tbuckley/cabot-search huggingface dataset:
Incidence of Metastatic Nonseminomatous Germ Cell Tumor Outside the Boundaries of a Modified Postchemotherapy Retroperitoneal Lymph Node Dissection
Authors: Brett S. Carver, Bobby Shayegan, Scott Eggener, Jason Stasi, Robert J. Motzer, George J. Bosl, Joel Sheinfeld
Journal: Journal of Clinical Oncology (2007)

Introduction Modified template retroperitoneal lymph node dissections (RPLND) have become increasing applied in the postchemotherapy (PC) setting. We evaluated our experience with PC-RPLND to determine the incidence of disease extending outside the boundaries of a modified PC-RPLND. Patients and Methods From 1989 through 2003, a total of 532 men underwent PC-RPLND for metastatic nonseminomatous germ cell tumor (NSGCT). Of these, 269 (51%) had either viable germ cell tumor (GCT) or teratoma present in the RPLND specimen. After Institutional Review Board approval, clinical and pathologic data were obtained from our prospective surgical database. The incidence of retroperitoneal disease outside the boundaries of five modified templates was reported for the presence of viable GCT or teratoma. Results Of the 269 patients with viable GCT or teratoma, 20 to 86 (7% to 32%) patients had evidence of extratemplate retroperitoneal disease, depending on the boundaries of the modified template. There was no difference in the histologic distribution for patients with disease confined to or outside of the modified templates. Despite the absence of preoperative radiographic evidence of disease outside the boundaries of the Testicular Tumor Study Group template, the incidence of extratemplate metastasis for men with residual retroperitoneal masses less than 1, 1 to 2, 2 to 5, and more than 5 cm was two of 24 (8%), seven of 38 (18%), 27 of 92 (29%), and 14 of 55 (25%), respectively. Conclusion Our data suggest a bilateral RPLND is a prudent approach for the management of men with metastatic NSGCT after chemotherapy, given that at least 7% to 32% of men will have teratoma or viable GCT outside the boundaries of a modified template.
Epicardium-Derived Cardiac Mesenchymal Stem Cells: Expanding the Outer Limit of Heart Repair
Authors: Manvendra K. Singh, Jonathan A. Epstein
Journal: Circulation Research (2012)

T he epicardium is derived from the proepicardial organ, a source of multipotent progenitor cells.Epicardium contribution to the developing coronary vasculature and to cardiac interstitial cells has been established.Studies over the past several years have suggested that epicardium-derived cells can adopt cardiomyocyte and vascular smooth muscle fates and can contribute to cardiac repair when activated by injury. 1,2Recently, Chong et al 3 have provided a detailed characterization of a population of epicardium-derived multipotent cardiac progenitor cells (cCFU-Fs).These cells, which do not arise from the bone marrow, neural crest, or myocardium, resemble mesenchymal stem cells (MSCs) and may participate in cardiac development, homeostasis, and repair. 3uring early cardiac development, cells derived from the proepicardial organ (a cluster of cells located dorsal and adjacent to the looped heart tube) migrate over the myocardium to form the epicardium.Subsequently, epicardiumderived progenitor cells undergo epithelial-to-mesenchymal transition, invade the underlying myocardium, and differentiate into various cardiac lineages. 4,5Signals and cellular contributions from the epicardium have been shown to be indispensable for the establishment of normal coronary vasculature and myocardial architecture. 6Cardiac interstitial cells arise from epicardium, and recent studies have suggested that reactivation of the epicardium after injury could contribute to scarring or myocardial repair after injury. 1,2,6,7n this context, the recent report from Chong et al 3 is particularly relevant, because they used rigorous gene expression, culture, and fate lineage analysis to characterize a population of multipotent MSC-like cells resident in the heart that they called cardiac colony-forming units-fibroblast (cCFU-Fs).These cells derive from the proepicardium, not
Cyclosporine inhibits the renal response to L-arginine in human kidney transplant recipients.
Authors: R S Gaston, S D Schlessinger, P W Sanders, C V Barker, J J Curtis, D G Warnock
Journal: Journal of the American Society of Nephrology (1995)

