tbuckley/cabot-search huggingface dataset:
Abstract 3244: Compensatory function of the homologous proteins MIF and D-DT in regulation of AMPK-dependent metabolic-stress pathways in non-small cell lung carcinoma
Authors: Stephanie Erin Brock, Beatriz Rendon, Robert Mitchell
Journal: Cancer Research (2012)

Abstract Macrophage migration inhibitory factor (MIF) is over-expressed in most solid malignancies and is important for many pro-tumorigenic pathways. Several studies reveal that genetic deletion or inhibition of MIF results in anti-cancer phenotypes, but these phenotypes are not nearly as profound as one would anticipate given its reported activities. We recently discovered that MIF's only related family member, D-dopachrome tautomerase (D-DT), functionally compensates for MIF-dependent promotion of angiogenic potential in non-small cell lung carcinoma (NSCLC). This finding not only provides an explanation for why MIF individual targeting has not provided more efficacious anti-cancer activities, but also suggests that therapeutic targeting of MIF and D-DT simultaneously may provide a highly effective and novel new class of anti-lung cancer pharmacologic agents. Here we present further evidence of the important cooperative function of these two homologous proteins in NSCLC cells. We reveal a strong collaborative effect of MIF and D-DT on the negative regulation of AMP-activated protein kinase (AMPK) activation. AMPK is phosphorylated by the tumor suppressor, LKB1, in response to metabolic stress, resulting in AMPK-dependent p53 activation and mTOR inhibition. We show that while siRNA-mediated knockdown of endogenous MIF or D-DT individually has modest effects on AMPK activation in NSCLC cells, combined knockdown of both MIF and D-DT results in a significant activation of AMPK-dependent regulation of p53 and mTOR pathways. Importantly, this re-activation of AMPK by MIF and D-DT occurs in LKB1 mutant NSCLC cell lines. In addition, overexpression of MIF or D-DT alone by adenoviral delivery causes a substantial reduction in p53 expression, with a dramatic increase in mTOR pathway activation. Our findings suggest that MIF and D-DT promote a unique and well conserved adaptation pathway that is usurped by the malignant cells in order to counter metabolic stress-induced, AMPK-dependent, tumor suppression. Because the LKB1 tumor suppressor locus is mutated in over 30% of NSCLC lesions rendering these tumors insensitive to AMPK-dependent growth suppression, the identification of unique AMPK agonists would be expected to have a tremendous impact on NSCLC disease management for clinicians. Taken together, simultaneous therapeutic targeting of both MIF and D-DT represents an innovative and clinically efficacious approach to re-activating metabolic stress-induced tumor suppression in NSCLC malignant lesions. 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 3244. doi:1538-7445.AM2012-3244
Challenges to implementing NPfIT: Problems are inevitable but goal is worth while
Authors: Robert J Young
Journal: BMJ (2005)

Junior doctors' shifts and sleep deprivation New on-call rotas do not workEditor-Clearly the editorial by Murray et al on junior doctors' shifts has struck a chord with many, as on-call rotas are something close to many doctors hearts. 1 2 To most it seems the grass is not greener on the other side.Having worked most rotas, be it a traditional one in four, with full weekends, to partial, hybrid, and full shift patterns, I am in a reasonable position to comment on what I think makes a liveable on-call rota.I was under the impression that the European Working Time Directive was set out to improve the health and safety of workers, make working conditions better, but also make life away from work better because doctors would be less tired.The directive scores a "no" against all of these.I find myself more tired at work and at home, less enthusiastic, and less motivated by what is becoming a regular chore.Instead of being on call once a week, I find myself doing an on-call shift two or three times a week (on average), being late home more often than not because fewer juniors are around, and spending less time with my young children.The "old" rota system of a 24 hour oncall, with at least six on a rota, made on-call shifts less frequent, more tolerable, and even enjoyable.It also left plenty of time for training, and so long as there were six or more on rota, it made the annual leave far more flexible and workable.Anaesthetists rarely complained, certainly compared with other specialties' rotas, and everyone knew that however busy, you were always going to go home to a full day off in the morning.Why not listen to those doing the rota, and affected family members, and respect within reason what the workers want to work.
Locomotor disability in very elderly people: value of a programme for screening and provision of aids for daily living.
Authors: D Hart, A Bowling, M Ellis, A Silman
Journal: BMJ (1990)

