gebhart/patrepeval huggingface dataset:
Integrin-mediated Migration of Murine B82L Fibroblasts Is Dependent on the Expression of an Intact Epidermal Growth Factor Receptor (1999)

To evaluate the mechanisms by which epidermal growth factor (EGF) regulates actin-based cellular processes such as cell migration, we first examined the effects of EGF on cell adhesion, which is essential for cell migration. In mouse B82L fibroblasts transfected with the full-length EGF receptor, EGF promotes cell rounding and attenuates cell spreading on fibronectin, laminin, and vitronectin, and thus appears to reduce the strength of cell adhesion. Moreover, EGF synergizes with multiple extracellular matrix (ECM) components in the promotion of integrin-mediated cell migration of several different cell types, including fibroblasts and various carcinoma and osteosarcoma cell lines. Interestingly, co-presentation (co-positioning) of EGF with laminin or fibronectin is essential for EGF-stimulated migration. When EGF is mixed with the cells instead of the ECM components, it has little effect on cell migration. These results suggest that co-presentation of EGF with ECM components can enhance the polarization events required for directional cell movement. To identify the EGF receptor elements critical for the EGF stimulation of cell migration, B82L fibroblasts were transfected with either mutated or wild-type EGF receptors. Surprisingly, we found that B82L-Parental cells that lack the EGF receptor are not able to migrate to fibronectin, even though they can adhere to fibronectin. However, the introduction of wild-type EGF receptors into these fibroblasts enables them to migrate toward fibronectin even in the absence of EGF. The requirement of the EGF receptor for cell migration does not appear to result from the secretion of EGF or TGF-alpha by the cells transfected with the EGF receptor. Furthermore, cells expressing EGF receptors that are kinase-inactive, or C-terminally truncated, exhibit little migration toward fibronectin, indicating that an intact EGF receptor kinase is required for fibronectin-induced cell migration. In addition, neutralizing anti-EGF receptor antibodies attenuate cell migration in the presence of EGF, and inhibit migration to fibronectin or laminin alone. These results further suggest that the EGF receptor is downstream of integrin activation in the signal transduction pathways leading to fibroblast migration.
Protein Ectodomain Shedding (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein Ectodomain SheddingJoaquín Arribas and Aldo BorrotoView Author Information Laboratori de Recerca Oncològica, Servei d'Oncologia Mèdica, Hospital Universitari Vall d'Hebron, Psg. Vall d'Hebron 119-129, Barcelona 08035, Spain Cite this: Chem. Rev. 2002, 102, 12, 4627–4638Publication Date (Web):October 19, 2002Publication History Received15 February 2002Published online19 October 2002Published inissue 1 December 2002https://pubs.acs.org/doi/10.1021/cr010202thttps://doi.org/10.1021/cr010202tresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views1667Altmetric-Citations204LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cells,Inhibitors,Molecules,Peptides and proteins,Receptors Get e-Alerts
Penetration Kinetics of Liposomal Hydrocortisone in Human Skin (1987)

The applicability of liposomal hydrocortisone (HC) as a selective drug delivery system for cutaneous administration of glucocorticoids has been studied. With the liposomal form, a considerably better concentration-time profile was obtained in the individual layers of human skin than with the corresponding HC ointment. The pronounced carrier ability of liposomes for HC holds promise for an increase in its therapeutic efficacy, thus reducing unwanted side effects of the topical glucocorticoid therapy.
Induction of Keratinocyte Migration via Transactivation of the Epidermal Growth Factor Receptor by the Antimicrobial Peptide LL-37 (2005)