To evaluate the association of cyclosporine (CsA)-related nephrotoxicity with nitric oxide (NO) and endothelin, the effects of L-arginine (LA) and branched-chain amino acid (BCAA) infusions on renal hemodynamics in 5 normal volunteers and 12 renal transplant recipients were assessed. In normal humans, LA, but not BCAA, reduced mean arterial pressure and renal vascular resistance while increasing RPF and urinary nitrate (NO3-) excretion. Group 1 included six transplant recipients not on CsA; Group 2 subjects (N = 6) were receiving CsA. In both groups, mean arterial pressure declined during the infusion of LA (116 +/- 4 to 109 +/- 4 mm Hg; P < 0.001) but not BCAA (116 +/- 3 to 115 +/- 3; P = not significant). In Group 1, LA increased RPF 33 +/- 13% (329 +/- 48 to 436 +/- 77 mL/min per 1.73 m2; P = 0.01) and GFR 37 +/- 16% (95 +/- 7 to 130 +/- 18 mL/min per 1.73 m2; P = 0.01); renal vascular resistance declined 27 +/- 6%. In Group 2, LA did not affect renal hemodynamics. No changes occurred with BCAA in either group. LA increased urinary NO3-excretion by 27 +/- 17% in Group 1 (P < 0.05), but only by 16 +/- 13% in Group 2 (P = not significant). Urinary endothelin excretion was higher in Group 2 subjects (10.1 +/- 1.3 versus 5.3 +/- 0.8 pg/mL of GFR, P < 0.01). LA-induced renal vasodilation is associated with the increased urinary excretion of NO3-.(ABSTRACT TRUNCATED AT 250 WORDS)
Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa
Authors: M Pera, J Heppell, R Poulsom, F V Teixeira, J Williams
Journal: Gut (2001)

Chronic ulcerative conditions in the gastrointestinal tract result in the appearance of the ulcer associated cell lineage (UACL). The glands of this new cell lineage secrete epidermal growth factor, transforming growth factor alpha, and the trefoil factor family (TFF) peptides, which are known to participate in repair processes. Pouchitis is the most frequent complication of ileal pouch-anal anastomosis.Our aim was to determine whether the mucosal ulceration present in pouchitis can induce the development of UACL glands.Biopsies from ileal pouches with pouchitis (n=10), healthy pouches (n=5), and normal terminal ileum (n=5) were studied. Expression of TFF mRNA was assessed by in situ hybridisation. TFF1 and TFF2 proteins were localised by immunochemistry.UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis. In some glands, there was TFF3 mRNA as has been reported for Crohn's UACL. None of the biopsies from ileal reservoirs without pouchitis showed UACL glands (p<0.05). Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis.UACL glands arise de novo in ileal pouch mucosa of patients with pouchitis and express all three TFF peptide genes. Chronic inflammation alone, present in healthy pouches, is not enough to stimulate the growth of the UACL, and additional stimuli consequent on ulceration may be needed.
Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells.
Authors: S Constant, C Pfeiffer, A Woodard, T Pasqualini, K Bottomly
Journal: The Journal of Experimental Medicine (1995)

Naive CD4+ T cells can differentiate into cells predominantly involved in humoral immunity, known as T helper type 2 cells (Th2), or cells involved in cell-mediated immunity, known as Th1 cells. In this report, we show that priming of CD4+ T cells bearing a transgene-encoded T cell receptor can lead to differentiation into Th1-like cells producing abundant interferon gamma when the cells are exposed to high antigen doses, while low doses of the same peptide induce cells with the same T cell receptor to differentiate into Th2-like cells producing abundant interleukin 4. Thus antigen dose is one factor that can control the differentiation fate of a naive CD4+ T cell.
Elongation Factor 2 and Fragile X Mental Retardation Protein Control the Dynamic Translation of Arc/Arg3.1 Essential for mGluR-LTD
Authors: Sungjin Park, Joo Min Park, Sangmok Kim, Jin-Ah Kim, Jason D. Shepherd, Constance L. Smith-Hicks, Shoaib Chowdhury, Walter Kaufmann, Dietmar Kuhl, Alexey G. Ryazanov, Richard L. Huganir, David J. Linden, Paul F. Worley
Journal: Neuron (2008)
Glucocorticoid receptor-binding characteristics in severe asthma
Authors: C. Bonnans, P. Chanez, H. Meziane, P. Godard, J. Bousquet, I. Vachier
Journal: European Respiratory Journal (2003)

