tbuckley/cabot-search huggingface dataset:
ASSESSING GLOBAL SCAR BURDEN USING ECHOCARDIOGRAPHY IN PATIENTS UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY: A COMPARISON OF 2D AND 3D SPECKLE TRACKING WITH CARDIAC MAGNETIC RESONANCE IMAGING
Authors: Anna Kydd, Fakhar Khan, Liam McCormick, Deepa Gopalan, Munmohan Virdee, David Dutka
Journal: Journal of the American College of Cardiology (2012)
A Randomized Phase II Trial of Two Schedules of Docetaxel in Elderly or Poor Performance Status Patients with Advanced Non-small Cell Lung Cancer
Authors: Rogerio Lilenbaum, Mark Rubin, Joyce Samuel, Laszlo Boros, Tarek Chidiac, Leonard Seigel, Afshin Dowlati, Patricia Graham, Jennifer Beaumont, Hongyan Du
Journal: Journal of Thoracic Oncology (2007)
Former head of GSK China is charged with bribery
Authors: J. Parry
Journal: BMJ (2014)

Mark Reilly, the former general manager of GlaxoSmithKline’s operations in China, has been charged with corporate bribery, bribing non-government officials, and bribing business units.

The charges are in connection with a scandal that broke in July last year when China’s Public Security Bureau announced that senior Chinese executives of GlaxoSmithKline (China) Investment Co had confessed to widespread bribery and tax crimes.1 The firm was accused of paying up to ¥3bn (£300m; €350m; $490m) to travel agencies as a means to facilitate bribes to doctors, boosting drug sales. Reilly left China when the scandal broke but then returned voluntarily to help with ongoing investigations into the company’s …
Effect of calcium deposition on copper IUDs.
Authors: J F Miller, M Elstein
Journal: BMJ (1977)

A response to Mr. J. Guillebaud's letter (10 September 77, p. 705) concerning the effect of calcium deposition on copper (Cu) IUDs is reproted. Cumulative event rates in 1752 women with Cu 7 IUDs in situ for up to 3 years reveal that all 3 major IUD complications (pregnancy, bleeding pain removal, and expulsion) decreased with time, and there is nothing to suggest that the fall in rate of Cu release is associated with a rise in pregnancy rate. On the basis of the evidence on the pregnancy rate of women wearing Cu-carrying IUDs for longer than 2 years, it is recommended that these IUDs can safely remain in situ for longer than 2 years.
CLINICAL DATA ON MALIGNANT RENAL TUMORS
Authors: W. F. BRAASCH
Journal: JAMA (1913)

allied, might offer to infected flies means of migration to distant places, and cause isolated infections, thus accounting for sporadic cases, the histories of which show no apparent exposure to the disease.CONCLUSIONS [f pellagra is caused by an infection, especially if of protozoa!origin, and is transmitted by an insect, the •present state of our knowledge leads us to the provisional belief that the following deductions may be tenable.Under conditions existing in the region of pellagrous enilemieitv ¡u »South Carolina, the lice, fleas, mosquitoes and bedbugs show characteristics of habit, distribution and abundance which appear to exclude them from serious consideration in this connection.The biting habits and, to a certain extent, the dis¬ tribution of the flies of the genus Simulium, together with their lack of habits which bring them into close association with man, seem lo present weighty argu¬ ments against the incrimination of these gnats as the active agent in the transmission of pellagra.'the cosmopolitan biting Btable-fly, Stomoxys calcit- rans, from its distributional and biting habits, its close association with man, ils conformation to the obvious requirements of the disease-transmitting insect and the agreemeni of its special characteristics with the phe¬ nomena incident to the occurrence of pellagra, oilers strong relisons for its consideration under the premises.Il is hoped that attention may be directed to this fly ami observations bearing on its possible relation to the disease he generally made.We would add thai, should u causative organism he shown to exist which is a bacterium rather than a proto¬ zoan, and .shouldthis organism invade the body through either the mouth or the skin, the house or typhoid fly, M usai domestica, and the flies whose habits at all resemble it, would lie under strong suspicion.It is needless to say that the house-lly is excessively abundant and of universal distribution in the region studied.We are also aware thai Ihe communication of pellagra in a purely mechanical manner by biting insects ¡s a possibility and, if shown to exist, would radically change our aleas as to the insects which may he involved.finally, we wish to repeat that essential uniformity of causation must be assumed to exist universally and thai the demonstrated failure of a supposed etiologic factor to account for the phenomena of pellagra in one locality must serve to exclude it from consideration as a factor in another.Cause of Beriberi.-Oouzicnlias been studying the records in regard lo beriberi in the penitentiary al Hanoi in French China from 1908 to 1910.lie concludes thai rioe undoubtedly
Pseudotumor Cerebri Associated With Corticosteroid Therapy in an Adult
Authors: Kevin J. Ivey
Journal: JAMA (1969)

