tbuckley/cabot-search huggingface dataset:
Oral Desensitization for Penicillin Sensitivity
Authors: Barbara J. Stark
Journal: JAMA (1987)

<h3>To the Editor.—</h3> In the recent report of a successful parenteral desensitization of a pregnant, penicillin-allergic woman with syphilis, Ziaya and colleagues<sup>1</sup>proposed that parenteral desensitization is preferable to the more widely studied oral desensitization method.<sup>2-4</sup>Fatal and near-fatal anaphylactic reactions during parenteral desensitization are well documented<sup>2</sup>and should have been considered more carefully. Four important considerations suggest that oral desensitization is safer. First, deaths from orally administered penicillins are exceedingly rare.<sup>2</sup>In one large study, all of 72 fatal anaphylactic reactions to penicillin were induced by parenteral therapy,<sup>5</sup>despite the more prevalent use of oral therapy. Second, the drug polymers and penicillin-mold protein conjugates that contaminate therapeutic materials, thought to be important elicitors of anaphylaxis,<sup>6</sup>would not be expected to be absorbed after oral administration. Third, blood levels gradually rise after oral administration, favoring univalent (harmless) conjugation, in contrast to the locally very
PPAR action in insulin resistance unraveled by metabolomics: potential clinical implications
Authors: Andrew D Patterson, Jeffrey M Peters
Journal: Genome Medicine (2011)

Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activated receptor β/δ (PPARβ/δ) and PPARγ. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes. See related research article: http://genomebiology.com/2011/12/8/R75
Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesis
Authors: Eric Letouzé, Yves Allory, Marc A Bollet, François Radvanyi, Frédéric Guyon
Journal: Genome biology (2010)

Abstract We present a computational method, TuMult, for reconstructing the sequence of copy number changes driving carcinogenesis, based on the analysis of several tumor samples from the same patient. We demonstrate the reliability of the method with simulated data, and describe applications to three different cancers, showing that TuMult is a valuable tool for the establishment of clonal relationships between tumor samples and the identification of chromosome aberrations occurring at crucial steps in cancer progression.
Emerging Therapies to Prevent Skeletal Morbidity in Men With Prostate Cancer
Authors: Philip J. Saylor, Richard J. Lee, Matthew R. Smith
Journal: Journal of Clinical Oncology (2011)

Skeletal morbidity is a prominent burden to men with advanced prostate cancer throughout the natural history of the disease. Bone metastases can cause pain and greatly elevate the risk for fractures and other structural complications. Distinct from the problem of metastases, treatment-related osteoporosis and associated fragility fractures are potential complications of androgen-deprivation therapy. Bone-targeted therapies for prostate cancer have therefore been the focus of considerable research and drug development efforts. The osteoclast is a validated therapeutic target in the management of prostate cancer. Osteoclast inhibition with zoledronic acid (a bisphosphonate) or with denosumab (a monoclonal antibody to RANK ligand) reduces risk for skeletal events in men with castration-resistant prostate cancer metastatic to bone. Osteoclast inhibition with any of several bisphosphonates improves bone mineral density, a surrogate for osteoporotic fracture risk. Denosumab and toremifene (a selective estrogen receptor modulator) have each been shown to reduce osteoporotic fracture risk among men receiving androgen-deprivation therapy. Beta-emitting radiopharmaceuticals reduce pain due to metastatic disease. Investigations involving alpha-emitting radium-223, endothelin-A receptor antagonists atrasentan and zibotentan, proto-oncogene tyrosine-protein kinase (SRC) inhibitor dasatinib, and tyrosine kinase inhibitor cabozantinib (XL184) are ongoing in clinical trials and are also discussed.
Evoked and Spontaneous Purinergic Junctional Ca <sup>2+</sup> Transients (jCaTs) in Rat Small Arteries
Authors: Christine Lamont, W. Gil Wier
Journal: Circulation Research (2002)

