tbuckley/cabot-search huggingface dataset:
Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia
Authors: Kathryn G. Roberts, Ryan D. Morin, Jinghui Zhang, Martin Hirst, Yongjun Zhao, Xiaoping Su, Shann-Ching Chen, Debbie Payne-Turner, Michelle L. Churchman, Richard C. Harvey, Xiang Chen, Corynn Kasap, Chunhua Yan, Jared Becksfort, Richard P. Finney, David T. Teachey, Shannon L. Maude, Kane Tse, Richard Moore, Steven Jones, Karen Mungall, Inanc Birol, Michael N. Edmonson, Ying Hu, Kenneth E. Buetow, I-Ming Chen, William L. Carroll, Lei Wei, Jing Ma, Maria Kleppe, Ross L. Levine, Guillermo Garcia-Manero, Eric Larsen, Neil P. Shah, Meenakshi Devidas, Gregory Reaman, Malcolm Smith, Steven W. Paugh, William E. Evans, Stephan A. Grupp, Sima Jeha, Ching-Hon Pui, Daniela S. Gerhard, James R. Downing, Cheryl L. Willman, Mignon Loh, Stephen P. Hunger, Marco A. Marra, Charles G. Mullighan
Journal: Cancer Cell (2012)
Prevention of Gram-Negative Bacillary Pneumonia Using Aerosol Polymyxin as Prophylaxis. I. EFFECT ON THE COLONIZATION PATTERN OF THE UPPER RESPIRATORY TRACT OF SERIOUSLY ILL PATIENTS
Authors: Sheldon Greenfield, Daniel Teres, Leonard S. Bushnell, John Hedley-Whyte, David S. Feingold
Journal: Journal of Clinical Investigation (1973)

A prospective study used polymyxin B by aerosol to reduce colonization of the upper respiratory tract with nosocomial gram-negative bacilli. 58 high-risk patients from the Respiratory-Surgical Intensive Care Unit entered the trial. 33 were randomly selected to receive 2.5 mg/kg/day of polymyxin B by hand atomizer into the pharynx, and tracheal tube if present. 17 of 25 control patients became colonized with gram-negative bacilli as compared with 7 of 33 polymyxin-treated patients (p < 0.01). Control patients became colonized with a total of 33 gram-negative bacilli: 3 were Pseudomonas aeruginosa, 21 were species of Enterobacteriaceae. The polymyxin-treated patients became colonized with a total of 11 gram-negative bacilli: no P. aeruginosa and only 3 species of Enterobacteriaceae were recovered. Colonization increased with duration in Respiratory-Surgical Intensive Care Unit and with time of required controlled ventilation. Polymyxin most effectively prevented the increase in colonization in treated patients who stayed in the Respiratory-Surgical Intensive Care Unit for longer than 1 wk and who required controlled ventilation for at least 72 h.
The Story of Hyperparathyroidism at the Massachusetts General Hospital
Authors: Oliver Cope
Journal: New England Journal of Medicine (1966)

HYPERPARATHYROIDISM was discovered nearly simultaneously in Europe and America just forty years ago (1925 and 1926).1 2 3 4 5 The manner of discovery on either side of the Atlantic was basically different. Neither side was aware of what was happening on the other, but all on both sides thought of it then as a disease of bone and rare. Over the years, however, we have come to realize that the primary glandular disorder appears in a variety of clinical forms and the disease is by no means uncommon. It was the American approach to the discovery that led to the wider recognition of . . .
Abstract 5713: Significant systemic therapeutic effects of high-LET immunoradiation by 212Pb-Trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice
Authors: Zongqing Tan, Pingping Chen, Nathan Schneider, Samuel Glover, Lingling Cui, Julien Torgue, Oliver Rixe, Henry B. Spitz, Zhongyun Dong
Journal: Cancer Research (2012)