A 20-year-old woman had pseudotumor cerebri attributable to corticosteroid therapy. To our knowledge, this is the second case reported in an adult. The patient had severe ulcerative colitis, and headache, blurring of vision, and papilledema occurred with reduction of corticosteroid dosage. Symptoms disappeared with further gradual withdrawal of the drug over the next five weeks. All patients taking corticosteroids who complain of headache or blurring of vision should be examined for pseudotumor cerebri.
Retracted: Posttranslational regulation of polycystin‐2 protein expression as a novel mechanism of cholangiocyte reaction and repair from biliary damage
Authors: Carlo Spirli, Ambra Villani, Valeria Mariotti, Luca Fabris, Romina Fiorotto, Mario Strazzabosco
Journal: Hepatology (2015)

Polycystin‐2 (PC2 or TRPPC2), a member of the transient receptor potential channel family, is a nonselective calcium channel. Mutations in PC2 are associated with polycystic liver diseases. PC2‐defective cholangiocytes show increased production of cyclic adenosine monophosphate, protein kinase A–dependent activation of the extracellular signal–regulated kinase 1/2 (ERK1/2) pathway, hypoxia‐inducible factor 1α (HIF‐1α)–mediated vascular endothelial growth factor (VEGF) production, and stimulation of cyst growth and progression. Activation of the ERK/HIF‐1α/VEGF pathway in cholangiocytes plays a key role during repair from biliary damage. We hypothesized that PC2 levels are modulated during biliary damage/repair, resulting in activation of the ERK/HIF‐1α/VEGF pathway. PC2 protein expression, but not its gene expression, was significantly reduced in mouse livers with biliary damage (Mdr2 –/– knockout, bile duct ligation, 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine treatment). Treatment of cholangiocytes with proinflammatory cytokines, nitric oxide donors, and endoplasmic reticulum stressors increased ERK1/2 phosphorylation, HIF‐1α transcriptional activity, secretion of VEGF, and VEGF receptor type 2 phosphorylation and down‐regulated PC2 protein expression without affecting PC2 gene expression. Expression of homocysteine‐responsive endoplasmic reticulum–resident ubiquitin‐like domain member 1 protein and NEK, ubiquitin‐like proteins that promote proteosomal PC2 degradation, was increased. Pretreatment with the proteasome inhibitor MG‐132 restored the expression of PC2 in cells treated with cytokines but not in cells treated with nitric oxide donors or with endoplasmic reticulum stressors. In these conditions, PC2 degradation was instead inhibited by interfering with the autophagy pathway. Treatment of 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine mice and of Mdr2 –/– mice with the proteasome inhibitor bortezomib restored PC2 expression and significantly reduced the ductular reaction, fibrosis, and phosphorylated ERK1/2. Conclusion : In response to biliary damage, PC2 expression is modulated posttranslationally by the proteasome or the autophagy pathway, and PC2 down‐regulation is associated with activation of ERK1/2 and an increase of HIF‐1α‐mediated VEGF secretion; treatments able to restore PC2 expression and to reduce ductular reaction and fibrosis may represent a new therapeutic approach in biliary diseases.(H epatology 2015;62:1828–1839)
Characterization of stable complexes involving apolipoprotein E and the amyloid β peptide in Alzheimer's disease brain
Authors: Jan Näslund, Johan Thyberg, Lars O. Tjernberg, Christer Wernstedt, Anders R. Karlström, Nenad Bogdanovic, Samuel E. Gandy, Lars Lannfelt, Lars Terenius, Christer Nordstedt
Journal: Neuron (1995)