OBJECTIVE--To assess the prevalence of potentially reversible locomotor disabilities in elderly subjects and the cost effectiveness of providing aids for daily living. DESIGN--Population based randomised controlled trial of subjects aged greater than or equal to 85 living independently in an inner London borough. SETTING--21 Electoral wards of the London Borough of Hackney. SUBJECTS--1255 Subjects aged greater than or equal to 85 living in their own home whose names were obtained from general practitioner lists and cross checked against the electoral register, 511 of whom were subsequently found to be ineligible. Of the 744 remaining, those with disability on screening were randomised and allocated to an intervention group (36) or a control group (43), in which intervention was postponed until four weeks, after the follow up assessment. Subjects with aids supplied previously were excluded from the intervention phase. INTERVENTIONS--Provision of raised toilet seat, teapot tipper, tap turner, shoe horn and elastic laces, and double handled saucepan. MAIN OUTCOME MEASURES--Degree of difficulty (grades 1-4) with specific tasks (getting on and off a toilet, pouring from a teapot into a cup, turning taps on and off, carrying a saucepan of standard weight, and putting on shoes) and time taken to perform them. RESULTS--545 (73%) Of the 744 eligible subjects assessed; 428 had no disability and 118 had difficulty with at least one task. Some had had their disability recognised before the study and already had aids, representing half of those with difficulty getting on and off the toilet but 24% for putting on shoes and 13% for pouring from a teapot and turning on a tap. The mean number of difficulties was similar between the groups (intervention group 1.7, control group 1.6). Time taken to complete the tasks corresponded with the observed grade of difficulty. All aids were associated with reduced difficulty according to observer assessment (% improvement intervention group v control group: raised toilet seat, 71 v 13 teapot tipper 100 v 33; tap turner 100 v 0; saucepan 88 v 0; shoe horn 50 v 13) and time taken to complete the tasks. A cost benefit analysis of this screening-intervention programme suggested a total cost of 32 pounds per individual benefit. CONCLUSIONS--Appreciable degrees of unrecognised locomotor disability are detected on screening of very elderly people living independently. Providing aids offers a feasible and cost effective means of improving function in such people.
Misdiagnosis of HIV Infection
Authors: Walter Palmas
Journal: Annals of Internal Medicine (1999)

Letters5 October 1999Misdiagnosis of HIV InfectionWalter Palmas, MDWalter Palmas, MDNew York Presbyterian Hospital; New York, NY 10032 (Palmas)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-7-199910050-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:There is a continuing effort to detect HIV in the acute phase of the infection. Because the antibody response takes time to develop, the direct detection of a viral component is expected to be more sensitive than antibody detection. Rich and colleagues (1) described three patients with false-positive results on viral load assays. This report merits consideration of certain issues pertinent to all diagnostic tests.When a test has more than two possible outcomes, its accuracy can be reported as pairs of sensitivity and specificity corresponding to each degree of abnormality. This approach, the basis for receiver-operating ...References1. Rich JD, Merriman NA, Mylonakis E, Greenough TC, Flanigan TP, Mady BJ, et al . Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series. Ann Intern Med. 1999;130:37-9. LinkGoogle Scholar2. Hanley JA. Receiver operating characteristic (ROC) methodology: the state of the art. Crit Rev Diagn Imaging. 1989;29:307-35. MedlineGoogle Scholar3. Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-Based Medicine. How to Practice and Teach EBM. New York: Churchill Livingstone; 1997:227-34. Google Scholar Author, Article, and Disclosure InformationAffiliations: New York Presbyterian Hospital; New York, NY 10032 (Palmas) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHave We Treated AIDS Too Well? Rationing and the Future of AIDS Exceptionalism David J. Casarett and John D. Lantos Misdiagnosis of HIV Infection by HIV-1 Plasma Viral Load Testing: A Case Series Josiah D. Rich , Nathan A. Merriman , Eleftherios Mylonakis , Thomas C. Greenough , Timothy P. Flanigan , Brian J. Mady , and Charles C.J. Carpenter Misdiagnosis of HIV Infection Charmagne Goodman , Wesley Emmons , and James Newton Misdiagnosis of HIV Infection Josiah D. Rich , Eleftherios Mylonakis , and Timothy P. Flanigan Metrics 5 October 1999Volume 131, Issue 7Page: 546-547KeywordsAntibody productionBlood plasmaHIVHIV infectionsProspective studiesSpecificityViral load Issue Published: 5 October 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
THE RELATION BETWEEN THE TYPE SPECIFIC CARBOHYDRATES OF PNEUMOCOCCI AND THE BLOOD GROUP SPECIFIC SUBSTANCE A
Authors: Ernst Witebsky, Erwin Neter, Harry Sobotka
Journal: The Journal of Experimental Medicine (1935)

