tbuckley/cabot-search huggingface dataset:
Abstract 4995: Glucose-regulated protein 78 regulates crosstalk between apoptosis and autophagy to determine antiestrogen responsiveness
Authors: Katherine L. Cook, Ayesha N. Shajahan, Lu Jin, Anni Warri, Leena A. Hilakivi-Clarke, Robert Clarke
Journal: Cancer Research (2012)

Abstract While over 70% of breast cancers express estrogen receptor α (ER+), drugs targeting these receptors such as Tamoxifen (TAM) or Faslodex (fulvestrant, ICI) often fail to cure these patients. Many ER+ patients fail to respond (de novo resistance) or lose drug responsiveness (acquired resistance), making endocrine resistance a major clinically relevant problem. The molecular mechanisms of endocrine therapy resistance still remain unclear. We show that antiestrogen resistant cells with an acquired resistant phenotype overexpress glucose-regulated protein 78 (GRP78), which is not observed in de novo resistance. Moreover, we show increased expression of GRP78 in MCF7/LCC9 (estrogen independent, ICI resistant, TAM cross-resistant) when compared to the MCF7/LCC1 (estrogen independent, TAM and ICI sensitive) breast cancer cells and tumors. These data reflect the response of aromatase inhibitor resistant breast cancers to second line antiestrogen therapy, and further support the hypothesis that antiestrogen resistance and estrogen independence are separate phenotypes. Targeting GRP78 with RNAi restored antiestrogen sensitivity in endocrine therapy resistant cells (MCF7-RR and MCF7/LCC9), whereas expressing GRP78 cDNA conferred resistance on antiestrogen sensitive breast cancer cells (MCF7 and MCF7/LCC1). We show that GRP78 integrates cellular signaling to inhibit apoptosis (as determined by cleaved caspase-7, cleaved PARP, and annexin V staining) and stimulate prosurvival autophagy (as determined by LC3-II, p62, and GFP-LC3 punctate). Moreover, GRP78-stimulated autophagy is dependent on TSC2/AMPK-mediated mTOR inhibition. Endocrine resistance induced by GRP78 overexpression is prevented through an inhibition of autophagy by ATG5 knockdown, while caspase inhibition prevented GRP78 RNAi-mediated therapy resensitization. Furthermore, knockdown of GRP78 and beclin 1 (BECN1) synergistically restores antiestrogen sensitivity in resistant cells. The use of GRP78 to integrate the cellular functions of apoptosis and autophagy to control cell fate raises the provocative question that this signaling may be widely applicable and represent a major stress response that explains how many different cell types could respond to stressors and acquire resistance to therapeutic interventions. 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 4995. doi:1538-7445.AM2012-4995
Nitrous Oxide in Myocardial Infarction-Reply
Authors: Peter L. Thompson
Journal: JAMA (1976)

Evaluation of possible adverse effects of inhaling nitrous oxide in the presence of myocardial infarction was a major concern of our study. Our findings demonstrating the safety of 35% nitrous oxide in 89 patients with acute myocardial infarction concur with the more detailed hemodynamic studies of Kerr et al<sup>1</sup>using 50% nitrous oxide. Nevertheless, no effective therapeutic agent is entirely free of adverse effects. Dr Dolan's comments emphasize the need for careful supervision, especially when the patient begins inhaling nitrous oxide. Dr Dolan's major point of disagreement is based on the reports of adverse hemodynamic effects in patients receiving nitrous oxide and high dose morphine (0.5 to 3.0 mg/kg) during cardiac surgery. These dose levels are 35 to 210 mg for a 70-kg man, many times the "usual" dose of morphine, 5 to 10 mg. It seems unlikely (and it was not observed in our study) that
Cytology brush entrapment: a hazard in the stomach postoperatively.
Authors: A C Wicks, A V Dain, K P Harris
Journal: BMJ (1986)

