tbuckley/cabot-search huggingface dataset:
Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer
Authors: Ahmed Boucharaba, Claire-Marie Serre, Sandra Grès, Jean Sébastien Saulnier-Blache, Jean-Claude Bordet, Julien Guglielmi, Philippe Clézardin, Olivier Peyruchaud
Journal: Journal of Clinical Investigation (2004)

The role of lysophosphatidic acid (LPA) in cancer is poorly understood. Here we provide evidence for a role of LPA in the progression of breast cancer bone metastases. LPA receptors LPA1, LPA2, and LPA3 were expressed in human primary breast tumors and a series of human breast cancer cell lines. The inducible overexpression of LPA1 in MDA-BO2 breast cancer cells specifically sensitized these cells to the mitogenic action of LPA in vitro. In vivo, LPA1 overexpression in MDA-BO2 cells enhanced the growth of subcutaneous tumor xenografts and promoted bone metastasis formation in mice by increasing both skeletal tumor growth and bone destruction. This suggested that endogenous LPA was produced in the tumor microenvironment. However, MDA-BO2 cells or transfectants did not produce LPA. Instead, they induced the release of LPA from activated platelets which, in turn, promoted tumor cell proliferation and the LPA1-dependent secretion of IL-6 and IL-8, 2 potent bone resorption stimulators. Moreover, platelet-derived LPA deprivation in mice, achieved by treatment with the platelet antagonist Integrilin, inhibited the progression of bone metastases caused by parental and LPA1-overexpressing MDA-BO2 cells and reduced the progression of osteolytic lesions in mice bearing CHO-β3wt ovarian cancer cells. Overall, our data suggest that, at the bone metastatic site, tumor cells stimulate the production of LPA from activated platelets, which enhances both tumor growth and cytokine-mediated bone destruction.
Quantitative PCR on 5 genes reliably identifies CTCL patients with 5% to 99% circulating tumor cells with 90% accuracy
Authors: Michael Nebozhyn, Andrey Loboda, Laszlo Kari, Alain H. Rook, Eric C. Vonderheid, Stuart Lessin, Carole Berger, Richard Edelson, Calen Nichols, Malik Yousef, Lalitha Gudipati, Meiling Shang, Michael K. Showe, Louise C. Showe
Journal: Blood (2006)
Chemokine Receptor Expression Identifies Pre–T Helper (Th)1, Pre–Th2, and Nonpolarized Cells among Human CD4+ Central Memory T Cells
Authors: Laura Rivino, Mara Messi, David Jarrossay, Antonio Lanzavecchia, Federica Sallusto, Jens Geginat
Journal: The Journal of Experimental Medicine (2004)

We previously reported that central–memory T cells (TCM cells), which express lymph node homing receptors CCR7 and CD62L, are largely devoid of effector functions but acquire characteristics of effector–memory T cells (TEM cells) (i.e., CCR7− T helper [Th]1 or Th2 cells) after stimulation with T cell receptor agonists or homeostatic cytokines. Here we show that three chemokine receptors identify functional subsets within the human CD4+ TCM cell pool. TCM cells expressing CXCR3 secreted low amounts of interferon γ, whereas CCR4+ TCM cells produced some interleukin (IL)-4, but not IL-5. In response to IL-7 and IL-15, CXCR3+ TCM and CCR4+ TCM cells invariably generated fully differentiated CCR7− Th1 and Th2 cells, respectively, suggesting that they represent pre-Th1 and pre-Th2 cells. Conversely, CXCR5+ TCM cells lacking CXCR3 and CCR4 remained nonpolarized and retained CCR7 and CD62L expression upon cytokine-driven expansion. Unlike naive cells, all memory subsets had a low T cell receptor rearrangement excision circle content, spontaneously incorporated bromodeoxyuridine ex vivo, and contained cells specific for tetanus toxoid. Conversely, recall responses to cytomegalovirus and vaccinia virus were largely restricted to CXCR3+ TCM and TEM cells. We conclude that antigen-specific memory T cells are distributed between TEM cells and different subsets of TCM cells. Our results also explain how the quality of primary T cell responses could be maintained by TCM cells in the absence of antigen.
Budesonide/Formoterol for Bronchiolitis Obliterans after Hematopoietic Stem Cell Transplantation
Authors: Anne Bergeron, Sylvie Chevret, Karine Chagnon, Cendrine Godet, Emmanuel Bergot, Régis Peffault de Latour, Stéphane Dominique, Thierry de Revel, Karine Juvin, Natacha Maillard, Oumedaly Reman, Nathalie Contentin, Marie Robin, Agnès Buzyn, Gérard Socié, Abdellatif Tazi
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects.Objectives: To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT.Methods: In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account.Measurements and Main Results: At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment.Conclusions: Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT.Clinical trial registered with www.clinicaltrials.gov (NCT00624754).
Underinsurance in the United States: An Interaction of Costs to Consumers, Benefit Design, and Access to Care
Authors: Shana Alex Lavarreda, E. Richard Brown, Claudie Dandurand Bolduc
Journal: Annual Review of Public Health (2011)