Confocal microscopy of fluo-4 fluorescence in pressurized rat mesenteric small arteries subjected to low-frequency electrical field stimulation revealed Ca 2+ transients in perivascular nerves and novel, spatially localized Ca 2+ transients in adjacent smooth muscle cells. These muscle Ca 2+ transients occur with a very brief latency to the stimulus pulse (most &lt;3 ms). They are wider (≈5 μm) and last longer (t 1/2 , 145 ms) than Ca 2+ sparks. They are abolished by the purinergic receptor (P2X) antagonist suramin, but they are totally unaffected by the α 1 -adrenoceptor antagonist prazosin or by capsaicin (which inhibits the function of perivascular sensory nerves). We conclude that these novel Ca 2+ transients represent Ca 2+ entering smooth muscle cells through P2X receptors activated by ATP released from sympathetic nerves, and we therefore call them “junctional Ca 2+ transients” or jCaTs. As expected from spontaneous neurotransmitter release, jCaTs also occur spontaneously, with characteristics identical to evoked jCaTs. Visualization of sympathetic neurotransmission shows that purinergic components dominate at low frequencies of sympathetic nerve fiber activation.
The molecular evolution of the alcohol dehydrogenase and alcohol dehydrogenase-related genes in the Drosophila melanogaster species subgroup.
Authors: P S Jeffs, E C Holmes, M Ashburner
Journal: Molecular Biology and Evolution (1994)

The DNA sequences of the Adh genes of three members of the Drosophila melanogaster species subgroup have been determined. This completes the Adh sequences of the eight species of this subgroup. Two species, D. yakuba and D. teissieri, possess processed Adh pseudogenes. In all of the species of the subgroup, a gene of unknown function, Adhr, is located about 300 bp 3' to Adh. Although this gene is experiencing a higher rate of synonymous substitution than Adh, it is more constrained at the amino acid level. Phylogenetic relationships between all eight members of the melanogaster subgroup have been analyzed using a variety of methods. All analyses suggested that the D. yakuba and D. teissieri pseudogenes have a single common ancestor, rather than evolving independently in each species, and that D. melanogaster is the sister species to D. simulans, D. sechellia, and D. mauritiana. The evolutionary relationships of the latter three species remain equivocal.
Expression of endogenous murine leukemia viruses during the course of a protracted immunological disorder.
Authors: M Y Armstrong, N H Ruddle, F F Richards
Journal: The Journal of Experimental Medicine (1977)

Mice of the low leukemia (BALB/cJ x A/J)F1 hybrid (CAF1) strain express B-and N-tropic infectious murine leukemia virus (MuLV) after the age of 6 mo. Initation of a protracted immunological disorder, the graft-versus-host reaction (GVHR), at 7 wk of age, accelerates the induction of both these mouse-tropic endogenous viruses, and preferentially enhances the replication of B-tropic MuLV. The earlier appearance of B-tropic MuLV in a greater proportion of mice and in higher titer is thought to be casually related to the eventual development of lymphoreticular tumors in the GVHR mice, since previous studies have shown that these same tumors can be reproduced by inoculating syngeneic recipients with serially passaged GVHR extracts containing B-tropic MuLV.
CYP2C19 Genotype, Clopidogrel Metabolism, Platelet Function, and Cardiovascular Events
Authors: Michael V. Holmes, Pablo Perel, Tina Shah, Aroon D. Hingorani, Juan P. Casas
Journal: JAMA (2011)

The US Food and Drug Administration recently recommended that CYP2C19 genotyping be considered prior to prescribing clopidogrel, but the American Heart Association and American College of Cardiologists have argued evidence is insufficient to support CYP2C19 genotype testing.To appraise evidence on the association of CYP2C19 genotype and clopidogrel response through systematic review and meta-analysis.PubMed and EMBASE from their inception to October 2011.Studies that reported clopidogrel metabolism, platelet reactivity or clinically relevant outcomes (cardiovascular disease [CVD] events and bleeding), and information on CYP2C19 genotype were included.We extracted information on study design, genotyping, and disease outcomes and investigated sources of bias.We retrieved 32 studies of 42,016 patients reporting 3545 CVD events, 579 stent thromboses, and 1413 bleeding events. Six studies were randomized trials ("effect-modification" design) and the remaining 26 reported individuals exposed to clopidogrel ("treatment-only" design). In treatment-only analysis, individuals with 1 or more CYP2C19 alleles associated with lower enzyme activity had lower levels of active clopidogrel metabolites, less platelet inhibition, lower risk of bleeding (relative risk [RR], 0.84; 95% CI, 0.75-0.94; absolute risk reduction of 5-8 events per 1000 individuals), and higher risk of CVD events (RR, 1.18; 95% CI, 1.09-1.28; absolute risk increase of 8-12 events per 1000 individuals). However, there was evidence of small-study bias (Harbord test P = .001). When analyses were restricted to studies with 200 or more events, the point estimate was attenuated (RR, 0.97; 95% CI, 0.86-1.09). In effect-modification studies, CYP2C19 genotype was not associated with modification of the effect of clopidogrel on CVD end points or bleeding (P > .05 for interaction for both). Other limitations included selective outcome reporting and potential for genotype misclassification due to problems with the * allele nomenclature for cytochrome enzymes.Although there was an association between the CYP2C19 genotype and clopidogrel responsiveness, overall there was no significant association of genotype with cardiovascular events.
An in vivo and in vitro study of the mechanism of prednisone-induced insulin resistance in healthy subjects.
Authors: G Pagano, P Cavallo-Perin, M Cassader, A Bruno, A Ozzello, P Masciola, A M Dall'omo, B Imbimbo
Journal: Journal of Clinical Investigation (1983)