1. A relationship between the soluble specific substances of pneumococci and the blood group substance A of man can be demonstrated by the inhibition of sheep cell hemolysis by a group specific A-antiserum. However, there are quantitative differences between the various types. 2. A striking difference exists between the acetyl and the de-acetylated polysaccharide of Pneumococcus Type I: The de-acetylated carbohydrate fails to react with the group specific A-antiserum, while the acetyl carbohydrate shows a strong reactivity. 3. The minimum amount of the acetyl polysaccharide, which inhibits sheep cell hemolysis by A-antiserum, is almost as small as that of the group specific carbohydrate isolated by Freudenberg and Eichel from urines of group A. 4. The reactivity of the acetyl polysaccharide can be demonstrated not only by the hemolysis inhibition test, but also by complement fixation and by inhibition of group specific iso-agglutination. 5. Feces filtrates, which possess the ability to destroy the blood group specific substances A and B of man, also affect the acetyl polysaccharide of Pneumococcus Type I. After incubation with an effective feces filtrate, the acetyl polysaccharide almost completely loses its potency toward the group specific A-antiserum and also its ability to inhibit the iso-agglutination of A blood cells. 6. Acetyl polysaccharide of Pneumococcus Type I, having lost its reactivity toward the group-specific A-antiserum after treatment with feces filtrate, still reacts with Type I pneumococcus antiserum which was previously absorbed with de-acetylated polysaccharide, Type I. Thus, the essential effect of the feces filtrate on acetyl polysaccharide, Type I, is not the cleavage of acetyl group, but some other chemical alteration.
THE SPECIFIC AND NON-SPECIFIC LESIONS OF THE BRAIN RESULTING FROM SYPHILIS AND THEIR INFLUENCE UPON DIAGNOSIS, PROGNOSIS AND TREATMENT.
Authors: J. T. ESKRIDGE
Journal: JAMA (1902)

That syphilis is due to a specific poison that is capable of causing the development of luetic lesions in non-infected persons is an indisputed fact. Whether this micro-organism belongs to the vegetable kingdom and may be classed among the bacteria, or whether it may be found in the lower forms of the animal kingdom and may be classed with the plasmodia, or whether it may occupy a place between the bacteria and plasmodia must be determined by the scientific investigator. We are as ignorant of the true nature of the virus as was Fernelius, when nearly 400 years ago he formulated the seven laws of syphilis. Syphilis of the brain can not be acquired except the virus enter the blood or other juices of the body through a denuded mucous or cutaneous surface. From the external manifestations of syphilis that we are able to observe, we are justified in reasoning
Treatment of acute myeloid leukemia in the elderly with low‐dose cytarabine, hydroxyurea, and calcitriol
Authors: Christopher A. Slapak, Jane F. Desforges, Terry Fogaren, Kenneth B. Miller
Journal: American Journal of Hematology (1992)

Abstract Twenty‐nine patients aged 62–82 years with acute myeloid leukemia (AML) were treated with a 21‐day course of continuous infusion cytarabine, oral hydroxyurea, and 1,25‐dihydroxyvitamin D 3 (calcitriol). Ten patients had an antecedent myelodysplastic syndrome. Calcitriol was continued as the only postremission therapy. Thirteen patients (45%) obtained a complete remission, and 10 patients (34%) had a partial response for an overall 79% response rate. There were three early deaths. The median remission duration was 9.8 months. Overall median survival was 12 months for all patients and 14 months for responding patients. All responding patients had marked bone marrow hypoplasia. Twenty patients received part or all of their chemotherapy as outpatients. This regimen has acceptable toxicity and can result in prolonged remissions in elderly, high‐risk patients with AML. The favorable results may be related to the synergistic effect of hydroxyurea, cytarabine, and calcitriol. © 1992 Wiley‐Liss, Inc.
Induction Chemotherapy with Carboplatin, Irinotecan, and Paclitaxel Followed by High Dose Three-Dimension Conformal Thoracic Radiotherapy (74 Gy) with Concurrent Carboplatin, Paclitaxel, and Gefitinib in Unresectable Stage IIIA and Stage IIIB Non-small Cell Lung Cancer
Authors: Thomas E. Stinchcombe, David E. Morris, Carrie B. Lee, Dominic T. Moore, D Neil Hayes, Jan S. Halle, M Patricia Rivera, Julian G. Rosenman, Mark A. Socinski
Journal: Journal of Thoracic Oncology (2008)
Hemangiomas of the Skull on Radionuclide Brain Imaging
Authors: BELUR CHANDRAMOULY, THOMAS SCAGNELLI, DIPAK SHETH
Journal: Clinical Nuclear Medicine (1989)

