tbuckley/cabot-search huggingface dataset:
Abstract 2912: Protein pathway activation mapping of leukemia-associated JAK1 mutants
Authors: Valentina Fodale, Elisabetta Flex, Emilia Stellacci, Eleonora Policicchio, Jianghong Deng, Valerie S. Calvert, Lance A. Liotta, Emanuel F. Petricoin, Marco Tartaglia
Journal: Cancer Research (2011)

Abstract The Janus kinase 1 (JAK1) is a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors and plays a nonredundant role in lymphoid cell precursor proliferation, survival and differentiation. We documented that somatic mutations in JAK1 occur in individuals with acute lymphoblastic leukemia (ALL) (Flex et al. 2008, J Exp Med 205:751-8). JAK1 mutations were more prevalent among adult subjects with T-cell precursor ALL, where they accounted for approximately 20% of cases, and were associated with poor response to therapy and overall prognosis. In order to understand the molecular and cellular mechanisms by which aberrant JAK1 function contribute to leukemogenesis we analysed the signaling architecture of BaF3 cell lines stably expressing a series of leukemia-associated JAK1 gene mutations by Reverse Phase Protein Microarray (RPMA). We utilized BaF3 cell lines, stably expressing human wild type JAK1 and five ALL-associated mutants bearing missense mutations in different domains of the kinase. Cells were serum starved for 16 hours and lysed before and after induction with IL-3 for 20 minutes. RPMA analysis was performed to determine the phosphorylation/activation state of 102 different key signalling proteins involved in the major intracellular signal transduction pathways. Results showed that intacellular signaling downstream JAK/STAT is differentially modulated between cell lines expressing the different ALL-associated JAK1 mutants. Statistical analysis revealed that mutations affecting the pseudo-kinase and in the kinase domains resulted in a different phosphorylation pathway network compared to mutations involving the FERM and SH2 domains. Our results support a model in which mutations affecting distinct domains of JAK1 have a differential perturbing effect on JAK1 function and signalling. Characterization of the consequences of leukemia-associated JAK1 mutants on the protein signalling network may help to identify new therapeutic targets for ALL. The present findings further document that functional protein pathway activation mapping using RPMA represents a powerful approach to uncovering mutation-driven events, and elucidating the specific events associated with different mutations within a single protein. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2912. doi:10.1158/1538-7445.AM2011-2912
Book Review On the Fabric of the Human Body: Book I: The bones and cartilages (Norman Anatomy Series. No. 1.) By Andreas Vesalius. Translated by William Frank Richardson, in collaboration with John Burd Carman. 416 pp., illustrated. San Francisco, Norman, 1998. $225. 0-930405-73-0
Authors: Charles E. Slonecker
Journal: New England Journal of Medicine (1998)
SDF-1 is both necessary and sufficient to promote proliferative retinopathy
Authors: Jason M. Butler, Steven M. Guthrie, Mehmet Koc, Aqeela Afzal, Sergio Caballero, H. Logan Brooks, Robert N. Mames, Mark S. Segal, Maria B. Grant, Edward W. Scott
Journal: Journal of Clinical Investigation (2005)

