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Sample records for factor bfgf zur

  1. Basic Fibroblast Growth Factor (bFGF, FGF-2) Potentiates Leukocyte Recruitment to Inflammation by Enhancing Endothelial Adhesion Molecule Expression

    PubMed Central

    Zittermann, Sandra I.; Issekutz, Andrew C.

    2006-01-01

    Basic fibroblast growth factor (bFGF, FGF-2) is a potent angiogenic factor and endothelial cell mitogen. Although bFGF levels are increased in chronically inflamed tissue, its role in inflammation is unclear. We investigated the effect of bFGF on acute dermal inflammation and the recruitment of monocytes, T cells, and neutrophils. Leukocyte recruitment to inflamed sites was quantified with radiolabeled leukocytes. Intradermal injection of bFGF in rats did not induce leukocyte recruitment or inflammation. However, the recruitment of leukocytes to inflammation induced by tumor necrosis factor-α, interferon-γ, C5a, or a delayed hypersensitivity reaction was enhanced by bFGF by 55 to 132% (P < 0.05). Either acute or prolonged bFGF treatment of dermal sites had this effect. The potentiating effect of bFGF on leukocyte recruitment was also seen in joints. There was no associated modulation of vascular permeability, blood flow, or angiogenesis in the sites by bFGF. However, the expression of the endothelial cell adhesion molecules (CAMs) for leukocytes, P-selectin, E-selectin, and ICAM-1, was significantly up-regulated in the inflamed tissue by bFGF, as quantified by radiolabeled anti-CAM antibody binding in vivo. Thus, although not directly proinflammatory, bFGF synergistically potentiates inflammatory mediator-induced leukocyte recruitment, at least in part, by enhancing CAM up-regulation on endothelium. PMID:16507899

  2. Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis

    PubMed Central

    Hu, Mingming; Hu, Ying; He, Jiabei; Li, Baolan

    2016-01-01

    Background Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis. Method Studies were identified by an electronic search of PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang databases, including publications prior toAugust 2014. Pooled hazard ratios (HR) for overall survival (OS) were aggregated and quantitatively analyzed by meta-analysis. Results Twenty-two studies (n = 2154) were evaluated in the meta-analysis. Combined HR suggested that bFGF overexpression had an adverse impact on survival of patients with lung cancer(HR = 1.202,95%CI, 1.022–1.382). Our subgroup analysis revealed that the combined HR evaluating bFGF expression on OS in operable non-small cell lung cancer (NSCLC) was 1.553 (95%CI, 1.120–1.986); the combined HR in small cell lung cancer (SCLC) was 1.667 (95%CI, 1.035–2.299). There was no significant impact of bFGF expression on survival in advanced NSCLC. Conclusion This meta-analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC, but is not associated with outcome in advanced NSCLC. The data suggests that high bFGF expression is highly related to poor prognosis. Nevertheless,more high-quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer. PMID:26824699

  3. Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration.

    PubMed

    Hafenbreidel, Madalyn; Twining, Robert C; Rafa Todd, Carolynn; Mueller, Devin

    2015-12-01

    Drug exposure results in structural and functional changes in brain regions that regulate reward and these changes may underlie the persistence of compulsive drug seeking and relapse. Neurotrophic factors, such as basic fibroblast growth factor (bFGF or FGF2), are necessary for neuronal survival, growth, and differentiation, and may contribute to these drug-induced changes. Following cocaine exposure, bFGF is increased in addiction-related brain regions, including the infralimbic medial prefrontal cortex (IL-mPFC). The IL-mPFC is necessary for extinction, but whether drug-induced overexpression of bFGF in this region affects extinction of drug seeking is unknown. Thus, we determined whether blocking bFGF in IL-mPFC would facilitate extinction following cocaine self-administration. Rats were trained to lever press for intravenous infusions of cocaine before extinction. Blocking bFGF in IL-mPFC before four extinction sessions resulted in facilitated extinction. In contrast, blocking bFGF alone was not sufficient to facilitate extinction, as blocking bFGF and returning rats to their home cage had no effect on subsequent extinction. Furthermore, bFGF protein expression increased in IL-mPFC following cocaine self-administration, an effect reversed by extinction. These results suggest that cocaine-induced overexpression of bFGF inhibits extinction, as blocking bFGF during extinction permits rapid extinction. Therefore, targeted reductions in bFGF during therapeutic interventions could enhance treatment outcomes for addiction.

  4. Entrapment of basic fibroblast growth factor (bFGF) in a succinylated chitosan nanoparticle delivery system and release profile.

    PubMed

    Butko, Alison; Bonat Celli, Giovana; Paulson, Allan; Ghanem, Amyl

    2016-07-01

    Basic fibroblast growth factor (bFGF) helps to regulate the proliferation and migration of fibroblasts, the proliferation of endothelial cells, and aids the development of angiogenesis. Its in vivo half-life is on the order of minutes due to extensive degradation and inactivation, which could be potentially reduced by controlled release vehicles. In this study, bFGF was entrapped into chitosan (CS) and N-succinyl-chitosan (SC) nanoparticles, with and without heparin, at two levels of initial loading, followed by further characterization of the particles. Release studies were conducted using radiolabeled bFGF-loaded nanoparticles. Both types of nanoparticles loaded similar amounts of bFGF (60.2 and 68.6% for CS and SC, respectively). The release profile varied greatly among the samples, and a burst release was observed in most cases, with the release amount approaching its final value in the first 6 h. The final amount released varied from 1.5 to 18% of the amount of bFGF-entrapped. The concomitant encapsulation of heparin and the use of SC as a nanoparticle matrix contributed to the largest amount of bFGF release (18%) over the time investigated.

  5. Comparison of human dermal fibroblasts (HDFs) growth rate in culture media supplemented with or without basic fibroblast growth factor (bFGF).

    PubMed

    Abdian, Narges; Ghasemi-Dehkordi, Payam; Hashemzadeh-Chaleshtori, Morteza; Ganji-Arjenaki, Mahbobe; Doosti, Abbas; Amiri, Beheshteh

    2015-12-01

    Basic fibroblast growth factor (bFGF or FGF-2) is a member of the FGF family secreted by different kinds of cells like HDFs and it is an important nutritional factor for cell growth and differentiation. The HDFs release bFGF in culture media at very low. The present study aims to investigate the HDFs growth rate in culture media supplemented either with or without bFGF. In brief, HDFs were isolated from human foreskin sample and were cultured in vitro in media containing bFGF and lack of this factor. The cells growth rate was calculated by trypan blue. The karyotyping was performed using G-banding to investigate the chromosomal abnormality of HDFs in both groups. Total RNA of each groups were extracted and cDNA samples were synthesized then, real-time Q-PCR was used to measure the expression level of p27kip1 and cyclin D1 genes normalized to internal control gene (GAPDH). The karyotype analysis showed that HDFs cultured in media or without bFGF had normal karyotype (46 chromosomes, XY) and chromosomal abnormalities were not observed. The cell growth rates in both groups were normal with proliferated exponentially but the slope of growth curve in HDFs cultured in media containing bFGF was increased. Karyotyp test showed that bFGF does not affect on cytogenetic stability of cells. The survey of p27kip1 and cyclin D1 genes by real-time Q-PCR showed that the expression level of these genes were up-regulated when adding bFGF in culture media (p < 0.05). The findings of the present study demonstrate that appropriate supplementation of culture media with growth factor like bFGF could enhance the proliferation and differentiation capacity of cells and improve cells growth rate. Similarly, fibroblast growth factors did not induce any chromosomal abnormality in cells. Furthermore, in HDFs cultured in bFGF supplemented media, the p27kip1 and cyclin D1 genes were up-regulated and suggesting an important role for bFGF in cell-cycle regulation and progression and fibroblast

  6. Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells by controlling bFGF and PDGF autocrine/paracrine loops.

    PubMed

    Ma, Yang; Han, Chen-Chen; Li, Yifan; Wang, Yang; Wei, Wei

    2016-09-16

    Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) produced by hepatocellular carcinoma (HCC) cells are responsible for the growth of HCC cells. Accumulating evidence shows that insulin-like growth factor-binding protein-3 (IGFBP-3) suppresses HCC cell proliferation in both IGF-dependent and independent manners. It's unknown, however, whether treatment with exogenous IGFBP-3 inhibits bFGF and PDGF production in HCC cells. The present study demonstrates that IGFBP-3 suppressed IGF-1-induced bFGF and PDGF expression while it does not affect their expression in the absence of IGF-1. To delineate the underlying mechanism, western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1 (EGR1) is involved in IGFBP-3 regulation of bFGF and PDGF. IGFBP-3 inhibition of type 1 insulin-like growth factor receptor (IGF1R), ERK and AKT activation is IGF-1-dependent. Furthermore, transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1, bFGF and PDGF expression. In conclusion, these findings suggest that IGFBP-3 suppresses transcription of EGR1 and its target genes bFGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation. It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation, suggesting that IGFBP-3 could be a target for the treatment of HCC. PMID:27521890

  7. Growth factor expression during rat development: a comparison of TGF-beta 3, TGF-alpha, bFGF, PDGF and PDGF-R.

    PubMed Central

    Burton, P. B.; Quirke, P.; Sorensen, C. M.; Nehlsen-Cannarella, S. L.; Bailey, L. L.; Knight, D. E.

    1993-01-01

    At least part of the mechanism underlying fetal development appears to be the production of a number of growth factors considered important in the process of tumour formation. Using immunocytochemistry, we have investigated the temporal and spatial pattern of expression of some of the important growth factors, by the fetus. We describe here the cellular localization of transforming growth factor beta 3 (TGF-beta 3), platelet derived growth factor (PDGF) and its receptor (PDGF-R), TGF-alpha and basic fibroblast growth factor (bFGF) in the fetal rat from day 13 to 21 of gestation. Using antisera raised against an N-terminal portion of TGF-beta 3, immunoreactivity peaked around day 16 and was seen predominantly within epithelial cells. However, using antisera raised against the C-terminal of this molecule immunoreactivity was seen exclusively within the extracellular matrix underlying adjacent epithelia, and was maintained up until day 21 of gestation. Strong expression of TGF-alpha was seen in cells of most organs throughout the gestation period studied. Immunoreactivity for bFGF, PDGF and PDGF-R peaked around day 18 in both epithelial and mesenchymal cells of all major organ systems and then declined by day 21. These data suggest distinct roles for each factor during embryogenesis and tumorigenesis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8471538

  8. 5. Accelerated Fracture Healing Targeting Periosteal Cells: Possibility of Combined Therapy of Low-Intensity Pulsed Ultrasound (LIPUS), Bone Graft, and Growth Factor (bFGF).

    PubMed

    Uchida, Kentaro; Urabe, Ken; Naruse, Koji; Mikuni-Takagaki, Yuko; Inoue, Gen; Takaso, Masashi

    2016-08-01

    We have studied the mechanism of fracture healing, and the effect of LIPUS, bone graft and growth factor on accelerating fracture healing. We present here the results of our research. To examine callus formation cells in fracture healing, we made marrow GFP chimera mice and a fracture model of marrow mesenchymal stem cell GFP chimera mice. It was demonstrated that periosteal cells were essential for callus formation. We focused on periosteal cells and examined the effect of LIPUS. In an in vitro experiment using a cultured part of the femur, LIPUS promoted ossification of the periosteal tissue. Further, LIPUS accelerated VEGF expression in the experiment using the femoral fracture model of mice. From these results, it was suggested that activation of periosteal cells might play a role in the fracture healing mechanism of LIPUS. Next, we discussed the possibility of combined therapy of LIPUS, bone graft and growth factor. Therapy involving the topical administration of bFGF using a controlled release system and bone graft could promote callus formation. In addition, LIPUS was able to promote membranaceous ossification after the bone graft. It was suggested that combined therapy of LIPUS, bone graft and bFGF could be a new option for treating fractures. PMID:27441766

  9. Stem cells with FGF4-bFGF fused gene enhances the expression of bFGF and improves myocardial repair in rats

    SciTech Connect

    Chen, Xiang-Qi; Chen, Liang-Long Fan, Lin; Fang, Jun; Chen, Zhao-Yang; Li, Wei-Wei

    2014-04-25

    Highlights: • BFGF exists only in the cytoplasm of live cells. • BFGF cannot be secreted into the extracellular space to promote cell growth. • We combine the secretion-promoting signal peptide of FGF4. • We successfully modified BMSCs with the fused genes of FGF4-bFGF. • We promoted the therapeutic effects of transplanted BMSCs in myocardial infarction. - Abstract: The aim of this study was to investigate whether the modification of bone marrow-derived mesenchymal stem cells (BMSCs) with the fused FGF4 (fibroblast growth factor 4)-bFGF (basic fibroblast growth factor) gene could improve the expression and secretion of BFGF, and increase the efficacies in repairing infarcted myocardium. We used In-Fusion technique to construct recombinant lentiviral vectors containing the individual gene of bFGF, enhanced green fluorescent protein (EGFP), or genes of FGF4-bFGF and EGFP, and then transfected these lentiviruses into rat BMSCs. We conducted an in vitro experiment to compare the secretion of bFGF in BMSCs infected by these lentiviruses and also examined their therapeutic effects in the treatment of myocardial infraction in a rodent study. Sixty rats were tested in the following five conditions: Group-SHAM received only sham operation as controls; Group-AMI received only injection of placebo PBS buffer; Group-BMSC, Group-bFGF and Group-FGF4-bFGF received implantation of BMSCs with empty lentivirus, bFGF lentivirus, and FGF4-bFGF lentivirus, respectively. Our results found out that the transplanted FGF4-bFGF BMSCs had the highest survival rate, and also the highest myocardial expression of bFGF and microvascular density as evidenced by Western blotting and immunohistochemistry, respectively. As compared to other groups, the Group-FGF4-BFGF rats had the lowest myocardial fibrotic fraction, and the highest left ventricular ejection fraction. These results suggest that the modification of BMSCs with the FGF4-bFGF fused gene can not only increase the expression of

  10. Effects of bFGF incorporated into a gelatin sheet on wound healing.

    PubMed

    Miyoshi, Michiyo; Kawazoe, Takeshi; Igawa, Hiroharu H; Tabata, Yasuhiko; Ikada, Yoshito; Suzuki, Shigehiko

    2005-01-01

    Basic fibroblast growth factor (bFGF) is well known to promote the proliferation of almost all cells associated with wound healing. However, as the activation duration of bFGF is very short in vivo, we incorporated bFGF into an acidic gelatin hydrogel and studied the sustained release of bFGF in vivo. In addition, we investigated the effects of the acidic gelatin sheet containing bFGF on wound healing. To distinguish wound contraction from neoepithelialization, we measured both the wound area and neoepithelium length. Other histological parameters such as thickness of granulation tissue and number of capillaries were also determined as indices of wound healing. Fibrous tissue was assessed using an Elastica van Gieson and Azan stain. A skin defect (1.5 x 1.5 cm) of full thickness was created on the back of each test mouse and the wound was covered with an acidic gelatin hydrogel, referred to as a gelatin sheet in this study (2 x 2 cm), with bFGF (100 microg/site) (A) or without bFGF (B). 1, 2, 3, 5, 7 and 14 days after covering, mice were killed and an enzyme-linked immunosorbent assay (ELISA) was performed to estimate the concentration of bFGF in the plasma. In another experiment, each wound was covered with (A), (B) or a hydrogel dressing (control group, C) and the wound area was measured 1 or 2 weeks postoperatively with a computer planimeter. The histological parameters, as mentioned above, were assessed using a light microscope. Sustained release of bFGF from the gelatin sheet was observed and the gelatin sheet containing bFGF promoted neoepithelialization, granulation, neovascularization and wound closure. This gelatin sheet containing bFGF was concluded to be effective for wound healing and promising for clinical use. PMID:16128295

  11. Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts

    PubMed Central

    1996-01-01

    Myogenic cells provide excellent in vitro models for studying the cell growth and differentiation. In this study we report that lysophosphatidic acid (LPA), a bioactive phospholipid contained in serum, stimulates the growth and inhibits the differentiation of mouse C2C12 myoblast cells, in a distinct manner from basic fibroblast growth factor (bFGF) whose mitotic and anti-differentiation actions have been well investigated. These actions of LPA were both blocked by pertussis toxin, suggesting the involvement of Gi class of G proteins, whereas bFGF acts through receptor tyrosine kinases. Detailed analysis revealed that LPA and bFGF act differently in regulating the myogenic basic helix-loop-helix (bHLH) proteins, the key players in myogenic differentiation process. LPA stimulates the proliferation of undifferentiated myoblasts allowing the continued expression of MyoD, but in contrast, bFGF does so with the MyoD expression suppressed at the mRNA level. Both compounds maintain the myf-5 expression, and suppress the myogenin expression. In addition, while LPA did not inhibit cell-cell contact-induced differentiation, bFGF strongly inhibited this process. Furthermore, LPA and bFGF act cooperatively in their mitogenic and anti-differentiation abilities. These findings indicate that LPA and bFGF differently stimulate intracellular signaling pathways, resulting in proliferating myoblasts each bearing a distinct expression pattern of myogenic bHLH proteins and distinct differentiation potentials in response to cell-cell contact, and illustrate the biological significance of Gi-mediated and tyrosine kinase-mediated signals. PMID:8567722

  12. Autologous fibrin scaffolds cultured dermal fibroblasts and enriched with encapsulated bFGF for tissue engineering.

    PubMed

    de la Puente, Pilar; Ludeña, Dolores; Fernández, Ana; Aranda, Jose L; Varela, Gonzalo; Iglesias, Javier

    2011-12-15

    Autologous fibrin scaffolds (AFSs) enriched with cells and specific growth factors represent a promising biocompatible scaffold for tissue engineering. Here, we analyzed the in vitro behavior of dermal fibroblasts (DFs) (cellular attachment, distribution, viability and proliferation, histological and immunohistochemical changes), comparing AFS with and without alginate microcapsules loaded with basic fibroblast growth factor (bFGF), to validate our scaffold in a future animal model in vivo. In all cases, DFs showed good adhesion and normal distribution, while in scaffolds with bFGF at 14 days, the cell counts detected in proliferation and viability assays were greatly improved, as was the proliferative state, and there was a decrease in muscle specific actin expression and collagen synthesis in comparison with the scaffolds without bFGF. In addition, the use of plasma without fibrinogen concentration methods, together with the maximum controlled release of bFGF at 14 days, favored cell proliferation. To conclude, we have been able to create an AFS enriched with fully functional DFs and release-controlled bFGF that could be used in multiple applications for tissue engineering.

  13. Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions.

    PubMed

    Comeau, Wendy; Gibb, Robbin; Hastings, Erica; Cioe, Jan; Kolb, Bryan

    2008-03-01

    We investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90-day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion-induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF. PMID:18286581

  14. Detecting the developmental toxicity of bFGF in the embryonic stem cell test using differential gene expression of differentiation-related genes.

    PubMed

    Deng, Shu-Qin; Xu, Hua; He, Qing; Jiang, Hai-Xiang; Su, Ben-Jin; Zhang, Qi-Hao

    2014-06-01

    Basic fibroblast growth factor (bFGF) is a mitogenic cytokine that can stimulate mesoderm-and neuroectoderm-originated cell proliferation. This study was performed to investigate the effects of bFGF on cell differentiation and the expression of specific markers at different embryonic developmental stages. We firstly evaluated the embryotoxic potential of bFGF in vitro using a modified EST protocol. Sequentially, we further investigated how bFGF impact the different tissue-special genes and proteins expressions during the differentiation of murine ES cells in vitro and attempt to reveal the effects of bFGF on differentiation processes. This analysis was focused on key tissue- and stage-specific genes involved in ectodermal, mesodermal, and endodermal differentiation, including ectodermal-specific gene Nestin, Oligo2 and Syn, mesodermal-specific gene MHC and MyoD, and endodermal-specific gene GATA6, TTR and ALB, as well as undifferentiated gene Sox-2 and Oct-4. The results demonstrate that bFGF could promote expression of ectodermal-specific genes and protein, but suppress the expressions of endoderm-specific and some mesoderm-specific gene and protein. A conclusion can be drawn that bFGF exhibits weak embryotoxicity and mainly promotes ES cell differentiation towards the ectodermal lineages but suppress differentiation into endoderm lineages. These opposing effects of bFGF on the embryonic development of the three germ layers may be related to its weak embryotoxic potential. More specifically, inhibition of expression of the endodermal-specific markers transthyretin (TTR), and albumin (ALB) by bFGF may be of more value in detecting the embryotoxic potential of bFGF.

  15. Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab

    PubMed Central

    Li, Jiu-Ke; Wei, Fang; Jin, Xiao-Hong; Dai, Yuan-Min; Cui, Hu-Shan; Li, Yu-Min

    2015-01-01

    AIM To evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR). METHODS This study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively. RESULTS In PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis. CONCLUSION We found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB

  16. Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

    PubMed Central

    Cai, Pingtao; Ye, Jingjing; Zhu, Jingjing; Liu, Dan; Chen, Daqing; Wei, Xiaojie; Johnson, Noah R.; Wang, Zhouguang; Zhang, Hongyu; Cao, Guodong; Xiao, Jian; Ye, Junming; Lin, Li

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress. PMID:27493838

  17. Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model.

    PubMed

    Cai, Pingtao; Ye, Jingjing; Zhu, Jingjing; Liu, Dan; Chen, Daqing; Wei, Xiaojie; Johnson, Noah R; Wang, Zhouguang; Zhang, Hongyu; Cao, Guodong; Xiao, Jian; Ye, Junming; Lin, Li

    2016-08-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress.

  18. Neural progenitor cell survival in mouse brain can be improved by co-transplantation of helper cells expressing bFGF under doxycycline control.

    PubMed

    Liang, Yajie; Ågren, Louise; Lyczek, Agatha; Walczak, Piotr; Bulte, Jeff W M

    2013-09-01

    Cell-based therapy of neurological disorders is hampered by poor survival of grafted neural progenitor cells (NPCs). We hypothesized that it is possible to enhance the survival of human NPCs (ReNcells) by co-transplantation of helper cells expressing basic fibroblast growth factor (bFGF) under control of doxycycline (Dox). 293 cells or C17.2 cells were transduced with a lentiviral vector encoding the fluorescent reporter mCherry and bFGF under tetracycline-regulated transgene expression (Tet-ON). The bFGF secretion level in the engineered helper cells was positively correlated with the dose of Dox (Pearson correlation test; r=0.95 and 0.99 for 293 and C17.2 cells, respectively). Using bioluminescence imaging (BLI) as readout for firefly luciferase-transduced NPC survival, the addition of both 293-bFGF and C17.2-bFGF helper cells was found to significantly improve cell survival up to 6-fold in vitro, while wild-type (WT, non-transduced) helper cells had no effect. Following co-transplantation of 293-bFGF or C17.2-bFGF cells in the striatum of Rag2(-/-) immunodeficient mice, in vivo human NPC survival could be significantly improved as compared to no helper cells or co-transplantation of WT cells for the first two days after co-transplantation. This enhancement of survival in C17.2-bFGF group was not achieved without Dox administration, indicating that the neuroprotective effect was specific for bFGF. The present results warrant further studies on the use of engineered helper cells, including those expressing other growth factors injected as mixed cell populations.

  19. Comparative evaluation of the wound-healing potency of recombinant bFGF and ski gene therapy in rats.

    PubMed

    Peng, Yan; Li, Ping; Zhao, Zi-Ai; Chen, Lei; Zhao, Xiao-Guang; Chen, Xing; Zhao, Yan; Xiong, Ren-Ping; Ning, Ya-Lei; Yang, Nan; Ye, Jian; Zhou, Yuan-Guo

    2016-08-01

    We previously demonstrated that cellular Sloan-Kettering Institute (c-Ski) played a dual role, both promoting wound healing and alleviating scar formation. However, its mechanism and therapeutic effects are not clear, especially compared with widely used treatments, such as basic fibroblast growth factor (bFGF) administration. However, Ski treatment led to an even shorter healing time and a more significant reduction in scar area than bFGF treatment. The mechanism underlying this difference was related to a reduced inflammatory response, more rapid re-epithelialization, less collagen after healing and a greater reduction in the proportion of alpha-smooth muscle actin and SMemb-positive cells after Ski treatment. These results not only confirm that Ski plays a dual role in promoting healing and reducing scarring but also suggest that Ski yields better treatment effects than bFGF, indicating better potential therapeutic effects in wound repair.

  20. Human amniotic fluid stem cells support undifferentiated propagation and pluripotency of human embryonic stem cell without b-FGF in a density dependent manner.

    PubMed

    Ma, Xiaorong; Li, Huanqi; Xin, Shujia; Ma, Yueting; Ouyang, Tianxiang

    2014-01-01

    Human embryonic stem cells (hESCs) are pluripotent cells which can give rise to almost all adult cell lineages. Culture system of hESCs is complex, requiring exogenous b-FGF and feeder cell layer. Human mesenchymal stem cells (MSCs) not only synthesize soluble cytokines or factors such as b-FGF, but also provide other mechanism which might play positive role on sustaining hESCs propagation and pluripotency. Human amniotic fluid stem (AFS) cells, which share characteristics of both embryonic and adult stem cells, have been regarded as promising cells for regenerative medicine. Taking advantage by AFS cells, we studied the ability of AFS cells in supporting undifferentiated propagation and pluripotency of Chinese population derived X-01 hESCs. Human AF-type amniotic fluid stem cells (hAF-AFSCs) transcribed genes including Activin A, TGF-β1, Noggin and b-FGF, which involved in maintaining pluripotency and self-renewal of hESCs. Compared to mouse embryonic fibroblasts (MEFs), hAF-AFSCs secreted higher concentration of b-FGF which was important in hESCs culture (P < 0.05). The hESCs were propagated more than 30 passages on hAF-AFSCs layer with exogenous b-FGF supplementation, keeping undifferentiated status. While exogenous b-FGF was obviated, propagation of hESCs with undifferentiated status was dependent on density of hAF-AFSC feeder layer. Lower density of hAF-AFSCs resulted in rapid decline in undifferentiated clone number, while higher ones hindered the growth of colonies. The most appropriate hAF-AFSCs feeder density to maintain the X-01 hESC line without exogenous b-FGF was 15-20×10(4)/well. To the best of our knowledge, this is the first study demonstrating that hAF-AFSCs could support undifferentiated propagation and pluripotency of Chinese population derived hESCs without exogenous b-FGF supplementation.

  1. b-FGF Induces Corneal Blood and Lymphatic Growth in a Spatially Distinct Pattern

    PubMed Central

    Hajrasouliha, Amir R.; Sadrai, Zahra; Chauhan, Sunil K.; Dana, Reza

    2013-01-01

    Purpose To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by b-FGF. Methods b-FGF micropellets (80ng) were implanted in the temporal side of the cornea of Balbc/c mice. On days 1, 3, and 7 blood (heme) and lymph-angiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative RT-PCR. Each cornea was divided in two different area defines as (i) pre-pellet area and (ii) opposite-pellet area. Expression of VEGF ligands were evaluated using Real-time PCR in each respective zone. Results Blood vessels grew into the cornea from the pre-pellet area while corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet while VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas. Conclusion A single inducing factor, i.e., b-FGF, may simultaneously provoke heme-and lymph-angiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination. PMID:22467003

  2. Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF.

    PubMed

    Carwile, M E; Culbert, R B; Sturdivant, R L; Kraft, T W

    1998-06-01

    We employed a morphological assay of outer segment collapse to determine if growth factors or other supplements directly affect dissociated rod photoreceptors in vitro. The morphological changes in outer segments were correlated with the light responsiveness of rods. Time-lapse video microscopy was used to observe the collapse of rod outer segments from isolated single cells and small clumps of cells. A consistent pattern of outer segment collapse into the inner segment was observed, yielding a convenient assay of the effects of neurotrophic factors on photoreceptor functional maintenance. The functional state of rods, defined as light-responsiveness, was measured with suction electrode recordings and matched with the various stages of outer segment collapse. Ciliary neurotrophic factor (CNTF) and glial cell-line-derived neurotrophic factor (GDNF) at a high concentration, yielded statistically significant improvements in rat outer segment survival times. Basic fibroblast growth factor (bFGF), which rescues photoreceptors in several rodent models of retinal degeneration, produced a significant increase in survival time in the presence of the cofactor heparin. In 4 out of 10 cases using human tisue, bFGF also yielded a significant increase in survival times. When brain-derived neurotrophic factor (BDNF) was applied to rat rods, outer segment survival times did not change. Outer segments collapsed more quickly when either pigment epithelial cell derived factor (PEDF) or sugar N-acetyl D-galactosamine (NAD-gal) were present. Our results show that rod photoreceptors can respond to bFGF, GDNF and CNTF in vitro and provide evidence for a direct effect of these neurotrophic factors on rods. The rapid collapse of isolated photoreceptors in this model provides a convenient means for testing various neurotrophic agents and the induced cellular responses. PMID:9657912

  3. Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF.

    PubMed

    Yang, Fan; Liu, Yunhui; Tu, Jie; Wan, Jun; Zhang, Jie; Wu, Bifeng; Chen, Shanping; Zhou, Jiawei; Mu, Yangling; Wang, Liping

    2014-12-17

    Astrocytes provide neuroprotective effects against degeneration of dopaminergic (DA) neurons and play a fundamental role in DA differentiation of neural stem cells. Here we show that light illumination of astrocytes expressing engineered channelrhodopsin variant (ChETA) can remarkably enhance the release of basic fibroblast growth factor (bFGF) and significantly promote the DA differentiation of human embryonic stem cells (hESCs) in vitro. Light activation of transplanted astrocytes in the substantia nigra (SN) also upregulates bFGF levels in vivo and promotes the regenerative effects of co-transplanted stem cells. Importantly, upregulation of bFGF levels, by specific light activation of endogenous astrocytes in the SN, enhances the DA differentiation of transplanted stem cells and promotes brain repair in a mouse model of Parkinson's disease (PD). Our study indicates that astrocyte-derived bFGF is required for regulation of DA differentiation of the stem cells and may provide a strategy targeting astrocytes for treatment of PD.

  4. Additive and synergistic effects of bFGF and hypoxia on leporine meniscus cell-seeded PLLA scaffolds

    PubMed Central

    Gunja, Najmuddin J.; Athanasiou, Kyriacos A.

    2009-01-01

    Injuries to avascular regions of menisci do not heal and result in significant discomfort to patients. Current treatments, such as partial meniscectomy, alleviate these symptoms in the short-term, but lead to premature osteoarthritis as a result of compromised stability and changes in knee biomechanics. Thus, tissue engineering of the meniscus may provide an alternative treatment modality to overcome this problem. In this experiment, a scaffold-based tissue engineering approach was utilized to regenerate the meniscus. Meniscus cells were cultured on poly-l-lactic acid scaffolds in normoxic (~21% oxygen) or hypoxic (~2% oxygen) conditions in the presence or absence of the growth factor, basic fibroblast growth factor (bFGF). At t = 4 wks, histological sections of constructs showed presence of collagen and glycosaminoglycan (GAG) in all groups. Immunohistochemical staining showed presence of collagen I in all groups, and collagen II in groups cultured in hypoxic conditions. bFGF in the culture medium significantly increased cell number/construct by 25%, regardless of culturing condition. For GAG/construct, synergistic increases were observed in constructs cultured in hypoxic conditions and bFGF (2-fold) when compared to constructs cultured in normoxic conditions. Compressive tests showed synergistic increases in the relaxation modulus and coefficient of viscosity, and additive increases in the instantaneous modulus for constructs cultured in hypoxic conditions and bFGF when compared to constructs cultured in normoxic conditions. Overall, these results demonstrate that bFGF and hypoxia can significantly enhance the ability of meniscus cells to produce GAGs and improve the compressive properties of tissue engineered meniscus constructs in vitro. PMID:19937913

  5. THE EFFECT OF IBUPROFEN ON bFGF, VEGF SECRETION AND CELL PROLIFERATION IN THE PRESENCE OF LPS IN HMEC-1 CELLS.

    PubMed

    Wiktorowska-Owczarek, Anna; Namiecińska, Magdalena; Owczarek, Jacek

    2015-01-01

    Ibuprofen belongs to the group of non-selective cyclooxygenase (COX) inhibitors, also known as traditional non-steroidal anti-inflammatory drugs (NSAIDs). Bacterial lipopolysaccharide, an inflammatory mimicking agent, is responsible for the production of prostaglandins and growth factors (VEGF and bFGF), and as inflammation and angiogenesis are closely associated with osteoarthritis, these factors play a functional role in the cardiovascular system. Therefore, the main aim of our study was to examine the effect of ibuprofen on cell viability and proliferation of HMEC-1 cells and VEGF and bFGF secretion under the inflammatory conditions. The effect of NSAID and LPS on bFGF and VEGF was analyzed by ELISA. Cell viability was measured by the MTT method and the proliferation by the [3H-thymidine test. LPS at 100 µg/mL stimulated the secretion of VEGF and bFGF by HMEC-1 cells. Ibuprofen at concentrations of 0.1 and 1 mM intensified the secretion of LPS-induced VEGF in a statistically significant manner (p < 0.05). Both concentrations of ibuprofen inhibited LPS-stimulated bFGF secretion (p < 0.05) in HMEC-1 in a concentration-dependent manner. The non-selective COX inhibitor decreased proliferation and cell viability induced by LPS in a concentration-dependent manner. The observed effects of ibuprofen on endothelial cells may further explain its effects as well as other NSAIDs on the cardiovascular system function in cardiovascular diseases.

  6. Pravastatin induces cell cycle arrest and decreased production of VEGF and bFGF in multiple myeloma cell line.

    PubMed

    Trojan, P J J; Bohatch-Junior, M S; Otuki, M F; Souza-Fonseca-Guimarães, F; Svidnicki, P V; Nogaroto, V; Fernandes, D; Krum, E A; Favero, G M

    2016-02-01

    Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFβ were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line. PMID:26909624

  7. The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals

    PubMed Central

    Ye, Libing; Yang, Ying; Zhang, Xie; Cai, Pingtao; Li, Rui; Chen, Daqing; Wei, Xiaojie; Zhang, Xuesong; Xu, Huazi; Xiao, Jian; Li, Xiaokun; Lin, Li; Zhang, Hongyu

    2015-01-01

    Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury. PMID:26729092

  8. Zur (FurB) is a key factor in the control of the oxidative stress response in Anabaena sp. PCC 7120.

    PubMed

    Sein-Echaluce, Violeta C; González, Andrés; Napolitano, Mauro; Luque, Ignacio; Barja, Francisco; Peleato, M Luisa; Fillat, María F

    2015-06-01

    Iron and zinc are necessary nutrients whose homeostasis is tightly controlled by members of the ferric uptake regulator (FUR) superfamily in the cyanobacterium Anabaena sp. PCC7120. Although the link between iron metabolism and oxidative stress management is well documented, little is known about the connection between zinc homeostasis and the oxidative stress response in cyanobacteria. Zinc homeostasis in Anabaena is controlled by Zur, also named FurB. When overexpressed in Escherichia coli, Zur (FurB) improved cell survival during oxidative stress. In order to investigate the possible correlation between Zur and the oxidative stress response in Anabaena, zur deletion and zur-overexpressing strains have been constructed, and the consequences of Zur imbalance evaluated. The lack of Zur increased sensitivity to hydrogen peroxide (H2 O2 ), whereas an excess of Zur enhanced oxidative stress resistance. Both mutants displayed pleiotropic phenotypes, including alterations on the filament surfaces observable by scanning electron microscopy, reduced content of endogenous H2 O2 and altered expression of sodA, catalases and several peroxiredoxins. Transcriptional and biochemical analyses unveiled that the appropriate level of Zur is required for proper control of the oxidative stress response and allowed us to identify major antioxidant enzymes as novel members of the Zur regulon.

  9. Zur (FurB) is a key factor in the control of the oxidative stress response in Anabaena sp. PCC 7120.

    PubMed

    Sein-Echaluce, Violeta C; González, Andrés; Napolitano, Mauro; Luque, Ignacio; Barja, Francisco; Peleato, M Luisa; Fillat, María F

    2015-06-01

    Iron and zinc are necessary nutrients whose homeostasis is tightly controlled by members of the ferric uptake regulator (FUR) superfamily in the cyanobacterium Anabaena sp. PCC7120. Although the link between iron metabolism and oxidative stress management is well documented, little is known about the connection between zinc homeostasis and the oxidative stress response in cyanobacteria. Zinc homeostasis in Anabaena is controlled by Zur, also named FurB. When overexpressed in Escherichia coli, Zur (FurB) improved cell survival during oxidative stress. In order to investigate the possible correlation between Zur and the oxidative stress response in Anabaena, zur deletion and zur-overexpressing strains have been constructed, and the consequences of Zur imbalance evaluated. The lack of Zur increased sensitivity to hydrogen peroxide (H2 O2 ), whereas an excess of Zur enhanced oxidative stress resistance. Both mutants displayed pleiotropic phenotypes, including alterations on the filament surfaces observable by scanning electron microscopy, reduced content of endogenous H2 O2 and altered expression of sodA, catalases and several peroxiredoxins. Transcriptional and biochemical analyses unveiled that the appropriate level of Zur is required for proper control of the oxidative stress response and allowed us to identify major antioxidant enzymes as novel members of the Zur regulon. PMID:25244409

  10. Immunohistochemical analysis of bFGF, TGF-beta1 and catalase in rectus abdominis muscle from cattle foetuses at 180 and 260 days post-conception.

    PubMed

    Orzechowski, A; Gajkowska, B; Wojewódzka, U; Cassar-Malek, I; Picard, B; Hocquette, J F

    2002-12-01

    The potential for muscle growth depends on myoblast proliferation, which occurs essentially during the first two thirds of the foetal period in cattle. Thereafter, myofibres acquire their contractile and metabolic properties. Proliferation is regulated by molecular growth factors and by the tissue oxidative activity. The aim of this study was the quantification by immunochemistry of basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGF-beta1) and also of enzyme catalase (CAT) activity in rectus abdominis muscle. Samples were collected from cattle foetuses of different growth potential at 180 and 260 days post-conception (dpc). One major conclusion from this work is that protein contents of the muscle tissue bFGF and, to a lower extent, CAT activity decreased with increasing age during the foetal life. No differences were found between the different genotypes of cattle. However, the CAT to bFGF ratio tended to be lower in fast-growing cattle and increased with foetal age. TGF-beta1 did not change with age and was localised mostly at the vascular bed. CAT was detected in smooth and rough reticulum in striated muscles at 180dpc, and additionally in mitochondria at 260dpc. In conclusion, the balance between intracellular growth factors (bFGF and TGF-beta1) and the activity of antioxidant enzyme CAT may participate in the regulation of the transition from myoblast proliferation to differentiation. Thus, increased ratio of CAT to bFGF might be a good index indicating initiation of muscle maturation in cattle foetus prior to birth.

  11. Acceleration of segmental bone regeneration in a rabbit model by strontium-doped calcium polyphosphate scaffold through stimulating VEGF and bFGF secretion from osteoblasts.

    PubMed

    Gu, Zhipeng; Zhang, Xu; Li, Li; Wang, Qiguang; Yu, Xixun; Feng, Ting

    2013-01-01

    The development of suitable bioactive three-dimensional scaffold for the promotion of bone regeneration is critical in bone tissue engineering. The purpose of this study was to investigate in vivo osteogenesis of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds for bone repair, as well as the relationship between osteogenic properties of SCPP scaffolds and the secretion of bFGF and VEGF from osteoblasts stimulated by SCPP. Besides, the advantages of scaffolds seeded with mesenchymal stem cells (MSCs) for bone repair were also studied. Firstly, the bone repair evaluation of scaffolds was performed on a rabbit segmental bony defects model over a period of 16 weeks by histology combined with X-ray microradiography. And then, in order to avoid the influence from the other factors such as hypoxia which emerge in vivo study and affect the secretion of VEGF and bFGF from host cells, human osteoblast-like cells (MG63) were seeded to SCPP, CPP and HA scaffolds in vitro to determine the ability of these scaffolds to stimulate the secretion of angiogenic growth factors (VEGF and bFGF) from MG63 and further explore the reason for the better osteogenic properties of SCPP scaffolds. The histological and X-ray microradiographic results showed that the SCPP scaffolds presented better osteogenic potential than CPP and HA scaffolds, when combined with MSCs, the SCPP scaffolds could further accelerate the bone repair. And the amounts of VEGF measured by ELISA assay in SCPP, CPP and HA groups after cultured for 7 days were about 364.989 pg/mL, 244.035 pg/mL and 232.785 pg/mL, respectively. Accordingly, the amounts of bFGF were about 27.085 pg/mL, 15.727 pg/mL and 8.326 pg/mL. The results revealed that the SCPP scaffolds significantly enhanced the bFGF and VEGF secretion compared with other scaffolds. The results presented in vivo and in vitro study demonstrated that the SCPP could accelerate bone formation through stimulating the secretion of VEGF and bFGF from

  12. Accelerated wound closure of pressure ulcers in aged mice by chitosan scaffolds with and without bFGF.

    PubMed

    Park, Chan J; Clark, Sherrie G; Lichtensteiger, Carol A; Jamison, Russell D; Johnson, Amy J Wagoner

    2009-07-01

    Pressure ulcers are a significant healthcare concern, especially for elderly populations. Our work served to ameliorate the chronicity of these ulcers by addressing ischemia-reperfusion injury mediated by neutrophils and the concomitant loss of vasculature in these wounds. To this end, chitosan scaffolds loaded with basic fibroblast growth factor (bFGF) contained in gelatin microparticles were developed and tested for clinical relevance in an aged mouse model. Pressure ulcers were induced in aged mice, and efficacy of treatment was assessed. On days 3 and 7, both chitosan and chitosan-bFGF scaffolds significantly accelerated wound closure compared to gauze control. By day 10, all wounds achieved similar closure. Delivery and angiogenic function of bFGF was verified through ELISA and histology. Elevated neutrophil levels were observed in chitosan and chitosan-bFGF groups. Since neutrophil elastase contributes to the proteolytic environments of pressure ulcers, the effect of chitosan on elastase was assessed. In vitro, chitosan inhibited elastase activity. In vivo, elastase protein levels in wounds were reduced with chitosan-bFGF scaffolds by day 10. These results suggest that chitosan is an effective material for growth factor delivery and can help to heal chronic ulcers. Collectively, our data show that chitosan-bFGF scaffolds are effective in accelerating wound closure of pressure ulcers in aged animals.

  13. Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

    SciTech Connect

    Saiga, Kenta; Furumatsu, Takayuki; Yoshida, Aki; Masuda, Shin; Takihira, Shota; Abe, Nobuhiro; Ozaki, Toshifumi

    2010-11-12

    Research highlights: {yields} bFGF/GDF-5 treatment increases cellular proliferation and migration of MCL fibroblasts. {yields} bFGF/GDF-5 hydrogels stimulate the healing of MCL injury in vivo. {yields} bFGF/GDF-5 hydrogels stimulate Col1a1 expression and type I collagen synthesis. {yields} Combined use of bFGF/GDF-5 enhances MCL healing. -- Abstract: Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.

  14. Cellular Dichotomy Between Anchorage-Independent Growth Responses to bFGF and TA Reflects Molecular Switch in Commitment to Carcinogenesis

    SciTech Connect

    Waters, Katrina M.; Tan, Ruimin; Opresko, Lee K.; Quesenberry, Ryan D.; Bandyopadhyay, Somnath; Chrisler, William B.; Weber, Thomas J.

    2009-11-01

    We have investigated gene expression patterns underlying reversible and irreversible anchorage-independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely non-overlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA- and bFGF-regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired non-tumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF- and TPA-dependent AIG are regulated by c-Myc, SP-1 and HNF-4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG.

  15. Basic fibroblast growth factor in human rhabdomyosarcoma cells: implications for the proliferation and neovascularization of myoblast-derived tumors

    SciTech Connect

    Schweigerer, L.; Neufeld, G.; Mergia, A.; Abraham, J.A.; Fiddes, J.C.; Gospodarowicz, D.

    1987-02-01

    Cultured human embryonal rhabdomyosarcoma cells express the basic fibroblast growth factor (bFGF) gene and they produced bFGF, which is apparently composed of two microheterogenous forms with M/sub r/s of 16,500 and 17,200, respectively. bFGF was purified by radioreceptor binding assays or cross-linking experiments. bFGF derived from the rhabdomyosarcoma cells stimulates their own proliferation and that of human or bovine vascular endothelial cells. It is conceivable that the rhabdomyosarcoma-derived bFGF stimulates the growth and neovascularization of human rhabdomyosarcomas and that it may thereby contribute to the development of these tumors.

  16. Angiogenesis and osteogenesis enhanced by bFGF ex vivo gene therapy for bone tissue engineering in reconstruction of calvarial defects.

    PubMed

    Qu, Dan; Li, Jihua; Li, Yubao; Gao, Ying; Zuo, Yi; Hsu, Yuchun; Hu, Jing

    2011-03-01

    Reconstruction of bone defects by tissue engineered substitutes requires coordinated coupling between osteogenesis and angiogenesis. Basic fibroblast growth factor (bFGF or FGF-2) is a protein which acts actively in osteogenesis and angiogenesis during skeletal healing and development. It is hypothesized that BMSCs transfected with bFGF can directly stimulate regeneration of vascular tissue, and subsequently enhance osseous formation and remodeling after implantation of the tissue engineered bone. This study was designed to examine the impact of bFGF-BMSCs, seeded on nano-hydroxyapatite/polyamide66 (n-HA/PA66) composite scaffold, to enhance angiogenesis and osteogenesis in a calvarial critical-sized defect model in rats. To investigate the vascularization and bone formation of tissue engineered bone, the substrate was removed and processed for immunohistochemical, scanning electron microscopic examinations (SEM), reverse transcriptase-polymerase chain reaction (RT-PCR), dual energy X-ray absorptiometry (DEXA), microvessels counting, and new bone volume assay. The results demonstrate that bFGF mediated ex vivo gene transfer based on BMSCs can accelerate vascularization and bone regeneration on these composite scaffolds. The n-HA/PA66 scaffold combined with the bFGF-BMSCs may mimic the natural process of osteogenesis during repair of defect by tissue engineered bone.

  17. Neurogenesis of Neural Crest Derived Periodontal Ligament Stem Cells by EGF and bFGF

    PubMed Central

    Fortino, Veronica R.; Chen, Ren-Shiang; Pelaez, Daniel; Cheung, Herman S.

    2013-01-01

    Neuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem cell sources exist, including: mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), the limited cellular potency, technical difficulties, and ethical considerations associated with these make finding alternate sources a desirable goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were induced into neural-like cells using a combination of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Morphological changes were evident in our treated group, seen under both light microscopy and scanning electron microscopy (SEM). A statistically significant increase in the expression of neuron-specific β-tubulin III and the neural stem/progenitor cell marker nestin, along with positive immunohistochemical staining for glial fibrillary acidic protein (GFAP), demonstrated the success of our treatment in inducing both neuronal and glial phenotypes. Positive staining for synaptophysin demonstrated neural connections and electrophysiological recordings indicated that when subjected to whole cell patch clamping, our treated cells displayed inward currents conducted through voltage-gated sodium (Na+) channels. Taken together, our results indicate the success of our treatment in inducing PDLSCs to neural-like cells. The ease of sourcing and expansion, their embryologic neural crest origin, and the lack of ethical implications in their use make PDLSCs an attractive source for use in neuroregenerative medicine. PMID:24105823

  18. The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.

    PubMed

    Green, J B; Howes, G; Symes, K; Cooke, J; Smith, J C

    1990-01-01

    respond to the natural inducer at least until stage 10, and perhaps until stage 10.5, this suggests that bFGF cannot be the sole inducer of mesoderm in vivo. Taken together, these results are consistent with XTC-MIF being a dorsoanterior inducer and XbFGF a ventroposterior inducer, suggesting that body pattern is established by the interaction of two types of inducing signal. This model is discussed in view of the qualitative and quantitative differences between the factors.

  19. MicroRNA expression profile of bone marrow mesenchymal stem cell-derived neural progenitor by microarray under the influence of EGF, bFGF and IGF-1

    PubMed Central

    Huat, Tee Jong; Khan, Amir Ali; Abdullah, Jafri Malin; Idris, Fauziah Mohamad; Jaafar, Hasnan

    2015-01-01

    Recently there has been growing interest in the differentiation of mesenchymal stem cells (MSCs) into neural lineages. Research suggests that MSCs can be differentiated into neural progenitor-like cells (NPCs) under the specific influence of paracrine factors particularly epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Our recent research has found that the addition of insulin-like growth factor 1 (IGF-1) with the combination of the EGF and bFGF could significantly improve the growth and survivability of MSC-derived NPCs. To unravel the molecular mechanism of the improved differentiation we compared the microRNA expression profiles of the differentiation under various combinations of growth factors. MSCs were differentiated into neural lineage in 3 groups; Group A (EGF + bFGF), Group B (EGF + bFGF + IGF-1), and Group C (without growth factor). Regulated microRNAs during the early differentiation were identified by detailed microRNA profiling using Affymetrix GeneChip version 2.0 at three time intervals (day 1, day 3 and day 5). The data were deposited in the Gene Expression Omnibus, series GSE60060. PMID:26484256

  20. A Novel In Vivo Model of Focal Light Emitting Diode-Induced Cone-Photoreceptor Phototoxicity: Neuroprotection Afforded by Brimonidine, BDNF, PEDF or bFGF

    PubMed Central

    García-Ayuso, Diego; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Bernal-Garro, José Manuel; Nieto-López, Leticia; Nadal-Nicolás, Francisco Manuel; Villegas-Pérez, María Paz; Wheeler, Larry A.; Vidal-Sanz, Manuel

    2014-01-01

    We have investigated the effects of light-emitting diode (LED)-induced phototoxicity (LIP) on cone-photoreceptors and their protection with brimonidine (BMD), brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF) or basic fibroblast growth factor (bFGF). In anesthetized, dark adapted, adult albino rats a blue (400 nm) LED was placed perpendicular to the cornea (10 sec, 200 lux) and the effects were investigated using Spectral Domain Optical Coherence Tomography (SD-OCT) and/or analysing the retina in oriented cross-sections or wholemounts immune-labelled for L- and S-opsin and counterstained with the nuclear stain DAPI. The effects of topical BMD (1%) or, intravitreally injected BDNF (5 µg), PEDF (2 µg), CNTF (0.4 µg) or bFGF (1 µg) after LIP were examined on wholemounts at 7 days. SD-OCT showed damage in a circular region of the superotemporal retina, whose diameter varied from 1,842.4±84.5 µm (at 24 hours) to 1,407.7±52.8 µm (at 7 days). This region had a progressive thickness diminution from 183.4±5 µm (at 12 h) to 114.6±6 µm (at 7 d). Oriented cross-sections showed within the light-damaged region of the retina massive loss of rods and cone-photoreceptors. Wholemounts documented a circular region containing lower numbers of L- and S-cones. Within a circular area (1 mm or 1.3 mm radius, respectively) in the left and in its corresponding region of the contralateral-fellow-retina, total L- or S-cones were 7,118±842 or 661±125 for the LED exposed retinas (n = 7) and 14,040±1,860 or 2,255±193 for the fellow retinas (n = 7), respectively. BMD, BDNF, PEDF and bFGF but not CNTF showed significant neuroprotective effects on L- or S-cones. We conclude that LIP results in rod and cone-photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Intravitreal BDNF, PEDF or bFGF, or topical BMD afford significant cone neuroprotection in this model

  1. EphA2-Induced Angiogenesis in Ewing Sarcoma Cells Works through bFGF Production and Is Dependent on Caveolin-1

    PubMed Central

    Sáinz-Jaspeado, Miguel; Huertas-Martinez, Juan; Lagares-Tena, Laura; Martin Liberal, Juan; Mateo-Lozano, Silvia; de Alava, Enrique; de Torres, Carmen; Mora, Jaume; del Muro, Xavier Garcia; Tirado, Oscar M.

    2013-01-01

    Angiogenesis is the result of the combined activity of the tumor microenvironment and signaling molecules. The angiogenic switch is represented as an imbalance between pro- and anti-angiogenic factors and is a rate-limiting step in the development of tumors. Eph receptor tyrosine kinases and their membrane-anchored ligands, known as ephrins, constitute the largest receptor tyrosine kinase (RTK) subfamily and are considered a major family of pro-angiogenic RTKs. Ewing sarcoma (EWS) is a highly aggressive bone and soft tissue tumor affecting children and young adults. As other solid tumors, EWS are reliant on a functional vascular network for the delivery of nutrients and oxygen and for the removal of waste. Based on the biological roles of EphA2 in promoting angiogenesis, we explored the functional role of this receptor and its relationship with caveolin-1 (CAV1) in EWS angiogenesis. We demonstrated that lack of CAV1 results in a significant reduction in micro vascular density (MVD) on 3 different in vivo models. In vitro, this phenomenon correlated with inactivation of EphA2 receptor, lack of AKT response and downregulation of bFGF. We also demonstrated that secreted bFGF from EWS cells acted as chemoattractant for endothelial cells. Furthermore, interaction between EphA2 and CAV1 was necessary for the right localization and signaling of the receptor to produce bFGF through AKT and promote migration of endothelial cells. Finally, introduction of a dominant-negative form of EphA2 into EWS cells mostly reproduced the effects occurred by CAV1 silencing, strongly suggesting that the axis EphA2-CAV1 participates in the promotion of endothelial cell migration toward the tumors favoring EWS angiogenesis. PMID:23951165

  2. Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits

    PubMed Central

    Jiang, Xincheng; Lin, Houwei; Jiang, Dapeng; Xu, Guofeng; Fang, Xiaoliang; He, Lei; Xu, Maosheng; Tang, Bingqiang; Wang, Zhiyong; Cui, Daxiang; Chen, Fang; Geng, Hongquan

    2016-01-01

    Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits. PMID:26854200

  3. The role of bFGF on the ability of MSC to activate endogenous regenerative mechanisms in an ectopic bone formation model.

    PubMed

    Tasso, Roberta; Gaetani, Massimiliano; Molino, Erica; Cattaneo, Angela; Monticone, Massimiliano; Bachi, Angela; Cancedda, Ranieri

    2012-03-01

    The view depicting bone marrow (BM)-derived mesenchymal stem cells (MSC) as a uniform population differentiating into new-tissue builder cells is evolving toward the concept of a heterogeneous population of stem/progenitor cells secreting bioactive molecules, and contributing to establish an on-site regenerative microenvironment. We report that in an ectopic bone formation model the intrinsic MSC capability to activate endogenous regenerative mechanisms is critically dependent on the commitment level of implanted MSC. We demonstrate that the presence of bFGF in the culture medium during mouse MSC expansion in vitro is the key factor for the selection of subpopulations inducing host regenerative responses. We developed a novel strategy combining SILAC-LC-MS/MS quantitative proteomics of conditioned culture media and gene expression profiling to disentangle the major role of MSC in modulating the microenvironment toward the damage resolution. The correspondence between results provided by the applied techniques proved that the most statistically significant biological processes favored by the bFGF treatment were carried out by secreted factors. In particular, the immune response, the inflammatory response, the response to wounding and chemotaxis were all upregulated in bFGF-selected MSC. We propose these processes as majorly involved in activating the endogenous responses triggered by trophic effects of implanted bFGF-selected MSC.

  4. Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits

    NASA Astrophysics Data System (ADS)

    Jiang, Xincheng; Lin, Houwei; Jiang, Dapeng; Xu, Guofeng; Fang, Xiaoliang; He, Lei; Xu, Maosheng; Tang, Bingqiang; Wang, Zhiyong; Cui, Daxiang; Chen, Fang; Geng, Hongquan

    2016-02-01

    Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits.

  5. Effect of basic fibroblast growth factor in mouse embryonic stem cell culture and osteogenic differentiation.

    PubMed

    Rose, Laura C; Fitzsimmons, Ross; Lee, Poh; Krawetz, Roman; Rancourt, Derrick E; Uludağ, Hasan

    2013-05-01

    Embryonic stem cells are actively explored as a cell source in tissue engineering and regenerative medicine involving bone repair. Basic fibroblast growth factor (bFGF) has been a valuable growth factor to support the culture of human stem cells as well as their osteogenic differentiation, but the influence of bFGF on mouse embryonic stem (mES) cells is not known. Towards this goal, D3 cells were treated with bFGF during maintenance conditions and during spontaneous and osteogenic differentiation. In feeder-free monolayers, up to 40 ng/ml of exogenous bFGF did not support self-renewal of mES without LIF during cell expansion. During spontaneous differentiation in high-density cultures, bFGF stimulated cell proliferation under certain conditions but did not influence differentiation, as judged by stage-specific embryonic antigen-1 expression. The addition of bFGF reduced the alkaline phosphatase (ALP) activity associated with osteoblast activity during differentiation induced by osteogenic supplements, although the extent of mineralization was unaffected by bFGF. The bFGF increased the mesenchymal stem cell marker Sca-1 in an mES cell population and led to an enhanced increase in osteocalcin and runx2 expression in combination with BMP-2. These results suggest that bFGF could be utilized to expand the cell population in high-density cultures in addition to enriching the BMP-2 responsiveness of mES cells. PMID:22674886

  6. Heparin modulation of the neurotropic effects of acidic and basic fibroblast growth factors and nerve growth factor on PC12 cells

    SciTech Connect

    Neufeld, G.; Gospodarowicz, D.; Dodge, L.; Fujii, D.K.

    1987-04-01

    Nerve growth factor (NGF) and acidic or basic fibroblast growth factor (aFGF and bFGF, respectively) induce neurite outgrowth from the rat pheochromocytoma cell line, PC12. The neurites induced by these three factors are stable for up to a month in cell culture in the continued presence of any of the above growth factors. bFGF (ED50 = 30 pg/ml) is 800 fold more potent in stimulating neurite outgrowth than aFGF (ED50 = 25 ng/ml) and 260 fold more potent than NGF (ED50 = 8 ng/ml). While the neurotropic activities of aFGF and NGF are potentiated by heparin, that of bFGF is both partially inhibited or stimulated, depending upon the concentration of bFGF. Radioreceptor binding experiments show that aFGF and bFGF bind to a common binding site on the PC12 cell surface. Affinity labeling studies demonstrate a single receptor with an apparent molecular weight of 145,000 daltons, which corresponds to the high molecular weight receptor identified in BHK-21 cells. NGF does not appear to compete with aFGF or bFGF for binding to the receptor. Heparin blocked the binding of bFGF to the receptor but had only a small inhibitory effect on the binding of aFGF to the receptor. Thus, it appears that heparin inhibition of the neurotropic effects of bFGF occurs, at least in part, by impairing the interaction of bFGF with the receptor, while having little effect on that of aFGF. The stimulatory effects of heparin on the neurotropic activity of aFGF, bFGF, and NGF may occur through a site not associated with the respective cellular receptor for the growth factors.

  7. Scleroderma fibroblasts show increased responsiveness to endothelial cell-derived IL-1 and bFGF.

    PubMed

    Denton, C P; Xu, S; Black, C M; Pearson, J D

    1997-03-01

    Fibroblasts cultured from lesional skin in scleroderma (systemic sclerosis) demonstrate an activated phenotype that may be important in pathogenesis. Endothelial cell-derived cytokines can modulate fibroblast properties, and endothelial cell changes occur early in scleroderma. Thus, endothelial cell and fibroblast dysfunction may be linked through the paracrine activity of soluble endothelial cell products. We have explored endothelial cell-fibroblast interactions in vitro by investigating the modulation of scleroderma and control fibroblast properties by endothelial cell-conditioned medium (EC-CM). EC-CM caused a concentration-dependent stimulation of fibroblast DNA and protein synthesis and upregulation of cell surface ICAM-1 expression. Scleroderma fibroblasts showed consistently greater responses than control cells. Medium conditioned by mechanically wounded endothelial cells had a greater effect than that from resting endothelial cells. Pre-incubation of EC-CM with anti-bFGF significantly reduced the promotion of fibroblast thymidine incorporation but did not affect endothelial cell-induced leucine incorporation. Conversely, anti-IL-1 antibodies abrogated EC-CM-induced leucine incorporation and ICAM-1 expression but did not diminish thymidine incorporation. Recombinant bFGF or IL-1 modulated fibroblast properties similarly. These data demonstrate that endothelial cell-derived IL-1 and bFGF modulate fibroblast properties independently and that lesional scleroderma strains are more responsive than control fibroblasts to endothelial cell-induced modulation, which supports the hypothesis that altered endothelial cell-fibroblast communication may be involved in the pathogenesis of scleroderma.

  8. Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco.

    PubMed

    Wang, Yun-Peng; Wei, Zheng-Yi; Zhong, Xiao-Fang; Lin, Chun-Jing; Cai, Yu-Hong; Ma, Jian; Zhang, Yu-Ying; Liu, Yan-Zhi; Xing, Shao-Chen

    2015-12-23

    Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins.

  9. Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco

    PubMed Central

    Wang, Yun-Peng; Wei, Zheng-Yi; Zhong, Xiao-Fang; Lin, Chun-Jing; Cai, Yu-Hong; Ma, Jian; Zhang, Yu-Ying; Liu, Yan-Zhi; Xing, Shao-Chen

    2015-01-01

    Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins. PMID:26703590

  10. Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco.

    PubMed

    Wang, Yun-Peng; Wei, Zheng-Yi; Zhong, Xiao-Fang; Lin, Chun-Jing; Cai, Yu-Hong; Ma, Jian; Zhang, Yu-Ying; Liu, Yan-Zhi; Xing, Shao-Chen

    2016-01-01

    Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins. PMID:26703590

  11. Stimulation of circus movement by activin, bFGF and TGF-beta 2 in isolated animal cap cells of Xenopus laevis.

    PubMed

    Minoura, I; Nakamura, H; Tashiro, K; Shiokawa, K

    1995-01-01

    Lobopodium is a hyaline cytoplasmic protrusion which rotates circumferencially around a cell. This movement is called circus movement, which is seen in dissociated cells of amphibian embryos. Relative abundance of the lobopodia-forming cells changes temporally and spatially within Xenopus embryos, reflecting stage-dependent difference of morphogenetic movements. The lobopodia-forming activity of dissociated animal cap cells was stimulated strongly by activin and bFGF, and weakly by TGF-beta 2. In addition, activin A was found to stimulate cellular attachment to the substratum when the cultivation lasted long. Thus, mesoderm-inducing growth factors stimulate lobopodia formation and cellular movements which may be necessary for gastrulation and neurulation in Xenopus early embryos.

  12. MicroRNA Expression Profile of Neural Progenitor-Like Cells Derived from Rat Bone Marrow Mesenchymal Stem Cells under the Influence of IGF-1, bFGF and EGF

    PubMed Central

    Huat, Tee Jong; Khan, Amir Ali; Abdullah, Jafri Malin; Idris, Fauziah Mohamad; Jaafar, Hasnan

    2015-01-01

    Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms of the NPCs derivation, microarray analysis using GeneChip® miRNA arrays was performed. The profiles were compared among the groups. Annotated microRNA fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down-regulated compared to group C. The expressions of selected microRNAs were validated by real-time PCR. Among the 46 microRNAs, 30 were consistently expressed for minimum of two consecutive time intervals. In Group B, only miR-496 was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a-3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated. Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214, miR-125a-3p, miR-320 and let-7 family) are associated with reduction of apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in the differentiation of BMSCs into NPCs. These findings may provide clues to further our understanding of the mechanisms and roles of microRNAs as key regulators of BMSC-derived NPC maintenance. PMID:25938966

  13. Recombinant snake venom cystatin inhibits tumor angiogenesis in vitro and in vivo associated with downregulation of VEGF-A165, Flt-1 and bFGF.

    PubMed

    Xie, Qun; Tang, Nanhong; Wan, Rong; Qi, Yuanlin; Lin, Xu; Lin, Jianyin

    2013-05-01

    Previous studies have shown that recombinant snake venom cystatin (sv-cystatin) inhibits the invasion and metastasis of tumor cells in vitro and in vivo. The purpose of this study was to investigate the ability of recombinant sv-cystatin to inhibit tumor angiogenesis in vitro and in vivo, and the mechanisms underlying this effect. Recombinant sv-cystatin inhibited proliferation of human umbilical vein endothelial cells (HUVECs) at 100 and 200 μg/mL after 72, 96 and 120 h. Recombinant sv-cystatin also inhibited tumor-endothelial cell adhesion at 25, 50, 100 and 200 μg/mL. Recombinant sv-cystatin inhibited capillary-like tube formation by HUVECs at 10, 25, 50, 100 and 200 μg/mL following 12, 24 and 36 h incubation. Furthermore, recombinant sv-cystatin significantly suppressed microvessel density (MVD) of lung tumor colonies in C57BL/6 mice inoculated in the lateral tail vein with B16F10 melanoma cells. Administration of recombinant sv-cystatin significantly decreased MVD of primary tumor tissues in nude mice implanted subcutaneously with human hepatocellular carcinoma cells (MHCC97H). Exposure of B16F10 and MHCC97H cells to increasing doses of recombinant sv-cystatin suppressed secretion of vascular endothelial growth factor (VEGF)-A165 and basic fibroblast growth factor (bFGF) into the surrounding medium (P < 0.05). The expression of fms-related tyrosine kinase 1 (Flt-1) protein in HUVECs was decreased by 25, 50, 100 and 200 μg/mL recombinant sv-cystatin (P < 0.05). This study demonstrates that recombinant sv-cystatin inhibits tumor angiogenesis associated with downregulation of VEGF-A165, Flt-1 and bFGF. This suggests that recombinant sv-cystatin may have potential pharmaceutical applications as an antiangiogenic and antimetastatic therapeutic agent.

