tbuckley/cabot-search huggingface dataset:
hnRNP A2/B1 Modulates Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines
Authors: Jordi Tauler, Enrique Zudaire, Huaitian Liu, Joanna Shih, James L. Mulshine
Journal: Cancer Research (2010)

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been reported to be overexpressed in lung cancer and in other cancers such as breast, pancreas, and liver. However, a mechanism linking hnRNP A2/B1 overexpression and progression to cancer has not yet been definitively established. To elucidate this mechanism, we have silenced hnRNPA2/B1 mRNA in non-small-cell lung cancer cell lines A549, H1703, and H358. These cell lines present different levels of expression of epithelial-to-mesenchymal transition (EMT) markers such as E-cadherin, fibronectin, and vimentin. Microarray expression analysis was performed to evaluate the effect of silencing hnRNP A2/B1 in A549 cells. We identified a list of target genes, affected by silencing of hnRNP A2/B1, that are involved in regulation of migration, proliferation, survival, and apoptosis. Silencing hnRNP A2/B1 induced formation of cell clusters and increased proliferation. In the anchorage-independent assay, silencing hnRNP A2/B1 increased colony formation by 794% in A549 and 174% in H1703 compared with a 25% increase in proliferation, in both cell lines, in a two-dimensional proliferation assay. Silencing hnRNP A2/B1 decreased migration in intermediate cell line A549 and mesenchymal cell line H1703; however, no changes in proliferation were observed in epithelial cell line H358. Silencing hnRNP A2/B1 in A549 and H1703 cells correlated with an increase of E-cadherin expression and downregulation of the E-cadherin inhibitors Twist1 and Snai1. These data suggest that expression of hnRNP A2/B1 may play a role in EMT, in nonepithelial lung cancer cell lines A549 and H1703, through the regulation of E-cadherin expression.
Patient–Ventilator Interactions. Implications for Clinical Management
Authors: Daniel Gilstrap, Neil MacIntyre
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Assisted/supported modes of mechanical ventilation offer significant advantages over controlled modes in terms of ventilator muscle function/recovery and patient comfort (and sedation needs). However, assisted/supported breaths must interact with patient demands during all three phases of breath delivery: trigger, target, and cycle. Synchronous interactions match ventilator support with patient demands; dyssynchronous interactions do not. Dyssynchrony imposes high pressure loads on ventilator muscles, promoting muscle overload/fatigue and increasing sedation needs. On current modes of ventilation there are a number of features that can monitor and enhance synchrony. These include adjustments of the trigger variable, the use of pressure versus fixed flow targeted breaths, and a number of manipulations of the cycle variable. Clinicians need to know how to use these modalities and monitor them properly, especially understanding airway pressure and flow graphics. Future strategies are emerging that have theoretical appeal but they await good clinical outcome studies before they become commonplace.
Environmental influences on the immune system and allergic reactions.
Authors: N F Adkinson
Journal: Environmental Health Perspectives (1977)

Environmental interactions with the immune system may result in two types of adverse outcomes: immunodeficiency and immunopathology. Serious immunodeficiency most commonly results from ionizing radiation or as a recognized side effect of iatrogenic drug therapy, usually cancer chemotherapy. At present there is little basis for believing that biologically significant suppression of immune competence in man results from more subtle interactions with environmental agents. On the other hand, environmentally triggered immunopathology is a source of considerable morbidity and mortality. Additional research is needed in the following areas: (a) basic mechanisms of immunopathological reactions; (b) development of methods for accurately implicating or excluding immunological mechanisms in the etiology of hypersensitivity states; (c) development of methods for assessing in advance the potential immunogenicity of new industrial chemicals and occupational allergens; (d) identification of the risk factors which predispose to immunopathological outcomes when individuals are exposed to sensitizing chemicals or other
Novel Therapeutic Agents for the Management of Patients with Multiple Myeloma and Renal Impairment
Authors: Asher A. Chanan-Khan, Jesús F. San Miguel, Sundar Jagannath, Heinz Ludwig, Meletios A. Dimopoulos
Journal: Clinical Cancer Research (2012)

