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Growth Factor Beta (growth + factor_beta)
Kinds of Growth Factor Beta Selected AbstractsTGFBI gene mutations in Hungary , polymorphic corneal amyloidosis caused by the novel F547S mutationACTA OPHTHALMOLOGICA, Issue 2009A BERTA Purpose To identify mutations in the Transforming Growth Factor Beta Induced (TGFBI) gene in Hungarian patients with corneal dystrophy and to characterize their histological features. Methods Exons of TGFBI gene were sequenced in 38 members of 15 unrelated families with corneal dystrophy. Exon 12 was sequenced in 100 healthy controls. Immunohistological analysis of corneal buttons excised during penetrating keratoplasty was performed. Results Molecular genetic analysis revealed a heterozygous R124C mutation in 18 patients with lattice type I dystrophy. A R555W heterozygous mutation was detected in five patients with granular Groenouw type I corneal dystrophy and the R555Q heterozygous mutation was found in four patients clinically diagnosed with Reis-Bücklers (one patient) and Thiel-Behnke (three patients) dystrophy. Three patients with "atypical granular" dystrophy later diagnosed as Avellino dystrophy were heterozygous for the R124H mutation. No other than the novel heterozygous T1640C mutation causing the F547S amino acid exchange was detected in a patient with polymorphic corneal amyloidosis. The mutation could not be found in healthy controls. Immunohistochemistry showed the presence of BIGH3 protein deposits in all examined corneal buttons. Electron microscopy confirmed the presence of amyloid fibrils in the case of the novel mutation. Conclusion Our results indicate that molecular genetic analysis is required to confirm the diagnosis of corneal dystrophies. We report the first cases of Avellino dystrophy from Central-Eastern Europe. The novel F547S mutation causes polymorphic corneal amyloidosis. [source] Expression and functional analysis of Tgif during mouse midline developmentDEVELOPMENTAL DYNAMICS, Issue 2 2006Jiu-Zhen Jin Abstract The Tgif gene encodes a homeodomain protein that functions as a transforming growth factor beta (TGF-,) repressor by binding to Smad2. Mutations in the TGIF gene are associated with human holoprosencephaly, a common birth defect caused by the failure of anterior ventral midline formation. However, Smad2-mediated TGF-, signaling in the axial mesendoderm has been demonstrated to be essential for ventral midline formation, and loss of a Smad2 antagonist should in principle promote rather than inhibit ventral midline formation. This suggests a more complex mechanism for the function of TGIF in controlling ventral midline formation. To explore the role of TGIF in ventral forebrain formation and patterning, we investigated Tgif expression and function during mouse development by in situ hybridization and gene targeting. We found that Tgif is highly expressed in the anterior neural plate, consistent with the proposed neural differentiation model in which TGF-, suppression is required for normal neural differentiation. This result suggests a possible role for Tgif in anterior neural differentiation and patterning. However, targeted disruption of the Tgif gene during mouse development does not cause any detectable defects in development and growth. Both histological examination and gene expression analysis showed that Tgif,/, embryos have a normal ventral specification in the central nervous system, including the forebrain region. One interpretation of these results is that the loss of TGIF function is compensated by other TGF-, antagonists such as c-Ski and SnoN during vertebrate anterior neural development. Developmental Dynamics 235:547,553, 2006. © 2005 Wiley-Liss, Inc. [source] Altered subcellular location of phosphorylated Smads in Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006Uwe Ueberham Abstract A number of growth factors and cytokines, such as transforming growth factor beta 1 (TGF-,1), is elevated in Alzheimer's disease (AD), giving rise to activated intracellular mitogenic signaling cascades. Activated mitogenic signaling involving the mitogen-activated protein kinases (MAPKs) and other protein kinases might alter the phosphorylation states of structural proteins such as tau, resulting in hyperphosphorylated deposits. Many intracellular signaling proteins are potential targets of misregulated phosphorylation and dephosphorylation. Recently, a crosstalk between MAPKs and Smad proteins, both involved in mediating TGF-,1 signaling, has been reported. Although TGF-,1 has previously been shown to be involved in the pathogenesis of AD, the role of Smad proteins has not been investigated. In this study we thus analysed the subcellular distribution of phosphorylated Smad2 and Smad3 in the hippocampus of both normal and AD brains. Here we report on strong nuclear detection of phosphorylated Smad2 and Smad3 in neurons of control brains. In AD brains these phosphorylated proteins were additionally found in cytoplasmic granules in hippocampal neurons, within amyloid plaques and attached to neurofibrillary tangles. Our data suggest a critical role of Smad proteins in the pathogenesis of AD. [source] Generation of mice with a conditional allele for transforming growth factor beta 1 geneGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 6 2009Mohamad Azhar Abstract Transforming growth factor ,1 (TGF,1) is a multifunctional growth factor involved in wound healing, tissue fibrosis, and in the pathogenesis of many syndromic diseases (e.g., Marfan syndrome, Camurati-Engelmann disease) and muscular, neurological, ophthalmic, cardiovascular and immunological disorders, and cancer. Since the generation of Tgfb1 knockout mice, there has been extraordinary progress in understanding its physiological and pathophysiological function. Here, we report the generation of a conditional knockout allele for Tgfb1 in which its exon 6 is flanked with LoxP sites. As proof of principle, we crossed these mice to LckCre transgenic mice and specifically disrupted Tgfb1 in T cells. The results indicate that T-cell-produced TGF,1 is required for normal in vivo regulation of peripheral T-cell activation, maintenance of T-cell homeostasis, and suppression of autoimmunity. genesis 47:423,431, 2009. © 2009 Wiley-Liss, Inc. [source] TGF-,1/SMAD signaling induces astrocyte fate commitment in vitro: Implications for radial glia developmentGLIA, Issue 10 2007Joice Stipursky Abstract Radial glial (RG) cells are specialized type of cell, which functions as neuronal precursors and scaffolding guides to migrating neurons during cerebral cortex development. After neurogenesis and migration are completed, most of RG cells transform into astrocytes. Mechanism and molecules involved in this process are not completely elucidated. We