tbuckley/cabot-search huggingface dataset:
Abstract 3798: Heat shock cognate protein HSPA8 (Hsc70) regulates migration and xenograft growth of breast tumor cell lines.
Authors: Maria F. Pino, Ge Zhang, Charles J. Rosser, Steve Goodison, Virginia Urquidi
Journal: Cancer Research (2013)

Abstract In order to identify genes involved in the metastatic phenotype we had previously developed isogenic cell lines from the human breast carcinoma cell line MDA-MB-435 that have different metastatic phenotypes in immunocompromised mice. Proteomic profiling of the extracellular component of this model identified the heat shock cognate protein HSPA8 (Hsc70) as over-expressed in the metastatic cell line (M4A4) relative to its non-metastatic counterpart (NM2C5). Heat shock proteins are primarily implicated in a cytoprotective role when cells are exposed to stressful stimuli. They are intracellular molecular chaperones but are also found in the surface of embryonic stem cells and a variety of tumor cells. With the purpose of investigating the role of HSPA8 in tumor growth and metastasis, we first verified that this protein was expressed on the cell surface and in the conditioned medium of M4A4 cells, in addition to its intracellular location. Then we generated stable HSPA8 knockdown clones of the M4A4 cells and cell behavior was tested in a panel of analyses in vitro and xenograft growth was tested in immunocompromised mice. Knockdown of HSPA8 expression in M4A4 cells resulted in reduction of cell doubling time and of their migration potential in vitro. When individual M4A4-HSPA8 knocked down cell clones were injected into the mammary fat pad of immunocompromised mice significant reduction of the tumor size was observed relative to non-silencing control cells. The invasive and metastatic potential of the M4A4-HSPA8 knockdown clones as well as their transcriptional profile are currently under investigation. Our findings suggest that HSPA8 plays a role in cell growth in vitro and in vivo and may be involved in metastasis of breast cancer cells. Extracellular heat shock proteins have recently been shown to mediate a range of powerful effects in inflammatory, neuronal and immune cells through a number of cell surface receptors. The mechanisms involved in tumor dissemination and metastasis are potential targets for therapeutic intervention Citation Format: Maria F. Pino, Ge Zhang, Charles J. Rosser, Steve Goodison, Virginia Urquidi. Heat shock cognate protein HSPA8 (Hsc70) regulates migration and xenograft growth of breast tumor cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3798. doi:10.1158/1538-7445.AM2013-3798
Skeletal muscle glycogenolysis is more sensitive to insulin than is glucose transport/phosphorylation. Relation to the insulin-mediated inhibition of hepatic glucose production.
Authors: L Rossetti, M Hu
Journal: Journal of Clinical Investigation (1993)

The effects of minimal increments in plasma insulin concentrations on hepatic glucose production and glucose uptake, skeletal muscle net glycogen synthesis and glycogenolysis, glycogen synthase and phosphorylase activity, glucose-6-phosphate and uridinediphosphoglucose (UDPG) concentrations were examined in 24-h and in 6-h fasted conscious rats. Insulin was infused for 120 min at rates of 1.5, 3, 6, 12, 24, and 108 pmol/kg per min in 24-h fasted rats and at rates of 3, 6, 9, 12, 36, and 108 pmol/kg per min in 6-h fasted rats while endogenous insulin release was inhibited by SRIF infusion and plasma glucose was maintained at the basal level. All rats received an infusion of [3-3H]glucose. The portion of the muscle glucose-6-phosphate (G6P) pool derived from net glycogenolysis was estimated from the ratio of specific activities of muscle UDPG and plasma glucose. Minimal increments in the circulating insulin levels, which did not stimulate glucose uptake, caused: (a) the increase in skeletal muscle glycogen synthase activity and the decrease in the rate of muscle glycogenolysis and in the G6P concentration; (b) the inhibition of hepatic glucose production. Net muscle glycogen synthesis was not stimulated despite submaximal activation of glycogen synthase, and its onset correlated with the rise in muscle G6P levels. Thus, insulin's inhibition of muscle glycogenolysis is the most sensitive insulin action on skeletal muscle and its dose-response characteristics resemble those for the inhibition of hepatic glucose production. These findings indicate that skeletal muscle glycogen synthase may play a major role in carbohydrate homeostasis even under postabsorptive (basal insulin) conditions and support the notion that insulin may exert some of its effects on the liver through an indirect or peripheral mechanism.
AIDS Law Today: A New Guide for the Public
Authors: Ralf Jürgens
Journal: JAMA (1994)

