tbuckley/cabot-search huggingface dataset:
Prolonged Airway Activity and Improved Selectivity of Budesonide Possibly Due to Esterification
Authors: ANNA MILLER-LARSSON, P. JANSSON, A. RUNSTRÖM, R. BRATTSAND
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We addressed the question of whether the prolonged local retention of the glucocorticoid (GC) budesonide (BUD) within airway tissue, due to reversible fatty acid esterification, is associated with protracted topical anti-inflammatory activity and improved airway selectivity, when compared with fluticasone propionate (FP). BUD or FP at 25 nmol/kg was administered intratracheally or subcutaneously to adrenalectomized rats, followed by lipopolysaccharide (LPS) intratracheal instillation. The trachea and main bronchi were lavaged 6 h after LPS, and tumor necrosis factor-alpha (TNF-alpha) concentration and cell number in the lavage fluid were measured. Instilled 1 h before LPS, both GCs reduced TNF-alpha by 70% (p < 0.05) and mononuclear cells by 55% (p < 0.01), with no reduction in neutrophils. Instilled 6 h before LPS, a significant reduction of TNF-alpha (59%, p < 0.02) and mononuclear cells (47%, p < 0.05) was achieved only with BUD. After subcutaneous administration, no significant effects were observed. BUD did not exert higher systemic activity than FP, measured as plasma corticosterone suppression. In conclusion, BUD exerted a more prolonged topical anti-inflammatory activity, and a higher airway selectivity than FP, possibly because of its reversible fatty acid esterification within airway tissue. This may contribute to the high efficacy and safety of BUD in asthma, even with once-daily inhalation.
Ductal dilatation and stenting for residual hepatolithiasis
Authors: J E J KRIGE, I J BECKINGHAM, J TERBLANCHE, S J BENINGFIELD
Journal: Gut (1999)

EDITOR,-In reply, I would like to state that, while we agree that sphincter of Oddi hypertension may be an important contributor to the phenomenon of acalculus biliary pain, the purpose of the CCK provocation test is to select patients who might benefit from cholecystectomy.Whether subselection can be made on the basis of sphincter of Oddi testing remains to be seen but, certainly, the CCK provocation test should not be recommended as a selection tool for symptom relief after a cholecystectomy.
Sparse representation of whole-brain fMRI signals for identification of functional networks
Authors: Jinglei Lv, Xi Jiang, Xiang Li, Dajiang Zhu, Hanbo Chen, Tuo Zhang, Shu Zhang, Xintao Hu, Junwei Han, Heng Huang, Jing Zhang, Lei Guo, Tianming Liu
Journal: Medical Image Analysis (2014)
Impact of Prosthesis-Patient Mismatch on Survival After Mitral Valve Replacement
Authors: Julien Magne, Patrick Mathieu, Jean G. Dumesnil, David Tanné, François Dagenais, Daniel Doyle, Philippe Pibarot
Journal: Circulation (2007)

Background— We recently reported that valve prosthesis-patient mismatch (PPM) is associated with persisting pulmonary hypertension after mitral valve replacement. Thus, the objective of this study was to evaluate the impact of PPM on mortality in patients undergoing mitral valve replacement. Methods and Results— The indexed valve effective orifice area was estimated for each type and size of prosthesis being implanted in 929 consecutive patients and used to define PPM as not clinically significant if &gt;1.2 cm 2 /m 2 , as moderate if &gt;0.9 and ≤1.2 cm 2 /m 2 , and as severe if ≤0.9 cm 2 /m 2 . Moderate PPM was present in 69% of patients; severe PPM was seen in 9%. For patients with severe PPM, 6-year survival (74±5%) and 12-year survival (63±7%) were significantly less than for patients with moderate PPM (84±1% and 76±2%; P =0.027) or nonsignificant PPM (90±2% and 82±4%; P =0.002). On multivariate analysis, severe PPM was associated with higher mortality (hazard ratio, 3.2; 95% confidence interval, 1.5 to 6.8; P =0.003). Conclusions— Severe PPM is an independent predictor of mortality after mitral valve replacement. As opposed to other independent risk factors, PPM may be avoided or its severity may be reduced with the use of a prospective strategy at the time of operation. For patients identified as being at risk for severe PPM, every effort should be made to implant a prosthesis with a larger effective orifice area.
The coding genome of splenic marginal zone lymphoma: activation of <i>NOTCH2</i> and other pathways regulating marginal zone development
Authors: Davide Rossi, Vladimir Trifonov, Marco Fangazio, Alessio Bruscaggin, Silvia Rasi, Valeria Spina, Sara Monti, Tiziana Vaisitti, Francesca Arruga, Rosella Famà, Carmela Ciardullo, Mariangela Greco, Stefania Cresta, Daniela Piranda, Antony Holmes, Giulia Fabbri, Monica Messina, Andrea Rinaldi, Jiguang Wang, Claudio Agostinelli, Pier Paolo Piccaluga, Marco Lucioni, Fabrizio Tabbò, Roberto Serra, Silvia Franceschetti, Clara Deambrogi, Giulia Daniele, Valter Gattei, Roberto Marasca, Fabio Facchetti, Luca Arcaini, Giorgio Inghirami, Francesco Bertoni, Stefano A. Pileri, Silvia Deaglio, Robin Foà, Riccardo Dalla-Favera, Laura Pasqualucci, Raul Rabadan, Gianluca Gaidano
Journal: The Journal of Experimental Medicine (2012)

