tbuckley/cabot-search huggingface dataset:
Abstract 4886: Knockdown of EZH2 inhibits the malignant phenotype of lung cancer cells
Authors: Fang Liu, Sichuan Xi, Mary Zhang, Clinton Kemp, Mahadev Rao, Yuwei Zhang, David Schrump
Journal: Cancer Research (2010)

Abstract Polycomb group (PcG) proteins, which are global epigenetic gene silencers, play key roles in the maintenance of stem cell pluripotency, multicellular development, and tumorigenesis. EZH2, a core component of PcG and H3K27 methyltranferase, is highly expressed during embryogenesis and malignant transformation. Presently the mechanism by which EZH2 mediates tumorigenesis and metastasis are unclear. Our recent studies indicate that cigarette smoke condensate (CSC) increases EZH2 expression and global levels of H3K27Me3 in immortalized human bronchial epithelial cells (HBEC). In the present study, we sought to further investigate the role of EZH2 in modulating the malignant phenotype of lung cancer cells. Western blot experiments demonstrated that EZH2 was significantly over-expressed in lung cancer cell lines but not in normal human bronchial epithelial cells (NHBE) or small airway epithelial cells (SAEC). EZH2-shRNA lentiviral vectors were used to knockdown EZH2 in A549 and Calu-6 lung cancer cells as well as CSC-treated HBEC. Knockdown of EZH2 decreased H3K27Me3 levels, and diminished proliferation and clonogenicity of these cells in soft agar. These observations coincided with down-regulation of Cyclin D1. Additional western blot and flow cytometry experiments are underway to examine the impact of EZH2 knockdown on cell cycle progression and apoptosis in lung cancer cells. Illumina gene expression array experiments are also in progress to identify PcG target genes upregulated by knockdown of EZH2 that correlate with reduced proliferation and decreased clonogenicity of these cells. Collectively, these data indicate that knockdown of EZH2 inhibits the malignant phenotype of lung cancer cells, and suggest that EZH2 is a promising target for lung cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4886.
Surgical management of metastatic inguinal lymphadenopathy: The term deep inguinal nodes should be abandoned
Authors: Simon C Gibson, Stephen Kettlewell, Dominique S Byrne, Alan J McKay
Journal: BMJ (2005)

Electronic data protection: procedures need drastic improvementEditor-Gulena et al are correct to challenge overzealous interpretation of data protection law in their questionnaire survey of patients' and visitors' views about having their names displayed in hospital. 1Measures taken by doctors to safeguard patient confidentiality, especially electronic records, are, however, severely deficient and fuel the concerns of those entrusted to police data security.We invited 32 surgical trainees to complete a questionnaire regarding their Data Protection Act registration and electronic data confidentiality practices.Of 29 responders, 26 trainees regularly computerised and stored patients' data.One person was registered with the Data Protection Act.Only three of 14 desktops, eight of 19 laptops, and three of 14 handheld computers forced a password logon.Sixteen of 29 trainees used the same password for all machines, and 25 of 27 passwords were less than eight characters long.All desktops, 16 of 19 laptops, and five of 14 handhelds were routinely connected to the internet, and half of these had not had their online security settings adjusted.Of 29 trainees, 28 did not encrypt their sensitive data files.Ten trainees had sent patients' data unencrypted over the internet, using a non-secure server.Electronic data confidentiality practices among surgical trainees are unsafe, and this is unlikely to be confined to our study population.A breach in confidentiality would have widespread implications for public trust.][4] Existing passwords should be improved, and biometric logon systems (fingerprint scanning) considered.Files containing sensitive data should be routinely encrypted.Magnetic and solid state computer storage devices (including hard disks, floppy disks, CD Roms, DVD Roms, and memory sticks) should undergo routine physical or electronic data shredding after their final use. 5 We are implementing medical information technology security training for this particu-lar group of doctors and would urge others to initiate similar programmes before a serious breach occurs.
<scp>IgE</scp>‐mediated anaphylaxis and allergic reactions to idursulfase in patients with<scp>H</scp>unter syndrome
Authors: J. Kim, M. R. Park, D. S. Kim, J. O. Lee, S. H. Maeng, S. Y. Cho, Y. Han, K. Ahn, D. K. Jin
Journal: Allergy (2013)