Underinsurance is most commonly defined as the state in which people with medical coverage are still exposed to financial risk. We argue that the adequacy of health insurance coverage should also be assessed in terms of the adequacy of specific benefits coverage and access to care. Underinsurance can be understood conceptually as comprising three separate domains: (a) the economic features of health insurance, (b) the benefits covered, and (c) access to health services. The literature provides ample evidence that people who are underinsured have high financial risk and face barriers in access to care similar to those who are completely uninsured. In response to the growing recognition of the problems associated with underinsurance, the Patient Protection and Affordable Care Act of 2010 includes numerous provisions designed to limit costs to consumers, to assure a minimum set of benefits, and to enhance access to care, especially primary care.
Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis: bone marrow oedema predicts erosive progression
Authors: E A Haavardsholm, P Boyesen, M Ostergaard, A Schildvold, T K Kvien
Journal: Annals of the Rheumatic Diseases (2007)

To examine the spectrum and severity of magnetic resonance imaging (MRI) findings in patients with early rheumatoid arthritis (RA), and to investigate the predictive value of MRI findings for subsequent development of conventional radiographic (CR) damage and MRI erosions.84 consecutive patients with RA with disease duration <1 year were enrolled. Patients were treated according to standard clinical practice, and evaluated at baseline, 3, 6 and 12 months by core measures of disease activity, conventional radiographs of both hands and wrists and MRI of the dominant wrist. MR images were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging score (RAMRIS), and conventional radiographs according to the van der Heijde modified Sharp score.MRI findings reflecting inflammation (synovitis, bone marrow oedema and tenosynovitis) decreased during follow-up, while there was a small increase in MRI erosion score and CR damage. The proportion of patients with erosive progression at 1 year was 48% for conventional radiography and 66% for MRI. Baseline MRI bone marrow oedema (score >2 RAMRIS units) was identified as an independent predictor of both CR (odds ratio = 2.77 (95% confidence interval (CI) 1.06 to 7.21)) and MRI erosive progression (B = 0.21 (95% CI 0.08 to 0.34)).MRI findings were common in early RA, and MRI bone marrow oedema was an independent predictor of radiographic damage. These results suggest that MRI scans of the dominant wrist may help clinicians to determine which patients need early and aggressive treatment to avoid subsequent joint damage.
HLA-DRB1 allele distributions in Danish sarcoidosis patients. Increased prevalence of HLA-DRB1*15
Authors: Nils Milman, Claus Bo Svendsen, Thomas van Overeem Hansen, Lars Ryder, Klaus Richter Larsen
Journal: European Respiratory Journal (2012)

Background: The MHC class II region appears to play an important role in the development and clinical picture of sarcoidosis, probably due to the influence on the immune response against yet unknown antigen(s). A previous HLA-class II study in Danes has shown that HLA-DR3 antigen is associated with a favorable prognosis and HLA-DRw6 with susceptibility to sarcoidosis (Odum et al, Exp Clin Immunogenet 1991;8:227-321).

Subjects and methods: HLA-DRB1 allele classification was performed by PCR in ethnic Danish patients with biopsy-verified sarcoidosis (n=94). Danish blood donors (n = 10146) served as controls.

Results: The prevalence of DRB1*01 was lower and the prevalence of DRB1*15 was higher in sarcoidosis patients compared to controls.

Conclusions: There exist no specific biochemical markers of sarcoidosis. Diagnosis relies on histological examination of tissue biopsy specimens in combination with the exclusion of infection with mycobacteria and other causes of the granulomatous response. Due to the paucity of prognostic markers, we suggest that analysis of HLA-DRB1 (and BTNL2 genotype (Milman et al, Clin Respir J 2011;5:105-11)) should be incorporated in the evaluation of sarcoidosis patients.