  14. Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis

    PubMed Central

    1988-01-01

    We have found that the spontaneous migration of bovine aortic endothelial cells from the edge of a denuded area in a confluent monolayer is dependent upon the release of endogenous basic fibroblast growth factor (bFGF). Cell movement is blocked by purified polyclonal rabbit IgG to bFGF as well as affinity purified anti-bFGF IgG and anti- bFGF F(ab')2 fragments. The inhibitory effect of the immunoglobulins is dependent upon antibody concentration, is reversible, is overcome by the addition of recombinant bFGF, and is removed by affinity chromatography of the antiserum through a column of bFGF-Sepharose. Cell movement is also reversibly inhibited by the addition of protamine sulfate and suramin; two agents reported to block bFGF binding to its receptor. The addition of recombinant bFGF to wounded monolayers accelerates the movement of cells into the denuded area. Transforming growth factor beta which has been shown to antagonize several other effects of bFGF also inhibits cell movement. The anti-bFGF IgG prevents the movement of bovine capillary endothelial cells, BHK-21, NIH 3T3, and human skin fibroblasts into a denuded area. Antibodies to bFGF, as well as suramin and protamine sulfate also suppress the basal levels of plasminogen activator and DNA synthesis in bovine aortic endothelial cells. PMID:3417781

  15. Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis

    PubMed Central

    Shin, Jung-Ho; Helmann, John D.

    2016-01-01

    Bacteria respond dynamically to the changes in zinc availability. Repression by the Bacillus subtilis transcription factor Zur requires Zn(II), which binds with negative cooperativity to two regulatory sites per dimer to form, sequentially, Zur2:Zn3 and Zur2:Zn4 forms of the repressor. Here we show that, as cells transition from zinc sufficiency to deficiency, operons regulated by Zur are derepressed in three distinct waves. The first includes the alternative RpmEB(L31*) and RpmGC(L33*) ribosomal proteins, which mobilize zinc from the ribosome, whereas the second includes the ZnuACB uptake system and the YciC metallochaperone. Finally, as zinc levels decrease further, the Zur2:Zn3 form loses Zn(II) leading to derepression of RpsNB(S14*) and FolE2, which allow continued ribosome assembly and folate synthesis, respectively. We infer that zinc mobilization from intracellular zinc stores takes priority over energy-dependent import, and our results link the biochemistry of zinc sensing by Zur to the molecular logic of the zinc deprivation response. PMID:27561249

  16. Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis.

    PubMed

    Shin, Jung-Ho; Helmann, John D

    2016-01-01

    Bacteria respond dynamically to the changes in zinc availability. Repression by the Bacillus subtilis transcription factor Zur requires Zn(II), which binds with negative cooperativity to two regulatory sites per dimer to form, sequentially, Zur2:Zn3 and Zur2:Zn4 forms of the repressor. Here we show that, as cells transition from zinc sufficiency to deficiency, operons regulated by Zur are derepressed in three distinct waves. The first includes the alternative RpmEB(L31*) and RpmGC(L33*) ribosomal proteins, which mobilize zinc from the ribosome, whereas the second includes the ZnuACB uptake system and the YciC metallochaperone. Finally, as zinc levels decrease further, the Zur2:Zn3 form loses Zn(II) leading to derepression of RpsNB(S14*) and FolE2, which allow continued ribosome assembly and folate synthesis, respectively. We infer that zinc mobilization from intracellular zinc stores takes priority over energy-dependent import, and our results link the biochemistry of zinc sensing by Zur to the molecular logic of the zinc deprivation response. PMID:27561249

  17. Wound dressing composed of hyaluronic acid and collagen containing EGF or bFGF: comparative culture study.

    PubMed

    Yu, Akane; Niiyama, Hayato; Kondo, Shinya; Yamamoto, Akiko; Suzuki, Ryusuke; Kuroyanagi, Yoshimitsu

    2013-01-01

    We developed a novel wound dressing composed of a hyaluronic acid (HA) and collagen (Col) spongy sheet containing epidermal growth factor (EGF) or basic fibrolast growth factor (bFGF) by freeze-drying method (EGF-wound dressing or bFGF-wound dressing, respectively). A wound dressing without any growth factor was prepared as a control in a similar manner as above (C-wound dressing). Intermolecular cross-linkage between Col molecules was induced by UV irradiation. The release behavior of free HA from the wound dressing was investigated using a C-wound dressing. The weight of C-wound dressing after 1 day, 3, 5, and 7 days of incubation on top of a Col gel sheet at the air-water interface (wound surface model) was 55, 36, 30, and 19% of the original weight, respectively. Most free HA and a part of Col was released from the cross-linked Col network in the wound dressing during incubation, as the original Col content in the wound dressing was 33%. Next, fibroblast proliferation was assessed in conventional culture medium preconditioned by immersion of a piece of C-, EGF-, or bFGF-wound dressing, i.e. C-conditioned medium, EGF-conditioned medium, or bFGF-conditioned medium. Cell proliferation in C-conditioned medium increased to approximately the same level as that in conventional medium. Cell proliferation in EGF- and bFGF-conditioned medium was 1.9 times and 2.6 times greater than that in conventional medium after 7 days of cultivation, respectively. Finally, cytokine production of fibroblasts was assessed in a wound surface model using a fibroblast-incorporating Col gel sheet (cultured dermal substitute [CDS]). CDS was elevated to the air-medium interface, on which each wound dressing was placed and cultured for 7 days. Fibroblasts in CDS covered with EGF-wound dressing released 3.6 times more vascular endothelial growth factor (VEGF) and 4.6 times more hepatocyte growth factor (HGF) when compared with the C-wound dressing. Fibroblasts in CDS covered with b

  18. Accelerated tissue integration into porous materials by immobilizing basic fibroblast growth factor using a biologically safe three-step reaction.

    PubMed

    Kakinoki, Sachiro; Sakai, Yusuke; Fujisato, Toshia; Yamaoka, Tetsuji

    2015-12-01

    Soft tissue integration into a porous structure is important to prevent bacterial infection of percutaneous devices and improve tissue regeneration using porous scaffolds. Here, basic fibroblast growth factor (bFGF) was immobilized on porous polymer materials using a mild and biologically safe three-step reaction: (1) modification with a novel surface-modification peptide (penta-lysine-mussel adhesive sequence, which reacts with various matrices), (2) electrostatic binding of heparin with introduced penta-lysine, and (3) biologically specific binding of bFGF to heparin. Porous polyethylene specimens (PPSs) (D = 6.0 mm, H = 2.0 mm) with a good size for tissue integration were selected as a base material, immobilized with bFGF, and subcutaneously implanted into mice. Half of the unmodified PPSs extruded out of the body on day 112 postimplantation; however, the three-step reaction completely prevented sample rejection. Tissue integration was greatly accelerated by immobilizing bFGF. Direct physical coating of bFGF on PPS resulted in greater immobilization but lesser tissue integration than that after the three-step bFGF immobilization, indicating that heparin binds and enhances bFGF efficacy. This three-step bFGF immobilization reaction will be applicable to various polymeric, metallic, and ceramic materials and is a simple strategy to integrate tissue on porous medical devices or scaffolds for tissue regeneration. PMID:26034014

  19. Accelerated tissue integration into porous materials by immobilizing basic fibroblast growth factor using a biologically safe three-step reaction.

    PubMed

    Kakinoki, Sachiro; Sakai, Yusuke; Fujisato, Toshia; Yamaoka, Tetsuji

    2015-12-01

    Soft tissue integration into a porous structure is important to prevent bacterial infection of percutaneous devices and improve tissue regeneration using porous scaffolds. Here, basic fibroblast growth factor (bFGF) was immobilized on porous polymer materials using a mild and biologically safe three-step reaction: (1) modification with a novel surface-modification peptide (penta-lysine-mussel adhesive sequence, which reacts with various matrices), (2) electrostatic binding of heparin with introduced penta-lysine, and (3) biologically specific binding of bFGF to heparin. Porous polyethylene specimens (PPSs) (D = 6.0 mm, H = 2.0 mm) with a good size for tissue integration were selected as a base material, immobilized with bFGF, and subcutaneously implanted into mice. Half of the unmodified PPSs extruded out of the body on day 112 postimplantation; however, the three-step reaction completely prevented sample rejection. Tissue integration was greatly accelerated by immobilizing bFGF. Direct physical coating of bFGF on PPS resulted in greater immobilization but lesser tissue integration than that after the three-step bFGF immobilization, indicating that heparin binds and enhances bFGF efficacy. This three-step bFGF immobilization reaction will be applicable to various polymeric, metallic, and ceramic materials and is a simple strategy to integrate tissue on porous medical devices or scaffolds for tissue regeneration.

  20. Basic Fibroblast Growth Factor Regulates Persistent ERK Osciliations in Premaligant but not Malignant JB6 Cells

    SciTech Connect

    Weber, Thomas J.; Shankaran, Harish; Wiley, H. S.; Opresko, Lee K.; Chrisler, William B.; Quesenberry, Ryan D.

    2010-05-02

    basic fibroblast growth factor (bFGF or FGF2) plays an important role in epidermal wound healing in vivo and is associated with a persistent increased in the extracellular signal-regulated kinase (ERK) pathway in vitro. Here we have examined whether bFGF induces the closure of an experimental scratch wound in JB6 mouse epidermal cells and have explored the regulation of the ERK pathway by bFGF in the context of kinase oscillations. bFGF stimulation is associated with increases in cellular phospho-ERK and phospho-c-Jun levels. In addition, bFGF increases cell proliferation and a change in cell morphology (stellate appearance) in a dose-dependent fashion (0.1 – 100 ng/ml). bFGF treatment also promoted the closure of an experimental scratch wound in vitro. JB6 cells were stably transfected with an ERK1-GFP chimera to follow temporal ERK subcellular distribution patterns. We observe a persistent upregulation of the ERK pathway, as evidenced by a significant increase in nuclear ERK1-GFP levels at time points up to 24 hr after bFGF treatment. Interestingly, at the single cell level, ERK is observed to oscillate between nuclear and cytosolic compartments in response to bFGF treatment. Because this oscillatory behavior is asynchronous in the cell population, it is only clearly resolved at the single cell level. Collectively, data presented here are consistent with an important role for bFGF in wound healing and suggest a more complex regulation of the ERK pathway by bFGF than has previously been appreciated.

  1. Basic fibroblast growth factor protects against excitotoxicity and chemical hypoxia in both neonatal and adult rats.

    PubMed

    Kirschner, P B; Henshaw, R; Weise, J; Trubetskoy, V; Finklestein, S; Schulz, J B; Beal, M F

    1995-07-01

    Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 micrograms/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke.

  2. Effect of Nonviral Plasmid Delivered Basic Fibroblast Growth Factor and Low Intensity Pulsed Ultrasound on Mandibular Condylar Growth: A Preliminary Study

    PubMed Central

    Uludağ, Hasan

    2014-01-01

    Objective. Basic fibroblast growth factor (bFGF) is an important regulator of tissue growth. Previous studies have shown that low intensity pulsed ultrasound (LIPUS) stimulates bone growth. The objective of this study was to evaluate the possible synergetic effect of LIPUS and local injection of nonviral bFGF plasmid DNA (pDNA) on mandibular growth in rats. Design. Groups were control, blank pDNA, bFGF pDNA, LIPUS, and bFGF pDNA + LIPUS. Treatments were performed for 28 days. Significant increase was observed in mandibular height and condylar length in LIPUS groups. MicroCT analysis showed significant increase in bone volume fraction in bFGF pDNA + LIPUS group. Histomorphometric analysis showed increased cell count and condylar proliferative and hypertrophic layers widths in bFGF pDNA group. Results. Current study showed increased mandibular condylar growth in either bFGF pDNA or LIPUS groups compared to the combined group that showed only increased bone volume fraction. Conclusion. It appears that there is an additive effect of bFGF + LIPUS on the mandibular growth. PMID:24967367

  3. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.

    PubMed

    Zhang, Changsong; Yang, Guangshun; Lu, Dewen; Ling, Yang; Chen, Guihua; Zhou, Tianbao

    2014-08-01

    The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; P<0.01). In addition, the numbers of cells in the liver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (P<0.0001). Furthermore, the numbers of cells positive for VEGF and bFGF expression in the spleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (P<0.01). VEGF and bFGF mRNA expression levels were also increased from 1 day following the surgery and reached a peak at day 3, prior to declining gradually and remaining at a relatively high level. VEGF and bFGF mRNA expression levels changed dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.

  4. Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction.

    PubMed

    Yu, Jun-Min; Zhang, Xiao-Bo; Jiang, Wen; Wang, Hui-Dong; Zhang, Yi-Na

    2015-11-01

    The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty‑four hours after surgery, the rats were divided into low‑dose, high‑dose, control and sham surgery groups (n=8 per group). The low‑ and high‑dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post‑treatment. Twenty‑four hours post‑surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST‑treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low‑ and high‑dose groups was noted, however, an increase in the bFGF expression levels was detected in the high‑dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST‑treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST‑induced increase in angiogenesis in rat models of MI.

  5. Effect of basic fibroblast growth factor on pluripotent marker expression and colony forming unit capacity of stem cells isolated from human exfoliated deciduous teeth.

    PubMed

    Sukarawan, Waleerat; Nowwarote, Nunthawan; Kerdpon, Piyarat; Pavasant, Prasit; Osathanon, Thanaphum

    2014-07-01

    Human dental pulp of exfoliated deciduous teeth contains the population of cells that exhibited mesenchymal stem cell (MSC) characters. Though, a cell amplification process is indeed required to secure an adequate cell number for such a potential employment. Several publications suggested the alteration of MSCs upon in vitro culture, for example, the decrease in proliferation and the loss of stem cell characters. Here, we investigated an influence of basic fibroblast growth factor (bFGF) on stem cells isolated from human exfoliated deciduous teeth (SHEDs) with respect to cell proliferation, colony forming unit efficiency and stem cell marker expression in both short- and long-term cultures. For short-term bFGF treatment, SHEDs were treated with bFGF for 48 h. While, in long-term bFGF supplementation, SHEDs were maintained in culture and continuous passage upon confluence in medium supplemented with bFGF. Cells at passage (P) 5 and 10 were employed for characterization. Our results showed that short-term bFGF treatment enhanced OCT4, REX1, and NANOG mRNA expression as well as colony forming unit ability. The FGFR inhibitor pretreatment was able to attenuate the influence of bFGF on pluripotent stem cell marker expression, confirming bFGF function. In addition, cells cultured in high passage number had decreased in cell proliferation, colony forming unit capacity, and pluripotent stem cell maker mRNA expression. However, bFGF supplementation in culture medium enhanced both pluripotent stem cell marker expression and colony forming unit capacity in later passage, though the effect was not robust. Together, these results indicate that high passage number may attenuate pluripotent properties of SHEDs and bFGF supplementation could be the beneficial approach to maintain SHEDs' stemness properties.

  6. A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells

    SciTech Connect

    Liu Yanxia; Song Zhihua; Zhao Yang; Qin Han; Cai Jun; Zhang Hong; Yu Tianxin; Jiang Siming; Wang Guangwen; Ding Mingxiao; Deng Hongkui . E-mail: hongkui_deng@pku.edu.cn

    2006-07-21

    Traditionally, undifferentiated human embryonic stem cells (hESCs) are maintained on mouse embryonic fibroblast (MEF) cells or on matrigel with an MEF-conditioned medium (CM), which hampers the clinical applications of hESCs due to the contamination by animal pathogens. Here we report a novel chemical-defined medium using DMEM/F12 supplemented with N2, B27, and basic fibroblast growth factor (bFGF) [termed NBF]. This medium can support prolonged self-renewal of hESCs. hESCs cultured in NBF maintain an undifferentiated state and normal karyotype, are able to form embryoid bodies in vitro, and differentiate into three germ layers and extraembryonic cells. Furthermore, we find that hESCs cultured in NBF possess a low apoptosis rate and a high proliferation rate compared with those cultured in MEF-CM. Our findings provide a novel, simplified chemical-defined culture medium suitable for further therapeutic applications and developmental studies of hESCs.

  7. Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation

    SciTech Connect

    Kato, Y.; Iwamoto, M. )

    1990-04-05

    The effects of basic fibroblast growth factor (bFGF) on terminal differentiation of chondrocytes and cartilage-matrix calcification were investigated. Rabbit growth-plate chondrocytes maintained as a pelleted mass in a centrifuge tube produced an abundant proteoglycan matrix during the matrix-maturation stage, yielding a cartilage-like tissue. Thereafter, they terminally differentiated to hypertrophic chondrocytes which produced high levels of alkaline phosphatase. These cells induced extensive calcification of the matrix in the absence of additional phosphate. Addition of bFGF to the chondrocyte cultures abolished the increases in alkaline phosphatase activity, {sup 45}Ca deposition, and the calcium content. These effects were dose-dependent, reversible, and observed in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. The inhibitory effects could be observed only when chondrocytes were exposed to bFGF in a transition period between the matrix-maturation and hypertrophic stages. As chondrocytes differentiated to hypertrophic cells, bFGF became less effective in inhibiting the expression of the mineralization-related phenotypes. The present study also shows that although the rate of ({sup 35}S)sulfate incorporation into large, chondroitin sulfate proteoglycan in the cell-matrix fraction is very high during the matrix-maturation stage, it abruptly decreases by 90% after terminal differentiation. Furthermore, the terminal differentiation-associated decrease in proteoglycan synthesis was delayed by bFGF. These results provide evidence that bFGF inhibits terminal differentiation of chondrocytes and calcification.

  8. The angiogenic peptide vascular endothelial growth factor-basic fibroblast growth factor signaling is up-regulated in a rat pressure ulcer model.

    PubMed

    Yang, Jing-Jin; Wang, Xue-Ling; Shi, Bo-Wen; Huang, Fang

    2013-08-01

    The purpose of this study is to investigate the mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in pressure ulcers, and to elucidate the molecular mechanism by which VEGF and bFGF are involved in pressure ulcer formation. A rat model of ischemia-reperfusion pressure ulcer was established by magnetic disk circulating compression method. Real-time fluorescence quantitative PCR and Western blot assays were conducted to detect the mRNA and protein expression of VEGF and bFGF in the tissues of rat I-, II-, and III-degree pressure ulcers, the surrounding tissues, and normal skin. Our study confirmed that the mRNA and protein expression levels of VEGF and bFGF in the tissues of rat I-degree pressure ulcer were significantly higher than that in the II- and III-degree pressure ulcer tissues (P < 0.05). The expression of VEGF and bFGF in the tissues surrounding I- and II-degree pressure ulcers were higher than the rats with normal skin. The expression of VEGF and bFGF in the tissues of rat III-degree pressure ulcer was lower than that in the surrounding tissues and normal skin (P < 0.05). There was a significant positive correlation between change in the VEGF and bFGF. The results showed that with an increase in the degree of pressure ulcers, the expression of VEGF and bFGF in pressure ulcers tissue are decreased. This leads to a reduction in angiogenesis and may be a crucial factor in the formation of pressure ulcers.

  9. Intratumoral hemorrhage-related differences in the expression of vascular endothelial growth factor, basic fibroblast growth factor and thioredoxin reductase 1 in human glioblastoma

    PubMed Central

    Kaya, Bulent; Çiçek, Onur; Erdi, Fatih; Findik, Siddika; Karatas, Yasar; Esen, Hasan; Keskin, Fatih; Kalkan, Erdal

    2016-01-01

    The present study was designed to evaluate the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and thioredoxin reductase 1 (TrxR1) in glioblastoma multiforme (GBM) with and without intratumoral hemorrhage. Surgically resected human GBM samples from 20 patients who underwent surgery at our institute were extracted from the histopathological specimens and divided into two groups. A total of 10 samples from each type of GBM (World Health Organization grade IV, intratumoral hemorrhage-positive or -negative) were included in each group. VEGF, bFGF and TrxR1 expression was analyzed using immunohistochemistry and the results were compared between groups. VEGF and bFGF immunoreactivity was significantly higher in GBMs containing intratumoral hemorrhage. Furthermore, VEGF, bFGF and TrxR1 immunointensity was significantly higher in GBMs containing intratumoral hemorrhage. Thus, the present study demonstrated a higher VEGF, bFGF and TrxR1 expression in GBMs contain intratumoral hemorrhage, indicatiogn a role of VEGF, bFGF and TrxR1 expression in the promotion of tumoral angiogenesis and tumoral growth by complex mechanisms that require further elucidation.

  10. Expression of vascular endothelial growth factor and basic fibroblast growth factor in extramammary Paget disease

    PubMed Central

    Xu, Xiaoyun; Shao, Ning; Qiao, Di; Wang, Zengjun; Song, Ningjing; Song, Ninghong

    2015-01-01

    Extramammary Paget’s disease (EMPD) is a special type of cancers. The etiology of the disease is still unclear. We aimed to study the expression differences of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in EMPD tissues and corresponding adjacent normal tissues. The mRNA expression was detected by RT-PCR and the protein expression was explored by immunohistochemistry. Higher immunostaining signal scores of bFGF and VEGF in EMPD tissues had been found (z = -3.827, P < 0.001, z = -3.729, P < 0.001, respectively). In addition, the mRNA expression of bFGF and VEGF was higher in EMPD tissues, which had been validated by RT-PCR (t = 5.771, P < 0.001, t = 3.304, P = 0.004, respectively). The VEGF and bFGF might be the key signaling proteins in angiogenesis of EMPD. How to block the VEGF and bFGF in EMPD and to destroy the blood supply of the tumor cells becomes the focus of our future research. PMID:26045818

  11. Astrocyte growth is regulated by neuropeptides through Tis 8 and basic fibroblast growth factor.

    PubMed Central

    Hu, R M; Levin, E R

    1994-01-01

    The important intracellular mechanisms of astrocyte growth are not well defined. Using an inhibitor of astrocyte proliferation, atrial natriuretic peptide (ANP), and the glial mitogen endothelin (ET-3), we sought a common pathway for growth regulation in these neural cells. In cultured fetal rat diencephalic astrocytes, ANP selectively and rapidly inhibited the Tis 8 immediate early gene and protein. After 4 h, ANP selectively inhibited the basic fibroblast growth factor (bFGF) gene and protein. ET-3 significantly stimulated both Tis 8 and bFGF mRNAs and protein, but also stimulated several other immediate early and growth factor/receptor genes. An antisense oligonucleotide to Tis 8 strongly prevented ET-stimulated thymidine incorporation, while the inhibitory action of ANP was enhanced. The Tis 8 antisense oligonucleotide also significantly reversed ET-stimulated bFGF transcription and enhanced the bFGF inhibition caused by ANP. In addition, an antisense oligonucleotide to bFGF significantly reversed the ET-stimulated thymidine incorporation and enhanced the ANP inhibition of DNA synthesis. The sequential modulation of Tis 8, followed by bFGF, provides a novel mechanism for both positive and negative regulation of astrocyte growth by endogenous neuropeptides. Images PMID:8163680

  12. A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor

    NASA Astrophysics Data System (ADS)

    Nguyen, Thi H.; Kim, Sung-Hye; Decker, Caitlin G.; Wong, Darice Y.; Loo, Joseph A.; Maynard, Heather D.

    2013-03-01

    Basic fibroblast growth factor (bFGF) is a protein that plays a crucial role in diverse cellular functions, from wound healing to bone regeneration. However, a major obstacle to the widespread application of bFGF is its inherent instability during storage and delivery. Here, we describe the stabilization of bFGF by covalent conjugation with a heparin-mimicking polymer, a copolymer consisting of styrene sulfonate units and methyl methacrylate units bearing poly(ethylene glycol) side chains. The bFGF conjugate of this polymer retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors—such as heat, mild and harsh acidic conditions, storage and proteolytic degradation—unlike native bFGF. Following the application of stress, the conjugate was also significantly more active than the control conjugate system in which the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for the stabilization of heparin-binding growth factors in general.

  13. Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis.

    PubMed

    Tzeng, Huey-En; Chen, Po-Chun; Lin, Kai-Wei; Lin, Chih-Yang; Tsai, Chun-Hao; Han, Shao-Min; Teng, Chieh-Lin; Hwang, Wen-Li; Wang, Shih-Wei; Tang, Chih-Hsin

    2015-07-01

    Chondrosarcoma, a common malignant tumour, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in the tumour microenvironment. Numerous studies indicate that EPCs (endothelial progenitor cells) promote angiogenesis and contribute to tumour growth. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis, and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumour progression by recruiting EPCs in human chondrosarcoma is rarely discussed. In the present study, we found that bFGF induced VEGF (vascular endothelial growth factor) expression via the FGFR1 (fibroblast growth factor receptor 1)/c-Src/p38/NF-κB (nuclear factor κB) signalling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells. Our in vivo data revealed that tumour-secreted bFGF promotes angiogenesis in both mouse plug and chick CAM (chorioallantoic membrane) assays. Xenograft mouse model data, due to bFGF-regulated angiogenesis, showed the bFGF regulates angiogenesis-linked tumour growth. Finally, bFGF was highly expressed in chondrosarcoma patients compared with normal cartilage, positively correlating with VEGF expression and tumour stage. The present study reveals a novel therapeutic target for chondrosarcoma progression.

  14. Comparative Study of Heparin-Poloxamer Hydrogel Modified bFGF and aFGF for in Vivo Wound Healing Efficiency.

    PubMed

    Wu, Jiang; Zhu, Jingjing; He, Chaochao; Xiao, Zecong; Ye, Jingjing; Li, Yi; Chen, Anqi; Zhang, Hongyu; Li, Xiaokun; Lin, Li; Zhao, Yingzheng; Zheng, Jie; Xiao, Jian

    2016-07-27

    Wound therapy remains a clinical challenge. Incorporation of growth factors (GFs) into heparin-functionalized polymer hydrogel is considered as a promising strategy to improve wound healing efficiency. However, different GFs incorporation into the same heparin-based hydrogels often lead to different wound healing effects, and the underlying GF-induced wound healing mechanisms still remain elusive. Herein, we developed a thermos-sensitive heparin-poloxamer (HP) hydrogel to load and deliver different GFs (aFGF and bFGF) for wound healing in vivo. The resulting GFs-based hydrogels with and without HP hydrogels were systematically evaluated and compared for their wound healing efficiency by extensive in vivo tests, including wound closure rate, granulation formation, re-epithelization, cell proliferation, collagen, and angiogenesis expressions. While all GFs-based dressings with and without HP hydrogels exhibited better wound healing efficacy than controls, both HP-aFGF and HP-bFGF hydrogels demonstrated their superior healing activity to improve wound closure, granulation formation, re-epithelization, and blood vessel density by up-regulation of PCNA proliferation and collagen synthesis, as compared to GF dressings alone. More importantly, HP-aFGF dressings exhibited the higher healing efficacy than HP-bFGF dressings, indicating that different a/bFGF surface properties lead to different binding and release behaviors in HP hydrogels, both of which will affect different wound healing efficiency. On the basis of experimental observations, the working mechanisms of different healing effects of HP-GFs on full skin removal wound were proposed. This work provides different views of the design and development of an effective hydrogel-based delivery system for GFs toward rapid wound healing.

  15. Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

    PubMed Central

    Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

    1997-01-01

    We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

  16. Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model

    PubMed Central

    Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho; Bless, Diane M.

    2016-01-01

    Objectives Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Methods Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. Results A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Conclusion Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring. PMID:26976028

  17. Angiogenic factors in human proliferative sickle cell retinopathy

    PubMed Central

    Cao, J.; Mathews, M. K.; McLeod, D; Merges, C.; Hjelmeland, L.; Lutty, G.

    1999-01-01

    BACKGROUND/AIMS—Preretinal neovascular formations called sea fans develop at the border of non-perfused peripheral retina in sickle cell retinopathy. Angiogenic factors which could contribute to their development, however, have not been examined previously. The objective of this study was to determine immunohistochemically if vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) were associated with sea fan formations.
METHODS—Immunohistochemistry on cryosections was used to localise bFGF, VEGF, heparan sulphate proteoglycan, human serum albumin, collagens IV and II, and von Willebrand factor in tissue from five sickle cell and one control subject.
RESULTS—The greatest immunoreactivity for VEGF and bFGF was in the feeder and preretinal vessels of sea fans (p<0.01). The most prominent reaction product was localised to vascular endothelial cells. In retinal vessels, VEGF and bFGF immunoreactivities were greater in sickle cell subjects (both proliferative and non-proliferative) than in the control subject (p<0.01 and p<0.02 respectively). In the sickle cell retina, no angiogenic factor immunoreactivity was detected in non-perfused periphery and there was no significant difference in bFGF or VEGF immunoreactivity between perfused retina and the border of perfused and non-perfused areas.
CONCLUSION—Our results demonstrate for the first time that VEGF and bFGF are associated with sea fan formations in sickle cell retinopathy. Both factors may function in an autocrine manner because immunoreactivity for these factors was greater within the neovascularisation than in adjacent retina.

 PMID:10381672

  18. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    PubMed

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

  19. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca)

    PubMed Central

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W.; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  20. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    PubMed

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  1. Basic fibroblast growth factor is pro-adipogenic in rat skeletal muscle progenitor clone, 2G11 cells.

    PubMed

    Nakano, Shin-ichi; Nakamura, Katsuyuki; Teramoto, Naomi; Yamanouchi, Keitaro; Nishihara, Masugi

    2016-01-01

    Intramuscular adipose tissue (IMAT) formation is a hallmark of marbling in cattle. IMAT is considered to originate from skeletal muscle progenitor cells with adipogenic potential. However, the mechanism involved in IMAT formation from these progenitor cells in vivo remains unclear. In the present study, among the growth factors tested, which were known to be expressed in skeletal muscle, we found only basic fibroblast growth factor (bFGF) has a pro-adipogenic effect on skeletal muscle derived adipogenic progenitor clone, 2G11 cells. Pre-exposure of 2G11 cells to bFGF did not affect initial gene expressions of CCAAT/enhancer-binding protein (C/EBP)β and C/EBPδ, while resulting in an enhancement of subsequent expressions of C/EBPα and proliferator-activated receptor gamma (PPARγ) during adipogenesis, indicating that bFGF is acting on the transcriptional regulation of C/EBPα and PPARγ. In addition, the effect of bFGF is mediated via two types of FGF receptor (FGFR) isoforms: FGFR1 and FGFR2 IIIc, and both receptors are prerequisite for bFGF to express its pro-adipogenic effect. These results suggest that bFGF plays an important role as a key trigger of IMAT formation in vivo.

  2. Effects of basic fibroblast growth factor and insulin-like growth factor on cultured cartilage cells from skate Raja porasa

    NASA Astrophysics Data System (ADS)

    Fan, Tingjun; Jin, Lingyun; Wang, Xiaofeng

    2003-12-01

    Effects of basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF-II) on cartilage cells from proboscis of skate, Raja porasa Günther, were investigated in this study. The cartilage cells were cultured in 20% FBS-supplemented MEM medium at 24°C. Twelve hours after culture initiation, the cartilage cells were treated with bFGF and IGF-II at different concentration combinations. It was found that 20 ng/ml of bFGF or 80 ng/ml of IGF-II was enough to have obvious stimulating effect on the growth and division of skate cartilage cells. Test of bFGF and IGF-II together, revealed that 20 ng/ml of bFGF and 80 ng/ml of IGF-II together had the best stimulating effect on the growth and division of skate cartilage cells. The cartilage cells cultured could form a monolayer at day 7.

  3. Characterization of release of basic fibroblast growth factor from bovine retinal endothelial cells in monolayer cultures.

    PubMed Central

    Brooks, R A; Burrin, J M; Kohner, E M

    1991-01-01

    Release of basic fibroblast growth factor (bFGF) was investigated in bovine retinal endothelial cells (BREC) maintained in monolayer culture. Confluent cells released bFGF into serum-free culture medium or medium containing 5% serum at rates of up to 105.2 and 61.3 pM/day respectively. bFGF release coincided with a decrease in monolayer cell number and increases in lactate dehydrogenase (LDH) concentration and cells and cell-debris particles in the medium, which suggested that cell damage and lysis were responsible for growth-factor release. Maximum bFGF release at 24 h (230 +/- 10 pM) occurred when the cells were treated with lipopolysaccharide (10 micrograms/ml), which also produced the greatest changes in parameters of cell damage. Sub-confluent cells showed little overt damage at 24 h, but released bFGF (78 +/- 20 pM) along with LDH, indicating that some cell lysis had occurred. Insulin-like growth factor 1 (IGF-1) was also released into serum-free culture medium at a rate of 0.34 nM/day, but not into medium containing serum or when the cells were treated with lipopolysaccharide. This implies that the mechanism of IGF-1 release is different from that of bFGF and is not related to cell damage. Culture medium conditioned by BREC stimulated the proliferation of these cells, as measured by an increase in their incorporation of [methyl-3H]thymidine from 7550 +/- 479 to 10467 +/- 924 d.p.m. These results demonstrate that bFGF is released from damaged BREC and that medium conditioned by these cells can stimulate retinal-endothelial-cell proliferation. This strengthens the case for an involvement of this growth factor in retinal neovascularization. Images Fig. 1. PMID:2039465

  4. Concomitant Retrograde Coronary Venous Infusion of Basic Fibroblast Growth Factor Enhances Engraftment and Differentiation of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair after Myocardial Infarction

    PubMed Central

    Wang, Xiao; Zhen, Lei; Miao, Huangtai; Sun, Qiwei; Yang, Ya; Que, Bin; Lopes Lao, Edmundo Patricio; Wu, Xingxin; Ren, Hongmei; Shi, Shutian; Lau, Wayne B.; Ma, Xinliang; Ma, Changsheng; Nie, Shaoping

    2015-01-01

    Aim: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model. Methods and Results: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×108 cells) (n=5), MSCs (1×108 cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05). Conclusions: Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury. PMID:26155315

  5. Differential activation of mitogen-activated protein kinase in response to basic fibroblast growth factor in skeletal muscle cells.

    PubMed Central

    Campbell, J S; Wenderoth, M P; Hauschka, S D; Krebs, E G

    1995-01-01

    In the MM14 mouse myoblast cell line, fibroblast growth factor (FGF) stimulates proliferation and represses differentiation. However, the intracellular signaling pathways used by FGF to affect these cellular processes are unknown. The predominant FGF receptor present on MM14 cells, FGFR1, is a receptor tyrosine kinase capable of activating the mitogen-activated protein kinase (MAPK) cascade in fibroblast and neuronal cell lines. To determine whether the FGF signal is mediated via the MAPK cascade in myoblasts, MM14 cells were stimulated with basic FGF (bFGF) and activities of the various kinases were measured. After withdrawal from serum and bFGF for 3 hr, bFGF stimulated MAPK kinase (MAPKK) activity, but MAPK and S6 peptide kinase activities were not detected. In contrast, when serum and bFGF were withdrawn for 10 hr, the activities of MAPKK, MAPK, and S6 peptide kinase were all stimulated by bFGF treatment. The inability of bFGF to stimulate MAPK after 3 hr of withdrawal may be due, in part, to the presence of a MAPK phosphatase activity that was detected in MM14 cell extracts. This dephosphorylating activity diminishes during commitment to terminal differentiation and is inhibited by sodium orthovanadate. Thus, the ability of bFGF to stimulate MAPK in MM14 cells is correlated with the loss of a MAPK phosphatase activity. These results show that although bFGF activates MAPKK in proliferating myoblasts, the mitogenic signal does not progress to the downstream kinases, providing a physiological example of an uncoupling of the MAPK cascade. Images Fig. 4 Fig. 5 PMID:7846069

  6. The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands

    PubMed Central

    Kobayashi, Fumitaka; Matsuzaka, Kenichi; Inoue, Takashi

    2016-01-01

    This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, α-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration. PMID:27025261

  7. Effect of basic fibroblast growth factor released from chitosan-fucoidan nanoparticles on neurite extension.

    PubMed

    Huang, Yi-Cheng; Yang, Ya-Ting

    2016-05-01

    Exogenous growth factors are an integral part of an effective nerve tissue-engineering strategy. Basic fibroblast growth factor (bFGF) has a marked positive effect on angiogenesis and neuronal cell survival. However, bFGF is limited by its short half-life and easy degradation by enzymes. Therefore, in this study novel biodegradable chitosan-fucoidan nanoparticles (CS-F NPs) were designed to carry bFGFs and maintain their activities. The experimental results indicated that chitosan and fucoidan form stable nanoparticles approximately 200 nm in size via electrostatic interactions. Additionally, the effectiveness of nanoparticles is related to their chitosan:fucoidan weight ratio. The CS-F NPs control the release of bFGFs and protect bFGF from deactivation by heat and enzymes. In vitro cell studies demonstrate that CS-F NPs have no cytotoxicity to PC12 cells, as the concentration of NPs is 125 ng/ml. Moreover, the CS-F NPs significantly decrease the amount of bFGF needed for neurite extension. The cumulative release of bFGF from CS-F NPs at 24 h is 0.168 ng/ml, markedly lower than that in solution (4.2 ng/ml). Importantly, CS-F NPs are potential carriers for delivering bFGFs for nerve tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity.

    PubMed

    Ulbrich, Claudia; Westphal, Kriss; Baatout, Sarah; Wehland, Markus; Bauer, Johann; Flick, Burkhard; Infanger, Manfred; Kreutz, Reinhold; Vadrucci, Sonia; Egli, Marcel; Cogoli, Augusto; Derradji, Hanane; Pietsch, Jessica; Paul, Martin; Grimm, Daniela

    2008-07-01

    Fibroblast growth factors interact with appropriate endothelial cell (EC) surface receptors and initiate intracellular signal cascades, which participate in modulating blood vessel growth. EC, upon exposure to basic fibroblast growth factors (bFGFs) undergo profound functional alterations, which depend on their actual sensitivity and involve gene expression and de novo protein synthesis. We investigated the effects of bFGF on signaling pathways of EA.hy926 cells in different environments. EC were cultured under normal gravity (1 g) and simulated microgravity (micro g) using a three-dimensional (3D) clinostat. Microgravity induced early and late apoptosis, extracellular matrix proteins, endothelin-1 (ET-1) and TGF-beta(1) expression. Microgravity reduced eNOS mRNA within 24 h. Moreover, a six- to eightfold higher amount of IL-6 and IL-8 was secreted within 24 h micro g. In addition, microgravity induced a duplication of NF-kappaB p50, while p65 was quadrupled. At 1 g, bFGF application (4 h) reduced ET-1, TGF-beta(1) and eNOS gene expression. After 24 h, bFGF enhanced fibronectin, VEGF, Flk-1, Flt-1, the release of IL-6, IL-8, and TGF-beta(1). Furthermore, bFGF promoted apoptosis, reduced NFkB p50, but enhanced NFkB p65. After 4 h micro g, bFGF decreased TGF-beta(1), eNOS, and ET-1 gene expression. After 24 h micro g, bFGF elevated fibronectin, Flk-1 and Flt-1 protein, and reduced IL-6 and IL-8 compared with vehicle treated micro g cultures. In micro g, bFGF enhanced NF-KappaB p50 by 50%, Bax by 25% and attenuated p65, activation of caspase-3 and annexin V-positive cells. bFGF differently changes intracellular signals in ECs depending whether it is applied under microgravity or normal gravity conditions. In microgravity, bFGF contributes to protect the EC from apoptosis.

  9. Effects of growth factors on temporomandibular joint disc cells.

    PubMed

    Detamore, Michael S; Athanasiou, Kyriacos A

    2004-07-01

    The effects of growth factors on cartilaginous tissues are well documented. An exception is the temporomandibular joint (TMJ) disc, where data for growth factor effects on proliferation and biosynthesis are very limited. The purpose of this study was to quantify proliferation of and synthesis by TMJ disc cells cultured in monolayer with either platelet derived growth factor-AB (PDGF), basic fibroblast growth factor (bFGF) or insulin-like growth factor-I (IGF), at either a low (10 ng/ml) or high (100 ng/ml) concentration. Proliferation was assessed with a DNA quantitation technique, collagen synthesis was measured via a hydroxyproline assay, and GAG synthesis was determined with a dimethylmethylene blue dye binding assay at 14 days. Overall, the most beneficial growth factor was bFGF, which was most potent in increasing proliferation and GAG synthesis, and also effective in promoting collagen synthesis. At the high concentration, bFGF resulted in 96% more cells than the control and 30 to 45% more cells than PDGF and IGF. PDGF and bFGF were the most potent upregulators of GAG synthesis, producing 2-3 times more GAG than the control. IGF had no significant effect on GAG production, although at its higher concentration it increased collagen production by 4.5 times over the control. Collagen synthesis was promoted by bFGF at its lower concentration, with levels 4.2 times higher than the control, whereas PDGF had no significant effect on collagen production. In general, higher concentrations increased proliferation, whereas lower concentrations favoured biosynthesis. PMID:15126139

  10. Expression and localization of basic fibroblast growth factor and its mRNA in solitary fibrous tumor.

    PubMed

    Li, X; Maeda, S; Hosone, M; Katayama, H; Sawada, N; Sun, Y; Ishiwata, T; Yokoyama, M; Naito, Z; Asano, G

    2001-10-01

    Solitary fibrous tumors (SFTs) represent a distinct neoplasm that should be included in the differential diagnosis of spindle-cell neoplasms of the soft tissue. Basic fibroblast growth factor (bFGF or FGF-2) is a mitogenic and angiogenic polypeptide produced by diverse cell types, including the cells derived from normal tissue and neoplastic lesions. In this study, the expression of bFGF, vimentin, CD 34, c-kit (or CD 117), desmin, S-100 protein, and alpha-smooth muscle actin (alpha-SMA) in SFTs, hemangiopericytomas (HPC), gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans (DFSP) were evaluated to assess their usefulness in the differential diagnosis of these lesions. The expression of bFGF mRNA was also examined in SFTs by in situ hybridization (ISH) using a digoxigenin-labeled bFGF oligonucleotide probe. All the SFTs, GISTs and DFSPs exhibited strong and diffuse immunoreactivity for CD34 and vimentin, and were completely negative for desmin, S-100 protein and alpha-SMA. The HPCs were positive for vimentin, but negative for CD34. In all the SFTs, strong and diffuse nuclear immunostaining was observed with bFGF antibody, contrasting with the negative staining observed in the majority of the HPCs, GISTs, and DFSPs. The bFGF mRNA was also expressed in the SFT cells. The constitutive expression of the bFGF in the SFT widens the spectrum of available markers for these tumors, providing a useful addition to their differential diagnosis in difficult cases, and contributing to the understanding of their histogenesis and molecular pathogenesis.

  11. Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy.

    PubMed

    Zhao, Ying-Zheng; Zhang, Ming; Tian, Xin-Qiao; Zheng, Lei; Lu, Cui-Tao

    2016-01-01

    Basic fibroblast growth factor (bFGF)-loaded liposome (bFGF-lip) combined with ultrasound-targeted microbubble destruction (UTMD) technique was investigated to prevent diabetic cardiomyopathy (DCM). Cardiac function and myocardial ultrastructure were assessed. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, immunohistochemistry staining, and Western blot assay were used to investigate the signal pathway underlying the expression of bFGF in DCM treatment. From Mason staining and TUNEL staining, bFGF-lip + UTMD group showed significant differences from the diabetes group and other groups treated with bFGF or bFGF-lip. The diabetes group showed similar results (myocardial capillary density, collagen volume fraction, and cardiac myocyte apoptosis index) to other bFGF treatment groups. Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis, and metabolic disturbances could be suppressed by the different extents of twice-weekly bFGF treatments for 12 consecutive weeks (free bFGF or bFGF-lip +/- UTMD), with the strongest improvements observed in the bFGF-lip + UTMD group. The group combining bFGF-lip with UTMD demonstrated the highest level of bFGF expression among all the groups. The bFGF activated the PI3K/AKT signal pathway, causing the reduction of myocardial cell apoptosis and increase of microvascular density. This strategy using bFGF-lip and UTMD is a potential strategy in early intervention of DCM in diabetes. PMID:26937188

  12. Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy.

    PubMed

    Zhao, Ying-Zheng; Zhang, Ming; Tian, Xin-Qiao; Zheng, Lei; Lu, Cui-Tao

    2016-01-01

    Basic fibroblast growth factor (bFGF)-loaded liposome (bFGF-lip) combined with ultrasound-targeted microbubble destruction (UTMD) technique was investigated to prevent diabetic cardiomyopathy (DCM). Cardiac function and myocardial ultrastructure were assessed. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, immunohistochemistry staining, and Western blot assay were used to investigate the signal pathway underlying the expression of bFGF in DCM treatment. From Mason staining and TUNEL staining, bFGF-lip + UTMD group showed significant differences from the diabetes group and other groups treated with bFGF or bFGF-lip. The diabetes group showed similar results (myocardial capillary density, collagen volume fraction, and cardiac myocyte apoptosis index) to other bFGF treatment groups. Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis, and metabolic disturbances could be suppressed by the different extents of twice-weekly bFGF treatments for 12 consecutive weeks (free bFGF or bFGF-lip +/- UTMD), with the strongest improvements observed in the bFGF-lip + UTMD group. The group combining bFGF-lip with UTMD demonstrated the highest level of bFGF expression among all the groups. The bFGF activated the PI3K/AKT signal pathway, causing the reduction of myocardial cell apoptosis and increase of microvascular density. This strategy using bFGF-lip and UTMD is a potential strategy in early intervention of DCM in diabetes.

  13. Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy

    PubMed Central

    Zhao, Ying-Zheng; Zhang, Ming; Tian, Xin-Qiao; Zheng, Lei; Lu, Cui-Tao

    2016-01-01

    Basic fibroblast growth factor (bFGF)-loaded liposome (bFGF-lip) combined with ultrasound-targeted microbubble destruction (UTMD) technique was investigated to prevent diabetic cardiomyopathy (DCM). Cardiac function and myocardial ultrastructure were assessed. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, immunohistochemistry staining, and Western blot assay were used to investigate the signal pathway underlying the expression of bFGF in DCM treatment. From Mason staining and TUNEL staining, bFGF-lip + UTMD group showed significant differences from the diabetes group and other groups treated with bFGF or bFGF-lip. The diabetes group showed similar results (myocardial capillary density, collagen volume fraction, and cardiac myocyte apoptosis index) to other bFGF treatment groups. Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis, and metabolic disturbances could be suppressed by the different extents of twice-weekly bFGF treatments for 12 consecutive weeks (free bFGF or bFGF-lip +/− UTMD), with the strongest improvements observed in the bFGF-lip + UTMD group. The group combining bFGF-lip with UTMD demonstrated the highest level of bFGF expression among all the groups. The bFGF activated the PI3K/AKT signal pathway, causing the reduction of myocardial cell apoptosis and increase of microvascular density. This strategy using bFGF-lip and UTMD is a potential strategy in early intervention of DCM in diabetes. PMID:26937188

  14. Blood cell induction in Xenopus animal cap explants: effects of fibroblast growth factor, bone morphogenetic proteins, and activin.

    PubMed

    Miyanaga, Y; Shiurba, R; Asashima, M

    1999-02-01

    Cultures of Xenopus blastula animal caps were used to explore the haematopoietic effects of three candidate inducers of mesoderm: basic fibroblast growth factor (bFGF), bone morphogenetic proteins (BMPs) and activin A. In response to either bFGF or activin A, explants expanded into egg-shaped structures, and beneath an outer layer of epidermis, a ventral mesodermal lining surrounded a fluid-filled cavity containing "blood-like cells". Immunocytochemistry identified some of these cells as early leukocytes, but erythrocytes were rare. BMP-2 or BMP-4 induced primitive erythrocytes as well as leukocytes, and a high concentration was required for these cells to differentiate in only a small proportion of explants. BMP-2 but not BMP-4 induced ventral mesoderm concomitantly. High concentrations of activin A dorsalized explants, which contained infrequent leukocytes, and an optimal combination of activin A and bFGF caused differentiation of muscle with few blood cells. By contrast, BMP-2 or BMP-4 plus activin A synergistically increased the numbers of both leukocytes and erythrocytes. Explants treated with BMPs plus activin contained a well organized cell mass in which yolk-rich cells mixed with blood cells and pigmented cells did not. BMP-2 plus bFGF also induced numerous leukocytes and fewer erythrocytes, but BMP-4 antagonized the leukopoietic effect of bFGF. The data suggest that the signalling pathways these three factors use to induce leukopoiesis overlap and that erythropoiesis may be activated when inducers are present in combination.

  15. Untersuchungen zur Entwicklung von Satellitengalaxien

    NASA Astrophysics Data System (ADS)

    Seidel, Björn

    2002-01-01

    fraction of dark matter but only a small amount of visible matter. Dark and visible matter may form different morphological structures. (2) Depending on the concentrations of the components, self-gravity may be the decisive factor for determining the morphology. (3) The dissolution of the core of the satellite occurs at perigalacticon (PG), but it does not decay before apogalacticon. (4) At PG the core densities of the components, their ratio and the velocity dispersions fall off in steps, the velocity dispersions along the line of sight show a high narrow peak. Some of these effects are just projection effects. (5) The radial dependence of the velocity dispersion is dependent on the orbital position; it is analysed in detail. (6) The satellite decays through a cycle of mass loss, an increasingly shallow potential and decreasing tidal radius.

  16. Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles.

    PubMed

    van Wezel, I L; Umapathysivam, K; Tilley, W D; Rodgers, R J

    1995-12-29

    Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis. PMID:8824888

  17. Induction of angiogenesis via topical delivery of basic-fibroblast growth factor from polyvinyl alcohol-dextran blend hydrogel in an ovine model of acute myocardial infarction.

    PubMed

    Fathi, Ezzatollah; Nassiri, Seyed Mahdi; Atyabi, Nahid; Ahmadi, Seyed Hossein; Imani, Mohammad; Farahzadi, Raheleh; Rabbani, Shahram; Akhlaghpour, Shahram; Sahebjam, Mohammad; Taheri, Mohammad

    2013-09-01

    Hydrogels are currently used as interesting constructs for the delivery of proteins. In this study, a novel polyvinyl alcohol-dextran (PVA-Dex) blend hydrogel was used for controlled delivery of basic-fibroblast growth factor (bFGF). These biocompatible constructs were sutured to the epicardium as patches on the heart surface to provide slow release of bFGF to the infarcted site in an ovine model of myocardial infarction (MI). Eighteen sheep were randomly divided into three groups (n = 6 each), including group I (control without any patch and bFGF), group II (patch without bFGF) and group III (patch incorporating 100 µg bFGF). They were subjected to coronary artery ligation after lateral thoracotomy, and then in groups II and III the patches were implanted 20-30 min after MI. Cardiac function was assessed by both echocardiography and magnetic resonance imaging (MRI) 2 months after implantation. Then the animals were sacrificed and the hearts subjected to histopathological examination, immunohistochemistry and electron microscopy. Heart lysates were subject to protein expression analysis through western blotting. The results showed that sustained release of bFGF using PVA-Dex blend hydrogel strongly stimulated angiogenesis and increased wall thickness index in the infarcted myocardium. The patch also significantly attenuated the increase in left ventricular end-systolic diameter, but it did not improve cardiac function within 2 months of myocardial infarction. In conclusion, PVA-Dex gel incorporating bFGF can be used as a sustained release construct for therapeutic angiogenesis in ischaemic heart disease.

  18. Linear Ordered Collagen Scaffolds Loaded with Collagen-Binding Basic Fibroblast Growth Factor Facilitate Recovery of Sciatic Nerve Injury in Rats

    PubMed Central

    Ma, Fukai; Xiao, Zhifeng; Chen, Bing; Hou, Xianglin

    2014-01-01

    Natural biological functional scaffolds, consisting of biological materials filled with promoting elements, provide a promising strategy for the regeneration of peripheral nerve defects. Collagen conduits have been used widely due to their excellent biological properties. Linear ordered collagen scaffold (LOCS) fibers are good lumen fillers that can guide nerve regeneration in an ordered direction. In addition, basic fibroblast growth factor (bFGF) is important in the recovery of nerve injury. However, the traditional method for delivering bFGF to the lesion site has no long-term effect because of its short half-life and rapid diffusion. Therefore, we fused a specific collagen-binding domain (CBD) peptide to the N-terminal of native basic fibroblast growth factor (NAT-bFGF) to retain bFGF on the collagen scaffolds. In this study, a natural biological functional scaffold was constructed using collagen tubes filled with collagen-binding bFGF (CBD-bFGF)-loaded LOCS to promote regeneration in a 5-mm rat sciatic nerve transection model. Functional evaluation, histological investigation, and morphometric analysis indicated that the natural biological functional scaffold retained more bFGF at the injury site, guided axon growth, and promoted nerve regeneration as well as functional restoration. PMID:24188561

  19. Vascular endothelial growth factor and basic fibroblast growth factor present in Kaposi's sarcoma (KS) are induced by inflammatory cytokines and synergize to promote vascular permeability and KS lesion development.

    PubMed Central

    Samaniego, F.; Markham, P. D.; Gendelman, R.; Watanabe, Y.; Kao, V.; Kowalski, K.; Sonnabend, J. A.; Pintus, A.; Gallo, R. C.; Ensoli, B.

    1998-01-01

    All forms of Kaposi's sarcoma (KS) are characterized by spindle cell proliferation, angiogenesis, inflammatory cell infiltration, and edema. We have previously reported that spindle cells of primary KS lesions and KS-derived spindle cell cultures express high levels of basic fibroblast growth factor (bFGF), which is promoted by the inflammatory cytokines identified in these lesions. These cytokines, namely, tumor necrosis factor, interleukin-1, and interferon-gamma, induce production and release of bFGF, which stimulates angiogenesis and spindle cell growth in an autocrine fashion. Here we show that both AIDS-KS and classical KS lesions co-express vascular endothelial growth factor (VEGF) and bFGF. VEGF production by KS cells is promoted synergistically by inflammatory cytokines present in conditioned media from activated T cells and in KS lesions. KS cells show synthesis of VEGF isoforms that are mitogenic to endothelial cells but not to KS spindle cells, suggesting a prevailing paracrine effect of this cytokine. This may be due to the level of expression of the flt-1-VEGF receptor that is down-regulated in KS cells as compared with endothelial cells. KS-derived bFGF and VEGF synergize in inducing endothelial cell growth as shown by studies using both neutralizing antibodies and antisense oligodeoxynucleotides directed against these cytokines. In addition, VEGF and bFGF synergize to induce angiogenic KS-like lesions in nude mice and vascular permeability and edema in guinea pigs. These results indicate that inflammatory cytokines present in KS lesions stimulate the production of bFGF and VEGF, which, in turn, cooperate to induce angiogenesis, edema, and KS lesion formation. Images Figure 1 Figure 3 PMID:9626048

  20. Newtons Universum. Materialien zur Geschichte des Kraftbegriffes.

    NASA Astrophysics Data System (ADS)

    Mit einem Vorwort von E. Seibold und einer Einführung von W. Neuser. This book is a selection of 15 articles published in the journal "Spektrum der Wissenschaft". The original English versions of the papers were first published in "Scientific American". Contents: 1. Impetustheorie und Intuition in der Physik (M. McCloskey). 2. Mittelalterliche Ursprünge der industriellen Revolution (T. S. Reynolds). 3. Leonardo da Vincis Beiträge zur theoretischen Mechanik (V. Foley, W. Soedel). 4. Nikolaus Kopernikus und Tycho Brahe (O. Gingerich). 5. Keplers Entdeckung der ersten beiden Planetengesetze (C. Wilson). 6. Galileis Entdeckung des Fallgesetzes (S. Drake). 7. Galileis Beobachtung des Neptun (S. Drake, C. T. Kowal). 8. Galileo Galilei und der Schatten des Giordano Bruno (L. S. Lerner, E. A. Gosselin). 9. Der Fall Galilei (O. Gingerich). 10. Newtons Apfel und Galileis "Dialog" (S. Drake). 11. Newtons Gravitationsgesetz - aus Formeln wird eine Idee (I. B. Cohen). 12. Christopher Wren: Astronom und Architekt (H. Dorn, R. Mark). 13. Atomismus und Kräfte in der Geschichte (L. Holliday). 14. Ein Elitezirkel vor 200 Jahren: Die Lunar Society von Birmingham (L. Ritchie-Calder). 15. Sadi Carnot: Technik und Theorie der Dampfmaschine (S. S. Wilson).

  1. Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats.

    PubMed

    Fisher, M; Meadows, M E; Do, T; Weise, J; Trubetskoy, V; Charette, M; Finklestein, S P

    1995-11-01

    Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 micrograms/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague-Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 +/- 1.0 in vehicle-treated and 1.5 +/- 1.3 in bFGF-treated rats (mean +/- SD; N = 12 vs. 11; p = 0.009). Infarct volume was 297 +/- 65 mm3 in vehicle- and 143 +/- 135 mm3 in bFGF-treated animals (p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood-brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.

  2. Binding, internalization, and degradation of basic fibroblast growth factor in human microvascular endothelial cells

    SciTech Connect

    Bikfalvi, A.; Dupuy, E.; Inyang, A.L.; Tobelem, G. ); Fayein, N.; Courtois, Y. ); Leseche, G. )

    1989-03-01

    The binding, internalization, and degradation of basic fibroblast growth factor (bFGF) in human omental microvascular endothelial cells (HOME cells) were investigated. Binding studies of bFGF in human endothelial cells have not yet been reported. Basic FGF bound to HOME cells. The number of low-affinity binding sites was found to be variable. Washing the cells with 2 M phosphate-buffered saline removed completely {sup 125}I-bFGF bound to low-affinity binding sites but decreased also the high-affinity binding. The majority of the surface-bound {sup 125}I-bFGF was removed by washing the cells with acetic acid buffer at pH 3. At this temperature, degradation of the internalized ligand was followed after 1 hour by the appearance of three major bands of 15,000 10,000, and 8,000 Da and was inhibited by chloroquine. These results demonstrated two classes of binding sites for bFGF in HOME cells; the number of high-affinity binding sites being larger than the number reported for bovine capillary endothelial cells. The intracellular processing of bFGF in HOME cells seems to be different from that of heparin binding growth factor-1 in murine lung capillary endothelial cells and of eye-derived growth factor-1 in Chinese hamster fibroblasts.

  3. Osmotic Induction of Angiogenic Growth Factor Expression in Human Retinal Pigment Epithelial Cells

    PubMed Central

    Reichenbach, Andreas; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas

    2016-01-01

    Background Although systemic hypertension is a risk factor of age-related macular degeneration, antihypertensive medications do not affect the risk of the disease. One condition that induces hypertension is high intake of dietary salt resulting in increased blood osmolarity. In order to prove the assumption that, in addition to hypertension, high osmolarity may aggravate neovascular retinal diseases, we determined the effect of extracellular hyperosmolarity on the expression of angiogenic cytokines in cultured human retinal pigment epithelial (RPE) cells. Methodology/Principal Findings Hyperosmolarity was induced by the addition of 100 mM NaCl or sucrose to the culture medium. Hypoxia and oxidative stress were induced by the addition of the hypoxia mimetic CoCl2 and H2O2, respectively. Alterations in gene expression were determined with real-time RT-PCR. Secretion of bFGF was evaluated by ELISA. Cell viability was determined by trypan blue exclusion. Nuclear factor of activated T cell 5 (NFAT5) expression was knocked down with siRNA. Hyperosmolarity induced transcriptional activation of bFGF, HB-EGF, and VEGF genes, while the expression of other cytokines such as EGF, PDGF-A, TGF-β1, HGF, and PEDF was not or moderately altered. Hypoxia induced increased expression of the HB-EGF, EGF, PDGF-A, TGF-β1, and VEGF genes, but not of the bFGF gene. Oxidative stress induced gene expression of HB-EGF, but not of bFGF. The hyperosmotic expression of the bFGF gene was dependent on the activation of p38α/β MAPK, JNK, PI3K, and the transcriptional activity of NFAT5. The hyperosmotic expression of the HB-EGF gene was dependent on the activation of p38α/β MAPK, ERK1/2, and JNK. The hyperosmotic expression of bFGF, HB-EGF, and VEGF genes was reduced by inhibitors of TGF-β1 superfamily activin receptor-like kinase receptors and the FGF receptor kinase, respectively. Hyperosmolarity induced secretion of bFGF that was reduced by inhibition of autocrine/paracrine TGF-β1

  4. A mutein of human basic fibroblast growth factor TGP-580 accelerates colonic ulcer healing by stimulating angiogenesis in the ulcer bed in rats.

    PubMed

    Satoh, H; Szabo, S

    2015-10-01

    Previously, we reported that TGP-580, a mutein of human basic fibroblast growth factor (bFGF), accelerated the healing of gastric and duodenal ulcers in rats. In the present study, we examined the effect of TGP-580 on the healing of colonic ulcers. In male Sprague Dawley rats, ulcers were induced in the colon 6 cm from the anus by enema of 50 μl of 3% N-ethylmaleimide, a sulfhydryl alkylator. The lesions were examined under a dissecting microscope (x10). The concentration of bFGF in the ulcerated colon was measured by enzyme immunoassay, and both the distribution of bFGF and the density of microvessels in the ulcer bed were examined by immunohistochemical staining. The content of bFGF in the ulcerated colon was markedly increased associated with ulcer healing, and ulcer healing was significantly delayed by intravenous administration of a monoclonal antibody for bFGF (MAb 3H3) once daily for 10 days. In the ulcer bed, many cells such as fibroblasts, vascular endothelial cells and macrophages were positively stained with bFGF antiserum. TGP-580, human bFGF or dexamethasone was given intracolonally twice daily for 10 days, starting the day after ulcer induction. TGP-580 (0.2 - 20 μg/ml, 200 μl/rat) dose-dependently accelerated ulcer healing, and its effect was more than 10 times stronger than that of human bFGF. Density (μm/0.01 mm(2)) of microvessels in the ulcer bed was significantly increased by treatment with TGP-580, and there was a good correlation between the density of microvessels and the decrease of ulcerated area (R(2) = 0.633). On the other hand dexamethasone (20 μg/ml) inhibited angiogenesis in the ulcer bed and delayed ulcer healing. These results suggest that angiogenesis in the ulcer bed plays an important role in ulcer healing, and that bFGF mutein TGP-580 accelerated colonic ulcer healing, at least in part, by stimulating angiogenesis, whereas glucocorticoids may delay the healing by inhibiting angiogenesis.

  5. Intein mediated hyper-production of authentic human basic fibroblast growth factor in Escherichia coli

    PubMed Central

    Kwong, Keith W. Y.; Sivakumar, T.; Wong, W. K. R.

    2016-01-01

    Human basic fibroblast growth factor is a functionally versatile but very expensive polypeptide. In this communication, employing a novel amplification method for the target gene and genetic optimization of a previously engineered expression construct, pWK3R, together with a refined fed-batch fermentation protocol, we report an achievement of a phenomenal yield of 610 mg/L of the 146 aa authentic human basic fibroblast growth factor (bFGF) in Escherichia coli. Construct pWK3R was first modified to form plasmid pWK311ROmpAd, which was devoid of the ompA leader sequence and possessed two copies of a DNA segment encoding a fusion product comprising an intein, Saccharomyces cerevisiae vascular membrane ATPase (VMA), and bFGF. When E. coli transformant JM101 [pWK311ROmpAd] was cultivated using the refined fed-batch fermentation protocol, superb expression resulting in a total yield of 610 mg/L of bFGF was detected. Despite existing in high levels, the bFGF remained to be soluble and highly bioactive. PMID:27653667

  6. Peptide growth factors in tracheal aspirates of mechanically ventilated preterm neonates.

    PubMed

    Ambalavanan, Namasivayam; Novak, Zuzana E

    2003-02-01

    Basic fibroblast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1) are peptide growth factors (PGF) mediating normal lung development, maturation, injury, and repair. These PGF may therefore be involved in the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized that elevated levels of these PGF in tracheal aspirates would be associated with a) BPD and/or death; b) markers of cell injury and apoptosis; and c) chorioamnionitis, a risk factor for BPD. Tracheal aspirates collected in 29 preterm (<34 wk gestation, 500-2000 g birth weight), mechanically ventilated infants on d 1 of life were assayed for PGF and histone-associated DNA fragments by ELISA and for LDH by enzyme assay. Clinical and pathologic examination was performed for chorioamnionitis. BPD was defined as oxygen requirement/mechanical ventilation at 28 d postnatal age. The birth weight (mean +/- SE) was 1009 +/- 85 g and median gestational age was 26 wk (range, 22-33). Eighteen infants died or developed BPD. bFGF levels were elevated in infants who died or developed BPD [median (25%,75%) level of 36 (23, 44) pg/mL versus 14 (6, 30) in the survivors without BPD, p = 0.01]. bFGF levels correlated with apoptosis (r = 0.73, p < 0.001) and LDH levels (r = 0.59, p < 0.001). VEGF and ET-1 levels were not associated with apoptosis or with BPD/death. PGF levels were not associated with chorioamnionitis. We conclude that elevated bFGF levels in the preterm trachea correlate with BPD/death and markers of cell injury and apoptosis but not with chorioamnionitis. We speculate that bFGF may play a role in the development of BPD.

