tbuckley/cabot-search huggingface dataset:
Array-Based Comparative Genomic Hybridization Identifies <i>CDK4</i> and <i>FOXM1</i> Alterations as Independent Predictors of Survival in Malignant Peripheral Nerve Sheath Tumor
Authors: Jinsheng Yu, Hrishikesh Deshmukh, Jacqueline E. Payton, Christopher Dunham, Bernd W. Scheithauer, Tarik Tihan, Richard A. Prayson, Abhijit Guha, Julia A. Bridge, Rosalie E. Ferner, Guy M. Lindberg, Rebecca J. Gutmann, Ryan J. Emnett, Lorena Salavaggione, David H. Gutmann, Rakesh Nagarajan, Mark A. Watson, Arie Perry
Journal: Clinical Cancer Research (2011)

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with variable patient survival and few known prognostically relevant genomic biomarkers. To identify survival-associated genomic biomarkers, we performed high-resolution array-based comparative genomic hybridization (aCGH) on a large set of MPNSTs.Candidate gene alterations identified by aCGH in 38 MPNSTs were validated at the DNA, RNA, and protein levels on these same tumors and an independent set of 87 MPNST specimens.aCGH revealed highly complex copy number alterations, including both previously reported and completely novel loci. Four regions of copy number gain were associated with poor patient survival. Candidate genes in these regions include SOX5 (12p12.1), NOL1 and MLF2 (12p13.31), FOXM1 and FKBP1 (12p13.33), and CDK4 and TSPAN31 (12q14.1). Alterations of these candidate genes and several others of interest (ERBB2, MYC and TP53) were confirmed by at least 1 complementary methodology, including DNA and mRNA quantitative real-time PCR, mRNA expression profiling, and tissue microarray-based fluorescence in situ hybridization and immunohistochemistry. Multivariate analysis showed that CDK4 gain/amplification and increased FOXM1 protein expression were the most significant independent predictors for poor survival in MPNST patients (P < 0.05).Our study provides new and independently confirmed candidate genes that could serve as genomic biomarkers for overall survival in MPNST patients.
Immunogenic Tumor Cell Death for Optimal Anticancer Therapy: The Calreticulin Exposure Pathway
Authors: Laurence Zitvogel, Oliver Kepp, Laura Senovilla, Laurie Menger, Nathalie Chaput, Guido Kroemer
Journal: Clinical Cancer Research (2010)

Abstract In response to some chemotherapeutic agents such as anthracyclines and oxaliplatin, cancer cells undergo immunogenic apoptosis, meaning that their corpses are engulfed by dendritic cells and that tumor cell antigens are presented to tumor-specific CD8+ T cells, which then control residual tumor cells. One of the peculiarities of immunogenic apoptosis is the early cell surface exposure of calreticulin (CRT), a protein that usually resides in the lumen of the endoplasmic reticulum (ER). When elicited by anthracyclines or oxaliplatin, the CRT exposure pathway is activated by pre-apoptotic ER stress and the phosphorylation of the eukaryotic translation initiation factor eIF2α by the kinase PERK, followed by caspase-8-mediated proteolysis of the ER-sessile protein BAP31, activation of the pro-apoptotic proteins Bax and Bak, anterograde transport of CRT from the ER to the Golgi apparatus and exocytosis of CRT-containing vesicles, finally resulting in CRT translocation onto the plasma membrane surface. Interruption of this complex pathway abolishes CRT exposure, annihilates the immunogenicity of apoptosis, and reduces the immune response elicited by anticancer chemotherapies. We speculate that human cancers that are incapable of activating the CRT exposure pathway are refractory to the immune-mediated component of anticancer therapies. Clin Cancer Res; 16(12); 3100–4. ©2010 AACR.
Urinary free and conjugated 5-S-cysteinyldopa in normal subjects and in patients with melanoma
Authors: V. GRAEF, E. PAUL
Journal: British Journal of Dermatology (1982)

