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Sample records for related growth factors

  1. Angiopoietin-related growth factor level in preeclampsia

    OpenAIRE

    2012-01-01

    Abstract Aim. Angiopoietin-related growth factor (AGF) is associated with angiogenesis but it can also affect glucose and energy metabolism. The aim of this study was to determine AGF levels in preeclampsia. Method. The study included 32 women with preeclampsia (preeclampsia group) and 32 non-preeclamptic, healthy, third trimester pregnant women (Control group). We analyzed serum levels of AGF and other biochemical and anthropometric markers in all subjects. Results. Serum AGF levels were sig...

  2. Growth factors in idiopathic pulmonary fibrosis: relative roles

    Directory of Open Access Journals (Sweden)

    Allen Jeremy T

    2001-11-01

    Full Text Available Abstract Treatment of idiopathic pulmonary fibrosis patients has evolved very slowly; the fundamental approach of corticosteroids alone or in combination with other immunosuppressive agents has had little impact on long-term survival. The continued use of corticosteroids is justified because of the lack of a more effective alternative. Current research indicates that the mechanisms driving idiopathic pulmonary fibrosis reflect abnormal, dysregulated wound healing within the lung, involving increased activity and possibly exaggerated responses by a spectrum of profibrogenic growth factors. An understanding of the roles of these growth factors, and the way in which they modulate events at cellular level, could lead to more targeted therapeutic strategies, improving patients' quality of life and survival.

  3. Distribution and number of epidermal growth factor receptors in skin is related to epithelial cell growth

    DEFF Research Database (Denmark)

    Green, M R; Basketter, D A; Couchman, J R

    1983-01-01

    Epidermal growth factor (EGF), a low-molecular-weight polypeptide (G. Carpenter and S. Cohen, 1979, Annu. Rev. Biochem. 48, 193-216), stimulates the proliferation and keratinisation of cultured embryonic epidermis (S. Cohen, 1965, Dev. Biol. 12, 394-407) and promotes epidermal growth, thickening,...

  4. Growth factors, aging and age-related diseases.

    Science.gov (United States)

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases.

  5. Self-assembling peptide amphiphiles and related methods for growth factor delivery

    Science.gov (United States)

    Stupp, Samuel I.; Donners, Jack J. J. M.; Silva, Gabriel A.; Behanna, Heather A.; Anthony, Shawn G.

    2009-06-09

    Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

  6. Through thick and thin: A circulating growth factor inhibits age-related cardiac hypertrophy

    OpenAIRE

    McPherron, Alexandra C.

    2013-01-01

    In an intriguing new study, Loffredo et al., report that joining the circulation of old mice with that of young mice reduces age-related cardiac hypertrophy. They also found that the growth factor GDF11 is a circulating negative regulator of cardiac hypertrophy which suggests that raising GDF11 levels may be useful to treat cardiac hypertrophy associated with aging.

  7. Stress-Related Growth among Suicide Survivors: The Role of Interpersonal and Cognitive Factors.

    Science.gov (United States)

    Levi-Belz, Yossi

    2015-01-01

    Although stress-related growth had been documented in bereaved individuals, it is still not clear to what extent it can be experienced by suicide survivors or which psychological processes facilitate it. The current study examined the role of interpersonal factors-self disclosure and social supports as well as cognitive coping strategies in stress-related growth among suicide survivors. The sample consisted of 135 suicide survivors (104 women and 31 men) aged 18-70. All participants completed the stress-related growth questionnaire as well as instruments measuring interpersonal activities, cognitive strategies, and demographic characteristics concerning the bereavement. The findings showed significant positive correlations between time elapsed since death, self-disclosure, social support, adaptive cognitive strategies, and stress-related growth. Furthermore, hierarchical regression analysis revealed that together these variables accounted for over 38% of the variance in stress-related growth. Interpersonal activities such as talking and interacting with others, as well as a cognitive focus on planning for the future emerged as important factors in personal transformation after suicide loss.

  8. Distribution and number of epidermal growth factor receptors in skin is related to epithelial cell growth

    DEFF Research Database (Denmark)

    Green, M R; Basketter, D A; Couchman, J R

    1983-01-01

    receptors are detected on the epithelial cells overlying the basement membranes of the epidermis, sebaceous gland, and regions of the hair follicle all of which have proliferative capacity. In marked contrast, tissues which have started to differentiate and lost their growth potential, carry either...... and temporal control of epithelial proliferation....

  9. Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer

    Institute of Scientific and Technical Information of China (English)

    Michael Hopfner; Detlef Schuppan; Hans Scherübl

    2008-01-01

    Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer (HCC). Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors ("small molecule inhibitors") and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin (mTOR) upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, mTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.

  10. Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration

    OpenAIRE

    Oike, Yuichi; Yasunaga, Kunio; Ito, Yasuhiro; Matsumoto, Shun-ichiro; Maekawa, Hiromitsu; Morisada, Tohru; Arai, Fumio; Nakagata, Naomi; Takeya, Motohiro; Masuho, Yasuhiko; Suda, Toshio

    2003-01-01

    We report here the identification of an angiopoietin-related growth factor (AGF). To examine the biological function of AGF in vivo, we created transgenic mice expressing AGF in epidermal keratinocytes (K14-AGF). K14-AGF mice exhibited swollen and reddish ears, nose and eyelids. Histological analyses of K14-AGF mice revealed significantly thickened epidermis and a marked increase in proliferating epidermal cells as well as vascular cells in the skin compared with nontr...

  11. Growth of pulsed electric field exposed Escherichia coli in relation to inactivation and environmental factors.

    Science.gov (United States)

    Aronsson, Kristina; Borch, Elisabeth; Stenlöf, Bo; Rönner, Ulf

    2004-05-15

    Pulsed electric fields (PEF) have been proven to inactivate microorganisms during nonthermal conditions and have the potential to replace thermal processing as a method for food preservation. However, there is a need to understand the recovery and growth of survivors and potentially injured microorganisms following PEF processing. The purpose of this investigation was to study the growth of Escherichia coli at 10 degrees C following exposure to electrical field strengths (15, 22.5 and 30 kV/cm) in relation to inactivation and the amount of potentially sublethally injured cells. One medium was used as both a treatment medium and an incubation medium, to study the influence of environmental factors on the inactivation and the growth of the surviving population. The pH (5.0, 6.0 and 7.0) and water activity (1.00, 0.985 and 0.97) of the medium was varied by adding HCl and glycerol, respectively. Growth was followed continuously by measuring the optical density. The time-to-detection (td) and the maximum specific growth rate (micromax) were calculated from these data. Results showed that the PEF process did not cause any obvious sublethal injury to the E. coli cells. The number of survivors was a consequence of the combination of electrical field strength and environmental factors, with pH being the most prominent. Interestingly, the micromax of subsequent growth was influenced by the applied electrical field strength during the process, with an increased micromax at more intense electrical field strengths. In addition, the micromax was also influenced by the pH and water activity. The td, which could theoretically be considered as an increase in shelf life, was found to depend on a complex correlation between electrical field strength, pH and water activity. That could be explained by the fact that the td is a combination of the number of survivors, the recovery of sublethal injured cells and the growth rate of the survivors.

  12. Soluble α-klotho and its relation to kidney function and fibroblast growth factor-23

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Liu, Ying; Pedersen, Lise

    2014-01-01

    CONTEXT: Relations between fibroblast growth factor-23 (FGF-23), soluble α-klotho (s-α-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-α-klotho requires further study. OBJECTIVES: Our objectives were to analyze the relation of s-α-klotho to......CONTEXT: Relations between fibroblast growth factor-23 (FGF-23), soluble α-klotho (s-α-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-α-klotho requires further study. OBJECTIVES: Our objectives were to analyze the relation of s......-α-klotho to estimated glomerular filtration rate (eGFR), FGF-23, and other parameters of calcium-phosphate metabolism and to investigate the response of s-α-klotho to cholecalciferol. PATIENTS, DESIGN, AND SETTING: Twenty-four CKD (stage 1-5) patients participated in this 8-week randomized controlled trial (vitamin D....... When patients were subdivided based on FGF-23 concentrations, a positive association of s-α-klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-α-klotho below 204 pg/mL showed higher age, lower phosphate...

  13. Transforming growth factor-beta 1 does not relate to hypertension in pre-eclampsia.

    Science.gov (United States)

    Hennessy, A; Orange, S; Willis, N; Painter, D M; Child, A; Horvath, J S

    2002-11-01

    1. Pre-eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end-organ damage, if severe. Pre-eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed. 2. Transforming growth factor (TGF)-beta1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end-organ disease related to increases in endothelin release. Transforming growth factor-beta1 is also an important factor in placental implantation. Alterations in TGF-beta1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre-eclampsia. 3. The aim of the present study was to examine the placental distribution and serum concentration of TGF-beta1 in patients with pre-eclampsia compared with normal pregnancy. 4. Patients with pre-eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor-beta1 was determined by TGF-beta1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF-beta1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining. 5. Patients with pre-eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 +/- 0.4 weeks. There was no difference in TGF-beta1 concentration between the two groups (mean (+/-SEM) 27.1 +/- 1.0 vs 26.4 +/- 0.7 pg/mL for normal pregnancy and pre-eclampsia, respectively; P = 0.73, Mann-Whitney U-test). There was no correlation between systolic or diastolic blood pressure and TGF-beta1 concentration (regression analysis P = 0.4 and 0.2). Immunostaining was absent in the villous trophoblast cells and endovascular and

  14. Hepatoma-derived growth factor-related protein 2 promotes DNA repair by homologous recombination

    Science.gov (United States)

    Baude, Annika; Aaes, Tania Løve; Zhai, Beibei; Al-Nakouzi, Nader; Oo, Htoo Zarni; Daugaard, Mads; Rohde, Mikkel; Jäättelä, Marja

    2016-01-01

    We have recently identified lens epithelium-derived growth factor (LEDGF/p75, also known as PSIP1) as a component of the homologous recombination DNA repair machinery. Through its Pro-Trp-Trp-Pro (PWWP) domain, LEDGF/p75 binds to histone marks associated with active transcription and promotes DNA end resection by recruiting DNA endonuclease retinoblastoma-binding protein 8 (RBBP8/CtIP) to broken DNA ends. Here we show that the structurally related PWWP domain-containing protein, hepatoma-derived growth factor-related protein 2 (HDGFRP2), serves a similar function in homologous recombination repair. Its depletion compromises the survival of human U2OS osteosarcoma and HeLa cervix carcinoma cells and impairs the DNA damage-induced phosphorylation of replication protein A2 (RPA2) and the recruitment of DNA endonuclease RBBP8/CtIP to DNA double strand breaks. In contrast to LEDGF/p75, HDGFRP2 binds preferentially to histone marks characteristic for transcriptionally silent chromatin. Accordingly, HDGFRP2 is found in complex with the heterochromatin-binding chromobox homologue 1 (CBX1) and Pogo transposable element with ZNF domain (POGZ). Supporting the functionality of this complex, POGZ-depleted cells show a similar defect in DNA damage-induced RPA2 phosphorylation as HDGFRP2-depleted cells. These data suggest that HDGFRP2, possibly in complex with POGZ, recruits homologous recombination repair machinery to damaged silent genes or to active genes silenced upon DNA damage. PMID:26721387

  15. Resistance to antivascular endothelial growth factor treatment in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tranos P

    2013-06-01

    Full Text Available Paris Tranos,1 Athanasios Vacalis,1 Solon Asteriadis,1 Stavrenia Koukoula,1 Athanasios Vachtsevanos,1 Georgia Perganta,1 Ilias Georgalas21Retina Centre, Thessaloniki, Greece; 2Department of Ophthalmology, "G Gennimatas" Hospital of Athens, University of Athens, Athens, GreeceAbstract: Age-related macular degeneration (AMD is the main cause of visual impairment and blindness in people aged over 65 years in developed countries. Vascular endothelial growth factor (VEGF is a positive regulator of angiogenesis and its proven role in the pathological neovascularization in wet AMD has provided evidence for the use of anti-VEGF agents as potential therapies. In this study, we review the literature for the possible causes of failure after treatment with anti-VEGF agents and attempt to propose an algorithm of suggestive actions to increase the chances of successful management of such difficult cases.Keywords: antiVEGF, age related macular degeneration, treatment

  16. Expression of transforming growth factors in hepatocellular carcinoma and its relations with clinicopathological parameters and prognosis

    Institute of Scientific and Technical Information of China (English)

    Yun Lu; Li-Qun Wu; Chang-Sheng Li; Shou-Guang Wang; Bing Han

    2008-01-01

    BACKGROUND:Transforming growth factors (TGF)-β1, TGF-βR2 and Smad4 belong to the TGF family, and play important roles in carcinogenesis and the development of carcinoma, especially hepatocellular carcinoma (HCC). TGF-β1 is a multipotent polypeptide, which inhibits the growth of epithelial cells including hepatoma cell lines and hepatocytes by inducing apoptosis. TGF-βR2 forms a heterodimeric complex upon binding to TGF-β, and then generates the ifrst step in the signal transduction pathway leading to growth inhibition in coordination with the type 1 receptor. Smad4 protein is an important mediator in the TGF-β signaling pathway, and negatively regulates the growth of epithelial cells. This study aimed to detect the expression of TGF-β1, TGF-βR2 and Smad4 in HCCs and their adjacent normal tissues, while assessing its relations with the clinicopathological parameters of HCC. METHODS:Forty-seven HCC specimens and their adjacent normal tissues were obtained surgically at the Afifliated Hospital of Medical College, Qingdao University. The expression of TGF-β1, TGF-βR2 and Smad4 was separately detected by immunohistochemistry in all HCC specimens and their adjacent normal tissues, and its relations with the clinicopathological parameters of HCC were assessed. RESULTS:The positive expression of TGF-β1 was 72.34%in the HCC specimens, which was higher than that in the adjacent normal tissues (P CONCLUSIONS:TGF-β1 may play an important role in the occurrence and development of HCC. Combined detection of TGF-β1, TGF-βR2 and Smad4 may be useful for the determination of the degree of malignancy and the prognosis of HCC.

  17. New microbial growth factor

    Science.gov (United States)

    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.

  18. Vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 expression in non-small cell lung cancer patients: relation to prognosis

    DEFF Research Database (Denmark)

    Bonnesen, Barbara; Pappot, Helle; Holmstav, Julie;

    2009-01-01

    elements in neoplastic cells and their microenvironment have recently been and are continuously developed including drugs inhibiting the angiogenic system. Angiogenic factor vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) seem to play key...

  19. Endorsement of Growth Factors and Its Relation to Stage of Group Development in Experiential Groups

    Science.gov (United States)

    Kiweewa, John M.

    2010-01-01

    This dissertation utilized critical incidents methodology to examine participants' endorsement of twelve primary growth factors during a Master's level group counseling class. Additionally, the study examined whether some factors are more salient than others at each stage of development (i.e., forming, storming, norming, performing) as defined by…

  20. Changes in serum growth factors in stroke rehabilitation patients and their relation to hemiparesis improvement.

    Science.gov (United States)

    Okazaki, Hideto; Beppu, Hidehiko; Mizutani, Kenmei; Okamoto, Sayaka; Sonoda, Shigeru

    2014-07-01

    Predicting recovery from hemiparesis after stroke is important for rehabilitation. A few recent studies reported that the levels of some growth factors shortly after stroke were positively correlated with the clinical outcomes during the chronic phase. The aim of this study was to examine the relationships between the serum levels of growth factors (vascular endothelial growth factor [VEGF], insulin-like growth factor-I [IGF-I], and hepatocyte growth factor [HGF]) and improvement in hemiparesis in stroke patients who received rehabilitation in a postacute rehabilitation hospital. Subjects were 32 stroke patients (cerebral infarction: 21 and intracerebral hemorrhage [ICH]: 11). We measured serum levels of VEGF, IGF-I, and HGF and 5 items of the Stroke Impairment Assessment Set (SIAS) for hemiparesis on admission and at discharge. Age-matched healthy subjects (n=15) served as controls. Serum levels of VEGF and HGF in cerebral infarct patients on admission were higher than those in control subjects, and the serum levels of IGF-I in stroke patients were lower than those in controls. The level of HGF in ICH patients on admission was negatively correlated with gains in SIAS, and higher outliers in HGF concentration were correlated with lower gains in SIAS. Focusing on the extremely high levels of these factors may be a predictor of the low recovery from hemiparesis after stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Vascular Endothelial Growth Factor-Related Pathways in Hemato-Lymphoid Malignancies

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2010-01-01

    Full Text Available Angiogenesis is essential for malignant tumor growth. This has been documented for solid tumors, and there is an emerging evidence suggesting that tumor progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation. The most important proangiogenic agent is vascular endothelial growth factor (VEGF, activating VEGF receptors 1 and 2. The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. Several antiangiogenic agents targeting VEGF-related pathways are also being utilized in clinical trials for the treatment of hemato-lymphoid malignancies, and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hemato-lymphoid malignancies and the translation of such basic findings into clinical studies.

  2. Overweight among Four-Year-Old Children in Relation to Early Growth Characteristics and Socioeconomic Factors

    Directory of Open Access Journals (Sweden)

    Jörgen Thorn

    2010-01-01

    Full Text Available Objectives. To assess early growth characteristics and socioeconomic factors of children in relation to body mass index (BMI and presence of overweight among four-year-old children. Methods. Two Child Health Centres (CHC participated in the study. They were selected to obtain two populations of children featuring divergent socio-economic characteristics. Growth data registered at the CHCs from birth to the 4-year check-up were recovered. Overweight was defined by the BMI cut-offs established by IOTF. BMI values expressed as BMI standard deviation score (BMISDS were used for analysis. Results. At the 4-year check-up, the BMISDS and the proportion of children with overweight (including the obese were significantly higher in the district with lower socio-economic status. High BMI at birth and low socio-economic status of the population in the CHC-district were shown to be independent determinants for overweight and BMISDS at four years of age. Conclusions. More research is needed to understand the mechanisms and how intervention programs should be designed in order to prevent the development of overweight and obesity in children.

  3. Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population

    Institute of Scientific and Technical Information of China (English)

    Yunus; Bulgu; Gokhan; Ozan; Cetin; Vildan; Caner; Ebru; Nevin; Cetin; Volkan; Yaylali; Cem; Yildirim

    2014-01-01

    AIM:To assess the association between age-related macular degeneration(AMD) and three single nucleotide polymorphisms(SNPS) related to the vascular endothelial growth factor(VEGF) gene.METHODS:The patients who were diagnosed with AMD were included in this prospective study. Three SNPs(rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS:The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group(P =0.072 and P =0.058).However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD(P =0.005 and P =0.010,respectively). One of the SNPs(rs1413711) was also found to be associated with the severity of AMD(P =0.001)with significant genotype distribution between early,intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION:VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

  4. Antivascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Ilias Zampros

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV, which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA are also discussed for their promising outcomes.

  5. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Energy Technology Data Exchange (ETDEWEB)

    Do, Ji Yeon; Choi, Young Keun [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kook, Hyun [Department of Pharmacology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Lee, In-Kyu [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Dong Ho, E-mail: sarasate2222@gmail.com [Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2015-05-01

    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O{sub 2}). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice.

  6. Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors.

    Science.gov (United States)

    Yamanaka, Yasunari; Kitano, Ayumi; Takao, Keizo; Prasansuklab, Anchalee; Mushiroda, Taisei; Yamazaki, Keiko; Kumada, Tomohiro; Shibata, Minoru; Takaoka, Yuki; Awaya, Tomonari; Kato, Takeo; Abe, Takaya; Iwata, Nakao; Miyakawa, Tsuyoshi; Nakamura, Yusuke; Nakahata, Tatsutoshi; Heike, Toshio

    2011-01-01

    The neurobiological mechanisms of emotional modulation and the molecular pathophysiology of anxiety disorders are largely unknown. The fibroblast growth factor (FGF) family has been implicated in the regulation of many physiological and pathological processes, which include the control of emotional behaviors. The present study examined mice with a targeted deletion of the fgf-bp3 gene, which encodes a novel FGF-binding protein, in animal models relevant to anxiety. To define the behavioral consequences of FGF-BP3 deficiency, we evaluated fgf-bp3-deficient mice using anxiety-related behavioral paradigms that provide a conflict between the desire to explore an unknown area or objects and the aversion to a brightly lit open space. The fgf-bp3-deficient mice exhibited alterations in time spent in the central area of the open-field arena, were less active in the lit areas of a light/dark transition test, and had a prolonged latency to feed during a novelty-induced hypophagia test. These changes were associated with alterations in light-induced orbitofrontal cortex (OFC) activation in an extracellular signal-regulated kinase (ERK) pathway-dependent manner. These results demonstrate that FGF-BP3 is a potent mediator of anxiety-related behaviors in mice and suggest that distinct pathways regulate emotional behaviors. Therefore, FGF-BP3 plays a critical role in the regulation of emotional states and in the development of anxiety disorders and should be investigated as a therapeutic target for anxiety disease in humans.

  7. Current status of vascular endothelial growth factor inhibition in age-related macular degeneration.

    Science.gov (United States)

    Mousa, Shaker A; Mousa, Shaymaa S

    2010-06-01

    Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized.

  8. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

    Science.gov (United States)

    Solomon, Sharon D; Lindsley, Kristina; Vedula, Satyanarayana S; Krzystolik, Magdalena G; Hawkins, Barbara S

    2014-08-29

    Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Two review authors independently screened records, extracted data, and

  9. Amblyomma americanum tick saliva insulin-like growth factor binding protein-related protein 1 binds insulin but not insulin-like growth factors.

    Science.gov (United States)

    Radulović, Ž M; Porter, L M; Kim, T K; Bakshi, M; Mulenga, A

    2015-10-01

    Silencing Amblyomma americanum insulin-like growth factor binding protein-related protein 1 (AamIGFBP-rP1) mRNA prevented ticks from feeding to repletion. In this study, we used recombinant (r)AamIGFBP-rP1 in a series of assays to obtain further insight into the role(s) of this protein in tick feeding regulation. Our results suggest that AamIGFBP-1 is an antigenic protein that is apparently exclusively expressed in salivary glands. We found that both males and females secrete AamIGFBP-rP1 into the host during feeding and confirmed that female ticks secrete this protein from within 24-48 h after attachment. Our data suggest that native AamIGFBP-rP1 is a functional insulin binding protein in that both yeast- and insect cell-expressed rAamIGFBP-rP1 bound insulin, but not insulin-like growth factors. When subjected to anti-blood clotting and platelet aggregation assays, rAamIGFBP-rP1 did not have any effect. Unlike human IGFBP-rP1, which is controlled by trypsinization, rAamIGFBP-rP1 is resistant to digestion, suggesting that the tick protein may not be under mammalian host control at the tick feeding site. The majority of tick-borne pathogens are transmitted 48 h after the tick has attached. Thus, the demonstrated antigenicity and secretion into the host within 24-48 h of the tick starting to feed makes AamIGFBP-rP1 an attractive target for antitick vaccine development.

  10. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, van J.; Cats, A.; Depla, A.; Timmer, R.; Witteman, B.J.M.; Wesseling, J.; Kampman, E.; van't Veer, L.J.

    2009-01-01

    Context: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are correla

  11. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.; Wesseling, J.; Kampman, E.; Veer, L.J. van 't

    2009-01-01

    CONTEXT: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are correla

  12. Expression of transforming growth factor beta 1-related signaling proteins in irradiated vessels

    Energy Technology Data Exchange (ETDEWEB)

    Preidl, Raimund H.M.; Moebius, Patrick; Weber, Manuel; Neukam, Friedrich W.; Schlegel, Andreas; Wehrhan, Falk [University of Erlangen- Nuernberg, Department of Oral and Maxillofacial Surgery, Erlangen (Germany); University of Erlangen- Nuernberg, Erlangen (Germany); Amann, Kerstin [University of Erlangen- Nuernberg, Erlangen (Germany)

    2014-12-09

    Microvascular free tissue transfer is a standard method in head and neck reconstructive surgery. However, previous radiotherapy of the operative region is associated with an increased incidence in postoperative flap-related complications and complete flap loss. As transforming growth factor beta (TGF-β) 1 and galectin-3 are well known markers in the context of fibrosis and lectin-like oxidized low-density lipoprotein 1 (LOX-1) supports vascular atherosclerosis, the aim of this study was to evaluate the expression of TGF-β1 and related markers as well as LOX-1 in irradiated vessels. To evaluate the expression of galectin-3, Smad 2/3, TGF-β1, and LOX-1, 20 irradiated and 20 nonirradiated arterial vessels were used for immunohistochemical staining. We semiquantitatively assessed the ratio of stained cells/total number of cells (labeling index). Expression of galectin-3, Smad 2/3, and TGF-β1 was significantly increased in previously irradiated vessels compared with nonirradiated controls. Furthermore, LOX-1 was expressed significantly higher in irradiated compared with nonirradiated vessels. Fibrosis-related proteins like galectin-3, Smad 2/3, and TGF-β1 are upregulated after radiotherapy and support histopathological changes leading to vasculopathy of the irradiated vessels. Furthermore, postoperative complications in irradiated patients can be explained by increased endothelial dysfunction caused by LOX-1 in previously irradiated patients. Consequently, not only TGF-β1 but also galectin-3inhibitors may decrease complications after microsurgical tissue transfer. (orig.) [German] Der freie mikrovaskulaere Gewebetransfer gilt heute als fester Standard in der rekonstruktiven Kopf-Hals-Chirurgie. Es zeigte sich jedoch, dass im Falle einer stattgehabten Bestrahlung im Operationsgebiet mit einer erhoehten Rate an transplantatbezogenen Komplikationen gerechnet werden muss. Sowohl TGF-β1 als auch Galektin-3 sind bekannte Mediatoren in Bezug auf die Fibroseentstehung

  13. Conserved Transcription Factors Steer Growth-Related Genomic Programs in Daphnia

    Science.gov (United States)

    Spanier, Katina I.; Jansen, Mieke; Decaestecker, Ellen; Hulselmans, Gert; Becker, Dörthe; Colbourne, John K.; Orsini, Luisa

    2017-01-01

    Abstract Ecological genomics aims to understand the functional association between environmental gradients and the genes underlying adaptive traits. Many genes that are identified by genome-wide screening in ecologically relevant species lack functional annotations. Although gene functions can be inferred from sequence homology, such approaches have limited power. Here, we introduce ecological regulatory genomics by presenting an ontology-free gene prioritization method. Specifically, our method combines transcriptome profiling with high-throughput cis-regulatory sequence analysis in the water fleas Daphnia pulex and Daphnia magna. It screens coexpressed genes for overrepresented DNA motifs that serve as transcription factor binding sites, thereby providing insight into conserved transcription factors and gene regulatory networks shaping the expression profile. We first validated our method, called Daphnia-cisTarget, on a D. pulex heat shock data set, which revealed a network driven by the heat shock factor. Next, we performed RNA-Seq in D. magna exposed to the cyanobacterium Microcystis aeruginosa. Daphnia-cisTarget identified coregulated gene networks that associate with the moulting cycle and potentially regulate life history changes in growth rate and age at maturity. These networks are predicted to be regulated by evolutionary conserved transcription factors such as the homologues of Drosophila Shavenbaby and Grainyhead, nuclear receptors, and a GATA family member. In conclusion, our approach allows prioritising candidate genes in Daphnia without bias towards prior knowledge about functional gene annotation and represents an important step towards exploring the molecular mechanisms of ecological responses in organisms with poorly annotated genomes. PMID:28854641

  14. Treatment related changes of the serum epidermal growth factor receptor in advanced colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, K G; Aalund Olsen, Dorte; Brandslund, I

    2009-01-01

    .001), and a correlation between the magnitude of increase and a higher degree of skin toxicity, a well known indicator of clinical benefit to EGFR inhibitors. sEGFR in rectal cancer patients displayed a decreasing tendency during CRT (p...e22096 Background: The epidermal growth factor receptor (EGFR) is an established target for therapy in colorectal cancer. The extracellular domain of the receptor is shed into circulation and detectable by ELISA. We investigated the changes in sEGFR levels during preoperative chemoradiation (CRT......) in rectal cancer patients and third-line treatment with cetuximab and irinotecan (CETIRI) in advanced disease, to elucidate the predictive or prognostic value in these settings. METHODS: We included 126 healthy controls and 118 patients with chemorefractory mCRC treated with cetuximab (initial 400/m(2) mg...

  15. Growth pattern in Ethiopian infants - the impact of exposure to maternal HIV infection in relation to socio-economic factors.

    Science.gov (United States)

    König Walles, John; Balcha, Taye Tolera; Winqvist, Niclas; Björkman, Per

    2017-01-01

    Infants exposed to maternal HIV infection who remain HIV-uninfected (HIV-exposed/uninfected; HIV-EU) may be at increased risk of growth retardation, which could be due both to directly HIV-related effects and to socio-economic factors overrepresented among HIV-positive women. To investigate growth development at 9-12 months of age in HIV-EU infants participating in prevention of mother-to-child transmission (PMTCT) care compared to HIV unexposed (HIV-U) infants in relation to socio-economic conditions. Anthropometric and socio-economic data were collected retrospectively from PMTCT registers (for HIV-EU infants), with HIV-U controls recruited at measles vaccination at public health facilities in Ethiopia. Growth was compared with regard to HIV exposure and socio-economic variables in multivariate regression analysis. The following growth measurements were found for 302 HIV-EU and 358 HIV-U infants at 9-12 months of age, respectively: mean weight-for-age z-score (WAZ) 0.04 and -0.21, p education (p education (p = 0.019). Lower LAZ was associated with male sex (p education (p education (p = 0.014). At 9-12 months of age, HIV-EU infants had non-inferior growth and higher mean WAZ than HIV-U controls. Poor growth development was associated with socio-economic factors. This suggests health benefits from PMTCT participation for infant growth. Similar interventions could be considered for Ethiopian infants, irrespective of HIV exposure, with a particular focus on children with poor socio-economic status.

  16. Transforming growth factor-beta and insulin-like growth factor-I in relation to diabetes-induced impairment of wound healing.

    Science.gov (United States)

    Bitar, M S; Labbad, Z N

    1996-02-15

    Impaired wound healing is a well-documented phenomenon in diabetes mellitus, yet little is known of the fundamental cause of this pathology. This study examined the effects of streptozotocin (STZ)-induced diabetes on the healing process using three wound models: (i) a linear skin incision (tensile strength), (ii) subcutaneously implanted polyvinyl alcohol sponge PVAs (collagen deposition), and (iii) stainless steel mesh chamber (TGF-beta, IGF-I and its binding proteins, extracellular matrix remodeling enzymes). RIA specific for IGF-I revealed that diabetes induced a 42% (wound fluid) and a 48% (serum) reduction in IGF-I levels. IGF-II western ligand blots found that diabetes produced a marked reduction in the level of a wound fluid 46 kDa IGF binding proteins. A proliferation-based bioassay indicates that TGF-beta level is also reduced in diabetic wound fluid (55%). Diabetes of graded metabolic severity induced by variable doses of STZ (25 mg-200 mg/kg) showed stepwise reduction in wound tensile strength and PVAs collagen deposition. In contrast, zymographic analysis of extracellular matrix proteases revealed that the diabetic wound fluid contains increased levels of 21, 69, and 72 kDa gelatinases. A single dose of TGF-beta (2 micrograms) in a collagen vehicle partially reversed the diabetes-related decrease in the tensile strength of standardized incisions. These data support the premise that wound-healing impairment in diabetes is due, at least in part, to a deficiency in growth factor activity within the wound environment.

  17. Relation between fibroblast growth factor-21, adiposity, metabolism, and weight reduction.

    Science.gov (United States)

    Mai, Knut; Schwarz, Franziska; Bobbert, Thomas; Andres, Janin; Assmann, Anke; Pfeiffer, Andreas F H; Spranger, Joachim

    2011-02-01

    Fibroblast growth factor-21 (FGF-21) has been proposed as a novel metabolic regulator, and animal experiments suggested that FGF-21 may affect energy balance. In humans, FGF-21 was correlated with obesity. Until now, no data exist regarding the relationship of FGF-21 and weight reduction in humans. We therefore investigated whether FGF-21 is modified by a moderate intended weight loss in a human trial. Thirty obese individuals (24 female, 6 male) participated in a weight reduction program for 6 months. In addition to several anthropometric and metabolic parameters, FGF-21 was measured before and after weight loss. Baseline serum FGF-21 was independently associated with markers of lipid metabolism and waist circumference. The multimodal intervention induced a moderate weight loss (97.4 ± 3.1 vs 92.2 ± 3.1 kg, P < .001), which was accompanied by a significant improvement of lipid and glucose metabolism. However, FGF-21 levels were not modified by moderate weight reduction; and FGF-21 levels at baseline were not a predictive marker for subsequent weight loss. The results presented here confirmed that FGF-21 levels are associated with markers of lipid metabolism and an estimate of abdominal adiposity. The finding that moderate weight loss did not induce changes of FGF-21 levels in humans suggests that FGF-21 is not directly regulated by fat mass under those conditions. © 2011 Elsevier Inc. All rights reserved.

  18. Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders

    Science.gov (United States)

    Vahdatpour, Cyrus; Dyer, Adam H.; Tropea, Daniela

    2016-01-01

    Insulin-Like Growth Factor 1 (IGF-1) is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS) growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD), both recombinant IGF-1 (mecasermin) and related derivatives, such as (1-3)IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders. PMID:27746717

  19. Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Cyrus Vahdatpour

    2016-09-01

    Full Text Available Insulin-Like Growth Factor 1 (IGF-1 is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD, both recombinant IGF-1 (mecasermin and related derivatives, such as (1-3 IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In broader ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders.

  20. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    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.

  1. Expression of extracellular matrix components and related growth factors in human tendon and muscle after acute exercise

    DEFF Research Database (Denmark)

    Heinemeier, K M; Bjerrum, S S; Schjerling, P

    2013-01-01

    the patellar tendon and vastus lateralis muscle of each leg at 2 (n = 10), 6 (n = 11), or 26 h (n = 10) after exercise. Levels of messenger ribonucleic acid mRNA for collagens, noncollagenous matrix proteins, and growth factors were measured with real-time reverse transcription polymerase chain reaction......Acute kicking exercise induces collagen synthesis in both tendon and muscle in humans, but it is not known if this relates to increased collagen transcription and if other matrix genes are regulated. Young men performed 1 h of one-leg kicking at 67% of max workload. Biopsies were taken from....... In tendon, gene expression was unchanged except for a decrease in insulin-like growth factor-IEa (IGF-IEa; P ...

  2. Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation.

    Science.gov (United States)

    Ledeganck, Kristien J; De Winter, Benedicte Y; Van den Driessche, Annelies; Jürgens, Angelika; Bosmans, Jean-Louis; Couttenye, Marie M; Verpooten, Gert A

    2014-05-01

    Cyclosporine (CsA) treatment is associated with hypomagnesaemia due to a renal Mg(2+) leak. In animal studies a role for the Mg(2+) channel TRPM6 localized in the distal convoluted tubule and stimulated by epidermal growth factor (EGF) is suggested. We hypothesize that CsA-induced hypomagnesaemia is due to a renal magnesium leak, also in patients, resulting from a downregulation of the renal EGF production, thereby inhibiting the activation of TRPM6. Renal transplant patients treated with CsA (n = 55) and 35 chronic kidney disease (CKD) patients were included. At three time points, with an interval of at least 1 month, blood and urine samples were taken to determine creatinine, Mg(2+), sodium and EGF. Serum Mg(2+) was significantly lower in the CsA group versus the CKD group with significantly more CsA-treated patients developing hypomagnesaemia. Although the fractional excretion (FE) Mg(2+) did not differ significantly between the two groups, subanalysis of the patients with hypomagnesaemia showed a significantly higher FE Mg(2+) in CsA-treated patients compared with CKD patients (P = 0.05). The urinary EGF excretion was significantly decreased in the CsA group and was a predictor of the FE Mg(2+) in the two groups. Serum sodium was significantly decreased in the CsA group simultaneously with an increased FE Na(+). In CsA-treated patients, the association of a low urinary EGF excretion and a decreased renal Mg(2+) reabsorption is in accordance with in vitro and animal studies. In the whole study population, log urinary EGF excretion is an independent predictor of the FE Mg(2+), supporting the role of EGF in magnesium reabsorption.

  3. Postprandial regulation of growth- and metabolism-related factors in zebrafish.

    Science.gov (United States)

    Seiliez, Iban; Médale, Françoise; Aguirre, Peyo; Larquier, Mélanie; Lanneretonne, Laura; Alami-Durante, Hélène; Panserat, Stéphane; Skiba-Cassy, Sandrine

    2013-06-01

    Zebrafish (Danio rerio) have been proposed as a possible model organism for nutritional physiology. However, this potential has not yet been realized and studies on the field remain scarce. In this work, we investigated in this species the effect of a single meal as well as that of an increase in the ratio of dietary carbohydrates/proteins on the postprandial expression of several hepatic and muscle metabolism-related genes and proteins. Fish were fed once either a commercial diet (experiment 1) or one of two experimental diets (experiment 2) containing different protein and carbohydrate levels after 72 h of starvation. Refeeding induced the postprandial expression of genes of glycolysis (GK, HK1) and lipogenesis (FAS, G6PDH, ACCa) and inhibited those of gluconeogenesis (cPEPCK) and beta-oxidation (CPT1b) in the viscera. In the muscle, refeeding increased transcript levels of myogenesis (Myf5, Myogenin), inhibited those of Ub-proteasomal proteolytic system (Atrogin1, Murf1a, Murf1b), and induced the activation of key signaling factors of protein synthesis (Akt, 4EBP1, S6K1, S6). However, diet composition had a low impact on the studied factors. Together, these results highlight some specificity of the zebrafish metabolism and demonstrate the interest and the limits of this species as a model organism for nutritional physiology studies.

  4. Epidermal growth factor receptor-related protein inhibits cell growth and induces apoptosis of BxPC3 pancreatic cancer cells.

    Science.gov (United States)

    Zhang, Yuxiang; Banerjee, Sanjeev; Wang, Zhi-wei; Marciniak, Dorota J; Majumdar, Adhip P N; Sarkar, Fazlul H

    2005-05-01

    Dysregulation of the epidermal growth factor receptor (EGFR) signaling network has been frequently reported in pancreatic cancer. Inhibition of EGFR was associated with antitumor effects in both in vitro and in vivo studies of pancreatic cancer. We have previously reported the isolation and characterization of an EGFR-related protein (ERRP), which seems to be a negative regulator of EGFR. In the present investigation, we tested our hypothesis whether recombinant ERRP could be an effective inhibitor of growth of BxPC3 pancreatic cancer cells. Cell growth and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptosis ELISA assay, respectively, in the presence and absence of recombinant ERRP in BxPC3 cells. To evaluate activation of EGFR and its downstream signaling events, levels of phospho-EGFR, phospho-AKT, and phospho-extracellular signal-regulated kinase (phospho-ERK) were determined by Western blot analysis. NF-kappaB activity was measured by electrophoretic mobility shift assay. Our data show, for the first time, that ERRP inhibits the growth of BxPC3 cells in a dose- and time-dependent manner. The EGF or transforming growth factor (TGF)-alpha-induced stimulation of cell growth and activation of EGFR was also inhibited by ERRP. These changes were accompanied by a concomitant attenuation of activation of mitogen-activated protein (MAP) kinases, AKT, and NF-kappaB. ERRP also induced apoptosis as evidenced by increased poly(ADP-ribose) polymerase cleavage and reduction in procaspase3. From these results, we conclude that ERRP is a potent inhibitor of growth of BxPC-3 pancreatic cancer cells, which could be due to attenuation of EGFR cellular signaling processes. We also suggest that ERRP could be a potential therapeutic agent for pancreatic cancer.

  5. Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells.

    Science.gov (United States)

    Okuda, S; Myoui, A; Ariga, K; Nakase, T; Yonenobu, K; Yoshikawa, H

    2001-11-15

    Age-related fluctuations in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells were investigated. The purpose of this study was to determine whether synthetic responses to insulin-like growth factor-I decline with age and to explore the possibility that an age-related increase in the expression of insulin-like growth factor binding proteins suppresses matrix synthesis in intervertebral disc cells. Several studies have reported that the responsiveness of chondrocytes to insulin-like growth factor-I decreases with age and furthermore that this phenomenon may be related to increased expression of insulin-like growth factor binding proteins by chondrocytes. Nucleus pulposus tissue and cells were obtained from the coccygeal vertebrae of 8-week-old, 40-week-old, and 120-week-old rats. Age-related changes in the expression of insulin-like growth factor-I and its receptor were assessed together with insulin-like growth factor-I dependent proteoglycan synthesis by the cultured nucleus pulposus cells. Also, western blot analysis of insulin-like growth factor binding protein-1 was carried out, and further examination was performed of insulin-like growth factor-I signal transduction through tyrosine phosphorylation of insulin receptor substrate-1, which is a signal transducer of insulin-like growth factor-I. Semiquantitative reverse transcription polymerase chain reaction analysis indicated that the expression of insulin-like growth factor-I receptor in 120-week cells decreased clearly in comparison with the cells of younger animals. By contrast, insulin-like growth factor-I dependent proteoglycan synthesis decreased with age, and the sharpest decline of synthesis was found between 8-week and 40-week cells, although the level of insulin-like growth factor-I/insulin-like growth factor-I receptor gene expression was maintained in 40-week-old animals. Consistent with the results of proteoglycan synthesis, the expression of

  6. Keratinocyte growth factor and the expression of wound-healing-related genes in primary human keratinocytes from burn patients.

    Science.gov (United States)

    Chomiski, Verônica; Gragnani, Alfredo; Bonucci, Jéssica; Correa, Silvana Aparecida Alves; Noronha, Samuel Marcos Ribeiro de; Ferreira, Lydia Masako

    2016-08-01

    To evaluate the effect of keratinocyte growth factor (KGF) treatment on the expression of wound-healing-related genes in cultured keratinocytes from burn patients. Keratinocytes were cultured and divided into 4 groups (n=4 in each group): TKB (KGF-treated keratinocytes from burn patients), UKB (untreated keratinocytes from burn patients), TKC (KGF-treated keratinocytes from controls), and UKC (untreated keratinocytes from controls). Gene expression analysis using quantitative polymerase chain reaction (qPCR) array was performed to compare (1) TKC versus UKC, (2) UKB versus UKC, (3) TKB versus UKC, (4) TKB versus UKB, (5) TKB versus TKC, and (6) UKB versus TKC. Comparison 1 showed one down-regulated and one up-regulated gene; comparisons 2 and 3 resulted in the same five down-regulated genes; comparison 4 had no significant difference in relative gene expression; comparison 5 showed 26 down-regulated and 7 up-regulated genes; and comparison 6 showed 25 down-regulated and 11 up-regulated genes. There was no differential expression of wound-healing-related genes in cultured primary keratinocytes from burn patients treated with keratinocyte growth factor.

  7. Targeting Vascular Endothelial Growth Factor Receptor 2 and Protein Kinase D1 Related Pathways by a Multiple Kinase Inhibitor in Angiogenesis and Inflammation Related Processes In Vitro

    OpenAIRE

    Attila Varga; Pál Gyulavári; Zoltán Greff; Krisztina Futosi; Tamás Németh; Laura Simon-Szabó; Krisztina Kerekes; Csaba Szántai-Kis; Diána Brauswetter; Márton Kokas; Gábor Borbély; Anna Erdei; Attila Mócsai; György Kéri; Tibor Vántus

    2015-01-01

    Emerging evidence suggests that the vascular endothelial growth factor receptor 2 (VEGFR2) and protein kinase D1 (PKD1) signaling axis plays a critical role in normal and pathological angiogenesis and inflammation related processes. Despite all efforts, the currently available therapeutic interventions are limited. Prior studies have also proved that a multiple target inhibitor can be more efficient compared to a single target one. Therefore, development of novel inflammatory pathway-specific...

  8. Posttraumatic growth in the aftermath of trauma: A literature review about related factors and application contexts

    OpenAIRE

    Catarina Ramos; Isabel Leal

    2013-01-01

    Aim: In the face of one traumatic event, individuals may perceive, along with the inherent negative responses, a number of positive changes, which reveal posttraumatic growth. This concept has increased its expression in literature over the years, and it has been recognized that people exposed to highly traumatic events, such as bereavement, war combat, disasters, disease or other stressful or life-threatening events, may perceive positive changes from the struggling with those events. Thus, ...

  9. Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle

    DEFF Research Database (Denmark)

    Heinemeier, K M; Olesen, J L; Haddad, F

    2009-01-01

    Tendon tissue and the extracellular matrix of skeletal muscle respond to mechanical loading by increased collagen expression and synthesis. This response is likely a secondary effect of a mechanically induced expression of growth factors, including transforming growth factor-beta1 (TGF-beta1......) and insulin-like growth factor-I (IGF-I). It is not known whether unloading of tendon tissue can reduce the expression of collagen and collagen-inducing growth factors. Furthermore, the coordinated response of tendon and muscle tissue to disuse, followed by reloading, is unclear. Female Sprague-Dawley rats...... tissue growth factor (CTGF), myostatin, and IGF-I isoforms were measured by real-time RT-PCR in Achilles tendon and soleus muscle. The tendon mass was unchanged, while the muscle mass was reduced by 50% after HS (P

  10. Relative Expression of Apoptotic and Vascular Epithelial Growth Factor Receptor Genes in Gamma-Irradiated Rat Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyang; Chun, Ki Jung; Kim, Jin Kyu [Korea Atomic research Institute, Deajeon (Korea, Republic of); Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    2005-07-01

    by confirming the apoptosis and the expression of renewal receptors to signals for angiogenesis-related growth factors after irradiation.

  11. Fibroblast Growth Factor Receptor 1 (FGFR1), Partly Related to Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and Microvessel Density, is an Independent Prognostic Factor for Non-Small Cell Lung Cancer

    Science.gov (United States)

    Pu, Dan; Liu, Jiewei; Li, Zhixi; Zhu, Jiang; Hou, Mei

    2017-01-01

    Background This study aimed to explore the correlation between FGFR1 and clinical features, including survival analysis and the promotion of angiogenesis by fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2). FGFR1 gene amplification has been found in non-small cell lung cancer (NSCLC). However, the prognostic value of FGFR1 and the correlation between FGFR1 and clinical features are still controversial. Material/Methods A total of 92 patients with NSCLC who underwent R0 resection between July 2006 and July 2008 were enrolled in the study. The expression of FGFR1, VEGFR2, and CD34 was detected by immunohistochemistry. The correlations between the aforementioned markers and the patients’ clinical features were analyzed by the chi-square test. The impact factors of prognosis were evaluated by Cox regression analyses. Results The expression ratios of FGFR1 and VEGFR2 were 26.1% and 43.4%, respectively. The intensity of FGFR1 expression was related to VEGFR2 and histopathology. To some extent, the average microvessel density (MVD) had correlation to the expression of FGFR1 and VGEFR2. The pathological stages III–IV and high expression of FGFR1 were found to be independent prognostic factors. Conclusions The expression intensity of FGFR1 and VEGFR2 was associated with MVD, and the expression of FGFR1 is one of the independent prognostic indicators for NSCLC. PMID:28088809

  12. The acid-labile subunit of the ternary insulin-like growth factor complex in cirrhosis: relation to liver dysfunction

    DEFF Research Database (Denmark)

    Møller, S; Juul, A; Becker, U;

    2000-01-01

    BACKGROUND/AIMS: In the circulation, insulin-like growth factor-I (IGF-I) is bound in a trimeric complex of 150 kDa with IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). Whereas circulating IGF-I and IGFBP-3 are reported to be low in patients with chronic liver failure, the level...... of ALS has not been described in relation to hepatic dysfunction. The aim of the present study was therefore to measure circulating and hepatic venous concentrations of ALS in relation to hepatic function and the IGF axis. METHODS: Twenty-five patients with cirrhosis (Child class A/B/C:5/10/10) and 30...... controls with normal liver function were studied. During a haemodynamic investigation, blood samples were collected from the hepatic vein and femoral artery, and the plasma concentrations of ALS, IGF-I and IGFBP-3 were determined. RESULTS: Hepatic venous and arterial concentrations of ALS were...

  13. Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Alison E Harvey

    Full Text Available Calorie restriction (CR prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02 and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2 was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

  14. Insulin-like growth factor type 1 and its relation with neuropsychiatric disorders

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    Jonathan Adrián Zegarra-Valdivia

    2017-08-01

    Full Text Available Resumen El estudio de distintos factores neurotróficos, entre ellos, el factor de crecimiento insulínico tipo 1, ha alcanzado relevancia en los últimos años por su rol en la actividad cerebral y sus potenciales aplicaciones terapéuticas. En el presente artículo se realiza una revisión del factor de crecimiento insulínico tipo 1 vinculado a trastornos neuropsiquiátricos como el autismo, la ansiedad, depresión, trastorno de estrés post traumático y la enfermedad de Alzheimer. Esto nos permitirá conocer su relación e importancia en dichos trastornos, en distintas etapas del desarrollo. Se realizó una búsqueda exhaustiva de distintos artículos originales, estudios clínicos, experimentales y de revisión, en las bases de datos de MEDLINE/PubMed y ScienceDirect, seleccionando 80 publicaciones de alto impacto posteriores al año 2000. Se concluye que a pesar de las muchas funciones del factor de crecimiento insulínico tipo 1 que han sido estudiadas en el sistema nervioso en desarrollo, así como en el cerebro adulto y especialmente con modelos animales, no se comprende completamente su papel en el cerebro humano con trastornos neuropsiquiátricos. Los datos son contradictorios en lo referente a trastornos altamente prevalentes, como los que afectan al estado del ánimo. Sin embargo, se encuentran mayores implicancias en los trastornos neurodegenerativos. Adicionalmente se señala su alto potencial como recurso terapéutico en trastornos neuropsiquiátricos de difícil abordaje, como el autismo y la enfermedad de Alzheimer. No obstante ello, es necesario efectuar una mayor investigación, tanto a nivel básico y clínico aplicado, para entender completamente su relevancia en estos trastornos.

  15. Insulin-like growth factor-I and its receptor in neovascular age-related macular degeneration

    NARCIS (Netherlands)

    A.C. Lambooij; K.H.M. van Wely (Karel); D.J. Lindenbergh-Kortleve (Dicky); R.W.A.M. Kuijpers (Robert); M. Kliffen (Mike); C.M. Mooy (Cornelia)

    2003-01-01

    textabstractPURPOSE: The insulin-like growth factor (IGF)-I protein is a growth-promoting polypeptide that can act as an angiogenic agent in the eye. The purpose of the current study was to localize the expression of IGF-I and its receptor (IGF-IR) mRNA and IGF-IR protein in situ i

  16. Comparison of angiogenesis-related factor expression in primary tumor cultures under normal and hypoxic growth conditions

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    Brower Stacey L

    2008-07-01

    Full Text Available Abstract Background A localized hypoxic environment occurs during tumor growth necessitating an angiogenic response or tumor necrosis results. Novel cancer treatment strategies take advantage of tumor-induced vascularisation by combining standard chemotherapeutic agents with angiogenesis-inhibiting agents. This has extended the progression-free interval and prolonged survival in patients with various types of cancer. We postulated that the expression levels of angiogenesis-related proteins from various primary tumor cultures would be greater under hypoxic conditions than under normoxia. Methods Fifty cell sources, including both immortalized cell lines and primary carcinoma cells, were incubated under normoxic conditions for 48 hours. Then, cells were either transferred to a hypoxic environment (1% O2 or maintained at normoxic conditions for an additional 48 hours. Cell culture media from both conditions was collected and analyzed via an ELISA-based assay to determine expression levels of 11 angiogenesis-related factors: VEGF, PDGF-AA, PDGF-AA/BB, IL-8, bFGF/FGF-2, EGF, IP-10/CXCL10, Flt-3 ligand, TGF-β1, TGF-β2, and TGF-β3. Results A linear correlation between normoxic and hypoxic growth conditions exists for expression levels of eight of eleven angiogenesis-related proteins tested including: VEGF, IL-8, PDGF-AA, PDGF-AA/BB, TGF-β1, TGF-β2, EGF, and IP-10. For VEGF, the target of current therapies, this correlation between hypoxia and higher cytokine levels was greater in primary breast and lung carcinoma cells than in ovarian carcinoma cells or tumor cell lines. Of interest, patient cell isolates differed in the precise pattern of elevated cytokines. Conclusion As linear correlations exist between expression levels of angiogenic factors under normoxic and hypoxic conditions in vitro, we propose that explanted primary cells may be used to probe the in vivo hypoxic environment. Furthermore, differential expression levels for each sample

  17. Nerve growth factor eye drops improve visual acuity and electrofunctional activity in age-related macular degeneration: a case report

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    Alessandro Lambiase

    2009-12-01

    Full Text Available Age-related macular degeneration (ARMD is a severe disease affecting visual function in the elderly. Currently available surgical and medical options do not guarantee a significant impact on the outcome of the disease. We describe the effects of nerve growth factor eye drop treatment in a 94 years old female with ARMD, whose visual acuity was progressively worsening in spite of previous surgical and medical treatments. NGF eye drops improved visual acuity and electrofunctional parameters as early as 3 months after initiation of treatment. These results are in line with previous reports on a neuroprotective effect of NGF on retinal cells and on NGF eye drops bioavailability in the retina and optic nerve. No side effects were observed after five years of follow-up, suggesting that topical NGF treatment may be a safe and effective therapy for ARMD.

  18. Animal protein intakes during early life and adolescence differ in their relation to the growth hormone-insulin-like-growth-factor axis in young adulthood.

    Science.gov (United States)

    Joslowski, Gesa; Remer, Thomas; Assmann, Karen E; Krupp, Danika; Cheng, Guo; Garnett, Sarah P; Kroke, Anja; Wudy, Stefan A; Günther, Anke L B; Buyken, Anette E

    2013-07-01

    Recent studies provide evidence that insulin-like-growth-factor I (IGF-I) and its binding proteins (IGFBP) IGFBP-2 and IGFBP-3 are related to the risk of several common cancers. It remains to be clarified whether their concentrations can be programmed by protein intake from different sources during growth. This study addressed the hypothesis that animal protein intakes during infancy, mid-childhood, and adolescence differ in their relevance for the growth-hormone (GH)-IGF-I axis in young adulthood. Data from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study participants with at least 2 plausible 3-d weighed dietary records during adolescence (age: girls, 9-14 y; boys, 10-15 y; n = 213), around the adiposity rebound (age 4-6 y; n = 179) or early life (age 0.5-2 y; n = 130), and one blood sample in young adulthood were included in the study. Mean serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 were compared between tertiles of habitual animal protein intake using multivariable regression analysis. Habitually higher animal protein intakes in females during puberty were related to higher IGF-I (P-trend = 0.005) and IGFBP-3 (P-trend = 0.01) and lower IGFBP-2 (P-trend = 0.04), but not to IGFBP-1 in young adulthood. In turn, IGF-I concentrations in young adulthood were inversely related to animal protein intakes in early life among males only (P-trend = 0.03), but not to animal protein intake around adiposity rebound (P-trend > 0.5). Our data suggest that, among females, a habitually higher animal protein intake during puberty may precipitate an upregulation of the GH-IGF-I axis, which is still discernible in young adulthood. By contrast, among males, higher animal protein intakes in early life may exert a long-term programming of the GH-IGF-I axis.

  19. Age-Related Insulin-Like Growth Factor Binding Protein-4 Overexpression Inhibits Osteogenic Differentiation of Rat Mesenchymal Stem Cells

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    Jinhui Wu

    2017-06-01

    Full Text Available Background/Aims: Insulin-like growth factor binding proteins (IGFBP play important roles in bone metabolism. IGFBP4 is involved in senescent-associated phenomena in mesenchymal stem cells (MSCs. The goal of the present study was to determine whether age-related IGFBP4 overexpression is associated with the impaired osteogenic differentiation potential of aged bone marrow derived MSCs. Methods: MSCs were isolated from Sprague-Dawley rats aged 3–26 months. The bone morphogenetic protein (BMP-2-induced osteogenic differentiation of rat MSCs was assessed by analyzing the expression levels of osteoblast marker genes [runt-related transcription factor 2 (RUNX2, alkaline phosphatase (ALP, and osteocalcin (OC], ALP activity and calcification. Results: Our study showed that IGFBP4 mRNA and protein expression increased with age in parallel with impaired osteogenic differentiation of MSCs cultured in BMP2-containing osteogenic medium, as evidenced by the downregulation of osteoblast marker genes, and decreased ALP activity and calcium deposits. IGFBP4 overexpression impaired BMP2-induced osteogenic differentiation potential of young MSCs, whereas IGFBP4 knockdown restored the osteogenic potency of aged MSCs. Moreover, IGFBP4 knockdown stimulated the activation of Erk and Smad by increasing phosphorylation. Conclusion: Collectively, our results demonstrate that IGFBP4 overexpression plays a role in the impairment of MSC differentiation potential via the Erk and Smad pathways, suggesting potential targets to improve MSC function for cell therapy applications.

  20. Paraneoplastic hormones: parathyroid hormone-related protein (PTHrP) and erythropoietin (EPO) are related to vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma.

