tbuckley/cabot-search huggingface dataset:
Myocardial lipid composition in turkeys with dilated cardiomyopathy
Authors: D. Lax, R. T Holman, S. B Johnson, S.-L. Zhang, Y. Li, G. R Noren, N. A Staley, S. Einzig
Journal: Cardiovascular Research (1994)

The aim was to determine if reduced heart lipid peroxidation in turkeys with two forms of dilated cardiomyopathy, previously reported, was related to an alteration in the lipid composition of the ventricle.Myocardial lipid composition was measured in turkeys with two types of dilated cardiomyopathy. Twenty six turkeys with naturally occurring dilated cardiomyopathy, six with furazolidone induced dilated cardiomyopathy, and 18 age matched control birds were used at 1 day, 9-10 days, and 38-78 days of age. Left ventricular fatty acid composition of the phospholipid, triglyceride, free fatty acid, and cholesterol ester fractions was analysed using gas chromatography.Significant age related changes were identified in the fatty acid composition of the heart. In the phospholipid fraction, linoleic acid (18:2 omega 6) values increased with age, while arachidonic acid values decreased. The saturated to unsaturated fatty acid ratio in control hearts was unchanged as a function of age in the phospholipid fraction. In the triglyceride fraction, however, this ratio decreased substantially between newly hatched and nine day old birds and then markedly increased in two month old controls. There was a striking alteration in the saturated to unsaturated fatty acid ratio in the triglyceride fraction of 2 month old cardiomyopathic birds; this ratio was markedly increased in the furazolidone induced cardiomyopathic turkey hearts (5.14 v 2.79 in controls) and markedly diminished (ie, 0.97 to 1.21) in the spontaneously cardiomyopathic turkeys. A significant increase in myristic (14:0) and decrease in linoleic (18:2 omega 6) acid concentration in the furazolidone group v control and a marked decrease in myristic and increase in linoleic acid concentrations in the spontaneously cardiomyopathic group v controls was present.(1) There is an age related alteration in the fatty acid composition of control turkey hearts. (2) Previously identified reduced lipid peroxidation in furazolidone induced and spontaneous cardiomyopathy in turkeys does not appear to be related to reduced concentration of polyunsaturated fatty acids. (3) The two forms of dilated cardiomyopathy are associated with markedly disparate alterations in the concentration of polyunsaturated fatty acids in the triglyceride fraction of 1-2 month old turkey hearts. The changes may be related, in part, to the pathogenesis in these two different forms of dilated cardiomyopathy.
Abstract 1991: PDCD4 de-repression of Bcl-xl IRES-mediated translation leads to enhanced chemo-resistance of glioblastoma multiforme tumors.
Authors: Urszula Liwak, Lindsay E. Jordan, Federico Roncaroli, Martin Holcik
Journal: Cancer Research (2013)

Abstract Glioblastoma multiforme (GBM) is the most prevalent form of tumor of the central nervous system with an average survival time of less than one year. Given the location and characteristics of GBM only limited treatment options are available, thus understanding the mechanisms of GBM formation or progression may lead to the development of novel treatment options. Strikingly, a common feature of GBM is the loss of expression of the tumor suppressor programmed cell death 4 (PDCD4) which correlates with adverse outcomes for patients in response to chemo- or radiation therapy. Through both transcriptional and translational regulation, PDCD4 has been shown to regulate many proteins within the cell, although the precise mechanism of target selection is not known. We have hypothesised that silencing of PDCD4 in glioblastomas leads to an altered expression of apoptosis-regulating proteins resulting in the suppression of apoptotic signals and enhanced chemo-resistance. Indeed, we show that low levels of PDCD4 correlate with an increase in the anti-apoptotic Bcl-xL protein. Importantly, Bcl-xL is regulated at the level of protein synthesis through the internal ribosome entry site (IRES) in its 5’ untranslated region (UTR). We further show that PDCD4 regulates the activity of the Bcl-xL IRES, and is therefore an IRES specific translational regulator. Importantly, reintroduction of PDCD4 into glioblastoma cells or directly inhibiting Bcl-xL with the chemical inhibitor ABT-737 sensitizes these cells to doxorubicin, thus enhancing cell death. In summary, our work provides a novel role for PDCD4 as a translational regulator of Bcl-xL as well as a potential therapeutic option for the treatment of GBM. Citation Format: Urszula Liwak, Lindsay E. Jordan, Federico Roncaroli, Martin Holcik. PDCD4 de-repression of Bcl-xl IRES-mediated translation leads to enhanced chemo-resistance of glioblastoma multiforme tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1991. doi:10.1158/1538-7445.AM2013-1991
The who and why of pain: analysis by social class.
Authors: A G Larson, D Marcer
Journal: BMJ (1984)