A 56-year-old woman sustained head trauma without loss of consciousness after falling down several steps. A radionuclide cerebral blood flow and static brain scan was performed which showed two right parasagittal mass lesions. These lesions were further confirmed by CT scan and cerebral angiography. Surgical pathologic diagnosis was two hemanglomas of the skull.
384 Telomerase dependent conditionally replicating adenovirus expressing CARex-PTDs displays enhanced oncolytic properties in nonpermissive tumors
Authors: N. Woller, B. Schulte, D. Milewska, P. Schache, E. Guerlevik, M.P. Manns, S. Kubicka, F. Kuehnel
Journal: Journal of Hepatology (2006)
Rehabilitation after heart attack
Authors: C. Bundy
Journal: BMJ (1997)

Editor–I agree with Richard Mayou that doubts remain about the efficacy and delivery of rehabilitation programmes,1 but the picture is not as devoid of evidence as he implies. Although there is no definitive study showing a significant reduction in mortality from exercise based cardiac rehabilitation, many studies suggest that exercise based cardiac rehabilitation reduces all cause mortality (see West's recent overview for details2). …
Do potassium channel openers compete with ATP to activate ATP sensitive potassium channels?
Authors: P. Henry, D. Escande
Journal: Cardiovascular Research (1994)

Journal Article Do potassium channel openers compete with ATP to activate ATP sensitive potassium channels? Get access Patrick Henry, Patrick Henry Laboratoire de Physiologie Cellulaire, URA CNRS 1121, Bât 443. Université Paris XI, 91405-Orsay, France: P Henry, D Escande Correspondence to Dr Escande. Search for other works by this author on: Oxford Academic PubMed Google Scholar Denis Escande Denis Escande Laboratoire de Physiologie Cellulaire, URA CNRS 1121, Bât 443. Université Paris XI, 91405-Orsay, France: P Henry, D Escande Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 6, June 1994, Pages 754–759, https://doi.org/10.1093/cvr/28.6.754 Published: 01 June 1994 Article history Received: 06 January 1994 Accepted: 14 February 1994 Published: 01 June 1994
The Hospital and Social Medicine
Authors: George A. Silver
Journal: New England Journal of Medicine (1963)

BECAUSE there are certain ambiguities in the use of the term "social medicine" and because the designation of a department of social medicine has not been firmly established in the hospital's table of organization, some effort at definition is in order. For the purposes of this discussion social medicine will be taken to mean the branch of medicine that concerns itself with social factors that influence the practice of medicine.1 It was in this sense that the term was recognized by Dr. E. M. Bluestone, then director of the Montefiore Hospital, in naming the Division of Social Medicine.It will . . .
Down-regulation of Caspase-2 by Rottlerin via Protein Kinase C-δ–Independent Pathway
Authors: Alakananda Basu, Brett Adkins, Chandreyi Basu
Journal: Cancer Research (2008)