The closure of skin wounds is essential for resistance against microbial pathogens, and keratinocyte migration is an important step in skin wound healing. Cathelicidin hCAP18/LL-37 is an innate antimicrobial peptide that is expressed in the skin and acts to eliminate microbial pathogens. Because hCAP18/LL-37 is up-regulated at skin wound sites, we hypothesized that LL-37 induces keratinocyte migration. In this study, we found that 1 microg/ml LL-37 induced the maximum level of keratinocyte migration in the Boyden chamber assay. In addition, LL-37 phosphorylated the epidermal growth factor receptor (EGFR) after 10 min, which suggests that LL-37-induced keratinocyte migration occurs via EGFR transactivation. To test this assumption, we used inhibitors that block the sequential steps of EGFR transactivation, such as OSU8-1, CRM197, anti-EGFR no. 225 Ab, and AG1478. All of these inhibitors completely blocked LL-37-induced keratinocyte migration, which indicates that migration occurs via HB-EGF-mediated EGFR transactivation. Furthermore, CRM197, anti-EGFR no. 225, and AG1478 blocked the LL-37-induced phosphorylation of STAT3, and transfection with a dominant-negative mutant of STAT3 abolished LL-37-induced keratinocyte migration, indicating the involvement of the STAT3 pathway downstream of EGFR transactivation. Finally, we tested whether the suppressor of cytokine signaling (SOCS)/cytokine-inducible Src homology 2-containing protein (CIS) family of negative regulators of STAT3 regulates LL-37-induced keratinocyte migration. Transfection with SOCS1/Jak2 binding protein or SOCS3/CIS3 almost completely abolished LL-37-induced keratinocyte migration. In conclusion, LL-37 induces keratinocyte migration via heparin-binding-EGF-mediated transactivation of EGFR, and SOCS1/Jak 2 binding and SOCS3/CIS3 negatively regulate this migration. The results of this study suggest that LL-37 closes skin wounds by the induction of keratinocyte migration.
Abberant α-Synuclein Confers Toxicity to Neurons in Part through Inhibition of Chaperone-Mediated Autophagy (2009)

Expression of mutant A53T, and, in some cases, WT ASYN in neuronal cells leads to CMA dysfunction, and this in turn leads to compensatory induction of macroautophagy. Inhibition of these lysosomal effects mitigates ASYN toxicity. Therefore, CMA dysfunction mediates aberrant ASYN toxicity, and may be a target for therapeutic intervention in PD and related disorders. Furthermore, macroautophagy induction in the context of ASYN over-expression, in contrast to other settings, appears to be a detrimental response, leading to neuronal death.
A 2.4 GHz polarization-diversity planar printed dipole antenna for WLAN and wireless communication applications (2002)

This article presents the design simulation, fabrication and measured performance of a 2.4 GHz polarization-diversity printed dipole antenna for wireless communication applications. Two orthogonal printed dipole antennas, each with a microstrip via-hole balun for vertical and horizontal polarization, an combined and fabricated on a PCB substrate. PIN diodes are used as switches to select the desired antenna polarization. The 3D finite-element-method (FEM) electromagnetic EM simulator, HFSS, is used in the design simulation of this planar antenna structure. Numerical and measured results of the antenna radiation characteristics, including input SWR, radiation pattern coverage and polarization-diversity, are presented and compared.
Dabigatran Etexilate, An Oral Direct Thrombin Inhibitor, Represses Fibrotic Changes In A Murine Model Of Pulmonary Fibrosis (2010)

RATIONALE: Activation of the coagulation cascade and generation of thrombin has been extensively documented in pulmonary fibrosis, both in acute and chronic lung injury, and in animal models of lung injury and fibrosis. The oral direct thrombin inhibitor (DTI), dabigatran etexilate, modulates the coagulation cascade and inhibits thrombin-induced profibrotic signaling in lung fibroblasts. This study tested whether thrombin inhibition by dabigatran etexilate attenuates bleomycin-induced pulmonary fibrosis in a murine model of lung injury.
Mutations in the Murine Fitness 1 Gene Result in Defective Hematopoiesis (1997)

