tbuckley/cabot-search huggingface dataset:
Cell type-specific gene expression in the neuroendocrine system. A neuroendocrine-specific regulatory element in the promoter of chromogranin A, a ubiquitous secretory granule core protein.
Authors: H Wu, D J Rozansky, N J Webster, D T O'Connor
Journal: Journal of Clinical Investigation (1994)

The acidic secretory protein chromogranin A universally occurs in amine and peptide hormone and neurotransmitter storage granules throughout the neuroendocrine system. What factors govern the activity of the chromogranin A gene, to yield such a widespread yet neuroendocrine-selective pattern of expression? To address this question, we isolated the mouse chromogranin A gene promoter. The promoter conferred cell type-specific expression in several neuroendocrine cell types (adrenal medullary chromaffin cells, anterior pituitary corticotropes, and anterior pituitary somatolactotropes) but not in control (fibroblast or kidney) cells. In neuroendocrine cells, analysis of promoter deletions established both positive and negative transcriptional regulatory domains. A distal positive domain (-4.8/-2.2 kbp) was discovered, as well as negative (-258/-181 bp) and positive (-147/-61 bp) domains in the proximate promoter. The proximate promoter contained a minimal neuroendocrine-specific element between -77 and -61 bp. Sequence alignment of the mouse promoter with corresponding regions in rat and bovine clones indicated that the mouse sequence shares over 85% homology with rat and 52% with bovine promoters. DNaseI footprinting and electrophoretic gel mobility shift assays demonstrated the presence of nuclear factors in neuroendocrine cells that recognized the proximate promoter. We conclude that the chromogranin A promoter contains both positive and negative domains governing its cell type-specific pattern of transcription, and that a small proximate region of the promoter, containing novel as well as previously described elements, interacts specifically with neuroendocrine nuclear proteins, and is thereby sufficient to ensure widespread neuroendocrine expression of the gene.
Prenatal Exposure to Organohalogens, Including Brominated Flame Retardants, Influences Motor, Cognitive, and Behavioral Performance at School Age
Authors: Elise Roze, Lisethe Meijer, Attie Bakker, Koenraad N.J.A. Van Braeckel, Pieter J.J. Sauer, Arend F. Bos
Journal: Environmental Health Perspectives (2009)

Organohalogen compounds (OHCs) are known to have neurotoxic effects on the developing brain.We investigated the influence of prenatal exposure to OHCs, including brominated flame retardants, on motor, cognitive, and behavioral outcome in healthy children of school age.This study was part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens) study. It included 62 children in whose mothers the following compounds had been determined in the 35th week of pregnancy: 2,2'-bis-(4 chlorophenyl)-1,1'-dichloroethene, pentachlorophenol (PCP), polychlorinated biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4OH-CB-107), 4OH-CB-146, 4OH-CB-187, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), BDE-99, BDE-100, BDE-153, BDE-154, and hexabromocyclododecane. Thyroid hormones were determined in umbilical cord blood. When the children were 5-6 years of age, we assessed their neuropsychological functioning: motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory, and attention), and behavior.Brominated flame retardants correlated with worse fine manipulative abilities, worse attention, better coordination, better visual perception, and better behavior. Chlorinated OHCs correlated with less choreiform dyskinesia. Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative abilities, better attention, and better visual perception. The wood protective agent (PCP) correlated with worse coordination, less sensory integrity, worse attention, and worse visuomotor integration.Our results demonstrate for the first time that transplacental transfer of polybrominated flame retardants is associated with the development of children at school age. Because of the widespread use of these compounds, especially in the United States, where concentrations in the environment are four times higher than in Europe, these results cause serious concern.
The antiarrhythmic effect of ischaemic preconditioning in isolated rat heart involves a pertussis toxin sensitive mechanism
Authors: L. Piacentini, C. L Wainwright, J. R Parratt
Journal: Cardiovascular Research (1993)