When the first edition of this book (called<i>AIDS and the Law: A Guide for the Public</i>) went to press in 1988, the legal profession had just recently "discovered" the acquired immunodeficiency syndrome (AIDS). There were only a handful of judicial decisions involving the human immunodeficiency virus (HIV) and AIDS and few books that covered the legal issues raised by the epidemic. Since then, AIDS has become the most litigated of diseases in the United States. <i>AIDS and the Law</i>was written in lay terms and intended as a guide for the public rather than for lawyers. The book consists of a first chapter titled "A Little Law for Non-Lawyers," a section reviewing the medical background of AIDS, a comparison to other epidemics in history, an analysis of the relationship between lawyers and physicians, and 16 essays on a wide range of social, political, financial, and practical issues related to
The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias
Authors: Anna K Andersson, Jing Ma, Jianmin Wang, Xiang Chen, Amanda Larson Gedman, Jinjun Dang, Joy Nakitandwe, Linda Holmfeldt, Matthew Parker, John Easton, Robert Huether, Richard Kriwacki, Michael Rusch, Gang Wu, Yongjin Li, Heather Mulder, Susana Raimondi, Stanley Pounds, Guolian Kang, Lei Shi, Jared Becksfort, Pankaj Gupta, Debbie Payne-Turner, Bhavin Vadodaria, Kristy Boggs, Donald Yergeau, Jayanthi Manne, Guangchun Song, Michael Edmonson, Panduka Nagahawatte, Lei Wei, Cheng Cheng, Deqing Pei, Rosemary Sutton, Nicola C Venn, Albert Chetcuti, Amanda Rush, Daniel Catchpoole, Jesper Heldrup, Thoas Fioretos, Charles Lu, Li Ding, Ching-Hon Pui, Sheila Shurtleff, Charles G Mullighan, Elaine R Mardis, Richard K Wilson, Tanja A Gruber, Jinghui Zhang, James R Downing
Journal: Nature Genetics (2015)
THE PHARMACOLOGY OF DIETHYLOXYACETYL UREA.
Authors: E. M. HOUGHTON
Journal: JAMA (1905)

Some weeks ago my attention was called to a new group of chemical bodies belonging to the methane series. According to A. H. C. Heitmann and Erik Clemmensen, the discoverers, they are condensation products of urea and the various oxyacetic acids. A consideration of the chemical structure of these compounds led to the belief that all would possess considerable hypnotic power, but the ethyl compound was thought to be the more promising for therapeutic purposes. The originators accordingly prepared and placed at my disposal sufficient quantities of the ethyl derivative in its pure state, and a little later its sodium salt, to undertake a series of animal experiments to demonstrate its pharmacologic properties. Perhaps the most desirable chemical name that can be given to the compound, as indicating its structure, is the one mentioned in the title of the paper, diethyloxyacetyl urea. The chemical formula is given by Clemmensen and
The Heart: Its Function in Health and Disease
Authors: J. Willis Hurst
Journal: JAMA (1966)

<h3>Managing Your Coronary</h3> by William A. Brams, ed 3; 175 pp, with illustrations by Hertha Furth, $3.75, Philadelphia: J. B. Lippincott Co., 1966. In his preface to<i>The Heart</i>, Dr. Selzer states, "It is hoped that this book will fill the gap between 'popular' publications and books written for those with a medical background." He acomplishes just that. The book is written lucidly and presents a good survey of heart function and heart disease as it exists in 1966. The format is standard. Beginning with a brief history of the development of knowledge related to the heart, Dr. Selzer describes the normal heart and blood vessels, and discusses the medical history, physical examination, and laboratory procedures. He then considers heart disease—including heart failure, alterations of rhythm, acute heart disease, coronary disease, hypertension, valve disease, congenital heart disease, pulmonary circulation, and diseases of the blood vessels. The author appends an excellent
Agglutinin Response to Pertussis Vaccination in the Child
Authors: J. D. Abbott, N. W. Preston, R. I. Mackay
Journal: BMJ (1971)