The cellular mechanisms associated with severe asthma are still poorly understood. This study investigated the association between glucocorticoid-receptor (GR) alterations and continuous oral glucocorticoid therapy requirement in severe asthma. GR-binding affinity (K<sub>d</sub>) and receptor number (n) in peripheral blood monocytes (PBM) obtained from 10 normal subjects, 10 untreated, intermittent asthmatics and 10severe asthmatics were assessed. Moreover, one ability of dexamethasone to inhibit regulated on activation, T-cells expressed and secreted (RANTES) release by these cells <i>in vitro</i> was investigated. GR-binding characteristics were studied in PBM using a <sup>3</sup>H dexamethasone ligand-binding assay and Scatchard analysis. RANTES release was measured in the supernatant of PBM at 24 h using an enzyme-linked immunosorbent assay. No significant differences in K<sub>d</sub> and n were found between the three groups of patients. Dexamethasone <i>in vitro</i> was able to inhibit RANTES release (mean±sem), with the same concentration/response curve in intermittent, untreated asthmatics (0.47±0.22 <i>versus</i> 1.64±0.31 ng·mL<sup>−1</sup>) and severe asthmatics (1.49±0.64 <i>versus</i> 2.59±0.77 ng·mL<sup>−1</sup>). This study showed that, despite long-term treatment with oral glucocorticoids, there was no evidence of abnormalities in glucocorticoid receptor-binding characteristics in severe asthma, and moreover, it was demonstrated that glucocorticoid receptors were functional <i>in vitro</i>.
Acute resetting in two functionally different types of carotid baroreceptors.
Authors: J L Seagard, L A Gallenberg, F A Hopp, C Dean
Journal: Circulation Research (1992)

The presence of two types of carotid sinus baroreceptors, as characterized by two different stimulus-response curves in an earlier study, suggests that each type may play a different role in the regulation of blood pressure. The discontinuous hyperbolic curve of the type I baroreceptors, marked by higher firing rates and greater sensitivity than the sigmoidal curve of type II baroreceptors, suggests that these baroreceptors would contribute more to the buffering of arterial pressure changes than the "tonically" active type II baroreceptors, which fired over greater pressure ranges and generally had spontaneous subthreshold discharge. The firing characteristics of type II baroreceptors suggest that these receptors would contribute more to regulation of tonic, baseline levels of arterial pressure. If this functional differentiation exists, the acute resetting characteristics of the two types of baroreceptors could be different. Resetting is defined as a shift in the response curve of a baroreceptor, marked by shifts in pressure threshold, in the same direction as the change in pressure to which it is exposed. Type I baroreceptors would be more likely to reset in response to a sustained acute change in pressure, since their primary role would be to prevent the initial change in pressure. However, type II baroreceptors would not reset to the acute change in pressure, since their primary role would be to maintain consistent information on the level of existing pressure. Therefore, this study was performed to examine the acute resetting ability of both types of baroreceptors by using a vascularly isolated carotid sinus preparation in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)
Ischemic Acute Renal Failure Induces Differential Expression of Small Heat Shock Proteins
Authors: WILLIAM E. SMOYER, RICHARD RANSOM, RAYMOND C. HARRIS, MICHAEL J. WELSH, GUDRUN LUTSCH, RAINER BENNDORF
Journal: Journal of the American Society of Nephrology (2000)

AlphaB-crystallin and heat shock protein (hsp) 25 are structurally and functionally related small stress proteins induced by a variety of insults, including heat and ischemia. Cytoprotection by these two hsp is thought to result from molecular chaperoning and/or cytoskeletal stabilization. Because renal ischemia is characterized by disruption of the renal tubular cell actin cytoskeleton, this study was conducted to determine the localization and quantify the expression and phosphorylation of both hsp in renal cortex, isolated glomeruli, outer medulla, and inner medulla of rats after bilateral renal ischemia. Sham-operated kidneys had similarly small amounts of hsp25 and alphaB-crystallin in cortex and glomeruli, with substantially greater amounts of alphaB-crystallin versus hsp25 in outer and inner medulla. Ischemia resulted in significantly increased hsp25 (and hsp70i) but variable alphaB-crystallin levels in cortex and outer medulla, and progressively decreased glomerular hsp25 phosphorylation. In sham-operated kidneys, hsp25 localized to glomeruli, vessels, and collecting ducts, with alphaB-crystallin primarily in medullary thin limbs and collecting ducts. After ischemia, hsp25 accumulated in proximal tubules in cortex and outer medulla, while alphaB-crystallin labeling became nonhomogeneous in outer medulla, and increased in Bowman's capsule. It is concluded that: (1) There is striking differential expression of hsp25 and alphaB-crystallin in various renal compartments; and (2) Renal ischemia results in differential accumulation of hsp25 and alphaB-crystallin, with hsp25 part of a generalized stress response in renal proximal tubular cells, which may play a role in recovery from ischemia-induced actin filament disruption.
Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection
Authors: Claire Séror, Marie-Thérèse Melki, Frédéric Subra, Syed Qasim Raza, Marlène Bras, Héla Saïdi, Roberta Nardacci, Laurent Voisin, Audrey Paoletti, Frédéric Law, Isabelle Martins, Alessandra Amendola, Ali A. Abdul-Sater, Fabiola Ciccosanti, Olivier Delelis, Florence Niedergang, Sylvain Thierry, Najwane Said-Sadier, Christophe Lamaze, Didier Métivier, Jérome Estaquier, Gian Maria Fimia, Laura Falasca, Rita Casetti, Nazanine Modjtahedi, Jean Kanellopoulos, Jean-François Mouscadet, David M. Ojcius, Mauro Piacentini, Marie-Lise Gougeon, Guido Kroemer, Jean-Luc Perfettini
Journal: The Journal of Experimental Medicine (2011)