  7. Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

    PubMed Central

    Mortensen, Brittany L.; Rathi, Subodh; Chazin, Walter J.

    2014-01-01

    Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia in intensive care units, and the increasing rates of antibiotic resistance make treating these infections challenging. Consequently, there is an urgent need to develop new antimicrobials to treat A. baumannii infections. One potential therapeutic option is to target bacterial systems involved in maintaining appropriate metal homeostasis, processes that are critical for the growth of pathogens within the host. The A. baumannii inner membrane zinc transporter ZnuABC is required for growth under low-zinc conditions and for A. baumannii pathogenesis. The expression of znuABC is regulated by the transcriptional repressor Zur. To investigate the role of Zur during the A. baumannii response to zinc limitation, a zur deletion mutant was generated, and transcriptional changes were analyzed using RNA sequencing. A number of Zur-regulated genes were identified that exhibit increased expression both when zur is absent and under low-zinc conditions, and Zur binds to predicted Zur box sequences of several genes affected by zinc levels or the zur mutation. Furthermore, the zur mutant is impaired for growth in the presence of both high and low zinc levels compared to wild-type A. baumannii. Finally, the zur mutant exhibits a defect in dissemination in a mouse model of A. baumannii pneumonia, establishing zinc sensing as a critical process during A. baumannii infection. These results define Zur-regulated genes within A. baumannii and demonstrate a requirement for Zur in the A. baumannii response to the various zinc levels experienced within the vertebrate host. PMID:24816603

  8. Role of transiently altered sarcolemmal membrane permeability and basic fibroblast growth factor release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro.

    PubMed Central

    Kaye, D; Pimental, D; Prasad, S; Mäki, T; Berger, H J; McNeil, P L; Smith, T W; Kelly, R A

    1996-01-01

    One of the trophic factors that has been implicated in initiating or facilitating growth in response to increased mechanical stress in several tissues and cell types is basic fibroblast growth factor (bFGF; FGF-2). Although mammalian cardiac muscle cells express bFGF, it is not known whether it plays a role in mediating cardiac adaptation to increased load, nor how release of the cytosolic 18-kD isoform of bFGF would be regulated in response to increased mechanical stress. To test the hypothesis that increased mechanical activity induces transient alterations in sarcolemmal permeability that allow cytosolic bFGF to be released and subsequently to act as an autocrine and paracrine growth stimulus, we examined primary isolates of adult rat ventricular myocytes maintained in serum-free, defined medium that were continually paced at 3 Hz for up to 5 d. Paced myocytes, but not nonpaced control cells, exhibited a "hypertrophic" response, which was characterized by increases in the rate of phenylalanine incorporation, total cellular protein content, and cell size. These changes could be mimicked in control cells by exogenous recombinant bFGF and could be blocked in continually paced cells by a specific neutralizing anti-bFGF antibody. In addition, medium conditioned by continually paced myocytes contained significantly more bFGF measured by ELISA and more mitogenic activity for 3T3 cells, activity that could be reduced by a neutralizing anti-bFGF antibody. The hypothesis that transient membrane disruptions sufficient to allow release of cytosolic bFGF occur in paced myocytes was examined by monitoring the rate of uptake into myocytes from the medium of 10-kD dextran linked to fluorescein. Paced myocytes exhibited a significantly higher rate of fluoresceinlabeled dextran uptake. These data are consistent with the hypothesis that nonlethal, transient alterations in sarcolemmal membrane permeability with release of cytosolic bFGF is one mechanism by which increased

  9. Fibroblast Growth Factor Receptor-2 Contributes to the Basic Fibroblast Growth Factor-Induced Neuronal Differentiation in Canine Bone Marrow Stromal Cells via Phosphoinositide 3-Kinase/Akt Signaling Pathway

    PubMed Central

    Nakano, Rei; Edamura, Kazuya; Nakayama, Tomohiro; Narita, Takanori; Okabayashi, Ken; Sugiya, Hiroshi

    2015-01-01

    Bone marrow stromal cells (BMSCs) are considered as candidates for regenerative therapy and a useful model for studying neuronal differentiation. The role of basic fibroblast growth factor (bFGF) in neuronal differentiation has been previously studied; however, the signaling pathway involved in this process remains poorly understood. In this study, we investigated the signaling pathway in the bFGF-induced neuronal differentiation of canine BMSCs. bFGF induced the mRNA expression of the neuron marker, microtubule associated protein-2 (MAP2) and the neuron-like morphological change in canine BMSCs. In the presence of inhibitors of fibroblast growth factor receptors (FGFR), phosphatidylinositol 3-kinase (PI3K) and Akt, i.e., SU5402, LY294002, and MK2206, respectively, bFGF failed to induce the MAP2 mRNA expression and the neuron-like morphological change. bFGF induced Akt phosphorylation, but it was attenuated by the FGFR inhibitor SU5402 and the PI3K inhibitor LY294002. In canine BMSCs, expression of FGFR-1 and FGFR-2 was confirmed, but only FGFR-2 activation was detected by cross-linking and immunoprecipitation analysis. Small interfering RNA-mediated knockdown of FGFR-2 in canine BMSCs resulted in the attenuation of bFGF-induced Akt phosphorylation. These results suggest that the FGFR-2/PI3K/Akt signaling pathway is involved in the bFGF-induced neuronal differentiation of canine BMSCs. PMID:26523832

  10. Growth factor modulation of fibroblast proliferation, differentiation, and invasion: implications for tissue valve engineering.

    PubMed

    Narine, Kishan; De Wever, Olivier; Van Valckenborgh, Dillis; Francois, Katrien; Bracke, Marc; DeSmet, Stefaan; Mareel, Marc; Van Nooten, Guido

    2006-10-01

    We have previously shown that transforming growth factor-beta1 (TGF-beta1) stimulates transdifferentiation of fibroblasts into smooth muscle alpha-actin (alpha-SMA) positive myofibroblasts. However, TGF-beta, as such, is unsuitable for effective population of a heart valve matrix, because it dose-dependently inhibits growth of fibroblasts. The aim of this study was to investigate combinations of other growth factors with TGF-beta to stimulate the proliferation of suitably differentiated cells and to enhance their invasion into aortic valve matrices. Human dermal mesenchymal cells (hDMC1.1) were treated with combinations of growth factors to stimulate these cells to trans-differentiate into myofibroblasts, to proliferate, and to invade. Growth factors were chosen after expression of their respective receptors was confirmed in hDMC1.1 using reverse transcriptase polymerase chain reaction. We combined TGF-beta with several growth factors such as insulin-like growth factor (IGF-1, IGF-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF-AA, PDGF-BB, and PDGFAB). Nuclear Ki67 staining, MTT assay, and cell counting revealed that only EGF and bFGF were capable of overcoming TGF-beta-induced growth inhibition. However, bFGF but not EGF inhibited TGF-beta-induced alpha-SMA expression, as evidenced by immuno-cytochemistry and Western blotting. A growth factor cocktail (TGF-beta, EGF, bFGF) has been established that maintains TGF-beta-induced trans-differentiation but overcomes TGF-beta-induced growth inhibition while stimulating fibroblast proliferation and invasion. PMID:17518640

  11. Robust, flexible, and bioadhesive free-standing films for the co-delivery of antibiotics and growth factors.

    PubMed

    Chen, Dongdong; Wu, Mingda; Chen, Jie; Zhang, Chunqiu; Pan, Tiezheng; Zhang, Bing; Tian, Huayu; Chen, Xuesi; Sun, Junqi

    2014-11-25

    Free-standing polymer films that adhere strongly to tissue and can codeliver multiple therapeutic agents in a controlled manner are useful as medical plasters. In this study, a bilayer polymer film comprising a drug reservoir layer and a supporting layer is fabricated by spin-coating poly(lactic-co-glycolic acid) (PLGA) on top of a layer-by-layer assembled film of poly(β-amino esters) (PAE), alginate sodium (ALG), and recombinant human basic fibroblast growth factor (bFGF). Apart from bFGF, the bilayer film can also load antibiotic drug ceftriaxone sodium (CTX) by a postdiffusion process. The PLGA supporting layer facilitates the direct peeling of the bilayer film from substrate to produce a robust and flexible free-standing film with excellent adhesion onto the human skin and porcine liver. The excellent adhesion of the bilayer film originates from the ALG component in the drug reservoir layer. CTX is quickly released by easily breaking its electrostatic interaction with the drug reservoir layer, whereas the sustained release of bFGF is due to the slow degradation of PAE component in the drug reservoir layer. Wounds can be synergetically treated by fast release of CTX to effectively eradicate invasive bacteria and by sustained release of bFGF to accelerate wound healing. Our results serve as a basis for designing multifunctional free-standing films with combination therapy for biomedical applications. PMID:25353985

  12. Biodegradable micro-osmotic pump for long-term and controlled release of basic fibroblast growth factor.

    PubMed

    Ryu, WonHyoung; Huang, Zhinong; Prinz, Fritz B; Goodman, Stuart B; Fasching, Rainer

    2007-12-01

    Microelectromechanical system (MEMS) technology not only provides the possibility of integration of multiple functions but also enables more precise control of dosing of therapeutic agents when the therapeutic window is very limited. Local delivery of basic fibroblast growth factor (bFGF) over a specific dose and time course is critical for mesenchymal tissue regeneration. However, bFGF is degraded quickly in vivo and difficulty of controlling the dose level impedes its effective use in angiogenesis and tissue regeneration. We constructed biodegradable micro-osmotic pumps based on MEMS technology for long-term controlled release of bFGF. The devices were constructed by micro-molding and thermal assembly of 85/15 poly(L-lactide-co-glycolide) sheets. The release of bFGF was regulated at 40 ng/day for four weeks; bioactivity was assessed by monitoring the growth of 3T3 fibroblasts. The proposed devices can be further miniaturized and used for the delivery of multiple therapeutic agents at the individual releasing schedules.

  13. Basic fibroblast growth factor promotes stem Leydig cell development and inhibits LH-stimulated androgen production by regulating microRNA expression.

    PubMed

    Liu, Hui; Yang, Yan; Zhang, Lei; Liang, Rui; Ge, Ren-Shan; Zhang, Yufei; Zhang, Qihao; Xiang, Qi; Huang, Yadong; Su, Zhijian

    2014-10-01

    Leydig cells are the primary source of testosterone in the testes, and their steroidogenic function is strictly controlled by the hypothalamus-pituitary-gonad axis. Emerging evidence has indicated that fibroblast growth factors play a role in regulating stem Leydig cell development and steroidogenesis, but little is known about the regulatory mechanism. Using a seminiferous tubule culture system, we demonstrated that basic fibroblast growth factor (bFGF) can promote stem Leydig cell proliferation and commitment toward differentiation in testosterone-producing Leydig cells. However, these promoting effects decreased with an increase in the bFGF dose. Previous studies have reported that bFGF inhibits luteinizing hormone (LH)-stimulated androgen production by downregulating the mRNA expression of steroidogenic genes in immature Leydig cells. However, the expression levels of 677 microRNAs did not change significantly during the LH-mediated process of testosterone synthesis. Five microRNAs (miR-29a, -29c, -142-3p, -451 and -335) were identified, and their expression in immature Leydig cells was regulated simultaneously by bFGF and LH. These results suggested that the inhibition of LH-stimulated androgen production may be modulated by a change in bFGF-mediated microRNA expression, which further impacts the signaling pathway of testosterone biosynthesis and steroidogenic gene expression.

  14. Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide.

    PubMed

    Chen, Xiang; Wang, Xianhuo; Wang, Yongsheng; Yang, Li; Hu, Jia; Xiao, Wenjing; Fu, Afu; Cai, Lulu; Li, Xia; Ye, Xia; Liu, Yalin; Wu, Wenshuang; Shao, Ximing; Mao, Yongqiu; Wei, Yuquan; Chen, Lijuan

    2010-07-01

    Fibroblast growth factor receptors (FGFRs), overexpressed on the surface of a variety of tumor cells and on tumor neovasculature in situ, are potential targets for tumor- and vascular-targeting therapy. This study aimed to develop a FGFR-mediated drug delivery system to target chemotherapeutic agents to FGFR-overexpressed tumor cells and tumor neovasculature endothelial cells in vitro and in vivo. Here we designed a truncated human basic fibroblast growth factor peptide (tbFGF), which was attached to the surface of cationic liposomal doxorubicin (LPs-DOX) and paclitaxel (LPs-PTX) via electrostatic force. Then we characterized the tbFGF-modified liposome (tbFGF-LPs) and examined internalization of doxorubicin in tumor cells (TRAMP-C1, B16) and HUVEC cells in vitro. In vivo, we evaluated the biodistribution and antitumor efficacy of tbFGF-LPs-DOX and tbFGF-LPs-PTX in C57BL/6J mice bearing TRAMP-C1 prostate carcinoma and B16 melanoma, respectively. The tbFGF-LPs-DOX significantly improved the uptake of doxorubicin in TRAMP-C1, B16 and HUVEC cells, respectively. Biodistribution study in B16 tumor-bearing mice showed that tbFGF-LPs-PTX achieved 7.1-fold (72.827+/-7.321mgh/L vs 10.292+/-0.775mgh/L, mean+/-SD, P<0.01) accumulation of paclitaxel in tumor tissue than those of free paclitaxel. More importantly, treatment of tumor-bearing mice with tbFGF-LPs-DOX and tbFGF-LPs-PTX showed the significant inhibition in tumor growth and improvement in survival rate as compared with mice treated with free and liposomal drugs in TRAMP-C1 and B16 tumor models, respectively. Furthermore, repeated intravenous administration of tbFGF-LPs-DOX/PTX did not induce anti-bFGF antibodies. These results suggested that this FGFR-mediated drug delivery system may provide a new treatment strategy for tumors which overexpress FGFRs. PMID:20307599

  15. Use of Decellularized Scaffolds Combined with Hyaluronic Acid and Basic Fibroblast Growth Factor for Skin Tissue Engineering

    PubMed Central

    Wu, Zhengzheng; Fan, Lina; Xu, Bin; Lin, Yongliang; Zhang, Peng

    2015-01-01

    Skin damage is one of the common clinical skin diseases, and the main cure is the use of skin graft, especially for large area of skin injury or deep-skin damage. However, skin graft demand is far greater than that currently available. In this study, xenogeneic decellularized scaffold was prepared with pig peritoneum by a series of biochemical treatments to retain normal three-dimensional tissue scaffold and remove cells and antigenic components from the tissue. Scaffold was combined with hyaluronic acid (HA) plus two different concentrations of basic fibroblast growth factor (bFGF) and tested for its use for the repair of skin wounds. HA enhanced bFGF to adsorb to the decellularized scaffolds and slowed the release of bFGF from the scaffolds in vitro. A total of 20 rabbits were sacrificed on day 3, 6, 11, or 14 postsurgery. The wound healing rate and the thickness of dermis layer of each wound were determined for analyzing the wound repair. Statistical analysis was performed by the two-tailed Student's t-test. Wounds covered with scaffolds containing 1 μg/mL bFGF had higher wound healing rates of 47.24%, 74.69%, and 87.54%, respectively, for days 6, 11, and 14 postsurgery than scaffolds alone with wound healing rates of 28.17%, 50.31%, and 61.36% and vaseline oil gauze with wound healing rates of 24.84%, 42.75%, and 57.62%. Wounds covered with scaffolds containing 1 μg/mL bFGF showed more dermis regeneration than the other wounds and had dermis layer of 210.60, 374.40, and 774.20 μm, respectively, for days 6, 11, and 14 postsurgery compared with scaffolds alone with dermis layer of 116.60, 200.00, and 455.40 μm and vaseline oil gauze with dermis layer of 82.60, 186.20, and 384.40 μm. There was no significant difference in wound healing rates and thickness of dermis layer between wounds covered with scaffolds containing 1 and 3 μg/mL bFGF on days 3, 6, 11, and 14 postsurgery. The decellularized scaffolds combined with HA and bFGF can be further

  16. Collagenase-3 (MMP-13) Expression in Chondrosarcoma Cells and Its Regulation by Basic Fibroblast Growth Factor

    PubMed Central

    Uría, José A.; Balbín, Milagros; López, José M.; Alvarez, Jesús; Vizoso, Francisco; Takigawa, Masaharu; López-Otín, Carlos

    1998-01-01

    Human collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family of enzymes that was originally identified in breast carcinomas and subsequently detected during fetal ossification and in arthritic processes. In this work, we have found that collagenase-3 is produced by HCS-2/8 human chondrosarcoma cells. An analysis of the ability of different cytokines and growth factors to induce the expression of collagenase-3 in these cells revealed that basic fibroblast growth factor (bFGF or FGF-2) strongly up-regulated the expression of this gene. By contrast, other factors, including interleukin-1β and transforming growth factor-β, previously found to induce collagenase-3 expression in other cell types, did not exhibit any effect on the expression of this gene in chondrosarcoma cells. Further analysis of the bFGF-induced expression of collagenase-3 in human chondrosarcoma cells revealed that its effect was time and dose dependent, but independent of the de novo synthesis of proteins. Western blot analysis revealed that the up-regulatory effect of bFGF on collagenase-3 was also reflected at the protein level as demonstrated by the increase of immunoreactive protein in the conditioned medium of HCS-2/8 cells treated with bFGF. Immunohistochemical analysis of the presence of collagenase-3 in a series of 8 benign and 16 malignant cartilage-forming neoplasms revealed that all analyzed malignant chondrosarcomas stained positively for collagenase-3, whereas only 2 of 8 benign lesions produced this protease. In addition, the finding that bFGF was detected in all analyzed chondrosarcomas, together with the above in vitro studies on HCS-2/8 cells, suggest that this growth factor may be an in vivo modulator of collagenase-3 expression in these malignant tumors. These results extend the pattern of tumor types with ability to produce this matrix metalloproteinase and suggest that collagenase-3 up-regulation may contribute to the progression of human chondrosarcomas

  17. Hypoxia-mediated induction of acidic/basic fibroblast growth factor and platelet-derived growth factor in mononuclear phagocytes stimulates growth of hypoxic endothelial cells.

    PubMed Central

    Kuwabara, K; Ogawa, S; Matsumoto, M; Koga, S; Clauss, M; Pinsky, D J; Lyn, P; Leavy, J; Witte, L; Joseph-Silverstein, J

    1995-01-01

    Wound repair and tumor vascularization depend upon blood vessel growth into hypoxic tissue. Although hypoxia slows endothelial cell (EC) proliferation and suppresses EC basic fibroblast growth factor (bFGF) expression, we report that macrophages (MPs) exposed to PO2 approximately 12-14 torr (1 torr = 133.3 Pa) synthesize and release in a time-dependent manner platelet-derived growth factor (PDGF) and acidic/basic FGFs (a/bFGFs), which stimulate the growth of hypoxic ECs. Chromatography of hypoxic MP-conditioned medium on immobilized heparin with an ascending NaCl gradient resolved three peaks of mitogenic activity: activity of the first peak was neutralized by antibody to PDGF; activity of the second peak was neutralized by antibody to aFGF; and activity of the third peak was neutralized by antibody to bFGF. Metabolically labeled lysates and supernatants from MPs exposed to hypoxia showed increased synthesis and release of immunoprecipitable PDGF and a/bFGF in the absence of changes in cell viability. Possible involvement of a heme-containing oxygen sensor in MP elaboration of growth factors was suggested by the induction of bFGF and PDGF by normoxic MPs exposed to nickel or cobalt, although metabolic inhibitors such as sodium azide were without effect. These results suggest a paracrine model in which hypoxia stimulates MP release of PDGF and a/bFGF, inducing EC proliferation and potentially promoting angiogenesis in hypoxic environments. Images Fig. 1 Fig. 3 Fig. 4 PMID:7538678

  18. Effects of growth factors and trefoil peptides on migration and replication in primary oxyntic cultures.

    PubMed

    Kato, K; Chen, M C; Nguyen, M; Lehmann, F S; Podolsky, D K; Soll, A H

    1999-05-01

    Restitution, the lateral migration of cells over an intact basement membrane, maintains mucosal integrity. We studied the regulation of migration and proliferation of enzyme-dispersed canine oxyntic mucosa cells in primary culture. Confluent monolayers were wounded and cultured in serum-free medium, and cells migrating into the wound were counted. [3H]thymidine incorporation into DNA was studied using subconfluent cultures. Considerable migration occurred in untreated monolayers; however, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I), two trefoil peptides, and interleukin (IL)-1beta further enhanced migration. The specific EGF receptor (EGFR) monoclonal antibody, MAb-528, inhibited both basal and TGF-alpha- or IL-1beta-stimulated migration, but not the response to trefoil peptide, bFGF, or IGF-I. Exogenous TGF-beta inhibited cell proliferation but did not alter migration. Immunoneutralization with anti-TGF-beta blocked the response to exogenous TGF-beta and produced a small enhancement of basal thymidine incorporation but did not attenuate basal or TGF-alpha-stimulated migration. In conclusion, endogenous EGFR ligands regulate proliferation and migration. TGF-beta inhibits mitogenesis; it did not upregulate migration in these cultures. Although bFGF, IGF-I, and IL-1beta enhance gastric epithelial migration, only IL-1beta acted in a TGF-alpha-dependent fashion.

  19. S1-Leitlinie zur UV-Phototherapie und Photochemotherapie.

    PubMed

    Herzinger, Thomas; Berneburg, Mark; Ghoreschi, Kamran; Gollnick, Harald; Hölzle, Erhard; Hönigsmann, Herbert; Lehmann, Percy; Peters, Thorsten; Röcken, Martin; Scharffetter-Kochanek, Karin; Schwarz, Thomas; Simon, Jan; Tanew, Adrian; Weichenthal, Michael

    2016-08-01

    Die heilsame Wirkung des Sonnenlichts war teilweise schon im Altertum bekannt und fand in der zweiten Hälfte des 19. Jahrhunderts wieder zunehmend Beachtung. Den Beginn der modernen Phototherapien markiert die Entwicklung einer Apparatur zur ultravioletten Bestrahlung der Hauttuberkulose durch Finnsen zu Beginn des zwanzigsten Jahrhunderts. Zur Therapie von Hauterkrankungen finden beinahe ausschließlich die spektralen Bereiche unterhalb des sichtbaren Lichtes (ultraviolett) Anwendung. Seit den 1970er Jahren stehen zunehmend leistungsfähige künstliche Strahlenquellen bereit für die Therapie mit UVB, UVA und die Kombination von UVA mit Photosensibilisatoren (Photochemotherapie). Hohe strukturelle und prozedurale Qualitätsstandards sind unabdingbare Voraussetzung für die Durchführung einer gleichermaßen wirkungsvollen wie auch sicheren Phototherapie. Die Leitlinie formuliert den aktuellen Konsens führender Experten auf dem Gebiet der Phototherapie in Bezug auf die Indikationen für die jeweiligen Therapieverfahren, deren Gegenanzeigen und Nebenwirkungen und insbesondere für die Wahl der korrekten Dosis zu Beginn und im Verlauf einer Therapie sowie das Management von Nebenwirkungen. PMID:27509439

  20. M/sub r/ 25,000 heparin-binding protein from guinea pig brain is a high molecular weight form of basic fibroblast growth factor

    SciTech Connect

    Moscatelli, D.; Joseph-Silverstein, J.; Manejias, R.; Rifkin, D.B.

    1987-08-01

    A M/sub r/ 25,000 form of basic fibroblast growth factor (bFGF) has been isolated from guinea pig grain along with the typical M/sub r/ 18,000 form. Both forms were purified to homogeneity by a combination of heparin-affinity chromatography and ion-exchange chromatography on an FPLC Mono S column. The M/sub r/ 25,000 form, like the M/sub r/ 18,000 form was not eluted from the heparin-affinity column with 0.95 M NaCl, but was eluted with 2 M NaCl. The M/sub r/ 25,000 guinea pig protein stimulated plasminogen activator production by cultured bovine capillary endothelial cells in a dose-dependent manner at concentration of 0.1-10 ngml, the same range that was effective for guinea pig and human M/sub r/ 18,000 bFGFs. The binding of human /sup 125/I-labeled bFGF to baby hamster kidney cells is inhibited equally by the M/sub r/ 25,000 guinea pig protein and the M/sub r/ 18,000 guinea pig and human bFGFs. Polyclonal antibodies raised against human bFGF recognize both the M/sub r/ 25,000 and 18,000 guinea pig proteins in an immunoblot analysis. In a radioimmunoassay, both the M/sub r/ 25,000 and M/sub r/ 18,000 guinea pig proteins compete equally well with iodinated human bFGF for binding to the anti-human bFGF antibodies. When treated with low concentrations of trypsin, the M/sub r/ 25,000 guinea pig bFGF was converted to a M/sub r/ 18,000 protein. These results show that the two molecules are closely related and suggest that the M/sub r/ 25,000 protein shares substantial homology with the M/sub r/ 18,000 bFGF

  1. Modulation of extracellular signal-related kinase, cyclin D1, glial fibrillary acidic protein, and vimentin expression in estradiol-pretreated astrocyte cultures treated with competence and progression growth factors.

    PubMed

    Bramanti, Vincenzo; Grasso, Sonia; Tibullo, Daniele; Giallongo, Cesarina; Raciti, Giuseppina; Viola, Maria; Avola, Roberto

    2015-09-01

    The present study seeks to elucidate the interactions between the "competence" growth factor basic fibroblast growth factor (bFGF) and/or estrogen 17β-estradiol and the "progression" growth factors epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and insulin (INS) on DNA labeling and also cyclin D1, extracellular signal-related kinase 1/2 (ERK1/2), glial fibrillary acidic protein (GFAP), and vimentin expression in astroglial cultures under different experimental conditions. Pretreatment for 24 hr with bFGF and subsequent exposure for 36 hr to estradiol (E2 ) and EGF, IGF-I, or INS stimulated DNA labeling in the last 12 hr, especially when the cultures were treated with progression growth factors. bFGF pretreatment and subsequent treatment with E2 for 36 hr stimulated DNA labeling. The 36-hr E2 treatment alone did not significantly decrease DNA labeling, but contemporary addition of E2 with two or three growth factors stimulated DNA labeling remarkably. When E2 was coadded with growth factors, a significantly increased DNA labeling was observed, demonstrating an astroglial synergistic mitogenic effect evoked by contemporary treatment with growth factors in the presence of estrogens. Cyclin D1 expression was markedly increased when astrocyte cultures were pretreated for 36 hr with E2 and subsequently treated with two or three competence and progression growth factors. A highly significant increase of ERK1/2 expression was observed after all the treatments (EGF, bFGF, INS, IGF-I alone or in combination with two or three growth factors). GFAP and vimentin expression was markedly increased when the cultures were treated with two or three growth factors. In conclusion, our data demonstrate estradiol-growth factor cross-talk during astroglial cell proliferation and differentiation in culture.

  2. Growth factor array fabrication using a color ink jet printer.

    PubMed

    Watanabe, Kohei; Miyazaki, Takeshi; Matsuda, Ryoichi

    2003-04-01

    We have developed a novel method for growth factor analysis using a commercial color ink jet printer to fabricate substrata patterned with growth factors. We prepared substrata with insulin printed in a simple pattern or containing multiple areas of varying quantities of printed insulin. When we cultured the mouse myoblast cell line, C2C12, on the insulin-patterned substrata, the cells were grown in the same pattern with the insulin-printed pattern. Cell culture with the latter substrata demonstrated that quantity control of insulin deposition by a color ink jet printer is possible. For further applications, we developed substrata with insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) spotted in 16 different areas in varying combinations and concentrations (growth factor array). With this growth factor array, C2C12 cells were cultured, and the onset of muscle cell differentiation was monitored for the expression of the myogenic regulator myogenin. The ratio of cells expressing myogenin varied with the doses of IGF-I and bFGF in the sections, demonstrating a feasibility of growth factor array fabrication by a color ink jet printer. Since a printer manipulates several colors, this method can be easily applied to multivariate analyses of growth factors and attachment factors affecting cell growth and differentiation. This method may provide a powerful tool for cell biology and tissue engineering, especially for stem cell research in investigating unknown conditions for differentiation.

  3. Stability and biological activity evaluations of PEGylated human basic fibroblast growth factor

    PubMed Central

    Hadadian, Shahin; Shamassebi, Dariush Norouzian; Mirzahoseini, Hasan; Shokrgozar, Mohamad Ali; Bouzari, Saeid; Sepahi, Mina

    2015-01-01

    Background: Human basic fibroblast growth factor (hBFGF) is a heparin-binding growth factor and stimulates the proliferation of a wide variety of cells and tissues causing survival properties and its stability and biological activity improvements have received much attention. Materials and Methods: In the present work, hBFGF produced by engineered Escherichia coli and purified by cation exchange and heparin affinity chromatography, was PEGylated under appropriate condition employing 10 kD polyethylene glycol. The PEGylated form was separated by size exclusion chromatography. Structural, biological activity, and stability evaluations were performed using Fourier transform infrared (FITR) spectroscopy, 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay and effect denaturing agent, respectively. Results: FITR spectroscopy revealed that both PEGylated and native forms had the same structures. MTT assay showed that PEGyalated form had a 30% reduced biological activity. Fluorescence spectrophotometry indicated that the PEGylated form denatured at higher concentrations of guanidine HCl (1.2 M) compared with native, which denatured at 0.8 M guanidine HCl. Conclusions: PEGylation of hBFGF makes it more stable against denaturing agent but reduces its bioactivity up to 30%. PMID:26605215

  4. Heparinized magnetic mesoporous silica nanoparticles as multifunctional growth factor delivery carriers

    NASA Astrophysics Data System (ADS)

    Wu, Qiang; Liu, Chaoqun; Fan, Luna; Shi, Jiahua; Liu, Zhiqiang; Li, Ruifang; Sun, Liwei

    2012-12-01

    Well-defined magnetic mesoporous silica nanoparticles (MMSNs) with a core/shell structure were prepared via a one pot synthesis. Sphere-like magnetite aggregates were obtained as cores of the final nanoparticles by assembly in the presence of polyvinyl pyrrolidone and cetyltrimethylammonium bromide. The nanoparticles have the property of superparamagnetism with a saturation magnetization value of 20.3 emu g-1. In addition, the combination of heparin and fluorescence-labeled MMSNs endows the resultant particles (denoted as MFMSNs-HP) with magnetism and fluorescence properties, excellent dispersity in the buffer solutions and cell culture media, anticoagulant activity in the blood stream, and the controlled release of basic fibroblast growth factor (bFGF). Furthermore, the bFGF cell viability assays indicate that MFMSNs-HP has nearly no toxicity to human umbilical vein endothelial cells (HUVEC) up to a concentration of 200 μg ml-1, and the proliferation activity of bFGF incorporated into MFMSNs-HP could be retained for at least 6 days. All of these suggest that MFMSNs-HP may serve as a multifunctional carrier for the delivery of growth factors.

  5. Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors conjugated iron oxide nanoparticles for tissue engineering

    PubMed Central

    Ziv-Polat, Ofra; Skaat, Hadas; Shahar, Abraham; Margel, Shlomo

    2012-01-01

    Novel tissue-engineered magnetic fibrin hydrogel scaffolds were prepared by the interaction of thrombin-conjugated iron oxide magnetic nanoparticles with fibrinogen. In addition, stabilization of basal fibroblast growth factor (bFGF) was achieved by the covalent and physical conjugation of the growth factor to the magnetic nanoparticles. Adult nasal olfactory mucosa (NOM) cells were seeded in the transparent fibrin scaffolds in the absence or presence of the free or conjugated bFGF-iron oxide nanoparticles. The conjugated bFGF enhanced significantly the growth and differentiation of the NOM cells in the fibrin scaffolds, compared to the same or even five times higher concentration of the free bFGF. In the presence of the bFGF-conjugated magnetic nanoparticles, the cultured NOM cells proliferated and formed a three-dimensional interconnected network composed mainly of tapered bipolar cells. The magnetic properties of these matrices are due to the integration of the thrombin- and bFGF-conjugated magnetic nanoparticles within the scaffolds. The magnetic properties of these scaffolds may be used in future work for various applications, such as magnetic resonance visualization of the scaffolds after implantation and reloading the scaffolds via magnetic forces with bioactive agents, eg, growth factors bound to the iron oxide magnetic nanoparticles. PMID:22419873

  6. Diagnostic and prognostic value of serum nitric oxide, tumor necrosis factor-alpha, basic fibroblast growth factor and copper as angiogenic markers in premenopausal breast cancer patients: a case-control study.

    PubMed

    Hewala, T I; Abd El-Moneim, N A; Ebied, S Abd El-Moneim; Sheta, M I; Soliman, K; Abu-Elenean, A

    2010-01-01

    Many studies demonstrate that increased microvessel density (MVD) surrounding primary tumour is associated with decreased overall survival in patients with breast cancer. This study compares the diagnostic and prognostic values of the angiogenic serum factors nitric oxide (NO), tumour necrosis factor-alpha (TNFalpha), basic fibroblast growth factor (bFGF) and copper with those of serum CA15-3 as the standard tumour marker in breast cancer patients. Microvessel density was estimated in CD31-immunostained sections from breast cancer patients. Before surgery, NO, TNFalpha, bFGF, copper and CA 15-3 were measured in serum samples from 30 premenopausal breast cancer patients in comparison with 15 healthy controls. The diagnostic values of the assayed parameters were compared using receiver operating characteristic (ROC) curve analysis. Univariate survival analysis of patients was assessed using the Kaplan-Meier method. Breast cancer tissues showed higher MVD than did normal breast tissues adjacent to the tumour (P = 0.008). Before surgery, tumour MVD correlated significantly with serum NO, TNFalpha, bFGF and copper (r = 0.458, P = .011; r = 0.379, P = .039; r = 0.513, P = .004 and r = 0.613, P = 0.000, respectively). Serum NO, TNFalpha, bFGF, copper and CA 15-3 levels in patients were significantly elevated compared with controls (P = 0.011, P = 0.004, P = 0.039, P = 0.000 and P = 0.001, respectively). Kaplan-Meier analysis revealed that patients with elevated serum TNFalpha, CA 15-3 and copper (P = 0.035, P = 0.040, P = 0.0339, respectively) had an overall survival significantly shorter than those who had lower levels of these parameters. These data suggest that serum TNFalpha, CA 15-3 and copper are useful predictive markers for overall survival in premenopausal breast cancer patients.

  7. Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-β1 genes in a rat model of lung ischemia/reperfusion

    PubMed Central

    Şimşek, Hasan; Demiryürek, Şeniz; Demir, Tuncer; Atabay, Hüsne Didem; Çeribasi, Ali Osman; Bayraktar, Recep; Kaplan, Davut Sinan; Öztuzcu, Serdar; Cengiz, Beyhan

    2016-01-01

    Objective(s): Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue’s life. Materials and Methods: It is investigated expressions of Smad1, Bmp-2, Bcl-XL, b-FGF, Caspase-3, TGF-β1, PDGFR-α genes for molecular changes in lung tissues, after I/R is formed, in this study. For this, we included 40 Wistar albino rats to this study and divided 4 groups (n=10). The Groups were determined as Control (C), Group 1= 1 hr ischemia (I), Group 2= 1 hr ischemia+2 hr reperfusion (I+2R), Group 3= 1 hr ischemia+4 hr reperfusion (I+4R). Besides, molecular analysis and histopathologic examinations of tissues were performed, and the results were evaluated by normalization and statistics analysis. Results: We have found a significant increase in expression of Bcl-XL (P=0.046) and Caspase-3 (P=0.026) genes of group 1, and it was not monitored any significant difference in Group 2 and Group 3. In all groups, the changes in b-FGF (P=0.087), Bmp-2 (P=0.457), TGF-β1 (P=0.201) and PDGFR-α (P=0.116) were not significant compared to control group. We did not see any mRNA expression of Smad1 gene in all groups include control. Conclusion: These findings suggest that I/R injury may trigger apoptotic mechanism in lung. PMID:27081467

  8. Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity

    PubMed Central

    1990-01-01

    Cultured bovine capillary endothelial (BCE) cells synthesize heparan sulfate proteoglycans (HSPG), which are both secreted into the culture medium and deposited in the cell layer. The nonsoluble HSPGs can be isolated as two predominant species: a larger 800-kD HSPG, which is recovered from preparations of extracellular matrix, and a 250-kD HSPG, which is solubilized by nonionic detergent extraction of the cells. Both HSPG species bind bFGF. 125I-bFGF bound to BCE cell cultures is readily released by either heparinase or plasmin. When released by plasmin, the growth factor is recovered from the incubation medium as a complex with the partly degraded high molecular mass HSPG. Endogenous bFGF activity is released by a proteolytic treatment of cultured BCE cells. The bFGF-binding HSPGs are also released when cultures are incubated with the inactive proenzyme plasminogen. Under such experimental conditions, the release of the extracellular proteoglycans can be enhanced by treating the cells either with bFGF, which increases the plasminogen activating activity expressed by the cells, or decreased by treating the cells with transforming growth factor beta, which decreases the plasminogen activating activity of the cells. Specific immune antibodies raised against bovine urokinase also block the release of HSPG from BCE cell cultures. We propose that this plasminogen activator-mediated proteolysis provides a mechanism for the release of biologically active bFGF-HSPG complexes from the extracellular matrix and that bFGF release can be regulated by the balance between factors affecting the pericellular proteolytic activity. PMID:2137829

  9. Blockade of Ca2+-activated K+ channels inhibits proliferation of human endothelial cells induced by basic fibroblast growth factor.

    PubMed

    Wiecha, J; Münz, B; Wu, Y; Noll, T; Tillmanns, H; Waldecker, B

    1998-01-01

    Basic fibroblast growth factor (bFGF) exerts angiogenic and mitogenic properties in human tissue. Since changes in ion currents modulate essential Ca2+-dependent intracellular pathways in endothelial cells, we have investigated a possible contribution of Ca2+-activated K+ channels (BKCa) on bFGF-induced endothelial cell proliferation. The patch-clamp technique was used to identify BKCa and to study their modulation by bFGF in cultured endothelial cells of human umbilical cord veins (HUVEC). Cell counts of HUVEC were carried out on different days to analyze bFGF-induced cell proliferation and its influence by the specific BKCa blocker iberiotoxin (IBX). Using single-channel recordings, we found characteristic BKCa with a single-channel slope conductance of 170.3 +/- 2.1 pS (n = 7), half-maximal activation at internal pCa = 5.7 (n = 5; test potential: 80 mV), and dose-dependent block by IBX (25-100 nmol/l). In cell-attached patches bFGF (50 ng/ml) caused a significant increase in the open-state probability (NPo) after 6 min at test potentials of 80 and 100 mV (n = 28; p < 0.001), respectively, which lasted up to 30 min. After preincubation with pertussis toxin (100 ng/ml; 4 h) bFGF superfusion did not cause a significant increase in BKCa activity until 25 min had passed (n = 20; p < 0.01). Addition of 100 nmol/l IBX to the pipette solution caused a total block of BKCa within 2 min in cell-attached patches, whereas bFGF (50 ng/ml) was not able to activate BKCa. When incubated with IBX (25-100 nmol/l) every 2 days, bFGF-induced proliferation of HUVEC was significantly decreased by 50 (-41%) and 100 nmol/l (-50%) IBX (n = 5; p < 0.001) after 7 days. We conclude that activation of BKCa by bFGF may play an important role in bFGF-induced proliferation of human endothelial cells and thus might be important in the process of angiogenesis and vascular remodelling.

  10. Basic fibroblast growth factor promotes melanocyte migration via increased expression of p125(FAK) on melanocytes.

    PubMed

    Wu, Ching-Shuang; Lan, Cheng-Che E; Chiou, Min-Hsi; Yu, Hsin-Su

    2006-01-01

    Vitiligo is an acquired pigmentary disorder characterized by depigmentation of skin and hair. Melanocyte migration is an important event in re-pigmentation of vitiligo. We have demonstrated that narrow-band ultraviolet B (UVB) irradiation stimulated cultured keratinocytes to release a significant amount of basic fibroblast growth factor (bFGF). Furthermore, narrow-band UVB enhanced migration of melanocytes via increased expression of phosphorylated focal adhesion kinase (p125(FAK)) on melanocytes. The aim of this study was to investigate the effect of recombinant human bFGF (rhbFGF) on melanocyte migration. The relationship between the expression of p125(FAK) and melanocyte migration induced by rhbFGF was also studied. Our results demonstrated that rhbFGF significantly enhanced migration of melanocytes and p125(FAK) expression on melanocytes. Herbimycin A, a potent p125(FAK) inhibitor, effectively abolished rhbFGF-induced melanocyte migration. The combined results indicated that p125(FAK) plays an important role in the signal transduction pathway of melanocyte migration induced by bFGF.

  11. Generation and characterization of leukemia inhibitory factor-dependent equine induced pluripotent stem cells from adult dermal fibroblasts.

    PubMed

    Whitworth, Deanne J; Ovchinnikov, Dmitry A; Sun, Jane; Fortuna, Patrick R J; Wolvetang, Ernst J

    2014-07-01

    In this study we have reprogrammed dermal fibroblasts from an adult female horse into equine induced pluripotent stem cells (equiPSCs). These equiPSCs are dependent only on leukemia inhibitory factor (LIF), placing them in striking contrast to previously derived equiPSCs that have been shown to be co-dependent on both LIF and basic fibroblast growth factor (bFGF). These equiPSCs have a normal karyotype and have been maintained beyond 60 passages. They possess alkaline phosphatase activity and express eqNANOG, eqOCT4, and eqTERT mRNA. Immunocytochemistry confirmed that they produce NANOG, REX1, SSEA4, TRA1-60, and TRA1-81. While our equiPSCs are LIF dependent, bFGF co-stimulates their proliferation via the PI3K/AKT pathway. EquiPSCs lack expression of eqXIST and immunostaining for H3K27me3, suggesting that during reprogramming the inactive X chromosome has likely been reactivated to generate cells that have two active X chromosomes. EquiPSCs form embryoid bodies and in vitro teratomas that contain derivatives of all three germ layers. These LIF-dependent equiPSCs likely reflect a more naive state of pluripotency than equiPSCs that are co-dependent on both LIF and bFGF and so provide a novel resource for understanding pluripotency in the horse.

  12. Growth Factors Cross-Linked to Collagen Microcarriers Promote Expansion and Chondrogenic Differentiation of Human Mesenchymal Stem Cells.

    PubMed

    Bertolo, Alessandro; Arcolino, Fanny; Capossela, Simona; Taddei, Anna Rita; Baur, Martin; Pötzel, Tobias; Stoyanov, Jivko

    2015-10-01

    Tissue engineering is a field in progressive expansion and requires constant updates in methods and devices. One of the central fields is the development of biocompatible, biodegradable, and injectable scaffolds, such as collagen microcarriers. To enhance cell attachment and produce a cost-effective cell culture solution with local stimulation of cells, basic fibroblast growth factor (bFGF) or transforming growth factor-β1 (TGF-β1) was covalently immobilized on microcarriers either by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) or riboflavin/UV (RB/UV) light-mediated cross-linking. Collagen microcarriers cross-linked with bFGF or TGF-β1 were used for expansion and chondrogenic differentiation of human mesenchymal stem cells (MSCs). Evaluation methods included cell viability test, chondrogenic marker expression (aggrecan and collagen type I and type II), histological detection of proteoglycans, and immunohistochemical analysis. Cross-linking strengthened the collagen structure of the microcarriers and reduced collagenase-mediated degradation. MSCs effectively proliferated on microcarriers cross-linked with bFGF, especially by EDC/NHS cross-linking. Chondrogenic differentiation of MSCs was induced by TGF-β1 cross-linked on microcarriers, promoting gene expression and protein accumulation of aggrecan and collagen type I and type II, as well as proteoglycans. Cross-linking by RB/UV enhanced chondrogenesis more than any other group. In addition, cross-linking reduced scaffold shrinkage exerted by MSCs during chondrogenesis, a desirable feature for microcarriers if used as tissue defect filler. In conclusion, cross-linking of bFGF or TGF-β1 to collagen microcarriers supported in vitro proliferation and chondrogenesis, respectively. If translated in vivo and in clinical practice, such approach might lead a step closer to development of a cost-effective and locally acting device for cell-based therapy. PMID:26222829

  13. Effect of Control-released Basic Fibroblast Growth Factor Incorporated in β-Tricalcium Phosphate for Murine Cranial Model

    PubMed Central

    Shimizu, Azusa; Tajima, Satoshi; Tobita, Morikuni; Tanaka, Rica; Tabata, Yasuhiko

    2014-01-01

    Background: β-Tricalcium phosphate (β-TCP) is used clinically as a bone substitute, but complete osteoinduction is slow. Basic fibroblast growth factor (bFGF) is important in bone regeneration, but the biological effects are very limited because of the short half-life of the free form. Incorporation in gelatin allows slow release of growth factors during degradation. The present study evaluated whether control-released bFGF incorporated in β-TCP can promote bone regeneration in a murine cranial defect model. Methods: Bilateral cranial defects of 4 mm in diameter were made in 10-week-old male Sprague-Dawley rats treated as follows: group 1, 20 μl saline as control; group 2, β-TCP disk in 20 μl saline; group 3, β-TCP disk in 50 μg bFGF solution; and group 4, β-TCP disk in 50 μg bFGF-containing gelatin hydrogel (n = 6 each). Histological and imaging analyses were performed at 1, 2, and 4 weeks after surgery. Results: The computed tomography value was lower in groups 3 and 4, whereas the rate of osteogenesis was higher histologically in group 4 than in the other groups. The appearance of tartrate-resistant acid phosphate–positive cells and osteocalcin-positive cells and disappearance of osteopontin-positive cells occurred earlier in group 4 than in the other groups. Conclusions: These findings suggest that control-released bFGF incorporated in β-TCP can accelerate bone regeneration in the murine cranial defect model and may be promising for the clinical treatment of cranial defects. PMID:25289319

  14. Front End Schaltung zur Online Auswertung von EKG-Signalen

    NASA Astrophysics Data System (ADS)

    Ayari, E.; Tielert, R.

    2007-06-01

    Ein mobiles EKG-System zur Online Auswertung von EKG-Signalen wird dargestellt. Die Auswertung beruht auf ein energiesparendes Verfahren, das den Vorteil einer zulässigen Unterabtastung des Signals bietet und eine Interaktion zwischen der messenden Elektronik und dem funkgebundenen Auswertungsrechner ermöglicht. Diese Interaktion besteht darin, sowohl die Front End Schaltung im EKG-Sensor als auch den im ATmega8L eingebetteten A/D-Wandler vom Auswertungsrechner zu steuern und den Datenbedarf des Rechners dynamisch an die Erfordernisse des Analyseprogramms anzupassen. Das entwickelte EKG-System liefert erfolgreiche Charakterisierungen erfasster Elektrokardiogramme. A mobile ecg-system for an online analysis of electrocardiogram signals is presented. The analysis is based on an energy-saving procedure, which offers the advantage of an acceptable undersampling of the signal, and which allows an interaction between the measuring electronic and the radio-bound analysis-computer. In this interaction both the front-end circuit in the ecg-sensor and the A/D converter, which is embedded in the ATmega8L, are steered by the analysis computer. The data requirement of the computer is also dynamically adapted to the requirements of the analysis-program. The developed ecg-system supplies successful characterisations of measured electrocardiograms.

  15. Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes.

    PubMed Central

    Imokawa, G; Yada, Y; Morisaki, N; Kimura, M

    1998-01-01

    To clarify the paracrine linkage between human fibroblasts and melanocytes in cutaneous pigmentation, we studied the effects of human fibroblast-derived factors on the proliferation of human melanocytes. In medium conditioned for 4 days with human fibroblast culture, factors were produced that markedly stimulated DNA synthesis of human melanocytes. The stimulatory effect was higher in medium conditioned with fibroblasts from aged skin than in medium conditioned with fibroblasts from young skin, and was interrupted by inhibitors of tyrosine kinase, such as tyrphostin, genistein and herbimycin, but not by inhibitors of protein kinases C and A, such as H-7 and phloretin. The conditioned medium was also capable of activating mitogen-activated protein kinase of human melanocytes, with old fibroblasts being more effective than young ones. Analysis of factors released into the conditioned medium revealed that levels of hepatocyte growth factor (HGF) and stem cell factor (SCF) were increased in old-fibroblast-conditioned medium compared with young-fibroblast-conditioned medium. In contrast, levels of basic fibroblast growth factor (bFGF) were similar in both media. When the conditioned medium was treated with HGF antibody with or without SCF antibody, the increase in DNA synthesis by human melanocytes was decreased to 20% of the elevated level, whereas antibodies to bFGF had no effect. Analysis of the medium conditioned for 4 days after cytokine application demonstrated that, of the cytokines tested, interleukin 1alpha and tumour necrosis factor alpha are highly effective in stimulating HGF secretion by old fibroblasts. HGF and SCF, but not bFGF, were markedly increased in culture medium in the presence of IL-1alpha, and this stimulatory effect was confined to young human fibroblasts. These findings suggest that SCF and HGF derived from human fibroblasts may play a part in regulating cutaneous pigmentation during inflammation and aging. PMID:9494091

  16. The constitutive level of vascular endothelial growth factor (VEGF) is more important than hypoxia-induced VEGF up-regulation in the angiogenesis of human melanoma xenografts

    PubMed Central

    Danielsen, T; Rofstad, E K

    2000-01-01

    Angiogenesis of tumours might develop as a result of environmental conditions, such as hypoxia, and/or as a result of genetic alterations specific for tumour cells. The relative contributions of these mechanisms were investigated by comparing the in vivo expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to the hypoxic fraction, the angiogenic potential and the vascular density of four human melanoma lines (A-07, D-12, R-18, U-25) grown intradermally in Balb/c nu/nu mice. VEGF expression, bFGF expression and expression of pimonidazole, a marker of hypoxic cells, were investigated by immunohistochemistry. An association between high VEGF and bFGF expression and high angiogenic potential was detected, suggesting an important role for VEGF/bFGF in the angiogenesis of melanomas. High VEGF/bFGF expression was also related to low hypoxic fraction and high vascular density. Thus, the constitutive, genetically determined level of VEGF was probably more important than hypoxia-induced upregulation in the angiogenesis of the melanoma xenografts. © 2000 Cancer Research Campaign PMID:10789719

  17. Basic fibroblast growth factor induces matrix metalloproteinase-13 via ERK MAP kinase-altered phosphorylation and sumoylation of Elk-1 in human adult articular chondrocytes

    PubMed Central

    Im, Hee-Jeong; Sharrocks, Andrew D; Lin, Xia; Yan, Dongyao; Kim, Jaesung; van Wijnen, Andre J; Hipskind, Robert A

    2009-01-01

    Degradation of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) and release of basic fibroblast growth factor (bFGF) are principal aspects of the pathology of osteoarthritis (OA). ECM disruption leads to bFGF release, which activates the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway and its downstream target the Ets-like transcription factor Elk-1. Previously we demonstrated that the bFGF-ERK-Elk-1 signaling axis is responsible for the potent induction of MMP-13 in human primary articular chondrocytes. Here we report that, in addition to phosphorylation of Elk-1, dynamic posttranslational modification of Elk-1 by small ubiquitin-related modifier (SUMO) serves as an important mechanism through which MMP-13 gene expression is regulated. We show that bFGF activates Elk-1 mainly through the ERK pathway and that increased phosphorylation of Elk-1 is accompanied by decreased conjugation of SUMO to Elk-1. Reporter gene assays reveal that phosphorylation renders Elk-1 competent for induction of MMP-13 gene transcription, while sumoylation has the opposite effect. Furthermore, we demonstrate that the SUMO-conjugase Ubc9 acts as a key mediator for Elk-1 sumoylation. Taken together, our results suggest that sumoylation antagonizes the phosphorylation-dependent transactivation capacity of Elk-1. This attenuates transcription of its downstream target gene MMP-13 to maintain the integrity of cartilage ECM homeostasis.

  18. Effect of intestinal ischemia-reperfusion on expressions of endogenous basic fibroblast growth factor and transforming growth factor betain lung and its relation with lung repair.

    PubMed

    Fu, Xiao-Bing; Yang, Yin-Hui; Sun, Tong-Zhu; Gu, Xiao-Man; Jiang, Li-Xian; Sun, Xiao-Qing; Sheng, Zhi-Yong

    2000-06-01

    AIM:To study the changes of endogenous transforming growth factor beta(TGFbeta) and basic fibroblast growth factor (bFGF) in lung following intestinal ischemia and reperfusion injury and their effects on lung injury and repair.METHODS:Sixty Wistar rats were divided into five groups, which underwent sham-operation, ischemia (45 minutes), and reperfusion (6, 24 and 48 hours, respectively) after ischemia (45 minutes). Immunohistochemical method was used to observe the localization and amounts of both growth factors.RESULTS:Positive signals of both growth factors could be found in normal lung, mainly in alveolar cells and endothelial cells of vein. After ischemia and reperfusion insult, expressions of both growth factors were increased and their amounts at 6 hours were larger than those of normal control or of 24 and 48 hours after insult.CONCLUSION:The endogenous bFGF and TGF beta expression appears to be upregulated in the lung following intestinal ischemia and reperfusion, suggesting that both growth factors may be involved in the process of lung injury and repair. PMID:11819596

  19. Interleukin-8 and vascular endothelial growth factor mRNA and protein levels are down-regulated in ovarian carcinoma cells in serous effusions.

    PubMed

    Davidson, Ben; Reich, Reuven; Kopolovic, Juri; Berner, Aasmund; Nesland, Jahn M; Kristensen, Gunnar B; Tropé, Claes G; Bryne, Magne; Risberg, Bjørn; van de Putte, Gregg; Goldberg, Iris

    2002-01-01

    Angiogenic factors are involved in tumor growth and spread. The aim of this study was to evaluate the expression of angiogenesis-related genes in malignant serous effusions of patients with advanced-stage (FIGO stage III and IV) ovarian carcinoma. In addition, to compare the results for carcinoma cells in effusions with corresponding primary tumors and metastatic lesions, and analyze their prognostic role. Sections from 66 effusions and 90 primary and metastatic lesions from 62 ovarian and primary peritoneal carcinoma patients, were evaluated for expression of basic fibroblast factor (bFGF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) using mRNA in situ hybridization (ISH). Protein expression was evaluated in a subset of specimens using immunohistochemistry (IHC). ISH results were correlated with clinical parameters. In both effusions and solid tumors, bFGF mRNA was the most commonly expressed factor (93% of effusions and 95% of solid tumors) followed by IL-8, while VEGF was expressed in a minority of the specimens (P < 0.001 for bFGF vs. IL-8 and VEGF). In solid tumors, angiogenic mRNA expression was seen in both tumor and stromal cells in the majority of positive cases. ISH results did not differ in primary and metastatic tumors. However, carcinoma cells in effusions showed down-regulated expression of VEGF, when compared with both primary tumors (P = 0.029) and metastases (P = 0.015). IL-8 showed a similar down-regulation in effusions, when compared with metastases (P = 0.005). IHC showed excellent agreement with mRNA findings on protein level. In the study of clinico-pathologic parameters, IL-8 mRNA expression in effusions was associated with higher tumor grade (P = 0.044). Angiogenic gene expression in effusions showed no correlation with patient age, previous treatment, residual tumor size, FIGO stage or disease outcome in survival analysis (P > 0.05). Peritoneal and pleural effusions showed similar expression patterns. In conclusion

  20. Corynebacterium glutamicum Zur acts as a zinc-sensing transcriptional repressor of both zinc-inducible and zinc-repressible genes involved in zinc homeostasis.

    PubMed

    Teramoto, Haruhiko; Inui, Masayuki; Yukawa, Hideaki

    2012-12-01

    Zur is a zinc-dependent transcriptional repressor of zinc uptake systems in bacteria. In the present study, we examined the role of Corynebacterium glutamicum Zur in the zinc-inducible expression of two genes: one encoding a cation diffusion facilitator (zrf) and the other a metal-translocating P-type ATPase (zra). Both genes were shown to be involved in zinc resistance. Disruption of the zur gene encoding Zur resulted in constitutive expression of zrf and zra mRNAs. An electrophoretic mobility shift assay revealed that the Zur protein binds to the zrf and zra promoters, for which the in vivo activities were up-regulated in response to excess zinc. Interestingly, the in vitro DNA binding activity of Zur was inhibited by zinc, in contrast to its zinc-dependent binding to the promoter region of a zinc-repressible ABC transporter gene znuB2. A 21-bp motif found in the Zur binding site overlaps the putative -35 region of both the zrf and zra promoters. This new motif is a 10-1-10 direct repeat sequence distinct from the 10-1-10 inverted repeat sequence of a previously identified Zur box for zinc-dependent binding. Nevertheless, their 10-bp elements share some sequence similarities. Overexpression of zur in the zur deletion mutant background, as well as deletion of zur in the zrf and zra double deletion mutant background, resulted in decreased resistance to zinc. These results suggest that the direct negative control of both zinc uptake and export systems by Zur is central to C. glutamicum zinc homeostasis and is effected in distinct ways. PMID:23061624

  1. The catalytic domain of endogenous urokinase-type plasminogen activator is required for the mitogenic activity of platelet-derived and basic fibroblast growth factors in human vascular smooth muscle cells.

    PubMed

    Padró, Teresa; Mesters, Rolf M; Dankbar, Berno; Hintelmann, Heike; Bieker, Ralf; Kiehl, Michael; Berdel, Wolfgang E; Kienast, Joachim

    2002-05-01

    Emerging data suggest that urokinase-type plasminogen activator (UPA), beyond its role in pericellular proteolysis, may also act as a mitogen. We investigated the function of endogenous UPA in mediating the mitogenic effects of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) on human vascular smooth muscle cells (SMC). Growth-arrested SMC constitutively expressed UPA, but UPA expression and secretion increased several times upon stimulation with either PDGF or bFGF. Inhibition of endogenous UPA with a polyclonal antibody significantly reduced DNA synthesis and proliferation of PDGF or bFGF stimulated SMC, this effect already being evident when the cells entered S-phase. The proliferative activity of endogenous UPA was dependent on a functional catalytic domain as demonstrated by inhibition experiments with a specific monoclonal antibody (394OA) and p-aminobenzamidine, respectively. In contrast, neither plasmin generation nor binding of UPA to its receptor (CD87) were required for UPA-mediated mitogenic effects. The results demonstrate that endogenous UPA is not only overexpressed in SMC upon stimulation with PDGF/bFGF, but also mediates the mitogenic activity of the growth factors in a catalytic-domain-dependent manner. Specific inhibition of this UPA domain may represent an attractive target for pharmacological interventions in atherogenesis and restenosis after angioplasty. PMID:11956327

  2. Bacillus licheniformis Contains Two More PerR-Like Proteins in Addition to PerR, Fur, and Zur Orthologues

    PubMed Central

    Ju, Shin-Yeong; Yang, Yoon-Mo; Ryu, Su-Hyun; Kwon, Yumi; Won, Young-Bin; Lee, Yeh-Eun; Youn, Hwan; Lee, Jin-Won

    2016-01-01

    The ferric uptake regulator (Fur) family proteins include sensors of Fe (Fur), Zn (Zur), and peroxide (PerR). Among Fur family proteins, Fur and Zur are ubiquitous in most prokaryotic organisms, whereas PerR exists mainly in Gram positive bacteria as a functional homologue of OxyR. Gram positive bacteria such as Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus encode three Fur family proteins: Fur, Zur, and PerR. In this study, we identified five Fur family proteins from B. licheniformis: two novel PerR-like proteins (BL00690 and BL00950) in addition to Fur (BL05249), Zur (BL03703), and PerR (BL00075) homologues. Our data indicate that all of the five B. licheniformis Fur homologues contain a structural Zn2+ site composed of four cysteine residues like many other Fur family proteins. Furthermore, we provide evidence that the PerR-like proteins (BL00690 and BL00950) as well as PerRBL (BL00075), but not FurBL (BL05249) and ZurBL (BL03703), can sense H2O2 by histidine oxidation with different sensitivity. We also show that PerR2 (BL00690) has a PerR-like repressor activity for PerR-regulated genes in vivo. Taken together, our results suggest that B. licheniformis contains three PerR subfamily proteins which can sense H2O2 by histidine oxidation not by cysteine oxidation, in addition to Fur and Zur. PMID:27176811

  3. Bacillus licheniformis Contains Two More PerR-Like Proteins in Addition to PerR, Fur, and Zur Orthologues.

    PubMed

    Kim, Jung-Hoon; Ji, Chang-Jun; Ju, Shin-Yeong; Yang, Yoon-Mo; Ryu, Su-Hyun; Kwon, Yumi; Won, Young-Bin; Lee, Yeh-Eun; Youn, Hwan; Lee, Jin-Won

    2016-01-01

    The ferric uptake regulator (Fur) family proteins include sensors of Fe (Fur), Zn (Zur), and peroxide (PerR). Among Fur family proteins, Fur and Zur are ubiquitous in most prokaryotic organisms, whereas PerR exists mainly in Gram positive bacteria as a functional homologue of OxyR. Gram positive bacteria such as Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus encode three Fur family proteins: Fur, Zur, and PerR. In this study, we identified five Fur family proteins from B. licheniformis: two novel PerR-like proteins (BL00690 and BL00950) in addition to Fur (BL05249), Zur (BL03703), and PerR (BL00075) homologues. Our data indicate that all of the five B. licheniformis Fur homologues contain a structural Zn2+ site composed of four cysteine residues like many other Fur family proteins. Furthermore, we provide evidence that the PerR-like proteins (BL00690 and BL00950) as well as PerRBL (BL00075), but not FurBL (BL05249) and ZurBL (BL03703), can sense H2O2 by histidine oxidation with different sensitivity. We also show that PerR2 (BL00690) has a PerR-like repressor activity for PerR-regulated genes in vivo. Taken together, our results suggest that B. licheniformis contains three PerR subfamily proteins which can sense H2O2 by histidine oxidation not by cysteine oxidation, in addition to Fur and Zur.

  4. Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium.

    PubMed Central

    Malek, A M; Gibbons, G H; Dzau, V J; Izumo, S

    1993-01-01

    Fluid shear stress has been shown to be an important regulator of vascular structure and function through its effect on the endothelial cell. We have explored the effect of shear stress on the expression of the heparin-binding growth factors platelet-derived growth factor B chain (PDGF-B) and basic fibroblast growth factor (bFGF) in bovine aortic endothelial cells using a purpose-built cone-plate viscometer. Using morphometric analysis, we have mimicked the endothelial cell shape changes encountered in vivo in response to shear stress and correlated these with changes in gene expression. Steady laminar shear stress of 15 and 36 dyn/cm2 both resulted in endothelial cell shape change, but the higher shear stress induced greater and more uniform alignment in the direction of flow and nuclear protrusion after 24 h. Steady laminar shear stress of both 15 and 36 dyn/cm2 induced a significant 3.9- and 4.2-fold decrease, respectively, in PDGF-B mRNA at 9 h. In contrast, steady laminar shear of 15 dyn/cm2 induced a mild and transient 1.5-fold increase in bFGF mRNA while shear of 36 dyn/cm2 induced a significant 4.8-fold increase at 6 h of shear which remained at 2.9-fold at 9 h. Pulsatile and turbulent shear stress showed the same effect as steady laminar shear stress (all at 15 dyn/cm2 time-average magnitude) on PDGF-B and bFGF mRNA content. Cyclic stretch (20% strain, 20/min) of cells grown on silicone substrate did not significantly affect either PDGF-B or bFGF mRNA levels. These results suggest that expression of each peptide growth factor gene is differentially regulated by fluid shear stress in the vascular endothelial cell. These results may have implications on vascular structure and function in response to hemodynamic forces and present a model for the study of transduction of mechanical stimuli into altered gene expression. Images PMID:8408655

  5. Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways.