Abstract Purpose The purpose of this study was to determine therapeutic effects and systemic toxicity of 212Pb-Trastuzumab in an orthotopic model of human prostate cancer cells in nude mice. Experimental Design TCMC-Trastuzumab was radiolabeled with 212Pb. The activity and integrity of 212Pb-Trastuzumab was confirmed by a competitive binding assay and SDS-PAGE analysis. Therapeutic effects were determined in an orthotopic model of human prostate cancer in nude mice. Body weight, blood cell counts, serum alanine transaminase (ALT), blood urea nitrogen (BUN), and tissue histology were examined to evaluate systemic toxicity of 212Pb-Trastuzumab therapy. Results The 212Pb-Trastuzumab generated from the procedure was intact and had high binding affinity with a dissociation constant (Kd) of 3.9 ± 0.99 nM. PC-3MM2 cells, which expressed relatively a lower level of Her2 both in culture and in tumors, were used in the study. A single injection of 212Pb-Trastuzumab reduced tumor growth by 60-80%, reduced aortic lymph node metastasis, and prolonged the survival of tumor-bearing mice. Treatment with 212Pb-Trastuzumab did not cause significant changes in body weight, serum SGPT and BUN, hematological profiles, and histological morphology of several major organs of tumor-bearing mice. Conclusion The data presented in this report demonstrated that the 212Pb-Trastuzumab therapy did not cause significant systemic toxicity and was very effective in retarding tumor growth and prolonging survival of mice bearing tumors that express very low levels of Her2. These findings suggest that 212Pb-Trastuzumab, used alone or in combination with other means, could be an effective modality for management of advanced human prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5713. doi:1538-7445.AM2012-5713
Features of the Metabolic Syndrome and Diabetes Mellitus as Predictors of Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis
Authors: Ronit Katz, Nathan D. Wong, Richard Kronmal, Junichiro Takasu, David M. Shavelle, Jeffrey L. Probstfield, Alain G. Bertoni, Matthew J. Budoff, Kevin D. O’Brien
Journal: Circulation (2006)

Background— Calcific aortic valve disease is common in the elderly, is correlated with common cardiovascular risk factors, and is associated with increased cardiovascular event risk; however, whether metabolic syndrome is associated with an increased prevalence of aortic valve calcium (AVC) is not known. Methods and Results— The prevalence of AVC, as assessed by computed tomography, was compared in 6780 Multi-Ethnic Study of Atherosclerosis (MESA) participants with metabolic syndrome (n=1550; National Cholesterol Education Program’s Adult Treatment Panel III [ATP III] criteria), diabetes mellitus (n=1016), or neither condition (n=4024). The prevalence of AVC for those with neither condition, metabolic syndrome, or diabetes mellitus was, respectively, 8%, 12%, and 17% in women ( P &lt;0.001) and 14%, 22%, and 24% in men ( P &lt;0.001). Compared with those with neither condition, the adjusted relative risks for the presence of AVC were 1.45 (95% CI 1.11 to 1.90) for metabolic syndrome and 2.12 (95% CI 1.54 to 2.92) for diabetes mellitus in women and 1.70 (95% CI 1.32 to 2.19) for metabolic syndrome and 1.73 (95% CI 1.33 to 2.25) for diabetes mellitus in men. There was a graded, linear relationship between AVC prevalence and the number of metabolic syndrome components in both women and men (both P &lt;0.001). Similar results were obtained when the International Diabetes Federation metabolic syndrome definition was used. Conclusions— In the MESA cohort, the metabolic syndrome and diabetes mellitus are associated with increased risk of AVC, and AVC prevalence is increased with increasing number of metabolic syndrome components.
Genomic Landscape of Ewing Sarcoma Defines an Aggressive Subtype with Co-Association of <i>STAG2</i> and <i>TP53</i> Mutations
Authors: Franck Tirode, Didier Surdez, Xiaotu Ma, Matthew Parker, Marie Cécile Le Deley, Armita Bahrami, Zhaojie Zhang, Eve Lapouble, Sandrine Grossetête-Lalami, Michael Rusch, Stéphanie Reynaud, Thomas Rio-Frio, Erin Hedlund, Gang Wu, Xiang Chen, Gaelle Pierron, Odile Oberlin, Sakina Zaidi, Gordon Lemmon, Pankaj Gupta, Bhavin Vadodaria, John Easton, Marta Gut, Li Ding, Elaine R. Mardis, Richard K. Wilson, Sheila Shurtleff, Valérie Laurence, Jean Michon, Perrine Marec-Bérard, Ivo Gut, James Downing, Michael Dyer, Jinghui Zhang, Olivier Delattre
Journal: Cancer Discovery (2014)