previously demonstrated that neurons activate the promoter of the astrocyte maturation marker GFAP in astrocytes by secretion of transforming growth factor beta 1 (TGF-,1) in vitro. Here, we studied the role of neurons and TGF-,1 pathway in RG differentiation. To address this question, we employed cortical progenitor cultures enriched in GLAST/nestin double-labeled cells, markers of RG cells. TGF-,1 and conditioned medium derived from neuron-astrocyte cocultures (CM) decreased the number of cells expressing the precursor marker nestin and increased that expressing GFAP in cortical progenitor cultures. These events were impaired by addition of neutralizing antibodies against TGF-,1. Increase in the number of GFAP positive cells was associated with Smads 2/3 nuclear translocation, a hallmark of TGF-,1 pathway activation. PCR-assays revealed a decrease in the levels of mRNA for the RG marker, BLBP (brain lipid binding protein), due to TGF-,1 and CM treatment. We further identified TGF-,1 receptor in cortical progenitor cultures suggesting that these cells might be target for TGF-,1 during development. Our work provides strong evidence that TGF-,1 might be a novel factor involved in RG-astrocyte transformation and highlights the role of neuron-glia interaction in this process. © 2007 Wiley-Liss, Inc. [source] Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection,HEPATOLOGY, Issue 1 2010Nabora Soledad Reyes de Mochel Oxidative stress has been identified as a key mechanism of hepatitis C virus (HCV),induced pathogenesis. Studies have suggested that HCV increases the generation of hydroxyl radical and peroxynitrite close to the cell nucleus, inflicting DNA damage, but the source of reactive oxygen species (ROS) remains incompletely characterized. We hypothesized that HCV increases the generation of superoxide and hydrogen peroxide close to the hepatocyte nucleus and that this source of ROS is reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase 4 (Nox4). Huh7 human hepatoma cells and telomerase-reconstituted primary human hepatocytes, transfected or infected with virus-producing HCV strains of genotypes 2a and 1b, were examined for messenger RNA (mRNA), protein, and subcellular localization of Nox proteins along with the human liver. We found that genotype 2a HCV induced persistent elevations of Nox1 and Nox4 mRNA and proteins in Huh7 cells. HCV genotype 1b likewise elevated the levels of Nox1 and Nox4 in telomerase-reconstituted primary human hepatocytes. Furthermore, Nox1 and Nox4 proteins were increased in HCV-infected human liver versus uninfected liver samples. Unlike Nox1, Nox4 was prominent in the nuclear compartment of these cells as well as the human liver, particularly in the presence of HCV. HCV-induced ROS and nuclear nitrotyrosine could be decreased with small interfering RNAs to Nox1 and Nox4. Finally, HCV increased the level of transforming growth factor beta 1 (TGF,1). TGF,1 could elevate Nox4 expression in the presence of infectious HCV, and HCV increased Nox4 at least in part through TGF,1. Conclusion: HCV induced a persistent elevation of Nox1 and Nox4 and increased nuclear localization of Nox4 in hepatocytes in vitro and in the human liver. Hepatocyte Nox proteins are likely to act as a persistent, endogenous source of ROS during HCV-induced pathogenesis. Hepatology 2010 [source] CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis,HEPATOLOGY, Issue 4 2010Mirko Moreno Zaldivar Liver fibrosis is a major cause of morbidity and mortality worldwide. Platelets are involved in liver damage, but the underlying molecular mechanisms remain elusive. Here, we investigate the platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) as a molecular mediator of fibrotic liver damage. Serum concentrations and intrahepatic messenger RNA of CXCL4 were measured in patients with chronic liver diseases and mice after toxic liver injury. Platelet aggregation in early fibrosis was determined by electron microscopy in patients and by immunohistochemistry in mice. Cxcl4,/, and wild-type mice were subjected to two models of chronic liver injury (CCl4 and thioacetamide). The fibrotic phenotype was analyzed by histological, biochemical, and molecular analyses. Intrahepatic infiltration of immune cells was investigated by fluorescence-activated cell sorting, and stellate cells were stimulated with recombinant Cxcl4 in vitro. The results showed that patients with advanced hepatitis C virus,induced fibrosis or nonalcoholic steatohepatitis had increased serum levels and intrahepatic CXCL4 messenger RNA concentrations. Platelets were found directly adjacent to collagen fibrils. The CCl4 and thioacetamide treatment led to an increase of hepatic Cxcl4 levels, platelet activation, and aggregation in early fibrosis in mice. Accordingly, genetic deletion of Cxcl4 in mice significantly reduced histological and biochemical liver damage in vivo, which was accompanied by changes in the expression of fibrosis-related genes (Timp-1 [tissue inhibitor of matrix metalloproteinase 1], Mmp9 [matrix metalloproteinase 9], Tgf -, [transforming growth factor beta], IL10 [interleukin 10]). Functionally, Cxcl4,/, mice showed a strongly decreased infiltration of neutrophils (Ly6G) and CD8+ T cells into the liver. In vitro, recombinant murine Cxcl4 stimulated the proliferation, chemotaxis, and chemokine expression of hepatic stellate cells. Conclusion: The results underscore an important role of platelets in chronic liver damage and imply a new target for antifibrotic therapies. (HEPATOLOGY 2010.) [source] Fenofibrate differentially regulates plasminogen activator inhibitor-1 gene expression via adenosine monophosphate,activated protein kinase,dependent induction of orphan nuclear receptor small heterodimer partner,HEPATOLOGY, Issue 3 2009Dipanjan Chanda Plasminogen activator inhibitor type I (PAI-1) is a marker of the fibrinolytic system and serves as a possible predictor for hepatic metabolic syndromes. Fenofibrate, a peroxisome proliferator-activated receptor , (PPAR,) agonist, is a drug used for treatment of hyperlipidemia. Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in transcriptional repression of crucial genes involved in various metabolic pathways. In this study, we show that fenofibrate increased SHP gene expression in cultured liver cells and in the normal and diabetic mouse liver by activating the adenosine monophosphate,activated protein kinase (AMPK) signaling pathway in a PPAR,-independent manner. Administration of transforming growth factor beta (TGF-,) or a methionine-deficient and choline-deficient (MCD) diet to induce the progressive fibrosing steatohepatitis model in C57BL/6 mice was significantly reversed by fenofibrate via AMPK-mediated induction of SHP gene expression with a dramatic decrease in PAI-1 messenger RNA (mRNA) and protein expression along with other fibrotic marker genes. No reversal was observed in SHP null mice treated with fenofibrate. Treatment with another PPAR, agonist, WY14643, showed contrasting effects on these marker gene expressions in wild-type and SHP null mice, demonstrating the specificity of fenofibrate in activating AMPK signaling. Fenofibrate exhibited a differential inhibitory pattern on PAI-1 gene expression depending on the transcription factors inhibited by SHP. Conclusion: By demonstrating that a PPAR,-independent fenofibrate-AMPK-SHP regulatory cascade can play a key role in PAI-1 gene down-regulation and reversal of fibrosis, our study suggests that various AMPK activators regulating SHP might provide a novel pharmacologic option in ameliorating hepatic metabolic syndromes. (HEPATOLOGY 2009.) [source] Liver stem cells and hepatocellular carcinoma,HEPATOLOGY, Issue 1 2009Lopa Mishra Although the existence of cancer stem cells (CSCs) was first proposed over 40 years ago, only in the past decade have these cells been identified in hematological malignancies, and more recently in solid tumors that include liver, breast, prostate, brain, and colon. Constant proliferation of stem cells is a vital component in liver tissues. In these renewing tissues, mutations will most likely result in expansion of the altered stem cells, perpetuating and increasing the chances of additional mutations and tumor progression. However, many details about hepatocellular cancer stem cells that are important for early detection remain poorly understood, including the precise cell(s) of origin, molecular genetics, and the mechanisms responsible for the highly aggressive clinical picture of hepatocellular carcinoma (HCC). Exploration of the difference between CSCs from normal stem cells is crucial not only for the understanding of tumor biology but also for the development of specific therapies that effectively target these cells in patients. These ideas have drawn attention to control of stem cell proliferation by the transforming growth factor beta (TGF-,), Notch, Wnt, and Hedgehog pathways. Recent evidence also suggests a key role for the TGF-, signaling pathway in both hepatocellular cancer suppression and endoderm formation, suggesting a dual role for this pathway in tumor suppression as well as progression of differentiation from a stem or progenitor stage. This review provides a rationale for detecting and analyzing tumor stem cells as one of the most effective ways to treat cancers such as HCC. (HEPATOLOGY 2009;49:318,329.) [source] Impaired liver regeneration and increased oval cell numbers following T cell,mediated hepatitis,HEPATOLOGY, Issue 1 2007Ian N. Hines The regeneration of liver tissue following transplantation is often complicated by inflammation and tissue damage induced by a number of factors, including ischemia and reperfusion injury and immune reactions to the donor tissue. The purpose of the current study is to characterize the effects of T cell,mediated hepatitis induced by concanavalin A (ConA) on the regenerative response in vivo. Liver regeneration following a partial (70%) hepatectomy (pHx) was associated with elevations in serum enzymes and the induction of key cell cycle proteins (cyclin D, cyclin E, and Stat3) and hepatocyte proliferation. The induction of T cell,mediated hepatitis 4 days before pHx increased serum enzymes 48 hours after pHx, reduced early cyclin D expression and Stat3 activation, and suppressed hepatocyte proliferation. This inhibition of proliferation was also associated with increased expression of p21, the activation of Smad2, the induction of transforming growth factor beta and interferon gamma expression, and reduced hepatic interleukin 6 production. Moreover, the ConA pretreatment increased the numbers of separate oval cell-like CD117+ cells and hematopoietic-like Sca-1+ cell populations 48 hours following pHx. The depletion of natural killer (NK) cells, an important component of the innate immune response, did not affect liver injury or ConA-induced impairment of hepatocyte proliferation but did increase the numbers of both CD117-positive and Sca-1,positive cell populations. Finally, splenocytes isolated from ConA-pretreated mice exerted cytotoxicity toward autologous bone marrow cells in an NK cell,dependent manner. Conclusion: T cell,mediated hepatitis alters early cytokine responses, reduces hepatocellular regeneration, and induces NK cell,sensitive oval cell and hematopoietic-like cell expansion following pHx. (HEPATOLOGY 2007;46:229,241.) [source] Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis,HEPATOLOGY, Issue 5 2006Pierre J. Zindy The molecular mechanisms underlying the progression of cirrhosis toward hepatocellular carcinoma were investigated by a combination of DNA microarray analysis and literature data mining. By using a microarray screening of suppression subtractive hybridization cDNA libraries, we first analyzed genes differentially expressed in tumor and nontumor livers with cirrhosis from 15 patients with hepatocellular carcinomas. Seventy-four genes were similarly recovered in tumor (57.8% of differentially expressed genes) and adjacent nontumor tissues (64% of differentially expressed genes) compared with histologically normal livers. Gene ontology analyses revealed that downregulated genes (n = 35) were mostly associated with hepatic functions. Upregulated genes (n = 39) included both known genes associated with extracellular matrix remodeling, cell communication, metabolism, and post-transcriptional regulation gene (e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple endocrine neoplasia type 1; MEN1). MEN1 was further identified as an important node of a regulatory network graph that integrated array data with array-independent literature mining. Upregulation of MEN1 in tumor was confirmed in an independent set of samples and associated with tumor size (P = .016). In the underlying liver with cirrhosis, increased steady-state MEN1 mRNA levels were correlated with those of collagen ,2(I) mRNA (P < .01). In addition, MEN1 expression was associated with hepatic stellate cell activation during fibrogenesis and involved in transforming growth factor beta (TGF-,),dependent collagen ,2(I) regulation. In conclusion, menin is a key regulator of gene networks that are activated in fibrogenesis associated with hepatocellular carcinoma through the modulation of TGF-, response. (HEPATOLOGY 2006;44:1296,1307.) [source] Interleukin-4 antagonizes oncostatin M and transforming growth factor beta-induced responses in articular chondrocytesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Mohammed El Mabrouk Abstract Oncostatin M (OSM) stimulates cartilage degradation in rheumatoid arthritis (RA) by inducing matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS; a disintegrin and metalloproteinase with thrombospondin motif). Transforming growth factor beta (TGF-,1) induces cartilage repair in joints but in excessive amounts, promotes inflammation. OSM and TGF-,1 also induce tissue inhibitor of metalloproteinase-3 (TIMP-3), an important natural inhibitor of MMPs, aggrecanases, and tumor necrosis factor alpha converting enzyme (TACE), the principal proteases involved in arthritic inflammation and cartilage degradation. We studied cartilage protective mechanisms of the antiinflammatory cytokine, interleukin-4 (IL-4). IL-4 strongly (MMP-13 and TIMP-3) or minimally (ADAMTS-4) suppressed OSM-induced gene expression in chondrocytes. IL-4 did not affect OSM-stimulated phosphorylation of extracellular signal-regulated kinases (ERKs), protein 38 (p38), c-Jun N-terminal kinase (JNK) and Stat1. Lack of additional suppression with their inhibitors suggested that MMP-13, ADAMTS-4, and TIMP-3 inhibition was independent of these mediators. IL-4 also downregulated TGF-,1-induced TIMP-3 gene expression, Smad2, and JNK phosphorylation. Additional suppression of TIMP-3 RNA by JNK inhibitor suggests JNK implication. The cartilage protective effects of IL-4 in animal models of arthritis may be due to its inhibition of MMPs and ADAMTS-4 expression. However, suppression of TIMP-3 suggests caution for using IL-4 as a cartilage protective therapy. J. Cell. Biochem. 103: 588,597, 2008. © 2007 Wiley-Liss, Inc. [source] Nicotine inhibits myofibroblast differentiation in human gingival fibroblastsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2005Yiyu Fang Abstract Cigarette smoking has been suggested as a risk factor for several periodontal diseases. It has also been found that smokers respond less favorably than non-smokers to periodontal therapy. Previous work in our lab has shown that nicotine inhibits human gingival cell migration. Since myofibroblasts play an important role in wound closure, we asked if nicotine affects gingival wound healing process by regulating myofibroblast differentiation. Human gingival fibroblasts (HGFs) from two patients were cultured in 10% fetal bovine serum cell culture medium. Cells were pretreated with different doses of nicotine (0, 0.01, 0.1, and 1 mM) for 2 h, and then incubated with transforming growth factor beta (TGF-,1) (0, 0.25, 0.5, and 1 ng/ml) with or without nicotine for 30 h. The expression level of ,-smooth muscle actin (,-SMA), a specific marker for myofibroblasts, was analyzed by Western blots, immunocytochemistry, and real-time polymerase chain reaction (real-time PCR). Phosphorylated p38 mitogen-activated protein kinase (Phospho-p38 MAPK) activity was analyzed by Western blots. TGF-,1 induced an increase of ,-SMA protein and mRNA expression, while nicotine (1 mM) inhibited the TGF-,1-induced expression of ,-SMA but not ,-actin. Nicotine treatment down-regulated TGF-,1-induced p38 MAPK phosphorylation. Our results demonstrated for the first time that nicotine inhibits myofibroblast differentiation in human gingival fibroblasts in vitro; supporting the hypothesis that delayed wound healing in smokers may be due to decreased wound contraction by myofibroblasts. © 2005 Wiley-Liss, Inc. [source] Localization of Transforming Growth Factors, TGF,1 and TGF,3, in Hypothalamic Magnocellular Neurones and the NeurohypophysisJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2004M. Fčvre-Montange Abstract The distribution of transforming growth factor beta (TGF,) in the rat and human hypothalamus and neurohypophysis was investigated by immunocytochemical techniques using rabbit polyclonal antisera against TGF,1 and TGF,3. Colocalization of TGF,1 or TGF,3 and arginine vasopressin (AVP) in the rat hypothalamus was studied by double immunolabelling in light microscopy, while their subcellular localization in the rat neurohypophysis was investigated by immunoelectron microscopy. TGF,1 and TGF,3 immunoreactivity was demonstrated in the cell bodies and processes of neurones in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). The TGF,-immunoreactive cells were more numerous in the SON compared to the PVN. TGF,/AVP double-labelled cells were seen in both nuclei, but some neurones in the SON were labelled for TGF,1 or TGF,3, although not for AVP. In the rat and human neurohypophysis, TGF,3 immunolabelling was more diffuse and stronger than TGF,1 immunolabelling. TGF,1 expression was seen in axonal vesicles and in neurosecretory granules of the axonal endings, while TGF,3 was observed in axonal fibres. Colocalization of TGF,3 or TGF,1 and AVP was observed in some neurosecretory granules, but many were either single-labelled for TGF, or AVP or unlabelled. Our results demonstrate, for the first time, the colocalization of TGF, and neurohypophysial hormones in magnocellular neurones. We suggest that TGF, secreted by the neurohypophysis regulates the proliferation and secretion of certain anterior pituitary cells. [source] Transforming growth factor-,1 induced alteration of skeletal morphogenesis in vivoJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2004Cristin M. Ferguson Abstract Transforming growth factor beta (TGF-,) is expressed in the growth plate and is an important regulator of chondrocyte maturation. Loss of function results in premature chondrocyte maturation both in vitro and in vivo. While TGF-, inhibits chondrocyte maturation in cell cultures, the effect of increased TGF-, has not been well characterized in an in vivo development model. Addition of Affi-gel agarose beads loaded with TGF-,1 (10 ng/,l) to developing stage 24,25 chick limb buds resulted in limb shortening and altered morphology. In situ hybridization studies showed down regulation of Indian hedgehog (ihh), bone morphogenetic protein 6 (bmp6), and collagen type X (colX) expression, markers of chondrocyte maturation, in TGF-,1 treated limbs. TGF-,1 also decreased chondrocyte proliferation in the developing anlage. The findings confirm a critical role for TGF-, during skeletal development. A more complete understanding of the role of TGF-, and its down-stream signals will lead to improved understanding and treatment of cartilage diseases. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Ethanol Alters Production and Secretion of Estrogen-Regulated Growth Factors That Control Prolactin-Secreting Tumors in the PituitaryALCOHOLISM, Issue 12 2007Dipak K. Sarkar Background:, Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol's mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine whether ethanol's lactotropic cell-proliferating action, like estradiol's, is associated with alteration in the production of 3 peptides that regulate cell growth: transforming growth factor beta 1 (TGF-,1), TGF-,3 and basic fibroblast growth factor (bFGF). Methods:, Using ovariectomized Fischer-344 female rats, we determined ethanol's and estradiol's actions on lactotropic cell proliferation and growth-regulatory peptide production and release in the pituitary gland during tumorigenesis. Results:, Ethanol increased basal and estradiol-enhanced mitosis of lactotropes in the pituitary glands of ovariectomized rats. The level of growth-inhibitory TGF-,1 was reduced in the pituitary following ethanol and/or estradiol treatment for 2 and 4 weeks. In contrast, ethanol and estradiol alone as well as together increased levels of growth-stimulatory TGF-,3 and bFGF in the pituitary at 2 and 4 weeks. In primary cultures of pituitary cells, both ethanol and estradiol reduced TGF-,1 release and increased TGF-,3 and bFGF release at 24 hours. Ethanol's effect on growth factor levels in the pituitary or growth factor release from the pituitary cells was less than that of estradiol. When ethanol and estradiol were applied together, their individual effects on these growth factors were amplified. Conclusions:, These results confirm estradiol's modulation of pituitary growth factor production and release, and provide evidence that ethanol, like estradiol, alters the production and secretion of growth-regulatory peptides controlling lactotropic cell proliferation. [source] Quantitative Analysis of Inflammatory and Immune Responses in Dogs with Gastritis and Their Relationship to Helicobacter spp.JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2005Infection The present study sought to quantitatively examine mucosal inflammatory and immune responses in dogs with gastritis and the relationship of these responses to infection with Helicobacter. Gastric biopsies from 30 dogs were evaluated for B- and T-lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. Mucosal atrophy, fibrosis, cellularity, and severity of gastritis were graded qualitatively. Messenger-RNA (mRNA) for actin, interleukin-1, (IL-1,), IL-4, IL-8, and IL-10, transforming growth factor beta (TGF-,), and interferon gamma (IFN-,) was quantified by polymerase chain reaction (PCR). The presence of Helicobacter spp. was determined by urease activity, histology, PCR, and enzyme-linked immunosorbent assay. mRNA for IL-1,, IL-8, IL-10, TGF-,, and IFN-, was detected in most dogs. IL-4 mRNA was detected in only 1 dog. Correlations were observed for IL-1, versus IL-8 and IL-10; IL-8 versus IL-10, IFN-,, and TGF-,; and IL-10 versus IFN-,. Mucosal pathology was related to cytokine mRNA expression (neutrophils to IL-8 and IFN-,, macrophages and lymphocytes to IFN-,, and fibrosis to IL-1,). Gastritis was categorized as lymphoplasmacytic in all dogs, and its histologic severity correlated with atrophy, infiltration with lymphocytes and macrophages, and expression of IL-10 and IFN-,. Of the dogs examined, 76.7% were infected with Helicobacter spp. Infection was associated with increased expression of TGF-, and fibrosis. Circulating anti- Helicobacter immunoglobulin G titers were higher in uninfected than infected dogs. We conclude that lymphoplasmacytic gastritis in dogs is characterized by concurrent activation of proinflammatory and immunomodulatory cytokines, with increased mRNA expression related to mucosal pathology. No significant associations between Helicobacter infection and proinflammatory cytokine expression, severity of gastritis, or differences in the pathogenicity of different Helicobacter spp. were found. [source] Expression of extracellular matrix genes in cultured hepatic oval cells: an origin of hepatic stellate cells through transforming growth factor beta?LIVER INTERNATIONAL, Issue 4 2009Ping Wang Abstract Background: Hepatic oval cells, progenitor cells in the liver, can differentiate into hepatocytes and bile duct cells both in vitro and in vivo. Although hepatic stellate cells are another important cell component in the liver, less attention has been focused on the relationship between hepatic oval cells and hepatic stellate cells. Methods: Hepatic oval cells were isolated from rats fed a choline-deficient diet supplemented with 0.1% ethionine for 6 weeks and characterized by electron microscopy, flow cytometry, reverse transcription polymerase chain reaction, Western blot and bi-direction differentiation. After treatment with transforming growth factor-,1 (TGF-,1), changes in cell viability, morphology, extracellular matrix (ECM) expression and immune phenotype were analysed in these cultured and adherent hepatic oval cells. Results: The primary cultured hepatic oval cells were positive for the oval cell-specific markers OV-6, BD-1/BD-2 and M2PK as well as the hepatocyte markers albumin and ,-foetoprotein. These hepatic oval cells differentiated bipotentially into hepatocytes or bile duct-like cells under appropriate conditions. It is noteworthy that these bipotential hepatic oval cells expressed ECM genes stably, including collagens, matrix metalloproteinases and tissue inhibitor of mellatoproteinase. Furthermore, except for growth inhibition and morphological changes in the hepatic oval cells after exposure to TGF-,1, there was an increased expression of ECM genes, the onset expression of snail and loss expression of E-cadherin. During this process, TGF-,1 treatment induced an upregulation of marker genes for hepatic stellate cells in hepatic oval cells, such as desmin and GFAP. Conclusion: Except for the expression of ECM, the cultured hepatic oval cells could induce an increased expression of hepatic stellate cell markers by TGF-,1 through an epithelial,mesenchymal transition process, which might indicate the contribution of hepatic oval cells to liver fibrosis. [source] Transcriptional profiling using a novel cDNA array identifies differential gene expression during porcine embryo elongationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2005So Hyun Lee Abstract A novel porcine cDNA array, containing 1,015 PCR products selected for embryonic expression, was used for transcriptional profiling of conceptuses at four stages of peri-implantation development. Total conceptus RNA from small spherical, large spherical, tubular, and filamentous stages was amplified, converted to cDNA, and hybridized to membranes. Initially, normalized signal intensities obtained using cDNA from total RNA or from amplified RNA were compared. Uniform distribution of P -values associated with t -tests conducted for each gene indicated no evidence that amplification introduced bias. Analysis of data obtained by using amplified targets and the novel array identified genes differentially expressed across stages. Such genes were identified by testing for significant stage effects in gene-specific mixed models. A total of nine genes were declared differentially expressed. Six of the