We measured free and total 5‐S‐cystcinyldopa excretion in 24‐h urine specimens from nine patients with malignant melanoma and forty‐five controls, and found that the levels of 5‐S‐cysteinyldopa excretion (measured by a fluorometric method) were greatly increased in the melanoma patients. The conjugates were hydrolysed by enzymatic treatment with β‐glucuroni‐dase/arylsulphatase, and we found that the percentage of conjugated 5‐S‐cysteinyldopa was higher in urines with a low content of free 5‐S‐cysteinyldopa than in those with a higher concentration.
The Metabolic Syndrome and Concentrations of C-Reactive Protein Among U.S. Youth
Authors: Earl S. Ford, Umed A. Ajani, Ali H. Mokdad
Journal: Diabetes Care (2005)

OBJECTIVE—Adults with the metabolic syndrome show biochemical evidence of low-grade inflammation. We sought to examine whether this is true among U.S. youth with the metabolic syndrome. RESEARCH DESIGN AND METHODS—We used data from 1,366 participants aged 12–17 years from the National Health and Nutrition Examination Survey 1999–2000. A modification of the definition of the metabolic syndrome proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults was used. C-reactive protein (CRP) was measured by latex-enhanced nephelometry. RESULTS—Mean and median concentrations of CRP were higher among participants who had the metabolic syndrome (mean 3.8 mg/l, geometric mean 1.8 mg/l) than among those who did not (mean 1.4 mg/l, geometric mean 0.4 mg/l). The percentage of participants with a concentration of CRP &amp;gt;3.0 mg/l was 38.4% among those with the metabolic syndrome and 10.3% among those without the syndrome (P = 0.007). Of the five components of the syndrome, only abdominal obesity was significantly and independently associated with log-transformed concentrations of CRP in multiple linear regression analysis. CONCLUSIONS—Our results show that a large percentage of children and adolescents with the metabolic syndrome have elevated concentrations of CRP. Whether the elevated concentrations of CRP among children and adolescents who have the metabolic syndrome predict future adverse health events remains to be determined.
Acute Myeloid Leukemia and Myelodysplastic Syndromes After Radiation Therapy Are Similar to De Novo Disease and Differ From Other Therapy-Related Myeloid Neoplasms
Authors: Valentina Nardi, Karen M. Winkfield, Chi Young Ok, Andrzej Niemierko, Michael J. Kluk, Eyal C. Attar, Guillermo Garcia-Manero, Sa A. Wang, Robert P. Hasserjian
Journal: Journal of Clinical Oncology (2012)

Therapy-related myeloid neoplasms (t-MN) represent a unique clinical syndrome occurring in patients treated with chemotherapy and/or external-beam radiation (XRT) and are characterized by poorer prognosis compared with de novo disease. XRT techniques have evolved in recent years and are associated with significantly reduced bone marrow exposure. The characteristics of post-XRT t-MN in the current era have not been studied.We analyzed patients who developed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) after XRT alone (47 patients) or cytotoxic chemotherapy/combined-modality therapy (C/CMT, 181 patients) and compared them with patients with de novo MDS or AML (222 patients). We estimated bone marrow exposure to radiation and compared the clinical, pathologic, and cytogenetic features and outcome of the XRT patients with the C/CMT patients and with patients with de novo MDS and AML.Patients with t-MN after XRT alone had superior overall survival (P = .006) and lower incidence of high-risk karyotypes (P = .01 for AML and < .001 for MDS) compared with patients in the C/CMT group. In contrast, there were no significant differences in survival or frequency of high-risk karyotypes between the XRT and de novo groups.AML and MDS diagnosed in the past decade in patients after receiving XRT alone differ from t-MN occurring after C/CMT and share genetic features and clinical behavior with de novo AML/MDS. Our results suggest that post-XRT MDS/AML may not represent a direct consequence of radiation toxicity and warrant a therapeutic approach similar to de novo disease.
Colorectal cancer molecular biology moves into clinical practice
Authors: C. C. Pritchard, W. M. Grady
Journal: Gut (2010)

The promise of personalised medicine is now a clinical reality, with colorectal cancer genetics at the forefront of this next major advance in clinical medicine. This is no more evident than in the recent advances in testing of colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor. In this review, genetic mechanisms of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers) and the prediction of treatment responses (predictive markers) are examined.
The Role of Aquaporins in Dendritic Cell Macropinocytosis
Authors: Annegret de Baey, Antonio Lanzavecchia
Journal: The Journal of Experimental Medicine (2000)