Prednisone-induced insulin resistance may depend on either reduced sensitivity (receptor defect) or reduced response to insulin (postreceptor defect). To clarify the mechanism of prednisone-induced insulin resistance, a [3H]glucose infusion (1 microCi/min) was performed for 120 min before and during a euglycemic clamp repeated at approximately 100, approximately 1,000, and approximately 10,000 microU/ml steady state plasma insulin concentration in 10 healthy, normal weight subjects, aged 35 +/- 7 yr. Each test was repeated after 7-d administration of placebo or prednisone (15 plus 15 mg/d per subject), in a randomized sequence with an interval of 1 mo between the two tests. Mean fasting blood glucose (89.5 +/- 2.1 vs. 83.7 +/- 1.9 mg/dl) and mean fasting plasma insulin values (17.8 +/- 1.2 vs. 14.3 +/- 0.8 microU/ml) were significantly higher (P less than 0.01) after prednisone. The insulin sensitivity index (glucose metabolic clearance rate in ml/kg per min) was significantly lower (P less than 0.001) after prednisone at all three steady state plasma insulin levels: 2.8 +/- 0.3 vs. 7.4 +/- 1.1 at approximately 100 microU/ml; 6.0 +/- 0.5 vs. 12.2 +/- 1.1 at approximately 1,000 microU/ml; 7.4 +/- 0.6 vs. 14.4 +/- 0.5 at approximately 10,000 microU/ml. Fasting glucose production (in mg/kg per min) was significantly higher after prednisone: 3.7 +/- 0.2 vs. 2.9 +/- 0.2, P less than 0.001. Suppression of glucose production at steady state plasma insulin level of approximately 100 microU/ml was less after prednisone (1.01 +/- 0.35 vs. 0.14 +/- 0.13, NS), and total at approximately 1,000 and approximately 10,000 microU/ml after both prednisone and placebo. The metabolic kinetic parameters of insulin after prednisone were not significantly different from those after placebo. In addition, insulin binding and 3-ortho-methyl-glucose transport were studied in vitro on fat cells from 16 normal-weight surgical candidates aged 40 +/- 8 yr (10 treated with placebo and 6 with prednisone as above). No significant difference was observed with regard to specific insulin binding (tested with 1 ng/ml hormone only), whereas significant transport differences were noted at the basal level (0.40 +/- 0.10 vs. 0.54 +/- 0.12 pmol/10(5) cells, P less than 0.05), and at increasing concentrations up to the maximum stimulation values (5 ng/ml): 0.59 +/- 0.04 vs. 0.92 +/- 0.12 pmol/10(5) cells, P less than 0.005. These results suggest that (a) administration of an anti-inflammatory dose of prednisone for 7 d induces insulin resistance in man; (b) this is more dependent on depressed peripheral glucose utilization than on increased endogenous production; (c) total insulin binding on isolated adipocytes is not significantly affected; (d) insulin resistance is primarily the outcome of postreceptor defect (impaired glucose transport).
Mining the mutanome: developing highly personalized Immunotherapies based on mutational analysis of tumors
Authors: Willem W Overwijk, Ena Wang, Francesco M Marincola, Hans-Georg Rammensee, Nicholas P Restifo
Journal: Journal for ImmunoTherapy of Cancer (2013)

T cells can mediate remarkable tumor regressions including complete cure in patients with metastatic cancer. Genetic alterations in an individual's cancer cells (the mutanome) encode unique peptides (m-peptides) that can be targets for T cells. The recent advances in next-generation sequencing and computation prediction allows, for the first time, the rapid and affordable identification of m-peptides in individual patients. Despite excitement about the extended spectrum of potential targets in personalized immunotherapy, there is no experience or consensus on the path to their successful clinical application. Major questions remain, such as whether clinical responses to cytokine therapy, T cell transfer, and checkpoint blockade are primarily mediated by m-peptide-specific reactivity, whether m-peptides can be effectively used as vaccines, and which m-peptides are most potently recognized. These and other technological, immunological and translational questions will be explored during a 1-day Workshop on Personalized Cancer Immunotherapy by the Society for Immunotherapy of Cancer, directly before the Annual Meeting, on November 7, 2013 at the National Harbor, MD near Washington, DC.
Patients with systemic lupus erythematosus show a normal responsive search score in exploratory eye movement analysis: comparison with schizophrenia
Authors: Y Matsukawa
Journal: Annals of the Rheumatic Diseases (2002)

