tbuckley/cabot-search huggingface dataset:
Tumor necrosis factor α prevents tumor necrosis factor receptor-mediated mouse hepatocyte apoptosis, but not fas-mediated apoptosis: Role of nuclear factor-κB
Authors: Masahito Nagaki, Takafumi Naiki, David A. Brenner, Yosuke Osawa, Motoaki Imose, Hideki Hayashi, Yoshiko Banno, Shigeru Nakashima, Hisataka Moriwaki
Journal: Hepatology (2000)

Tumor necrosis factor α (TNF–α) binding to the TNF receptor (TNFR) initiates apoptosis and simultaneously activates the transcription factor, nuclear factor–κB (NF–κB), which suppresses apoptosis by an unknown mechanism. Pretreatment with TNF–α or interleukin–1β (IL–1β), which activated NF–κB in the liver, dramatically prevented TNF–α–induced liver–cell apoptosis in D–galactosamine (GalN)–sensitized mice, but not anti–Fas antibody–induced hepatotoxicity. This protective effect of TNF–α continued for 5 hours after TNF–α administration, a time course similar to that found in NF–κB activation after TNF–α administration. In mice treated with adenoviruses expressing a mutant form of IκB, the antiapoptotic effect of TNF–α was inhibited in part. Prior TNF–α administration was not found to block the activation of caspase–8, although caspase–3 was inhibited in mice treated with TNF–α plus GalN/TNF–α compared with mice treated with GalN/TNF–α. These results indicate that TNFR and Fas independently regulate murine apoptotic liver failure, and that a rapid defense mechanism induced by the activation of NF–κB blocks death–signaling at the initiation stage of hepatic apoptosis mediated by TNFR, probably downstream of caspase–8, but not by Fas.
Multiple division cycles and long-term survival of hepatocytes are distinctly regulated by extracellular signal-regulated kinases ERK1 and ERK2
Authors: Christophe Frémin, Anne Bessard, Frédéric Ezan, Luc Gailhouste, Morgane Régeard, Jacques Le Seyec, David Gilot, Gilles Pagès, Jacques Pouysségur, Sophie Langouët, Georges Baffet
Journal: Hepatology (2009)

We investigated the specific role of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway in the regulation of multiple cell cycles and long-term survival of normal hepatocytes. An early and sustained epidermal growth factor (EGF)-dependent MAPK activation greatly improved the potential of cell proliferation. In this condition, almost 100% of the hepatocytes proliferated, and targeting ERK1 or ERK2 via RNA interference revealed the specific involvement of ERK2 in this regulation. However, once their first cell cycle was performed, hepatocytes failed to undergo a second round of replication and stayed blocked in G1 phase. We demonstrated that sustained EGF-dependent activation of the MAPK/ERK kinase (MEK)/ERK pathway was involved in this blockage as specific transient inhibition of the cascade repotentiated hepatocytes to perform a new wave of replication and multiple cell cycles. We identified this mechanism by showing that this blockage was in part supported by ERK2-dependent p21 expression. Moreover, continuous MEK inhibition was associated with a lower apoptotic engagement, leading to an improvement of survival up to 3 weeks. Using RNA interference and ERK1 knockout mice, we extended these results by showing that this improved survival was due to the specific inhibition of ERK1 expression/phosphorylation and did not involve ERK2. Conclusion: Our results emphasize that transient MAPK inhibition allows multiple cell cycles in primary cultures of hepatocytes and that ERK2 has a key role in the regulation of S phase entry. Moreover, we revealed a major and distinct role of ERK1 in the regulation of hepatocyte survival. Taken together, our results represent an important advance in understanding long-term survival and cell cycle regulation of hepatocytes. (HEPATOLOGY 2009.)
Communicating risk: Journalists take note
Authors: D. S Rivers
Journal: BMJ (2003)

<h3>OBJECTIVE:</h3> To evaluate the clinical, biochemical, neuroradiological, and neurophysiological findings of patients with X-linked adrenoleukodystrophy. <h3>METHODS:</h3> Retrospective study evaluating the data of 10 X-linked adrenoleukodystrophy patients diagnosed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. <h3>RESULTS:</h3> The common presenting symptoms were deterioration in school performance, vision and hearing, behavioral changes, and seizures. Eight patients survived 1-4 years and one patient 12 years after the initial presentation, while one patient expired. Six patients had the childhood form, 3 had the adolescent form and one had the adrenomyeloneuropathy form. Six are in an advanced stage of the disease and 3 have mild to moderate spasticity. All except 2 manifested moderate to severe dementia with variable degrees of visual loss. Decreased hearing and features of adrenal insufficiency were seen in 7 patients. Very long chain fatty acids were significantly increased in seven and mildly elevated in 2 patients, however the C26 to C22 ratio was increased in all. The characteristic high-signal intensity of parieto-occipital white matter on brain magnetic resonance imaging T2-weighted images was observed in all patients. Two patients had functional study of the brain, which showed hypometabolic activity in gray and white matter of the occipital lobes. Various neurophysiological abnormalities were detected. The response to different treatment modalities was not promising. <h3>CONCLUSION:</h3> The disease is more common than had been previously recognized due to phenotypic variability and a wide spectrum of presentations. This report describes various aspects of this disorder and emphasizes the importance of early identification and treatment of asymptomatic but biochemically affected individuals, since all current therapeutic approaches are disappointing if overt neurological abnormalities have been already developed.
Psychiatrist and Nonphysician Mental Health Provider Staffing Levels in Health Maintenance Organizations
Authors: Thomas H. Dial, Christopher Bergsten, Mark G. Haviland, Harold Alan Pincus
Journal: American Journal of Psychiatry (1998)