The outcome of acute myocarditis with cardiogenic shock is poor. In some children in whom aggressive medical treatment fails, artificial replacement of heart function may offer lifesaving support until the myocardium has recovered. Four previously healthy children (three boys aged 4, 6, and 1 years; one girl aged 5) developed acute myocarditis with ventricular failure and multiorgan dysfunction caused by low cardiac output. Biventricular assist devices (BVAD) were implanted for prolonged support. In three children cardiac function improved and after up to 21 days mechanical support could be withdrawn. They had full recovery of heart function. In the fourth patient there was no myocardial recovery after a period of 20 days. He underwent orthotopic heart transplantation with an uneventful postoperative course. Prolonged circulatory support with BVAD is an effective method for bridging until cardiac recovery or transplantation in children.
Abstract P1-07-12: Kaiso is a novel regulator of epithelial-to-mesenchymal transition in triple negative breast cancer cells
Authors: BI Bassey, C Crawford, JM Daniel
Journal: Cancer Research (2013)

Abstract Introduction: Breast cancer (BC) is the most frequent form of female cancer and a principal cause of female deaths worldwide. Most BC deaths are attributed to tumor metastasis to vital organs, and many studies have proposed a role for epithelial-to-mesenchymal transition (EMT) in BC metastasis especially the Triple Negative BC (TNBC) subtype. This theory is further strengthened by the observation that many triple-negative tumors display low E-cadherin expression, which is a hallmark of EMT. The TNBC subtype lack expression of the estrogen-receptor (ER), progesterone-receptor (PR) and human epidermal growth factor receptor-2, HER2. These tumors are highly aggressive with limited treatment options or targeted-therapies, and consequently TNBC patients have poor outcomes. Recently, increased nuclear expression of the transcription factor Kaiso was significantly correlated with high grade, BRCA1-related and basal/TNBCs. Kaiso is a novel transcription factor that we originally identified as a binding partner of p120-catenin (p120), a Src Kinase substrate and regulator of E-cadherin stability and turnover. Rationale and Research Objective: Though not much is known about the function of Kaiso in breast tumor progression and metastasis, Kaiso has been implicated in regulating E-cadherin expression, which raised the possibility that Kaiso might play a role in EMT. Thus we sought to elucidate the role of Kaiso in EMT and TNBC metastasis. Results: To achieve this goal, we created a stable Kaiso-depleted TNBC cell line (MDA-MB-231) to analyze the consequences of Kaiso-depletion on features attributed to metastasis, using immunoblot, wound healing and Matrigel invasion assays among other techniques. Interestingly, Kaiso-depletion led to reduced transcript and expression levels of the EMT markers Snail, Slug, ZEB1/2, TGFbRII, vimentin, and up-regulation of E-cadherin. Kaiso-depleted MDA-MB-231 cells also showed a gradual change in morphology from a mesenchymal to an epithelial phenotype referred to as mesenchymal to epithelial transition (MET). Loss of Kaiso further resulted in reduced cell motility and invasion. Ongoing studies seek to evaluate the effect of Kaiso-depletion on metastasis in vivo. Since there is evidence that the TGFβ signaling pathway drives EMT, and Kaiso-depletion resulted in reduced transcript levels of TGFβRII, future studies will determine if Kaiso plays a role in EMT/MET via promotion of the TGFβ signaling pathway. Overall Significance: Our study is the first to demonstrate a link between Kaiso and EMT/MET of TNBC cells and suggest that Kaiso may be a novel regulator of EMT in TNBC. Consequently, Kaiso might be useful as a therapeutic or prognostic tool in the treatment of TNBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-07-12.
Health policy in Europe: factors critical for success
Authors: J. P. Mackenbach, M. Karanikolos, M. McKee
Journal: BMJ (2013)

Large health gains could be made if all countries in Europe adopted the health policies of the best performing country. <b>Johan P Mackenbach</b>, <b>Marina Karanikolos</b>, and <b>Martin McKee</b> examine the differences between countries and the reasons behind them
Six doctors demand reopening of inquest into death of David Kelly
Authors: C. Dyer
Journal: BMJ (2009)

Six doctors are taking legal action to try to get the inquest into the death of the government scientist David Kelly reopened because they believe the original verdict of suicide to be unsafe.

Dr Kelly, 59, a weapons expert, was found dead in woods near his Oxfordshire home more than six years ago after he had gone out for a walk. His wrist was found to have been slashed, and he had painkillers in his bloodstream, although not at a lethal level.

