tbuckley/cabot-search huggingface dataset:
Abstract LB-27: Dissecting signaling transduction network to infer master regulators of non small cell lung cancer
Authors: Mukesh Bansal, Mukesh Bansal, Manjunath Kustagi, Celine Lefebvre, Gabrielle Rieckhof, Luc Girard, David Merberg, Klarisa Rikova, John Minna, Michael J. Comb, Michael White, Andrea Califano
Journal: Cancer Research (2011)

Abstract Abstract The dissection of signal transduction networks is lagging significantly with respect to their transcriptional and protein-complex counterparts. Innovative use of multiplex and microarray-based approaches, where multiple antibodies can be used to probe an ensemble of phosphoproteins, is starting to become sufficiently mature to allow characterization of small pathways. Yet, this is still far from providing an unbiased, genome-wide view of signal-transduction processes. Using data from the first genome-wide profiling of phosphopeptide abundance in normal and tumor related lung tissue1, we have designed a novel algorithm, pARACNe, to generate an unbiased, genome-wide network representing tyrosine kinase signal transduction pathways. Specifically, pARACNe was used to infer tyrosine kinase substrates in non-small cell lung cancer (NSCLC) from tandem mass-spec abundance profiling of phosphotyrosine enriched peptides from ∼250 samples derived from primary tumors, cell lines, and normal lung tissue. SILAC validation of EGFR, MET and ALK substrates, confirmed &amp;gt;80% of the pARACNe inferred interactions. Further analysis of large-scale NSCLC microarray expression profile data, using the MINDy algorithm2, showed significant convergence between the signal transduction pathways inferred by proteomics and gene expression based methods. The availability of an accurate NSCLC Tyrosine Kinase Interaction Network (TKIN) has significant implications for our ability to elucidate master regulators of oncogenesis and tumor progression and for the identification and prioritization of druggable targets. We used the MARINa algorithm and the TKIN to infer a complete repertoire of master regulator (MRs) kinases of 46 cell lines. Initial validation shows that the method could recapitulate both cancer specific MRs, such as EGFR, as well as cell line specific ones, such as ALK and PTK2 in H2228 cells. Follow up experimental assays have shown that the PTK2, which is active in tumor-related but not in normal cells, is required for H2228 cell viability and may constitute a novel oncogene addiction in NSCLC and a candidate therapeutic target. The TKI suggests that current pathway models are incomplete and sets the stage for quantitative, network-based methods to identify key regulators of physiologic and pathologic cell phenotypes. References 1. Rikova K et al. Cell 2007;131:1190–203. 2. Wang K et al. Nat Biotechnol 2009;27:829–39. 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 LB-27. doi:10.1158/1538-7445.AM2011-LB-27
Graduate Education in Public Health
Journal: JAMA (1976)

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 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) 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
The Principles of Clinical Pathology in Practice: A Guide to the Interpretation of Laboratory Investigations for the Use of Those Engaged in the Practice of Medicine.
Journal: JAMA (1930)

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 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) 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
Blunt erythropoietin secretion in liver cirrhosis: Lack of relationship to TNF, IL-1 and IL-6 serum concentrations , Istituto di Patologia Medica and *Istituto di Semeiotica Medica, Universit� Cattolica del Sacro Cuore, Roma, Italy
Journal: Hepatology (1995)