Immature dendritic cells (DCs) constitutively take up large volumes of fluid by macropinocytosis and concentrate the macrosolutes in the endocytic compartment. This concentration mechanism that is the basis of their high capacity to present soluble antigens requires that DCs be capable of rapidly exchanging water across their membranes. We report that two members of the aquaporin family, AQP3 and AQP7, are expressed in immature DCs and are downregulated after maturation. Treatment of DCs with p-chloromercuribenzenesulphonate (pCMBS), a mercuric drug that blocks aquaporins, inhibited uptake and concentration of macrosolutes taken up by fluid phase endocytosis and led to dramatic cell swelling. In contrast, pCMBS did not affect receptor-mediated endocytosis via the mannose receptor. These findings indicate that aquaporins represent essential elements of a volume control mechanism that allows DCs to concentrate macrosolutes taken up via macropinocytosis.
A TRIAL OF 5 IODO-2'-DEOXYURIDINE IN HERPES SIMPLEX.
Authors: F. A. IVE
Journal: British Journal of Dermatology (1964)

Journal Article A TRIAL OF 5 IODO‐2′‐DEOXYURIDINE IN HERPES SIMPLEX. Get access F. A. IVE, M.B., B.S. F. A. IVE, M.B., B.S. Registrar to the Skin Department. St. George's Hospital, Hyde Park Corner, London, S.W.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 11, 1 November 1964, Pages 463–464, https://doi.org/10.1111/j.1365-2133.1964.tb15485.x Published: 01 November 1964
Dietary glycemic index and glucose, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein 3, and leptin levels in patients with acne
Authors: Yesim Kaymak, Esra Adisen, Nilsel Ilter, Aysun Bideci, Demet Gurler, Bulent Celik
Journal: Journal of the American Academy of Dermatology (2007)
Randomized trial to evaluate azithromycin's effects on serum and upper airway IL-8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis
Authors: Avraham Beigelman, Megan Isaacson-Schmid, Geneline Sajol, Jack Baty, Oscar M. Rodriguez, Erin Leege, Kevin Lyons, Toni L. Schweiger, Jie Zheng, Kenneth B. Schechtman, Mario Castro, Leonard B. Bacharier
Journal: Journal of Allergy and Clinical Immunology (2014)
Molecular Basis and Evolutionary Origins of Color Diversity in Great Star Coral Montastraea cavernosa (Scleractinia: Faviida)
Authors: I. V. Kelmanson
Journal: Molecular Biology and Evolution (2003)

Natural pigments are normally products of complex biosynthesis pathways where many different enzymes are involved. Corals and related organisms of class Anthozoa represent the only known exception: in these organisms, each of the host-tissue colors is essentially determined by a sequence of a single protein, homologous to the green fluorescent protein (GFP) from Aequorea victoria. This direct sequence-color linkage provides unique opportunity for color evolution studies. We previously reported the general phylogenetic analysis of GFP-like proteins, which suggested that the present-day diversity of reef colors originated relatively recently and independently within several lineages. The present work was done to get insight into the mechanisms that gave rise to this diversity. Three colonies of the great star coral Montastraea cavernosa (Scleractinia, Faviida) were studied, representing distinct color morphs. Unexpectedly, these specimens were found to express the same collection of GFP-like proteins, produced by at least four, and possibly up to seven, different genetic loci. These genes code for three basic colors—cyan, green, and red—and are expressed differently relative to one another in different morphs. Phylogenetic analysis of the new sequences indicated that the three major gene lineages diverged before separation of some coral families. Our results suggest that color variation in M. cavernosa is not a true polymorphism, but rather a manifestation of phenotypic plasticity (polyphenism). The family level depth of its evolutionary roots indicates that the color diversity is adaptively significant. Relative roles of gene duplication, gene conversion, and point mutations in its evolution are discussed.
Rap1b is required for normal platelet function and hemostasis in mice
Authors: Magdalena Chrzanowska-Wodnicka, Susan S. Smyth, Simone M. Schoenwaelder, Thomas H. Fischer, Gilbert C. White
Journal: Journal of Clinical Investigation (2005)