Physicians with an interest in pain have long suggested that the poor complain more and have a higher prevalence of neuroticism than do higher social groups. This assumption was tested by analysing the pain patterns in 500 consecutive patients attending a pain relief clinic. Results implied that scores for presenting pain, anxiety, and depression were similar to all social groups. After treatment scores for residual pain were significantly lower in all social classes, with greatest reduction in classes III, IV, and V. Almost identical results were obtained in a subgroup of patients with cancer but not in a subgroup with sciatica. That patients from the lower social classes have a higher perception of pain and are more neurotic than other group is a myth, probably resulting from poor communication between clinicians and patients of dissimilar socioeconomic class.
Treatment of Hepatic Coma in Cirrhosis by Plasmapheresis and Plasma Infusion (Plasma Exchange)
Authors: STANLEY SABIN
Journal: Annals of Internal Medicine (1968)

Three patients with proved active fatty nutritional cirrhosis were treated with plasma exchange after at least 72 hr of refractory hepatic coma. In each case coma cleared after this treatment. The role of plasma exchange in hepatic coma is discussed.
Duration of effectiveness of pertussis vaccine: evidence from a 10 year community study
Authors: D. Jenkinson
Journal: BMJ (1988)

A 10 year study of whooping cough in a discrete general practice community was performed to assess longitudinally the efficacy of pertussis vaccine from one to seven years after immunisation. Of the 436 cases of whooping cough over 10 years, 326 occurred in children aged 1-7 years. The rate of immunisation was known for each cohort of children born during each year, and the attack rate of whooping cough was thus calculated for those immunised and unimmunized. The attack rates were highest in those cohorts exposed to the epidemics of 1977-9, 1981-3, and 1985-7. The efficacy of the vaccine was calculated as a percentage as (attack rate in unimmunized group--attack rate in immunised group) x 100/attack rate in unimmunized group. It fell from 100% in the first year to 46% in the seventh, being 84% in the fourth and only 52% in the fifth. Thus the pertussis vaccine or its schedule of use does not seem to provide sufficient herd immunity to prevent outbreaks of whooping cough. Matters might be improved if vaccination against pertussis were included in the preschool immunisation programme.
Re-thinking the causes, processes, and consequences of simulation
Authors: Betty Chang, Nicolas Vermeulen
Journal: Behavioral and Brain Sciences (2010)

Abstract We argue that the meaning of smiles is interpreted from physical/contextual cues, and simulation may simply reinforce the information derived from these cues. We suggest that, contrary to the claim of the SIMS model, positive and negative smiles may invoke similar simulation processes. Finally, we provide alternative explanations for the role of eye contact in the processing of smiles.
An acquired antithrombin autoantibody directed toward the catalytic center of the enzyme.
Authors: P Sié, A Bezeaud, D Dupouy, G Archipoff, J M Freyssinet, J M Dugoujon, G Serre, M C Guillin, B Boneu
Journal: Journal of Clinical Investigation (1991)

Antibody inhibitors against human thrombin are rare and have remained poorly characterized. We report the case of a 40-yr-old patient who developed a potent thrombin inhibitor revealed by mild bleeding symptoms and marked prolongation of most laboratory clotting times. After two years of evolution, he died from cerebral hemorrhage. The inhibitor, a polyclonal IgG, was associated with hematological and immunological criteria of autoimmune disorder. Antithrombin IgG was isolated from the patient's plasma by protein A- and thrombin-affinity chromatography. Fab fragments inhibited amidolytic activity of alpha thrombin, and thrombin-thrombomodulin catalyzed protein C activation with a Ki of approximately 10(-8) M in a noncompetitive manner. Alpha to gamma conversion of thrombin resulted in a moderate loss of affinity for the inhibitor. Upon complex formation of thrombin with staphylocoagulase or alpha 2-macroglobulin (alpha 2M), inhibition was decreased by two orders of magnitude and acquired an apparent competitive character. In Western blot experiments, the antibody reacted with active alpha-thrombin, did not react with chloromethylketone-inhibited thrombin and reacted with a lower affinity with iPr2P-thrombin. The inhibitor did not block thrombin binding to benzamidine-, heparin-, or fibrin-Sepharose, but displaced proflavin from its complex with thrombin. Taken together, these results indicate that the patient's autoantibody recognized a conformational structure which includes, at least in part, the apolar binding site adjacent to the catalytic site of thrombin.
PWE-039 Buried Treasure: Developing An Accurate, Low Cost Assessment Of Flexible Sigmoidoscopy Completion Using A Hand-held Metal Detector
Authors: HC Matthews, G Sadler, R Leicester
Journal: Gut (2014)