nine genes had P -values less than 0.001, and a false discovery rate of approximately 17% was associated with this significance threshold. Two out of six genes were significant when using the Bonferroni method to control the probability of one or more false positives. The other three genes had P -values between 0.001 and 0.01 and exhibited differences greater than twofold between stages. All four genes selected for confirmation (steroidogenic acute regulatory protein, interleukin 1 beta, transforming growth factor beta 3, and thymosin beta 10) were shown to be differentially expressed by using quantitative real time RT-PCR. Our study shows that RNA amplification is useful for transcriptional profiling with limiting porcine embryonic RNA, and that this novel targeted array can detect differential gene expression during trophoblastic elongation. Finally, our results contribute to an increased understanding of the temporal patterns of expression of known genes controlling conceptus development, as well as identify novel genes also differentially regulated during implantation. Mol. Reprod. Dev. 71: 129,139, 2005. © 2005 Wiley-Liss, Inc. [source] Role of transforming growth factor beta in peritoneal fibrosisNEPHROLOGY, Issue 5 2002Reem H AL-JAYYOUSI SUMMARY: Technique survival of peritoneal dialysis is seriously limited by the development of peritoneal fibrosis. the mesothelial cell layer lining the peritoneum is important in the pathogenesis of peritoneal fibrosis. Mesothelial cells are able to produce transforming growth factor beta (TGF-,), and respond to stimulation by this cytokine. In this review, we will detail the evidence available so far for the role of the complex interaction between TGF-, and mesothelial cells in the development of peritoneal fibrosis. [source] Association of lower airway inflammation with physiologic findings in young children with cystic fibrosis,PEDIATRIC PULMONOLOGY, Issue 5 2009Stacey L. Peterson-Carmichael MD Abstract Background The relationship between lower airway markers of inflammation and infection with physiologic findings is poorly understood in young children with cystic fibrosis (CF). The goal of this study was to evaluate the association of bronchoalveolar lavage fluid (BALF) markers of infection and inflammation, including mediators linked to airway remodeling, to infant lung function values in young children with CF undergoing clinically indicated bronchoscopy. Methods Plethysmography and the raised volume rapid thoracoabdominal compression (RVRTC) technique were performed in 16 sedated infants and young children with CF prior to bronchoscopy. BALF was collected and analyzed for pathogen density, cell count, % neutrophils, transforming growth factor beta 1 (TGF-,1), matrix metalloproteinases (MMP), and interleukin-8 (IL-8). Results There was a significant direct correlation between functional residual capacity (FRC), the ratio of residual volume to total lung capacity (RV/TLC) and FRC/TLC with % neutrophils (P,<,0.05). Forced expiratory flows were inversely correlated to % neutrophils (P,<,0.01). Lung function parameters did not differentiate those with and without lower airway infection; however, pathogen density directly correlated with FRC and inversely correlated with flows (P,<,0.05). In a subset of the population, MMP-2 directly correlated with RV/TLC and inversely correlated with flows (P,<,0.05) and TGF-,1 directly correlated with FRC (P,<,0.05). Conclusions Results from this study suggest that lower airway inflammation as well as mediators linked to airway remodeling play an active role in pulmonary deterioration in CF infants and young children undergoing clinically indicated bronchoscopy. Pediatr Pulmonol. 2009; 44:503,511. © 2009 Wiley-Liss, Inc. [source] Bone microenvironment-related growth factors modulate differentially the anticancer actions of zoledronic acid and doxorubicin on PC-3 prostate cancer cellsTHE PROSTATE, Issue 2 2004Roxane Tenta Abstract OBJECTIVES We analyzed the actions of zoledronic acid (10,250 ,M) and doxorubicin (10,250 nM) on PC-3 prostate cancer cells using both continuous (48,96 hr) and pulsatile exposures (15 min/day for up to three consecutive days). RESULTS The proliferation of PC-3 cells was inhibited by either continuous or pulsatile exposures of zoledronic acid in a dose-dependent manner. In contrast, pulsatile exposures of doxorubicin failed to inhibit the growth of PC-3 cells. In addition, the inhibition of PC-3 cells by zoledronic acid was partially neutralized by exogenous administration of geranylgeranyl pyrophosphate (GGPP), however, not by farnesyl pyrophosphate (FPP). Furthermore, exogenous administration of transforming growth factor beta 1 (TGF-,1), interleukin 6 (IL-6), basic fibroblast growth factor (bFGF), and more potently, insulin-like growth factor 1 (IGF-1) inhibited the doxorubicin-induced apoptosis of PC-3 cells. Under identical experimental conditions, these growth factors failed to alter the cytotoxicity of PC-3 cells induced by zoledronic acid. CONCLUSIONS These data suggest that (i) repetitive and pulsatile (15 min/day) exposure to zoledronic acid inhibited the growth of PC-3 cells, (ii) this anticancer action of zoledronic acid was partially mediated by the attenuation of GGPP production, and (iii) bone microenvironment-related growth factors do not alter the anticancer actions of zoledronic acid on PC-3 cells. © 2004 Wileey-Liss, Inc. [source] Detection of Rare Nonsynonymous Variants in TGFB1 in Otosclerosis PatientsANNALS OF HUMAN GENETICS, Issue 2 2009M. Thys Summary Otosclerosis is one of the most common forms of hearing loss in the European population. We have identified a SNP in the TGFB1 (transforming growth factor beta 1) gene that is associated with susceptibility to otosclerosis. The protective allele of this variant, with isoleucine at position 263 of the protein, is more biologically active than the risk allele, which has a threonine in this position. Because recent studies have shown that not only common, but also rare variants can be involved in complex diseases, we performed DNA sequence analysis of the exons and intron-exon boundaries of TGFB1 in 755 otosclerosis patients and 877 control samples. We found 3 different nonsynonymous variants (E29, A29 and I241) in four otosclerosis patients, but no such changes were found in controls. In silico analysis shows that these variations could influence TGF-,1 function and activity. Taking into account that most rare missense alleles are thought to have a biological effect, the data suggest that multiple rare amino acid changing variants in TGF-,1 may contribute to susceptibility to otosclerosis. [source] Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in human mammary adenocarcinomas in vitro and in vivo,APMIS, Issue 6 2007SUSANNE