Rap1b, an abundant small GTPase in platelets, becomes rapidly activated upon stimulation with agonists. Though it has been implicated to act downstream from G protein–coupled receptors (GPCRs) and upstream of integrin αIIbβ3, the precise role of Rap1b in platelet function has been elusive. Here we report the generation of a murine rap1b knockout and show that Rap1b deficiency results in a bleeding defect due to defective platelet function. Aggregation of Rap1b-null platelets is reduced in response to stimulation with both GPCR-linked and GPCR-independent agonists. Underlying the defective Rap1b-null platelet function is decreased activation of integrin αIIbβ3 in response to stimulation with agonists and signaling downstream from the integrin αIIbβ3. In vivo, Rap1b-null mice are protected from arterial thrombosis. These data provide genetic evidence that Rap1b is involved in a common pathway of integrin activation, is required for normal hemostasis in vivo, and may be a clinically relevant antithrombotic therapy target.
Trajectories of risk after hospitalization for heart failure, acute myocardial infarction, or pneumonia: retrospective cohort study
Authors: K. Dharmarajan, A. F. Hsieh, V. T. Kulkarni, Z. Lin, J. S. Ross, L. I. Horwitz, N. Kim, L. G. Suter, H. Lin, S.-L. T. Normand, H. M. Krumholz
Journal: BMJ (2015)

<b>Objective</b> To characterize the absolute risks for older patients of readmission to hospital and death in the year after hospitalization for heart failure, acute myocardial infarction, or pneumonia. <b>Design</b> Retrospective cohort study. <b>Setting</b> 4767 hospitals caring for Medicare fee for service beneficiaries in the United States, 2008-10. <b>Participants</b> More than 3 million Medicare fee for service beneficiaries, aged 65 years or more, surviving hospitalization for heart failure, acute myocardial infarction, or pneumonia. <b>Main outcome measures</b> Daily absolute risks of first readmission to hospital and death for one year after discharge. To illustrate risk trajectories, we identified the time required for risks of readmission to hospital and death to decline 50% from maximum values after discharge; the time required for risks to approach plateau periods of minimal day to day change, defined as 95% reductions in daily changes in risk from maximum daily declines after discharge; and the extent to which risks are higher among patients recently discharged from hospital compared with the general elderly population. <b>Results</b> Within one year of hospital discharge, readmission to hospital and death, respectively, occurred following 67.4% and 35.8% of hospitalizations for heart failure, 49.9% and 25.1% for acute myocardial infarction, and 55.6% and 31.1% for pneumonia. Risk of first readmission had declined 50% by day 38 after hospitalization for heart failure, day 13 after hospitalization for acute myocardial infarction, and day 25 after hospitalization for pneumonia; risk of death declined 50% by day 11, 6, and 10, respectively. Daily change in risk of first readmission to hospital declined 95% by day 45, 38, and 45; daily change in risk of death declined 95% by day 21, 19, and 21. After hospitalization for heart failure, acute myocardial infarction, or pneumonia, the magnitude of the relative risk for hospital admission over the first 90 days was 8, 6, and 6 times greater than that of the general older population; the relative risk of death was 11, 8, and 10 times greater. <b>Conclusions</b> Risk declines slowly for older patients after hospitalization for heart failure, acute myocardial infarction, or pneumonia and is increased for months. Specific risk trajectories vary by discharge diagnosis and outcome. Patients should remain vigilant for deterioration in health for an extended time after discharge. Health providers can use knowledge of absolute risks and their changes over time to better align interventions designed to reduce adverse outcomes after discharge with the highest risk periods for patients.
Countdown to 2015 and beyond: fulfilling the health agenda for women and children
Authors: Jennifer Harris Requejo, Jennifer Bryce, Aluisio JD Barros, Peter Berman, Zulfiqar Bhutta, Mickey Chopra, Bernadette Daelmans, Andres de Francisco, Joy Lawn, Blerta Maliqi, Elizabeth Mason, Holly Newby, Carole Presern, Ann Starrs, Cesar G Victora
Journal: The Lancet (2014)
Inhibition of adenosine 5'-monophosphate- and methacholine-induced bronchoconstriction in asthma by inhaled frusemide
Authors: R Polosa, LC Lau, ST Holgate
Journal: European Respiratory Journal (1990)