Renal impairment is a major complication of multiple myeloma. Patients presenting with severe renal impairment represent a greater therapeutic challenge and generally have poorer outcome. However, once patients with renal impairment achieve remission, their outcomes are comparable with those of patients without renal impairment. Therapies that offer substantial activity in this setting are needed. Bortezomib, thalidomide, and lenalidomide have substantially improved the survival of patients with multiple myeloma. Here we review the pharmacokinetics, activity, and safety of these agents in patients with renal impairment. Bortezomib can be administered at the full approved dose and schedule in renally impaired patients; similarly, no dose reductions are required with thalidomide. The pharmacokinetics of lenalidomide is affected by its renal route of excretion, and dose adjustments are recommended for moderate/severe impairment. Substantial evidence has emerged showing that these novel agents improve outcomes of patients with renal impairment, including impairment reversal. Bortezomib, thalidomide, and lenalidomide (at the recommended doses) are active options for patients with mild to moderate impairment, although limited data are available for thalidomide. Information on lenalidomide-based combinations is still emerging, but the available data indicate considerable activity. Substantial evidence indicates that bortezomib-high-dose dexamethasone with or without a third drug (e.g., cyclophosphamide, thalidomide, or doxorubicin) is an appropriate option for patients with any degree of renal impairment.
Effects of controlled inspiratory muscle training in patients with COPD: a meta-analysis
Authors: F. Lötters, B. van Tol, G. Kwakkel, R. Gosselink
Journal: European Respiratory Journal (2002)

The purpose of this meta-analysis is to review studies investigating the efficacy of inspiratory muscle training (IMT) in chronic obstructive pulmonary disease (COPD) patients and to find out whether patient characteristics influence the efficacy of IMT. A systematic literature search was performed using the Medline and Embase databases. On the basis of a methodological framework, a critical review was performed and summary effect-sizes were calculated by applying fixed and random effects models. Both IMT alone and IMT as adjunct to general exercise reconditioning significantly increased inspiratory muscle strength and endurance. A significant effect was found for dyspnoea at rest and during exercise. Improved functional exercise capacity tended to be an additional effect of IMT alone and as an adjunct to general exercise reconditioning, but this trend did not reach statistical significance. No significant correlations were found for training effects with patient characteristics. However, subgroup analysis in IMT plus exercise training revealed that patients with inspiratory muscle weakness improved significantly more compared to patients without inspiratory muscle weakness. From this review it is concluded that inspiratory muscle training is an important addition to a pulmonary rehabilitation programme directed at chronic obstructive pulmonary disease patients with inspiratory muscle weakness. The effect on exercise performance is still to be determined.
Renal artery stenosis stent revascularization of 587 patients: 4 year effect upon blood pressure control, serum creatinine, and survival
Authors: G. Dorros, M.R. Jaff, S.R. Ramee, E.B. Diethrich, J.A. Rodriguez-Lopez, R.L. Minor, R.H. Hamer, Z. Krajcer, K. Rosenfield, K.J. Murphy, T. He
Journal: Journal of the American College of Cardiology (1998)
Induction of immunological tolerance requires that the B cells can respond to the polyclonal B-cell-activating properties of the thymus-independent antigens.
Authors: C Fernandez, G Möller
Journal: The Journal of Experimental Medicine (1977)

Mice were rendered specifically tolerant to the fluorescein isothiocyanatedextran (FITC) epitope by injection of FITC-dextran B512. Their spleen cells were removed at various times and cultivated in vitro with different polyclonal B-cell activators, such as lipopolysaccharide (LPS), purified protein derivative of tuberculin, and native dextran. LPS caused the appearance of high affinity anti-FITC plaque-forming cells to an equal extent with cells from untreated and tolerant animals, whereas native dextran failed to activate cells from tolerant mice, although it was a potent activator of normal cells. It was concluded that tolerance induction only affects those B cells that could respond to the polyclonal B-cell-activating properties of the tolerogen, but not other B cells having an identical set of Ig receptors directed against the tolerogen.
Erythroleukemia induction by replication-competent type C viruses cloned from the anemia- and polycythemia-inducing isolates of Friend leukemia virus.
Authors: M E MacDonald, T W Mak, A Bernstein
Journal: The Journal of Experimental Medicine (1980)