    Science.gov (United States)

    Feng, Chen-chen; Ding, Guan-xiong; Song, Ning-hong; Li, Xuan; Wu, Zhong; Jiang, Hao-wen; Ding, Qiang

    2013-12-01

    To investigate the correlation between parathyroid hormone-related protein (PTHrP), erythropoietin (EPO), and vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemical studies on PTHrP, EPO and VEGF were performed in 249 patients with ccRCC. Serum calcium level and haematocrit were analyzed. The expression of the factors and clinicopathological parameters were studied statistically for possible correlations. The incidence for hypercalcaemia and polycythaemia were 15.3% and 2.0% respectively. Expression of PTHrP, EPO, and VEGF were respectively related to advanced stage (P PTHrP was not related to tumour grade. Expressions of EPO and VEGF were correlated to tumour grade significantly. All factors were expressed higher in hypercalcaemic patients. PTHrP, EPO, and VEGF were positively correlated with each other in non-hypercalcaemic patients yet not in hypercalcaemic ones. PTHrP and EPO are related to VEGF expression and to the progression of ccRCC. This finding offers us new insight on the behaviour of ccRCC and offers possible targets in RCC treatment.

  1. A systematic review of built environment factors related to physical activity and obesity risk: implications for smart growth urban planning.

    Science.gov (United States)

    Durand, C P; Andalib, M; Dunton, G F; Wolch, J; Pentz, M A

    2011-05-01

    Smart growth is an approach to urban planning that provides a framework for making community development decisions. Despite its growing use, it is not known whether smart growth can impact physical activity. This review utilizes existing built environment research on factors that have been used in smart growth planning to determine whether they are associated with physical activity or body mass. Searching the MEDLINE, Psycinfo and Web-of-Knowledge databases, 204 articles were identified for descriptive review, and 44 for a more in-depth review of studies that evaluated four or more smart growth planning principles. Five smart growth factors (diverse housing types, mixed land use, housing density, compact development patterns and levels of open space) were associated with increased levels of physical activity, primarily walking. Associations with other forms of physical activity were less common. Results varied by gender and method of environmental assessment. Body mass was largely unaffected. This review suggests that several features of the built environment associated with smart growth planning may promote important forms of physical activity. Future smart growth community planning could focus more directly on health, and future research should explore whether combinations or a critical mass of smart growth features is associated with better population health outcomes.

  2. Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study

    Science.gov (United States)

    Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

    2016-01-01

    Background The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. Results 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Methods Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (μm) and group B with RTA equal to or more than 250 μm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Conclusions The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity. PMID:27391437

  3. Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types

    DEFF Research Database (Denmark)

    Heinemeier, K M; Olesen, J L; Haddad, F

    2007-01-01

    Acute exercise induces collagen synthesis in both tendon and muscle, indicating an adaptive response in the connective tissue of the muscle-tendon unit. However, the mechanisms of this adaptation, potentially involving collagen-inducing growth factors (such as transforming growth factor-beta-1 (TGF......-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and mRNA levels for collagens I and III, TGF-beta-1, connective tissue growth factor (CTGF), lysyl oxidase (LOX...... induced in tendon, especially LOX (up to 37-fold), which could indicate a loading-induced increase in cross-linking of tendon collagen. In skeletal muscle, a similar regulation of gene expression was observed, but in contrast to the tendon response, the effect of eccentric training was significantly...

  4. C-Terminal to Intact Fibroblast Growth Factor 23 Ratio in Relation to Estimated Glomerular Filtration Rate in Elderly Population

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    Maria Bożentowicz-Wikarek

    2016-08-01

    Full Text Available Background/Aims: An analytical equivalence between intact fibroblasts growth factor(iFGF23 and C-terminal(cFGF23 assays is logically expected, however, numerous studies demonstrate lack of a strong association between them. Previously, we have demonstrated the increase in cFGF23 slightly precedes the increase of iFGF23 with the impairment of kidney excretory function; without actually analyzing the ratio between both assays, which are postulated to be affected by declining kidney function. Therefore, the aim of this study was to analyze the ratio between C and iFGF23 in relation to the estimated glomerular filtration rate (eGFR in an elderly population. Methods: We analysed the variability of c/iFGF23 ratio in the population of 3264 elderly PolSenior study participants (≥ 65years in the relation to eGFR calculated according full Modification of Diet in Renal Disease, serum levels of C-reactive protein (hs-CRP, and iron. Results: The log10(c/i FGF23 ratio increased in the subsequent CKD stages. Serum iron and CRP levels reduced the log10 and increased it with age in multivariate regression analysis. Conclusions: Our results suggest impairment in the cleavage of the C-terminal FGF23 fragments with the deterioration of kidney excretory function and age in the elderly population. Inflammation and low serum iron level seems to diminish degradation capacity of FGF23 fragments.

  5. Fibroblast growth factors in neurodevelopment and psychopathology

    NARCIS (Netherlands)

    Terwisscha van Scheltinga, Afke F; Bakker, Steven C; Kahn, René S; Kas, Martien J H

    2013-01-01

    In psychiatric disorders, the effect of genetic and environmental factors may converge on molecular pathways and brain circuits related to growth factor functioning. In this review, we describe how disturbances in fibroblast growth factors (FGFs) and their receptors influence behavior by affecting b

  6. Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring.

    Directory of Open Access Journals (Sweden)

    Patrice Gallet

    Full Text Available PURPOSE: Beside its efficacy in cancer treatment, radiotherapy induces degeneration of healthy tissues within the irradiated area. The aim of this study was to analyze the variations of proinflammatory (IL-1α, IL-2, IL-6, TNF-α, IFN-γ, profibrotic (TGF-β1, proangiogneic (VEGF and stem cell mobilizing (GM-CSF cytokines and growth factors in an animal model of radiation-induced tissue degeneration. MATERIALS AND METHODS: 24 rats were irradiated unilaterally on the hindlimb at a monodose of 30 Gy. Six weeks (n=8, 6 months (n=8 and 1 year (n=8 after irradiation the mediators expression in skin and muscle were analyzed using Western blot and the Bio-Plex® protein array (BPA technology. Additional histological severity for fibrosis, inflammation, vascularity and cellularity alterations scoring was defined from histology and immnunohistochemistry analyses. RESULTS: A significant increase of histological severity scoring was found in irradiated tissue. Skin tissues were more radio-sensitive than muscle. A high level of TGF-β1 expression was found throughout the study and a significant relation was evidenced between TGF-β1 expression and fibrosis scoring. Irradiated tissue showed a chronic inflammation (IL-2 and TNF-α significantly increased. Moreover a persistent expression of GM-CSF and VEGF was found in all irradiated tissues. The vascular score was related to TGF-β1 expression and the cellular alterations score was significantly related with the level of IL-2, VEGF and GM-CSF. CONCLUSION: The results achieved in the present study underline the complexity and multiplicity of radio-induced alterations of cytokine network. It offers many perspectives of development, for the comprehension of the mechanisms of late injuries or for the histological and molecular evaluation of the mode of action and the efficacy of rehabilitation techniques.

  7. Growth factors in orthopedic surgery.

    Science.gov (United States)

    Zaharia, Comeliu; Niculescu, Marius; Despa, Nicoleta; Simionescu, Maya; Jinga, Victor; Fleseriu, Irina

    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.

  8. Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: Prevalence and relation with different clinical variables

    Science.gov (United States)

    Kasana, Basharat Ahmad; Dar, Waseem Raja; Aziz, Sheikh Aijaz; Lone, Abdul Rashid; Sofi, Najeeb Ullah; Dar, Imtiyaz Ahmad; Latief, Muzamil; Arshad, Faheem; Hussain, Moomin; Hussain, Mir

    2016-01-01

    Introduction: Lung cancer is one of the most common causes of cancer deaths worldwide. Adenocarcinoma is taking over squamous cell lung cancer as the predominant histological subtype. Several cytotoxic drugs are available for the treatment of lung cancer, but side effects limit their use. Recently, targeted therapies for cancers have come into clinical practice. Aims and Objectives: To determine the prevalence of epidermal growth factor receptor (EGFR) mutation in adenocarcinoma lung in a North Indian population and its relation with different clinical variables. Materials and Methods: A total of 57 patients who met inclusion criteria were recruited into the study. Relevant history, clinical examination and investigations were done. EGFR mutation was done in all patients. Results: A total of twenty patients tested positive for EGFR mutation. EGFR was more frequently detected in female patients (53.8%), while as only 19.4% of the male patients expressed EGFR mutation, which was statistically very significant (P = 0.007). EGFR mutation was more frequently detected in nonsmokers (52%) as compared to smokers (21.9%) which also was statistically significant (P value of 0.018). EGFR mutation was more common in Stage III and IV adenocarcinomas (48%) as compared to Stage I and II (21.4%) which was statistically significant (P value 0.034). Conclusion: EGFR mutation should be routinely done in all patients of adenocarcinoma lung particularly non-smoker females with Stage III and IV disease. PMID:27688613

  9. The role of vascular endothelial growth factor and other endogenous interplayers in age-related macular degeneration.

    Science.gov (United States)

    Grisanti, Salvatore; Tatar, Olcay

    2008-07-01

    Age-related macular degeneration (AMD) is a multifaceted disease characterized by early subclinical changes at the choroidea-retinal pigment epithelium interface. Both the causal and formal pathogenesis of the disease is still puzzling. Similarly, the reason for progression into two distinct late forms which are "geographic atrophy" and "choroidal neovascularization" remains enigmatic. Late changes are usually responsible for the dramatic loss in central function that has a devastating effect on quality of life. In industrialized countries the disease is a major cause for visual disability among persons over 60 years of age. Due to demographic right-shift and increased life expectancy, AMD is not only a medical problem but will have a pronounced socio-economic effect. Neovascular AMD with the development of choroidal neovascularization in the macular area accounts for 80% of the severe loss of visual acuity due to AMD. In the last decades, treatment modes were merely based on the destruction or surgical removal of the neovascular complex. In the present, however, the philosophical approach to treat the disease is changing to a pathology modifying manner. Intelligent targeting of the involved relevant factors and pathways should stop disease progression, reduce complications and improve vision. The first step into this new era has been accomplished with the introduction of antiangiogenic agents. The new agents act either directly on vascular endothelial growth factor (VEGF) or indirectly on its functional cascade. VEGF makes a fundamental contribution to neovascular processes but it also acts in physiological pathways. The main purpose of this review is to summarize its physiological role especially within the eye, the role in the development of AMD and to understand and foresee both the benefits and potential side-effects of the anti-VEGF-based therapy.

  10. Growth hormone, growth factors, and acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Ludecke, D.K.; Tolis, G.T.

    1987-01-01

    This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.

  11. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  12. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Directory of Open Access Journals (Sweden)

    Debashis Nandy

    2011-02-01

    Full Text Available Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF, insulin-like growth factor (IGF, platelet derived growth factor (PDGF, fibroblast growth factor (FGF, epidermal growth factor (EGF, and transforming growth factor (TGF in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  13. Growth of self-perceived clinical competence in postgraduate training for general practice and its relation to potentially influencing factors.

    NARCIS (Netherlands)

    Kramer, A.W.M.; Zuithoff, P.; Jansen, J.J.M.; Tan, L.H.; Grol, R.P.T.M.; Vleuten, C.P.M. van der

    2007-01-01

    OBJECTIVE: To examine the increase in self-perceived clinical competence during a three-year postgraduate training in general practice and to explore the relation between the growth of self-perceived competence and several background variables. DESIGN: Cohort, 1995-1998. SETTING: Three-year Postgrad

  14. Growth of Self-Perceived Clinical Competence in Postgraduate Training for General Practice and Its Relation to Potentially Influencing Factors

    Science.gov (United States)

    Kramer, A. W. M.; Zuithoff, P.; Jansen, J. J. M.; Tan, L. H. C.; Grol, R. P. T. M.; van der Vleuten, C. P. M.

    2007-01-01

    Objective: To examine the increase in self-perceived clinical competence during a three-year postgraduate training in general practice and to explore the relation between the growth of self-perceived competence and several background variables. Design: Cohort, 1995-1998. Setting: Three-year Postgraduate Training for General practice in the…

  15. Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with lifestyle factors on postmenopausal breast cancer risk.

    Science.gov (United States)

    Jung, Su Yon; Ho, Gloria; Rohan, Thomas; Strickler, Howard; Bea, Jennifer; Papp, Jeanette; Sobel, Eric; Zhang, Zuo-Feng; Crandall, Carolyn

    2017-07-01

    Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, and data from 1003 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying via obesity and lifestyle modifiers, we assessed the role of IGF-I/IR traits (fasting IGF-I, IGF-binding protein 3, insulin, glucose, and homeostatic model assessment-insulin resistance) in breast cancer risk as a mediator or influencing factor. Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E non-users and users. The mediation effects of IGF-I/IR traits on the relationship between these SNPs and cancer differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways-genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP-cancer relationship explained by traits varied 45-50% between the strata. Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce breast cancer risk.

  16. Adipocyte exosomes induce transforming growth factor beta pathway dysregulation in hepatocytes: a novel paradigm for obesity-related liver disease.

    Science.gov (United States)

    Koeck, Emily S; Iordanskaia, Tatiana; Sevilla, Samantha; Ferrante, Sarah C; Hubal, Monica J; Freishtat, Robert J; Nadler, Evan P

    2014-12-01

    The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has been attributed to increased systemic inflammation and insulin resistance mediated by visceral adipose tissue (VAT), although the exact mechanisms are undefined. Exosomes are membrane-derived vesicles containing messenger RNA, microRNA, and proteins, which have been implicated in cancer, neurodegenerative, and autoimmune diseases, which we postulated may be involved in obesity-related diseases. We isolated exosomes from VAT, characterized their content, and identified their potential targets. Targets included the transforming growth factor beta (TGF-β) pathway, which has been linked to NAFLD. We hypothesized that adipocyte exosomes would integrate into HepG2 and hepatic stellate cell lines and cause dysregulation of the TGF-β pathway. Exosomes from VAT from obese and lean patients were isolated and fluorescently labeled, then applied to cultured hepatic cell lines. After incubation, culture slides were imaged to detect exosome uptake. In separate experiments, exosomes were applied to cultured cells and incubated 48-h. Gene expression of TGF-β pathway mediators was analyzed by polymerase chain reaction, and compared with cells, which were not exposed to exosomes. Fluorescent-labeled exosomes integrated into both cell types and deposited in a perinuclear distribution. Exosome exposure caused increased tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and integrin ανβ-5 expression and decreased matrix metalloproteinase-7 and plasminogen activator inhibitor-1 expression in to HepG2 cells and increased expression of TIMP-1, TIMP-4, Smad-3, integrins ανβ-5 and ανβ-8, and matrix metalloproteinase-9 in hepatic stellate cells. Exosomes from VAT integrate into liver cells and induce dysregulation of TGF-β pathway members in vitro and offers an intriguing possibility for the pathogenesis of NAFLD. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Vascular endothelial growth factor before and after locoregional treatment and its relation to treatment response in hepatocelluar carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Heba Sedrak; Noaman El-Garem; Mervat Naguib; Heba El-Zawahry; Mohamed Esmat; Lila Rashed

    2015-01-01

    Objective: To evaluate vascular endothelial growth factor (VEGF) levels in hepatocel-lular carcinoma patients before and after transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) and its relation to treatment response. Methods: A total of 40 patients with unrespectable hepatocelluar carcinoma were assessed clinically. Twenty patients were suitable to be treated by TACE, while other 20 patients were treated with PEI. Serum VEGF levels were measured before and 1 month after each procedure by ELISA. Response was assessed after 1 month according to Union Internationale Contre le Cancer evaluation criteria based on change in tumor size as measured by ultrasound. Results: There was no significant difference between TACE and PEI groups with regard to age, sex, tumor size, response to local therapy, or VEGF and alpha-fetoprotein before and after therapy. VEGF levels after TACE were significantly higher than before TACE [(298.1 ± 123.6) pg/mL vs. (205.8 ± 307.3) pg/mL;P=0.001]. Also, VEGF levels were significantly higher after PEI than before PEI [(333.8 ± 365.6) pg/mL vs. (245.3 ± 301.8) pg/mL;P=0.000]. Non-responders of both groups had significantly high VEGF levels than responder's, both before [(985.0 ± 113.2) pg/mL vs. (117.1 ± 75.3) pg/mL;P Conclusions: Both TACE and PEI were associated with an increase in serum VEGF in hepatocelluar carcinoma patients. Higher levels of VEGF before and after therapy were found in non-responders, suggesting that VEGF is a useful marker in predicting treatment response.

  18. SERUM INSULIN-LIKE GROWTH FACTOR 1 IN LEBANESE SCHOOLCHILDREN AND ITS RELATION TO VITAMIN D AND FERRITIN LEVELS.

    Science.gov (United States)

    Gannagé-Yared, Marie-Hélène; Chahine, Elise; Farah, Vanessa; Ibrahim, Tony; Asmar, Nadia; Halaby, Georges

    2017-04-02

    The aims of our study were to establish reference values for insulin-like growth factor 1 (IGF-1) in Lebanese schoolchildren and to evaluate the relationship between IGF-1 and age, sex, body mass index (BMI), vitamin D, and ferritin. This cross-sectional study included 952 Lebanese schoolchildren (495 boys and 457 girls) aged 8 to 18 years. Blood samples were taken from children attending 10 schools with different socio-economic status (SES). Chemiluminescent immunoassays were used for IGF-1, 25 hydroxyvitamin D (25(OH)D), testosterone, and ferritin measurements. The mean age was 13.46 ± 2.80 with no significant difference according to sex. IGF-1 was correlated with age in both sexes (Pferritin values. After adjustment for age, BMI, and height, the correlation between IGF-1 and 25(OH)D disappeared, whereas the relationship with ferritin persisted (Pferritin. An association was also noted in boys for BMI and testosterone. Our results showed higher and earlier peak IGF-1 values in the pediatric Lebanese population compared to western populations. In addition, an independent inverse relationship was observed between IGF-1 and ferritin. Further studies are needed to identify the reason(s) underlying these results. BMI = body mass index CRP = C-reactive protein CV = coefficient of variation GH = growth hormone IGF-1 = insulin-like growth factor 1 25(OH)D = 25 hydroxyvitamin D SES = socio-economic status TSH = thyroid-stimulating hormone.

  19. Changes in the insulin-like growth factor-system may contribute to in vitro age-related impaired osteoblast functions

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Rattan, Suresh

    2000-01-01

    Age-related bone loss is thought to be due to impaired osteoblast functions. Insulin-like growth factors (IGFs) have been shown to be important stimulators of bone formation and osteoblast activities in vitro and in vivo. We tested the hypothesis that in vitro osteoblast senescence is associated ...

  20. Changes in the insulin-like growth factor-system may contribute to in vitro age-related impaired osteoblast functions

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Rattan, Suresh

    2000-01-01

    Age-related bone loss is thought to be due to impaired osteoblast functions. Insulin-like growth factors (IGFs) have been shown to be important stimulators of bone formation and osteoblast activities in vitro and in vivo. We tested the hypothesis that in vitro osteoblast senescence is associated ...

  1. Polymorphisms in vascular endothelial growth factor receptor 2 are associated with better response rates to ranibizumab treatment in age-related macular degeneration

    NARCIS (Netherlands)

    Hermann, M.M.; Asten, F. van; Muether, P.S.; Smailhodzic, D.; Lichtner, P.; Hoyng, C.B.; Kirchhof, B.; Grefkes, C.; Hollander, A.I. den; Fauser, S.

    2014-01-01

    PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) injections are currently the standard treatment for neovascular age-related macular degeneration (AMD), but a broad range of response rates has been observed. We evaluated the association of single nucleotide polymorphisms (SNPs) i

  2. NEW WIND WAVE GROWTH RELATIONS

    Institute of Scientific and Technical Information of China (English)

    WU Shu-ping; HOU Yi-jun; YIN Bao-shu

    2004-01-01

    In the present paper combining the relationship between wave steepness and wave age with the significant wave energy balance equation for wind wave,a new wind wave growth relation is presented.Comparisons with the other existing wind wave growth relations show that the results in present paper accord better with the wind wave growth process.

  3. Substance P and Calcitonin Gene Related Peptide Mediate Pain in Chronic Pancreatitis and Their Expression is Driven by Nerve Growth Factor

    Science.gov (United States)

    Liu, LianSheng; Shenoy, Mohan; Pasricha, Pankaj Jay

    2014-01-01

    Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the up-regulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin gene-related peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin gene-related peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic

  4. The Effects of Taekwondo Training on Peripheral Neuroplasticity-Related Growth Factors, Cerebral Blood Flow Velocity, and Cognitive Functions in Healthy Children: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Su-Youn Cho

    2017-04-01

    Full Text Available Although regular Taekwondo (TKD training has been reported to be effective for improving cognitive function in children, the mechanism underlying this improvement remains unclear. The purpose of the present study was to observe changes in neuroplasticity-related growth factors in the blood, assess cerebral blood flow velocity, and verify the resulting changes in children’s cognitive function after TKD training. Thirty healthy elementary school students were randomly assigned to control (n = 15 and TKD (n = 15 groups. The TKD training was conducted for 60 min at a rating of perceived exertion (RPE of 11–15, 5 times per week, for 16 weeks. Brain-derived neurotrophic factor (BDNF, vascular endothelial growth factor (VEGF, and insulin-like growth factor-1 (IGF-1 levels were measured by blood sampling before and after the training, and the cerebral blood flow velocities (peak systolic [MCAs], end diastolic [MCAd], mean cerebral blood flow velocities [MCAm], and pulsatility index [PI] of the middle cerebral artery (MCA were measured using Doppler ultrasonography. For cognitive function assessment, Stroop Color and Word Tests (Word, Color, and Color-Word were administered along with other measurements. The serum BDNF, VEGF, and IGF-1 levels and the Color-Word test scores among the sub-factors of the Stroop Color and Word Test scores were significantly higher in the TKD group after the intervention (p < 0.05. On the other hand, no statistically significant differences were found in any factors related to cerebral blood flow velocities, or in the Word test and Color test scores (p > 0.05. Thus, 16-week TKD training did not significantly affect cerebral blood flow velocities, but the training may have been effective in increasing children’s cognitive function by inducing an increase in the levels of neuroplasticity-related growth factors.

  5. Growth factors and new periodontology

    Directory of Open Access Journals (Sweden)

    Paknejad M

    1999-06-01

    Full Text Available Growth factors are biological mediators that have a key roll in proliferation, chemotaxy and"ndifferentiation by acting on specific receptors on the surface of cells and regulating events in wound"nhealing.They can be considered hormones that are not released in to the blood stream but have one a"nlocal action. Some of these factors can regulate premature change in GO to Gl phase in cell devesion"ncycle and even may stimulate synthesis of DNA in suitable cells, Growth substances, primarily secreted"nby fibroblasts, endothelia! cells, macrophages and platelet, include platelet derived growth factor"n(PDGF, insulin like growth factor (IGF transforming growth factor (TGFa and (3 and bone"nmorphogenetic proteins BMPs that approximately are the most important of them. (BMPs could be"nused to control events during periodontal, craniofacial and implant wound healing through favoring bone"nformation"nAccording toLynch, combination of PGDF and IGF1 would be effective in promoting growth of all the"ncomponents of the periodontium."nThe aim of this study was to characterize growth factor and review the literature to determine the"nmechanism of their function, classification and application in implant and periodontal treatment.

  6. Effect of ozone on vascular endothelial growth factor (VEGF) and related inflammatory cytokines in rats with diabetic retinopathy.

    Science.gov (United States)

    Xie, T Y; Yan, W; Lou, J; Chen, X Y

    2016-05-13

    The aim of this study was to investigate the effect of ozone on inflammatory cytokines in diabetic retinopathy (DR) rats. Male rats (40) weighing 300-360 g were included in this study. Thirty rats were randomly divided into the model and ozone groups after DR was induced by streptozotocin. Ten rats served as the blank group. After the diabetic models were established for one month, the rats in the ozone group were treated with 50 mg/kg ozone coloclysis for one month (three times a week). After the rats were anesthetized by intraperitoneal injection, blood samples from the abdominal aorta were collected, and the supernatant was obtained by centrifugation. Vascular endothelial growth factor (VEGF) and inflammatory cytokine content in the serum was detected by enzyme linked immunosorbent assay. The values of VEGF, intercellular cell adhesion molecule-1, interleukin-1 beta, tumor necrosis factor-a, and IL-6 were significantly different among the three groups (P ozone group was higher than that in the blank group. Compared with the model group, the cytokine levels in the ozone group were significantly reduced (P Ozone had no effect on the blood glucose of diabetic rats. Treatment with ozone coloclysis may effectively reduce the secretion of VEGF and inflammatory cytokines in diabetic retinopathy rats.

  7. The Effects of Taekwondo Training on Peripheral Neuroplasticity-Related Growth Factors, Cerebral Blood Flow Velocity, and Cognitive Functions in Healthy Children: A Randomized Controlled Trial.

    Science.gov (United States)

    Cho, Su-Youn; So, Wi-Young; Roh, Hee-Tae

    2017-04-25

    Although regular Taekwondo (TKD) training has been reported to be effective for improving cognitive function in children, the mechanism underlying this improvement remains unclear. The purpose of the present study was to observe changes in neuroplasticity-related growth factors in the blood, assess cerebral blood flow velocity, and verify the resulting changes in children's cognitive function after TKD training. Thirty healthy elementary school students were randomly assigned to control (n = 15) and TKD (n = 15) groups. The TKD training was conducted for 60 min at a rating of perceived exertion (RPE) of 11-15, 5 times per week, for 16 weeks. Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) levels were measured by blood sampling before and after the training, and the cerebral blood flow velocities (peak systolic [MCAs], end diastolic [MCAd], mean cerebral blood flow velocities [MCAm], and pulsatility index [PI]) of the middle cerebral artery (MCA) were measured using Doppler ultrasonography. For cognitive function assessment, Stroop Color and Word Tests (Word, Color, and Color-Word) were administered along with other measurements. The serum BDNF, VEGF, and IGF-1 levels and the Color-Word test scores among the sub-factors of the Stroop Color and Word Test scores were significantly higher in the TKD group after the intervention (p 0.05). Thus, 16-week TKD training did not significantly affect cerebral blood flow velocities, but the training may have been effective in increasing children's cognitive function by inducing an increase in the levels of neuroplasticity-related growth factors.

  8. Ceramic materials and growth factors

    Energy Technology Data Exchange (ETDEWEB)

    Ohgushi, H.; Yoshikawa, T.; Okumura, M.; Nakajima, H.; Takakura, Y. [Nara Medical Univ. (Japan). Dept. of Orhtopaedic Surgery; Dohi, Y. [Nara Medical Univ. (Japan). Dept. of Public Health; Noshi, T.; Ikeuchi, M. [Nara Medical Univ. (Japan). Dept. of Oral and Maxillofacial Surgery

    2001-07-01

    Recently, many types of growth factors have been purified and used for promoting cell differentiation cascade. The activity of growth factors can be detected in vitro such as culture condition. However, the activity is difficult to detect when these factors are locally administered in vivo, because these dissipate soon after the administration. In order to retain growth factors in local milieu, these can be incorporated with biocompatible porous ceramic materials. Such ceramic/factors composites when implanted in vivo, can trigger certain types of cell differentiation cascade resulted in new tissue formation and tissue regeneration. The paper describes the ceramic / growth factors composites especially hydroxyapatite ceramic (HA) / bone morphogenetic protein (BMP) composite to induce osteoblastic differentiation of mesenchymal stem cells. The HA/BMP composite supported the osteoblastic differentiation on the HA surface and finally resulted in bone bonding to the HA. When the marrow mesenchymal stem cells (MSCs) were impregnated in pore areas of HA ceramics, the composites showed more and rapid bone formation than the HA/BMP and HA/MSCs composite, indicating the synergistic effect of BMP and MSCs. These findings indicate the importance of ceramic surface to evoke osteoblastic differentiation as well as to capture the molecules of growth factors for the cell differentiation. (orig.)

  9. Aspects of Growth Hormone and Insulin-Like Growth Factor-I Related to Neuroprotection, Regeneration, and Functional Plasticity in the Adult Brain

    Directory of Open Access Journals (Sweden)

    N. David Åberg

    2006-01-01

    Full Text Available Apart from regulating somatic growth and metabolic processes, accumulating evidence suggests that the growth hormone (GH/insulin-like growth factor-I (IGF-I axis is involved in the regulation of brain growth, development, and myelination. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are attributable to circulating IGF-I, while others may be due to IGF-I produced locally within the brain. Some of the shared effects in common to GH and IGF-I may also be explained by cross-talk between the GH and IGF-I transduction pathways, as indicated by recent data from other cell systems. Otherwise, it also seems that GH may act directly without involving IGF-I (either circulating or locally. Plasticity in the central nervous system (CNS may be viewed as changes in the functional interplay between the major cell types, neurons, astrocytes, and oligodendrocytes. GH and IGF-I affect all three of these cell types in several ways. Apart from the neuroprotective effects of GH and IGF-I posited in different experimental models of CNS injury, IGF-I has been found to increase progenitor cell proliferation and new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. It appears that the MAPK signaling pathway is required for IGF-I–stimulated proliferation in vitro, whereas the PI3K/Akt or MAPK/Erk signaling pathway appears to mediate antiapoptotic effects. The increase of IGF-I on endothelial cell phenotype may explain the increase in cerebral arteriole density observed after GH treatment. The functional role of GH and IGF-I in the adult brain will be reviewed with reference to neurotransmitters, glucose metabolism, cerebral blood flow, gap junctional communication, dendritic arborization, exercise, enriched environment, depression, learning, memory, and aging.Briefly, these findings suggest that IGF-I functions as a putative regenerative agent in the adult CNS. Hitherto

  10. Idiopathic pulmonary fibrosis in relation to gene polymorphisms of transforming growth factor-β1 and plasminogen activator inhibitor 1

    Institute of Scientific and Technical Information of China (English)

    LI Xin-xia; LI Ning; BAN Cheng-jun; ZHU Min; XIAO Bai; DAI Hua-ping

    2011-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrotic lung disease of unknown etiology.Host susceptibility or genetic factors may be important for the predisposition to it. Transforming growth factor-pi (TGF-β1,a potent profibrotic cytokine) and plasminogen activator inhibitor 1 (PAI-1) play important roles in the development of pulmonary fibrosis. The objective of the study was to investigate the association between the gene polymorphisms of TGF-β1 869 T>C and PAI-1 4G/5G and the susceptibility to IPF in Han ethnicity.Methods Polymerase chain reaction (PCR) and restriction fragment length polymorphism were performed to analyse the gene polymorphisms of TGF-β1 in 869T>C and PAI-1 4G/5G in 85 IPF patients and 85 healthy controls matched in age, gender, race and smoker status.Results There was a significant difference in 869T>Cgenotype distribution of TGF-β1 between IPF cases and controls,a significant negative association between TC genotype and the development of IPF (OR=0.508, 95% Cl: 0.275-0.941)and a positive association between CC genotype and the development of IPF (OR=1.967, 95% Cl: 1.063-3.641). There was a significant positive association between PAI-1 5G/SG genotype and the development of IPF (OH=0.418, 95% Cl:0.193-0.904).Conclusions Gene polymorphisms of TGF-pi in 869T<C and PAI-1 4G/SG may affect the susceptibility to IPF in Han ethnicity. Further investigations are needed to confirm these findings and assess their biological significance in the development of the disease in this ethnic population.

  11. Premenopausal mammographic density in relation to cyclic variations in endogenous sex hormone levels, prolactin, and insulin-like growth factors.

    Science.gov (United States)

    Walker, Kate; Fletcher, Olivia; Johnson, Nichola; Coupland, Ben; McCormack, Valerie A; Folkerd, Elizabeth; Gibson, Lorna; Hillier, Stephen G; Holly, Jeff M; Moss, Sue; Dowsett, Mitchell; Peto, Julian; dos Santos Silva, Isabel

    2009-08-15

    Mammographic density is strongly associated with breast cancer risk, and endogenous hormones, which are risk factors for breast cancer, may be involved in the mechanism. This cross-sectional study of 494 premenopausal women is the first to account for cyclic variations in estrogen levels, by measuring urinary estrone glucuronide (E1G) in the periovulatory and luteal phases of the menstrual cycle, and to assess the role of androgens. Computer-assisted density readings were obtained from digitized mammograms. Mean ovulatory E1G level and daily E1G load were both positively associated with percent density before adjustment for body mass index (BMI), with women in the top fourth having 10.2% (95% CI: 2.9%, 18.1%) and 8.9% (1.7%, 16.7%), respectively, higher density than those in the bottom fourth (Ptrend before/after BMI adjustment=0.006/0.11 and 0.01/0.13, respectively). Neither the peak nor luteal E1G levels were predictive of density after adjustment for E1G levels at other points in the cycle. The plasma androgens testosterone, androstenedione, and dehydroepiandrosterone sulfate were negatively associated with density. In mutually adjusted analyses, density was positively associated with insulin-like growth factor (IGF)-I and negatively with IGF-II (Ptrend=0.006 for both) but not with IGF binding protein-3. There was also weak evidence of a positive association of prolactin with density. The study supports the hypothesis that endogenous hormones affect density in premenopausal women; in particular, it shows a positive association between estrogen levels and density and suggests that the mean level throughout the cycle is the most biologically relevant measure. Most of these hormone-density associations were attenuated with further adjustment for BMI.

  12. Age-Related Yield of Adipose-Derived Stem Cells Bearing the Low-Affinity Nerve Growth Factor Receptor

    Directory of Open Access Journals (Sweden)

    Raquel Cuevas-Diaz Duran

    2013-01-01

    Full Text Available Adipose-derived stem cells (ADSCs are a heterogeneous cell population that may be enriched by positive selection with antibodies against the low-affinity nerve growth factor receptor (LNGFR or CD271, yielding a selective cell universe with higher proliferation and differentiation potential. This paper addresses the need for determining the quantity of ADSCs positive for the CD271 receptor and its correlation with donor's age. Mononuclear cells were harvested from the lower backs of 35 female donors and purified using magnetic beads. Multipotency capacity was tested by the expression of stemness genes and through differentiation into preosteoblasts and adipocytes. A significant statistical difference was found in CD271+ concentrations between defined age intervals. The highest yield was found within women on the 30–40-year-old age range. CD271+ ADSCs from all age groups showed differentiation capabilities as well as expression of typical multipotent stem cell genes. Our data suggest that the amount of CD271+ cells correlates inversely with age. However, the ability to obtain these cells was maintained through all age ranges with a yield higher than what has been reported from bone marrow. Our findings propose CD271+ ADSCs as the primary choice for tissue regeneration and autologous stem cell therapies in older subjects.

  13. Characterization of a gene coding for a putative adenosine deaminase-related growth factor by RNA interference in the basidiomycete Flammulina velutipes.

    Science.gov (United States)

    Sekiya, Shuichi; Yamada, Masato; Shibata, Kou; Okuhara, Toru; Yoshida, Masumi; Inatomi, Satoshi; Taguchi, Goro; Shimosaka, Makoto

    2013-04-01

    A full-length cDNA coding for a putative adenosine deaminase (Fv-ada) was isolated from the basidiomycete Flammulina velutipes. Fv-ada encodes a polypeptide consisting of 537 amino acid residues, which has a consensus sequence conserved among adenosine deaminase-related growth factors (ADGF) found in several metazoa, including chordates and insects. Fv-ada transcript was detected at all stages of growth in dikaryotic F. velutipes cells, with a peak at the primordial stage. Heterologous expression of Fv-ada in the yeast Pichia pastoris produced recombinant Fv-ADA that catalyzed the conversion of adenosine to inosine. Dikaryotic mycelia from F. velutipes were transformed with the binary plasmid pFungiway-Fv-ada, which was designed to suppress the expression of Fv-ada through RNA interference. The growth rates of the resulting transformants were retarded in response to the degree of suppression, indicating that Fv-ada plays an important role in the mycelial growth of F. velutipes. These results suggested that ADGF could function as growth factors in fungi, as is seen in other eukaryotes.

  14. Cytokine profiles of seventeen cytokines, growth factors and chemokines in cord blood and its relation to perinatal clinical findings.

    Science.gov (United States)

    Takahashi, Naoto; Uehara, Ritei; Kobayashi, Mami; Yada, Yukari; Koike, Yasunori; Kawamata, Ryou; Odaka, Jun; Honma, Yoko; Momoi, Mariko Y

    2010-03-01

    Few papers have investigated the cytokine profiles of multiple cytokines in cord blood. We obtained cord blood samples from 224 infants admitted to our neonatal intensive care unit. Cytokine profiles of 17 cytokines were investigated using cytometric bead array technology. We found a wide variety of cytokines of various levels which ranged from 0.59pg/ml (in Interleukin (IL)-4) to 222.0pg/ml (in macrophage inflammatory protein-1beta. Pro-inflammatory cytokines were highly correlated with each other and with granulocyte-colony stimulating factor and IL-8. On the contrary, IL-5, IL-13, and IL-17 did not show any significant correlation with other cytokines. Several maternal factors were strongly related to several cytokines in cord blood. IL-6, IL-8 and monocyte chemotactic protein-1 were closely related to certain neonatal diseases in preterm neonates. Some cytokines may be regulated independently of each other, while others appear to work as a network affecting physiological and pathological conditions in the fetus.

  15. Growth Factors in Synaptic Function

    Directory of Open Access Journals (Sweden)

    Vivian Yi Nuo Poon

    2013-09-01

    Full Text Available Synapses are increasingly recognized as key structures that malfunction in disorders like schizophrenia, mental retardation, and neurodegenerative diseases. The importance and complexity of the synapse has fuelled research into the molecular mechanisms underlying synaptogenesis, synaptic transmission, and plasticity. In this regard, neurotrophic factors such as netrin, Wnt, transforming growth factor-beta (TGF-beta, tumor necrosis factor-α (TNF-α, and others have gained prominence for their ability to regulate synaptic function. Several of these factors were first implicated in neuroprotection, neuronal growth, and axon guidance. However, their roles in synaptic development and function have become increasingly clear, and the downstream signaling pathways employed by these factors have begun to be elucidated. In this review, we will address the role of these factors and their downstream effectors in synaptic function in vivo and in cultured neurons.

  16. Intraocular cytokines in retinal vein occlusion and its relation to the efficiency of anti-vascular endothelial growth factor therapy

    Directory of Open Access Journals (Sweden)

    Andrey G Shchuko

    2015-01-01

    Full Text Available Purpose: To analyze the change in the concentration of intraocular cytokines (ICs in patients with retinal vein occlusion (RVO before and after intravitreal ranibizumab therapy (IVR, and to find the correlations of IC with clinical activity of RVO and efficiency of treatment. Materials and Methods: Forty-four patients aged 46–79 years old (mean age: 60.7 ± 7.5 years old with RVO and macular edema (18 patients – with central RVO, 26 – with branch RVO treated with IVR were included into the study. The concentrations of 27 cytokines were simultaneously measured in aqueous humor by flow fluorometry using Bio-Plex Pro Human Cytokine Panel, 27-Plex (Bio-Rad Laboratories, USA at baseline and after the first IVR. Control group consisted of 20 age-matched patients. Results: The levels of 11 cytokines (vascular endothelial growth factor [VEGF], receptor antagonist interleukin-1, interleukin-6 [IL-6], IL-8, IL-9, IL-10, IL-12r70, IL-13, IL-15, monocyte chemotactic protein-1 [MCP-1], regulated on activation, normal T expressed and secreted were significantly (P < 0.05 different compared to control and significantly (P < 0.05 changed after IVR both in central and branch RVO. The patients were divided into two groups: the first -"effective" and the second - "partially effective" therapy. The second group characterized by the higher concentrations of VEGF, IL-8, IL-10, IL-17, and MCP-1 at baseline compared to the first group. Conclusion: The patients with RVO were characterized by the increased levels of VEGF and other pro- and anti-inflammatory cytokines and chemokines. Aqueous concentration of cytokines were different in patients with central and branch RVO and significantly changed after IVR. Insufficient response to IVR was associated with activation of immune-inflammatory processes.

  17. Change of the growth hormone-insulin-like growth factor-I axis in patients with gastrointestinal cancer: related to tumour type and nutritional status.

    Science.gov (United States)

    Huang, Qi; Nai, Yong-Jun; Jiang, Zhi-Wei; Li, Jie-Shou

    2005-06-01

    Changes in the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis, especially acquired GH resistance, develop in many severe illnesses, including cachexia. To study changes in the GH-IGF-I axis in patients with cancer cachexia, biochemical markers and body composition parameters were measured in eighty-eight gastric cancer patients, thirty colorectal cancer patients (subclassified according to the presence or absence of cachexia) and twenty-four healthy control subjects. Fifty-nine patients were defined as cachectic, based on the percentage of weight loss compared with their previous normal weight. The remaining fifty-nine patients were defined as non-cachectic. Measurements were repeated in twenty-seven patients (sixteen with gastric cancer and eleven with colorectal cancer) 3 months after radical operation. Compared with the controls, the cachectic gastric cancer patients had high GH levels (1.36 v. 0.32 ng/ml; P=0.001), a trend towards high IGF-I levels (223.74 v. 195.15 ng/ml; P=0.128 compared with non-cachectic patients) and a low log IGF-I/GH ratio (2.55 and 2.66 v. 3.00; P=0.002), along with a decreased BMI; the cachectic colorectal cancer patients showed the biochemical characteristics of acquired GH resistance: high GH (0.71 v. 0.32 ng/ml; P=0.016), a trend towards decreased IGF-I levels (164.18 v. 183.24 ng/ml; P=0.127) and a low log IGF-I/GH ratio (2.54 v. 2.99; P=0.005), with increased IGF-I levels following radical surgery (200.49 v. 141.91 ng/ml; P=0.046). These findings suggest that normal GH reaction and sensitivity occur in gastric cancer patients, controlled by nutritional status, whereas acquired GH resistance develops in cachectic colorectal cancer patients, which may be caused by tumour itself.

  18. Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus.

    Directory of Open Access Journals (Sweden)

    Clint L Miller

    Full Text Available Coronary heart disease (CHD is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin is a member of the basic-helix-loop-helix (bHLH transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1 element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β and Wilms tumor 1 (WT1 pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.

  19. Expression of transforming growth factor-beta (TGF-beta) isoforms in osteosarcomas: TGF-beta3 is related to disease progression.

    Science.gov (United States)

    Kloen, P; Gebhardt, M C; Perez-Atayde, A; Rosenberg, A E; Springfield, D S; Gold, L I; Mankin, H J

    1997-12-15

    Transforming growth factor-beta (TGF-beta) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-beta has been reported in different malignancies, suggesting a role for this growth factor in tumorigenesis. Using immunohistochemistry, the expression, prevalence, and distribution of TGF-beta isoforms were evaluated in 25 high grade human osteosarcomas. The Cox proportional hazards models and Kaplan-Meier curves were calculated correlating disease free survival with TGF-beta expression. Expression of one or more TGF-beta isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-beta1 and TGF-beta3 generally was stronger than for TGF-beta2. The cytoplasm of the tumor cells showed stronger staining than their surrounding extracellular stroma. Most notably, osteoclasts showed strong to intense staining for all three isoforms. In 11 of 25 specimens angiogenic activity was noted with staining of multiple small vessels in the tumor stroma. Expression of TGF-beta3, but not of TGF-beta2 or TGF-beta1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-beta3 increased. All osteosarcomas expressed TGF-beta in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-beta in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-beta3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF-beta isoforms, especially TGF-beta3, may play a role in osteosarcoma progression.

  20. The relative expression levels of insulin-like growth factor 1 and myostatin mRNA in the asynchronous development of skeletal muscle in ducks during early development.

    Science.gov (United States)

    Hu, Yan; Liu, Hongxiang; Shan, Yanju; Ji, Gaige; Xu, Wenjuan; Shu, Jingting; Li, Huifang

    2015-08-10

    Genetic selection is a powerful tool for modifying poultry muscle yield. Insulin-like growth factor I (IGF-I) and myostatin (MSTN) are important regulators of muscle growth, especially in the myogenesis stage. This study compared the developmental pattern of the pectoralis major (PM) and lateral gastrocnemius (LM) muscles, mRNA expression characterization of IGF-I and MSTN-A and their correlation between 14 days in ovo and 1 week post-hatch in two Chinese local duck breeds. During early development, the growth of duck PM and LM followed an asynchronous pattern. Variations in PM growth rate observed with development followed the relative variations of MSTN and IGF-I expression; however, the same behavior was not observed in LM. Moreover, the profile of IGF-I expression in duck skeletal muscles indicated that genetic selection for high meat-yield poultry has altered the temporal expression of IGF-I and affected cellular characteristics and mass by hatch in a PM-specific manner. The MSTN-A expression profile showed synchronization with the growth of skeletal muscle and peaks of myofiber proliferation. The expression patterns of IGF-I and MSTN suggest that duck pectoralis fibers are prioritized for proliferation in embryogenesis. The IGF-1/MSTN-A mRNA ratios in PM and LM presented very similar trends in the changes of myofiber characteristics, and differences in the IGF-1/MSTN-A mRNA ratio in PM between the two breeds corresponded to the timing of differences in PM mass between the varieties. Our results support the hypothesis that relative levels of IGF-I and MSTN mRNA may participate in ordering muscle growth rates with selected development. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Insulin-like growth factors and insulin-like growth factor-binding proteins in relation to disease status and incidence of hypoglycaemia in patients with a gastrointestinal stromal tumour.

    NARCIS (Netherlands)

    Rikhof, B.; Doorn, J. van; Suurmeijer, A.J.H.; Rautenberg, M.W.; Groenen, P.J.T.A.; Verdijk, M.A.J.; Jager, P.L.; Jong, Sijbrand J. de; Gietema, J.A.; Graaf, W.T.A. van der

    2009-01-01

    OBJECTIVE: Patients with a gastrointestinal stromal tumour (GIST) suffering from non-islet cell tumour-induced hypoglycaemia (NICTH), being associated with increased plasma levels of pro-insulin-like growth factor (IGF)-IIE[68-88], have been reported occasionally. We studied the clinical relevance

  2. Insulin-like growth factors and insulin-like growth factor-binding proteins in relation to disease status and incidence of hypoglycaemia in patients with a gastrointestinal stromal tumour

    NARCIS (Netherlands)

    Rikhof, B.; van Doorn, J.; Suurmeijer, A. J. H.; Rautenberg, M. W.; Groenen, P. J. T. A.; Verdijk, M. A. J.; Jager, P. L.; de Jong, S.; Gietema, J. A.; van der Graaf, W. T. A.

    Patients and methods: Twenty-four patients were included. Plasma samples were collected before 1 week and median 5 months after start of treatment with imatinib, and levels of IGF-I, total IGF-II, pro-IGF-IIE[68-88], insulin-like growth factor-binding protein (IGFBP)-2, -3 and -6 were determined.

  3. Care-Related and Maternal Risk Factors Associated with the Antenatal Nondetection of Intrauterine Growth Restriction: A Case-Control Study from Bremen, Germany

    Directory of Open Access Journals (Sweden)

    Sinja Alexandra Ernst

    2017-01-01

    Full Text Available Objective. To identify care-related and maternal risk factors for the antenatal nondetection of IUGR. Methods. In this hospital-based case-control study we compared antenatally undetected IUGR neonates (cases to detected IUGR neonates (controls. Data were collected using newborn documentation sheets and standardized personal interviews with the mothers. We calculated antenatal detection rates and used uni- and multivariable logistic regression models to assess the association of antenatal nondetection of IUGR and maternal and care-related factors. Results. A total of 161 neonates from three hospitals were included in the study. Suboptimal fetal growth was identified antenatally in n=77 pregnancies while in n=84 it was not detected antenatally (antenatal detection rate: 47.8%. Severity of IUGR, maternal complications, and a Doppler examination during the course of pregnancy were associated with IUGR detection. We did not find statistically significant differences regarding parental socioeconomic status and maternal migration background. Conclusions. In our study, about half of all pregnancies affected by suboptimal growth remained undetected. Future in-depth studies with larger study populations should further examine factors that could increase antenatal detection rates for IUGR.

  4. [Effect of basic fibroblast growth factor and parathyroid hormone-related protein on early and late chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells induced by transforming growth factor beta 1].

    Science.gov (United States)

    Liu, Yin; He, Liping; Tian, Jing

    2013-02-01

    To explore the impact of basic fibroblast growth factor (bFGF) and parathyroid hormone-related protein (PTHrP) on early and late chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells (BMSCs) induced by transforming growth factor beta 1 (TGF-beta1). BMSCs were isolated from 3 healthy Japanese rabbits (2-month-old, weighing 1.6-2.1 kg, male or female), and were clutured to passage 3. The cells were put into pellet culture system and were divided into 5 groups according to different induce conditions: TGF-beta1 group (group A), TGF-beta1/bFGF group (group B), TGF-beta1/21 days bFGF group (group C), TGF-beta1/PTHrP group (group D), and TGF-beta1/21 days PTHrP group (group E). At the beginning, TGF-beta1 (10 ng/mL) was added to all groups, then bFGF and PTHrP (10 ng/mL) were added to groups B and D respectively; bFGF and PTHrP (10 ng/mL) were added to groups C and E at 21 days respectively. The gene expressions of collagen type I (Col I), Col II, Col X, matrix metalloproteinases (MMP)-13, and alkaline phosphatase (ALP) activity were detected once every week for 6 weeks. The 1, 9-dimethylmethylene blue (DMMB) staining was used to observe the extracellular matrix secretion at 6 weeks. The expression of Col I in groups C and E showed a significant downward trend after 3 weeks; the expression in group A was significantly higher than that in groups C and E at 4 and 5 weeks (P PTHrP can inhibit early and late chondrogenic differentiation of BMSCs by changing synthesis and decomposition of the cartilage extracellular matrix. The inhibition is not only by suppressing Col X expression, but also possibly by suppressing other chondrogenic protein.

  5. Epidermal growth factor receptor-related protein inhibits cell growth and induces apoptosis of BxPC3 pancreatic cancer cells

    National Research Council Canada - National Science Library

    Zhang, Yuxiang; Banerjee, Sanjeev; Wang, Zhi-wei; Marciniak, Dorota J; Majumdar, Adhip P N; Sarkar, Fazlul H

    2005-01-01

    ...), which seems to be a negative regulator of EGFR. In the present investigation, we tested our hypothesis whether recombinant ERRP could be an effective inhibitor of growth of BxPC3 pancreatic cancer cells...

  6. Modulation of gap junctional intercellular communication between human smooth muscle cells by leukocyte-derived growth factors and cytokines in relation to atherogenesis

    NARCIS (Netherlands)

    Mensink, A.

    1997-01-01


    In this thesis, the effect of leukocyte-derived growth factors and cytokines on GJIC between SMC was investigated. GJIC is regarded as an important mechanism in the control of cell growth, cell differentiation and tissue homeostasis. Disturbance of SMC growth control is regarded to be a k

  7. Serum free and total insulin-like growth factor-1, insulin-like growth factor binding protein-1 and insulin-like growth factor binding protein-3 levels in healthy elderly individuals - Relation to self-reported duality of health and disability

    NARCIS (Netherlands)

    Janssen, JAMJL; Stolk, RP; Pols, HAP; Grobbee, DE; Lamberts, SWJ

    1998-01-01

    Background: Little is known about the influence of the free insulin-like growth factor-I/insulin-like growth factor binding protein (IGF-I/IGFBP) system on the quality of health and on disability in the elderly population. Design: In a cross-sectional population based study of 218 healthy elderly

  8. Age-related changes in rat myocardium involve altered capacities of glycosaminoglycans to potentiate growth factor functions and heparan sulfate-altered sulfation.

    NARCIS (Netherlands)

    Huynh, M.B.; Morin, C.; Carpentier, G.; Garcia-Filipe, S.; Talhas-Perret, S.; Barbier-Chassefiere, V.; Kuppevelt, T. van; Martelly, I.; Albanese, P.; Papy-Garcia, D.

    2012-01-01

    Glycosaminoglycans (GAGs) are essential components of the extracellular matrix, the natural environment from which cell behavior is regulated by a number or tissue homeostasis guarantors including growth factors. Because most heparin-binding growth factor activities are regulated by GAGs, structural

  9. Vitamin B₁₂ dependent changes in mouse spinal cord expression of vitamin B₁₂ related proteins and the epidermal growth factor system.

    Science.gov (United States)

    Mutti, Elena; Lildballe, Dorte L; Kristensen, Lise; Birn, Henrik; Nexo, Ebba

    2013-03-29

    Chronic vitamin B12 (cobalamin) deficiency in the mammalian central nervous system causes degenerative damage, especially in the spinal cord. Previous studies have shown that cobalamin status alters spinal cord expression of epidermal growth factor (EGF) and its receptor in rats. Employing a mouse model of cobalamin-depletion and loading, we have explored the influence of Cbl status on spinal cord expression of cobalamin related proteins, as well as all four known EGF receptors and their activating ligands. Following four weeks of osmotic minipump infusion (n=7 in each group) with cobinamide (4.25nmol/h), saline or cobalamin (1.75nmol/h) the spinal cords were analyzed for cobalamin and for the mRNA levels of cobalamin related proteins and members of the EGF system using quantitative reverse transcription PCR. The median spinal cord cobalamin content was 17, 32, and 52pmol/gr of tissues in cobinamide, saline, and cobalamin treated animals, respectively. Both cobinamide and cobalamin induced a significant decrease in the expression of the lysosomal membrane cobalamin transporter. All four EGF receptors and their activating ligands, except for EGF, were expressed in the spinal cord. Notably, the expression of one of the EGF receptors, HER3, and the ligands heparin-binding EGF-like growth factor, transforming growth factor-α, and neuregulins 1α was increased in cobalamin treated mice. Our studies show that four weeks treatment of mice with cobinamide induces spinal cord cobalamin depletion and that cobalamin loading induces an altered expression pattern of the EGF system thus confirming a spinal cord cross talk between Cbl and the EGF system.

  10. The relative value of growth.

    Science.gov (United States)

    Mass, Nathaniel J

    2005-04-01

    Most executives would say that adding a point of growth and gaining a point of operating-profit margin contribute about equally to shareholder value. Margin improvements hit the bottom line immediately, while growth compounds value over time. But the reality is that the two are rarely equivalent. Growth often is far more valuable than managers think. For some companies, convincing the market that they can grow by just one additional percentage point can be worth six, seven, or even ten points of margin improvement. This article presents a new strategic metric, called the relative value of growth (RVG), which gives managers a clear picture of how growth projects and margin improvement initiatives affect shareholder value. Using basic balance sheet and income sheet data, managers can determine their companies' RVGs, as well as those of their competitors. Calculating RVGs gives managers insights into which corporate strategies are working to deliver value and whether their companies are pulling the most powerful value-creation levers. The author examines a number of well-known companies and explains what their RVG numbers say about their strategies. He reviews the unspoken assumption that growth and profits are incompatible over the long term and shows that a fair number of companies are effective at delivering both. Finally, he explains how managers can use the RVG framework to help them define strategies that balance growth and profitability at both the corporate and business unit levels.

  11. Role of ERRF, a novel ER-related nuclear factor, in the growth control of ER-positive human breast cancer cells.

    Science.gov (United States)

    Su, Dan; Fu, Xiaoying; Fan, Songqing; Wu, Xiao; Wang, Xin-Xin; Fu, Liya; Dong, Xue-Yuan; Ni, Jianping Jenny; Fu, Li; Zhu, Zhengmao; Dong, Jin-Tang

    2012-03-01

    Whereas estrogen-estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)-negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER-mediated growth of breast cancer cells and could, thus, be a potential therapeutic target.

  12. Studies on the growth of penaeid prawns: 1. Length-weight relation and condition factor under different levels of feeding

    Digital Repository Service at National Institute of Oceanography (India)

    Nair, S.R.S.; Iyer, H.K.; Devi, C.B.L.; Kutty, M.K.

    Length-weight relation and earthworm feeding conditions under different levels for @iPenaeus indicus@@ and @iMetapenaeus dobsoni@@ were estimated. Length-weight exponent in both species was unaffected by the feeding levels and the consequent...

  13. Physiological factors influencing capillary growth.

    Science.gov (United States)

    Egginton, S

    2011-07-01

    (1) Angiogenesis (growth of new capillaries from an existing capillary bed) may result from a mismatch in microvascular supply and metabolic demand (metabolic error signal). Krogh examined the distribution and number of capillaries to explore the correlation between O(2) delivery and O(2) consumption. Subsequently, the heterogeneity in angiogenic response within a muscle has been shown to reflect either differences in fibre type composition or mechanical load. However, local control leads to targetted angiogenesis in the vicinity of glycolytic fibre types following muscle stimulation, or oxidative fibres following endurance training, while heterogeneity of capillary spacing is maintained during ontogenetic growth. (2) Despite limited microscopy resolution and lack of specific markers, Krogh's interest in the structure of the capillary wall paved the way for understanding the mechanisms of capillary growth. Angiogenesis may be influenced by the response of perivascular or stromal cells (fibroblasts, macrophages and pericytes) to altered activity, likely acting as a source for chemical signals modulating capillary growth such as vascular endothelial growth factor. In addition, haemodynamic factors such as shear stress and muscle stretch play a significant role in adaptive remodelling of the microcirculation. (3) Most indices of capillarity are highly dependent on fibre size, resulting in possible bias because of scaling. To examine the consequences of capillary distribution, it is therefore helpful to quantify the area of tissue supplied by individual capillaries. This allows the spatial limitations inherent in most models of tissue oxygenation to be overcome generating an alternative approach to Krogh's tissue cylinder, the capillary domain, to improve descriptions of intracellular oxygen diffusion. © 2010 The Author. Acta Physiologica © 2010 Scandinavian Physiological Society.

