tbuckley/cabot-search huggingface dataset:
Leukocytosis and the Retinoic Acid Syndrome in Patients With Acute Promyelocytic Leukemia Treated With Arsenic Trioxide
Authors: Luis H. Camacho, Steven L. Soignet, Suzanne Chanel, Raymond Ho, Glenn Heller, David A. Scheinberg, Ralph Ellison, Raymond P. Warrell
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Arsenic trioxide, like all-trans-retinoic acid (RA), induces differentiation of acute promyelocytic leukemia (APL) cells in vivo. Treatment of APL patients with all-trans RA is commonly associated with leukocytosis, and approximately 50% of patients develop the RA syndrome. We reviewed our clinical experience with arsenic trioxide to determine the incidence of these two phenomena. PATIENTS AND METHODS: Twenty-six patients with relapsed or refractory APL were treated with arsenic trioxide for remission induction at daily doses that ranged from 0.06 to 0.17 mg/kg. RESULTS: Twenty-three patients (88%) achieved complete remission. Leukocytosis was observed in 15 patients (58%). The median baseline leukocyte count for patients with leukocytosis was 3,900 cells/μL (range, 1,200 to 72,300 cells/μL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/μL; range, 500 to 5,400 cells/μL; P = .01). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in eight patients (31%). Patients who developed leukocytosis were significantly more likely to develop the RA syndrome (P &lt; .001), and no patient without a peak leukocyte count greater than 10,000 cells/μL developed the syndrome. Among the patients with leukocytosis, there was no observed relation between the leukocyte peak and the probability of developing the syndrome (P = .37). CONCLUSION: Induction therapy of APL with all-trans RA and arsenic trioxide is associated with leukocytosis and the RA syndrome. These clinical effects seem to be intrinsically related to the biologic responsiveness and the differentiation process induced by these new agents.
Lupus erythematosus profundus (Kaposi-Irgang) with monoclonal gammopathy
Authors: ELEASAR J. FEUERMAN, SIMA HALEVY
Journal: British Journal of Dermatology (1977)

The appearance of subcutaneous nodules of lupus erythematosus profundus on the face and neck of a woman with a long history of lupus erythematosus (LE) is reported. Of note were the three distinct stages in the course of the disease: (i) discoid LE, first appearing at the age of 42; (2) systemic LE, appearing 10 years later; (3) LE profundus, appearing 21 years after the diagnosis of discoid LE was made. The finding of monoclonal gammopathy is of particular interest, although its relationship to the basic disease has not been clarified.
Targets of Tumor Immunity After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yishay Ofran, Jerome Ritz
Journal: Clinical Cancer Research (2008)

Abstract The effectiveness of allogeneic hematopoietic stem cell transplantation for hematologic malignancies results from the donor immunity to antigens expressed in leukemia cells in the recipient. Similar immune responses have now been identified in patients with renal cell cancer with tumor regression after allogeneic hematopoietic stem cell transplantation. Further studies to identify relevant antigens and mechanisms of resistance may improve the effectiveness of this approach in patients with solid tumors.
Pregnancy in Patients with Cystic Fibrosis
Authors: Judy Palmer, Cindy Dillon-Baker, Jan S. Tecklin, Barbara Wolfson, Beth Rosenberg, Barbara Burroughs, Douglas S. Holsclaw, Thomas F. Scanlin, Nancy N. Huang, Edward M. Sewell
Journal: Annals of Internal Medicine (1983)

As more patients with cystic fibrosis reach adulthood, questions arise about the potential hazards of pregnancy. We reviewed the medical records of eight women with cystic fibrosis who had a total of 11 completed pregnancies and had been evaluated within 1 year before conception. In five women (Group 1), the overall maternal condition was little affected by the pregnancy, and in three women (Group 2), the mother's condition deteriorated during and after pregnancy and did not return to the pregravid state. With regard to pregravid status, significant differences between patients in Group 1 and Group 2 were found in Shwachman-Kulczycki clinical scores, weight for height values, Brasfield chest radiograph scores, and pulmonary function. A quantitative assessment of pregravid nutritional and pulmonary status is useful in counseling women with cystic fibrosis about the risk of pregnancy.
Characterization of sheep afferent lymph dendritic cells and their role in antigen carriage.
Authors: R Bujdoso, J Hopkins, B M Dutia, P Young, I McConnell
Journal: The Journal of Experimental Medicine (1989)

