tbuckley/cabot-search huggingface dataset:
Abstract 5609: Mechanisms of acquired resistance to selective PI3K inhibitors in breast cancer cell lines
Authors: Carol Lynn O'Brien, Jill Spoerke, Mark Lackner, Scott Sproul, Peter Haverty, Garret Hampton
Journal: Cancer Research (2012)

Abstract GDC-0941 is a class I PI3 kinase inhibitor of all 4 isoforms currently in phase II clinical trials in multiple indications, including ER+ breast cancer. The PI3 kinase pathway plays an important role in proliferation and survival and is known to be one of the most altered pathways in cancer. These alterations include PI3 kinase amplification, PI3 kinase mutations and PTEN loss, as well as numerous others. We have previously shown in-vitro and in-vivo data that alterations in this pathway can potentially help identify patients that are more likely to respond to a PI3 kinase inhibitor. A major outstanding question is mechanisms of intrinsic and acquired resistance to PI3K inhibitors. To address these questions we have selected multiple breast cancer cell lines harboring different pathway alterations (HER2, PIK3K mutations, PTEN loss) for resistance to PI3 kinase inhibition. Some of the resistant lines show cross resistance to inhibitors of mTOR and AKT (ie general pathway resistance), while others show specific resistance to PI3K or PI3K/mTOR inhibitors. We have characterized these resistant cell lines in detail at the molecular level and in terms of signaling pathway activation. Analyses performed include deep sequencing, reverse phase protein arrays, as well as focused Western blots and RTK arrays. We will discuss these results in detail and comment on candidate resistance mechanisms. 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 5609. doi:1538-7445.AM2012-5609
Imaging in rheumatoid arthritis using liposomes labelled with technetium.
Authors: B D Williams, M M O'Sullivan, G S Saggu, K E Williams, L A Williams, J R Morgan
Journal: BMJ (1986)

fracton are compatible with so alled vasomotor nephropathy as the cause of renal failure.2Perhaps the differnces in renal haemodynamic properties between P blockers and the a and P blocker labetalol lead more readily to acute renal failure after an overdose of labetalol.Hypoteion leading to acute oliguric renal failure is accompanied by intense pregknoerular vasoconstriction, which makes filtration highly dependent on an adequately maintained postglomerular resistance.2In thaWpeutic doses labetalol leads to a fall in renal vascular resistance; ,this is in contrast with most i blockers, which cause an increase.34A fall in postglomerular resistance induced by labetalol, perhaps enhanced by the renal vasodilating effects ofdopamine in the dose used in our patient, may have been responsible for the failure of filtration.51 Prichard BNC, Battasby LA,Cuicksh-nkJM.Overdosge with beta-adrenergic blocking agents.Ad,m DYugRzctCAOsaPoiSuixgRev 19843:91-111. Oken DE .iemodynamibasis forhuman acute renal failure (vasomotor nephropathy).
THE ANTIMYCOBACTERIAL ACTIVITY OF A PEPTIDE PREPARATION DERIVED FROM CALF THYMUS
Authors: René J. Dubos, James G. Hirsch
Journal: The Journal of Experimental Medicine (1954)

A stable, water-soluble substance which possesses potent antimycobacterial activity under certain conditions in vitro has been prepared from calf thymus. This substance has been tentatively named thymus peptide. In final concentrations of 1 to 10 microg. per ml. of an albumin medium it inhibits the growth of various strains of mammalian mycobacteria, but manifests only little or no inhibitory activity against a variety of other microbial species. The ability of thymus peptide to inhibit the multiplication of tubercle bacilli diminishes when the inoculum is large, or when the medium is acidic. It is also markedly antagonized by addition of enzymatic hydrolysate of casein or beef heart infusion broth to the culture medium. Thymus peptide does not exert a rapid bactericidal action on tubercle bacilli, but organisms exposed to this compound for longer than 2 weeks could not be made to multiply in ordinary culture media. Substances similar or identical to the thymus peptide preparation could be extracted from calf spleen, sheep thymus, beef lymph nodes, and calf pancreas, but not from calf lung or calf liver.
Obstetric outcome should be analysed by parity.
Authors: M Turner, M Finn
Journal: BMJ (1993)

