tbuckley/cabot-search huggingface dataset:
DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-SIN1 association mediates ultraviolet B (UVB)-induced Akt Ser-473 phosphorylation and skin cell survival
Authors: Ying Tu, Chao Ji, Bo Yang, Zhi Yang, Hua Gu, Chun-Cheng Lu, Rong Wang, Zhong-Lan Su, Bin Chen, Wei-Ling Sun, Ji-Ping Xia, Zhi-Gang Bi, Li He
Journal: Molecular Cancer (2013)

The exposure of skin keratinocytes to Ultraviolet (UV) irradiation leads to Akt phosphorylation at Ser-473, which is important for the carcinogenic effects of excessive sun exposure. The present study investigated the underlying mechanism of Akt Ser-473 phosphorylation by UVB radiation.We found that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and mammalian target of rapamycin (mTOR) complex 2 (mTORC2) were both required for UVB-induced Akt Ser-473 phosphorylation in keratinocytes. Inhibition of DNA-PKcs activity via its inhibitor NU7026, a dominant-negative kinase-dead mutation, RNA interference (RNAi) or gene depletion led to the attenuation of UVB-induced Akt Ser-473 phosphorylation. Meanwhile, siRNA silencing or gene depletion of SIN1, a key component of mTORC2, abolished Akt Ser-473 phosphorylation by UVB. Significantly, we discovered that DNA-PKcs was associated with SIN1 in cytosol upon UVB radiation, and this complexation appeared required for Akt Ser-473 phosphorylation. Meanwhile, this DNA-PKcs-SIN1 complexation by UVB was dependent on epidermal growth factor receptor (EGFR) activation, and was disrupted by an EGFR inhibitor (AG1478) or by EGFR depletion. UVB-induced complexation between DNA-PKcs and mTORC2 components was also abolished by NU7026 and DNA-PKcs mutation. Finally, we found that both DNA-PKcs and SIN1 were associated with apoptosis resistance of UVB radiation, and inhibition of them by NU7026 or genetic depletion significantly enhanced UVB-induced cell death and apoptosis.Taken together, these results strongly suggest that DNA-PKcs-mTORC2 association is required for UVB-induced Akt Ser-473 phosphorylation and cell survival, and might be important for tumor cell transformation.
Cyclooxygenase-2–Derived Prostaglandin E2 Activates β-Catenin in Human Cholangiocarcinoma Cells: Evidence for Inhibition of These Signaling Pathways by ω3 Polyunsaturated Fatty Acids
Authors: Kyu Lim, Chang Han, Lihong Xu, Kumiko Isse, Anthony J. Demetris, Tong Wu
Journal: Cancer Research (2008)

Abstract Cholangiocarcinoma is a highly malignant neoplasm of the biliary tree. It has a high rate of mortality, and currently, there is no effective chemoprevention and treatment. This study was designed to investigate the potential effect of ω3 polyunsaturated fatty acids (ω3-PUFA) on human cholangiocarcinoma cell growth and to determine their mechanisms of actions. Treatment of three human cholangiocarcinoma cells (CCLP1, HuCCT1, SG231) with two ω3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), for 12 to 72 h resulted in a dose- and time-dependent inhibition of cell growth; in contrast, arachidonic acid, a ω6-PUFA, had no significant effect. The ω3-PUFA effect is due to the induction of apoptosis, given that DHA induced the cleaved form of PARP, caspase-3, and caspase-9. DHA and EPA treatment caused dephosphorylation (and hence, the activation) of glycogen synthase kinase-3β (GSK-3β) with a decline of β-catenin protein. Accordingly, DHA treatment also decreased the β-catenin–mediated T cell factor/lymphoid enhancer factor (TCF/LEF) reporter activity, and inhibited the expression of c-Met, a β-catenin–controlled downstream gene implicated in cholangiocarcinogenesis. The GSK-3β inhibitor, SB216763, partially prevented DHA-induced reduction of β-catenin protein and TCF/LEF reporter activity, and restored cell growth, suggesting the involvement of GSK-3β dephosphorylation in ω3-PUFA–induced β-catenin degradation. In parallel, DHA treatment also induced the formation of the β-catenin/Axin/GSK-3β binding complex, further leading to β-catenin degradation. Moreover, DHA inhibited the expression of cyclooxygenase-2 (COX-2) and enhanced the expression of 15-hydroxyprostaglandin dehydrogenase, a physiologic COX-2 antagonist, in human cholangiocarcinoma cells. These findings suggest that ω3-PUFAs block cholangiocarcinoma cell growth at least in part through inhibition of Wnt/β-catenin and COX-2 signaling pathways. Thus, utilization of ω3-PUFAs may represent an effective and safe therapeutic approach for the chemoprevention and treatment of human cholangiocarcinoma. [Cancer Res 2008;68(2):553–60]
FDA approves drugs even when experts on its advisory panels raise safety questions
Authors: L. Landow
Journal: BMJ (1999)