Genetic evidence suggests a role for apolipoprotein E (apoE) in Alzheimer's disease (AD) amyloidogenesis. Here, amyloid-associated apoE from 32 AD patients was purified and characterized. We found that brain amyloid-associated apoE apparently exists not as free molecules but as complexes with polymers of the amyloid beta peptide (A beta). Brain A beta-apoE complexes were detected irrespective of the apoE genotype, and similar complexes could be mimicked in vitro. The fine structure of purified A beta-apoE complexes was fibrillar, and immunogold labeling revealed apoE immunoreactivity along the fibrils. Thus, we conclude that A beta-apoE complexes are principal components of AD-associated brain amyloid and that the data presented here support a role for apoE in the pathogenesis of AD.
The Treatment of Pleurisy with Effusion
Authors: V. D. Harris
Journal: BMJ (1890)

towards confirming me in the view that I have for a long time held, that empyema and simple pleuritic effusion have very little in common either in their clinical march, their pathology, or their ultimate event.Of the 40 cases of empyema, 32 cases are well, 6 are dead, and of 2 there is no return.Of the 6 fatal cases, 1 died of chronic Bright's disease (not lardaceous), 1 died of croup when 4 years old, 2 died in hospital of "exhaustion from prolonged discharge," and in 2 cases the cause of death could not be ascertained.My own conclusions, based upon grounds of which the preceding observations form only a part, are practically those ap- pended by Mayor' to an excellent thesis on the after-event in pleuritic effusion, namely:1. "The majority of cases of simple idiopathic pleurisy, or of pleurisy from exposure to cold, conceal or reveal a tuberculous process."2. "A careful study of the lung in the neighbourhood of the effu- sion is more important in regard to the prognosis in any given case than the study of the effusion itself."3. "The immediate prognosis in cases of pleuritic effusion is,under present conditions of treatment, almost always favourable; the remoter prognosis, on the contrary, should always be most guarded."
Carcinoid Liver Metastases Accuracy of Radionuclide Liver/Spleen Imaging Compared to Computed Tomography
Authors: R A HALVORSEN, R H WILKINSON, J M FELDMAN
Journal: Clinical Nuclear Medicine (1987)

Carcinoid liver metastases may be more easily detected by radionuclide liver-spleen studies (RN imaging study) than by computed tomography (CT). While multiple studies have suggested that CT is a more sensitive test than the Tc-99m sulfur colloid study for the detection of most types of liver metastases, carcinoid tumors appear to be an exception. The results of 23 pairs of CT and RN imaging studies that were obtained within one month of each other in patients with proven carcinoid tumors are reported. Comparison of the initial reports of the studies as well as a blinded reinterpretation of the studies suggest that in this group of patients the RN imaging study appeared to be superior to CT in the evaluation of the response to therapy.
Efficacy of epicardially delivered adipose stroma cell sheets in dilated cardiomyopathy
Authors: Hadhami Hamdi, Solène Emmanuelle Boitard, Valérie Planat-Benard, Julia Pouly, Hany Neamatalla, Pierre Joanne, Marie-Cécile Perier, Valérie Bellamy, Louis Casteilla, Zhenlin Li, Albert Alain Hagège, Mathias Mericskay, Philippe Menasché, Onnik Agbulut
Journal: Cardiovascular Research (2013)

Few studies have assessed the effects of cell therapy in non-ischaemic cardiomyopathies which, however, contribute to a large number of cardiac failures. Assuming that such conditions are best suited for a global delivery of cells, we assessed the effects of epicardially delivered adipose tissue-derived stroma cell (ADSC) sheets in a mouse model of dilated cardiomyopathy based on cardiac-specific and tamoxifen-inducible invalidation of serum response factor. Three weeks after tamoxifen administration, the function of the left ventricle (LV) was assessed by echocardiography. Twenty-nine mice were then allocated to control (n = 9, non-transgenic), sham (n = 10, transgenic non-treated), and treated (n = 10, transgenic) groups. In the treated group, 3 × 106 allogeneic ADSCs were cultured for 2 days onto temperature-responsive polymers and the generated sheets were then transplanted over the surface of the heart. In 10 additional mice, the sheet was made of green fluorescent protein (GFP)-labelled ADSCs to track cell fate. Function, engraftment, and fibrosis were blindly assessed after 3 weeks. In the non-treated group, fractional shortening declined compared with baseline, whereas the sheet application resulted in its stabilization. This correlated with a lesser degree of LV remodelling, as LV end-diastolic and end-systolic diameters did not differ from baseline values. Many GFP+ cells were identified in the epicardial graft and in the myocardium. Treated animals also displayed a reduced expression of the stress-induced atrial natriuretic factor and beta-myosin heavy chain genes. These protective effects were also accompanied by a reduction of myocardial fibrosis. These results strongly suggest the functional relevance of epicardially delivered cell-seeded biomaterials to non-ischaemic heart failure.
Abstract 4092: Cancer-type regulation of MIG-6 expression by 5-Aza-2′-deoxycytidine and Trichostatin A
Authors: Yu-Wen Zhang, Ben Staal, George F. Vande Woude
Journal: Cancer Research (2012)