among the 119 recorded as dying in 1990 or how many would not have taken an overdose had they been aware that paracetamol, if taken in large quantities, often results in a painful and lingering death due to liver failure.By diverting attention towards the 1143 deaths due to overdose of drugs other than paracetamol Spooner disregards the fact that paracetamol is consistently one of the most common drugs used in suicide and far exceeds any other over the counter medication as a method of death by poisoning.It is also by far the most common substance used in deliberate self poisoning attempts.In a review of 3263 admissions after deliberate self poisoning in South West Thames region in 1989 I found that 957 were a result of paracetamol overdose (unpublished study).The next most common class of drugs used was benzodiazepines, which accounted for 584 admissions.Benzodiazepines, of course, are prescription only drugs, and an overdose is far less likely to cause death.Combining paracetamol with methionine, as Bray suggests, may not be the answer, but surely the manufacturers of paracetamol should take a more responsible attitude by at least placing a more specific warning of the effects of overdose on the packaging.
DECREASED TUMOUR NECROSIS FACTOR ALPHA (TNF-Α) IN SERUM OF PATIENTS WITH ACHILLES TENDINOPATHY: FURTHER EVIDENCE AGAINST THE ROLE OF INFLAMMATION IN THE CHRONIC STAGE
Authors: J Gaida, H Alfredson, S Forsgren, J Cook
Journal: British Journal of Sports Medicine (2014)

Background Altered expression of several cytokines and growth factors has been shown in biopsies of tendinopathy tissue. Biopsy studies are however challenged by capacity to obtain i) healthy tissue for comparison, ii) multiple samples to monitor cytokine dynamics, and iii) tissue from recent onset tendinopathy. An alternative is to study cytokines in blood samples. Whether cytokines in blood samples reflect tissue levels and the degree of tendinopathy is unknown. Objective To measure serum concentration of six cytokines and growth factors suggested to have a role in tendon response to load among individuals with chronic Achilles tendinopathy and controls. Design In this cross-sectional study, serum cytokine concentrations were measured from fasting blood samples on the BioPlex-200. Setting Sports Medicine Unit, Umeå University. Participants Participants were recreationally active individuals. Achilles tendinopathy (n=22) was diagnosed on clinical criteria and confirmed with ultrasound examination. The control group (n=10) had no history of tendon pain and had normal ultrasound findings. Independent variables Serum concentration of tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), basic fibroblast growth factor (bFGF), platelet derived growth factor BB (PDGF-BB), interferon gamma (IFN-γ), and vascular-derived endothelial growth factor (VEGF) were the independent variables. Main outcome measurements A diagnosis of Achilles tendinopathy (yes/no) was defined as the key outcome variable prior to data collection. Results TNF-α concentration was lower in the tendinopathy group than the control group (P=.018); there were no other group differences. Conclusions The observations indicate a lowering of the TNF-α concentration in the chronic phase of Achilles tendinopathy. As TNF-α levels are elevated in chronic inflammatory conditions, this reinforces that chronic Achilles tendinopathy is not an inflammatory disorder. Collecting a blood sample to study disease biomarkers leaves the tendon intact and therefore this design can be used to study cytokine dynamics with multiple sampling during disease progression and recovery.
Unusual Abdominal Involvement in Rickettsial Diseases-Reply
Authors: William D. Bradford
Journal: JAMA (1983)

<h3>In Reply.—</h3> Dr Mansueto and co-work-ers describe two unusual and in teresting patients with BF and intra-abdominal lesions. Although gastrointestinal (GI) symptoms are frequent in RMSF (63% of 131 patients described by Kaplowitz et al having nausea, vomiting, or diarrhea before treatment),<sup>1</sup>our knowledge of intra-abdominal pathological lesions in RMSF is limited to usually mild hepatic involvement in fatal cases.<sup>2</sup>It is possible that GI symptoms are caused by rickettsial infection in the blood vessels of the intestine, peritoneum, or other abdominal viscera; on the other hand, nausea and vomiting might be caused by rickettsial encephalitis, probably the most important component of severe RMSF. The parallel rise of RMSF in the United States and BF in Italy is important knowledge. Ecologic changes, including those affecting tick populations in the United States and the Mediterranean basin, must be elucidated. Physicians must be aware that infection with<i>R conorii</i>may
Human serum amyloid A. Three hepatic mRNAs and the corresponding proteins in one person.
Authors: B Kluve-Beckerman, F E Dwulet, M D Benson
Journal: Journal of Clinical Investigation (1988)