Identification and characterization of mutations that disrupt normal hematopoiesis are essential for understanding the genetic pathways that control the development and regulation of the mammalian hematopoietic system. Previously, the fitness 1 gene was identified by five, independent mutations in N-ethyl-N-nitrosourea (ENU) saturation mutagenesis experiments within the albino (c) region of mouse chromosome 7 (MMU7). We report here that fit1 mutants are anemic, display numerous peripheral blood defects, and are deficient in early hematopoietic progenitor cell populations. The number of both erythroid and myeloid progenitors, as well as B cells, are reduced. These results implicate fit1 involvement in normal hematopoiesis and suggest that further characterization of the fit1 gene, and the five presumed point mutations of the gene, will lead to an improved understanding of normal hematopoiesis in the mouse.
Gas1 is induced by VE-cadherin and vascular endothelial growth factor and inhibits endothelial cell apoptosis (2003)

The junctional membrane protein vascular endothelial (VE)-cadherin mediates contact inhibition of growth and inhibits apoptosis of endothelial cells. In this article we show that VE-cadherin induces expression of growth arrest-specific 1 (Gas1), an integral membrane protein up-regulated in nonproliferating cells. By comparing syngenic endothelial cell lines, we found that Gas1 mRNA was increased by 3-fold in VE-cadherin-positive cells in comparison to VE-cadherin-null cells. Ectopic expression of Gas1 in endothelial or 293 cells strongly reduced apoptosis without affecting cell growth. Addition of vascular endothelial growth factor (VEGF) also up-regulated Gas1 and this effect was augmented more so in confluent nonproliferating cells than in sparse cultures. VE-cadherin-blocking antibody partially inhibited VEGF-induced Gas1, suggesting that VE-cadherin clustering is required for an optimal response to this stimulus. Inhibition of phosphoinositole-3-OH kinase (PI3-kinase) pathway by Wortmannin prevented Gas1 synthesis and the antiapoptotic effect of VEGF, but, in cells ectopically expressing Gas1, Wortmannin was ineffective. Furthermore, inhibition of Gas1 expression by short interfering RNA (siRNA) both in vitro and in allantois organ cultures made endothelial cells refractory to the antiapoptotic effect of VEGF. Overall these data indicate that Gas1 induction by VE-cadherin and VEGF in endothelial cells requires activation of PI3-kinase. Gas1 expression positively correlates with inhibition of endothelial cell apoptosis and may contribute to the integrity of resting endothelium.
Zinc Sulfate Supplementation for Treatment of Recurring Oral Ulcers (1977)

Use of zinc sulfate in promotion of wound healing and in maintenance of epithelial integrity suggested its possible use in the treatment or prevention of recurrent oral ulcers. In a series of 32 patients with recurrent aphthous ulcers (RAU), serum zinc levels were observed. Seventeen patients, eight with initial serum zinc levels above 110microng/dl and nine with serum zinc levels below 110microng/dl, were provided zinc sulfate supplementation up to a total of 660 mg/day. All patients with initial serum zinc levels less than or equal to 110 microng/dl showed improvement; three of the eight patients with initial serum zinc levels above 110 microng/dl improved, five did not. Improvement consisted of 50% to 100% reduction in frequency of episodes. This suggests a combination of causes of RAU, one of which may be a local or general deficiency of zinc or a defect in metabolism, perhaps at the cellular level, related to zinc.
Silencing in Arabidopsis T-DNA Transformants: The Predominant Role of a Gene-Specific RNA Sensing Mechanism versus Position Effects (2004)

Pronounced variability of transgene expression and transgene silencing are commonly observed among independent plant lines transformed with the same construct. Single-copy T-DNA lines harboring reporter genes of various kind and number under the control of a strong promoter were established in Arabidopsis thaliana for a comprehensive analysis of transgene expression. Characterization of 132 independent transgenic lines revealed no case of silencing as a result of site of T-DNA integration. Below a certain number of identical transgenes in the genome, gene copy number and expression were positively correlated. Expression was high, stable over all generations analyzed, and of a comparable level among independent lines harboring the same copy number of a particular transgene. Conversely, RNA silencing was triggered if the transcript level of a transgene surpassed a gene-specific threshold. Transcript level-mediated silencing effectively accounts for the pronounced transgene expression variability seen among transformants. It is proposed that the RNA sensing mechanism described is a genome surveillance system that eliminates RNA corresponding to excessively transcribed genes, including transgenes, and so plays an important role in genome defense.
Age-related human mtDNA deletions: a heterogeneous set of deletions arising at a single pair of directly repeated sequences. (1994)