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches.
Hepatocyte Growth Factor Ameliorates Renal Interstitial Inflammation in Rat Remnant Kidney by Modulating Tubular Expression of Macrophage Chemoattractant Protein-1 and RANTES
Authors: Rujun Gong, Abdalla Rifai, Evelyn M. Tolbert, Purba Biswas, Jason N. Centracchio, Lance D. Dworkin
Journal: Journal of the American Society of Nephrology (2004)

Hepatocyte growth factor (HGF) has been shown to reduce renal injury in a variety of animal models of chronic renal disease. Suggested mechanisms to explain this action include prevention of tubular cell apoptosis, blocking epithelial-to-mesenchymal transition, and promotion of extracellular matrix degradation. Inflammation is another common finding in kidneys that progress to end-stage renal failure; however, the effect of HGF on inflammation has hardly been investigated. For examining this issue, beginning 2 wk after subtotal nephrectomy, rats received a continuous infusion of recombinant HGF, neutralization of endogenous HGF by daily injection of an anti-HGF antibody, or preimmune IgG for an additional 2 wk. HGF infusion halted the progression of proteinuria and decreased renal collagen accumulation. Renal inflammation in both glomeruli and tubulointerstitium was significantly attenuated, associated with reductions in the tubular expression of the chemokines macrophage chemoattractant protein-1 (MCP-1) and RANTES (regulated upon expression normal T cell expressed and secreted). In contrast, HGF neutralization worsened renal fibrosis, aggravated renal inflammation, and enhanced tubular expression of MCP-1 and RANTES. In vitro, HGF suppressed basal and TNF-α–induced expression of these chemokines at both the mRNA and protein levels in a time- and dose-dependent manner in proximal tubular epithelial cells. HGF also blunted TNF-α–induced nuclear translocation and activation of NF-κB, a pivotal transcription factor that regulates chemokine expression. Immunohistochemistry showed that activated NF-κB was evident in tubules in remnant kidneys and increased remarkably with anti-HGF treatment. HGF infusion markedly suppressed expression of activated NF-κB in remnant kidneys. These findings suggest that the beneficial effect of HGF in chronic renal disease is attributable, at least in part, to a direct anti-inflammatory action, likely via NF-κB, on tubular epithelial cells.
Integration of Arabidopsis thaliana stress-related transcript profiles, promoter structures, and cell-specific expression
Authors: Shisong Ma, Hans J Bohnert
Journal: Genome biology (2007)