Children were immunized with plain pertussis vaccine made by three manufacturers in 1967. After a primary course of three injections at monthly intervals, starting at 3-4 months of age, the agglutinin response was poor. Even after a "booster" dose, given five months later, not all of the vaccines had stimulated a response to all three pertussis agglutinogens. A further investigation with current vaccines of different kinds administered according to more than one schedule is recommended.
Letter by Bhindi and Ormerod Regarding Article, “Lack of Association Between Migraine Headache and Patent Foramen Ovale: Results of a Case-Control Study”
Authors: Ravinay Bhindi, Oliver J. Ormerod
Journal: Circulation (2010)

To the Editor:Garg and colleagues 1 demonstrate no association between migraines and patent foramen ovale (PFO) in their recent case control study.Although their observations are interesting, the implications of this, another small case control study, must be considered carefully when adding to the already murky association data linking migraine with PFOs.Notwithstanding methodological issues highlighted by the authors themselves, the study is considerably underpowered in detecting differences between patients with more/less severe migraine, those with/without aura, and shunt severity.The baseline characteristics of the patient's including ethnicity are different, and 10% of all patients are on aspirin.It is also possible that the exclusion of patients with previous stroke may confound the issue, as patients with clinically significant prior paradoxical embolization events may have a more "malignant" PFO phenotype more likely to be associated with migraine.Although this study argues against an association between migraines and PFOs, it has significant limitations, and its conclusions should be kept in perspective.Larger, more inclusive studies need to be performed before this matter can be put to rest.
The Role of SPECT Imaging in Pediatric Renal Transplants
Authors: EDWIN E. YEO, JOHN H. MILLER
Journal: Clinical Nuclear Medicine (1994)

Post-transplant hypertension can be a diagnostic dilemma. In a select population of pediatric patients, in whom other diagnostic methods failed to reveal an abnormality, renal cortical SPECT imaging, using either Tc-99m GH or Tc-99m DMSA, revealed information that was not apparent on conventional planar renal scintigraphy. Abnormalities detected by this methodology included unsuspected renal infarct and areas of segmental perfusion deficit. The authors conclude that this methodology is a valuable tool in the evaluation of post renal transplantation hypertension in pediatric patients.
Abstract 2141: cAMP/PKA signaling enhances activity of Deleted in Liver Cancer 1 (DLC1) tumor suppressor in suppressing liver cancer tumorigenesis
Authors: Chi Fat Ko, Lo Kong Chan, Edith Yuk-Ting Tse, Yin-Shan Yeung, Karen Man-Fong Sze, Irene Oi-Lin Ng, Judy Wai Ping Yam
Journal: Cancer Research (2012)

Abstract Deleted in Liver Cancer 1 (DLC1) which encodes a RhoGTPase-activating protein (RhoGAP) is a tumor suppressor frequently inactivated in a wide spectrum of human cancers. The RhoGAP activity has been shown to play a predominant role in the biological activities of DLC1. It has been shown that cells with silenced DLC1 exhibit increased active RhoA level. This finding provides evidence about the activation of RhoA as the consequence of deregulated DLC1 and points to the importance of RhoGAP activity in the biological activity of DLC1. In this regard, it is important to comprehend how RhoGAP activity of DLC1 is related. Here, we show that DLC1 was robustly phosphorylated by cyclic AMP (cAMP)/Protein kinase A (PKA) signaling in cells. Phosphorylation of DLC1 was enhanced by forskolin, a known activator of PKA while suppressed when H-89, an inhibitor of PKA was added. Direct phosphorylation of DLC1 by PKA was further confirmed by the in vitro kinase assay. Using specific phospho-DLC1 antibodies, PKA was shown to phosphorylate DLC1 at S431 and S549. Functional assays demonstrate that phosphorylation at S549 plays a critical role in provoking the inhibitory activity of DLC1 in suppressing growth and motility of Ras-transduced p53 null mouse hepatoblasts. When compared with the stable clone of wild-type DLC1, stable clone of DLC1 phosphomimetic mutant, S549D, displayed a largely reduced growth of subcutaneous and orthotopic liver implanted tumors and an enhanced apoptosis. The migration and invasion rates of S549D cells were also significantly inhibited. Furthermore, S549D expression abolished stress fiber formation but failed to alter filopodia protrusions. These functional effects exerted by S549D were ascribed to the enhanced RhoGAP activity against RhoA. To further investigate the mechanism through which the RhoGAP activity is enhanced, we found that DLC1 dimerized upon S549 phosphorylation. Our findings have revealed for the first time about the regulation of RhoGAP activity of DLC1 via dimerization. Our study suggests a molecular link between PKA and DLC1/Rho pathways and underscores the importance of S549 phosphorylation in the regulation of RhoGAP activity of DLC1. (This study was funded by the Small Project Funding Program, The University of Hong Kong 200907176125) 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 2141. doi:1538-7445.AM2012-2141
A 62-Year-Old Woman With Skin Cancer Who Experienced Wrong-Site Surgery
Authors: Thomas H. Gallagher
Journal: JAMA (2009)