Splenic marginal zone lymphoma (SMZL) is a B cell malignancy of unknown pathogenesis, and thus an orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis, we show that the SMZL exome carries at least 30 nonsilent gene alterations. Mutations in NOTCH2, a gene required for marginal-zone (MZ) B cell development, represent the most frequent lesion in SMZL, accounting for ∼20% of cases. All NOTCH2 mutations are predicted to cause impaired degradation of the NOTCH2 protein by eliminating the C-terminal PEST domain, which is required for proteasomal recruitment. Among indolent B cell lymphoproliferative disorders, NOTCH2 mutations are restricted to SMZL, thus representing a potential diagnostic marker for this lymphoma type. In addition to NOTCH2, other modulators or members of the NOTCH pathway are recurrently targeted by genetic lesions in SMZL; these include NOTCH1, SPEN, and DTX1. We also noted mutations in other signaling pathways normally involved in MZ B cell development, suggesting that deregulation of MZ B cell development pathways plays a role in the pathogenesis of ∼60% SMZL. These findings have direct implications for the treatment of SMZL patients, given the availability of drugs that can target NOTCH, NF-κB, and other pathways deregulated in this disease.
Distinct Effects of Soluble and Membrane‐Bound Fas Ligand on Fibroblast‐like Synoviocytes From Rheumatoid Arthritis Patients
Authors: Rachel Audo, Flavia Calmon‐Hamaty, Laura Papon, Bernard Combe, Jacques Morel, Michael Hahne
Journal: Arthritis & Rheumatology (2014)

Injection of agonistic anti-Fas antibody has been shown to decrease disease symptoms in mouse models of arthritis. Additionally, membrane-bound FasL (mFasL) has been shown to induce cell death in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. However, levels of soluble FasL (sFasL) are increased in the joints of RA patients and have been associated with disease severity, indicating that mFasL and sFasL play opposing roles in RA. The purpose of this study was to analyze the effects of FasL on RA FLS responses.The responses of FLS from RA and osteoarthritis (OA) patients to soluble and oligomeric FasL, the latter mimicking mFasL, were analyzed by fluorescence-activated cell sorting and proliferation assays, using 3 different FasL variants. The signaling pathways that trigger FasL responses were characterized by Western blotting.We found that mFasL and sFasL have distinct roles in RA FLS. Crosslinked FasL preferentially induced apoptosis, whereas sFasL stimulated proliferation. Moreover, sFasL activated several signaling pathways in RA FLS, such as ERK-1/2, phosphatidylinositol 3-kinase, caspase 8, and JNK, with a prominent role of JNK, since only the blockade of this pathway rendered FLS more susceptible to FasL-induced apoptosis. Crosslinked FasL induced apoptosis in FLS from OA patients, but sFasL failed to stimulate their proliferation.Our findings suggest that sFasL is a disease promoter in RA, a finding consistent with previous reports describing a tumor-promoting role of FasL. Therefore, blocking of sFasL could be a therapeutic strategy for RA.
Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials
Authors: Jan A Staessen, Jerzy Gasowski, Ji G Wang, Lutgarde Thijs, Elly Den Hond, Jean-Pierre Boissel, John Coope, Tork Ekbom, François Gueyffier, Lisheng Liu, Karla Kerlikowske, Stuart Pocock, Robert H Fagard
Journal: The Lancet (2000)
Androgenic Suppression of ATP-binding Cassette Transporter A1 Expression in LNCaP Human Prostate Cancer Cells
Authors: Junichi Fukuchi, Richard A. Hiipakka, John M. Kokontis, Stephen Hsu, Andrew L. Ko, Michael L. Fitzgerald, Shutsung Liao
Journal: Cancer Research (2004)