He was under pressure after being named as the source of a BBC …
Active Bleeding After Renal Transplantation Diagnosed by Tc-99m DTP A Scanning
Authors: H. M. PARK, C. C. MORAN, A. R. SIDDIQUI
Journal: Clinical Nuclear Medicine (1990)

Active bleeding sites were detected by Tc-99m DTPA scintigraphy in two patients with renal transplantation. One showed evidence of active bleeding at the site where a percutaneous transplant kidney biopsy specimen was taken, and the other at the arterial anastomotic site. Hematomas appearing as photopenic defects around the kidney are common findings soon after renal transplantation. Demonstration of active bleeding by Tc-99m DTPA is, however, a rarity. Complications of taking an allograft renal biopsy specimen include intrarenal and extrarenal arteriovenous fistula, arteriocalyceal fistula, false-arterial aneurysm, massive hematuria, and persistent clot anuria. All of these are associated with active bleeding. Tc-99m DTPA may be a convenient agent to check for active bleeding after a percutaneous biopsy specimen of a transplant kidney is taken.
Enhancement of nitric oxide production by pulmonary cells following silica exposure.
Authors: V Castranova, L J Huffman, D J Judy, J E Bylander, L N Lapp, S L Weber, J A Blackford, R D Dey
Journal: Environmental Health Perspectives (1998)

In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. In vitro exposure of AM to silica does not stimulate .NO production or enhance iNOS message. However, treatment of naive AM with conditioned media from BALC harvested from silica-exposed rats does increase iNOS message and .NO production by these AM. The potency of this conditioned medium is dependent on interaction between AM and PMN. In the rat model, a relationship exists between the ability of various dusts to cause PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > carbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest radiograph, and a silica-exposed coal miner with an abnormal chest radiograph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of .NO-dependent CL from AM. These data suggest that .NO may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced .NO production in response to an inflammatory insult.
The Dumping Syndrome--I: I. Factors Responsible for the Symptoms
Authors: L. P. Le Quesne, M. Hobsley, B. H. Hand
Journal: BMJ (1960)

The dumping syndrome is one cause of an unsatisfactory result after the operation of subtotal gastrectomy.Symptoms come on towards the end of or shortly after meals, the main features being feelings of abdominal distension, often accompanied by borborygmi, and of extreme exhaustion with faintness, dizziness, sweating, and p:lpitations.These symptoms, which are exacer- bated by standing and relieved by recumbency, last for some 30-45 minutes.A severe attack may culminate in the passage of a loose motion.The onset or fear of symptoms restricts the size of meals, and many patients notice that carbohydrate food is particularly apt to produce symptoms.The true incidence of the condition is difficult to assess, because in the first few weeks after gastrectomy many patients experience these symptoms to a greater or less extent, but in the majority a spontaneous improvement occurs.The syndrome may also, but less often, develop after gastro-enterostomy.It was shown by MaChella (1949) that in patients with the dumping syndrome the symptoms could be reproduced by the ingestion of hypertonic glucose, sucrose, laevulose, and casein hydrolysate solutions, and
TET2 Inactivation Results in Pleiotropic Hematopoietic Abnormalities in Mouse and Is a Recurrent Event during Human Lymphomagenesis
Authors: Cyril Quivoron, Lucile Couronné, Véronique Della Valle, Cécile K. Lopez, Isabelle Plo, Orianne Wagner-Ballon, Marcio Do Cruzeiro, Francois Delhommeau, Bertrand Arnulf, Marc-Henri Stern, Lucy Godley, Paule Opolon, Hervé Tilly, Eric Solary, Yannis Duffourd, Philippe Dessen, Hélène Merle-Beral, Florence Nguyen-Khac, Michaëla Fontenay, William Vainchenker, Christian Bastard, Thomas Mercher, Olivier A. Bernard
Journal: Cancer Cell (2011)
Chlamydial disease pathogenesis. Ocular hypersensitivity elicited by a genus-specific 57-kD protein.
Authors: R P Morrison, K Lyng, H D Caldwell
Journal: The Journal of Experimental Medicine (1989)