    PubMed

    Shi, Hongxue; Lin, Beibei; Huang, Yan; Wu, Jiang; Zhang, Hongyu; Lin, Cai; Wang, Zhouguang; Zhu, Jingjing; Zhao, Yingzhen; Fu, Xiaobing; Lou, Zhencai; Li, Xiaokun; Xiao, Jian

    2016-09-01

    Vitiligo is a depigmentation disorder characterized by loss of functional melanocytes of the skin epidermis. The pathogenesis of vitiligo remains elusive. The purpose of this study is to investigate the effects of basic fibroblast growth factor (bFGF) on melanocyte migration, including its biochemical mechanism using transwell assay in vitro. We found that melanocyte treated with bFGF showed a significant increase in migration and cytoskeletal rearrangement. These changes were associated with increased activation of PI3K/Akt, Rac1, FAK, JNK, and ERK. Likewise, reduction of PI3K/Akt, Rac1, FAK, JNK, and ERK activity using selective inhibitors or siRNA was associated with impediment of bFGF-induced melanocyte migration. In addition, activity of Rac1, FAK, and JNK was reduced in cells in which PI3K/Akt was inhibited, activity of FAK and JNK was reduced in cells in which the Rac1 was inhibited, and activity of JNK was reduced in cells in which the FAK was inhibited. Collectively, these data demonstrate that bFGF facilitated melanocyte migration via PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways. © 2016 IUBMB Life, 68(9):735-747, 2016. PMID:27350596

  6. Evaluation of Polycaprolactone Scaffold with Basic Fibroblast Growth Factor and Fibroblasts in an Athymic Rat Model for Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben; Petrigliano, Frank A.; McAllister, David R.

    2015-01-01

    Anterior cruciate ligament (ACL) rupture is a common ligamentous injury often necessitating surgery. Current surgical treatment options include ligament reconstruction with autograft or allograft, which have their inherent limitations. Thus, there is interest in a tissue-engineered substitute for use in ACL regeneration. However, there have been relatively few in vivo studies to date. In this study, an athymic rat model of ACL reconstruction was used to evaluate electrospun polycaprolactone (PCL) grafts, with and without the addition of basic fibroblast growth factor (bFGF) and human foreskin fibroblasts. We examined the regenerative potential of tissue-engineered ACL grafts using histology, immunohistochemistry, and mechanical testing up to 16 weeks postoperatively. Histology showed infiltration of the grafts with cells, and immunohistochemistry demonstrated aligned collagen deposition with minimal inflammatory reaction. Mechanical testing of the grafts demonstrated significantly higher mechanical properties than immediately postimplantation. Acellular grafts loaded with bFGF achieved 58.8% of the stiffness and 40.7% of the peak load of healthy native ACL. Grafts without bFGF achieved 31.3% of the stiffness and 28.2% of the peak load of healthy native ACL. In this in vivo rodent model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regenerative potential of our electrospun PCL ligament graft. PMID:25744933

  7. Evaluation of polycaprolactone scaffold with basic fibroblast growth factor and fibroblasts in an athymic rat model for anterior cruciate ligament reconstruction.

    PubMed

    Leong, Natalie Luanne; Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben; Petrigliano, Frank A; McAllister, David R

    2015-06-01

    Anterior cruciate ligament (ACL) rupture is a common ligamentous injury often necessitating surgery. Current surgical treatment options include ligament reconstruction with autograft or allograft, which have their inherent limitations. Thus, there is interest in a tissue-engineered substitute for use in ACL regeneration. However, there have been relatively few in vivo studies to date. In this study, an athymic rat model of ACL reconstruction was used to evaluate electrospun polycaprolactone (PCL) grafts, with and without the addition of basic fibroblast growth factor (bFGF) and human foreskin fibroblasts. We examined the regenerative potential of tissue-engineered ACL grafts using histology, immunohistochemistry, and mechanical testing up to 16 weeks postoperatively. Histology showed infiltration of the grafts with cells, and immunohistochemistry demonstrated aligned collagen deposition with minimal inflammatory reaction. Mechanical testing of the grafts demonstrated significantly higher mechanical properties than immediately postimplantation. Acellular grafts loaded with bFGF achieved 58.8% of the stiffness and 40.7% of the peak load of healthy native ACL. Grafts without bFGF achieved 31.3% of the stiffness and 28.2% of the peak load of healthy native ACL. In this in vivo rodent model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regenerative potential of our electrospun PCL ligament graft. PMID:25744933

  8. Evaluation of polycaprolactone scaffold with basic fibroblast growth factor and fibroblasts in an athymic rat model for anterior cruciate ligament reconstruction.

    PubMed

    Leong, Natalie Luanne; Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben; Petrigliano, Frank A; McAllister, David R

    2015-06-01

    Anterior cruciate ligament (ACL) rupture is a common ligamentous injury often necessitating surgery. Current surgical treatment options include ligament reconstruction with autograft or allograft, which have their inherent limitations. Thus, there is interest in a tissue-engineered substitute for use in ACL regeneration. However, there have been relatively few in vivo studies to date. In this study, an athymic rat model of ACL reconstruction was used to evaluate electrospun polycaprolactone (PCL) grafts, with and without the addition of basic fibroblast growth factor (bFGF) and human foreskin fibroblasts. We examined the regenerative potential of tissue-engineered ACL grafts using histology, immunohistochemistry, and mechanical testing up to 16 weeks postoperatively. Histology showed infiltration of the grafts with cells, and immunohistochemistry demonstrated aligned collagen deposition with minimal inflammatory reaction. Mechanical testing of the grafts demonstrated significantly higher mechanical properties than immediately postimplantation. Acellular grafts loaded with bFGF achieved 58.8% of the stiffness and 40.7% of the peak load of healthy native ACL. Grafts without bFGF achieved 31.3% of the stiffness and 28.2% of the peak load of healthy native ACL. In this in vivo rodent model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regenerative potential of our electrospun PCL ligament graft.

  9. Growth Factor-Bearing Polymer Brushes--Versatile Bioactive Substrates Influencing Cell Response.

    PubMed

    Psarra, Evmorfia; Foster, Elena; König, Ulla; You, Jungmok; Ueda, Yuichiro; Eichhorn, Klaus-J; Müller, Martin; Stamm, Manfred; Revzin, Alexander; Uhlmann, Petra

    2015-11-01

    In this study we present the development of responsive nanoscale substrates exhibiting cell-guiding properties based on incorporated bioactive signaling cues. The investigative approach considered the effect of two different surface-bound growth factors (GFs) on cell behavior and response: hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF). Two surface biofunctionalization strategies were explored in order to conceive versatile, bioactive thin polymer brush films. Polymer brushes made of tethered poly(acrylic)acid (PAA) polymer layers with a high grafting density of polymer chains were biofunctionalized with GFs either by physisorption or chemisorption. Both GFs showed high binding efficiencies to PAA brushes based on their initial loading concentrations. The GF release kinetics can be distinguished depending on the applied biofunctionalization method. Specifically, a high initial burst followed by a constant slow release was observed in the case of both physisorbed HGF and bFGF. In contrast, the release kinetics of chemisorbed GFs were quite different. Remarkably, chemisorbed HGF remained bound to the brush surface for over 1 week, whereas 50% of chemisorbed bFGF was released slowly. Furthermore, the effect of these GF-biofunctionalized PAA brushes on different cells was investigated. A human hepatoma cell line (HepG2) was used to analyze the bioactivity of HGF-modified PAA brushes by measuring cell growth inhibition and scattering effects. Additionally, the differentiation of mouse embryonic stem cells (mESCs) toward endoderm was studied on bFGF-modified PAA brush surfaces. Finally, the results illustrate that PAA brushes, particularly those biofunctionalized with chemisorbed GFs, produce an expected measurable effect on both cell types. Therefore, PAA polymer brushes biofunctionalized with GFs can be used as bioactive cell culture substrates with tuned efficiency. PMID:26447354

  10. Basic fibroblast growth factor alleviates brain injury following global ischemia reperfusion in rabbits

    PubMed Central

    Zhang, Mao; Ma, Yue-feng; Gan, Jian-xin; Jiang, Guan-yu; Xu, Shan-xiang; Tao, Xiang-luo; Hong, An; Li, Jiao-kun

    2005-01-01

    The aim of this study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 μg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 μg/(kg·h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-α was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-α and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities. PMID:15973765

  11. Neuere Untersuchungen zur Prädiktion von EEG-Signalen bei Epilepsie

    NASA Astrophysics Data System (ADS)

    Niederhöfer, C.; Tetzlaff, R.

    2007-06-01

    Seit einigen Jahren ist die Analyse von EEG-Signalen bei Epilepsie Gegenstand zahlreicher wissenschaftlicher Arbeiten; Zielvorstellung ist dabei die Entwicklung von Verfahren zur Erkennung eines möglichen Voranfallszustandes. Im Vordergrund steht beispielsweise die Approximation einer so genannten effektiven Korrelationsdimension, die Bestimmung der maximalen Lyapunov-Exponenten, Detektionsverfahren für Muster bei Zellularen Nichtlinearen Netzwerken, die Bestimmung der mittleren Phasenkohärenz und Verfahren zur nichtlinearen Prädiktion von EEG-Signalen. Trotz umfangreicher Bemühungen kann bis heute eine Erkennung von Anfallsvorboten mit einer Sensitivität und Spezifität, die eine automatisierte Anfallsvorhersage ermöglichen würde, noch nicht durchgeführt werden. In diesem Beitrag werden neue Ergebnisse zur Prädiktion von EEG-Signalen bei Epilepsie vorgestellt. Dabei werden Signale, welche mittels intrakranieller electrocorticographischer (ECoG) und stereoelectroencephalographischer (SEEG) Ableitungen registriert wurden, segmentweise analysiert. Unter der Annahme, dass sich Änderungen des Systems ,,Gehirn" als Änderungen im Prädiktor, d.h. in seinen Systemparametern widerspiegeln, könnte eine nähere Betrachtung der Prädiktoreigenschaften zu einer Erkennung von Anfallsvorboten führen.

  12. Das Blüte-Bestäuber-Netz auf Brachflächen : biozönologische Untersuchung zur Bedeutung von Brachen in einer intensiv genutzten Agrarlandschaft

    NASA Astrophysics Data System (ADS)

    Hahn, Robert

    2002-11-01

    In der vorliegenden Dissertation wird die Bedeutung von Brachen für Artenvielfalt und Stabilität von Blüte-Bestäuber-Nahrungsnetzen in agrarisch genutzten Landschaften anhand ausgewählter blütenbesuchender Insektengruppen (Syrphidae, Lepidoptera) untersucht. Die Freilandarbeiten fanden von 1998-2000 im Raum der Feldberger Seenlandschaft, Mecklenburg-Vorpommern, statt. Es werden die beiden Hauptnahrungsquellen Nektar und Pollen betrachtet, dabei fanden Untersuchungen zur Intensität der Blüte-Bestäuber-Interaktion auf Stilllegungsflächen, zum flächenbezogenen quantitativen Nektarangebot im Jahresverlauf, zur individuellen Pollennutzung bei Syrphiden und zur Breite und Überlappung der Nahrungsnischen bei den dominanten Arten Episyrphus balteatus, Metasyrphus corollae, Syritta pipiens und Sphaerophoria scripta statt. Im Ergebnis zeigt sich eine hohe Bedeutung der Brachflächen für die Stabilität des Blüte-Bestäuber-Netzes, während die Diversität von anderen, eher landschaftsbezogenen Faktoren abhängig ist. This dissertation examines the importance of fallow land for the diversity and stability of pollination webs in agricultural landscapes as exemplified by selected groups of anthophilous insects (syrphidae and lepidoptera). The field studies were carried out between 1998 and 2000 in the Feldberg lakeland area in the north-east German State of Mecklenburg-Western Pomerania. Observations were made of nectar and pollen as the two main sources of food. Studies were conducted into the intensity of plant-pollinator interaction in set-aside areas, the site-specific quantity of nectar available during the vegetation period and the individual pollen intake of syrphid flies. Different methods were employed to establish the breadth of the trophic niches among the predominant species (Episyrphus balteatus, Metasyrphus corollae, Syritta pipiens and Sphaerophoria scripta) and the extent to which they overlapped. The studies showed that, while fallow land is very

  13. Beitraege zur Astronomiegeschichte, Band 5 (Acta Historica Astronomiae Vol. 18)

    NASA Astrophysics Data System (ADS)

    Duerbeck, H. W.; Dick, W. R.; Hamel, J.

    2003-01-01

    The 18th volume of the Acta Historica Astronomiae is at the same time the sixth collection of essays on the history of astronomy ("Beitræge zur Astronomiegeschichte, Band 6"), edited by the historians of astronomy W.R. Dick (Potsdam) and J. Hamel (Berlin). Besides a few short notices and book reviews, the book contains eight major articles, which deal with astronomical topics covering the time from the 16th to the 19th centuries. The first article by Michael Weichenhan (Berlin) deals with "the invention of the disk-shaped earth: a chapter of Copernican apologetics". The author shows that the concept of a "disc-shaped Earth" was by no means widespread in the middle ages, but restricted to the father of the church Lactantius and some adherents. Nevertheless, it was used by adherents of Copernicus to show the absurd consequences of a strictly literal biblical interpretation -- here concerning the Earth's shape, disc versus sphere, there the geocentric versus the heliocentric system. This thorough philosophical study is followed by two very short articles. "The measuring accuracy of Tycho's large sextant" by Johann Wünsch investigates O-C values of planet-star distances, as based on Tycho's observations as published in the Historia Coelestis (a compilation, which is also based on Tycho's manuscripts, and published in Regensburg in 1672). The result is that standard deviations are 80 arcseconds for Saturn and 89 arcseconds for Jupiter and Mars, an unexpectedly poor result in view of the general opinion that Tycho was famous for his precision work. "The astronomer Christoph Grienberger and the Galilei trial" by Franz Daxecker deals with a Jesuit astronomer who was both the disciple and successor of the mathematician-astronomer Christopher Clavius at the Collegium Romanum. While he was inclined to Galilei early on, he was forced to propagate Aristotelian doctrine. The brief article is very concise, but extremely tiresome to read (3 pages of pure text are embellished by

  14. Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis.

    PubMed Central

    Yoshida, S; Ono, M; Shono, T; Izumi, H; Ishibashi, T; Suzuki, H; Kuwano, M

    1997-01-01

    Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms. PMID:9199336

  15. Nanoscale Growth Factor Patterns by Immobilization on a Heparin Mimicking Polymer

    PubMed Central

    Christman, Karen L.; Vázquez-Dorbatt, Vimary; Schopf, Eric; Kolodziej, Christopher M.; Li, Ronald C.; Broyer, Rebecca M.; Chen, Yong; Maynard, Heather D.

    2009-01-01

    In this study, electrostatic interactions between sulfonate groups of an immobilized polymer and the heparin binding domains of growth factors important in cell signaling were exploited to nanopattern the proteins. Poly(sodium 4-styrenesulfonate-co-poly(ethylene glycol) methacrylate) (pSS-co-pPEGMA) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using ethyl S-thiobenzoyl-2-thiopropionate as a chain transfer agent and 2,2′azoisobutyronitrile (AIBN) as the initiator. The resulting polymer (1) was characterized by 1H NMR, GPC, FT-IR, and UV-Vis and had a number average molecular weight (Mn) of 24,000 and a polydispersity index (PDI) of 1.17. The dithioester end group of 1 was reduced to the thiol, and the polymer subsequently immobilized on a gold substrate. Binding of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) to the polymer via the heparin binding domains was then confirmed by surface plasmon resonance (SPR). The interactions were stable at physiological salt concentrations. Polymer 1 was cross-linked onto silicon wafers using an electron beam writer forming micron- and nano- patterns. Resolutions of 100 nm and arbitrary nanoscale features such as concentric circles and contiguous squares and triangles were achieved. Fluorescence microscopy confirmed that bFGF and VEGF were subsequently immobilized to the polymer micro- and nano- patterns. PMID:19554729

  16. Ein stochastisches Modell zur Beschreibung von Signalen in digitalen Schaltungen basierend auf quadratischer Optimierung

    NASA Astrophysics Data System (ADS)

    Kleeberger, V. B.; Maier, P.; Schlichtmann, U.

    2013-07-01

    Die kontinuierlich fortschreitende Miniaturisierung in integrierten Schaltungen führt zu einem erhöhten Modellierungsbedarf verschiedenster Effekte, wie z.B. Alterung oder Stromverbrauch. Diese hängen von den auftretenden Signalen innerhalb der Schaltung ab, wodurch deren statistische Modellierung ein zentrales Problem darstellt. Dieser Beitrag stellt eine neue Methode zur stochastischen Signalmodellierung basierend auf quadratischer Optimierung vor. Die Methode wird mit Hilfe von realen Daten mit existierenden Ansätzen verglichen. Die Testergebnisse zeigen hierbei im vorgestellten Modell einen Genauigkeitszuwachs von bis zu einem Faktor 10 im Vergleich zu bereits existierenden Modellen.

  17. Effects of prolonged infusion of basic fibroblast growth factor and IGF-I on adrenocortical differentiation in the autotransplanted adrenal: an immunohistochemical study.

    PubMed

    Vendeira, P; Pignatelli, D; Neves, D; Magalhães, M M; Magalhães, M C; Vinson, G P

    1999-07-01

    Adrenocortical regeneration after adrenal autotransplantation provides a model for the study of local autocrine/paracrine mechanisms involved in the growth and differentiation of the adrenal cortex. To study the possible involvement of some growth factors, namely basic fibroblast growth factor (bFGF, FGF-2) and insulin-like growth factor I (IGF-I), in cell differentiation, immunohistochemical and ultrastructural studies were carried out on adrenal autotransplants in adult male rats. To distinguish between fasciculata and glomerulosa-like cells with accuracy, tissue sections were immunostained with IZAb, which recognizes the inner zone antigen (IZAg) present in fasciculata and reticularis cells but absent from the glomerulosa, and by electron microscopy. IGF-I-treated animals exhibited a clear glomerulosa-like zone that was devoid of IZAb immunostaining. In this outer subcapsular area, ultrastructural examination showed cells containing mitochondria with irregular cristae resembling those of the fetal or immature glomerulosa cells. In contrast, no significant morphological differences were observed in bFGF-treated animals when compared with those from saline-treated controls, in both of which, IZAb immunostaining occurred in almost all adrenocortical cells, with no clear zonation or glomerulosa, as seen in the intact animal. Plasma aldosterone and corticosterone concentrations were lower in autotransplanted control animals than in intact controls, although plasma renin activities were similar. IGF-I treatment significantly increased aldosterone concentrations, whereas corticosterone and plasma renin activity were reduced. bFGF infusion further reduced plasma aldosterone, although plasma renin activity and corticosterone were unaffected. These results suggest that the two growth factors have different effects on zonal differentiation and function in the autotransplanted gland. In particular, bFGF, by reducing glomerulosa function, appears partly to replicate the

  18. Post-transcriptional regulation of neurofibromin level in cultured human melanocytes in response to growth factors.

    PubMed

    Griesser, J; Kaufmann, D; Maier, B; Mailhammer, R; Kuehl, P; Krone, W

    1997-03-01

    Among the symptoms that characterize neurofibromatosis type 1 (NF1) are pigmentation anomalies such as cafe au lait spots. It has been suggested that the reduction of the neurofibromin level in the epidermis of NF1 patients is responsible for the observed signs such as altered melanogenesis and altered density of melanocytes. Our studies show that in cultured normal human melanocytes, the neurofibromin level can be varied in vitro over a wide range by using different culture conditions. The influence of factors that control differentiation and proliferation of melanocytes on neurofibromin levels was studied. Immunoprecipitation followed by western blotting showed a 3- to 4-fold increase of neurofibromin after stimulation by PMA or bFGF, respectively, and a 1.5-fold increase in cells stimulated with steel factor. The increase of neurofibromin was not paralleled by a higher NF1 mRNA level as proved by northern blotting. Pulse-chase experiments with 35S-labeled melanocytes revealed an approximately 3-fold increase in the half-life of neurofibromin in bFGF- or PMA-stimulated cells compared to controls. These results indicate that the neurofibromin level of cultured melanocytes can be regulated by a mechanism independent of NF1 gene transcription and translation, which might influence the degradation rate of the protein.

  19. Cynaropicrin from Cynara scolymus L. suppresses photoaging of skin by inhibiting the transcription activity of nuclear factor-kappa B.

    PubMed

    Tanaka, Yuka Tsuda; Tanaka, Kiyotaka; Kojima, Hiroyuki; Hamada, Tomoji; Masutani, Teruaki; Tsuboi, Makoto; Akao, Yukihiro

    2013-01-15

    Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors. Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation. Nuclear factor kappa B (NF-κB) is one of the representative transcription factors active in conjunction with inflammation. NF-κB is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1). We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF-κB. One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF-κB transactivation. As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF-κB-mediated transactivation of bFGF and MMP-1. Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes. These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. PMID:23232059

  20. Cynaropicrin from Cynara scolymus L. suppresses photoaging of skin by inhibiting the transcription activity of nuclear factor-kappa B.

    PubMed

    Tanaka, Yuka Tsuda; Tanaka, Kiyotaka; Kojima, Hiroyuki; Hamada, Tomoji; Masutani, Teruaki; Tsuboi, Makoto; Akao, Yukihiro

    2013-01-15

    Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors. Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation. Nuclear factor kappa B (NF-κB) is one of the representative transcription factors active in conjunction with inflammation. NF-κB is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1). We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF-κB. One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF-κB transactivation. As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF-κB-mediated transactivation of bFGF and MMP-1. Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes. These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation.

  1. Acoustic droplet-hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness.

    PubMed

    Fabiilli, Mario L; Wilson, Christopher G; Padilla, Frédéric; Martín-Saavedra, Francisco M; Fowlkes, J Brian; Franceschi, Renny T

    2013-07-01

    Wound healing is regulated by temporally and spatially restricted patterns of growth factor signaling, but there are few delivery vehicles capable of the "on-demand" release necessary for recapitulating these patterns. Recently we described a perfluorocarbon double emulsion that selectively releases a protein payload upon exposure to ultrasound through a process known as acoustic droplet vaporization (ADV). In this study, we describe a delivery system composed of fibrin hydrogels doped with growth factor-loaded double emulsion for applications in tissue regeneration. Release of immunoreactive basic fibroblast growth factor (bFGF) from the composites increased up to 5-fold following ADV and delayed release was achieved by delaying exposure to ultrasound. Releasates of ultrasound-treated materials significantly increased the proliferation of endothelial cells compared to sham controls, indicating that the released bFGF was bioactive. ADV also triggered changes in the ultrastructure and mechanical properties of the fibrin as bubble formation and consolidation of the fibrin in ultrasound-treated composites were accompanied by up to a 22-fold increase in shear stiffness. ADV did not reduce the viability of cells suspended in composite scaffolds. These results demonstrate that an acoustic droplet-hydrogel composite could have broad utility in promoting wound healing through on-demand control of growth factor release and/or scaffold architecture. PMID:23535233

  2. Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness

    PubMed Central

    Fabiilli, Mario L.; Wilson, Christopher G.; Padilla, Frédéric; Martín-Saavedra, Francisco M.; Fowlkes, J. Brian; Franceschi, Renny T.

    2013-01-01

    Wound healing is regulated by temporally and spatially restricted patterns of growth factor signaling, but there are few delivery vehicles capable of the “on-demand” release necessary for recapitulating these patterns. Recently we described a perfluorocarbon double emulsion that selectively releases a protein payload upon exposure to ultrasound through a process known as acoustic droplet vaporization (ADV). In this study, we describe a delivery system composed of fibrin hydrogels doped with growth factor-loaded double emulsion for applications in tissue regeneration. Release of immunoreactive basic fibroblast growth factor (bFGF) from the composites increased up to 5-fold following ADV and delayed release was achieved by delaying exposure to ultrasound. Releasates of ultrasound-treated materials significantly increased the proliferation of endothelial cells compared to sham controls, indicating that the released bFGF was bioactive. ADV also triggered changes in the ultrastructure and mechanical properties of the fibrin as bubble formation and consolidation of the fibrin in ultrasound-treated composites were accompanied by up to a 22-fold increase in shear stiffness. ADV did not reduce the viability of cells suspended in composite scaffolds. These results demonstrate that an acoustic droplet–hydrogel composite could have broad utility in promoting wound healing through on-demand control of growth factor release and/or scaffold architecture. PMID:23535233

  3. In vitro and in vivo activation of endothelial cells by colony-stimulating factors.

    PubMed Central

    Bussolino, F; Ziche, M; Wang, J M; Alessi, D; Morbidelli, L; Cremona, O; Bosia, A; Marchisio, P C; Mantovani, A

    1991-01-01

    This study was designed to identify the set of functions activated in cultured endothelial cells by the hematopoietic growth factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-colony-stimulating factor (GM-CSF), and to compare them with those elicited by prototypic cytokines active on these cells. Moreover, indications as to the in vivo relevance of in vitro effects were obtained. G-CSF and GM-CSF induced endothelial cells to proliferate and migrate. In contrast, unlike appropriate reference cytokines (IL-1 and tumor necrosis factor, IFN-gamma), G-CSF and GM-CSF did not modulate endothelial cell functions related to hemostasis-thrombosis (production of procoagulant activity and of platelet activating factor), inflammation (expression of leukocyte adhesion molecule-1 and production of platelet activating factor), and accessory function (expression of class II antigens of MHC). Other colony-stimulating factors (IL-3 and macrophage-colony-stimulating factor) were inactive on all functions tested. In comparison to basic fibroblast growth factor (bFGF), G-CSF and GM-CSF induced lower maximal proliferation of endothelial cells, whereas migration was of the same order of magnitude. G-CSF and GM-CSF stimulated repair of mechanically wounded endothelial monolayers. Exposure to both cytokines induced shape changes and cytoskeletal reorganization consistent with a migratory phenotype. To explore the in vivo relevance of the in vitro effects of these cytokines on endothelium, we studied the angiogenic activity of human G-CSF in the rabbit cornea. G-CSF, but not the heat-inactivated molecule, had definite angiogenic activity, without any sign of inflammatory reactions. G-CSF was less active than bFGF. However, the combination of a nonangiogenic dose of bFGF with G-CSF resulted in an angiogenic response higher than that elicited by either individual cytokines. Thus, G-CSF and GM-CSF induce endothelial cells to express an activation

  4. Molekulare Methoden zum Nachweis, zur Quantifizierung und zum Monitoring der Mykotoxinbildung lebensmittelrelevanter Pilze

    NASA Astrophysics Data System (ADS)

    Geisen, Rolf

    Schimmelpilze kommen ubiquitär vor und spielen besonders bei pflanzlichen Lebensmitteln und Rohprodukten eine besondere Rolle als Verderbsorganismen. Es wird geschätzt, dass 20-25 % der jährlichen Produktion an pflanzlichen Produkten durch Schimmelpilze verdorben werden (Smith et al., 1994). Viele der lebensmittelrelevanten Schimmelpilze sind zudem in der Lage, Mykotoxine, toxische Sekundärmetabolite, zu bilden, was das Ausmaß des Problems deutlich macht. Die wichtigsten mykotoxinbildenden Spezies gehören zu den Fusarien (Trichothecene, Fumonisine, Zearalenon), Aspergillen (Aflatoxin, Ochratoxin, Cyclopiazonsäure) und Penicillien (Patulin, Ochratoxin). Für viele Mykotoxine, wie die Aflatoxine, Ochratoxin, Fumonisine und Trichothecene sind Grenzwerte erlassen worden, die die Verkehrsfähigkeit betroffener Produkte regeln. Die Einhaltung der Grenzwerte kann sehr genau durch offizielle chemisch-analytische Methoden, wie HPLC, GC-MS etc. kontrolliert werden. Diese analytischen Methoden sind aber für die Anwendung eines HACCP-Ansatzes zur Kontrolle der Mykotoxinbildung nur bedingt geeignet, da sie Endpunktkontrollen darstellen und nur das über eine längere Zeit gebildete Mykotoxin bestimmen. Sie sagen daher nichts über die biologischen Bedingungen zur Zeit der Bildung durch den Pilz aus.

  5. Identifikationsverfahren zur Analyse von EEG-Signalen bei Epilepsie mit Reaktions-Diffusions Netzwerken

    NASA Astrophysics Data System (ADS)

    Gollas, F.; Tetzlaff, R.

    2007-06-01

    Partielle Differentialgleichungen des Reaktions-Diffusions-Typs beschreiben Phänomene wie Musterbildung, nichtlineare Wellenausbreitung und deterministisches Chaos und werden oft zur Untersuchung komplexer Vorgänge auf den Gebieten der Biologie, Chemie und Physik herangezogen. Zellulare Nichtlineare Netzwerke (CNN) sind eine räumliche Anordnung vergleichsweise einfacher dynamischer Systeme, die eine lokale Kopplung untereinander aufweisen. Durch eine Diskretisierung der Ortsvariablen können Reaktions-Diffusions-Gleichungen häufig auf CNN mit nichtlinearen Gewichtsfunktionen abgebildet werden. Die resultierenden Reaktions-Diffusions-CNN (RD-CNN) weisen dann in ihrer Dynamik näherungsweise gleiches Verhalten wie die zugrunde gelegten Reaktions-Diffusions-Systeme auf. Werden RD-CNN zur Identifikation neuronaler Strukturen anhand von EEG-Signalen herangezogen, so besteht die Möglichkeit festzustellen, ob das gefundene Netzwerk lokale Aktivität aufweist. Die von Chua eingeführte Theorie der lokalen Aktivität Chua (1998); Dogaru und Chua (1998) liefert eine notwendige Bedingung für das Auftreten von emergentem Verhalten in zellularen Netzwerken. Änderungen in den Parametern bestimmter RD-CNN könnten auf bevorstehende epileptische Anfälle hinweisen. In diesem Beitrag steht die Identifikation neuronaler Strukturen anhand von EEG-Signalen durch Reaktions-Diffusions-Netzwerke im Vordergrund der dargestellten Untersuchungen. In der Ergebnisdiskussion wird insbesondere auch die Frage nach einer geeigneten Netzwerkstruktur mit minimaler Komplexität behandelt.

  6. Assessment of Retrograde Coronary Venous Infusion of Mesenchymal Stem Cells Combined with Basic Fibroblast Growth Factor in Canine Myocardial Infarction Using Strain Values Derived from Speckle-Tracking Echocardiography.

    PubMed

    Sun, Qi-Wei; Zhen, Lei; Wang, Qin; Sun, Yan; Yang, Jiao; Li, Yi-Jia; Li, Rong-Juan; Ma, Ning; Li, Zhi-An; Wang, Lu-Ya; Nie, Shao-Ping; Yang, Ya

    2016-01-01

    Speckle-tracking echocardiography was used to assess retrograde coronary venous infusion of mesenchymal stem cells (MSCs) combined with basic fibroblast growth factor (bFGF) in a canine model of acute myocardial infarction (AMI). AMI was induced by ligation of the left anterior descending coronary artery. Coronary venous retroperfusion was performed at 1 wk after AMI. Twenty-eight animals were randomized into four groups: saline, bFGF+saline, saline+MSCs and bFGF+MSCs. Echocardiography was performed before AMI, at 7 d post-AMI and 40 d after retroperfusion. Apoptotic cardiomyocytes in the border zone of the ischemic region were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Vascular endothelial growth factor and factor VIII concentrations were measured by western blotting. The left ventricular end-systolic volume increased significantly, whereas the left ventricular ejection fraction and global and segmental strain values decreased significantly after AMI. After retroperfusion, the strain values of the infarct zone, but not conventional echocardiographic parameters, were significantly different between control and bFGF+MSC groups. Cardiomyocyte apoptosis decreased, whereas vascular endothelial growth factor and factor VIII concentrations were higher in the bFGF+MSC, bFGF and MSC groups. Cardiomyocyte apoptosis was well correlated with the strain values. Although retrograde coronary venous infusion of bFGF and MSCs promoted neo-vascularization of the infarcted myocardium and inhibited apoptosis, there was only a slight strain improvement without a substantial increase in global cardiac functions.

  7. Expression of growth factors, proto-oncogenes, and p53 in nasopharyngeal angiofibromas.

    PubMed

    Nagai, M A; Butugan, O; Logullo, A; Brentani, M M

    1996-02-01

    Biopsies from 25 juvenile nasopharyngeal angiofibromas (JNAs) and respective normal inferior turbinates were examined and compared. The expression patterns of the messenger RNAs (mRNAs) for various growth factors possibly involved in the growth of mesenchymal cells, as well as angiogenesis and fibrosis, were also compared. These growth factors included insulin-like growth factor II (IGF-II), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factors-beta1 (TGF-beta1) and platelet-derived growth factors (PDGF-A and PDGF-B). Quantification of mRNA coding for proto-oncogenes and suppressor genes related to proliferation (i.e., c-myc, c-fos, p53) was also undertaken. Tumor and turbinates expressed similar levels of bFGF, VEGF, TGF-beta1, c-myc, c-fos, and PDGF-A mRNAs. The presence of TGF-beta1 protein was confirmed by immunohistochemistry in several structures that characterize the lesions of JNA, which suggests that TGF-beta1 may play a role in the development of the fibrous component of this tumor. PDGF-B and p53 were overexpressed (i.e., twice the mean level found in turbinates) in 50% and 32% of JNAs, respectively but there was no statistical significance when compared with controls. Statistically significant increased expression of IGF-II mRNA was observed in JNA (P = .04). IGF-II mRNA levels were correlated to p53 (P = .05) and PDGF-B (P = .034), indicating a possible synergistic action of such factors in JNA. The results of this study suggest that IGF-II might be a potential growth regulator of nasopharyngeal angiofibromas.

  8. Zur Biologie des Planktons des Königshafens (Nordsylter Wattenmeer)

    NASA Astrophysics Data System (ADS)

    Martens, P.

    1982-06-01

    From May 1979 on, the following parameters were measured at a station in the inlet of Königshafen near List (Island of Sylt): temperature, salinity, mesozooplankton (>76 µm), chlorophyll-a, seston dry weight, oxygen and phytoplankton-nutrients (NH4-N, NO2-N, NO3-N, PO4-P, SiO3-Si). A multiple regression analysis showed the interrelationships between the parameters measured. Tidal influences on zooplankton and seston dry weight could be observed. At low tide, the amount of zooplankton (not counting the harpacticoid copepods) declines and the number of harpacticoid copepods rises as does the seston dry weight too. The chlorophyll-a content is a function of the phytoplankton-nutrients. An increase in chlorophyll-a leads to a decrease in nitrogen and silicate concentrations. Phosphate, due possibly to a sewage inlet into the Königshafen, is not a limiting factor. The availability of nutrients is influenced by temperature, salinity and the tidal cycle. The amount of oxygen is dependent on water temperature and seston dry weight. High water temperatures and a high seston content lead to a decrease in oxygen concentrations.

  9. In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases

    PubMed Central

    1989-01-01

    The role of basic fibroblast growth factor-(bFGF) induced proteinases in basement membrane (BM) invasion by bovine capillary endothelial (BCE) cells was studied using a quantitative in vitro assay previously described (Mignatti et al., 1986). 125I-iododeoxyuridine-labeled BCE cells were grown for 72 h on the human amnion BM, and cell invasion was determined by measuring the radioactivity associated with the tissue after removal of the noninvasive cell layer. BCE cells were noninvasive under normal conditions. Addition of human bFGF to either the BM or to the stromal aspect of the amnion induced BCE cell invasion with a dose- dependent response. This effect was maximal in the presence of 70 ng/ml bFGF, and was inhibited by anti-FGF antibody. Transforming growth factor beta, as well as plasmin inhibitors and anti-tissue type plasminogen activator antibody inhibited BCE cell invasion. The tissue inhibitor of metalloproteinases, 1-10 phenanthroline, anti-type IV and anti-interstitial collagenase antibodies had the same effect. On the contrary, anti-stromelysin antibody and Eglin, an inhibitor of elastase, were ineffective. The results obtained show that both the plasminogen activator-plasmin system and specific collagenases are involved in the invasive process occurring during angiogenesis. PMID:2465298

  10. Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor.

    PubMed

    Gritti, A; Parati, E A; Cova, L; Frolichsthal, P; Galli, R; Wanke, E; Faravelli, L; Morassutti, D J; Roisen, F; Nickel, D D; Vescovi, A L

    1996-02-01

    It has been established that the adult mouse forebrain contains multipotential (neuronal/glial) progenitor cells that can be induced to proliferate in vitro when epidermal growth factor is provided. These cells are found within the subventricular zone of the lateral ventricles, together with other progenitor cell populations, whose requirements for proliferation remain undefined. Using basic fibroblast growth factor (bFGF), we have isolated multipotential progenitors from adult mouse striatum. These progenitors proliferate and can differentiate into cells displaying the antigenic properties of astrocytes, oligodendrocytes, and neurons. The neuron-like cells possess neuronal features, exhibit neuronal electrophysiological properties, and are immunoreactive for GABA, substance P, choline acetyl-transferase, and glutamate. Clonal analysis confirmed the multipotency of these bFGF-dependent cells. Most significantly, subcloning experiments demonstrated that they were capable of self-renewal, which led to a progressive increase in population size over serial passaging. These results demonstrate that bFGF is mitogenic for multipotential cells from adult mammalian forebrain that possess stem cell properties. PMID:8558238

  11. The influence of occlusal stimuli on basic fibroblast growth factor expression in the periodontal healing of replanted teeth.

    PubMed

    Hu, Fang-Wei; Hosomichi, Jun; Kanno, Zuisei; Soma, Kunimichi

    2008-03-01

    Occlusal stimuli and the periodontal healing of replanted teeth have been reported to be related. However, the mechanism for preventing dentoalveolar ankylosis remains unclear. Basic fibroblast growth factor (bFGF/FGF-2) is considered as a key factor in wound healing. The purpose of this study was to evaluate the relationship between occlusal stimuli, bFGF, and the periodontal healing after tooth replantation. Five-week-old male rats were divided into non-occluded, occluded, and recovery groups. The right maxillary first molars were replanted in all groups, and the left maxillary first molars in the 2-week occluded group without replantation were served as nontreated. An anterior bite plate was attached to the maxillary and mandibular incisors to produce occlusal hypofunction in the non-occluded group and was then removed after 1 week in the recovery group. Histological observations were performed after 1 and 2 weeks of the experimental period. After 2 weeks, the non-occluded group had detectable ankylosis and obvious periodontal tissue stricture. Meanwhile, the occluded and recovery groups showed enlarged and thickened periodontia without ankylosis. The number of bFGF-positive cells in the occluded and recovery groups significantly increased as compared to in the non-occluded group. These results suggest that occlusal stimuli enhance the production of bFGF in the periodontal healing of replanted teeth and prevent dentoalveolar ankylosis.

  12. Transforming growth factor-beta1-induced activation of the Raf-MEK-MAPK signaling pathway in rat lung fibroblasts via a PKC-dependent mechanism.

    PubMed

    Axmann, A; Seidel, D; Reimann, T; Hempel, U; Wenzel, K W

    1998-08-19

    In fibroblasts transforming growth factor-beta1 (TGF-beta1) regulates cell proliferation and turnover of macromolecular components of the extracellular matrix. Here, intracellular signaling events in growth-inhibited embryonic rat lung fibroblasts (RFL-6) upon stimulation with TGF-beta1 were investigated. TGF-beta1 rapidly induced the activation of c-Raf-1, MEK-1, and MAPK p42 and p44. The activation of this pathway by TGF-beta1 did not depend on autocrine platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF). Inhibition of the binding of growth factors to their tyrosine kinase receptors did not affect MAPK activation by TGF-beta1. Ras activation by TGF-beta1 was significantly lower compared to the activation by PDGF or bFGF. The intracellular transduction of the TGF-beta1 signal was completely suppressed by depletion or inhibition of protein kinase C (PKC). It is shown that calcium-dependent isoforms of PKC are required for MAPK activation by TGF-beta1. PMID:9712718

  13. Versuche zur Gewinnung von katalytischen Antikörpern zur Hydrolyse von Arylcarbamaten und Arylharnstoffen. (English Title: Attempts to produce catalytic antibodies for hydrolysis of arylcarbamates and arylureas)

    NASA Astrophysics Data System (ADS)

    Werner, Deljana

    2002-05-01

    Im Rahmen dieser Arbeit gelang es, katalytische Antikörper zur Hydrolyse von Benzylphenylcarbamaten sowie zahlreiche monoklonale Antikörper gegen Haptene herzustellen. Es wurden verschiedene Hapten-Protein-Konjugate unter Verwendung unterschiedlicher Kopplungsmethoden hergestellt und charakterisiert. Zur Generierung der hydrolytisch aktiven Antikörper wurden Inzuchtmäuse mit KLH-Konjugaten von 4 Übergangszustandsanaloga (ÜZA) immunisiert. Mit Hilfe der Hybridomtechnik wurden verschiedene monoklonale Antikörper gegen diese ÜZA gewonnen. Dabei wurden sowohl verschiedene Immunisierungsschemata als auch verschiedene Inzuchtmausstämme und Fusionstechniken verwendet. Insgesamt wurden 32 monoklonale Antikörper gegen die verwendeten ÜZA selektiert. Diese Antikörper wurden in groen Mengen hergestellt und gereinigt. Zum Nachweis der Antikörper-vermittelten Katalyse wurden verschiedene Methoden entwickelt und eingesetzt, darunter immunologische Nachweismethoden mit Anti-Substrat- und Anti-Produkt-Antikörpern und eine photometrische Methode mit Dimethylaminozimtaldehyd. Der Nachweis der hydrolytischen Aktivität gelang mit Hilfe eines Enzymsensors, basierend auf immobilisierter Tyrosinase. Die Antikörper N1-BC1-D11, N1-FA7-C4, N1-FA7-D12 und R3-LG2-F9 hydrolysierten die Benzylphenylcarbamate POCc18, POCc19 und Substanz 27. Der Nachweis der hydrolytischen Aktivität dieser Antikörper gelang auch mit Hilfe der HPLC. Der katalytische Antikörper N1-BC1-D11 wurde kinetisch und thermodynamisch untersucht. Es wurde eine Michaelis-Menten-Kinetik mit Km von 210 µM, vmax von 3 mM/min und kcat von 222 min-1 beobachtet. Diese Werte korrelieren mit den Werten der wenigen bekannten Diphenylcarbamat-spaltenden Abzyme. Die Beschleunigungsrate des Antikörpers N1-BC1-D11 betrug 10. Das ÜZA Hei3 hemmte die hydrolytische Aktivität. Dies beweist, dass die Hydrolyse in der Antigenbindungsstelle stattfindet. Weiter wurde zwischen der Antikörperkonzentration und der

  14. Brain-derived neurotrophic factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by activation of basic fibroblast growth factor signaling.

    PubMed

    Berk, B-A; Vogler, S; Pannicke, T; Kuhrt, H; Garcia, T B; Wiedemann, P; Reichenbach, A; Seeger, J; Bringmann, A

    2015-06-01

    Water accumulation in retinal glial (Müller) and neuronal cells resulting in cellular swelling contributes to the development of retinal edema and neurodegeneration. Intravitreal administration of neurotrophins such as brain-derived neurotrophic factor (BDNF) is known to promote survival of retinal neurons. Here, we show that exogenous BDNF inhibits the osmotic swelling of Müller cell somata induced by superfusion of rat retinal slices or freshly isolated cells with a hypoosmotic solution containing barium ions. BDNF also inhibited the osmotic swelling of bipolar cell somata in retinal slices, but failed to inhibit the osmotic soma swelling of freshly isolated bipolar cells. The inhibitory effect of BDNF on Müller cell swelling was mediated by activation of tropomyosin-related kinase B (TrkB) and transactivation of fibroblast growth factor receptors. Exogenous basic fibroblast growth factor (bFGF) fully inhibited the osmotic swelling of Müller cell somata while it partially inhibited the osmotic swelling of bipolar cell somata. Isolated Müller cells displayed immunoreactivity of truncated TrkB, but not full-length TrkB. Isolated rod bipolar cells displayed immunoreactivities of both TrkB isoforms. Data suggest that the neuroprotective effect of exogenous BDNF in the retina is in part mediated by prevention of the cytotoxic swelling of retinal glial and bipolar cells. While BDNF directly acts on Müller cells by activation of TrkB, BDNF indirectly acts on bipolar cells by inducing glial release of factors like bFGF that inhibit bipolar cell swelling.

  15. The ZnuABC high-affinity zinc uptake system and its regulator Zur in Escherichia coli.

    PubMed

    Patzer, S I; Hantke, K

    1998-06-01

    In Escherichia coli, lacZ operon fusions were isolated that were derepressed under iron repletion and repressed under iron depletion. Two fusions were localized in genes that formed an operon whose gene products had characteristics of a binding protein-dependent transport system. The growth defect of these mutants on TY medium containing 5mM EGTA was compensated for by the addition of Zn2+. In the presence of 0.5mM EGTA, only the parental strain was able to take up 65Zn2+. This high-affinity transport was energized by ATP. The genes were named znuACB (for zinc uptake; former name yebLMI) and localized at 42 min on the genetic map of E. coli. At high Zn2+ concentrations, the znu mutants took up more 65Zn2+ than the parental strain. The high-affinity 65Zn2+ uptake was repressed by growth in the presence of 10 microM Zn2+. A znuA-lacZ operon fusion was repressed by 5 microM Zn2+ and showed a more than 20-fold increase in beta-galactosidase activity when Zn2+ was bound to 1.5 microM TPEN [tetrakis-(2-pyridylmethyl) ethylenediamine]. To identify the Zn2+-dependent regulator, constitutive mutants were isolated and tested for complementation by a gene bank of E. coli. A complementing gene, yjbK of the E. coli genome, was identified and named zur (for zinc uptake regulation). The Zur protein showed 27% sequence identity with the iron regulator Fur. High-affinity 65Zn2+ transport of the constitutive zur mutant was 10-fold higher than that of the uninduced parental strain. An in vivo titration assay suggested that Zur binds to the bidirectional promoter region of znuA and znuCB. PMID:9680209

  16. Glial cell line-derived neurotrophic factor in combination with insulin-like growth factor 1 and basic fibroblast growth factor promote in vitro culture of goat spermatogonial stem cells.

    PubMed

    Bahadorani, M; Hosseini, S M; Abedi, P; Abbasi, H; Nasr-Esfahani, M H

    2015-01-01

    Growth factors are increasingly considered as important regulators of spermatogonial stem cells (SSCs). This study investigated the effects of various growth factors (GDNF, IGF1, bFGF, EGF and GFRalpha-1) on purification and colonization of undifferentiated goat SSCs under in vitro and in vivo conditions. Irrespective of the culture condition used, the first signs of developing colonies were observed from day 4 of culture onwards. The number of colonies developed in GDNF + IGF1 + bFGF culture condition was significantly higher than the other groups (p < 0.05). In contrast, the size of colonies developed in GDNF + EGF + LIF culture condition was significantly higher than the other groups (p < 0.05). Immunocytochemical stationing for specific biomarkers of somatic cells (vimentin, alpha-inhibin and α-SMA) and spermatogonial cells (PLZF, THY 1, VASA, alpha-1 integrin, bet-1 integrin and DBA) revealed that both cell types existed in developing colonies, irrespective of the culture condition used. Even though, the relative abundance of VASA, FGFR3, OCT4, PLZF, BCL6B and THY1 transcription factors in GDNF + IGF1 + bFGF treatment group was significantly higher than the other groups (p < 0.05). Additionally, goat SSCs developed in the latter culture condition could colonize within the seminiferous tubules of the germ-cell depleted recipient mice following xenotransplantation. Obtained results demonstrated that combination of GDNF with IGF1 and bFGF promote in vitro culture of goat SSCs while precludes uncontrolled proliferation of somatic cells. PMID:26154310

  17. Glial cell line-derived neurotrophic factor in combination with insulin-like growth factor 1 and basic fibroblast growth factor promote in vitro culture of goat spermatogonial stem cells.

    PubMed

    Bahadorani, M; Hosseini, S M; Abedi, P; Abbasi, H; Nasr-Esfahani, M H

    2015-01-01

    Growth factors are increasingly considered as important regulators of spermatogonial stem cells (SSCs). This study investigated the effects of various growth factors (GDNF, IGF1, bFGF, EGF and GFRalpha-1) on purification and colonization of undifferentiated goat SSCs under in vitro and in vivo conditions. Irrespective of the culture condition used, the first signs of developing colonies were observed from day 4 of culture onwards. The number of colonies developed in GDNF + IGF1 + bFGF culture condition was significantly higher than the other groups (p < 0.05). In contrast, the size of colonies developed in GDNF + EGF + LIF culture condition was significantly higher than the other groups (p < 0.05). Immunocytochemical stationing for specific biomarkers of somatic cells (vimentin, alpha-inhibin and α-SMA) and spermatogonial cells (PLZF, THY 1, VASA, alpha-1 integrin, bet-1 integrin and DBA) revealed that both cell types existed in developing colonies, irrespective of the culture condition used. Even though, the relative abundance of VASA, FGFR3, OCT4, PLZF, BCL6B and THY1 transcription factors in GDNF + IGF1 + bFGF treatment group was significantly higher than the other groups (p < 0.05). Additionally, goat SSCs developed in the latter culture condition could colonize within the seminiferous tubules of the germ-cell depleted recipient mice following xenotransplantation. Obtained results demonstrated that combination of GDNF with IGF1 and bFGF promote in vitro culture of goat SSCs while precludes uncontrolled proliferation of somatic cells.

  18. Silk fibroin sponges with cell growth-promoting activity induced by genetically fused basic fibroblast growth factor.

    PubMed

    Kambe, Yusuke; Kojima, Katsura; Tamada, Yasushi; Tomita, Naohide; Kameda, Tsunenori

    2016-01-01

    Transgenic silkworm technology has enabled the biological properties of silk fibroin protein to be altered by fusion to recombinant bioactive proteins. However, few studies have reported the fabrication of genetically modified fibroin proteins into three-dimensional spongy structures to serve as scaffolds for tissue engineering. We generated a transgenic silkworm strain that produces fibroin fused to basic fibroblast growth factor (bFGF) and processed the fibroin into a spongy structure using a simple freeze/thaw method. NIH3T3 mouse embryonic fibroblasts grown on bFGF-fused fibroin sponges proliferated and spread out well, showing half the population doubling time of cells cultured on wild-type fibroin sponges. Furthermore, the number of primary rabbit articular chondrocytes growing on bFGF-fused fibroin sponges was around five-times higher than that of the wild-type control at 3-days post cell-seeding. As the physical properties of wild-type and bFGF-fused fibroin sponges were almost identical, it is suggested that bFGF fused to fibroin retained its biological activity, even after the bFGF-fused fibroin was fabricated into the spongy structure. The bFGF-fused fibroin sponge has the potential for widespread application in the field of tissue engineering, and the method of fabricating this structure could be applicable to other recombinant bioactive fibroin proteins.

  19. Modulation of the binding of basic fibroblast growth factor and heparanase activity by purified λ-carrageenan oligosaccharides.

    PubMed

    Niu, Ting-Ting; Zhang, Dong-Sheng; Chen, Hai-Min; Yan, Xiao-Jun

    2015-07-10

    Inhibitors of angiogenesis and tumor metastasis are increasingly emerging as promising agents for cancer therapy. Here, we report λ-carrageenan oligosaccharides (λ-COs), highly-sulfated oligosaccharides acting as a basic fibroblast growth factor (bFGF) antagonist and heparanase inhibitor. λ-COs with degree of polymerization (DP) from 2 to 8 degraded by λ-carrageenase were separated and purified. The structures were identified by mass spectrometry. The activities of λ-COs are closely related with DP. λ-COs showed no cytotoxicity, but inactivated bFGF-induced cell proliferation; among them, λ-carraheptaose showed highest capability. Only λ-carraheptaose can effectively bind to bFGF. Binding kinetics showed that λ-carraheptaose and suramin had different binding modes, i.e., suramin displayed a fast association and fast dissociation, but λ-carraheptaose exhibited a slow association and slow dissociation. In addition, λ-COs showed the highest heparanase inhibitory ability and abolished the endothelial cell invasion. Thus, λ-COs may provide a tool to develop of new carbohydrate-based therapeutics against cancer and angiogenesis.

  20. Vergleich von rekombinanten Vaccinia- und DNA-Vektoren zur Tumorimmuntherapie im C57BL/6-Mausmodell

    NASA Astrophysics Data System (ADS)

    Johnen, Heiko

    2002-10-01

    In der vorliegenden Arbeit wurden Tumorimpfstoffe auf der Basis des Plasmid-Vektors pCI, modified vaccinia virus Ankara (MVA) und MVA-infizierten dendritischen Zellen entwickelt und durch Sequenzierung, Western blotting und durchflußzytometrische Analyse überprüft. Die in vivo Wirksamkeit der Vakzinen wurde in verschiedenen Tumormodellen in C57BL/6 Mäusen verglichen. Die auf dem eukaryotischen Expressionsvektor pCI basierende DNA-Vakzinierung induzierte einen sehr wirksamen, antigenspezifischen und langfristigen Schutz vor Muzin, CEA oder beta-Galactosidase exprimierenden Tumoren. Eine MVA-Vakzinierung bietet in den in dieser Arbeit durchgeführten Tumormodellen keinen signifikanten Schutz vor Muzin oder beta-Galactosidase exprimierenden Tumoren. Sowohl humane, als auch murine in vitro generierte dendritische Zellen lassen sich mit MVA – im Vergleich zu anderen viralen Vektoren – sehr gut infizieren. Die Expressionsrate der eingefügten Gene ist aber gering im Vergleich zur Expression in permissiven Wirtszellen des Virus (embryonale Hühnerfibroblasten). Es konnte gezeigt werden, daß eine MVA-Infektion dendritischer Zellen ähnliche Auswirkungen auf den Reifezustand humaner und muriner dendritischer Zellen hat, wie eine Infektion mit replikationskompetenten Vakzinia-Stämmen, und außerdem die Hochregulation von CD40 während der terminalen Reifung von murinen dendritischen Zellen inhibiert wird. Die während der langfristigen in vitro Kultur auf CEF-Zellen entstandenen Deletionen im MVA Genom führten zu einer starken Attenuierung und dem Verlust einiger Gene, die immunmodulatorische Proteine kodieren, jedoch nicht zu einer Verminderung des zytopathischen Effekts in dendritischen Zellen. Die geringe Expressionsrate und die beobachtete Inhibition der Expression kostimulatorischer Moleküle auf dendritischen Zellen kann für eine wenig effektive Induktion einer Immunantwort in MVA vakzinierten Tieren durch cross priming oder die direkte Infektion

  1. Vergleich von rekombinanten Vaccinia- und DNA-Vektoren zur Tumorimmuntherapie im C57BL/6-Mausmodell

    NASA Astrophysics Data System (ADS)

    Johnen, Heiko

    2002-10-01

    In der vorliegenden Arbeit wurden Tumorimpfstoffe auf der Basis des Plasmid-Vektors pCI, modified vaccinia virus Ankara (MVA) und MVA-infizierten dendritischen Zellen entwickelt und durch Sequenzierung, Western blotting und durchflußzytometrische Analyse überprüft. Die in vivo Wirksamkeit der Vakzinen wurde in verschiedenen Tumormodellen in C57BL/6 Mäusen verglichen. Die auf dem eukaryotischen Expressionsvektor pCI basierende DNA-Vakzinierung induzierte einen sehr wirksamen, antigenspezifischen und langfristigen Schutz vor Muzin, CEA oder beta-Galactosidase exprimierenden Tumoren. Eine MVA-Vakzinierung bietet in den in dieser Arbeit durchgeführten Tumormodellen keinen signifikanten Schutz vor Muzin oder beta-Galactosidase exprimierenden Tumoren. Sowohl humane, als auch murine in vitro generierte dendritische Zellen lassen sich mit MVA – im Vergleich zu anderen viralen Vektoren – sehr gut infizieren. Die Expressionsrate der eingefügten Gene ist aber gering im Vergleich zur Expression in permissiven Wirtszellen des Virus (embryonale Hühnerfibroblasten). Es konnte gezeigt werden, daß eine MVA-Infektion dendritischer Zellen ähnliche Auswirkungen auf den Reifezustand humaner und muriner dendritischer Zellen hat, wie eine Infektion mit replikationskompetenten Vakzinia-Stämmen, und außerdem die Hochregulation von CD40 während der terminalen Reifung von murinen dendritischen Zellen inhibiert wird. Die während der langfristigen in vitro Kultur auf CEF-Zellen entstandenen Deletionen im MVA Genom führten zu einer starken Attenuierung und dem Verlust einiger Gene, die immunmodulatorische Proteine kodieren, jedoch nicht zu einer Verminderung des zytopathischen Effekts in dendritischen Zellen. Die geringe Expressionsrate und die beobachtete Inhibition der Expression kostimulatorischer Moleküle auf dendritischen Zellen kann für eine wenig effektive Induktion einer Immunantwort in MVA vakzinierten Tieren durch cross priming oder die direkte Infektion

  2. Differentiation of ionic currents in CNS progenitor cells: dependence upon substrate attachment and epidermal growth factor.

    PubMed

    Feldman, D H; Thinschmidt, J S; Peel, A L; Papke, R L; Reier, P J

    1996-08-01

    Multipotential progenitor cells grown from central nervous system (CNS) tissues in defined media supplemented with epidermal growth factor (EGF), when attached to a suitable substratum, differentiate to express neural and glial histochemical markers and morphologies. To assess the functional characteristics of such cells, expression of voltage-gated Na+ and K+ currents (INa, IK) was studied by whole-cell patch clamp methods in progenitors raised from postnatal rat forebrain. Undifferentiated cells were acutely dissociated from proliferative "spheres," and differentiated cells were studied 1-25 days after plating spheres onto polylysine/laminin-treated coverslips. INa and IK were detected together in 58%, INa alone in 11%, and IK alone in 19% of differentiated cells recorded with K(+)-containing pipettes. With internal Cs+ (to isolate INa), INa up to 45 pA/pF was observed in some cells within 1 day after plating. I Na ranged up to 150 pA/pF subsequently. Overall, 84% of cells expressed I Na, with an average of 38 pA/pF. INa had fast kinetics, as in neurons, but steadystate inactivation curves were strongly negative, resembling those of glial INa. Inward tail currents sensitive to [K+]out were observed upon repolarization after the 10-ms test pulse with internal Cs+, indicating the expression of K+ channels in 82% of cells. In contrast to the substantial currents observed in differentiating cells, little or no INa or Ik-tail currents were detected in recordings from cells acutely dissociated from spheres. Thus, in the presence of EGF, ionic currents develop early during differentiation induced by attachment to an appropriate substratum. Cells switched from EGF to basic fibroblast growth factor (bFGF) when plated onto coverslips showed greatly reduced proliferation and developed less neuron-like morphologies than cells plated in the presence of EGF. INa was observed in only 53% of bFGF-treated cells, with an average of 9 pA/pF. Thus, in contrast to reports that bFGF

  3. Einstellung und Wissen von Lehramtsstudierenden zur Evolution - ein Vergleich zwischen Deutschland und der Türkei

    NASA Astrophysics Data System (ADS)

    Graf, Dittmar; Soran, Haluk

    Es wird eine Untersuchung vorgestellt, in der Wissen und Überzeugungen von Lehramtsstudierenden aller Fächer zum Thema Evolution an zwei Universitäten in Deutschland und der Türkei erhoben worden sind. Die Befragung wurde in Dortmund und in Ankara durchgeführt. Es stellte sich heraus, dass ausgeprägte Defizite im Verständnis der Evolutionsmechanismen herrschen. Viele Studierende, insbesondere aus der Türkei, sind nicht von der Faktizität der Evolution überzeugt. Dies gilt sowohl für Studierende mit Fach Biologie als auch für Studierende mit anderen Fächern. Näher untersucht worden sind die Faktoren, die die Überzeugungen zur Evolution beeinflussen können, was ja in Anbetracht der hohen Ablehnungsrate der Evolution von besonderem Interesse ist. Das Vertrauen in die Wissenschaft spielt hierbei eine besondere Rolle: Wer der Wissenschaft vertraut, ist auch eher von der Evolution überzeugt, als diejenigen, die skeptisch gegenüber der Wissenschaft sind.

  4. [COPD und Klangtherapie: Pilotstudie zur Wirksamkeit einer Behandlung mit Körpertambura bei COPD-Patienten].

    PubMed

    Hartwig, Bernhard; Schmidt, Stefan; Hartwig, Isabella

    2016-01-01

    Hintergrund: Erkrankungen der Atemorgane treten mit steigendem Alter öfter auf, nehmen weltweit zu und sind häufige Ursachen für Morbidität und Mortalität. In dieser Pilotstudie wurde der Frage nachgegangen, ob eine einmalige 10-minütige Behandlung mit einer Körpertambura eine signifikante und effektive Verbesserung der Lungenfunktion von Patienten mit chronisch-obstruktiver Lungenerkrankung (COPD; GOLD-Stadium A oder B) erbringen kann. Patienten und Methoden: 54 Probanden konnten je zur Hälfte in eine Behandlungsgruppe (Körpertambura) und eine aktive Kontrollgruppe (Atemtherapie) randomisiert werden. Eine Bestimmung der Lungenfunktionsmessparameter «Einsekundenkapazität» (FEV1) und «inspiratorische Vitalkapazität» (IVC) zu den Zeitpunkten T1 (Baseline), T2 (direkt nach Behandlung) und als Follow-up etwa 3 Wochen nach T1 (T3). Ergebnisse: Die Behandlungsgruppe zeigte sich der Kontrollgruppe in beiden Werten signifikant überlegen. Die Zeit-×-Gruppe-Interaktion (Varianzanalyse) ergab p = 0,001 (FEV1) bzw. p = 0,04 (IVC). Die Behandlungsgruppe zeigte bei beiden Werten eine Verbesserung von klinischer Relevanz. Schlussfolgerung: Diese Ergebnisse zeigen, dass die Klangbehandlung mittels einer Körpertambura - neben den schulmedizinischen, leitliniengerechten Therapien - eine zusätzliche, nebenwirkungsarme, aber durchaus klinisch wirksame Option für die Behandlung von COPD-Patienten darstellen kann, um deren Lebensqualität zu stabilisieren und zu verbessern. PMID:27606616

  5. Molecular Imaging for Comparison of Different Growth Factors on Bone Marrow-Derived Mesenchymal Stromal Cells' Survival and Proliferation In Vivo.

    PubMed

    Qiao, Hongyu; Zhang, Ran; Gao, Lina; Guo, Yanjie; Wang, Jinda; Zhang, Rongqing; Li, Xiujuan; Li, Congye; Chen, Yundai; Cao, Feng

    2016-01-01

    Introduction. Bone marrow-derived mesenchymal stromal cells (BMSCs) have emerged as promising cell candidates but with poor survival after transplantation. This study was designed to investigate the efficacy of VEGF, bFGF, and IGF-1 on BMSCs' viability and proliferation both in vivo and in vitro using bioluminescence imaging (BLI). Methods. BMSCs were isolated from β-actin-Fluc(+) transgenic FVB mice, which constitutively express firefly luciferase. Apoptosis was induced by hypoxia preconditioning for up to 24 h followed by flow cytometry and TUNEL assay. 10(6) BMSCs with/without growth factors were injected subcutaneously into wild type FVB mice's backs. Survival of BMSCs was longitudinally monitored using bioluminescence imaging (BLI) for 5 weeks. Protein expression of Akt, p-Akt, PARP, and caspase-3 was detected by Western blot. Results. Hypoxia-induced apoptosis was significantly attenuated by bFGF and IGF-1 compared with VEGF and control group in vitro (P < 0.05). When combined with matrigel, IGF-1 showed the most beneficial effects in protecting BMSCs from apoptosis in vivo. The phosphorylation of Akt had a higher ratio in the cells from IGF-1 group. Conclusion. IGF-1 could protect BMSCs from hypoxia-induced apoptosis through activation of p-Akt/Akt pathway. PMID:27419126

  6. The effect of diclofenac on proliferation and production of growth factors by endothelial cells (HMEC-1) under hypoxia and inflammatory conditions.

    PubMed

    Wiktorowska-Owczarek, Anna

    2014-03-01

    Diclofenac belongs to non-steroidal anti-inflammatory drugs (NSAIDs) and non-selective COX inhibitors. The aim of this study was to examine the effect of diclofenac on endothelial cell proliferation under the influence of hypoxia or inflammatory conditions. Another goal was to check whether diclofenac modulates the secretion of angiogenic factors such as VEGF and bFGF in human microvascular endothelial cells (HMEC-1) in the presence of CoCl2 or lipopolysaccharide (LPS), which could influence the endothelial cells in an autocrine manner or other cells in a paracrine manner. HMEC-1 cells were treated with 0.1 and 0.3 mmol L-1 diclofenac in the presence of 100 μg mL-1 LPS or 200 μmol L-1 CoCl2. Diclofenac decreased cell viability under hypoxia and inflammatory conditions. The stimulation of bFGF secretion by LPS in microvascular endothelial cells (HMEC-1 cell) was attenuated by diclofenac. Diclofenac increased the secretion of VEGF induced by LPS and hypoxia.

  7. Neurologic disease described in the Journal of Empirical Psychology (Gnothi Sauton oder Magazin zur Erfahrungsseelenkunde), 1783-1793.