Abstract Background Enzyme replacement therapy ( ERT ) with recombinant human idursulfase is effective for the treatment of Hunter syndrome, mucopolysaccharidosis ( MPS ) type II . However, various adverse events can occur by the infusion of idursulfase. The purpose was to evaluate the occurrence of infusion‐related allergic reactions, including anaphylaxis, to idursulfase in patients with MPS II receiving ERT and to elucidate its possible mechanism. Methods A total of 34 patients with MPS II were enrolled to receive ERT with Elaprase ® at a dose of 0.5 mg/kg intravenously once a week. Information regarding the symptoms, frequency, and timing of anaphylaxis during treatment was analyzed. Presence of anti‐idursulfase IgE antibody was assessed by skin prick test ( SPT ) and enzyme‐linked immunosorbent assay ( ELISA ). Western blotting was performed to confirm the reaction between idursulfase and specific IgE . Results Three patients (8.8%) showed anaphylaxis by infusion of idursulfase. No deaths occurred during the study. Anti‐idursulfase IgE antibody was detected by SPT and ELISA . Immunoblotting with patients’ sera and Elaprase ® showed a single band of specific IgE binding to the protein around 70 kD, and idursulfase did not display amino acid sequence homology to known allergens. SPT with idursulfase demonstrated positive results in all patients with anaphylaxis. However, we failed to reveal any risk factors for the development of infusion‐related immediate‐type allergic reactions. Conclusions Anaphylaxis related to infusion of idursulfase is mediated by anti‐idursulfase IgE antibody, which might be produced by de novo synthesis. SPT is useful in predicting the occurrence of anti‐idursulfase IgE ‐mediated anaphylaxis during infusion.
Diastolic Murmur of Renal Failure
Authors: Samuel Vaisrub
Journal: JAMA (1977)

Is the murmur "innocent" or is it indicative of valvular involvement? But a short while ago this question would arise only when the murmur was systolic, never diastolic. A systolic murmur left the door open to benign interpretation, particularly if it was heard late in systole. Its "innocence" then would be taken for granted. In contrast, a diastolic murmur was always taken seriously. Its "organic" origin was not in question, and if the murmur occurred early in diastole and was soft, blowing, decrescendo in character, the diagnosis of aortic or pulmonary valve incompetence was almost certain. A reappraisal—if not a turnabout—in interpreting late systolic and early diastolic murmurs has taken place in recent years. In 1963, Barlow<sup>1</sup>established the association of the late systolic murmur with mitral valve prolapse. The systolic click-murmur syndrome has since become a subject of investigation and controversy. No such drastic change has occurred in
Research on Humans Published in JAMA-Reply
Authors: Thomas R. Hendrix
Journal: JAMA (1987)

<h3>In Reply.—</h3> The research reported in the article "Unsuspected Human Immunodeficiency Virus in Critically Ill Emergency Patients" by Baker et al<sup>1</sup>was reviewed by the Joint Committee on Clinical Investigation (the IRB for The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital). The charge to IRBs is first to evaluate the risk to the study group. The second consideration is the risk-benefit ratio. If the risk is greater than that encountered by the individual in their daily lives, this must be presented to them in written form, clearly spelling out the balance between risks of the study and the benefits. In this study, no blood was taken specifically for study purposes. It is the policy of the Department of Emergency Medicine at The Johns Hopkins Hospital when drawing blood from patients in the emergency department to draw sufficient blood to ensure that there is an adequate
Selective Defect in Nitric Oxide Synthesis May Explain the Impaired Endothelium-Dependent Vasodilation in Patients With Essential Hypertension
Authors: Carmine Cardillo, Crescence M. Kilcoyne, Arshed A. Quyyumi, Richard O. Cannon, Julio A. Panza
Journal: Circulation (1998)