<h3>Introduction</h3> Flexible sigmoidoscopy (FS) is a validated screening test to reduce the incidence of colorectal cancer. Bowel Scope screening is due to be implemented in the UK by 2016. There is variability in FS performance between operators; internal colonoscopic markings are unreliable for colonoscope position. Three dimensional magnetic imaging systems eg Scopeguide™ (Olympus) (SG) represent real time instrument position but are not widely available. Hand-held metal detectors (HHMD) can easily localise metal objects within the body. We assessed use of HHMD to confirm flexible endoscopic tip placement at the splenic flexure (SF). <h3>Methods</h3> Adult subjects undergoing outpatient FS/colonoscopy were eligible. When examination was judged complete to the SF, an independent observer placed the HHMD at the left 10th intercostal space, anterior-axillary line (corresponding to the internal fixation of the colon at the SF). A positive result was recorded if the HHMD beeped. Position was then assessed by SG. If SF could not be reached, the patient was excluded. We evaluated 3 HHMD from different manufacturers. Patient experience was also studied. Ethical review NREC no. 13/LO/1065. <h3>Results</h3> 44 subjects were recruited consecutively: mean age 64 years (range 17–74), 50% male (n = 22), mean BMI 27 kg/m<sup>2</sup> (range 20–41). Endoscopic confirmation of position at SF showed concordance with Scopeguide<sup>™</sup> in 95% (42/44). Subjects 1–6 were examined using BDS200 (Black and Decker) HHMD. Despite promising results on training models, this proved insensitive in humans and was abandoned. For subjects 7–30 (n = 24) studied with GMS120 (Bosch), positive reading at the correct anatomical marking was recorded in 88% of examinations with SG validation. Of the 3 failures, 2 had a BMI of &gt;30 kg/m<sup>2</sup>. Use of an X-Ray screening trolley improved specificity. For subjects 31–44 (n = 14), a detector with increased sensitivity and directional capabilities, GPP (Garrett Metal Detectors, USA), was used on standard endoscopy trolleys. This showed concordance with SG in 100% of cases (n = 14) including 4 patients with BMI &gt;30 kg/m<sup>2</sup>. There was one true HHMD negative versus endoscopic assessment confirmed by 3D imaging. The technique was further validated by loss of signal on scope withdrawal. Patient questionnaires showed high acceptability. <h3>Conclusion</h3> Use of HHMD in FS has shown excellent concordance with Scopeguide<sup>™</sup> for colonoscope localisation at SF. Specificity and sensitivity are improved by adapting the specifications of the HHMD. A HHMD is an accurate and very cheap (£100 per unit) means of assuring quality during FS and further studies may confirm its role as a useful training tool especially during future service expansion. <h3>References</h3> 1 Atkin W <i>et al</i>. BMJ 2010 2 Leicester R <i>et al</i>. Lancet 1981 <h3>Disclosure of Interest</h3> None Declared.
DEFICIENCY OF C1r IN HUMAN SERUM
Authors: R. J. Pickering, G. B. Naff, R. M. Stroud, R. A. Good, H. Gewurz
Journal: The Journal of Experimental Medicine (1970)

THE EXPERIMENTS PRESENTED HERE UTILIZE A HUMAN SERUM MARKEDLY DEFICIENT IN HEMOLYTIC COMPLEMENT ACTIVITY TO SHOW THAT: (a) The hemolytic deficiency is the result of a selective deficiency in hemolytic C1. (b) The relative absence of hemolytic C1 is due to a profound deficit in C1r function associated with less than normal C1s protein and hemolytic function and normal C1q protein concentration and function. This deficit in C1r in the face of normal C1q suggests that different cell types are responsible for the synthesis of each of these components. (c) Whatever the basis for the deficiency of C1r function, this defect results in an inadequate association of the remaining C1 subcomponents, C1q and C1s, even in the presence of calcium ions, thus suggesting that C1r has an important role in the assembly and/or maintenance of macromolecular C1.
MEASURES FOR THE PREVENTION AND CONTROL OF RESPIRATORY INFECTIONS IN MILITARY CAMPS
Authors: JOSEPH A. CAPPS
Journal: JAMA (1918)