To assess whether a difference in psychiatric vulnerability exists between patients with systemic lupus erythematosus (SLE) and those with schizophrenia.Twenty women with SLE underwent exploratory eye movement analysis, and a responsive search score (RSS) was obtained, two months after the onset of the disease. Fifteen women with schizophrenia in remission also underwent this analysis. Exploratory eye movement was recorded by an eye mark recorder, which detects corneal reflection of infrared light. The number of eye fixations (instance of more than 0.2 seconds of eye fixation time) was recorded, and the RSS was calculated from eye fixation analysis.Mean (SD) RSS differed significantly between patients with SLE and those with schizophrenia (9.85 (1.87) v 7.27 (1.58) points, respectively, p<0.0001), whereas no difference in mean RSS was found between patients with SLE and 19 normal women. No difference in mean RSS was found between patients with active SLE and those with inactive SLE (9.51 (1.87) v 10.0 (1.77) points).The psychiatric vulnerability in patients with SLE, measured by the RSS, differs from that in patients with schizophrenia.
Calcitonin gene related peptide and neuropeptide Y in skeletal muscle after eccentric exercise: a microdialysis study
Authors: S Jonhagen, P Ackermann, T Saartok, P A Renstrom
Journal: British Journal of Sports Medicine (2006)

Objectives: To detect neuropeptides in human skeletal muscle at rest and after eccentric exercise. Method: Eight healthy subjects participated in the study. Microdialysis of the distal part of the vastus lateralis of the quadriceps muscle and pain evaluation were performed immediately after eccentric exercise, after two days, and at rest. Calcitonin gene related peptide (CGRP) and neuropeptide Y (NPY), representatives of the sensory and autonomic nervous system, were analysed by radioimmunoassay. Results: Overall, the measured concentrations were low, some even below the limit of detection. At rest, CGRP was detected in two of seven samples, but after eccentric exercise it was detected in 27 of 30 samples. At rest, all NPY concentrations were below the limit of detection, but after exercise it was found in six of 30 samples. Conclusion: The significant increase in detectability of CGRP after eccentric exercise may be related to the increased experience of pain. Therefore the occurrence of CGRP after heavy eccentric exercise may be associated with the regulation of delayed onset muscle soreness and possibly also the stimulation of tissue regeneration.
Haptoglobin Genotype and the Rate of Renal Function Decline in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study
Authors: Trevor J. Orchard, Wanjie Sun, Patricia A. Cleary, Saul M. Genuth, John M. Lachin, Paula McGee, Andrew D. Paterson, Philip Raskin, Yefim Anbinder, Andrew P. Levy, Dcct
Journal: Diabetes Care (2013)
P08.14 * SURVIVAL OF BREAST CANCER PATIENTS WITH SYNCHRONOUS OR METACHRONOUS CNS METASTASES
Authors: V. K. Y. Ho, J. M. M. Gijtenbeek, D. Brandsma, L. V. Beerepoot, G. S. Sonke, M. van der Heiden-van der Loo
Journal: Neuro-Oncology (2014)

