tbuckley/cabot-search huggingface dataset:
Abstract 3688: A flexible kinase inhibitor assay for active, non-activated, and impure kinase preparations
Authors: Steven Riddle, Connie Lebakken, Jason Ellefson, Laurie Reichling, Jill Wolken
Journal: Cancer Research (2010)

Abstract Kinase activity-based assays are cost-effective and widely used to drive early drug discovery and lead identification, however, they typically require purified, active kinase preparations to be produced that are shown to phosphorylate a known substrate. While it is possible to satisfy these requirements for well-studied kinases, there are many kinases which lack one or more of these requirements, such as CDK8 and STK33, making drug discovery efforts difficult. To solve for these assay development problems, we have developed a TR-FRET binding assay platform which allows for characterization of compounds with kinases that are not sufficiently purified, completely lack activity, or do not have a known substrate. These new assay options for addressing kinase assay requirements in early drug discovery should enable more targets to be screened sooner, resulting in compounds being made available for lead optimization faster. The ability to detect and characterize binding of compounds to non-activated kinases is also a benefit to the lead optimization process, as compounds that bind preferentially to kinases in their non-activated state, such as Gleevec®, are generally preferred due to their selectivity. In this poster, we present solutions for kinases that are difficult to address with activity assays and provide a comparison of compound affinities for active and non-activated forms of a diverse set of kinases to enable faster lead optimization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3688.
Poor lung function is five times commoner in teenagers exposed to high particulate concentrations
Authors: Scott Gottlieb
Journal: BMJ (2004)

Current concentrations of air pollution can have chronic adverse effects on lung development in children, which lead to clinically important deficits in lung function by adulthood, a new study has shown ( New England Journal of Medicine 2004;357: 1057-67

Until now, whether exposure to air pollution adversely affected the increase in lung function during the period of …
Respiratory depression after alfentanil infusion
Authors: A. T Cohen
Journal: BMJ (1985)

common in the younger patients and that the distribution of the various virus infections corresponded to expectations with respect to age.Our range of testing was limited, and many common virus infections-for instance, ECHO virus, parainfluenza virus, and so on-would have gone undetected.Our incidence of 30 4% is, therefore, almost certainly an underestimate.Both the incidence and the density of S aureus carriage in the nasopharynx increase dramatically during viral upper respiratory tract infections.4We believe that this, taken with the temporary suppression of host defence mechanisms during acute virus infections,3 may explain many cases of S aureus septicaemia and endocarditis of apparently spontaneous onset.Confirmation of these findings would suggest vaccination, where feasible, against common virus infections for patients with valvular heart disease, especially when young or after heart surgery.
Experiences With Two-Way Television in a Teaching Hospital Complex
Authors: John P. Tampas
Journal: JAMA (1968)

Television has been developed and used extensively at the University of Vermont College of Medicine for consultation, patient care, teaching, and research. Present uses include televised monitoring of fluoroscopic examinations, radiographs, electrocardiograms, microscopic images, teaching conferences, operative procedures, and patients undergoing radiation therapy. Projected plans include the development of a two-way audiovisual transmission between the medical center and peripheral community hospitals for teaching and consultation purposes.
ACUTE LEFT SIDED NUMBNESS AND WEAKNESS IN A WEIGHTLIFTER
Authors: J Reeser
Journal: British Journal of Sports Medicine (2014)