Recurrent or persistent infections with Chlamydia trachomatis are thought to provide the antigenic stimulus for the chronic inflammation associated with blinding trachoma. We used the guinea pig model of inclusion conjunctivitis to identify chlamydial antigens that may be involved in this deleterious immune response. We purified from chlamydial elementary bodies a genus-specific 57-kD protein that elicited an ocular hypersensitivity response when placed topically onto the conjunctiva of ocular immune guinea pigs. This response was characterized by a predominantly mononuclear macrophage and lymphocyte cellular infiltrate of the submucosal epithelium. The clinical and histological findings were consistent with those of a delayed hypersensitivity response. These data demonstrated that the 57-kD chlamydial protein was a potent stimulator of ocular delayed hypersensitivity. Our findings may be critical to understanding the pathogenesis of the debilitating chlamydial diseases associated with chronic inflammation, such as trachoma and many urogenital syndromes.
Foreign Bodies in the Gastrointestinal Tract
Authors: Watson W. Eldridge
Journal: JAMA (1961)

THE APPEARANCE in various publications, from time to time, of reports of cases of foreign body in the gastrointestinal tract<sup>1</sup>always interests me because so often the author appears to be surprised when a foreign body of unusual shape or size is successfully passed without surgical intervention. In 1920 I had the opportunity to organize the Medical and Surgical Division of Saint Elizabeths Hospital, Washington, D.C., where I remained as Director during the ensuing 36 years, until my retirement in 1956. Like all hospitals caring for the mentally ill, we had our quota of those patients who occasionally or habitually swallowed foreign bodies. We learned very early in our experience that nearly all of such patients would successfully pass these foreign bodies if given time and patience. During that period of 36 years I saw many dozens, probably several hundreds, of such cases. The foreign bodies ingested included not
Effect of frusemide on Cl- channel in rat peritoneal mast cells
Authors: G Meyer, S Doppierio, P Vallin, L Daffonchio
Journal: European Respiratory Journal (1996)

Frusemide can be used as an antiasthma drug and appears to inhibit the release (conditioned by activation of Cl- channels) of mast cell proinflammatory mediators. We studied the cause of the effects of frusemide, checking its action on Cl- channels. The patch-clamp technique was used to study single-channel currents, and differences in electrical potential of the cellular membrane of rat peritoneal mast cells were measured. In inside-out configuration, outwardly-rectifying Cl- channels were identified whose conductance was 2.4/1.7 pS at positive and negative voltages. In cell-attached configuration, the open probability (Po) of the channel increased with depolarization or with the presence of cyclic adenosine monophosphate (cAMP) in the incubation medium. Po increased with a rise of cytoplasmic free calcium concentration [Ca2+] and was inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and by 4-4'-diisothiocyanatoostilbene-2-2'-disulphonic acid (DIDS). These channels seem to be the main cause of mast cell Cl- conductance. Frusemide (10(-5) and 10(-3) M) did not affect Cl- channel activity when using excised patches. In cell-attached configuration experiments, the presence of frusemide (from 10(-5) to 10(-3) M) in the cell incubation medium, increasingly reduced Po (median inhibitory concentration (IC50) = 4.3 x 10(-7) M). In similar conditions, bumetanide also inhibited Po (IC50 = 5.7 x 10(-3) M). The results of this study suggest that frusemide can inhibit mast cell Cl- channels only via an indirect mechanisms, which probably involves an inhibition of a Na(+)-K(+)-2Cl- symport.
A WATERPROOF LAPAROTOMY PAD OF GAUZE AND CELLOPHANE
Authors: Frank H. Lahey
Journal: JAMA (1935)

A cellophane pad that I devised has now been employed for more than two years. A description of it together with the illustration is presumed with the possibility that it may prove useful to others. It consists of a pad measuring 14 by 16 inches, in the center of which is a layer of cellophane, on each side of which are two, three or four thicknesses of gauze either with selvage edges or with the edges turned in. A layer of stitching an inch or two from the edge of the gauze is carried around the entire pad, thus fixing the cellophane in place. The advantages of this pad are particularly that it is waterproof so that it can be used to drape over wound edges during gastric and colon resections, thus protecting them from contamination. It can be sterilized in the autoclave with no ill effects and has the
Fat Embolism
Authors: James H. Garner
Journal: JAMA (1967)