Patients with essential hypertension have impaired endothelial NO activity, but the mechanism underlying this abnormality is unknown.To investigate whether the endothelial dysfunction of hypertensive patients is related to a selective defect in NO synthesis, we studied the forearm blood flow responses to intra-arterial infusion of acetylcholine (7.5 to 30 microg/min), an endothelial agonist linked to NO synthase through the Ca2+ signaling pathway, and isoproterenol (50 to 200 ng/min), a beta-adrenoceptor agonist that stimulates NO production by increasing intracellular cAMP, in 12 normotensive subjects and 12 hypertensive patients. The infusion of isoproterenol was repeated during the concurrent blockade of NO synthesis by NG-monomethyl-L-arginine (L-NMMA; 4 micromol/min). The vasodilator response to acetylcholine was significantly reduced in hypertensives compared with normotensives (maximum blood flow: 10.4+/-4.6 versus 14.4+/-3.7 mL x min[-1] x dL[-1]; P=.008). However, the vasodilator effect of isoproterenol was similar in normotensives and hypertensives (maximum blood flow: 14.4+/-5.4 versus 13.5+/-5 mL x min[-1] x dL[-1]; P=.56) and was significantly (both P<.01) and equally blunted by L-NMMA in both groups (maximum blood flow: 11+/-3 mL x min[-1] x dL[-1] in normotensives versus 10.8+/-3.9 mL x min[-1] x dL[-1] in hypertensives; P=.77). The vasodilator response to sodium nitroprusside (0.8 to 3.2 microg/min), an exogenous NO donor, was similar in both groups and was not modified by L-NMMA.Hypertensive patients have impaired endothelium-dependent vasodilation in response to acetylcholine but preserved NO activity in response to beta-adrenergic stimulation. These findings suggest that the endothelial dysfunction in essential hypertension is due to a selective abnormality of NO synthesis, probably related to a defect in the phosphatidylinositol/Ca2+ signaling pathway.
Immunophilins: Switched on protein binding domains?
Authors: Michael T.G. Ivery
Journal: Medicinal Research Reviews (2000)

Peptidylprolyl isomerases (PPIases) are a group of cytosolic enzymes first characterized by their ability to catalyze the cis–trans isomerization of cis-peptidylprolyl bonds. Subsequently, some PPIases were also identified as the initial targets of the immunosuppressant drugs—cyclosporin A (CsA), FK506, and rapamycin—have been called immunophilins. Immunophilins have been found to be both widely distributed and abundantly expressed leading to suggestions that they may play a general role in cellular biochemistry. However, the nature of this role has been difficult to elucidate and is still controversial in vivo. A number of roles for these enzymes have been identified in vitro including the ability to catalyze the refolding of partly denatured proteins and stabilize multiprotein complexes such as Ca2+ channels, inactive steroid receptor complexes, and receptor protein tyrosine kinases. Generally, these effects appear to depend on the ability of immunophilins to selectively bind to other proteins. This review will examine in detail experimental and structural investigations of the mechanism of PPIase activity for both FKBPs and cyclophilins and suggest a mechanism for these enzymes, which depends on their ability to recognize a specific peptide conformation rather than sequence. Examination of structures of immunophilin–protein complexes will then be used to further suggest that the ability of these enzymes to recognize specific peptide conformations is central to the formation of these complexes and may constitute a general function of immunophilin enzymes. The binding of ligand to immunophilins will also be shown to stabilize specific conformations in surface loops of these proteins that are observed to play a critical role in a number of immunophilin–protein complexes suggesting that the immunophilins may constitute a class of ligand-triggered selective protein binders. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 6, 452–484, 2000
Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia
Authors: Constantine S. Tam, Susan O'Brien, William Wierda, Hagop Kantarjian, Sijin Wen, Kim-Anh Do, Deborah A. Thomas, Jorge Cortes, Susan Lerner, Michael J. Keating
Journal: Blood (2008)
US company at centre of dialysis scare
Authors: Carl Kovac
Journal: BMJ (2001)

Baxter International, a US manufacturer of medical devices, late last week initiated a global recall of several types of its membrane dialysers following the deaths earlier this month of 21 kidney patients in Croatia.

A Baxter kidney blood filter was also linked to the deaths in August of 12 patients having haemodialysis treatment in hospitals in Spain, but the filter has since been given a clean bill of health.

The Croatian patients all died between 8 October and 13 October. All had been undergoing treatment at hospitals in Zagreb, Dubrovnik, Sibenik, and Pula with membrane dialysis filters manufactured by US based Baxter International. Some died while having treatment; others choked to death or died of coronary problems shortly after treatment.