After a life-threatening complication of an injection for neck pain several years ago, Ms W experienced a wrong-site surgery to remove a squamous cell lesion from her nose, followed by pain, distress, and shaken trust in clinicians. Her experience highlights the challenges of communicating with patients after errors. Harmful medical errors occur relatively frequently. Gaps exist between patients' expectations for disclosure and apology and physicians' ability to deliver disclosures well. This discrepancy reflects clinicians' fear of litigation, concern that disclosure might harm patients, and lack of confidence in disclosure skills. Many institutions are developing disclosure programs, and some are reporting success in coupling disclosures with early offers of compensation to patients. However, much has yet to be learned about effective disclosure strategies. Important future developments include increased emphasis on institutions' responsibility for disclosure, involving trainees and other team members in disclosure, and strengthening the relationship between disclosure and quality improvement.
Acute impairment of endothelium-dependent relaxations to aggregating platelets following reperfusion injury in canine coronary arteries.
Authors: P J Pearson, H V Schaff, P M Vanhoutte
Journal: Circulation Research (1990)

Experiments were designed to determine whether endothelial injury contributes to augmented coronary vascular tone seen during myocardial reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia followed by reperfusion (60 minutes each). Rings (3-4 mm) of the reperfused artery and of normal left circumflex (control) coronary artery segments were prepared. Rings were suspended for isometric force measurement in organ chambers containing modified Krebs' Ringer bicarbonate solution (37 degrees C, 95% O2-5% CO2). Endothelium-independent contractions to KCl and prostaglandin F2 alpha were unaltered after reperfusion. Endothelium-dependent relaxations to nitric oxide, sodium nitroprusside, and isoproterenol were comparable in control and reperfused arteries. However, reperfused coronary arteries contracted with prostaglandin F2 alpha lost the ability to express endothelium-dependent relaxations to aggregating platelets. Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to acetylcholine, the calcium ionophore A23187, and the platelet-derived compounds ADP and serotonin. Quiescent (noncontracted) reperfused arterial rings exhibited larger contractions than controls when exposed to aggregating platelets. In such quiescent rings, the endothelium-dependent increase in tension to hemoglobin was unaltered after reperfusion. Thus, coronary reperfusion impairs the normal endothelium-dependent relaxations to aggregating platelets and vasoactive drugs. This impairment of platelet-mediated coronary relaxation could help explain the increased vascular tone and tendency toward vasospasm commonly observed after reperfusion of the coronary arteries.
Aetiology of Reye's Syndrome
Authors: A. Elkeles
Journal: BMJ (1973)