MAUEL Transforming growth factor beta (TGF-ß) is able to inhibit proliferation of epithelial cells and is involved in the carcinogenesis of human mammary tumours. Three latent transforming growth factor-ß binding proteins (LTBP-1, -3 and -4) are involved in TGF-ß function. The aim of the study was to analyze the expression profiles of TGF-ß 1 and 2 and LTBP-4 in human mammary carcinoma cell lines as well as in human mammary tumours. Expression analysis was performed at the transcription and protein level under in vivo and in vitro conditions. LTBP-4 expression was quantitatively analysed in human carcinomas of the mammary gland and in healthy mammary tissues of the same patients. Downregulation of LTBP-4 in all investigated human mammary tumours compared to normal tissues could be demonstrated. Results also revealed that protein levels of TGF-ß 1 are downregulated and of TGF-ß 2 are upregulated in human mammary carcinoma cell lines compared to primary (normal) human mammary epithelial cells. LTBP-4 reduction in neoplasms leads to a possible decrease of TGF-ß 1 extracellular deposition with reduced TGF-ß 1 bioavailability. TGF-ß 2 was upregulated, which indicates a possible compensatory mechanism. This study demonstrated a possible functional role of LTBP-4 for TGF-ß bioavailability with respect to carcinogenesis of human mammary tumours in vivo and in vitro. [source] Overview of the TGFBI corneal dystrophiesACTA OPHTHALMOLOGICA, Issue 2009GK KLINTWORTH Several phenotypically distinct clinicopathologic entities involving the cornea are caused by mutations in the transforming growth factor beta induced (TGFBI) gene. These disorders include different types of granular corneal dystrophy (GCD): GCD type 1, GCD type 2 (Avellino corneal dystrophy), GCD type 3 (Reis-Bücklers corneal dystrophy) as well variants of lattice corneal dystrophy type 1 and Thiel-Benhke corneal dystrophy. Investigations of these inherited corneal diseases throughout the world strongly suggest that specific mutations in the TGFBI gene account for the specific phenotypes and that the corneal opacities that account for the clinical features of the different phenotypes result from the deposition of all or part of the mutated encoded protein. To date the mutated protein is only known to accumulate in the cornea eventhough the TGFBI is widely expressed throughout the body in experimental animals. This presentation will provide an overview of the TGFBI corneal dystrophies and offer a hypothesis to explain the different phenotypes caused by different mutations in TGFBI. [source] Role of ocular pigment epithelial cells in regional ocular immunityACTA OPHTHALMOLOGICA, Issue 2008S SUGITA Purpose To whether soluble factors by retinal pigment epithelial cells (RPE) promote the generation of T regulatory cells in vitro. Methods Primary cultured RPE cells were established from normal C57BL/6 mice. T cells were co-cultured with RPE, x-irradiated, and used as regulators (RPE Treg cells). Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. T-cell activation was assessed for proliferation by [3H],thymidine incorporation. Expression of cytotoxic T lymphocyte antigen-2, (CTLA-2,) and cathepsin L on RPE and T cells was evaluated with oligonucleotide microarray, RT-PCR, immune staining, western blots and flow cytometry. Recombinant mouse CTLA-2, and anti-mouse CTLA-2, abs were used for the assay. For induction of experimental autoimmune uveitis (EAU), mice were immunized with interphotoreceptor retinoid-binding protein peptide emulsified in complete Freund's adjuvant. Results RPE converted CD4+ T cells into Treg cells by producing and secreting CTLA-2,, a cathepsin L inhibitor. CTLA-2, secreted by RPE cells selectively inhibited cathepsin L in the T cells and the cathepsin L-lacking T cells exhibited Treg phenotype, i.e. expression of Foxp3 and production of transforming growth factor beta (TGF,). CTLA-2, enhanced their production of active forms of TGF,. In addition, CD4+ T cells from EAU-induced cathepsin L knockout (KO) donors contained high population of Foxp3+ T cells and EAU in cathepsin L KO mice was significantly less than those in wild type mice. Furthermore, treatment with recombinant CTLA-2, significantly suppressed EAU. Conclusion These results indicate that immunosuppressive factors derived from RPE participate in the establishment of immune regulation in the posterior segment of the eye. [source] Transforming growth factor beta 1 plays an important role in inducing CD4+CD25+forhead box P3+ regulatory T cells by mast cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2010W. Zhang Summary The role of mast cells (MCs) in the generation of adaptive immune responses especially in the transplant immune responses is far from being resolved. It is reported that mast cells are essential intermediaries in regulatory T cell (Treg) transplant tolerance, but the mechanism has not been clarified. To investigate whether bone marrow-derived mast cells (BMMCs) can induce Tregs by expressing transforming growth factor beta 1 (TGF-,1) in vitro, bone marrow cells obtained from C57BL/6 (H-2b) mice were cultured with interleukin (IL)-3 (10 ng/ml) and stem cell factor (SCF) (10 ng/ml) for 4 weeks. The purity of BMMCs was measured by flow cytometry. The BMMCs were then co-cultured with C57BL/6 T cells at ratios of 1:2, 1:1 and 2:1. Anti-CD3, anti-CD28 and IL-2 were administered into the co-culture system with (experiment groups) or without (control groups) TGF-,1 neutralizing antibody. The percentages of CD4+CD25+forkhead box P3 (FoxP3)+ Tregs in the co-cultured system were analysed by flow cytometry on day 5. The Treg percentages were significantly higher in all the experiment groups compared to the control groups. These changes were deduced by applying TGF-,1 neutralizing antibody into the co-culture system. Our results indicated that the CD4+ T cells can be induced into CD4+CD25+FoxP3+ T cells by BMMCs via TGF-,1. [source] The use of porous calcium phosphate scaffolds with transforming growth factor beta 1 as an onlay bone graft substituteCLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2004An experimental study in rats Abstract Objectives: Autogeneous bone grafting is regarded to be the golden standard for onlay grafts, but it requires a harvesting procedure and the remodeling pattern over time is unpredictable. New materials are constantly being sought to overcome these problems. An in vivo experiment was carried out to evaluate whether (1) porous calcium phosphate cement is a suitable biomaterial for onlay bone grafting, and (2) the addition of transforming growth factor beta 1 (TGF-,1) accelerates de novo bone formation inside the cement porosity. Material and methods: A carrier of porous calcium phosphate cement (Calcibon®) was designed and 16 