Recent studies have shown that inhaled frusemide exerts a protective effect against various bronchoconstrictor stimuli in asthma including exercise, fog and allergen. Since mast cell activation seems to be a component of bronchoconstriction by these stimuli it is possible that inhibition of mediator release accounts for some or all of the inhibitory effects of frusemide in asthma. Since inhaled adenosine 5'-monophosphate (AMP) is another stimulus that produces bronchoconstriction by augmenting mast cell mediator release, we have investigated the ability of this drug to antagonise the airway effects of inhaled AMP and methacholine in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Inhaled frusemide (approximately 28 mg) administered 5 min prior to challenge increased the provocation concentration of inhaled AMP and methacholine required to reduce forced expiratory volume in one second (FEV) by 20% from baseline from 30 to 96 mg.ml-1 (p less than 0.01) and from 1.1 to 1.8 mg.ml-1 (p less than 0.01), respectively. The protection that frusemide afforded against AMP was significantly greater than that against methacholine (p less than 0.05). These data suggest that inhaled frusemide may serve as a functional antagonist against a smooth muscle spasmogen, such as methacholine, possibly by augmenting prostanoid generation. Its more potent activity against AMP and other bronchoconstrictor stimuli, that are considered to involve mast cell mediators, suggests an additional action on mast cell functions possibly at the level of the Ca++/Mg(++)-ATPase.
Imaging mass spectrometry reveals modified forms of histone H4 as new biomarkers of microvascular invasion in hepatocellular carcinomas
Authors: Nicolas Poté, Theodore Alexandrov, Julie Le Faouder, Samira Laouirem, Thibaut Léger, Mouniya Mebarki, Jacques Belghiti, Jean-Michel Camadro, Pierre Bedossa, Valérie Paradis
Journal: Hepatology (2013)

Microvascular invasion (MiVI) is a major risk factor in postoperative tumor recurrence and mortality in hepatocellular carcinoma (HCC). Unfortunately, this histological feature is usually missed by liver biopsy because of limited sampling, and MiVI is commonly detected only after surgery and examination of the full resected specimen. To date, there exists no reliable tool for identifying MiVI prior to surgical procedures. This study aimed to compare the proteome of HCC with and without MiVI in order to identify surrogate biomarkers of MiVI. A training cohort comprising surgically resected primary HCC with MiVI (n = 30) and without MiVI (n = 26) was subjected to matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS). Comparative analysis of acquired mass spectra of the two groups yielded 30 differential protein peaks, among which 28 were more strongly expressed in HCC with MiVI. Among these, two peaks were identified as N-term acetylated histone H4 dimethylated at lysine (K) 20, and N-term acetylated histone H4 dimethylated at K20 and acetylated at K16. Both peaks were validated in the training cohort and in an independent validation cohort (n = 23) by immunohistochemistry and western blot. Conclusion : These results demonstrate the potential of MALDI IMS for uncovering new relevant biomarkers of MiVI in HCC, and highlight the role of epigenetic modifications in the prognosis of HCC. Preoperative detection of modified forms of histone H4 expression in tumor biopsies would be helpful in management of patients with HCC. (Hepatology 2013;53:983–994)
Helper activity for immunoglobulin synthesis of T helper type 1 (Th1) and Th2 human T cell clones: the help of Th1 clones is limited by their cytolytic capacity.
Authors: G F Del Prete, M De Carli, M Ricci, S Romagnani
Journal: The Journal of Experimental Medicine (1991)

A large number of CD4+ human T helper type 1 (Th1) clones specific for purified protein derivative and of Th2 clones specific for the excretory/secretory antigen of Toxocara canis, derived from the same individuals, were analyzed for both cytotoxic capacity and helper function for immunoglobulin (Ig) synthesis. The great majority of Th1, but only a minority of Th2 clones exhibited cytolytic activity. All Th2 (noncytolytic) clones induced IgM, IgG, IgA, and IgE synthesis by autologous B cells in the presence of the specific antigen, and the degree of response was proportional to the number of Th2 cells added to B cells. Under the same experimental conditions, Th1 (cytolytic) clones provided helper function for IgM, IgG, and IgA, but not IgE, synthesis with a peak response at 1:1 T/B cell ratio. At higher T/B cell ratios, a strong decrease of Ig synthesis was observed. All Th1 clones lysed Epstein-Barr virus transformed autologous B cells pulsed with the specific antigen. The decrease of Ig production at high T/B cell ratios correlated with the lytic activity of Th1 clones against autologous antigen-presenting B cell targets. These data suggest that Th1 differ from Th2 human T cell clones not only for their profile of cytokine secretion, but also for cytolytic potential and mode of help for B cell Ig synthesis.