This study attempts to determine the ratio of full-time-equivalent psychiatrists to members and that of nonphysician mental health professionals to psychiatrists in staff and group model health maintenance organizations (HMOs), and to compare the psychiatrist-to-member ratio with previous estimates of the required psychiatrist-to-population ratios in fee-for-service and managed care environments.The Group Health Association of America (now the American Association of Health Plans) collected data on mental health staffing, enrollments, and other characteristics for 30 staff and group model HMOs. The authors evaluated the number of full-time-equivalent psychiatrists and nonphysician mental health professionals per 100,000 HMO members, and the ratio of full-time-equivalent nonphysician mental health professionals to psychiatrists.The overall mean number of full-time-equivalent psychiatrists and nonphysician mental health professionals per 100,000 members in the responding HMOs was 6.8 and 22.9, respectively. The overall mean ratio of nonphysician professionals to psychiatrists was 4.5. The overall number of psychiatrists per 100,000 members is less than half the requirement estimated by the Graduate Medical Education National Advisory Committee in 1980, which assumed a fee-for-service environment, but it is about 40% to 80% greater than that estimated by other studies under the assumption of a managed care environment.Although a practice environment dominated by managed care may not require as high a psychiatrist-to-population ratio as a predominantly fee-for-service environment, it may well support a greater number of psychiatrists than previous studies have suggested.
Organs from animals.
Authors: R Calne
Journal: BMJ (1993)

The introduction of anal endosonography in the investiga- tion of women with idiopathic faecal incontinence has revealed an unexpectedly high incidence of anal sphincter defects, reaching 87% in one study,12 providing further evidence that the major cause of faecal incontinence in women is damage to the deep parts of the anal sphincter and its innervation during childbirth.These findings imply a need for closer monitoring of the anal sphincter and of the posterior part of the pelvic floor during vaginal delivery.Can this devastating social handicap yet be prevented?
An Objective Evaluation of Clinical Competence
Authors: John P. Hubbard, Edithe J. Levit, Charles F. Schumacher, Truman G. Schnabel
Journal: New England Journal of Medicine (1965)

APPROXIMATELY five years ago the National Board of Medical Examiners undertook to study and, if possible, to devise new means of evaluating the complex and subtle aspects of clinical competence that traditional testing methods barely touch. Examinations in the preclinical sciences (as in Part I of the National Board examinations) and in the clinical sciences (Part II) had been well established as highly reliable tests of medical knowledge and a candidate's ability to apply his knowledge to the problem in hand.1 , 2 Could methods be developed to evaluate with equal validity and reliability such essential components of medical competence as skill . . .
Bladder Disturbance Due to Apresoline
Authors: Max R. Goldstein, Walter A. Schloss, Samuel H. Cohn
Journal: New England Journal of Medicine (1952)

THE usefulness of I-hydrazinophthalazine (Apresoline) in lowering the blood pressure of hypertensive patients is well established.1 However, side effects have been observed, such as occipital headache, tachycardia, palpitation, dizziness, weakness, nausea, vomiting, as well as (less frequently), numbness and tingling of the extremities, flushing, varying degrees of nasal congestion, lacrimation and conjunctival inflammation. Rarely, skin rash and fever have been reported.2 As therapy with Apresoline is continued, these side effects generally subside and are persistently troublesome enough to cause discontinuance of therapy in only a few cases.This report describes the part that Apresoline may play in causing difficulty in . . .
A Leg to Stand On: Sir William Osler and Wilder Penfield's “Neuroethics”
Authors: Joseph J. Fins
Journal: The American Journal of Bioethics (2008)