Journal Article The antiarrhythmic effect of ischaemic preconditioning in isolated rat heart involves a pertussis toxin sensitive mechanism Get access Lucia Piacentini, Lucia Piacentini Cardiovascular Research, Department of Physiology and Pharmacology, University of Strathclyde, Royal College, 204 Royal Street, Glasgow G1 lXW, United Kingdom: L Piacentini, C L Wainwright, J R Parratt. Correspondence to Professor Parratt. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cherry L Wainwright, Cherry L Wainwright Cardiovascular Research, Department of Physiology and Pharmacology, University of Strathclyde, Royal College, 204 Royal Street, Glasgow G1 lXW, United Kingdom: L Piacentini, C L Wainwright, J R Parratt. Search for other works by this author on: Oxford Academic PubMed Google Scholar James R Parratt James R Parratt Cardiovascular Research, Department of Physiology and Pharmacology, University of Strathclyde, Royal College, 204 Royal Street, Glasgow G1 lXW, United Kingdom: L Piacentini, C L Wainwright, J R Parratt. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 4, April 1993, Pages 674–680, https://doi.org/10.1093/cvr/27.4.674 Published: 01 April 1993 Article history Received: 28 August 1992 Accepted: 26 January 1993 Published: 01 April 1993
Bilirubin Turnover Studies in Normal and Pathologic States Using Bilirubin-^14C
Authors: PETER V. D. BARRETT
Journal: Annals of Internal Medicine (1968)

Bilirubin-14C in tracer quantities was administered to 26 patients in 29 studies to determine the plasma bilirubin-14C specific activity disappearance rates. Unconjugated bilirubin was separated from the conjugated pigments by a solvent method. The plasma disappearance curve was found to take the form of the sum of two exponentials, the more rapid of which had an average half-life of 21.5 min. A multicompartmental model of bilirubin metabolism is proposed on the basis of the data, and calculations of bilirubin production and intercompartmental rate constants are made. A mechanism is postulated to explain the hyperbilirubinemia of Gilbert's disease. Eight patients were studied with a nonradioactive bilirubin infusion test, and the results were compared with the isotope studies. It is concluded that the bilirubin-14C method provided a more accurate evaluation of bilirubin production and of hepatic excretion patterns.
A Reappraisal of the Application of the Trendelenburg Operation to Massive Fatal Embolism
Authors: Gordon A. Donaldson, Conger Williams, J. Gordon Scannell, Robert S. Shaw
Journal: New England Journal of Medicine (1963)

ALTHOUGH Trendelenburg1 had proposed and attempted pulmonary-artery embolectomy for massive embolism sixteen years previously it remained for Kirschner,2 in 1924, to perform the first successful operative procedure. Thereafter, within a seven-year period, Meyer,3 Crafoord4 and Nyström5 recorded a total of 8 embolectomies with survival. Enthusiasm for the undertaking was dampened only by Churchill's6 report, in 1934, of 10 consecutive unsuccessful arteriotomies performed at the Massachusetts General Hospital. During the preceding five-year period at this institution embolectomy operative kits had been kept in readiness in the operating suite at all times. The patient suspected of harboring a massive embolus was closely . . .
Effective treatment for malignant mediastinal teratoma.
Authors: D Parker, C P Holford, R H Begent, E S Newlands, G J Rustin, A R Makey, K D Bagshawe
Journal: Thorax (1983)

<h3>Objective</h3> The quality of medical documentation is integral to audit, clinical governance, education, medico-legal aspects and continuity of patient care. This study aims to investigate the introduction of a dedicated ‘Airway Registry Form’ (ARF) on the quality of documentation in prehospital rapid sequence intubation. <h3>Methods</h3> A retrospective review and comparison of 96 cases predating the introduction of the ARF and 90 cases immediately following its introduction were performed. <h3>Results</h3> The introduction of the ARF yielded significant improvement in the recording of selected data points: difficult airway indicators (p&lt;0.0001), Cormack–Lehane grade of laryngoscopy at first attempt (p&lt;0.0001), documentation of confirmation of tracheal intubation with end-tidal carbon dioxide monitoring (p=0.015) and recording of intubator9s details (p&lt;0.0001). <h3>Conclusions</h3> This study validates the use of a dedicated ARF for the improvement of documentation and data collection related to prehospital rapid sequence intubation when compared with post-event extraction of data from a generic case-record.
The Effect of Zidovudine on Patient Subgroups
Authors: John D. Hamilton
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The recent articles by Lagakos et al<sup>1</sup>and Easterbrook et al<sup>2</sup>provide data on the effects of zidovudine on black and Hispanic human immunodeficiency virus (HIV)-infected patients. Neither study, however, was originally designed to assess these subgroups of patients prospectively. Both articles were prompted by reports from the US Department of Veterans Affairs (VA) Cooperative Study 298—first to the Food and Drug Administration Antiviral Advisory Committee in February 1991 and then in abstract form<sup>3</sup>—suggesting that minority patients may respond differently to zidovudine than white patients do. Lagakos et al combined data from two studies by the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group (ACTG), which were designed to evaluate the efficacy of zidovudine vs placebo in symptomatic (ACTG trial 016) and asymptomatic (ACTG trial 019) HIV infection. Subset analyses showed that zidovudine was equally effective in delaying the onset of AIDS in black,
Management of pregnancy in patients with hypertrophic cardiomyopathy.
Authors: G D Oakley, K McGarry, D G Limb, C M Oakley
Journal: BMJ (1979)