Deletions in mtDNA accumulate during the human aging process, arising from either intramolecular illegitimate recombination or strand slippage during replication, which results in subgenomic mtDNA molecules. We identify here two classes of mtDNA deletions--class A deletions, which are homogeneous at the breakpoints, with all subgenomic molecules therefore being identical in size, and class B deletions, which arise from a less stringent process that gives rise to heterogeneity at the breakpoints, with the subgenomic molecules being of slightly different sizes. A novel approach is described that offers a global overview of the populations of different deletions in individual tissues. It is based on PCR cycle-sequencing reactions that are carried out directly on mtDNA segments, amplified by PCR from total cellular DNA. The results show a clear size homogeneity of the subgenomic mtDNA molecules representative of class A, which carry a commonly detected 4,977-bp deletion occurring at a pair of 13-bp directly repeated sequences. In this case, precisely one copy of the repeat is retained in the subgenomic molecules. We then describe a class B situation comprising a family of at least nine closely related 8.04-kb deletions involving the same pair of 5-bp direct repeats. In this situation, the breakpoints differ at the base-pair level (8,037-8,048-bp deletions); the subgenomic molecules retain > 1 copy, 1 copy, or < 1 copy of the 5-bp repeat. In different tissues from either the same individual or among different individuals, there is a widely variable occurrence of particular deletions in the subgenomic mtDNA population within this class B set. Class B deletions offer a new approach for studying the accumulation of mtDNA deletions, thereby providing insight into the independent somatic origin of mutated mtDNA molecules, both in aging and in mitochondrial diseases. We also report a convenient method for ascertaining whether a given PCR product results from the amplification of a subgenomic mtDNA template, on the basis of the selective degradation of full-length mtDNA molecules prior to PCR.
Percutaneous Radiofrequency Neurotomy in the Treatment of Cervical Zygapophysial Joint Pain (1995)

Percutaneous radiofrequency neurotomy has been used in the treatment of pain from the cervical zygapophysial joints, but the results have been modest and not compelling. Several factors might account for its apparent poor success rate, including inadequate patient selection, inaccurate surgical anatomy, and technical errors. In an effort to overcome these confounders, we used comparative local anesthetic blocks to preoperatively, definitively diagnose cervical zygapophysial joint pain and developed an amended operative technique based on formal anatomical studies. An audit was conducted of our experience with 19 patients to determine whether there was sufficient merit in the amended procedure to justify a randomized, double-blind, controlled trial. The duration of complete pain relief was the principal outcome measure. Side effects and complications were also monitored. Of the 10 patients who underwent third occipital neurotomy for the treatment of C2-C3 zygapophysial joint pain, only 4 obtained long-lasting relief. The other six patients reported an early return of their pain and constituted technical failures; the third occipital nerve was inadequately coagulated and recovered in the immediate postoperative period. Of the 10 patients who underwent lower cervical medial branch neurotomy, 7 obtained complete pain relief for clinically useful periods and were able to resume their activities of daily living and employment. After procedures at all levels, a brief period of postoperative pain was experienced by the patients and ataxia was a side effect of third occipital neurotomy. There were no cases of postoperative infection or anesthesia dolorosa. Given the high technical failure rate of third occipital neurotomy, we recommend that this procedure be abandoned until the technical problems can be overcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Refractory depression in children and adolescents (1997)