Background Dietary supplements unregulated by the USFDA carry a risk not only of unintentional doping but of other health disturbances as well. Objective To describe a case of neurological dysfunction following prolonged supplement consumption. Design Case study. Setting Outpatient clinic and tertiary hospital. Patient An 18-yr male with a history of multiple concussions presented with acute progressive left-sided numbness and paresthesias while weight-lifting. Within the hour, he noted numbness and paresthesias in the left lower limb and left face. Past history was significant for a sustained weight loss of 23 kg over the past two years, coincident with dietary supplementation, and dedicated weight-lifting. He had developed symptoms of acrocyanosis over this interval. He took no prescribed medications. On exam he was sleepy and minimally confused. He demonstrated subtle motor weakness in both the left upper and lower limbs. There was no hyperreflexia. Light touch was subjectively diminished on the left. Intervention He was admitted for observation with the following differential diagnosis: 1) Right hemispheric stroke, 2) Thoracic outlet syndrome, 3) Cervical radiculopathy/myelopathy. Results MRI of the cervical spine and brain were unremarkable. Delayed MRA of the brain also proved benign, as did 2D Echocardiograpy. Serology for hypercoaguable state was unremarkable. Subsequent testing revealed a toxic B6 level, (3×the upper limit of the normal reference range). Clinical outcome The majority of symptoms resolved within 18 hours. He was advised to discontinue all nutritional supplements. His cognitive symptoms steadily improved. Three months post-incident he continued to complain of acrocyanosis. Final diagnosis: 1) Sequelae of probable cerebral vasospasm, possibly due to valsalva, 2) Hypervitaminosis B6. Conclusion Practitioners should be aware of the potential adverse nutritional consequences of supplement consumption. The extent to which this case was influenced by the history of concussions is unknown, but should not be dismissed.
Non-specific presentation of illness.
Authors: H M Hodkinson
Journal: BMJ (1973)

Presentation of illness in the elderly is often misleadingly dif ferent from that in younger age groups, and in particular, it may be entirely non-specific. Some differences may reflect the altered responses of the elderly in mechanisms such as the pro duction of fever or pain. For example, myocardial infarction occurs quite commonly in the elderly but is usually not ac companied by typical transverse chest pain and shock. Often pain is totally absent and the patient presents with an episode of collapse, confusion, or breathlessness. Similarly in the old, lobar pneumonia?instead of having its presence indicated by cough, fever, and leucocytosis, as in the young?may present insidiously with confusion, drowsiness, unsteadiness, and slight breath lessness. These vague patterns of illness are common in the elderly and this article will consider some of the more frequent presenting syndromes.
Breast-feeding, α1-Antitrypsin Deficiency, and Liver Disease?-Reply
Authors: John N. Udall
Journal: JAMA (1985)

In Reply.—  Sveger's data confirm our findings: α 1 -AT-deficient infants who are breast-fed for more than one month are less likely to develop severe liver disease than infants breast-fed for less than one month. However, as Dr Sveger notes, additional studies are needed regarding the effect of early feeding patterns on the development of severe liver disease in children with α 1 -AT deficiency. This recommendation correlates closely with that of the 1984 Surgeon General's Workshop on Breastfeeding and Human Lactation: We need a national data base on the initiation and the duration of lactation. Multicenter, longitudinal, and cross-sectional studies are needed to investigate benefits and contraindications of breastfeeding and to evaluate strategies and interventions to promote it. Interagency coordination of projects would ensure a unified approach to research questions and timely dissemination of research findings. 1 Indeed, controlled prospective studies are required to document not only the effect
Patient with motor neurone disease can be allowed to die, court rules
Authors: C. Dyer
Journal: BMJ (2012)

An advance decision to refuse treatment made by a man with motor neurone disease, who communicated only through eye movements, is valid and his life can “peacefully end,” a judge has ruled at the Court of Protection in London.

Mrs Justice Theis said she was “entirely satisfied” that he had the capacity to take the decision after hearing evidence from doctors, carers, and the man’s wife.

His wife had downloaded an advance decision template from the internet, and the document was read to him last November in the presence of a doctor, his wife, and …
Percutaneous radiofrequency thermal ablation of renal cell carcinoma: Is it possible a day-hospital treatment?
Authors: Gianpaolo Carrafiello, Domenico Laganà, Andrea Ianniello, Monica Mangini, Federico Fontana, Elisa Cotta, Laura Concollato, Alberto Marconi, Chiara Recaldini, Gianlorenzo Dionigi, Francesca Rovera, Luigi Boni, Salvatore Cuffari, Carlo Fugazzola
Journal: International Journal of Surgery (2008)
Blood donation--altruism or profit?
Authors: A. Oakley
Journal: BMJ (1996)

In an increasingly commercialised world, the one thing we do not have to buy is our bodies. We own our bodies, for a time at least, and this gives us some freedom (too much, some doctors would say) to do with them what we wish. Blood is something other people need, and it is also ours to give. But how does this giving and receiving of a substance that lies outside the profit motive fit in with the current marketisation of health care?