The outcome of 54 pregnancies in 23 patients with hypertrophic cardiomyopathy was analysed. No mother or infant died in the perinatal period. Six patients developed dyspnoea requiring treatment with diuretics. Beta-adrenergic blocking drugs were given in 18 pregnancies and three of the infants in this were small for dates and in two fetal bradycardia occurred. The results comfirmed that pregnancy is safe in patients with hypertrophic cardiomyopathy. A flexible approach should be adopted towards administering beta-adrenergic blocking drugs to pregnant women with hypertrophic cardiomyopathy. Many such patients do well without these drugs and can thus avoid the potential hazards--namely, small-for-dates babies and fetal bradycardia--that are associated with them.
P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury
Authors: M. Huls, C. Kramers, E.N. Levtchenko, M.J.G. Wilmer, H.B.P.M. Dijkman, L.A.J. Kluijtmans, J.W.A. van der Hoorn, F.G.M. Russel, R. Masereeuw
Journal: Kidney International (2007)
Serial measures of total body oxygen consumption in an awake canine model of septic shock.
Authors: P Q Eichacker, W D Hoffman, R L Danner, S M Banks, S Richmond, Y Fitz, C Natanson
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We examined serial changes in total body oxygen consumption (Vo2) in a permanently tracheotomized canine sepsis model. On Day 0, beagles had an Escherichia coli-infected (septic) or sterile (control) clot surgically placed in the peritoneum. During the 21-d study, 10 of the 16 septic animals and none of the six control animals died (p = 0.02). After clot placement septic versus control animals had decreased mean arterial blood pressure (mm Hg; Day 1: 106 versus 128, p = 0.055; Day 2: 95 versus 125, p = 0.004, respectively) and left ventricular ejection fraction (Day 1: 0.44 versus 0.69, p = 0.0006; Day 2: 0.33 versus 0.57, p = 0.0001, respectively). Despite significant lethality and cardiovascular dysfunction, in the septic group on Days 1 and 2, septic versus control animals had no significant differences in mean metabolic cart measured (Vo2DIR, ml/kg/min; Day 1: 11.9 versus 12.4, p = 0.81; Day 2: 14.2 versus 13.5, p = 0.72, respectively) and intravascular catheter calculated (Vo2INDIR, ml/kg/min; Day 1: 11.2 versus 11.2, p = 0.99; Day 2: 12.8 versus 15.4, p = 0.49, respectively). On Day 1 in septic and control animals, volume infusion produced increases (p < 0.001) in oxygen delivery (Do2). In septic and control animals these changes in Do2 were similar and were associated with similar increases in Vo2DIR (p = 0.001), and Vo2INDIR (p = 0.001). In fact, at all time points studied (baseline, Day 1, 2, and 21), both before and after volume infusion, levels of Do2, Vo2DIR, and Vo2INDIR did not differ between septic and control animals, nor did they differ between septic survivors and nonsurvivors. Because levels of Vo2DIR and Vo2INDIR were similar in both groups, we pooled data from septic and control animals. Throughout the study, Vo2 showed a moderate association with Vo2INDIR (r = 0.55, p = 0.003), but mean Vo2DIR was lower at baseline (p = 0.001) and on Day 21 (p = 0.07) and greater on Day 2 (p < 0.01). In summary, our techniques, which detected small changes in both Vo2DIR and Vo2INDIR occurring with volume infusion, did not demonstrate differences in these parameters comparing control and septic animals. These results in euvolemic septic animals suggest that total body Vo2 may not reflect pathogenetic mechanisms during sepsis and septic shock. Furthermore, these results suggest that although the level of total body Vo2 may reflect the effects of therapeutic interventions such as volume loading, it should not itself serve as a therapeutic target.
JAMA should change its policy on investigating competing interests, AMA says
Authors: J. H. Tanne
Journal: BMJ (2009)

The American Medical Association has recommended that the editors of its journal ( JAMA ) change its procedures for dealing with complaints over undisclosed conflicts of interest by journal authors. The journal laid out its procedures, which attracted much criticism, in an editorial in March ( BMJ 2009;338:b1352, doi:10.1136/bmj.b1352).