  14. Fibroblast growth factor 23 and dietary factors in renal disease

    NARCIS (Netherlands)

    da Cunha Baia, Leandro

    2015-01-01

    Omega-3 poly-unsaturated fatty acids and mineral metabolism: novel therapy for cardiovascular disease in renal patients? Deregulations in mineral metabolism, particularly related to phosphate and its regulating hormone fibroblast growth factor 23 (FGF23), are common in patients with chronic kidney d

  15. The insulin like growth factor system in cirrhosis. Relation to changes in body composition following adrenoreceptor blockade

    DEFF Research Database (Denmark)

    Bonefeld, Karen; Hobolth, Lise; Juul, Anders;

    2012-01-01

    OBJECTIVE: Circulating levels of IGF-I and IGFBP-3 are low in cirrhosis and are related to liver dysfunction. Metabolic disturbances include malnutrition with altered body composition and osteopenia. Since the effects of IGF-I may be associated to changes in body composition and bone mineral...... content (BMC) in cirrhotic patients, we investigated the relations between changes in the IGF-system and body composition and the effects of long-term alpha- and beta-blockade. DESIGN: The study was designed as a combined cross-sectional and prospective randomised controlled study of 62 patients...

  16. Placental insulin-like growth factor II (IGF-II) and its relation to litter size in the common marmoset monkey (Callithrix jacchus).

    Science.gov (United States)

    Rutherford, Julienne N; Eklund, Amy; Tardif, Suzette

    2009-12-01

    The primate placenta produces a wide variety of hormones throughout gestation that regulate placental function and fetal growth. One such hormone is insulin-like growth factor-II (IGF-II), a peptide implicated in cell division, differentiation, and amino acid transport. IGF-II concentrations were measured in 23 common marmoset (Callithrix jacchus) term placentas from twin and triplet litters in order to determine whether previously described differences in fetoplacental phenotype such as placental and litter mass and placental surface area were related to differences in endocrine function. IGF-II was extracted from frozen tissue samples and measured using an enzyme-linked immunosorbent assay kit designed for human tissue, which was validated for marmoset placenta. IGF-II concentrations were not related to placental or litter mass, and twin and triplet placentas did not differ in total concentration. However, per individual fetus, triplets were associated with a significant 42% reduction in IGF-II concentration (P = 0.03), and IGF-II concentration per gram of fetal mass was a third lower in triplet litters. The triplet placenta exhibits a global expansion of the surface area which was contrasted by a per unit area reduction in IGF-II concentration (r = -0.75, P = 0.01), a pattern that explains why twin and triplet placentas overall did not differ in concentration. Per fetus, triplet pregnancies are associated with relatively less maternal mass, placental mass and microscopic surface area suggesting that the intrauterine growth of triplets is supported by systems that increase the efficiency of nutrient transfer. The finding that individual triplet fetuses are also associated with significantly lower IGF-II concentrations is consistent with the view that the marmoset fetoplacental unit exhibits a flexible pattern of placental allocation and metabolism. Plasticity in placental endocrine and metabolic function is likely to play an important role in the ability of the

  17. Factors Behind Industrial Profit Growth

    Institute of Scientific and Technical Information of China (English)

    郑玉歆; 李玉红

    2008-01-01

    This paper analyzes Chinese enterprise industrial profit distribution and profitability rise between 1998 and 2005. Looking at it from the perspective of drivers of total growth, this paper will provide an in-depth analysis of the origins and industry-level factors involved in this growth. It reaches the conclusion that structural change in profits was the main driving force for profit increases, to which heavy industry contributed greatly. Light and machine building industry profit rates improved due to increases in productivity levels, while energy and raw material industry profits increased due to increases in product prices. In addition, average wages grew slower than GDP, and wages among industries varied widely. In general however, this paper sets out to determine which enterprises gained from increases in industrial profitability, and how this gain came about.

  18. Role of LncRNA-activated by transforming growth factor beta in the progression of hepatitis C virus-related liver fibrosis.

    Science.gov (United States)

    Fu, Na; Niu, Xuemin; Wang, Yang; Du, Huijuan; Wang, Baoyu; Du, Jinghua; Li, Ya; Wang, Rongqi; Zhang, Yuguo; Zhao, Suxian; Sun, Dianxing; Qiao, Liang; Nan, Yuemin

    2016-08-01

    Long non-coding RNA (LncRNA)-activated by transforming growth factor-beta (LncRNA-ATB) is a key regulator of transforming growth factor-beta (TGF-β) signaling pathway, and is positively correlated with the development of liver cirrhosis and vascular invasion of hepatocellular carcinoma (HCC). However, the role of LncRNA-ATB in hepatitis C virus (HCV)-related liver fibrosis remains largely unknown. In the present study, we confirmed a high expression level of LncRNA-ATB in the liver tissues and plasma samples of patients with HCV-related hepatic fibrosis, and the plasma level of LncRNA-ATB was significantly correlated with liver fibrosis stages. Furthermore, increased expression level of LncRNA-ATB was also present in activated hepatic stellate cells (HSCs), and knockdown of LncRNA-ATB inhibited the expression of alpha-smooth muscle actin (α-SMA) and alpha-1 type I collagen (Col1A1). LncRNA-ATB was found to share the common miRNA responsive element of miR-425-5p with TGF-β type II receptor (TGF-βRII) and SMAD2. Ectopic expression of LncRNA-ATB in HSCs could upregulate the protein expression of TGF-βRII and SMAD2 by inhibiting the endogenous miR-425-5p. Moreover, overexpression of miR-425-5p could partly abrogate the expression of TGF-βRII and SMAD2 induced by LncRNA-ATB. Hence, we conclude that LncRNA-ATB promotes HCV-induced liver fibrogenesis by activating HSCs and increasing collagen I production through competitively binding to miR-425-5p. LncRNA-ATB may be a novel diagnostic biomarker and a potential therapeutic target for HCV-related hepatic fibrosis.

  19. Increased insulin-like growth factor-1 in relation to cardiovascular function in polycystic ovary syndrome: friend or foe?

    Science.gov (United States)

    Desai, Namrata Ajaykumar; Patel, Snehal S

    2015-10-01

    The incidence of cardiovascular disease (CVD) in patients with polycystic ovary syndrome (PCOS) is very high and conventional risk factors only partially explain excessive risk of developing CVD in patients of PCOS. The pathophysiology of PCOS is very unique, and several hormonal and metabolic changes occur. Several observations suggest that serum IGF-1 levels decrease in insulin resistance, which results in IGF-1 deficiency. In patient of PCOS, close relationships have been demonstrated between insulin resistance and serum IGF-1 levels. Hyperinsulinemic insulin resistance results in a general augmentation of steroidogenesis and LH release in PCOS. The action of IGF-1 varies in different tissues possibly via autocrine or paracrine mechanisms. The increase or decrease in IGF-1 in different tissues results in differential outcomes. Several studies suggest that lowered circulating IGF-1 levels play important role in the initiation of the cardiac hypertrophic response which results in the risk of cardiovascular disease. While recent results suggests that individual with elevated IGF-1 is protected against cardiovascular disease. Thus IGF-1 shows versatile pleiotropic actions. This review provides a current perspective on increased level of IGF-1 in PCOS and also adds to the current controversy regarding the roles of IGF-1 in cardiovascular disease.

  20. A Comparative Study of Age-Related Hearing Loss in Wild Type and Insulin-Like Growth Factor I Deficient Mice

    Science.gov (United States)

    Riquelme, Raquel; Cediel, Rafael; Contreras, Julio; Lourdes, Rodriguez-de la Rosa; Murillo-Cuesta, Silvia; Hernandez-Sanchez, Catalina; Zubeldia, Jose M.; Cerdan, Sebastian; Varela-Nieto, Isabel

    2010-01-01

    Insulin-like growth factor-I (IGF-I) belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss) is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR) recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to prevent or

  1. A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficient mice

    Directory of Open Access Journals (Sweden)

    Raquel Riquelme

    2010-06-01

    Full Text Available Insulin-like growth factor-I (IGF-I belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to

  2. Substrate-energy metabolism and metabolic risk factors for cardiovascular disease in relation to fetal growth and adult body composition.

    Science.gov (United States)

    Kensara, Osama A; Wooton, Steve A; Phillips, David I W; Patel, Mayank; Hoffman, Daniel J; Jackson, Alan A; Elia, Marinos

    2006-08-01

    The effect of fetal programming on intermediary metabolism is uncertain. Therefore, we examined whether fetal programming affects oxidative and nonoxidative macronutrient metabolism and the prevalence of the metabolic syndrome in adult life. Healthy older men, aged 64-72 years, with either a lower birth weight (LBW, or=75th %ile; n = 13) had measurements of 1) net oxidative metabolism using indirect calorimetry before and for 6 h after a mixed meal (3,720 kJ) and 2) postprandial oxidation of exogenous [13C]palmitic acid. Body composition was measured using dual-energy X-ray absorptiometry. After adjustment for current weight and height, the LBW group had a lower resting energy expenditure (REE) in the preprandial (4.01 vs. 4.54 kJ/min, P = 0.015) and postprandial state (4.60 vs. 5.20 kJ/min, P = 0.004), and less fat-free mass than the HBW group. The BW category was a significant, independent, and better predictor of REE than weight plus height. There were no significant differences between groups in net oxidative and nonoxidative macronutrient (protein, fat, carbohydrate) metabolism (or of exogenous [13C]palmitate) or in the prevalence of the metabolic syndrome, which was present almost twice as commonly in the LBW than in the HBW group. The study suggests that fetal programming affects both pre- and postprandial EE in older life by mechanisms that are at least partly related to the mass of the fat-free body. BW was found to be a significant predictor of REE that was independent of adult weight plus height.

  3. LATHYROIDES, Encoding a WUSCHEL-Related Homeobox1 Transcription Factor, Controls Organ Lateral Growth, and Regulates Tendril and Dorsal Petal Identities in Garden Pea (Pisum sativum L.)

    Institute of Scientific and Technical Information of China (English)

    Li-Li Zhuang; Mike Ambrose; Catherine Rameau; Lin Weng; Jun Yang; Xiao-He Hu; Da Luo; Xin Li

    2012-01-01

    During organ development,many key regulators have been identified in plant genomes,which play a conserved role among plant species to control the organ identities and/or determine the organ size and shape.It is intriguing whether these key regulators can acquire diverse function and be integrated into different molecular pathways among different species,giving rise to the immense diversity of organ forms in nature.In this study,we have characterized and cloned LATHYROIDES (LATH),a classical locus in pea,whose mutation displays pleiotropic alteration of lateral growth of organs and predominant effects on tendril and dorsal petal development.LATH encodes a WUSCHEL-related homeobox1 (WOX1) transcription factor,which has a conserved function in determining organ lateral growth among different plant species.Furthermore,we showed that LATH regulated the expression level of TENDRIL-LESS (TL),a key factor in the control of tendril development in compound leaf,and LATH genetically interacted with LOBED STANDARD (LST),a floral dorsal factor,to affect the dorsal petal identity.Thus,LATH plays multiple roles during organ development in pea:it maintains a conserved function controlling organ lateral outgrowth,and modulates organ identities in compound leaf and zygomorphic flower development,respectively.Our data indicated that a key regulator can play important roles in different aspects of organ development and dedicate to the complexity of the molecular mechanism in the control of organ development so as to create distinct organ forms in different species.

  4. Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

    Directory of Open Access Journals (Sweden)

    Chanock Stephen J

    2010-03-01

    Full Text Available Abstract Background Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here. Methods Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI. The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3. Results The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis. Conclusion Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.

  5. EXPRESSION OF MATRIX METALLOPROTEINASE-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN HUMAN GLIOMA AND THEIR RELATION TO THE INVASION OF THE TUMOR

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To study the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in different grade human glioma. To investigate their relation to the pathological grade and invasion of the tumor. Methods The expression of MMP-2 and VEGF were determined by immunohistochemical technique in 48 cases of human glioma and 10 specimens of normal brain tissue. Results The expression levels of MMP-2 and VEGF in human glioma were positively related to tumor grades (P<0.01), and their expressions in the glioma of grade Ⅲ and Ⅳ were significantly different from those in the glioma of grade Ⅰ-Ⅱand normal brain tissue (P<0.01). The expression of MMP-2 was positively correlated to that of VEGF (P<0.01). Conclusion MMP-2 and VEGF were highly expression in human glioma and were positively related to the tumor grades. The synergic interaction of MMP-2 and VEGF promoted the angiogenesis and invasion of human glioma.

  6. Hypoxia related growth factors and p53 in preoperative sera from patients with colorectal cancer--evaluation of the prognostic significance of these agents.

    Science.gov (United States)

    Sulkowski, Stanislaw; Wincewicz, Andrzej; Zalewski, Bogdan; Famulski, Waldemar; Lotowska, Joanna Maria; Koda, Mariusz; Sobaniec-Lotowska, Maria Elzbieta; Mysliwiec, Michal; Baltaziak, Marek; Pawlak, Krystyna; Sulkowska, Mariola

    2009-01-01

    Insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) belong to a group of hypoxia related proteins. IGF-I induces expression of VEGF and decomposes wild type p53 in cancer cell lines. The goal of our study was to evaluate serum IGF-I, VEGF and p53 with respect to overall and disease free survival of patients with colorectal cancer (CRC) patients compared with healthy volunteers. Preoperative blood samples from 125 patients with CRC and 16 healthy volunteers were examined using ELISA for serum IGF-I, p53 and VEGF concentrations. Concentrations of p53 and VEGF were significantly higher in CRC patients than in controls (p<0.0006 and p<0.0001, respectively). IGF-I was not statistically different between both groups. Serum IGF-I showed negative correlation with p53 in CRC patients (p<0.04, r=-0.193). IGF-I and VEGF showed negative correlation in poorly differentiated cancers (G3) (p<0.03, r=-0.339). Patients with VEGF concentrations that were above average for the cancer population survived for a shorter period of time (p=0.065 in evaluation of overall survival and 0.071 in estimation of disease-free survival during a 3-year follow-up) compared with patients with serum VEGF lower than the highest values seen in controls. Comparisons between serum IGF-I and p53 appear to confirm the metabolism of p53 by IGF-I. Serum VEGF showed prognostic significance in our study. Serum concentrations of IGF-I and VEGF did not show positive correlation, as expected due to IGF-I induction of VEGF in malignant colon cell lines.

  7. Hepatocyte growth factor and vascular endothelial growth factor in ischaemic heart disease.

    Science.gov (United States)

    Suzuki, Hiroshi; Murakami, Mikitaka; Shoji, Makoto; Iso, Yoshitaka; Kondo, Takeshi; Shibata, Masayuki; Ezumi, Hitoshi; Hamazaki, Yuji; Koba, Shinji; Katagiri, Takashi

    2003-06-01

    Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors, but the production of these growth factors in cardiomyocytes has also been demonstrated. However, there have been no reports focusing their attention on the changes in these growth factors after coronary intervention. We investigated the time-course changes of the serum VEGF and HGF levels in angina pectoris (AP) and acute myocardial infarction (AMI). The serum HGF and VEGF levels were measured in 60 patients with AP, in 62 patients with AMI (AP, before heparin administration, and at 24 and 48 hours, and one week after intervention; AMI, before heparin, and at 48 and 72 hours, and one, two, three and four weeks) and in 56 patients with neurocirculatory asthenia as controls. We defined the patients with remodelling who showed an increase in left ventricular end-diastolic volume index (LVEDVI) in the sub-acute phase of AMI. Hepatocyte growth factor levels in the AP and AMI were significantly higher than that in the control (p<0.0001). The AMI level was also significantly higher than AP (p<0.001). In the AMI and AP, HGF peaked at 48 hours. Vascular endothelial growth factor level in the AMI was significantly higher than that in the control and AP (p<0.0001). In the AMI, VEGF peaked at two weeks. There was a significant positive correlation between the peak VEGF and LVEDVI in the sub-acute phase of AMI (p=0.0089, r=0.436). Peak VEGF in the remodelling (+) group was significantly higher than that in the remodelling (-) group (p<0.001). In the AP, VEGF was unchanged. While both myocardial and vascular damage contribute to an increase in HGF level, vascular damage is not associated with the increase in VEGF. Vascular endothelial growth factor might be related to left ventricular remodelling in the sub-acute phase of myocardial infarction.

  8. CCN family member 2/connective tissue growth factor (CCN2/CTGF has anti-aging effects that protect articular cartilage from age-related degenerative changes.

    Directory of Open Access Journals (Sweden)

    Shinsuke Itoh

    Full Text Available To examine the role of connective tissue growth factor CCN2/CTGF (CCN2 in the maintenance of the articular cartilaginous phenotype, we analyzed knee joints from aging transgenic mice (TG overexpressing CCN2 driven by the Col2a1 promoter. Knee joints from 3-, 14-, 40-, and 60-day-old and 5-, 12-, 18-, 21-, and 24-month-old littermates were analyzed. Ccn2-LacZ transgene expression in articular cartilage was followed by X-gal staining until 5 months of age. Overexpression of CCN2 protein was confirmed through all ages in TG articular cartilage and in growth plates. Radiographic analysis of knee joints showed a narrowing joint space and other features of osteoarthritis in 50% of WT, but not in any of the TG mice. Transgenic articular cartilage showed enhanced toluidine blue and safranin-O staining as well as chondrocyte proliferation but reduced staining for type X and I collagen and MMP-13 as compared with those parameters for WT cartilage. Staining for aggrecan neoepitope, a marker of aggrecan degradation in WT articular cartilage, increased at 5 and 12 months, but disappeared at 24 months due to loss of cartilage; whereas it was reduced in TG articular cartilage after 12 months. Expression of cartilage genes and MMPs under cyclic tension stress (CTS was measured by using primary cultures of chondrocytes obtained from wild-type (WT rib cartilage and TG or WT epiphyseal cartilage. CTS applied to primary cultures of mock-transfected rib chondrocytes from WT cartilage and WT epiphyseal cartilage induced expression of Col1a1, ColXa1, Mmp-13, and Mmp-9 mRNAs; however, their levels were not affected in CCN2-overexpressing chondrocytes and TG epiphyseal cartilage. In conclusion, cartilage-specific overexpression of CCN2 during the developmental and growth periods reduced age-related changes in articular cartilage. Thus CCN2 may play a role as an anti-aging factor by stabilizing articular cartilage.

  9. Methods of modelling relative growth rate

    Institute of Scientific and Technical Information of China (English)

    Arne Pommerening; Anders Muszta

    2015-01-01

    Background:Analysing and modelling plant growth is an important interdisciplinary field of plant science. The use of relative growth rates, involving the analysis of plant growth relative to plant size, has more or less independently emerged in different research groups and at different times and has provided powerful tools for assessing the growth performance and growth efficiency of plants and plant populations. In this paper, we explore how these isolated methods can be combined to form a consistent methodology for modelling relative growth rates. Methods:We review and combine existing methods of analysing and modelling relative growth rates and apply a combination of methods to Sitka spruce (Picea sitchensis (Bong.) Carr.) stem-analysis data from North Wales (UK) and British Douglas fir (Pseudotsuga menziesi (Mirb.) Franco) yield table data. Results:The results indicate that, by combining the approaches of different plant-growth analysis laboratories and using them simultaneously, we can advance and standardise the concept of relative plant growth. Particularly the growth multiplier plays an important role in modelling relative growth rates. Another useful technique has been the recent introduction of size-standardised relative growth rates. Conclusions:Modelling relative growth rates mainly serves two purposes, 1) an improved analysis of growth performance and efficiency and 2) the prediction of future or past growth rates. This makes the concept of relative growth ideally suited to growth reconstruction as required in dendrochronology, climate change and forest decline research and for interdisciplinary research projects beyond the realm of plant science.

  10. Methods of modelling relative growth rate

    Directory of Open Access Journals (Sweden)

    Arne Pommerening

    2015-03-01

    Full Text Available Background Analysing and modelling plant growth is an important interdisciplinary field of plant science. The use of relative growth rates, involving the analysis of plant growth relative to plant size, has more or less independently emerged in different research groups and at different times and has provided powerful tools for assessing the growth performance and growth efficiency of plants and plant populations. In this paper, we explore how these isolated methods can be combined to form a consistent methodology for modelling relative growth rates. Methods We review and combine existing methods of analysing and modelling relative growth rates and apply a combination of methods to Sitka spruce (Picea sitchensis (Bong. Carr. stem-analysis data from North Wales (UK and British Douglas fir (Pseudotsuga menziesii (Mirb. Franco yield table data. Results The results indicate that, by combining the approaches of different plant-growth analysis laboratories and using them simultaneously, we can advance and standardise the concept of relative plant growth. Particularly the growth multiplier plays an important role in modelling relative growth rates. Another useful technique has been the recent introduction of size-standardised relative growth rates. Conclusions Modelling relative growth rates mainly serves two purposes, 1 an improved analysis of growth performance and efficiency and 2 the prediction of future or past growth rates. This makes the concept of relative growth ideally suited to growth reconstruction as required in dendrochronology, climate change and forest decline research and for interdisciplinary research projects beyond the realm of plant science.

  11. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hong Shik; Hong, Eun-Hee [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae [Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Baek, Jeong-Hwa [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Yim, Ji-Hye; Um, Hong-Duck [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hwang, Sang-Gu, E-mail: sgh63@kcch.re.kr [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2013-09-27

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer.

  12. Study of the relationship of serum insulin-like growth factor-related indicators and interleukins with pregnancy-induced hypertension

    Institute of Scientific and Technical Information of China (English)

    Minawar.Aziz

    2016-01-01

    Objective:To study the relationship of serum insulin-like growth factor-related indicators and interleukins with pregnancy-induced hypertension.Methods:34 patients with gestational hypertension, 27 patients with mild preeclampsia, 18 patients with severe preeclampsia and 50 healthy women were selected as the research subjects, serum was collected to determine serum IGF-I, IGF-II, IGFBP-1, IL-6, IL-8 and IL-18 content, and the placenta was collect to determine IGF-I, IGF-II, IGFBP-1, IL-6, IL-8 and IL-18 content.Results: IGF-I and IGF-II levels in placenta tissue and serum of gestational hypertension group, mild preeclampsia group and severe preeclampsia group were significantly lower than those of control group, and IGFBP-1, IL-6, IL-8 and IL-18 levels were significantly higher than those of control group; serum IGF-I and IGF-II levels were negatively correlated with IL-6, IL-8 and IL-18 levels, and serum IGFBP-1 level was positively correlated with IL-6, IL-8 and IL-18 levels.Conclusion:decreased serum IGF-I, IGF-II levels and increased serum IGFBP-1, IL-6, IL-8 and IL-18 levels are associated with pregnancy-induced hypertension, and decreased IGF-I and IGF-II levels and increased IGFBP-1 level are closely related to increased levels of interleukins.

  13. Growth factors and cytokines in acute renal failure.

    Science.gov (United States)

    Harris, R C

    1997-04-01

    The mammalian kidney is susceptible to injury by ischemia/reperfusion and toxins, and regeneration after injury is characterized by hyperplasia and recovery of the damaged epithelial cells that line the tubules. Locally produced growth factors may serve as mediators of nephrogenesis and differentiation during renal development and of renal regeneration after acute injury. In cultured cells, administration of one or a mixture of growth factors to quiescent cells will initiate progression through the cell cycle and cell division. In the adult kidney, cell division normally is very low, but will increase up to 10-fold after acute injury. In addition to proliferation after lethal injury, there also is cellular repair in cells that have undergone sublethal injury. Recent studies indicate that growth factors inhibit programmed cell death in response to acute injury. Growth factors also may initiate or promote protein and lipid biosynthesis and provide an intracellular milieu that promotes cellular repair. In addition to cellular repair, growth factors also may be involved in the re-establishment of cell-extracellular matrix and cell-cell integrity. Finally, growth factors may limit injury by decreasing the factors that induce damage. Increased local renal expression of growth factors in response to acute injury include heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I), transforming growth factor-beta, parathyroid hormone-related peptide, and acidic fibroblast growth factor. In a number of experimental models of acute renal injury, administration of exogenous growth factors has been shown to accelerate both structural and functional recovery. Specifically, EGF, IGF-1, and HGF all have been shown to be effective in this regard. These studies are reviewed and potential therapeutic uses of growth factors and cytokines will be discussed.

  14. Epidermal Growth Factor Receptor in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira-Cunha, Melissa, E-mail: melissacunha@doctors.org.uk [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Newman, William G. [Genetic Medicine, MAHSC, University of Manchester, St Mary' s Hospital, Oxford Road, Manchester, M13 9WL (United Kingdom); Siriwardena, Ajith K. [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom)

    2011-03-24

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer.

  15. Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

    Science.gov (United States)

    Opgenorth, A; Nation, N; Graham, K; McFadden, G

    1993-02-01

    The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

  16. Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas.

    Science.gov (United States)

    Chen, Xiaochuan; Rozance, Paul J; Hay, William W; Limesand, Sean W

    2012-05-01

    Placental insufficiency results in intrauterine growth restriction (IUGR), impaired fetal insulin secretion and less fetal pancreatic β-cell mass, partly due to lower β-cell proliferation rates. Insulin-like growth factors (IGFs) and fibroblast growth factors (FGFs) regulate fetal β-cell proliferation and pancreas development, along with transcription factors, such as pancreatic and duodenal homeobox 1 (PDX-1). We determined expression levels for these growth factors, their receptors and IGF binding proteins in ovine fetal pancreas and isolated islets. In the IUGR pancreas, relative mRNA expression levels of IGF-I, PDX-1, FGF7 and FGFR2IIIb were 64% (P pancreas compared with controls. In isolated islets from IUGR fetuses, IGF-II and IGFBP-2 mRNA concentrations were 1.5- and 3.7-fold greater (P < 0.05), and insulin mRNA was 56% less (P < 0.05) than control islets. The growth factor expression profiles for IGF and FGF signaling pathways indicate that declines in β-cell mass are due to decreased growth factor signals for both pancreatic progenitor epithelial cell and mature β-cell replication.

  17. Gene Expression Analysis of Murine and Human Osteoarthritis Synovium Reveals Elevation of Transforming Growth Factor beta-Responsive Genes in Osteoarthritis-Related Fibrosis

    NARCIS (Netherlands)

    Remst, D. F. G.; Blom, A. B.; Vitters, E. L.; Bank, R. A.; van den Berg, W. B.; Davidson, E. N. Blaney; van der Kraan, P. M.

    Objective. Synovial fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). Transforming growth factor beta (TGF beta), which is elevated in OA, plays a key role in the onset and persistence of synovial fibrosis. However, blocking of TGF beta in OA as a therapeutic intervention

  18. Vitamin B(12) dependent changes in mouse spinal cord expression of vitamin B(12) related proteins and the epidermal growth factor system

    DEFF Research Database (Denmark)

    Mutti, Elena; Lildballe, Dorte L; Kristensen, Lise

    2013-01-01

    Chronic vitamin B(12) (cobalamin) deficiency in the mammalian central nervous system causes degenerative damage, especially in the spinal cord. Previous studies have shown that cobalamin status alters spinal cord expression of epidermal growth factor (EGF) and its receptor in rats. Employing a mo...

  19. New detection methods of growth hormone and growth factors.

    Science.gov (United States)

    Bidlingmaier, Martin

    2012-01-01

    Human growth hormone (GH), but also GH related growth factors like the insulin-like growth factor-1 (IGF-1) are known to be abused in sports. Although the scientific evidence supporting a distinct effect of GH on performance in healthy trained subjects is limited, it has been repeatedly found with athletes or trainers, and the recent introduction of a first test to detect GH doping has led to a number of positive cases. Currently, there is no test for the detection of IGF-1 introduced worldwide, but confiscation of the drug from sports teams can be taken as indirect evidence for its abuse. The major biochemical difficulty for the detection of GH is that the recombinant form is identical in physicochemical properties to the endogenous GH secreted by the pituitary gland. Furthermore, the very short half-life of GH in circulation inherently shortens the window of opportunity where the drug can be detected. Two strategies have been followed for more than a decade to develop a test to detect the application of recombinant GH: the marker approach, which is based on the elevation of GH-dependent markers above the level seen under physiological conditions evoked by administration of recombinant GH, and the isoform approach, which is based on a change in the pattern of GH isoforms in circulation following the injection of recombinant GH.

  20. Aqueous Interleukin-6 Levels Are Superior to Vascular Endothelial Growth Factor in Predicting Therapeutic Response to Bevacizumab in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Kakarla V. Chalam

    2014-01-01

    Full Text Available Objective. To prospectively evaluate the effect of intravitreal bevacizumab on aqueous levels of interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF in patients with exudative age-related macular degeneration (AMD and correlate clinical outcomes with cytokine levels. Methods. 30 eyes of 30 patients with exudative AMD underwent intravitreal injection of bevacizumab three times at monthly intervals. The aqueous samples prior to the 1st injection (baseline and 3rd injection were analyzed for VEGF and IL-6 levels. Subjects were subgrouped based upon change in the central subfield (CSF macular thickness on SD-OCT at 8 weeks. Group 1 included patients (n=14 with a decrease in CSF thickness greater than 10% from the baseline (improved group. Group 2 included patients (n=16 who had a decrease in CSF thickness 10% or less (treatment-resistant. Results. In subgroup analysis, in both groups 1 and 2 patients, compared to aqueous VEGF, aqueous IL-6 levels showed a better correlation with CSF thickness on SD-OCT (r=0.72 and 0.71, resp.. Conclusions. Aqueous IL-6 may be an important marker of treatment response or resistance in wet macular degeneration. Future therapeutic strategies may include targeted treatment against both VEGF and IL-6, in patients who do not respond to anti-VEGF treatment alone.

  1. Anti-vascular endothelial growth factor pharmacotherapy for age-related macular degeneration: a report by the American Academy of Ophthalmology.

    Science.gov (United States)

    Ip, Michael S; Scott, Ingrid U; Brown, Gary C; Brown, Melissa M; Ho, Allen C; Huang, Suber S; Recchia, Franco M

    2008-10-01

    To examine the evidence about the safety and efficacy of anti-vascular endothelial growth factor (VEGF) pharmacotherapies for the treatment of neovascular age-related macular degeneration (AMD). Literature searches were conducted in May and October 2007 in PubMed with no date restrictions, limited to articles published in English, and in the Cochrane Central Register of Controlled Trials without a language limitation and yielded 310 citations. The first author reviewed the abstracts of these articles and selected 73 articles of possible clinical relevance for review by the panel. The panel deemed 64 of these articles sufficiently clinically relevant to review in full text and assigned ratings of level of evidence to each of the selected articles with the guidance of the panel methodologists. Eleven studies provided level I evidence for intravitreal pegaptanib and ranibizumab for neovascular AMD; there were no studies rated level I for bevacizumab for neovascular AMD. Five studies were rated as level II, which included studies of ranibizumab and bevacizumab, and the remaining 38 articles retrieved were rated as level III. The studies do not provide information about long-term results or the value (comparative effectiveness) and cost-effectiveness of combined therapies. Review of the available literature to date suggests that anti-VEGF pharmacotherapy, delivered by intravitreal injection, is a safe and effective treatment for neovascular AMD for up to 2 years. There is level I evidence to support this conclusion for pegaptanib and ranibizumab, but none for bevacizumab at this time.

  2. A Case of Transforming Growth Factor-β-Induced Gene-Related Oculorenal Syndrome: Granular Corneal Dystrophy Type II with a Unique Nephropathy

    Science.gov (United States)

    Iwafuchi, Yoichi; Morioka, Tetsuo; Oyama, Yuko; Nozu, Kandai; Iijima, Kazumoto; Narita, Ichiei

    2016-01-01

    Many types of inherited renal diseases have ocular features that occasionally support a diagnosis. The following study describes an unusual example of a 40-year-old woman with granular corneal dystrophy type II complicated by renal involvement. These two conditions may coincidentally coexist; however, there are some reports that demonstrate an association between renal involvement and granular corneal dystrophy type II. Granular corneal dystrophy type II is caused by a mutation in the transforming growth factor-β-induced (TGFBI) gene. The patient was referred to us because of the presence of mild proteinuria without hematuria that was subsequently suggested to be granular corneal dystrophy type II. A kidney biopsy revealed various glomerular and tubular basement membrane changes and widening of the subendothelial space of the glomerular basement membrane by electron microscopy. However, next-generation sequencing revealed that she had no mutation in a gene that is known to be associated with monogenic kidney diseases. Conversely, real-time polymerase chain reaction, using a simple buccal swab, revealed TGFBI heteromutation (R124H). The TGFBI protein plays an important role in cell-collagen signaling interactions, including extracellular matrix proteins which compose the renal basement membrane. This mutation can present not only as corneal dystrophy but also as renal disease. TGFBI-related oculorenal syndrome may have been unrecognized. It is difficult to diagnose this condition without renal electron microscopic studies. To the best of our knowledge, this is the first detailed report of nephropathy associated with a TGFBI mutation.

  3. EXPRESSION OF IGFBP-6 IN COLORECTAL CANCER: THE RELATION WITH INSULIN-LIKE GROWTH FACTOR RECEPTOR, ADIPONECTIN LEVEL AND ITS RECEPTORS

    Directory of Open Access Journals (Sweden)

    N. V. Yunusova

    2015-01-01

    Full Text Available The aim of the study was to investigate the expression of insulin-like growth factor binding protein 6 (IGFBP-6 in cancer tissues in relation with clinical and morphological parameters, IGF-IR expression, serum adiponectin level and its receptors (AdipoR1, AdipoR2 in patients with colorectal cancer.Material and Methods. The study included 31 patients with colorectal cancer (T2–4N0–2M0. Serum adiponectin level, AdipoR1 and AdipoR2 expression were evaluated with ELISA. IGF-IR expression was evaluated in tumor tissue by flow cytometry. IGFBP-6 expression was evaluated with Western blotting.Results. The dependence of IGFBP-6 expression, AdipoR1, AdipoR2 on tumor invasion and lymph nodes status were revealed. There is no association IGFBP-6 expression, AdipoR1 and AdipoR2 expression and serum adiponectin level with metabolic syndrome. The revealed positive relationships between IGFBP-6 expression and AdipoR1 expression, between IGFBP-6 expression and AdipoR2 expression, between IGF-IR and AdipoR1 expression show cross-talk between IGF-IR and adiponectin/AdipoR1 pathways in colorectal carcinomas.

  4. Dickkopf‑related protein 1 induces angiogenesis by upregulating vascular endothelial growth factor in the synovial fibroblasts of patients with temporomandibular joint disorders.

    Science.gov (United States)

    Jiang, Sheng-Jun; Li, Wei; Li, Ying-Jie; Fang, Wei; Long, Xing

    2015-10-01

    Angiogenesis has an important role in the progression of temporomandibular joint disorders (TMD). The aim of the present study was to explore the association between dickkopf‑related protein 1 (DKK‑1) and angiogenesis in TMD. The expression levels of DKK‑1 and vascular endothelial growth factor (VEGF) were quantified by an ELISA assay of the synovial fluid from patients with TMD. The correlation between DKK‑1 and VEGF was analyzed by Pearson correlation test. Synovial fibroblasts were isolated from patients with TMD and were subsequently treated with recombinant human DKK‑1, anti‑DKK‑1 antibody, hypoxia inducible factor‑1α (HIF‑1α), or small interfering RNA (siRNA). The expression levels of DKK‑1, HIF‑1α, and VEGF were subsequently quantified. The present study also investigated the effects of DKK‑1 on the migration of human umbilical vein endothelial cells (HUVEC). Increased expression levels of DKK‑1 were concordant with increased expression levels of VEGF in the synovial fluid from patients with TMD. In the synovial fibroblasts, DKK‑1 increased the expression levels of VEGF, and promoted HIF‑1α nuclear localization. In addition, DKK‑1 induced HUVEC migration, and HIF‑1α siRNA inhibited DKK‑1‑induced cell migration. The results of the present study indicate that DKK‑1 is associated with angiogenesis in the synovial fluid of patients with TMD. Furthermore, HIF‑1α may be associated with DKK‑1‑induced HUVEC activation.

  5. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Mrejen, Sarah; Jung, Jesse J; Chen, Christine; Patel, Samir N; Gallego-Pinazo, Roberto; Yannuzzi, Nicolas; Xu, Luna; Marsiglia, Marcela; Boddu, Sucharita; Freund, K Bailey

    2015-07-08

    With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1-6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4-13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

  6. Oxalomalate reduces expression and secretion of vascular endothelial growth factor in the retinal pigment epithelium and inhibits angiogenesis: Implications for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Sung Hwan Kim

    2016-12-01

    Full Text Available Clinical and experimental observations indicate a critical role for vascular endothelial growth factor (VEGF, secreted by the retinal pigment epithelium (RPE, in pathological angiogenesis and the development of choroidal neovascularization (CNV in age-related macular degeneration (AMD. RPE-mediated VEGF expression, leading to angiogenesis, is a major signaling mechanism underlying ocular neovascular disease. Inhibiting this signaling pathway with a therapeutic molecule is a promising anti-angiogenic strategy to treat this disease with potentially fewer side effects. Oxalomalate (OMA is a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase (IDH, which plays an important role in cellular signaling pathways regulated by reactive oxygen species (ROS. Here, we have investigated the inhibitory effect of OMA on the expression of VEGF, and the associated underlying mechanism of action, using in vitro and in vivo RPE cell models of AMD. We found that OMA reduced the expression and secretion of VEGF in RPE cells, and consequently inhibited CNV formation. This function of OMA was linked to its capacity to activate the pVHL-mediated HIF-1α degradation in these cells, partly via a ROS-dependent ATM signaling axis, through inhibition of IDH enzymes. These findings reveal a novel role for OMA in inhibiting RPE-derived VEGF expression and angiogenesis, and suggest unique therapeutic strategies for treating pathological angiogenesis and AMD development.

  7. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Sarah Mrejen

    2015-07-01

    Full Text Available With the advent of anti-vascular endothelial growth factor (VEGF therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD, a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes were followed over an average of 3.5 years (range 1–6.6 with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6 (± standard deviation intravitreal anti-VEGF injections/year (range 4–13. The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

  8. Growth factors and acute renal failure.

    Science.gov (United States)

    Hirschberg, R; Ding, H

    1998-03-01

    During acute renal injury, there are alterations in the expression of several growth factors and their receptors in the kidney. The increased expression of several growth factors and/or their receptors at sites of nephron injury suggests important contributions to repair. Exogenous administration of some growth factors, such as IGF-I, EGF and HGF, accelerates recovery of renal function in experimental acute renal failure (ARF). In ARF growth factors act through several mechanisms, which may include altered cell cycle regulation and mitogenesis, differentiation of recovered cells, regulation of apoptosis, improved renal hemodynamics, and others. There is evidence for interactions of growth factors with other growth factors as well as with other genes resulting in complex orchestration of biologic events contributing to recovery from ARF.

  9. Association of Interferon- and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

    Science.gov (United States)

    Christmann, Romy B.; Sampaio-Barros, Percival; Stifano, Giuseppina; Borges, Claudia L.; de Carvalho, Carlos R.; Kairalla, Ronaldo; Parra, Edwin R.; Spira, Avrum; Simms, Robert; Capellozzi, Vera L.; Lafyatis, Robert

    2015-01-01

    Objective Systemic sclerosis (SSc)–related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc-related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease. Methods Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc-related ILD and in 4 controls. High-resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2–3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein. Results Lung microarray data distinguished patients with SSc-related ILD from healthy controls. In the lungs of patients with SSc-related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor β (TGFβ)– and interferon (IFN)–regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < −0.1), including IFN and macrophage markers, chemokines, and heat-shock proteins. Conclusion These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc-related

  10. Effects of insulin-like growth factor binding protein-related protein 1 in mice with hepatic fibrosis induced by thioacetamide

    Institute of Scientific and Technical Information of China (English)

    LIU Li-xin; ZHANG Hai-yan; ZHANG Qian-qian; GUO Xiao-hong

    2010-01-01

    Background Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) can activate hepatic stellate cells and increase extracellular matrix (ECM) in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study.Methods Intraperitoneal injection of thioacetamide (TAA) is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, α-smooth muscle actin (α-SMA) and ECM in liver tissues, and the expression of transforming growth factor-β1 (TGF-β1) and Smad3. Data were statistically analyzed using one-way analysis of variance (ANOVA), the SNK-q test for inter-group differences.Results The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased (P <0.01), and it was significantly decreased in TAA5w/alGFBPrP1 group compared with in TAA5w group (P <0.01). The expression of hepatic IGFBPrP1, α-SMA, TGF-β1, Smad3, collagen I and fibronectin (FN) was significantly up-regulated in the TAA5w group (P <0.01). Anti-IGFBPrP1 treatment reversed these changes (P <0.01).Conclusions IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM (namely, collagen I and FN). The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways.

  11. A Clear Cell Renal Cell Carcinoma Inhibiting the Response to Intravitreal Antivascular Endothelial Growth Factor Therapy in Wet Age-Related Macular Disease

    Directory of Open Access Journals (Sweden)

    Manuel S. Falcão

    2012-12-01

    Full Text Available Purpose: Wet age-related macular degeneration (AMD is an ocular disorder that can be successfully treated with intravitreal antivascular endothelial growth factor (VEGF therapy. We report a case of incomplete response to intravitreal therapy associated with a clear cell renal cell carcinoma (ccRCC. Methods: A 72-year-old male with wet AMD responded poorly to intravitreal bevacizumab and ranibizumab injections. The removal of a ccRCC led to the spontaneous stabilization of the choroidal neovascular lesion. The renal carcinoma was examined for Von Hippel-Lindau (VHL gene alterations. Immunohistochemical profiling of the hypoxia-inducible factor (HIF pathway addressing the marker HIF-1α and its downstream targets VEGF, glucose transporter 1 and carbonic anhydrase IX was performed. Results: Genotyping of the ccRCC revealed the presence of a truncating VHL mutation (p.E134fs*25. Immunohistochemistry displayed HIF pathway target activation and VEGF expression in the ccRCC tumour cells. Following tumour removal, the neovascular lesion remained stable for 6 months without any further anti-VEGF therapy. Conclusion: The somatic VHL mutation correlates with persistent high levels of HIF-1α pathway targets and VEGF expression in the ccRCC. We postulate that this increased VEGF in the tumour and subsequently in the plasma levels could have caused the incomplete response to intravitreal anti-VEGF therapy. Stabilization of the wet AMD following tumour removal indicates that the angiogenic secreting tumour (ccRCC abrogates the response to VEGF inhibitor therapy. Thus, in cases of poor response to intravitreal anti-VEGF therapy, systemic evaluation including plasma levels of VEGF and/or systemic screening for VEGF-producing tumours should be considered.

  12. Change of retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in exudative age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Moosang Kim

    2016-01-01

    Full Text Available Purpose: The study aimed to investigate the quantitative changes of retinal pigment epithelial (RPE atrophy during a 24-month follow-up period of anti-vascular endothelial growth factor (VEGF for exudative age-related macular degeneration (AMD. Materials and Methods: This is a retrospective study. Sixty-five eyes of 62 consecutive patients with naοve exudative AMD who had received treatment with anti-VEGF therapy and followed for more 24 months were enrolled. All patients received three initial monthly injections of anti-VEGF (ranibizumab or bevacizumab, followed by pro re nata or treat-and-extend protocol. Color fundus image, optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy. Multiple regression analysis was performed to investigate the predictive factors found during univariate analysis to identify an association with increased RPE atrophic areas. Results: The mean number of anti-VEGF treatments was 9.18. RPE atrophic area was 1.293 ± 1.298 mm 2 at baseline and enlarged to 2.394 ± 1.940 mm 2 after 24 months, which differed significantly (P = 0.001. Multiple regression analysis revealed that larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF treatments were associated with increased RPE atrophic areas. Conclusions: RPE atrophy progresses in eyes with exudative AMD during anti-VEGF treatment. Larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF injections were associated with an increased risk of progression of RPE atrophy the following treatment. These findings may be useful to clinicians using intravitreal anti-VEGF for the treatment of exudative AMD, both for selecting an appropriate treatment plan and for predicting the progression of RPE atrophy.

  13. A Clear Cell Renal Cell Carcinoma Inhibiting the Response to Intravitreal Antivascular Endothelial Growth Factor Therapy in Wet Age-Related Macular Disease

    Science.gov (United States)

    Falcão, Manuel S.; Vinagre, João; Soares, Paula; Lopes, José Manuel; Brandão, Elisete; Carneiro, Ângela M.

    2012-01-01

    Purpose Wet age-related macular degeneration (AMD) is an ocular disorder that can be successfully treated with intravitreal antivascular endothelial growth factor (VEGF) therapy. We report a case of incomplete response to intravitreal therapy associated with a clear cell renal cell carcinoma (ccRCC). Methods A 72-year-old male with wet AMD responded poorly to intravitreal bevacizumab and ranibizumab injections. The removal of a ccRCC led to the spontaneous stabilization of the choroidal neovascular lesion. The renal carcinoma was examined for Von Hippel-Lindau (VHL) gene alterations. Immunohistochemical profiling of the hypoxia-inducible factor (HIF) pathway addressing the marker HIF-1α and its downstream targets VEGF, glucose transporter 1 and carbonic anhydrase IX was performed. Results Genotyping of the ccRCC revealed the presence of a truncating VHL mutation (p.E134fs*25). Immunohistochemistry displayed HIF pathway target activation and VEGF expression in the ccRCC tumour cells. Following tumour removal, the neovascular lesion remained stable for 6 months without any further anti-VEGF therapy. Conclusion The somatic VHL mutation correlates with persistent high levels of HIF-1α pathway targets and VEGF expression in the ccRCC. We postulate that this increased VEGF in the tumour and subsequently in the plasma levels could have caused the incomplete response to intravitreal anti-VEGF therapy. Stabilization of the wet AMD following tumour removal indicates that the angiogenic secreting tumour (ccRCC) abrogates the response to VEGF inhibitor therapy. Thus, in cases of poor response to intravitreal anti-VEGF therapy, systemic evaluation including plasma levels of VEGF and/or systemic screening for VEGF-producing tumours should be considered. PMID:23341823

  14. Synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  15. Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

    DEFF Research Database (Denmark)

    Bor, M V; Sørensen, B S; Vinter-Jensen, L

    2000-01-01

    as the expression of transforming growth factor-alpha peptide. The level of epidermal growth factor receptor and transforming growth factor-alpha mRNA expression was found to correlate both in control and growth factor-treated animals, whereas the expression of epidermal growth factor receptor and epidermal growth...

  16. Organisational Factors of Rapid Growth of Slovenian Dynamic Enterprises

    Directory of Open Access Journals (Sweden)

    Pšeničny Viljem

    2013-01-01

    Full Text Available The authors provide key findings on the internal and external environmental factors of growth that affect the rapid growth of dynamic enterprises in relation to individual key organisational factors or functions. The key organisational relationships in a growing enterprise are upgraded with previous research findings and identified key factors of rapid growth through qualitative and quantitative analysis based on the analysis of 4,511 dynamic Slovenian enterprises exhibiting growth potential. More than 250 descriptive attributes of a sample of firms from 2011 were also used for further qualitative analysis and verification of key growth factors. On the basis of the sample (the study was conducted with 131 Slovenian dynamic enterprises, the authors verify whether these factors are the same as the factors that were studied in previous researches. They also provide empirical findings on rapid growth factors in relation to individual organisational functions: administration - management - implementation (entrepreneur - manager - employees. Through factor analysis they look for the correlation strength between individual variables (attributes that best describe each factor of rapid growth and that relate to the aforementioned organisational functions in dynamic enterprises. The research findings on rapid growth factors offer companies the opportunity to consider these factors during the planning and implementation phases of their business, to choose appropriate instruments for the transition from a small fast growing firm to a professionally managed growing company, to stimulate growth and to choose an appropriate growth strategy and organisational factors in order to remain, or become, dynamic enterprises that can further contribute to the preservation, growth and development of the Slovenian economy

  17. Modeling turkey growth with the relative growth rate.

    Science.gov (United States)

    Maruyama, K; Potts, W J; Bacon, W L; Nestor, K E

    1998-01-01

    Six sigmoidal growth curves and two growth curves derived from a two-phase relative growth rate model were evaluated, using an experimental body-weight data from male and female turkeys of two genetic lines; a fast-growing (F) line and a randombred control (RBC) line from which the F line was developed. When their root mean square error was compared to the root mean square error of the local regression smoother, all sigmoidal growth curves: the logistic, Gompertz, von Bertalanffy, Richards, Weibull, and Morgan-Mercer-Flodin growth curves demonstrated a lack of fit. The primary source of the systematic lack of fit was identified with nonparametric estimates of the relative growth rate (the growth rate as a fraction of the body weight) of 20 turkeys. When the relative growth rate was estimated from the above sigmoidal growth curves, none could accommodate features of the nonparametric estimates of the relative growth rate. Based on the feature of the relative growth rate, two new growth curves were derived from a segmented two-phase model. Both models, in which the relative growth rate decreases in two linear phases with slopes of beta1 and beta2 joined together at time=kappa, gave growth curves that fit the experimental data acceptably. The linear-linear model with the smooth transition rendered better fit over the model with the abrupt transition. When the growth curves of male and female turkeys were compared, beta1, beta2, and kappa were smaller in males. When the F line was compared to the RBC line, beta1 and kappa were smaller and beta2 was closer to zero, indicating that the relative growth rate declined rapidly until about 61 days of age in the F line, while it declined less rapidly until about 71 days of age in the RBC line.

  18. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  19. Growth factor involvement in tension-induced skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  20. Reduction of relative centrifugation force within injectable platelet-rich-fibrin (PRF) concentrates advances patients' own inflammatory cells, platelets and growth factors: the first introduction to the low speed centrifugation concept.

    Science.gov (United States)

    Choukroun, J; Ghanaati, S

    2017-03-10

    The aim of this study was to analyze systematically the influence of the relative centrifugation force (RCF) on leukocytes, platelets and growth factor release within fluid platelet-rich fibrin matrices (PRF). Systematically using peripheral blood from six healthy volunteers, the RCF was reduced four times for each of the three experimental protocols (I-III) within the spectrum (710-44 g), while maintaining a constant centrifugation time. Flow cytometry was applied to determine the platelets and leukocyte number. The growth factor concentration was quantified 1 and 24 h after clotting using ELISA. Reducing RCF in accordance with protocol-II (177 g) led to a significantly higher platelets and leukocytes numbers compared to protocol-I (710 g). Protocol-III (44 g) showed a highly significant increase of leukocytes and platelets number in comparison to -I and -II. The growth factors' concentration of VEGF and TGF-β1 was significantly higher in protocol-II compared to -I, whereas protocol-III exhibited significantly higher growth factor concentration compared to protocols-I and -II. These findings were observed among 1 and 24 h after clotting, as well as the accumulated growth factor concentration over 24 h. Based on the results, it has been demonstrated that it is possible to enrich PRF-based fluid matrices with leukocytes, platelets and growth factors by means of a single alteration of the centrifugation settings within the clinical routine. We postulate that the so-called low speed centrifugation concept (LSCC) selectively enriches leukocytes, platelets and growth factors within fluid PRF-based matrices. Further studies are needed to evaluate the effect of cell and growth factor enrichment on wound healing and tissue regeneration while comparing blood concentrates gained by high and low RCF.

  1. [Growth Hormone-Insulin Growth Factor I (GH-IGF-I) axis and growth].

    Science.gov (United States)

    Castell, A-L; Sadoul, J-L; Bouvattier, C

    2013-10-01

    Normal human linear growth results from an evolutionary process expressing the sum effect of multiple genes. The growth hormone (GH) - insulin like growth factor (IGF)-I axis is one of the main actors in the growth process. Defects in this axis can be responsible for short or tall stature. Short stature is defined as smaller than - 2 standard deviations (SD). It is a very common reason for consultation in pediatrics; indeed, 2.5 % of children are concerned. Multiple causes make diagnosis difficult. In this article, we detail the most common constitutional causes of small size, including those related to a defect in the GH-IGF-I axis. Then, we report, the first results of the clinical and genetic study conducted on 213 patients with gigantism. Tall stature is defined by a height superior to 2 SD. Finally, recent work linking epigenetics and growth - via signaling pathways of GH-IGF-I axis - will be presented.

  2. Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate adhesion-related responses

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-05-01

    Full Text Available Hsian-Yu Wang,1,2 Min-Kung Hsu,3,4 Kai-Hsuan Wang,1 Ching-Ping Tseng,2,4 Feng-Chi Chen,3,4 John T-A Hsu1,4 1Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 2Institute of Molecular Medicine and Bioengineering, National Chiao Tung University (NCTU, Hsinchu, 3Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 4Department of Biological Science and Technology, National Chiao Tung University (NCTU, Hsinchu, Taiwan, Republic of China Background: Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs, such as gefitinib, erlotinib, and afatinib, have greatly improved treatment efficacy in non-small cell lung cancer (NSCLC patients with drug-sensitive EGFR mutations. However, in some TKI responders, the benefits of such targeted therapies are limited by the rapid development of resistance, and strategies to overcome this resistance are urgently needed. Studies of drug resistance in cancer cells typically involve long term in vitro induction to obtain stably acquired drug-resistant cells followed by elucidation of resistance mechanisms, but the immediate responses of cancer cells upon drug treatment have been ignored. The aim of this study was to investigate the immediate responses of NSCLC cells upon treatment with EGFR TKIs.Results: Both NSCLC cells, ie, PC9 and H1975, showed immediate enhanced adhesion-related responses as an apoptosis-countering mechanism upon first-time TKI treatment. By gene expression and pathway analysis, adhesion-related pathways were enriched in gefitinib-treated PC9 cells. Pathway inhibition by small-hairpin RNAs or small-molecule drugs revealed that within hours of EGFR TKI treatment, NSCLC cells used adhesion-related responses to combat the drugs. Importantly, we show here that the Src family inhibitor, dasatinib, dramatically inhibits

  3. Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease-related growth retardation.

    Science.gov (United States)

    Troib, Ariel; Landau, Daniel; Kachko, Leonid; Rabkin, Ralph; Segev, Yael

    2013-11-01

    Linear growth retardation in children with chronic kidney disease (CKD) has been ascribed to insensitivity to growth hormone. This resistance state has been attributed to impaired growth hormone signaling through the JAK2/STAT5 pathway in liver and skeletal muscle leading to reduced insulin-like growth factor-I (IGF-I). Here we determine whether systemic and growth plate alterations in growth hormone signaling contribute to CKD-induced linear growth retardation using partially nephrectomized and pair-fed control 20-day-old rats. Serum growth hormone did not change in rats with CKD, yet serum IGF-I levels were decreased and growth retarded. The tibial growth plate hypertrophic zone was wider and vascularization at the primary ossification center was reduced in CKD. This was associated with a decrease in growth plate vascular endothelial growth factor (VEGF) mRNA and immunostainable VEGF and IGF-I levels. Growth plate growth hormone receptor and STAT5 protein levels were unchanged, while JAK2 was reduced. Despite comparable growth hormone and growth hormone receptor levels in CKD and control rats, relative STAT5 phosphorylation was significantly depressed in CKD. Of note, the mRNA of SOCS2, an inhibitor of growth hormone signaling, was increased. Thus, linear growth impairment in CKD can in part be explained by impaired long bone growth plate growth hormone receptor signaling through the JAK2/STAT5 pathway, an abnormality that may be caused by an increase in SOCS2 expression.

  4. Age-related changes in rat myocardium involve altered capacities of glycosaminoglycans to potentiate growth factor functions and heparan sulfate-altered sulfation.

    Science.gov (United States)

    Huynh, Minh Bao; Morin, Christophe; Carpentier, Gilles; Garcia-Filipe, Stephanie; Talhas-Perret, Sofia; Barbier-Chassefière, Véronique; van Kuppevelt, Toin H; Martelly, Isabelle; Albanese, Patricia; Papy-Garcia, Dulce

    2012-03-30

    Glycosaminoglycans (GAGs) are essential components of the extracellular matrix, the natural environment from which cell behavior is regulated by a number or tissue homeostasis guarantors including growth factors. Because most heparin-binding growth factor activities are regulated by GAGs, structural and functional alterations of these polysaccharides may consequently affect the integrity of tissues during critical physiological and pathological processes. Here, we investigated whether the aging process can induce changes in the myocardial GAG composition in rats and whether these changes can affect the activities of particular heparin-binding growth factors known to sustain cardiac tissue integrity. Our results showed an age-dependent increase of GAG levels in the left ventricle. Biochemical and immunohistological studies pointed out heparan sulfates (HS) as the GAG species that increased with age. ELISA-based competition assays showed altered capacities of the aged myocardial GAGs to bind FGF-1, FGF-2, and VEGF but not HB EGF. Mitogenic assays in cultured cells showed an age-dependent decrease of the elderly GAG capacities to potentiate FGF-2 whereas the potentiating effect on VEGF(165) was increased, as confirmed by augmented angiogenic cell proliferation in Matrigel plugs. Moreover, HS disaccharide analysis showed considerably altered 6-O-sulfation with modest changes in N- and 2-O-sulfations. Together, these findings suggest a physiological significance of HS structural and functional alterations during aging. This can be associated with an age-dependent decline of the extracellular matrix capacity to efficiently modulate not only the activity of resident or therapeutic growth factors but also the homing of resident or therapeutic cells.