    PubMed

    Förstl, H

    1992-02-01

    Know Thyself or Journal of Empirical Psychology (Gnothi Sauton oder Magazin zur Erfahrungsseelenkunde), 1783-1793, was the first of its kind--concentrating on nervous and mental disturbances and marking the beginning of periodical neuropsychiatric publications. The editor, Karl Philipp Moritz, and the contributors, many of them lay people, were particularly interested in disturbances of language and consciousness. Descriptions of epilepsy, Sydenham's chorea, jargon aphasia, and dementia are briefly summarized. The case material from the Journal was soon translated and integrated in later work. The Journal itself and its "empirical" approach became a model for publications that followed. PMID:1736853

  8. Variabilität des Reviergesangs des Buchfinken (Fringilla coelebs) zur Raum-Zeit-Beschreibung von Metapopulationen

    NASA Astrophysics Data System (ADS)

    Nolte, Björn

    2003-10-01

    Der Buchfinkengesang wurde in Potsdam in zwei Hauptpopulationen über drei Jahre aufgenommen. Jedes Individuum wurde eindeutig am individuellen Strophentypenrepertoire identifiziert. Ein weiterer Punkt der die individuelle Wiedererkennung bestätigt ist die hohe Standorttreue der adulten Männchen. Die beschriebene Methode eignet sich für die Untersuchung von gesamten Populationen, um den Wandel des Gesangs von Populationen in Raum und Zeit zu beschreiben. Die Haupterkenntnisse der Arbeit sind: - Die Gesamtanzahl der Grundstrophentypen innerhalb einer Population bleibt über Jahre konstant. - Die relative Häufigkeit jedes einzelnen Strophentyps variiert von Jahr zu Jahr und von Population zu Population. - Gesangslernen erfolgt exakt mit einem Korrektheitsgrad von mindestens 96%. - Das Song-Sharing ist innerhalb der Population hoch. Die diskutierten Mechanismen für das Song-Sharing sind: Die Lebenserwartung, das Zugverhalten, das Lernverhalten, die Etabliertheit von Strophentypen, Weibchenpräferenzen und die Reaktionen der territorialen Männchen. - Weiterhin wurde ein Modell zur kulturellen Evolution des Buchfinkengesangs programmiert, um die Rolle der Einflussfaktoren, wie Fehlerquote, Abwanderungsrate und Laufzeit zu ermitteln. Der Wandel des Dialektes erfolgt graduell in Raum und Zeit. Daher sind keine scharfen Dialektgrenzen anzutreffen. Trotz dieser Tatsache markieren die etablierten Strophentypen die Population. 50 % der Juvenilen siedeln am Geburtsort, auf diese Weise bleibt der Dialekt erhalten und Inzest wird vermieden. -Analysiert man das Repertoire benachbarten Männchen bei isolierten Alleen, so entspricht die Gesangsangleichung in etwa dem Zufall. -Intraindividuelle Vergleiche der quantitativen Parameter des jeweiligen Strophentyps wurden saisonal und annuell durchgeführt. Saisonal konnten für einen Strophentyp ein Trend ermittelt werden. Bei jährlichen Vergleichen konnten intraindividuell ausschließlich nicht signifikante Ergebnisse ermittelt

  9. Variabilität des Reviergesangs des Buchfinken (Fringilla coelebs) zur Raum-Zeit-Beschreibung von Metapopulationen

    NASA Astrophysics Data System (ADS)

    Nolte, Björn

    2003-10-01

    Der Buchfinkengesang wurde in Potsdam in zwei Hauptpopulationen über drei Jahre aufgenommen. Jedes Individuum wurde eindeutig am individuellen Strophentypenrepertoire identifiziert. Ein weiterer Punkt der die individuelle Wiedererkennung bestätigt ist die hohe Standorttreue der adulten Männchen. Die beschriebene Methode eignet sich für die Untersuchung von gesamten Populationen, um den Wandel des Gesangs von Populationen in Raum und Zeit zu beschreiben. Die Haupterkenntnisse der Arbeit sind: - Die Gesamtanzahl der Grundstrophentypen innerhalb einer Population bleibt über Jahre konstant. - Die relative Häufigkeit jedes einzelnen Strophentyps variiert von Jahr zu Jahr und von Population zu Population. - Gesangslernen erfolgt exakt mit einem Korrektheitsgrad von mindestens 96%. - Das Song-Sharing ist innerhalb der Population hoch. Die diskutierten Mechanismen für das Song-Sharing sind: Die Lebenserwartung, das Zugverhalten, das Lernverhalten, die Etabliertheit von Strophentypen, Weibchenpräferenzen und die Reaktionen der territorialen Männchen. - Weiterhin wurde ein Modell zur kulturellen Evolution des Buchfinkengesangs programmiert, um die Rolle der Einflussfaktoren, wie Fehlerquote, Abwanderungsrate und Laufzeit zu ermitteln. Der Wandel des Dialektes erfolgt graduell in Raum und Zeit. Daher sind keine scharfen Dialektgrenzen anzutreffen. Trotz dieser Tatsache markieren die etablierten Strophentypen die Population. 50 % der Juvenilen siedeln am Geburtsort, auf diese Weise bleibt der Dialekt erhalten und Inzest wird vermieden. -Analysiert man das Repertoire benachbarten Männchen bei isolierten Alleen, so entspricht die Gesangsangleichung in etwa dem Zufall. -Intraindividuelle Vergleiche der quantitativen Parameter des jeweiligen Strophentyps wurden saisonal und annuell durchgeführt. Saisonal konnten für einen Strophentyp ein Trend ermittelt werden. Bei jährlichen Vergleichen konnten intraindividuell ausschließlich nicht signifikante Ergebnisse ermittelt

  10. Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor

    SciTech Connect

    Story, M.T. )

    1989-05-01

    To determine if fibroblasts could be a source of fibroblast growth factor (FGF) in tissue, cells were initiated in culture from newborn human foreskin. Fibroblast cell lysates promoted radiolabeled thymidine uptake by cultured quiescent fibroblasts. Seventy-nine percent of the growth-promoting activity of lysates was recovered from heparin-Sepharose. The heparin-binding growth factor reacted on immunoblots with antiserum to human placenta-derived basic FGF and competed with iodinated basic FGF for binding to antiserum to (1-24)bFGF synthetic peptide. To confirm that fibroblasts were the source of the growth factor, cell lysates were prepared from cells incubated with radiolabeled methionine. Heparin affinity purified material was immunoprecipitated with basic FGF antiserum and electrophoresed. Radiolabeled material was detected on gel autoradiographs in the same molecular weight region as authentic iodinated basic FGF. The findings are consistant with the notion that cultured fibroblasts express basic FGF. As these cells also respond to the mitogen, it is possible that the regulation of their growth is under autocrine control. Fibroblasts may be an important source of the growth factor in tissue.

  11. Control of zinc homeostasis in Agrobacterium tumefaciens via zur and the zinc uptake genes znuABC and zinT.

    PubMed

    Bhubhanil, Sakkarin; Sittipo, Panida; Chaoprasid, Paweena; Nookabkaew, Sumontha; Sukchawalit, Rojana; Mongkolsuk, Skorn

    2014-11-01

    The Agrobacterium tumefaciens zinc uptake regulator (Zur) was shown to negatively regulate the zinc uptake genes znuABC, encoding a zinc transport system belonging to the ATP-binding cassette (ABC) transporter family, and zinT, which encodes a periplasmic zinc-binding protein. The expression of znuABC and zinT was inducible when cells were grown in medium containing a metal chelator (EDTA), and this induction was shown to be specific for zinc depletion. The expression of znuABC was reduced in response to increased zinc in a dose-dependent manner, and zinT had a less pronounced but similar pattern of zinc-regulated expression. The inactivation of zur led to constitutively high expression of znuABC and zinT. In addition, a zur mutant had an increased total zinc content compared to the WT NTL4 strain, whereas the inactivation of zinT caused a reduction in the total zinc content. The zinT gene is shown to play a dominant role and to be more important than znuA and znuB for A. tumefaciens survival under zinc deprivation. ZinT can function even when ZnuABC is inactivated. However, mutations in zur, znuA, znuB or zinT did not affect the virulence of A. tumefaciens. PMID:25227896

  12. Re-Imagining "Bildung Zur Humanität": How I Developed the Dialogos Approach to Practical Philosophy through Action Inquiry Research

    ERIC Educational Resources Information Center

    Helskog, Guro Hansen

    2015-01-01

    This paper presents an account of how I developed the Dialogos approach to practical philosophy through action inquiry research. The process of development is understood as a contribution to the reconstruction of the notion "Bildung zur Humanität" as an ideal in education. Core perspectives, traditions and purposes involved in the action…

  13. Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer's disease.

    PubMed

    Zhang, Chi; Chen, Jie; Feng, Chengcheng; Shao, Xiayan; Liu, Qingfeng; Zhang, Qizhi; Pang, Zhiqing; Jiang, Xinguo

    2014-01-30

    Disabilities caused by neurodegeneration have become one of the main causes of mortality in elderly population, with drug distribution to the brain remaining one of the most difficult challenges in the treatment of the central nervous system (CNS) diseases due to the existence of blood-brain barrier. Lectins modified polyethylene glycol-polylactide-polyglycolide (PEG-PLGA) nanoparticles could enhance the drug delivery to the brain following intranasal administration. In this study, basic fibroblast growth factor (bFGF) was entrapped in nanoparticles conjugated with Solanum tuberosum lectin (STL), which selectively binds to N-acetylglucosamine on the nasal epithelial membrane for its brain delivery. The resulting nanoparticles had uniform particle size and negative zeta potential. The brain distribution of the formulations following intranasal administration was assessed using radioisotopic tracing method. The areas under the concentration-time curve of (125)I-bFGF in the olfactory bulb, cerebrum, and cerebellum of rats following nasal application of STL modified nanoparticles (STL-bFGF-NP) were 1.79-5.17 folds of that of rats with intravenous administration, and 0.61-2.21 and 0.19-1.07 folds higher compared with intranasal solution and unmodified nanoparticles, respectively. Neuroprotective effect was evaluated using Mirror water maze task in rats with intracerebroventricular injection of β-amyloid25-35 and ibotenic acid. The spatial learning and memory of Alzheimer's disease (AD) rats in STL-bFGF-NP group were significantly improved compared with AD model group, and were also better than other preparations. The results were consistent with the value of choline acetyltransferase activity of rat hippocampus as well as the histological observations of rat hippocampal region. The histopathology assays also confirmed the in vivo safety of STL-bFGF-NP. These results clearly indicated that STL-NP was a promising drug delivery system for peptide and protein drugs such as

  14. Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer's disease.

    PubMed

    Zhang, Chi; Chen, Jie; Feng, Chengcheng; Shao, Xiayan; Liu, Qingfeng; Zhang, Qizhi; Pang, Zhiqing; Jiang, Xinguo

    2014-01-30

    Disabilities caused by neurodegeneration have become one of the main causes of mortality in elderly population, with drug distribution to the brain remaining one of the most difficult challenges in the treatment of the central nervous system (CNS) diseases due to the existence of blood-brain barrier. Lectins modified polyethylene glycol-polylactide-polyglycolide (PEG-PLGA) nanoparticles could enhance the drug delivery to the brain following intranasal administration. In this study, basic fibroblast growth factor (bFGF) was entrapped in nanoparticles conjugated with Solanum tuberosum lectin (STL), which selectively binds to N-acetylglucosamine on the nasal epithelial membrane for its brain delivery. The resulting nanoparticles had uniform particle size and negative zeta potential. The brain distribution of the formulations following intranasal administration was assessed using radioisotopic tracing method. The areas under the concentration-time curve of (125)I-bFGF in the olfactory bulb, cerebrum, and cerebellum of rats following nasal application of STL modified nanoparticles (STL-bFGF-NP) were 1.79-5.17 folds of that of rats with intravenous administration, and 0.61-2.21 and 0.19-1.07 folds higher compared with intranasal solution and unmodified nanoparticles, respectively. Neuroprotective effect was evaluated using Mirror water maze task in rats with intracerebroventricular injection of β-amyloid25-35 and ibotenic acid. The spatial learning and memory of Alzheimer's disease (AD) rats in STL-bFGF-NP group were significantly improved compared with AD model group, and were also better than other preparations. The results were consistent with the value of choline acetyltransferase activity of rat hippocampus as well as the histological observations of rat hippocampal region. The histopathology assays also confirmed the in vivo safety of STL-bFGF-NP. These results clearly indicated that STL-NP was a promising drug delivery system for peptide and protein drugs such as

  15. Heterogeneity of cytokine and growth factor gene expression in human melanoma cells with different metastatic potentials.

    PubMed

    Singh, R K; Gutman, M; Radinsky, R

    1995-01-01

    The purpose of this study was to determine the mRNA expression level of multiple cytokine and growth factor genes in human malignant melanoma. Melanoma cells were isolated from several surgical specimens, adapted to growth in culture, characterized for their ability to produce experimental metastases in nude mice, and assessed for cytokine and growth factor steady-state gene expression. Highly metastatic in vivo- and in vitro-derived variants isolated from a single melanoma, A375, were also analyzed. Northern blot analyses revealed that all melanomas analyzed constitutively expressed steady-state mRNA transcripts for the growth and angiogenic factors, basic fibroblast growth factor (bFGF), and transforming growth factor alpha (TGF-alpha), which correlated with metastatic propensity. Only one highly metastatic melanoma, TXM-1, originally isolated from a lymph node metastasis, expressed mRNA transcripts specific for monocyte chemotactic and activating factor (MCAF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, of the nine melanomas examined, only TXM-1 expressed interleukin (IL)-1 alpha, IL-1 beta, and IL-6, important immunomodulatory cytokines. These data demonstrate the differential and heterogeneous expression of cytokine and growth factor genes in human malignant melanoma. PMID:7648437

  16. Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved.

    PubMed

    Pratsinis, Harris; Kletsas, Dimitris

    2015-01-01

    Intervertebral disc (IVD) degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D) organotypic milieu, comprising characteristic molecules of IVD's extracellular matrix. In particular, annulus fibrosus (AF) cells were cultured inside collagen type-I gels, while nucleus pulposus (NP) cells in chondroitin sulfate A (CSA) supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF), and Insulin-Like Growth Factor-I (IGF-I) were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration. PMID:26583105

  17. Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

    PubMed Central

    Pratsinis, Harris; Kletsas, Dimitris

    2015-01-01

    Intervertebral disc (IVD) degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D) organotypic milieu, comprising characteristic molecules of IVD's extracellular matrix. In particular, annulus fibrosus (AF) cells were cultured inside collagen type-I gels, while nucleus pulposus (NP) cells in chondroitin sulfate A (CSA) supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF), and Insulin-Like Growth Factor-I (IGF-I) were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration. PMID:26583105

  18. Regulation of serotonin transporter gene expression in human glial cells by growth factors.

    PubMed

    Kubota, N; Kiuchi, Y; Nemoto, M; Oyamada, H; Ohno, M; Funahashi, H; Shioda, S; Oguchi, K

    2001-04-01

    The aims of this study were to identify monoamine transporters expressed in human glial cells, and to examine the regulation of their expression by stress-related growth factors. The expression of serotonin transporter mRNA was detected by reverse transcriptase-polymerase chain reaction in normal human astrocytes, whereas the dopamine transporter (DAT) and the norepinephrine transporter (NET) were not detected. The cDNA sequence of the "glial" serotonin transporter in astrocytes was consistent with that reported for the "neuronal" serotonin transporter (SERT). Moreover, we also demonstrated SERT expression in glial fibrillary acidic protein-positive cells by immunocytochemical staining in normal human astrocytes. Serotonin transporter gene expression was also detected in glioma-derived cell lines (A172, KG-1-C and KGK). Addition of basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) for 2 days increased serotonin transporter gene expression in astrocytes and JAR (human choriocarcinoma cell line). Basic fibroblast growth factor, but not epidermal growth factor, increased specific [3H]serotonin uptake in astrocytes in a time (1-4 days)- and concentration (20-100 ng/ml)-dependent manner. The expression of genes for basic fibroblast growth factor and epidermal growth factor receptors was detected in astrocytes. These findings suggest that the expression of the serotonin transporter in human glial cells is positively regulated by basic fibroblast growth factor. PMID:11301061

  19. Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

    SciTech Connect

    Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

    1984-05-01

    The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble /sup 3/H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl/sub 2/ (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of /sup 3/H preceded the appearance of Factor IXa activity, and the percentage of /sup 3/H released remained constant when the mole fraction of /sup 3/H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of /sup 3/H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant.

  20. Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

    PubMed

    Kumagai, Motoyuki; Marui, Akira; Tabata, Yasuhiko; Takeda, Takahide; Yamamoto, Masaya; Yonezawa, Atsushi; Tanaka, Shiro; Yanagi, Shigeki; Ito-Ihara, Toshiko; Ikeda, Takafumi; Murayama, Toshinori; Teramukai, Satoshi; Katsura, Toshiya; Matsubara, Kazuo; Kawakami, Koji; Yokode, Masayuki; Shimizu, Akira; Sakata, Ryuzo

    2016-05-01

    As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-μg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.

  1. Thymidine phosphorylase in cancer cells stimulates human endothelial cell migration and invasion by the secretion of angiogenic factors

    PubMed Central

    Bijnsdorp, I V; Capriotti, F; Kruyt, F A E; Losekoot, N; Fukushima, M; Griffioen, A W; Thijssen, V L; Peters, G J

    2011-01-01

    Background: Thymidine phosphorylase (TP) is often overexpressed in tumours and has a role in tumour aggressiveness and angiogenesis. Here, we determined whether TP increased tumour invasion and whether TP-expressing cancer cells stimulated angiogenesis. Methods: Angiogenesis was studied by exposing endothelial cells (HUVECs) to conditioned medium (CM) derived from cancer cells with high (Colo320TP1=CT-CM, RT112/TP=RT-CM) and no TP expression after which migration (wound-healing-assay) and invasion (transwell-assay) were determined. The involvement of several angiogenic factors were examined by RT–PCR, ELISA and blocking antibodies. Results: Tumour invasion was not dependent on intrinsic TP expression. The CT-CM and RT-CM stimulated HUVEC-migration and invasion by about 15 and 40%, respectively. Inhibition by 10 μ TPI and 100 μ L-dR, blocked migration and reduced the invasion by 50–70%. Thymidine phosphorylase activity in HUVECs was increased by CT-CM. Reverse transcription-polymerase chain reaction revealed a higher mRNA expression of bFGF (Colo320TP1), IL-8 (RT112/TP) and TNF-α, but not VEGF. Blocking antibodies targeting these factors decreased the migration and invasion that was induced by the CT-CM and RT-CM, except for IL-8 in CT-CM and bFGF in RT-CM. Conclusion: In our cell line panels, TP did not increase the tumour invasion, but stimulated the migration and invasion of HUVECs by two different mechanisms. Hence, TP targeting seems to provide a potential additional strategy in the field of anti-angiogenic therapy. PMID:21386840

  2. Role of fibroblast growth factor receptors in astrocytic stem cells

    PubMed Central

    Galvez-Contreras, Alma Y.; Gonzalez-Castaneda, Rocio E; Luquin, Sonia; Gonzalez-Perez, Oscar

    2012-01-01

    There are two well-defined neurogenic regions in the adult brain, the subventricular zone (SVZ) lining the lateral wall of the lateral ventricles and, the subgranular zone (SGZ) in the dentate gyrus at the hippocampus. Within these neurogenic regions, there are neural stem cells with astrocytic characteristics, which actively respond to the basic fibroblast growth factor (bFGF, FGF2 or FGF-β) by increasing their proliferation, survival and differentiation, both in vivo and in vitro. FGF2 binds to fibroblast growth factor receptors 1 to 4 (FGFR1, FGFR2, FGFR3, FGFR4). Interestingly, these receptors are differentially expressed in neurogenic progenitors. During development, FGFR-1 and FGFR-2 drive oligodendrocytes and motor neuron specification. In particular, FGFR-1 determines oligodendroglial and neuronal cell fate, whereas FGFR-2 is related to oligodendrocyte specification. In the adult SVZ, FGF-2 promotes oligodendrogliogenesis and myelination. FGF-2 deficient mice show a reduction in the number of new neurons in the SGZ, which suggests that FGFR-1 is important for neuronal cell fate in the adult hippocampus. In human brain, FGF-2 appears to be an important component in the anti-depressive effect of drugs. In summary, FGF2 is an important modulator of the cell fate of neural precursor and, promotes oligodendrogenesis. In this review, we describe the expression pattern of FGFR2 and its role in neural precursors derived from the SVZ and the SGZ. PMID:22347841

  3. Die qualitätskontrolle als hilfsmittel zur festlegung der produktionsparameter bei der herstellung von lwr-brennstoffen

    NASA Astrophysics Data System (ADS)

    Sondermann, T.

    1982-04-01

    ZusammenfassungDer bekannte Vorteil des AUC-Verfahrens, ein UO 2-Pulver zu liefern, das ohne Zwischenschritte direkt zu Tabletten verpreβt werden kann, geht mit einer weiteren, weniger bekannten positiven Eigenschaft einher: Mit der Wahl der Produktionsparameter bei der UO 2-Pulverherstellung können die Qualitätsmerkmale der Brennstofftabletten direkt gesteuert werden. Wie umfangreiche Untersuchungen gezeigt haben, besteht ein mathematisch formulierbarer Zusammenhang zwischen den Produktionsparametern und den Pulver-bzw. Tablettenqualitäten. Das so erhaltene mathematische Modell gestattet es nun, exakt die Produktionsparameter einzustellen, die zur gewünschten Qualität führen, wobei gleichzeitig die wirtschaftliche Fahrweise gewählt werden kann.

  4. Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair

    PubMed Central

    Grulova, I.; Slovinska, L.; Blaško, J.; Devaux, S.; Wisztorski, M.; Salzet, M.; Fournier, I.; Kryukov, O.; Cohen, S.; Cizkova, D.

    2015-01-01

    Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate -based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG +GFs), compared to SCI animals without biomaterial treatment. PMID:26348665

  5. Book Review: Beitraege zur Astronomiegeschichte, Band 5 (Acta Historica Astronomiae Vol. 15)

    NASA Astrophysics Data System (ADS)

    Duerbeck, H. W.; Dick, W. R.; Hamel, J.

    2002-12-01

    The 15th volume of the Acta Historica Astronomiae is at the same time the fifth collection of essays on the history of astronomy (Beitraege zur Astronomiegeschichte, Band 5), edited by the historians of astronomy W.R. Dick (Potsdam) and J. Hamel (Berlin). Besides a few short notices and book reviews, the book contains 11 major articles, which deal with astronomical topics covering the time from the 16th to the 20th centuries. The first article, on the analysis and interpretation of historical horoscopes as a source of the history of science, is based on the inaugural lecture of its author, Guenther Oestmann. After a general introduction, which deals with the principles of horoscope making, the author discusses the horoscope of Count Heinrich Ranzau (1526-1598), the Danish governor of Schleswig-Holstein, who was a friend of Tycho Brahe. Oestmann shows that the astronomical-mathematical basis of such a horoscope can be reconstructed and interpreted. However, it is hardly possible to gain an insight in the process how the interpretation of a horoscope was done in detail. The second and third articles, by Franz Daxecker, deal with Athanasius Kircher and Christoph Scheiner, two catholic astronomers of the 17th century. Kircher's Organum Mathematicum is a calculating device that can be used in the fields of arithmetic, geometry, chronology, astronomy, astrology and others. The author provides extracts of the description of the Organum taken from a book by Caspar Schott, which deal with chronology and astronomy. A photograph of the Organum indicates that this tool consists of a set of tables glued on wooden or cardboard, but details of its contents and applications remain pretty obscure for the reader - a few elaborated examples would have been helpful. The second paper deals with the life of Christoph Scheiner SJ, the co-discoverer of sunspots (next to Galileo), after leaving Rome in 1633 - the year of the Galileo trial. Scheiner spent his later years in the Austrian and

  6. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    PubMed Central

    Dyondi, Deepti; Webster, Thomas J; Banerjee, Rinti

    2013-01-01

    Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF), and bone morphogenetic protein 7 (BMP7) were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure. PMID:23293519

  7. Chondroitin sulfate chains on syndecan-1 and syndecan-4 from normal murine mammary gland epithelial cells are structurally and functionally distinct and cooperate with heparan sulfate chains to bind growth factors. A novel function to control binding of midkine, pleiotrophin, and basic fibroblast growth factor.

    PubMed

    Deepa, Sarama Sathyaseelan; Yamada, Shuhei; Zako, Masahiro; Goldberger, Olga; Sugahara, Kazuyuki

    2004-09-01

    A comparative analysis was carried out of heparan sulfate (HS) and chondroitin sulfate (CS) chains of the ectodomains of hybrid type transmembrane proteoglycans, syndecan-1 and -4, synthesized simultaneously by normal murine mammary gland epithelial cells. Although the HS chains were structurally indistinguishable, intriguingly the CS chains were structurally and functionally distinct, probably reflecting the differential regulation of sulfotransferases involved in the synthesis of HS and CS. The CS chains of the two syndecans comprised nonsulfated, 4-O-, 6-O-, and 4,6-O-disulfated N-acetylgalactosamine-containing disaccharide units and were significantly different, with a higher degree of sulfation for syndecan-4. Functional analysis using a BIAcore system showed that basic fibroblast growth factor (bFGF) specifically bound only to the HS chains of both syndecans, whereas midkine (MK) and pleiotrophin (PTN) bound not only to the HS but also to the CS chains. Stronger binding of MK and PTN to the CS chains of syndecan-4 than those of syndecan-1 was revealed, supporting the structural and functional differences. Intriguingly, removal of the CS chains decreased the association and dissociation rate constants of MK, PTN, and bFGF for both syndecans, suggesting the simultaneous binding of these growth factors to both types of chains, producing a ternary complex that transfers the growth factors to the corresponding cell surface receptors more efficiently compared with the HS chains alone. The involvement of the core protein was also shown in the binding of MK and PTN to syndecan-1, suggesting the possibility of cooperation with the HS and/or CS chains in the binding of these growth factors and their delivery to the cell surface receptors.

  8. Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

    PubMed

    McClain, D A; Paterson, A J; Roos, M D; Wei, X; Kudlow, J E

    1992-09-01

    We have investigated the regulation of the expression of two growth factors found in vascular smooth muscle, transforming growth factor alpha (TGF alpha) and basic fibroblast growth factor (bFGF). Cells cultured in medium containing 30 mM glucose exhibited a 2-fold increase in TGF alpha mRNA and a 3-fold increase in bFGF mRNA compared with cells grown in normal (5.5 mM) glucose. Glucosamine was more potent than glucose, leading to a 6-fold increase in TGF alpha mRNA. TGF alpha protein levels were also increased by glucosamine treatment, and the predominant species present was the membrane-bound precursor form of TGF alpha. To examine further the regulation of growth factors by sugars, cultured rat aortic smooth muscle cells were transfected with a plasmid construct consisting of a 1.2-kilobase-pair fragment of the TGF alpha promoter linked to a luciferase reporter gene. Increasing the concentration of glucose in the culture medium from 5.5 mM to 30 mM led to a rapid, 1.7-fold increase in the activity of the TGF alpha promoter. Glucosamine was much more potent than glucose in this stimulation, with 2 mM glucosamine causing a 12-fold increase in TGF alpha promoter activity. Insulin had no effect on luciferase activity in either the presence or the absence of added sugars. The glucose response element of the TGF alpha gene maps to a 130-base-pair segment that includes three potential binding sites for the transcription factor Sp1. We conclude that high glucose concentrations such as are reached in diabetes mellitus can stimulate the transcription of the genes for growth factors in vascular smooth muscle cells. This signaling pathway apparently involves the metabolism of glucose to glucosamine. This effect could be representative of nutritional regulation of a family of genes and could contribute to the toxicity of hyperglycemia and the vascular complications of diabetes. PMID:1518840

  9. Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

    PubMed Central

    McClain, D A; Paterson, A J; Roos, M D; Wei, X; Kudlow, J E

    1992-01-01

    We have investigated the regulation of the expression of two growth factors found in vascular smooth muscle, transforming growth factor alpha (TGF alpha) and basic fibroblast growth factor (bFGF). Cells cultured in medium containing 30 mM glucose exhibited a 2-fold increase in TGF alpha mRNA and a 3-fold increase in bFGF mRNA compared with cells grown in normal (5.5 mM) glucose. Glucosamine was more potent than glucose, leading to a 6-fold increase in TGF alpha mRNA. TGF alpha protein levels were also increased by glucosamine treatment, and the predominant species present was the membrane-bound precursor form of TGF alpha. To examine further the regulation of growth factors by sugars, cultured rat aortic smooth muscle cells were transfected with a plasmid construct consisting of a 1.2-kilobase-pair fragment of the TGF alpha promoter linked to a luciferase reporter gene. Increasing the concentration of glucose in the culture medium from 5.5 mM to 30 mM led to a rapid, 1.7-fold increase in the activity of the TGF alpha promoter. Glucosamine was much more potent than glucose in this stimulation, with 2 mM glucosamine causing a 12-fold increase in TGF alpha promoter activity. Insulin had no effect on luciferase activity in either the presence or the absence of added sugars. The glucose response element of the TGF alpha gene maps to a 130-base-pair segment that includes three potential binding sites for the transcription factor Sp1. We conclude that high glucose concentrations such as are reached in diabetes mellitus can stimulate the transcription of the genes for growth factors in vascular smooth muscle cells. This signaling pathway apparently involves the metabolism of glucose to glucosamine. This effect could be representative of nutritional regulation of a family of genes and could contribute to the toxicity of hyperglycemia and the vascular complications of diabetes. Images PMID:1518840

  10. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules

    SciTech Connect

    Bashkin, P.; Doctrow, S.; Klagsbrun, M.; Svahn, C.M.; Folkman, J.; Vlodavsky, I. )

    1989-02-21

    Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ECM-bound FGF, but there was little or no release of FGF by modified nonanticoagulant heparins such as totally desulfated heparin, N-desulfated heparin, and N-acetylated heparin. FGF released from ECM was biologically active, as indicated by its stimulation of cell proliferation and DNA synthesis in vascular endothelial cells and 3T3 fibroblasts. Similar results were obtained in studies on release of endogenous FGF-like mitogenic activity from Descement's membranes of bovine corneas. It is suggested that ECM storage and release of bFGF provide a novel mechanism for regulation of capillary blood vessel growth. Whereas ECM-bound FGF may be prevented from acting on endothelial cells, its displacement by heparin-like molecules and/or HS-degrading enzymes may elicit a neovascular response.

  11. Growth factors in the treatment of early osteoarthritis

    PubMed Central

    Civinini, Roberto; Nistri, Lorenzo; Martini, Caterina; Redl, Birgit; Ristori, Gabriele; Innocenti, Massimo

    2013-01-01

    Summary Regenerative medicine is the science that studies the regeneration of biological tissues obtained through use of cells, with the aid of support structures and with biomolecules such as growth factors. As regards the growth factors the PRP, or the platelet-rich plasma, obtained from a withdrawal of autologous blood, concentrating the platelets, represents a safe, economical, easy to prepare and easy to apply source of growth factors. Numerous growth factors are in fact within the platelets and in particular a large number of them have a specific activity on neo-proliferation, on cartilage regeneration and in particular also an antiapoptotic effect on chondroblasts: - The PDGF which regulates the secretion and synthesis of collagen;- The EGF that causes cellular proliferation, endothelial chemotaxis and angiogenesis;- The VEGF that increases angiogenesis and vascular permeability;- The TGF-beta that stimulates the proliferation of undifferentiated MSC, stimulates chemotaxis of endothelial cells and angiogenesis;- The bFGF that promotes the growth and differentiation of chondrocytes and osteoblasts stimulates mitogenesis of mesenchymal cells, chondrocytes and osteoblasts. These properties have led to the development of studies that evaluated the efficacy of treatment of infiltrations in the knee and hip with platelet-derived growth factors. Regarding the knee it was demonstrated that in patients with moderate degree of gonarthrosis, the PRP is able to significantly reduce the pain and improve joint function, both on placebo and towards infiltrations with hyaluronic acid. The success of the treatment was proportional to the age of and inversely proportional to the severity of osteoarthritis according to Kellgren and Lawrence classification. The possibility of infiltrations guided with ultrasound into the hip led us to extend the indications also to hip arthrosis, as already showed by Sanchez. Even in coxarthrosis preliminary results at 6 and 12 months show that

  12. Protective effect of basic fibroblast growth factor on retinal injury induced by argon laser photocoagulation

    NASA Astrophysics Data System (ADS)

    Chen, P.; Zhang, C. P.; San, Q.; Wang, C. Z.; Yang, Z. F.; Kang, H. X.; Qian, H. W.

    2010-12-01

    Laser photocoagulation treatment is often complicated by a side effect of visual impairment, which is caused by the unavoidable laser-induced retinal destruction. At present no specific is found to cure this retinopathy. The aim of this study was to observe the neuroprotective effect of bFGF on laser-induced retinal injury. Chinchilla rabbits were divided into three groups and argon laser lesions were created in the retinas. Then bFGF or dexamethasone, a widely used ophthalmic preparation, or saline was given severally by retrobulbar injection. The retinal lesions were evaluated histologically and morphometrically, and visual function was examined by ERG. The results showed that bFGF administration better preserved morphology of retinal photoreceptors and significantly diminished the area of the lesions. Furthermore, bFGF promoted the restoration of the ERG b-wave amplitude. In rabbits treated with dexamethasone, however, the lesions showed almost no ameliorative changes. This is the first study to investigate the potential role of bFGF as a remedial agent in laser photocoagulation treatment. These findings suggest that bFGF has significant neuroprotective properties in the retina and this type of neuroprotection may be of clinical significance in reducing iatrogenic laser-induced retinal injuries in humans.

  13. Effects of nerve growth factor and basic fibroblast growth factor dual gene modification on rat bone marrow mesenchymal stem cell differentiation into neuron-like cells in vitro

    PubMed Central

    HU, YANG; ZHANG, YAN; TIAN, KANG; XUN, CHONG; WANG, SHOUYU; LV, DECHENG

    2016-01-01

    Recent studies regarding regenerative medicine have focused on bone marrow mesenchymal stem cells (BMSCs), which have the potential to undergo neural differentiation, and may be transfected with specific genes. BMSCs can differentiate into neuron-like cells in certain neurotropic circumstances in vitro. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are often used to induce neural differentiation in BMSCs in vitro. However, previous studies regarding their combined actions are insufficient. The present study is the first, to the best of our knowledge, to thoroughly assess the enhancement of neural differentiation of BMSCs following transfection with bFGF and NGF. Sprague-Dawley (SD) rat BMSCs were separated through whole bone marrow adherence, and were then passaged to the third generation. The cells were subsequently divided into five groups: The control group, which consisted of untransfected BMSCs; the plv-blank-transfected BMSCs group; the plv-bFGF-trans-fected BMSCs group; the plv-NGF-transfected BMSCs group; and the plv-NGF-bFGF co-transfected BMSCs group. Cell neural differentiation was characterized in terms of stem cell molecular expression, and the neuronal morphology and expression of neural-like molecules was detected in each of the groups. A total of 72 h post-transfection, the expression levels of neuron-specific enolase, glial fibrillary acidic protein, and nestin protein, were higher in the co-transfected group, as compared with the other groups, the expression levels of β-tubulin III were also increased in the co-transfected cells, thus suggesting the maturation of differentiated neuron-like cells. Furthermore, higher neuronal proliferation was observed in the co-transfected group, as compared with the other groups at passages 2, 4, 6 and 8. Western blotting demonstrated that the transfected groups exhibited a simultaneous increase in phosphorylation of the AKT and extracellular signal-regulated kinases (ERK) signaling pathway

  14. Book Review: Beitraege zur Astronomiegeschichte, Band 5 (Acta Historica Astronomiae Vol. 15)

    NASA Astrophysics Data System (ADS)

    Duerbeck, H. W.; Dick, W. R.; Hamel, J.

    2002-12-01

    The 15th volume of the Acta Historica Astronomiae is at the same time the fifth collection of essays on the history of astronomy (Beitraege zur Astronomiegeschichte, Band 5), edited by the historians of astronomy W.R. Dick (Potsdam) and J. Hamel (Berlin). Besides a few short notices and book reviews, the book contains 11 major articles, which deal with astronomical topics covering the time from the 16th to the 20th centuries. The first article, on the analysis and interpretation of historical horoscopes as a source of the history of science, is based on the inaugural lecture of its author, Guenther Oestmann. After a general introduction, which deals with the principles of horoscope making, the author discusses the horoscope of Count Heinrich Ranzau (1526-1598), the Danish governor of Schleswig-Holstein, who was a friend of Tycho Brahe. Oestmann shows that the astronomical-mathematical basis of such a horoscope can be reconstructed and interpreted. However, it is hardly possible to gain an insight in the process how the interpretation of a horoscope was done in detail. The second and third articles, by Franz Daxecker, deal with Athanasius Kircher and Christoph Scheiner, two catholic astronomers of the 17th century. Kircher's Organum Mathematicum is a calculating device that can be used in the fields of arithmetic, geometry, chronology, astronomy, astrology and others. The author provides extracts of the description of the Organum taken from a book by Caspar Schott, which deal with chronology and astronomy. A photograph of the Organum indicates that this tool consists of a set of tables glued on wooden or cardboard, but details of its contents and applications remain pretty obscure for the reader - a few elaborated examples would have been helpful. The second paper deals with the life of Christoph Scheiner SJ, the co-discoverer of sunspots (next to Galileo), after leaving Rome in 1633 - the year of the Galileo trial. Scheiner spent his later years in the Austrian and

  15. Effects of ganglioside GM1 and neural growth factor on neural stem cell proliferation and differentiation.

    PubMed

    Wang, Q; Song, Y H; Tang, Z; Wang, Z P; Xu, Q; Bao, N

    2016-01-01

    Neurogenesis, recovery from nerve injury, neurodegeneration, and Parkinson's disease affect people's health, yet the underlying molecular mechanisms remain elusive. Here, we investigated the effect of ganglioside GM1 and neural growth factor (NGF) on neural stem cell (NSC) proliferation and differentiation in vitro to provide a scientific basis for comprehensive treatment of nervous system diseases via NSC application. As widely applied methods of relatively high accuracy, cell counts and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays were used to assess NSC proliferation. In addition, western blotting was employed to determine NSC differentiation. Cell counts and MTT assays demonstrated that in epidermal growth factor (EGF)- and basic fibroblast growth factor (bFGF)-containing medium, a high concentration of GM1, but not NGF, significantly elevated NSC proliferation. In NSC cultures lacking EGF and bFGF, cell counts and MTT values were significantly increased compared to those in the negative control group on days 4, 7, and 10 after GM1 (25, 100, and 200 ng/mL) but not NGF (25, 50, 100, and 200 ng/mL) treatment. Western blotting revealed significantly increased expression of nestin (an NSC marker) in NSCs treated with GM1, and upregulation of glial fibrillary acidic protein (a glial cell marker) and neuron-specific enolase (a neuron marker) in those administered NGF. Our results suggest that GM1 and NGF induce NSC proliferation and differentiation, respectively, in a dose-dependent manner. PMID:27525911

  16. The isolation and characterization of growth regulatory factors produced by a herpes simplex virus Type 2 transformed mouse tumor cell line, H238

    SciTech Connect

    Stagg, R.B.

    1988-01-01

    This study was performed in an attempt to associate HSV-2-transformation with specific growth factors in order to develop a testable model for HSV-2-transformation. We report here the isolation and characterization of four growth regulatory factors produced by H238, an HSV-2-transformed mouse tumor cell line. These factors were separated from the H238-CM by heparin-sepharose affinity chromatography into three peaks of mitogenic activity and a fourth containing inhibitory activity for splenocytes. The three peaks of mitogenic activity have been identified based on physiochemical characteristics: the first supported the anchorage-independent growth of EGF treated NRK-c-49 cells and resembles transforming growth factor-{beta} (TGF-{beta}); the second bound to lectin-coated sepharose beads and was sensitive to trypsin, neuroaminidase, and the reducing agent dithiothreitol (DTT) and, resembled a platelet-derived growth factor (PDGF)-like factor; and the third displaced ({sup 125}I)-labeled basic fibroblast growth factor (bFGF) in a dose-dependent fashion when tested with a radioimmune assay. The fourth peak was inhibitory for a variety of splenocyte function assays. A model for the interaction of these factors in vivo is presented with an emphasis on testability.

  17. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    PubMed

    Lakshmanan, Rajesh; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

  18. Markers of angiogenesis and epidermal growth factor receptor signalling in patients with pancreatic and gastroesophageal junction cancer.

    PubMed

    Rohrberg, Kristoffer Staal; Skov, Birgit Guldhammer; Lassen, Ulrik; Christensen, Ib Jarle; Høyer-Hansen, Gunilla; Buysschaert, Ian; Pappot, Helle

    2010-01-01

    The epidermal growth factor receptor (EGFR) and angiogenesis are well established targets in anti-cancer therapy. Several targeted anti-cancer therapies are in clinical trials in pancreatic and gastroesophageal (GEJ) cancer. However, many patients do not respond to these targeted therapies and there is therefore an increasing need for biomarkers for selection of patients to these therapies. We investigated the expression of EGFR, vascular endothelial growth factor A (VEGF-A), and VEGF receptor 2 (VEGFR-2) in tumour tissue by immunohistochemistry, and soluble EGFR (sEGFR), soluble VEGFR-2 (sVEGFR-2), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), plasminogen activator inhibitor 1 (PAI-1), and different forms of the urokinase plasminogen activator receptor (uPAR): uPAR (I), uPAR (I-III), and uPAR (I-III)+(II-III) in plasma by quantitative immunoassays in 14 patients with pancreatic and GEJ cancer. We found expression in tumour tissue and the plasma levels to be similar to those found in patients with other tumour types. No correlation was found between the blood levels of soluble receptors and the corresponding tumour tissue levels. We conclude that these markers are present in pancreatic and GEJ cancer patients, and could be investigated further as predictive biomarkers in such patients treated with EGFR or angiogenesis targeted therapies.

  19. Zur Determination der zeitlichen Verteilung von Fortpflanzungsprozessen in Laborkulturen des Polychaeten Typosyllis prolifera

    NASA Astrophysics Data System (ADS)

    Franke, H.-D.

    1980-03-01

    Factors controlling the timing of reproduction in laboratory cultures of the polychaete Trposyllis prolifera. Typosyllis prolifera (Krohn) from Poreč (Yugoslavia) has been cultured for 12 successive generations. The life cycle of the species in the laboratory is described briefly. During their life individuals reproduce several times (up to 15) by stolonization which, under constant laboratory conditions (LD 16:8, 20 °C), is cyclic and takes place about every 30 days. Based on the investigations of Durchon (1959) and Wissocq (1966), experiments on extirpation and transplantation of the proventriculus have been carried out. The results suggest that an endocrine system anatomically connected to the proventriculus is important in the control of reproduction. Most likely, the endogenous reproductive cycle of an individual is controlled by periodical changes of the activity of this system. During the period following stolonization, the endocrine system of the proventriculus, which at this time shows its maximal activity, inhibits sexual development and enables regeneration of the segments lost as stolon. A subsequent decrease of the hormonal activity induces sexual maturation and epitokous metamorphosis, thus leading to further stolonization. Exogenous factors influencing the timing of reproduction probably affect the endocrine function of the proventriculus. Short-day photoperiods (LD 10:14) and low temperatures (12 °C) given simultaneously (i.e. winter conditions) totally suppress reproduction. Under normally favourable conditions (LD 16:8, 20 °C), reproductive processes can be prevented by starving or amputation of caudal segments. In all these cases, however, stolonization can be induced by removing the proventriculus. Exogenous factors also play a decisive role in synchronizing reproductive events within the species population. Under field conditions reproduction shows a lunar periodicity. The endogenous reproductive cycles of cultured specimens can be

  20. Delivery of basic fibroblast growth factors from heparinized decellularized adipose tissue stimulates potent de novo adipogenesis.

    PubMed

    Lu, Qiqi; Li, Mingming; Zou, Yu; Cao, Tong

    2014-01-28

    Scaffolds based on decellularized adipose tissue (DAT) are gaining popularity in adipose tissue engineering due to their high biocompatibility and adipogenic inductive property. However, previous studies involving DAT-derived scaffolds have not fully revealed their potentials for in vivo adipose tissue construction. With the aim of developing a more efficient adipose tissue engineering technique based on DAT, in this study, we investigated the in vivo adipogenic potential of a basic fibroblast growth factor (bFGF) delivery system based on heparinized DAT (Hep-DAT). To generate this system, heparins were cross-linked to mouse DATs by using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide and N-Hydroxysuccinimide. The bFGF-binding Hep-DATs were first tested for controlled release ability in vitro and then transplanted subcutaneously. Highly vascularized adipose tissues were formed 6weeks after transplantation. Histology and gene expression analysis revealed that majority of the Hep-DAT scaffolds were infiltrated with host-derived adipose tissues that possessed similar adipogenic and inflammatory gene expression as endogenous adipose tissues. Additionally, strong de novo adipogenesis could also be induced when bFGF-binding Hep-DATs were thoroughly minced and injected subcutaneously. In conclusion, our study demonstrated that bFGF-binding Hep-DAT could be an efficient, biocompatible and injectable adipogenic system for in vivo adipose tissue engineering.

  1. Erweiterte Modelle zur Analyse der Farb- und Helligkeitsprofile von Edge-on-Galaxien.

    NASA Astrophysics Data System (ADS)

    Mayr, S.

    In this work the influence of radial gradients in galactic disks on the vertical luminosity and colour profiles of edge-on galaxies is investigated. The model of a galactic disk used for this purpose consists of a stellar and a dust component. The radially exponential, self-gravitating stellar component consists of isothermal subpopulations with different ages according to the star formation history. The velocity dispersion of the stars increases with age due to a disk heating process. The star formation history and the history of metallicity enrichment are chosen from consistent models for the chemical evolution of galactic disks. With the method of photometric evolutionary synthesis the time development of the luminosities of the stars is computed. Absorption and reddening of the star light caused by the dust are modelled by a radially and vertically exponential dust distribution. The effect of an increasing scale height of the stars with galactocentric radius on the luminosity and colour profiles of edge-on galaxies is investigated to explain new observations of an increasing scale height with galactocentric radius. It is found, that for an increase of the scale height (a factor 3) of the stars is necessary. An increase of the scale height of the stars affects the luminosity profiles but only very little the colour profiles. The effect of a variation of the star formation history and the history of metallicity enrichment on the vertical luminosity and colour profiles is investigated. Radial colour gradients result which are in a qualitative way equivalent to those obtained in observations (eg. NGC 5907).

  2. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue.

    PubMed

    Hsiao, Sarah Tzu-Feng; Asgari, Azar; Lokmic, Zerina; Sinclair, Rodney; Dusting, Gregory James; Lim, Shiang Yong; Dilley, Rodney James

    2012-08-10

    Human adult mesenchymal stem cells (MSCs) support the engineering of functional tissue constructs by secreting angiogenic and cytoprotective factors, which act in a paracrine fashion to influence cell survival and vascularization. MSCs have been isolated from many different tissue sources, but little is known about how paracrine factor secretion varies between different MSC populations. We evaluated paracrine factor expression patterns in MSCs isolated from adipose tissue (ASCs), bone marrow (BMSCs), and dermal tissues [dermal sheath cells (DSCs) and dermal papilla cells (DPCs)]. Specifically, mRNA expression analysis identified insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor-D (VEGF-D), and interleukin-8 (IL-8) to be expressed at higher levels in ASCs compared with other MSC populations whereas VEGF-A, angiogenin, basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) were expressed at comparable levels among the MSC populations examined. Analysis of conditioned media (CM) protein confirmed the comparable level of angiogenin and VEGF-A secretion in all MSC populations and showed that DSCs and DPCs produced significantly higher concentrations of leptin. Functional assays examining in vitro angiogenic paracrine activity showed that incubation of endothelial cells in ASC(CM) resulted in increased tubulogenic efficiency compared with that observed in DPC(CM). Using neutralizing antibodies we concluded that VEGF-A and VEGF-D were 2 of the major growth factors secreted by ASCs that supported endothelial tubulogenesis. The variation in paracrine factors of different MSC populations contributes to different levels of angiogenic activity and ASCs maybe preferred over other MSC populations for augmenting therapeutic approaches dependent upon angiogenesis.

  3. [Assessment of parental stress using the "Eltern-Belastungs-Screening zur Kindeswohlgefährdung" (EBSK) - association with emotional and behavioral problems in children].

    PubMed

    Eichler, Anna K; Glaubitz, Katharina A; Hartmann, Luisa C; Spangler, Gottfried

    2014-07-01

    Parental stress is increased in clinical contexts (e.g., child psychiatry) and correlates with behavioral and emotional problems of children. In addition, parental stress can result in a biased parental perception of child's behavior and emotions. These interrelations were examined in a normal (N = 320) and a clinical (N = 75) sample. The "Eltern-Belastungs-Screening zur Kindeswohlgefährdung" (EBSK; Deegener, Spangler, Körner & Becker, 2009) was used for the assessment of parental stress. As expected, increased EBSK scores were overrepresented in the clinical sample. In both samples stressed parents reported having children with more behavioral and emotional problems. Children of stressed parents in turn reported significantly less problems than their parents did. The rating of independent third persons, e.g. teachers, was not available and should be added in future research. Restrictions in methodology and conclusions for practice are discussed. PMID:25005899

  4. Ixora coccinea Enhances Cutaneous Wound Healing by Upregulating the Expression of Collagen and Basic Fibroblast Growth Factor.

    PubMed

    Upadhyay, Aadesh; Chattopadhyay, Pronobesh; Goyary, Danswrang; Mitra Mazumder, Papiya; Veer, Vijay

    2014-01-01

    Background. Ixora coccinea L. (Rubiaceae) has been documented for traditional use in hypertension, menstrual irregularities, sprain, chronic ulcer, and skin diseases. In the present study, I. coccinea was subjected to in vitro and in vivo wound healing investigation. Methods. Petroleum ether, chloroform, methanol, and water sequential I. coccinea leaves extracts were evaluated for in vitro antioxidant, antimicrobial, and fibroblast proliferation activities. The promising I. coccinea methanol extract (IxME) was screened for in vivo wound healing activity in Wistar rat using circular excision model. Wound contraction measurement, hydroxyproline quantification, and western blot for collagen type III (COL3A1), basic fibroblast growth factor (bFGF), and Smad-2, -3, -4, and -7 was performed with 7-day postoperative wound granulation tissue. Gentamicin sulfate (0.01% w/w) hydrogel was used as reference standard. Results. IxME showed the potent antimicrobial, antioxidant activities, with significant fibroblast proliferation inducing activity, as compared to all other extracts. In vivo study confirmed the wound healing accelerating potential of IxME, as evidenced by faster wound contraction, higher hydroxyproline content, and improved histopathology of granulation tissue. Western blot analysis revealed that the topical application of I. coccinea methanol extract stimulates the fibroblast growth factor and Smad mediated collagen production in wound tissue. PMID:24624303

  5. A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production.

    PubMed

    Honda, Kenjiro; Okamoto, Koji; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Maesato, Kyoko; Ikee, Ryota; Moriya, Hidekazu; Hidaka, Sumi; Ohtake, Takayasu; Doi, Kent; Fujita, Toshiro; Kobayashi, Shuzo; Noiri, Eisei

    2011-12-01

    Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities because they did not respond to conventional therapies. Significant increases of hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT (P < 0.05), but no significant change was found for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), or tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 μg/ml ES group (P < 0.01). Furthermore, protease inhibitors suppressed the increase of HGF (P < 0.05). The HGF expression was increased in proportion to the ES protein concentration of 0.025 to 0.5 μg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than chymotrypsin or bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing therapy.

  6. Aerosol delivery of eukaryotic translation initiation factor 4E-binding protein 1 effectively suppresses lung tumorigenesis in K-rasLA1 mice.

    PubMed

    Chang, S-H; Kim, J-E; Lee, J-H; Minai-Tehrani, A; Han, K; Chae, C; Cho, Y-H; Yun, J-H; Park, K; Kim, Y-S; Cho, M-H

    2013-06-01

    Conventional radiotherapy or chemotherapy for the long-term survival of patients with lung cancer is still difficult for treatment in metastatic and advanced tumors. Therefore, the safe and effective approaches to the treatment of lung cancer are needed. In this study, the effect of delivered eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) on lung cancer progression was evaluated. Recombinant adeno-associated virus (rAAV)-M3/4E-BP1 was delivered into 6-week-old K-rasLA1 lung cancer model mice through a nose-only inhalation system twice a week for 4 weeks. Long-term repeated delivery of 4E-BP1 effectively reduced tumor progression in the lungs of K-rasLA1 mice. Reduction of eIF4E by overexpression of 4E-BP1 resulted in suppression of cap-dependent protein expression of basic fibroblast growth factor (bFGF or FGF-2) and vascular endothelial growth factor (VEGF). In addition, delivered 4E-BP1 inhibited the proliferation of lung cancer cells in K-rasLA1 mice model. Our results suggest that long-term repeated viral delivery of 4E-BP1 may provide a useful tool for designing lung cancer treatment. PMID:23640516

  7. Zur Bahndynamik niedrigfliegender Satelliten.

    NASA Astrophysics Data System (ADS)

    Scheinert, M.

    The satellite mission ARISTOTELES and STEP give the chance to determine the gravitational field of the Earth with high accuracy and up to the short-wave domain. This is due to the expected highly sensitive observations of gravitational gradients and tracking information obtained by GPS. The goal of the dissertation is to investigate especially the potentiality of the GPS tracking data to solve the coefficients of the long-wave domain in particular. The theory of Hill's equations forms an excellent tool to analyse the orbit perturbations of the satellites moving in nearly polar, nearly circular orbits of very low altitude. The derivation of the linear perturbation theory is dealt with in detail. On the basis of the linear theory numerical simulations were carried out which proofed the impossibility to solve the long-wave domain completely from tracking data of only one of the discussed satellites. But the orbit analysis allows to set up a so-called Tailored Model in each case which may support and complete the processing of the gradiometry data.

  8. Zur Geschichte der Geophysik

    NASA Astrophysics Data System (ADS)

    Strobach, Klaus

    1980-07-01

    Alfred Wegener's most important work, the theory of continental drift, has a key position in the history of geophysics and has crucially advanced the discussion of this central problem of geodynamics amongst supporters and adversaries. The aim of this paper is to paint a portrait of Wegener's personality, of his stations of life, and of his interests and research work. The conceptions of the origin of continents and oceans prior to Wegener, and the further development of his ideas after his death on the ice cup of Greenland 50 years ago are discussed.

  9. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    SciTech Connect

    Colleoni, Silvia; Giannelli, Serena G.; Armentero, Marie-Therese; Blandini, Fabio; Broccoli, Vania; Lazzari, Giovanna

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  10. Factor XII (Hageman factor) deficiency

    MedlinePlus

    ... takes longer than normal to clot in a test tube. Factor XII deficiency is a rare inherited disorder. Symptoms There are usually no symptoms. Exams and Tests Factor XII deficiency is most often found when ...

  11. Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation.

    PubMed

    Tada, A; Suzuki, I; Im, S; Davis, M B; Cornelius, J; Babcock, G; Nordlund, J J; Abdel-Malek, Z A

    1998-07-01

    Endothelin (ET)-1, alpha-melanocyte stimulating hormone (alpha-melanotropin; alpha-MSH), and basic fibroblast growth factor (bFGF) are keratinocyte-derived factors that interact synergistically to stimulate human melanocyte proliferation. ET-1 has a dose-dependent mitogenic effect on human melanocytes and a biphasic effect on melanogenesis: a stimulatory effect at subnanomolar concentrations, and an inhibitory effect at concentrations equal to or higher than 1 nM. Human melanocytes express ET B receptors. Brief treatment of melanocytes with ET-1 caused up-regulation of alpha-MSH receptor mRNA but did not alter ET B receptor mRNA level. ET-1 modulates the response of human melanocytes to UV rays (UVRs). Treatment of melanocytes with 10 nM ET-1 immediately after exposure to UVRs enabled them to overcome the G1 growth arrest. However, ET-1 did not inhibit p53 accumulation or p21(Waf-1/SDI-1/Cip-1) overexpression, nor did it reverse the hypophosphorylated state of pRb or the reduction in Bcl2 level in irradiated melanocytes. These results substantiate the role of ET-1 as a paracrine regulator that modulates the response of human melanocytes to UVRs.

  12. Combined therapeutic effects of vinblastine and Astragalus saponins in human colon cancer cells and tumor xenograft via inhibition of tumor growth and proangiogenic factors.

    PubMed

    Auyeung, Kathy K W; Law, P C; Ko, Joshua K S

    2014-01-01

    Our previous study had demonstrated that Astragalus saponins (AST) could reduce the side effects of orthodox chemotherapeutic drugs, while concurrently promote antitumor activity. In the present study, we attempted to investigate the potential synergistic anticarcinogenic effects of AST and a vinca alkaloid vinblastine (VBL). Reduced expression of key proangiogenic and metastatic factors including VEGF, bFGF, metalloproteinase (MMP)-2, and MMP-9 was detected in VBL-treated colon cancer cells, with further downregulation by combined VBL/AST treatment. Subsequently, VBL or AST decreased LoVo cell invasiveness, with further reduction when the drugs were cotreated. Significant growth inhibition and cell cycle arrest at G2/M phase were achieved by either drug treatment with apparent synergistic effects. VBL-induced apoptosis was confirmed but found to be unrelated to induction of the novel apoptotic protein NSAID-activated gene 1. In vivo study in tumor xenograft indicates that combined VBL/AST treatment resulted in sustained regression of tumor growth, with attenuation of the neutropenic and anemic effects of VBL. In addition, downregulation of proangiogenic and proliferative factors was also visualized, with boosting effect by combined drug treatment. These findings have provided evidence that AST combined with adjuvant chemotherapeutics like VBL could alleviate cancer development through diversified modes of action, including the regulation of angiogenesis.

  13. Influence of basic fibroblast growth factor and astroglial cells on the ultrastructure of developing rat brain neuronal precursors in vitro.

    PubMed

    Miehe, M; Leterrier, J F; Deloulme, J C; Gensburger, C; Knoetgen, M F; Sensenbrenner, M

    1996-01-01

    We have examined the ultrastructural aspect of neuronal precursors derived from 14-day-old rat embryos during their development under various culture conditions. Cells maintained in serum-free medium which have developed for 1 week in vitro present ultrastructural features of young neurons. They contain many free ribosomes and microtubules, but few other organelles and incompletely developed Golgi apparatus. In the presence of basic fibroblast growth factor (bFGF), besides cells remaining in aggregates and displaying morphological features of undifferentiated cells, dispersed neuroblasts underwent accelerated ultrastructural maturation. They present well-developed Golgi apparatus, axodendritic synapses and dense-core vesicles already after 3 days in culture. By contrast, in the presence of astroglial-conditioned medium a more homogeneous population developed showing ultrastructural features of relatively mature neurons. However, the neuronal precursors acquired the most mature ultrastructural aspect when they were cocultured with astroglial cells. The neuronal cell bodies contain highly developed Golgi complexes, well-differentiated ergastoplasm and Niss1 body formations, while in the complex neurite network much more numerous mature synapses with clear and dense-core vesicles are visible. These observations indicate that a combination of soluble factors and membrane-bound factors is essential for extensive ultrastructural development of neuronal precursors in vitro. Another finding was that in these cultured neurons neurofilaments (NF) were never seen, while NF protein subunits were found. These data suggest that the polymerization of the three NF subunits into intermediate filaments might need particular cellular factors which probably do not exist under our in vitro conditions.

  14. Enhanced trophic factor secretion by mesenchymal stem/stromal cells with Glycine-Histidine-Lysine (GHK)-modified alginate hydrogels

    PubMed Central

    Jose, Soumia; Hughbanks, Marissa L.; Binder, Bernard Y.K.; Ingavle, Ganesh C.; Leach, J. Kent

    2014-01-01

    Recombinant proteins and cytokines are under broad preclinical and clinical investigation to promote angiogenesis, but their success is limited by ineffective delivery, lack of long-term stability, and excessive cost. Mesenchymal stem/stromal cells (MSC) secrete bioactive trophic factors, and thus, may provide an effective alternative to address these challenges. Glycine-Histidine-Lysine (GHK) is a peptide fragment of osteonectin (SPARC), a matricellular protein with reported proangiogenic potential. We examined the capacity of GHK to upregulate secretion of proangiogenic factors from human MSC in culture and when covalently coupled to alginate hydrogels. GHK had no apparent cytotoxic effects on MSC in culture over a wide range of concentrations. We detected a dose-dependent increase in vascular endothelial growth factor (VEGF) concentration in media conditioned by GHK-treated MSC, which increased endothelial cell proliferation, migration, and tubule formation. We covalently coupled GHK to alginate using carbodiimide chemistry, and human MSC were entrapped in alginate hydrogels to assess VEGF secretion. Similar to monolayer culture, MSC responded to GHK-modified gels by secreting increased concentrations of VEGF and basic fibroblast growth factor (bFGF) compared to unmodified gels. The pre-treatment of MSC with antibodies to α6 and β1 integrins prior to entrapment in GHK-modified gels abrogated VEGF secretion, suggesting that the proangiogenic response of MSC was integrin-mediated. These data demonstrate that the proangiogenic potential of MSC can be significantly increased by the presentation of GHK with a biodegradable carrier, therefore increasing their clinical potential when used for tissue repair. PMID:24468583

  15. Protective effect of basic fibroblast growth factor on laser induced retinopathy

    PubMed Central

    Kartal, Unal; Koptagel, Emel; Bulut, H. Eray; Erdogan, Haydar

    2013-01-01

    AIM To investigate the side effects of the commonly used laser treatment along with testing the neuroprotective effect of bFGF on a potential retinal impairment. METHODS To do this, 30 chinchilla pigmented adult male rabbits were divided into the control and experimental groups. The control and experimental groups underwent both laser application and bFGF treatment. The retinal tissue impairment and its renewal rate were tested under the light and electron microscopical levels. RESULTS The focal laser application on rabbit eyes caused morphological alterations both in the application region and in the neighbouring areas. In the damaged areas, the outer nuclear layer of the neural retina was almost disappeared, retina pigment epithelium was interrupted, the retina pigment epithelium migrated intraretinally, and the damaged region along with neighbouring areas seemed to be not separated. bFGF application just after the laser photocoagulation, revealed better results in application areas. CONCLUSION It could be suggested that the bFGF application following laser photocoagulation might have protective, repairing and wound healing effects on the retina. PMID:24392319

  16. Real-time monitoring of cAMP response element binding protein signaling in porcine granulosa cells modulated by ovarian factors.

    PubMed

    He, Pei Jian; Fujimoto, Yasunori; Yamauchi, Nobuhiko; Hattori, Masa-Aki

    2006-10-01

    The present study was performed to establish a real-time monitoring of the cAMP response element binding protein (CREB) signalling using granulosa cells, and to assess the modulation of CREB activity by potential ovarian autocrine/paracrine and oocyte-derived factors. Granulosa cells were isolated from porcine follicles and cultured for 2 days, and then transfected with CRE-containing pGL3. The cells were directly stimulated or cultured with FSH, LH, forskolin, or a permeable cAMP analog, and/or IGF-I, EGF, bFGF, TGF-beta2 or TNF-alpha, or cumulus-oocyte complex (COCs) for the real-time monitoring of CREB signaling. The activation pattern of CREB signaling consisted of three distinct phases, i.e., burst, attenuation and refractory. In contrast to FSH, LH, and forskolin, a cAMP analog induced the prolonged activation, although three distinct phases were observed at its high concentration. Of all the autocrine/paracrine factors, only IGF-I slightly induced CREB activity. On the other hand, TGF-beta2 and TNF-alpha significantly repressed FSH-stimulated transcriptional activation of CREB by 30% (P < 0.05) and 45% (P < 0.05), respectively. Additionally, coculture with COCs caused a significant suppression of transcriptional activation of CREB signaling stimulated by FSH. These results indicate that ovarian autocrine/paracrine factors such as IGF-I, TGF-beta2, TNF-alpha and oocyte-derived factors modulate the CREB signaling. The present study provides a new approach for direct signaling study on transcription factors under the influences of potential factors.

  17. Potentiation by the lithium ion of morphogenetic responses to a Xenopus inducing factor.

    PubMed

    Cooke, J; Symes, K; Smith, E J

    1989-03-01

    We have cultured explants of Xenopus blastular animal cap tissue from embryos that had received an earlier treatment with LiCl and from their untreated siblings, in various concentrations of XTC-cell-derived mesoderm-inducing factor (XTC-MIF, Smith, 1987; Smith et al. 1988). The pretreatment with lithium that we used transforms later morphogenesis in the whole embryo to give radialized body forms with anterior/dorsal levels of structure grossly over-represented. In addition, animal caps from 'Li+' embryos were allowed to develop without exposure to in vitro MIF (Li+ controls) and compared with normal uninduced control explants, and explants were made from normal early blastulae but given various initial treatments with LiCl in culture. The results confirm that the lithium ion itself will not induce mesoderm in competent, animal cap tissue of Xenopus. It does, however, enhance the responsiveness of this tissue to XTC-MIF, in a way that parallels its recently reported effect in the case of another mesoderm inducer of different character, bFGF (Slack et al. 1988). The effects observed are sufficient to imply that the altered body pattern that follows lithium treatment, in whole embryos, could be caused by modulation of the responses to an unaltered pattern of in situ inductive stimuli. We also observe evidence that appreciable inductive signals reach animal pole tissue beyond the limits of mesoderm formation in normal development. Relatively low concentrations of MIF prevent the development of an epidermis-specific marker in dissociated blastular animal cap cells (Symes et al. 1988). When such experiments are repeated in relation to the lithium pretreatment of embryos, such treatment is seen to have sensitized the cell population, so that the MIF concentration range that assures complete suppression of the marker is reduced. The results are discussed in relation to induction considered as pattern formation.