In this study, the biological properties of the replication-competent viruses, F-MuLVA, present in the anemia-inducing isolate of Friend leukemia virus complex (FV-A); and F-MuLVP, present in the polycythemia-inducing isolate of Friend leukemia virus complex (FV-P) have been examined. BALB/c mice infected as newborns with clonal isolates of F-MuLVA or F-MuLVP become anemic and show splenic enlargement characterized by an increased proportion of cells that resemble immature nucleated erythroid cells. In addition, the spleens of these F-MuLVA- or F-MuLVP-infected mice contain a markedly increased proportion of both erythropoietin-dependent erythroid progenitor cells and spectrin-containing erythroid cells. These results suggest that Friend murine leukemia virus (F-MuLV) by itself can induce an erythroleukemic transformation in newborn BALB/c mice similar to that induced by the anemia-inducing spleen focus-forming virus (SFFVA) in newborn or adult mice. Kinetic studies indicated that the alterations in hemopoietic cell populations induced by F-MuLVA or F-MuLVP in newborn BALB/c mice occurred more slowly than the rapid changes observed after infection with FV-A. In addition, adult BALB/c mice were fully susceptible to the erythroleukemic transformation induced by either SFFVA or SFFVP, whereas only newborn mice were susceptible to F-MuLV. Taken together, these results suggest that, although the replication-defective Friend spleen focus-forming viruses appear to be the major determinant of erythroleukemia induction in adults, the replication-competent helper F-MuLV also have erythroleukemic potential when assayed in newborn animals.
Stretch-dependent modulation of [Na+]i, [Ca2+]i, and pHi in rabbit myocardium—a mechanism for the slow force response
Authors: C LUERS, F FIALKA, A ELGNER, D ZHU, J KOCKSKAMPER, D VONLEWINSKI, B PIESKE
Journal: Cardiovascular Research (2005)

Journal Article Stretch-dependent modulation of [Na+]i, [Ca2+]i, and pHi in rabbit myocardium–a mechanism for the slow force response Get access Claus Luers, Claus Luers Department of Cardiology and Pneumology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Florian Fialka, Florian Fialka Department of Cardiology and Pneumology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Andreas Elgner, Andreas Elgner Department of Cardiology and Pneumology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Danan Zhu, Danan Zhu Department of Cardiology and Pneumology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Jens Kockskämper, Jens Kockskämper Department of Cardiology and Pneumology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Dirk von Lewinski, Dirk von Lewinski Department of Cardiology and Pneumology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Burkert Pieske Burkert Pieske * Department of Cardiology and Pneumology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany *Corresponding author. Tel.: +49 551 39 8925; fax: +49 551 39 19127. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 68, Issue 3, December 2005, Pages 454–463, https://doi.org/10.1016/j.cardiores.2005.07.001 Published: 01 December 2005 Article history Received: 24 June 2004 Revision received: 28 June 2005 Accepted: 05 July 2005 Published: 01 December 2005
Scavenger Receptor-A–Targeted Leukocyte Depletion Inhibits Peritoneal Ovarian Tumor Progression
Authors: S. Peter Bak, Julie Jo Walters, Motohiro Takeya, Jose R. Conejo-Garcia, Brent L. Berwin
Journal: Cancer Research (2007)

Abstract Immunosuppressive leukocytes are emerging as a critical factor in facilitating tumor progression. These leukocytes are converted by the tumor microenvironment to become tolerogenic, facilitate metastasis, and to aid in neovascularization. The predominant variety of suppressive leukocytes found in human and murine ovarian cancer are called vascular leukocytes (VLC), due to sharing functions and cell surface markers of both dendritic cells and endothelial cells. Using the ID8 murine model of ovarian cancer, the aim of this study was to test the efficacy of VLC elimination as an ovarian tumor therapy. We show that carrageenan-mediated depletion of peritoneal tumor-associated leukocytes inhibits ovarian tumor progression. We then identified scavenger receptor-A (SR-A) as a cell surface receptor that is robustly and specifically expressed within human and murine ovarian tumor ascites upon VLCs. Administration of anti–SR-A immunotoxin to mice challenged with peritoneal ID8 tumors eliminated tumor-associated VLCs and, importantly, substantially inhibited peritoneal tumor burden and ascites accumulation. Moreover, the toxin required targeting to SR-A because mice that received untargeted toxin did not exhibit inhibition of tumor progression. We conclude that SR-A constitutes a novel and specific target for efficacious immunotherapeutic treatment of peritoneal ovarian cancer. [Cancer Res 2007;67(10):4783–9]
Bicuspid Aortic Valves Are Associated With Aortic Dilatation Out of Proportion to Coexistent Valvular Lesions
Authors: M. G. Keane, S. E. Wiegers, T. Plappert, A. Pochettino, J. E. Bavaria, M. G. St. J. Sutton
Journal: Circulation (2000)