Click to increase image sizeClick to decrease image size ACKNOWLEDGEMENT An earlier version of this article was presented as The John P. McGovern Award Lectureship of the American Osler Society at the Society's Annual Meeting on May 2, 2006, in Halifax, Nova Scotia. That article was published by the Society as a monograph. An edited and significantly expanded version is presented here with the kind permission of the American Osler Society. I would like to acknowledge grant support from the Charles A. Dana Foundation (Mending the Brain, Minding Our Ethics II) and the Buster Foundation (Neuroethics and Disorders of Consciousness) as well as the insights of Nicholas D. Schiff, Elizabeth G. Nilson, Cathleen A. Acres, and Amy B. Ehrlich and very constructive comments of the journal's peer reviewers.
Sweet Talk: Media Coverage of Artificial Sweeteners
Authors: Marilyn G. Stephenson
Journal: JAMA (1986)

The question addressed in this small book is whether the media have fairly covered the scientific picture with respect to the artificial sweetener debate. To consider this question, the author concentrated on a few of the most powerful media outlets that serve a large national audience: two newspapers,<i>The New York Times and The Washington Post</i>; two major news weeklies,<i>Time</i>and<i>Newsweek</i>; and the three largest national television networks. The primary focus is the debate concerning aspartame, but previous controversies about saccharin and cyclamate also are examined in an attempt to determine whether media coverage has followed any special pattern and whether the coverage has improved. The history up to the present and the most important elements in the scientific debate about each of the sweeteners are summarized. Because the book is written by a nonscientist for the purpose of critiquing journalists, evaluation of scientific judgments concerning the individual
Ethics and multicentre research projects.
Authors: R. Horwitz, C. H. Cheetham
Journal: BMJ (1992)

Ethics and multicentre research projects SIR,-We strongly support Peter Moodie's suggestion that there should be a "national committee to give conditional approval" to multicentre trials.' We have concerns about the role of local research ethics committees in these trials, which have been expressed by others.2Recent guidance from the Department of Health, which merely advised "that committees should arrive at a voluntary arrangement under which one [local' research ethics committee] is nominated to consider the issue on behalf of them all" simply dodges all the difficulties and will do nothing to help the organisers of large projects to get prompt, authori- tative advice on ethics.4Major research projects must have ethical review by independent professionals who are expert in many disciplines, including statistics, pharmacology, epidemiology, toxicology, and sociology, as well as having a practical understanding of ethical issues.Our district's local research ethics committee simply does not possess all this skill, though it does have knowledge of local circum- stances.We suspect that this may be true in other districts.In the past two years our committee has considered 114 research projects, of which no less than 70% have been multicentre drug trials.In considering these projects we have been repeating the work of many other such committees.Each local research ethics committee has its own application form, so researchers have to redraft their applications to suit the styles of different districts.This is an expensive waste of effort whose main effect is to deter research.Surely there should be, as Moodie suggests, an authoritative expert committee that could comment on multicentre research projects.These comments would be available to both local research ethics committees and researchers.This would both ensure high standards and smoothe the process of ethical approval.
Is Cancer Prevention Better Than Cure?
Authors: Emil J Freireich
Journal: JAMA (1979)

Some members of Congress are urging that the fight against cancer be shifted from treatment to prevention. This is an appealing concept, especially when coupled with the widely held notion that virtually all cancers are caused by environmental factors and that lends credence to the conclusion that we should abandon treatment as the major approach to solving the cancer problem and invest all of our financial and intellectual resources in a cancer prevention campaign. While attractive on the surface, the prevention strategy has serious limitations. We know that the process of developing a cancer generally requires long periods of exposure to causative agents, and, therefore, prevention will have to be consistently applied for long periods, perhaps decades, to be effective. Moreover, even among those persons most heavily exposed to cancer-causing agents, such as cigarette smokers, the risk of the development of cancer is still fairly low. These limitations have important
Abstract 5489: CRK protein domains diminish cell invasiveness of non-small cell lung cancer.
Authors: Matthew Rettig, Fariborz (Fred) Mortazavi
Journal: Cancer Research (2013)