  18. Amplification of fibroblast growth factor receptor-1 in breast cancer and the effects of brivanib alaninate.

    PubMed

    Shiang, Christine Y; Qi, Yuan; Wang, Bailiang; Lazar, Vladimir; Wang, Jing; Fraser Symmans, W; Hortobagyi, Gabriel N; Andre, Fabrice; Pusztai, Lajos

    2010-10-01

    Fibroblast growth factor receptor-1 (FGFR-1) is amplified in 10% of human breast cancers. The goal of this study was to test the correlation between FGFR-1 amplification and expression and sensitivity to brivanib, an FGFR-1 small molecule inhibitor, in breast cancer cell lines in vitro. Using CGH array and gene expression profiling, FGFR-1 DNA copy number, mRNA, and protein expression were measured in 21 cell lines and correlated with growth inhibition by brivanib. We examined FGFR-1 autophosphorylation and kinase activity, as well as phosphorylation of downstream signaling molecules in response to bFGF and brivanib exposure. CAMA, MDA-MB-361, and HCC38 cells had FGFR-1 amplification and protein overexpression. Brivanib GI(50) values were significantly lower in the gene amplified (15.17 μM, n = 3) compared to normal copy number (69.09 μM, n = 11) or FGFR-1 deleted (76.14 μM, n = 7) cells (P = 0.0107). Among nonamplified cells, there was no correlation between FGFR-1 mRNA or protein expression levels and brivanib sensitivity. Two of three FGFR-1 amplified cells were sensitive to bFGF-induced growth stimulation, which was blocked by brivanib. In cells with amplified FGFR-1, brivanib decreased receptor autophosphorylation, inhibited bFGF-induced tyrosine kinase activity, and reduced phosphorylation of ERK and AKT. Breast cancer cell lines with FGFR-1 gene amplification and protein overexpression are more sensitive to growth inhibition by brivanib than nonamplified cells. These findings suggest that FGFR-1 amplification or protein overexpression in breast cancers may be an indicator for brivanib treatment, where it may have direct anti-proliferative effects in addition to its' anti-angiogenic effects.

  19. Heterogeneity of B lineage acute lymphoblastic leukemias (B-ALL) with regard to their in vitro spontaneous proliferation, growth factor response and BCL-2 expression.

    PubMed

    Pontvert-Delucq, S; Hibner, U; Vilmer, E; Baillou, C; Rohrlich, P; Heymann, D; Najman, A; Guigon, M; Lemoine, F M

    1996-04-01

    The spontaneous proliferation and the effects of 8 various growth factors (GF) were evaluated on leukemic cells from 27 patients with B-lineage ALL. Two groups of ALLs were distinguished. ALLs from group I (21 patients) exhibited a low spontaneous proliferative rate and were stimulated by IL-3 + IL-7 +/- SCF and/or LIF, while ALLs from group II (6 patients) had a high spontaneous proliferative rate and did no longer require this combination of GFs for proliferation. No effect of bFGF, IGF-I, IL-10 and IL-11 alone or in combination, was observed. Such differences in the behaviour of B-ALLs indicated that the GF requirement of ALL blasts was not related to the presence of serum in the culture nor to the pattern of reactivity of ALL blasts for B lymphoid markers or CD34 antigen. Furthermore, we showed in 1/9 cases that high proliferation might be due to an overexpression of the bcl-2 proto-oncogene and to the acquisition of an autocrine secretion.

  20. Growth factors

    SciTech Connect

    Golde, D.W.; Herschman, H.R.; Lusis, A.J.; Groopman, J.E.

    1980-05-01

    Humoral regulation of somatic and hematopoietic cell growth has been intensely investigated during the past decade. Growth hormone is unique because it regulates the size of the person within the constraints of the genetic program. The somatomedins and insulin growth factors are low molecular weight polypeptides believed to mediate some functions of growth hormone. Epithelial growth factor and nerve growth factor are well-characterized polypeptides that influence the growth and differentiation of epithelial and neural tissues and interact with specific cell surface receptors. The hematopoietins are a family of polypeptide hormones that specifically regulate the proliferation and differentiation of stem cells giving rise to erythrocytes, granulocytes, monocytes, megakaryocytes, and B and T lymphocytes. Platelet-derived growth factor modulates the proliferation of fibroblasts in vitro and may have a role in the development of atherosclerosis and myelofibrosis. New knowledge on the biochemistry and physiology of growth factors will probably have a substantial impact on our understanding of human diseases involving abnormal cell growth.

  1. Zur Ökophysiologie, Sexualität und Populationsgenetik litoraler Gammaridea — ein Überblick

    NASA Astrophysics Data System (ADS)

    Bulnheim, H.-P.

    1991-09-01

    Comparative investigations on the physiological capacities in the euryhaline amphipods Gammarus locusta, G. oceanicus, G. salinus, G. zaddachi and G. duebeni were reviewed. In order to assess the adaptations of these species to the abiotic conditions of their environment, the following criteria were examined: oxygen consumption in relation to ambient salinity and temperature levels, respiratory responses following osmotic stress, resistance capacities to oxygen deficiency, resistance to aerial exposure and the simultaneous presence of hydrogen sulphide. Covering the range from marine to typically brackish-water inhabitants, the 5 species show adaptive responses in the above-mentioned order. Respiration is less intensely modified by external factors, and oxygen consumption decreases. Accompanied by faster rates of acclimation to new steady states of performance, resistance capacities increase. The significance of the findings obtained is discussed in relation to the environmental requirements of the amphipods considered. Based on breeding experiments, the sex-determining systems reported thus far in Gammarus species are outlined. As demonstrated in G. duebeni, a more or less pronounced influence of external factors such as photoperiod may become effective. A preponderance of males was noted when offspring were raised under long-day photoperiods, whereas females prevailed under short-day conditions. In terms of the critical daylength, the light per day was estimated as being between 13 and 14 h (Elbe estuary population). Feminizing microporidians ( Octosporea effeminans, Thelohania herediteria), which are transovarially transmitted, can interfere with the system of sex determination and sex differentiation of the host. As reflected in various G. duebeni populations, they cause a maternally transferred sex-ratio condition by the production of all-female broods, thereby mimicking extrachromosomal inheritance. An increase of the salinity level to 25 30‰ results in a

  2. Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction.

    PubMed

    Zhao, Liyan; Liu, Xiaolin; Zhang, Yuelin; Liang, Xiaoting; Ding, Yue; Xu, Yan; Fang, Zhen; Zhang, Fengxiang

    2016-05-15

    Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease. PMID:27025401

  3. Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord.

    PubMed

    Karimi-Abdolrezaee, Soheila; Eftekharpour, Eftekhar; Wang, Jian; Schut, Desiree; Fehlings, Michael G

    2010-02-01

    The transplantation of neural stem/progenitor cells (NPCs) is a promising therapeutic strategy for spinal cord injury (SCI). However, to date NPC transplantation has exhibited only limited success in the treatment of chronic SCI. Here, we show that chondroitin sulfate proteoglycans (CSPGs) in the glial scar around the site of chronic SCI negatively influence the long-term survival and integration of transplanted NPCs and their therapeutic potential for promoting functional repair and plasticity. We targeted CSPGs in the chronically injured spinal cord by sustained infusion of chondroitinase ABC (ChABC). One week later, the same rats were treated with transplants of NPCs and transient infusion of growth factors, EGF, bFGF, and PDGF-AA. We demonstrate that perturbing CSPGs dramatically optimizes NPC transplantation in chronic SCI. Engrafted NPCs successfully integrate and extensively migrate within the host spinal cord and principally differentiate into oligodendrocytes. Furthermore, this combined strategy promoted the axonal integrity and plasticity of the corticospinal tract and enhanced the plasticity of descending serotonergic pathways. These neuroanatomical changes were also associated with significantly improved neurobehavioral recovery after chronic SCI. Importantly, this strategy did not enhance the aberrant synaptic connectivity of pain afferents, nor did it exacerbate posttraumatic neuropathic pain. For the first time, we demonstrate key biological and functional benefits for the combined use of ChABC, growth factors, and NPCs to repair the chronically injured spinal cord. These findings could potentially bring us closer to the application of NPCs for patients suffering from chronic SCI or other conditions characterized by the formation of a glial scar.

  4. Zur mathematischen Simulation tierischer Wachstumskurven

    NASA Astrophysics Data System (ADS)

    Krüger, F.

    1982-12-01

    Advantages and limitations of different functions, employed to describe growth processes of animals, are briefly discussed. In this paper, a modification of a growth formula proposed by Johnson (1935) and used by the author is presented. Its parameters are described, but further testing is required to evaluate to which extent the altered function delivers better approximations to the growth data observed.

  5. A comparison of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor).

    PubMed

    Fujikawa, K; Coan, M H; Enfield, D L; Titani, K; Ericsson, L H; Davie, E W

    1974-02-01

    A comparison has been made of the electrophoretic behavior, chemical composition, amino-terminal sequence, and immunological properties of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor). Some immunological crossreactivity was found between the antibody to prothrombin and factor X although prothrombin and factor X differ substantially in amino-acid and carbohydrate composition. Considerable amino-acid sequence homology was found in the amino-terminal portion of prothrombin, factor IX, and the light chain of factor X. These data provide further evidence to support the hypothesis that at least three of the vitamin K-dependent clotting factors have evolved from a common ancestral gene.

  6. Factor V deficiency

    MedlinePlus

    ... in blood plasma. These proteins are called blood coagulation factors. Factor V deficiency is caused by a ... Gailani D, Neff AT. Rare coagulation factor deficiencies. In: ... HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and ...

  7. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S.

    PubMed

    Di Scipio, R G; Hermodson, M A; Yates, S G; Davie, E W

    1977-02-22

    Human prothrombin, factor IX, and factor X have been idolated in high yield and characterized as the their amino-terminal sequence, molecular weight, amino acid composition, and migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An additional human plasma protein, called protein S, has also been purified and its properties have been compared with those of prothrombin, factor IX, and factor X. Prothrombin (mol wt 72 000), factor IX (mol wt 57 000), and protein S (mol wt 69 000) are single-chain glycoproteins, while factor X (mol wt 59 000) is a glycoprotein composed of two polypeptide chains held together by a disulfide bond(s). The amino-terminal sequence of the light chain of human factor X is homologous with prothrombin, factor IX, and protein S. The heavy chain of human factor X is slightly larger than the heavy chain of bovine factor X and differs from bovine factor X in its amino-terminal sequence.

  8. Basic FGF attenuates amyloid beta-peptide-induced oxidative stress, mitochondrial dysfunction, and impairment of Na+/K+-ATPase activity in hippocampal neurons.

    PubMed

    Mark, R J; Keller, J N; Kruman, I; Mattson, M P

    1997-05-01

    Basic fibroblast growth factor (bFGF) exhibits trophic activity for many populations of neurons in the brain, and can protect those neurons against excitotoxic, metabolic and oxidative insults. In Alzheimer's disease (AD), amyloid beta-peptide (A beta) fibrils accumulate in plaques which are associated with degenerating neurons. A beta can be neurotoxic by a mechanism that appears to involve induction of oxidative stress and disruption of calcium homeostasis. Plaques in AD brain contain high levels of bFGF suggesting a possible modulatory role for bFGF in the neurodegenerative process. We now report that bFGF can protect cultured hippocampal neurons against A beta25-35 toxicity by a mechanism that involves suppression of reactive oxygen species (ROS) accumulation and maintenance of Na+/K+-ATPase activity. A beta25-35 induced lipid peroxidation, accumulation of H2O2, mitochondrial ROS accumulation, and a decrease in mitochondrial transmembrane potential; each of these effects of A beta25-35 was abrogated in cultures pre-treated with bFGF. Na+/K+-ATPase activity was significantly reduced following exposure to A beta25-35 in control cultures, but not in cultures pre-treated with bFGF. bFGF did not protect neurons from death induced by ouabain (a specific inhibitor of the Na+/K+-ATPase) or 4-hydroxynonenal (an aldehydic product of lipid peroxidation) consistent with a site of action of bFGF prior to induction of oxidative stress and impairment of ion-motive ATPases. By suppressing accumulation of oxyradicals, bFGF may slow A beta-induced neurodegenerative cascades. PMID:9187334

  9. ISS Payload Human Factors

    NASA Technical Reports Server (NTRS)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  10. Activation of human factor IX (Christmas factor).

    PubMed

    Di Scipio, R G; Kurachi, K; Davie, E W

    1978-06-01

    Human Factor IX (Christmas factor) is a single-chain plasma glycoprotein (mol wt 57,000) that participates in the middle phase of the intrinsic pathway of blood coagulation. It is present in plasma as a zymogen and is converted to a serine protease, Factor IXabeta, by Factor XIa (activated plasma thromboplastin antecedent) in the presence of calcium ions. In the activation reaction, two internal peptide bonds are hydrolyzed in Factor IX. These cleavages occur at a specific arginyl-alanine peptide bond and a specific arginyl-valine peptide bond. This results in the release of an activation peptide (mol wt approximately equal to 11,000) from the internal region of the precursor molecule and the generation of Factor IXabeta (mol wt approximately equal to 46,000). Factor IXabeta is composed of a light chain (mol wt approximately equal to 18,000) and a heavy chain (mol wt approximately equal to 28,000), and these chains are held together by a disulfide bond(s). The light chain originates from the amino terminal portion of the precursor molecule and has an amino terminal sequence of Tyr-Asn-Ser-Gly-Lys. The heavy chain originates from the carboxyl terminal region of the precursor molecule and contains an amino terminal sequence of Val-Val-Gly-Gly-Glu. The heavy chain of Factor IXabeta also contains the active site sequence of Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro. The active site serine residue is shown in capital letters. Factor IX is also converted to Factor IXaalpha by a protease from Russell's viper venom. This activation reaction, however, occurs in a single step and involves only the cleavage of the internal arginyl-valine peptide bond. Human Factor IXabeta was inhibited by human antithrombin III by the formation of a one-to-one complex of enzyme and inhibitor. In this reaction, the inhibitor was tightly bound to the heavy chain of the enzyme. These data indicate that the mechanism of activation of human Factor IX and its

  11. Differential effects of retinoic acid and growth factors on osteoblastic markers and CD10/NEP activity in stromal-derived osteoblasts.

    PubMed

    Benayahu, D; Fried, A; Shamay, A; Cunningham, N; Blumberg, S; Wientroub, S

    1994-09-01

    The effects of retinoic acid (RA) on the expression of osteoblastic-related cell markers was examined. A marrow stromal osteogenic cell line, MBA-15, was analyzed by Northern blotting for the expression of bone matrix proteins. These cells constitutively express mRNA encoding for procollagen alpha 2 (I), osteonectin, osteopontin, biglycan, and alkaline phosphatase (ALK-P). Gene expression was unchanged in response to RA triggering for 24 hr. Furthermore, cell growth and enzymatic activities of ALK-P and neutral endopeptidase (CD10/NEP) were studied. These parameters were examined in MBA-15 and clonal populations representing different stages of differentiation. The cell's growth rate was unchanged, while ALK-P activity was greatly increased during the culture period under RA treatment in MBA-15 and in the clonal cell lines examined while CD10/NEP activity displayed a different pattern. MBA-15.4, a preosteoblast cell line, exhibited an inhibition in CD10/NEP activity at the beginning of the culture period, reaching basal level with time. This activity was greatly increased over control level in MBA-15.6, a mature stage of osteoblasts. Furthermore, the response of cell lines to various growth factors was tested subsequent to priming the cultures with RA. A synergistic effect was monitored for ALK-P activity in MBA-15.4 and MBA-15.6 cells under rh-bone morphogenic protein (BMP-2) and purified osteogenin (BMP-3), and an antagonist effect was measured when cells were exposed to transforming growth factor beta (TGF beta). Contrarily, BMP-2 and BMP-3 inhibited the CD10/NEP activity that had remained unchanged following priming of the cell with RA. Insulin-like growth factor I (IGF-I) and basic fibroblast growth factors (bFGF) did not affect either ALK-P nor CD10/NEP activities in both cloned cells. Cellular response to bone-seeking hormone, parathyroid hormone (PTH), and prostaglandin E2 (PGE2) was monitored by activation of intracellular cAMP. Treatment with RA caused a

  12. Factor VII deficiency

    MedlinePlus

    ... may be done include: Partial thromboplastin time ( PTT ) Plasma factor VII activity Prothrombin time ( PT ) Mixing study ... controlled by getting intravenous (IV) infusions of normal plasma, concentrates of factor VII, or genetically produced (recombinant) ...

  13. Factoring Polynomials and Fibonacci.

    ERIC Educational Resources Information Center

    Schwartzman, Steven

    1986-01-01

    Discusses the factoring of polynomials and Fibonacci numbers, offering several challenges teachers can give students. For example, they can give students a polynomial containing large numbers and challenge them to factor it. (JN)

  14. Multilevel Mixture Factor Models

    ERIC Educational Resources Information Center

    Varriale, Roberta; Vermunt, Jeroen K.

    2012-01-01

    Factor analysis is a statistical method for describing the associations among sets of observed variables in terms of a small number of underlying continuous latent variables. Various authors have proposed multilevel extensions of the factor model for the analysis of data sets with a hierarchical structure. These Multilevel Factor Models (MFMs)…

  15. A Factor Simplicity Index.

    ERIC Educational Resources Information Center

    Lorenzo-Seva, Urbano

    2003-01-01

    Proposes an index for assessing the degree of factor simplicity in the context of principal components and exploratory factor analysis. The index does not depend on the scale of the factors, and its maximum and minimum are related only to the degree of simplicity in the loading matrix. (SLD)

  16. Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

    PubMed Central

    Giatromanolaki, A; Koukourakis, M I; Sivridis, E; Turley, H; Talks, K; Pezzella, F; Gatter, K C; Harris, A L

    2001-01-01

    Hypoxia inducible factors HIF1α and HIF2α are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1α and 2α protein levels, as a consequence of a redox-sensitive stabilization. The HIFαs enter the nucleus, heterodimerize with the HIF1β protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1α and HIF2α expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2α expression with HIF1α expression showed a significant association (P < 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P < 0.004), PD-ECGF (P < 0.003) and bFGF (P < 0.04) was noted. HIF1α correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2α was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2α protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2α expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1α expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2α expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1

  17. Factors influencing base flow in the Swiss Midlands - Can results from different base flow separation methods help to identify these factors?

    NASA Astrophysics Data System (ADS)

    Meyer, Raphael; Schädler, Bruno; Viviroli, Daniel; Weingartner, Rolf

    2010-05-01

    is generally accepted in the literature, secondly in land cover, and, especially for the Swiss Midlands, in aquifer area and aquifer volumes. In this contribution the results of the different methods are presented and conclusions as to control factors are drawn from the results. The data base for river flow analysis in the low flow range is ideal in Switzerland. There are long time series, a dense gauge network and a comprehensive knowledge about uncertainty of the runoff measurements during low flow. This allows, in addition to the obtained process understanding, a well-founded comparison between the methods applied, which is going to be presented as well. Demuth, S. (1993) Untersuchungen zum Niedrigwasser in West-Europa (European low flow study). Freiburger Schriften zur Hydrologie, Band 1, Freiburg, Germany. Institue of Hydrology (1980) Low Flows Studies Report, 3 volumes. Institute of Hydrology, Wallingford, UK. Kille, K. (1970) Das Verfahren MoMNQ, ein Beitrag zur Berechnung der mittleren langjährigen Grundwasserneubildung mit Hilfe der monatlichen Niedrigwasserabflüsse. Zeitschrift der deutschen Geologischen Gesellschaft, Sonderheft Hydrogeologie Hydrogeochemie, 89-95. Wittenberg, H. (1999) Baseflow recession and recharge as nonlinear storage processes. Hydrol. Process., 13, 715-726.

  18. Aerostructural safety factor criteria

    NASA Technical Reports Server (NTRS)

    Verderaime, V.

    1992-01-01

    The present modification of the conventional safety factor method for aircraft structures evaluation involves the expression of deterministic safety factors in probabilistic tolerance limit ratios; these are found to involve a total of three factors that control the interference of applied and resistive stress distributions. The deterministic expression is extended so that it may furnish a 'relative ultimate safety' index that encompasses all three distribution factors. Operational reliability is developed on the basis of the applied and the yield stress distribution interferences. Industry standards are suggested to be derivable from factor selections that are based on the consequences of failure.

  19. Bayesian Exploratory Factor Analysis

    PubMed Central

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.; Piatek, Rémi

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates from a high dimensional set of psychological measurements. PMID:25431517

  20. New scale factor measure

    NASA Astrophysics Data System (ADS)

    Bousso, Raphael

    2012-07-01

    The computation of probabilities in an eternally inflating universe requires a regulator or “measure.” The scale factor time measure truncates the Universe when a congruence of timelike geodesics has expanded by a fixed volume factor. This definition breaks down if the generating congruence is contracting—a serious limitation that excludes from consideration gravitationally bound regions such as our own. Here we propose a closely related regulator which is well defined in the entire spacetime. The new scale factor cutoff restricts to events with a scale factor below a given value. Since the scale factor vanishes at caustics and crunches, this cutoff always includes an infinite number of disconnected future regions. We show that this does not lead to divergences. The resulting measure combines desirable features of the old scale factor cutoff and of the light-cone time cutoff, while eliminating some of the disadvantages of each.

  1. Analytic Couple Modeling Introducing Device Design Factor, Fin Factor, Thermal Diffusivity Factor, and Inductance Factor

    NASA Technical Reports Server (NTRS)

    Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

    2014-01-01

    A set of convenient thermoelectric device solutions have been derived in order to capture a number of factors which are previously only resolved with numerical techniques. The concise conversion efficiency equations derived from governing equations provide intuitive and straight-forward design guidelines. These guidelines allow for better device design without requiring detailed numerical modeling. The analytical modeling accounts for factors such as i) variable temperature boundary conditions, ii) lateral heat transfer, iii) temperature variable material properties, and iv) transient operation. New dimensionless parameters, similar to the figure of merit, are introduced including the device design factor, fin factor, thermal diffusivity factor, and inductance factor. These new device factors allow for the straight-forward description of phenomenon generally only captured with numerical work otherwise. As an example a device design factor of 0.38, which accounts for thermal resistance of the hot and cold shoes, can be used to calculate a conversion efficiency of 2.28 while the ideal conversion efficiency based on figure of merit alone would be 6.15. Likewise an ideal couple with efficiency of 6.15 will be reduced to 5.33 when lateral heat is accounted for with a fin factor of 1.0.

  2. Effects of acupotomylysis on basic fibroblast growth factor and CD34 levels in rabbits with third lumbar vertebral transverse foramen syndrome.

    PubMed

    Li, X-H; Liu, N-G; Guo, C-Q; Sun, H-M; Wu, H-X; Xu, H; Zhang, Y

    2015-08-19

    This study observed the local tissue homogenates in rabbits with third lumbar vertebral transverse foramen syndrome and explored the mechanism of acupotomylysis in local tissue revascularization. Thirty Japanese white rabbits were randomly divided into the following 5 groups of 6 rabbits each: normal, model, acupotomy, electroacupuncture (EA), and acupotomy-EA groups. All except the normal group were comprised of animal models of third lumbar vertebral transverse foramen syndrome prepared by embedding sponge in the left third lumbar transverse process. The rabbits in the acupotomy and EA groups underwent bilateral acupotomylysis intervention; those in the acupotomy-EA group underwent acupotomylysis and EA interventions. On the 28th day after modeling, the double-antibody ELISA was used to detect b-FGF and CD34 levels in the serum and homogenates of a muscle tissue sample from the left side of the third lumbar transverse process. The b-FGF levels in local muscle homogenates were significantly higher in the modeled rabbits than in the normal rabbits (P < 0.01), and the CD34 levels in the modeled group were significantly lower than in the normal group (P < 0.01). The b-FGF and CD34 levels in the EA, acutopomy, and acutopomy-EA groups were significantly lower than those in the modeled group (P < 0.01); the CD34 levels were significantly higher in the acupotomy-EA group than in the model group (P < 0.05); and the differences among the EA, acupotomy, and acupotomy-EA groups were not significant (P > 0.05). In conclusion, acupotomylysis regulates the levels of b-FGF and CD34 levels in serum and muscle tissue as well as local tissue revascularization.

  3. Exploratory Bi-Factor Analysis

    ERIC Educational Resources Information Center

    Jennrich, Robert I.; Bentler, Peter M.

    2011-01-01

    Bi-factor analysis is a form of confirmatory factor analysis originally introduced by Holzinger. The bi-factor model has a general factor and a number of group factors. The purpose of this article is to introduce an exploratory form of bi-factor analysis. An advantage of using exploratory bi-factor analysis is that one need not provide a specific…

  4. Factors of schizoid personality.

    PubMed

    Raine, A; Allbutt, J

    1989-02-01

    The increasing use of schizoid personality scales with normals has led to a number of validation studies, but to date there are no published analyses of the factorial structure of these scales. This study presents results of factor analyses of schizoid personality scales in an initial attempt to delineate their factorial structure. Questionnaires were administered to 114 male and female undergraduates and factor analysed using Varimax, Quartimax, and Oblique rotations. A two-factor varimax solution yielded a first factor accounting for 49 per cent of total unrotated variance with high (0.70 to 0.91) loadings from Hallucinatory predisposition, Perceptual aberration, Schizophrenism, STA and STB scales, and was interpreted as reflecting a general factor of schizoid personality disorder. Psychoticism and Social anhedonia loaded on a second factor accounting for 20 per cent of the variance which was uncorrelated (r = 0.09) with factor 1. This factor solution was closely replicated using quartimax and oblimin rotation criteria. It is concluded that Social anhedonia and Psychoticism represent a separate dimension from other scales which reflect the more positive features of schizoid personality.

  5. FACTORS AFFECTING PITCH DISCRIMINATION.

    ERIC Educational Resources Information Center

    BERGAN, JOHN R.

    EFFECTS OF TONAL MEMORY OF TWO KINDS OF FACTORS WERE STUDIED. THE FACTORS WERE (1) THE CHARACTERISTICS OF STIMULI PRESENTED TO THE SUBJECT IN A PITCH IDENTIFICATION TASK, AND (2) THOSE EFFECTING THE RESPONSE THAT THE SUBJECT MAKES IN SUCH A TASK. FIVE HYPOTHESES WERE ADVANCED FOR STUDY. THE UNDERLYING ASSUMPTION WAS THAT THERE ARE IMPORTANT…

  6. Block LU factorization

    NASA Technical Reports Server (NTRS)

    Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

    1992-01-01

    Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

  7. [Vascular factors in dementia].

    PubMed

    Bidzan, Leszek

    2005-01-01

    Cerebrovascular factors are a common cause of dementia or contribute to cognitive decline in other dementias. Studies showing that cerebrovascular factors are the risk factors for neurodegenerative dementias, especially Alzheimer's disease. Practically all neurodegenerative dementias have a vascular component that reduces cerebral perfusion and has great impact on the clinical picture. Recent data support the view that the neurodegenerative process is caused by cerebrovascular mechanisms. The results showed that patients with vascular cognitive impairment have a typical clinical picture. Various important non-cognitive features are caused by cerebrovascular factors and are associated with a more rapid course of illness. On the other hand the term vascular diseases or cerebrovascular factors include a variety of vascular pathologies. PMID:16358596

  8. Wnt/β-catenin signaling pathway activation is required for proliferation of chicken primordial germ cells in vitro

    PubMed Central

    Lee, Hyung Chul; Lim, Sumi; Han, Jae Yong

    2016-01-01

    Here, we investigated the role of the Wnt/β-catenin signaling pathway in chicken primordial germ cells (PGCs) in vitro. We confirmed the expression of Wnt signaling pathway-related genes and the localization of β-catenin in the nucleus, revealing that this pathway is potentially activated in chicken PGCs. Then, using the single-cell pick-up assay, we examined the proliferative capacity of cultured PGCs in response to Wnt ligands, a β-catenin-mediated Wnt signaling activator (6-bromoindirubin-3′-oxime [BIO]) or inhibitor (JW74), in the presence or absence of basic fibroblast growth factor (bFGF). WNT1, WNT3A, and BIO promoted the proliferation of chicken PGCs similarly to bFGF, whereas JW74 inhibited this proliferation. Meanwhile, such treatments in combination with bFGF did not show a synergistic effect. bFGF treatment could not rescue PGC proliferation in the presence of JW74. In addition, we confirmed the translocation of β-catenin into the nucleus by the addition of bFGF after JW74 treatment. These results indicate that there is signaling crosstalk between FGF and Wnt, and that β-catenin acts on PGC proliferation downstream of bFGF. In conclusion, our study suggests that Wnt signaling enhances the proliferation of chicken PGCs via the stabilization of β-catenin and activation of its downstream genes. PMID:27687983

  9. In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia

    SciTech Connect

    Brenner, R.E.; Bartmann, P.; Terinde, R.

    1996-05-17

    Thanatophoric dysplasia (TD) is characterized by a disorganized growth plate with markedly reduced proliferative and hypertrophic cartilage zones. Therefore, we studied in vitro the proliferation rates of articular chondrocytes from five TD patients and age-matched controls in response to bFGF, IGF-I, IGF-II, and TGF-{beta}1. In human fetal controls bFGF was the most potent growth factor. Clonal growth of articular chondrocytes in response to bFGF was reduced in two of five TD patients and slightly below the range of controls in a third case. Stimulation of chondrocyte proliferation by IGF I and II was reduced in the patient whose response to bFGF was most markedly impaired. The effect of TGF-{beta}1 ranged from normal to slightly elevated values in TD fetuses. These results indicate heterogeneity of the underlying defects in TD. Low proliferative responses of chondrocytes to bFGF and IGF-I/II are likely to play a key role in the pathogenesis of some cases. In two of five patients studied, the mechanisms of bFGF and IGF-signal transduction are candidates for the primary molecular defect. 22 refs., 6 tabs.

  10. Risk Factors for Tuberculosis

    PubMed Central

    Narasimhan, Padmanesan; Wood, James; MacIntyre, Chandini Raina; Mathai, Dilip

    2013-01-01

    The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV), malnutrition, and young age), emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli. PMID:23476764

  11. Growth factor signalling.

    PubMed

    de Laat, S W; Boonstra, J; Defize, L H; Kruijer, W; van der Saag, P T; Tertoolen, L G; van Zoelen, E J; den Hertog, J

    1999-01-01

    Signalling between cells in the developing vertebrate embryo is essential for normal embryonic development. In the mid 1970's, signal transduction research started at the Hubrecht Laboratory with special emphasis on analysis of the signalling mechanisms that direct cell proliferation and differentiation. The introduction of in vitro model systems contributed tremendously to the success of the signal transduction research at the Hubrecht Laboratory. Initially neuroblastoma cell lines, and later embryonal carcinoma and embryonal stem cells played an important role in identification of the molecular key players in developmental signalling. For instance, embryonal carcinoma cells were used to identify and characterise polypeptide growth factors. Growth factor signalling research was extended to analysis of growth factor receptor activation. Moreover, the second messenger systems that are linked to growth factor receptors were studied, as well as the nuclear responses to growth factor receptor activation. Finally, the role of growth factor signalling in differentiation was established using embryonal carcinoma cells. Here, we will review work that was characteristic for the growth factor receptor signalling research that was done at the Hubrecht Laboratory between 1980 and the early 1990's.

  12. Conundrums with uncertainty factors.

    PubMed

    Cooke, Roger

    2010-03-01

    The practice of uncertainty factors as applied to noncancer endpoints in the IRIS database harkens back to traditional safety factors. In the era before risk quantification, these were used to build in a "margin of safety." As risk quantification takes hold, the safety factor methods yield to quantitative risk calculations to guarantee safety. Many authors believe that uncertainty factors can be given a probabilistic interpretation as ratios of response rates, and that the reference values computed according to the IRIS methodology can thus be converted to random variables whose distributions can be computed with Monte Carlo methods, based on the distributions of the uncertainty factors. Recent proposals from the National Research Council echo this view. Based on probabilistic arguments, several authors claim that the current practice of uncertainty factors is overprotective. When interpreted probabilistically, uncertainty factors entail very strong assumptions on the underlying response rates. For example, the factor for extrapolating from animal to human is the same whether the dosage is chronic or subchronic. Together with independence assumptions, these assumptions entail that the covariance matrix of the logged response rates is singular. In other words, the accumulated assumptions entail a log-linear dependence between the response rates. This in turn means that any uncertainty analysis based on these assumptions is ill-conditioned; it effectively computes uncertainty conditional on a set of zero probability. The practice of uncertainty factors is due for a thorough review. Two directions are briefly sketched, one based on standard regression models, and one based on nonparametric continuous Bayesian belief nets. PMID:20030767

  13. Factorizations in finite groups

    SciTech Connect

    Kulikov, Viktor S

    2013-02-28

    A necessary condition for uniqueness of factorizations of elements of a finite group G with factors belonging to a union of some conjugacy classes of G is given. This condition is sufficient if the number of factors belonging to each conjugacy class is big enough. The result is applied to the problem on the number of irreducible components of the Hurwitz space of degree d marked coverings of P{sup 1} with given Galois group G and fixed collection of local monodromies. Bibliography: 9 titles.

  14. Factor II deficiency

    MedlinePlus

    ... blood. It leads to problems with blood clotting (coagulation). Factor II is also known as prothrombin. ... blood clots form. This process is called the coagulation cascade. It involves special proteins called coagulation, or ...

  15. New microbial growth factor

    NASA Technical Reports Server (NTRS)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  16. Rheumatoid Factors: Clinical Applications

    PubMed Central

    Castelli, Roberto

    2013-01-01

    Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy. PMID:24324289

  17. Automated Factor Slice Sampling

    PubMed Central

    Tibbits, Matthew M.; Groendyke, Chris; Haran, Murali; Liechty, John C.

    2013-01-01

    Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the “factor slice sampler”, a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples. PMID:24955002

  18. Aerospace Human Factors

    NASA Technical Reports Server (NTRS)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  19. von Willebrand Factor Test

    MedlinePlus

    ... Platelet Count , Platelet Function Tests , Complete Blood Count , Coagulation Factor VIII , PT , PTT At a Glance Test ... a protein , one of several components of the coagulation system that work together to stop bleeding and ...

  20. WRKY transcription factors.

    PubMed

    Rushton, Paul J; Somssich, Imre E; Ringler, Patricia; Shen, Qingxi J

    2010-05-01

    WRKY transcription factors are one of the largest families of transcriptional regulators in plants and form integral parts of signalling webs that modulate many plant processes. Here, we review recent significant progress in WRKY transcription factor research. New findings illustrate that WRKY proteins often act as repressors as well as activators, and that members of the family play roles in both the repression and de-repression of important plant processes. Furthermore, it is becoming clear that a single WRKY transcription factor might be involved in regulating several seemingly disparate processes. Mechanisms of signalling and transcriptional regulation are being dissected, uncovering WRKY protein functions via interactions with a diverse array of protein partners, including MAP kinases, MAP kinase kinases, 14-3-3 proteins, calmodulin, histone deacetylases, resistance proteins and other WRKY transcription factors. WRKY genes exhibit extensive autoregulation and cross-regulation that facilitates transcriptional reprogramming in a dynamic web with built-in redundancy.

  1. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Takahashi, Kazuyuki

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  2. Interest rates factor model

    NASA Astrophysics Data System (ADS)

    Lee, Sangwook; Kim, Min Jae; Kim, Soo Yong

    2011-07-01

    Interdependence of the interest rates of the US, the UK, and Japan is analyzed in this work by means of spectral analysis and network methods. A predominant effective factor in the interest rate market is which country floats a bond issue, and a minor effective factor is time to maturity of bonds. Power-law cross-correlation among different countries is analyzed by the detrended cross-correlation analysis method. Long-range cross-correlation is found between the first factors of interest rate, while there is no cross-correlation between some of the second factors. The tail dependency is indicated by tail indices from Archimedean copulas, including an empirical copula. In contrast to other pairs, the US-UK first factor pair has tail dependencies in both the upper-tail and lower-tail. Dynamic properties of interest rate are modeled by a stochastic volatility model. The properties of mean reverting and volatility clustering are observed and reflected in this model. The proposed simulation method combines the dependence structures and the factor dynamics model; it simultaneously describes the interest rates of different countries.

  3. Purification and characterization of an abnormal factor IX (Christmas factor) molecule. Factor IX Chapel Hill.

    PubMed

    Chung, K S; Madar, D A; Goldsmith, J C; Kingdon, H S; Roberts, H R

    1978-11-01

    Human Factor IX (Christmas factor) was isolated from the plasma of a patient with mild hemophilia B. The patient's plasma contained 5% Factor IX clotting activity but 100% Factor IX antigenic activity as determined by immunological assays, which included inhibitor neutralization and a radioimmunoassay for Factor IX. This abnormal Factor IX is called Factor IX Chapel Hill (Factor IXCH). Both normal Factor IX and Factor IXCH have tyrosine as the NH2-terminal amino acid. The two proteins have a similar molecular weight, a similar amino acid analysis, the same number of gamma-carboxyglutamic acid residues (10 gamma-carboxyglutamic acid residues), and a similar carbohydrate content. Both exist as a single-chain glycoprotein in plasma. The major difference between normal Factor IX and Factor IXCH is that the latter exhibits delayed activation to Factor IXa in the presence of Factor XIa and Ca2+. Thus, Factor IXCH differs from other previously described abnormal Factor IX molecules.

  4. bFGF interaction and in vivo angiogenesis inhibition by self-assembling sulfonic acid-based copolymers.

    PubMed

    García-Fernández, L; Aguilar, M R; Ochoa-Callejero, L; Abradelo, C; Martínez, A; San Román, J

    2012-01-01

    The antiangiogenic activity of different families of biocompatible and non-toxic polymer drugs based on 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or polymethacrylic derivatives of 5-aminonaphthalen sulfonic acid (MANSA) is analyzed using directed in vivo angiogenesis assay and correlated with in vitro results. These active compounds were copolymerized with butylacrylate (BA) and N-vinylpyrrolidone in order to obtain two families of copolymers with different properties in aqueous media. The most hydrophobic copolymers poly(BA-co-MANSA) and poly(BA-co-AMPS) formed amphiphilic copolymers and presented micellar morphology in aqueous media. This supramolecular organization of the copolymers had a clear effect on bioactivity. Poly(BA-co-MANSA) copolymers showed the best antiangiogenic activity and very low toxicity at relatively low dose, with the possibility to be injected directly in the solid tumors alone or in combination with other therapeutic agents such as anti-VEGF drugs. The obtained results demonstrate that not only the chemical structure but also the supramolecular organization of the macromolecules plays a key role in the anti-angiogenic activity of these active polymers.

  5. Preparative two-step purification of recombinant human basic fibroblast growth factor from high-cell-density cultivation of Escherichia coli.

    PubMed

    Garke, G; Deckwer, W D; Anspach, F B

    2000-01-14

    Aggregation and precipitation are major pitfalls during bioprocessing and purification of recombinant human basic fibroblast growth factor (rh-bFGF). In order to gain high yields of the soluble protein monomer with high biological activity, an efficient downstream process was developed, focussing on the combination of expanded bed adsorption (EBA) and heparin chromatography. After expression in E. coli TG1:plambdaFGFB, cells were harvested and washed; then the rh-bFGF was released via high pressure homogenization. The high viscosity of the feedstock of about 40 mPa s, showing non-newtonian behaviour, was reduced to 2 mPa s by the addition of DNase. The homogenate (5.6 l) was loaded directly on an expanded bed column (C-50) packed with the strong cation-exchanger Streamline SP. In the eluates, histone-like (HU) protein was identified as the main protein contaminant by sequence analysis. The thermodynamics and kinetics of rh-bFGF adsorption from the whole broth protein mixture were determined in view of competition and displacement effects with host-derived proteins. Optimal binding and elution conditions were developed with knowledge of the dependence of rh-bFGF adsorption isotherms on the salt concentration to allow direct application of eluates onto Heparin HyperD. This affinity support maintained selectivity and efficiency under CIP and over a wide range of flow-rates; both is advantageous for the flexibility of the purification protocol in view of a scalable process. Remaining DNA and HU protein were separated by Heparin HyperD. The endotoxin level decreased from approximately 1,000,000 EU/ml in the whole broth to 10 EU in 3 mg bFGF per ml. The final purification protocol yields >99% pure rh-bFGF as judged from SDS-PAGE and MALDI-TOF mass spectrometry with high mitogenic activity (ED50=1-1.5 ng/ml) of the lyophilized sample. In comparison to the conventional process, the overall protein recovery rose by 15% to 65% with saving time and costs. PMID:10681038

  6. Factor Loading Estimation Error and Stability Using Exploratory Factor Analysis

    ERIC Educational Resources Information Center

    Sass, Daniel A.

    2010-01-01

    Exploratory factor analysis (EFA) is commonly employed to evaluate the factor structure of measures with dichotomously scored items. Generally, only the estimated factor loadings are provided with no reference to significance tests, confidence intervals, and/or estimated factor loading standard errors. This simulation study assessed factor loading…

  7. A load factor formula

    NASA Technical Reports Server (NTRS)

    Miller, Roy G

    1927-01-01

    The ultimate test of a load factor formula is experience. The chief advantages of a semi rational formula over arbitrary factors are that it fairs in between points of experience and it differentiates according to variables within a type. Structural failure of an airplane apparently safe according to the formula would call for a specific change in the formula. The best class of airplanes with which to check a load factor formula seems to be those which have experienced structural failure. Table I comprises a list of the airplanes which have experienced failure in flight traceable to the wing structure. The load factor by formula is observed to be greater than the designed strength in each case, without a single exception. Table II comprises the load factor by formula with the designed strength of a number of well-known service types. The formula indicates that by far the majority of these have ample structural strength. One case considered here in deriving a suitable formula is that of a heavy load carrier of large size and practically no reserve power.

  8. Antiretroviral restriction factors.

    PubMed

    Hatziioannou, Theodora; Bieniasz, Paul D

    2011-12-01

    Studies of retroviruses have been instrumental in revealing the existence of an array of antiviral proteins, or restriction factors, and the mechanisms by which they function. Some restriction factors appear to specifically inhibit retrovirus replication, while others have a broader antiviral action. Here, we briefly review current understanding of the mechanisms by which several such proteins exert antiviral activity. We also discuss how retroviruses have evolved to evade or antagonize antiviral proteins, including through the action of viral accessory proteins. Restriction factors, their viral targets and antagonists have exerted evolutionary pressure on each other, resulting in specialization and barriers to cross-species transmission. Potentially, this recently revealed intrinsic system of antiviral immunity might be mobilized for therapeutic benefit.

  9. Geothermal Plant Capacity Factors

    SciTech Connect

    Greg Mines; Jay Nathwani; Christopher Richard; Hillary Hanson; Rachel Wood

    2015-01-01

    The capacity factors recently provided by the Energy Information Administration (EIA) indicated this plant performance metric had declined for geothermal power plants since 2008. Though capacity factor is a term commonly used by geothermal stakeholders to express the ability of a plant to produce power, it is a term frequently misunderstood and in some instances incorrectly used. In this paper we discuss how this capacity factor is defined and utilized by the EIA, including discussion on the information that the EIA requests from operations in their 923 and 860 forms that are submitted both monthly and annually by geothermal operators. A discussion is also provided regarding the entities utilizing the information in the EIA reports, and how those entities can misinterpret the data being supplied by the operators. The intent of the paper is to inform the facility operators as the importance of the accuracy of the data that they provide, and the implications of not providing the correct information.

  10. Electromagnetic nucleon form factors

    SciTech Connect

    Bender, A.; Roberts, C.D.; Frank, M.R.

    1995-08-01

    The Dyson-Schwinger equation framework is employed to obtain expressions for the electromagnetic nucleon form factor. In generalized impulse approximation the form factor depends on the dressed quark propagator, the dressed quark-photon vertex, which is crucial to ensuring current conservation, and the nucleon Faddeev amplitude. The approach manifestly incorporates the large space-like-q{sup 2} renormalization group properties of QCD and allows a realistic extrapolation to small space-like-q{sup 2}. This extrapolation allows one to relate experimental data to the form of the quark-quark interaction at small space-like-q{sup 2}, which is presently unknown. The approach provides a means of unifying, within a single framework, the treatment of the perturbative and nonperturbative regimes of QCD. The wealth of experimental nucleon form factor data, over a large range of q{sup 2}, ensures that this application will provide an excellent environment to test, improve and extend our approach.

  11. DSN human factors project

    NASA Technical Reports Server (NTRS)

    Chafin, R. L.; Martin, T. H.

    1980-01-01

    The project plan was to hold focus groups to identify the factors influencing the ease of use characteristics of software and to bond the problem. A questionnaire survey was conducted to evaluate those factors which were more appropriately measured with that method. The performance oriented factors were analyzed and relationships hypothesized. The hypotheses were put to test in the experimental phase of the project. In summary, the initial analysis indicates that there is an initial performance effect favoring computer controlled dialogue but the advantage fades fast as operators become experienced. The user documentation style is seen to have a significant effect on performance. The menu and prompt command formats are preferred by inexperienced operators. The short form mnemonic is least favored. There is no clear best command format but the short form mnemonic is clearly the worst.

  12. Multi-factor authentication

    SciTech Connect

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  13. Psychological Factors in Asthma

    PubMed Central

    2008-01-01

    Asthma has long been considered a condition in which psychological factors have a role. As in many illnesses, psychological variables may affect outcome in asthma via their effects on treatment adherence and symptom reporting. Emerging evidence suggests that the relation between asthma and psychological factors may be more complex than that, however. Central cognitive processes may influence not only the interpretation of asthma symptoms but also the manifestation of measurable changes in immune and physiologic markers of asthma. Furthermore, asthma and major depressive disorder share several risk factors and have similar patterns of dysregulation in key biologic systems, including the neuroendocrine stress response, cytokines, and neuropeptides. Despite the evidence that depression is common in people with asthma and exerts a negative impact on outcome, few treatment studies have examined whether improving symptoms of depression do, in fact, result in better control of asthma symptoms or improved quality of life in patients with asthma. PMID:20525122

  14. Factor D Enzyme

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The trauma caused by the open heart surgery often triggers massive inflammation because the immune system overreacts. Factor D, the protein which plays a key role in the biological steps that activate this immune response prevents the imune system from inappropriately rurning out of control, allowing the patient to recover more rapidly. Factor D blockers, with their great potential to alleviate the complication of inflammation associated with heart surgery, are now being developed for clinical trials. These new drugs, developed from space research, should be commercially available as soon as year 2001.

  15. The Transcription Factor Encyclopedia

    PubMed Central

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe. PMID:22458515

  16. The transcription factor encyclopedia.

    PubMed

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  17. Peptide growth factors, part A

    SciTech Connect

    Barnes, D.; Sirbasku, D.A.

    1987-01-01

    This book contains information on the following topics: Epidermal Growth Factor;Transforming Growth Factors;Bone and Cartilage Growth Factors;Somatomedin/Insulin-Like Growth Factors;Techniques for the Study of Growth Factor Activity;Assays, Phosphorylation, and Surface Membrane Effects.

  18. Radiation View Factor With Shadowing

    1992-02-24

    FACET calculates the radiation geometric view factor (alternatively called shape factor, angle factor, or configuration factor) between surfaces for axisymmetric, two-dimensional planar and three-dimensional geometries with interposed third surface obstructions. FACET was developed to calculate view factors as input data to finite element heat transfer analysis codes.

  19. Factor Analysis and Counseling Research

    ERIC Educational Resources Information Center

    Weiss, David J.

    1970-01-01

    Topics discussed include factor analysis versus cluster analysis, analysis of Q correlation matrices, ipsativity and factor analysis, and tests for the significance of a correlation matrix prior to application of factor analytic techniques. Techniques for factor extraction discussed include principal components, canonical factor analysis, alpha…

  20. Transforming growth factor-beta1 induces activation of Ras, Raf-1, MEK and MAPK in rat hepatic stellate cells.

    PubMed

    Reimann, T; Hempel, U; Krautwald, S; Axmann, A; Scheibe, R; Seidel, D; Wenzel, K W

    1997-02-10

    The transdifferentiation of hepatic stellate cells into myofibroblast-like cells and the proliferation of the transdifferentiated cells are controlled by TGF-beta1. Little is known about the intracellular signal transducers of TGF-beta1. In this paper we show that in cultured hepatic stellate cells TGF-beta1 induces activation of Ras, Raf-1, MEK and MAPK p42 and p44. The activation of MAPK depends on the activation of MEK. Our data exclude that the observed effects are mediated by a bFGF or PDGF autocrine loop. PMID:9038360

  1. Assessment of Human Factors

    NASA Technical Reports Server (NTRS)

    Mount, Frances; Foley, Tico

    1999-01-01

    Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

  2. ERYTHROPOIETIC FACTOR PURIFICATION

    DOEpatents

    White, W.F.; Schlueter, R.J.

    1962-05-01

    A method is given for purifying and concentrating the blood plasma erythropoietic factor. Anemic sheep plasma is contacted three times successively with ion exchange resins: an anion exchange resin, a cation exchange resin at a pH of about 5, and a cation exchange resin at a pH of about 6. (AEC)

  3. Thyroid Cancer Risk Factors

    MedlinePlus

    ... and radiation fallout from power plant accidents or nuclear weapons. Having had head or neck radiation treatments in childhood is a risk factor for ... should be done using the lowest dose of radiation that still provides a clear ... from nuclear weapons or power plant accidents. For instance, thyroid ...

  4. Factor Analysis and AIC.

    ERIC Educational Resources Information Center

    Akaike, Hirotugu

    1987-01-01

    The Akaike Information Criterion (AIC) was introduced to extend the method of maximum likelihood to the multimodel situation. Use of the AIC in factor analysis is interesting when it is viewed as the choice of a Bayesian model; thus, wider applications of AIC are possible. (Author/GDC)

  5. Introduction to human factors

    SciTech Connect

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  6. Common conversion factors.

    PubMed

    2001-05-01

    This appendix presents tables of some of the more common conversion factors for units of measure used throughout Current Protocols manuals, as well as prefixes indicating powers of ten for SI units. Another table gives conversions between temperatures on the Celsius (Centigrade) and Fahrenheit scales. PMID:18770653

  7. Inelastic Scattering Form Factors

    1992-01-01

    ATHENA-IV computes form factors for inelastic scattering calculations, using single-particle wave functions that are eigenstates of motion in either a Woods-Saxon potential well or a harmonic oscillator well. Two-body forces of Gauss, Coulomb, Yukawa, and a sum of cut-off Yukawa radial dependences are available.

  8. Peptide growth factors, part B

    SciTech Connect

    Barnes, D.; Sirbasku, D.A.

    1987-01-01

    This book discusses the following topics: Platelet-Derived Growth Factor;Nerve and Glial Growth Factors;PC12 Pheochromocytoma Cells;Techniques for the Study of Growth Factor Activity;Genetic Approaches and Biological Effects.

  9. [Streptococcus pyogenes pathogenic factors].

    PubMed

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection. PMID:25456681

  10. Analytic pion form factor

    NASA Astrophysics Data System (ADS)

    Lomon, Earle L.; Pacetti, Simone

    2016-09-01

    The pion electromagnetic form factor and two-pion production in electron-positron collisions are simultaneously fitted by a vector dominance model evolving to perturbative QCD at large momentum transfer. This model was previously successful in simultaneously fitting the nucleon electromagnetic form factors (spacelike region) and the electromagnetic production of nucleon-antinucleon pairs (timelike region). For this pion case dispersion relations are used to produce the analytic connection of the spacelike and timelike regions. The fit to all the data is good, especially for the newer sets of timelike data. The description of high-q2 data, in the timelike region, requires one more meson with ρ quantum numbers than listed in the 2014 Particle Data Group review.

  11. Precipitating factors of asthma.

    PubMed

    Lee, T H

    1992-01-01

    Asthma is characterised by bronchial hyperresponsiveness. This feature of the asthmatic diathesis predisposes patients to wheezing in response to a number of different factors. These precipitating factors include specific allergen acting via sensitised mediator cells through an IgE-dependent mechanism. There are irritants which may work through a non-specific manner, or stimuli such as exercise and hyperventilation, which probably also act through mediator release via a non-IgE-dependent manner. The mechanism whereby physical stimuli such as exercise induce bronchoconstriction is of interest, because it increases the context in which the mast cell may participate in acute asthmatic bronchoconstriction. Respiratory infections also commonly provoke asthma, especially in infants and may, indeed, precipitate the asthmatic state itself. Finally, drugs can often trigger asthma attacks and the mechanisms of asthma precipitated by non-steroidal anti-inflammatory drugs such as aspirin have been the subject of recent research.

  12. Helicopter human factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  13. Human factors workplace considerations

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

    Computer workstations assume many different forms and play different functions today. In order for them to assume the effective interface role which they should play they must be properly designed to take into account the ubiguitous human factor. In addition, the entire workplace in which they are used should be properly configured so as to enhance the operational features of the individual workstation where possible. A number of general human factors workplace considerations are presented. This ongoing series of notes covers such topics as achieving comfort and good screen visibility, hardware issues (e.g., mouse maintenance), screen symbology features (e.g., labels, cursors, prompts), and various miscellaneous subjects. These notes are presented here in order to: (1) illustrate how one's workstation can be used to support telescience activities of many other people working within an organization, and (2) provide a single complete set of considerations for future reference.

  14. Growth factors for nanobacteria

    NASA Astrophysics Data System (ADS)

    Ciftcioglu, Neva; Kajander, E. Olavi

    1999-12-01

    Nanobacteria are novel microorganisms recently isolated from fetal bovine serum and blood of cows and humans. These coccoid, gram negative bacteria in alpha-2 subgroup of Proteobacteria grow slowly under mammalian cell culture conditions but not in common media for microbes. Now we have found two different kinds of culture supplement preparations that improve their growth and make them culturable in the classical sense. These are supernatant fractions of conditioned media obtained from 1 - 3 months old nanobacteria cultures and from about a 2 weeks old Bacillus species culture. Both improved multiplication and particle yields and the latter increased their resistance to gentamicin. Nanobacteria cultured with any of the methods shared similar immunological property, structure and protein pattern. The growth supporting factors were heat-stabile and nondialyzable, and dialysis improved the growth promoting action. Nanobacteria formed stony colonies in a bacteriological medium supplemented with the growth factors. This is an implication that nanobacterial growth is influenced by pre-existing bacterial flora.

  15. FACTORS INFLUENCING THE DESIGN OF BIOACCUMULATION FACTOR AND BIOTA-SEDIMENT ACCUMULATION FACTOR FIELD STUDIES

    EPA Science Inventory

    A series of modeling simulations were performed to develop an understanding of the underlying factors and principles involved in developing field sampling designs for measuring bioaccumulation factors (BAFs) and biota-sediment accumulation factors (BSAFs. These simulations reveal...

  16. FACTORS INFLUENCING THE DESIGN OF BIOACCUMULATION FACTOR AND BIOTA-SEDIMENT ACCUMULATION FACTOR FIELD STUDIES

    EPA Science Inventory

    General guidance for designing field studies to measure bioaccumulation factors (BAFs) and biota-sediment accumulation factors (BSAFs) is not available. To develop such guidance, a series of modeling simulations were performed to evaluate the underlying factors and principles th...

  17. Factorization of simulations

    SciTech Connect

    Barrett, C. L.; Mortveit, H. S.; Reidys, C. M.

    2001-01-01

    A simulation is collection of agents that, according to some schedule, are making decisions based on information about other agents in that collection. In this paper we present a class of dynamical systems called Sequential Dynamical Systems (SDS) that was developed to capture these key features of computer simulations. Here, as an example of the use of SDS, we demonstrate how one can obtain information about a simulation by a factorization into smaller simulations.

  18. Human Factors Review Plan

    SciTech Connect

    Paramore, B.; Peterson, L.R.

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  19. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Kees de Jager

    2004-08-01

    Although nucleons account for nearly all the visible mass in the universe, they have a complicated structure that is still incompletely understood. The first indication that nucleons have an internal structure, was the measurement of the proton magnetic moment by Frisch and Stern (1933) which revealed a large deviation from the value expected for a point-like Dirac particle. The investigation of the spatial structure of the nucleon, resulting in the first quantitative measurement of the proton charge radius, was initiated by the HEPL (Stanford) experiments in the 1950s, for which Hofstadter was awarded the 1961 Nobel prize. The first indication of a non-zero neutron charge distribution was obtained by scattering thermal neutrons off atomic electrons. The recent revival of its experimental study through the operational implementation of novel instrumentation has instigated a strong theoretical interest. Nucleon electro-magnetic form factors (EMFFs) are optimally studied through the exchange of a virtual photon, in elastic electron-nucleon scattering. The momentum transferred to the nucleon by the virtual photon can be selected to probe different scales of the nucleon, from integral properties such as the charge radius to scaling properties of its internal constituents. Polarization instrumentation, polarized beams and targets, and the measurement of the polarization of the recoiling nucleon have been essential in the accurate separation of the charge and magnetic form factors and in studies of the elusive neutron charge form factor.

  20. Zur Ätiologie des Mongolismus

    NASA Astrophysics Data System (ADS)

    Wagenbichler, P.

    1981-02-01

    Beside the rare cases of translocation mongolism, Down syndrom is caused by meiotic malsegregation of chromosomes No. 21. The meiotic error can take place in both sexes and was found twice as frequently in the female as in the male. The same 2∶1 ratio was found concerning nondisjunction in the first and in the second meiotic division. The rate of meiotic errors, which occur at random, is largely dependent on age; this tendency is more pronounced in oogenesis than in spermatogenesis. The results of prenatal chromosomal diagnosis indicate that the recurrence risk of trisomy 21 is not above the age-dependent average.

  1. Zur chemie der marsoberfläche

    USGS Publications Warehouse

    Keil, Klaus; Clark, Benton C.; Baird, A.K.; Toulmin, Priestley; Rose, Harry J.

    1978-01-01

    Analyses of 13 samples of Martian surface materials with the Viking X-ray fluorescence spectrometers show SiO2 similar to that of terrestrial mafic rocks, whereas Fe2O3, Cl, and S are higher and Al2O3, K2O, Rb, Sr, Y, and Zr are lower. Low totals suggest presence of CO2, H2O, and Na2O. Duricrust fragments are higher in S than fines, but samples from both landing sites are surprisingly similar. We suggest that Martian surface materials are aeolian deposits of complex mixtures of weathering products of maficultramafic rocks, possibly consisting of iron-rich clays, sulfates, iron oxides, carbonates, and chlorides.

  2. Zur Entwicklung der medizinischen Wissenschaften in China

    NASA Astrophysics Data System (ADS)

    Müller, Hans Kurt

    1980-02-01

    Three periods or stages can be recognized in the development of medicine in China. The first one, being the indigenous medical practice, has its own philosophical approach and can therefore not simply be combined with Western medicine. The second period, in which medical missionaries introduced modern medicine was still a time of laissez-faire and pestilence. The third stage was ushered in by the liberation in 1949 and is characterized by the fact that the government no longer regards health as the private affair of the individual but as a task for the whole community. A number of endemic and epidemic diseases were conquered mainly through close cooperation between the population and medical workers. Success must be regarded as in an important part due to land reform and the eradication of famine. Further improvement in health care will depend to a great deal on improvement in living standards and a lessening of population pressure. As family planning meets resistance for economic and other reasons, only specific measures by the state can bring about a change in attitude. The progress in preventive measures is matched by advances in the technical aspects of medicine and especially too in medical education.

  3. Zur Biologie des marinen Heterotardigraden Tetrakentron synaptae

    NASA Astrophysics Data System (ADS)

    Kristensen, R. M.

    1980-06-01

    The life cycle of Tetrakentron synaptae Cuénot, 1892, a tardigrade closely associated with the sea cucumber Leptosynapta galliennei Herapath, was investigated in the littoral zone at Roscoff (France). Eggs and juveniles were found only in June and July, adults only from May to October. There are vagile males and stationary dwarf males. The dorsoventrally flattened body, an enlarged slimy epicuticle in females and dwarf males, the full set of claws also in juveniles, and the anus, which is in a dorsocaudal position, are indicative for an epizoic, sessile life. There is strong evidence that T. synaptae punctures the cells of L. galliennei and sucks out their content, which is indicative of parasitism.

  4. Zur Biologie von Paramphiascella fulvofasciata (Copepoda, Harpacticoida)

    NASA Astrophysics Data System (ADS)

    Dahms, Hans-Uwe

    1986-09-01

    The benthic harpacticoid copepod Paramphiascella fulvofasciata Rosenfield & Coull was collected from holdfasts of Laminaria hyperborea from a subtidal area of Helgoland (North Sea). All developmental stages of P. fulvofasciata are raptorial feeders. The feeding of the nauplii is advanced by a marginal setule-crest of the labrum which prevents food-particles from being swept away. The oral appendages of the copepodites circumscribe a frustal space ventral to the mouth which facilitates uptake of food-particles. The nauplii are not able to swim and perform stalking movements with their antennal endopodites. Good swimming ability as well as digging-in-behaviour and negative phototaxis of the copepodites indicate epi- as well as inbenthic mode of life. Several life-cycle characters are described. Precopula lasts ca. one day. The mean egg-number is 27, and mean egg-diameter is 87 × 75 µm. The number of nauplii per egg (double)-sac amounts to 25 30. Developmental time at 19°C is 6 9 days (nauplii) and 20 24 days (copepodites). The whole developmental period lasts 28 days. The maximal lifespan in the laboratory is 193 days. Sex-ratio is almost balanced. Females produce egg-sacs more than 3.5 times during their life period. Seasonal effects on reproductive activity have not been detected in laboratory cultures.

  5. Risk Factors for Eating Disorders

    ERIC Educational Resources Information Center

    Striegel-Moore, Ruth H.; Bulik, Cynthia M.

    2007-01-01

    The authors review research on risk factors for eating disorders, restricting their focus to studies in which clear precedence of the hypothesized risk factor over onset of the disorder is established. They illustrate how studies of sociocultural risk factors and biological factors have progressed on parallel tracks and propose that major advances…

  6. From compatible factorization to near-compatible factorization

    NASA Astrophysics Data System (ADS)

    Aldiabat, Raja'i.; Ibrahim, Haslinda

    2014-12-01

    A compatible factorization of order ν, is an ν× ν-1/2 array in which the entries in row i form a near-one-factor with focus i, and the triples associated with the rows contain no repetitions. In this paper, we aim to amend this compatible factorization so that we can display ν(ν-1)/2 - 2ν/3 triples with the minimum repeated triples. Throughout this paper we propose a new type of factorization called near-compatible factorization. First, we present the compatible factorization towards developing a near-compatible factorization. Second, we discuss briefly the necessary and sufficient conditions for the existence of near-compatible factorization. Then, we exemplify the construction for case ν = 9 as a groundwork in developing near-compatible factorization.

  7. Milestones and Impact Factors

    PubMed Central

    2010-01-01

    Environmental Health has just received its first Impact Factor by Thomson ISI. At a level of 2.48, this achievement is quite satisfactory and places Environmental Health in the top 25% of environmental science journals. When the journal was launched in 2002, it was still unclear whether the Open Access publishing model could be made into a viable commercial enterprise within the biomedical field. During the past eight years, Open Access journals have become widely available, although still covering only about 15% of journal titles. Major funding agencies and institutions, including prominent US universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent of digital media and its decentralized mode of distribution - the internet - have dramatically changed the control and financing of scientific information dissemination, while facilitating peer review, accelerating editorial handling, and supporting much needed transparency. Both the meaning and means of "having an impact" are therefore changing, as will the degree and way in which scientific journals remain "factors" in that impact. PMID:20615249

  8. Neutron quality factor

    SciTech Connect

    1995-06-01

    Both the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP) have recommended that the radiation quality weighting factor for neutrons (Q{sub n}, or the corresponding new modifying factor, w{sub R}) be increased by a value of two for most radiation protection practices. This means an increase in the recommended value for Q{sub n} from a nominal value of 10 to a nominal value of 20. This increase may be interpreted to mean that the biological effectiveness of neutrons is two times greater than previously thought. A decision to increase the value of Q{sub n} will have a major impact on the regulations and radiation protection programs of Federal agencies responsible for the protection of radiation workers. Therefore, the purposes of this report are: (1) to examine the general concept of {open_quotes}quality factor{close_quotes} (Q) in radiation protection and the rationale for the selection of specific values of Q{sub n}; and (2) to make such recommendations to the Federal agencies, as appropriate. This report is not intended to be an exhaustive review of the scientific literature on the biological effects of neutrons, with the aim of defending a particular value for Q{sub n}. Rather, the working group examined the technical issues surrounding the current recommendations of scientific advisory bodies on this matter, with the aim of determining if these recommendations should be adopted by the Federal agencies. Ultimately, the group concluded that there was no compelling basis for a change in Q{sub n}. The report was prepared by Federal scientists working under the auspices of the Science Panel of the Committee on Interagency Radiation Research and Policy Coordination (CIRRPC).