Abstract Protein kinase C-δ (PKCδ) plays an important role in DNA damage–induced apoptosis. We have previously shown that the PKCδ inhibitor rottlerin protects against cisplatin-induced apoptosis acting upstream of caspase-9. In the present study, we have investigated if rottlerin regulates caspase-2 activation. Knockdown of caspase-2 by siRNA inhibited processing of apical caspase-9 and caspase-8, whereas depletion of caspase-9 had little effect on caspase-2 processing. Rottlerin inhibited activation and processing of caspase-9 and caspase-8 and cleavage of poly(ADP)ribose polymerase. We made a novel observation that rottlerin induced down-regulation of caspase-2 but not of caspase-3, caspase-7, caspase-8, or caspase-9. Pharmacologic inhibitors of PKC, such as Gö 6983 and bisindolylmaleimide, or depletion of PKCδ by siRNA had no effect on the down-regulation of caspase-2 by rottlerin. The proteasome inhibitor MG132 reversed caspase-2 down-regulation by rottlerin, whereas calpain inhibitor had no effect. These results suggest that rottlerin induces down-regulation of caspase-2 via PKCδ-independent but ubiquitin proteasome–mediated pathway. Furthermore, down-regulation of caspase-2 by rottlerin can explain its antiapoptotic function during DNA damage–induced apoptosis. [Cancer Res 2008;68(8):2795–802]
Apparent response of refractory post‐transfusion purpura to splenectomy
Authors: C. Casey Cunningham, Stuart E. Lind
Journal: American Journal of Hematology (1989)

Abstract Post transfusion purpura (PTP) is a rare disorder characterized by the abrupt onset of severe thrombocytopenia following transfusion. A patient with PTP and massive bleeding was refractory to corticosteroids, gamma globulin, and plasma exchange but developed an immediate and sustained rise in platelet count following splenectomy. Splenectomy may be a useful therapeutic modality in patients with refractory PTP.
Twenty five years of requests for euthanasia and physician assisted suicide in Dutch general practice: trend analysis
Authors: R L Marquet
Journal: BMJ (2003)

Concerns have been expressed that the Dutch policy on euthanasia (E) and physician assisted suicide (PAS) may lead to an exponential increase in the number of requests and use. 1 Many Dutch general practitioners, nursing home physicians, and pharmacists have a fairly positive attitude and have become more tolerant over the years. 2 We investigated the effect of increasing acceptance on the number of and underlying reasons for requests for E/PAS in Dutch general practice from 1977 to 2001. Methods and resultsThe data were derived from the Dutch Sentinel Practice Network, which constitutes a sample of about 60 general practitioners, covers about 1% of the Dutch population, and is fairly representative of the total population (16 million) with regard to age, sex, geographical distribution, and level of urbanisation. 3 Every year general practitioners reported data on requests for E/PAS from terminally ill patients, including age, sex, underlying disease, reasons for request, and presence of a living will.We estimated trends with multilevel analysis.Over the 25 years the network received 915 requests (equivalent to 3660 requests/year; 2.6 requests/year/10 000 inhabitants).General practitioners in cities received 3.3 requests per 10 000 patients compared with 1.9 requests in rural areas.Over half (503) of the requests were from men (mean age 67 years, range 31-96 years); the mean age of women was 68 years (range 32-88 years).Most patients (769) were nursed at home; 503 had stated a wish for E/PAS in a living will (increasing from 15% in 1984 to 87% in 2001), with no differences in age and sex.The mean proportion of requests for PAS, separately recorded from 1987 onwards, was 6.7%, decreasing from 9.5% in 1988 to none in 2001.The number of requests increased from 1600 in 1979 to 4000 in 1985 (extrapolated data, figure).The number then stabilised at about 5000 requests a year.Most patients (74%) had cancer, mainly gastrointestinal and lung cancer.Less common were cardiovascular diseases (7%) and chronic obstructive pulmonary disease (5%).Among the other diseases, those of the musculoskeletal system, neurological diseases, and AIDS were most frequently mentioned.Fear of pain (37%), deterioration (31%), hopelessness (22%), and dyspnoea (15%) were the most important
Methylation-Dependent Transition Rates Are Dependent on Local Sequence Lengths and Genomic Regions
Authors: Zhongming Zhao, Cizhong Jiang
Journal: Molecular Biology and Evolution (2006)

Recently, Fryxell and Moon (2005) examined methylation-dependent transition rates (5mC deamination rates), which were calculated by the difference between the CpG transition and GpC transition rates, using 4,437 transition mutations in CpG or GpC dinucleotides. They concluded that 5mC deamination rates were highly dependent on local GC content but not on local sequence lengths over which GC content was calculated or the genomic regions where the mutations occurred. Here, we reexamined these statements by using 292,216 CpG→TpG/CpA and GpC→GpT/ApC mutations, an increase of 66 times as much data. Contrary to Fryxell and Moon's conclusions, our analysis indicated that 5mC deamination rates in the human genome were dependent on both the local sequence length and the genomic region. Some explanations for their conclusions were provided.