of milk, eggs, cocoa, etc., to the dietary, or by sup- plementing this with some readily assimilable carbo- hydrate as, for example, lactose in a beverage.22.For the roentgen examination of old cavities with fistulas, we have found thorium nitrate in 10 and 15 per cent, solutions to be of value.Its advan- tages over pastes of various kinds are its ease of intro- duction and of withdrawal.A 20 per cent, aqueous solution of potassium iodid appears to give results about equivalent to those secured with the solution of thorium, and is more easily obtained and less expensive.Like thorium nitrate, it is distinctly though mildly irritating.23.The increased expansion of the lung following the use of Dakin's solution leads to the hope that extensive intrathoracic operations, such as decortica- tion of the lung, may in most cases prove unnecessary.Such procedures should be undertaken only after most prolonged efforts to obtain expansion of the lung have failed, and then only when the surgeon has at his command every facility in the shape of intratracheal anesthesia, assistants and armamentarium.
Abstract LB-100: Exploring the mechanisms of resistance to Salinomycin, a cancer stem cell-specific agent, in budding yeast as a model.
Authors: Donald Rozario, Sammer Zeglam, Wolfram Siede
Journal: Cancer Research (2013)

Abstract Introduction The antibiotic salinomycin (SM) represents a selective potassium ionophore. It has recently attracted considerable attention due to its stem-cell specific mode of action that has been elucidated in a breast cancer stem cell model [1]. Further studies revealed additional benefits, e.g. the triggering of apoptosis in resistant cancer cell lines and reversal of multidrug resistance [2,3]. In budding yeast, we discovered that this agent prominently causes mitochondrial damage as revealed by the emergence of respiration-defective cells (“petites”), similar to nigericin. We also noted the frequent occurrence of SM-resistant clones - a possible obstacle in therapy. Methods We used the collection of systematic gene deletions in haploid Saccharomyces cerevisiae to characterize genes whose deletion confers SM sensitivity or resistance if a carbon source is provided (glycerol) that requires active respiration for growth. In parallel, the emergence of reactive oxygen species (ROS) was measured by flow cytometry. With this toxicogenomics approach in a model organism, we attempt to elucidate cancer-stem cell specific therapy targets and suggest strategies to avoid the development of salinomycin resistance. Results and Conclusions Among SM-sensitive deletion mutants, mutants that compromise vacuole/Golgi function and autophagy dominate. Novel genes which confer SM sensitivity if deleted were also uncovered, such as CAJ1, a heat shock protein of the dnaJ family. In almost all cases, a strong correlation between SM and nigericin sensitivity was observed. Among the most SM-resistant mutants were deletions of the E2-ubiquitin conjugating enzymes Ubc13 and Mms2 as well as deletions of TOR pathway components Sch9 and Tco89. In the presence of SM, Sch9 (homolog of human Akt) underwent dephosphorylation; a deletion of Sch9 was shown to improve growth in glycerol media and to counteract petite induction in glucose media in SM-treated cells. The observed mitochondria-dependent ROS production by SM, however, was unaltered and we suggest that, while initial damage is not affected, cells acquire resistance to the consequences of such damage. [1] Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, et al. (2009) Cell 138: 645-659. [2] Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C (2009) Biochem Biophys Res Commun 390: 743-749. [3] Fuchs D, Daniel V, Sadeghi M, Opelz G, Naujokat C (2010) Biochem Biophys Res Commun 394: 1098-1104. Supported by Cancer Prevention and Research Institute of Texas. Citation Format: Donald Rozario, Sammer Zeglam, Wolfram Siede. Exploring the mechanisms of resistance to Salinomycin, a cancer stem cell-specific agent, in budding yeast as a model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-100. doi:10.1158/1538-7445.AM2013-LB-100
Kidneys on demand
Authors: Anne Griffin
Journal: BMJ (2007)