In their paper in this issue of the BMJ, Howden-Chapman et al (p 1131) report on the attitudes of blood donors to changes in the blood transfusion service in New Zealand.1 Over half of the 345 donors surveyed were opposed to profits being made from blood; 71% expressed concern about the quality of blood in …
Absorption of irrigating fluid during transcervical resection of endometrium
Authors: J Wiener, L Gregory
Journal: BMJ (1990)

a result of their effect on the indigenous anaerobic flora associated with overgrowth and contributing to carriage.6Quinolones are more selective.Consideration of the above data should lead to a new approach to the management of salmonellosis.Firstly, in the case of an outbreak we recommend that all of those affected receive an oral quinolone to treat the infected focus (inflammation of the gut) and to prevent development of the carrier state.After a few days food handlers can return to work (V pamjenovic and others, unpublished work).
Total synthesis of cajanine and its antiproliferative activity against human hepatoma cells
Authors: Xing-yue Ji, Si-tu Xue, Guang-hui Zheng, Yan-xing Han, Zong-ying Liu, Jian-dong Jiang, Zhuo-rong Li
Journal: Acta Pharmaceutica Sinica B (2011)

Cajanine, a constituent of Cajanaus cajan L., used in traditional Chinese medicine, is a promising drug candidate because of its broad range of bioactivities. However, the total synthesis of cajanine and its derivatives has never been reported. Herein, we report the total synthesis of cajanine in nine steps with an overall yield of 10% together with its analog, longistyline A, in 8% yield. The antiproliferative activity of the two compounds against a human hepatoma cell line is also reported.
Alcohol and the Writer
Authors: Frank Fagan
Journal: JAMA (1973)

To the Editor.—  In The Muse and the Martini (224:35, 1973), Donald W. Goodwin, MD, wonders how Anthony Burgess overlooked alcohol addiction in his enumeration of the occupational hazards of writing.  Mr. Burgess has, in fact, contributed some illuminating passages on the subject in his essay, The Writer As Drunk. Discussing the fatal alcoholism of Brendan Behan and Dylan Thomas, Mr. Burgess musingly considers the causes of the poets' addiction with a perceptiveness that seems to go beyond—certainly historically beyond.—Dr. Goodwin's own salient observations:  I would say that both men drank because pub-drinking remains the last of our creative social acts: for a man desperate to communicate in words, only the rising tide of alcohol in a cozy, stuffy atmosphere, the delirious prospect of the seventh veil dropping from the mind, can provide the right bardic satisfaction. Communication on paper is never enough; one needs a flesh-and-blood audience. But a
Mental Retardation: A Family Study
Authors: Marjorie C. Meehan
Journal: JAMA (1965)

An extraordinary investigation of the familial distribution of mental retardation, including data on more than 80,000 persons, gathered over half a century, is here reported. Between 1911 and 1918, genetics research workers at the State School and Hospital at Faribault, Minn, collected medical, social, and psychological information about patients and their families. They used hospital records and reports of psychological tests (Kuhlmann, one of the earliest workers on such tests, was psychologist at the institution) and engaged in extensive fieldwork. Although the originally planned research was never completed or published, all the data were preserved. In 1949, a new group of investigators reread the material and selected 289 cases for extensive follow-up. Through search of records, correspondence, telephone calls, and visits they collected data on all the discoverable descendants of the grandparents of the original subjects. The total amounted to 82,217 persons, including sometimes seven generations of a family. The
New NICE guidelines for hypertension
Authors: L. D. Ritchie, N. C. Campbell, P. Murchie
Journal: BMJ (2011)