The journal’s editorial said that people complaining about such conflicts of interest should remain silent while their complaints were investigated.

The editorial has now disappeared from JAMA ’s website, and a new, milder editorial appears in the 8 July issue of the journal ( JAMA 2009:302:198-9, doi:10.1001/jama.302.2.198).

The BMJ sent emails to JAMA ’s editor, Catherine DeAngelis, and the journal’s media relations office asking about the disappearance of the March editorial. The BMJ also asked whether Dr DeAngelis could explain why the new July editorial had toned down the policy outlined in the March editorial.

The response …
Prospective trial comparing the use of sulphasalazine and auranofin as second line drugs in patients with rheumatoid arthritis.
Authors: D Porter, R Madhok, J A Hunter, H A Capell
Journal: Annals of the Rheumatic Diseases (1992)

Two hundred patients with rheumatoid arthritis were studied in a prospective open trial comparing treatment with sulphasalazine and auranofin in patients with active disease over 12 months. The two drugs improved many parameters of disease activity at 12, 24, and 48 weeks. At 12 weeks, the group treated with sulphasalazine had a lower platelet count (Mann-Whitney U test), erythrocyte sedimentation rate, and articular index, with a greater decrease in erythrocyte sedimentation rate (Students t test) and C reactive protein between 0 and 12 weeks. There were no significant differences between sulphasalazine and auranofin treatment after 24 and 48 weeks. Life table analysis showed no significant differences in the rate of side effects which caused treatment to be stopped. Sulphasalazine works more rapidly, may be a more effective disease modifying antirheumatic drug, and is as well tolerated as auranofin.
Can human irrationality be experimentally demonstrated?
Authors: L. Jonathan Cohen
Journal: Behavioral and Brain Sciences (1981)

Abstract The object of this paper is to show why recent research in the psychology of deductive and probabilistic reasoning does not have "bleak implications for human rationality," as has sometimes been supposed. The presence of fallacies in reasoning is evaluated by referring to normative criteria which ultimately derive their own credentials from a systematisation of the intuitions that agree with them. These normative criteria cannot be taken, as some have suggested, to constitute a part of natural science, nor can they be established by metamathematical proof. Since a theory of competence has to predict the very same intuitions, it must ascribe rationality to ordinary people. Accordingly, psychological research on this topic falls into four categories. In the first, experimenters investigate conditions under which their subjects suffer from genuine cognitive illusions. The search for explanations of such performance errors may then generate hypotheses about the ways in which the relevant information-processing mechanisms operate. In the second category, experimenters investigate circumstances in which their subjects exhibit mathematical or scientific ignorance: these are tests of the subjects' intelligence or education. In the third and fourth categories, experimenters impute a fallacy where none exists, either because they are applying the relevant normative criteria in an inappropriate way or because the normative criteria being applied are not the appropriate ones.
A Phase I pharmacokinetic (PK) study of single dose oral therapy with a uPA inhibitor (WX-671)
Authors: P. Bevan, C. Mala, M. Buergle, W. A. Schmalix, N. G. Neville
Journal: Journal of Clinical Oncology (2006)