<h3>SUMMARY</h3> The Global Biobank Meta-analysis Initiative (GBMI), through its genetic and demographic diversity, provides a valuable opportunity to study population-wide and ancestry-specific genetic associations. However, with multiple ascertainment strategies and multi-ethnic study populations across biobanks, the GBMI provides a distinct set of challenges in implementing statistical genetics methods. Transcriptome-wide association studies (TWAS) are a popular tool to boost detection power for and provide biological context to genetic associations by integrating single nucleotide polymorphism to trait (SNP-trait) associations from genome-wide association studies (GWAS) with SNP-based predictive models of gene expression. TWAS presents unique challenges beyond GWAS, especially in a multi-biobank and meta-analytic setting like the GBMI. In this work, we present the GBMI TWAS pipeline, outlining practical considerations for ancestry and tissue specificity and meta-analytic strategies, as well as open challenges at every step of the framework. Our work provides a strong foundation for adding tissue-specific gene expression context to biobank-linked genetic association studies, allowing for ancestry-aware discovery to accelerate genomic medicine.
Identification of hepatitis B virus-DNA in the liver by in situ hybridisation using a biotinylated probe. Relation to HBcAg expression and histology
Authors: Nikolai V. Naoumov, Helena M. Daniels, Fergus Davison, Adrian L.W.F. Eddleston, Graeme J.M. Alexander, Roger Williams
Journal: Journal of Hepatology (1993)
SOME OBSERVATIONS ON THE MENTAL DEVELOPMENT OF FEEBLEMINDED CHILDREN
Authors: R. G. Gordon, R. S. Thomas
Journal: BMJ (1930)

Lesions in thle Skin IProdefed b( th e Jlastomi,es.The lesions in the skin ( autsed bv thte blastom Ces; con- stitulte what is genieallv known as blastomycetic (lermatitis.They begin as groups of small, reddish-brown-i nodulles, whiclh incr-ease and coallesee to form irregular p)atches, which mi-ay be dry and harid or-mi-loist and(i soft, and(1 ar-e separatedl hy fissu rs from whic'h ooe a o ero-l)lillQiit or sailnguineou s discharge, which wells ouit whten the l)at(lhb s are squeezed.The border-s of the patches are well (lefined anrd abrupt, andl usually slope gradlually, down to the healthy skin.T lesions so closely resemiible the verriicose type of tubercul-osis euti-s that tlhev are -usially mistaken in -the first instance for it, an(l tle (liagnosis is only esta4lished
London hospital slated for "chaotic" ultrasound service
Authors: O. Dyer
Journal: BMJ (2002)

The Commission for Health Improvement, the government's NHS watchdog, has branded the diagnostic screening service of a London hospital a “chaotic shambles,” in what is probably its most damning investigative report to date.

North London's Chase Farm Hospital had 2700 patients waiting for ultrasound scans when the CHI decided to investigate in February. Some of the referrals dated back more than a year.

It became, said the report, “routinely acceptable for ultrasound requests to be left unactioned. The unprocessed referrals were not hidden away and many staff at all levels knew that they were there.” …
II. PHYSIOLOGIC OBSERVATIONS AND METHODS
Authors: EDWARD C. SCHNEIDER
Journal: JAMA (1918)

The resistance and compensatory power of the nor- mal man against low oxygen have been found to be practically the same qualities as "condition" or "train- ing" in the athlete; and lack of compensatory power equivalent to being "out of training."In its more extreme forms it is identical with a "weak heart."From this it follows in theory, as the cardiovascular division in the Research Laboratory has in fact dis- covered, that the methods based on the rebreathing apparatus are not only applicable for measuring "fit- ness" and "staleness" in the aviator, but also offer hope for development into that long sought and greatly needed aid to cardiovascular diagnosis : a general test and measure of the "functional power of the heart."It will be evident, however, that by the expression "functional power of the heart" we mean much more than merely the strength of that organ.We mean, rather, the totality of the processes of the body's gaseous exchanges with its atmospheric environment.
Hemolytic anemia caused by penicillin. Report of a case in which antipenicillin antibodies cross-reacted with cephalothin sodium
Authors: L. W. Nesmith
Journal: JAMA (1968)

Following the administration of ampicillin sodium, methicillin sodium, and penicillin G sodium to a patient with bronchopneumonia a direct Coombs' test was positive and hemolytic anemia developed. The patient's indirect Coombs' test was positive with group O erythrocytes previously incubated with penicillin G, ampicillin, methicillin, or cephalothin sodium. Adsorption of his serum with penicillin-treated erythrocytes reversed the positive reaction to the indirect Coombs' test with both penicillin-treated and cephalothin-treated erythrocytes. Eluates prepared from erythrocytes, which had been treated with either penicillin G or cephalothin and incubated with his serum, gave a positive indirect Coombs' test with penicillin-treated and with cephalothin-treated erythrocytes. The half-life of autologous erythrocytes treated with penicillin G and sodium chromate Cr 51 was less than 40 minutes. Although the patient had never received cephalothin before, the half-life of autologous cephalothin-treated erythrocytes was 135 minutes.