We have ablated peripheral lymph nodes in sheep and subsequently cannulated the pseudo-afferent lymphatic vessel that arises as a consequence of afferent lymphatic vessels reanastomosing with the former efferent duct. This technique allows the collection of lymph with a cellular composition that resembles true afferent fluid, and in particular, containing 1-10% dendritic cells. A 16-h collection of this lymph may contain between 10(6) and 10(7) dendritic cells. This dendritic cell population may be enriched to greater than 75% by a single-density gradient centrifugation step. We have generated a mAb that recognizes sheep CD1. This monoclonal not only reacts with afferent dendritic cells, but with dendritic cells in the skin and paracortical T cell areas of lymph nodes. The expression of CD1 suggests afferent dendritic cells are related to skin Langerhans' cells and other dendritic cells that act as accessory cells for T cell responses. Consistent with this is the high level of expression by dendritic cells of molecules involved in antigen recognition by T cells, including MHC class I and class II. Afferent dendritic cells express high levels of the cellular adhesion molecule LFA-3, and at the same time express a ligand for this molecule, namely CD2. The accessory functions of afferent dendritic cells resemble those displayed by mature Langerhans' cells and by lymph node interdigitating cells. These include clustering with resting T cells and stimulating their proliferation in a primary response to antigen. Afferent dendritic cells are capable of acquiring soluble protein antigen in vivo or in vitro and presenting the material directly to autologous T cells in an antigen-specific manner. We conclude that afferent dendritic cells represent a lymph-borne Langerhans' cell involved in antigen carriage to the lymph node.
Self reported receipt of care consistent with 32 quality indicators: national population survey of adults aged 50 or more in England
Authors: N. Steel, M. Bachmann, S. Maisey, P. Shekelle, E. Breeze, M. Marmot, D. Melzer
Journal: BMJ (2008)

<b>Objective</b> To assess the receipt of effective healthcare interventions in England by adults aged 50 or more with serious health conditions. <b>Design</b> National structured survey questionnaire with face to face interviews covering medical panel endorsed quality of care indicators for both publicly and privately provided care. <b>Setting</b> Private households across England. <b>Participants</b> 8688 participants in the English longitudinal study of ageing, of whom 4417 reported diagnoses of one or more of 13 conditions. <b>Main outcome measures</b> Percentage of indicated interventions received by eligible participants for 32 clinical indicators and seven questions on patient centred care, and aggregate scores. <b>Results</b> Participants were eligible for 19 082 items of indicated care. Receipt of indicated care varied substantially by condition. The percentage of indicated care received by eligible participants was highest for ischaemic heart disease (83%, 95% confidence interval 80% to 86%), followed by hearing problems (79%, 77% to 81%), pain management (78%, 73% to 83%), diabetes (74%, 72% to 76%), smoking cessation (74%, 71% to 76%), hypertension (72%, 69% to 76%), stroke (65%, 54% to 76%), depression (64%, 57% to 70%), patient centred care (58%, 57% to 60%), poor vision (58%, 54% to 63%), osteoporosis (53%, 49% to 57%), urinary incontinence (51%, 47% to 54%), falls management (44%, 37% to 51%), osteoarthritis (29%, 26% to 32%), and overall (62%, 62% to 63%). Substantially more indicated care was received for general medical (74%, 73% to 76%) than for geriatric conditions (57%, 55% to 58%), and for conditions included in the general practice pay for performance contract (75%, 73% to 76%) than excluded from it (58%, 56% to 59%). <b>Conclusions</b> Shortfalls in receipt of basic recommended care by adults aged 50 or more with common health conditions in England were most noticeable in areas associated with disability and frailty, but few areas were exempt. Efforts to improve care have substantial scope to achieve better health outcomes and particularly need to include chronic conditions that affect quality of life of older people.
Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics
Authors: Christina Orsmark-Pietras, Anna James, Jon R. Konradsen, Björn Nordlund, Cilla Söderhäll, Ville Pulkkinen, Christophe Pedroletti, Kameran Daham, Maciek Kupczyk, Barbro Dahlén, Juha Kere, Sven-Erik Dahlén, Gunilla Hedlin, Erik Melén
Journal: European Respiratory Journal (2012)