Most …
Factors That Contribute to Hypertransaminasemia in Patients With Celiac Disease or Functional Gastrointestinal Syndromes
Authors: Barbara Zanini, Roberta Baschè, Alice Ferraresi, Marie Graciella Pigozzi, Chiara Ricci, Francesco Lanzarotto, Vincenzo Villanacci, Alberto Lanzini
Journal: Clinical Gastroenterology and Hepatology (2013)
Drug infusion and monitoring of blood pressure by radio-telemetry in unrestrained pigs
Authors: C. J. Bulpitt, C. T. Dollery, J. E. Pallett, E. Emons, L. Chenery, A. Johnston, E. M. Kohner, D. A. Archer
Journal: Cardiovascular Research (1970)

A system is described for drug infusion and blood pressure recording by telemetry in unrestrained pigs. Catheters are inserted in the aorta and inferior vena cava via the external iliac vessels. An instrument box carried by the animal contains arterial and venous fluid reservoirs connected to the catheters through a radio-controlled pump. The arterial catheter is connected to a pressure transducer which transmits the arterial pressure by means of a voltage-controlled oscillator and radio transmitter.
Osteoblastic differentiation of human bone marrow stromal cells in self-assembled BMP-2 receptor-binding peptide-amphiphiles
Authors: Jue-Yeon Lee, Jung-Eun Choo, Young-Suk Choi, Jin-Sook Suh, Seung-Jin Lee, Chong-Pyoung Chung, Yoon-Jeong Park
Journal: Biomaterials (2009)
An intronic silencer element is responsible for specific zonal expression of glutamine synthetase in the rat liver
Authors: Frank Gaunitz, Danilo Deichsel, Kerstin Heise, Max Werth, Ulf Anderegg, Rolf Gebhardt
Journal: Hepatology (2005)

The most striking phenomenon of glutamine synthetase (GS) expression in the liver is its unique restriction to cells surrounding the terminal hepatic venules. Expression is positively regulated by elements located in the 5′-upstream region and in the first intron of the gene. It was long believed that transcription factors present in GS-positive cells and absent in GS-negative cells are responsible for the phenomenon of zonal expression. However, strong enhancers are equally active in both types of cells. Therefore, the existence of a silencer mechanism in GS-negative hepatocytes was postulated. In the present study, a GS silencer element was investigated that was previously identified within the first intron and was shown to be able to prevent glucocorticoid-induced expression in cells negative for a transacting factor designated GS silencer element–binding protein. Reporter gene assays with the silencer element in combination with the most potent 5′-enhancer of the GS gene demonstrate that the silencer element is able to prevent enhancement mediated by the 5′-enhancer in combination with a heterologous as well as with the homologous promoter. More importantly, the effect of the silencer is shown to be restricted to GS-negative hepatocytes. In conclusion, the phenomenon of zonal expression of GS in the liver is caused by a protein present in GS-negative cells and absent in GS-positive cells that interacts with the silencer element in the first intron and not by a differential expression of enhancer-binding proteins. (HEPATOLOGY 2005.)
ALTERING THE MEDICAL CURRICULUM
Authors: RAY LYMAN WILBUR
Journal: JAMA (1927)

The medical curriculum has been the apple of discord thrown regularly into the midst of every medical faculty and of every other medical group interested in the advance of medical education. It has had its share of praise and blame. It has become something of a fetish to be guarded by boards of medical examiners and by the overdepartmentalized members of our medical faculties. In one way it symbolizes our efforts to date to bring into a short space of medical training all that laboratory science and clinical experience have contributed to the diagnosis and care of the sick. As it stands now it is a wofully inadequate structure which in spite of the best of spirit has not served to give those who have struggled and suffered through it the capacity to practice medicine or surgery.  The curriculum is simply a compromise effort on the part of those looking
Myocarditis and Cardiomyopathy Associated with Clozapine Use in the United States
Authors: Lois La Grenade, David Graham, Anne Trontell
Journal: New England Journal of Medicine (2001)