Abstract Mitogen inducible gene 6 (MIG-6) is a tumor suppressor gene located in chromosome 1p36 which is frequently lost in many human cancers. It is mainly viewed as a negative feedback regulator of epidermal growth factor receptor (EGFR) family members by directly binding to the receptors and thereby negatively regulating the signaling. Mice with Mig-6 deficiency are prone to develop epithelial hyperplasia or tumors in various tissues including lung, gallbladder, bile duct, uterus and skin. Previously, we reported a few mutations in MIG-6 gene in human lung cancer, but such event is rare. To determine if MIG-6 is regulated by epigenetic silencing, we identified a group of cancer cell lines with low or no MIG-6 expression and investigated the status of DNA methylation and histone deacetylation in MIG-6 promoter. We found that DNA methylation inhibitor 5-Aza-2′-deoxycytidine (5-Aza-dC) induced MIG-6 expression in the melanoma but not in the lung cancer cell lines, while histone deacetylase inhibitor Trichostatin A (TSA) induced MIG-6 expression in lung cancer lines but not in melanoma cell lines. However, the MIG-6 promoter itself does not seem to be directly affected by methylation or histone deacetylation, indicating they are indirectly regulated and most likely mediated by transcription factor(s). Luciferase reporter assays revealed that a short segment of exon-1 in MIG-6 gene is responsible for the induction of its expression by TSA in the lung cancer cells. Our data suggest that MIG-6 gene expression is differentially regulated by the inhibitors of methylation and histone deacetylation in lung cancer and melanoma cells respectively, without directly modifying the promoter. 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 4092. doi:1538-7445.AM2012-4092
IgG, IgA, IgM, and IgD antiglobulins in juvenile rheumatoid arthritis.
Authors: A Florin-Christensen, R M Arana, O G Morteo, M E Roux, O Hubscher
Journal: Annals of the Rheumatic Diseases (1974)

Usual techniques for the detection of antigammaglobulin factors (DAT, SCAT, HEAT, Latex FII) are based upon agglutination reactions and are therefore useful when IgM antibodies are involved.It is well known that antiglobulins also belong to IgG and IgA classes.In our experience, 50 per cent. of patients with JRA are persistently seronegative when sera are tested only with conventional agglutination tech- niques (Garcia Morteo, Hubscher, and Arana, 1970).Recent papers reported elevated IgG antiglobulins in seronegative RA and JRA demonstrated by means of immunoadsorption techniques employing human, horse, and rabbit gammaglobulin rendered insoluble either with glutaraldehyde or with bis- diazobenzidine.These adsorbents had non-specific elution of immunoglobulins (Torrigiani and Roitt, 1967; Torrigiani, Ansell, Chown, and Roitt, 1969; Torrigiani, Roitt, Lloyd, and Corbett, 1970; Bianco, Panush, Stillman, and Schur, 1970).The purpose of this work was to evaluate anti- gammaglobulin factors in seronegative JRA using a quantitative immunoadsorption technique which would have no non-specific elution of immuno- globulins.
Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics
Authors: Evaggelia Liaskou, Henning W. Zimmermann, Ka-Kit Li, Ye H. Oo, Shankar Suresh, Zania Stamataki, Omar Qureshi, Patricia F. Lalor, Jean Shaw, Wing-kin Syn, Stuart M. Curbishley, David H. Adams
Journal: Hepatology (2012)

Liver fibrosis is a wound healing response to chronic liver injury and inflammation in which macrophages and infiltrating monocytes participate in both the development and resolution phase. In humans, three monocyte subsets have been identified: the classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. We studied the phenotype and function of these monocyte subsets in peripheral blood and liver tissue from patients with chronic inflammatory and fibrotic liver diseases. The frequency of intrahepatic monocytes increased in disease compared with control liver tissue, and in both nondiseased and diseased livers there was a higher frequency of CD14++CD16+ cells with blood. Our data suggest two nonexclusive mechanisms of CD14++CD16+ accumulation in the inflamed liver: (1) recruitment from blood, because more than twice as many CD14++CD16+ monocytes underwent transendothelial migration through hepatic endothelial cells compared with CD14++CD16- cells; and (2) local differentiation from CD14++CD16- classical monocytes in response to transforming growth factor β and interleukin (IL)-10. Intrahepatic CD14++CD16+ cells expressed both macrophage and dendritic cell markers but showed high levels of phagocytic activity, antigen presentation, and T cell proliferation and secreted proinflammatory (tumor necrosis factor α, IL-6, IL-8, IL-1β) and profibrogenic cytokines (IL-13), chemokines (CCL1, CCL2, CCL3, CCL5), and growth factors (granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor), consistent with a role in the wound healing response.
Advising patients on dealing with acute chest pain
Authors: A Khavandi, K Potts, P R Walker
Journal: BMJ (2007)