EDITOR—After reading the editorial questioning whether the Food and Drug Administration is approving drugs too fast I was perplexed by the conclusion—”probably not.”1 Apparently the authors failed to read the transcript of the meeting of the administration's advisory committee for mibefradil (NDA 20-689), which is on the administration's websiteK—one of three drugs recently recalled by the administration because of deaths and serious morbidity.

If they had read this transcript they would have been overwhelmed by the …
Prognostic Value of Child-Turcotte Criteria in Medically Treated Cirrhosis
Authors: Erik Christensen, Poul Schlichting, Lis Fauerholdt, Christian Gluud, Per Kragh Andersen, Erik Juhl, Hemming Poulsen, Niels Tygstrup
Journal: Hepatology (1984)

The Child-Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC in conservatively treated cirrhosis. Patients (n = 245) with histologically verified cirrhosis from a control group of a controlled clinical trial were studied. Data at entry into the trial were used to classify patients according to CTC. Survival curves for up to 16 years were made, and survival rates were compared using the log-rank test. Survival decreased significantly with increasing degree of abnormality (A ± B ± C) of albumin (p < 0.001), ascites (p < 0.001), bilirubin (p = 0.02) and nutritional status (p = 0.03). Survival was insignificantly influenced by neurological status (p = 0.11) probably because none of the patients had hepatic coma at entry into the trial. The five variables in CTC were combined to a score. With increasing score, the median survival time decreased from 6.4 years (score 5) to 2 months (scores 12 or more). Furthermore, the mortality from hepatic failure, gastrointestinal bleeding or hepatocellular carcinoma increased significantly with increasing score. CTC provide valuable and easily obtainable prognostic information in cirrhosis. However, CTC are inferior to a prognostic index based on multivariate analysis of prognostic factors.
DO WE OBEY THE CODE OF ETHICS.
Authors: R. G. ECCLES
Journal: JAMA (1899)

The laws of ethics are as firmly fixed in the nature of things as are the laws of astronomy or of chemistry. Disobedience to their mandates is as certain to bring disaster to those who disobey as disregard of the law of gravity brings pain and suffering to those who try to walk over a precipice. Every true law of ethics is fundamentally fixed in the make-up of society and is in no sense a mere empiric order of things without adequate reason. Whenever we disobey such a law we do so at our peril. Good conduct is conduct that comports itself in such a way as to lead to the highest social good. It is conduct that harmonizes with the best interests of society. When certain lines of conduct are interdicted by our fellows we may be quite sure that it is now, or at
Austin-Flint Murmur versus the Murmur of Organic Mitral Stenosis
Authors: William Nasser, Morton E. Tavel, Harvey Feigenbaum, Charles Fisch
Journal: New England Journal of Medicine (1966)

INDIANAPOLIS, INDIANAINTERPRETATION of the significance of the apical diastolic rumbling murmur in the presence of aortic insufficiency has continued to plague clinicians since the report by Austin Flint1 in 1862. The Austin-Flint murmur is an apical rumbling diastolic murmur that may occur in mid-diastole or presystole, or both, in patients with severe aortic insufficiency.2 Segal, Harvey and Corrado3 suggested historical, auscultatory, electrocardiographic and roentgeno-graphic means of differentiation between the Austin-Flint murmur and mitral stenosis. In most cases an accurate diagnosis can be made by means of these clinical criteria, but hemodynamic studies are occasionally necessary for definitive confirmation. It . . .
Diabetes mellitus and early mortality from stroke.
Authors: S M Oppenheimer, B I Hoffbrand, G A Oswald, J S Yudkin
Journal: BMJ (1985)