  9. Electromagnetic pion form factor

    SciTech Connect

    Roberts, C.D.

    1995-08-01

    A phenomenological Dyson-Schwinger/Bethe-Salpeter equation approach to QCD, formalized in terms of a QCD-based model field theory, the Global Color-symmetry Model (GCM), was used to calculate the generalized impulse approximation contribution to the electromagnetic pion form factor at space-like q{sup 2} on the domain [0,10] GeV{sup 2}. In effective field theories this form factor is sometimes understood as simply being due to Vector Meson Dominance (VMD) but this does not allow for a simple connection with QCD where the VMD contribution is of higher order than that of the quark core. In the GCM the pion is treated as a composite bound state of a confined quark and antiquark interacting via the exchange of colored vector-bosons. A direct study of the quark core contribution is made, using a quark propagator that manifests the large space-like-q{sup 2} properties of QCD, parameterizes the infrared behavior and incorporates confinement. It is shown that the few parameters which characterize the infrared form of the quark propagator may be chosen so as to yield excellent agreement with the available data. In doing this one directly relates experimental observables to properties of QCD at small space-like-q{sup 2}. The incorporation of confinement eliminates endpoint and pinch singularities in the calculation of F{sub {pi}}(q{sup 2}). With asymptotic freedom manifest in the dressed quark propagator the calculation yields q{sup 4}F{sub {pi}}(q{sup 2}) = constant, up to [q{sup 2}]- corrections, for space-like-q{sup 2} {approx_gt} 35 GeV{sup 2}, which indicates that soft, nonperturbative contributions dominate the form factor at presently accessible q{sup 2}. This means that the often-used factorization Ansatz fails in this exclusive process. A paper describing this work was submitted for publication. In addition, these results formed the basis for an invited presentation at a workshop on chiral dynamics and will be published in the proceedings.

  10. Human Factors Model

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  11. Nucleon elastic form factors

    SciTech Connect

    D. Day

    2007-03-01

    The nucleon form factors are still the subject of active investigation even after an experimental effort spanning 50 years. This is because they are of critical importance to our understanding of the electromagnetic properties of nuclei and provide a unique testing ground for QCD motivated models of nucleon structure. Progress in polarized beams, polarized targets and recoil polarimetry have allowed an important and precise set of data to be collected over the last decade. I will review the experimental status of elastic electron scattering from the nucleon along with an outlook for future progress.

  12. Factors Affecting Internal Blast

    NASA Astrophysics Data System (ADS)

    Granholm, R. H.; Sandusky, H. W.; Felts, J. E.

    2007-12-01

    Internal blast refers to explosion effects in confined spaces, which are dominated by the heat output of the explosive. Theoretical temperatures and pressures may not be reached due to heat losses and incomplete gas mixing. Gas mixing can have the largest effect, potentially reducing peak quasi-static pressure by a factor of two due to lack of thermal equilibrium between products and atmosphere in the space, separate from the effect of incomplete combustion of excess fuel when that atmosphere is air. Chamber and test geometry affect gas mixing, which has been inferred through temperature and pressure measurements and compared to calculations. Late-time combustion is observed for TNT compared to HMX.

  13. Enhanced target factor analysis.

    PubMed

    Rostami, Akram; Abdollahi, Hamid; Maeder, Marcel

    2016-03-10

    Target testing or target factor analysis, TFA, is a well-established soft analysis method. TFA answers the question whether an independent target test vector measured at the same wavelengths as the collection of spectra in a data matrix can be excluded as the spectrum of one of the components in the system under investigation. Essentially, TFA cannot positively prove that a particular test spectrum is the true spectrum of one of the components, it can, only reject a spectrum. However, TFA will not reject, or in other words TFA will accept, many spectra which cannot be component spectra. Enhanced Target Factor Analysis, ETFA addresses the above problem. Compared with traditional TFA, ETFA results in a significantly narrower range of positive results, i.e. the chance of a false positive test result is dramatically reduced. ETFA is based on feasibility testing as described in Refs. [16-19]. The method has been tested and validated with computer generated and real data sets.

  14. Factors regulating cheese shreddability.

    PubMed

    Childs, J L; Daubert, C R; Stefanski, L; Foegeding, E A

    2007-05-01

    Two sets of cheeses were evaluated to determine factors that affect shred quality. The first set of cheeses was made up of 3 commercial cheeses, Monterey Jack, Mozzarella, and process. The second set of cheeses was made up of 3 Mozzarella cheeses with varying levels of protein and fat at a constant moisture content. A shred distribution of long shreds, short shreds, and fines was obtained by shredding blocks of cheese in a food processor. A probe tack test was used to directly measure adhesion of the cheese to a stainless-steel surface. Surface energy was determined based on the contact angles of standard liquids, and rheological characterization was done by a creep and recovery test. Creep and recovery data were used to calculate the maximum and initial compliance and retardation time. Shredding defects of fines and adhesion to the blade were observed in commercial cheeses. Mozzarella did not adhere to the blade but did produce the most fines. Both Monterey Jack and process cheeses adhered to the blade and produced fines. Furthermore, adherence to the blade was correlated positively with tack energy and negatively with retardation time. Mozzarella cheese, with the highest fat and lowest protein contents, produced the most fines but showed little adherence to the blade, even though tack energy increased with fat content. Surface energy was not correlated with shredding defects in either group of cheese. Rheological properties and tack energy appeared to be the key factors involved in shredding defects. PMID:17430914

  15. SARSCEST (human factors)

    NASA Technical Reports Server (NTRS)

    Parsons, H. Mcilvaine

    1988-01-01

    People interact with the processes and products of contemporary technology. Individuals are affected by these in various ways and individuals shape them. Such interactions come under the label 'human factors'. To expand the understanding of those to whom the term is relatively unfamiliar, its domain includes both an applied science and applications of knowledge. It means both research and development, with implications of research both for basic science and for development. It encompasses not only design and testing but also training and personnel requirements, even though some unwisely try to split these apart both by name and institutionally. The territory includes more than performance at work, though concentration on that aspect, epitomized in the derivation of the term ergonomics, has overshadowed human factors interest in interactions between technology and the home, health, safety, consumers, children and later life, the handicapped, sports and recreation education, and travel. Two aspects of technology considered most significant for work performance, systems and automation, and several approaches to these, are discussed.

  16. Factors in risk perception

    PubMed

    Sjoberg

    2000-02-01

    Risk perception is a phenomenon in search of an explanation. Several approaches are discussed in this paper. Technical risk estimates are sometimes a potent factor in accounting for perceived risk, but in many important applications it is not. Heuristics and biases, mainly availability, account for only a minor portion of risk perception, and media contents have not been clearly implicated in risk perception. The psychometric model is probably the leading contender in the field, but its explanatory value is only around 20% of the variance of raw data. Adding a factor of "unnatural risk" considerably improves the psychometric model. Cultural Theory, on the other hand, has not been able to explain more than 5-10% of the variance of perceived risk, and other value scales have similarly failed. A model is proposed in which attitude, risk sensitivity, and specific fear are used as explanatory variables; this model seems to explain well over 30-40% of the variance and is thus more promising than previous approaches. The model offers a different type of psychological explanation of risk perception, and it has many implications, e.g., a different approach to the relationship between attitude and perceived risk, as compared with the usual cognitive analysis of attitude. PMID:10795334

  17. Design and application of chitosan/biphasic calcium phosphate porous scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Sendemir-Urkmez, Aylin

    For the restoration of maxillofacial bone tissue, design of novel tissue engineering scaffolds capable of inducing bone remodeling through the delivery of mesenchymal stem cells (MSCs) and an angiogenic growth factor, directly at the site of the defect was investigated in order to replace autogenous cancellous bone grafts with synthetic materials. Porous, three dimensional scaffolds were fabricated by a freeze drying method. In culture media, biphasic calcium phosphate particles within chitosan produced a surface reprecipitate of a composition similar to natural apatite that led to a uniform distribution of cells and mineralized ECM through chemotaxis. Further, the reprecipitation regulated the differentiation pathway and phenotype commitment of stem cells by altering the initial cell attachment morphology and actin cytoskeleton organization. In order to induce neovascularization after implantation, constructs were designed to be loaded with gelatin microspheres that delivered basic fibroblast growth factor (bFGF), a potent angiogenic factor. In vitro proliferation tests performed on fibroblastic cells showed no detectible loss of bFGF activity when delivered through enzymatic degradation of gelatin. Laser scanning confocal microscopy was used to demonstrate that gelatin microspheres can be injected evenly into cell-scaffold constructs owing to the spongy characteristics of the scaffold. To examine the binding interactions of bFGF with surface bound gelatin, a label free biosensor system, Biomolecular INteraction Detection sensor (BIND) was used. Results confirm that the principal interaction that takes place between bFGF and gelatin is electrostatic. Cell loaded tissue engineered constructs were produced in vitro at clinically relevant sizes and implanted with and without bFGF into a porcine mandibular defect model. Tissue engineered constructs facilitated the healing of mandibular defects only if combined with delivery of bFGF via gelatin microspheres. bFGF

  18. 125I-labeled anti-bFGF monoclonal antibody inhibits growth of hepatocellular carcinoma

    PubMed Central

    Hu, Peng-Hui; Pan, Lan-Hong; Wong, Patrick Ting-Yat; Chen, Wen-Hui; Yang, Yan-Qing; Wang, Hong; Xiang, Jun-Jian; Xu, Meng

    2016-01-01

    AIM: To investigate the inhibitory efficacy of 125I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC). METHODS: bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with 125I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of 125I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), 125I-bFGF mAb, 125I plus bFGF mAb, bFGF mAb, or 125I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction. RESULTS: The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 °C. After coupling, 125I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 °C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 1.88 ± 0.25, 1.625 ± 0.21, 1.5 ± 0.18, 1.41 ± 0.16, and 0.98 ± 0.11 g, respectively. The tumor inhibition ratio in the 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the 125I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the 125I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for 125I group) compared with the control group. CONCLUSION: 125I-bFGF m

  19. Pathophysiological factors underlying heatstroke.

    PubMed

    Yan, You-E; Zhao, Yong-Qi; Wang, Hui; Fan, Ming

    2006-01-01

    Heatstroke is a life-threatening illness characterized by an elevated core body temperature (>40 degrees C) and dysfunction of central nervous system, which results in delirium, convulsions, or coma. Despite adequate hypothermia or other care-therapy, heatstroke is often fatal. On the basis of our knowledge of the pathophysiology on heatstroke, we hypothesized that heatstroke is a form of hyperthermia associated with the acute physiological alterations, the cytotoxicity of heat, systemic inflammatory response, oxidative damage and attenuated heat-shock response leading to a syndrome of multi-organ dysfunction. In view of above-mentioned situation, the physiological factors underlying heatstroke and the corresponding possible therapeutic strategies to avert the complications of this disorder would be summarized in this review so as to provide some therapeutic guidelines for heatstroke. Heatstroke is a very complicated process. Acute physiological alterations, such as low arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischemia, and increased intracellular metabolism rate, occurred while exposed to a high ambient temperature. Hyperpyrexia caused cytotoxicity, resulting the degradation and aggregation of extensive intracellular proteins, influencing the change of membrane stability and fluidity, damaging the transmembrane transport of protein and the function of surface receptor, and inducing different cytoskeletal changes. Heatstroke resembles sepsis in many aspects, and endotoxemia and cytokines may be implicated in its pathogenesis. The concentration of interleukin-6 was positively correlated with the severity of heatstroke. The excessive accumulation of cytotoxic free radicals and oxidative damage may occur in the brain tissues during the genesis and development of heatstroke. The circulatory shock and cerebral ischemia resultant from heatstroke correlated closely with the free radicals (especially free radicals of peroxide and

  20. Fish collagen-based scaffold containing PLGA microspheres for controlled growth factor delivery in skin tissue engineering.

    PubMed

    Cao, Huan; Chen, Ming-Mao; Liu, Yan; Liu, Yuan-Yuan; Huang, Yu-Qing; Wang, Jian-Hua; Chen, Jing-Di; Zhang, Qi-Qing

    2015-12-01

    To design a scaffold controlled release system for skin tissue engineering, fish collagen/chitosan/chondroitin sulfate scaffolds were fabricated by freeze-drying and incorporated with bFGF-loaded PLGA microspheres (MPs). SEM showed that the scaffolds exhibited an interconnected porous structure, and the spherical MPs were uniformly distributed into the scaffolds. The higher swelling and degradation rate of scaffolds/MPs could lead to a higher diffusion rate of MPs from the scaffolds, causing an increase in the protein release. The release rate of proteins could be adjusted by the size of MPs and the ratio of collagen to chitosan of scaffolds. Circular dichroism spectroscopy and MTT of bFGF after release indicated that the released bFGF retained its structural integrity and bioactivity during preparation. Cell proliferation and in vivo evaluation results suggested that the scaffolds/MPs had a good biocompatibility and an ability to promote fibroblast cell proliferation and skin tissue regeneration. These results demonstrated that this scaffold/MP controlled release system has the potential for skin tissue engineering.

  1. Factorization and non-factorization in diffractive hard scattering

    SciTech Connect

    Berera, Arjun

    1997-04-20

    Factorization, in the sense defined for inclusive hard scattering, is discussed for diffractive hard scattering. A factorization theorem similar to its inclusive counterpart is presented for diffractive DIS. For hadron-hadron diffractive hard scattering, in contrast to its inclusive counterpart, the expected breakdown of factorization is discussed. Cross section estimates are given from a simple field theory model for non-factorizing double-pomeron-exchange (DPE) dijet production with and without account for Sudakov suppression.

  2. Pediatric rhinitis risk factors

    PubMed Central

    Ji, Yaofeng; Liu, Yin; Yang, Na

    2016-01-01

    Rhinitis is a common global disorder that impacts on the quality of life of the sufferer and caregivers. Treatment for pediatric rhinitis is empirical and does not include a detailed history of the allergy triggers or allergy testing. Thus, allergen avoidance advice is not tailored to the child's sensitivities, which may result in adenoid hypertrophy. However, infant onset rhinitis, especially its relationship with respiratory viruses, remains to be further clarified. Rhinitis basically involves inflammation of the upper nasal lining, presenting typically with symptoms of runny nose (rhinorrhea), nasal blockage, and/or sneezing. While not typically fatal, it does impose significant health, psychological, and monetary burden to its sufferers, and is thus considered a global health problem. Previous findings showed that immunotherapy had significant clinical efficacy in children with allergic rhinitis. The present review article aims to highlight recent perspectives pertaining to the rhinitis risk factors especially in pediatric patients. PMID:27698737

  3. Human factors in aviation

    NASA Technical Reports Server (NTRS)

    Wiener, Earl L. (Editor); Nagel, David C. (Editor)

    1988-01-01

    The fundamental principles of human-factors (HF) analysis for aviation applications are examined in a collection of reviews by leading experts, with an emphasis on recent developments. The aim is to provide information and guidance to the aviation community outside the HF field itself. Topics addressed include the systems approach to HF, system safety considerations, the human senses in flight, information processing, aviation workloads, group interaction and crew performance, flight training and simulation, human error in aviation operations, and aircrew fatigue and circadian rhythms. Also discussed are pilot control; aviation displays; cockpit automation; HF aspects of software interfaces; the design and integration of cockpit-crew systems; and HF issues for airline pilots, general aviation, helicopters, and ATC.

  4. Psychosomatic factors in pruritus.

    PubMed

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). PMID:23245971

  5. Exposure factors handbook

    SciTech Connect

    Konz, J.J.; Lisi, K.; Friebele, E.; Dixon, D.A.

    1989-07-01

    The document provides a summary of the available data on various factors used in assessing human exposure including drinking-water consumption, consumption rates of broad classes of food including fruits, vegetables, beef, dairy products, and fish; soil ingestion; inhalation rate; skin area; lifetime; activity patterns; and body weight. Additionally, a number of specific exposure scenarios are identified with recommendations for default values to use when site-specific data are not available. The basic equations using these parameters to calculate exposure levels are also presented for each scenario. Default values are presented as ranges from typical to reasonable worst case and as frequency distributions where appropriate data were available. Finally, procedures for assessing the uncertainties in exposure assessments are also presented with illustrative examples. These procedures include qualitative and quantitative methods such as Monte Carlo and sensitivity analysis.

  6. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Marc Vanderhaeghen; Charles Perdrisat; Vina Punjabi

    2007-10-01

    There has been much activity in the measurement of the elastic electromagnetic proton and neutron form factors in the last decade, and the quality of the data has greatly improved by performing double polarization experiments, in comparison with previous unpolarized data. Here we review the experimental data base in view of the new results for the proton, and neutron, obtained at JLab, MAMI, and MIT-Bates. The rapid evolution of phenomenological models triggered by these high-precision experiments will be discussed, including the recent progress in the determination of the valence quark generalized parton distributions of the nucleon, as well as the steady rate of improvements made in the lattice QCD calculations.

  7. Pion form factor

    SciTech Connect

    Ryong Ji, C.; Pang, A.; Szczepaniak, A.

    1994-04-01

    It is pointed out that the correct criterion to define the legal PQCD contribution to the exclusive processes in the lightcone perturbative expansion should be based on the large off-shellness of the lightcone energy in the intermediate states. In the lightcone perturbative QCD calculation of the pion form factor, the authors find that the legal PQCD contribution defined by the lightcone energy cut saturates in the smaller Q{sup 2} region compared to that defined by the gluon four-momentum square cut. This is due to the contribution by the highly off-energy-shell gluons in the end point regions of the phase space, indicating that the gluon four-momentum-square cut may have cut too much to define the legal PQCD.

  8. Psychosomatic factors in pruritus.

    PubMed

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease).

  9. Psychosomatic factors in pruritus

    PubMed Central

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). PMID:23245971

  10. Unity power factor converter

    NASA Technical Reports Server (NTRS)

    Wester, Gene W. (Inventor)

    1980-01-01

    A unity power factor converter capable of effecting either inversion (dc-to-dc) or rectification (ac-to-dc), and capable of providing bilateral power control from a DC source (or load) through an AC transmission line to a DC load (or source) for power flow in either direction, is comprised of comparators for comparing the AC current i with an AC signal i.sub.ref (or its phase inversion) derived from the AC ports to generate control signals to operate a switch control circuit for high speed switching to shape the AC current waveform to a sine waveform, and synchronize it in phase and frequency with the AC voltage at the AC ports, by selectively switching the connections to a series inductor as required to increase or decrease the current i.

  11. Pediatric rhinitis risk factors

    PubMed Central

    Ji, Yaofeng; Liu, Yin; Yang, Na

    2016-01-01

    Rhinitis is a common global disorder that impacts on the quality of life of the sufferer and caregivers. Treatment for pediatric rhinitis is empirical and does not include a detailed history of the allergy triggers or allergy testing. Thus, allergen avoidance advice is not tailored to the child's sensitivities, which may result in adenoid hypertrophy. However, infant onset rhinitis, especially its relationship with respiratory viruses, remains to be further clarified. Rhinitis basically involves inflammation of the upper nasal lining, presenting typically with symptoms of runny nose (rhinorrhea), nasal blockage, and/or sneezing. While not typically fatal, it does impose significant health, psychological, and monetary burden to its sufferers, and is thus considered a global health problem. Previous findings showed that immunotherapy had significant clinical efficacy in children with allergic rhinitis. The present review article aims to highlight recent perspectives pertaining to the rhinitis risk factors especially in pediatric patients.

  12. Helicopter Human Factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  13. Epidermal growth factor receptor not equal to nerve growth factor.

    PubMed

    Williams, L R

    1989-01-01

    I am perplexed by the authors' complete lack of definition of neurotrophic factors. The agents Butcher and Woolf want to blame are neurite promoting factors, not neurotrophic factors. Treatment of Alzheimer's disease with NGF antagonists might instead exacerbate the death of both basal forebrain neurons and their cortical target neurons, accelerating the progress of dementia.

  14. Factor Rotation and Standard Errors in Exploratory Factor Analysis

    ERIC Educational Resources Information Center

    Zhang, Guangjian; Preacher, Kristopher J.

    2015-01-01

    In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

  15. Phonological Awareness: Factors of Influence

    ERIC Educational Resources Information Center

    Frohlich, Linda Paulina; Petermann, Franz; Metz, Dorothee

    2013-01-01

    Early child development is influenced by various genetic and environmental factors. This study aims to identify factors that affect the phonological awareness of preschool and first grade children. Based on a sample of 330 German-speaking children (mean age = 6.2 years) the following domains were evaluated: Parent factors, birth and pregnancy,…

  16. Factor Analysis of Intern Effectiveness

    ERIC Educational Resources Information Center

    Womack, Sid T.; Hannah, Shellie Louise; Bell, Columbus David

    2012-01-01

    Four factors in teaching intern effectiveness, as measured by a Praxis III-similar instrument, were found among observational data of teaching interns during the 2010 spring semester. Those factors were lesson planning, teacher/student reflection, fairness & safe environment, and professionalism/efficacy. This factor analysis was as much of a…

  17. Risk Factor Assessment Branch (RFAB)

    Cancer.gov

    The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

  18. Factor Analysis via Components Analysis

    ERIC Educational Resources Information Center

    Bentler, Peter M.; de Leeuw, Jan

    2011-01-01

    When the factor analysis model holds, component loadings are linear combinations of factor loadings, and vice versa. This interrelation permits us to define new optimization criteria and estimation methods for exploratory factor analysis. Although this article is primarily conceptual in nature, an illustrative example and a small simulation show…

  19. The Estimation of Factor Indeterminacy.

    ERIC Educational Resources Information Center

    Budescu, David V.

    1983-01-01

    The degree of indeterminacy of the factor score estimates is biased and can lead to erroneous conclusion regarding the nature of the results. The magnitude of this bias is illustrated and guidelines for describing factor analytic studies using factor scores are offered. (Author/PN)

  20. Quantification of Emission Factor Uncertainty

    EPA Science Inventory

    Emissions factors are important for estimating and characterizing emissions from sources of air pollution. There is no quantitative indication of uncertainty for these emission factors, most factors do not have an adequate data set to compute uncertainty, and it is very difficult...

  1. Factors determining growth and vertical distribution of planktonic algae in extremely acidic mining lakes (pH 2.7)

    NASA Astrophysics Data System (ADS)

    Bissinger, Vera

    2003-04-01

    In this thesis, I investigated the factors influencing the growth and vertical distribution of planktonic algae in extremely acidic mining lakes (pH 2-3). In the focal study site, Lake 111 (pH 2.7; Lusatia, Germany), the chrysophyte, Ochromonas sp., dominates in the upper water strata and the chlorophyte, Chlamydomonas sp., in the deeper strata, forming a pronounced deep chlorophyll maximum (DCM). Inorganic carbon (IC) limitation influenced the phototrophic growth of Chlamydomonas sp. in the upper water strata. Conversely, in deeper strata, light limited its phototrophic growth. When compared with published data for algae from neutral lakes, Chlamydomonas sp. from Lake 111 exhibited a lower maximum growth rate, an enhanced compensation point and higher dark respiration rates, suggesting higher metabolic costs due to the extreme physico-chemical conditions. The photosynthetic performance of Chlamydomonas sp. decreased in high-light-adapted cells when IC limited. In addition, the minimal phosphorus (P) cell quota was suggestive of a higher P requirement under IC limitation. Subsequently, it was shown that Chlamydomonas sp. was a mixotroph, able to enhance its growth rate by taking up dissolved organic carbon (DOC) via osmotrophy. Therefore, it could survive in deeper water strata where DOC concentrations were higher and light limited. However, neither IC limitation, P availability nor in situ DOC concentrations (bottom-up control) could fully explain the vertical distribution of Chlamydomonas sp. in Lake 111. Conversely, when a novel approach was adopted, the grazing influence of the phagotrophic phototroph, Ochromonas sp., was found to exert top-down control on its prey (Chlamydomonas sp.) reducing prey abundance in the upper water strata. This, coupled with the fact that Chlamydomonas sp. uses DOC for growth, leads to a pronounced accumulation of Chlamydomonas sp. cells at depth; an apparent DCM. Therefore, grazing appears to be the main factor influencing the

  2. Uterine factors and infertility.

    PubMed

    Sanders, Barry

    2006-03-01

    A literature review was performed to explore the available information regarding the association of uterine factors--intrauterine adhesions, uterine septa, uterine myomas and endometrial polyps--with infertility and reproductive loss. The literature was reviewed also to ascertain evidence that treatment of these abnormalities improves fertility. A MEDLINE search was performed to identify the relevant publications in the English-language literature. There is minimal published evidence to demonstrate that intrauterine adhesions lead to infertility or pregnancy loss, but the literature does contain several observational series that demonstrate successful fertility, with term pregnancy rates ranging from 32% to 87% following hysteroscopic division of intrauterine adhesions. The evidence supporting a direct link between a septate uterus and reproductive loss/infertility is derived from the results of metroplasty. Several case series demonstrated a reduction in the spontaneous abortion rate, from 91% to 17%, on average, after hysteroscopic metroplasty. Furthermore, following metroplasty, the mean pregnancy rate in previously infertile patients is 47%. Little has been written regarding the association of endometrial polyps and infertility. One study did demonstrate a pregnancy rate of 78% after hysteroscopic polypectomy as compared to 42% in infertile patients with normal endometrial cavities. The literature that associates myomas with infertility/reproductive loss is more extensive but quite controversial. Evidence from the in vitro fertilization literature suggests that only those myomas that distort the endometrial cavity impair fertility. Pregnancy rates approximating 50% are achieved with myomectomy by laparotomy, laparoscopy or hysteroscopy.

  3. Factorizing monolithic applications

    SciTech Connect

    Hall, J.H.; Ankeny, L.A.; Clancy, S.P.

    1998-12-31

    The Blanca project is part of the US Department of Energy`s (DOE) Accelerated Strategic Computing Initiative (ASCI), which focuses on Science-Based Stockpile Stewardship through the large-scale simulation of multi-physics, multi-dimensional problems. Blanca is the only Los Alamos National Laboratory (LANL)-based ASCI project that is written entirely in C++. Tecolote, a new framework used in developing Blanca physics codes, provides an infrastructure for gluing together any number of components; this framework is then used to create applications that encompass a wide variety of physics models, numerical solution options, and underlying data storage schemes. The advantage of this approach is that only the essential components for the given model need be activated at runtime. Tecolote has been designed for code re-use and to isolate the computer science mechanics from the physics aspects as much as possible -- allowing physics model developers to write algorithms in a style quite similar to the underlying physics equations that govern the computational physics. This paper describes the advantages of component architectures and contrasts the Tecolote framework with Microsoft`s OLE and Apple`s OpenDoc. An actual factorization of a traditional monolithic application into its basic components is also described.

  4. [Environmental factors in ALS].

    PubMed

    Juntas-Morales, Raul; Pageot, Nicolas; Corcia, Philippe; Camu, William

    2014-05-01

    ALS is likely to be a disorder of multifactorial origin. Among all the factors that may increase the risk of ALS, environmental ones are being studied for many years, but in the recent years, several advances have pointed to a new interest in their potential involvement in the disease process, especially for the cyanotoxin BMAA. Food containing BMAA has been found on Guam, a well-known focus of ALS/parkinsonism/dementia and high levels of BMAA have been identified into the brain of these patients. The BMAA cyanotoxin is potentially ubiquitous and have also been found into the food of patients who died from ALS both in Europe and USA. BMAA can be wrongly integrated into the protein structure during mRNA traduction, competing with serine. This may induce abnormal protein folding and a subsequent cell death. Heavy metals, such as lead or mercury may be directly toxic for neuronal cells. Several works have suggested an increased risk of ALS in individuals chronically exposed to these metals. Exposure to pesticides has been suggested to be linked to an increased risk of developing ALS. The mechanism of their toxicity is likely to be mediated by paraoxonases. These proteins are in charge of detoxifying the organism from toxins, and particularly organophosphates. To date, there are insufficient scientific data to suggest that exposure to electromagnetic fields may increase the risk of having ALS. We are particularly missing longitudinal cohorts to demonstrate that risk.

  5. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byme, Vicky; Arsintescu, Lucia

    2008-01-01

    Future space missions will be significantly longer than current Shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. Training efforts in FY07 strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center operations. Beginning in January 2008, the training research effort will include team training prototypes and tools. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  6. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin; Sandor, Aniko

    2009-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 08 (FY08) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: (1) Risk associated with poor task design (2) Risk of error due to inadequate information (3) Risk associated with reduced safety and efficiency due to poor human factors design

  7. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin

    2010-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 09 (FY09) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; and 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  8. CXCR2 and its related ligands play a novel role in supporting the pluripotency and proliferation of human pluripotent stem cells.

    PubMed

    Jung, Ji-Hye; Lee, Seung Jin; Kim, JiHea; Lee, SongHee; Sung, Hwa-Jung; An, Jungsuk; Park, Yong; Kim, Byung Soo

    2015-04-15

    Basic fibroblast growth factor (bFGF) is a crucial factor sustaining human pluripotent stem cells (hPSCs). We designed this study to search the substitutive factors other than bFGF for the maintenance of hPSCs by using human placenta-derived conditioned medium without exogenous bFGF (hPCCM-), containing chemokine (C-X-C motif) receptor 2 (CXCR2) ligands, including interleukin (IL)-8 and growth-related oncogene α (GROα), which were developed on the basis of our previous studies. First, we confirmed that IL-8 and/or GROα play independent roles to preserve the phenotype of hPSCs. Then, we tried CXCR2 blockage of hPSCs in hPCCM- and verified the significant decrease of pluripotency-associated genes expression and the proliferation of hPSCs. Interestingly, CXCR2 suppression of hPSCs in mTeSR™1 containing exogenous bFGF decreased the proliferation of hPSCs while maintaining pluripotency characteristics. Lastly, we found that hPSCs proliferated robustly for more than 35 passages in hPCCM- on a gelatin substratum. Higher CXCR2 expression of hPSCs cultured in hPCCM- than those in mTeSR™1 was observable. Our findings suggest that CXCR2 and its related ligands might be novel factors comparable to bFGF supporting the characteristics of hPSCs and hPCCM- might be useful for the maintenance of hPSCs as well as for the accurate evaluation of CXCR2 role in hPSCs without the confounding influence of exogenous bFGF.

  9. Osteosarcoma cell-calcium signaling through tissue factor-factor VIIa complex and factor Xa.

    PubMed

    Daubie, Valéry; De Decker, Robert; Nicaise, Charles; Pochet, Roland

    2007-06-12

    The cells responsible for bone formation express protease-activated receptors. Although serine protease thrombin has been shown to elicit functional responses in bone cells that impact on cell survival and alkaline phosphatase activity, nothing is known about tissue factor, factor VIIa, and factor Xa, the serine proteases that act upstream of thrombin in the coagulation cascade. This paper demonstrates that tissue factor is expressed in the osteoblast-like cell line SaOS-2 and, that tissue factor in a factor VIIa-bound complex induces a transient intracellular Ca(2+) increase through protease-activated receptor-2. In SaOS-2 cells, factor Xa induced a sustained intracellular Ca(2+) response, as does SLIGRL, a PAR2-activating peptide, and PAR-1-dependent cell viability. PMID:17509570

  10. [Causality: risk factors and interventions].

    PubMed

    Dekkers, Olaf M; Vandenbroucke, Jan P

    2013-01-01

    A risk factor has a causal effect on a disease when the disease would not have occurred in the absence of the risk factor. Analogous reasoning applies to the effect of a particular therapy. Thinking in terms of contrasts is fundamental to causal reasoning in medicine. The contrast determines the content of the causal claim; the most important assumption here is that the prognosis between groups is comparable. Causal effects of risk factors are not always the same as the causal effect of an intervention: removal of a risk factor (e.g. smoking) for a disease does not necessarily mean that the risk will subsequently normalize. A second problem is that risk factors cannot always easily be translated into interventions. This applies to factors that cannot be changed (e.g. gender) or that can have multiple causes themselves (e.g. obesity).

  11. Women's Career Success: A Factor Analytic Study of Contributing Factors.

    ERIC Educational Resources Information Center

    Gaskill, LuAnn Ricketts

    1991-01-01

    A survey of 466 women employed in retailing received 205 responses identifying (1) factors influencing the success and advancement of women in retailing and (2) how those factors differ for women in upper versus middle positions. Upper-level executives placed more importance on ambition and abilities; midlevel executives credited opportunity and…

  12. Factorized molecular wave functions: Analysis of the nuclear factor

    SciTech Connect

    Lefebvre, R.

    2015-06-07

    The exact factorization of molecular wave functions leads to nuclear factors which should be nodeless functions. We reconsider the case of vibrational perturbations in a diatomic species, a situation usually treated by combining Born-Oppenheimer products. It was shown [R. Lefebvre, J. Chem. Phys. 142, 074106 (2015)] that it is possible to derive, from the solutions of coupled equations, the form of the factorized function. By increasing artificially the interstate coupling in the usual approach, the adiabatic regime can be reached, whereby the wave function can be reduced to a single product. The nuclear factor of this product is determined by the lowest of the two potentials obtained by diagonalization of the potential matrix. By comparison with the nuclear wave function of the factorized scheme, it is shown that by a simple rectification, an agreement is obtained between the modified nodeless function and that of the adiabatic scheme.

  13. Immunologic studies of factor IX (Christmas factor). II. Immunoradiometric assay of factor IX antigen.

    PubMed

    Yang, H C

    1978-06-01

    A solid-phase two-site immunoradiometric assay has been developed which measures factor IX antigen levels as low as 0.0004 u per ml of plasma. In normal individuals, the factor IX antigen level correlated with the factor IX procoagulant level. In haemophilia B, 14 patients had markedly reduced antigen levels (less than 0.06 u/ml) and five had normal levels (greater than 0.60 u/ml).

  14. Peripheral nerve regeneration through a silicone chamber implanted with negative carbon ions: Possibility to clinical application

    NASA Astrophysics Data System (ADS)

    Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Tsuji, Hiroshi; Yasuda, Tadashi; Matsuda, Shuichi

    2014-08-01

    We investigated whether a tube with its inner surface implanted with negative-charged carbon ions (C- ions) would enable axons to extend over a distance greater than 10 mm. The tube was found to support nerves regenerating across a 15-mm-long inter-stump gap. We also investigated whether a C- ion-implanted tube pretreated with basic fibroblast growth factor (bFGF) promotes peripheral nerve regeneration. The C- ion implanted tube accelerated nerve regeneration, and this effect was enhanced by bFGF. Silicone treated with C- ions showed increased hydrophilic properties and cellular affinity, and axon regeneration was promoted with this increased biocompatibility.

  15. Oncogenes, genes, and growth factors

    SciTech Connect

    Guroff, G.

    1989-01-01

    This book contains 12 chapters. Some of the chapter titles are: The Epidermal Growth Factor Receptor Gene; Structure and Expression of the Nerve Growth Factor Gene; The Erythropoietin Gene; The Interleukin-2 Gene; The Transferrin Gene; and The Transferrin Receptor Gene.

  16. Matrix factorizations and elliptic fibrations

    NASA Astrophysics Data System (ADS)

    Omer, Harun

    2016-09-01

    I use matrix factorizations to describe branes at simple singularities of elliptic fibrations. Each node of the corresponding Dynkin diagrams of the ADE-type singularities is associated with one indecomposable matrix factorization which can be deformed into one or more factorizations of lower rank. Branes with internal fluxes arise naturally as bound states of the indecomposable factorizations. Describing branes in such a way avoids the need to resolve singularities. This paper looks at gauge group breaking from E8 fibers down to SU (5) fibers due to the relevance of such fibrations for local F-theory GUT models. A purpose of this paper is to understand how the deformations of the singularity are understood in terms of its matrix factorizations. By systematically factorizing the elliptic fiber equation, this paper discusses geometries which are relevant for building semi-realistic local models. In the process it becomes evident that breaking patterns which are identical at the level of the Kodaira type of the fibers can be inequivalent at the level of matrix factorizations. Therefore the matrix factorization picture supplements information which the conventional less detailed descriptions lack.

  17. Factorization with genus 2 curves

    NASA Astrophysics Data System (ADS)

    Cosset, Romain

    2010-04-01

    The elliptic curve method (ECM) is one of the best factorization methods available. It is possible to use hyperelliptic curves instead of elliptic curves but it is in theory slower. We use special hyperelliptic curves and Kummer surfaces to reduce the complexity of the algorithm. Our implementation GMP-HECM is faster than GMP-ECM for factoring large numbers.

  18. Factors That Influence Teacher Attrition.

    ERIC Educational Resources Information Center

    Gonzalez, Patricia

    1995-01-01

    External, employment, and personal factors which influence teacher decisions to stay, leave, or transfer from teaching assignments are discussed, with emphasis on special education teachers. Factors attributed to teacher attrition in urban and rural environments also are briefly reviewed, along with attrition of related services professionals.…

  19. Statistical Factors in Complexation Reactions.

    ERIC Educational Resources Information Center

    Chung, Chung-Sun

    1985-01-01

    Four cases which illustrate statistical factors in complexation reactions (where two of the reactants are monodentate ligands) are presented. Included are tables showing statistical factors for the reactions of: (1) square-planar complexes; (2) tetrahedral complexes; and (3) octahedral complexes. (JN)

  20. [Risk factors for arterial disease].

    PubMed

    Madoery, Roberto; Rubin, Graciela; Luquez, Hugo; Luquez, Cecilia; Cravero, Cecilia

    2004-01-01

    The risk factors of arterial disease (FREA) predict a future damage over the vascular system of the human body. Its detection are considered a key for the diagnostic as well as for the preventive and even curative strategies. For a long time, scientist considered those factors originated as a consecuence of large studies during the middle of the last century, with current validity up to our days. A simple classification spoke of them as traditionals. Further investigations described the so called new or emergents.factors that where joint together accordingly to their actions: coagulation factors, psicosocial, inflamatories and infectious. A recent classification, taking into account the type of impact, divided them into; causatives, predisposals and conditionals. Also, it was described a mechanism, the oxidative power, with consecuences over the endothelium, in the last part of the process. Before, another mechanism was described: the insulin resistance and the hiperinsulinism, bases for the Metabolic Syndrome, that includes a number of traditional risk factors.

  1. Great Lakes management: Ecological factors

    NASA Astrophysics Data System (ADS)

    Sonzogni, W. C.; Robertson, A.; Beeton, A. M.

    1983-11-01

    Although attempts to improve the quality of the Great Lakes generally focus on chemical pollution, other factors are important and should be considered Ecological factors, such as invasion of the lakes by foreign species, habitat changes, overfishing, and random variations in organism populations, are especially influential. Lack of appreciation of the significance of ecological factors stems partly from the inappropriate application of the concept of eutrophication to the Great Lakes. Emphasis on ecological factors is not intended to diminish the seriousness of pollution, but rather to point out that more cost-effective management, as well as more realistic expectations of management efforts by the public, should result from an ecosystem management approach in which ecological factors are carefully considered.

  2. Possible involvement of basic FGF in the upregulation of PDGFRβ in pericytes after ischemic stroke.

    PubMed

    Nakamura, Kuniyuki; Arimura, Koichi; Nishimura, Ataru; Tachibana, Masaki; Yoshikawa, Yoji; Makihara, Noriko; Wakisaka, Yoshinobu; Kuroda, Junya; Kamouchi, Masahiro; Ooboshi, Hiroaki; Kitazono, Takanari; Ago, Tetsuro

    2016-01-01

    Central nervous system (CNS) pericytes have been recognized as an indispensable component of the neurovascular unit. The expression of platelet-derived growth factor receptor β (PDGFRβ) is markedly increased in CNS pericytes after brain ischemia. It has been elucidated that PDGFRβ, expressed in pericytes and pericyte-derived fibroblast-like cells, plays important roles in the maintenance of the blood-brain barrier (BBB) and in the repair process in infarct areas. The aim of this study was to uncover how the PDGFRβ expression is regulated in pericytes after brain ischemia. We found that basic fibroblast growth factor (bFGF), but neither hypoxia at 1% O2 nor acidification at pH 6.5, significantly upregulated the PDGFRβ expression in human cultured CNS pericytes. SU5402, an inhibitor of FGF receptor (FGFR), and inhibitors of its downstream effectors Akt and Erk abolished the bFGF-induced upregulation of PDGFRβ. On the other hand, acidification significantly upregulated the expression of bFGF, while hypoxia upregulated the expression of FGFR1 in the pericytes. The expression of bFGF and FGFR1 was markedly induced in the ischemic hemisphere after ischemic insult in a middle cerebral artery occlusion stroke model. Immunofluorescent double labeling demonstrated that the expression of bFGF and FGFR1 was co-localized with PDGFRβ-positive cells in peri-infarct areas. Moreover, treatment with bFGF enhanced cell growth and the PDGF-BB-induced migratory activity of cultured pericytes, which were significantly suppressed by SU5402 or Sunitinib, an inhibitor of PDGFR. These data suggested that increased bFGF upregulates the expression of PDGFRβ and may enhance PDGFRβ-mediated pericyte functions after brain ischemia.

  3. Using Bayes factors for multi-factor, biometric authentication

    NASA Astrophysics Data System (ADS)

    Giffin, A.; Skufca, J. D.; Lao, P. A.

    2015-01-01

    Multi-factor/multi-modal authentication systems are becoming the de facto industry standard. Traditional methods typically use rates that are point estimates and lack a good measure of uncertainty. Additionally, multiple factors are typically fused together in an ad hoc manner. To be consistent, as well as to establish and make proper use of uncertainties, we use a Bayesian method that will update our estimates and uncertainties as new information presents itself. Our algorithm compares competing classes (such as genuine vs. imposter) using Bayes Factors (BF). The importance of this approach is that we not only accept or reject one model (class), but compare it to others to make a decision. We show using a Receiver Operating Characteristic (ROC) curve that using BF for determining class will always perform at least as well as the traditional combining of factors, such as a voting algorithm. As the uncertainty decreases, the BF result continues to exceed the traditional methods result.

  4. GATA factors in endocrine neoplasia.

    PubMed

    Pihlajoki, Marjut; Färkkilä, Anniina; Soini, Tea; Heikinheimo, Markku; Wilson, David B

    2016-02-01

    GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted.

  5. Corrosion effects on friction factors

    SciTech Connect

    Magleby, H.L.; Shaffer, S.J.

    1996-03-01

    This paper presents the results of NRC-sponsored material specimen tests that were performed to determine if corrosion increases the friction factors of sliding surfaces of motor-operated gate valves, which could require higher forces to close and open safety-related valves when subjected to their design basis differential pressures. Friction tests were performed with uncorroded specimens and specimens subjected to accelerated corrosion. Preliminary tests at ambient conditions showed that corrosion increased the friction factors, indicating the need for additional tests duplicating valve operating parameters at hot conditions. The additional tests showed friction factors of corroded specimens were 0.1 to 0.2 higher than for uncorroded specimens, and that the friction factors of the corroded specimens were not very dependent on contact stress or corrosion film thickness. The measured values of friction factors for the three corrosion films tested (simulating three operating times) were in the range of 0.3 to 0.4. The friction factor for even the shortest simulated operating time was essentially the same as the others, indicating that the friction factors appear to reach a plateau and that the plateau is reached quickly.

  6. Risk Factors For Chronic Rhinosinusitis

    PubMed Central

    Min, Jin-Young; Tan, Bruce K.

    2015-01-01

    Purpose of review To review the recent literature on risk factors for chronic rhinosinusitis (CRS) with an emphasis on genetic, comorbid diseases and environmental factors associated with CRS. Through identifying potential risk factors for CRS, we glean insights into the underlying pathogenic mechanisms and essential for developing effective therapeutic strategies. Recent findings Recent findings demonstrate that genetics, comorbid medical conditions including airway diseases, gastroesophageal reflux disease, inflammatory and autoimmune diseases and various demographic and environmental factors are associated with having a CRS diagnosis. Limitations of current studies include, variable application of disease definitions, lack of prospective longitudinal studies and a disproportionate focus on tertiary care populations. Summary CRS has a broad spectrum of associations ranging from genetics to comorbid diseases and environmental factors. These predisposing factors provide valuable information for possible designing therapeutic and preventive interventions. However, to better understand whether these associations cause CRS, further studies are needed to independently replicate findings, establish temporal relationships between exposure and disease onset, evaluate the influence of exposure dose on disease severity, and to understand the biological effects of these risk factors in the context of CRS. PMID:25479315

  7. Factors Affecting Medical Service Quality

    PubMed Central

    MOSADEGHRAD, Ali Mohammad

    2014-01-01

    Abstract Background A better understanding of factors influencing quality of medical service can pinpoint better strategies for quality assurance in medical services. This study aimed to identify factors affecting the quality of medical services provided by Iranian physicians. Methods Exploratory in-depth individual interviews were conducted with sixty-four physicians working in various medical institutions in Iran. Results Individual, organizational and environmental factors enhance or inhibit the quality of medical services. Quality of medical services depends on the personal factors of the physician and patient, and factors pertaining to the healthcare setting and the broader environment. Conclusion Differences in internal and external factors such as availability of resources, patient cooperation and collaboration among providers affect the quality of medical services and patient outcomes. Supportive leadership, proper planning, education and training and effective management of resources and processes improve the quality of medical services. This article contributes to healthcare theory and practice by developing a conceptual framework for understanding factors that influence medical services quality. PMID:26060745

  8. Sequence Factorization with Multiple References

    PubMed Central

    Wandelt, Sebastian; Leser, Ulf

    2015-01-01

    The success of high-throughput sequencing has lead to an increasing number of projects which sequence large populations of a species. Storage and analysis of sequence data is a key challenge in these projects, because of the sheer size of the datasets. Compression is one simple technology to deal with this challenge. Referential factorization and compression schemes, which store only the differences between input sequence and a reference sequence, gained lots of interest in this field. Highly-similar sequences, e.g., Human genomes, can be compressed with a compression ratio of 1,000:1 and more, up to two orders of magnitude better than with standard compression techniques. Recently, it was shown that the compression against multiple references from the same species can boost the compression ratio up to 4,000:1. However, a detailed analysis of using multiple references is lacking, e.g., for main memory consumption and optimality. In this paper, we describe one key technique for the referential compression against multiple references: The factorization of sequences. Based on the notion of an optimal factorization, we propose optimization heuristics and identify parameter settings which greatly influence 1) the size of the factorization, 2) the time for factorization, and 3) the required amount of main memory. We evaluate a total of 30 setups with a varying number of references on data from three different species. Our results show a wide range of factorization sizes (optimal to an overhead of up to 300%), factorization speed (0.01 MB/s to more than 600 MB/s), and main memory usage (few dozen MB to dozens of GB). Based on our evaluation, we identify the best configurations for common use cases. Our evaluation shows that multi-reference factorization is much better than single-reference factorization. PMID:26422374

  9. Sigma Factors for Cyanobacterial Transcription

    PubMed Central

    Imamura, Sousuke; Asayama, Munehiko

    2009-01-01

    Cyanobacteria are photosynthesizing microorganisms that can be used as a model for analyzing gene expression. The expression of genes involves transcription and translation. Transcription is performed by the RNA polymerase (RNAP) holoenzyme, comprising a core enzyme and a sigma (σ) factor which confers promoter selectivity. The unique structure, expression, and function of cyanobacterial σ factors (and RNAP core subunits) are summarized here based on studies, reported previously. The types of promoter recognized by the σ factors are also discussed with regard to transcriptional regulation. PMID:19838335

  10. Predisposition Factors in Anorexia Nervosa.

    ERIC Educational Resources Information Center

    Nagel, K. L.; Jones, Karen H.

    1992-01-01

    Reviews literature concerned with investigating psychiatric disturbances and genetic variables hypothesized as predisposing factors in etiology of anorexia nervosa. Gives particular emphasis to research which discusses association between anorexia nervosa and depression. Reviews psychopharmacological evidence and family genetics studies. Offers…

  11. Factorization-based texture segmentation

    DOE PAGES

    Yuan, Jiangye; Wang, Deliang; Cheriyadat, Anil M.

    2015-06-17

    This study introduces a factorization-based approach that efficiently segments textured images. We use local spectral histograms as features, and construct an M × N feature matrix using M-dimensional feature vectors in an N-pixel image. Based on the observation that each feature can be approximated by a linear combination of several representative features, we factor the feature matrix into two matrices-one consisting of the representative features and the other containing the weights of representative features at each pixel used for linear combination. The factorization method is based on singular value decomposition and nonnegative matrix factorization. The method uses local spectral histogramsmore » to discriminate region appearances in a computationally efficient way and at the same time accurately localizes region boundaries. Finally, the experiments conducted on public segmentation data sets show the promise of this simple yet powerful approach.« less

  12. Formulas for Image Factor Scores

    ERIC Educational Resources Information Center

    Hakstian, A. Ralph

    1973-01-01

    Formulas are presented in this paper for computing scores associated with factors of G, the image covariance matrix, under three conditions. The subject of the paper is restricted to "pure" image analysis. (Author/NE)

  13. Environmental Factors Inducing Human Cancers

    PubMed Central

    Parsa, N

    2012-01-01

    Background An explosion of research has been done in discovering how human health is affected by environmental factors. I will discuss the impacts of environmental cancer causing factors and how they continue to cause multiple disruptions in cellular networking. Some risk factors may not cause cancer. Other factors initiate consecutive genetic mutations that would eventually alter the normal pathway of cellular proliferations and differentiation. Genetic mutations in four groups of genes; (Oncogenes, Tumor suppressor genes, Apoptosis genes and DNA repairing genes) play a vital role in altering the normal cell division. In recent years, molecular genetics have greatly increased our understanding of the basic mechanisms in cancer development and utilizing these molecular techniques for cancer screening, diagnosis, prognosis and therapies. Inhibition of carcinogenic exposures wherever possible should be the goal of cancer prevention programs to reduce exposures from all environmental carcinogens. PMID:23304670

  14. Radiant-interchange Configuration Factors

    NASA Technical Reports Server (NTRS)

    Hamilton, D C :; Morgan, W R

    1952-01-01

    A study is presented of the geometric configuration factors required for computing radiant heat transfer between opaque surfaces separated by a nonabsorbing medium and various methods of determining the configuration factors are discussed. Configuration-factor solutions available in the literature have been checked and the more complicated equations are presented as families of curves. Cases for point, line, and finite-area sources are worked out over a wide range of geometric proportions. These cases include several new configurations involving rectangles, triangles, and cylinders of finite length which are integrated and tabulated. An analysis is presented, in which configuration factors are employed of the radiant heat transfer to the rotor blades of a typical gas turbine under different conditions of temperature and pressure. (author)

  15. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  16. Factorization-based texture segmentation

    SciTech Connect

    Yuan, Jiangye; Wang, Deliang; Cheriyadat, Anil M.

    2015-06-17

    This study introduces a factorization-based approach that efficiently segments textured images. We use local spectral histograms as features, and construct an M × N feature matrix using M-dimensional feature vectors in an N-pixel image. Based on the observation that each feature can be approximated by a linear combination of several representative features, we factor the feature matrix into two matrices-one consisting of the representative features and the other containing the weights of representative features at each pixel used for linear combination. The factorization method is based on singular value decomposition and nonnegative matrix factorization. The method uses local spectral histograms to discriminate region appearances in a computationally efficient way and at the same time accurately localizes region boundaries. Finally, the experiments conducted on public segmentation data sets show the promise of this simple yet powerful approach.

  17. Human factors of visual displays

    NASA Technical Reports Server (NTRS)

    Snyder, H. L.

    1984-01-01

    Several human factors issues in visual displays are addressed in this report. They are as follows: (1) the importance of luminance range and contrast; (2) uniformity of visual displays; (3) image quality; (4) color contrast; and (5) dot matrix fonts.

  18. Factors That Impair Wound Healing.

    PubMed

    Anderson, Kristin; Hamm, Rose L

    2012-12-01

    The body's response to tissue injury in a healthy individual is an intricate, sequential physiologic process that results in timely healing with full re-epithelialization, resolution of drainage, and return of function to the affected tissue. Chronic wounds, however, do not follow this sequence of events and can challenge the most experienced clinician if the underlying factors that are impairing wound healing are not identified. The purpose of this article is to present recent information about factors that impair wound healing with the underlying pathophysiological mechanism that interferes with the response to tissue injury. These factors include co-morbidities (diabetes, obesity, protein energy malnutrition), medications (steroids, non-steroidal anti-inflammatory drugs or NSAIDs, anti-rejection medications), oncology interventions (radiation, chemotherapy), and life style habits (smoking, alcohol abuse). Successful treatment of any chronic wound depends upon identification and management of the factors for each individual.

  19. Chemical Specific Adjustment Factors Workshop

    EPA Science Inventory

    The World Health Organization, through the International Programme on Chemical Safety (IPCS), has established guidance on the use of mechanistic data to replace default uncertainty factors for interspecies extrapolation and intraspecies variability in deriving risk values such as...

  20. Human Factors In Aircraft Automation

    NASA Technical Reports Server (NTRS)

    Billings, Charles

    1995-01-01

    Report presents survey of state of art in human factors in automation of aircraft operation. Presents examination of aircraft automation and effects on flight crews in relation to human error and aircraft accidents.

  1. Hidden Risk Factors for Women

    MedlinePlus

    ... high cholesterol. “Those are the most common risk factors,” according to Steven J. Kittner, M.D., director of the Maryland Stroke Center at the University of Maryland School of Medicine in Baltimore. “But ...

  2. Topical application of Cleome viscosa increases the expression of basic fibroblast growth factor and type III collagen in rat cutaneous wound.

    PubMed

    Upadhyay, Aadesh; Chattopadhyay, Pronobesh; Goyary, Danswrang; Mazumder, Papiya M; Veer, Vijay

    2014-01-01

    Cleome viscosa L. (Cleomaceae) is an important traditional medicine of the Indian-Ayurvedic and Chinese-medicine system documented for rheumatic arthritis, hypertension, malaria, neurasthenia, and wound healing. The plant is also known as Asian spider flower and is distributed throughout the greater part of India. The present study explored the wound healing property of C. viscosa methanol extract (CvME) and its related mechanism using Wistar rat cutaneous excision wound model. Wound contraction rate, hydroxyproline quantification, and histopathological examination of wound granulation tissue were performed. The healing potential was comparatively assessed with a reference gentamicin sulfate hydrogel (0.01% w/w). Western blot for COL3A1, bFGF, and Smad-2, Smad-3, Smad-4, and Smad-7 was performed with 7-day postoperative granulation tissue. Results revealed that the topical application of CvME (2.5% w/w) significantly accelerated the wound contraction rate (95.14%, 24 postoperative days), increased the hydroxyproline content (3.947 mg/100 mg tissue), and improved histopathology of wound tissue as compared to control groups. Western blot analysis revealed that CvME significantly upregulated the expression of COL3A1 and bFGF and increased the Smad-mediated collagen production in granulation tissue. These findings suggest that C. viscosa promoted the wound repair process by attenuating the Smad-mediated collagen production in wound granulation tissue. PMID:24864253

  3. Antiretroviral restriction factors in mice.

    PubMed

    Nair, Smita; Rein, Alan

    2014-11-26

    One of the most exciting areas in contemporary retrovirus research is the discovery of "restriction factors". These are cellular proteins that act after virus entry to inhibit infection by or replication of retroviruses (and other viruses and intracellular pathogens). We briefly discuss here three antiretroviral restriction factors in mice: Fv1, APOBEC3, and tetherin, touching on both biological and molecular aspects of these restriction systems.

  4. Interstitial fibrosis and growth factors.

    PubMed Central

    Lasky, J A; Brody, A R

    2000-01-01

    Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety of inhaled agents including mineral particles, organic dusts, and oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for therapy. Our laboratory has focused on the molecular mechanisms through which three selected peptide growth factors could play a role in the development of IPF. Hundreds of growth factors and cytokines could be involved in the complex disease process. We are studying platelet-derived growth factor because it is the most potent mesenchymal cell mitogen yet described, transforming growth factor beta because it is a powerful inducer of extracellular matrix (scar tissue) components by mesenchymal cells, and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches. Images Figure 1 Figure 2 PMID:10931794

  5. Industrial Power Factor Analysis Guidebook.

    SciTech Connect

    Electrotek Concepts.

    1995-03-01

    Power factor is a way of measuring the percentage of reactive power in an electrical system. Reactive power represents wasted energy--electricity that does no useful work because the electrical current is out of phase with the voltage. Reactive power is used by inductive loads (such as, motors, transformers, fluorescent lights, arc welders and induction furnaces) to sustain their magnetic fields. Electric systems with many motors exhibit low power factors, increased conductor and transformer losses, and lower voltages. Utilities must supply both active and reactive power and compensate for these losses. Power factor can be improved by the addition of shunt capacitors. Capacitors act in opposition to inductive loads, thereby minimizing the reactive power required to serve them. In raising the power factor, shunt capacitors release energy to the system, reduce system losses, and ultimately decrease power costs. Improving system power factor can reduce reactive and active power losses for both industry and utilities through the addition of shunt capacitors. This Guide Book gives electric utility technical staff, industrial end-users, consultants and BPA employees a step-by-step method for evaluating the cost effectiveness of installing power factor correction capacitors in an industrial plant.

  6. Structural Biology Of Factor VIIa/Tissue Factor Initiated Coagulation

    PubMed Central

    Vadivel, Kanagasabai; Paul Bajaj, S.

    2012-01-01

    Factor VII (FVII) consists of an N-terminal gamma-carboxyglutamic acid domain followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C-terminal protease domain. Activation of FVII results in a two-chain FVIIa molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain (protease domain) held together by a single disulfide bond. During coagulation, the complex of tissue factor (TF, a transmembrane glycoprotein) and FVIIa activates factor IX (FIX) and factor X (FX). FVIIa is structurally “zymogen-like” and when bound to TF, it is more “active enzyme-like.” FIX and FX share structural homology with FVII. Three structural biology aspects of FVIIa/TF are presented in this review. One, regions in soluble TF (sTF) that interact with FVIIa as well as mapping of Ca2+, Mg2+, Na+ and Zn2+ sites in FVIIa and their functions; two, modeled interactive regions of Gla and EGF1 domains of FXa and FIXa with FVIIa/sTF; and three, incompletely formed oxyanion hole in FVIIa/sTF and its induction by substrate/inhibitor. Finally, an overview of the recognition elements in TF pathway inhibitor is provided. PMID:22652793

  7. Microfluidic analysis of extracellular matrix-bFGF crosstalk on primary human myoblast chemoproliferation, chemokinesis, and chemotaxis

    PubMed Central

    Ferreira, Meghaan M.; Dewi, Ruby E.; Heilshorn, Sarah C.

    2015-01-01

    Exposing myoblasts to basic fibroblast growth factor (bFGF), which is released after muscle injury, results in receptor phosphorylation, faster migration, and increased proliferation. These effects occur on time scales that extend across three orders of magnitude (100 – 103 minutes). Finite element modeling of Transwell assays, which are traditionally used to assess chemotaxis, revealed that the bFGF gradient formed across the membrane pore is short-lived and diminishes 45% within the first minute. Thus, to evaluate bFGF-induced migration over 102 minutes, we employed a microfluidic assay capable of producing a stable, linear concentration gradient to perform single-cell analyses of chemokinesis and chemotaxis. We hypothesized that the composition of the underlying extracellular matrix (ECM) may affect the behavioral response of myoblasts to soluble bFGF, as previous work with other cell types has suggested crosstalk between integrin and fibroblast growth factor (FGF) receptors. Consistent with this notion, we found that bFGF significantly reduced the doubling time of myoblasts cultured on laminin but not fibronectin or collagen. Laminin also promoted significantly faster migration speeds (13.4 μm/h) than either fibronectin (10.6 μm/h) or collagen (7.6 μm/h) without bFGF stimulation. Chemokinesis driven by bFGF further increased migration speed in a strictly additive manner, resulting in an average increase of 2.3 μm/h across all ECMs tested. We observed relatively mild chemoattraction (~ 67% of myoblast population) in response to bFGF gradients of 3.2 ng/mL/mm regardless of ECM identity. Thus, while ECM-bFGF crosstalk did impact chemoproliferation, it did not have a significant effect on chemokinesis or chemotaxis. These data suggest that the main physiological effect of bFGF on myoblast migration is chemokinesis and that changes in the surrounding ECM, resulting from aging and/or disease may impact muscle regeneration by altering myoblast migration and

  8. Factors influencing healthcare service quality

    PubMed Central

    Mosadeghrad, Ali Mohammad

    2014-01-01

    Background: The main purpose of this study was to identify factors that influence healthcare quality in the Iranian context. Methods: Exploratory in-depth individual and focus group interviews were conducted with 222 healthcare stakeholders including healthcare providers, managers, policy-makers, and payers to identify factors affecting the quality of healthcare services provided in Iranian healthcare organisations. Results: Quality in healthcare is a production of cooperation between the patient and the healthcare provider in a supportive environment. Personal factors of the provider and the patient, and factors pertaining to the healthcare organisation, healthcare system, and the broader environment affect healthcare service quality. Healthcare quality can be improved by supportive visionary leadership, proper planning, education and training, availability of resources, effective management of resources, employees and processes, and collaboration and cooperation among providers. Conclusion: This article contributes to healthcare theory and practice by developing a conceptual framework that provides policy-makers and managers a practical understanding of factors that affect healthcare service quality. PMID:25114946

  9. [Risk factors of necrotizing enterocolitis].

    PubMed

    Tapia-Rombo, C A; Velasco-Lavín, M R; Nieto-Caldelas, A

    1993-09-01

    The purpose of the present study is to compare risk factors of necrotizing enterocolitis (NEC) between two group: group A, newborns with the disease and group B, newborns with other diseases different from NEC, in order to know if these risk factors are more frequent or not in the first group. We assessed the clinical records of all the patients hospitalized in the Neonatal Intensive Care Unit and Neonatology Service of the La Raza General Hospital between 1987 and 1991 with the diagnosis of NEC. They were compared with 65 clinical records chosen at random of patients hospitalized in the same Unit with other diagnosis at the same time, and who were discharged by improvement or deceased. In all of them were look for known risk factors for NEC generally accepted such as: prematurity, neonatal asphyxia, poliglobulia, cyanotic congenital heart disease, patent ductus arteriosus, respiratory distress syndrome, catheterization of umbilical vessels, early feeding of elevated formula increases, exchange exchange transfusion, hypoxic ischemic encephalopathy, infection, etc. Just 25 records of the possible 50 with the diagnosis of NEC full filled inclusion criteria. There were no statistically significant difference in weight, sex, mortality and known risk factors of NEC between both groups. Were concluded that NEC is a disease of unknown etiology that should be studied more thoroughly. The known risk factors must be avoided because the patient susceptibility probably play an important role. PMID:8373546

  10. Geomorphological factors of flash floods

    NASA Astrophysics Data System (ADS)

    Kuznetsova, Yulia

    2016-04-01

    Growing anthropogenic load, rise of extreme meteorological events frequency and total precipitation depth often lead to increasing danger of catastrophic fluvial processes worldwide. Flash floods are one of the most dangerous and less understood types of them. Difficulties of their study are mainly related to short duration of single events, remoteness and hard access to origin areas. Most detailed researches of flash floods focus on hydrological parameters of the flow itself and its meteorological factors. At the same time, importance of the basin geological and geomorphological structure for flash floods generation and the role they play in global sediment redistribution is yet poorly understood. However, understanding and quantitative assessment of these features is a real basis for a complete concept of factors, characteristics and dynamics of flash floods. This work is a review of published data on flash floods, and focuses on the geomorphological factors of the phenomenon. We consider both individual roles and interactions between different geomorphological features (the whole basin parameters, characteristics of the single slopes and valley bottom). Special attention is paid to critical values of certain factors. This approach also highlights the gaps or less studied factors of flash floods. Finally, all data is organized into a complex diagram that may be used for flash floods modeling. This also may help to reach a new level of flash flood predictions and risk assessment.