Abstract Background Arabidopsis thaliana transcript profiles indicate effects of abiotic and biotic stresses and tissue-specific and cell-specific gene expression. Organizing these datasets could reveal the structure and mechanisms of responses and crosstalk between pathways, and in which cells the plants perceive, signal, respond to, and integrate environmental inputs. Results We clustered Arabidopsis transcript profiles for various treatments, including abiotic, biotic, and chemical stresses. Ubiquitous stress responses in Arabidopsis , similar to those of fungi and animals, employ genes in pathways related to mitogen-activated protein kinases, Snf1 -related kinases, vesicle transport, mitochondrial functions, and the transcription machinery. Induced responses to stresses are attributed to genes whose promoters are characterized by a small number of regulatory motifs, although secondary motifs were also apparent. Most genes that are downregulated by stresses exhibited distinct tissue-specific expression patterns and appear to be under developmental regulation. The abscisic acid-dependent transcriptome is delineated in the cluster structure, whereas functions that are dependent on reactive oxygen species are widely distributed, indicating that evolutionary pressures confer distinct responses to different stresses in time and space. Cell lineages in roots express stress-responsive genes at different levels. Intersections of stress-responsive and cell-specific profiles identified cell lineages affected by abiotic stress. Conclusion By analyzing the stress-dependent expression profile, we define a common stress transcriptome that apparently represents universal cell-level stress responses. Combining stress-dependent and tissue-specific and cell-specific expression profiles, and Arabidopsis 5'-regulatory DNA sequences, we confirm known stress-related 5' cis -elements on a genome-wide scale, identify secondary motifs, and place the stress response within the context of tissues and cell lineages in the Arabidopsis root.
Neutralization resistance of hepatitis C virus can be overcome by recombinant human monoclonal antibodies
Authors: Jannie Pedersen, Thomas H.R. Carlsen, Jannick Prentoe, Santseharay Ramirez, Tanja B. Jensen, Xavier Forns, Harvey Alter, Steven K.H. Foung, Mansun Law, Judith Gottwein, Nina Weis, Jens Bukh
Journal: Hepatology (2013)

Immunotherapy and vaccine development for hepatitis C virus (HCV) will depend on broadly reactive neutralizing antibodies (NAbs). However, studies in infectious strain JFH1-based culture systems expressing patient-derived Core-NS2 proteins have suggested neutralization resistance for specific HCV strains, in particular, of genotype 2. To further examine this phenomenon, we developed a panel of HCV genotype 2 recombinants for testing of sensitivity to neutralization by chronic-phase patient sera and lead human monoclonal antibodies (HMAbs). The novel Core-NS2 recombinants, with patient-derived genotype 2a (strain T9), 2b (strains DH8 and DH10), and 2c (strain S83) consensus sequences, were viable in Huh7.5 hepatoma cells without requirement for adaptive mutations, reaching HCV infectivity titers of 3.9-4.5 log10 focus-forming units per milliliter. In in vitro neutralization assays, we demonstrated that the novel genotype 2 viruses as well as prototype strains J6/JFH1(2a) and J8/JFH1(2b), all with authentic envelope proteins, were resistant to neutralization by genotype 2a, 2b, 2c, 2j, 2i, and 2q patient sera. However, these patient sera had high titers of HCV-specific NAbs, because they efficiently reduced the infectivity of J6(2a) and J8(2b) with deleted hypervariable region 1. The genotype 2a, 2b, and 2c viruses, found resistant to polyclonal patient sera neutralization, were efficiently neutralized by two lead HMAbs (AR4A and HC84.26).Using novel 2a, 2b, and 2c cell-culture systems, expressing authentic envelope proteins, we demonstrated resistance of HCV to patient-derived polyclonal high-titer NAbs. However, the same genotype 2 culture viruses were all sensitive to HMAbs recognizing conformational epitopes, indicating that neutralization resistance of HCV can be overcome by applying recombinant antibodies. These findings have important implications for HCV immunotherapy and vaccine development.
Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies
Authors: B. Poppe
Journal: Blood (2003)

MLL amplification was recently recognized as a recurrent aberration in acute myeloid leukemia (AML) and myelodys-plastic syndrome (MDS), associated with adverse prognosis and karyotype complexity. Here we present detailed results of fluorescence in situ hybridization (FISH) and expression analyses of MLL and 5 selected 11q candidate oncogenes (CBL, DDX6, ETS1, FLI1, and PLZF) in 31 patient samples and one cell line with 11q23 gain. FISH analyses revealed that the 11q23 amplicon invariably encompassed MLL, DDX6, ETS1, and FLI1, whereas expression analyses identified MLL and DDX6 as the most differentially expressed genes among samples with and without 11q23 copy gain or amplification. In MLL-amplified samples, a significant transcriptional up-regulation of MEIS1, PROML1, ADAM10, NKG2D, and ITPA was noted. Further analyses, designed to elucidate a possible role of the 11q overexpressed genes (MLL, DDX6, FLI1, and ETS1) in unselected MDS and AML samples, revealed a significant upregulation of MLL in MDS. Our findings confirm the MLL gene as a prominent target of 11q23 amplification and provide further evidence for an etiologic role for MLL gain of function in myeloid malignancies. In addition, our results indicate that the transcriptional program associated with MLL rearrangements and MLL overexpression displays significant similarities.