The contribution of cytochrome P450 isozymes CYP2E1 and CYP2B1/2 to chloroform-induced hepatotoxicity taken at 18 hr after the treatment was investigated in rats treated with n-hexane as an inducer of CYP2E1, 2-hexanone as an inducer of CYP2E1 and CYP2B1/2, and phenobarbital (PB) as an inducer of CYP2B1/2. Hepatic damage was evaluated by gross measurement of plasma alanine aminotransferase activity and histopathological examination. All treatments potentiated chloroform-induced hepatic damage. In n-hexane-pretreated rats, the damage was maximal with the middle dose of chloroform (0.2 ml/kg), whereas the damage increased with dose in rats treated with 2-hexanone or PB. The degree of hepatic damage induced with the three pretreatments was in the following order: n-hexane > 2-hexanone = PB with the middle dose of chloroform and PB ⪢ 2-hexanone >n-hexane with the high dose (0.5 ml/kg); little difference among the pretreatments was seen with the low dose (0.1 ml/kg). These findings suggest that CYP2E1 is a low Km isoform and CYP2B1/2 a high Km isoform for chloroform activation. CYP2E1-dependent hepatic damage was characterized by ballooned hepatocytes, which were restricted to the centrilobular area; with CYP2B1/2, more necrotic than ballooned hepatocytes were seen and the necrotic hepatocytes were found not only in the centrilobular but also in the midzonal and periportal areas. Chloroform treatment did not affect the activity of N-nitrosodimethylamine N-demethylase in pretreated rats; the high dose increased the activity in control rats. In contrast, the high dose of chloroform decreased the activity of 7-pentoxyresorufin O-depentylase in all induced rats but not in controls. Immunoinhibition and immunoblot analyses showed that the high dose of chloroform induced CYP2E1 in control rats but decreased CYP2B1/2 in all pretreated rats. These results suggest that although both CYP2E1 and CYP2B1/2 contribute to chloroform-induced hepatic damage, they do so quite differently.
Moth Dermatitis
Authors: Alfredo Alvarado
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The article by Zaias et al on dermatitis from contact with moths (<b>207</b>:525, 1969) points out a fairly common problem in the practice of tropical medicine. Published reports have been sporadic and have had no particular effect on the recognition of this entity more frequently. Another aspect of the subject is the difficulty in treating this highly pruritic form of dermatitis. About ten years ago I observed an epidemic of dermatitis from contact with moths when working with the Colombian Navy at a distant post in Puerto Lequizamo, Colombia, on the border with Peru, in an area of the jungle on the Putumayo River, which is a tributary of the Amazon, very close to the equator. At that time I was fascinated with the subject and wrote an article about it. One thing which impressed me was the clinical charge described by these authors after experimental
Temple of learning or tower of babel?
Authors: H. Stevens
Journal: JAMA (1969)

I am presuming to deliver a message across a barrier of time, that is, to communicate with an audience that belongs to another generation. This is a difficult and often bootless endeavor since you and I, although only one generation apart, are separated by many light years. And you in turn may be even more rapidly and completely alienated from the next generation, including your own children. Accelerated isolation of each succeeding generation from the one before began with the industrial revolution and now continues at an exponential rate. The long slow turn of time as the geologist reckons it, and the leisurely cycle of seasons repeated for thousands of generations living in an agricultural society, suddenly has been jet-propelled into social evolution, fantastically speeded by industrial technology. So rapidly has this change progressed that a growing child today strives to master the mores of a culture which might, compared
Naninvasive Detection of Coronary Collaterals Using Dipyridamole Rubidium-82 Position Emission Tomography
Authors: Deblia Garza, Andrew Van Tosh, Mitchell Baruchin, Roberto Roberti, Carl Reimers, Matt Bach, Janet Strain, John Fox, Steven F. Horowitz
Journal: Clinical Nuclear Medicine (1993)

Garza, Deblia; Tosh, Andrew Van; Baruchin, Mitchell; Roberti, Roberto; Reimers, Carl; Bach, Matt; Strain, Janet; Fox, John; Horowitz, Steven F. Author Information
Reaction Products of Chlorine Dioxide
Authors: Alan A. Stevens
Journal: Environmental Health Perspectives (1982)