  5. Plant-based diets relatively low in bioavailable phosphate and calcium may aid prevention and control of prostate cancer by lessening production of fibroblast growth factor 23.

    Science.gov (United States)

    McCarty, Mark F

    2017-02-01

    Fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism produced primarily in bone by osteocytes and mature osteoblasts, is now known to have growth factor activity for many prostate cancers. In some of these cancers, autocrine production of FGF23 drives their proliferation. FGF23 synthesized within bone likely promotes the expansion of prostate cancer bone metastases. Hence, dietary or lifestyle factors which boost bone's production of FGF23 may encourage the induction and spread of prostate cancer. High dietary intakes of bioavailable phosphorus and of calcium have been found to boost FGF23 levels, and this accords well with prospective epidemiology pointing to high intakes of both phosphate and calcium as risk factors for aggressive prostate cancer. Hence, prospective studies correlating baseline FGF23 levels with subsequent risk for prostate cancer, or advanced prostate cancer, are needed. Natural plant-based diets, though not inherently low in calcium or phosphorus, provide forms of these that are less bioavailable than those in animal products, and hence may be expected to down-regulate bone's production of FGF23. This may play a role in the lower risk for clinical prostate cancer observed in vegans and quasi-vegan cultures. Other factors, such as decreased IGF-I levels and mTORC1 activity, may also play a role in this regard.

  6. Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

    Science.gov (United States)

    Kaymakcalan, Marina D; Xie, Wanling; Albiges, Laurence; North, Scott A; Kollmannsberger, Christian K; Smoragiewicz, Martin; Kroeger, Nils; Wells, J Connor; Rha, Sun-Young; Lee, Jae Lyun; McKay, Rana R; Fay, André P; De Velasco, Guillermo; Heng, Daniel Y C; Choueiri, Toni K

    2016-02-01

    Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) factors to predict the risk of TrTD. In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. © 2015 American Cancer Society.

  7. Transforming growth factor alpha and epidermal growth factor in laryngeal carcinomas demonstrated by immunohistochemistry

    DEFF Research Database (Denmark)

    Christensen, M E; Therkildsen, M H; Poulsen, Steen Seier

    1993-01-01

    Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF recep...

  8. Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Hong SD

    2014-10-01

    Full Text Available Shaodong Hong,1,* Wenfeng Fang,1,* Wenhua Liang,1,* Yue Yan,1 Ting Zhou,1 Tao Qin,1 Xuan Wu,1 Yuxiang Ma,1 Yuanyuan Zhao,1 Yunpeng Yang,1 Zhihuang Hu,1 Cong Xue,1 Xue Hou,1 Yue Chen,2 Yan Huang,1 Hongyun Zhao,1 Li Zhang1 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China; 2Medical School, University of South China, Hengyang, Hunan, People's Republic of China *These authors contributed equally to this work Background: Vascular endothelial growth factor receptor (VEGFR tyrosine kinase inhibitors (TKIs have widely been used in advanced cancer. However, these drugs may also lead to serious adverse events. The present meta-analysis aimed to determine the overall incidence and risk of deaths due to VEGFR-TKIs with more detailed subgroup analysis. Materials and methods: PubMed, Web of Science, and Cochrane databases were searched for randomized controlled trials (RCTs that compared VEGFR-TKIs with non-VEGFR-TKIs in the treatment of solid cancer. Pooled incidence, odds ratios (ORs and 95% confidence intervals (CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of included trials. Results: A total of 14,139 participants from 41 RCTs were enrolled. The pooled incidence of death due to VEGFR-TKIs was 1.9% (95% CI: 1.6%–2.3% with an OR of 1.85 (95% CI: 1.33–2.58; P<0.01 when compared with control groups. On subgroup analysis, significantly increased risk of death was found in patients with nonsmall-cell lung cancer (OR: 2.37; 95% CI: 1.19–4.73; P=0.01 and colorectal cancer (OR: 2.84; 95% CI: 1.02–7.96; P=0.05. Among different VEGFR-TKIs, sorafenib and sunitinib had significant risk of death when compared with control arms, respectively. VEGFR-TKIs in combination with other antineoplastic agents, but not VEGFR-TKI monotherapy, significantly increased the risk of treatment-related

  9. Growth Factors for the Treatment of Ischemic Brain Injury (Growth Factor Treatment

    Directory of Open Access Journals (Sweden)

    Amara Larpthaveesarp

    2015-04-01

    Full Text Available In recent years, growth factor therapy has emerged as a potential treatment for ischemic brain injury. The efficacy of therapies that either directly introduce or stimulate local production of growth factors and their receptors in damaged brain tissue has been tested in a multitude of models for different Central Nervous System (CNS diseases. These growth factors include erythropoietin (EPO, vascular endothelial growth factor (VEGF, brain-derived neurotrophic factor (BDNF, and insulin-like growth factor (IGF-1, among others. Despite the promise shown in animal models, the particular growth factors that should be used to maximize both brain protection and repair, and the therapeutic critical period, are not well defined. We will review current pre-clinical and clinical evidence for growth factor therapies in treating different causes of brain injury, as well as issues to be addressed prior to application in humans.

  10. Growth factors for the treatment of ischemic brain injury (growth factor treatment).

    Science.gov (United States)

    Larpthaveesarp, Amara; Ferriero, Donna M; Gonzalez, Fernando F

    2015-04-30

    In recent years, growth factor therapy has emerged as a potential treatment for ischemic brain injury. The efficacy of therapies that either directly introduce or stimulate local production of growth factors and their receptors in damaged brain tissue has been tested in a multitude of models for different Central Nervous System (CNS) diseases. These growth factors include erythropoietin (EPO), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor (IGF-1), among others. Despite the promise shown in animal models, the particular growth factors that should be used to maximize both brain protection and repair, and the therapeutic critical period, are not well defined. We will review current pre-clinical and clinical evidence for growth factor therapies in treating different causes of brain injury, as well as issues to be addressed prior to application in humans.

  11. Growth factors for treating diabetic foot ulcers

    DEFF Research Database (Denmark)

    Martí-Carvajal, Arturo J; Gluud, Christian; Nicola, Susana

    2015-01-01

    with a foot ulcer. Trials were eligible for inclusion if they compared a growth factor plus standard care (e.g., antibiotic therapy, debridement, wound dressings) versus placebo or no growth factor plus standard care, or compared different growth factors against each other. We considered lower limb amputation......, vascular, or combined) was poorly defined in all trials. The trials were conducted in ten countries. The trials assessed 11 growth factors in 30 comparisons: platelet-derived wound healing formula, autologous growth factor, allogeneic platelet-derived growth factor, transforming growth factor β2, arginine...... with complete wound healing (345/657 (52.51%) versus 167/482 (34.64%); RR 1.51, 95% CI 1.31 to 1.73; I(2) = 51%, 12 trials; low quality evidence). The result is mainly based on platelet-derived wound healing formula (36/56 (64.28%) versus 7/27 (25.92%); RR 2.45, 95% 1.27 to 4.74; I(2) = 0%, two trials...

  12. Factores de crecimiento IV: Factor de crecimiento epidérmico,Factores estimuladores de colonias, Neurotropinas Growth factors: epidermal growth factor, colony stimulating factors and neurotropins

    Directory of Open Access Journals (Sweden)

    Hilda Norha Jaramillo Londoño

    1999-02-01

    Full Text Available En esta cuarta entrega sobre los factores de crecimiento se revisan el factor de crecimiento epidérmico (EGF, los factores estimuladores de colonias (CSF y las neurotropinas. Como se ha venido presentando en las anteriores entregas, se hace referencia a su estructura bioquímica, su mecanismo de acción, sus efectos biológicos y sus interacciones. Las neurotropinas y el EGF, por tratarse de factores que actúan predominantemente en el microambiente tisular, no pueden manejarse en el contexto de concentraciones circulantes, situación que sí es factible para los CSF. De otro lado, se revisan los mecanismos de las neurotropinas en el sistema nervioso. In this fourth review of growth factors we summarize, as in previous papers, topics related to biochemical structure, mechanisms of action, biological effects and cross-interactions for epidermal growth factor (EGF, colony stimulating factors (CSF and neurotropins. Since the effects of EGF and neurotropins are exerted predominantly at the microenvironment level, they can not be evaluated by means of its circulating levels, a fact that could be possible for CSFs.

  13. Family Factors in Small Family Business Growth

    National Research Council Canada - National Science Library

    Jim Cater; Marilyn Young

    2016-01-01

    .... We suggest that while all three patterns of small family business growth may lead to individual company success and sustainability, businesses with units in multiple trade areas may be most adept at managing the six family factors.

  14. Placental growth factor and vascular endothelial growth factor receptor-2 in human lung development.

    Science.gov (United States)

    Janér, Joakim; Andersson, Sture; Haglund, Caj; Karikoski, Riitta; Lassus, Patrik

    2008-08-01

    We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants. Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of 10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week. In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 +/- 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity. The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression in capillary endothelium in bronchopulmonary dysplasia

  15. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier;

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  16. Parathyroid Hormone-Related Protein Interacts With the Transforming Growth Factor-β/Bone Morphogenetic Protein-2/Gremlin Signaling Pathway to Regulate Proinflammatory and Profibrotic Mediators in Pancreatic Acinar and Stellate Cells.

    Science.gov (United States)

    Bhatia, Vandanajay; Cao, Yanna; Ko, Tien C; Falzon, Miriam

    2016-01-01

    Transforming growth factor β (TGF-β) regulates immune and fibrotic responses of chronic pancreatitis. The bone morphogenetic protein 2 (BMP-2) antagonist gremlin is regulated by TGF-β. Parathyroid hormone-related protein (PTHrP) levels are elevated in chronic pancreatitis. Here, we investigated the cross-talk between TGF-β/BMP-2/gremlin and PTHrP signaling. Reverse transcription/real-time polymerase chain reaction, chromatin immunoprecipitation, Western blotting, and transient transfection were used to investigate PTHrP regulation by TGF-β and BMP-2 and gremlin regulation by PTHrP. The PTHrP antagonist PTHrP (7-34) and acinar cells with conditional Pthrp gene deletion (PTHrP) were used to assess PTHrP's role in the proinflammatory and profibrotic effects of TGF-β and gremlin. Transforming growth factor β increased PTHrP levels in acinar cells and pancreatic stellate cells (PSCs) through a Smad3-dependent pathway. Transforming growth factor β's effects on levels of IL-6 and intercellular adhesion molecule 1 (ICAM-1) (acinar cells) and procollagen I and fibronectin (PSCs) were inhibited by PTHrP (7-34). PTHrP suppressed TGF-β's effects on IL-6 and ICAM-1. Parathyroid hormone-related hormone increased gremlin in acinar cells, and inhibiting gremlin action suppressed TGF-β's and PTHrP's effects on IL-6 and ICAM-1. Transforming growth factor β-mediated gremlin up-regulation was suppressed in PTHrP cells. Bone morphogenetic protein 2 suppressed PTHrP levels in PSCs. Parathyroid hormone-related hormone functions as a novel mediator of the proinflammatory and profibrotic effects of TGF-β. Transforming growth factor β and BMP-2 regulate PTHrP expression, and PTHrP regulates gremlin levels.

  17. Quantitative relations between corruption and economic factors

    CERN Document Server

    Shao, Jia; Podobnik, Boris; Stanley, H Eugene

    2007-01-01

    We report quantitative relations between corruption level and economic factors, such as country wealth and foreign investment per capita, which are characterized by a power law spanning multiple scales of wealth and investments per capita. These relations hold for diverse countries, and also remain stable over different time periods. We also observe a negative correlation between level of corruption and long-term economic growth. We find similar results for two independent indices of corruption, suggesting that the relation between corruption and wealth does not depend on the specific measure of corruption. The functional relations we report have implications when assessing the relative level of corruption for two countries with comparable wealth, and for quantifying the impact of corruption on economic growth and foreign investments.

  18. Fibroblast growth factor 23 and bone mineralisation

    Institute of Scientific and Technical Information of China (English)

    Yu-Chen Guo; Quan Yuan

    2015-01-01

    Fibroblast growth factor 23 (FGF23) is a hormone that is mainly secreted by osteocytes and osteoblasts in bone. The critical role of FGF23 in mineral ion homeostasis was first identified in human genetic and acquired rachitic diseases and has been further characterised in animal models. Recent studies have revealed that the levels of FGF23 increase significantly at the very early stages of chronic kidney disease (CKD) and may play a critical role in mineral ion disorders and bone metabolism in these patients. Our recent publications have also shown that FGF23 and its cofactor, Klotho, may play an independent role in directly regulating bone mineralisation instead of producing a systematic effect. In this review, we will discuss the new role of FGF23 in bone mineralisation and the pathophysiology of CKD-related bone disorders.

  19. Insulin-like growth factor 1 and hair growth.

    Science.gov (United States)

    Su, H Y; Hickford, J G; Bickerstaffe, R; Palmer, B R

    1999-11-01

    Insulin-like growth factor 1 (IGF-1) has been identified as an important growth factor in many biological systems.[1] It shares considerable structural homology with insulin and exerts insulin-like effects on food intake and glucose metabolism. Recently it has been suggested to play a role in regulating cellular proliferation and migration during the development of hair follicles. [2,3] To exert its biological effects, the IGF-1 is required to activate cells by binding to specific cell-surface receptors. The type I IGF receptor (IGF-1R) is the only IGF receptor to have IGF-mediated signaling functions.[1] In circulation, this growth factor mediates endocrine action of growth hormone (GH) on somatic growth and is bound to specific binding proteins (BPs). The latter control IGF transport, efflux from vascular compartments and association with cell surface receptors.[4] In tissues, IGF-1 is produced by mesenchymal type cells and acts in a paracrine and autocrine fashion by binding to the IGF-1R. This binding activates the receptor tyrosine kinase (RTK) that triggers the downstream responses and finally stimulates cell division.[5] IGF-1 may therefore be able to stimulate the proliferation of hair follicle cells through cellular signaling pathways of its receptors. Local infusion of IGF-1 into sheep has been reported to be capable of stimulating protein synthesis in the skin.[6] It may also increase the production of wool keratin. Recently, transgenic mice overexpressing IGF-1 in the skin have been shown to have earlier hair follicle development than controls.[7] In addition, this growth factor plays an important role in many cell types as a survival factor to prevent cell death.[8] This anti-apoptotic function of IGF-1 may be important to the development of follicle cells as follicles undergo a growth cycle where the regressive, catagen phase is apoptosis driven. In this review, the effects of IGF-1 on follicle cell proliferation and differentiation are discussed. In

  20. Organic growth factor requirements of some yeasts.

    Science.gov (United States)

    Madan, M; Gulati, N

    1980-01-01

    Some sporogenous yeasts (Brettanomyces bruxellensis, Debaryomyces hansenii, Hansenula ciferrii, Hansenula polymorpha, Pichia polymorpha, Saccharomycopsis guttulata, and Saccharomyces chevalieri), isolated from various fruits have been examined for their organic growth factor requisites. H. ciferrii was completely deficient in thiamine, biotin, inositol, riboflavin, niacin, and partially deficient in pantothenic acid. It required an external supply of 0.1-1.0 ppm thiamine, 0.01-0.1 ppm biotin, 10.0 ppm inositol, 0.10 ppm niacin and riboflavin for its optimum growth. H. polymorpha showed partial deficiency only in xanthine. P. polymorpha gave indications of partial deficiencies in thiamine and biotin. S. guttulata was completely deficient in biotin, and partially deficient in adenine sulphate. It required 0.01 ppm biotin for optimum growth. S chevalieri was completely deficient in pyridoxine and partially deficient in thiamine. It required 0.1 ppm pyridoxine for maximum growth. D. hansenii and B bruxellensis were auxoautotrophic for the various growth factors studied.

  1. Angiogenic factors in relation to embryo implantation

    Directory of Open Access Journals (Sweden)

    Azadeh Bagheri

    2014-08-01

    Full Text Available Disturbances in uterine blood supply are associated with higher perinatal morbidity and mortality caused by preterm delivery, preeclampsia or intrauterine growth restriction. Adaptation of the uterine vasculature to the rising needs of the fetus occurs through both vasodilation and development of new vessels. Angiogenesis is the process of neovascularization from pre-existing blood vessels in response to hypoxic condition of tissues. The endometrium, decidua and placenta are rich sources of angiogenic growth factors. In general, the angiogenic process is initiated by growth factors such as VEGF, placental growth factor (PlGF or bFGF. Through a complex signal transduction machinery mediated by respective receptor-tyrosine kinases, an increase in the permeability of the maternal vessels is achieved to permit growth and invasion of endothelial cells. Their chemotactic migration, formation of a vessel lumen, and functional maturation of new capillaries complete the angiogenic process that involves the expression of specific adhesion receptors and extracellular matrix-degrading proteases. During vasculogenesis, endothelial progenitor cells--angioblasts--form a primitive vascular network. This process occurs mainly during fetal development, although recruitment of angioblasts from bone marrow and peripheral blood in response to ischemic insult have been described in adults. In this review article we have described a recent complication related to angiogenic involvement in embryo implantation. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 872-879

  2. Elevation in fibroblast growth factor 23 and its value for identifying subclinical atherosclerosis in first-degree relatives of patients with diabetes

    Science.gov (United States)

    Hu, Xiang; Ma, Xiaojing; Luo, Yuqi; Xu, Yiting; Xiong, Qin; Pan, Xiaoping; Bao, Yuqian; Jia, Weiping

    2016-01-01

    Accumulating evidence supported an association between diabetes and fibroblast growth factor 23 (FGF23). The goal of the present study was to explore alteration in serum FGF23 levels and to assess its value for identifying subclinical atherosclerosis in normoglycemic individuals with a first-degree family history of diabetes (FHD). The study enrolled 312 subjects with a first-degree FHD and 1407 subjects without an FHD. Serum FGF23 levels were detected by a sandwich enzyme-linked immunosorbent assay. Serum FGF23 levels were much higher in subjects with a first-degree FHD than in those without an FHD (P = 0.006). A first-degree FHD was positively associated with serum FGF23 levels, independent of C-IMT and cardiovascular factors (both P < 0.05). In subjects with a first-degree FHD, only those with serum FGF23 levels in the upper quartile were more likely to have an increased C-IMT (odds ratio = 2.263, P < 0.05). As conclusions, a first-degree FHD contributes to the increased serum FGF23 levels independently. Subjects with a first-degree FHD need higher serum FGF23 levels to indicate subclinical atherosclerosis. The influence of a first-degree FHD on serum FGF23 levels should be considered to avoid overestimating the risk of cardiovascular disease in normoglycemic individuals with a first-degree FHD. PMID:27698482

  3. Transforming growth factor-β1 expression in endangered age-0 shortnose suckers (Chasmistes brevirostris) from Upper Klamath Lake, OR relative to histopathology, meristic, spatial, and temporal data

    Science.gov (United States)

    Ottinger, Christopher A.; Densmore, Christine L.; Robertson, Laura S.; Iwanowicz, Deborah; Vanderkooi, Scott P.

    2015-01-01

    During July – September of 2008, 2009, and 2010 endangered age-0 juvenile shortnose suckers were sampled from Upper Klamath Lake, OR in a health evaluation that included the measurement of transforming growth factor – beta (TGF-β) expression in spleen in combination with a histopathology assessment. This analysis was performed to determine if the expression of this immuno-regulator could be used as a component of a larger health evaluation intended to identify potential risk-factors that may help to explain why very few of these fish survive to age-1. Potential associations between TGF-β1 expression, histopathological findings, meristic data as well as temporal and spatial data were evaluated using analysis-of-variance. In this analysis, the absence or presence of opercula deformity and hepatic cell necrosis were identified as significant factors in accounting for the variance in TGF-β1 expression observed in age-0 shortnose suckers (n = 122, squared multiple R = 0.989). Location of sample collection and the absence or presence of anchor worms (Lernaea spp.) were identified as significant cofactors. The actual mechanisms involved with these relationships have yet to be determined. The strength, however, of our findings support the concept of using TGF-β1 expression as part of a broader fish health assessment and suggests the potential for using additional immunologic measures in future studies. Specifically, our results indicate that the measure of TGF-β1 expression in age-0 shortnose sucker health assessments can facilitate the process of identifying disease risks that are associated with the documented lack of recruitment into the adult population.

  4. Lifetime growth in wild meerkats: incorporating life history and environmental factors into a standard growth model.

    Science.gov (United States)

    English, Sinéad; Bateman, Andrew W; Clutton-Brock, Tim H

    2012-05-01

    Lifetime records of changes in individual size or mass in wild animals are scarce and, as such, few studies have attempted to model variation in these traits across the lifespan or to assess the factors that affect them. However, quantifying lifetime growth is essential for understanding trade-offs between growth and other life history parameters, such as reproductive performance or survival. Here, we used model selection based on information theory to measure changes in body mass over the lifespan of wild meerkats, and compared the relative fits of several standard growth models (monomolecular, von Bertalanffy, Gompertz, logistic and Richards). We found that meerkats exhibit monomolecular growth, with the best model incorporating separate growth rates before and after nutritional independence, as well as effects of season and total rainfall in the previous nine months. Our study demonstrates how simple growth curves may be improved by considering life history and environmental factors, which may be particularly relevant when quantifying growth patterns in wild populations.

  5. Engineering growth factors for regenerative medicine applications.

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Aaron C.; Briquez, Priscilla S.; Hubbell, Jeffrey A.; Cochran, Jennifer R.

    2016-01-15

    Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications.

  6. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes

    Directory of Open Access Journals (Sweden)

    Rutter Joni L

    2004-03-01

    Full Text Available Abstract Background Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs in eight genes involved in base excision repair (XRCC1, APEX, POLD1, BRCA1 protein interaction (BRIP1, ZNF350, BRCA2, and growth regulation (TGFß1, IGFBP3 were evaluated. Methods Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748 identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. Results Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR = 2.3; 95% CI 1.3–3.8; XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1–3.9; and BRIP1 (or BACH1 P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6–29.3. The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFß1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1 1845C>T, L66P, R501S, and S472P. Conclusion Some variants in genes within the base-excision repair pathway (XRCC1 and

  7. THE RELATIONS AMONG FIBROBLAST GROWTH FACTOR-1 FIBROBLAST GROWTH FACTOR RECEPTOR-1 AND THE PATHOLOGICAL GRADING IN HUMAN MENINGIOMAS%FGF-1及FGFR-1与人脑膜瘤病理分级的关系

    Institute of Scientific and Technical Information of China (English)

    姚曙光; 袁贤瑞

    2009-01-01

    Objective To study the ralations among the expressions of FGF-1,FGFR-1 and the pathological grading in human meningiomas by immunohistochemical staining method.Methods According to the hematoxylin and eosin staining,All of the 68 cases were assorted into 4 groups.The numbers of tumor cells immunohistochemically stained by FGF-1 and FGFR-1 were counted and analized.Results As to the expression of FGF-1,the differences between the two adjacent groups(Grade 0~Ⅰ,Ⅰ~Ⅱ and Ⅱ~Ⅲ) showed no significance(P>0.05),but significant diffences were found in other groups(P<0.01).As to the expression of FGFR-1,all groups except the groups of GradeⅡ~Ⅲ showed significant differences(P<0.05).Pearson correlations were significant at the 0.05 level between the expressions of FGF-1/FGFR-1 and the pathological grading,though partial correlation between FGF-1 and FGFR-1 was insignificant.Conclusion The expressions of FGF-1 and FGFR-1 have close relations to the pathological grading of human meningiomas.They may reflect the proliferative activities of meningioma cells but there is no correlation between them.%目的 应用免疫组织化学方法研究成纤维细胞生长因子-1(FGF-1)和成纤维细胞生长因子受体-1(FGFR-1)在人正常脑组织和脑膜瘤组织中的表达及其与人脑膜瘤病理分级的关系和二者间的相关关系.方法 68例标本常规HE染色,依据WHO 1990年脑膜瘤分型标准分为0~3级4组.按照石蜡切片微波修复抗原染色程序分别作FGF-1和FGFR-1免疫组织化学染色,观察其表达情况,计数阳性和阴性细胞,进行统计学分析.结果 病理级别相邻组间FGF-1表达阳性率的差别P>0.05,相隔组间FGF-1表达阳性率的差别P0.05,其它各组间FGFR-1表达阳性率的差别P0.05.结论 人脑膜瘤中FGF-1和FGFR-1的表达与其病理分级密切相关,可在一定程度上反应人脑膜瘤的恶性程度,恶性程度越高,表达越强;但FGF-1和FGFR-1二者间并无相关关系.

  8. Transforming growth factor-β and fibrosis

    Institute of Scientific and Technical Information of China (English)

    Franck Verrecchia; Alain Mauviel

    2007-01-01

    Transforming growth factor-β (TGF-β), a prototype of multifunctional cytokine, is a key regulator of extracellular matrix (ECM) assembly and remodeling. Specifically, TGF-β isoforms have the ability to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. Elevated TGF-β expression in affected organs, and subsequent deregulation of TGF-β functions, correlates with the abnormal connective tissue deposition observed during the onset of fibrotic diseases. During the last few years, tremendous progress has been made in the understanding of the molecular aspects of intracellular signaling downstream of the TGF-β receptors. In particular, Smad proteins, TGF-β receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, have been studied extensively. The role of Smad3 in the transcriptional regulation of type I collagen gene expression and in the development of fibrosis, demonstrated both in vitro and in animal models with a targeted deletion of Smad3, is of critical importance because it may lead to novel therapeutic strategies against these diseases. This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes.

  9. Fibroblast growth factor expression in the postnatal growth plate.

    Science.gov (United States)

    Lazarus, Jacob E; Hegde, Anita; Andrade, Anenisia C; Nilsson, Ola; Baron, Jeffrey

    2007-03-01

    Fibroblast growth factor (FGF) signaling is essential for endochondral bone formation. Mutations cause skeletal dysplasias including achondroplasia, the most common human skeletal dysplasia. Most previous work in this area has focused on embryonic chondrogenesis. To explore the role of FGF signaling in the postnatal growth plate, we quantitated expression of FGFs and FGF receptors (FGFRs) and examined both their spatial and temporal regulation. Toward this aim, rat proximal tibial growth plates and surrounding tissues were microdissected, and specific mRNAs were quantitated by real-time RT-PCR. To assess the FGF system without bias, we first screened for expression of all known FGFs and major FGFR isoforms. Perichondrium expressed FGFs 1, 2, 6, 7, 9, and 18 and, at lower levels, FGFs 21 and 22. Growth plate expressed FGFs 2, 7, 18, and 22. Perichondrial expression was generally greater than growth plate expression, supporting the concept that perichondrial FGFs regulate growth plate chondrogenesis. Nevertheless, FGFs synthesized by growth plate chondrocytes may be physiologically important because of their proximity to target receptors. In growth plate, we found expression of FGFRs 1, 2, and 3, primarily, but not exclusively, the c isoforms. FGFRs 1 and 3, thought to negatively regulate chondrogenesis, were expressed at greater levels and at later stages of chondrocyte differentiation, with FGFR1 upregulated in the hypertrophic zone and FGFR3 upregulated in both proliferative and hypertrophic zones. In contrast, FGFRs 2 and 4, putative positive regulators, were expressed at earlier stages of differentiation, with FGFR2 upregulated in the resting zone and FGFR4 in the resting and proliferative zones. FGFRL1, a presumed decoy receptor, was expressed in the resting zone. With increasing age and decreasing growth velocity, FGFR2 and 4 expression was downregulated in proliferative zone. Perichondrial FGF1, FGF7, FGF18, and FGF22 were upregulated. In summary, we have

  10. Insulin-like growth factor-related components and the risk of liver cancer in a nested case-control study.

    Science.gov (United States)

    Adachi, Yasushi; Nojima, Masanori; Mori, Mitsuru; Matsunaga, Yasutaka; Akutsu, Noriyuki; Sasaki, Shigeru; Endo, Takao; Kurozawa, Youichi; Wakai, Kenji; Tamakoshi, Akiko

    2016-11-01

    Insulin-like growth factor-1 (IGF1) is a potent mitogen. IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 levels and low IGFBP3 levels are associated with increased risk of several cancers. We examined relationships between serum levels of these factors and hepatoma risk in a case-control study nested in a prospective cohort study (the Japan Collaborative Cohort Study (JACC Study)). A baseline survey was conducted from 1988 to 1990, and 39,242 subjects donated blood samples. Participants diagnosed with hepatoma by 1997 were considered cases for nested case-control studies. Ninety-one cases and 263 sex- and age-matched controls were analyzed. A conditional logistic model was used to estimate odds ratios (ORs) for the incidence of hepatoma associated with serum IGF1 and IGFBP3 levels. Neither IGF1 nor the molar ratio of IGF1/IGFBP3 was correlated with hepatoma risk. After adjustment for hepatitis viral infection, body mass index, smoking, and alcohol intake, a higher molar difference of (IGFBP3 - IGF1) was associated with a decreased hepatoma risk more than IGFBP3 alone (p for trend <0.001 and = 0.003, respectively). People in the highest quartile had a lower risk (OR = 0.098; 95 % confidence interval = 0.026-0.368). In subgroup analyses of males and females, the molar difference was associated with a decreased hepatoma risk (p for trend <0.05). In non-elderly individuals, the difference was inversely correlated with the incidence of hepatoma (p for trend <0.01). The molar difference of (IGFBP3 - IGF1) may be inversely associated with the incidence of hepatoma.

  11. Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept).

    Science.gov (United States)

    El Bagdadi, K; Kubesch, A; Yu, X; Al-Maawi, S; Orlowska, A; Dias, A; Booms, P; Dohle, E; Sader, R; Kirkpatrick, C J; Choukroun, J; Ghanaati, S

    2017-03-21

    Purpose The present study evaluated the platelet distribution pattern and growth factor release (VEGF, TGF-β1 and EGF) within three PRF (platelet-rich-fibrin) matrices (PRF, A-PRF and A-PRF+) that were prepared using different relative centrifugation forces (RCF) and centrifugation times. Materials and methods immunohistochemistry was conducted to assess the platelet distribution pattern within three PRF matrices. The growth factor release was measured over 10 days using ELISA. Results The VEGF protein content showed the highest release on day 7; A-PRF+ showed a significantly higher rate than A-PRF and PRF. The accumulated release on day 10 was significantly higher in A-PRF+ compared with A-PRF and PRF. TGF-β1 release in A-PRF and A-PRF+ showed significantly higher values on days 7 and 10 compared with PRF. EGF release revealed a maximum at 24 h in all groups. Toward the end of the study, A-PRF+ demonstrated significantly higher EGF release than PRF. The accumulated growth factor releases of TGF-β1 and EGF on day 10 were significantly higher in A-PRF+ and A-PRF than in PRF. Moreover, platelets were located homogenously throughout the matrix in the A-PRF and A-PRF+ groups, whereas platelets in PRF were primarily observed within the lower portion. ​Discussion the present results show an increase growthfactor release by decreased RCF. However, further studies must be conducted to examine the extent to which enhancing the amount and the rate of released growth factors influence wound healing and biomaterial-based tissue regeneration. ​Conclusion These outcomes accentuate the fact that with a reduction of RCF according to the previously LSCC (described low speed centrifugation concept), growth factor release can be increased in leukocytes and platelets within the solid PRF matrices.

  12. Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein.

    Science.gov (United States)

    Demont, Yohann; Corbet, Cyril; Page, Adeline; Ataman-Önal, Yasemin; Choquet-Kastylevsky, Genevieve; Fliniaux, Ingrid; Le Bourhis, Xuefen; Toillon, Robert-Alain; Bradshaw, Ralph A; Hondermarck, Hubert

    2012-01-13

    The precursor of nerve growth factor (proNGF) has been described as a biologically active polypeptide able to induce apoptosis in neuronal cells, via the neurotrophin receptor p75(NTR) and the sortilin receptor. Herein, it is shown that proNGF is produced and secreted by breast cancer cells, stimulating their invasion. Using Western blotting and mass spectrometry, proNGF was detected in a panel of breast cancer cells as well as in their conditioned media. Immunohistochemical analysis indicated an overproduction of proNGF in breast tumors, when compared with benign and normal breast biopsies, and a relationship to lymph node invasion in ductal carcinomas. Interestingly, siRNA against proNGF induced a decrease of breast cancer cell invasion that was restored by the addition of non-cleavable proNGF. The activation of TrkA, Akt, and Src, but not the MAP kinases, was observed. In addition, the proNGF invasive effect was inhibited by the Trk pharmacological inhibitor K252a, a kinase-dead TrkA, and siRNA against TrkA sortilin, neurotensin, whereas siRNA against p75(NTR) and the MAP kinase inhibitor PD98059 had no impact. These data reveal the existence of an autocrine loop stimulated by proNGF and mediated by TrkA and sortilin, with the activation of Akt and Src, for the stimulation of breast cancer cell invasion.

  13. Skin tags and acanthosis nigricans in patients with hepatitis C infection in relation to insulin resistance and insulin like growth factor-1 levels

    Directory of Open Access Journals (Sweden)

    Omar Soliman El Safoury

    2012-01-01

    Full Text Available Background: Skin tags (ST are papillomas commonly found in the neck, axillae of middle-aged and elderly people Aim: Insulin and insulin-like growth factor (IGF-1 levels are affected by hepatitis C virus (HCV infection and both of them may be implicated in the etiopathogenesis of ST and acanthosis nigricans (AN through their proliferative and differentiating properties. So, the aim of this work was to evaluate the impact of HCV infection on ST and AN through the estimation of insulin resistance and IGF-1. Materials and Methods: Participants were arranged into four groups: (ST +ve / HCV +ve 23 subjects, (ST+ / HCV -ve 19 subjects, (HCV -ve / ST-ve 20 subjects and (ST-ve /HCV +ve 22 subjects. Age, ST size, color, number, AN, fasting glucose, fasting insulin, insulin resistance, IGF-1, HCV-antibodies (Ab were recorded. Results: The mean number of ST in Group 1 was half the number of ST in Group 2 (11.0±9.3 / 22.3±14.0 (P=0.005. The difference in insulin resistance between the same groups was non-significant (13.1±10.6 / 9.0±5.5 (P=0.441 while the difference in IGF-1 was statistically significant (218.6±46.2 /285.4±32.8 (P=0.002. The multivariate logistic regression for the variables revealed that insulin resistance is the only factor affecting the occurrence of ST (OR=1.096, P=0.023. Multivariate regression analysis for the variables showed that HCV was borderline but not a significant factor affecting the number of ST (Beta=-0.409, P=0.053. The number of patients with AN was doubled in Group 2 in comparison to Group 1 but this was non significant 3(13% / 6(32% (P=0.2800. Conclusion: HCV is associated with a significant decrease in the ST number and in the serum level of IGF-1 together with an obvious decrease in the occurrence of AN. Our results may point to the entrant effect of insulin resistance and IGF-1 in ST and AN development. The current study suggests the evaluation of IGF-1-lowering agents in the control of ST and AN especially in

  14. Effect of hepatocyte growth factor and transforming growth factor-β1 on atrial fibroblasts fibrosis

    Institute of Scientific and Technical Information of China (English)

    张建成

    2012-01-01

    Objective To investigate the effect of hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGFβ1) on the expression of α-smooth muscle actin(α-SMA) and collagen I in human atrial fibroblast in vitro, and to explore the possible molecular mechanism of atrial fibrosis in patients

  15. Simultaneous inhibition of epidermal growth factor receptor (EGFR) signaling and enhanced activation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-mediated apoptosis induction by an scFv : sTRAIL fusion protein with specificity for human EGFR

    NARCIS (Netherlands)

    Bremer, E; Samplonius, DF; van Genne, L; Dijkstra, MH; Kroesen, BJ; de Leij, LFMH; Helfrich, W

    2005-01-01

    Epidermal growth factor receptor (EGFR) signaling inhibition by monoclonal antibodies and EGFR-specific tyrosine kinase inhibitors has shown clinical efficacy in cancer by restoring susceptibility of tumor cells to therapeutic apoptosis induction. Tumor necrosis factor-related apoptosis-inducing lig

  16. Identifying factors related to Achilles tendon stress, strain, and stiffness before and after 6 months of growth in youth 10-14 years of age.

    Science.gov (United States)

    Neugebauer, Jennifer M; Hawkins, David A

    2012-09-21

    The purposes of this study were (1) determine if youth peak Achilles tendon (AT) strain, peak AT stress, and AT stiffness, measured during an isometric plantar flexion, differed after six months (mos) of growth, and (2) determine if sex, physical activity level (Physical Activity Questionnaire (PAQ-C)), and/or growth rate (GR) were related to these properties. AT stress, strain, and stiffness were quantified in 20 boys (13.47±0.81 years) and 22 girls (11.18±0.82 years) at 2 times (0 and 6 mos). GR (change in height in 6 mos) was not significantly different between boys and girls (3.5±1.4 and 3.4±1.1cm/6 mos respectively). Peak AT strain and stiffness (mean 3.8±0.4% and 128.9±153.6N/mm, respectively) did not differ between testing sessions or sex. Peak AT stress (22.1±2.4 and 24.0±2.1MPa at 0 and 6 mos, respectively) did not differ between sex and increased significantly at 6 mos due to a significant decrease in AT cross-sectional area (40.6±1.3 and 38.1±1.6mm(2) at 0 and 6 mos, respectively) with no significant difference in peak AT force (882.3±93.9 and 900.3± 65.5N at 0 and 6 mos, respectively). Peak AT stress was significantly greater in subjects with greater PAQ-C scores (9.1% increase with 1 unit increase in PAQ-C score) and smaller in subjects with faster GRs (13.8% decrease with 1cm/6 mos increase in GR). These results indicate that of the AT mechanical properties quantified, none differed between sex, and only peak AT stress significantly differed after 6 months and was related to GR and physical activity.

  17. Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.

    Science.gov (United States)

    Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Ovsiannikov, Daniel; Moormann, Oliver; Guballa, Christoph; Kress, Alexander; Truss, Michael C; Gerullis, Holger; Otto, Thomas; Barski, Dimitri; Niegisch, Günter; Albers, Peter; Frees, Sebastian; Brenner, Walburgis; Thüroff, Joachim W; Angeli-Greaves, Miriam; Seidel, Thilo; Roth, Gerhard; Volkert, Frank; Ebbinghaus, Rainer; Prager, Hans-Martin; Lukas, Cordula; Bolt, Hermann M; Falkenstein, Michael; Zimmermann, Anna; Klein, Torsten; Reckwitz, Thomas; Roemer, Hermann C; Hartel, Mark; Weistenhöfer, Wobbeke; Schöps, Wolfgang; Rizvi, S Adibul Hassan; Aslam, Muhammad; Bánfi, Gergely; Romics, Imre; Ickstadt, Katja; Hengstler, Jan G; Golka, Klaus

    2012-02-01

    Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

  18. Influence of single nucleotide polymorphisms in the myostatin and myogenic factor 5 muscle growth-related genes on the performance traits of Marchigiana beef cattle.

    Science.gov (United States)

    Sarti, F M; Lasagna, E; Ceccobelli, S; Di Lorenzo, P; Filippini, F; Sbarra, F; Giontella, A; Pieramati, C; Panella, F

    2014-09-01

    The Marchigiana is famous for its large body size and favorable dressing percentage. A myostatin (MSTN) gene mutation (a G to T transversion) was identified in the breed. The homozygote "GG" yields a "normal" phenotype, the homozygote "TT" yields a double muscled body shape but sometimes causes survival problems, and the heterozygote genotype produces an extremely muscled body without defects. In practice, Marchigiana "TT" homozygotes are culled from reproduction, but the heterozygotes are chosen as sires. The objective of this study was to assess genes involved in Marchigiana muscle development to improve selection procedures. The effects of the MSTN and myogenic factor 5 (MYF5) genes on the growth and muscle traits in the Marchigiana breed were assessed. The effects of MSTN together with the genotype of the causative mutation (g.874G > T) and the effects of the two SNP in the promoter were studied (g.-371T > A and g.-805G > C). The SNP effects were evaluated in a comparison between the means of the several genotypes or for the average gene substitution and dominance effect. Two hundred forty-nine bullocks were evaluated using a performance test. At the beginning and end of the trial, the animals were weighed and their bodies were measured every 21 d up to 12 mo of age. In addition to these observations, morphological scores and the BLUP indices were estimated at the end of the performance test. The obtained results suggested that the MSTN g.874G > T and MYF5 SNP could be considered in the selection program of the Marchigiana breed. A MSTN g.874G > T genotyping service for the breeders could help to avoid the "TT" genotype and to select for the "GT" genotype. The "AA" MYF5 SNP genotype could also be selected for even if good muscle development yields a certain size reduction.

  19. Fibroblast growth factor receptors in in vitro and in vivo chondrogenesis: relating tissue engineering using adult mesenchymal stem cells to embryonic development.

    Science.gov (United States)

    Hellingman, Catharine A; Koevoet, Wendy; Kops, Nicole; Farrell, Eric; Jahr, Holger; Liu, Wei; Baatenburg de Jong, Robert J; Frenz, Dorothy A; van Osch, Gerjo J V M

    2010-02-01

    Adult mesenchymal stem cells (MSCs) are considered promising candidate cells for therapeutic cartilage and bone regeneration. Because tissue regeneration and embryonic development may involve similar pathways, understanding common pathways may lead to advances in regenerative medicine. In embryonic limb development, fibroblast growth factor receptors (FGFRs) play a role in chondrogenic differentiation. The aim of this study was to investigate and compare FGFR expression in in vivo embryonic limb development and in vitro chondrogenesis of MSCs. Our study showed that in in vitro chondrogenesis of MSCs three sequential stages can be found, as in embryonic limb development. A mesenchymal condensation (indicated by N-cadherin) is followed by chondrogenic differentiation (indicated by collagen II), and hypertrophy (indicated by collagen X). FGFR1-3 are expressed in a stage-dependent pattern during in vitro differentiation and in vivo embryonic limb development. In both models FGFR2 is clearly expressed by cells in the condensation phase. No FGFR expression was observed in differentiating and mature hyaline chondrocytes, whereas hypertrophic chondrocytes stained strongly for all FGFRs. To evaluate whether stage-specific modulation of chondrogenic differentiation in MSCs is possible with different subtypes of FGF, FGF2 and FGF9 were added to the chondrogenic medium during different stages in the culture process (early or late). FGF2 and FGF9 differentially affected the amount of cartilage formed by MSCs depending on the stage in which they were added. These results will help us understand the role of FGF signaling in chondrogenesis and find new tools to monitor and control chondrogenic differentiation.

  20. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  1. Factors that determine the evolution of high-growth businesses

    Directory of Open Access Journals (Sweden)

    Oriol Amat

    2013-09-01

    Full Text Available Objective: The study herein discusses research aimed at elucidating the factors that contribute to a business’ ability to maintain high growth. Design/Methodology/Perspective: The database from the Iberian Balance Sheet Analysis System (SABI, from its initials in Spanish was used to identify 250 industrial Catalonian businesses with high growth during 2004-2007. These companies participated in a survey on strategies and management practices; in 2013, they were re-analyzed to investigate the factors that contributed to continued growth for certain companies. Contributions: Through diverse statistical techniques, business policies related to quality, innovation, internationalization and finance were shown to influence business growth and sustainability over time. Limitations of the Research: This study focuses on industrial businesses at least ten years old in Catalonia; thus, the conclusions may differ in other geographic locations and economic sectors, as well as for smaller businesses. Practical Implications: Because growth is a measure of business success, identifying variables that contribute to high growth and its sustainability is helpful for businesses that seek to adopt effective policies. Social Implications: Generating employment is one of the primary contributions by high-growth businesses. For years with high unemployment, authorities may be interested in corporate policies that strengthen high-growth businesses. Originality/Added Value: High-growth businesses have been studied throughout the world, but this is the first study to investigate the evolution of businesses after a high-growth phase.

  2. Growth factor interactions in bone regeneration

    NARCIS (Netherlands)

    Kempen, D.H.R.; Creemers, L.B.; Alblas, J.; Lu, L.; Verbout, A.J.; Yaszemski, M.J.; Dhert, W.J.A.

    2010-01-01

    Growth factor interactions in bone regeneration. Diederik H R Kempen, Laura B Creemers, Jacqueline Alblas, Lichun Lu, Abraham J Verbout, Michael J Yaszemski and Wouter J A Dhert 1 Department of Orthopedics, University Medical Center , Utrecht, The Netherlands . AbstractBuy the PDF Pubmed abstract

  3. Growth Factor Interactions in Bone Regeneration

    NARCIS (Netherlands)

    Kempen, Diederik H. R.; Creemers, Laura B.; Alblas, Jacqueline; Lu, Lichun; Verbout, Abraham J.; Yaszemski, Michael J.; Dhert, Wouter J. A.

    2010-01-01

    Bone regeneration is a complex process regulated by a large number of bioactive molecules. Many growth factors and cytokines involved in the natural process of bone healing have been identified and tested as potential therapeutic candidates to enhance the regeneration process. Although many of these

  4. Growth factor interactions in bone regeneration

    NARCIS (Netherlands)

    Kempen, D.H.R.; Creemers, L.B.; Alblas, J.; Lu, L.; Verbout, A.J.; Yaszemski, M.J.; Dhert, W.J.A.

    2010-01-01

    Growth factor interactions in bone regeneration. Diederik H R Kempen, Laura B Creemers, Jacqueline Alblas, Lichun Lu, Abraham J Verbout, Michael J Yaszemski and Wouter J A Dhert 1 Department of Orthopedics, University Medical Center , Utrecht, The Netherlands . AbstractBuy the PDF Pubmed abstract Ge

  5. Discerning environmental factors affecting current tree growth in Central Europe.

    Science.gov (United States)

    Cienciala, Emil; Russ, Radek; Šantrůčková, Hana; Altman, Jan; Kopáček, Jiří; Hůnová, Iva; Štěpánek, Petr; Oulehle, Filip; Tumajer, Jan; Ståhl, Göran

    2016-12-15

    We examined the effect of individual environmental factors on the current spruce tree growth assessed from a repeated country-level statistical landscape (incl. forest) survey in the Czech Republic. An extensive set of variables related to tree size, competition, site characteristics including soil texture, chemistry, N deposition and climate was tested within a random-effect model to explain growth in the conditions of dominantly managed forest ecosystems. The current spruce basal area increment was assessed from two consecutive landscape surveys conducted in 2008/2009 and six years later in 2014/2015. Tree size, age and competition within forest stands were found to be the dominant explanatory variables, whereas the expression of site characteristics, environmental and climatic drives was weaker. The significant site variables affecting growth included soil C/N ratio and soil exchangeable acidity (pH KCl; positive response) reflecting soil chemistry, long-term N-deposition (averaged since 1975) in combination with soil texture (clay content) and Standardized Precipitation Index (SPI), a drought index expressing moisture conditions. Sensitivity of growth to N-deposition was positive, although weak. SPI was positively related to and significant in explaining tree growth when expressed for the growth season. Except SPI, no significant relation of growth was determined to altitude-related variables (temperature, growth season length). We identified the current spruce growth optimum at elevations about 800ma.s.l. or higher in the conditions of the country. This suggests that at lower elevations, limitation by a more pronounced water deficit dominates, whereas direct temperature limitation may concern the less frequent higher elevations. The mixed linear model of spruce tree growth explained 55 and 65% of the variability with fixed and random effects included, respectively, and provided new insights on the current spruce tree growth and factors affecting it within the

  6. A growth factor phenotype map for ovine preimplantation development.

    Science.gov (United States)

    Watson, A J; Watson, P H; Arcellana-Panlilio, M; Warnes, D; Walker, S K; Schultz, G A; Armstrong, D T; Seamark, R F

    1994-04-01

    The reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the patterns of expression for several growth factor ligand and receptor genes during ovine preimplantation development. Transcripts for insulin-like growth factor (IGF)-I, IGF-II, and the receptors for insulin and IGF-I were detected throughout ovine preimplantation development from the 1-cell to the blastocyst stage. Transforming growth factor alpha (TGF alpha) transcripts were also detected throughout ovine preimplantation development. The mRNAs encoding basic fibroblast growth factor (bFGF) were detected in all stages of the ovine preimplantation embryo, although the relative abundance of this transcript consistently decreased from the 1-cell to the blastocyst stage, suggesting that it may represent a maternal transcript in early sheep embryos. Transcripts encoding ovine trophoblast protein (oTP) were detected only within blastocyst-stage embryos. Primary ovine oviduct cell cultures express the transcripts for IGF-II, IGF-I, TGF alpha, bFGF, TGF beta 1, and the receptors for insulin and IGF-I, suggesting that paracrine growth factor circuits may exist between the oviduct epithelium and the early ovine embryo. Transcripts for insulin, epidermal growth factor (EGF), and nerve growth factor (NGF) were not detected in any stage of the ovine preimplantation embryo or within the oviduct cell preparations. The expression of growth factor transcripts very early in mammalian development would predict that these molecules fulfil a necessary role(s) in supporting the progression of early embryos through the preimplantation interval. Our future efforts will be directed to understanding the nature of these putative regulatory pathways.

  7. Fibroblast growth factor 23 and its receptors.

    Science.gov (United States)

    Yu, Xijie; White, Kenneth E

    2005-08-01

    Fibroblast growth factor 23 (FGF23) is a circulating factor that plays critical roles in phosphate and vitamin D metabolism, as evidenced by the fact that FGF23 missense mutations cause autosomal dominant hypophosphatemic rickets (ADHR). Autosomal dominant hypophosphatemic rickets is characterized by hypophosphatemia with inappropriately normal 1,25-dihydroxyvitamin D concentrations, as well as bone pain, fracture and rickets. This phenotype parallels that of patients with tumor induced osteomalacia (TIO), X-linked hypophosphatemic rickets (XLH), and fibrous dysplasia (FD), in whom elevated serum FGF23 levels are often observed. The fibroblast growth factor receptors (FGFR1-4) play key roles in skeletal development, as well as in normal metabolic processes. Several FGFR isoforms that potentially mediate the activity of FGF23 have been implicated. In the short term, these findings will lead to further understanding of FGF23 function, and potentially in the long term, to targeted therapies in disorders of hypo- and hyperphosphatemia that involve FGF23.

  8. The epidermal growth factor system in Caenorhabditis elegans.

    Science.gov (United States)

    Moghal, Nadeem; Sternberg, Paul W

    2003-03-10

    The single known epidermal growth factor-like growth factor and single epidermal growth factor receptor in Caenorhabditis elegans mediate two types of processes, each via a distinct signal transduction pathway. Several instances of cell fate specification during organogenesis require the RAS-MAP kinase pathway, as well as multiple nuclear factors. By contrast, appropriate myoepithelial contractions during ovulation involve IP3-mediated signal transduction. Positive modulators of the RAS pathway include KSR, SUR-8, phosphatase PP2A, and a zinc cation diffusion facilitator. Negative regulators of the RAS pathway include homologs of CBL, GAP-1, ACK, and MAP kinase phosphatase, while negative regulators of the IP3 pathway are enzymes that modify IP3. In addition to its stimulation of RAS activity, the GRB2 homolog SEM-5 acts negatively on both signaling pathways, as does the Ack-related kinase ARK-1.

  9. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    LENUS (Irish Health Repository)

    Sands, Michelle

    2011-01-25

    Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2) or hypoxia (10% O2) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or potentiate the

  10. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    Directory of Open Access Journals (Sweden)

    McLoughlin Paul

    2011-01-01

    Full Text Available Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2 or hypoxia (10% O2 for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA, VEGFB, placenta growth factor (PlGF, VEGF receptor 1 (VEGFR1 and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or

  11. Future directions with platelet growth factors.

    Science.gov (United States)

    Kuter, D J

    2000-04-01

    Since the purification of thrombopoietin 6 years ago, c-Mpl ligands such as recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) have undergone extensive clinical investigation. Both recombinant forms have been shown to reduce the thrombocytopenia associated with nonmyeloablative chemotherapy. Several areas of research have been identified for further clinical development of c-Mpl ligands. One future direction is to continue to explore the intravenous route of administration of rhTPO and PEG-rHuMGDF, as well as fusion proteins of interleukin-3-thrombopoietin and thrombopoietin peptide mimetics, which may be as potent as thrombopoietin, but may lack antigenicity. Another focus would be on the use of these molecules in treating non-chemotherapy-induced thrombocytopenia associated with myelodysplastic syndrome (MDS), idiopathic thrombocytopenic purpura (ITP), human immunodeficiency virus (HIV)-related ITP, and liver disease. Additionally, c-Mpl ligands may have a role in improving apheresis yields when administered to normal platelet donors. Considerable data demonstrate the effectiveness of PEG-rHuMGDF in raising the platelet yields in apheresis donors. In the past few years, investigation into the use of thrombopoietin for ex vivo expansion of pluripotent stem cells has been extensive. Last, thrombopoietin may serve as a radioprotectant by preventing radiation-induced apoptosis of pluripotent stem cells. In the coming years, the clinical role of rhTPO, PEG-rHuMGDF, and related molecules such as the thrombopoietin peptide mimetics will probably be established for both chemotherapeutic and nonchemotherapeutic indications.

  12. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

    Science.gov (United States)

    Tolonen, Jukka; Grönblad, Mats; Vanharanta, Heikki; Virri, Johanna; Guyer, Richard D; Rytömaa, Tapio; Karaharju, Erkki O

    2006-05-01

    Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus

  13. Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

    Directory of Open Access Journals (Sweden)

    Ashraf Soliman

    2014-01-01

    Full Text Available Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS. The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS.

  14. Dual delivery of vascular endothelial growth factor and hepatocyte growth factor coacervate displays strong angiogenic effects.

    Science.gov (United States)

    Awada, Hassan K; Johnson, Noah R; Wang, Yadong

    2014-05-01

    Controlled delivery of multiple growth factors (GFs) holds great potential for the clinical treatment of ischemic diseases and might be more therapeutically effective to reestablish vasculature than the provision of a single GF. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are two potent angiogenic factors. However, due to rapid degradation and dilution in the body, their clinical potential will rely on an effective mode of delivery. A coacervate, composed of heparin and a biodegradable polycation, which protects GFs from proteolysis and potentiates their bioactivities, is developed. Here, the coacervate incorporates VEGF and HGF and sustains their release for at least three weeks. Their strong angiogenic effects on endothelial cell proliferation and tube formation in vitro are confirmed. Furthermore, it is demonstrated that coacervate-based delivery of these factors has stronger effects than free application of both factors and to coacervate delivery of each GF separately.

  15. The prognostic value of epidermal growth factor receptor is related to tumor differentiation and the overall treatment time of radiotherapy in squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Steiniche, Torben; Askaa, Jon;

    2004-01-01

    Accelerated repopulation in head-and-neck carcinomas might be related to the expression of proliferative factors such as epidermal growth factor receptor (EGFr). The present study focuses on the prognostic value of EGFr for T-site control and the relation to tumor cell differentiation and overall......-size and well-differentiated tumors was associated with a high degree of staining (p = 0.001 and p = 0.002, respectively). EGFr was of poor prognostic influence regarding local control in patients treated with 9 weeks split-course, whereas the opposite was found for patients given accelerated treatment in 5...... weeks. A similar relationship between outcome, overall treatment time, and differentiation has previously been shown. The two parameters were analyzed together by separating the tumors with low EGFr and/or poor differentiation from tumors with well/moderate differentiation and high EGFr, resulting...

  16. Fibroblast growth factor 23--et fosfatregulerende hormon

    DEFF Research Database (Denmark)

    Beck-Nielsen, Signe Sparre; Pedersen, Susanne Møller; Kassem, Moustapha

    2010-01-01

    Fibroblast growth factor 23 (FGF23) is a recently identified phosphatonin. Its main physiological functions are to maintain serum phosphate within its reference range and to counter regulate the effects of vitamin D. Diseases correlated to high serum values of FGF23 are hypophosphatemic rickets......, fibrous dysplasia, and tumour-induced osteomalacia. In contrast, hyperphosphatemic tumoral calcinosis is associated with accelerated degradation of FGF23. Measuring FGF23 serves as a differential diagnostic tool in elucidating conditions of long-lasting hypophosphatemia....

  17. Cellular signaling by fibroblast growth factor receptors.

    Science.gov (United States)

    Eswarakumar, V P; Lax, I; Schlessinger, J

    2005-04-01

    The 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosine kinases (RTKs) designated FGFR1, FGFR2, FGFR3 and FGFR4. Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and to induce the pleiotropic responses that lead to the variety of cellular responses induced by this large family of growth factors. A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development. Gain of function mutations in FGFRs were also identified in a variety of human cancers such as myeloproliferative syndromes, lymphomas, prostate and breast cancers as well as other malignant diseases. The binding of FGF and HSPG to the extracellular ligand domain of FGFR induces receptor dimerization, activation and autophosphorylation of multiple tyrosine residues in the cytoplasmic domain of the receptor molecule. A variety of signaling proteins are phosphorylated in response to FGF stimulation including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape. The docking proteins FRS2alpha and FRS2beta are major mediators of the Ras/MAPK and PI-3 kinase/Akt signaling pathways as well as negative feedback mechanisms that fine-tune the signal that is initiated at the cell surface following FGFR stimulation.