rats received one preshaped implant each. In 8 out of 16 implants 0.75 ,g TGF-,1 was applied. The animals were killed after 4 weeks and the characteristics of tissue ingrowth into the onlay graft were evaluated. Results: Histologic and quantitative histomorphometrical measurements demonstrated osteoid-like tissue formation in both experimental groups. The addition of TGF-,1 did not induce significantly more osteoid-like tissue formation. On the other hand, in TGF-,-loaded implants, a higher number of pores contained an inflammatory infiltrate. Conclusion: This study indicated that porous calcium phosphate cement is a promising material for clinical situations where bone formation has to be supported. Résumé La greffe osseuse autogčne est considérée comme la meilleure technique actuelle pour les greffons onlay mais elle requiert un processus de prélevement et le remodelage qui s'en suit est imprévisible. De nouveaux matériaux sont donc constamment recherchés. Cette étude in vitro a essayé d'évaluer si 1) le cément phosphate calcium poreux était un biomatériel favorable pour le greffage osseux onlay, 2) si l'addition de TGF-,1 accélérait la néoformation osseuse ŕ l'intérieur de la porosité du cément. Un porteur de cément phosphate calcium poreux (Calcibon®) a été fabriqué et seize rats ont reçu chacun un implant prédécoupé. Au niveau de huit des seize implants 0,75 ,g de TGF ,1 a été appliqué. Les animaux ont été euthanasiés aprčs quatre semaines et les caractéristiques de la croissance interne tissulaire dans le greffon onlay ont étéévaluées. Les mesures histologiques et histomorphométriques quantitatives ont démontré une formation tissulaire semblable ŕ l'ostéogénie dans les deux groupes expérimentaux. L'addition de TGF-ß1 n'induisait pas plus de formation tissulaire ressemblant ŕ celle d'ostéogénie. D'un autre côté, dans les implants chargés de TGF-,1, un nombre plus important de pores contenaient un infiltrat inflammatoire. Cette étude indique que le cément phosphate calcium poreux est un matériau prometteur pour les situations cliniques dans lesquelles la formation osseuse doit ętre améliorée. Zusammenfassung Ziel: Die Transplantation von autologem Knochen wird heute als Goldstandard für die Onlay-Transplantate betrachtet. Es braucht dazu aber einen zusätzlichen Eingriff für die Entnahme und eine Prognose bezüglich der anschliessenden Remodellationsvorgänge sind kaum möglich. Man sucht ständig nach neuen Produkten, um diese Probleme zu überwinden. Man führte eine in vivo Studie durch und untersucht, ob (1) ein poröser Kalziumphosphatzement ein brauchbares Biomaterial für ein Onlay-Transplantat ist, und (2) der Zusatz von TGF-,1 die Neubildung von Knochen in den Porositäten des Zementes positiv beeinflusst. Material und Methode: Man entwickelte einen Trägerzement aus porösem Kalziumphosphat (Calcibon®) und 16 Ratten erhielten je ein vorgeformtes Implantat eingesetzt. Bei 8 der 16 Implantate fügte man zusätzlich 0.75 ,g TGF-,1 dazu. Vier Wochen später opferte man die Tiere und konnte nun die Charakteristika des in die Implantate einwachsenden Gewebes untersuchen. Resultate: Die histologischen und quantitativen histomorphometrischen Messungen zeigten in beiden experimentellen Gruppen osteoidähnliche Gewebsbildungen. Der Zusatz von TGF-,1 bewirkte keine signifikante Zunahme dieser osteoidähnlichen Gewebsbildungen. Die mit TGF-,1 durchsetzten Implantate enthielten aber mehr mit entzündlichem Infiltrat angefüllte Poren. Zusammenfassung: Diese Arbeit zeigte uns, dass ein poröser Kalziumphosphatzement bei klinischen Situationen, wo die Knochenbildung unterstützt werden muss, ein erfolgsversprechendes Material ist. Resumen Objetivos: El injerto de hueso autógeno está considerado como el estándar de oro para injertos superpuestos, pero requiere un procedimiento de recolección y el patrón de remodelado a lo largo del tiempo es impredecible. Constantemente se están buscando materiales nuevos para superar estos problemas. Se llevó a cabo un experimento in vivo para evaluar si (1) el cemento de fosfato cálcico poroso es un biomaterial apropiado para injerto óseo superpuesto, y (2) la adición de TGF-,1 acelera la formación de hueso de novo dentro de la porosidad del cemento. Material y Métodos: Se diseńó un portador de cemento de fosfato cálcico (Calcibon®) y 16 ratas recibieron un implante preformado cada una. En 8 de 16 implantes se aplicaron 0.75 ,g de TGF-,1. Los animales se sacrificaron tras 4 semanas y se evaluaron las características del tejido crecido hacia adentro del injerto superpuesto. Resultados: Las mediciones histológicas e histomorfométricas cuantitativas demostraron formación de tejido tipo osteoide en ambos grupos experimentales. La adición de TGF-,1 no indujo significativamente más formación de tejido tipo osteoide. Por otro lado, en los implantes cargados con TGF-,1, un mayor número de de poros contenían infiltrado inflamatorio. Conclusión: Este estudio indica que el cemento de fosfato cálcico poroso es un material prometedor para situaciones clínicas donde la formación de hueso ha de ser favorecida. [source] Comparison of three different preparations of platelet concentrates for growth factor enrichmentCLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2002Thorsten R. Appel Abstract: The aim of the present study was to compare three different systems for preparing platelet concentrates: two commercially available bed-side techniques (Curasan system and PCCS) and a procedure used routinely in transfusion medicine. Platelet concentrates were prepared from venous blood of 12 healthy male volunteers using the three different systems. Platelet and leucocyte counts were performed and platelet derived growth factor and transforming growth factor beta were assayed by enzyme linked immunoassay. Handling was also considered. The three systems were able to collect 19.0 ± 16.6% (laboratory system), 41.9 ± 9.7% (Curasan system) and 49.6 ± 21.0% (PCCS) of the absolute number of platelets which were originally in the venous blood volume within the platelet concentrate. Due to the amount of plasma which is left in the platelet concentrate portion, the platelet concentration could be increased between 1.4 ± 1.3 times (laboratory system), 5.0 ± 2.3 times (PCCS) and 11.7 ± 2.4 times (Curasan system) compared to the venous blood. The amount of growth factors correlated with the number of platelets within the platelet concentrates. The two systems for intraoperative use are similar in their effects on the platelets. The absolute gain of platelets seems to be the highest with the PCCS; the highest concentration of platelets per µL is gained with the Curasan system. The laboratory system may offer an alternative if an intraoperative system is not available. 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