The aim of this study was to evaluate the association and interaction of genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and environmental factors with lung cancer in Taiwan. Two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed in association with lung cancer susceptibility, and discussed their joint effects with individual habits on lung cancer risk. Patients and Methods: In total, 358 patients with lung cancer and 716 healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped. Results: The MTHFR C677T genotype, but not the A1298C, was differently distributed between the lung cancer and control groups. The T allele of MTHFR C677T was significantly more frequently found in controls than in cancer patients. As for A1298C polymorphism, there was no difference in distribution between the lung cancer and control groups. Gene interactions with smoking were significant for MTHFR C677T polymorphism. The MTHFR C677T CT and TT genotypes in association with smoking conferred a decreased risk of 0.706 (95% confidence interval=0.531-0.939) for lung cancer. Conclusion: Our results provide the first evidence that the C allele of MTHFR C677T may be associated with the development of lung cancer and may be a novel useful marker for primary prevention and anticancer intervention.
Regular Source of Ambulatory Care and Medical Care Utilization by Patients Presenting to a Public Hospital Emergency Department
Authors: David W. Baker
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine the regular source of care and the relationship between usual provider and use of medical services among ambulatory emergency department patients. <h3>Design.</h3> —Cross-sectional survey. <h3>Setting.</h3> —A public hospital in Los Angeles County, California. <h3>Patients.</h3> —A total of 1190 stable, ambulatory adults presenting to the emergency department during a 2-week period. <h3>Main Outcome Measures.</h3> —Self-reported regular source of care, usual health status, and recent physician visits. <h3>Results.</h3> —A total of 16% of the patients identified an emergency department as their regular source of care. One fourth of this group reported fair or poor health. African Americans and Latinos were more likely than whites to identify an emergency department as their regular source of care. Patients who identified an emergency department as their regular source of care had 25% fewer physician visits and were less likely to have seen a physician during the preceding 3 months than patients who were usually seen in an office or clinic (relative risk, 0.45; 95% confidence interval, 0.28 to 0.70). Of all patients, 56% identified a regular source of care other than an emergency department, but 24% to 36% of all their recent physician visits still occurred in an emergency department. <h3>Conclusion.</h3> —Our patients rely heavily on emergency departments for ambulatory physician visits, regardless of their reported regular source of care. However, patients who identify an emergency department as their regular source of ambulatory care used physician services less frequently than patients with access to providers in other settings. These issues require further evaluation with populationbased surveys. (<i>JAMA</i>. 1994;271:1909-1912)
The Electrical Potential Difference Across the Cell Membrane of Heart Muscle
Authors: ERNEST PAGE
Journal: Circulation (1962)

The electrical potential difference across the cell membrane of heart muscle cells is a diffusion potential arising from the interaction of fixed charges within the membrane pores with NaCl and KCl diffusing into and out of the cell. The magnitude and sign of this potential difference depend on the relative permeabilities, of the membrane to K, Na, and Cl. The resting membrane is predominantly permeable to K, while the action potential is characterized by a transient increase in Na permeability. An intracellular solution of high K concentration and low Na concentration is separated by the cell membrane from an extracellular solution having a low K concentration and a high Na concentration. These concentration differences are maintained by active transport processes that utilize the energy derived from cellular metabolic reactions to transport Na and K "uphill" against electrical and concentration gradients.
Walk-in primary medical care centres: lessons from Canada
Authors: M. Jones
Journal: BMJ (2000)

The current reforms of the United Kingdom's primary healthcare sector intend to improve accessibility to health care. 1 One of the proposals is to introduce "walk-in" primary care centres. 2 The intention is to pilot "a series of nurse led centres which can be used on a 'drop in' basis, providing minor treatment, health information and self help advice."The Canadian medical system has many similarities to the British system.Canada's health system is funded through general taxation (and Medicare premiums), 3 and its general practitioners (family physicians) have a gatekeeper role to secondary care in most provinces.Canada has had walk-in centres for over 20 years.However, these centres are a doctor led service.The lessons learnt in Canada about walk-in centres may be relevant to the NHS.In this article I review the available literature about Canadian walk-in centres. MethodsI conducted a search using standard techniques on Medline and PubMed, with manual search and search by author.The MeSH phrases used were "walk-in," "primary care," "family medicine," and "ambulatory care."I have included papers from Canada and the United Kingdom.Papers from the United States and other countries and those covering open access to secondary care or special needs groups (such as drugs programmes) were excluded.The initial PubMed search identified 147 items, and Medline identified 66.Further examination showed a total of 28 (24 included) relevant articles including service evaluations, letters, and a literature review from 1989.The table shows the papers presenting original data.