  18. Fibroblast growth factor 19 entry into brain

    OpenAIRE

    Hsuchou, Hung; Pan, Weihong; Kastin, Abba J.

    2013-01-01

    Background Fibroblast growth factor (FGF)-19, an endocrine FGF protein mainly produced by the ileum, stimulates metabolic activity and alleviates obesity. FGF19 modulates metabolism after either intravenous or intracerebroventricular injection, and its receptor FGFR4 is present in the hypothalamus. This led to the question whether blood-borne FGF19 crosses the blood-brain barrier (BBB) to exert its metabolic effects. Methods We determined the pharmacokinetics of FGF19 permeation from blood to...

  19. Circulating vascular endothelial growth factor during the normal menstrual cycle

    NARCIS (Netherlands)

    Kusumanto, YH; Hospers, GAP; Sluiter, WJ; Dam, WA; Meijer, C; Mulder, NH

    2004-01-01

    Background: The purpose of the study was to investigate whether cycle-related variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would increase the metastatic potential at specific times during the menstrual cycle. Materials and Methods: VEGF levels in serum and whole blood

  20. Circulating vascular endothelial growth factor during the normal menstrual cycle

    NARCIS (Netherlands)

    Kusumanto, YH; Hospers, GAP; Sluiter, WJ; Dam, WA; Meijer, C; Mulder, NH

    2004-01-01

    Background: The purpose of the study was to investigate whether cycle-related variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would increase the metastatic potential at specific times during the menstrual cycle. Materials and Methods: VEGF levels in serum and whole blood w

  1. Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Steffensen, Karina Dahl; Olsen, Dorte Aalund

    2012-01-01

    New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis.......New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis....

  2. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications

    Science.gov (United States)

    Ciarmela, Pasquapina; Islam, Md. Soriful; Reis, Fernando M.; Gray, Peter C.; Bloise, Enrrico; Petraglia, Felice; Vale, Wylie; Castellucci, Mario

    2011-01-01

    BACKGROUND Growth factors are proteins secreted by a number of cell types that are capable of modulating cellular growth, proliferation and cellular differentiation. It is well accepted that uterine cellular events such as proliferation and differentiation are regulated by sex steroids and their actions in target tissues are mediated by local production of growth factors acting through paracrine and/or autocrine mechanisms. Myometrial mass is ultimately modified in pregnancy as well as in tumour conditions such as leiomyoma and leiomyosarcoma. Leiomyomas, also known as fibroids, are benign tumours of the uterus, considered to be one of the most frequent causes of infertility in reproductive years in women. METHODS For this review, we searched the database MEDLINE and Google Scholar for articles with content related to growth factors acting on myometrium; the findings are hereby reviewed and discussed. RESULTS Different growth factors such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), heparin-binding EGF (HB-EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and TGF-β perform actions in myometrium and in leiomyomas. In addition to these growth factors, activin and myostatin have been recently identified in myometrium and leiomyoma. CONCLUSIONS Growth factors play an important role in the mechanisms involved in myometrial patho-physiology. PMID:21788281

  3. Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guangshun Zheng; Yongjie Yang; Xiubin Fang

    2006-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied.OBJECTIVE:To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion.DESIGN: Randomized controlled animal study.SETTING:Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University.MATERIALS:A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA),and NGF (1 × 106 U/L, 0.5 mL, Siweite Company, Dalian).METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to duly 20055. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1 ×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham

  4. Enhanced Phosphoproteomic Profiling Workflow For Growth Factor Signaling Analysis

    DEFF Research Database (Denmark)

    Sylvester, Marc; Burbridge, Mike; Leclerc, Gregory;

    2010-01-01

    Background Our understanding of complex signaling networks is still fragmentary. Isolated processes have been studied extensively but cross-talk is omnipresent and precludes intuitive predictions of signaling outcomes. The need for quantitative data on dynamic systems is apparent especially for our...... A549 lung carcinoma cells were used as a model and stimulated with hepatocyte growth factor, epidermal growth factor or fibroblast growth factor. We employed a quick protein digestion workflow with spin filters without using urea. Phosphopeptides in general were enriched by sequential elution from...... transfer dissociation adds confidence in modification site assignment. The workflow is relatively simple but the integration of complementary techniques leads to a deeper insight into cellular signaling networks and the potential pharmacological intervention thereof....

  5. Curcumin, the main active constituent of turmeric (Curcuma longa L.), induces apoptosis in hepatic stellate cells by modulating the abundance of apoptosis-related growth factors.

    Science.gov (United States)

    He, Ya-Jun; Kuchta, Kenny; Lv, Xia; Lin, Yu; Ye, Guo-Rong; Liu, Xu-You; Song, Hui-Dong; Wang, Le-Xin; Kobayashi, Yuta; Shu, Jian-Chang

    2015-11-01

    In order to elucidate the mechanism of action of curcumin against hepatic fibrosis, cultured rat hepatic stellate cells (HSC) (HSC-T6) were incubated with curcumin for 24 h, after which apoptosis was measured by flow-cytometry. The protein levels of the pro-apoptotic factors Fas and p53b as well as of the anti-apoptotic factor Bcl-2 were monitored by immunocytochemical ABC staining after incubation with curcumin for 24 h. In the case of 20 μM curcumin, not only was the respective apoptosis index increased, but also the abundance of the pro-apoptotic factors Fas and p53 were amplified, whereas that of the anti-apoptotic factor Bcl-2 decreased. All these effects were highly reproducible (P<0.05). Consequently, curcumin has an up-regulating effect on pro-apoptotic factors like Fas and p53 as well as a down-regulating effect of the anti-apoptotic factor Bcl-2, thus inducing apoptosis in HSC.

  6. Analytically Derived Wind Wave Growth Relations

    Institute of Scientific and Technical Information of China (English)

    管长龙; 孙群

    2002-01-01

    By the use of the 3/2 power law presented by Toba combined with the significant wave energy balance equation forwind wave, wind wave growth at a limited fetch is analytically investigated. The new wind wave growth relations(WWGRs) are analytically derived with sheltering coefficient and wind drag coefficient as parameters. The geometricalaverage of observational values of sheltering coefficient and the arithmetic average of observational values of wind drag co-efficient are applied to determine the new WWGRs. Comparisons with existing empirical WWGRs are made.

  7. Extracellular matrix-inspired growth factor delivery systems for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Martino, Mikaël M. [Osaka Univ. (Japan). Immunology Frontier Research Center; Briquez, Priscilla S. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Maruyama, Kenta [Osaka Univ. (Japan). Immunology Frontier Research Center; Hubbell, Jeffrey A. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Univ. of Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-04-17

    Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of the ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.

  8. Happiness and related factors in pregnant women.

    Science.gov (United States)

    Jayasvasti, Kanthika; Kanchanatawan, Buranee

    2005-09-01

    Pregnancy is a crisis in the human life cycle as an important turning point in aspects of anatomical, physiological and psychosocial changes. An unhappy pregnanus could influence the fetal growth and development and sense of maternal competence as well as bonding with the fetus which profoundly affect the nurture of the infant after delivery. The authors'purposes were to study happiness and related factors in pregnant women having antenatal care at King Chulalongkorn Memorial Hospital. Four hundred and thirty-eight pregnant women from the antenatal clinic at King Chulalongkorn Memorial Hospital were randomly selected to complete a set of questionnaires that consisted of personal information, pregnant information, The Oxford Happiness Questionnaire (OHQ), The Maudsley Personality Inventory (MPI) and The Marital Satisfaction Scale (MSS). Prevalence of happiness level was classified by descriptive analysis. Unpaired t-test, ANOVA and Pearson's Product Moment Correlation analyzed related factors to happiness in pregnant woman. Also Stepwise Multiple Regression Analysis was used to define predictive factors for happiness in pregnant women. The sample had a high level of happiness of 57.3%. Significant related factors to happiness were age between 31-35 years, high education level, high individual and family income, having saving deposition, no drug abuse, improved marital relationship, no conflict with relatives, extrovert and stable personality types and no concerns about post-partum body image. Four predictive factors for happiness in pregnant women were extrovert personality, stable personality, high family income and improved marital relationship. Level of happiness in pregnant women could be predicted by type of personality, family income and marital relationship.

  9. EXPRESSION OF GROWTH-FACTORS AND GROWTH-FACTOR RECEPTORS IN NORMAL AND TUMOROUS HUMAN THYROID TISSUES

    NARCIS (Netherlands)

    van der Laan, B.F.A.M.; FREEMAN, JL; ASA, SL

    1995-01-01

    A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates w

  10. The multiple interactions between growth factors and microenvironment in vivo

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Cell, growth factors and extracellular matrices (ECMs) coexist in a dynamic tissue envi- ronment. A knowledge of multiple interactions among them is highly important for effectively raising the biological activities of growth factors, regulating cell life cycle, designing and preparing exogenous mat- rices to control growth factors release in tissue or organ regeneration by engineering means. This paper addresses the characteristics and functions of growth factors, interactions between growth factors and ECMs, the manners and correlative signaling of growth factors acting on cells, and briefly summarizes the biomimetic requisites for controlled release mat- rices, hoping to provide a useful reference for co- rrelative research in tissue engineering.

  11. Port type is a possible risk factor for implantable venous access port-related bloodstream infections and no sign of local infection predicts the growth of gram-negative bacilli.

    Science.gov (United States)

    Hsu, Jui-Feng; Chang, Hsu-Liang; Tsai, Ming-Ju; Tsai, Ying-Ming; Lee, Yen-Lung; Chen, Pei-Huan; Fan, Wen-Chieh; Su, Yu-Chung; Yang, Chih-Jen

    2015-09-30

    Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial. We retrospectively reviewed all patients who received IVAPs at a Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous port, BardPort® 6.6 fr (Bard port) and Autosuture Chemosite® 7.5 fr (TYCO port) were used. All patients with clinically proven venous port-related BSIs were enrolled. A total of 552 patients were enrolled. There were 34 episodes of IVAP-related BSIs during the study period for a total incidence of 0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95% confidence interval (CI), 1.688-29.904), p = 0.0075), age > 65 years (HR = 2.320 (95 % CI, 1.179-4.564), p = 0.0148), and lung cancer (HR = 5.807 (95% CI, 2.946-11.447), p gram-negative bacilli (p = 0.031). TYCO venous ports, age > 65 years, and lung cancer were all significant risk factors for IVAP-related BSIs, and no sign of infection was significantly associated with the growth of gram-negative bacilli.

  12. Related factors of dilated cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Guangyong Huang; Hang Gao; Xiangang Meng; Zhonghua Yan; Xiangquan Kong; Lexin Wang

    2009-01-01

    Objective To investigate the etiology and relative factors of dilated cardiomyopathy (DCM) in Chinese patients. Methods A case-control study was conducted to compare 233 patients with DCM in high-incidence areas (case group) and 150 patients with stable angina pectoris (control group). Life styles and history of diseases information was collected by questionaire; human anti-myocardial antibody IgG (AMA- IgG), human Coxsackie B virus IgG (CBV- IgG) and human adenovirus antibody IgG (ADV- lgG) were measured with ELISA. General chemical and toxicological indicators in drink water from high and low prevalence areas and serum trace elements also were compared. Results 1 ) Compared with the control group, the case group had more farmers (P < 0.01), with low average incomes (P < 0.01), higher alcohol consumption (P < 0.01) and higher incidence of the history of myocarditis (P < 0.01 ). 2) AMA-IgG, CBV-IgG and ADV-IgG levels were low and the positive rates ofAMA-IgG, CBV-IgG and ADV-IgG of patients with DCM were respectively 7.78%, 6.67% and 6.67%, no statistical significance comparing with those in the control group. 3) The content of iron (1.36±2.18 vs 0.39±0.67 mg/L, P<0.05) and manganese (0.384±0.35 vs 0.15±0.14, P<0.01 ) in drinking water of high-incidence areas was significantly higher than that in low-incidence areas. 4) The content of serum iron (69.14±57.8 vs 20.04±17.5 μ mol/L, P<0.01 ) and copper (25.74±4.2 vs 19.7±4.5 μmol/L, P<0.01) in the case group evidently exceeded the normal range and obviously higher than that in the control group. Conclusions 1) The incidence of some DCM is related with low incomes, high alcohol consumption and myocarditis. 2) These data do not support that DCM is related with persistent virus infection and autoimmunization; 3) Iron and manganese contents exceeding standards in drinking water and the high content of serum iron and copper is comparatively related with the incidence of DCM.

  13. Parental factors associated with intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Hăşmăşanu Monica G.

    2015-01-01

    Full Text Available Introduction. Linear growth failure is caused by multiple factors including parental factors. Objective. The aim of this study was to evaluate parental risk factors for intrauterine growth restriction (IUGR on a population of Romanian newborn infants in a tertiary level maternity facility for a period of 2.5 years. Methods. A retrospective matched case-control study was conducted in the Emergency County Hospital of Cluj-Napoca, a university hospital in North-Western Romania. The sample was selected from 4,790 infants admitted to the Neonatal Ward at 1st Gynecology Clinic between January 2012 and June 2014. Results. The age of mothers was significantly lower in the IUGR group compared to controls (p=0.041. A significantly higher percentage of mothers had hypertension in the IUGR group compared to those in the control group (p0.13. The age of fathers of infants with IUGR proved significantly lower compared to controls (p=0.0278. The analysis of infants’ comorbidities revealed no significant difference between groups for respiratory distress, hyperbilirubinemia, hypocalcaemia, and heart failure (p>0.27. Intracranial hemorrhage, necrotizing enterocolitis and hypoglycemia were significantly higher in the IUGR group compared to controls. The logistic regression identified hypertension as a significant risk factor for IUGR (OR=2.4, 95% CI [1.3-4.5]. Conclusion. Although the age of the mothers and fathers proved significantly lower in the IUGR group compared to controls, only hypertension in the mothers proved significant risk factors for IUGR.

  14. Factores de crecimiento III: factores transformadores del crecimiento (TGF Growth factors III part: transforming growth factors (TGF

    Directory of Open Access Journals (Sweden)

    Hilda Norha Jaramillo Londoño

    1996-04-01

    Full Text Available Se presenta una revisión de los conceptos básicos sobre los factores transformadores del crecimiento, tanto alfa como beta, incluyendo los siguientes aspectos: consideraciones generales, estructura bioquímica, concentraciones, proteínas transportadoras, receptores, mecanismos de acción y efectos biológicos. A review is presented on the basic concepts of Transforming Growth Factors both a and p; it includes general considerations, biochemical structure, concentrations, binding proteins, receptors, mechanisms of action, and biological effects.

  15. Role of hypoxia-related proteins in invasion of ameloblastoma cells: crosstalk between NOTCH1, hypoxia-inducible factor 1α, a disintegrin and metalloproteinase 12, and heparin-binding epidermal growth factor.

    Science.gov (United States)

    da Costa, Natacha Malu Miranda; Fialho, Amanda Dalla Vechia; Proietti, Carolina Carmine; da Silva Kataoka, Maria Sueli; Jaeger, Ruy Gastaldoni; de Alves-Júnior, Sérgio Melo; de Jesus Viana Pinheiro, João

    2016-07-01

    Ameloblastoma AME is a benign tumour characterized by local invasiveness, high recurrence rates, and diverse histological patterns. The oxygen concentration is reduced in specific areas of the tumour microenvironment, which leads to intratumoral hypoxia. Crosstalk between NOTCH1, a disintegrin and metalloproteinase 12 (ADAM-12), hypoxia-inducible factor 1α (HIF-1α) and heparin-binding epidermal growth factor (HB-EGF) under hypoxic conditions has been implicated in invadopodia formation, tumour invasiveness, and metastasis development. The aim of this study was to analyse the expression of these proteins, in order to further elucidate the mechanisms underlying AME invasiveness. Twenty cases of AME, eight calcifying cystic odontogenic tumours CCOTs and 10 samples of dental follicle were used to investigate the expression of these proteins by immunohistochemistry with the primary antibodies anti-NOTCH1, anti-ADAM-12, anti-HIF-1α, and anti-HB-EGF. Immunostaining results were expressed as the percentage of stained area in images acquired in an AxioScope microscope equipped with an AxioCamHRc camera and a × 40 objective. The results showed that immunoexpression of all proteins was higher in the AME samples than in the CCOT and dental follicle samples (P < 0.05). AME showed an increased presence of proteins associated with tumour invasiveness, which indicates a possible role of these proteins in the biological behaviour of this tumour. © 2015 John Wiley & Sons Ltd.

  16. Fibroblast growth factor 23 - et fosfatregulerende hormon

    DEFF Research Database (Denmark)

    Beck-Nielsen, Signe; Pedersen, Susanne Møller; Kassem, Moustapha

    2010-01-01

    Fibroblast growth factor 23 (FGF23) er et nyligt identificeret fosfatonin. FGF23's fysiologiske hovedfunktion er at opretholde normalt serumfosfat og at virke som et D-vitaminmodregulatorisk hormon. Sygdomme, der er koblet til forhøjet serum FGF23, er hypofosfatæmisk rakitis, fibrøs dysplasi og...... tumorinduceret osteomalaci. Hyperfosfatæmisk familiær tumoral calcinosis er derimod associeret med forhøjet nedbrydning af FGF23. Måling af FGF23 er et differentialdiagnostisk redskab ved udredning af tilstande med længerevarende hypofosfatæmi. Udgivelsesdato: 2010-May 17...

  17. Collagenous matrices as release carriers of exogenous growth factors.

    Science.gov (United States)

    Kanematsu, Akihiro; Yamamoto, Shingo; Ozeki, Makoto; Noguchi, Tetsuya; Kanatani, Isao; Ogawa, Osamu; Tabata, Yasuhiko

    2004-08-01

    We have investigated the use of natural and synthetic collagenous matrices as carriers of exogenous growth factors. A bladder acellular matrix (BAM) was processed from rat bladder and compared with sponge matrix of porcine type 1 collagen. The lyophilized matrices were rehydrated by the aqueous solutions of basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), platelet derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), insulin like growth factor-1 (IGF-1) and heparin binding epidermal growth factor-like growth factor (HB-EGF), to obtain the matrix incorporating each growth factor. The rehydration method enabled the growth factor protein to distribute into the matrix homogeneously. In vivo release test in the mouse subcutis revealed that, the property of BAM for growth factor release was similar to that of collagen sponge. Among the growth factors examined, bFGF release was the most sustained, followed by HGF and PDGF-BB. bFGF released from the two matrices showed similar in vivo angiogenic activity at the mouse subcutis in a dose-dependent manner. These findings demonstrate that the collagenous matrices function as release carriers of growth factors. This feature is promising to create a scaffold, which has a nature to control the tissue regeneration actively.

  18. Serum free insulin-like growth factor-I is dose-dependently decreased by methylprednisolone and related to body weight changes in rats.

    Science.gov (United States)

    Skjaerbaek, C; Frystyk, J; Grøfte, T; Flyvbjerg, A; Lewitt, M S; Baxter, R C; Orskov, H

    1999-02-01

    Glucocorticoids usually inhibit growth despite a paradoxical increase in total IGF-I. To investigate the effect of methylprednisolone on free IGF-I, rats were treated with for 3 days (0, 1, 2, 4, and 6 mg/kg per day). A dose-dependent decrease in ultrafiltrated serum free IGF-I was observed, being lowest after 6 mg/kg (P < 0.001 all groups vs controls). Total IGF-I was increased in the groups receiving 2 mg/kg (P < 0.05). Weight change in the 24 h prior to blood sampling was positively correlated with free IGF-I (R = 0.46, P = 0.0002), but not with total IGF-I. Immunoassayable IGFBP-1 was decreased in rats given 4 mg/kg (P = 0.001), whereas there was no change in IGFBP-3 or acid-labile subunit. We propose that in rats the glucocorticoid-induced weight loss may in part be due to suppression of circulating free IGF-I.

  19. Higher vascular endothelial growth factor-C concentration in plasma is associated with increased forearm capillary filtration capacity in breast cancer-related lymphedema

    DEFF Research Database (Denmark)

    Jensen, Mads Radmer; Simonsen, Lene; Karlsmark, Tonny

    2015-01-01

    Breast cancer-related lymphedema (BCRL) is a frequent, chronic and debilitating swelling that mainly affects the ipsilateral arm and develops as a complication to breast cancer treatment. The pathophysiology is elusive opposing development of means for prediction and treatment. We have earlier...

  20. From risk genes to psychiatric phenotypes - Studies of fibroblast growth factor-related and genome-wide genetic variants in humans and mice

    NARCIS (Netherlands)

    Terwisscha van Scheltinga, A.F.

    2013-01-01

    Schizophrenia is a severe mental disorder with a high heritability. This thesis describes studies on the association between genetic variants and phenotypes related to schizophrenia, such as brain volume and IQ, in order to learn about which processes are affected by schizophrenia-associated genetic

  1. SERUM TRANSFORMING GROWTH FACTOR B1 AND PROSTATE

    African Journals Online (AJOL)

    tein expression associated with fibrotic condi- ... TGF—B1 AND PSA AS MARKERS OF PROSTATE CANCER ..... transforming growth factor-beta is significantly the cell surface in tumor progression ... growth factor for clear cell renal carcinoma.

  2. Familial growth hormone releasing factor deficiency in pseudopseudohypoparathyroidism.

    OpenAIRE

    Stirling, H F; Barr, D G; Kelnar, C J

    1991-01-01

    A mother with pseudopseudohypoparathyroidism and her short son showed poor spontaneous growth hormone secretion, and provocation tests suggested a deficiency of growth hormone releasing factor. This is the first report of growth hormone releasing factor deficiency in pseudopseudohypoparathyroidism. The boy has responded well to growth hormone treatment over a period of three years.

  3. Joint Assessment of Intended and Unintended Effects of Medications: An Example Using Vascular Endothelial Growth Factor Inhibitors for Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Adrian R. Levy

    2009-01-01

    Full Text Available Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events on quality-of-life among persons with neovascular age-related macular degeneration. Methods. We designed a probabilistic decision-analytic model using published data. It employed 17 visual health states and three for unintended effects. We calculated incremental net health benefits by subtracting the harms of each medication from the benefit using the quality-adjusted life year (QALY. Results. In a hypothetical cohort of 1,000 75-year olds with new-onset bilateral age-related macular degeneration followed for ten years, the mean QALYs per patient is 3.7 for usual care, 4.2 for pegaptanib, and 4.3 for ranibizumab. Net benefits decline with increasing baseline rates of unintended effects. Interpretation. Net health benefits present a quantitative, potentially useful tool to assist patients and ophthalmologists in balancing the benefits and harms of interventions for age-related macular degeneration.

  4. Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and β-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.

    Science.gov (United States)

    Hurley, Marja M; Gronowicz, Gloria; Zhu, Li; Kuhn, Liisa T; Rodner, Craig; Xiao, Liping

    2016-03-01

    FGF-2 stimulates preosteoblast replication, and knockout of the FGF-2 gene in mice resulted in osteopenia with age, associated with decreased Wnt-β-Catenin signaling. In addition, targeted expression of FGF-2 in osteoblast progenitors increased bone mass in mice via Wnt-β-Catenin signaling. We posited that diminution of the intrinsic proliferative capacity of human mesenchyme-derived progenitor cells (HMDPCs) with age is due in part to reduction in FGF-2. To test this hypothesis HMDPCs from young (27-38), middle aged (47-56), and old (65-76) female human subjects were isolated from bone discarded after orthopedic procedures. HMDPCs cultures were mostly homogeneous with greater than 90% mesenchymal progenitor cells, determined by fluorescence-activated cell sorting. There was a progressive decrease in FGF-2 and FGFR1 mRNA and protein in HMDPCs with age. Since FGF-2 activates β-catenin, which can enhance bone formation, we also assessed its age-related expression in HMDPCs. An age-related decrease in total-β-Catenin mRNA and protein expression was observed. However there were increased levels of p-β-Catenin and decreased levels of activated-β-Catenin in old HMDSCs. FGF-2 treatment increased FGFR1 and β-Catenin protein, reduced the level of p-β-Catenin and increased activated-β-Catenin in aged HMDPCs. In conclusion, reduction in FGF-2 expression could contribute to age-related impaired function of HMDPCs via modulation of Wnt-β-catenin signaling.

  5. Gelatin methacrylate microspheres for controlled growth factor release.

    Science.gov (United States)

    Nguyen, Anh H; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C

    2015-02-01

    Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles (MPs) formulated with a wide range of different cross-linking densities (15-90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor than conventional GA cross-linked MPs, despite the GA MPs having an order of magnitude greater gelatin content. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 and basic fibroblast growth factor and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery.

  6. Angiopoietin-related Growth Factor and Its Relationship with Preeclampsia%血管生成素相关生长因子及其与子痫前期的关系

    Institute of Scientific and Technical Information of China (English)

    夏桂玉

    2012-01-01

    血管生成素相关生长因子(angiopoietin-related growth factor,AGF),也称为ARP5/ANGPTL6,是一种肝源性的血管生成素相关蛋白家族(ARPs)的新成员,具有促进血管形成及拮抗肥胖与胰岛素抵抗的作用,在调节血管生成和代谢性疾病中起着重要的作用.子痫前期是一种严重的妊娠期并发症,且病因与发病机制不明.研究AGF与妊娠生理与病理的关系意义重大,目前关于AGF与妊娠及相关疾病的研究较少.综述AGF的研究进展及其与妊娠和子痫前期的关系.%Angiopoietin-related growth factor(AGF,also known as ARP5/ANGPTL6) is a new member of angiopoietin-related protein family and a novel liver-derived circulating protein which significantly promotes angiogenesis but also antagonistic obesity and insulin resistance and plays an important role in regulating angiogenesis and metabolic diseases. Preeclampsia is a serious pregnancy complication, and the etiology and pathogenesis is unclear. It is important to study the relationship between AGF and pregnancy in physiological and pathological functions. Currently, the research of AGF and pregnancy-related disease is less. In this article,we provide a brief review about AGF in pregnancy and preeclampsia.

  7. Winter Wheat Root Growth and Nitrogen Relations

    DEFF Research Database (Denmark)

    Rasmussen, Irene Skovby

    Root growth is an essential parameter regarding nitrogen (N) uptake efficiency, as more and deeper roots may improve the uptake from deeper soil layers and reduce nitrate leaching losses. During this PhD project, it was studied how different agronomic practices influence root growth and N relations...... in winter wheat (Triticum aestivum L). Field experiments on the effect of sowing date, N fertilization and cultivars were conducted on a sandy loam soil in Taastrup, Denmark. The root studies were conducted by means of the minirhizotron method. Also, a field experiment on the effect of defoliation and N...... fertilization was conducted in Canberra, Australia. Here the root studies were done by means of the core-break method and root washing....

  8. Winter Wheat Root Growth and Nitrogen Relations

    DEFF Research Database (Denmark)

    Rasmussen, Irene Skovby

    Root growth is an essential parameter regarding nitrogen (N) uptake efficiency, as more and deeper roots may improve the uptake from deeper soil layers and reduce nitrate leaching losses. During this PhD project, it was studied how different agronomic practices influence root growth and N relations...... in winter wheat (Triticum aestivum L). Field experiments on the effect of sowing date, N fertilization and cultivars were conducted on a sandy loam soil in Taastrup, Denmark. The root studies were conducted by means of the minirhizotron method. Also, a field experiment on the effect of defoliation and N...... fertilization was conducted in Canberra, Australia. Here the root studies were done by means of the core-break method and root washing....

  9. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  10. Modulation of gap junction channels and hemichannels by growth factors.

    Science.gov (United States)

    Schalper, Kurt A; Riquelme, Manuel A; Brañes, María C; Martínez, Agustín D; Vega, José Luis; Berthoud, Viviana M; Bennett, Michael V L; Sáez, Juan C

    2012-03-01

    Gap junction hemichannels and cell-cell channels have roles in coordinating numerous cellular processes, due to their permeability to extra and intracellular signaling molecules. Another mechanism of cellular coordination is provided by a vast array of growth factors that interact with relatively selective cell membrane receptors. These receptors can affect cellular transduction pathways, including alteration of intracellular concentration of free Ca(2+) and free radicals and activation of protein kinases or phosphatases. Connexin and pannexin based channels constitute recently described targets of growth factor signal transduction pathways, but little is known regarding the effects of growth factor signaling on pannexin based channels. The effects of growth factors on these two channel types seem to depend on the cell type, cell stage and connexin and pannexin isoform expressed. The functional state of hemichannels and gap junction channels are affected in opposite directions by FGF-1 via protein kinase-dependent mechanisms. These changes are largely explained by channels insertion in or withdrawal from the cell membrane, but changes in open probability might also occur due to changes in phosphorylation and redox state of channel subunits. The functional consequence of variation in cell-cell communication via these membrane channels is implicated in disease as well as normal cellular responses.

  11. Effects of Hypergravity Rearing on Growth Hormone and Insulin-Like Growth Factor in Rat Pups

    Science.gov (United States)

    Baer, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.

    2003-01-01

    Body weights of rat pups reared during exposure to hypergravity (hg) are significantly reduced relative to 1 g controls. In the present study, we examined in hg-reared rat pups two major contributors to growth and development, namely growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Beginning on Gestational day (G)11 of the rats 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g or 2.0-g. On Postnatal day (P)l0, plasma GH and IGF-1 were analyzed using radioimmunoassay (RIA). Both hormones were significantly elevated in hg pups relative to 1-g control pups. Together, these findings suggest that GH and IGF-1 are not primary determinants of reduced body weights observed in hg-reared pups. The significant elevations in pup GH and IGF-1 may be related to increased physical stimulation in hypergravity.

  12. Nerve growth factor interactions with mast cells.

    Science.gov (United States)

    Kritas, S K; Caraffa, A; Antinolfi, P; Saggini, A; Pantalone, A; Rosati, M; Tei, M; Speziali, A; Saggini, R; Pandolfi, F; Cerulli, G; Conti, P

    2014-01-01

    Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini, is a neurotrophin family compound which is important for survival of nociceptive neurons during their development. Therefore, NGF is an important neuropeptide which mediates the development and functions of the central and peripheral nervous system. It also exerts its proinflammatory action, not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be activated by neuropeptides to release potent mediators of inflammation, and they are found throughout the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation. NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion, these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.

  13. The expression of the epidermal growth factor (EGF) during odontogenesis:

    OpenAIRE

    Peixoto, Breno C.; Integrated Federal School of Diamantina - MG; dos Santos, Cássio R. R.; Integrated Federal School of Diamantina - MG; Canuto, Conceição E.; Integrated Federal School of Diamantina - MG

    2010-01-01

    The objective of this study was to verify, through the technique of Immunohistochemistry, the expression of theepidermal growth factor (EGF) in the odontogenesis of the first upper molar in Mus musculus mice, relating it tothe microscopic morphologic analysis. The sample consisted of 23 animals, with age from the 13th day of intrauterinelife to the 20th day of postnatal life. The results showed EGF being expressed by several tissues and cellsparticipating of the odontogenesis. However the den...

  14. Chance, creativity, and the discovery of the nerve growth factor.

    Science.gov (United States)

    de Romo, Ana Cecilia Rodríguez

    2007-01-01

    This essay analyzes the history of the Nerve Growth Factor (NGF) discovery, relating some of the principles of the theory of scientific creativity to the cognitive and personal qualities of the scientists that participated in the discovery, particularly Rita Levi-Montalcini and Viktor Hamburger. The discovery of NGF is especially attractive for the history of science as it involves chance, luck, creativity, and some extraordinary scientists.

  15. Epidermal growth factor in the rat lung

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Poulsen, Steen Seier; Nexø, Ebba

    1991-01-01

    Epidermal Growth Factor (EGF) in pharmacological doses is able to induce precoccious lung maturation in rabbits and sheeps. As EGF is probably acting in a para- or autocrine way, we have searched for EGF in the lungs. We report EGF immunoreactivity to be present in the type II pneumocytes...... of the rat from a couple of days prior to birth and throughout life. Further, we report EGF immunoreactivity to be present in cells in the bronchi and the bronchioles from day 20-21 of gestation and throughout life. G-200 gelchromatography of lung extracts indicates that the EGF-reactive material is a high...... molecular weight form of EGF. Since previous studies have shown that EGF in pharmacological doses is able to promote lung maturation, our results may imply a physiological role for EGF in the lungs....

  16. Plasma rich in growth factors in dentistry

    Directory of Open Access Journals (Sweden)

    Ana Glavina

    2017-06-01

    Full Text Available Background Plasma rich in growth factors (PRGF has wider use in many fields of dentistry due to its endogenous biocompatible regenerative potential i.e., their potential to stimulate and accelerate tissue healing and bone regeneration. Aims This review shows the increasing use of PRGF technology in various fields of dentistry. Methods In the last nine years PubMed has been searched in order to find out published articles upon PRGF in dentistry and 36 papers have been included. Results PRGF technology has many advantages with positive clinical and biological outcomes in tissue healing and bone regeneration. Conclusion In order to determine the most effective therapeutic value for patients, further research is required.

  17. Aldosterone as a renal growth factor.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-04-05

    Aldosterone regulates blood pressure through its effects on the cardiovascular system and kidney. Aldosterone can also contribute to the development of hypertension that leads to chronic pathologies such as nephropathy and renal fibrosis. Aldosterone directly modulates renal cell proliferation and differentiation as part of normal kidney development. The stimulation of rapidly activated protein kinase cascades is one facet of how aldosterone regulates renal cell growth. These cascades may also contribute to myofibroblastic transformation and cell proliferation observed in pathological conditions of the kidney. Polycystic kidney disease is a genetic disorder that is accelerated by hypertension. EGFR-dependent proliferation of the renal epithelium is a factor in cyst development and trans-activation of EGFR is a key feature in initiating aldosterone-induced signalling cascades. Delineating the components of aldosterone-induced signalling cascades may identify novel therapeutic targets for proliferative diseases of the kidney.

  18. Autologous growth factor injections in chronic tendinopathy.

    Science.gov (United States)

    Sandrey, Michelle A

    2014-01-01

    de Vos RJ, van Veldhoven PLJ, Moen MH, Weir A, Tol JL. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull. 2010;95:63-77. The authors of this systematic review evaluated the literature to critically consider the effects of growth factors delivered through autologous whole-blood and platelet-rich-plasma (PRP) injections in managing wrist-flexor and -extensor tendinopathies, plantar fasciopathy, and patellar tendinopathy. The primary question was, according to the published literature, is there sufficient evidence to support the use of growth factors delivered through autologous whole-blood and PRP injections for chronic tendinopathy? The authors performed a comprehensive, systematic literature search in October 2009 using PubMed, MEDLINE, EMBASE, CINAHL, and the Cochrane library without time limits. The following key words were used in different combinations: tendinopathy, tendinosis, tendinitis, tendons, tennis elbow, plantar fasciitis, platelet rich plasma, platelet transfusion, and autologous blood or injection. The search was limited to human studies in English. All bibliographies from the initial literature search were also viewed to identify additional relevant studies. Studies were eligible based on the following criteria: (1) Articles were suitable (inclusion criteria) if the participants had been clinically diagnosed as having chronic tendinopathy; (2) the design had to be a prospective clinical study, randomized controlled trial, nonrandomized clinical trial, or prospective case series; (3) a well-described intervention in the form of a growth factor injection with either PRP or autologous whole blood was used; and (4) the outcome was reported in terms of pain or function (or both). All titles and abstracts were assessed by 2 researchers, and all relevant articles were obtained. Two researchers independently read the full text of each article to determine if it met the inclusion criteria. If opinions differed on

  19. Neuropeptides as lung cancer growth factors.

    Science.gov (United States)

    Moody, Terry W; Moreno, Paola; Jensen, Robert T

    2015-10-01

    This manuscript is written in honor of the Festschrift for Abba Kastin. I met Abba at a Society for Neuroscience meeting and learned that he was Editor-in-Chief of the Journal Peptides. I submitted manuscripts to the journal on "Neuropeptides as Growth Factors in Cancer" and subsequently was named to the Editorial Advisory Board. Over the past 30 years I have published dozens of manuscripts in Peptides and reviewed hundreds of submitted manuscripts. It was always rewarding to interact with Abba, a consummate professional. When I attended meetings in New Orleans I would sometimes go out to dinner with him at the restaurant "Commanders Palace". When I chaired the Summer Neuropeptide Conference we were honored to have him receive the Fleur Strand Award one year in Israel. I think that his biggest editorial contribution has been the "Handbook of Biologically Active Peptides." I served as a Section Editor on "Cancer/Anticancer Peptides" and again found that it was a pleasure working with him. This review focuses on the mechanisms by which bombesin-like peptides, neurotensin and vasoactive intestinal peptide regulate the growth of lung cancer. Published by Elsevier Inc.

  20. Epidermal growth factor (urogastrone) in human tissues.

    Science.gov (United States)

    Hirata, Y; Orth, D N

    1979-04-01

    Human epidermal growth factor (hEGF), which stimulates the growth of a variety of tissues, was first isolated from mouse submandibular glands, but is also excreted in large amounts (about 50 micrograms/day) in human urine and is probably identical to human beta-urogastrone (hUG), a potent inhibitor of stimulated gastric acid secretion. However, the primary tissue source of hEGF/hUG is as yet unknown. The hEGF/hUG in homogenates of human salivary glands and a wide variety of other endocrine and nonendocrine tissues was extracted by Amberlite CG-50 cation exchange chromatography and immune affinity chromatography using the immunoglobulin fraction of rabbit anti-hEGF serum covalently bound to agarose. The extracts were subjected to homologous hEGF RIA. Immunoreactive hEGF was found in extracts of adult submandibular gland, thyroid gland, duodenum, jejunum, and kidney, but not in several fetal tissues. The tissue immunoreactive hEGF was similar to standard hEGF in terms of immunoreactivity and elution from Sephadex G-50 Fine resin, but its concentrations were very low (1.3-5.5 ng/g wet tissue). Thus, it is not certain that these tissues represent the only source of the large amounts of hEGF/hUG that appear to be filtered by the kidneys each day.

  1. Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer

    DEFF Research Database (Denmark)

    Maae, Else; Olsen, Dorte Aalund; Steffensen, Karina Dahl;

    2012-01-01

    Placenta growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) are angiogenic growth factors interacting competitively with the same receptors. VEGF-A is essential in both normal and pathologic conditions, but the functions of PlGF seem to be restricted to pathologic conditions...

  2. Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer

    DEFF Research Database (Denmark)

    Maae, Else; Olsen, Dorte Aalund; Dahl Steffensen, Karina

    2012-01-01

    Background: Placenta growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) are angiogenic growth factors interacting competitively with the same receptors. VEGF-A is essential in both normal and pathologic conditions, but the functions of PlGF seem to be restricted to pathologic ...

  3. Factor-structure of economic growth in E-commerce

    Institute of Scientific and Technical Information of China (English)

    吴隽; 刘洪久; 栾天行

    2003-01-01

    In order to analyze the factors having effect on economic growth of E-commerce, the economic growthprocess of E-commerce is divided into three stages; growth stage, stabilization stage and re-growth stage. Thesethree different stages are analysed using several economic growth theories, a set of factor-structure is proposedfor each stage of the economic growth process of E-commerce.

  4. CATTELL AND EYSENCK FACTOR SCORES RELATED TO COMREY PERSONALITY FACTORS.

    Science.gov (United States)

    Comrey, A L; Duffy, K E

    1968-10-01

    The Eysenck Personality Inventory, the Cattell 16 PF Inventory, and the Comrey Personality Inventory were administered to 272 volunteers. Eysenck and Cattell factor scores were correlated with scores over homogeneous item groups (FHIDs) which define the Comrey test factors. This matrix was factor analyzed to relate the Eysenck and Cattell factor scores to the factor structure underlying the Comrey test. The Eysenck Neuroticism, Comrey Neuroticism, and Cattell second-order Anxiety factors appeared to match. The Eysenck Introversion and the Comrey Shyness factors also matched. The 16 Cattell primary factors overlapped but did not match with the Comrey factors.

  5. Placental growth factor is a survival factor for tumor endothelial cells and macrophages.

    Science.gov (United States)

    Adini, Avner; Kornaga, Tad; Firoozbakht, Farshid; Benjamin, Laura E

    2002-05-15

    The vascular endothelial growth factor (VEGF)-related factor, placental growth factor (PlGF),has been shown recently to play an important role in pathological VEGF-driven angiogenesis. In this study, we examine the effects of mPlGF/PlGF-2 overexpression in tumors grown from glioma cells containing a tetracycline-regulated mPlGF cDNA. Overexpression of mPlGF leads to increased tumor growth and vascular survival. When tetracycline is used to abruptly withdraw mPlGF overexpression, we see increased apoptosis in both vascular cells and macrophages. In addition, PlGF-2 induces survival gene expression and inhibits apoptosis in vitro. Thus, we propose that PlGF-2 contributes to tumor angiogenesis by providing increased survival function to endothelial cells and macrophages.

  6. Growth factors adsorbed on polyglycolic acid mesh augment growth of bioengineered intestinal neomucosa.

    Science.gov (United States)

    Wulkersdorfer, Beatrix; Kao, Kenneth K; Agopian, Vatche G; Dunn, James C; Wu, Ben M; Stelzner, Matthias

    2011-08-01

    Production of tissue engineered small intestine (TESI) has been limited by the relatively large amount of native tissue required to generate neomucosa. The influence of growth factors and three-dimensional (3D) extracellular matrices on TESI has been studied both in vitro and in vivo, and positive growth effects on tissue mass and differentiation were noted. The present study investigates the impact of single doses of glucagon-like peptide-2 (GLP-2), hepatocyte growth factor (HGF), or holo-transferrin adsorbed onto a polyglycolic (PGA) mesh scaffold using a rat small-intestinal organoid transplant model. In Experiment I, intestinal organoids were seeded onto PGA mesh discs, suspended in either Matrigel (n=8) or a vehicle control (n=8), and implanted into syngenic recipients. In Experiment II, GLP-2 (n=8), HGF (n=8), or transferrin (n=8) were adsorbed onto PGA mesh discs. Intestinal organoids were then suspended in Matrigel and seeded onto each growth factor-loaded PGA disc or onto control discs without growth factors (n=12). In addition, organoids were suspended in vehicle and seeded onto control discs (n=12). All discs were implanted into syngenic recipients. After 4 wk, histologic analysis of the samples revealed significantly greater neomucosal surface area (3.62±0.33 mm(2)versus 0.92±0.11 mm(2), Pvehicle controls. The addition of holo-transferrin to the scaffolds further augmented neomucosal surface area (9.11±0.66 mm(2)versus 3.01±0.22 mm(2), P<0.01), whereas that of GLP-2 stimulated the formation of increased numbers of cysts (8.88±0.46 versus 4.18±0.25, P<0.01). These data suggest that Matrigel and growth factors adsorbed to polymer scaffolds can be used to manipulate the morphology of TESI.

  7. Epidermal growth factor: a critical factor in fetal maturation?

    Science.gov (United States)

    Thorburn, G D; Waters, M J; Young, I R; Dolling, M; Buntine, D; Hopkins, P S

    1981-01-01

    Epidermal growth factor (EGF) infused over 3-14 days into fetal sheep of 110-125 days gestation resulted in a number of morphological and endocrine changes. Striking hypertrophy of the skin, wool follicles and their accessory structures was seen, together with a reduction in the ratio of secondary to primary follicles and degenerative changes in wool fibres associated with shedding of fibres. Adrenal, thyroid, liver and kidney weights were increased while thymus weight was decreased. The increase in adrenal size resulted from cortical hypertrophy and was associated with increased cortisol secretion. Thyroid hypertrophy was accompanied by an increase in colloid stores, decreased plasma thyroxine and reverse triiodothyronine (T3) concentrations, unchanged plasma T3 and thyroid-binding globulin and raised thyrotropin (TSH) levels. Thyrotropin receptor affinity and content per gram of tissue were unchanged. Fetal and maternal plasma prolactin and growth hormone levels, and fetal plasma placental lactogen levels, were unchanged, although there was a significant rise in maternal plasma placental lactogen concentrations with high doses of EGF. Other maturational parameters such as switching from fetal to adult haemoglobin and liver glycogen content were unaffected.

  8. The importance of neuronal growth factors in the ovary.

    Science.gov (United States)

    Streiter, S; Fisch, B; Sabbah, B; Ao, A; Abir, R

    2016-01-01

    The neurotrophin family consists of nerve growth factor (NGF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5), in addition to brain-derived neurotrophic factor (BDNF) and the neuronal growth factors, glial cell line-derived neurotrophic factor (GDNF) and vasointestinal peptide (VIP). Although there are a few literature reviews, mainly of animal studies, on the importance of neurotrophins in the ovary, we aimed to provide a complete review of neurotrophins as well as neuronal growth factors and their important roles in normal and pathological processes in the ovary. Follicular assembly is probably stimulated by complementary effects of NGF, NT4/5 and BDNF and their receptors. The neurotrophins, GDNF and VIP and their receptors have all been identified in preantral and antral follicles of mammalian species, including humans. Transgenic mice with mutations in the genes encoding for Ngf, Nt4/5 and Bdnf and their tropomyosin-related kinase β receptor showed a reduction in preantral follicles and an abnormal ovarian morphology, whereas NGF, NT3, GDNF and VIP increased the in vitro activation of primordial follicles in rats and goats. Additionally, NGF, NT3 and GDNF promoted follicular cell proliferation; NGF, BDNF and VIP were shown to be involved in ovulation; VIP inhibited follicular apoptosis; NT4/5, BDNF and GDNF promoted oocyte maturation and NGF, NT3 and VIP stimulated steroidogenesis. NGF may also exert a stimulatory effect in ovarian cancer and polycystic ovarian syndrome (PCOS). Low levels of NGF and BDNF in follicular fluid may be associated with diminished ovarian reserve and high levels with endometriosis. More knowledge of the roles of neuronal growth factors in the ovary has important implications for the development of new therapeutic drugs (such as anti-NGF agents) for ovarian cancer and PCOS as well as various infertility problems, warranting further research.

  9. The relative volume growth of minimal submanifolds

    DEFF Research Database (Denmark)

    Markvorsen, Steen; Palmer, V.

    2002-01-01

    The volume growth of certain well-defined subsets of minimal submanifolds in riemannian spaces are compared with the volume growth of balls and spheres ill space forms of constant curvature.......The volume growth of certain well-defined subsets of minimal submanifolds in riemannian spaces are compared with the volume growth of balls and spheres ill space forms of constant curvature....

  10. Role of vascular endothelial growth factor and other growth factors in post-stroke recovery

    Directory of Open Access Journals (Sweden)

    Tanu Talwar

    2014-01-01

    Full Text Available Stroke is a major health problem world-wide and its burden has been rising in last few decades. Until now tissue plasminogen activator is only approved treatment for stroke. Angiogenesis plays a vital role for striatal neurogenesis after stroke. Administration of various growth factors in an early post ischemic phase, stimulate both angiogenesis and neurogenesis and lead to improved functional recovery after stroke. However vascular endothelial growth factors (VEGF is the most potent angiogenic factor for neurovascularization and neurogenesis in ischemic injury can be modulated in different ways and thus can be used as therapy in stroke. In response to the ischemic injury VEGF is released by endothelial cells through natural mechanism and leads to angiogenesis and vascularization. This release can also be up regulated by exogenous administration of Mesenchymal stem cells, by various physical therapy regimes and electroacupuncture, which further potentiate the efficacy of VEGF as therapy in post stroke recovery. Recent published literature was searched using PubMed and Google for the article reporting on methods of up regulation of VEGF and therapeutic potential of growth factors in stroke.

  11. Annual shoot growth components related to growth of Pinus brutia.

    Science.gov (United States)

    Isik, Fikret; Isik, Kani; Yildirim, Tolga; Li, Bailian

    2002-01-01

    Shoot elongation patterns of Pinus brutia Ten. were studied in six natural populations and 10 open-pollinated families within each population. The data were collected from a provenance-progeny trial that was thinned at Ages 13 and 17 years. Annual height increment was partitioned into first flush (spring shoot) and subsequent flushes (summer shoots) and the contribution of each to annual height increment was measured from Ages 7 to 17. Spring shoot elongation patterns were similar in all populations and families for 9 out of 10 years. In contrast, at all ages, populations differed significantly in total summer shoot growth and number of summer flushes. Families within populations differed in number of summer flushes in 7 out of 10 years. Summer shoot growth was the major cause of the differences in annual height growth among the six populations. Significant and high correlations were observed between summer shoot growth at Ages 7 to 12 and height at Age 13. A population from near the middle of the species' altitudinal range had more summer flushes than populations from higher or lower elevations, indicating an opportunistic growth pattern. Compared with mid-elevation populations, low- and high-elevation populations had more conservative growth patterns that depended mainly on growth of spring shoots. We conclude that summer shoot growth can serve as an explanatory variable to predict height growth of populations. Differences in shoot elongation patterns among Pinus brutia populations may be useful for selecting seed sources and for gene conservation programs.

  12. Gene expression of growth factors and growth factor receptors for potential targeted therapy of canine hepatocellular carcinoma.

    Science.gov (United States)

    Iida, Gentoku; Asano, Kazushi; Seki, Mamiko; Sakai, Manabu; Kutara, Kenji; Ishigaki, Kumiko; Kagawa, Yumiko; Yoshida, Orie; Teshima, Kenji; Edamura, Kazuya; Watari, Toshihiro

    2014-03-01

    The purpose of this study was to evaluate the gene expression of growth factors and growth factor receptors of primary hepatic masses, including hepatocellular carcinoma (HCC) and nodular hyperplasia (NH), in dogs. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to measure the expression of 18 genes in 18 HCCs, 10 NHs, 11 surrounding non-cancerous liver tissues and 4 healthy control liver tissues. Platelet-derived growth factor-B (PDGF-B), transforming growth factor-α, epidermal growth factor receptor, epidermal growth factor and hepatocyte growth factor were found to be differentially expressed in HCC compared with NH and the surrounding non-cancerous and healthy control liver tissues. PDGF-B is suggested to have the potential to become a valuable ancillary target for the treatment of canine HCC.

  13. Nutrition, insulin, insulin-like growth factors and cancer.

    Science.gov (United States)

    Giovannucci, E

    2003-01-01

    The incidence of colon, pancreatic, and kidney cancers, as well as aggressive prostate cancer in men, and breast and endometrial cancer in women is invariably high in Western countries. Nutritional and related factors have been typically implicated. This review presents a model integrating nutrition, insulin and IGF-1 physiology ("bioactive" IGF-1), and carcinogenesis based on the following: (1) insulin and the IGF-1 axis function in an integrated fashion to promote cell growth and survival; (2) chronic exposure to these growth properties enhances carcinogenesis; (3) factors that influence bioactive IGF-1 will affect cancer risk. The model presented here summarizes the data that chronic exposure to high levels of insulin and IGF-1 may mediate many of the risk factors for some cancers that are high in Western populations. This hypothesis may help explain some of the epidemiologic patterns observed for these cancers, both from a cross-national perspective and within populations. Of particular importance is that some of relevant factors are modifiable through nutritional and lifestyle interventions. Out of a variety of perspectives presented, nutritional manipulation through the insulin pathway may be more feasible than attempting to influence total IGF-1 concentrations, which are determined largely by growth hormone. Further study is required to test these conclusions.

  14. Soluble vascular endothelial growth factor in various blood transfusion components

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T;

    1999-01-01

    BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors....... The potential content of VEGF in various blood components for transfusion was evaluated. STUDY DESIGN AND METHODS: Soluble VEGF (sVEGF, isotype 165) was determined by an enzyme-linked immunosorbent assay (EIA) in serum and plasma samples and in lysed cells from healthy volunteers. Subsequently, total content...... of platelet-derived soluble plasminogen activator inhibitor type 1 (sPAI-1) was determined by an EIA in the same samples. Finally, the extracellular accumulation of sVEGF was determined in nonfiltered WB and SAGM blood during storage for 35 days and in BCP pools during storage for 7 days. RESULTS...

  15. Soluble vascular endothelial growth factor in various blood transfusion components

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T

    1999-01-01

    BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors....... The potential content of VEGF in various blood components for transfusion was evaluated. STUDY DESIGN AND METHODS: Soluble VEGF (sVEGF, isotype 165) was determined by an enzyme-linked immunosorbent assay (EIA) in serum and plasma samples and in lysed cells from healthy volunteers. Subsequently, total content......-reduced PRP. The sVEGF accumulated significantly in WB, SAGM blood, and BCP pools, depending on the storage time. CONCLUSION: The sVEGF (isotype 165) appears to be present in various blood transfusion components, depending on storage time....

  16. Transforming growth factor-β and smooth muscle differentiation

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Transforming growth factor(TGF)-β family members are multifunctional cytokines regulating diverse cel- lular functions such as growth,adhesion,migration, apoptosis,and differentiation.TGF-βs elicit their effects via specific typeⅠand typeⅡserine/threonine kinase receptors and intracellular Smad transcription factors. Knockout mouse models for the different components of the TGF-β signaling pathway have revealed their critical roles in smooth muscle cell(SMC)differentia- tion.Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular disorders such as aorta aneurysm and congenital heart diseases due to SMC defects.In this review,the current understanding of TGF-β function in SMC differentiation is highlighted,and the role of TGF-βsignaling in SMC- related diseases is discussed.

  17. Insulin-like growth factor 2

    DEFF Research Database (Denmark)

    Valleh, Mehdi Vafaye; Hyttel, Poul; Rasmussen, Mikkel Aabech;

    2014-01-01

    Intrinsic defects within the embryos, reflected by elevated cell death and low proliferative ability, are considered the most critical factors associated with bovine infertility. The identification of embryonic factors, which are responsible for successful embryo development, is thus critical...... in designing strategies for infertility intervention. In this experiment, the possible mechanisms involved in both blastomere proliferation and regulation of cell death were studied by analysis of relative expression patterns of IGF-II, BCL2-L1, BAK1, and HSP70 in 3 classes of morphological quality groups (e.......g., excellent, good, and poor) of bovine blastocysts produced by IVF. Variation in total blastocyst cell numbers as well as their allocation to inner cell mass and trophectoderm lineages were also determined by differential CDX2 staining. Results showed that transcript levels for IGF-II, BCL2-L1, and the BCL2-L...

  18. [Stem cells and growth factors in wound healing].

    Science.gov (United States)

    Pikuła, Michał; Langa, Paulina; Kosikowska, Paulina; Trzonkowski, Piotr

    2015-01-02

    Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound healing. Among the most important cells which take part in wound healing the following cells need to be distinguished: epidermal stem cells, dermal precursor of fibroblasts, adipose-derived stem cells as well as bone marrow cells. The activity of these cells is strictly regulated by various growth factors, inter alia epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF). Any disorders in functioning of stem cells and biological activity of growth factors may lead to the defects in wound healing, for instance delayed wound healing or creation of hypertrophic scars. Therefore, knowledge concerning the mechanisms of wound healing is extremely essential from clinical point of view. In this review the current state of the knowledge of the role of stem cells and growth factors in the process of wound healing has been presented. Moreover, some clinical aspects of wound healing as well as the possibility of the therapy based on stem cells and growth factors have included.

  19. Stem cells and growth factors in wound healing

    Directory of Open Access Journals (Sweden)

    Michał Pikuła

    2015-01-01

    Full Text Available Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound healing. Among the most important cells which take part in wound healing the following cells need to be distinguished: epidermal stem cells, dermal precursor of fibroblasts, adipose-derived stem cells as well as bone marrow cells. The activity of these cells is strictly regulated by various growth factors, inter alia epidermal growth factor (EGF, fibroblast growth factor (FGF, platelet-derived growth factor (PDGF, transforming growth factor (TGF, vascular endothelial growth factor (VEGF. Any disorders in functioning of stem cells and biological activity of growth factors may lead to the defects in wound healing, for instance delayed wound healing or creation of hypertrophic scars. Therefore, knowledge concerning the mechanisms of wound healing is extremely essential from clinical point of view. In this review the current state of the knowledge of the role of stem cells and growth factors in the process of wound healing has been presented. Moreover, some clinical aspects of wound healing as well as the possibility of the therapy based on stem cells and growth factors have included.

  20. Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1in Human Meningiomas

    Institute of Scientific and Technical Information of China (English)

    YI Wei; CHEN Jian; Filimon H. Golwa; XUE Delin

    2005-01-01

    The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1.The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.

  1. Insulinlike growth factor-binding protein proteolysis an emerging paradigm in insulinlike growth factor physiology.

    Science.gov (United States)

    Fowlkes, J L

    1997-10-01

    In biologic fluids, insulinlike growth factors (IGF-I and IGF-II) are bound to high-affinity insulinlike growth factor binding proteins (IGFBPs) of which seven have now been identified (IGFBPs 1-7). In a variety of biologic fluids, several IGFBPs undergo proteolytic degradation. Such degradation can lead to increased IGF bioavailability at the cell surface, facilitating receptor interactions. Herein, recent data identifying several IGFBP-degrading proteinases and their effects on IGF bioactivity is reviewed, and how IGFBP proteolysis is regulated by IGFs and IGFBPs, as well as how IGFBP cleavage analysis provides insights into the structure and function of IGFBPs, is explored. (Trends Endocrinol Metab 1997;8:299-306). (c) 1997, Elsevier Science Inc.