Refractory or treatments resistant depression in child and adolescent populations is a difficult construct to operationalize currently. To date, only one of the small number of completed double-blind placebo-controlled treatment investigations have not demonstrated a significant effect of antidepressants in comparison to placebo. However, it has been established that child and adolescent MDD is a serious disorder that appears to have clinical continuity with adult affective disorders and is generally of long duration with high rates of recurrence and eventual progression to mania, substance abuse, or other serious psychopathology. In addition, families of children with affective disorders evidence substantial genetic loading with high rates of affective disorders contributing both genetic vulnerability and potential environmental risk as well. There have been no empirically identified treatments that alter the long-term course of the illness. Thus treatment resistance is a significant issue for this population. This review will focus on controlled treatment trials and will examine the potential relevance of psychosocial impairment, genetic-familial risk, and neuromorphometric brain differences to treatment resistance in children and adolescents with major depression.
Hemorrhage and resuscitation alter the expression of ICAM-1 and P-selectin in mice. (1995)

Acute inflammatory lung injury is a common clinical occurrence following blood loss and trauma, and is characterized by massive neutrophil infiltration into the lung. In order to better examine cell trafficking that may contribute to lung injury in this setting, we investigated in vivo mRNA levels and immunohistochemically determined expression of the adhesion molecules P-selectin and the intercellular adhesion molecule (ICAM)-1 in murine lungs over the 3-day period following hemorrhage and resuscitation. Significant increases in P-selectin mRNA levels were present in lungs obtained 3 days after hemorrhage. ICAM-1 mRNA levels were significantly increased 6 and 72 hr after hemorrhage. Immunohistochemical staining for P-selectin was enhanced on pulmonary vascular endothelium in all visible vessels at 6, 24, and 72 hr after hemorrhage. ICAM-1 immunoreactivity was significantly increased on the alveolar epithelium at 6 and 72 hr post-hemorrhage. These results suggest that increased expression of adhesion molecules in the lung at early post-hemorrhage timepoints may contribute to neutrophil infiltration into the lungs and the frequent development of acute lung injury following blood loss and trauma.
Fibroblast growth factor receptor‐bearing neurons in the CNS: Identification by receptor‐mediated retrograde transport (1991)

Neurons that internalize and retrogradely accumulate acidic (aFGF) or basic (bFGF) fibroblast growth factor were identified by autoradiography after injections of 125 I-aFGF or 125I-bFGF into the adult rat central nervous system (CNS). Neuronal cell bodies within the lateral hypothalamus, pedunculpontine tegmental nucleus, laterodorsal tegmental nucleus, and the paracentral dorsal tegmental nucleus accumulated 125I-aFGF. Neurons in the hippocampus, subiculum, the centrolateral, paracentral, central medial, and parafascicular thalamic nuclei, the supramammillary nucleus, and substantia nigra compacta accumulated 125I-bFGF. The pattern of neuronal labeling with 125I-bFGF in adult rats was similar to that observed in newborn guinea pigs. No 125I-FGF labeling was observed in nerve growth factor (NGF) receptor-bearing neurons, including the basal forebrain cholinergic neurons. Time-course studies indicate that 125I-FGF was internalized at the terminals and retrogradely transported to the neuronal cell bodies. Neurons were retrogradely labeled either by injection of 125I-bFGF into the lateral ventricle or by injection into innervated target tissues. Co-injection of a 250-fold excess of unlabeled FGF with the 125I-FGF abolished the neuronal labeling. Co-injection of wheat germ agglutinin (WGA), which nonspecifically blocks binding of 125I-bFGF to its receptor, also prevented neuronal labeling. These studies demonstrate that specific neuronal populations within the CNS express functional receptors for aFGF and/or bFGF; in these neurons, aFGF and/or bFGF bind specifically to these receptors, are internalized and retrogradely transported to the neuronal soma in a manner analogous to NGF. The data indicate that FGF can provide trophic support to CNS neurons by both direct and indirect mechanisms.