Diabetic retinopathy is the leading cause of blindness in working-age adults. It is caused by oxygen starvation in the retina inducing aberrant formation of blood vessels that destroy retinal architecture. In humans, vitreal stromal cell–derived factor–1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses. Treatment of patients with triamcinolone decreases SDF-1 levels in the vitreous, with marked disease improvement. SDF-1 induces human retinal endothelial cells to increase expression of VCAM-1, a receptor for very late antigen–4 found on many hematopoietic progenitors, and reduce tight cellular junctions by reducing occludin expression. Both changes would serve to recruit hematopoietic and endothelial progenitor cells along an SDF-1 gradient. We have shown, using a murine model of proliferative adult retinopathy, that the majority of new vessels formed in response to oxygen starvation originate from hematopoietic stem cell–derived endothelial progenitor cells. We now show that the levels of SDF-1 found in patients with proliferative retinopathy induce retinopathy in our murine model. Intravitreal injection of blocking antibodies to SDF-1 prevented retinal neovascularization in our murine model, even in the presence of exogenous VEGF. Together, these data demonstrate that SDF-1 plays a major role in proliferative retinopathy and may be an ideal target for the prevention of proliferative retinopathy.
Public Reporting of Clinical Outcomes of Assisted Reproductive Technology Programs
Authors: Eli Y. Adashi, Ron Wyden
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Competing Mortality in Cancer Screening
Authors: Daniel Schneider, Douglas Arenberg
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Sarcoidosis and Hypercalcemia
Authors: M. NOPPEN
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 July 1986Sarcoidosis and HypercalcemiaM. NOPPEN, M.D., W. SCHANDEVIJL, M.D., W. MUSCH, W. VlNCKENM. NOPPEN, M.D.Search for more papers by this author, W. SCHANDEVIJL, M.D.Search for more papers by this author, W. MUSCHSearch for more papers by this author, W. VlNCKENSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-1-143_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Although the exact pathogenetic mechanism of hypercalcemia in sarcoidosis remains unknown, several studies (1-3) have suggested that the basic disturbance is an increase in circulating levels of 1,25-dihydroxyvitamin D. Increased levels of this substance are thought to be due to excessive synthesis, reflecting aberrant 1-alpha-hydroxylase activity (3). Sarcoid tissue may be the locus of this ectopic 1-alpha-hydroxylase activity (4). We present a clinical observation supporting the involvement of sarcoid tissue.A 47-year-old woman was hospitalized in May 1982 for persistent cough and wheezing due to extrinsic asthma. Chest roentgenograms showed an enlargement of the superior mediastinum, and...References1. BELLSTERNPANTZERSINHADE LUCA NPETN. Evidence that increased circulating 1,25-dihydroxy vitamin D is the probable cause of abnormal calcium metabolism in sarcoidosis. J Clin Invest. 1979;64:218-25. CrossrefMedlineGoogle Scholar2. PAPAPOULOSCLEMENSFRAHERLEWINSANDLERO'RIORDAN STLILJ. 1,25-dihydroxy cholecalciferol in the pathogenesis of the hypercalcemia of sarcoidosis. Lancet. 1979;1:627-30. CrossrefMedlineGoogle Scholar3. SANDLERWINEARLSFRAHERCLEMENSSMITHO'RIORDAN LCLTRJ. Studies of the hypercalcemia of sarcoidosis: effects of steroids and exogenous vitamin D3 on the circulating concentrations of 1,25 dihydroxy vitamin D3. Q J Med. 1984;210:165-80. Google Scholar4. MASONFRANKELCHANLISSNERPOSEN RTYDS. Vitamin D conversion by sarcoid lymph node homogenate. Ann Intern Med. 1984;100:59-61. LinkGoogle Scholar5. TAYLORLYNCHWYSOR RHW. Seasonal influence of sunlight on the hypercalcemia of sarcoidosis. Am J Med. 1963;34:221-7. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Academisch Ziekenhuis, Vrije Universiteit Brussel 1090 Brussels Belgium PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1986Volume 105, Issue 1Page: 143-144KeywordsAsthmaHypercalcemiaPathogensSarcoidosisThorax ePublished: 1 December 2008 Issue Published: 1 July 1986 PDF downloadLoading ...
1 The development of risk reduction strategies for the prevention of dermatitis in the printing industry
Authors: T.P. Brown, L. Rushton, H. Williams, J.S.C. English
Journal: British Journal of Dermatology (2003)