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HLA-DRB1 allele frequencies
Recent aspects of gonadal hormone and neurotransmitter interactions with synovial and immune cells: implications in rheumatoid arthritis
Authors: M. CUTOLO
Journal: Annals of the Rheumatic Diseases (2000)

Recent aspects of gonadal hormone and neurotransmitter interactions with synovial and immune cells: implications in rheumatoid arthritisThe hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axis involvement, and/or response to the immune system activation, is now recognised in the development and maintenance of inflammatory and autoimmune conditions such as rheumatoid arthritis (RA). 1 In female patients the immune response seems to depend more on the HPA axis, whereas in male patients it seems to depend more on the HPG axis.In particular, hypoandrogenism may have a pathogenetic role in male patients with RA, and in other autoimmune conditions (for example, systemic lupus erythematosus (SLE)), as androgens are considered natural immunosuppressors. 2 Conversely, physiological concentrations of oestrogens seem to exert some immunoenhancing activities, at least on the humoral response.In addition, a range of physical/ psychosocial stressors are also implicated in the activation of the HPA axis and the related altered HPG function in RA. 3 4
Pilus- gonococcal variants. Evidence for multiple forms of piliation control.
Authors: J Swanson, S Bergström, O Barrera, K Robbins, D Corwin
Journal: The Journal of Experimental Medicine (1985)

Pilus+ to pilus- transitions of gonococci (Gc) that involve rearrangement of pilin gene DNA yield the P-n phenotype, which is incapable of reversion (to pilus+). Reversion to pilus+ is found for nonpiliated Gc that have undergone no apparent pilin gene rearrangement. Among the reverting, nonpiliated Gc, two distinct phenotypes (P-rp- and P-rp+) occur and are differentiated according to their synthesis (or lack) of pilin subunits; both P-rp- and P-rp+ Gc contain pilin-specific mRNA. The occurrence of these different pilus- phenotypes strongly suggests that several mechanisms can account for changes in the piliation status of Gc; one of these involves pilin gene rearrangement but the others apparently operate at posttranscriptional levels. Reverting pilus- Gc may have a pathogenic advantage in being able to reversibly alter their host cell adherence-promoting surface properties through high frequency transitions in piliation status.
Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis
Authors: Susan Branford, Zbigniew Rudzki, Sonya Walsh, Ian Parkinson, Andrew Grigg, Jeff Szer, Kerry Taylor, Richard Herrmann, John F. Seymour, Chris Arthur, David Joske, Kevin Lynch, Tim Hughes
Journal: Blood (2003)
Anger and Hostility Predict the Development of Atrial Fibrillation in Men in the Framingham Offspring Study
Authors: Elaine D. Eaker, Lisa M. Sullivan, Margaret Kelly-Hayes, Ralph B. D’Agostino, Emelia J. Benjamin
Journal: Circulation (2004)

Conflicting findings in the literature with regard to the ability of type A behavior, expressions of anger, or hostility to predict incident coronary heart disease (CHD) have created controversy. In addition, there are no prospective studies relating these characteristics to the development of atrial fibrillation (AF).From 1984 to 1987, 3873 men and women, 18 to 77 years of age, participating in the Framingham Offspring Study, were examined and monitored for 10 years for the incidence of CHD, AF, and total mortality. Measures of type A behavior, anger, hostility, and risk factors for CHD and AF were collected at the baseline examination. After controlling for age, diabetes, hypertension, history of myocardial infarction, history of congestive heart failure, and valvular heart disease in Cox proportional hazards models, trait-anger (RR=1.1; 95% CI, 1.0 to 1.4; P=0.04), symptoms of anger (RR=1.2; 95% CI, 1.0 to 1.4; P=0.008), and hostility (RR=1.3; 95% CI, 1.1 to 1.5; P=0.003) were predictive of 10-year incidence of AF in men. After controlling for risk factors for CHD, none of the measures of anger, type A behavior, or hostility were related to incident CHD; however, trait-anger (RR=1.2; 95% CI, 1.1 to 1.4; P<0.01) was related to total mortality in men. None of the psychosocial variables were related to the 3 outcomes in women.This is the first study to examine and demonstrate a predictive relation between measures of anger and hostility to the development of AF in men. As opposed to type A behavior, measures of anger and hostility may be more productive avenues for research in studying the risk of arrhythmias and total mortality in men.
Monogenic Obesity in Humans
Authors: I. Sadaf Farooqi, Stephen O'Rahilly
Journal: Annual Review of Medicine (2005)

Until relatively recently, the small number of identifiable inherited human diseases associated with marked obesity were complex, pleiotropic developmental disorders, the molecular basis for which were entirely obscure. The molecular basis for many of these complex syndromes, such as Bardet Beidl syndrome, has been revealed, providing novel insights into processes essential for human hypothalamic function and energy balance. In addition to these discoveries, which were the fruits of positional cloning, the molecular constituents of the signaling pathways responsible for the control of mammalian energy homeostasis have been identified, largely through the study of natural or artificial mutations in mice. We discuss the increasing number of human disorders that result from genetic disruption of the leptin-melanocortin pathways that have been identified. Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged.
Identification of lactoferrin as the granulocyte-derived inhibitor of colony-stimulating activity production.
Authors: H E Broxmeyer, A Smithyman, R R Eger, P A Meyers, M de Sousa
Journal: The Journal of Experimental Medicine (1978)