Inspection of the available literature reveals that a detailed investigation of the aqueous organic chemistry of chlorine dioxide and systematic identification of products formed during water disinfection has not been considered. This must be done before an informed assessment can be made of the relative safety of using chlorine dioxide as a disinfectant alternative to chlorine. Although trihalomethanes are generally not formed by the action of chlorine dioxide, the products of chlorine dioxide treatment of organic materials are oxidized species, some of which also contain chlorine. The relative amounts of species types may depend on the amount of chlorine dioxide residual maintained and the concentration and nature of the organic material present in the source water. The trend toward lower concentrations of chlorinated by-products with increasing ClO2 concentration, which was observed with phenols, has not been observed with natural humic materials as measured by the organic halogen parameter. Organic halogen concentrations have been shown to increase with increasing chlorine dioxide dose, but are much lower than those observed when chlorine is applied. Aldehydes have been detected as apparent by-products of chlorine dioxide oxidation reactions in a surface water that is a drinking water source. Some other nonchlorinated products of chlorine dioxide treatment may be quinones and epoxides. The extent of formation of these moieties within the macromolecular humic structure is also still unknown.
OVARIAN THERAPY
Authors: EMIL NOVAK
Journal: JAMA (1924)

The known facts as to the function of the ovary are sufficient to supply a rational basis for ovarian therapy in certain indications. Especially important in this connection is the study of the phenomena produced by complete removal of ovarian tissue, such as the cessation of menstruation, the frequent appearance of troublesome subjective symptoms similar to those of the natural menopause, and the occurrence of certain metabolic changes. The obvious suggestion derived from such observations is that clinical symptoms thought to be due to ovarian deficiency might be cured or relieved by administering some form of ovarian substance. This fundamental idea has been subjected to some refinement as a result of studies aiming to stress some one or other of the ovarian constituents as the source of the active principle. Based on such investigations, several forms of ovarian therapy have developed, including the administration of whole ovary substance, of corpus
THE GLORIOUS FOURTH AND THE INGLORIOUS FIFTH.
Journal: JAMA (1904)

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 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) 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
Familial Glaucoma
Authors: John A. Cowan
Journal: JAMA (1965)

A study was undertaken to determine the prevalence of chronic simple glaucoma among blood relatives of persons blind from glaucoma, the occurrence of other ocular diseases among these relatives, and the effectiveness of a single tonometer reading in detecting glaucoma. Forty-three persons blind in one or both eyes yielded 173 blood relatives, of whom 136 participated in the study. Nine of these 136 persons, or 6.6%, had glaucoma or borderline glaucoma, three times the expected yield among the general population. One or more ocular diseases (excluding refractive errors) occurred in 53, or just less than two out of five relatives, but when glaucoma or suspect glaucoma was also excluded, only about one fourth had other ocular diseases. The effectiveness of a single tonometer reading could not be determined because the cases were not newly identified in the study.
Vasectomy and Health
Authors: Frank J. Massey
Journal: JAMA (1984)

In this historical cohort study we identified, located, and, if living, interviewed 10,590 vasectomized men from four cities, along with a paired neighborhood control for each. The times between procedure data and interview or death ranged from under one to 41 years, with median equal to 7.9 years and with 2,318 pairs having ten or more years of follow-up. Participant reports of diseases or conditions that might possibly be related to vasectomy through an immunopathological mechanism were validated by direct contact with physicians and review of medical records. Results of this study do not support the suggestions of immunopathological consequences of vasectomy within the period of follow-up. Except for epididymitis-orchitis, the incidence of diseases for vasectomized men was similar or lower than for their paired controls. (<i>JAMA</i>1984;252:1023-1029)
Local ablative therapy (LAT) for oligoprogressive, EGFR-mutant, non-small cell lung cancer (NSCLC) after treatment with osimertinib.
Authors: Chul Kim, Nitin Roper, Chuong D. Hoang, Laura Wisch, Maureen Connolly, Hsien-Chao Chou, Jun S. Wei, Manoj Tyagi, Constance Cultraro, Liqiang Xi, Maryam Waris, Eva Szabo, Emerson Padiernos, Aparna Hemant Kesarwala, Shaojian Gao, Seth M. Steinberg, Mark Raffeld, Arun Rajan, Javed Khan, Udayan Guha
Journal: Journal of Clinical Oncology (2018)