The causes of severe childhood asthma are poorly understood. Our aim was to define global patterns of gene expression in children with severe therapy-resistant and controlled asthma. White blood cells were isolated and the global transcriptome profile was characterised using the Affymetrix Human Gene ST 1.0 chip in children with severe, therapy-resistant asthma (n=17), controlled asthma (n=19) and healthy controls (n=18). Receptor expression was studied in separated leukocyte fractions from asthmatic adults (n=12). Overall, 1378 genes were differentially expressed between children with severe/controlled asthma and controls. Three significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were represented: natural killer cell-mediated cytotoxicity (upregulated in controlled asthma); N-glycan biosynthesis (downregulated in severe asthma); and bitter taste transduction receptors (TAS2Rs) (upregulated in severe asthma). Quantitative PCR experiments confirmed upregulation of TAS2Rs in severe asthmatics. TAS2R expression was replicated in leukocytes from adult asthmatics, in which TAS2R agonists also inhibited LPS-induced cytokine release. Significant correlations between expression of TAS2Rs and clinical markers of asthma severity were found in both adults and children. In conclusion, specific gene expression patterns were observed in children with severe, therapy-resistant asthma. The increased expression of bronchodilatory TAS2Rs suggests a new target for the treatment of asthma.
<i>Pneumocystis jirovecii</i>Pneumonia in Everolimus-Treated Renal Cell Carcinoma
Authors: Marie-Charlotte Loron, Steven Grange, Dominique Guerrot, Frédéric Di Fiore, Caroline Freguin, Mélanie Hanoy, Frank Le Roy, Gwenaelle Poussard, Isabelle Etienne, Bruno Legallicier, Christian Pfister, Michel Godin, Dominique Bertrand
Journal: Journal of Clinical Oncology (2014)
Netrin-4 Activates Endothelial Integrin α6β1
Authors: Frederic Larrieu-Lahargue, Alana L. Welm, Kirk R. Thomas, Dean Y. Li
Journal: Circulation Research (2011)

Netrin-4 regulates vascular development. Identity of netrin-4 endothelial receptor and its subsequent cell functions is controversial. We previously demonstrated that the inhibition of netrin-1 canonical receptors, Unc5B and neogenin, expressed by lymphatic endothelial cells, do not suppress netrin-4-induced cell signaling and functions. Netrin family members were shown to signal through a range of receptors, including integrins (such as α3β1, α6β1, and α6β4) in nonendothelial cells.We tested whether integrins are netrin-4 receptors in the endothelium.The α6β1 integrin is expressed by endothelial cells, and binds netrin-4 in a dose-dependent manner. Inhibition of α6 or β1 integrin subunits suppresses netrin-4-induced endothelial cell migration, adhesion, and focal adhesion contact. Netrin-4-stimulated phosphorylation of Src kinase family, effectors of endothelial cell migration, is also abolished by α6 or β1 inhibition. Finally, netrin-4 and α6β1 integrin expression colocalize in mouse embryonic, intestine, and tumor vasculature.The α6β1 integrin is a netrin-4 receptor in lymphatic endothelium and consequently represents a potential target to inhibit netrin-4-induced metastatic dissemination.
Comparative efficacy of self expanding and balloon expandable stents for the reduction of restenosis
Authors: R.O. Han, R.S. Schwartz, J.T. Mann, M.H. Sketch, R.L. Feldman, M.G. Midel, R.D. Safian, C.L. Brown, E.W. Rogers, M.P. Savage, B.E. Murphy, W. Werner, I.F. Palacios, S. Goldberg
Journal: Journal of the American College of Cardiology (1998)
Women remain confused about breast cancer
Authors: M. Spittle, D. Morgan
Journal: BMJ (1999)