Ewing sarcoma is a primary bone tumor initiated by EWSR1-ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants, and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2-immunonegative cells in relapsed tumors as compared with matched diagnostic samples.Whole-genome sequencing reveals that the somatic mutation rate in Ewing sarcoma is low. Tumors that harbor STAG2 and TP53 mutations have a particularly dismal prognosis with current treatments and require alternative therapies. Novel drugs that target epigenetic regulators may constitute viable therapeutic strategies in a subset of patients with mutations in chromatin modifiers.
Safety of Intracoronary γ-Radiation on Uninjured Reference Segments During the First 6 Months After Treatment of In-Stent Restenosis
Authors: Javed M. Ahmed, Gary S. Mintz, Ron Waksman, Neil J. Weissman, Roxana Mehran, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, Martin B. Leon
Journal: Circulation (2000)

Background —The effects of endovascular irradiation on uninjured reference segments during the treatment of in-stent restenosis are unknown. Methods and Results —In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized (blinded) to receive either γ-irradiation ( 192 Ir) or a placebo (dummy seeds). We identified all patients in whom the active (n=19) or dummy seeds (n=19) extended &gt;10 mm proximal and distal to the in-stent restenosis lesion. Serial (postirradiation and follow-up) external elastic membrane (EEM), lumen, and plaque and media (EEM−lumen) areas were measured (using intravascular ultrasound) every 1 mm over 5-mm-long reference segments that were 6 to 10 mm proximal and distal to the in-stent restenosis lesion. During follow-up, a similar small increase occurred in the plaque and media area in the proximal and distal reference segments in both 192 Ir and placebo patients. However, in the 192 Ir patients, an increase in both proximal and distal EEM area occurred; as a result, no change in lumen area occurred. Conversely, in the placebo patients, the proximal reference EEM area decreased, and no change occurred in the distal reference EEM area; this contributed to a decrease in lumen area. Conclusions —There was no evidence of a deleterious effect of γ-irradiation on angiographically normal uninjured reference segments in the first 6 months after the treatment of in-stent restenosis.
The Transcription Factor GATA3 Is Essential for the Function of Human Type 2 Innate Lymphoid Cells
Authors: Jenny Mjösberg, Jochem Bernink, Korneliusz Golebski, Julien J. Karrich, Charlotte P. Peters, Bianca Blom, Anje A. te Velde, Wytske J. Fokkens, Cornelis M. van Drunen, Hergen Spits
Journal: Immunity (2012)
One hundred and fifty years of service.
Authors: J D Havard
Journal: BMJ (1982)

change or change in school performance as complaints that, either alone or in association with headaches, should make the doctor include cerebral neoplasm in his differential diagnosis.Subacute sclerosing panencephalitis may present in the same way, especially in the older child.Compared with less than 10 years ago, when invasive diagnostic methods such as pneumoencephalography and angiography were necessary for investigating the child suspected of having a brain tumour, we are indeed fortunate in having a painless, rapid, and safe method of investigating children with ominous-sounding headaches and other symptoms and signs of recent onset.7 Nevertheless, we should use computed tomography scanning wisely and selectively.Honig and Charney, with their careful analysis of the clinical criteria for diagnosis, have helped us to do this.
Liothyronine With Levodopa in Parkinsonism
Authors: Arthur J. Prange
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Since levodopa treatment of parkinsonism is attended by significant side effects, efforts have been directed at improving its therapeutic efficiency.<sup>1</sup>The simultaneous use of a drug that blocks peripheral decarboxylation of the amino acid has been promising.<sup>2</sup> For the following reasons we entertained the possibility that a small dose of the thyroid hormone, liothyronine sodium, might potentiate the beneficial effects of levodopa. First, this hormone has been shown to potentiate the antidepressant activity of imipramine<sup>3,4</sup>and amitriptyline. While the mechanism of interaction is unproved, it plausibly involves augmentation of central adrenergic processes.<sup>3</sup>Hyperthyroid patients occasionally show a chorea that resembles the chorea seen in patients with parkinsonism after overdosage with levodopa.<sup>5</sup>Hypothyroid infants often show muscle hypertonia, a usual finding in patients with parkinsonism, and treatment with thyroid hormone reduces it.<sup>6</sup> Guided by these observations we treated seven patients with idiopathic parkinsonism with
Modification of the OMED Nomenclature: A System Approach Based on the SISCOPE Data Model
Authors: A. Gouveia-Oliveira, V. D. Raposo, N. C. Salgado, A. P. Azevedo, I. Almeida, F. Galvao de Melo, J. Pinto Correira
Journal: Endoscopy (1992)