Dicyclomine hydrochloride in infantile colicDicyclomine hydrochloride is often used to treat infantile colic in Sweden, although in the United Kingdom it is now regarded as being contraindicated in infants aged six months and under.Results from three previous studies suggested its effectiveness.53In these studies, however, the placebo did not taste like dicyclomine (in the most recent study, for instance, cherry syrup was used as the placebo3), and thus whether these studies were blind is not clear, as parents often taste their children's drugs.One aim of the present study was to investigate the effects of dicyclomine compared with a placebo with identical smell, taste, colour, and texture.Another goal was to identify factors, such as age and rhythm and amount of crying, that would predict whether treatment would be successful.
The last examiner
Authors: J. O. Drife
Journal: BMJ (1997)

![][1] 

Hong Kong University's steeply sloping campus is crammed with buildings and ingeniously engineered roads. Its guest house has trees, a fishpond, and distant harbour views, and the shirtsleeved visitors come mainly from China or North America. One, with white beard and shorts, might have come from a Tintin book. As for me, I wore my college bow tie and jetlagged suit, as befits a British external examiner.

The final MBBS examination in obstetrics and gynaecology was 49 days before handover, according to the countdown in the local paper. The students would be the first to graduate under Chinese rule. Hong Kong is …

 [1]: /embed/graphic-1.gif
The Multiproblem Patient
Authors: Kenneth M. Golden
Journal: JAMA (1978)

With greater accessibility of patients from lower socioeconomic backgrounds to medical care, the physician in private or clinical practice is increasingly confronted with patients whose medical problems either become quickly overshadowed by or entwined with seemingly hopeless socioeconomic or legal problems. Traditionally, these patients have sought help in charity hospitals and emergency rooms that are staffed with social workers, rehabilitation counselors, and other trained personnel who could deal with problems that were not specifically medical. As accessibility to physicians in private or clinical practice increases, the need for specific techniques in working with persons from this population becomes critical.
Textbook of Radiotherapy
Authors: Stanley Order
Journal: JAMA (1981)

Fletcher's textbook stands as a monument to the extensive clinical development of radiotherapy at M. D. Anderson Hospital, particularly in head and neck and gynecologic malignant disease. The chapter concerning the basic principles of radiotherapy by Withers and Peters is extensive and well written and covers many of the newer considerations such as hyperthermia, radiation and immunity, immunogenetics, and interaction between radiation and drugs. A well-written and useful chapter concerning dental care in irradiated patients will be welcomed by readers. The review of developments in head and neck radiotherapy is superb. Similarly, an outstanding review is presented by Bouchard of CNS tumors. The thoroughness of Montague's review of breast cancer represents an important experience. A well-written review of lymphomatous disease by Million is as thorough as the pages allow, but one cannot help but feel that the authority of Kaplan would have made this text of finer vintage. Chapters covering
P17.60 * NOVO-TTF 100A SYSTEM USED SUCCESSFULLY IN A PATIENT WITH A VENTRICULO-PERITONEAL SHUNT
Authors: M. M. Mrugala, C. A. Graham, J. K. Rockhill, D. L. Silbergeld
Journal: Neuro-Oncology (2014)

BACKGROUND: NovoTTF-100A system is a new modality of treatment approved for therapy of recurrent glioblastoma. Most patients with supratentorial tumors are eligible for therapy with the system, however, data on safety of this therapy in patients with intraventricular devices is very limited. METHODS: A 54-years old woman was originally diagnosed with oligodendroglioma WHO grade II 16 years ago. During the course of treatment she had 3 craniotomies for tumor resection, chemotherapy with 22 cycles of temozolomide, 2 cycles of PCV and radiotherapy, including stereotactic approach. Following her last resection, tumor specimen exhibited features of high-grade glioma with areas of high cellularity, microvascular proliferation and invasion of the leptomeninges. Patient's course was complicated by severe recurring cytopenias. She developed a subgaleal pseudomeningocele,following her last surgery which required placement of a ventriculo-peritoneal (VP) shunt with a non-programmable valve. At this stage her treatment options for progressive malignant glioma were very limited and we elected to use NovoTTF-100A system. RESULTS: The patient tolerated treatment well. There were no complications associated with the NovoTTF-100A system and VP shunt used concomitantly. Patients' pseudomeningocele responded very well to shunting and eventually resolved. Her compliance with NovoTTF-100A system was relatively low, averaging at 39.2%, nevertheless, after six months of therapy there was no radiographic evidence of disease progression. CONCLUSIONS: Based on this limited experience we conclude that NovoTTF-100A system can be safely used in patients with VP shunts and non-programmable valves. Moreover, encouraging progression free survival was seen in this patient with heavily pre-treated glioma using NovoTTF-100A system as a single modality.
CROUP.Read in the Section of Diseases of Children at the Forty-first Annual Meeting of the American Medical Association, Nashville, Tenn., May 21, 1890.
Authors: C. R. EARLEY
Journal: JAMA (1890)