Bicuspid aortic valves (BAVs) are associated with premature valve stenosis, regurgitation, and ascending aortic aneurysms. We compared aortic size in BAV patients with aortic size in control patients with matched valvular lesions (aortic regurgitation, aortic stenosis, or mixed lesions) to determine whether intrinsic aortic abnormalities in BAVs account for aortic dilatation beyond that caused by valvular hemodynamic derangement alone.Diameters of the left ventricular outflow tract, sinus of Valsalva, sinotubular junction, and proximal aorta were measured from transthoracic echocardiograms in 118 consecutive BAV patients. Annular area was measured by planimetry, and BAV eccentricity was expressed as the ratio of the right leaflet area to the total annular area. Seventy-seven control patients with tricuspid aortic valves were matched for sex and for combined severity of regurgitation and stenosis. BAV patients (79 men and 39 women, aged 44.1+/-15.5 years) had varying degrees of regurgitation (84 patients [71%]) and stenosis (48 patients [41%]). Within the bicuspid group, multivariate analysis demonstrated that aortic diameters increased with worsening aortic regurgitation (P:<0.001) and advancing age (P:<0.05) but not with the severity of aortic stenosis. BAV patients had larger aortic diameters than did control patients at all ascending aortic levels measured (P:<0.01), despite advanced age in the control patients.Aortic dimensions are larger in BAV patients than in control patients with comparable degrees of tricuspid aortic valve disease. Although more severe degrees of aortic regurgitation are associated with aortic dilatation in BAV patients, intrinsic pathology appears to be responsible for aortic enlargement beyond that predicted by hemodynamic factors.
Outcomes of Patients With Chronic Lymphocytic Leukemia and Richter's Transformation After Transplantation Failure
Authors: Uri Rozovski, Ohad Benjamini, Preetesh Jain, Philip A. Thompson, William G. Wierda, Susan O'Brien, Jan A. Burger, Alessandra Ferrajoli, Stefan Faderl, Elizabeth Shpall, Chitra Hosing, Issa F. Khouri, Richard Champlin, Michael J. Keating, Zeev Estrov
Journal: Journal of Clinical Oncology (2015)

Allogeneic stem-cell transplantation (SCT) induces long-term remission in a fraction of patients with high-risk chronic lymphocytic leukemia (CLL) or Richter's transformation (RT). Our purpose was to determine the outcomes of patients whose disease progressed after allogeneic SCT.We retrospectively analyzed the outcomes of 72 patients (52 with CLL and 20 with RT) who underwent allogeneic SCT between 1998 and 2011 and had documented progression after transplantation. Twenty-two (31%) never had a response, and 50 (69%) had a response but experienced relapse after a median of 7 months (range, 2 to 85 months). Forty-eight patients who were receiving or were candidates to receive post-SCT cell-based therapies were not included in this analysis.The median age at time of transplantation was 58 years (range, 30 to 72 years). Sixty-two patients (86%) received more than two treatment regimens and 37 (51%) received more than three treatment regimens before SCT. Sixty-six patients (92%) had active disease at the time of transplantation. The 2- and 5-year survival rates were 67% and 38% (patients with CLL) and 36% and 0% (patients with RT). The patients who developed acute or chronic graft-versus-host disease had a longer overall survival (OS; P = .05). In a multivariable analysis, RT or low hemoglobin at the time of SCT predicted shorter OS. Chronic graft-versus-host disease and an initial response to SCT predicted longer OS.Patients with CLL in whom allogeneic SCT fails may have a response to and benefit from salvage therapies, and their prognosis is relatively good.
The Contribution of Cultural Competence to Evidence-Based Care for Ethnically Diverse Populations
Authors: Stanley J. Huey, Jacqueline Lee Tilley, Eduardo O. Jones, Caitlin A. Smith
Journal: Annual Review of Clinical Psychology (2014)