  2. Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Poulsen, Steen Seier; Bretlau, P

    1993-01-01

    , the cells above the basal cell layer were positive for both TGF-alpha and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus......Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-alpha was detected...... with a monoclonal mouse antibody and EGF with polyclonal rabbit antiserum. Thirty-five of the tumours were positive for TGF-alpha and 26 of the tumours for EGF. None of the poorly differentiated tumours was positive for EGF, but they all were for TGF-alpha. In sections including normal differentiated oral mucosa...

  3. The population factor in economic growth theory

    NARCIS (Netherlands)

    Meilink, H.A.

    1974-01-01

    Reviews briefly the role of population growth in economic growth theory and makes a few critical remarks on the applied methodology and the underlying assumptions. Emphasis is laid on the possible relationships between population and economic growth in the developing countries, but also Malthus' the

  4. Transforming growth factor-beta, but not ciliary neurotrophic factor, inhibits DNA synthesis of adrenal medullary cells in vitro

    DEFF Research Database (Denmark)

    Wolf, N; Krohn, K; Bieger, S;

    1999-01-01

    by the neuroendocrine chromaffin cells, which also express the transforming growth factor-beta receptor type II. In contrast to the developmentally related sympathetic neurons, chromaffin cells continue to proliferate throughout postnatal life. Using 5-bromo-2'-deoxyuridine pulse labeling and tyrosine hydroxylase...... regulator of chromaffin cell division.......Transforming growth factor-betas are members of a superfamily of multifunctional cytokines regulating cell growth and differentiation. Their functions in neural and endocrine cells are not well understood. We show here that transforming growth factor-betas are synthesized, stored and released...

  5. The role of vascular endothelial growth factors and fibroblast growth factors in angiogenesis during otitis media.

    Science.gov (United States)

    Husseman, Jacob; Palacios, Sean D; Rivkin, Alexander Z; Oehl, Heinz; Ryan, Allen F

    2012-01-01

    The middle ear response to otitis media includes transformation and hyperplasia of the mucosal epithelium and subepithelial connective tissue. Significant neovascularization is also noted, which occurs both to support the hypertrophied mucosa and to mediate the increased trafficking of leukocytes. We investigated the role of two known potent angiogenic growth factor families, the fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs), in middle ear mucosal angiogenesis. DNA microarrays were used to evaluate the expression of FGFs and VEGFs, as well as their receptors and unique signaling proteins, in the middle ears of mice undergoing a complete course of acute bacterial otitis media. In addition, a member of each family was introduced to the middle ear submucosal compartment of the normal middle ears of guinea pigs, by a continuous-release osmotic minipump system over 1 week. During the course of bacterial otitis media, a significant regulation of a number of genes important for angiogenesis was identified. Histologic evaluation of middle ear mucosa following micropump infusion of both FGF1 and VEGF-A showed significant angiogenesis at the site of infusion in comparison to control saline infusion. These results support a role for FGFs and VEGFs in the neovascularization of the middle ear mucosa during otitis media, and offer a potential avenue for therapeutic intervention.

  6. [Epidermal growth factor, innovation and safety].

    Science.gov (United States)

    Esquirol Caussa, Jordi; Herrero Vila, Elisabeth

    2015-10-05

    Bioidentical recombinant human epidermal growth factor (rhEGF) is available in concentrations and purity suitable for therapeutic use in long time stable formulations. Beneficial effects in several skin pathologies and lesions have been reported (traumatic and surgical wound healing, laser induced wounds, abnormal scars, keloids, radiation or chemotherapy induced dermatitis, post inflammatory hyperpigmentation or for skin aging damage repairing) and also may be considered for the treatment of several oropharingeal and high gastroesophageal tract mucosa diseases (mouth sores, pharyngeal fistulas, ulcers), and several corneal or conjunctive mucosa lesions. rhEGF has not shown any important side or collateral effects in humans or in laboratory experimentation animals, showing optimal tolerability and safety with continuous use for months. Compounding gives advantages of versatility, individualization, personalization, molecular stability, safety and effectiveness in ideal conditions, showing good tissue penetration, both on intact skin and skin lesions that expose the lower planes to the surface. rhEGF compounds can be considered for prevention or as a treatment of diverse skin and mucosa diseases and conditions through compounding preparations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  7. Isoforms of receptors of fibroblast growth factors.

    Science.gov (United States)

    Gong, Siew-Ging

    2014-12-01

    The breadth and scope of Fibroblast Growth Factor signaling is immense, with documentation of its role in almost every organism and system studied so far. FGF ligands signal through a family of four distinct tyrosine kinase receptors, the FGF receptors (FGFRs). One contribution to the diversity of function and signaling of FGFs and their receptors arises from the numerous alternative splicing variants that have been documented in the FGFR literature. The present review discusses the types and roles of alternatively spliced variants of the FGFR family members and the significant impact of alternative splicing on the physiological functions of five broad classes of FGFR isoforms. Some characterized known regulatory mechanisms of alternative splicing and future directions in studies of FGFR alternative splicing are also discussed. Presence, absence, and/or the combination of specific exons within each FGFR protein impart upon each individual isoform its unique function and expression pattern during normal function and in diseased states (e.g., in cancers and birth defects). A better understanding of the diversity of FGF signaling in different developmental contexts and diseased states can be achieved through increased knowledge of the presence of specific FGFR isoforms and their impact on downstream signaling and functions. Modern high-throughput techniques afford an opportunity to explore the distribution and function of isoforms of FGFR during development and in diseases.

  8. Nerve growth factor enhances sleep in rabbits.

    Science.gov (United States)

    Takahashi, S; Krueger, J M

    1999-04-02

    Nerve growth factor (NGF) elicits rapid-eye-movement sleep (REMS) in cats. Removal of NGF receptor-positive cholinergic basal forebrain neurons inhibits REMS in rats. The aim of the present study was to determine the effects of NGF on sleep and brain temperature (Tbr) in rabbits. Male rabbits were implanted with electroencephalograph (EEG) electrodes, a brain thermistor and an intraventricular (i.c.v.) guide cannula. Rabbits received human beta-NGF i.c.v. (0.01, 0.1, 1.0 or 10 microg] and on a separate day, 25 microl pyrogen-free saline i.c.v. as control. EEG and Tbr were recorded for 23 h after injections. The highest two doses of NGF increased both non-REMS and REMS across the 23-h recording period. REMS was enhanced dose-dependently. Tbr was not affected by any dose of NGF. These results suggest that NGF is involved in both REMS and non-REMS regulation.

  9. The sustainability and transition of economic growth in China: from a perspective of factor structure

    Institute of Scientific and Technical Information of China (English)

    Wang Yafei; Wu Xiaohang

    2008-01-01

    After more than 20 years' high speed growth, the sustainable growth of Chinese economy faces serious lim-itation of resources and factors now and in the future. In order to maintain the economic growth, China has to trans, form the way of economic growth. Based on the analysis on the related theories of economic growth and the structur-al transformation in factors of production, this paper proposes that the transformation of the economic growth way has to impel the optimization and the promotion of the utilization structure of factors of production. Finally, based on the analysis of the necessity to change the pattern of economic growth, this paper proposes the strategic measures to promote the continuous economic growth and the transformation of patterns of economic growth.

  10. The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7).

    OpenAIRE

    Bagheri-Yarmand, R.; Kourbali, Y; Mabilat, C; Morère, J. F.; Martin, A; Lu, H; Soria, C; Jozefonvicz, J; Crépin, M

    1998-01-01

    Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL100), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the mitogenic activities of t...

  11. Endocrine fibroblast growth factor FGF19 promotes prostate cancer progression.

    Science.gov (United States)

    Feng, Shu; Dakhova, Olga; Creighton, Chad J; Ittmann, Michael

    2013-04-15

    Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require α-Klotho (KL) and/or β-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting.

  12. Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Hiroyuki Yamakawa

    2015-12-01

    Full Text Available Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF 2, FGF10, and vascular endothelial growth factor (VEGF, termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming.

  13. Fibroblast growth factor (FGF) signaling in development and skeletal diseases.

    Science.gov (United States)

    Teven, Chad M; Farina, Evan M; Rivas, Jane; Reid, Russell R

    2014-12-01

    Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.

  14. Fatores determinantes do crescimento infantil Determinant factors of infant growth

    Directory of Open Access Journals (Sweden)

    Sylvia de Azevedo Mello Romani

    2004-03-01

    Full Text Available Esta revisão enfoca os fatores que interferem no crescimento de crianças nos primeiros anos de vida. Foram utilizadas informações de artigos publicados em revistas científicas, teses e publicações de organizações internacionais. O crescimento infantil se constitui em um dos melhores indicadores de saúde da criança e o retardo estatural representa atualmente, a característica antropométrica mais representativa do quadro epidemiológico da desnutrição no Brasil. Ressaltando a importância do fator genético no crescimento, a revisão abrange com maior ênfase a atuação dos fatores extrínsecos, sabendo-se que o processo de crescimento resulta da interação entre a carga genética e os fatores do meio ambiente, os quais premitirão a maior ou menor expressão do potencial genético. Face a comprovada natureza multicausal do crescimento infantil, vários estudos têm sido desenvolvidos, buscando relacionar variáveis biológicas, socioeconômicas, maternas, ambientais, culturais, demográficas, nutricionais, entre outras, com a sua etiologia, seu desenvolvimento e sua manutenção. A revisão apresentada reforça o interesse em investigações sobre o crescimento na primeira infância que devem ser permanentes, devido, principalmente, às repercussões a longo prazo sobre a saúde infantil.This review focuses on factors interfering with growth during the first years of life. Information was collected from articles published in indexed scientific journals, theses, technical books and publications of international organizations. Infant growth is one of the best health indicators, and linear growth retardation is currently the most representative anthropometric characteristic of child nutrition epidemiology in Brazil. The review indicates the value of genetics in growth, focusing, however on the influence of the extrinsic factors. Growth process results from interaction between genetic and environmental factors, determining variation

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

    Science.gov (United States)

    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.

  16. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

    Science.gov (United States)

    Wu, Shufang; Yang, Wei; De Luca, Francesco

    2015-07-01

    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  17. Nerve growth factor improves ligament healing.

    Science.gov (United States)

    Mammoto, Takeo; Seerattan, Ruth A; Paulson, Kent D; Leonard, Catherine A; Bray, Robert C; Salo, Paul T

    2008-07-01

    Previous work has shown that innervation participates in normal ligament healing. The present study was performed to determine if exogenous nerve growth factor (NGF) would improve the healing of injured ligament by promoting reinnervation, blood flow, and angiogenesis. Two groups of 30 Sprague-Dawley rats underwent unilateral medial collateral ligament transection (MCL). One group was given 10 microg NGF and the other was given PBS via osmotic pump over 7 days after injury. After 7, 14, and 42 days, in vivo blood flow was measured using laser speckle perfusion imaging (LSPI). Morphologic assessments of nerve density, vascularity, and angiogenesis inhibitor production were done in three animals at each time point by immunohistochemical staining for the pan-neuronal marker PGP9.5, the endothelial marker vWF, and the angiogenesis inhibitor thrombospondin-2 (TSP-2). Ligament scar material and structural mechanical properties were assessed in seven rats at each time point. Increased nerve density was promoted by NGF at both 14 and 42 days. Exposure to NGF also led to increased ligament vascularity, as measured by histologic assessment of vWF immunohistochemistry, although LSPI-measured blood flow was not significantly different from controls. NGF treatment also led to decreased expression of TSP-2 at 14 days. Mechanical testing revealed that exposure to NGF increased failure load by 40%, ultimate tensile strength by 55%, and stiffness by 30% at 42 days. There were no detectable differences between groups in creep properties. The results suggest that local application of NGF can improve ligament healing by promoting both reinnervation and angiogenesis, and results in scars with enhanced mechanical properties.

  18. Fibroblast growth factor signaling in metabolic regulation

    Directory of Open Access Journals (Sweden)

    Vera eNies

    2016-01-01

    Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  19. Transforming growth factor-β and Smads.

    Science.gov (United States)

    Lan, Hui Yao; Chung, Arthur C K

    2011-01-01

    Diabetic nephropathy (DN) is a major diabetic complication. Transforming growth factor-β(TGF-β) is a key mediator in the development of diabetic complications. It is well known that TGF-β exerts its biological effects by activating downstream mediators, called Smad2and Smad3, which is negatively regulated by an inhibitory Smad7. Recent studies also demonstrated that under disease conditions Smads act as signal integrators and interact with other signaling pathways such as the MAPK and NF-κB pathways. In addition, Smad2and Smad3 can reciprocally regulate target genes of TGF-β signaling. Novel research into microRNA has revealed the complexity of TGF-β signaling during DN. It has been found that TGF-β and elevated glucose concentration can positively regulate miR-192 and miR-377, but negatively regulate miR-29a in a diabetic milieu. These microRNAs are found to contribute to DN. Although targeting TGF-β may exert adverse effects on immune system, therapeutic approach against TGF-β signaling during DN still draws much attention. Blocking TGF-β signaling by neutralizing antibody, anti-sense oligonucleotides, and soluble receptors have been tested, but effects are limited. Gene transfer of Smad7 into diseased kidneys demonstrates a prominent inhibition on renal fibrosis and amelioration of renal impairment. Alteration of TGF-β-regulated microRNA expression in diseased kidneys may provide an alternative therapeutic approach against DN. In conclusion, TGF-β/Smad signaling plays a critical role in DN. A better understanding of the role of TGF-β/Smad signaling in the development of DN should provide an effective therapeutic strategy to combat DN.

  20. [Effect of cryotherapy over the expression of vascular endothelial growth factor and pigment epithelium-derived factor].

    Science.gov (United States)

    Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier

    2014-01-01

    Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

  1. Relation between transforming growth factor-βtypeⅡreceptor and progmosis of patients with human epidermal growth factor receptor-negative breast tumors%转化生长因子βⅡ受体与人表皮生长因子受体2阴性乳腺癌患者预后的关系

    Institute of Scientific and Technical Information of China (English)

    殷科; 郭宇

    2014-01-01

    Objective To explore the relation between transforming growth factor-βtype II receptor ( TGF-βRⅡ) and the prognosis of hu-man epidermal growth factor receptor 2 ( HER2 ) -negative breast concer patients.Methods The expressions of TGF -β1 and TGF-βⅡwere de-tected by immunohistochemical in 102 HER2-negative breast tumours pa-tients.The correlation between the expressions and the clinicopathologic characteristics was analyzed.Results The positive expression rates of TGF-βⅡand TGF-β1 detected in HER2-negative breast cancer pa-tients were 39.22%and 31.37%.The 5-years overall survival rate of the TGF-βⅡ-positive patients (77.50%) was significantly higher than that of TGF-βⅡ-negitive patients (53.23%).The 5-years overall survival rate of the TGF-β1-positive patients (71.88%) was significantly higher than that of TGF -β1-negitive patients (45.71%).The COX proportion-al hazard model showed that expressions of TGF -βⅡand estrogen recep-tor ,tumor size and lymph node involvement were independent factors influ -encing on prognostic.Conclusion TGF-βⅡcan be used to judge the progrosis of HER2-negative breast cancer patients .%目的:评价转化生长因子βⅡ受体( TGF-βRⅡ)与人表皮生长因子受体2(HER2)阴性乳腺癌患者预后的关系。方法用免疫组化法检测102例HER2阴性乳腺癌组织中转化生长因子β1( TGF-β1)和TGF-βⅡ的表达,分析其与临床病理特征的关系。结果 HER2阴性乳腺癌患者TGF-βⅡ和TGF-β1阳性表达率分别为39.22%(40/102)和31.37%(32/102)。 TGF-βⅡ阳性者5年生存率(77.50%)显著高于TGF-βⅡ阴性者(53.23%),TGF-β1阳性者5年生存率(71.88%)显著高于TGF-β1阴性者(45.71%);Cox比例风险模型显示,TGF-βⅡ、雌激素受体( ER)、肿瘤大小和淋巴结转移是影响HER2阴性乳腺癌患者预后的独立因素。结论 TGF-βⅡ可作为判断HER2阴性乳腺癌患者预后的指标。

  2. Economic growth factors system: theoretical and methodological aspect

    Directory of Open Access Journals (Sweden)

    H.Ya. Hlukha

    2014-03-01

    Full Text Available The aim of the article. The main objective of the article is to create theoretical grounds to build the system of economic growth factors, to modernize their classification, to define exogenous and endogenous factors, to analyze them within the state economic policy structure. The results of the analysis. The article focuses on economic growth factors theoretical studies: - economic growth factors classification characteristics have been highlighted; - various approaches to determine exogenous and endogenous factors have been analyzed; - reflexive and elastic economic growth factors have been determined; - economic policy was given the role of reflective element within the system to ensure economic growth. The system of factors should be considered within the system that ensures economic growth. It comprises two important elements which enlist the economic growth factors system, economic growth rates system and two reflexive elements – the state economic policy and economic growth models system. While analyzing the economic growth factors, their quality and impact upon the economy should be considered. Economic growth depends on the factors, consideration of which is one of the most important aspects of the economic growth theory. Economic growth reasons are the factors that cause this growth. These are phenomena and processes that can increase the production output, improve efficiency and quality. Factors classification completeness and their diversity do not necessarily mean the dead end of the study. Any classification has the sense only if it fulfills the certain function. If we take into account economic growth modeling, factors diversification and their characteristics classification it implies that models are becoming more complex, the range of their parameters expands, however it does not necessarily lead to more accurate prognosis. All the factors have different impact upon the economic development. Their first type is elastic ones

  3. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter

    1994-01-01

    -growth-factor motifs and contains up to ten O-glycosylation and N-glycosylation sites, six of which are differentially glycosylated. Alignment to the translated sequences of Mus. musculus dlk and human dlk revealed 86% and 99% identity, respectively, to a 259-amino-acid residue overlap, and this high similarity...

  4. Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium

    NARCIS (Netherlands)

    Canzian, Federico; Cox, David G.; Setiawan, V. Wendy; Stram, Daniel O.; Ziegler, Regina G.; Dossus, Laure; Beckmann, Lars; Blanche, Helene; Barricarte, Aurelio; Berg, Christine D.; Bingham, Sheila; Buring, Julie; Buys, Saundra S.; Calle, Eugenia E.; Chanock, Stephen J.; Clavel-Chapelon, Francoise; DeLancey, John Oliver L.; Diver, W. Ryan; Dorronsoro, Miren; Haiman, Christopher A.; Hallmans, Goeran; Hankinson, Susan E.; Hunter, David J.; Huesing, Anika; Isaacs, Claudine; Khaw, Kay-Tee; Kolonel, Laurence N.; Kraft, Peter; Le Marchand, Loic; Lund, Eiliv; Overvad, Kim; Panico, Salvatore; Peeters, Petra H. M.; Pollak, Michael; Thun, Michael J.; Tjonneland, Anne; Trichopoulos, Dimitrios; Tumino, Rosario; Yeager, Meredith; Hoover, Robert N.; Riboli, Elio; Thomas, Gilles; Henderson, Brian E.; Kaaks, Rudolf; Feigelson, Heather Spencer

    2010-01-01

    There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide con

  5. Pattern of hormone receptors and human epidermal growth factor ...

    African Journals Online (AJOL)

    2015-02-05

    Feb 5, 2015 ... Key words: Breast cancer, human epidermal growth factor receptor 2/neu, immunohistochemistry, ... therapy.[6‑8] Of all these prognostic and predictive factors, ... one of the biggest private medical laboratories in Nigeria.

  6. Bisphenol A and Related Alkylphenols Exert Nongenomic Estrogenic Actions Through a G Protein-Coupled Estrogen Receptor 1 (Gper)/Epidermal Growth Factor Receptor (Egfr) Pathway to Inhibit Meiotic Maturation of Zebrafish Oocytes.

    Science.gov (United States)

    Fitzgerald, Amanda C; Peyton, Candace; Dong, Jing; Thomas, Peter

    2015-12-01

    Xenobiotic estrogens, such as bisphenol A (BPA), disrupt a wide variety of genomic estrogen actions, but their nongenomic estrogen actions remain poorly understood. We investigated nongenomic estrogenic effects of low concentrations of BPA and three related alkylphenols on the inhibition of zebrafish oocye maturation (OM) mediated through a G protein-coupled estrogen receptor 1 (Gper)-dependent epidermal growth factor receptor (Egfr) pathway. BPA (10-100 nM) treatment for 3 h mimicked the effects of estradiol-17beta (E2) and EGF, decreasing spontaneous maturation of defolliculated zebrafish oocytes, an effect not blocked by coincubation with actinomycin D, but blocked by coincubation with a Gper antibody. BPA displayed relatively high binding affinity (15.8% that of E2) for recombinant zebrafish Gper. The inhibitory effects of BPA were attenuated by inhibition of upstream regulators of Egfr, intracellular tyrosine kinase (Src) with PP2, and matrix metalloproteinase with ilomastat. Treatment with an inhibitor of Egfr transactivation, AG1478, and an inhibitor of the mitogen-activated protein kinase (MAPK) 3/1 pathway, U0126, increased spontaneous OM and blocked the inhibitory effects of BPA, E2, and the selective GPER agonist, G-1. Western blot analysis showed that BPA (10-200 nM) mimicked the stimulatory effects of E2 and EGF on Mapk3/1 phosphorylation. Tetrabromobisphenol A, 4-nonylphenol, and tetrachlorobisphenol A (5-100 nM) also inhibited OM, an effect blocked by cotreatment with AG1478, as well as with the GPER antagonist, G-15, and displayed similar binding affinities as BPA to zebrafish Gper. The results suggest that BPA and related alkylphenols disrupt zebrafish OM by a novel nongenomic estrogenic mechanism involving activation of the Gper/Egfr/Mapk3/1 pathway.

  7. Epidermal growth factor inhibits cysteamine-induced duodenal ulcers

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1983-01-01

    The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300...... mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also...... factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition...

  8. Clinical application of growth factors and cytokines in wound healing.

    Science.gov (United States)

    Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2014-01-01

    Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte-macrophage colony-stimulating factor, platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor. While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy.

  9. Health Scenario of Major Tribals of Northern Orissa in Relation to Human Growth, Development and Nutrition and the Role of Genetic Factors in Smell and Tasting Abilities in Children

    Directory of Open Access Journals (Sweden)

    Balgir RS

    2011-01-01

    Full Text Available The nature of physical growth and development of children depends primarily upon the genetic endowments, nutritional status, psychosocial attitude and surrounding physical environmental conditions. School going children are the most important segment of the society who are affected by under- and mal-nutrition. Good nutrition is an indispensable component of healthy life. Tribal children studying in Ashram schools can be taken as representatives of the predominant tribes of the area. This study was aimed at evaluating the health profile in relation to growth, development and nutrition of a randomly selected cross section of 1038 Ashram school children aged six through 15 years in the state of Orissa. Following the standard methodology, it was noticed that nutritional complications are compounded due to ignorance, bad food habits, food fads, and poverty. About 71% of the Ashram school children showed mild to moderate anemia. According to different grades of malnutrition, the frequency of grade III malnutrition was very low in Ashram-school boys (1.4% and girls (3.5%, with an average of 2.3%. The grade I as well as grade II malnutrition was also higher in girls (grade II =24.3%; grade I= 37.6% as compared to boys (grade II=16.7%; grade I=31.5% with an average of 19.9% and 34.1%, respectively for grade II and grade I malnutrition. There was a consistent pattern of increase in height and weight in the year six through fifteen of age, showing that height and weight of the Ashram school children increases with the corresponding advancement of age in both boys and girls. In general, the girls were shorter and lighter in weight than the boys. This pattern is consistent in the present study of Ashram school children in Orissa. It has been observed that apart from the genetic potential, the intra-uterine environment, mother’s nutritional status before, during and post pregnancy, and neonatal nutrition and associated traditional behavior drastically

  10. INTRAUTERINE GROWTH RETARDATION AT FULL TERM PREGNANCIES WITH ENDOCRINE FACTORS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate the relationship between intrauterine growth retardation (IUGR) and en docrine parameters so as to assess the effects of the main endocrine factors on IUGR. The concentrations of growth hormone (GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum. Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants' weight were taken as control. Growth hormone and insulin were mea sured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentra tions of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH 4. 63μg/L vs 7.01μg/L, insulin 10. 68μIU/ml vs 31.44μIU/ml, T4 87. 39nmol/L vs 138. 10nmol/L. P <0. 05, 0. 05 and 0. 05, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (10. 84μmIU/L vs 5. 75μmIU/L, P <0. 01). The concentration of growth hormone in maternal serum and the concen tration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1.77μg/L vs 2.74μg/L, P <0. 01, insulin 5. 84μIU/mi vs 15. 64μIU/ml, P <0. 01). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relative scarcity of growth hormone and insulin seems to be a factor to compromise the fetus' metabolism. Be sides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.

  11. Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis of H1299 cells via ROS-dependent and p53-independent NF-κB activation

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hong Shik [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Baek, Jeong-Hwa [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Yim, Ji-Hye [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Su-Jae [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Song, Jie-Young; Um, Hong-Duck; Park, Jong Kuk; Park, In-Chul [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hwang, Sang-Gu, E-mail: sgh63@kcch.re.kr [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2014-07-11

    Highlights: • HRP-3 is a radiation- and anticancer drug-responsive protein in H1299 cells. • Depletion of HRP-3 induces apoptosis of radio- and chemoresistant H1299 cells. • Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. • ROS generation enhances NF-κB activity, which acts as an upstream signal in the c-Myc/Noxa apoptotic pathway. - Abstract: We previously identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistant biomarker in p53 wild-type A549 cells and found that p53-dependent induction of the PUMA pathway was a critical event in regulating the radioresistant phenotype. Here, we found that HRP-3 knockdown regulates the radioresistance of p53-null H1299 cells through a distinctly different molecular mechanism. HRP-3 depletion was sufficient to cause apoptosis of H1299 cells by generating substantial levels of reactive oxygen species (ROS) through inhibition of the Nrf2/HO-1 antioxidant pathway. Subsequent, ROS-dependent and p53-independent NF-κB activation stimulated expression of c-Myc and Noxa proteins, thereby inducing the apoptotic machinery. Our results thus extend the range of targets for the development of new drugs to treat both p53 wild-type or p53-null radioresistant lung cancer cells.

  12. Molecular characterization of transforming growth factor-ß3.

    NARCIS (Netherlands)

    ten Dijke, P.

    1991-01-01

    Normal tissue homeostasis is controlled by a critical balance of positive and negative modulators. Chapter 2 gives an overview of the molecular aspects of growth control, in particular the role of growth factors and oncogene and anti-oncogene products. Uncontrolled growth of cancer cells may result

  13. Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia.

    Science.gov (United States)

    Wang, Zongwei; Olumi, Aria F

    2011-01-01

    Diabetes significantly increases the risk of benign prostatic hyperplasia (BPH) and low urinary tract symptoms (LUTS). The major endocrine aberration in connection with the metabolic syndrome is hyperinsulinemia. Insulin is an independent risk factor and a promoter of BPH. Insulin resistance may change the risk of BPH through several biological pathways. Hyperinsulinemia stimulates the liver to produce more insulin-like growth factor (IGF), another mitogen and an anti-apoptotic agent which binds insulin receptor/IGF receptor and stimulates prostate growth. The levels of IGFs and IGF binding proteins (IGFBPs) in prostate tissue and in blood are associated with BPH risk, with the regulation of circulating androgen and growth hormone. Stromal-epithelial interactions play a critical role in the development and growth of the prostate gland and BPH. Previously, we have shown that the expression of c-Jun in the fibroblastic stroma can promote secretion of IGF-I, which stimulates prostate epithelial cell proliferation through activating specific target genes. Here, we will review the epidemiologic, clinical, and molecular findings which have evaluated the relation between diabetes and development of BPH.

  14. Vascular Endothelial Growth Factor, diagnostic and therapeutic aspects

    NARCIS (Netherlands)

    Kusumanto, Yoka Hadiani

    2006-01-01

    This thesis focuses on the diagnostic and therapeutic potential of Vascular Endothelial Growth Factor, an angiogenic growth factor. Since the recognition of VEGF’s pivotal role in physiological and pathological angiogenesis research has evolved from cell culture and animal experiments to application

  15. Insulin-like growth factors and kidney disease.

    Science.gov (United States)

    Bach, Leon A; Hale, Lorna J

    2015-02-01

    Insulin-like growth factors (IGF-1 and IGF-2) are necessary for normal growth and development. They are related structurally to proinsulin and promote cell proliferation, differentiation, and survival, as well as insulin-like metabolic effects, in most cell types and tissues. In particular, IGFs are important for normal pre- and postnatal kidney development. IGF-1 mediates many growth hormone actions, and both growth hormone excess and deficiency are associated with perturbed kidney function. IGFs affect renal hemodynamics both directly and indirectly by interacting with the renin-angiotensin system. In addition to the IGF ligands, the IGF system includes receptors for IGF-1, IGF-2/mannose-6-phosphate, and insulin, and a family of 6 high-affinity IGF-binding proteins that modulate IGF action. Disordered regulation of the IGF system has been implicated in a number of kidney diseases. IGF activity is enhanced in early diabetic nephropathy and polycystic kidneys, whereas IGF resistance is found in chronic kidney failure. IGFs have a potential role in enhancing stem cell repair of kidney injury. Most IGF actions are mediated by the tyrosine kinase IGF-1 receptor, and inhibitors recently have been developed. Further studies are needed to determine the optimal role of IGF-based therapies in kidney disease. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  16. A role for platelet-derived growth factor-BB in rat postpneumonectomy compensatory lung growth.

    Science.gov (United States)

    Yuan, Shizeng; Hannam, Vicky; Belcastro, Rosetta; Cartel, Nicholas; Cabacungan, Judy; Wang, Jinxia; Diambomba, Yenge; Johnstone, Leslie; Post, Martin; Tanswell, A Keith

    2002-07-01

    Unilateral pneumonectomy leads to compensatory growth in the residual lung, the mediators of which are largely unknown. We hypothesized, based on its other known roles in lung cell growth, that platelet-derived growth factor (PDGF)-BB would be an essential mediator of postpneumonectomy compensatory lung growth. Left-sided pneumonectomies were performed on 21-d-old rats, for comparison with sham-operated or unoperated control animals. Body weights were not different between groups. Right lung weights and DNA content were significantly increased (p < 0.05), compared with controls, by 10 d after pneumonectomy. The rate of DNA synthesis was maximal on d 5 postpneumonectomy. Total right lung PDGF-B mRNA and PDGF-BB protein increased after pneumonectomy, but were apparently tightly regulated, relative to total right lung beta-actin mRNA and protein content, respectively. However, PDGF-BB expression after pneumonectomy was apparently not purely constitutive, in that daily i.p. injections of a truncated soluble PDGF beta-receptor both reduced activation of the native PDGF beta-receptor, and attenuated increased lung DNA synthesis on d 3 after pneumonectomy. These findings are consistent with a critical role for PDGF-BB in postpneumonectomy lung growth.

  17. Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

    Science.gov (United States)

    Chen, Guobao; Lv, Yonggang

    2015-01-01

    Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

  18. Epidermal growth factor receptor mutation enhances expression of vascular endothelial growth factor in lung cancer.

    Science.gov (United States)

    Hung, Ming-Szu; Chen, I-Chuan; Lin, Paul-Yann; Lung, Jr-Hau; Li, Ya-Chin; Lin, Yu-Ching; Yang, Cheng-Ta; Tsai, Ying-Huang

    2016-12-01

    Epidermal growth factor receptor (EGFR) activation has been demonstrated to have a critical role in tumor angiogenesis. In the present study, the correlation between EGFR mutations and vascular endothelial growth factor (VEGF) was investigated in lung cancer cell lines and non-small-cell lung cancer (NSCLC) tumor tissues. VEGF levels were significantly increased in culture medium of lung cancer cells and NSCLC tissues with EGFR mutations (H1650 vs. A549, P=0.0399; H1975 vs. A549, Plung cancer cell lines expressing mutant (exon 19 deletion, E746-A750; exon 21 missense mutation, L858R) and wild-type EGFR genes were established. Significantly increased expression of VEGF and stronger inhibitory effects of gefitinib to VEGF expression were observed in exon 19 deletion stable lung cancer cells (exon 19 deletion vs. wild-type EGFR, P=0.0005). The results of the present study may provide an insight into the association of mutant EGFR and VEGF expression in lung cancer, and may assist with further development of targeted therapy for NSCLC in the future.

  19. Efficacy of glial growth factor and nerve growth factor on the recovery of traumatic facial paralysis.

    Science.gov (United States)

    Yildiz, Mucahit; Karlidag, Turgut; Yalcin, Sinasi; Ozogul, Candan; Keles, Erol; Alpay, Hayrettin Cengiz; Yanilmaz, Muhammed

    2011-08-01

    The aim of this study was to assess the effects of Glial growth factor (GGF) and nerve growth factor (NGF) on nerve regeneration in facial nerve anastomosis. In this study, approximately a 1-mm segment was resected from the facial nerve and the free ends were anastomosed. All animals underwent the same surgical procedure and 30 rabbits were grouped randomly in three groups. Control group, the group without any medications; NGF group, the group receiving 250 ng/0.1 ml NGF in the epineurium at the site of anastomosis; GBF group, the group receiving 500 ng/0.1 ml GGF in the epineurium at the site of anastomosis. Medications were given at the time of surgery, and at 24 and 48 h postoperatively. After 2 months, the sites of anastomosis were excised and examined using the electron microscope. It was found that the best regeneration was in the group receiving GGF as compared to the control group in terms of nerve regeneration. Schwann cell and glial cell proliferation were found to be significantly higher in the group receiving GGF as compared to the group receiving NGF. Besides, the number of myelin debris, an indicator of degeneration, was significantly lower in the group with GGF as compared to NGF and control groups (p NGF in order to increase regeneration after nerve anastomosis in experimental traumatic facial nerve paralysis may be a hopeful alternative treatment option in the future. However, further studies on human studies are required to support these results.

  20. Stress-Related Growth in Racial/Ethnic Minority Adolescents: Measurement Structure and Validity

    Science.gov (United States)

    Vaughn, Allison A.; Roesch, Scott C.; Aldridge, Arianna A.

    2009-01-01

    Stress-related growth is defined as the perception or experience of deriving benefits from encountering stressful circumstances and, thus, has been identified as a protective factor against stress. The current study revised and subsequently validated scores on an existing measure of stress-related growth in a sample of racial/ethnic minority…

  1. Enhanced Phosphoproteomic Profiling Workflow For Growth Factor Signaling Analysis

    DEFF Research Database (Denmark)

    Sylvester, Marc; Burbridge, Mike; Leclerc, Gregory

    2010-01-01

    understanding of pathological processes. In our study we create and integrate data on phosphorylations that are initiated by several growth factor receptors. We present an approach for quantitative, time-resolved phosphoproteomic profiling that integrates the important contributions by phosphotyrosines. Methods...... A549 lung carcinoma cells were used as a model and stimulated with hepatocyte growth factor, epidermal growth factor or fibroblast growth factor. We employed a quick protein digestion workflow with spin filters without using urea. Phosphopeptides in general were enriched by sequential elution from...... in order to maximize identification of peptides as well as localization of phosphorylation sites. Results and Conclusions The combination of SIMAC with phosphotyrosine enrichment leads to a significant increase in identification of potential signaling events in growth factor receptor signaling networks...

  2. The growth of foot arches and influencing factors

    OpenAIRE

    Ferial Hadipoetro Idris

    2016-01-01

    Background Foot arches are important components for body sup- port. Foot arch deformity caused by growth abnormalities cause serious limitations in daily activities. Objectives To determine the patterns of foot arch growth, factors influencing foot arch growth, and the timing for intervention in er- rant growth patterns. Methods A cross-sectional study evaluated the foot arches of chil- dren aged 0-18 years according to age and sex. Subjects included had no evidence of...

  3. Potent, selective inhibitors of fibroblast growth factor receptor define fibroblast growth factor dependence in preclinical cancer models.

    Science.gov (United States)

    Squires, Matthew; Ward, George; Saxty, Gordan; Berdini, Valerio; Cleasby, Anne; King, Peter; Angibaud, Patrick; Perera, Tim; Fazal, Lynsey; Ross, Douglas; Jones, Charlotte Griffiths; Madin, Andrew; Benning, Rajdeep K; Vickerstaffe, Emma; O'Brien, Alistair; Frederickson, Martyn; Reader, Michael; Hamlett, Christopher; Batey, Michael A; Rich, Sharna; Carr, Maria; Miller, Darcey; Feltell, Ruth; Thiru, Abarna; Bethell, Susanne; Devine, Lindsay A; Graham, Brent L; Pike, Andrew; Cosme, Jose; Lewis, Edward J; Freyne, Eddy; Lyons, John; Irving, Julie; Murray, Christopher; Newell, David R; Thompson, Neil T

    2011-09-01

    We describe here the identification and characterization of 2 novel inhibitors of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases. The compounds exhibit selective inhibition of FGFR over the closely related VEGFR2 receptor in cell lines and in vivo. The pharmacologic profile of these inhibitors was defined using a panel of human tumor cell lines characterized for specific mutations, amplifications, or translocations known to activate one of the four FGFR receptor isoforms. This pharmacology defines a profile for inhibitors that are likely to be of use in clinical settings in disease types where FGFR is shown to play an important role.

  4. Growth related hormones in idiopathic scoliosis. An endocrine basis for accelerated growth.

    Science.gov (United States)

    Skogland, L B; Miller, J A

    1980-10-01

    In a total of 95 children with idiopathic scoliosis and 60 controls between the ages of 7 and 17 years, a prospective study of hormones related to growth and maturation was carried out. The pituitary release mechanism for growth hormone was evaluated using the propanolol/L-dopa stimulation test. In addition the blood levels of testosterone, sex hormone binding globulin, oestradiol, thyroxin, prolactin, cortisol, follicle stimulating hormone and luteinizing hormone were determined. The girls were divided into age groups and all results were evaluated according to chronological and skeletal age. The number of boys was too small (25) to allow subdivision into age groups. The girls with idiopathic scoliosis had a significantly higher response to the growth hormone stimulation test than had the controls between the ages of 7 and 12 years whereas no significant difference could be found for the older girls. In girls with a skeletal age between 9 and 12 years a significantly higher mean serum level of testosterone was found (P less than 0.05). No significant differences could be demonstrated for the remaining hormones. Growth hormone and testosterone are the most important growth factors in prepubertal and pubertal children. Thus, the present findings suggest a hormonal basis for the increased stature in children with idiopathic scoliosis which has previously been reported.

  5. Expression of vascular endothelial growth factor in malignant mesothelioma.

    Science.gov (United States)

    Aoe, Keisuke; Hiraki, Akio; Tanaka, Takehiro; Gemba, Ken-Ichi; Taguchi, Koji; Murakami, Tomoyuki; Sueoka, Naoko; Kamei, Toshiaki; Ueoka, Hiroshi; Sugi, Kazuro; Yoshino, Tadashi; Kishimoto, Takumi

    2006-01-01

    Malignant mesothelioma is the most common primary pleural neoplasm. Angiogenesis is an important component of a variety of pathological processes, including carcinogenesis and tumor metastases. Vascular endothelial growth factor (VEGF) is the most potent known endothelial, cell specific mitogen. The authors assessed the relation between VEGF expression and clinicopathological variables or overall survival, in malignant mesothelioma. We studied 37 patients with malignant pleural mesothelioma and found that 36 out of 37 (97.3%) malignant mesothelioma samples were stained positively for VEGF. An increased expression of VEGF was observed in the epithelioid type compared with the other histological types of malignant mesothelioma, including the biphasic and sarcomatoid types. No statistically significant association was observed between VEGF expression and gender, age, or clinical stage. Furthermore, the expression of VEGF did not impact on the survival of patients with malignant mesothelioma. Although VEGF expression might be important for tumor development and maintenance, it was not identified as a prognostic factor in malignant mesothelioma.

  6. Factores de crecimiento II: factores insulinoides de crecimiento Growth factors II: insuline-like growth binging proteins (GFBPs

    Directory of Open Access Journals (Sweden)

    Juan Guillermo Maldonado E.

    1996-03-01

    Full Text Available Se revisan los Factores Insulinoides de Crecimiento, también denominados ";Factores de Crecimiento Similares a la Insulina";, sobre los cuales se dispone de abundante información. Se sintetizan conocimientos recientes sobre dichos factores con énfasis en los siguientes aspectos: estructura bioquímica, concentraciones y sus cambios en los líquidos biológicos, proteínas fijadoras, receptores, mecanismos de acción y efectos biológicos. This review summarizes recent knowledge concerning Insulin.like growth factors I and II, with emphasis on their biochemical structure, concentrations, binding proteins, receptors, mechanisms of action, biological effects, and alterations of their concentrations in biological fluids.

  7. The impact of vascular endothelial growth factor and basic fibroblast growth factor on cardiac fibroblasts grown under altered gravity conditions

    DEFF Research Database (Denmark)

    Ulbrich, Claudia; Leder, Annekatrin; Pietsch, Jessica

    2010-01-01

    Myocardium is very sensitive to gravitational changes. During a spaceflight cardiovascular atrophy paired with rhythm problems and orthostatic intolerance can occur. The aim of this study was to investigate the impact of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor...

  8. Time-dependent release of growth factors from implant surfaces treated with plasma rich in growth factors.

    Science.gov (United States)

    Sánchez-Ilárduya, María Belén; Trouche, Elodie; Tejero, Ricardo; Orive, Gorka; Reviakine, Ilya; Anitua, Eduardo

    2013-05-01

    Plasma rich in growth factors (PRGFs) technology is an autologous platelet-rich plasma approach that provides a pool of growth factors and cytokines that have been shown to increase tissue regeneration and accelerate dental implant osseointegration. In this framework, the spatiotemporal release of growth factors and the establishment of a provisional fibrin matrix are likely to be key aspects governing the stimulation of the early phases of tissue regeneration around implants. We investigated the kinetics of growth factor release at implant surfaces functionalized either with PRGFs or platelet-poor plasma and correlated the results obtained with the morphology of the resulting interfaces. Our main finding is that activation and clot formation favors longer residence times of the growth factors at the interfaces studied, probably due to their retention in the adsorbed fibrin matrix. The concentration of the platelet-derived growth factors above the interfaces becomes negligible after 2-4 days and is significantly higher in the case of activated interfaces than in the case of nonactivated ones, whereas that of the plasmatic hepatocyte growth factor is independent of platelet concentration and activation, and remains significant for up to 9 days. Platelet-rich plasma preparations should be activated to permit growth factor release and thereby facilitate implant surface osseointegration.

  9. TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

    Science.gov (United States)

    TITLE:TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

  10. TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

    Science.gov (United States)

    TITLE:TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

  11. Polypeptide growth factors in the course of surgical periodontal treatment.

    Science.gov (United States)

    Pietruska, M D; Pietruski, J K; Stokowska, W

    2000-01-01

    The aim of the study was to evaluate the behaviour of certain polypeptide growth factors in patients with rapidly progressive periodontitis (RPP) during periodontal therapy using alloplastic grafts. Concentrations of epidermal growth factor (EGF), fibroblastic growth factor (FGF), platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta) were assayed in blood serum and saliva. Significant differences in the behaviour of growth factors in blood referred to EGF and PDGF. Their mean concentrations in serum of RPP patients were higher both in the preliminary examination and in the final investigation after 3 months compared with control group. However, mean FGF concentrations in serum were significantly higher only in the distant examination. In saliva, the concentrations of EGF, PDGF and FGF were not significantly different compared with control group. Salivary TGF beta in patients with RPP was significantly higher than in controls and increased in the final examination. The differences observed in the concentrations of growth factors in the serum and saliva of patients with RPP indicate that these factors can be involved in inflammation, destruction and regeneration of periodontal tissues.

  12. EDUCATION AS A FACTOR IN ECONOMIC GROWTH.

    Science.gov (United States)

    MACKERTICH, ALEX

    THE VALUE OF AN EDUCATION IN THE ECONOMIC GROWTH OF AN UNDERDEVELOPED COUNTRY (INDIA) WAS INVESTIGATED USING THE CASE STUDY APPROACH. DATA WERE GATHERED AT BOTH THE CENTRAL GOVERNMENT AND VILLAGE LEVELS THROUGH INTERVIEWS WITH INDIAN GOVERNMENT OFFICIALS AND FROM OFFICIAL GOVERNMENT PUBLICATIONS CONCERNING THE NATION'S EDUCATIONAL EFFORTS, AS…

  13. A secreted peptide growth factor, phytosulfokine, acting as a stimulatory factor of carrot somatic embryo formation.

    Science.gov (United States)

    Hanai, H; Matsuno, T; Yamamoto, M; Matsubayashi, Y; Kobayashi, T; Kamada, H; Sakagami, Y

    2000-01-01

    Somatic embryogenesis of the carrot (Daucus carota L.) depends on a set of factors, some of which accumulate in culture medium (conditioned medium, CM). When embryogenic cell clusters were transferred to an embryo-inducing medium, addition of CM derived from somatic embryo culture markedly stimulated somatic embryo formation. The active principles were purified using a simple bioassay system and identified to be phytosulfokines (PSKs), sulfated oligopeptide growth factors originally isolated from a CM derived from asparagus (Asparagus officinalis L.) mesophyll culture. Quantification studies using a competition ELISA system employing an anti-PSK-alpha polyclonal antibody showed that PSK production might be related to growth of cells, rather than development of somatic embryos. Thus the stimulatory effect of PSK on somatic embryo formation might be due to promotion of cell proliferation.

  14. Chemistry Related to Semiconductor Growth Involving Organometallics

    Science.gov (United States)

    1990-05-11

    NDR ) was also observed in a 50-period GaInAs (150A)/InP (80,k) superlattice. These NDRs may be interpreted as being caused by the resonant tunneling...impurity level of the Group V sources. Commercial arsine contains various concentrations of a germanium speciW which provides germanium donors to the... silicon compound. Most of the TEG/TBA and TEG/arsine growth investigations were carried out at 76 Torr. Atmospheric pressure growth showed that under these

  15. Development and validation of a radioimmunoassay for fish insulin-like growth factor I (IGF-I) and the effect of aquaculture related stressors on circulating IGF-I levels.

    Science.gov (United States)

    Dyer, Anthony R; Upton, Zee; Stone, David; Thomas, Philip M; Soole, Kathleen L; Higgs, Naomi; Quinn, Kirsty; Carragher, John F

    2004-02-01

    This paper describes the development and validation of a commercially available radioimmunoassay (RIA) for the detection of fish insulin-like growth factor-I (IGF-I). The assay was developed using recombinant barramundi IGF-I as antigen and recombinant tuna IGF-I as radiolabelled tracer and standard. Assay sensitivity was 0.15 ng/ml, inter-assay variation was 16% (n = 9) and intra-assay variation was 3% (n = 10). Cross reactivity of less than 0.01% was found with salmon insulin, salmon IGF-II and barramundi IGF-II, less than 0.5% with human IGF-I and less than 1% with human IGF-II. Parallel dose-response inhibition curves were shown for barramundi (Lates calcarifer), coho salmon (Oncorhynchus kisutch), Southern Bluefin tuna (Thunnus maccoyii), tilapia (Oreochromis mossambicus), and seabream (Pagrus auratus) IGF-I. The assay was then used to measure stress related changes in different aquacultured fish species. Salt water acclimated Atlantic salmon smolts (Salmo salar) bathed for 2 h in fresh water showed significantly lower IGF-I concentrations than control smolts two days after the bath (53.1 compared to 32.1 ng/ml), with levels of IGF-I also lower in smolts exhibiting stunted growth (stunts). Capture and confinement of wild tuna in sea-cages resulted in a significant decrease in IGF-I levels (28 ng/ml) when compared to tuna captured and sampled immediately (48 ng/ml), but had recovered to starting levels after 3 weeks (43 ng/ml). Handling and isolation in silver perch (Bidyanus bidyanus) led to a gradual decline in IGF-I over a 12 h period (36-19 ng/ml) but showed signs of recovery by 24 h (24 ng/ml) and had recovered fully 72 h after treatment (40 ng/ml). A similar trial in black bream (Acanthopagrus butcherii) showed comparable results with IGF-I levels gradually decreasing (40-26 ng/ml) over 24 h, results that were mirrored by cortisol concentrations which increased during this time (1-26 ng/ml). In the studies presented here changes in IGF-I levels were not

  16. Growth hormone, insulin-like growth factor-1 and the aging brain.

    Science.gov (United States)

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan.

  17. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies.

    Science.gov (United States)

    Sonntag, William E; Csiszar, Anna; deCabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-06-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span.

  18. High-growth-factor implosions (HEP4)

    Energy Technology Data Exchange (ETDEWEB)

    Landen, O.L.; Keane, C.J.; Hammel, B.A. [and others

    1996-06-01

    In inertial confinement fusion (ICF), the kinetic energy of an ablating, inward-driven, solid spherical shell is used to compressionally heat the low-density fuel inside. For a given drive, the maximum achievable compressed fuel density and temperature - and hence the maximum neutron production rate depend on the degree of shell isentropy and integrity maintained during the compression. Shell integrity will be degraded by hydrodynamic instability growth of areal density imperfections in the capsule. Surface imperfections on the shell grow as a result of the Richtmyer-Meshkov and Rayleigh-Taylor (RT) instabilities when the shell is accelerated by the ablating lower-density plasma. Perturbations at the outer capsule surface are transferred hydrodynamically to the inner surface, where deceleration of the shell by the lower-density fuel gives rise to further RT growth at the pusher-fuel interface.

  19. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins

    Directory of Open Access Journals (Sweden)

    Nedelkoska Liljana

    2007-12-01

    Full Text Available Abstract Background In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells. Methods To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the effects of cytokines typical of Th1 and Th2 lymphocytes and monocyte/macrophages (M/M on CNS glia after 6 hours of treatment. Results In this paper we focus on changes with potential relevance for neuroprotection and axon/glial interactions. Each mixture of cytokines induced a unique pattern of changes in genes for neurotrophins, growth and maturation factors and related receptors; most notably an alternatively spliced form of trkC was markedly downregulated by Th1 and M/M cytokines, while Th2 cytokines upregulated BDNF. Genes for molecules of potential importance in axon/glial interactions, including cell adhesion molecules, connexins, and some molecules traditionally associated with neurons showed significant changes, while no genes for myelin-associated genes were regulated at this early time point. Unexpectedly, changes occurred in several genes for proteins initially associated with retina, cancer or bone development, and not previously reported in glial cells. Conclusion Each of the three cytokine mixtures induced specific changes in gene expression that could be altered by pharmacologic strategies to promote protection of the central nervous system.

  20. ENOD40 encodes a peptide growth factor.

    OpenAIRE

    de Sande, van

    1997-01-01

    Rhizobium bacteria induce the formation of nodules on the roots of leguminous plants. The nodules create the right biological niche for the rhizobia to carry out biological nitrogen fixation by which atmospheric nitrogen is reduced to ammonia. The nodule is a new organ that provides the plant with a nitrogen source for its growth and development. The formation of a nitrogen fixing root nodule is the final result of an extensive collaboration between the plant and the bacterium, which starts w...

  1. Dual chain synthetic heparin-binding growth factor analogs

    Science.gov (United States)

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

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  2. Dual chain synthetic heparin-binding growth factor analogs

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY)

    2012-04-24

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  3. Intestinal hormones and growth factors: Effects on the small intestine

    Institute of Scientific and Technical Information of China (English)

    Laurie Drozdowski; Alan BR Thomson

    2009-01-01

    There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting,such as in persons with short bowel syndrome. In partⅠ, we focus first on insulin-like growth factors,epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.

  4. Viability and growth of feline preantral follicles in vitro cultured with insulin growth factor and epidermal growth factor supplemented medium.

    Science.gov (United States)

    Alves, A E; Padilha-Nakaghi, L C; Pires-Butler, E A; Apparicio, M; Silva, Nam; Motheo, T F; Vicente, Wrr; Luvoni, G C

    2017-04-01

    In vitro culture of ovarian preantral follicles has emerged as a reproductive technology aimed at obtaining large amount of oocytes for in vitro embryo production. The addition of growth factors (GF) in the in vitro culture of preantral follicles of different species has provided superior results of follicular development, antrum formation and proliferation of granulosa cells. However, there are only few reports regarding the use of these factors on feline preantral follicle in vitro culture. Thus, the aim of this study was to investigate the effect of a combination of IGF-1 and EGF on in vitro viability and growth of preantral follicles and enclosed oocytes collected from domestic cats. A total of 64 follicles characterized by multilayer granulosa cells were isolated and individually cultured for 6 days (T6) in minimum essential medium supplemented with IGF-1+ EGF (100 ng/ml each) or without (control). A higher percentage of follicles were viable after culture with GF than without, and an increase in size when IGF-1+ EGF were added to the medium (170 ± 32.4 μm (T0) vs. 201 ± 22.3 μm (T6); p  .05). These data suggest that the addition of IGF-1 and EGF to the culture medium promotes the in vitro development of preantral follicles of cats. © 2016 Blackwell Verlag GmbH.

  5. Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.

    Science.gov (United States)

    Wang, Jianguo; Zhu, Xiaoyan; Guo, Yazhou; Wang, Zhe; Zhao, Baoyu; Yin, Yunhou; Liu, Guowen

    2016-07-01

    To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.

  6. Therapeutic modulation of growth factors and cytokines in regenerative medicine.

    Science.gov (United States)

    Ioannidou, Effie

    2006-01-01

    Regeneration that takes place in the human body is limited throughout life. Therefore, when organs are irreparably damaged, they are usually replaced with an artificial device or donor organ. The term "regenerative medicine" covers the restoration or replacement of cells, tissues, and organs. Stem cells play a major role in regenerative medicine by providing the way to repopulate organs damaged by disease. Stem cells have the ability to self renew and to regenerate cells of diverse lineages within the tissue in which they reside. Stem cells could originate from embryos or adult tissues. Growth factors are proteins that may act locally or systemically to affect the growth of cells in several ways. Various cell activities, including division, are influenced by growth factors. Cytokines are a family of low-molecular-weight proteins that are produced by numerous cell types and are responsible for regulating the immune response, inflammation, tissue remodeling and cellular differentiation. Target cells of growth factors and cytokines are mesenchymal, epithelial and endothelial cells. These molecules frequently have overlapping activities and can act in an autocrine or paracrine fashion. A complex network of growth factors and cytokines guides cellular differentiation and regeneration in all organs and tissues. The aim of this paper is to review the role of growth factors and cytokines in different organs or systems and explore their therapeutic application in regenerative medicine. The role of stem cells combined with growth factors and cytokines in the regeneration of vascular and hematopoietic, neural, skeletal, pancreatic, periodontal, and mucosal tissue is reviewed. There is evidence that supports the use of growth factors and cytokines in the treatment of neurological diseases, diabetes, cardiovascular disease, periodontal disease, cancer and its complication, oral mucositis. After solving the ethical issues and establishing clear and reasonable regulations

  7. Biologic and structural differences of thrombopoietic growth factors.

    Science.gov (United States)

    Begley, C G; Basser, R L

    2000-04-01

    The search for a thrombopoietic agent has resulted in the identification of numerous cytokines and growth factors with thrombopoietic activity. However, with the exception of interleukin (IL)-11 and thrombopoietin (TPO), the megakaryopoietic activity of most of these molecules has not produced clearly identifiable clinical benefits. Despite the relatively modest effect of IL-11 on megakaryocyte and platelet production in vitro and in vivo, it does reduce the need for platelet transfusions in specialized clinical settings. In contrast, the c-Mpl ligand TPO has been shown to be a potent stimulator of megakaryocyte and platelet production both in vitro and in vivo. Clinical studies are being conducted with two different preparations of the c-Mpl ligand: recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). A recombinant form of the complete human molecule, rhTPO is glycosylated and produced in mammalian cells. PEG-rHuMGDF consists of only the receptor-binding domain linked to a polyethylene glycol (PEG) moiety and is generated in Escherichia coil. Although c-Mpl ligands are still being evaluated, preliminary evidence indicates that these molecules can elevate platelet counts and may be useful in a range of clinical contexts. This report discusses aspects of the biology behind the clinical actions of IL-11 and the c-Mpl ligands.

  8. Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

    Directory of Open Access Journals (Sweden)

    Andreas Bayer

    2017-01-01

    Full Text Available Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs or their clinically related formulations (e.g., Vivostat PRF® came recently into the physicians’ focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10 and late (transglutaminase-1 and involucrin differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR- dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo.