Serum amyloid A protein (SAA) is a major acute-phase protein in humans and most other mammals. In addition, it is the serum precursor of the major protein constituent of reactive amyloid fibrils. Sequence analyses have identified a number of polymorphic forms of human SAA and amyloid A protein (AA), but the question of the number of genes encoding SAA in the human has not been addressed. In addition, there are insufficient data to predict whether one form of SAA predisposes to amyloid fibril formation. In the present study three separate SAA proteins have been isolated from the plasma of one individual and completely sequenced. While two of the SAA forms (SAA2 alpha and SAA2 beta) differ from each other only at position 71, they differ from the most abundant form (SAA1) at seven and eight other positions, respectively. Nucleotide sequencing of cDNAs from a liver library of this individual identified all three mRNs coding for these proteins and proved that: (a) the often-reported absence of arginine at the amino terminus of SAA proteins must result from proteolytic processing of the protein; (b) the polymorphism involving histidine and arginine at position 71 is present at the DNA level and therefore is not due to an event at the translational level; (c) there are at least two genes coding for human SAA. Comparison of these data to published sequences of SAA and AA proteins may help in identifying genetically determined forms of SAA which predispose to reactive amyloid fibril formation.
Microenvironmental protection of CML stem and progenitor cells from tyrosine kinase inhibitors through N-cadherin and Wnt–β-catenin signaling
Authors: Bin Zhang, Min Li, Tinisha McDonald, Tessa L. Holyoake, Randall T. Moon, Dario Campana, Leonard Shultz, Ravi Bhatia
Journal: Blood (2013)
An unusual complication of Kocher's manoeuvre
Authors: A Pimpalnerkar, A Datta, D Longhino, N Mohtadi
Journal: BMJ (2004)

be able to keep in his visual field at least five objects at same time (two players of the attacking team, the last two players of the defending team, and the ball), and this may not be compatible with the normal eye function-especially as these five objects can be anywhere within the defenders' half of the pitch, an area of at least 3200 m 2 .This may explain at least some of the instances when television replays of a game clearly show that the offside rule was not properly implemented.The key factor in applying this rule correctly is that the player in question must be in the offside position at the exact time when the ball is passed from a team mate, not when the player receives the ball or when the ball is en route between the players.By reviewing the physiology of the eye movements likely to be involved in assessing an offside position, I have shown that the relative position of four players and the ball cannot be assessed simultaneously by a referee, and unavoidable errors will be made in the attempt.The use of modern technology during games-freeze frame television and frame by frame analysis-is advisable to limit these errors.I thank Nuria Navarro Zaragoza for her translation of the paper into English and Joaquín Zaragoza Celdrán for producing the figures.
THE INCIDENCE OF ECZEMA IN EARLY CHILDHOOD.
Authors: ROBERT B. WALKER, ROBERT P. WARIN
Journal: British Journal of Dermatology (1956)

Journal Article THE INCIDENCE OF ECZEMA IN EARLY CHILDHOOD. Get access ROBERT B. WALKER, M.R.C.S., L.R.C.P., D.P.H., ROBERT B. WALKER, M.R.C.S., L.R.C.P., D.P.H. The Bristol Royal Hospital for Sick Children Search for other works by this author on: Oxford Academic Google Scholar ROBERT P. WARIN, M.D., M.R.C.P. ROBERT P. WARIN, M.D., M.R.C.P. The Bristol Royal Hospital for Sick Children Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 5, 1 May 1956, Pages 182–183, https://doi.org/10.1111/j.1365-2133.1956.tb12805.x Published: 01 May 1956
A CASE OF UNDULANT FEVER IN DERBYSHIRE
Authors: P. H. J. Turton, C. F. Peckham
Journal: BMJ (1932)