13091 Background: WX-671 is an orally available prodrug of WX-UK1, a serine protease inhibitor that inhibits uPA as well as other serine proteases. WX-UK1 (Setyono-Han et al., Thromb Haemost 2005) and WX-671 have shown to efficiently reduce primary tumor growth and metastasis formation in a variety of animal models. First PK and safety data of the prodrug WX-671 were obtained in healthy volunteers. Methods: Male healthy volunteers received WX-671 as hydrogen sulfate given as single oral doses corresponding to 50, 100, 200 and 400 mg WX-671 free base. Each subject received two single doses, the first dose pre-prandially and the second dose one week later post-prandially. PK profiles were obtained over 48h for both the prodrug WX-671 and the active metabolite WX-UK1. Safety was assessed by measuring vital signs, laboratory parameters (hematology, blood chemistry, coagulation) and ECGs. Results: 16 healthy male volunteers were included, four per dose level. Both the C max levels as well as the plasma AUCs of both WX-671 and WX-UK1 were overproportionally related with dose levels. Administration with food slightly increased AUCs at the two higher doses. Terminal phase half life was fairly constant for WX-671 at all doses (approximately 5.8 h) and for WX-UK1 at least in the two highest dose groups with 17–21 h. Four subjects out of 16 (25%) experienced a total number of 11 adverse events. These events were nervous system disorders (headache, 7 events) and gastrointestinal disorders (diarrhea, 2 events; flatulence, 2 events). All adverse events occurred at the lower dose levels of 50 mg and 100 mg WX-671. No adverse events were observed at the dose levels of 200 and 400 mg WX-671. All adverse events were rated as mild and all subjects completely recovered within a maximum time period of 18h. Conclusions: The administration of oral doses of WX-671 (as hydrogen sulfate) resulted in the formation of WX-UK1 in the plasma uniformly across all individuals. At all dose levels tested, WX-671 was well tolerated systemically as judged by assessment of vital signs, ECG, general safety laboratory and coagulation data as well as by adverse event profiles. Two phase I PK and safety studies with daily dosing over 15 days at the above tested dose levels are currently ongoing, one in healthy volunteers and the other in patients. [Table: see text]
SOME UNUSUAL VARIATIONS OF THE ERYTHEMATOUS SYPHILIDE
Authors: A. Cooper
Journal: BMJ (1906)

IMNICLL Jou3L100.20 F. on the 12th.The conditions steadily improved, anid by the 14th the temperatuire was normal and the facial swelling lhad quite disappeared.The remnainder of the puerperium was satisfactory; the patient left her room on the twenty-eighth (lay.On February 15th the infant began to be fretful an-d restless.On February 16th the restlessness was more marked, and there was soImle vomiting and the bottle was taken badly; the temiiperature was 99.40 F. On February 17th therc was a most typical measles riash, and the temperature reached 101°F.which was the highest point reached.On Februiary 18th the rash was well miiarked all over the body.On Februiary 19th the rash began to fade on the face, but became distinct again if the child cried.FromiFebruary 20th onwards the child returned to its usual state, slept well, and took its bottles well; from this date there was some desquaination, most marked on the face and legs, but also present on the abdomen.The cases present somne points of interest: 1. Thoughl exposed at the same time and nieither lhaving liad a previous attack tlle symptoms niaiiifested themselves twenity-four hours soonier in the hlealthy boy than in the pregnant or puerperal womani.2. The attack was more severe in the case of the b3oy thani in the case of the puerperal patiellt.3. The attack was least severe in the case of the fortnigilt-old inifanit.A CASE OF ADHESIVE MEDIASTINO- PERICARDITIS.
Accelerated Onset and Increased Incidence of Ventricular Arrhythmias Induced by Ischemia in Cx43-Deficient Mice
Authors: Deborah L. Lerner, Kathryn A. Yamada, Richard B. Schuessler, Jeffrey E. Saffitz
Journal: Circulation (2000)

Myocardial ischemia causes profound changes in both active membrane currents and passive electrical properties. Because these complex changes develop and progress concomitantly, it has not been possible to elucidate the relative contributions of any one component to arrhythmogenesis induced by acute ischemia. Cx43+/- mice express 50% of the normal level of connexin43 (Cx43), the major ventricular electrical coupling protein, but are otherwise identical to wild-type (Cx43+/+) mice. Comparison of arrhythmogenesis in Cx43+/- and +/+ mice can provide insights into the role of changes in electrical coupling as an independent variable in the complex setting of acute ischemia.Acute ischemia was induced in isolated perfused mouse hearts by occlusion of the left anterior descending coronary artery. Spontaneous ventricular tachyarrhythmias (VT) occurred in more than twice as many Cx43+/- hearts than Cx43+/+ hearts. VT was induced in nearly 3 times as many Cx43+/- hearts. Multiple runs and prolonged runs of spontaneous VT were more frequent in Cx43+/- hearts. Onset of the first run of VT occurred significantly earlier in Cx43+/- hearts. Premature ventricular beats were also more frequent in Cx43+/- hearts. The size of the hypoperfused region was equivalent in both groups.Reduced expression of Cx43 accelerates the onset and increases the incidence, frequency, and duration of ventricular tachyarrhythmias after coronary artery occlusion. Thus diminished electrical coupling per se plays a critical role in arrhythmogenesis induced by acute ischemia.