EDITOR—Lavelle and Charlton correctly identify the need for a new baseline of women's views on breast cancer.1 A clear understanding of the fears and myths associated with the condition is useful to doctors and forms a critical component of any health education programme. A recent opinion poll conducted on behalf of Breakthrough Breast Cancer may help to shed some additional light …
Increased Daily Walking Improves Lipid Oxidation Without Changes in Mitochondrial Function in Type 2 Diabetes
Authors: Michael I. Trenell, Kieren G. Hollingsworth, Ee Lin Lim, Roy Taylor
Journal: Diabetes Care (2008)

OBJECTIVE—To determine whether increased daily physical activity improves mitochondrial function and/or lipid oxidation in type 2 diabetes. RESEARCH DESIGN AND METHODS—Volunteers with (n = 10) and without (n = 10) type 2 diabetes were matched for habitual physical activity, age, sex, and weight. Basal and maximal mitochondrial activity, physical activity, and resting substrate oxidation were measured at baseline and after 2 and 8 weeks of increased physical activity. RESULTS—Baseline physical activity (6,450 ± 851 vs. 7,638 ± 741 steps/day), basal ATP use (12 ± 1 vs. 12 ± 1 μmol · ml−1 · min−1), phosphocreatine recovery from exercise (31 ± 5 vs. 29 ± 3 s), and basal lipid oxidation (0.57 ± 0.07 vs. 0.65 ± 0.06 mg · kg body wt−1 · min−1) were similar in people with and without type 2 diabetes. There was a significant increase in physical activity after 8 weeks (12,322 ± 1,979 vs. 9,187 ± 1,159 steps/day, respectively). Following increased physical activity, there were no changes in basal ATP use or phosphocreatine recovery after exercise in either group. Basal lipid oxidation increased after 8 weeks of increased physical activity in people with type 2 diabetes (0.79 ± 0.08 mg · kg−1 · min−1) but not people without (0.68 ± 0.13 mg · kg body wt−1 · min−1). CONCLUSIONS—Resting and maximal ATP turnover are not impaired in people with well-controlled type 2 diabetes compared with control subjects matched for physical activity as well as age and weight. Increased unsupervised daily physical activity is sustainable and improves lipid oxidation independent of change in mitochondrial activity in people with type 2 diabetes.
A Phase II, Randomized, Placebo-Controlled Study of Vismodegib as Maintenance Therapy in Patients with Ovarian Cancer in Second or Third Complete Remission
Authors: Stanley B. Kaye, Louis Fehrenbacher, Robert Holloway, Amnon Amit, Beth Karlan, Brian Slomovitz, Paul Sabbatini, Ling Fu, Robert L. Yauch, Ilsung Chang, Josina C. Reddy
Journal: Clinical Cancer Research (2012)

Hedgehog pathway inhibition has been suggested as a potential maintenance treatment approach in ovarian cancer through disruption of tumor-stromal interactions. Vismodegib is an orally available Hedgehog pathway inhibitor with clinical activity in advanced basal cell carcinoma and medulloblastoma. This phase II, randomized, double-blind, placebo-controlled trial was designed to provide a preliminary estimate of efficacy in patients with ovarian cancer in second or third complete remission (CR).Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in second or third CR were randomized 1:1 to vismodegib (GDC-0449; 150 mg daily) or placebo three to 14 weeks after completing chemotherapy. Treatment continued until radiographic progression or toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS).One hundred four patients were randomized to vismodegib (n = 52) or placebo (n = 52); median PFS was 7.5 months and 5.8 months, respectively [HR 0.79; 95% confidence interval (CI), 0.46-1.35]. The HR was 0.66 (95% CI, 0.36-1.20) for second CR patients (n = 84) and 1.79 (95% CI, 0.50-6.48) for third CR patients (n = 20). The most common adverse events in the vismodegib arm were dysgeusia/ageusia, muscle spasms, and alopecia. Grade 3/4 adverse events occurred in 12 patients (23.1%) with vismodegib and six (11.5%) with placebo. Hedgehog expression was detected in 13.5% of archival tissues.In this study, the sought magnitude of increase in PFS was not achieved for vismodegib maintenance versus placebo in patients with ovarian cancer in second or third CR. The frequency of Hedgehog ligand expression was lower than expected.
As Smooth as Honey—The Historical Use of Honey as Topical Medication
Authors: Raheel Zubair, Nasir Aziz
Journal: JAMA Dermatology (2015)