The diagnosis was now definitely established-a case of so-called undulant fever.Reference to the accompanying chart will show that the temperature was not of the typical undulating form.The rise in temperature from March 2nd to 5th was due, I think, to active congestion of liver, particularly the left lobe, or possibly to a masked splenitis, the pain from which gave the patient two bad nights, and was completely relieved by a hypodermic injection of scopolaminemorphine, and did not recur.There had been no treatment Ir5126 127.28 129 1 1 2 3 1 4 Il 6 7 8 1 9 10111112 13 11 .1 IJ 16 MI _-L _C _Mf _I _ __ _ _r MI _ __ _ I L I 010 09 beyond rest in bed, nourishing light diet, and for the first few days salol for the bowel condition.As there is no known treatment I decided to try intramuscular injections of S.U,P.36.This wvas done on March 5th, 8th, and 12th-that is, at the end of the sixth week ot the disease,, and the second veek after I first sawV him.A glance at the chart will show a quite dramatic change, considering that the average duration of this disease is fifteen and a half weeks.Beyond that was the fact that the
Study on gelatin-containing artificial skin IV: a comparative study on the effect of antibiotic and EGF on cell proliferation during epidermal healing
Authors: Sung Ran Hong, Seung Jun Lee, Jong Won Shim, Young Seon Choi, Young Moo Lee, Kang Won Song, Moon Hyang Park, Young Soo Nam, Sang In Lee
Journal: Biomaterials (2001)
Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy
Authors: Jae Seok Lim, Woo-il Kim, Hoon-Chul Kang, Se Hoon Kim, Ah Hyung Park, Eun Kyung Park, Young-Wook Cho, Sangwoo Kim, Ho Min Kim, Jeong A Kim, Junho Kim, Hwanseok Rhee, Seok-Gu Kang, Heung Dong Kim, Daesoo Kim, Dong-Seok Kim, Jeong Ho Lee
Journal: Nature Medicine (2015)
Abstract 1374: Identification of a transcription factor driving BET dependency in SCLC
Authors: Susan Wee, Tai Wong
Journal: Cancer Research (2014)

Abstract The regulation, and subsequent recognition, of covalent chromatin modifications by an array of cellular proteins are key determinants of gene expression. For instance, the binding of bromodomain and extra terminal domain (BET) proteins to acetylated histone tails has been shown to regulate c-MYC transcription in some cell types. Consequently, pharmacological inhibition of BET proteins leads to an anti-proliferative activity in cancers dependent on c-MYC activity such as multiple myeloma and acute myelogenous leukemia. Since c-MYC has been implicated as a driver of cell proliferation in many cancer types, we investigated if BET inhibitors may have anti-proliferative activity in solid tumor cancer cell lines as well. Strikingly, in a panel of over 100 mixed histology lung cancer cell lines we identified selective growth inhibition of lines derived from small cell lung cancer (SCLC) histology. To better understand the mechanism of this dependency we performed 12-point dose response microarray analyses using the BET inhibitor, JQ1, in order to identify genes that are regulated by BET proteins in SCLC. In contrast to what has been observed in myeloma and leukemia, BET inhibition is not always accompanied by inhibition of c-MYC expression in the SCLC cell lines. From this analysis a lineage-specific transcription factor was found to be highly regulated in a dose-dependent manner. Previous studies have reported this transcription factor to be essential in maintaining the differentiated neuroendocrine phenotype characteristic of human SCLC. It has also been shown that loss of this transcription factor results in growth inhibition in SCLC tumor models. We have confirmed the growth dependency of SCLC to BET via dysregulation of this transcription factor using RNAi and a small molecule inhibitor. Furthermore, chromatin immunoprecipitation followed by deep-sequencing confirmed binding of BRD4, a BET family member, and RNA polymerase II, a marker of active gene transcription, to the enhancer region of this target gene in two sensitive SCLC cell lines. This binding is disrupted in the presence of BET compound treatment. SCLC is a disease with high unmet medical need, and the results of our studies have identified BET inhibition as a potential novel therapeutic opportunity for this subtype of lung cancer. Our results have also provided a mechanistic basis for the sensitivity of SCLC to BET inhibition, and a rationale for the clinical development of BET inhibitors beyond hematologic cancers. Citation Format: Susan Wee, Tai Wong, BMS. Identification of a transcription factor driving BET dependency in SCLC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1374. doi:10.1158/1538-7445.AM2014-1374
Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia
Authors: Karen A. Urtishak, Alena Y. Z. Edwards, Li-San Wang, Amanda Hudome, Blaine W. Robinson, Jeffrey S. Barrett, Kajia Cao, Lori Cory, Jonni S. Moore, Andrew D. Bantly, Qian-Chun Yu, I-Ming L. Chen, Susan R. Atlas, Cheryl L. Willman, Mondira Kundu, Andrew J. Carroll, Nyla A. Heerema, Meenakshi Devidas, Joanne M. Hilden, ZoAnn E. Dreyer, Stephen P. Hunger, Gregory H. Reaman, Carolyn A. Felix
Journal: Blood (2013)
Plasma Steroid and Luteinizing Hormone Levels during Prostaglandin F2 Administration in Luteal Phase of Menstrual Cycle
Authors: K. Hillier, A. Dutton, C. S. Corker, A. Singer, M. P. Embrey
Journal: BMJ (1972)