BACKGROUND: Central nervous system (CNS) metastases represent a serious complication for breast cancer patients. This retrospective survey examines overall survival of unselected patients diagnosed with synchronous or metachronous CNS metastases to establish patient and tumour characteristics as well as treatment modalities affecting patients' prognosis. PATIENTS AND METHODS: Information on 732 breast cancer patients with CNS metastases was retrieved from the Netherlands Cancer Registry (NCR) database. Over the period 2004-2010, we identified 163 patients who presented with synchronous CNS metastases, 142 of which involved brain parenchymal metastases. 569 Patients who were initially disease-free developed metachronous CNS metastases during follow-up, and 489 of them were diagnosed with brain metastases. We measured patients' overall survival from the date of metastatic diagnosis, and the impact of prognostic factors on survival was assessed both univariately and multivariately using extended Cox-regression models. RESULTS: For all patients, triple-negative breast cancer and abstinence of systemic therapy proved prognostically unfavourable. In addition, surgery for the primary tumour and metastasectomy appear to improve survival in patients with synchronous CNS metastasis. In patients with metachronous metastases, higher initial stage (III) and the occurrence of other metastases prior to and simultaneously with CNS metastasis were associated with poorer survival whereas younger age (<50 years) and a prolonged time interval until metastatic diagnosis (>1 year) are prognostically favourable. Although metastasectomy and radiation therapy also showed an association with improved survival, their impact varied time-dependently and they were therefore included in our model as time-varying covariates. CONCLUSIONS: Triple-negative disease and abstinence of systemic therapy constitute prognostically unfavourable factors for all patients with CNS metastases. Other factors affecting survival vary between synchronous and metachronous metastasis. With respect to therapeutic factors, the impact of selection bias and hence overestimation of treatment effects should be kept in mind.
β1,6-Branched Oligosaccharides Are Increased in Lymph Node Metastases and Predict Poor Outcome in Breast Carcinoma
Authors: Tamara Handerson, Robert Camp, Malini Harigopal, David Rimm, John Pawelek
Journal: Clinical Cancer Research (2005)

Abstract Purpose: This study was designed to provide a comprehensive assessment on the role of β1,6-branched oligosaccharides in the metastasis and outcome of breast carcinoma. Generation of these structures on N-glycans is initiated by β1,6-N-acetylglucosaminyltransferase V and used by both myeloid cells and cancer cells in systemic migration. Experimental Design: Tissue microarrays of &amp;gt;700 tumors (&amp;gt;400 patients; 30-year follow-up data) were stained through lectin histochemistry with leukocytic phytohemagglutinin (LPHA), a selective marker for β1,6-branched oligosaccharides. Node-negative and node-positive primary tumors and patient-matched lymph node metastases were scored by blinded observers. Results: Metastases stained at significantly greater intensities than did the patient-matched primary tumors (P &amp;lt; 0.0001), demonstrating for the first time that the abundance of β1,6-branched oligosaccharides was directly associated with breast carcinoma nodal metastasis. Multivariate analyses revealed that β1,6-branched oligosaccharides in primary tumors were a predictor of poor outcome, most notably in node-negative tumors, where an LPHA staining score of 3+ gave a risk factor of 3.3, independent of tumor size, nuclear grade, or patient age (P = 0.007). Conclusions: The data firmly establish a role for β1,6-N-acetylglucosaminyltransferase V activity and β1,6-branched oligosaccharides in breast carcinoma metastasis, and reemphasize the involvement, although poorly understood, of aberrant glycosylation in tumor progression.
Mental Health in Lesbian, Gay, Bisexual, and Transgender (LGBT) Youth
Authors: Stephen T. Russell, Jessica N. Fish
Journal: Annual Review of Clinical Psychology (2016)

Today's lesbian, gay, bisexual, and transgender (LGBT) youth come out at younger ages, and public support for LGBT issues has dramatically increased, so why do LGBT youth continue to be at high risk for compromised mental health? We provide an overview of the contemporary context for LGBT youth, followed by a review of current science on LGBT youth mental health. Research in the past decade has identified risk and protective factors for mental health, which point to promising directions for prevention, intervention, and treatment. Legal and policy successes have set the stage for advances in programs and practices that may foster LGBT youth mental health. Implications for clinical care are discussed, and important areas for new research and practice are identified.
Pulmonary transplantation of macrophage progenitors as effective and long-lasting therapy for hereditary pulmonary alveolar proteinosis
Authors: Christine Happle, Nico Lachmann, Jelena Škuljec, Martin Wetzke, Mania Ackermann, Sebastian Brennig, Adele Mucci, Adan Chari Jirmo, Stephanie Groos, Anja Mirenska, Christina Hennig, Thomas Rodt, Jens P. Bankstahl, Nicolaus Schwerk, Thomas Moritz, Gesine Hansen
Journal: Science Translational Medicine (2014)

Macrophage progenitors are an effective and long-lasting therapy of hereditary pulmonary alveolar proteinosis.
Comparison Of Montelukast Versus Salmeterol In Children With Asthma Carrying At-Risk β2adrenergic Receptor Polymorphism: A Genotype-Stratified Randomised Controlled Trial
Authors: K. Basu, H.P. Donald, B.J. Lipworth, R. Tavendale, D.F. Macgregor, S.A. Ogston, C.N.A. Palmer, S. Mukhopadhyay
Journal: Journal of Allergy and Clinical Immunology (2011)