Abstract CRK (c-Crk) as an adaptor protein is involved in several oncogenic signal transduction pathways, conveying oncogenic signals to its downstream effectors, and thereby affecting multiple cellular processes including proliferation, differentiation and migration. For example, CRK expression and phosphorylation have been linked to heightened invasiveness of non-small cell lung cancer (NSCLC) cells. In order to intervene in CRK signaling pathway, we examined whether CRK protein domains can be used as a therapeutic tool to interrupt CRK signaling thereby influencing cell invasiveness in NSCLC. For this purpose, Src homology domains of CRK-I (i.e., SH2 and SH3 domains) were overexpressed in H157, Rh2 and A549 cells. CRK-I SH3 domain expression induced epithelial morphology in H157 cells and enhanced epithelial morphology of A549 and Rh2 cells as compared to cells transfected with SH2 domain or control vector. In addition, CRK-I SH3 domain expression induced E-cadherin expression in H157 cells. Furthermore, CRK-I SH3 domain expression significantly decreased the motility of A549 and H157 cells and also decreased the invasiveness of H157 cells. In summary, these data provide evidence that CRK protein domains can be utilized to influence the malignant phenotype of NSCLC cells and also reduce the metastatic potential of these cells. Citation Format: Matthew Rettig, Fariborz (Fred) Mortazavi. CRK protein domains diminish cell invasiveness of non-small cell lung cancer. [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 5489. doi:10.1158/1538-7445.AM2013-5489
ANGIOGRAPHIC VALIDATION OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION'S CARDIAC CATHETERIZATION DATABASE
Authors: Anjan Chakrabarti, Maria Grau–Sepulveda, Sean O'Brien, Cassandra Abueg, Varun Kumar, Lakshmi Gopalakrishnan, Meghan E. Doherty, Angelo Ponirakis, Elizabeth DeLong, Eric Peterson, Kirk Garratt, Fred Edwards, William Weintraub, C. Michael Gibson
Journal: Journal of the American College of Cardiology (2013)
Acyclovir Plus Steroids for Herpes Zoster
Authors: Carl D. Atkins
Journal: Annals of Internal Medicine (1997)

Letters15 May 1997Acyclovir Plus Steroids for Herpes ZosterCarl D. Atkins, MDCarl D. Atkins, MDSouth Shore Hematology-Oncology Associates, Rockville Centre, NY 11570Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-10-199705150-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I am puzzled by Whitley and colleagues' statement that, for the treatment of herpes zoster, they “do not recommend that corticosteroids be used without concomitant antiviral therapy” [1]. Their 2 × 2 factorial design allows analysis of the contribution of acyclovir and prednisone to the effectiveness of treatment. This is shown in the last two columns of their Table 2, in which it can be seen that patients who received prednisone had statistically significantly better results than those who received placebo in all quality-of-life measures at their 1-month evaluation. On the other hand, acyclovir recipients showed improvement ...REFERENCE1. Whitley RJ, Weiss H, Gnann JW Jr, Tyring S, Mertz GJ, Pappas PG, et al. Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. Ann Intern Med. 1996; 125:376-83. Google Scholar Author, Article, and Disclosure InformationAffiliations: South Shore Hematology-Oncology Associates, Rockville Centre, NY 11570 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 1997Volume 126, Issue 10Page: 831KeywordsAntiviral therapyDrugsFactorial designSteroids Issue Published: 15 May 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
NEUTROPENIA FOLLOWING DINITROPHENOL, WITH IMPROVEMENT AFTER PENTNUCLEOTIDE AND LEUKOCYTE CREAM
Authors: Elizabeth N. Davidson
Journal: JAMA (1934)

Mrs. M. G., aged 31, admitted to the hospital, May 8, 1934, had suffered from progressive pain with swelling in the gums and submaxillary glands for forty hours prior to admission. Two chills had occurred in the twelve hours previous to admission, and the temperature ranged from 101.6 to 102.4 F. She had vomited once on the day of onset and once the following day, and she was constantly nauseated.  She stated that on April 13 she had begun taking, under direction of a physician, sodium alpha-dinitrophenol in 100 mg. capsules with meals, three times a day. According to her record of that date, her weight was 159 pounds (72 Kg.), the temperature 98.6, pulse 80 and blood pressure 140 systolic, 96 diastolic. By April 24, she had lost 5½ pounds (2.5 Kg.) and the record showed that the temperature was 98.6, pulse 104 and blood pressure 130 systolic, 90
Foscarnet Therapy in Five Patients with AIDS and Acyclovir-resistant Varicella-Zoster Virus Infection
Authors: Sharon Safrin
Journal: Annals of Internal Medicine (1991)

Objective: To determine whether foscarnet has potential efficacy in the treatment of acyclovir-resistant mucocutaneous varicella-zoster infection in patients with the acquired immunodeficiency syndrome (AIDS). Design: Open-label study. Setting: Three university medical centers. Patients: Five patients with AIDS who were infected with thymidine-kinase-deficient or -altered strains of varicella-zoster virus. Intervention: Foscarnet, 40 mg/kg body weight every 8 hours in 1-hour infusions for 10 or more days. Main Results: Four patients had healing in response to foscarnet therapy, and each of four tested patients became culture negative for virus during foscarnet therapy. Results of fluorescent antigen testing remained positive during therapy in two patients; one of these patients had concomitant clinical failure but the other patient healed fully. One patient had complete healing despite the emergence of resistance to foscarnet in serial specimens obtained during foscarnet therapy. Conclusion: Foscarnet is a potentially effective and tolerable antiviral agent for patients with acyclovir-resistant, varicella-zoster virus infection; however, the optimal dosage and duration of therapy require further study, as does the relation between clinical findings and in-vitro susceptibility results.