OBJECTIVE: In a prospective cohort of 704 Hispanics, we sought to investigate the association between 13 candidate genes and cognitive performance. BACKGROUND: Focusing on individuals of Western European origin, previous genetic studies have demonstrated that cognition is highly heritable and impacted by many genes. DESIGN/METHODS: The Northern Manhattan Study contains a subgroup of 704 stroke-free Hispanics (mean age 69), who were genotyped using the AffyMetrix Genome-Wide Human single nucleotide polymorphism (SNP) Array 6.0. Participants underwent a baseline neuropsychological evaluation. Test scores were Z-transformed and grouped into four factor analysis-derived domains: executive function, episodic memory, semantic memory, and processing speed. Linear regression analyses were performed between each SNP and cognitive domain after adjusting for age, sex, years of education, testing language, insurance status, and ancestry (top two principal components from Eigenstrat). Fully adjusted linear regression analyses were also performed to see if the SNPs were effect modifiers of age-related variability in cognitive performance. RESULTS: In the fully adjusted models, accounting for SNPs in linkage disequilibrium and applying a modified Bonferonni correction (P&lt;0.00028), we found no significant association between the genes, AKT1, ALDH5A1, BDNF, CCKAR, DTNBP1, FGF23, HTR2A, IL1B, KL, METTL23, REST, SNAP25, and SORL1, and the domains of cognition. We found a significant interaction on episodic memory between age and two SNPs in high linkage disequilibrium (Rsq=0.85 and D9=0.99), rs2101756 (β=0.046, P=1.1E-05) and rs985421 (β=0.040, P=5.08E-05), located in SORL1. While independently adjusting for rs2101756 and rs985421, age had a significant detrimental impact on episodic memory (β=-0.043, P=6.8E-30 and β=-0.043, P=5.24E-29, respectively). CONCLUSIONS: SORL1 encodes an apolipoprotein E receptor, and influences cognitive decline. Decreased expression of SORL1 has been associated with Alzheimer’s disease. Our data support SNPs rs2101756 and rs985421 as possible moderators of age-related episodic memory decline. Study Supported by: NINDS R37 NS029993, Evelyn F. McKnight Brain Institute, ACMG Foundation <b>Disclosure:</b> Dr. Katz has nothing to disclose. Dr. Dong has nothing to disclose. Dr. Stern has received personal compensation for activities with Elan, Bayer Pharmaceuticals Corporation, Cephalon, and GalaxoSmithKlein as a consultant. Dr. Wright has received royalty payments from UpToDate. Dr. Blanton has nothing to disclose. Dr. Sacco has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals.
Estrogens in Beefsteaks
Authors: Thomas H. Jukes
Journal: JAMA (1974)

IT WAS discovered in the 1940s that synthetic and natural estrogenic hormones increased fat production in chickens. As a result, pellets of diethylstilbestrol (DES) were implanted in young chickens to improve the quality of their carcasses. This practice was discontinued some years ago. The effect of DES, fed or implanted, on beef cattle differs from the effect on chickens; it leads to a more rapid production of lean meat and improves the efficiency of conversion of feed into beef. Diethylstilbestrol is metabolized by conversion into the glucuronide in the liver of cattle and is excreted in the urine. The residues in beef carcasses following DES treatment were very low, but they were detected in the livers of some animals. Diethylstilbestrol resembles all estrogens that have been tested in producing mammary tumors in susceptible strains of mice. Therefore, DES is a carcinogen. For many years, estrogens for clinical use have carried
Micropuncture Studies of Sodium Tranport in the Remnant Kidney of the Dog THE EFFECT OF GRADED VOLUME EXPANSION
Authors: Sung-Feng Wen, Norman L. M. Wong, Raphael L. Evanson, Earle A. Lockhart, John H. Dirks
Journal: Journal of Clinical Investigation (1973)