  11. General factors of the Korean exposure factors handbook.

    PubMed

    Jang, Jae-Yeon; Kim, So-Yeon; Kim, Sun-Ja; Lee, Kyung-Eun; Cheong, Hae-Kwan; Kim, Eun-Hye; Choi, Kyung-Ho; Kim, Young-Hee

    2014-01-01

    Risk assessment considers the situations and characteristics of the exposure environment and host. Various physiological variables of the human body reflects the characteristics of the population that can directly influence risk exposure. Therefore, identification of exposure factors based on the Korean population is required for appropriate risk assessment. It is expected that a handbook about general exposure factors will be used by professionals in many fields as well as the risk assessors of the health department. The process of developing the exposure factors handbook for the Korean population will be introduced in this article, with a specific focus on the general exposure factors including life expectancy, body weight, surface area, inhalation rates, amount of water intake, and soil ingestion targeting the Korean population. The researchers used national databases including the Life Table and the 2005 Time Use Survey from the National Statistical Office. The anthropometric study of size in Korea used the resources provided by the Korean Agency for Technology and Standards. In addition, direct measurement and questionnaire surveys of representative samples were performed to calculate the inhalation rate, drinking water intake, and soil ingestion.

  12. General Factors of the Korean Exposure Factors Handbook

    PubMed Central

    Kim, So-Yeon; Kim, Sun-Ja; Lee, Kyung-Eun; Cheong, Hae-Kwan; Kim, Eun-Hye; Choi, Kyung-Ho; Kim, Young-Hee

    2014-01-01

    Risk assessment considers the situations and characteristics of the exposure environment and host. Various physiological variables of the human body reflects the characteristics of the population that can directly influence risk exposure. Therefore, identification of exposure factors based on the Korean population is required for appropriate risk assessment. It is expected that a handbook about general exposure factors will be used by professionals in many fields as well as the risk assessors of the health department. The process of developing the exposure factors handbook for the Korean population will be introduced in this article, with a specific focus on the general exposure factors including life expectancy, body weight, surface area, inhalation rates, amount of water intake, and soil ingestion targeting the Korean population. The researchers used national databases including the Life Table and the 2005 Time Use Survey from the National Statistical Office. The anthropometric study of size in Korea used the resources provided by the Korean Agency for Technology and Standards. In addition, direct measurement and questionnaire surveys of representative samples were performed to calculate the inhalation rate, drinking water intake, and soil ingestion. PMID:24570802

  13. Factor substitution in nursing homes.

    PubMed

    Cawley, John; Grabowski, David C; Hirth, Richard A

    2006-03-01

    This paper studies factor substitution in one important sector: the nursing home industry. Specifically, we measure the extent to which nursing homes substitute materials for labor when labor becomes relatively more expensive. From a policy perspective, factor substitution in this market is important because materials-intensive methods of care are associated with greater risks of morbidity and mortality among nursing home residents. Studying longitudinal data from 1991 to 2000 on nearly every nursing home in the United States, we use the method of instrumental variables (IV) to address measurement error in nursing home wages. The results from the IV models yield evidence of factor substitution: higher nursing home wages are associated with greater use of psychoactive drugs and lower quality.

  14. Vascular growth factors in neuropsychiatry

    PubMed Central

    Newton, Samuel S.; Fournier, Neil M.; Duman, Ronald S.

    2014-01-01

    Recent advances in understanding the cellular and molecular basis of psychiatric illnesses have shed light on the important role played by trophic factors in modulating functional parameters associated with disease causality and drug action. Disease mechanisms are now thought to involve multiple cell types, including neurons and endothelial cells. These functionally distinct but interactively coupled cell types engage in cellular cross talk via shared and common signaling molecules. Dysregulation in their cellular signaling pathways influences brain function and alters behavioral performance. Multifunctional trophic factors such as VEGF and EPO that possess both neurotrophic and angiogenic actions are of particular interest due to their ability to rescue structural and plasticity deficits in neurons and vasculature. Obtaining insight into the behavioral, cellular and molecular actions of multi-functional trophic factors has the potential to open new and transformative therapeutic approaches. PMID:23475069

  15. Environmental risk factors for osteoporosis

    SciTech Connect

    Goyer, R.A.; Korach, K.S. ); Epstein, S. ); Bhattacharyya, M. ); Pounds, J. )

    1994-04-01

    Environmental risk factors for osteoporosis were reviewed at a conference held at the National Institute for Environmental Health Sciences 8-9 November 1993. The conference was co-sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Disease and the NIH Office of Research in Women's Health. The objective of the conference was to review what is known about risk factors for osteoporosis and to identify gaps in the present state of knowledge that might be addressed by future research. The conference was divided into two broad themes. The first session focused on current knowledge regarding etiology, risk factors, and approaches to clinical and laboratory diagnosis. This was followed by three sessions in which various environmental pollutants were discussed. Topics selected for review included environmental agents that interfere with bone and calcium metabolism, such as the toxic metals lead, cadmium, aluminum, and fluoride, natural and antiestrogens, calcium, and vitamin D.

  16. Factor models for cancer signatures

    NASA Astrophysics Data System (ADS)

    Kakushadze, Zura; Yu, Willie

    2016-11-01

    We present a novel method for extracting cancer signatures by applying statistical risk models (http://ssrn.com/abstract=2732453) from quantitative finance to cancer genome data. Using 1389 whole genome sequenced samples from 14 cancers, we identify an "overall" mode of somatic mutational noise. We give a prescription for factoring out this noise and source code for fixing the number of signatures. We apply nonnegative matrix factorization (NMF) to genome data aggregated by cancer subtype and filtered using our method. The resultant signatures have substantially lower variability than those from unfiltered data. Also, the computational cost of signature extraction is cut by about a factor of 10. We find 3 novel cancer signatures, including a liver cancer dominant signature (96% contribution) and a renal cell carcinoma signature (70% contribution). Our method accelerates finding new cancer signatures and improves their overall stability. Reciprocally, the methods for extracting cancer signatures could have interesting applications in quantitative finance.

  17. Stress factors in affective diseases.

    PubMed

    Bidzińska, E J

    1984-02-01

    An investigation carried out on 97 patients with affective disorders and on 100 healthy control subjects, revealed that acute and chronic stress factors occurred more in the group of patients with affective disorders than among healthy control over a similar time period. The frequency of stressful life situations was the same before the first affective episode in patients with unipolar and bipolar illness. The possible participation of such factors in triggering the first phase of illness is discussed. Similar factors appeared in both types of affective disorders. Significantly more frequent among patients than in the control group were: marital and family conflicts, health problems, emotional and ambitional failures, lack of success and work overload.

  18. [Personal contextual factors, part I].

    PubMed

    Viol, M; Grotkamp, S; van Treeck, B; Nüchtern, E; Hagen, T; Manegold, B; Eckardt, S; Penz, M; Seger, W

    2006-12-01

    The International Classification of Functioning, Disability and Health (ICF) does not yet classify personal contextual factors. To determine the interaction of these factors on activities and participation of a person as well as their influence on the probable outcome of interventions, they must be taken into account in individual sociomedical expertises. Therefore, a group of medical experts working for the social health insurance medical advisory boards in Germany compiled a proposal for a systematic classification of personal contextual factors into domains, categories and items with respect to the ethical guidelines of the ICF. In a second step the main issues were transferred into the preliminary draft for a short version which will be published later to give support for practical daily use in health insurance matters. PMID:17203449

  19. Bayes factors and multimodel inference

    USGS Publications Warehouse

    Link, W.A.; Barker, R.J.; Thomson, David L.; Cooch, Evan G.; Conroy, Michael J.

    2009-01-01

    Multimodel inference has two main themes: model selection, and model averaging. Model averaging is a means of making inference conditional on a model set, rather than on a selected model, allowing formal recognition of the uncertainty associated with model choice. The Bayesian paradigm provides a natural framework for model averaging, and provides a context for evaluation of the commonly used AIC weights. We review Bayesian multimodel inference, noting the importance of Bayes factors. Noting the sensitivity of Bayes factors to the choice of priors on parameters, we define and propose nonpreferential priors as offering a reasonable standard for objective multimodel inference.

  20. Campylobacter virulence and survival factors.

    PubMed

    Bolton, Declan J

    2015-06-01

    Despite over 30 years of research, campylobacteriosis is the most prevalent foodborne bacterial infection in many countries including in the European Union and the United States of America. However, relatively little is known about the virulence factors in Campylobacter or how an apparently fragile organism can survive in the food chain, often with enhanced pathogenicity. This review collates information on the virulence and survival determinants including motility, chemotaxis, adhesion, invasion, multidrug resistance, bile resistance and stress response factors. It discusses their function in transition through the food processing environment and human infection. In doing so it provides a fundamental understanding of Campylobacter, critical for improved diagnosis, surveillance and control.

  1. Growth factors in orthopedic surgery

    PubMed Central

    Zaharia, C; Despa, N; Simionescu, M; Jinga, V; Fleseriu, I

    2010-01-01

    Growth factors have represented an essential issue of interest for the researchers and clinicians in orthopedics and trauma over the last 40 years. In the last 10 to 15 years, the advances registered in this field have permitted the identification of the most active cellular and humoral factors as well as the improvement of their use in the orthopedic and trauma surgery. Their domain of application has been continuously enlarged and the results have been visible from the beginning. The authors present their appreciation on the actual state of this subject as well as their experience with results and related conclusions. PMID:20302195

  2. Psychological factors in the antarctic.

    PubMed

    Rothblum, E D

    1990-05-01

    For the people who live and work in the Antarctic, isolation and extreme physical conditions cause considerable stress. This article reviews psychological research on Antarctic residents, focusing on factors related to the isolation (effective personnel selection, positive adjustment, conflict, and reintegration into the home environment) and factors related to the physical environment (the extreme cold, high altitude, increased radiation, sensory deprivation, and seasonal changes in activity level). Finally, Antarctic research has been applied to the study of future space travel and space station habitation.

  3. Risk Factors in Adolescent Hypertension

    PubMed Central

    Ewald, D. Rose; Haldeman, Lauren A.

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  4. Risk Factors in Adolescent Hypertension.

    PubMed

    Ewald, D Rose; Haldeman PhD, Lauren A

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  5. Environmental factors associated with asthma.

    PubMed Central

    Walker, Bailus; Stokes, Lynette D.; Warren, Rueben

    2003-01-01

    Asthma, a disease of attacks and remission, continues to account for substantial morbidity and direct economic costs. Numerous studies--epidemiologic, toxicologic and clinical--present evidence for a broad spectrum of environmental risk factors associated with asthma. This review summarizes current thinking on a subset of these factors. Knowledge of potential environmental determinants of asthma is important to both the patient and healthcare professional in the application of multiple modalities of medical and environmental intervention for management of the development, and exacerbation of this chronic inflammatory disorder of the airways. PMID:12760611

  6. Factors associated with childhood obesity.

    PubMed

    Dietz, W

    1991-01-01

    Childhood obesity is associated with host factors that enhance susceptibility and environmental factors that increase food intake and decrease energy expenditure. Obese children underreport food intake and probably consume more food to maintain their weight at increased levels. Prevalence of obesity is related to family variables, including parental obesity, family size and age, and socioeconomic status. Television viewing is strongly associated with the prevalence of obesity through its impact on food intake and activity. How these environmental variables are behaviorally interrelated to the genesis of obesity is unclear.

  7. Causal Indicators Can Help to Interpret Factors

    ERIC Educational Resources Information Center

    Bentler, Peter M.

    2016-01-01

    The latent factor in a causal indicator model is no more than the latent factor of the factor part of the model. However, if the causal indicator variables are well-understood and help to improve the prediction of individuals' factor scores, they can help to interpret the meaning of the latent factor. Aguirre-Urreta, Rönkkö, and Marakas (2016)…

  8. Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons

    PubMed Central

    Tang, Jin Bo; Wu, Ya Fang; Cao, Yi; Chen, Chuan Hao; Zhou, You Lang; Avanessian, Bella; Shimada, Masaru; Wang, Xiao Tian; Liu, Paul Y.

    2016-01-01

    Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation, and (3) significantly increased tendon strength by 68–91% from week 2 after AAV2-bFGF treatment and by 82–210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion. PMID:26865366

  9. Entropy algebras and Birkhoff factorization

    NASA Astrophysics Data System (ADS)

    Marcolli, Matilde; Tedeschi, Nicolas

    2015-11-01

    We develop notions of Rota-Baxter structures and associated Birkhoff factorizations, in the context of min-plus semirings and their thermodynamic deformations, including deformations arising from quantum information measures such as the von Neumann entropy. We consider examples related to Manin's renormalization and computation program, to Markov random fields and to counting functions and zeta functions of algebraic varieties.

  10. Human factors in underwater systems.

    PubMed

    Crosson, D

    1993-10-01

    Applications of human factors to undersea engineering and the relationship to aerospace science are explored. Cooperative ventures include the TEKTITE underwater habitat and development of better procedures to prevent decompression sickness. Other research involved the use of alternate gases in diving systems, remote-operation vehicles, and diving system tests.

  11. Transcription factor-based biosensor

    SciTech Connect

    Dietrich, Jeffrey A; Keasling, Jay D

    2013-10-08

    The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

  12. Factors Affecting the Tutoring Process.

    ERIC Educational Resources Information Center

    Hartman, Hope J.

    1990-01-01

    Analyzes factors internal to the tutor and tutee (i.e., cognition, metacognition, and affect) and external to them (e.g., teacher/tutor background knowledge, educational environment, content to be learned, socioeconomic status, family background, and cultural forces) that influence the tutoring process. Suggests a theoretical framework for…

  13. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  14. Factors in Adolescent Rebellious Feelings.

    ERIC Educational Resources Information Center

    Clemens, Patricia W.; Rust, James O.

    1979-01-01

    This study examined 15- and 16-year-old youths' (Midteens') feelings of anomie and rebellion in relation to family and situational factors. Only parents' formal education level and midteens' approval of the way they were being reared correlated significantly with midteens' scores on the Anomia and Rebellion Scales. (Author/SJL)

  15. The Environmental Factors Influencing Attrition.

    ERIC Educational Resources Information Center

    Villella, Edward F.

    1986-01-01

    Offers an economics/business-management perspective on student attrition, focusing on the external macro-environment (including such factors as government funding of education, changing enrollment patterns, and the increased number of postsecondary institutions) and the internal micro-environment (exhibiting characteristics of intangibility,…

  16. Family Factors and Student Outcomes

    ERIC Educational Resources Information Center

    Xia, Nailing

    2009-01-01

    There is considerable debate about the relative importance of family versus school factors in producing academic and nonacademic student outcomes, and whether and how their impacts vary across different student groups. In addition to critically reviewing and synthesizing earlier work, this study extends the literature by (a) using the ECLS-K, a…

  17. Time dependent view factor methods

    SciTech Connect

    Kirkpatrick, R.C.

    1998-03-01

    View factors have been used for treating radiation transport between opaque surfaces bounding a transparent medium for several decades. However, in recent years they have been applied to problems involving intense bursts of radiation in enclosed volumes such as in the laser fusion hohlraums. In these problems, several aspects require treatment of time dependence.

  18. Neurophysiological Factors in Spatial Development.

    ERIC Educational Resources Information Center

    Harris, Lauren Jay

    Some of the major lines of investigation that point to neurophysiological factors in spatial skill are presented. These lines include: the two hemispheres of the brain, recent studies, tachistoscopic studies, morphological differences between the cerebral hemispheres, Geschwind and Levitsky's discovery, cerebral dominance re-examined, sex…

  19. 2012 Critical Success Factors Report

    ERIC Educational Resources Information Center

    North Carolina Community College System (NJ1), 2012

    2012-01-01

    The Critical Success Factors Report is the North Carolina Community College System's major accountability document. This annual performance report is based on data compiled from the previous year and serves to inform colleges and the public on the performance of North Carolina's 58 community colleges. In 1993, the State Board of Community Colleges…

  20. 2011 Critical Success Factors Report

    ERIC Educational Resources Information Center

    North Carolina Community College System (NJ1), 2011

    2011-01-01

    The Critical Success Factors Report is the North Carolina Community College System's major accountability document. This annual performance report serves to inform colleges and the public on the performance of North Carolina's 58 community colleges. In 1993, the State Board of Community Colleges began monitoring performance data on specific…

  1. Chrestenson transform FPGA embedded factorizations.

    PubMed

    Corinthios, Michael J

    2016-01-01

    Chrestenson generalized Walsh transform factorizations for parallel processing imbedded implementations on field programmable gate arrays are presented. This general base transform, sometimes referred to as the Discrete Chrestenson transform, has received special attention in recent years. In fact, the Discrete Fourier transform and Walsh-Hadamard transform are but special cases of the Chrestenson generalized Walsh transform. Rotations of a base-p hypercube, where p is an arbitrary integer, are shown to produce dynamic contention-free memory allocation, in processor architecture. The approach is illustrated by factorizations involving the processing of matrices of the transform which are function of four variables. Parallel operations are implemented matrix multiplications. Each matrix, of dimension N × N, where N = p (n) , n integer, has a structure that depends on a variable parameter k that denotes the iteration number in the factorization process. The level of parallelism, in the form of M = p (m) processors can be chosen arbitrarily by varying m between zero to its maximum value of n - 1. The result is an equation describing the generalised parallelism factorization as a function of the four variables n, p, k and m. Applications of the approach are shown in relation to configuring field programmable gate arrays for digital signal processing applications.

  2. Cognitive Factors in Academic Achievement.

    ERIC Educational Resources Information Center

    Cuasay, Peter

    1992-01-01

    This review explores the factors of cognitive processing, style, and metacognitive organization as they contribute to academic success. Specific discussions consider aspects of short- and long-term memory, including how these affect learning and academic performance, and the keys to attaining long-term memory capability by involving redundancy,…

  3. Anthranilamide inhibitors of factor Xa.

    PubMed

    Mendel, David; Marquart, Angela L; Joseph, Sajan; Waid, Philip; Yee, Ying K; Tebbe, Anne Louise; Ratz, Andrew M; Herron, David K; Goodson, Theodore; Masters, John J; Franciskovich, Jeffry B; Tinsley, Jennifer M; Wiley, Michael R; Weir, Leonard C; Kyle, Jeffrey A; Klimkowski, Valentine J; Smith, Gerald F; Towner, Richard D; Froelich, Larry L; Buben, John; Craft, Trelia J

    2007-09-01

    SAR about the B-ring of a series of N(2)-aroyl anthranilamide factor Xa (fXa) inhibitors is described. B-ring o-aminoalkylether and B-ring p-amine probes of the S1' and S4 sites, respectively, afforded picomolar fXa inhibitors that performed well in in vitro anticoagulation assays.

  4. Logistical Factors in Teachers' Motivation

    ERIC Educational Resources Information Center

    Daniels, Erika

    2016-01-01

    Research in education and psychology contributes to an understanding of how educators create contexts for learning that encourage intrinsic motivation and increase academic achievement. In this article, the researcher investigated how teachers themselves define effectiveness and identified what factors influence their motivation, both positively…

  5. Heredity Factors in Spatial Visualization.

    ERIC Educational Resources Information Center

    Vandenberg, S. G.

    Spatial visualization is not yet clearly understood. Some researchers have concluded that two factors or abilities are involved, spatial orientation and spatial visualization. Different definitions and different tests have been proposed for these two abilities. Several studies indicate that women generally perform more poorly on spatial tests than…

  6. Synthetic Division and Matrix Factorization

    ERIC Educational Resources Information Center

    Barabe, Samuel; Dubeau, Franc

    2007-01-01

    Synthetic division is viewed as a change of basis for polynomials written under the Newton form. Then, the transition matrices obtained from a sequence of changes of basis are used to factorize the inverse of a bidiagonal matrix or a block bidiagonal matrix.

  7. Factors Affecting Willingness to Mentor

    ERIC Educational Resources Information Center

    Ghislieri, Chiara; Gatti, Paola; Quaglino, Gian Piero

    2009-01-01

    The paper presents a survey among 300 employees in Northern Italy to assess the willingness to mentor and identify the factors that affect it. Men and respondents with previous mentoring experience indicate a higher willingness to be a mentor. Willingness is affected by personal characteristics that are perceived as necessary for a mentor and the…

  8. Factor reliability into load management

    SciTech Connect

    Feight, G.R.

    1983-07-01

    Hardware reliability is a major factor to consider when selecting a direct-load-control system. The author outlines a method of estimating present-value costs associated with system reliability. He points out that small differences in receiver reliability make a significant difference in owning cost. 4 figures.

  9. Factors Influencing College Science Success

    ERIC Educational Resources Information Center

    Tai, Robert H.; Sadler, Philip M.; Mintzes, Joel J.

    2006-01-01

    In this paper, the authors report some of the salient findings of a large-scale, four-year national study, conducted at the Harvard-Smithsonian Center for Astrophysics, entitled "Factors Influencing College Science Success" (FICSS), which surveyed college students who enrolled in first-year biology, chemistry, and physics courses throughout the…

  10. Chrestenson transform FPGA embedded factorizations.

    PubMed

    Corinthios, Michael J

    2016-01-01

    Chrestenson generalized Walsh transform factorizations for parallel processing imbedded implementations on field programmable gate arrays are presented. This general base transform, sometimes referred to as the Discrete Chrestenson transform, has received special attention in recent years. In fact, the Discrete Fourier transform and Walsh-Hadamard transform are but special cases of the Chrestenson generalized Walsh transform. Rotations of a base-p hypercube, where p is an arbitrary integer, are shown to produce dynamic contention-free memory allocation, in processor architecture. The approach is illustrated by factorizations involving the processing of matrices of the transform which are function of four variables. Parallel operations are implemented matrix multiplications. Each matrix, of dimension N × N, where N = p (n) , n integer, has a structure that depends on a variable parameter k that denotes the iteration number in the factorization process. The level of parallelism, in the form of M = p (m) processors can be chosen arbitrarily by varying m between zero to its maximum value of n - 1. The result is an equation describing the generalised parallelism factorization as a function of the four variables n, p, k and m. Applications of the approach are shown in relation to configuring field programmable gate arrays for digital signal processing applications. PMID:27652084

  11. Transforming Rubrics Using Factor Analysis

    ERIC Educational Resources Information Center

    Baryla, Ed; Shelley, Gary; Trainor, William

    2012-01-01

    Student learning and program effectiveness is often assessed using rubrics. While much time and effort may go into their creation, it is equally important to assess how effective and efficient the rubrics actually are in terms of measuring competencies over a number of criteria. This study demonstrates the use of common factor analysis to identify…

  12. NASA Space Human Factors Program

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This booklet briefly and succinctly treats 23 topics of particular interest to the NASA Space Human Factors Program. Most articles are by different authors who are mainly NASA Johnson or NASA Ames personnel. Representative topics covered include mental workload and performance in space, light effects on Circadian rhythms, human sleep, human reasoning, microgravity effects and automation and crew performance.

  13. Psychological Risk Factors in Headache

    PubMed Central

    Nicholson, Robert A.; Houle, Timothy T.; Rhudy, Jamie L.; Norton, Peter J.

    2008-01-01

    Headache is a chronic disease that occurs with varying frequency and results in varying levels of disability. To date, the majority of research and clinical focus has been on the role of biological factors in headache and headache-related disability. However, reliance on a purely biomedical model of headache does not account for all aspects of headache and associated disability. Using a biopsychosocial framework, the current manuscript expands the view of what factors influence headache by considering the role psychological (i.e., cognitive and affective) factors have in the development, course, and consequences of headache. The manuscript initially reviews evidence showing that neural circuits responsible for cognitive–affective phenomena are highly interconnected with the circuitry responsible for headache pain. The manuscript then reviews the influence cognitions (locus of control and self-efficacy) and negative affect (depression, anxiety, and anger) have on the development of headache attacks, perception of headache pain, adherence to prescribed treatment, headache treatment outcome, and headache-related disability. The manuscript concludes with a discussion of the clinical implications of considering psychological factors when treating headache. PMID:17371358

  14. Human factors in software development

    SciTech Connect

    Curtis, B.

    1986-01-01

    This book presents an overview of ergonomics/human factors in software development, recent research, and classic papers. Articles are drawn from the following areas of psychological research on programming: cognitive ergonomics, cognitive psychology, and psycholinguistics. Topics examined include: theoretical models of how programmers solve technical problems, the characteristics of programming languages, specification formats in behavioral research and psychological aspects of fault diagnosis.

  15. Soft Factors Influence College Enrollment

    ERIC Educational Resources Information Center

    Fogg, Neeta P.; Harrington, Paul E.

    2010-01-01

    Evidence about the role that "soft factors" like student engagement and school environment play in influencing whether high school students go on to enroll in college is hard to come by. Over the past two years, the Center for Labor Market Studies (CLMS) of Northeastern University, with support from the Nellie Mae Education Foundation and the…

  16. Human factors in underwater systems.

    PubMed

    Crosson, D

    1993-10-01

    Applications of human factors to undersea engineering and the relationship to aerospace science are explored. Cooperative ventures include the TEKTITE underwater habitat and development of better procedures to prevent decompression sickness. Other research involved the use of alternate gases in diving systems, remote-operation vehicles, and diving system tests. PMID:11541030

  17. Highly parallel sparse Cholesky factorization

    NASA Technical Reports Server (NTRS)

    Gilbert, John R.; Schreiber, Robert

    1990-01-01

    Several fine grained parallel algorithms were developed and compared to compute the Cholesky factorization of a sparse matrix. The experimental implementations are on the Connection Machine, a distributed memory SIMD machine whose programming model conceptually supplies one processor per data element. In contrast to special purpose algorithms in which the matrix structure conforms to the connection structure of the machine, the focus is on matrices with arbitrary sparsity structure. The most promising algorithm is one whose inner loop performs several dense factorizations simultaneously on a 2-D grid of processors. Virtually any massively parallel dense factorization algorithm can be used as the key subroutine. The sparse code attains execution rates comparable to those of the dense subroutine. Although at present architectural limitations prevent the dense factorization from realizing its potential efficiency, it is concluded that a regular data parallel architecture can be used efficiently to solve arbitrarily structured sparse problems. A performance model is also presented and it is used to analyze the algorithms.

  18. Risk factors for postoperative ileus

    PubMed Central

    Kutun, Suat; Ulucanlar, Haluk; Tarcan, Oguz; Demir, Abdullah; Cetin, Abdullah

    2011-01-01

    Purpose This study aimed to examine extended postoperative ileus and its risk factors in patients who have undergone abdominal surgery, and discuss the techniques of prevention and management thereof the light of related risk factors connected with our study. Methods This prospective study involved 103 patients who had undergone abdominal surgery. The effects of age, gender, diagnosis, surgical operation conducted, excessive small intestine manipulation, opioid analgesic usage time, and systemic inflammation on the time required for the restoration of intestinal motility were investigated. The parameters were investigated prospectively. Results Regarding the factors that affected the restoration of gastrointestinal motility, resection operation type, longer operation period, longer opioid analgesics use period, longer nasogastric catheter use period, and the presence of systemic inflammation were shown to retard bowel motility for 3 days or more. Conclusion Our study confirmed that unnecessary analgesics use in patients with pain tolerance with non-steroid anti-inflammatory drugs, excessive small bowel manipulation, prolonged nasogastric catheter use have a direct negative effect on gastrointestinal motility. Considering that an exact treatment for postoperative ileus has not yet been established, and in light of the risk factors mentioned above, we regard that prevention of postoperative ileus is the most effective way of coping with intestinal dysmotility. PMID:22111079

  19. Motivating factors among Iranian nurses

    PubMed Central

    Negarandeh, Reza; Dehghan-Nayeri, Nahid; Ghasemi, Elham

    2015-01-01

    Background: One of the most important challenges of Iranian health care system is “quality of care,” and it is assumed that motivated nurses are more ready to provide better care. There are limited studies investigating Iranian nurses’ motivations; however, factors which motivate them have not been studied yet. Identifying the motivating factors enables nurse managers to inspire nurses for continuous quality improvement. The aim of this study was to identify motivating factors for Iranian hospital nurses. Materials and Methods: This is a cross-sectional descriptive study in which 310 nurses working at 14 hospitals of Tehran University of Medical Sciences were selected by proportionate stratified random sampling. Data were collected in 2010 by a researcher-developed questionnaire. Descriptive statistics and independent t-test, analysis of variance, Tukey post-hoc test, Chi-Square and Fisher's exact test were used for statistical analysis by Statistical Package for Social Sciences (SPSS) version 16. Results: The mean score of motivation was 90.53 ± 10.76 (range: 59–121). Four motivating factors including “career development” (22.63 ± 5.66), “job characteristics” (34.29 ± 4), “job authority” (18.48 ± 2.79), and “recognition” (15.12 ± 2.5) were recognized. The least mean of the motivation score, considering the number of items, was 3.23 for career development, while the highest mean was 3.81 for job characteristics. Conclusions: The findings showed that motivation of nurses was at a medium level, which calls for improvement. The factors that have the greatest potential to motivate nurses were identified in this study and they can help managers to achieve the goal of continuous quality improvement. PMID:26257797

  20. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  1. Sequential coagulation factor VIIa domain binding to tissue factor

    SciTech Connect

    Oesterlund, Maria; Persson, Egon; Freskgard, Per-Ola . E-mail: msv@ifm.liu.se

    2005-12-02

    Vessel wall tissue factor (TF) is exposed to blood upon vascular damage which enables association with factor VIIa (FVIIa). This leads to initiation of the blood coagulation cascade through localization and allosteric induction of FVIIa procoagulant activity. To examine the docking pathway of the FVIIa-TF complex, various residues in the extracellular part of TF (sTF) that are known to interact with FVIIa were replaced with cysteines labelled with a fluorescent probe. By using stopped-flow fluorescence kinetic measurements in combination with surface plasmon resonance analysis, we studied the association of the resulting sTF variants with FVIIa. We found the docking trajectory to be a sequence of events in which the protease domain of FVIIa initiates contact with sTF. Thereafter, the two proteins are tethered via the first epidermal growth factor-like and finally the {gamma}-carboxyglutamic acid (Gla) domain. The two labelled sTF residues interacting with the protease domain of FVIIa bind or become eventually ordered at different rates, revealing kinetic details pertinent to the allosteric activation of FVIIa by sTF. Moreover, when the Gla domain of FVIIa is removed the difference in the rate of association for the remaining domains is much more pronounced.

  2. Continuous analogues of matrix factorizations

    PubMed Central

    Townsend, Alex; Trefethen, Lloyd N.

    2015-01-01

    Analogues of singular value decomposition (SVD), QR, LU and Cholesky factorizations are presented for problems in which the usual discrete matrix is replaced by a ‘quasimatrix’, continuous in one dimension, or a ‘cmatrix’, continuous in both dimensions. Two challenges arise: the generalization of the notions of triangular structure and row and column pivoting to continuous variables (required in all cases except the SVD, and far from obvious), and the convergence of the infinite series that define the cmatrix factorizations. Our generalizations of triangularity and pivoting are based on a new notion of a ‘triangular quasimatrix’. Concerning convergence of the series, we prove theorems asserting convergence provided the functions involved are sufficiently smooth. PMID:25568618

  3. Risk factors for surgical infection.

    PubMed

    Leaper, D J

    1995-06-01

    In the last century remarkable advances have been made in surgery, associated with the lowest recorded rates of infection or sepsis. Many surgical practices are time honoured but have little scientific basis to prevent postoperative infection whereas some local and systemic factors are well recognized and can be modified to lower infection risks. Surgical skill is not easily measurable but shorter operations in experienced hands leaving the minimum of tissue damage, haematoma or dead space have the lowest infection rates in general surgery: < 2% in clean and < 10% in contaminated operations. Adequate surgical scrub, appropriate suture materials and antibiotic prophylaxis, perioperative correction of dehydration and poor nutrition are examples of effective therapy which can be conformed to by all surgeons. Other factors, such as the use of wound guards, drains and surgical dressings are less easy to estimate for effectiveness or be sure that they could be changed or left out of surgical ritual.

  4. Shot-noise Fano factor

    NASA Astrophysics Data System (ADS)

    Rajdl, Kamil; Lansky, Petr

    2015-11-01

    A variability measure of the times of uniform events based on a shot-noise process is proposed and studied. The measure is inspired by the Fano factor, which we generalize by considering the time-weighted influence of the events given by a shot-noise response function. The sequence of events is assumed to be an equilibrium renewal process, and based on this assumption we present formulas describing the behavior of the variability measure. The formulas are derived for a general response function, restricted only by some natural conditions, but the main focus is given to the shot noise with exponential decrease. The proposed measure is analyzed and compared with the Fano factor.

  5. Nutritional Factors Affecting Mental Health

    PubMed Central

    Lim, So Young; Kim, Eun Jin; Kim, Arang; Lee, Hee Jae; Choi, Hyun Jin

    2016-01-01

    Dietary intake and nutritional status of individuals are important factors affecting mental health and the development of psychiatric disorders. Majority of scientific evidence relating to mental health focuses on depression, cognitive function, and dementia, and limited evidence is available about other psychiatric disorders including schizophrenia. As life span of human being is increasing, the more the prevalence of mental disorders is, the more attention rises. Lists of suggested nutritional components that may be beneficial for mental health are omega-3 fatty acids, phospholipids, cholesterol, niacin, folate, vitamin B6, and vitamin B12. Saturated fat and simple sugar are considered detrimental to cognitive function. Evidence on the effect of cholesterol is conflicting; however, in general, blood cholesterol levels are negatively associated with the risk of depression. Collectively, the aims of this review are to introduce known nutritional factors for mental health, and to discuss recent issues of the nutritional impact on cognitive function and healthy brain aging. PMID:27482518

  6. Factorization of chiral string amplitudes

    NASA Astrophysics Data System (ADS)

    Huang, Yu-tin; Siegel, Warren; Yuan, Ellis Ye

    2016-09-01

    We re-examine a closed-string model defined by altering the boundary conditions for one handedness of two-dimensional propagators in otherwise-standard string theory. We evaluate the amplitudes using Kawai-Lewellen-Tye factorization into open-string amplitudes. The only modification to standard string theory is effectively that the spacetime Minkowski metric changes overall sign in one open-string factor. This cancels all but a finite number of states: as found in earlier approaches, with enough supersymmetry (e.g., type II) the tree amplitudes reproduce those of the massless truncation of ordinary string theory. However, we now find for the other cases that additional fields, formerly thought to be auxiliary, describe new spin-2 states at the two adjacent mass levels (tachyonic and tardyonic). The tachyon is always a ghost, but can be avoided in the heterotic case.

  7. Factors influencing pacing in triathlon

    PubMed Central

    Wu, Sam SX; Peiffer, Jeremiah J; Brisswalter, Jeanick; Nosaka, Kazunori; Abbiss, Chris R

    2014-01-01

    Triathlon is a multisport event consisting of sequential swim, cycle, and run disciplines performed over a variety of distances. This complex and unique sport requires athletes to appropriately distribute their speed or energy expenditure (ie, pacing) within each discipline as well as over the entire event. As with most physical activity, the regulation of pacing in triathlon may be influenced by a multitude of intrinsic and extrinsic factors. The majority of current research focuses mainly on the Olympic distance, whilst much less literature is available on other triathlon distances such as the sprint, half-Ironman, and Ironman distances. Furthermore, little is understood regarding the specific physiological, environmental, and interdisciplinary effects on pacing. Therefore, this article discusses the pacing strategies observed in triathlon across different distances, and elucidates the possible factors influencing pacing within the three specific disciplines of a triathlon. PMID:25258562

  8. Graybody Factors and Infrared Divergences

    NASA Astrophysics Data System (ADS)

    Anderson, Paul; Fabbri, Alessandro; Balbinot, Roberto; Parentani, Renaud

    2015-04-01

    A method of computing the gray-body factors for static spherically symmetric and BEC acoustic black holes using a Volterra integral equation is given. The results are used to investigate infrared divergences in the particle number, two-point function, point-split stress-energy tensor and density-density correlation function. Infrared divergences in the particle number and two-point function occur if the gray-body factor approaches a nonzero constant in the zero frequency limit, as happens for Schwarzschild-de Sitter black holes and BEC acoustic black holes. However, no infrared divergences occur in the point-split stress-energy tensor or the density-density correlation function. Supported in part by the National Science Foundation under Grant Nos. PHY-0856050 and PHY-1308325.

  9. On factorization of molecular wavefunctions

    NASA Astrophysics Data System (ADS)

    Jecko, Thierry; Sutcliffe, Brian T.; Woolley, R. Guy

    2015-11-01

    Recently there has been a renewed interest in the chemical physics literature of factorization of the position representation eigenfunctions Φ of the molecular Schrödinger equation as originally proposed by Hunter in the 1970s. The idea is to represent Φ in the form φχ where χ is purely a function of the nuclear coordinates, while φ must depend on both electron and nuclear position variables in the problem. This is a generalization of the approximate factorization originally proposed by Born and Oppenheimer, the hope being that an ‘exact’ representation of Φ can be achieved in this form with φ and χ interpretable as ‘electronic’ and ‘nuclear’ wavefunctions respectively. We offer a mathematical analysis of these proposals that identifies ambiguities stemming mainly from the singularities in the Coulomb potential energy.

  10. Nutritional Factors Affecting Mental Health.

    PubMed

    Lim, So Young; Kim, Eun Jin; Kim, Arang; Lee, Hee Jae; Choi, Hyun Jin; Yang, Soo Jin

    2016-07-01

    Dietary intake and nutritional status of individuals are important factors affecting mental health and the development of psychiatric disorders. Majority of scientific evidence relating to mental health focuses on depression, cognitive function, and dementia, and limited evidence is available about other psychiatric disorders including schizophrenia. As life span of human being is increasing, the more the prevalence of mental disorders is, the more attention rises. Lists of suggested nutritional components that may be beneficial for mental health are omega-3 fatty acids, phospholipids, cholesterol, niacin, folate, vitamin B6, and vitamin B12. Saturated fat and simple sugar are considered detrimental to cognitive function. Evidence on the effect of cholesterol is conflicting; however, in general, blood cholesterol levels are negatively associated with the risk of depression. Collectively, the aims of this review are to introduce known nutritional factors for mental health, and to discuss recent issues of the nutritional impact on cognitive function and healthy brain aging. PMID:27482518

  11. Factors influencing pacing in triathlon.

    PubMed

    Wu, Sam Sx; Peiffer, Jeremiah J; Brisswalter, Jeanick; Nosaka, Kazunori; Abbiss, Chris R

    2014-01-01

    Triathlon is a multisport event consisting of sequential swim, cycle, and run disciplines performed over a variety of distances. This complex and unique sport requires athletes to appropriately distribute their speed or energy expenditure (ie, pacing) within each discipline as well as over the entire event. As with most physical activity, the regulation of pacing in triathlon may be influenced by a multitude of intrinsic and extrinsic factors. The majority of current research focuses mainly on the Olympic distance, whilst much less literature is available on other triathlon distances such as the sprint, half-Ironman, and Ironman distances. Furthermore, little is understood regarding the specific physiological, environmental, and interdisciplinary effects on pacing. Therefore, this article discusses the pacing strategies observed in triathlon across different distances, and elucidates the possible factors influencing pacing within the three specific disciplines of a triathlon.

  12. Host factors exploited by retroviruses.

    PubMed

    Goff, Stephen P

    2007-04-01

    Retroviruses make a long and complex journey from outside the cell to the nucleus in the early stages of infection, and then an equally long journey back out again in the late stages of infection. Ongoing efforts are identifying an enormous array of cellular proteins that are used by the viruses in the course of their travels. These host factors are potential new targets for therapeutic intervention.

  13. Human Factors in Space Exploration

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    The exploration of space is one of the most fascinating domains to study from a human factors perspective. Like other complex work domains such as aviation (Pritchett and Kim, 2008), air traffic management (Durso and Manning, 2008), health care (Morrow, North, and Wickens, 2006), homeland security (Cooke and Winner, 2008), and vehicle control (Lee, 2006), space exploration is a large-scale sociotechnical work domain characterized by complexity, dynamism, uncertainty, and risk in real-time operational contexts (Perrow, 1999; Woods et ai, 1994). Nearly the entire gamut of human factors issues - for example, human-automation interaction (Sheridan and Parasuraman, 2006), telerobotics, display and control design (Smith, Bennett, and Stone, 2006), usability, anthropometry (Chaffin, 2008), biomechanics (Marras and Radwin, 2006), safety engineering, emergency operations, maintenance human factors, situation awareness (Tenney and Pew, 2006), crew resource management (Salas et aI., 2006), methods for cognitive work analysis (Bisantz and Roth, 2008) and the like -- are applicable to astronauts, mission control, operational medicine, Space Shuttle manufacturing and assembly operations, and space suit designers as they are in other work domains (e.g., Bloomberg, 2003; Bos et al, 2006; Brooks and Ince, 1992; Casler and Cook, 1999; Jones, 1994; McCurdy et ai, 2006; Neerincx et aI., 2006; Olofinboba and Dorneich, 2005; Patterson, Watts-Perotti and Woods, 1999; Patterson and Woods, 2001; Seagull et ai, 2007; Sierhuis, Clancey and Sims, 2002). The human exploration of space also has unique challenges of particular interest to human factors research and practice. This chapter provides an overview of those issues and reports on sorne of the latest research results as well as the latest challenges still facing the field.

  14. [Nonallergic hypersensitivity to environmental factors].

    PubMed

    Rakhmanin, Iu A; Fedoseeva, V N; Makovetskaia, A K; Fedoskova, T G

    2013-01-01

    The prevalence and severity of manifestations of non-allergic hypersensitivity to chemical environmental factors pose the question about the need to study the mechanisms of its formation in population. It should be borne in mind that, in the absence of immunological mechanisms of formation of the mentioned state, the term "chemical sensitization" must be replaced by the term "non-allergic hypersensitivity." The investigation of this problem should permit to reduce the risk of formation of different types of hypersensitivity in population.

  15. Factor weighting in DRASTIC modeling.

    PubMed

    Pacheco, F A L; Pires, L M G R; Santos, R M B; Sanches Fernandes, L F

    2015-02-01

    Evaluation of aquifer vulnerability comprehends the integration of very diverse data, including soil characteristics (texture), hydrologic settings (recharge), aquifer properties (hydraulic conductivity), environmental parameters (relief), and ground water quality (nitrate contamination). It is therefore a multi-geosphere problem to be handled by a multidisciplinary team. The DRASTIC model remains the most popular technique in use for aquifer vulnerability assessments. The algorithm calculates an intrinsic vulnerability index based on a weighted addition of seven factors. In many studies, the method is subject to adjustments, especially in the factor weights, to meet the particularities of the studied regions. However, adjustments made by different techniques may lead to markedly different vulnerabilities and hence to insecurity in the selection of an appropriate technique. This paper reports the comparison of 5 weighting techniques, an enterprise not attempted before. The studied area comprises 26 aquifer systems located in Portugal. The tested approaches include: the Delphi consensus (original DRASTIC, used as reference), Sensitivity Analysis, Spearman correlations, Logistic Regression and Correspondence Analysis (used as adjustment techniques). In all cases but Sensitivity Analysis, adjustment techniques have privileged the factors representing soil characteristics, hydrologic settings, aquifer properties and environmental parameters, by leveling their weights to ≈4.4, and have subordinated the factors describing the aquifer media by downgrading their weights to ≈1.5. Logistic Regression predicts the highest and Sensitivity Analysis the lowest vulnerabilities. Overall, the vulnerability indices may be separated by a maximum value of 51 points. This represents an uncertainty of 2.5 vulnerability classes, because they are 20 points wide. Given this ambiguity, the selection of a weighting technique to integrate a vulnerability index may require additional

  16. Factors affecting distributed system security

    SciTech Connect

    Nessett, D.M.

    1985-11-13

    Recent work examining distributed system security requirements is critiqued. A notion of trust based on distributed system topology and distributed system node evaluation levels proposed in that work is shown to be deficient. The notion fails to make allowances for the distributed system physical security environment, security factors related to the management of distributed systems by more than one jurisdictive authority and interactions that can occur between nodes supporting different mandatory and discretionary security mechanisms.

  17. Impact fact-or fiction?

    PubMed

    Pulverer, Bernd

    2013-06-12

    The Journal Impact Factor dominates research assessment in many disciplines and in many countries. While research assessment will always have to rely to some extent on quantitative, standardized metrics, the focus on this single measure has gone so far as to hamper and distort scientific research. The Declaration on Research Assessment (DORA), signed by influential journals, funders, academic institutions and individuals across the natural sciences, aims to raise awareness and to redress the use of non-objective research assessment practices.

  18. Lifestyle factors and sperm aneuploidy.

    PubMed

    Jurewicz, Joanna; Radwan, Michał; Sobala, Wojciech; Radwan, Paweł; Jakubowski, Lucjusz; Hawuła, Wanda; Ulańska, Anna; Hanke, Wojciech

    2014-09-01

    Different environmental and lifestyle factors may interfere with the normal disjunction of sister chromatids/chromosomes during meiosis and may cause aneuploidy. The aim of the study was to examine the association between lifestyle factors and sperm aneuploidy. The study population consisted of 212 healthy men under 45 years of age attending an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20-300×10⁶mL or slight oligozoospermia (semen concentration of 15-20×10⁶/mL). All participants were interviewed and provided a semen sample. Sperm aneuploidy was assessed using multicolor FISH (DNA probes specific for chromosomes X, Y, 18, 13, 21). Results from the study suggest that lifestyle factors are related to sperm aneuploidy. A positive relationship was found between coffee drinking everyday and the lack of chromosome X or Y, as well as coffee drinking 1-6 times per week and additional chromosome 18. Wearing boxer shorts decrease the copy number changes in the whole chromosome 18, the number of additional chromosome 18 and the lack of chromosome 13. Additionally, obesity (BMI 30-40 kg/m²) was positively associated with additional chromosome 21 after being adjusted for potential confounders. These findings demonstrate that changing the men's lifestyle habits may contribute to reduction of the incidence of sperm aneuploidy. It is necessary that men continue to follow sensible health advice concerning excess weight, coffee drinking and wearing tight fitting underwear. As this is the first such study to examine different lifestyle factors and sperm aneuploidy, the results need to be confirmed on larger population.

  19. Factor V Leiden and Inflammation

    PubMed Central

    Perez-Pujol, Silvia; Aras, Omer; Escolar, Gines

    2012-01-01

    Factor V Leiden, is a variant of human factor V (FV), also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL) has been studied from the pathophysiologic point of view, and research has been focused on finding clinical approaches for the management of the FVL associated to a trombophilic state. Less attention has been paid about the possible role of FVL in inflammatory conditions known to be present in different disorders such as uremia, cirrhosis, liver transplantation, depression as well as sepsis, infection or, inflammatory bowel disease (IBD). Whether platelet FVL will increase the activation of coagulation and/or in which proportion is able to determine the final outcome in the previously mentioned inflammatory conditions is a subject that remains uncertain. This paper will review the association of FVL with inflammation. Specifically, it will analyze the important role of the endothelium and the contribution of other inflammatory components involved at both the immune and vascular levels. This paper will also try to emphasize the importance of being a FVL carrier in associations to diseases where a chronic inflammation occurs, and how this condition may be determinant in the progression and outcome of a specific clinic situation. PMID:22666576

  20. Human Factors in Financial Trading

    PubMed Central

    Leaver, Meghan; Reader, Tom W.

    2016-01-01

    Objective This study tests the reliability of a system (FINANS) to collect and analyze incident reports in the financial trading domain and is guided by a human factors taxonomy used to describe error in the trading domain. Background Research indicates the utility of applying human factors theory to understand error in finance, yet empirical research is lacking. We report on the development of the first system for capturing and analyzing human factors–related issues in operational trading incidents. Method In the first study, 20 incidents are analyzed by an expert user group against a referent standard to establish the reliability of FINANS. In the second study, 750 incidents are analyzed using distribution, mean, pathway, and associative analysis to describe the data. Results Kappa scores indicate that categories within FINANS can be reliably used to identify and extract data on human factors–related problems underlying trading incidents. Approximately 1% of trades (n = 750) lead to an incident. Slip/lapse (61%), situation awareness (51%), and teamwork (40%) were found to be the most common problems underlying incidents. For the most serious incidents, problems in situation awareness and teamwork were most common. Conclusion We show that (a) experts in the trading domain can reliably and accurately code human factors in incidents, (b) 1% of trades incur error, and (c) poor teamwork skills and situation awareness underpin the most critical incidents. Application This research provides data crucial for ameliorating risk within financial trading organizations, with implications for regulation and policy. PMID:27142394

  1. [Nutritional factors in preventing osteoporosis].

    PubMed

    Martín Jiménez, Juan Antonio; Consuegra Moya, Belkis; Martín Jiménez, María Teresa

    2015-07-18

    Osteoporosis, main risk factor for suffering fragility fractures, is an important public health problem which has undoubted social, health and economic impact; but mainly causes pain, functional limitation and severe alterations in the patient's quality of life. Its current prevalence is very high and a further increase is expected due to a higher life expectancy and the progressive ageing of the population. In the prevention of osteoporosis, the main goal is to prevent fragility fractures; for this reason, it is necessary to: 1) promote bone formation in youth, to get sufficient bone mass peak, 2) reduce bone loss in adulthood, especially after menopause, 3) maintain bone health throughout life, and 4) prevent falls. There is enough evidence that multifactorial strategies (assessment of risk factors, healthy lifestyle habits, smoking cessation, moderation in alcohol consumption, physical exercise, outdoor activity with prudent exposure to sunlight, and a varied and balanced diet), are effective in the population at risk. Regarding factors for the prevention of osteoporosis, current recommendations are: increased consumption of calcium, phosphorus, magnesium and fluoride; provide adequate vitamin D (even with fortified food if necessary); consumption of foods rich in omega-3 acids; reduction of salt and prepared ready meals; sufficient but moderate intake of protein and, in the absence of intolerance, promote the consumption of milk and dairy products, especially yogurt and fermented milk products.

  2. 14 CFR 25.619 - Special factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Special factors. 25.619 Section 25.619... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction General § 25.619 Special factors. The factor of safety prescribed in § 25.303 must be multiplied by the highest pertinent special factor of...

  3. 14 CFR 31.43 - Fitting factor.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fitting factor. 31.43 Section 31.43... STANDARDS: MANNED FREE BALLOONS Design Construction § 31.43 Fitting factor. (a) A fitting factor of at least... structure. This factor applies to all parts of the fitting, the means of attachment, and the bearing on...

  4. 14 CFR 23.619 - Special factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Special factors. 23.619 Section 23.619... Special factors. The factor of safety prescribed in § 23.303 must be multiplied by the highest pertinent special factors of safety prescribed in §§ 23.621 through 23.625 for each part of the structure...

  5. Comparisons of Exploratory and Confirmatory Factor Analysis.

    ERIC Educational Resources Information Center

    Daniel, Larry G.

    Historically, most researchers conducting factor analysis have used exploratory methods. However, more recently, confirmatory factor analytic methods have been developed that can directly test theory either during factor rotation using "best fit" rotation methods or during factor extraction, as with the LISREL computer programs developed by K. G.…

  6. Cardiac risk factors: environmental, sociodemographic, and behavioral cardiovascular risk factors.

    PubMed

    Anthony, David; George, Paul; Eaton, Charles B

    2014-06-01

    Several environmental exposures are associated with increased risk of coronary heart disease (CHD). Exposure to secondhand smoke may increase the risk by as much as 25% to 30%. Exposure to third hand smoke, residual components of tobacco smoke that remain in the environment after a cigarette is extinguished, also appears to increase risk. These residual components can remain in rooms and automobiles for up to 30 years and enter the body through the skin or via inhalation or ingestion. Exposure to particulate matter air pollution from automobile emissions, power plants, and other sources is yet another environmental risk factor for CHD, resulting in tens of thousands of deaths annually in the United States. Exposure to other environmental toxins, particularly bisphenol A and phthalates, also has been linked to CHD. There are sociodemographic risks for CHD, with numerous studies showing that lower socioeconomic status is associated with higher risk. Behavioral risk factors include poor diet, such as frequent consumption of fast food and processed meals; sleep disturbance; and psychological stress, particularly related to marital or work issues. Finally, although high alcohol consumption is associated with increased CHD risk, moderate alcohol consumption (ie, less than 1 to 2 drinks/day), particularly of wine and possibly beer, appears to reduce the risk.

  7. Scene kinetics mitigation using factor analysis with derivative factors.

    SciTech Connect

    Larson, Kurt W.; Melgaard, David Kennett; Scholand, Andrew Joseph

    2010-07-01

    Line of sight jitter in staring sensor data combined with scene information can obscure critical information for change analysis or target detection. Consequently before the data analysis, the jitter effects must be significantly reduced. Conventional principal component analysis (PCA) has been used to obtain basis vectors for background estimation; however PCA requires image frames that contain the jitter variation that is to be modeled. Since jitter is usually chaotic and asymmetric, a data set containing all the variation without the changes to be detected is typically not available. An alternative approach, Scene Kinetics Mitigation, first obtains an image of the scene. Then it computes derivatives of that image in the horizontal and vertical directions. The basis set for estimation of the background and the jitter consists of the image and its derivative factors. This approach has several advantages including: (1) only a small number of images are required to develop the model, (2) the model can estimate backgrounds with jitter different from the input training images, (3) the method is particularly effective for sub-pixel jitter, and (4) the model can be developed from images before the change detection process. In addition the scores from projecting the factors on the background provide estimates of the jitter magnitude and direction for registration of the images. In this paper we will present a discussion of the theoretical basis for this technique, provide examples of its application, and discuss its limitations.

  8. Cardiovascular diseases and psychosocial factors at work.

    PubMed

    Diène, Eloi; Fouquet, Aurélie; Esquirol, Yolande

    2012-01-01

    Besides the 'classic' cardiovascular risk factors (high blood pressure, dyslipidaemia, metabolic syndrome and diabetes), the work environment is playing an increasingly significant role in cardiovascular morbidity and mortality. Several elements contribute to the effect of the work environment: physical factors, chemical factors, shift work and psychosocial factors. The effects of psychosocial factors on the aetiology and progression of cardiovascular disease have been confirmed by several studies. Identification of these work-related psychosocial factors must be taken into account when evaluating cardiovascular risk factors, in order to ensure better prevention.

  9. Zur Elektronenstruktur hochsymmetrischer Verbindungen der f-Elemente 28. Experimentelle Erfassung und Simulation des Kristallfeld-Aufspaltungsmusters von Tris(bis(trimethylsilyl)amido)neodym(III) [Nd(Btmsa)3

    NASA Astrophysics Data System (ADS)

    Amberger, Von H.-D.; Jank, S.; Reddmann Und, H.; Edelstein, N. M.

    Die sigma- und pi-Absorptionsspektren eines orientierten Nd(Btmsa)3-Einkristalls wurden bei Raumtemperatur sowie bei tiefen Temperaturen vermessen. Auf der Basis der beobachteten Spektren wurde das zugrundeliegende partielle Kristallfeld (KF)-Aufspaltungsmuster abgeleitet und durch Anpassung der offenen Operators simuliert. Bei 84 Zuordnungen wurde eine RMS-Abweichung von 35.2cm erzielt. Auf der Grundlage der erhaltenen Wellenfunktionen des KF-Grundzustandes konnte das bei 5K aufgenommene ESR-Spektrum von gelostem Nd(Btmsa)3 erklart werden. Unter Verwendung der berechneten Wellenfunktionen und Eigenwerte sowie eines Orbitalreduktions 2faktors k = 0.975konnte die hangigkeit von eff einer gepulverten Nd(Btmsa)3-Probe reproduziert werden. The sigma and pi absorption spectra of an oriented single crystal of Nd(btmsa)3 were measured at room and low temperatures. From the spectra obtained a truncated crystal field (CF) splitting pattern is derived, and simulated by fitting the fr-e1 e parameters of an empirical Hamiltonian. For 84 assignments an RMS deviation of 35.2cm tions of the CF ground state obtained from these calculations the 5K EPR spectrum of dissolved Nd(btmsa)3 could be explained. Making use of the calculated wav 2efunctions and eigenvalues the experimentally determined temperature dependence of eff of powdered Nd(btmsa)3 could be reproduced by adopting an orbital reduction factor k = 0.975. Parameter eines empirischen H-a 1miltonexperimentell bestimmte Temperaturabis achieved. On the basis of the wavefuncplexe

  10. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  11. Understanding adverse events: human factors.

    PubMed

    Reason, J

    1995-06-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  12. [Conditioning factors of weight condition].

    PubMed

    San Mauro, Ismael; Megias, Ana; Bodega, Patricia; García de Angulo, Belén; Rodríguez, Paula; Grande, Graciela; Micó, Víctor; Romero, Elena; Fajardo, Diana; García, Nuria

    2015-01-01

    Introducción: Estudios epidemiológicos muestran que durante las últimas dos décadas la obesidad infantil ha aumentado convertirse en una de las principales preocupaciones de salud pública. Los hábitos dietéticos, la falta de actividad física y, el grado de obesidad empeoran con el paso de los años convirtiendo a los niños con sobrepeso en adultos con sobrepeso. Objetivo: Conocer la influencia de diversos factores modificables (hábitos alimentarios, práctica de actividad física, sedentarismo y horas de sueño), sobre el estado ponderal de un colectivo de niños en edad escolar. Método: Se realizó un estudio observacional de corte transversal retrospectivo de 129 escolares de Madrid entre 6 y 12 años con recogida de datos antropométricos (peso, talla y circunferencia de cintura), dietéticos (Kidmed), de actividad física (IPAQ adaptado), sedentarismo y horas de sueño. Resultados: El resultado más relevante fue el exceso ponderal de los niños (28,1%), aunque estos resultados no fueron significativos respecto a ninguno de los factores estudiados. Se estudió el factor de actividad física y el tiempo dedicado a actividades sedentarias en función del sexo, en ambos casos se vieron valores menores en niñas que en niños siendo estas diferencias estadísticamente significativas (p.

  13. Small peptides blocking inhibition of factor Xa and tissue factor-factor VIIa by tissue factor pathway inhibitor (TFPI).

    PubMed

    Dockal, Michael; Hartmann, Rudolf; Fries, Markus; Thomassen, M Christella L G D; Heinzmann, Alexandra; Ehrlich, Hartmut; Rosing, Jan; Osterkamp, Frank; Polakowski, Thomas; Reineke, Ulrich; Griessner, Andreas; Brandstetter, Hans; Scheiflinger, Friedrich

    2014-01-17

    Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that inhibits activated factor X (FXa) via a slow-tight binding mechanism and tissue factor-activated FVII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa complex. Inhibition of TFPI enhances coagulation in hemophilia models. Using a library approach, we selected and subsequently optimized peptides that bind TFPI and block its anticoagulant activity. One peptide (termed compound 3), bound with high affinity to the Kunitz-1 (K1) domain of TFPI (Kd ∼1 nM). We solved the crystal structure of this peptide in complex with the K1 of TFPI at 2.55-Å resolution. The structure of compound 3 can be segmented into a N-terminal anchor; an Ω-shaped loop; an intermediate segment; a tight glycine-loop; and a C-terminal α-helix that is anchored to K1 at its reactive center loop and two-stranded β-sheet. The contact surface has an overall hydrophobic character with some charged hot spots. In a model system, compound 3 blocked FXa inhibition by TFPI (EC50 = 11 nM) and inhibition of TF-FVIIa-catalyzed FX activation by TFPI (EC50 = 2 nM). The peptide prevented transition from the loose to the tight FXa-TFPI complex, but did not affect formation of the loose FXa-TFPI complex. The K1 domain of TFPI binds and inhibits FVIIa and the K2 domain similarly inhibits FXa. Because compound 3 binds to K1, our data show that K1 is not only important for FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the loose to the tight FXa-TFPI complex. This mode of action translates into normalization of coagulation of hemophilia plasmas. Compound 3 thus bears potential to prevent bleeding in hemophilia patients. PMID:24275667

  14. Small Peptides Blocking Inhibition of Factor Xa and Tissue Factor-Factor VIIa by Tissue Factor Pathway Inhibitor (TFPI)*

    PubMed Central

    Dockal, Michael; Hartmann, Rudolf; Fries, Markus; Thomassen, M. Christella L. G. D.; Heinzmann, Alexandra; Ehrlich, Hartmut; Rosing, Jan; Osterkamp, Frank; Polakowski, Thomas; Reineke, Ulrich; Griessner, Andreas; Brandstetter, Hans; Scheiflinger, Friedrich

    2014-01-01

    Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that inhibits activated factor X (FXa) via a slow-tight binding mechanism and tissue factor-activated FVII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa complex. Inhibition of TFPI enhances coagulation in hemophilia models. Using a library approach, we selected and subsequently optimized peptides that bind TFPI and block its anticoagulant activity. One peptide (termed compound 3), bound with high affinity to the Kunitz-1 (K1) domain of TFPI (Kd ∼1 nm). We solved the crystal structure of this peptide in complex with the K1 of TFPI at 2.55-Å resolution. The structure of compound 3 can be segmented into a N-terminal anchor; an Ω-shaped loop; an intermediate segment; a tight glycine-loop; and a C-terminal α-helix that is anchored to K1 at its reactive center loop and two-stranded β-sheet. The contact surface has an overall hydrophobic character with some charged hot spots. In a model system, compound 3 blocked FXa inhibition by TFPI (EC50 = 11 nm) and inhibition of TF-FVIIa-catalyzed FX activation by TFPI (EC50 = 2 nm). The peptide prevented transition from the loose to the tight FXa-TFPI complex, but did not affect formation of the loose FXa-TFPI complex. The K1 domain of TFPI binds and inhibits FVIIa and the K2 domain similarly inhibits FXa. Because compound 3 binds to K1, our data show that K1 is not only important for FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the loose to the tight FXa-TFPI complex. This mode of action translates into normalization of coagulation of hemophilia plasmas. Compound 3 thus bears potential to prevent bleeding in hemophilia patients. PMID:24275667

  15. Modifications of coronary risk factors.

    PubMed

    Albu, Jeanine; Gottlieb, Sheldon H; August, Phyllis; Nesto, Richard W; Orchard, Trevor J

    2006-06-19

    In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers.

  16. Human Factors in Space Flight

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara J.; Mount, Frances

    2005-01-01

    After forty years of experience with human space flight (Table 1), the current emphasis is on the design of space vehicles, habitats, and missions to ensure mission success. What lessons have we learned that will affect the design of spacecraft for future space exploration, leading up to exploring Mars? This chapter addresses this issue in four sections: Anthropometry and Biomechanics; Environmental Factors; Habitability and Architecture; and Crew Personal Sustenance. This introductory section introduces factors unique to space flight. A unique consideration for design of a habitable volume in a space vehicle is the lack of gravity during a space flight, referred to as microgravity. This affects all aspects of life, and drives special features in the habitat, equipment, tools, and procedures. The difference in gravity during a space mission requires designing for posture and motion differences. In Earth s gravity, or even with partial gravity, orientation is not a variable because the direction in which gravity acts defines up and down. In a microgravity environment the working position is arbitrary; there is no gravity cue. Orientation is defined primarily through visual cues. The orientation within a particular crew station or work area is referred to as local vertical, and should be consistent within a module to increase crew productivity. Equipment was intentionally arranged in various orientations in one module on Skylab to assess the efficiency in use of space versus the effects of inconsistent layout. The effects of that arrangement were confusion on entering the module, time spent in re-orientation, and conflicts in crew space requirements when multiple crew members were in the module. Design of a space vehicle is constrained by the three major mission drivers: mass, volume and power. Each of these factors drives the cost of a mission. Mass and volume determine the size of the launch vehicle directly; they can limit consumables such as air, water, and

  17. Environmental Risk Factors for ARDS

    PubMed Central

    Moazed, Farzad; Calfee, Carolyn S.

    2014-01-01

    The acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality in critically ill patients. Over the past several decades, alcohol abuse and cigarette smoke exposure have been identified as risk factors for the development of ARDS. The mechanisms underlying these relationships are complex and remain under investigation but are thought to involve pulmonary immune impairment as well as alveolar epithelial and endothelial dysfunction. This review summarizes the epidemiologic data supporting links between these exposures and ARDS susceptibility and outcomes and highlights key mechanistic investigations that provide insight into the pathways by which each exposure is linked to ARDS. PMID:25453414

  18. Biographical factors of occupational independence.

    PubMed

    Müller, G F

    2001-10-01

    The present study examined biographical factors of occupational independence including any kind of nonemployed profession. Participants were 59 occupationally independent and 58 employed persons of different age (M = 36.3 yr.), sex, and profession. They were interviewed on variables like family influence, educational background, occupational role models, and critical events for choosing a particular type of occupational career. The obtained results show that occupationally independent people reported stronger family ties, experienced fewer restrictions of formal education, and remembered fewer negative role models than the employed people. Implications of these results are discussed. PMID:11783553

  19. Human factors in spacecraft design.

    PubMed

    Harrison, A A; Connors, M M

    1990-01-01

    This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

  20. Weak-shock reflection factors

    SciTech Connect

    Reichenbach, H.; Kuhl, A.L.

    1993-09-07

    The purpose of this paper is to compare reflection factors for weak shocks from various surfaces, and to focus attention on some unsolved questions. Three different cases are considered: square-wave planar shock reflection from wedges; square-wave planar shock reflection from cylinders; and spherical blast wave reflection from a planar surface. We restrict ourselves to weak shocks. Shocks with a Mach number of M{sub O} < 1.56 in air or with an overpressure of {Delta}{sub PI} < 25 psi (1.66 bar) under normal ambient conditions are called weak.