An intravenous infusion of prostaglandin F<sub>2</sub>α (12.5-250μg/min) was administered in four volunteers in the mid-late luteal phase and three in the early luteal phase of the menstrual cycle. Frequent measurement of plasma progesterone, oestrogens, and luteinizing hormone (LH) showed that administration of high doses depressed plasma progesterone levels in the late luteal phase and caused concomitant side effects. Levels of progesterone in the early luteal phase were unaffected. In both phases oestrogen and LH levels were little altered. In two subjects, hourly progesterone levels measured throughout the day at a similar time in a subsequent control menstrual cycle showed an appreciable variation in one but steady levels in the second. This variation may contribute to the magnitude of the fall in progesterone noted during the infusion of prostaglandins.
Cutaneous presentation of prolymphocytic leukaemia
Authors: R.A. LOGAN, N.P. SMITH
Journal: British Journal of Dermatology (1988)

We report a case of prolymphocytic leukaemia which presented with annular, purpuric, erythematous plaques in the skin. Histology of the lesions showed cutaneous invasion with leukaemic cells. The lesions cleared with chlorambucil and prednisolone, and the leukaemic state responded to deoxycoformycin, an experimental anti T cell agent.
Fascicular Block and Acute Myocardial Infarction
Authors: Melvin M. Scheinman
Journal: JAMA (1980)

PROPER treatment of patients with acute myocardial infarction and fascicular block depends on understanding of the relationship between the ventricular specialized conduction system and its blood supply. In this article, we detail the importance of site of infarction, the type of ECG abnormality, and the clinical status of the patient in formulating a rational treatment program. <h3>VENTRICULAR SPECIALIZED CONDUCTION SYSTEM (VSCS) AND ITS BLOOD SUPPLY</h3> The VSCS begins with the branching portion of the His bundle in which fibers segregate into right and left bundle branches (Fig 1). The right bundle-branch (RBB) is long and slender and terminates into a Purkinje network relatively late in its course. In contrast, the left bundle-branch (LBB) divides early into a left anterior fascicle and a left posterior fascicle.<sup>1</sup>Special fibers derived from the left conducting system activate the septum. The blood supply to the His bundle is usually dual,<sup>2</sup>arising from
EFFECT OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND RECEPTOR BLOCKERS ON APPROPRIATE IMPLANTABLE CARDIAC DEFIBRILLATOR SHOCK: INSIGHTS FROM THE GRADE MULTICENTER STUDY
Authors: Wael AlJaroudi, Marwan Refaat, Robert Habib, Laila Al Shaar, Rebecca Gutmann, Heather Bloom, Samuel Dudley, Patrick Ellinor, Dennis McNamara, Samir Saba, Alaa Shalaby, Raoul Weiss, Barry London
Journal: Journal of the American College of Cardiology (2014)
Characterization of cDNA microarrays fabricated using thermal ink jets
Authors: M. Caren, P. Webb, L. Bruhn, D. Wiest, D. Ilsley, L. DaQuino, W. Fisher, R. Tella, H. Cattell, K. Schliefer, J. Bass, D. Roitman, G. Fulcrand, R. Simon, P. Tseng, M. Westal, M. Bittner, Y. Chen, P. Meltzer, J. Trent, D. Amorese
Journal: Nature Genetics (1999)