  9. 低出生体重早产儿宫外发育迟缓的相关因素分析%Related factors of extrauterine growth restriction in low birth weight preterm children

    Institute of Scientific and Technical Information of China (English)

    廖文君

    2014-01-01

    目的:探讨胎龄≤32周低出生体重早产儿宫外发育迟缓(EUGR)发生率及其相关影响因素。方法纳入126例胎龄≤32周低出生体重早产儿,记录胎龄(超声或出生时成熟度分析数据)、出生时体重、身长、头围、性别、是否低于胎龄儿、是否存在呼吸窘迫综合征、最大生理性体重减少率、恢复出生体重的天数、起始肠内喂养时间、完全肠内喂养时间(每天奶量>100 ml/kg·d),37~42周时测定早产儿体重、身长、头围,以体重、身长和头围计,分析EUGR发生率、其危险因素以及适于胎龄儿(AGA)和低于胎龄儿(SGA) EUGR发生率。结果 EUGR组胎龄、出生体重、出生身长、出生头围均低于非EUGR组(均P100 ml/kg·d) were recorded. During 37~42 weeks, weight, length, head circumference, body weight, length and head circumference of premature children were measured. Incidence of EUGR and risk factors, and incidences of EUGR in appropriate for gestational age children (AGA) and small for gestational age children (SGA) were analyzed. Results The gestational age, birth weight, birth length, and head circumference at birth of EUGR group were lower than those of the non-EUGR group (all P<0.01), while the rate of weight loss (%), time to regain birth weight, time for starting enteral feeding and giving full enteral feeding were greater than those of non-EUGR group (all P<0.01). The proportion of SGA was significantly greater than that of non-EUGR group (all P<0.05). Based on weight, length, head circumference, incidences of EUGR in all newborns were 47.6%, 39.7%and 4.8%. Toatally, extrauterine growth retardation rate of SGA was significantly higher than that of AGA (all P<0.01).Gestational age, birth weight, recovery time, and time for full enteral feeding were closely related with EUGR. Conclusion Gestation-al age, intrauterine growth retardation, poor nutritional intake and RDS are still the risk factors of EUGR in premature

  10. Growth of Automorphism Groups of Relatively Free Groups

    Institute of Scientific and Technical Information of China (English)

    V. Drensky; A.I. Papistas

    2001-01-01

    We introduce a new growth function for automorphism groups of residually nilpotent relatively free groups Fn(V) and study its behavior. We prove that, under some natural restrictions, the growth of the group of tame automorphisms of Fn(V) is equal to the growth of the automorphism group of Fn(V), and coincides with the growth of the Lie algebra over Q associated with Fn (V). Applications of our techniques are given.

  11. Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

    2013-10-01

    Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma.

  12. Cardiac Regeneration using Growth Factors: Advances and Challenges

    Science.gov (United States)

    Rebouças, Juliana de Souza; Santos-Magalhães, Nereide Stela; Formiga, Fabio Rocha

    2016-01-01

    Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine. PMID:27355588

  13. Transient expression of acidic fibroblast growth factor in pea (Pisum ...

    African Journals Online (AJOL)

    Yomi

    2012-03-15

    Mar 15, 2012 ... Key words: Pea plants, acidic fibroblast growth factor, leave injection, plant ... It plays important roles in various stages of development and morphogenesis and also in angiogenesis and wound healing processes (Basilico and.

  14. the significance of epidermal growth factor receptor and survivin ...

    African Journals Online (AJOL)

    2013-01-01

    Jan 1, 2013 ... SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE ... Objective: To assess whether epidermal growth factor receptor (EGFR) and survivin ..... lung cancer by the FDA in 2003 (28) and is currently.

  15. The effect of vascular endothelial growth factor-1 expression on ...

    African Journals Online (AJOL)

    Riyad Bendardaf

    2017-02-28

    Feb 28, 2017 ... The effect of vascular endothelial growth factor-1 expression on survival of ... Sharjah, Sharjah, United Arab Emirates; cFaculty of Medicine, Suez Canal University, ..... levels were significantly higher in patients who sub-.

  16. Insulin-like growth factors and pancreas beta cells.

    NARCIS (Netherlands)

    Haeften, T.W. van; Twickler, M.

    2004-01-01

    Abstract Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their signallin

  17. Insulin-like growth factors and pancreas beta cells

    NARCIS (Netherlands)

    van Haeften, TW; Twickler, TB

    2004-01-01

    Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their signalling pathway

  18. fibroblast growth factor, MTDH/Astrocyte elevated gene-1 ...

    African Journals Online (AJOL)

    2012-12-05

    Dec 5, 2012 ... Basic fibroblast growth factor (bFGF), also known as. FGF2 is a ..... lung metastases, but does not affect the tumor growth rate and decreases in .... Knox JD, Wolf C, McDaniel K, Clark V, Loriot M, Bowden GT, et al. Matrilysin.

  19. Beta cell proliferation and growth factors

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette

    1999-01-01

    Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood little...... increase in the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia of the beta cells is observed both in rodents and man. Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH......). Receptors for both GH and PRL are expressed in islet cells and are upregulated during pregnancy. By mutational analysis we have identified different functional domains of the cytoplasmic part of the GH receptor. Thus the mitotic signaling only requires the membrane proximal part of the receptor...

  20. Business factors related to manufacturing firms' performance

    Directory of Open Access Journals (Sweden)

    Stergios Vranakis

    2014-01-01

    Full Text Available Purpose: The main goal is to understand the way many factors affect the investment decision making process and business performance. Design/methodology/approach: This study proposes a new conceptual framework for examining the reasons that manufacturing firms decide to invest on the acquisition of new machinery and equipment in order to improve their infrastructure. It incorporates various factors related to the internal business environment (quality management, investment decisions etc. Findings and Originality/value: A new conceptual framework, establishing the relations between many factors, has been developed, allowing the determinants of adoption of many implications to be discussed and to relate them to the peculiarities of the Greek manufacturing industry. Originality/value: This study presents an overview of the impact of machinery and equipment investment on firm’s performance, giving grasp for further research of the inter-organizational relationships that exist between them. 

  1. Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis***

    Institute of Scientific and Technical Information of China (English)

    Zhihong Chen; Songhe Yang; Yaqiang He; Chengjun Song; Yongping Liu

    2013-01-01

    Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mel itus. In this study, a rat type 2 diabetes mel itus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, fol owing which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to al eviate hippocampal damage in diabetic rats.

  2. Organizational Creativity: A Substantial Factor to Growth

    Directory of Open Access Journals (Sweden)

    Malikeh Beheshtifar

    2013-03-01

    Full Text Available Organizations are increasingly seeking to foster creativity, because it is an important source of organizational innovation as well as competitive advantage. Creativity has been studied from different perspectives and is associated with a number of defining factors and elements. creative organization define as encompassing factors concerning the removal of barriers demonstrating managed innovation, idea evaluation procedures, motivational stimuli, communication procedures, development of idea sources, and evidence of the creative planning process; and organizational creativity is as the creation of a valuable, useful new product, service, idea, procedure, or process by individuals working together in a complex social system. The creative climate encourages people to generate new ideas and helps the organization to grow and increase its efficiency and at the same time it enables members to generate and implement creative ideas more effectively.

  3. The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth.

    Science.gov (United States)

    Sferruzzi-Perri, A N; Owens, J A; Pringle, K G; Roberts, C T

    2011-01-01

    Maternal insulin-like growth factors (IGFs) play a pivotal role in modulating fetal growth via their actions on both the mother and the placenta. Circulating IGFs influence maternal tissue growth and metabolism, thereby regulating nutrient availability for the growth of the conceptus. Maternal IGFs also regulate placental morphogenesis, substrate transport and hormone secretion, all of which influence fetal growth either via indirect effects on maternal substrate availability, or through direct effects on the placenta and its capacity to supply nutrients to the fetus. The extent to which IGFs influence the mother and/or placenta are dependent on the species and maternal factors, including age and nutrition. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing degenerative diseases in adult life, understanding the role of maternal IGFs during pregnancy is essential in order to identify mechanisms underlying altered fetal growth and offspring programming.

  4. Autocrine and/or paracrine insulin-like growth factor-I activity in skeletal muscle

    Science.gov (United States)

    Adams, Gregory R.

    2002-01-01

    Similar to bone, skeletal muscle responds and adapts to changes in loading state via mechanisms that appear to be intrinsic to the muscle. One of the mechanisms modulating skeletal muscle adaptation it thought to involve the autocrine and/or paracrine production of insulinlike growth factor-I. This brief review outlines components of the insulinlike growth factor-I system as it relates to skeletal muscle and provides the rationale for the theory that insulinlike growth factor-I is involved with muscle adaptation.

  5. Autocrine and/or paracrine insulin-like growth factor-I activity in skeletal muscle

    Science.gov (United States)

    Adams, Gregory R.

    2002-01-01

    Similar to bone, skeletal muscle responds and adapts to changes in loading state via mechanisms that appear to be intrinsic to the muscle. One of the mechanisms modulating skeletal muscle adaptation it thought to involve the autocrine and/or paracrine production of insulinlike growth factor-I. This brief review outlines components of the insulinlike growth factor-I system as it relates to skeletal muscle and provides the rationale for the theory that insulinlike growth factor-I is involved with muscle adaptation.

  6. Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation

    DEFF Research Database (Denmark)

    Kratchmarova, Irina; Blagoev, Blagoy; Haack-Sorensen, M.

    2005-01-01

    Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics...... it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences...... capable of changing cell fate....

  7. An allometric scaling relation based on logistic growth of cities

    CERN Document Server

    Chen, Yanguang

    2013-01-01

    The relationships between urban area and population size have been empirically demonstrated to follow the scaling law of allometric growth. This allometric scaling is based on exponential growth of city size and can be termed "exponential allometry", which is associated with the concepts of fractals. However, both city population and urban area comply with the course of logistic growth rather than exponential growth. In this paper, I will present a new allometric scaling based on logistic growth to solve the abovementioned problem. The logistic growth is a process of replacement dynamics. Defining a pair of replacement quotients as new measurements, which are functions of urban area and population, we can derive an allometric scaling relation from the logistic processes of urban growth, which can be termed "logistic allometry". The exponential allometric relation between urban area and population is the approximate expression of the logistic allometric equation when the city size is not large enough. The prop...

  8. Job-related motivational factors among Malaysian employees.

    Science.gov (United States)

    Manshor, Amat Taap; Abdullah, Adilah

    2002-12-01

    This study identified job-related motivational factors among Malaysian employees in several telecommunication companies. Responses were obtained from 1,179 employees at all levels up to senior managers and six different functional divisions, sales and marketing, human resources, finance, technical, information, technology, and support division. All employees were asked to rate the importance of Kovach's 10 job-motivational factors. These factors were good wages, job security, opportunity for career growth in the organization, good working conditions, interesting work, company loyalty to employees, tactful discipline, full appreciation of work done, sympathetic help with personal problems, and feeling of being involved in the organization. The top five factors employees identified as motivating them in their jobs were good wages, job security, company loyalty to employees, good working conditions, and full appreciation for work done. Findings were in accordance with Kovach for U.S. employees, in which the top motivational factors were good wages and job security.

  9. Growth-related alterations during liver carcinogenesis: Effect of promoters

    Energy Technology Data Exchange (ETDEWEB)

    Seglen, P.O.; Gerlyng, P. (Norwegian Radium Hospital, Oslo (Norway))

    1990-08-01

    Bromodeoxyuridine labeling of DNA, binuclearity counting, and flow cytometric analysis of isolated hepatocytes and hepatocyte nuclei has been used to assess heptocellular growth patterns related to liver carcinogenesis. Three growth patterns can be distinguished. Mononucleating growth is observed during liver regeneration and after treatment with the tumor promoter 2-acetylaminofluorene (2-AAF) and its analogue 4-AAF. In this growth mode binucleation does not occur, resulting in a decrease in the fraction of binucleated cells. Binucleating growth is observed during normal liver development and after treatment with compounds such as phenobarbital, characterized by progressive polyploidization and maintenance of a binucleated cell fraction. Diploid growth is the growth pattern of neoplastic liver hepatocytes. Most of the cells in neoplastic lesions (foci, nodules, and carcinomas) are diploid, in contrast to the normal liver. Diploid tumor cells have a much higher proliferative activity than tetraploid tumor cells, suggesting that the latter may posses a limited growth potential that makes abrogation of binucleation proliferatively advantageous.

  10. An immunologic approach to induction of epidermal growth factor deficiency

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier;

    1995-01-01

    Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and development in the fetus and the newborn. To investigate the opposite situation, the effects of insufficient amounts of EGF during development, we wanted to establish an in vivo model with a state of EGF deficiency......(-9) mol/L. The antibodies recognized purified EGF from the submandibular glands (6 kD) and from urine (45 kD) and further native EGF in saliva and urine. The cross-reactivity toward transforming growth factor-alpha was below 3%. Binding of EGF by antibodies inhibited its binding to the EGF...

  11. Insulin-like growth factor 2

    DEFF Research Database (Denmark)

    Valleh, Mehdi Vafaye; Hyttel, Poul; Rasmussen, Mikkel Aabech

    2014-01-01

    in designing strategies for infertility intervention. In this experiment, the possible mechanisms involved in both blastomere proliferation and regulation of cell death were studied by analysis of relative expression patterns of IGF-II, BCL2-L1, BAK1, and HSP70 in 3 classes of morphological quality groups (e...

  12. Neutrophil biology and the next generation of myeloid growth factors.

    Science.gov (United States)

    Dale, David C

    2009-01-01

    Neutrophils are the body's critical phagocytic cells for defense against bacterial and fungal infections; bone marrow must produce approximately 10 x 10(9) neutrophils/kg/d to maintain normal blood neutrophil counts. Production of neutrophils depends on myeloid growth factors, particularly granulocyte colony-stimulating factor (G-CSF). After the original phase of development, researchers modified these growth factors to increase their size and delay renal clearance, increase their biologic potency, and create unique molecules for business purposes. Pegylated G-CSF is a successful product of these efforts. Researchers have also tried to identify small molecules to serve as oral agents that mimic the parent molecules, but these programs have been less successful. In 2006, the European Medicines Agency established guidelines for the introduction of new biologic medicinal products claimed to be similar to reference products that had previously been granted marketing authorization in the European community, called bio-similars. Globally, new and copied versions of G-CSF and other myeloid growth factors are now appearing. Some properties of the myeloid growth factors are similar to other agents, offering opportunities for the development of alternative drugs and treatments. For example, recent research shows that hematopoietic progenitor cells can be mobilized with a chemokine receptor antagonist, chemotherapy, G-CSF, and granulocyte macrophage colony-stimulating factor. Advances in neutrophil biology coupled with better understanding and development of myeloid growth factors offer great promise for improving the care of patients with cancer and many other disorders.

  13. Relative growth rate of rich fen bryophytes

    DEFF Research Database (Denmark)

    Andersen, Dagmar Kappel; Ejrnæs, Rasmus; Riis, Tenna

    Rigkær er blandt den nordlige halvkugles mest artsrige naturtyper, og en lang række sjældne og truede plantearter er knyttet til netop disse områder. I dette forsøg undersøges den relative vækstrate hos to almindelige og to sjældne rigkærsmosser i relation til forskellige niveauer af næringsstoff...

  14. Endothelial heparan sulfate 6-O-sulfation levels regulate angiogenic responses of endothelial cells to fibroblast growth factor 2 and vascular endothelial growth factor

    NARCIS (Netherlands)

    Ferreras, C.; Rushton, G.; Cole, C.L.; Babur, Muhammad; Telfer, B.A.; Kuppevelt, A.H. van; Gardiner, J.M.; Williams, K.J.; Jayson, G.C.; Avizienyte, E.

    2012-01-01

    Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor 165 (VEGF(165)) are potent pro-angiogenic growth factors that play a pivotal role in tumor angiogenesis. The activity of these growth factors is regulated by heparan sulfate (HS), which is essential for the formation of FGF2/FG

  15. Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-hua; WEI Wei; XU Hao; WANG Yan-yan; WU Wen-xi

    2007-01-01

    Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells.Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA.The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells.Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

  16. EXPRESSION OF EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-a AND THEIR RECEPTOR IN HUMAN PITUITARY TUMORS

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Long

    2001-01-01

    [1]LIU Xu-wen, FU Pei-yu, GAO Zhi-xian. Expression of epidermal growth factor receptors in human glioma [J]. Chin J Neurosurgery 1998; 14:71.[2]Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas [J]. Proc Natl Acad Sci USA 1992; 89:4309.[3]Webster J, Ham J, Bevan JS. Preliminary characterization of growth factors secreted by human pituitary tumors [J]. J Clin Endocrinol Metab 1991; 72:687.[4]Klibanski A. Nonsecreting pituitary tumors [J]. Endocrinol Metab Clin North Am 1987; 16:793.[5]LeRiche VK, Asa SL, Ezzat S. Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness [J]. J Clin Endocrinol Metab 1996; 81:656.

  17. LU分解的增长因子%ON GROWTH FACTORS OF THE LU FACTORIZATION

    Institute of Scientific and Technical Information of China (English)

    魏木生; 刘巧华

    2008-01-01

    In this article, we derive upper bounds of different growth factors for the LU factorization, which are dominated by A11(k)-1A12(k),A21(k)A11(k)-1, where A11(k), A12(k), A21(k), A22(k) are sub-matrices of A. We also derive upper bounds of growth factors for the Cholesky factorization. Numerical examples are presented to verify our findings.

  18. Factors Related to Parenting Practices in Taiwan.

    Science.gov (United States)

    Chen, Fu-Mei; Luster Tom

    2002-01-01

    This study examined factors related to authoritarian and authoritative parenting practices among 463 Chinese mothers with preschoolers in Taiwan. Questionnaire findings suggested that maternal depression, child temperament, and degree of parenting daily hassles might have cross-culturally universal influence on parenting practices. Chinese…

  19. Epidermal growth factor induces changes of interaction between epidermal growth factor receptor and actin in intact cells

    Institute of Scientific and Technical Information of China (English)

    Wei Song; Haixing Xuan; Qishui Lin

    2008-01-01

    The epidermal growth factor receptor (EGFR) is a cyto-skeleton-binding protein. Although purified EGFR can interact with actins in vitro and normally at least 10% of EGFR exist in the insoluble cytoskeleton fraction of A431 cells, interaction of cytosolic EGFR with actin can only be visualized by fluorescence resonance energy transfer when epidermal growth factor presents in the cell medium. Results indicate that the correct orientation between EGFR and actin is important in the signal transduction process.

  20. Factors affecting growth and pigmentation of Penicillium caseifulvum

    DEFF Research Database (Denmark)

    Suhr, Karin Isabel; Haasum, I.; Steenstrup, L.D.;

    2002-01-01

    Color formation, metabolite production and growth of Penicillium caseifulvum were studied in order to elucidate factors contributing to. yellow discoloration of Blue Cheese caused by the mold. A screening experiment was set up to study the effect of pH, concentration of salt (NaCl), P, K, N, S, Mg...... and the trace metals Fe, Cu, Zn, Mn on yellow color formation, metabolite production and mold growth. Multivariate statistical analysis showed that the most important factor affecting yellow color formation was pH. The most pronounced formation of yellow color, supported by highest amount of colored metabolites......, appeared at low pH (pH 4). Mold growth was not correlated to the yellow color formation. Salt concentration was the most important factor affecting mold growth and length of lag phase. Production of secondary metabolites was strongly influenced by both pH and salt concentration. The screening results were...

  1. Growth factors: first part Factores de crecimiento I

    Directory of Open Access Journals (Sweden)

    Hilda Norha Jaramillo Londoño

    1996-02-01

    Full Text Available

    Los factores de crecimiento tienen como función activar o inhibir la transcripción génica; es así como la cascada enzimática que se inicia con la activación de los receptores de la membrana citoplasmática, ya sean de tipo segundo mensajero o catalíticos, tiene como efecto final la fosforilación de proteínas, las cuales pueden ser: 1 enzimas que intervienen en las vías metabólicas; 2 proteínas promotoras de la transcripción de genes o, por el contrario, represoras de los mismos (31,32; en algunos casos el efecto final consiste en la transcripción de protooncogenes (33 cuyos productos pueden ser otro factor de crecimiento o receptores para éstos (16; 3 algunos factores de crecimiento ejercen sus efectos sobre los eventos postranscripcionales y postraslacionales (23.

    Los Factores de Crecimiento, incluyendo las citoquinas, representan un número muy grande de polipéptidos, glucoproteínas y otras moléculas relacionadas. Todos ellos promueven la proliferación, la diferenciación y las funciones especializadas de casi cualquier tipo de célula. Juegan un papel importante mediando los modos paracrino, autocrino y endocrino de comunicación. En esta primera parte de una serie se definen y clasifican los factores de crecimiento; para la clasificación se proponen diversos sistemas basados en el período de desarrollo del individuo en que actúan, en el punto crítico del ciclo celular sobre el que ejercen su acción y en los efectos fisiológicos que producen; se discuten, además, someramente, la composición química, los mecanismos de acción y las funciones de estas sustancias.

  2. Growth Hormone-Insulin-Like Growth Factor Axis, Thyroid Axis, Prolactin, and Exercise.

    Science.gov (United States)

    Hackney, Anthony C; Davis, Hope C; Lane, Amy R

    2016-01-01

    This chapter addresses what is known about the endocrine system components growth hormone (GH)-insulin-like growth factor (IGF) axis, thyroid axis, and prolactin relative to exercise and exercise training. Each one of these hormone axes contributes to the maintenance of homeostasis in the body through impact on a multitude of physiological systems. The homeostatic disruption of exercise causes differing responses in each hormone axis. GH levels increase with sufficient stimulation, and IGFs are released in response to GH from the anterior pituitary providing multiple roles including anabolic properties. Changes in the thyroid hormones T3 and T4 vary greatly with exercise, from increases/decreases to no change in levels across different exercise types, intensities and durations. These ambiguous findings could be due to numerous confounding factors (e.g. nutrition status) within the research. Prolactin increases proportionally to the intensity of the exercise. The magnitude may be augmented with extended durations; conflicting findings have been reported with resistance training. While the responses to exercise vary, it appears there may be overall adaptive and regenerative impacts on the body into recovery by these hormones through immune and tissue inflammatory responses/mediations. Nonetheless, well-designed exercise research studies are still needed on each of these hormones, especially thyroid hormones and prolactin.

  3. Insulin-like growth factor system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wilczak, N; de Keyser, J; Cianfarani, S; Clemmons, DR; Savage, MO

    2005-01-01

    Insulin-like growth factor-I (IGF-I) is a neurotrophic factor with insulin-like metabolic activities, and possesses potential clinical applications, particularly in neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is a chronic progressive devastating disorder of the central nervous s

  4. Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: A three factor design

    DEFF Research Database (Denmark)

    Fazio, Alessandro; Jewett, Michael Christopher; Daran-Lapujade, Pascale;

    2008-01-01

    Background: Characterization of cellular growth is central to understanding living systems. Here, we applied a three-factor design to study the relationship between specific growth rate and genome-wide gene expression in 36 steady-state chemostat cultures of Saccharomyces cerevisiae. The three...... factors we considered were specific growth rate, nutrient limitation, and oxygen availability. Results: We identified 268 growth rate dependent genes, independent of nutrient limitation and oxygen availability. The transcriptional response was used to identify key areas in metabolism around which m...... transcription factor target sets, transcription factors that coordinate balanced growth were also identified. Our analysis shows that FhII, Rap1, and Sfp1, regulating protein biosynthesis, have significantly enriched target sets for genes up-regulated with increasing growth rate. Cell cycle regulators...

  5. Nucleotide sequence of a growth-related mRNA encoding a member of the prolactin-growth hormone family.

    OpenAIRE

    Linzer, D I; Nathans, D

    1984-01-01

    As part of the proliferative response to serum, mouse 3T3 cells produce a set of growth-related mRNAs identified by hybridization to cloned cDNAs. One of these mRNAs, which is about 1 kilobase long, appears within a few hours after stimulation of resting cells with serum or platelet-derived growth factor and reaches a high level during the transition from the G1 to the S phase of growth. This mRNA is translated in vitro into a protein of approximately 25 kilodaltons. The corresponding cloned ...

  6. Effects of Electromagnetic Field and Basic Fibroblast Growth Factor on Osteoblast's Growth

    Institute of Scientific and Technical Information of China (English)

    GUOYong; ZHANGXi-zheng; WANGHao; LIBin; LIRui-xin; WUJin-hui; ZHAOYun-shan; WUJi-min

    2004-01-01

    Osteoblasts of rat cultured in vitro were stimulated with pulsed 50 Hz electromagnetic field and basic fibroblast growth factor(bFGF). The MTT method, flow cytometry and histochemistry staining were used to detect cell proliferation, cell cycle and alkaline phosphatase. The results indicated : after stimulated by 1 mT electromagnetic field, the cells are more abundant,have more S phase percentages, 2 mT electromagnetic field have no evident effect on cells' growth;compared with electromagnetic field, the cells stimulated by bFGF are more abundant and have larger S phase ratios. Electromagnetic field and bFGF have no effect on cells, alkaline phosphatase. Therefore ,we concluded that electromagnetic field can enhance osteoblasts growth like some growth factor such as basic fibroblast growth factor, and the osteoblasts', characteristics was not changed.

  7. Chronic administration of epidermal growth factor to pigs induces growth, especially of the urinary tract with accumulation of epithelial glycoconjugates

    DEFF Research Database (Denmark)

    Vinter-Jensen, Lars; Juhl, C O; Poulsen, Steen Seier;

    1995-01-01

    of developmental processes like incisor eruption, inhibition of gastric acid secretion, morphologic changes in the pancreas resembling pancreatitis, and malignancies in mammary glands and the liver. The present investigation was initiated to explore the effects of systemic EGF administration to the mature organism......Epidermal growth factor (EGF) receptor hyperstimulation induced by systemically administered EGF or by the development of transgenic mice overexpressing transforming growth factor alpha (TGF alpha) or other EGF-related ligands is known to induce various effects, such as acceleration...

  8. THE INVESTMENTS, ECONOMIC GROWTH FACTORS OR CONSUMPTION OF DEVELOPMENT POTENTIAL?

    Directory of Open Access Journals (Sweden)

    Huru Dragos

    2008-05-01

    Full Text Available In Romania, in the last year the economic growth is a real phenomenon that is not our subject for demonstration or for analyze in this paper. Our concern is related with the way of manifestation for economic growth in the economic system. We study if not the economic growth on the contrary of development for current or further performance (regardless of economic aspect or level of analyze can unstuck in consumption of the availed resources for consolidate potential for development.

  9. Study on the clinical relativity of glial cell growth factor and prolactin pituitary tumor%胶质细胞生长因子与泌乳素垂体瘤的临床相关性研究

    Institute of Scientific and Technical Information of China (English)

    刘永军; 高翔; 刘吉祥; 李建华

    2014-01-01

    目的:探讨胶质细胞生长因子(GGF)与泌乳素垂体瘤临床的相关性,并分析其预测临床复发的价值。方法研究对象为本院收治的71例泌乳素垂体瘤(PRL )患者,采用免疫组织化学检测GGF在肿瘤组织中的表达情况,分析GGF表达水平与PRL水平、肿瘤大小、微血管密度(MVD)及肿瘤侵袭性的关系,并进一步分析GGF表达水平与泌乳素垂体腺瘤复发的临床联系,最后采用多因素Cox生存风险模型寻求可能的预后影响因素。结果不同PRL水平、肿瘤大小、M VD及肿瘤侵袭性的患者其GGF表达水平也具有明显差异,且差异有统计学意义(P<0.05);3年无复发生存分析显示,GGF高表达组患者的3年无复发生存率(71.4%)和生存期(28.0±2.2)个月均明显低于低表达GGF组88.9%和(32.8±1.5)个月,但差异无统计学意义(P>0.05);多因素Cox生存风险模型分析提示GGF可能是预测泌乳素垂体瘤患者复发预后的独立生物学指标( P<0.05)。结论 GGF与泌乳素垂体瘤患者临床基线资料密切相关,且可能成为预测患者复发预后的重要生物学指标。%Objective To explore clinical relevance of the glial cell growth factor (GGF) and pro‐lactin pituitary tumor ,and to analyze clinical value of its predicting recurrence .Methods Research ob‐ject for the records of 71 cases in our hospital ,prolactin (PRL ) of pituitary adenoma patients using immunohistochemical detection GGF expression in tumor tissue ,analysis GGF expression level and the level of PRL ,tumor size ,microvascular density (MVD) and the relationship between tumor invasive , and further analysis GGF expression level and prolactin pituitary adenoma recurrence of clinical rela‐tion ,finally using multiariable Cox survival risk model for possible prognostic factors .Results The dif‐ferent levels of PRL ,tumor size ,tumor MVD and expression level

  10. In situ formation of poly(vinyl alcohol–heparin hydrogels for mild encapsulation and prolonged release of basic fibroblast growth factor and vascular endothelial growth factor

    Directory of Open Access Journals (Sweden)

    Justine J Roberts

    2016-11-01

    Full Text Available Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native ability of heparin to bind and stabilize growth factors. Basic fibroblast growth factor and vascular endothelial growth factor are heparin-binding growth factors that synergistically enhance angiogenesis. Mild, in situ encapsulation of both basic fibroblast growth factor and vascular endothelial growth factor and subsequent bioactive dual release has not been demonstrated from heparin-crosslinked hydrogels, and the combined long-term delivery of both growth factors from biomaterials is still a major challenge. Both basic fibroblast growth factor and vascular endothelial growth factor were encapsulated in poly(vinyl alcohol-heparin hydrogels and demonstrated controlled release. A model cell line, BaF32, was used to show bioactivity of heparin and basic fibroblast growth factor released from the gels over multiple days. Released basic fibroblast growth factor promoted higher human umbilical vein endothelial cell outgrowth over 24 h and proliferation for 3 days than the poly(vinyl alcohol-heparin hydrogels alone. The release of vascular endothelial growth factor from poly(vinyl alcohol-heparin hydrogels promoted human umbilical vein endothelial cell outgrowth but not significant proliferation. Dual-growth factor release of basic fibroblast growth factor and vascular endothelial growth factor from poly(vinyl alcohol-heparin hydrogels resulted in a synergistic effect with significantly higher human umbilical vein endothelial cell outgrowth compared to basic fibroblast growth factor or vascular endothelial growth factor alone. Poly(vinyl alcohol-heparin hydrogels allowed bioactive growth factor encapsulation and provided controlled release of multiple growth factors which is beneficial toward tissue regeneration applications.

  11. Nerve growth factor signaling in prostate health and disease.

    Science.gov (United States)

    Arrighi, Nicola; Bodei, Serena; Zani, Danilo; Simeone, Claudio; Cunico, Sergio Cosciani; Missale, Cristina; Spano, Pierfranco; Sigala, Sandra

    2010-06-01

    The prostate is one of the most abundant sources of nerve growth factor (NGF) in different species, including humans. NGF and its receptors are implicated in the control of prostate cell proliferation and apoptosis and it can either support or suppress cell growth. The co-expression of both NGF receptors, p75(NGFR) and tropomyosin-related kinase A (trkA), represents a crucial condition for the antiproliferative effect of NGF; indeed, p75(NGFR) is progressively lost during prostate tumorigenesis and its disappearance represents a malignancy marker of prostate adenocarcinoma (PCa). Interestingly, a dysregulation of NGF signal transduction was found in a number of human tumors. This review summarizes the current knowledge on the role of NGF and its receptors in prostate and in PCa. Conclusions bring to the hypothesis that the NGF network could be a candidate for future pharmacological manipulation in the PCa therapy: in particular the re-expression of p75(NTR) and/or the negative modulation of trkA could represent a target to induce apoptosis and to reduce proliferation and invasiveness of PCa.

  12. 极低出生体重儿发育迟缓的相关因素探讨%Study on the relative factors of very low birth weight infants with growth retardation

    Institute of Scientific and Technical Information of China (English)

    张杜燕; 李经猷; 张冰; 李洁敏

    2016-01-01

    目的:探讨极低出生体重儿在宫外生长过程中发生发育迟缓的比率和影响因素。方法:从极低出生体重儿中选出181例胎龄<32周的早产儿,记录其胎龄、出生体重、身长、头围、性别、恢复出生体重时间、首次肠内营养供给时间、首次完全肠内营养供给时间。同时在其生长到37~42周时测量患儿的体重、身长、头围,研究宫外发育迟缓几率和各类危险因素,并同时研究适于胎龄儿和小于胎龄儿宫外发育迟缓发生几率。结果:发育迟缓的患儿胎龄、出生时的体重、身长以及头围均明显低于发育正常新生儿,同时其恢复出生体重时间、首次肠内营养供给时间、首次完全肠内营养供给时间均大于正常发育新生儿,且小于胎龄儿发育迟缓发生几率明显高于适于胎龄儿。结论:极低出生体重儿发育迟缓的影响因素包括胎龄、营养摄入时间等。%Objective To investigate the rate and influence factors of very low birth weight infants with extrauterine growth re-tardation.Method 181 premature infants of gestational age less than 32 weeks were selected from very low birth weight infant born, and recorded data such as gestational age,birth weight,height,head circumference,gender,gestational age children nature,respirato-ry distress rate,birth weight recovery time,the first time of enteral nutrition supply,the first full enteral nutrition feeding time.While growted to 37 ~42 weeks,then measured children′s weight,height,head circumference,studied the extrauterine growth retardation rates and all kinds of risk factors,and also studied the the extrauterine growth retardation rates of gestational age and below gesta-tional age children.Results Compared to normal neonates,the gestational age,birth weight,height,head circumfere nce of children with growth retardation were significantly lower,the birth weight recovery time,first time of enteral nutrition

  13. P01.02FIBROBLAST GROWTH FACTOR 4 CONTRIBUTES TO 3-DIMENSIONAL GROWTH OF HUMAN GLIOBLASTOMA

    OpenAIRE

    Lötsch, D.; Englinger, B.; Pichler, J; Hainfellner, J; Marosi, C; Czech, T.; Knosp, E.; Buchroithner, J; Spiegl-Kreinecker, S.; Berger, W

    2014-01-01

    Glioblastoma growth is driven by receptor tyrosine kinase (RTK)-mediated signals. One of the RTK systems recently coming into focus are the fibroblast growth factor (FGF) high-affinity receptors (FGFR1-FGFR4) due to mutation, overexpression or translocation in several cancer types. FGF/FGFR represents a complex signal network with essential functions in embryonic development, tissue homeostasis and wound healing but also for malignant transformation and growth as well as tumor neoangiogenesis...

  14. The role of connective tissue growth factor, transforming growth factor β1 and Smad signaling pathway in cornea wound healing

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The cornea is a highly specialized and unique organ in the human body. Its main function is to project light from the external environment onto the retina, and it has a specific transparency to perform its function properly. The transparency and integrity of the cornea is of vital importance. The corneal wound, especially laceration deep to Bowman's membrane and stroma, which will inevitably cause scar formation, may cause the degeneration or even loss of sight. Injury can activate many biological factors in cornea as a strong stimulating signal. Transforming growth factors (TGF) and connective tissue growth factors (CTGF) are thought to be related to scar formation after injury. TGF can stimulate stroma cells of cornea and promote synthesis of matrix. Over expression of TGF causes scar formation.1,2 CTGF is a 38 kD cysteine-rich protein molecule and belongs to CCN family (CTGF/Fisp12, Cyr 61/CEF-10, Nov). In 1991, CTGF was firstly found in endothelial cells of human umbilical vein cultured in vitro.3,4 CTGF acts as an important molecule that intermediates the processes of fibrosis, scarring, wound repairing, angiogenesis and embryonic development in many cell types. CTGF plays a unique role in proliferation, differentiation and adhesion of fibroblast cells, which in turn produces large amounts of collagen and other extracellular matrix (ECM) proteins.5-8 CTGF is upregulated in fibrotic diseases, including lung-, skin-, pancreas-, liver-and kidney fibrosis.9,10 This study reports the expressions and interactions of TGF-β1 and CTGF in corneal wound in vivo. This study aimed at determining the expressions and interactions of CTGF and TGF-β1 in Smad signaling pathway during the period when corneal wound was healing.

  15. Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

    Science.gov (United States)

    Wang, Angela; Leong, Daniel J.; He, Zhiyong; Xu, Lin; Liu, Lidi; Kim, Sun Jin; Hirsh, David M.; Hardin, John A.; Cobelli, Neil J.; Sun, Hui B.

    2016-01-01

    Procyanidins are a family of plant metabolites that have been suggested to mitigate osteoarthritis pathogenesis in mice. However, the underlying mechanism is largely unknown. This study aimed to determine whether procyanidins mitigate traumatic injury-induced osteoarthritis (OA) disease progression, and whether procyanidins exert a chondroprotective effect by, at least in part, suppressing vascular endothelial growth factor signaling. Procyanidins (extracts from pine bark), orally administered to mice subjected to surgery for destabilization of the medial meniscus, significantly slowed OA disease progression. Real-time polymerase chain reaction revealed that procyanidin treatment reduced expression of vascular endothelial growth factor and effectors in OA pathogenesis that are regulated by vascular endothelial growth factor. Procyanidin-suppressed vascular endothelial growth factor expression was correlated with reduced phosphorylation of vascular endothelial growth factor receptor 2 in human OA primary chondrocytes. Moreover, components of procyanidins, procyanidin B2 and procyanidin B3 exerted effects similar to those of total procyanidins in mitigating the OA-related gene expression profile in the primary culture of human OA chondrocytes in the presence of vascular endothelial growth factor. Together, these findings suggest procyanidins mitigate OA pathogenesis, which is mediated, at least in part, by suppressing vascular endothelial growth factor signaling. PMID:27941690

  16. Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

    Directory of Open Access Journals (Sweden)

    Angela Wang

    2016-12-01

    Full Text Available Procyanidins are a family of plant metabolites that have been suggested to mitigate osteoarthritis pathogenesis in mice. However, the underlying mechanism is largely unknown. This study aimed to determine whether procyanidins mitigate traumatic injury-induced osteoarthritis (OA disease progression, and whether procyanidins exert a chondroprotective effect by, at least in part, suppressing vascular endothelial growth factor signaling. Procyanidins (extracts from pine bark, orally administered to mice subjected to surgery for destabilization of the medial meniscus, significantly slowed OA disease progression. Real-time polymerase chain reaction revealed that procyanidin treatment reduced expression of vascular endothelial growth factor and effectors in OA pathogenesis that are regulated by vascular endothelial growth factor. Procyanidin-suppressed vascular endothelial growth factor expression was correlated with reduced phosphorylation of vascular endothelial growth factor receptor 2 in human OA primary chondrocytes. Moreover, components of procyanidins, procyanidin B2 and procyanidin B3 exerted effects similar to those of total procyanidins in mitigating the OA-related gene expression profile in the primary culture of human OA chondrocytes in the presence of vascular endothelial growth factor. Together, these findings suggest procyanidins mitigate OA pathogenesis, which is mediated, at least in part, by suppressing vascular endothelial growth factor signaling.

  17. Insulin-like growth factor-I in growth and metabolism

    DEFF Research Database (Denmark)

    Backeljauw, P; Bang, P; Dunger, D B;

    2010-01-01

    Deficiency of insulin-like growth factor-I (IGF-I) results in growth failure. A variety of molecular defects have been found to underlie severe primary IGF-I deficiency (IGFD), in which serum IGF-I concentrations are substantially decreased and fail to respond to GH therapy. Identification of mor...

  18. Insulin-like growth factor-I in growth and metabolism

    DEFF Research Database (Denmark)

    Backeljauw, P; Bang, P; Dunger, D B

    2010-01-01

    Deficiency of insulin-like growth factor-I (IGF-I) results in growth failure. A variety of molecular defects have been found to underlie severe primary IGF-I deficiency (IGFD), in which serum IGF-I concentrations are substantially decreased and fail to respond to GH therapy. Identification of more...

  19. Transforming growth factor alpha controls the transition from hypertrophic cartilage to bone during endochondral bone growth.

    Science.gov (United States)

    Usmani, Shirine E; Pest, Michael A; Kim, Gunwoo; Ohora, Sara N; Qin, Ling; Beier, Frank

    2012-07-01

    We have recently identified transforming growth factor alpha (TGFα) as a novel growth factor involved in the joint disease osteoarthritis. The role of TGFα in normal cartilage and bone physiology however, has not been well defined. The objective of this study was to determine the role of TGFα in bone development through investigation of the Tgfa knockout mouse. The gross skeletons as well as the cartilage growth plates of Tgfa knockout mice and their control littermates were examined during several developmental stages ranging from newborn to ten weeks old. Knockout mice experienced skeletal growth retardation and expansion of the hypertrophic zone of the growth plate. These phenotypes were transient and spontaneously resolved by ten weeks of age. Tgfa knockout growth plates also had fewer osteoclasts along the cartilage/bone interface. Furthermore, knockout mice expressed less RUNX2, RANKL, and MMP13 mRNA in their cartilage growth plates than controls did. Tgfa knockout mice experience a delay in bone development, specifically the conversion of hypertrophic cartilage to true bone. The persistence of the hypertrophic zone of the growth plate appears to be mediated by a decrease in MMP13 and RANKL expression in hypertrophic chondrocytes and a resulting reduction in osteoclast recruitment. Overall, TGFα appears to be an important growth factor regulating the conversion of cartilage to bone during the process of endochondral ossification. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. A Mechanistic Model of the Intravitreal Pharmacokinetics of Large Molecules and the Pharmacodynamic Suppression of Ocular Vascular Endothelial Growth Factor Levels by Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Hutton-Smith, Laurence A; Gaffney, Eamonn A; Byrne, Helen M; Maini, Philip K; Schwab, Dietmar; Mazer, Norman A

    2016-09-06

    Intravitreal injection of anti-VEGF (vascular endothelial growth factor) antibodies or antibody fragments has been shown to be a highly effective treatment for neovascular age-related macular degeneration (wet AMD). The ocular half-life (t1/2) of these large molecules, determined in ocular fluids or derived from serum levels, varies with molecular size and is larger in humans than in preclinical animal species. The high affinity binding of VEGF to these molecules lowers the free concentration of VEGF and reduces its occupancy on VEGF receptors in ocular tissues. To understand the biophysical determinants of t1/2 for anti-VEGF antibodies and the time-course of VEGF in ocular fluids, we developed a mechanistic model of intravitreal pharmacokinetics (IVT PK) for anti-VEGF antibodies and combined it with a mechanistic model of the pharmacodynamics (RVR PD) of VEGF suppression by ranibizumab, an anti-VEGF recombinant, humanized monoclonal antibody fragment (Fab). Our IVT PK model predicts that the ocular t1/2 of a large molecule will be approximately four-times the calculated value of its vitreous diffusion time (Tdiff), defined as rvit(2)/6D, where rvit is the radius of the vitreous chamber in that species (modeled as a sphere), and D is the diffusion coefficient of the molecule in physiological saline at 37 °C obtained from the Stokes-Einstein relation. This prediction is verified from a compilation of data and calculations on various large molecules in the human, monkey, rabbit, and rat and is consistent with the reported t1/2 values of ranibizumab in humans (mean value 7.9 days) and the calculated Tdiff of 1.59 days. Our RVR PD model is based on the publication of Saunders et al. (Br. J. Ophthalmol. 2015, 99, 1554-1559) who reported data on the time-course of VEGF levels in aqueous humor samples obtained from 31 patients receiving ranibizumab treatment for wet AMD and developed a compartmental mathematical model to describe the VEGF suppression profiles. We

  1. Making a tooth: growth factors, transcription factors, and stem cells

    Institute of Scientific and Technical Information of China (English)

    Yah Ding ZHANG; Zhi CHEN; Yi Qiang SONG; Chao LIU; Yi Ping CHEN

    2005-01-01

    Mammalian tooth development is largely dependent on sequential and reciprocal epithelial-mesenchymal interactions.These processes involve a series of inductive and permissive interactions that result in the determination, differentiation,and organization of odontogenic tissues. Multiple signaling molecules, including BMPs, FGFs, Shh, and Wnt proteins,have been implicated in mediating these tissue interactions. Transcription factors participate in epithelial-mesenchymal interactions via linking the signaling loops between tissue layers by responding to inductive signals and regulating the expression of other signaling molecules. Adult stem cells are highly plastic and multipotent. These cells including dental pulp stem cells and bone marrow stromal cells could be reprogrammed into odontogenic fate and participated in tooth formation. Recent progress in the studies of molecular basis of tooth development, adult stem cell biology, and regeneration will provide fundamental knowledge for the realization of human tooth regeneration in the near future.

  2. Lymphatic Vessel Function and Lymphatic Growth Factor Secretion after Microvascular Lymph Node Transfer in Lymphedema Patients

    Directory of Open Access Journals (Sweden)

    Tiina P. Viitanen, MD

    2013-05-01

    Conclusions: Reconstructing the lymphatic anatomy of the axilla with a lymph node flap may offer possibilities that other reconstructive options are lacking. However, we will need further reports and comparative studies about the clinical efficacy of this new promising technique. In addition to the transferred lymph nodes, lymphatic growth factor production may also be induced by other factors related to microvascular breast reconstruction.

  3. The Effects of Environmental Factors on the Growth and Competition of Algae

    Institute of Scientific and Technical Information of China (English)

    Jing; WANG; Jiazhang; CHEN; Shunlong; MENG

    2013-01-01

    In order to study the effect of environmental factors on the algae growth and competition,the author summarized overseas and domestic related researches in recent years.Most of the researches are about the influence of single factor on growth of algae.However,there is insufficient investment on the interaction of different factors and the competition between algae growth.This paper briefly introduced the classification of algae and the role they played in ecological system and focused on the influence which included temperature,illumination,nitrogen,phosphorus and pH on the growth and competition of algal.In the end,the author proposed key questions which were still needed to be studied in order to know more about the relationship between environment effects and growth and competition of algae.Therefore,people could better improve the community structure of algae and water ecological environment,and improve water primary productivity.

  4. Beclin 1 regulates growth factor receptor signaling in breast cancer.

    Science.gov (United States)

    Rohatgi, R A; Janusis, J; Leonard, D; Bellvé, K D; Fogarty, K E; Baehrecke, E H; Corvera, S; Shaw, L M

    2015-10-16

    Beclin 1 is a haploinsufficient tumor suppressor that is decreased in many human tumors. The function of beclin 1 in cancer has been attributed primarily to its role in the degradative process of macroautophagy. However, beclin 1 is a core component of the vacuolar protein sorting 34 (Vps34)/class III phosphatidylinositoI-3 kinase (PI3KC3) and Vps15/p150 complex that regulates multiple membrane-trafficking events. In the current study, we describe an alternative mechanism of action for beclin 1 in breast cancer involving its control of growth factor receptor signaling. We identify a specific stage of early endosome maturation that is regulated by beclin 1, the transition of APPL1-containing phosphatidyIinositol 3-phosphate-negative (PI3P(-)) endosomes to PI3P(+) endosomes. Beclin 1 regulates PI3P production in response to growth factor stimulation to control the residency time of growth factor receptors in the PI3P(-)/APPL(+)-signaling-competent compartment. As a result, suppression of BECN1 sustains growth factor-stimulated AKT and ERK activation resulting in increased breast carcinoma cell invasion. In human breast tumors, beclin 1 expression is inversely correlated with AKT and ERK phosphorylation. Our data identify a novel role for beclin 1 in regulating growth factor signaling and reveal a mechanism by which loss of beclin 1 expression would enhance breast cancer progression.

  5. The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth

    DEFF Research Database (Denmark)

    Bennewith, Kevin L; Huang, Xin; Ham, Christine M

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2...... adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms...

  6. Baltic Factor in Russia-France Relations

    Directory of Open Access Journals (Sweden)

    Maltsev Leonid A.

    2016-12-01

    Full Text Available The article aims to identify the role of the Baltic factor in Russia-France relations. Despite the fact that the Baltic Sea region (BSR no longer plays an important role in Russia-France bilateral relations, the authors attach significance to analysing the dynamics and changes of the BSR role in European politics in the post- Napoleonic period. The authors compare the Russian and the July Monarchies (1830—1848 in the context of the current Vienna system of international relations. The article describes the role of the 1830—1831 uprising in Poland, which was an event of particular importance. The monarchies of the two countries had to take into account new social phenomena, which were more pronounced in France. After the suppression of the uprising in the Polish part of the Russian Empire, Polish emigrants residing in France became the stumbling block for the development of Russia- France relations. The article explores the role of P. de Barante, Ambassador of France to Russia and describes France and Russia’s trade and economic interests in the Baltic Sea region. The authors conclude that the specificity of Russia-France bilateral relations became more apparent during the First and Second World Wars. However, the Baltic factor has lost its relevance over time.

  7. Perfusion-related stimuli for compensatory lung growth following pneumonectomy.

    Science.gov (United States)

    Dane, D Merrill; Yilmaz, Cuneyt; Gyawali, Dipendra; Iyer, Roshni; Ravikumar, Priya; Estrera, Aaron S; Hsia, Connie C W

    2016-07-01

    Following pneumonectomy (PNX), two separate mechanical forces act on the remaining lung: parenchymal stress caused by lung expansion, and microvascular distension and shear caused by increased perfusion. We previously showed that parenchymal stress and strain explain approximately one-half of overall compensation; the remainder was presumptively attributed to perfusion-related factors. In this study, we directly tested the hypothesis that perturbation of regional pulmonary perfusion modulates post-PNX lung growth. Adult canines underwent banding of the pulmonary artery (PAB) to the left caudal (LCa) lobe, which caused a reduction in basal perfusion to LCa lobe without preventing the subsequent increase in its perfusion following right PNX while simultaneously exaggerating the post-PNX increase in perfusion to the unbanded lobes, thereby creating differential perfusion changes between banded and unbanded lobes. Control animals underwent sham pulmonary artery banding followed by right PNX. Pulmonary function, regional pulmonary perfusion, and high-resolution computed tomography of the chest were analyzed pre-PNX and 3-mo post-PNX. Terminally, the remaining lobes were fixed for detailed morphometric analysis. Results were compared with corresponding lobes in two control (Sham banding and normal unoperated) groups. PAB impaired the indices of post-PNX extravascular alveolar tissue growth by up to 50% in all remaining lobes. PAB enhanced the expected post-PNX increase in alveolar capillary formation, measured by the prevalence of double-capillary profiles, in both unbanded and banded lobes. We conclude that perfusion distribution provides major stimuli for post-PNX compensatory lung growth independent of the stimuli provided by lung expansion and parenchymal stress and strain.

  8. DETERMINATION OF RELATIVE IMPORTANCE OF NONPROLIFERATION FACTORS

    Energy Technology Data Exchange (ETDEWEB)

    Richard Metcalf

    2009-07-01

    Methodologies to determine the proliferation resistance (PR) of nuclear facilities often rely on either expert elicitation, a resource-intensive approach without easily reproducible results, or numeric evaluations, which can fail to take into account the institutional knowledge and expert experience of the nonproliferation community. In an attempt to bridge the gap and bring the institutional knowledge into numeric evaluations of PR, a survey was conducted of 33 individuals to find the relative importance of a set of 62 nonproliferation factors, subsectioned into groups under the headings of Diversion, Transportation, Transformation, and Weaponization. One third of the respondents were self-described nonproliferation professionals, and the remaining two thirds were from secondary professions related to nonproliferation, such as industrial engineers or policy analysts. The factors were taken from previous work which used multi-attribute utility analysis with uniform weighting of attributes and did not include institutional knowledge. In both expert and non-expert groups, all four headings and the majority of factors had different relative importance at a confidence of 95% (p=0.05). This analysis and survey demonstrates that institutional knowledge can be brought into numeric evaluations of PR, if there is a sufficient investment of resources made prior to the evaluation.

  9. Fibroblast growth factor 21 - a key player in cardiovascular disorders?

    Science.gov (United States)

    Lenart-Lipińska, Monika; Duma, Dariusz; Hałabiś, Magdalena; Dziedzic, Marcin; Solski, Janusz

    2016-06-15

    Fibroblast growth factor 21 (FGF21) is a newly discovered adipokine, synthesized by several organs, mostly by the liver, which was introduced as a potent metabolic regulator and insulin-sensitizing factor. Numerous animal studies have demonstrated that FGF21 improves glucose and lipids metabolism and exerts anti-inflammatory effects. However, data obtained from human studies have shown contradictory results, in which circulating FGF21 levels were often elevated in obesity, dyslipidemia, type 2 diabetes (DM2) and other conditions connected with insulin resistance. This increase in basal FGF21 concentrations observed in patients with obesity and other conditions related to insulin resistance was being explained as a compensatory response to the underlying metabolic disturbances or tissue resistance to FGF21 action. Furthermore, the results of clinical trials have shown that increased FGF21 concentrations were associated with increased cardiovascular (CV) risk and had a prognostic value in CV outcomes. In recent years, it has been reported that FGF21 may exert cardioprotective effects. This mini-review aims to summarize the current state of knowledge about the role of FGF21 in CV disorders, and discuss the molecular mechanism underlying the anti-atherogenic properties of this compound.

  10. Transforming growth factor-beta1 induces transforming growth factor-beta1 and transforming growth factor-beta receptor messenger RNAs and reduces complement C1qB messenger RNA in rat brain microglia.

    Science.gov (United States)

    Morgan, T E; Rozovsky, I; Sarkar, D K; Young-Chan, C S; Nichols, N R; Laping, N J; Finch, C E

    2000-01-01

    Transforming growth factor-beta1 is a multifunctional peptide with increased expression during Alzheimer's disease and other neurodegenerative conditions which involve inflammatory mechanisms. We examined the autoregulation of transforming growth factor-beta1 and transforming growth factor-beta receptors and the effects of transforming growth factor-beta1 on complement C1q in brains of adult Fischer 344 male rats and in primary glial cultures. Perforant path transection by entorhinal cortex lesioning was used as a model for the hippocampal deafferentation of Alzheimer's disease. In the hippocampus ipsilateral to the lesion, transforming growth factor-beta1 peptide was increased >100-fold; the messenger RNAs encoding transforming growth factor-beta1, transforming growth factor-beta type I and type II receptors were also increased, but to a smaller degree. In this acute lesion paradigm, microglia are the main cell type containing transforming growth factor-beta1, transforming growth factor-beta type I and II receptor messenger RNAs, shown by immunocytochemistry in combination with in situ hybridization. Autoregulation of the transforming growth factor-beta1 system was examined by intraventricular infusion of transforming growth factor-beta1 peptide, which increased hippocampal transforming growth factor-beta1 messenger RNA levels in a dose-dependent fashion. Similarly, transforming growth factor-beta1 increased levels of transforming growth factor-beta1 messenger RNA and transforming growth factor-beta type II receptor messenger RNA (IC(50), 5pM) and increased release of transforming growth factor-beta1 peptide from primary microglia cultures. Interactions of transforming growth factor-beta1 with complement system gene expression are also indicated, because transforming growth factor-beta1 decreased C1qB messenger RNA in the cortex and hippocampus, after intraventricular infusion, and in cultured glia. These indications of autocrine regulation of transforming growth

  11. Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility.

    Science.gov (United States)

    Newcomb, Christina J; Sur, Shantanu; Lee, Sungsoo S; Yu, Jeong Min; Zhou, Yan; Snead, Malcolm L; Stupp, Samuel I

    2016-05-11

    The nanostructures of self-assembling biomaterials have been previously designed to tune the release of growth factors in order to optimize biological repair and regeneration. We report here on the discovery that weakly cohesive peptide nanostructures in terms of intermolecular hydrogen bonding, when combined with low concentrations of osteogenic growth factor, enhance both BMP-2 and Wnt mediated signaling in myoblasts and bone marrow stromal cells, respectively. Conversely, analogous nanostructures with enhanced levels of internal hydrogen bonding and cohesion lead to an overall reduction in BMP-2 signaling. We propose that the mechanism for enhanced growth factor signaling by the nanostructures is related to their ability to increase diffusion within membrane lipid rafts. The phenomenon reported here could lead to new nanomedicine strategies to mediate growth factor signaling for translational targets.

  12. Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility

    Energy Technology Data Exchange (ETDEWEB)

    Newcomb, Christina J.; Sur, Shantanu; Lee, Sungsoo S.; Yu, Jeong Min; Zhou, Yan; Snead, Malcolm L.; Stupp, Samuel I.

    2016-04-12

    The nanostructures of self-assembling biomaterials have been previously designed to tune the release of growth factors in order to optimize biological repair and regeneration. We report here on the discovery that weakly cohesive peptide nanostructures in terms of intermolecular hydrogen bonding, when combined with low concentrations of osteogenic growth factor, enhance both BMP-2 and Wnt mediated signaling in myoblasts and bone marrow stromal cells, respectively. Conversely, analogous nanostructures with enhanced levels of internal hydrogen bonding and cohesion lead to an overall reduction in BMP-2 signaling. We propose that the mechanism for enhanced growth factor signaling by the nanostructures is related to their ability to increase diffusion within membrane lipid rafts. The phenomenon reported here could lead to new nanomedicine strategies to mediate growth factor signaling for translational targets.

  13. Effects of Growth Factors on Dental Stem/ProgenitorCells

    Science.gov (United States)

    Kim, Sahng G.; Solomon, Charles; Zheng, Ying; Suzuki, Takahiro; Mo, Chen; Song, Songhee; Jiang, Nan; Cho, Shoko; Zhou, Jian; Mao, Jeremy J.