Journal Article 1 The development of risk reduction strategies for the prevention of dermatitis in the printing industry Get access T.P. Brown, T.P. Brown MRC Institute for Environment and Health, Leicester, U.K Search for other works by this author on: Oxford Academic Google Scholar L. Rushton, L. Rushton MRC Institute for Environment and Health, Leicester, U.K Search for other works by this author on: Oxford Academic Google Scholar H. Williams, H. Williams Department of Dermatology, Queens' Medical Centre, Nottingham, U.K Search for other works by this author on: Oxford Academic Google Scholar J.S.C. English J.S.C. English Department of Dermatology, Queens' Medical Centre, Nottingham, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 3, 1 March 2003, Page 618, https://doi.org/10.1046/j.1365-2133.2003.54012.x Published: 01 March 2003
When balance is bias
Authors: T. Jackson
Journal: BMJ (2011)

Sometimes the science is strong enough for the media to come down on one side of a debate

In his 2010 BBC television series Wonders of the Solar System , the physicist Brian Cox made a remark that offended some horoscope lovers. “Despite the fact that astrology is a load of rubbish, Jupiter can in fact have a profound influence on our planet. And it’s through a force . . . gravity.” The BBC received a number of complaints, including one from a viewer who said that Cox made his comment without an “alternative opinion being allowed.” The complainant griped that the programme made no attempt to “consider such questions from the perspective of an astrologer, who draws upon a very different body of observation and knowledge built over thousands of years.” Cox later gave the BBC a statement (which it declined to issue) saying, “I apologise to the astrology community for not making myself clear. I should have said that this new age drivel is undermining the very fabric of our civilisation.”

This tale, which beautifully points up the ridiculousness of always demanding balance in science communication, is told by Steve Jones, emeritus professor of human genetics at University College London, in a report published this year.1 The BBC Trust commissioned Jones to review the impartiality and accuracy of the BBC’s coverage of science; and although …
Current status of marijuana research. Symposium on marijuana held july 1978 in Reims, France
Authors: G. G. Nahas
Journal: JAMA (1979)

REPORTS of the current status of marijuana research were presented at a symposium on marijuana held in July 1978 in Reims, France, under the aegis of the Seventh International Congress of Pharmacology.<sup>1-2</sup>More than 100 scientists from 14 countries attended the meeting sponsored by the National Institute on Drug Abuse (NIDA), The French Ministry of Health, the French National Institute for Health and Research (INSERM), and the International Medical Council on Drug Use. Organizers of the symposium were Gabriel G. Nahas (Columbia University), W. D. M. Paton (Department of Pharmacology, Oxford University), and Monique Braude (NIDA). Analysis, metabolism, cellular responses, and effects on reproduction and on the brain were the topics discussed during the two-day meeting. <h3>Pharmacokinetics</h3> The pharmacokinetics (absorption, distribution, biotransformation, and elimination) of the psychoactive substance of marijuana—Δ<sup>9</sup>-tetrahydrocannabinol, or THC—and of its byproducts (metabolites) were described by E. R. Garrett (University of Florida). Unlike water-soluble
A Systems Analysis of Psychobiology and Behavior Therapy
Authors: Gary E. Schwartz
Journal: Psychotherapy and Psychosomatics (1981)

This article examines some basic principles of systems theory and applies them to the integration of psychobiology and behavior therapy in the evolution of behavioral medicine. Using the concepts of whole/part relationships, level and emergent property, and self-regulation and disregulation, it is proposed that all behavioral therapies involve psychobiological processes, and therefore, indirectly impinge on physical health. It is argued that the distinction between behavior and biology is one of level, and, therefore, behavioral therapies are ultimately biobehavioral therapies having biobehavioral consequences. It is proposed that contrary to traditional reductionistic logic, modern advances in biology are providing strong justification for the importance of including psychological methods in treating diseases manifested at the biological level. Various clinical examples are used to demonstrate how systems theory can be applied to differential diagnosis and treatment, computing cost/benefit ratios of different treatments, and conducting comprehensive clinical research and evaluation. Assessing the interaction of biological, psychological, and social treatment modalities becomes the hallmark of responsible patient care. Implications of the systems conception of behavioral medicine for collaboration among health care providers, the training of future clinicians in different disciplines, and policy decisions regarding the larger social consequences of health care are considered.
The Neurotoxin 1-Methyl-4-phenylpyridinium: A Selective Cytostatic Agent in Small-Cell Lung Cancer Cell Lines With Neuroendocrine Properties
Authors: A. M. Marini, R. Fridman, T. Kanemoto, G. R. Martin, Y. Guo, A. Passaniti
Journal: JNCI Journal of the National Cancer Institute (1992)