Dr. William Cullen calls this disease "Cynanche Trachealis." "This name has been given to an inflammation of the glottis, larynx, or upper part of the trachea, whether it affect the membranes of these parts, or the muscles adjoining. It may arise first in these parts, and continue to subsist in them alone; or it may come to affect these parts, from the cynanche tonsillaris or maligna spreading into them. In either way it has been a rare occurrence, and few instances of it have been marked and recorded by physicians. It is to be known by a peculiar ringing sound of the voice, by difficult respiration, with a sense of straitening about the larynx, and by a pyrexia attending it." We will now refer to the writings of Bartholomew Parr, M.D. "ANGINA TRACHEALIS." "In compliance with Dr. Johnson and consonantly with our observations in a former article, we mention this
Registration of Non-Resident Physicians Discontinued.
Authors: J. N. McCormack
Journal: JAMA (1902)

To the Editor:\p=m-\InThe Journal of the 14th inst.you com- ment on what you evidently consider an undesirable innovation in medical practice in England, viz., the dividing of the fee, in obstetric cases, with the nurse.This is not by any means a new custom in England, nor is it attended by the evil results that might be anticipated; and if it could be carried out in some localities in this country many a practitioner would be glad to practice a system that would save any "booking" of obstetric fees.
Pay of related ancillary workers
Authors: J. D Carr
Journal: BMJ (1980)

who continued treatment with tamoxifen alone did not have a response.We agree that tamoxifen-induced hyper- calcaemia probably is not uncommon, but as yet there is no firm evidence to support the suggestion that induced hypercalcaemia is indicative of a good response to tamoxifen or other additive hormones used in the treatment of breast cancer.
Correction: Therapeutic Substitution and Formulary Systems
Authors: Richard G. Farmer, Linda Johnson White
Journal: Annals of Internal Medicine (1990)

Letters15 October 1990Correction: Therapeutic Substitution and Formulary SystemsRichard G. Farmer, MD, Linda Johnson WhiteRichard G. Farmer, MDSearch for more papers by this author, Linda Johnson WhiteSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-8-640_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn our position paper on therapeutic substitution (1), we incorrectly cite cefazolin and cefotaxime as an example of therapeutic equivalents with the same pharmacokinetic and pharmacodynamic properties. The drugs are first- and third-generation cephalosporins. In reality, it is difficult to identify two drugs with exactly the same properties; the College's position paper deals with substitution of drugs with similar pharmacologic and therapeutic properties, as occurs in actual practice. We regret the error....Reference1. . Therapeutic substitution and formulary systems. Ann Intern Med. 1990;113:160-3. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1990Volume 113, Issue 8Page: 640-640KeywordsDrug therapyDrugsEmotionsPharmacodynamicsPharmacokinetics Issue Published: 15 October 1990 PDF downloadLoading ...
Antibiotics to Prevent Infective Endocarditis
Authors: Ann R. Punnoose, Cassio Lynm, Robert M. Golub
Journal: JAMA (2012)

Cross section of heart Right atriumLeft atrium I nfective endocarditis is an infection inside the chambers of the heart or on the heart valves.Infectious endocarditis may be triggered by a clot forming on the lining of the heart or on one of its valves in response to damage on the valve surface.Once this clot forms, bacteria that may be present in the bloodstream (bacteremia) can stick to the clot and proliferate (multiply) within it, eventually interfering with the heart's function.
Generic Drug Savings
Authors: Marie-Laure Laroche, Louis Merle
Journal: Annals of Internal Medicine (2005)