    2014-01-01

    Synopsis The primary goal of regenerative endodontics is to restore the vitality and functions of the dentin-pulp complex, as opposed to filing of the root canal with bioinert materials. Structural restoration is also important but is likely secondary to vitality and functions. Myriads growth factors regulate multiple cellular functions including migration, proliferation, differentiation and apoptosis of several cell types that are intimately involved in dentin-pulp regeneration: odontoblasts, interstitial fibroblasts, vascular-endothelial cells and sprouting nerve fibers. Recent work showing that growth factor delivery, without cell transplantation, can yield pulp-dentin like tissues in vivo provides one of the tangible pathways for regenerative endodontics. This review synthesizes our knowledge on a multitude of growth factors that are known or anticipated to be efficacious in dental pulp-dentin regeneration. PMID:22835538

  14. ANALYSIS OF FACTORS WHICH AFFECTING THE ECONOMIC GROWTH

    Directory of Open Access Journals (Sweden)

    Suparna Wijaya

    2017-03-01

    Full Text Available High economic growth and sustainable process are main conditions for sustainability of economic country development. They are also become measures of the success of the country's economy. Factors which tested in this study are economic and non-economic factors which impacting economic development. This study has a goal to explain the factors that influence on macroeconomic Indonesia. It used linear regression modeling approach. The analysis result showed that Tax Amnesty, Exchange Rate, Inflation, and interest rate, they jointly can bring effect which amounted to 77.6% on economic growth whereas the remaining 22.4% is the influenced by other variables which not observed in this study. Keywords: tax amnesty, exchange rates, inflation, SBI and economic growth

  15. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h......% of fetal, 20% of neonatal, and 2% of adult chromaffin cells. The ED50 value of IGF-I- and IGF-II-stimulated BrdUrd labeling in neonatal chromaffin cells was 0.3 nM and 0.8 nM, respectively. In neonatal and adult chromaffin cells, addition of 1 nM bFGF or 2 nM NGF stimulated nuclear BrdUrd incorporation...... to approximately the same level as 10 nM IGF-I or IGF-II. However, the response to bFGF or NGF in combination with either IGF-I or IGF-II was more than additive, indicating that the combined effect of the IGFs and bFGF or NGF is synergistic. The degree of synergism was 2- to 4-fold in neonatal chromaffin cells...

  16. Molecular cloning of a human gene that is a member of the nerve growth factor family

    Energy Technology Data Exchange (ETDEWEB)

    Jones, K.R.; Reichardt, L.F. (Howard Hughes Medical Institute, San Francisco, CA (USA))

    1990-10-01

    Cell death within the developing vertebrate nervous system is regulated in part by interactions between neurons and their innervation targets that are mediated by neurotrophic factors. These factors also appear to have a role in the maintenance of the adult nervous system. Two neurotrophic factors, nerve growth factor and brain-derived neurotrophic factor, share substantial amino acid sequence identity. The authors have used a screen that combines polymerase chain reaction amplification of genomic DNA and low-stringency hybridization with degenerate oligonucleotides to isolate human BDNF and a human gene, neurotrophin-3, that is closely related to both nerve growth factor and brain-derived neurotrophic factor. mRNA products of the brain-derived neurotrophic factor and neurotrophin-3 genes were detected in the adult human brain, suggesting that these proteins are involved in the maintenance of the adult nervous system. Neurotrophin-3 is also expected to function in embryonic neural development.

  17. Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model.

    Science.gov (United States)

    Santa Maria, Peter Luke; Weierich, Kendall; Kim, Sungwoo; Yang, Yunzhi Peter

    2015-08-01

    That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model. A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle. The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks. The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration. This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

  18. Expression and Purification of Active Recombinant Human Nerve Growth Factor from Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Introduction Nerve growth factor (NGF) was first discovered and purified by Rita Levi-Montalcini and Stanley Cohen in the 1950s[1,2]. It represents the first cellular growth factor ever discovered and involved in the growth, survival, and differentiation of specific nerve cell populations[3]. Although animal tests and phase-Ⅱ clinical trials indicate that rhNGF could be an effective treatment for diabetic[4] and HIV-related neuropathies[5] , a large-scale phase-Ⅲ clinical trial has failed to give similar result[6].

  19. Constructing a blood vessel on the porous scaffold modified with vascular endothelial growth factor and basic fibroblast growth factor

    Science.gov (United States)

    Sevostyanova, V. V.; Matveeva, V. G.; Antonova, L. V.; Velikanova, E. A.; Shabaev, A. R.; Senokosova, E. A.; Krivkina, E. O.; Vasyukov, G. Yu.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S.

    2016-11-01

    Incorporation of the growth factors into biodegradable polymers is a promising approach for the fabrication of tissue-engineered vascular grafts. Here we blended poly(ɛ-caprolactone) (PCL) with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) following incorporation of either vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) and then fabricated electrospun 2 mm diameter vascular grafts. Grafts without the growth factors were used as a control group. Structure of the grafts was assessed utilizing scanning electron microscopy. We further implanted our grafts into rat abdominal aorta for 1 and 3 months with the aim to test endothelialization, cell infiltration, and patency in vivo. Histological and immunofluorescence examination demonstrated enhanced endothelialization and cell infiltration of the grafts with either VEGF or bFGF compared to those without the growth factors. Grafts with VEGF showed higher patency compared to those with bFGF; however, bFGF promoted migration of smooth muscle cells and fibroblasts into the graft. Therefore, we conclude that incorporation of VEGF and bFGF into the inner and medial/outer layer, respectively, can be a promising option for the fabrication of tissue-engineered vascular grafts.

  20. Holography, chiral Lagrangian and form factor relations

    CERN Document Server

    Zuo, Fen

    2013-01-01

    We perform a detailed study of mesonic properties in a class of holographic models of QCD, which is described by the Yang-Mills plus Chern-Simons action. By decomposing the 5 dimensional gauge field into resonances and integrating out the massive ones, we reproduce the Chiral Perturbative Theory Lagrangian up to ${\\cal O}(p^6)$ and obtain all the relevant low energy constants (LECs). The numerical predictions of the LECs show minor model dependence, and agree reasonably with the determinations from other approaches. Interestingly, various model-independent relations appear among them. Some of these relations are found to be the large-distance limits of universal relations between form factors of the anomalous and even-parity sectors of QCD.

  1. Nutritional factors affecting growth of muscle and adipose tissue in ruminants.

    Science.gov (United States)

    Byers, F M

    1982-07-01

    Patterns of tissue growth determine composition of growth, and over intervals of time, these patterns of tissue growth will also be reflected in total tissue accumulated in the animal. Although patterns of tissue growth may be modified by the effects of specific carbon sources through direct impact on lipogenesis, the primary avenue through which nutritional factors regulate or direct protein and fat deposition is through effects of total absorbed energy provided on rates of growth in relation to an animal's daily needs for maintenance and protein growth. Even though mature size and genetic potential establish the maximum upper limits for daily protein growth, other factors determine the extent to which these theoretical limits will ever be achieved. The actual partitioning of absorbed nutrients between protein and fat deposition also depends on other factors, including stage of growth, sex class, hormonal regulation (endogenous and exogenous), and intake of required nutrients. The sex class of an animal establishes different biological limits for bulls, steers, and heifers that are otherwise similar in mature size, genetics, and nutritional adequacy. Also, the use of anabolic agents alters the physiological limit for daily protein growth at the cellular level and allows an animal to deposit protein at rates closer to theoretical genetic limits. Energy that is provided above maintenance and protein growth requirements enhances rates of lipid deposition and accumulation of fat. As a consequence, the rate of growth will direct these tissue responses, and effects of diet, energy level, level of nutrition, and plane of nutrition will impact composition of growth primarily through acceleration of rate of growth above daily limits for protein growth. Changes in tissue storage will impact total body composition to the extent of time and differential in composition of gain and of tissue present.

  2. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    Science.gov (United States)

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia.

  3. Relation between depression and sociodemographic factors

    Directory of Open Access Journals (Sweden)

    Akhtar-Danesh Noori

    2007-09-01

    Full Text Available Abstract Background Depression is one of the most common mental disorders in Western countries and is related to increased morbidity and mortality from medical conditions and decreased quality of life. The sociodemographic factors of age, gender, marital status, education, immigrant status, and income have consistently been identified as important factors in explaining the variability in depression prevalence rates. This study evaluates the relationship between depression and these sociodemographic factors in the province of Ontario in Canada using the Canadian Community Health Survey, Cycle 1.2 (CCHS-1.2 dataset. Methods The CCHS-1.2 survey classified depression into lifetime depression and 12-month depression. The data were collected based on unequal sampling probabilities to ensure adequate representation of young persons (15 to 24 and seniors (65 and over. The sampling weights were used to estimate the prevalence of depression in each subgroup of the population. The multiple logistic regression technique was used to estimate the odds ratio of depression for each sociodemographic factor. Results The odds ratio of depression for men compared with women is about 0.60. The lowest and highest rates of depression are seen among people living with their married partners and divorced individuals, respectively. Prevalence of depression among people who live with common-law partners is similar to rates of depression among separated and divorced individuals. The lowest and highest rates of depression based on the level of education is seen among individuals with less than secondary school and those with "other post-secondary" education, respectively. Prevalence of 12-month and lifetime depression among individuals who were born in Canada is higher compared to Canadian residents who immigrated to Canada irrespective of gender. There is an inverse relation between income and the prevalence of depression (p Conclusion The patterns uncovered in this

  4. Factors Related to Suicide in LGBT Populations.

    Science.gov (United States)

    Skerrett, Delaney Michael; Kõlves, Kairi; De Leo, Diego

    2016-09-01

    There is evidence of heightened vulnerability to nonfatal suicidal behaviors among LGBT populations yet a paucity of studies into fatal behaviors. The specific aim of this article was to identify factors related to suicide in LGBT individuals in Australia. The psychological autopsy (PA) method with a matched case-control study design was used. PA interviews were conducted with 27 next-of-kin of an LGBT person that had died by suicide. Three living LGBT controls per suicide case, matched by age and gender, were also interviewed. The key factors relating to suicide in LGBT people were a lack of acceptance by family and self (reflected in higher internalized homophobia and shame), negative feelings about own sexuality/gender, and dissatisfaction with appearance. LGBT people who died by suicide also tended to go through coming out milestones 2 years earlier than controls. There was a higher prevalence of aggressive behaviors and a more predominant history of physical and sexual abuse. Additionally, there was greater incidence of depression and anxiety and alcohol and substance use disorders. Specific predictive factors for suicide in LGBT populations in Australia were identified, including significantly poorer mental health outcomes and more violence across an array of measures.

  5. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  6. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  7. Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Wildschiødtz, Gordon; Juul, Anders

    2008-01-01

    Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have...... investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six...... severely obese subjects (BMI: 41+/-1 kg/m(2), 32+/-2 years of age), cross-sectional at baseline, and longitudinal after a dramatically diet-induced weight loss (36+/-7 kg). Ten age- and gender-matched nonobese subjects served as controls. Sleep duration (360+/-17 vs. 448+/-15 min/night; P

  8. Temperature affects insulin-like growth factor I and growth of juvenile southern flounder, Paralichthys lethostigma.

    Science.gov (United States)

    Luckenbach, J Adam; Murashige, Ryan; Daniels, Harry V; Godwin, John; Borski, Russell J

    2007-01-01

    Temperature profoundly influences growth of heterothermic vertebrates. However, few studies have investigated the effects of temperature on growth and insulin-like growth factor I (IGF-I) in fishes. The aim of this study was to examine effects of temperature on growth and establish whether IGF-I may mediate growth at different temperatures in southern flounder, Paralichthys lethostigma. In two experiments, juvenile flounder were reared at 23 and 28 degrees C and growth was monitored for either 117 or 197 days. Growth was similar across treatments in both experiments until fish reached approximately 100 mm total length. Body size then diverged with fish at 23 degrees C ultimately growing 65-83% larger than those at 28 degrees C. Muscle IGF-I mRNA, plasma IGF-I, and hepatosomatic index (HSI) were significantly higher in flounder at 23 degrees C, whereas hepatic IGF-I mRNA abundance did not differ with treatment. Muscle IGF-I mRNA was correlated with HSI, while plasma IGF-I was correlated with body size, hepatic IGF-I mRNA, and HSI. These results demonstrate a strong effect of temperature on flounder growth and show that temperature-induced variation in growth is associated with differences in systemic IGF-I and local (i.e., muscle) IGF-I mRNA levels. The results also support the use of plasma IGF-I and HSI as indicators of flounder growth status.

  9. Cheiradone: a vascular endothelial cell growth factor receptor antagonist

    Directory of Open Access Journals (Sweden)

    Ahmed Nessar

    2008-01-01

    Full Text Available Abstract Background Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing and pathological conditions (tumour development. Vascular endothelial growth factor (VEGF, fibroblast growth factor-2 (FGF-2 and epidermal growth factor (EGF are the major angiogenic regulators. We have identified a natural product (cheiradone isolated from a Euphorbia species which inhibited in vivo and in vitro VEGF- stimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in in vitro (proliferation, wound healing, invasion in Matrigel and tube formation and in vivo (the chick chorioallantoic membrane models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC50 was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated. Results Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC50 values in the range 5.20–7.50 μM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC50 values of 2.9 and 0.61 μM respectively. Conclusion Cheiradone inhibited VEGF-induced angiogenesis by binding to VEGF receptors -1 and -2 and may be a useful investigative tool to study the specific contribution of VEGF to angiogenesis and may have therapeutic potential.

  10. Factoring Algebraic Error for Relative Pose Estimation

    Energy Technology Data Exchange (ETDEWEB)

    Lindstrom, P; Duchaineau, M

    2009-03-09

    We address the problem of estimating the relative pose, i.e. translation and rotation, of two calibrated cameras from image point correspondences. Our approach is to factor the nonlinear algebraic pose error functional into translational and rotational components, and to optimize translation and rotation independently. This factorization admits subproblems that can be solved using direct methods with practical guarantees on global optimality. That is, for a given translation, the corresponding optimal rotation can directly be determined, and vice versa. We show that these subproblems are equivalent to computing the least eigenvector of second- and fourth-order symmetric tensors. When neither translation or rotation is known, alternating translation and rotation optimization leads to a simple, efficient, and robust algorithm for pose estimation that improves on the well-known 5- and 8-point methods.

  11. Recurrent acute pancreatitis and its relative factors

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Hong-Chao Shan; Yan Gu

    2005-01-01

    AIM: To evaluate the causes and the relative factors of recurrent acute pancreatitis.METHODS: From 1997 to 2000, acute pancreatitis relapsed in 77 of 245 acute pancreatitis patients. By reviewing the clinical treatment results and the follow-up data, we analyzed the recurrent factors of acute pancreatitis using univariate analysis and multivariate analysis.RESULTS: Of the 245 acute pancreatitis patients, 77 were patients with recurrent acute pancreatitis. Of them, 56 patients relapsed two times, 19 relapsed three times, each patient relapsed three and four times. Forty-seven patients relapsed in hospital and the other 30 patients relapsed after discharge. Eighteen patients relapsed in 1 year, eight relapsed in 1-3 years, and four relapsed after 3 years. There were 48 cases of biliary pancreatitis, 3 of alcohol pancreatitis, 5 of hyperlipidemia pancreatitis, 21 of idiopathic pancreatitis. Univariate analysis showed that the patients with local complications of pancreas, obstructive jaundice and hepatic function injury were easy to recur during the treatment period of acute pancreatitis (P = 0.022<0.05, P = 0.012<0.05 and P = 0.002<0.05, respectively). Multivariate analysis showed that there was no single factor related to recurrence. Of the 47 patients who had recurrence in hospital, 16 had recurrence in a fast period, 31 after refeeding. CONCLUSION: Acute pancreatitis is easy to recur even during treatment. The factors such as changes of pancreas structure and uncontrolled systemic inflammatory reaction are responsible for the recurrence of acute pancreatitis. Early refeeding increases the recurrence of acute pancreatitis. Defining the etiology is essential for reducing the recurrence of acute pancreatitis.

  12. Cow placenta extract promotes murine hair growth through enhancing the insulin - like growth factor-1

    Directory of Open Access Journals (Sweden)

    Dongliang Zhang

    2011-01-01

    Full Text Available Background: Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce the negative factors of obstructing hair growth and improve the hair number and size. Aim: In our experiment, we tried to prove that the cow placenta extract can promote hair growth by elongating hair shaft and increasing hair follicle number. Materials and Methods: Cow placenta extract (CPE, water and minoxidil applied separately on the back of depilated B57CL/6 mice for the case, negative and positive control respectively. We checked the proliferation of cells which are resident in hair sheath, and the expression of a few growth factors which stimulate hair growth. Results: Result shows that placenta extract more efficiently accelerates cell division and growth factor expression, by raising the insulin-like growth factor (IGF-1 mRNA and protein level to increase HF size and hair length. Conclusions: The extract is not a purified product; so, it is less effective than minoxidil, which is approved by the US FDA for the treatment of male pattern baldness. If refinement is done, the placenta extract would be a good candidate medicine for hair loss.

  13. Growth hormone and insulin-like growth factor-I as anabolic agents.

    Science.gov (United States)

    Welle, S

    1998-05-01

    The reduced growth hormone and insulin-like growth factor-I concentrations in growth hormone deficiency and normal ageing are associated with reduced muscle mass and strength, and slower muscle protein synthesis. Recent research has addressed the hypothesis that growth hormone and insulin-like growth factor-I have an anabolic effect in adults, including the elderly. These hormones stimulate whole-body and muscle protein synthesis, at least under some conditions. There is increasing evidence to justify long-term administration of growth hormone to promote muscle growth in growth hormone deficient adults. However, the long-term effects on muscle mass and function in the elderly do not seem beneficial enough to justify widespread hormone replacement therapy. These hormones may be useful anabolic agents to counteract muscle wasting under other conditions, including surgical stress, renal failure, muscular dystrophy, glucocorticoid administration and HIV infection, but more clinical trials are needed to determine the functional significance of the protein anabolic effects under these conditions.

  14. Basic fibroblast growth factor gene transfection in repair of internal carotid artery aneurysm wall

    Institute of Scientific and Technical Information of China (English)

    Lei Jiao; Ming Jiang; Jinghai Fang; Yinsheng Deng; Zejun Chen; Min Wu

    2012-01-01

    Surgery or interventional therapy has some risks in the treatment of cerebral aneurysm. We established an internal carotid artery aneurysm model by dripping elastase in the crotch of the right internal and external carotid arteries of New Zealand rabbits. Following model induction, lentivirus carrying basic fibroblast growth factor was injected through the ear vein. We found that the longer the action time of the lentivirus, the smaller the aneurysm volume. Moreover, platelet-derived growth factor expression in the aneurysm increased, but smooth muscle 22 alpha and hypertension-related gene 1 mRNA expression decreased. At 1, 2, 3, and 4 weeks following model establishment, following 1 week of injection of lentivirus carrying basic fibroblast growth factor, the later the intervention time, the more severe the blood vessel damage, and the bigger the aneurysm volume, the lower the smooth muscle 22 alpha and hypertension-related gene 1 mRNA expression. Simultaneously, platelet-derived growth factor expression decreased. These data suggest that recombinant lentivirus carrying basic fibroblast growth factor can repair damaged cells in the aneurysmal wall and inhibit aneurysm dynamic growth, and that the effect is dependent on therapeutic duration.

  15. An ideal preparation for dermal regeneration: skin renewal growth factors, the growth factor composites from porcine platelets.

    Science.gov (United States)

    Wang, Kuo-Hsien; Wu, Yo-Ping Greg; Lo, Wen-Cheng

    2012-12-01

    The use of growth factor composites from platelets has been introduced to many areas of clinical applications and studies. With the richest source of growth factors (GFs), beneficial effects have been shown on tissue regeneration and wound healing. However, animal and clinical studies have revealed inconsistent outcomes with the use of platelet-derived growth factors (PDGFs), which were likely due to variations in the presence and concentrations of GFs between various sources. Autologous PDGFs are considered to be safer, but they are limited by the feasibility of large-scale production to be used extensively in the acute phase, greater surface area, or general cosmetic applications. This study employed a simple process to obtain growth factor composites from activated platelets of porcine origin, namely skin renewal growth factors (SRGF). The functions of SRGF were subsequently evaluated on cultured human fibroblasts, keratinocytes, and melanocytes. Our data revealed that SRGF significantly promoted the proliferation of fibroblasts, accompanied by increased expression of collagens (types I, III, IV, and VIII) and proteoglycans. Diminished proliferation and arrested differentiation of keratinocytes were evidenced by the attenuated expression of laminin V and keratin 10. In addition, SRGF also suppressed the growth of melanocytes and reduced the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and paired box 3 (PAX3), which mediates melanogensis. Our results suggest that SRGF possesses beneficial properties and is a promising and cost-effective composition for the development of a safe cosmetic agent or topical products for skin regeneration. The development of SRGF may also provide an alternative strategy for tissue engineering.

  16. Growth factors for therapeutic angiogenesis in hypercholesterolemic erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Donghua Xie; Brian H. Annex; Craig F. Donatucci

    2008-01-01

    The past decade has seen an explosion of new information on the physiology of penile erection, and pathophysiology of erectile dysfunction (ED). Hypercholesterolemia is a chronic condition that can lead to degeneration in the vasculature bed and can result in ED if the penile vasculature is involved. Angiogenesis is the growth of new blood vessels from preexisting vasculature. Therapeutic angiogenesis seeks to harness the mechanisms of vascular growth to treat disorders of inadequate tissue perfusion, such as coronary artery disease and ED. There have been tremendous changes in the field of therapeutic angiogenesis over the past decade, and there is much promise for the future.Initial preclinical work with cytokine growth factor delivery resulted in a great deal of enthusiasm for the treatment of ischemic heart and/or peripheral vascular disease, though clinical studies have not achieved similar success. With an increased understanding of the complex mechanisms involved in angiogenesis, novel therapies which target multiple different angiogenic pathways are also being developed and tested. The penis is a convenient tissue target for gene therapy because of its external location and accessibility, the ubiquity of endothelial lined spaces, and low level of blood flow, especially in the flaccid state. Therapeutic angiogenesis is an exciting field that continues to evolve. This review will focus on the development of growth factors for hypercholesterolemic ED, the use of various growth factors for ED therapy, their routes of delivery, and the results in animal studies.

  17. Growth factors/cytokines/defensins and apoptosis in periodontal pathologies.

    Science.gov (United States)

    Laurina, Zane; Pilmane, Mara; Care, Ruta

    2009-01-01

    In the recent past there has been an increased emphasis on morphogenetic tissue research of periodontal tissues. The aim of this study was to find qualitative and quantitative correlations in distribution and appearance of growth factors/cytokines/defensins and apoptosis in periodontal pathologies. Tissue was obtained from 5 controls and 6 chronical periodontitis patients 30-50 years of age referred to Latvian Institute of Stomatology. Histological investigations were performed at the Institute of Anatomy and Anthropology of Riga Stradins University. Epithelial cells abundantly expressed IL10 in patients. The expression of b-defensins was very variable in both sulcular and gingival epithelium. TUNEL positive cells were observed in patients and control specimens with dominance in control group. Gingival epithelium showed moderate expression of bFGF whereas few to moderate cells were positive for bFGF in sulcular epithelium. Fibroblast growth factor receptor (FGF-1R) was abundant in gingival epithelium and in connective tissue cells, but almost not detectable in sulcular epithelium. Insulin-like growth factor receptor was not expressed in gingival epithelium and was weakly seen in basal layer of sulcular epithelium. Basic nerve growth factor expresion in both types of epithelium was numerous to abundant. Staining for the NGFR in the gingival epithelium was variable, with prevalence to be moderate whereas sulcular epithelium was free from any factor immunoreactivity. 1. Finding of apoptotic cells are variable and seems to correlate with the expression of defensins in oral epithelium in patients with periodontitis. 2. FGFR was expressed more than the bFGF, but in case with NGFR and bNGF situation was opposite. Although IGFRI was found in sulcular epithelium with no expression in gingival one suggesting about stimulation in regeneration/adaptation in periodontitis affected tissue. 3. The expression of growth factors and their receptors in sulcular epithelium was lower

  18. Functional upregulation of system xc- by fibroblast growth factor-2.

    Science.gov (United States)

    Liu, Xiaoqian; Resch, Jon; Rush, Travis; Lobner, Doug

    2012-02-01

    The cystine/glutamate antiporter (system xc-) is a Na(+)-independent amino acid transport system. Disruption of this system may lead to multiple effects in the CNS including decreased cellular glutathione. Since multiple neurological diseases involve glutathione depletion, and disruption of growth factor signaling has also been implicated in these diseases, it is possible that some growth factors effects are mediated by regulation of system xc-. We tested the growth factors fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), neuregulin-1 (NRG), neurotrophin-4 (NT-4), and brain derived neurotrophic factor (BDNF) on system xc- mediated 14C-cystine uptake in mixed neuronal and glial cortical cultures. Only FGF-2 significantly increased cystine uptake. The effect was observed in astrocyte-enriched cultures, but not in cultures of neurons or microglia. The increase was blocked by the system xc- inhibitor (s)-4-carboxyphenylglycine, required at least 12 h FGF-2 treatment, and was prevented by the protein synthesis inhibitor cycloheximide. Kinetic analysis indicated FGF-2 treatment increased the V(max) for cystine uptake while the K(m) remained the same. Quantitative PCR showed an increase in mRNA for xCT, the functional subunit of system xc-, beginning at 3 h of FGF-2 treatment, with a dramatic increase after 12 h. Blocking FGFR1 with PD 166866 blocked the FGF-2 effect. Treatment with a PI3-kinase inhibitor (LY-294002) or a MEK/ERK inhibitor (U0126) for 1 h prior to and during the FGF-2 treatment, each partially blocked the increased cystine uptake. The upregulation of system xc- by FGF-2 may be responsible for some of the known physiological actions of FGF-2. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

  19. 骨龄在评估颅面生长发育中的应用及其影响因素%The application of skeletal age in the assessment of craniofacial growth and development and related influencing factors

    Institute of Scientific and Technical Information of China (English)

    陈莉莉

    2016-01-01

    准确的骨龄评估可以评价个体发育所处的阶段,为正畸临床选择矫治时机和预测颅面生长发育潜力提供重要的参考依据。本文从骨龄评估颅面生长发育的研究现状、影响骨龄评估颅面生长发育准确性的因素、骨龄评估颅面生长发育的改进与发展趋势三个方面展开论述,观点总结如下。①手腕骨龄,尤其是Fishman手腕骨龄分期法是一种有机的、相对简单并可靠的骨龄评估方法;颈椎骨龄分期法不用接受额外的X线照射,易于观察下颌生长高峰期,尤其是适应当今影像数字化趋势的颈椎骨龄定量分期法;②骨龄准确性受种族、性别、评定方法本身特点等因素的影响,应找到适合特定患者的骨龄评估方法;③环境因素,尤其是生物钟长期紊乱可导致骨发育异常,影响骨龄评估的准确性,提出通过调节生物钟治疗颅面生长发育异常的新方法,并期望发现评价颅面生长发育的新指标、新标准,提高骨龄评估生长发育的准确性。%Accurate skeletal age evaluation can assess the stage of individual development,and therefore provide the important refer-ence for orthodontists to choose proper treatment timing and predict the growth potential. This paper explores three aspects,including the research status of the assessment of craniofacial growth and development,the influencing factors of skeletal age evaluation accuracy, and the improvement and development of skelatal age evaluation. The views are summarized as follows:①The hand-wrist skeletal age, especially Fishman Skeletal Maturity Indicators ( SMI) ,is organic, simple and reliable. The method of Cervical Vertebrae Maturation ( CVM) , especially Quantitative Cervical Vertebral Maturation ( QCVM) , has attracted more and more attention, and there is no need for additional x-ray exposure and it is easy to observe the mandibular growth peak. ②The accuracy of skeletal age

  20. Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion.

    Science.gov (United States)

    Gorin, Caroline; Rochefort, Gael Y; Bascetin, Rumeyza; Ying, Hanru; Lesieur, Julie; Sadoine, Jérémy; Beckouche, Nathan; Berndt, Sarah; Novais, Anita; Lesage, Matthieu; Hosten, Benoit; Vercellino, Laetitia; Merlet, Pascal; Le-Denmat, Dominique; Marchiol, Carmen; Letourneur, Didier; Nicoletti, Antonino; Vital, Sibylle Opsahl; Poliard, Anne; Salmon, Benjamin; Muller, Laurent; Chaussain, Catherine; Germain, Stéphane

    2016-03-01

    Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF.

  1. The role of transforming growth factor beta in tertiary dentinogenesis

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2008-03-01

    Full Text Available The most visible repair response to pulp injury is the deposition of a tertiary dentin matrix over the dentinal tubules of the primary or secondary dentin. Tertiary dentin is distinguished as reactionary and reparative dentin, depending on the severity of the initiating response and the conditions under which the newly deposited dentin matrix was elaborated. Transforming growth factor beta (TGF-b superfamily is a large group of growth factors that serve important roles in regulating cell growth, differentiation, and function. Members of this superfamily have been implicated in the repair process of the dental tissue after injury. Although numerous studies have proved that those bioactive molecules carry out an important role in the formation of tertiary dentin, comprehensive report regarding that phenomenon is not yet available. This review article aimed to summarize the role of TGF-b on tertiary dentinogenesis during the progression of a carious lesion.

  2. Modeling Relational Data via Latent Factor Blockmodel

    CERN Document Server

    Gao, Sheng; Gallinari, Patrick

    2012-01-01

    In this paper we address the problem of modeling relational data, which appear in many applications such as social network analysis, recommender systems and bioinformatics. Previous studies either consider latent feature based models but disregarding local structure in the network, or focus exclusively on capturing local structure of objects based on latent blockmodels without coupling with latent characteristics of objects. To combine the benefits of the previous work, we propose a novel model that can simultaneously incorporate the effect of latent features and covariates if any, as well as the effect of latent structure that may exist in the data. To achieve this, we model the relation graph as a function of both latent feature factors and latent cluster memberships of objects to collectively discover globally predictive intrinsic properties of objects and capture latent block structure in the network to improve prediction performance. We also develop an optimization transfer algorithm based on the general...

  3. Nerve growth factor: a novel mediator in asthma

    NARCIS (Netherlands)

    Vries, Annick de

    2001-01-01

    Nerve growth factor (NGF) is known for years for its properties to induce neurite outgrowth. Its role in inflammation has recently been discovered. In this thesis the role of NGF in allergic asthma is shown. In chapter 2 we showed that NGF can induce airway hyperresponsiveness in guinea pigs. Sim

  4. Vascular endothelial growth factor a in eyes with uveal melanoma.

    NARCIS (Netherlands)

    Missotten, G.S.; Notting, I.C.; Schlingemann, R.O.; Zijlmans, H.J.; Lau, C.; Eilers, P.H.; Keunen, J.E.E.; Jager, M.J.

    2006-01-01

    OBJECTIVES: To determine the presence of vascular endothelial growth factor A (VEGF-A) in the aqueous humor of eyes with uveal melanoma and to identify its source. METHODS: The VEGF-A concentrations were determined in aqueous humor samples obtained after enucleation from 74 eyes with untreated uveal

  5. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P; Barten, AD; Van Waarde, MAWH; Vujaskovic, Z; Van Tienhoven, G

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGF beta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and activ

  6. Fibroblast Growth Factor-2 Alters the Nature of Extinction

    Science.gov (United States)

    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  7. Gastric luminal epidermal growth factor is affected by diet

    African Journals Online (AJOL)

    vegetable,' and on contaminants in the diet such as fumonisins.' The first ... with low dietary intake of animal products (p = 0.002) and vegetables (p .... had an effect on EGF since a non-significant difference was seen. Vegetable .... growth factor administration on intestinal cell proliferation, crypt Ossion and polyp formation in ...

  8. Epidermal growth factor receptor expression in urinary bladder cancer

    Directory of Open Access Journals (Sweden)

    Dayalu S.L. Naik

    2011-01-01

    Full Text Available Objective : To evaluate the expression pattern of epidermal growth factor receptor (EGFR in urinary bladder cancer and its association with human epidermal growth factor receptor 2 (HER2, epidermal growth factor (EGF, interleukin-6 (IL-6, and high risk human papilloma virus (HPV types 16 and 18. Materials and Methods : Thirty cases of urothelial carcinoma were analyzed. EGFR, HER2, EGF, and IL-6 expressions in the tissue were evaluated by immunohistochemical staining. For HPV, DNA from tissue samples was extracted and detection of HPV was done by PCR technique. Furthermore, evaluation of different intracellular molecules associated with EGFR signaling pathways was performed by the western blot method using lysates from various cells and tissues. Results : In this study, the frequencies of immunopositivity for EGFR, HER2, EGF, and IL-6 were 23%, 60%, 47%, and 80%, respectively. No cases were positive for HPV-18, whereas HPV-16 was detected in 10% cases. Overall, expression of EGFR did not show any statistically significant association with the studied parameters. However, among male patients, a significant association was found only between EGFR and HER2. Conclusions : Overexpression of EGFR and/or HER2, two important members of the same family of growth factor receptors, was observed in a considerable proportion of cases. Precise knowledge in this subject would be helpful to formulate a rational treatment strategy in patients with urinary bladder cancer.

  9. Chemical strategies for the presentation and delivery of growth factors

    NARCIS (Netherlands)

    Cabanas Danés, Jordi; Huskens, Jurriaan; Jonkheijm, Pascal

    2014-01-01

    Since the first demonstration of employing growth factors (GFs) to control cell behaviour in vitro, the spatiotemporal availability of GFs in vivo has received continuous attention. In particular, the ability to physically confine the mobility of GFs has been used in various tissue engineering

  10. Signal transduction by growth factor receptors: signaling in an instant

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Blagoev, Blagoy;

    2007-01-01

    -out by mass spectrometry-based proteomics has allowed exciting views on the very early events in signal transduction. Activation profiles of regulated phosphorylation sites on epidermal growth factor receptor and downstream signal transducers showed different kinetics within the first ten seconds...

  11. Regulation of mechano growth factor in skeletal muscle and heart

    NARCIS (Netherlands)

    Ottens, M.

    2010-01-01

    The mechano growth factor (MGF) is expressed in mechanically overloaded skeletal muscle. MGF was discovered in 1996 as an alternative splice product of the IGF-1 gene. Since then, its significance has been investigated particularly in skeletal muscle, because the local expression of MGF could

  12. Extra nodal growth as a prognostic factor in malignant melanoma

    NARCIS (Netherlands)

    Koopal, SA; Tiebosch, ATMG; Daryanani, D; Plukker, JTM; Hoekstra, HJ

    Aim. Extra nodal growth (ENG) in lymph-node metastases may be an additional. indicator for poor prognosis and increased Loco-regional recurrence in patients with a cutaneous malignant melanoma (CMM). Most studies analyzing prognostic factors tack a proper definition or description of the

  13. Role of fibroblast growth factors in organ regeneration and repair.

    Science.gov (United States)

    El Agha, Elie; Kosanovic, Djuro; Schermuly, Ralph T; Bellusci, Saverio

    2016-05-01

    In its broad sense, regeneration refers to the renewal of lost cells, tissues or organs as part of the normal life cycle (skin, hair, endometrium etc.) or as part of an adaptive mechanism that organisms have developed throughout evolution. For example, worms, starfish and amphibians have developed remarkable regenerative capabilities allowing them to voluntarily shed body parts, in a process called autotomy, only to replace the lost parts afterwards. The bizarre myth of the fireproof homicidal salamander that can survive fire and poison apple trees has persisted until the 20th century. Salamanders possess one of the most robust regenerative machineries in vertebrates and attempting to draw lessons from limb regeneration in these animals and extrapolate the knowledge to mammals is a never-ending endeavor. Fibroblast growth factors are potent morphogens and mitogens that are highly conserved among the animal kingdom. These growth factors play key roles in organogenesis during embryonic development as well as homeostatic balance during postnatal life. In this review, we provide a summary about the current knowledge regarding the involvement of fibroblast growth factor signaling in organ regeneration and repair. We also shed light on the use of these growth factors in previous and current clinical trials in a wide array of human diseases.

  14. The epidermal growth factor receptor pathway in chronic kidney diseases

    NARCIS (Netherlands)

    Harskamp, Laura R.; Gansevoort, Ron T.; Goor, van Harry; Meijer, Esther

    2016-01-01

    The epidermal growth factor receptor (EGFR) pathway has a critical role in renal development, tissue repair and electrolyte handling. Numerous studies have reported an association between dysregulation of this pathway and the initiation and progression of various chronic kidney diseases such as diab

  15. Regulation of mechano growth factor in skeletal muscle and heart

    NARCIS (Netherlands)

    Ottens, M.

    2010-01-01

    The mechano growth factor (MGF) is expressed in mechanically overloaded skeletal muscle. MGF was discovered in 1996 as an alternative splice product of the IGF-1 gene. Since then, its significance has been investigated particularly in skeletal muscle, because the local expression of MGF could provid

  16. Epidermal growth factor receptor: Target for delivery and silencing

    NARCIS (Netherlands)

    Santos Oliveira, S.

    2008-01-01

    Epidermal growth factor receptor in cancer therapy Recently, cancer research has been able to identify molecular targets that are specific for (or highly expressed by) cancer cells. These molecular targets serve as models for the development of rationally designed anticancer drugs that target import

  17. Immunocytochemical expression of growth factors by odontogenic jaw cysts.

    Science.gov (United States)

    Li, T.; Browne, R. M.; Matthews, J. B.

    1997-01-01

    AIM: To determine the immunocytochemical pattern of expression of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and TGF beta in the three most common types of odontogenic jaw cyst. METHODS: Growth factor expression was detected in paraffin wax sections of odontogenic cysts (27 odontogenic keratocysts, 10 dentigerous cysts, and 10 radicular cysts) using a streptavidin-biotin peroxidase technique with monoclonal antibodies directed against TGF alpha (clone 213-4.4) and TGF beta (clone TB21) and a polyclonal antibody directed against EGF (Z-12). RESULTS: The epithelial linings of all cysts showed reactivity for TGF alpha which was mainly localised to basal and suprabasal layers. Odontogenic keratocyst linings expressed higher levels of TGF alpha than those of dentigerous and radicular cysts, with 89% (24/27) of odontogenic keratocysts exhibiting a strong positive reaction compared with 50% (five of 10) of dentigerous and radicular cysts, respectively. EGF reactivity was similar in all cyst groups, weaker than that for TGF alpha and predominantly suprabasal. TGF alpha and EGF were also detected in endothelial cells, fibroblasts and inflammatory cells within the cyst walls. The most intense TGF beta staining in odontogenic cysts was extracellular within the fibrous tissue capsules, irrespective of cyst type. CONCLUSIONS: These results, together with previous studies of EGF receptor, indicate differential expression of TGF alpha, EGF and their common receptor between the different types of odontogenic cyst, suggesting that these growth factors (via autocrine or paracrine, or both, pathways) may be involved in their pathogenesis. Images PMID:9208810

  18. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF...

  19. Controlled growth factor release from synthetic extracellular matrices

    Science.gov (United States)

    Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

    2000-12-01

    Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

  20. Fetal effects of epidermal growth factor deficiency induced in rats by autoantibodies against epidermal growth factor

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Jørgensen, P E

    1995-01-01

    , the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight ratio...

  1. Auxins as one of the factors of plant growth improvement by plant growth promoting rhizobacteria.

    Science.gov (United States)

    Ahmed, Ambreen; Hasnain, Shahida

    2014-01-01

    Plant growth promoting rhizobacteria (PGPR) promote plant growth by various mechanisms such as phytohormone production, enhanced water and nutrient uptake, improved nitrogen availability in the soil, production of ACC-deaminase for ethylene breakdown, phosphate solubilization, siderophore production etc. Microbial auxin production is the major factor not only responsible for strengthening the plant-microbe relationship but it also promotes plant growth and development in a positive manner. Thus, bacterial auxin production potential can be exploited for plant growth improvement that may be effective in reducing the hazardous effects of chemical fertilizers on the ecosystem used to obtain higher yields. The present review gives a better understanding of various factors and mechanisms involved in auxin production by PGPR that may be helpful in proper exploitation of these natural resources in a beneficial way.

  2. Stimulation of body weight increase and epiphyseal cartilage growth by insulin like growth factor

    Science.gov (United States)

    Ellis, S.

    1981-01-01

    The ability of insulin-like growth factor (IGF) to induce growth in hypophysectomized immature rats was tested by continuous infusion of the partially purified factor at daily doses of 6, 21, and 46 mU for an 8-day period. A dose-dependent growth of the proximal epiphyseal cartilage of the tibia and an associated stimulation of the primary spongiosa were produced by these amounts of IGF. The two highest doses of IGF also resulted in dose-dependent increases of body weight. Gel permeation of the sera at neutrality showed that the large-molecular-weight IGF binding protein was not induced by the infusion of IGF, whereas it ws generated in the sera of hypophysectomized rats that were infused with daily doses of 86 mU of human growth hormone.

  3. Steady impact factor growth for MDPI open access journals.

    Science.gov (United States)

    Thiesen, Alexander

    2012-09-12

    For the past three years MDPI has announced the newly released impact factors for its Open Access journals by the means of an annual editorial [1-3]. In 2012 we are-once again-pleased to report that the growth of the impact factors of MDPI's Open Access journals continues. This year's edition of the Journal Citation Reports (JCR), which is published annually by Thomson Reuters, includes 10 journals published by MDPI, including three that have received their first official Impact Factors- International Journal of Environmental Research and Public Health (IJERPH), Materials Nutrients. Table 1 reports the latest Impact Factors for 2011. Figure 1 graphically depicts the evolution of the Impact Factors for four MDPI open access journals that have received Impact Factors in the past. Table 2 reports the ranking of the MDPI journals within the subject categories of the Science Citation Index Expanded.

  4. Factors related to attempted suicide in Davanagere

    Directory of Open Access Journals (Sweden)

    Nagendra Gouda M

    2008-01-01

    Full Text Available Research Question: What are the factors responsible for suicidal attempts? Objectives: To study the socio-demographic factors, methods and reasons for suicidal attempts. Type of Study: Cross-sectional study. Setting: Bapuji and C.G. Hospitals attached to J.J.M. Medical College, Davanagere. Participants: A total of 540 suicidal attempters admitted to emergency wards. Methodology: A pretested proforma was administered to the subjects relating the factors responsible for the attempt. The data thus obtained was compiled and analyzed. Statistical Analysis: Proportions, Z -test and Chi-square test. Results: In this study, 61.3% were males and 38.7% were females. Peak occurrence of suicidal attempts was found in the second and third decades (15-29 years. Hindus constituted about 94.6% of the total suicidal attempters. Almost half (52.2% of the subjects had education below or up to matriculation and 83% of them were from the lower (classes IV and V socio-economic groups. Agriculturists, housewives and unskilled workers represented 75% of the total subjects. Fifty-five percent of the subjects were from nuclear families and most (62.4% of them were married; frequent mode of attempting suicides was by organo-phosphorus compounds (66.3% followed by overdosage of tablets (17.8%. Common cause was family problem (27.2% followed by illness (27%.

  5. Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults.

    Science.gov (United States)

    Skjaerbaek, C; Frystyk, J; Møller, J; Christiansen, J S; Orskov, H

    1996-12-01

    The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.

  6. Assessing poverty and related factors in Turkey.

    Science.gov (United States)

    Saatci, Esra; Akpinar, Ersin

    2007-10-01

    Poverty, a complex, multidimensional, and universal problem, has been conceptualized as income and material deprivation. In this article, we discuss poverty and related factors in Turkey. The absolute poverty line for Turkey was US$ 4 per capita per day. Turkey was ranked 92nd out of 177 countries with moderate human development in the 2006 Human Development Report. The individual food poverty rate was 1.35% and the non-food poverty rate was 25.6%. The highest poverty rate was among primary school graduates (42.5%; 38.5% for women and 46.8% for men). The rate for this group was higher in urban than in rural areas. Among poor people, 57.2% were married. The highest poverty rate was among agricultural workers (46.6%) and in Eastern and Southeastern Anatolia. Factors related to poverty were crowded households, unemployment, immigration, working for a daily wage in the agricultural and construction sector, low educational status, female sex or married status, lacking social insurance, and living in rural areas or in Eastern and Southeastern Anatolia.

  7. Autocrine growth regulation of human glomerular mesangial cells is primarily mediated by basic fibroblast growth factor.

    OpenAIRE

    Francki, A.; Uciechowski, P.; Floege, J; von der Ohe, J.; Resch, K.; Radeke, H. H.

    1995-01-01

    For various forms of human glomerulonephritis a close relationship between inflammatory injury and a local mesangial proliferative response has been described. Herein, we used primary cultures of human glomerular mesangial cells (HMCs) from five different donors to determine the autocrine growth-inducing capacity of their supernatants after stimulation with different cytokines and lipopolysaccharide (LPS) to determine whether this effect is due to basic fibroblast growth factor (bFGF). The ba...

  8. Transforming growth factor beta (TGF-β) in milk: a review

    OpenAIRE

    Fernanda Lopes da Silva; Michele da Silva Pinto; Antônio Fernandes Carvalho; Ítalo Tuler Perrone

    2016-01-01

    Bovine milk and colostrum contain growth factors such as insulin-like growth factor IGF-I, IGF-II, transforming growth factor TGF-β1, TGF-β2, epidermal growth factor EGF, basic fibroblast growth factor bFGF and platelet-derived growth factor PDGF. In recent years, intense scientific interest has been focused on the identification of factors within bovine milk that may be relevant to improving human health. Then a number of methodologies for the extraction of milk growth factors from milk, col...

  9. Expression of protooncogenes during lymphocyte activation by growth factors.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Yarilin, A A; Mazurenko, N N

    1997-09-01

    Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD(3+)-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.

  10. Maternal immune stimulation reduces both placental morphologic damage and down-regulated placental growth-factor and cell cycle gene expression caused by urethane: are these events related to reduced teratogenesis?

    Science.gov (United States)

    Sharova, L V; Sharov, A A; Sura, P; Gogal, R M; Smith, B J; Holladay, S D

    2003-07-01

    Activation of the maternal immune system in mice decreased cleft palate caused by the chemical teratogen, urethane. Direct and indirect mechanisms for this phenomenon have been suggested, including maternal macrophages that cross the placenta to find and eliminate pre-teratogenic cells, or maternal immune proteins (cytokines) that cross placenta to alleviate or partially alleviate toxicant-mediated effects in the developing fetus. A third mechanism to explain improved fetal developmental outcome in teratogen-challenged pregnant mice might involve beneficial effects of immune stimulation on the placenta. In the present experiments, urethane treatment altered placental morphology and impaired placental function, the latter indicated by down-regulated activity of cell cycle genes and of genes encoding cytokines and growth factors. Maternal immune stimulation with either Freund's complete adjuvant (FCA) or interferon-gamma (IFNgamma) reduced morphologic damage to the placenta caused by urethane and normalized expression of several genes that were down-regulated by urethane. Urethane treatment also shifted placental cytokine gene expression toward a T cell helper 1 (Th1) profile, while immunostimulation tended to restore a Th2 profile that may be more beneficial to pregnancy and fetal development. These data suggest that the beneficial effects of maternal immune stimulation on fetal development in teratogen-exposed mice may, in part, result from improved placental structure and function.

  11. Factors affecting growth and pigmentation of Penicillium caseifulvum

    DEFF Research Database (Denmark)

    Suhr, Karin Isabel; Haasum, I.; Steenstrup, L.D.

    2002-01-01

    Color formation, metabolite production and growth of Penicillium caseifulvum were studied in order to elucidate factors contributing to. yellow discoloration of Blue Cheese caused by the mold. A screening experiment was set up to study the effect of pH, concentration of salt (NaCl), P, K, N, S, Mg...... the factors contributing to yellow color formation, pH and salt concentration are easy to control for the cheesemaker, while the third factor, P-concentration, is not. Naturally occurring variations in the P-concentration in milk delivered to Blue Cheese plants, could be responsible for the yellow...

  12. Prognosis and risk factors for intrauterine growth retardation

    DEFF Research Database (Denmark)

    Sehested, Line Thousig; Pedersen, Pernille

    2014-01-01

    focusing on risk factors, catch up and neonatal outcome. MATERIAL AND METHODS: This was a retrospective descriptive study of IUGR neonates with a birth weight below 70% of the expected whose mothers were admitted to the Neonatal Ward at Hvidovre Hospital during 2007-2009. Obstetrical and maternal risk...... factors and neonatal growth and outcome at six weeks, five months and 12 months of age were collected. RESULTS: A total of 73 neonates and their mothers were included. Caesarean delivery was given in 78% of the cases. Maternal risk factors included gestational hypertension (33%), smoking (24...

  13. 关键词分析:影响我国心理康复研究文献增长的主要因素%Key Words Analysis: Factors Related with the Growth of Psychological Rehabilitation Literature in China

    Institute of Scientific and Technical Information of China (English)

    张爱民; 邱卓英; 蔡飞鸣; 荀芳; 李沁燚; 陈迪

    2011-01-01

    目的 研究我国心理康复文献增长主要关键词.方法 抽取"中国知网"收录的与心理康复有关的1426篇期刊论文进行关键词词频统计,对词频≥4的340个关键词年度累积词频为白变量,以年度累积文献量为因变量进行多无线性逐步回归分析.结果 共提取到10个关键词,分别为心理护理、心理问题、心理反应、精神病人、情绪障碍、A型行为、社会心理、SCL-90、假肢、精神医学.结论 我国心理康复的主要研究对象包括心理问题、心理反应、精神病人、情绪障碍、A型行为;主要研究方法 或研究工具有社会心理、SCL-90;主要研究者为护理人员、假肢工作者、精神卫生工作者.%Objective To investigate the key words related with the growth of psychological rehabilitation literature of psychological rehabilitation in China. Methods The journal articles associated with psychological rehabilitation in CNKI were analyzed with key word frequency. The relationship between the cumulative frequency of key words and the growth of literature were analyzed with Linear Regression Analysis. Result Based on the cumulative frequency of 340 key words frequencies more than 4 in each year, Linear Regression Analysis extracted 10 words that correlated with the literature growth,which were Psychological Nursing, Psychological Problem, Psychological Response, Psychotics, Emotional Disorder, Type A Behavior, Social Psychology, SCL-90, Prosthesis, and Psychiatry. Conclusion The major objects of the researches of psychological rehabilitation in China were psychological problem, psychological response, psychotics, emotional disorder, type A behavior; the major tools were social psychology, SCL-90; the researchers mainly come from the nurse, and the professionals of prosthesis and psychiatry.

  14. Effect of Temperature and Relative Humidity on the Growth of ...

    African Journals Online (AJOL)

    Nigerian Journal of Basic and Applied Science (2011), 19(1):127- 129. ISSN 0794-5698. Effect of ... influence of environmental factors on the growth of H. fulvum. Therefore ... dishes containing Czapek-Dox agar medium. The inoculated plates ...

  15. Vascular Endothelial Growth Factor from Embryonic Status to Cardiovascular Pathology

    Directory of Open Access Journals (Sweden)

    Mohsen Azimi-Nezhad

    2014-05-01

    Full Text Available Vascular endothelial growth factor (VEGF is a multifunctional cytokine with distinct functions in angiogenesis, lymphangiogenesis, vascular permeability, and hematopoiesis. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34 to 45 kDa produced by several cell types including fibroblasts, neutrophils, endothelial cells, and peripheral blood mononuclear cells, particularly T lymphocytes and macrophages. Six VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene, consisting of 121, 145, 165, 183, 189, or 206 amino acids. VEGF121, VEGF145, and VEGF165 are secreted whereas VEGF183, VEGF189, and VEGF206 are cell membrane-bound. VEGF145 has a key role during the vascularization of the human ovarian follicle and corpus luteum, in the placentation and embryonic periods, and in bone and wound healing, while VEGF165 is the most abundant and biologically active isoform. VEGF has been linked with a number of vascular pathologies including cardiovascular diseases such ischemic heart disease, heart failure, stroke, and diabetes and its related complications. In this review we aimed to present some important roles of VEGF in a number of clinical issues and indicate its involvement in several phenomena from the initial steps of the embryonic period to cardiovascular diseases.

  16. Functional Diversity of Fibroblast Growth Factors in Bone Formation

    Directory of Open Access Journals (Sweden)

    Yuichiro Takei

    2015-01-01

    Full Text Available The functional significance of fibroblast growth factor (FGF signaling in bone formation has been demonstrated through genetic loss-of-function and gain-of-function approaches. FGFs, comprising 22 family members, are classified into three subfamilies: canonical, hormone-like, and intracellular. The former two subfamilies activate their signaling pathways through FGF receptors (FGFRs. Currently, intracellular FGFs appear to be primarily involved in the nervous system. Canonical FGFs such as FGF2 play significant roles in bone formation, and precise spatiotemporal control of FGFs and FGFRs at the transcriptional and posttranscriptional levels may allow for the functional diversity of FGFs during bone formation. Recently, several research groups, including ours, have shown that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in mineralization defects in the bone. Thus, FGFs are involved in the positive and negative regulation of bone formation. In this review, we focus on the reciprocal roles of FGFs in bone formation in relation to their local versus systemic effects.

  17. Expression of epidermal growth factor receptors in human brain tumors.

    Science.gov (United States)

    Libermann, T A; Razon, N; Bartal, A D; Yarden, Y; Schlessinger, J; Soreq, H

    1984-02-01

    The expression of receptors for epidermal growth factor (EGF-R) was determined in 29 samples of brain tumors from 22 patients. Primary gliogenous tumors, of various degrees of cancer, five meningiomas, and two neuroblastomas were examined. Tissue samples were frozen in liquid nitrogen immediately after the operation and stored at -70 degrees until use. Cerebral tissue samples from 11 patients who died from diseases not related to the central nervous system served as controls. Immunoprecipitation of functional EGF-R-kinase complexes revealed high levels of EGF-R in all of the brain tumors of nonneuronal origin that were examined. The level of EGF-R varied between tumors from different patients and also between specimens prelevated from different areas of the same tumor. In contrast, the levels of EGF-R from control specimens were invariably low. The biochemical properties of EGF-R in brain tumor specimens were found to be indistinguishable from those of the well-characterized EGF-R from the A-431 cell line, derived from human epidermoid carcinomas. Human brain EGF-R displays a molecular weight of 170,000 by polyacrylamide-sodium dodecyl sulfate gel electrophoresis. It is phosphorylated mainly in tyrosine residues and shows a 2-dimensional phosphopeptide map similar to that obtained with the phosphorylated EGF-R from membranes of A-431 cells. Our observations suggest that induction of EGF-R expression may accompany the malignant transformation of human brain cells of nonneuronal origin.

  18. Fascia implantation with fibroblast growth factor on vocal fold paralysis.

    Science.gov (United States)

    Nagai, Hiromi; Nishiyama, Koichiro; Seino, Yutomo; Kimura, Yu; Tabata, Yasuhiko; Okamoto, Makito

    2013-01-01

    The purpose of this prospective study was to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on unilateral vocal fold paralysis (UVFP) in a rat model. Unilateral recurrent laryngeal nerve (RLN) section was performed on 15 rats. Ten rats received an autologous fascia implant and gelatin hydrogel with or without bFGF (1 μg) to their larynxes (fascia only, "fascia group"; bFGF + fascia, "fascia + bFGF group"), while the rest underwent RLN transection ("RLN section group"). Four months later, evaluation of the laryngeal glottal gap and histological analysis were performed. The glottal gap was significantly reduced in the fascia + bFGF group, and fat volume increased significantly relative to the RLN section. The volume of the remaining fascia in the bFGF + fascia group was significantly greater than that of the fascia group. ATFV with controlled release of bFGF may compensate for diminished laryngeal volume in UVFP by reducing resorption of the implanted fascia and increasing fat volume. Our findings suggest that this modality may represent an attractive option for treating UVFP. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Hepatocyte growth factor reduces CXCL10 expression in keratinocytes.

    Science.gov (United States)

    Hisadome, Mitsuhiro; Ohnishi, Tomokazu; Kakimoto, Kyoko; Kusuyama, Joji; Bandow, Kenjiro; Kanekura, Takuro; Matsuguchi, Tetsuya

    2016-10-01

    Keratinocytes secrete vascular endothelial growth factor (VEGF) and angioregulatory chemokines during cutaneous wound healing. Hepatocyte growth factor (HGF) promotes skin re-epithelialization by increasing VEGF expression in keratinocytes. Here, we investigated the regulatory roles of HGF in the expression of genes encoding angiogenic and angiostatic chemokines in keratinocytes and found that HGF specifically inhibits mRNA expression of the angiostatic chemokine CXCL10 in both mouse primary keratinocytes and in the human keratinocyte cell line HaCaT through the MEK/ERK cascade. Furthermore, HGF inhibited tumor necrosis factor-α-induced CXCL10 expression at both mRNA and protein levels in HaCaT cells. Thus, HGF may orchestrate angiogenesis in wounded skin by modulating both VEGF and CXCL10 expression in keratinocytes. © 2016 Federation of European Biochemical Societies.

  20. Role of myeloid growth factors in chemotherapy induced neutropenia

    Directory of Open Access Journals (Sweden)

    Ravinutala Srinath Bharadwaj

    2016-10-01

    Full Text Available Neutropenia is a major dose limiting toxicity of many chemo therapeutic regimens. Haemopoietic colony - stimulating factors (CSFs have been shown to reduce the duration and severity of chemotherapy induced neutropenia (CIN and risk of febrile neutropenia. Supportive care with myeloid growth factors improve chemotherapy delivery by minimizing chemotherapy dose reductions or treatment delays by enabling the delivery of full dose chemotherapy (dose dense in short time intervals. The goal of this article is to give comprehensive review of current literature regarding medical practice guidelines and risk assessment models for appropriate use of myeloid growth factors and management of febrile neutropenia. [Int J Basic Clin Pharmacol 2016; 5(5.000: 1715-1721