Small-cell lung cancer (SCLC) is a common malignancy that is usually fatal, since it metastasizes and recurs even after aggressive chemotherapy. While the cellular origin of this cancer is not well established, the cells of certain tumors exhibit neuroendocrine markers, including L-dopa decarboxylase.We designed in vitro and in vivo studies to investigate whether the neuroendocrine features in classic SCLC cell lines were sufficient to make them sensitive to 1-methyl-4-phenylpyridinium (MPP+), a known neurotoxin that destroys nigrostriatal dopaminergic neurons.Both classic SCLC cell lines (NCI-H345, NCI-H510, NCI-H187, and NCI-H146) and variant SCLC cell lines (NCI-H417, NCI-H82, NCI-H446, and NCI-H524) were exposed to MPP+ (0-512 microM) for 3 days. Inhibition of DNA synthesis was determined by [3H]thymidine incorporation assays. In a related experiment, MPP+ was removed from the classic cell line culture, and the incorporation of [3H]thymidine was determined. In the in vivo study, male athymic nude mice received subcutaneous injections of 0.5 mL tumor cells with matrigel for 10 days to enhance tumor growth, followed by MPP+ at doses of 100-400 micrograms/d given intraperitoneally for 2 days.All four classic SCLC cell lines showed great sensitivity to MPP+, with detachment from laminin substrates and inhibition of DNA synthesis. MPP+ interfered with [3H]thymidine incorporation and, thus, with DNA synthesis in classic SCLC cell lines at low doses (median +/- SD, 12 +/- 4 microM), whereas much higher doses (median, > 512 microM) were required to inhibit [3H]thymidine incorporation in the variant lines. Treated cells excluded trypan blue dye, showing that inhibition of DNA synthesis was not due to cytotoxicity, and the cells incorporated [3H]thymidine when MPP+ was removed from the culture medium, demonstrating that the inhibition was reversible. MPP+ inhibited the growth of the classic NCI-H187 and variant NCI-H417 cell lines implanted in nude mice.These results suggest that MPP+ differentially interferes with DNA synthesis in SCLC cell lines in vitro; the selective inhibitory effect on classic cell lines suggests that the neuroendocrine properties expressed by classic SCLC cells may be responsible for the differential effect.MPP+ exerts a cytostatic effect on these cell lines, and the differential sensitivity observed in vitro is maintained in vivo, suggesting that MPP+ or other pyridinium compounds may be of therapeutic value in SCLC.
Abstract 3239: Drug-Eluting Stents for the Treatment of Very Long Coronary Artery Stenosis: A Comparison of Serial Angiographic Follow-Up with Sirolimus, Paclitaxel, Zotarolimus and Tacrolimus-Eluting Stent: Multicenter Registry in Asia
Authors: Sunao Nakamura, Jang-Ho Bae, Yeo Hans Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Circulation (2006)
John Alan Pollock
Authors: Vincent Dawe
Journal: BMJ (2005)

​JohnJohn Alan Pollock set up the United Kingdom's first doctors' deputising organisation in 1960. At its height in the mid-1970s, Dr Pollock's “clinical organisation” (as he called it) had on its books more than 400 doctors of all specialties, including general practitioners, and covered all of south London below the Thames. Not only did his organisation provide much-needed on-call services for GP practices, it also provided locums for hospitals, which at that time were short of manpower.