Instructions about using GTN and when to call an ambulance need to be clearer

How long people with chest pain should wait before calling an ambulance is a question familiar to general practitioners and emergency doctors. The answer is complicated by the use of sublingual nitrate sprays, which promptly relieve the pain of stable angina.1 Ideally, patients would be able to distinguish stable angina from a potentially life threatening acute coronary syndrome, but in reality they do not. Therefore the decision about when to call an ambulance needs to balance between an overly cautious strategy that could overburden emergency medical services and one where delayed action leads to higher morbidity and mortality. The balance is difficult to find because international guidance indicates that consensus has not been reached, even among cardiologists.2 3 4

The British Heart Foundation advises patients with known ischaemic heart disease that chest pain that lasts more than 15 minutes is probably a heart attack.2 Within this time patients are advised to use their glyceryl trinitrate (GTN) spray three times at five minute intervals before calling an ambulance. Yet a recent British Heart Foundation campaign advises members of …
Glibenclamide, an ATP-Sensitive K <sup>+</sup> Channel Blocker, Inhibits Cardiac cAMP-Activated Cl <sup>−</sup> Conductance
Authors: Makoto Tominaga, Minoru Horie, Shigetake Sasayama, Yasunobu Okada
Journal: Circulation Research (1995)

Abstract Stimulation of the β-adrenoceptor activates a time-independent Cl − conductance that is known to be regulated via phosphorylation by cAMP-dependent protein kinase in guinea pig ventricular myocytes. Since epithelial cystic fibrosis transmembrane conductance regulator Cl − channels are known to be sensitive to an antidiabetic sulfonylurea, glibenclamide, we tested whether the drug modulates cardiac cAMP-activated Cl − conductance. Bath application of isoproterenol (1 μmol/L, n=11) or forskolin (1 μmol/L, n=17) or the intracellular application of cAMP (1 mmol/L, n=9) activated whole-cell Cl − currents recorded from single myocytes at 36°C. External glibenclamide (≥10 μmol/L, n=26) inhibited the Cl − current induced by either of the stimulants in a concentration-dependent manner. The half-maximal inhibition concentration (IC 50 ) of glibenclamide and the Hill coefficient were 24.5 to 37.9 μmol/L and 1.6 to 2.2, respectively. During current-clamp experiments, forskolin was found to shorten the action potential significantly (250±45 to 201±52 milliseconds, P &lt;.05) in 7 of 11 cells tested. Glibenclamide antagonized the forskolin-induced shortening (to 243±54 milliseconds, n=7, P &lt;.05). Intracellular administration of sodium orthovanadate (0.5 to ≈1 mmol/L, n=6) brought about persistent activation of Cl − current after brief bath application of forskolin. This Cl − current was not affected by H-89 (100 μmol/L, n=3), a specific inhibitor of cAMP-dependent protein kinase, and was suppressed by glibenclamide similarly, with an IC 50 of 29.7 μmol/L. Thus, it is concluded that glibenclamide inhibits cardiac cAMP-activated Cl − channels at some step(s) downstream from the phosphorylation/dephosphorylation process.
Protamine and protamine-insulins exacerbate the vascular response to injury.
Authors: E R Edelman, L A Pukac, M J Karnovsky
Journal: Journal of Clinical Investigation (1993)

Endothelial cells and smooth muscle cells produce heparinlike compounds that are growth inhibitory for vascular smooth muscle cells, and it has been suggested that these compounds play a regulatory role that is perturbed with vascular injury. Indeed, exogenous heparin preparations effectively suppress smooth muscle cell proliferation following injury imposed on vascular endothelium. We now report that protamine, an agent that binds heparin and negates its anticoagulant properties, has potent stimulatory effects on vascular smooth muscle cell proliferation. The administration of protamine, alone or as part of commonly used insulin preparations, stimulated the proliferation of cultured smooth muscle cells, exacerbated vascular smooth muscle cell proliferative lesions in laboratory rats, and interfered with the growth-inhibitory effects of heparin in culture and in vivo. These results confirm the importance of endogenous heparinlike compounds in arterial homeostasis and may require reconsideration of protamine use following vascular reparative procedures and in diabetics.