Abstract Alteration of lipid metabolism is commonly observed in sex hormone-dependent cancer cells, yet its mechanistic involvement in cancer cell proliferation and progression is unclear. We have found that the expression of the cholesterol transporter, ATP-binding cassette transporter A1 (ABCA1), was 15- to 20-fold higher in androgen-dependent than in androgen-independent LNCaP human prostate cancer cells, indicating a possible relationship between the expression levels of ABCA1 and prostate cancer progression. On the basis of real-time quantitative PCR and Western blot analysis, expression of ABCA1 in androgen-dependent cells was inhibited by androgen. The antiandrogen Casodex blocked the effect of androgen, implicating the androgen receptor in regulation of ABCA1 expression by androgens. Using an ABCA1 promoter-reporter gene assay, androgenic suppression was observed at the transcriptional level in androgen-dependent but not in androgen-independent prostate cancer cells. ABCA1 appears to have a role in modulating cell proliferation because knockdown of ABCA1 expression by RNA interference in androgen-dependent cells increased their rate of proliferation. Therefore, a suppressive effect of androgen on ABCA1 expression may be one of the mechanisms by which androgens regulate proliferation in prostate cancer cells. Attenuated ABCA1 expression in androgen-independent cells thus may contribute, in part, to prostate cancer progression.
Inflammatory markers and COPD phenotypes as predictors of COPD exacerbations
Authors: Solveig Tangedal, Marianne Aanerud, Pål Aukrust, Gunnar Husebø, Jon Hardie, Louise Persson, Per Bakke, Tomas Eagan
Journal: European Respiratory Journal (2013)

Background: COPD exacerbations accelerate disease progression.  Aims: To examine if COPD phenotypes and systemic inflammatory markers predict the risk for COPD exacerbations, defined as requiring treatment with either systemic steroids or antibiotics.  Methods: 433 COPD patients, GOLD stage II-IV, aged 40-76 yrs were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years. Examined baseline predictors were sex, age, body composition, smoking habits, exacerbations the last year prior to baseline, GOLD stage, Charlson comorbidity score (CCS), presence of hypoxemia (PaO2  Univariate and multivariable Poisson models with random effects were fitted to estimate the yearly incidence rate ratios (IRR).  Results: Univariately, all variables except sex and CCS were significantly associated with the outcome. Higher levels of the inflammatory markers each predicted an increased yearly IRR (95% CI) per unit increase of the markers with IRR 1.03 (1.01-1.05), 1.07 (1.03-1.13), 1.06 (1.001-1.13), and 1.08 (1.01-1.16), respectively.  Multivariately, significant predictors of COPD exacerbations were: age [IRR per 1 yr increase:1.02 (1.003-1.04)], female sex [1.35 (1.06-1.73)], >1 exacerbations last year before baseline [1,58 (1.17-2.13)], GOLD III [1.28 (1.01-1.64)], GOLD IV [2.73 (1.85-4.05)], chronic cough [1.61 (1.28-2.03)], use of inhaled steroids [1.67 (1.29-2.17)].  Conclusion: Clinical COPD characteristics were independent predictors of exacerbations.
Cohort Analysis of Patients With Localized, High-Risk, Extremity Soft Tissue Sarcoma Treated at Two Cancer Centers: Chemotherapy-Associated Outcomes
Authors: Janice N. Cormier, Xuelin Huang, Yan Xing, Peter F. Thall, Xuemei Wang, Robert S. Benjamin, Raphael E. Pollock, Cristina R. Antonescu, Robert G. Maki, Murray F. Brennan, Peter W.T. Pisters
Journal: Journal of Clinical Oncology (2004)

Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) have high risks of distant recurrence and death. The role of chemotherapy for these patients remains controversial despite several randomized trials and a meta-analysis.We reviewed the treatments and outcomes of 674 consecutive adult patients presenting with primary stage III extremity STS between 1984 and 1999. Pre- or postoperative doxorubicin-based chemotherapy was used in a nonrandomized fashion in approximately half of this high-risk population. The objective of this review was to evaluate the impact of chemotherapy while accounting for known prognostic variables.Among 674 patients, 338 (50%) were treated with local therapy only, and 336 (50%) were treated with local therapy plus chemotherapy. The median follow-up for survivors was 6.1 years. Five-year local and distant recurrence-free interval probabilities were 83% and 56%, respectively, for the two groups combined. The 5-year disease-specific survival (DSS) rate was 61%. Cox regression analyses showed a time-varying effect associated with chemotherapy. During the first year, the hazard ratio associated with DSS for patients treated with chemotherapy versus no chemotherapy was 0.37 (95% CI, 0.20 to 0.69; P = .002). Thereafter, this hazard ratio was 1.36 (95% CI, 1.02 to 1.81; P = .04).It seems that the clinical benefits associated with doxorubicin-based chemotherapy in patients with high-risk extremity STS are not sustained beyond 1 year. These results suggest that caution should be used in the interpretation of randomized clinical trials of adjuvant chemotherapy that seem to demonstrate clinical benefits with relatively short-term follow-up.
Absence of the G Protein–Coupled Receptor G2A in Mice Promotes Monocyte/Endothelial Interactions in Aorta
Authors: David T. Bolick, Angela M. Whetzel, Marcus Skaflen, Tracy L. Deem, Jianyi Lee, Catherine C. Hedrick
Journal: Circulation Research (2007)

The G protein–coupled receptor G2A is highly expressed on macrophages and lymphocytes and has been localized to atherosclerotic plaques. We examined the role of G2A in modulating monocyte/endothelial interactions in the vessel wall. We measured adhesion of WEHI 78/24 monocytes to aortas of C57BL/6 (B6) and G2A-deficient (G2A −/− ) mice using an ex vivo adhesion assay. G2A −/− mice had 10-fold elevations in adhesion of monocytes to aortas. Injection of GFP-expressing wild-type macrophages into B6 and G2A −/− mice in vivo showed increased macrophage accumulation in the aortic wall of G2A −/− mice. We isolated aortic endothelial cells (ECs) from B6 and G2A −/− mice and found a 2-fold increase in intercellular adhesion molecule-1 and E-selectin surface expression on G2A −/− ECs using flow cytometry. Using ELISA, we found a 3-fold increase in interleukin-6 and monocyte chemoattractant protein-1 production by G2A −/− ECs compared with B6 ECs. We found a dramatic increase in nuclear localization of the p65 subunit of nuclear factor κB in G2A −/− ECs. Transfection of G2A into G2A −/− ECs to restore normal expression levels reduced p65 nuclear localization to 35%. Restoration of G2A expression in G2A −/− ECs significantly reduced intercellular adhesion molecule-1 and endothelial selectin surface expression and reduced monocyte chemoattractant protein-1 and interleukin-6 production. Restoring G2A to G2A −/− ECs reduced monocyte adhesion by 80% compared with G2A −/− ECs in a flow chamber assay. Absence of G2A in endothelium results in proinflammatory signaling and increased monocyte/endothelial interactions in the aortic wall. Thus, endothelial G2A expression may aid in prevention of vascular inflammation and atherosclerosis.
Efficacy of ecabet sodium enema on steroid resistant or steroid dependent ulcerative colitis
Authors: M Iizuka
Journal: Gut (2006)

Ecabet sodium (ES), a 12-sulfodehydroabietic acid monosodium salt derived from an ingredient in pine resin, has been shown to topically enhance several gastric mucosal defensive factors.1 ES is widely used for the treatment of gastritis and gastric ulcer in Japan. A recent open label study demonstrated that ES also has therapeutic effects in active ulcerative colitis (UC).2 In that study, the authors demonstrated that six of seven UC patients with proctosigmoiditis achieved complete remission by treatment with ES enema. However, successive clinical trials of the efficacy of ES enema in UC patients have not been reported. Here we demonstrate the efficacy of ES enema in steroid resistant or steroid dependent UC patients. …
Efficacy of Rituximab in Hairy Cell Leukemia Treatment
Authors: Pier Luigi Zinzani, Stefano Ascani, Pier Paolo Piccaluga, Maurizio Bendandi, Stefano Pileri, Sante Tura
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.22.3875 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11078503 Efficacy of Rituximab in Hairy Cell Leukemia Treatment Pier Luigi ZinzanixPier Luigi ZinzaniSearch for articles by this author , Stefano AscanixStefano AscaniSearch for articles by this author , Pier Paolo PiccalugaxPier Paolo PiccalugaSearch for articles by this author , Maurizio BendandixMaurizio BendandiSearch for articles by this author , Stefano PilerixStefano PileriSearch for articles by this author , Sante TuraxSante TuraSearch for articles by this author Show More Institute of Hematology and Medical Oncology "Seràgnoli" University of Bologna Bologna, Italy https://doi.org/10.1200/JCO.2000.18.22.3875 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin.
Authors: C M Verfaillie, J B McCarthy, P B McGlave
Journal: The Journal of Experimental Medicine (1991)