Figure 1




To doctors, too, Dr Pollock's organisation provided a vital service, offering trainees at all stages of medical education a chance to earn extra money and to devise a more flexible way of earning a living while between jobs and studying for exams.

Dr Pollock eschewed the term “agency” to describe his organisation. He regarded it more as a not for profit body, where the money gleaned from its large turnover was simply the oil necessary to keep its complicated machinery going, not the end purpose in itself. He was proud of the fact that he never advertised.

In the early 1980s he was approached by the UK's largest locum agency, Aircall, to buy him out for a not inconsiderable sum, but Dr Pollock turned down the offer.

He did not set out to form a locum agency, but fell into doing so when he was engaged on a period of biomedical research after completing a stint as a senior house officer in Porthcawl, Glamorgan. He was constantly being asked by colleagues to stand in for them and was consequently asking others to stand in for him. He became so adept at juggling shifts that he decided to make it his second profession.

During the organisation's busy years, Dr Pollock's wife, Diana, also a doctor, worked full time with him, helping to run it. In the mid-1980s, they slimmed down the organisation to one offering out of hours on-call services to general practitioners in southeast London. After Diana's death in 1988, Dr Pollock carried on working by himself, until the early stages of dementia from Alzheimer's disease forced him to retire in 1996.

During the second world war Dr Pollock served as a captain in the Black Watch and then with No 5 Commando, and took part in the D Day landings and the recapture of Mandalay.

He leaves two daughters and four grandchildren.

John Alan Pollock, locum organiser south London (b 1923; q Guy's Hospital, London, 1953), d 5 February 2005.
Tobacco Smoking and Blood Group
Authors: I. T. T. Higgins, P. D. Oldham, R. J. Drummond, B. Bevan
Journal: BMJ (1963)

between smokers and non-smokers would release a spate of papers on this topic; but this has not been so.Cohen and Thomas (1962), however, have shown differ- ences in blood-group frequency associated with smoking.In a study of 1,005 white male blood-donors these workers found a significant excess of blood group B in non-smokers and occasional smokers when pooled and a corresponding deficiency of group B among heavy smokers of cigarettes.They also found a higher proportion of rhesus-negative persons (29.4%) among the small number of occasional smokers.In view of the low level of significance in this study confirmation of the association is clearly desirable.The purpose of this paper is to record our findings in a random sample of miners and ex-miners studied in 1961.The sample consisted of 1,250 miners and ex-miners aged 35-64 living in the Rhondda Fach, a mining valley in South Wales.The procedure adopted for sampling from the community and the methods used have been described elsewhere (Higgins, Oldham, Kilpatrick, Drummond, and Bevan, 1963).Briefly there were 500 men in each of the two decennial groups 35-44 and 55-64 and 250 men in the 45-54 group.The response rate is shown in Table I.TABLE I.-Random Sample of Miners and Ex-miners Stratified by Age a. Excluded Left Area Dead Refused Examined t o z o 6 Z X No. 5', No. %N .No. % No. % No.
Uganda to treat more people infected with HIV with antiretrovirals
Authors: H. Wasswa
Journal: BMJ (2008)

Uganda has introduced a programme to increase the number of people infected with HIV who are treated with antiretroviral drugs, setting a new CD4 cell count of 350×106/l at which patients will be given this treatment.

The country’s original national antiretroviral programme targeted people with a much lower CD4 cell count of 200×106/l, and infected patients with more CD4 cells were told to take co-trimoxazole tablets as prophylaxis. The higher cut-off is estimated …
The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma
Authors: Paul A. Spagnuolo, Jiayi Hu, Rose Hurren, Xiaoming Wang, Marcela Gronda, Mahadeo A. Sukhai, Ashley Di Meo, Jonathan Boss, Iman Ashali, Reza Beheshti Zavareh, Noah Fine, Craig D. Simpson, Sumaiya Sharmeen, Rob Rottapel, Aaron D. Schimmer
Journal: Blood (2010)