To the Editor: Bernard and coworkers (March 8 issue) 1 conclude that recombinant human activated protein C (drotrecogin alfa [activated]) is efficacious in patients with sepsis.The placebo and treatment groups appeared to be closely matched, with one important exception: the interval between the diagnosis of sepsis and the administration of appropriate antibiotic therapy.The authors state only that appropriate antibiotic therapy was started within 48 hours of the diagnosis of severe sepsis.It is axiomatic that the more severe the sepsis, the more important the requirement for prompt administration of appropriate antibiotic therapy.In a study of gram-negative bacterial sepsis in mice, we demonstrated that each hour that appropriate antibiotic therapy was delayed resulted in progressive increases in mortality. 2After a delay of three to eight hours, depending on the bacterial species, mortality by day 4 was no longer reducible.Windows of antibiotic effectiveness can also close so rapidly during severe sepsis in humans that even prompt initiation of antibiotic therapy may not reduce mortality significantly. 3 We agree that difficulty determining the time of onset of sepsis is a major impediment to progress in clinical trials, whereas animal models do not pose this problem. 4Nevertheless, because each hour of delay in initiating appropriate antibiotic therapy in patients with severe sepsis may affect the outcome, the greatest possible precision must be used in showing that this factor is similar in the study groups before any differences in outcome are attributed to other antisepsis treatments.In a previous trial in-volving sepsis, the investigators applied this principle, performing a statistical analysis to compare the study groups.
The Artist's Template
Authors: Walter Lentino, Sidney Rubenfeld
Journal: New England Journal of Medicine (1956)

CLINICAL measurement is notoriously inaccurate. Even radiotherapists, a select group of physicians specially trained in the measurement and estimation of tumor shrinkage, are completely inconsistent with themselves and with one another.A secretary in the Department of Radiotherapy of Bellevue Hospital had a benign nevus on her forearm. Different radiotherapists who attended the clinic were asked to measure the dimensions of this lesion with a standard ruler.The numerical data produced by these different examiners provided a variable picture of tumor shrinkage and growth. If the measurements were charted according to the day on which they were done, the curve . . .
Intracellular delivery of desulfated heparin with bile acid conjugation alleviates T cell-mediated inflammatory arthritis via inhibition of RhoA-dependent transcellular diapedesis
Authors: Jin Hee Kang, Seung Rim Hwang, Shijin Sung, Ji Ae Jang, Md Mahmudul Alam, Keum Hee Sa, Sang-Yeob Kim, In San Kim, Young Ro Byun, Young Mo Kang
Journal: Journal of Controlled Release (2014)
Immune reactants in cryoproteins. Relationship to complement activation.
Authors: M R Wilson, C M Arroyave, L Miles, E M Tan
Journal: Annals of the Rheumatic Diseases (1977)

Cryoproteins were isolated from the serum of 5 patients with essential cryoglobulinaemia 5 patients with rheumatoid arthritis, and 2 patients with Sjøgren's syndrome. These cryoprecipitates contained IgG, IgM, and IgA as well as complement proteins C1q, C4, C3, and factor B. The cryoprecipitates were analysed further for content of antibody and antigen, and were tested for their ability to activate complement. In the cryoprecipitates of 2 patients with Sjøgren's syndrome, nuclear antigen and antinuclear antibody characteristic of an immunological specificity found in Sjøgren's syndrome were shown. The cryoprecipitates of 6 other patients contained rheumatoid factor and antibody to a lymphocyte nuclear antigen. The solubilized cryoprecipitates were tested by in vitro assays for their ability to activate complement by the classical or alternative pathways. All 12 cryoprecipitates activated the classical pathway. 9 of the 12 cryoprecipitates also activated the alternative complement pathway under conditions which did not involve activation of C1 and C4. These studies show that a high percentage of cryoprecipitates consist at least in part of immune reactants. We discuss the relationship of these findings to pathogenetic mechanisms in disease.
CASE of ACUTE RACHITIC CURVATURE of TIBIAe BACKWARDS
Authors: J. Poland
Journal: BMJ (1898)

1 I'SIS recovery of the muscle would have been a matter of at least znany months.I publish the case partly for its general interest, as showing vicarious mus¢cular supply after nerve injuries, and partly for its special interest, as showing what may be expected in favourable cases in the way of recovery of function in cases of atrophy of the deltoid.