BCE) is an important regulatory step in the formation of capillary blood vessels. In vivo, the proliferation of these cells is stringently controlled. In vitro they can be stimulated by polypeptide growth factors, such as acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF). Since bFGF is synthesized and stored by vascular endothelial cells, this mitogen may play an important role in an autocrine growth regulation during angiogenesis. Here, evidence is presented for induction of the mRNA of bFGF by bFGF itself. A similar increase of bFGF mRNA was observed in response to thrombin and after treatment with phorbol ester. These results suggest that an autocrine loop may exist that may serve to modulate the mitogenic response in BCE under various physiological conditions, (e.g., wound healing and new capillary formation).
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0730-2312
    Keywords: VEGF ; PIGF ; KDR ; flt ; endothelial cells ; placenta ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Vascular endothelial growth factor (VEGF) is a newly identified growth and permeability factor with a unique specificity for endothelial cells. Recently the flt-encoded tyrosine kinase was characterized as a receptor for VEGF. A novel tyrosine kinase receptor encoded by the KDR gene was also found to bind VEGF with high affinity when expressed in CMT-3 cells. Screening for flt and KDR expression in a variety of species and tissue-derived endothelial cells demonstrates that flt is predominantly expressed in human placenta and human vascular endothelial cells. Placenta growth factor (PIGF), a growth factor significantly related to VEGF, is coexpressed with flt in placenta and human vascular endothelial cells. KDR is more widely distributed and expressed in all vessel-derived endothelial cells. These data demonstrate that cultured human endothelial cells isolated from different tissues express both VEGF receptors in relative high levels and, additionally, that all investigated nonhuman endothelial cells in culture are also positive for KDR gene expression.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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