The OMED nomenclature represented a turning point in endoscopic computer systems by supplying software developers with an internationally recognized scientific document on which prototypes could be based. The main pitfalls of the OMED system are related to its hierarchical structure, probably not the most effective design to represent endoscopic findings. Based on our experience during the development of SISCOPE, an integrated data management system for endoscopy, an alternative scheme is proposed: Endoscopic descriptions are modeled as a set of objects represented by a data structure whose elements are location, morphology, associated lesions and hemorrhage. 72 objects appear to be sufficient for an accurate representation of all endoscopic scenes and a consistent data model could be created with this approach. Efforts should be made to decrease redundancy in the OMED nomenclature, but extension to other endoscopic data types, such as clinical and pathological diagnosis, is more urgently required. Furthermore, if data exchange between systems is desired, the definition of an Endoscopy Metafile is an absolute requirement.
Practice made perfect
Authors: H M C Corfield
Journal: Journal of the Royal Society of Medicine (2004)

The comprehensive demolition of the fantasy of clinical freedom in the May issue of the JRSM1 is in danger of letting in another by the back door, the fantasy of the unblemished career. In reality only unblemished records exist.

Serious blemishes undeniably need serious medical attention, otherwise the putative benefits of belonging to a profession will vanish. Current appraisal however is comparable to selecting teenagers by the number of their spots. Cosmetic efforts to excise, explain or erase these often nominal blemishes take up more and more of less time, better spent on practical work.

The only case for this new fantasy and the dubious legality which promotes it would seem to be a period of involuntary work for all concerned, whatever their acronyms, in the other two-thirds of the world.
Fcγ receptor transmembrane domains: role in cell surface expression, γ chain interaction, and phagocytosis
Authors: Moo-Kyung Kim, Zhen-Yu Huang, Pyoung-Han Hwang, Brian A. Jones, Norihito Sato, Sharon Hunter, Tai-Hee Kim-Han, Randall G. Worth, Zena K. Indik, Alan D. Schreiber
Journal: Blood (2003)
CD4+ T Cells From Nasal Polyp Explants Contain Abundant Th2 Cells Expressing Functional Interleukin-25 Receptors Together With Th17 Cells
Authors: Emily Lam, Harsha H. Kariyawasam, Stephen R. Durham, Joanne Rimmer, Valerie J. Lund, David Cousins, Stephen Till
Journal: Journal of Allergy and Clinical Immunology (2014)
Evidence for Major Gene Transmission of Developmental Dyslexia
Authors: Bruce F. Pennington, Jeffrey W. Gilger, David Pauls, Sandra A. Smith, Shelley D. Smith, John C. DeFries
Journal: JAMA (1991)

<h3>Objective.</h3> —There is strong evidence that developmental dyslexia is both familial and heritable, but the mode of genetic transmission has remained unclear. In this article, we examine specific genetic hypotheses about the mode of transmission of developmental dyslexia by performing complex segregation analyses. <h3>Design.</h3> —A family study method was applied, whereby the relatives of dyslexic probands were examined for dyslexia. The families studied represent four independently ascertained samples. <h3>Setting.</h3> —The four samples of families were primarily from rural and suburban communities of Colorado, Washington State, and Iowa. <h3>Participants.</h3><h3>— A total of 204 families and 1698 individuals in the four samples combined.</h3><h3>Main Outcome Measures.</h3> —The complex segregation program, POINTER, was used to test competing genetic hypotheses of how a categorical trait (dyslexia) is transmitted in families. <h3>Results.</h3> —The results were consistent with major locus transmission in three of four samples and with polygenic transmission in the fourth. In these three samples, the estimates of penetrance for the<i>AA, Aa</i>, and<i>aa</i>genotypes (where<i>A</i>is the abnormal allele) were, respectively, 1.000, 1.000, and 0.001 to 0.039 in males, and 0.560 to 1.000, 0.550 to 0.897, and 0.000 in females. The estimated gene frequency of the major locus was between 3% and 5%. <h3>Conclusions.</h3> —Sex-influenced, additive, or dominant transmission occurs in a significant proportion of dyslexic families. Other evidence indicates, however, that dyslexia is etiologically heterogeneous and that there is genetic heterogeneity even among families selected for apparent dominant transmission. Thus, while no single major locus may account for all of dyslexia, it is important to pursue potential major loci for dyslexia using linkage techniques. (JAMA. 1991;266:1527-1534)
Abnormal oesophageal motility in patients with chronic cough
Authors: J A Kastelik
Journal: Thorax (2003)