Letters6 December 2005Generic Drug SavingsMarie-Laure Laroche, MD and Louis Merle, MD, PhDMarie-Laure Laroche, MDFrom Hôpital Universitaire Dupuytren, Limoges 87042, France.Search for more papers by this author and Louis Merle, MD, PhDFrom Hôpital Universitaire Dupuytren, Limoges 87042, France.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-11-200512060-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We agree with most of Haas and colleagues' statements (1) regarding the benefits of substituting generic drugs for brand-name drugs; however, we would like to stress that the authors assume that both the quality and the composition of generic and brand-name drugs are equivalent. From our pharmacovigilance experience in France and in Mauritania, we do not think this assumption applies everywhere. The use of poor-quality generic drugs could have obvious consequences when the long-term treatment of a serious condition, such as epilepsy, is at stake (2). Excipients that can induce cutaneous allergic reactions, such as macrogol, starch, ...References1. Haas JS, Phillips KA, Gerstenberger EP, Seger AC. Potential savings from substituting generic drugs for brand-name drugs: Medical Expenditure Panel Survey, 1997-2000. Ann Intern Med. 2005;142:891-7. [PMID: 15941695] LinkGoogle Scholar2. Laroche ML, Traore H, Merle L, Gaulier JM, Viana M, Preux PM. Quality of phenobarbital solid-dosage forms in the urban community of Nouakchott (Mauritania). Epilepsia. 2005;46:1293-6. [PMID: 16060942] CrossrefMedlineGoogle Scholar3. Merle L, Laroche ML, Dantoine T, Charmes JP. Predicting and preventing adverse drug reactions in the very old. Drugs Aging. 2005;22:375-92. [PMID: 15903351] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Hôpital Universitaire Dupuytren, Limoges 87042, France.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPotential Savings from Substituting Generic Drugs for Brand-Name Drugs: Medical Expenditure Panel Survey, 1997–2000 Jennifer S. Haas , Kathryn A. Phillips , Eric P. Gerstenberger , and Andrew C. Seger Generic Drug Savings Jennifer S. Haas , Kathryn A. Phillips , and Andrew C. Seger Metrics Cited byGENERIC AND BRAND-NAME DRUGS. ARE DIFFERENT CRITERIA SUFFICIENTLY TAKEN INTO ACCOUNT BEFORE GRANTING MARKET AUTHORISATION? 6 December 2005Volume 143, Issue 11Page: 844-845KeywordsAdverse reactionsDrug safetyDrugsElderlyEpilepsyHospitalizationsHyperglycemiaPharmacistsStarchesToxicity ePublished: 6 December 2005 Issue Published: 6 December 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Independent Medical Examinations: An Expanding Source of Physician Liability
Authors: Ken Baum
Journal: Annals of Internal Medicine (2005)

Employers frequently ask physicians to conduct medical examinations and review radiology films and other diagnostic tests of employees. Physicians also provide such services at the request of other third parties. These examinations are commonly called independent medical examinations. Increasingly, patients are bringing and prevailing in medical malpractice lawsuits against physicians who conduct independent medical examinations, in part because of physicians' misconceptions of their legal duties in this context. Despite the absence of a traditional physician–patient relationship, physicians who conduct independent medical examinations still owe various legal duties to the examinee patient, although the precise scope of those duties is a source of constant debate and change. Since 2001 alone, 4 state supreme courts have exercised their discretion to hear cases on this issue, bearing witness to its medical, legal, and social significance. Given the current medical malpractice climate, it is imperative that physicians understand the potential liability inherent in conducting independent medical examinations. This article summarizes controlling law, clarifying an otherwise muddied legal picture. It also offers practical suggestions for limiting physician liability in independent medical examinations.
A Novel Element Upstream of the Vγ2 Gene in the Murine T Cell Receptor γ Locus Cooperates with the 3′ Enhancer to Act as a Locus Control Region
Authors: Jeanne E. Baker, Joonsoo Kang, Na Xiong, Tempe Chen, Dragana Cado, David H. Raulet
Journal: The Journal of Experimental Medicine (1999)

Transgenic expression constructs were employed to identify a cis-acting transcription element in the T cell receptor (TCR)-γ locus, called HsA, between the Vγ5 and Vγ2 genes. In constructs lacking the previously defined enhancer (3′ECγ1), HsA supports transcription in mature but not immature T cells in a largely position-independent fashion. 3′ECγ1, without HsA, supports transcription in immature and mature T cells but is subject to severe position effects. Together, the two elements support expression in immature and mature T cells in a copy number–dependent, position-independent fashion. Furthermore, HsA was necessary for consistent rearrangement of transgenic recombination substrates. These data suggest that HsA provides chromatin-opening activity and, together with 3′ECγ1, constitutes a T cell–specific locus control region for the TCR-γ locus.