We have previously demonstrated that primitive progenitors from human bone marrow termed long term bone marrow culture initiating cells (LTBMC-IC) adhere avidly to irradiated bone marrow stroma, while more mature clonogenic progenitors fail to do so. In this study we examine the interaction between these progenitors and components of the bone marrow stroma. (a) We demonstrate that both primitive LTBMC-IC and more mature clonogenic progenitors adhere to intact fibronectin. (b) Primitive LTBMC-IC and multi-lineage CFU-MIX progenitors adhere to the 33/66 kD COOH-terminal heparin-binding cell-adhesion promoting fragment of fibronectin, but adhere significantly less to its 75 kD RGDS-dependent cell-binding fragment. In contrast, more differentiated single-lineage progenitors adhere equally well to the 33/66 kD RGDS independent and the 75 kD RGDS-dependent cell-adhesion fragments of fibronectin. (c) Both primitive LTBMC-IC and clonogenic progenitors adhere to the three known cell-attachment sites in the 33/66 kD cell-adhesion promoting fragment, FN-C/H I, FN-C/H II and CS1. However, LTBMC-IC and CFU-MIX progenitors adhere significantly better to FN-C/H II than to the flanking FN-C/H I and CS1 cell-attachment sites. In contrast, single-lineage progenitors adhere equally well to all three cell attachment sites in the 33/66 kD cell-adhesion promoting fragment. (d) Finally, adhesion of primitive LTBMC-IC to intact irradiated stroma can be inhibited partially by peptide FN-C/H II and almost completely by a combination of FN-C/H II and peptide FN-C/H I and CS1. This study demonstrates that adhesive interactions between primitive hematopoietic progenitors and the extracellular matrix component fibronectin can occur. Specific changes in adhesion to the 33/66 kD cell-adhesion promoting fragment and the 75 kD RGDS-dependent cell-adhesion fragment of fibronectin are associated with differentiation of primitive multi-lineage progenitors into committed single-lineage progenitors. Such differences in adhesive interaction with fibronectin may allow hematopoietic progenitors at various stages of differentiation to interact with specific supportive loci of the bone marrow microenvironment. Finally, the ability to block adhesion of LTBMC-IC to intact irradiated stroma with peptides FN-C/H II, FN-C/H I and CS1 suggests that receptors responsible for this interaction may be important in the homing of primitive progenitors to the bone marrow.
Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes
Authors: Shuta Motonishi, Masaomi Nangaku, Takehiko Wada, Yu Ishimoto, Takamoto Ohse, Taiji Matsusaka, Naoto Kubota, Akira Shimizu, Takashi Kadowaki, Kazuyuki Tobe, Reiko Inagi
Journal: Journal of the American Society of Nephrology (2014)

Recent studies have highlighted the renoprotective effect of sirtuin1 (SIRT1), a deacetylase that contributes to cellular regulation. However, the pathophysiologic role of SIRT1 in podocytes remains unclear. Here, we investigated the function of SIRT1 in podocytes. We first established podocyte-specific Sirt1 knockout (SIRT1(pod-/-)) mice. We then induced glomerular disease by nephrotoxic serum injection. The increase in urinary albumin excretion and BUN and the severity of glomerular injury were all significantly greater in SIRT1(pod-/-) mice than in wild-type mice. Western blot analysis and immunofluorescence showed a significant decrease in podocyte-specific proteins in SIRT1(pod-/-) mice, and electron microscopy showed marked exacerbation of podocyte injury, including actin cytoskeleton derangement in SIRT1(pod-/-) mice compared with wild-type mice. Protamine sulfate-induced podocyte injury was also exacerbated by podocyte-specific SIRT1 deficiency. In vitro, actin cytoskeleton derangement in H2O2-treated podocytes became prominent when the cells were pretreated with SIRT1 inhibitors. Conversely, this H2O2-induced derangement was ameliorated by SIRT1 activation. Furthermore, SIRT1 activation deacetylated the actin-binding and -polymerizing protein cortactin in the nucleus and facilitated deacetylated cortactin localization in the cytoplasm. Cortactin knockdown or inhibition of the nuclear export of cortactin induced actin cytoskeleton derangement and dissociation of cortactin from F-actin, suggesting the necessity of cytoplasmic cortactin for maintenance of the actin cytoskeleton. Taken together, these findings indicate that SIRT1 protects podocytes and prevents glomerular injury by deacetylating cortactin and thereby, maintaining actin cytoskeleton integrity.