THE ASSOCIATION of petechial hemorrhages with fat embolism was first noted by Benestad<sup>1</sup>in 1911. These petechial hemorrhages are the classic physical finding which firmly establishes the diagnosis of fat embolism.<sup>2</sup>They appear in crops anytime during the first week after injury, occurring in the axillae, across the chest and the base of the neck, and extending down the flanks into the thighs. Subconjunctival and submucous petechiae are also seen occasionally. Therefore, the appearance of petechial hemorrhages is an indication of fat embolism. Sevitt<sup>3</sup>found fat emboli in the superficial dermal capillaries in biopsy specimens of the skin about the petechiae. We have been unable to confirm this finding after examination of serial sections of skin specimens from patients having fat embolism with petechiae. Platelet counts in some of our patients who have fat embolism and spontaneous petechial hemorrhages have been very low. It is our present
His Bundle Recordings in Patients with Reciprocating Tachycardias and Wolff-Parkinson-White Syndrome
Authors: CESAR A. CASTILLO, AGUSTIN CASTELLANOS
Journal: Circulation (1970)

The mechanisms of reciprocating tachycardias were studied in three patients with WPW syndrome using the catheter technic of His bundle recordings. In the first case it could not be determined with certainty whether the tachycardias involved two anatomically independent fascicles or a single longitudinally dissociated pathway. They were terminated by carotid sinus pressure, which caused A-V nodal block, or by properly timed atrial stimuli, which interrupted the circuit. Short-lived paroxysms of atrial fibrillation in cases 1 and 2 were most probably related to atrial vulnerability. In case 3 there were three types of QRS complexes in lead II representing (a) exclusive His bundle conduction, (b) simultaneous His and Kent bundle conduction, and (c) coexisting His and infra-nodal preferential (Mahaim fiber[?]) conduction. This patient also had three types of reciprocating tachycardias-two of ventricular, and one of atrial origin. The reciprocating circuit probably involved the three pathways.
Sudden cardiac death in the young
Authors: Sanjay Sharma
Journal: British Journal of Sports Medicine (2011)

Lecture 30 The sudden death of a young (&lt;35 years old) is a particularly tragic event given the potential number of life years lost. There are between 10 and 12 sudden cardiac deaths in young individuals per week in the UK. Most deaths are secondary to inherited or congenital abnormalities of the heart, the commonest being the hereditary cardiomyopathies. The phenotypic manifestation of some of the disorders implicated is heterogeneous and therefore expert input is essential. Most disorders can be diagnosed using non-invasive investigations and treatments range from life style modifications to cardiac surgery. Objectives To define: magnitude of the problem demographics of the victims causes of sudden cardiac death clinical manifestations of disorders investigation and management of conditions causing sudden cardiac death.
Lymphatics of the Heart.
Authors: R. A. Johnson
Journal: Annals of Internal Medicine (1965)

s1 May 1965Lymphatics of the Heart.R. A. Johnson, M.D., Thomas M. Blake, M.D., F.A.C.P.R. A. Johnson, M.D.Search for more papers by this author, Thomas M. Blake, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1071_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptStudy of the lymphatic system has been handicapped by limitations of available methods. Meticulous injection techniques have been the primary means of investigation. In the present study of cardiac lymphatics, a simple and effective method is used that requires neither live specimens nor special preparation. A 1% solution of hydrogen peroxide applied topically initiates a chemical reaction, presumably with tissue enzymes producing oxygen, which distends lymphatic channels. Though the reaction is not specific, lymphatics have a characteristic morphology by which they are identified. After application of peroxide, clearing by a modified Spalteholz technique after injection has been utilized also. Cardiac... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: R. A. Johnson, M.D.; Thomas M. Blake, M.D., F.A.C.P.Affiliations: Jackson, Mississippi PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1071-1072KeywordsEnzymesHeartLymphatic systemOxygen ePublished: 1 December 2008 Issue Published: 1 May 1965 PDF downloadLoading ...
1117 DETECTION OF MINORITY HBV RESISTANT STRAINS IN HBV TREATMENT NAIVE PATIENTS USING A HIGHLY SENSITIVE ASSAY BASED ON ARMS RT-PCR WITH MOLECULAR BEACON
Authors: F. Ntziora, D. Paraskevis, G. Papatheodoridis, E. Manesis, S. Manolakopoulos, I. Elefsiniotis, C. Haida, A. Hatzakis
Journal: Journal of Hepatology (2011)