Proximal and distal tubule micropuncture studies were performed to examine the response to graded extracellular volume (ECV) expansion in 10 normal dogs (stage I), 11 dogs with a unilateral remnant kidney (stage II), and 7 dogs with a remnant kidney after removal of the contralateral kidney (stage III). Before ECV expansion in stage III, there was a suggestive reduction in proximal tubule as well as loop fractional reabsorption of sodium. After ECV expansion to 3% body weight proximal tubule reabsorption was depressed in all groups of animals, while little further inhibition was observed in this segment with additional expansion to 10% body weight. In contrast, the fraction of filtered sodium remaining in the distal tubule rose progressively in all three groups after graded ECV expansion, suggesting that the graded natriuretic response found in the final urine was largely due to a similar response in the loop of Henle rather than that in the proximal tubule. The distal tubule response of the remnant kidney in both stages II and III was greater than that in stage I. These data indicate that although enhanced sodium excretion per nephron in chronic renal failure may be related to uremia, its exaggerated response to ECV expansion is due, at least in part, to certain as yet unidentified intrarenal factors consequent to reduction in functioning renal mass.
Breath metabolomic profiling by nuclear magnetic resonance spectroscopy in asthma
Authors: B. Ibrahim, P. Marsden, J. A. Smith, A. Custovic, M. Nilsson, S. J. Fowler
Journal: Allergy (2013)

Background Metabolomic profiling of exhaled breath condensate offers opportunities for the development of noninvasive diagnostics in asthma. We aimed to determine and validate discriminatory metabolomic profiles in adult asthma and to explore profiles in clinically relevant disease phenotypes. Methods Nuclear magnetic resonance spectroscopy was used to analyse breath condensate samples from 82 subjects with asthma and 35 healthy volunteers. Multivariate modelling was performed on a 'training set' (70% of the total sample) in order to produce a discriminatory model classifying asthmatics from healthy controls, and the model tested in the remaining subjects. Secondary analyses were performed to determine the models for the identification of asthmatic subgroups based on sputum eosinophilia, neutrophilia, asthma control and inhaled corticosteroid use. Results A classification model consisting of five discriminating spectral regions was derived using data from the training set with an area under the receiver operating curve (AUROC) of 0.84. In the test set (the remaining 30% of subjects), the AUROC was 0.91, thus providing external validation for the model. The success of the technique for classifying asthma phenotypes was variable, with AUROC for: sputum eosinophilia (3% cut-off) 0.69; neutrophilia (65% cut-off) 0.88; asthma control (cut-off Asthma Control Questionnaire score of 1) 0.63; and inhaled corticosteroid use 0.89. Conclusion Nuclear magnetic resonance spectroscopy of breath condensate successfully differentiates asthmatics from healthy subjects. With identification of the discriminatory compounds, this technique has the potential to provide novel diagnostics and identify novel pathophysiological mechanisms, biomarkers and therapeutic targets.
Harvey in Space and Time
Authors: D. Guthrie
Journal: BMJ (1957)

How he did go at least nine hundred mile With one poore paire of shooes, saving alone-a He onely once did sole them at Verona So that it grew a question whether The shoes or feete were of more lasting leather.Coryat mentions the Bills of Health, which, as we shall see, caused Harvey so much annoyance, and he may have 2The full title is: " The Totall Discourse, of the Rare Adven- tures, and painefull Peregrinations of long nineteene Yeares Travayles, from Scotland to the most Famous Kingdomes in Europe, Asia, and Affrica." 3 "Coryat's Crudities, hastily gobled up in five moneths travells in France, Savoy, Italy, Rhetia commonly called the Grisons country Helvetia alias Switzerland, some parts of high Germany and the Netherlands: Newly digested in the hungry aire of Odcombe in the County of Somerset, and now dispersed to the nourishment of the travelling Members of this Kingdome."
Stresses in Current Medical Bibliography
Authors: Frank B. Rogers
Journal: New England Journal of Medicine (1962)

FROM the earliest days, scientists have exchanged visits and personal correspondence, and they have met together in conferences and societies to share information on their work. This is the oldest element of the communication system of science, and under the increased traffic of today it still provides an important link. As the number of scientists grew, the volume of information that they wished to communicate by letter led to the establishment of journals. By the beginning of the nineteenth century the volume of these primary publications had become so large that forms of secondary publication had to be devised — . . .
Corticotroph (Basophil) invasion of the pars nervosa in the human pituitary: Localization of proopiomelanocortin peptides, galanin and peptidylglycine α-amidating monooxygenase-like immunoreactivities
Authors: Ricardo V. Lloyd, Constance J. D’Amato, Michelle T. Thiny, Long Jin, Samuel P. Hicks, William F. Chandler
Journal: Endocrine Pathology (1993)