Lactoferrin (LF), the iron-binding protein present in the specific granules of mature granulocytes has been identified as colony inhibitory factor (CIF) which suppresses granulocyte--macrophage colony stimulating activity (CSA) production by monocytes and macrophages in vitro and rebound granulopoiesis in vivo. Separation of LF and CIF by isoelectric focusing confirmed that the regions of inhibitory activity corresponded in both to a pH of congruent to 6.5. In addition, the purified immunoglobulin fraction of rabbit anti-human LF antiserum, but not rabbit anti-transferrin (TF), inactivated the capacity of LF and CIF to inhibit CSA production, an effect blocked by prior incubation of anti-LF with neutralizing concentrations of LF. Suppression of CSA production correlated with the iron-saturation of LF; APO-LF (depleted of iron) was only active concentrations greater than 10(-7) M, native LF (8% iron saturated) was active at 10(-15) M, and fully iron-saturated LF inhibited at 10(-17) M. Suppression of CSA production occurred within a 1/2-h preincubation period with human blood monocytes but was reversed by bacterial lipopolysaccharide (LPS). This reversal was dependent on the relative concentrations of LF to LPS. Serum TF, a biochemically similar iron-binding protein which is antigenically distinct from LF, was only minimally active at concentrations greater than 10(-6) M. LF did not inhibit exogenously stimulated human granylocyte and macrophage colony-forming cells or erythropoietin-dependent human or murine erythroid colony- or erythroid burst-forming cells. Microgram quantities of LF acted in vivo to inhibit rebound granulopoiesis and CSA production in CD1 and C57Bl/6 mice pretreated with cyclophosphamide. These results strongly implicate LF as a physiological regulator of granulopoiesis.
Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure
Authors: Wolfram Doehner, Nina Schoene, Mathias Rauchhaus, Francisco Leyva-Leon, Darrell V. Pavitt, David A. Reaveley, Gerhard Schuler, Andrew J.S. Coats, Stefan D. Anker, Rainer Hambrecht
Journal: Circulation (2002)

Background — In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)–derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies. Methods and Results — In 10 CHF patients with normal serum uric acid (UA) levels (315±42 μmol/L) and 9 patients with elevated UA (535±54 μmol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 μg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients ( P &lt;0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558±21 μmol/L, range 455 to 743 μmol/L), treatment reduced UA by &gt;120 μmol/L in all patients (mean reduction 217±15 μmol/L, P &lt;0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%, P =0.027) and legs (+23%, P =0.029). Flow-dependent flow improved by 58% in arms ( P =0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment ( P &lt;0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment ( r =0.63, P &lt;0.05). Conclusions — In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.
Corneal Nerve Loss Detected With Corneal Confocal Microscopy Is Symmetrical and Related to the Severity of Diabetic Polyneuropathy
Authors: Ioannis N. Petropoulos, Uazman Alam, Hassan Fadavi, Omar Asghar, Patrick Green, Georgios Ponirakis, Andrew Marshall, Andrew J.M. Boulton, Mitra Tavakoli, Rayaz A. Malik
Journal: Diabetes Care (2013)

OBJECTIVE To establish if corneal nerve loss, detected using in vivo corneal confocal microscopy (IVCCM), is symmetrical between right and left eyes and relates to the severity of diabetic neuropathy. RESEARCH DESIGN AND METHODS Patients (n = 111) with type 1 and type 2 diabetes and 47 age-matched healthy control subjects underwent detailed assessment and stratification into no (n = 50), mild (n = 26), moderate (n = 17), and severe (n = 18) neuropathy. IVCCM was performed in both eyes and corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) and the tortuosity coefficient were quantified. RESULTS All corneal nerve parameters differed significantly between diabetic patients and control subjects and progressively worsened with increasing severity of neuropathy. The reduction in CNFD, CNBD, and CNFL was symmetrical in all groups except in patients with severe neuropathy. CONCLUSIONS IVCCM noninvasively detects corneal nerve loss, which relates to the severity of neuropathy, and is symmetrical, except in those with severe diabetic neuropathy.
Adjuvant and neo-adjuvant chemotherapy for Ewing's sarcoma family tumors and osteosarcoma of the extremity: further outcome for patients event-free survivors 5 years from the beginning of treatment
Authors: G. Bacci, A. Balladelli, C. Forni, S. Ferrari, A. Longhi, M.S. Benassi, A. Briccoli, M. Serra, P. Picci
Journal: Annals of Oncology (2007)