Despite compelling arguments for the dissemination of evidence-based treatments (EBTs), questions regarding their relevance to ethnically diverse populations remain. This review summarizes what is known about psychotherapy effects with ethnic minorities, with a particular focus on the role of cultural competence when implementing EBTs. Specifically, we address three questions: (a) does psychotherapy work with ethnic minorities, (b) do psychotherapy effects differ by ethnicity, and (c) does cultural tailoring enhance treatment effects? The evidence suggests that psychotherapy is generally effective with ethnic minorities, and treatment effects are fairly robust across cultural groups and problem areas. However, evidence for cultural competence is mixed. Ethnic minority-focused treatments frequently incorporate culturally tailored strategies, and these tailored treatments are mostly efficacious; yet support for cultural competence as a useful supplement to standard treatment remains equivocal at best. We also discuss research limitations, areas for future research, and clinical implications.
Platelet PECAM-1 inhibits thrombus formation in vivo
Authors: Shahrokh Falati, Sonali Patil, Peter L. Gross, Michelle Stapleton, Glenn Merrill-Skoloff, Natasha E. Barrett, Katherine L. Pixton, Harmut Weiler, Brian Cooley, Debra K. Newman, Peter J. Newman, Barbara C. Furie, Bruce Furie, Jonathan M. Gibbins
Journal: Blood (2005)
Are Bad Outcomes from Questionable Clinical Decisions Preventable Medical Errors? A Case of Cascade Iatrogenesis
Authors: Timothy P. Hofer
Journal: Annals of Internal Medicine (2002)

When a patient with multiple, complicated conditions is admitted to a hospital and risky procedures are performed that result in adverse outcomes, the difficulties inherent in determining whether and when a preventable medical error has occurred must be addressed. This article analyzes the case of a 40-year-old woman with a history of chronic aortic dissection and pericardial effusion who was admitted to a teaching hospital with unilateral swelling of her left breast and arm accompanied by dyspnea. During her hospitalization, the patient developed multiple complications from the diagnostic and therapeutic procedures that were performed. The authors argue that this case illustrates some limitations of routinely undertaking time-consuming and costly reviews, or "root-cause analyses," as a patient safety strategy when they are unlikely to reveal remediable "errors" or to suggest better systems of care that will prevent errors. The ability to establish causality through post hoc reviews is the linchpin in the recommendation for widespread adoption of error reporting and reviews. When causality is not established, it is impossible to know whether any changes adopted as a result of the reviews will be effective. This case, in which the causal pathways to the adverse events are very uncertain, may be much more typical than the egregious errors featured in a classic root-cause analysis. The authors recommend that the relative merits of this approach to patient safety be compared with other proven, cost-effective interventions to improve quality, such as appropriate treatment of myocardial infarction or depression, before scarce resources and enormous human capital are allocated for widespread implementation.
Inhibition of Breast Cancer Metastasis by Selective Synthetic Polypeptide against CXCR4
Authors: Zhongxing Liang, Tao Wu, Hong Lou, Xiwen Yu, Russell S. Taichman, Stephen K. Lau, Shuming Nie, Jay Umbreit, Hyunsuk Shim
Journal: Cancer Research (2004)

Abstract Metastasis shares many similarities with leukocyte trafficking. Among those chemokine receptors thought to be involved in hemopoietic cell homing, stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4 (CXCR4) have received considerable attention. Like hemopoietic cell homing, levels of stromal cell-derived factor-1 are high at sites of breast cancer metastasis including lymph node, lung, liver, and the marrow. Moreover, CXCR4 expression is low in normal breast tissues and high in malignant tumors, suggesting that a blockade of CXCR4 might limit tumor metastasis. We therefore investigated the role of a synthetic antagonist 14-mer peptide (TN14003) in inhibiting metastasis in an animal model. Not only was TN14003 effective in limiting metastasis of breast cancer by inhibiting migration, but it may also prove useful as a diagnostic tool to identify CXCR4 receptor-positive tumor cells in culture and tumors in paraffin-embedded clinical samples.