<b>Background:</b> Although gastro-oesophageal reflux is a recognised cause of chronic cough, the role of oesophageal dysmotility is unknown. The aim of this study was to determine the prevalence of abnormal oesophageal motility in a selected group of patients with chronic cough. <b>Methods:</b> Oesophageal manometry and 24 hour pH monitoring were performed in 43 patients with chronic cough, 34 of whom had symptoms suggestive of gastro-oesophageal reflux. Comparative manometric measurements were made in 21 healthy subjects. <b>Results:</b> Nine patients with chronic cough had normal manometry and 24 hour pH. Of the remaining 34 patients, 11 (32%) had abnormal manometry alone, five (15%) had abnormal 24 hour pH monitoring alone, and in 18 (53%) both tests were abnormal. Only one patient in the control group had manometric abnormalities. <b>Conclusions:</b> These results point to a previously unrecognised high prevalence of abnormal oesophageal manometry in patients presenting with chronic cough. Oesophageal dysmotility may therefore be important in the pathogenesis of cough in these patients.
Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia
Authors: Rüdiger Hehlmann, Ute Berger, Markus Pfirrmann, Hermann Heimpel, Andreas Hochhaus, Joerg Hasford, Hans-Jochem Kolb, Tanja Lahaye, Ole Maywald, Andreas Reiter, Dieter K. Hossfeld, Christoph Huber, Helmut Löffler, Hans Pralle, Wolfgang Queisser, Andreas Tobler, Christoph Nerl, Max Solenthaler, Mariele E. Goebeler, Martin Griesshammer, Thomas Fischer, Stephan Kremers, Hartmut Eimermacher, Michael Pfreundschuh, Wolf-Dietrich Hirschmann, Klaus Lechner, Barbara Wassmann, Christiane Falge, Hartmut H. Kirchner, Alois Gratwohl
Journal: Blood (2007)
Appearances of the jejunal mucosa in acute tropical sprue in Singapore.
Authors: N W England, W O'Brien
Journal: Gut (1966)

EDITORIAL SYNOPSIS A positive correlation has been found between the jejunal mucosal patterns and histological change and the severity of the malabsorption.Examination of the jejunal mucosa by biopsy is essential for diagnosis and in assessing the response to treatment of patients with malabsorption in the tropics.
Ragweeds Extract (RWE) Proteins That Lack NADPH Oxidase Activity (RWENOX-) Promote Th1 Response By Upregulating CD40 Expression Independent of MAP Kinases
Authors: A. Kalita, S. Vaidya, H. Murai, S. Stafford, A. Kurosky, I. Boldogh, T. Hazra, S. Sur
Journal: Journal of Allergy and Clinical Immunology (2010)
Evaluation of MYC status in oral lichen planus in patients with progression to oral squamous cell carcinoma
Authors: S. Segura, E. Rozas-Muñoz, A. Toll, G. Martín-Ezquerra, E. Masferrer, B. Espinet, M. Rodriguez, T. Baró, C. Barranco, R.M. Pujol
Journal: British Journal of Dermatology (2013)

Malignant transformation of oral lichen planus (OLP) to oral squamous cell carcinoma (OSCC) is controversial. C-MYC is a proto-oncogene involved in various solid tumours, including OSCC.To determine MYC status using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in OLP lesions from 10 patients with progression to OSCC (group I) and to compare this with OLP lesions from patients without progression to OSCC (group II).We constructed two tissue microarrays with 11 OSCC samples (group IA), 17 OLP samples from the same patients (group IB) and 13 OLP specimens from 12 control patients (group II). FISH evaluation of the MYC gains was determined in 100 nonoverlapping nuclei per sample. IHC evaluation was determined by calculating the percentage C-MYC expression in the epithelial cells.OSCC samples showed MYC copy number gains and C-MYC overexpression in 91% and 73% of cases, respectively. MYC gains were detected in 47% of samples from group IB and were absent from all samples from group II. C-MYC was overexpressed in 87% of cases from group IB and in only 44% of control specimens (group II). The differences in MYC status between groups IB and II were statistically significant.OLP lesions in patients with progression to OSCC show MYC gains and C-MYC overexpression. In patients with severe OLP, determining MYC status may predict a subgroup of subjects with a higher risk of progression to OSCC.