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Integrated analysis of recurrent properties of cancer genes to identify novel drivers
Authors: Matteo D'Antonio, Francesca D Ciccarelli
Journal: Genome biology (2013)

The heterogeneity of cancer genomes in terms of acquired mutations complicates the identification of genes whose modification may exert a driver role in tumorigenesis. In this study, we present a novel method that integrates expression profiles, mutation effects, and systemic properties of mutated genes to identify novel cancer drivers. We applied our method to ovarian cancer samples and were able to identify putative drivers in the majority of carcinomas without mutations in known cancer genes, thus suggesting that it can be used as a complementary approach to find rare driver mutations that cannot be detected using frequency-based approaches.
Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes
Authors: Sebastiaan van Heesch, Maarten van Iterson, Jetse Jacobi, Sander Boymans, Paul B Essers, Ewart de Bruijn, Wensi Hao, Alyson W MacInnes, Edwin Cuppen, Marieke Simonis
Journal: Genome biology (2014)

Long noncoding RNAs (lncRNAs) form an abundant class of transcripts, but the function of the majority of them remains elusive. While it has been shown that some lncRNAs are bound by ribosomes, it has also been convincingly demonstrated that these transcripts do not code for proteins. To obtain a comprehensive understanding of the extent to which lncRNAs bind ribosomes, we performed systematic RNA sequencing on ribosome-associated RNA pools obtained through ribosomal fractionation and compared the RNA content with nuclear and (non-ribosome bound) cytosolic RNA pools.The RNA composition of the subcellular fractions differs significantly from each other, but lncRNAs are found in all locations. A subset of specific lncRNAs is enriched in the nucleus but surprisingly the majority is enriched in the cytosol and in ribosomal fractions. The ribosomal enriched lncRNAs include H19 and TUG1.Most studies on lncRNAs have focused on the regulatory function of these transcripts in the nucleus. We demonstrate that only a minority of all lncRNAs are nuclear enriched. Our findings suggest that many lncRNAs may have a function in cytoplasmic processes, and in particular in ribosome complexes.
Oxidative Stress–Dependent Sphingosine Kinase-1 Inhibition Mediates Monoamine Oxidase A–Associated Cardiac Cell Apoptosis
Authors: Dimitri Pchejetski, Oxana Kunduzova, Audrey Dayon, Denis Calise, Marie-Hélène Seguelas, Nathalie Leducq, Isabelle Seif, Angelo Parini, Olivier Cuvillier
Journal: Circulation Research (2006)

The mitochondrial enzyme monoamine oxidase (MAO), its isoform MAO-A, plays a major role in reactive oxygen species-dependent cardiomyocyte apoptosis and postischemic cardiac damage. In the current study, we investigated whether sphingolipid metabolism can account for mediating MAO-A- and reactive oxygen species-dependent cardiomyocyte apoptosis. In H9c2 cardiomyoblasts, MAO-A-dependent reactive oxygen species generation led to mitochondria-mediated apoptosis, along with sphingosine kinase-1 (SphK1) inhibition. These phenomena were associated with generation of proapoptotic ceramide and decrease in prosurvival sphingosine 1-phosphate. These events were mimicked by inhibition of SphK1 with either pharmacological inhibitor or small interfering RNA, as well as by extracellular addition of C(2)-ceramide or H(2)O(2). In contrast, enforced expression of SphK1 protected H9c2 cells from serotonin- or H(2)O(2)-induced apoptosis. Analysis of cardiac tissues from wild-type mice subjected to ischemia/reperfusion revealed significant upregulation of ceramide and inhibition of SphK1. It is noteworthy that SphK1 inhibition, ceramide accumulation, and concomitantly infarct size and cardiomyocyte apoptosis were significantly decreased in MAO-A-deficient animals. In conclusion, we show for the first time that the upregulation of ceramide/sphingosine 1-phosphate ratio is a critical event in MAO-A-mediated cardiac cell apoptosis. In addition, we provide the first evidence linking generation of reactive oxygen species with SphK1 inhibition. Finally, we propose sphingolipid metabolites as key mediators of postischemic/reperfusion cardiac injury.