e21080 Background: EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatment for patients (pts) with EGFR-mutant NSCLC. Osimertinib is a 3rd-generation EGFR-TKI that is effective in 1st- and 2nd-line settings, but resistance to osimertinib is inevitable. Retrospective studies show a survival benefit to LAT in oligoprogressive EGFR-mutant NSCLC, but prospective trials are lacking. Methods: This is a prospective study of LAT in pts with EGFR-mutant NSCLC and oligoprogression after treatment with osimertinib (NCT02759835). Pts with no prior EGFR-TKI therapy (cohort 1) or pts with T790M-positive NSCLC after 1st-line EGFR-TKI treatment (cohort 2) start osimertinib. Upon progression, pts with ≤ 5 progressing sites (definition of oligoprogression) undergo LAT and resume osimertinib after LAT. Pts previously treated with osimertinib eligible for LAT upon development of oligoprogression are also enrolled (cohort 3). We aim to evaluate the safety and efficacy of reinitiation of osimertinib after LAT and to examine resistance mechanisms by multi-omics analyses of tumor and liquid biopsies. Results: Between 04/2016 and 01/2018, 24 pts were enrolled (cohort 1/2/3: 16/5/3). Response rates prior to LAT in cohorts 1 and 2 were 66.7 % (8/12) and 75% (3/4), respectively. Median overall PFS (PFS1+PFS2) was 11.2 months (95% CI: 6.6 months-undefined) and 15.8 months (95% CI: 6.7 months-undefined) in cohorts 1 and 2, respectively. 12 pts had progressive disease, 8 of which had oligoprogression and underwent LAT (cohort 1/2/3: 3/2/3). Two were treated with surgery and radiotherapy (RT), 4 pts with surgery, and 2 pts with RT. Median PFS2 among all cohorts was 2.3 months (95% CI: 1.0-5.9 months). Evaluation of tumor tissues revealed various resistance mechanisms: MET amplification (n = 3, 37.5%), EGFR C797S (n = 2, 25%), EGFR amplification (n = 2, 25%), transformation to small cell (n = 1, 12.5%). Whole exome and transcriptome data will be presented. Conclusions: Pts with EGFR-mutant NSCLC and oligoprogression after treatment with osimertinib can be safely treated with LAT. In select pts, this approach could maximize duration of EGFR-TKI therapy and prevent switching to other systemic therapies. Clinical trial information: NCT02759835.
A simulated patient-physician encounter using a talking computer
Authors: R. B. Friedman
Journal: JAMA (1977)

Computer-based clinical simulations provide a means for evaluating the information-gathering and patient-management competencies of physicians. The need for expensive computer terminals has restricted physician use of these simulations. This computer-based program permits physicians to complete computer-based encounters using a standard touch-tone telephone. (<i>JAMA</i>238:1927-1929, 1977)
Thrombocytosis Associated with Low-Molecular-Weight Heparin
Authors: David A. Rizzieri
Journal: Annals of Internal Medicine (1997)

Letters1 May 1997Thrombocytosis Associated with Low-Molecular-Weight HeparinDavid A. Rizzieri, MD and Jan P. Gockerman, MDDavid A. Rizzieri, MDDuke University Medical Center, Durham, NC 27710Search for more papers by this author and Jan P. Gockerman, MDDuke University Medical Center, Durham, NC 27710Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-9-199705010-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Williams's interest in our report of thrombocytosis associated with the use of enoxaparin in a patient with adrenocortical carcinoma. We argue that the patient's clinical course is not consistent with other known causes. Thrombocytosis in association with splenectomy is first noted within 2 weeks after the procedure and typically resolves over a few months, although the reactive process occasionally takes years to resolve [1, 2]. As Dr. Williams notes, neoplastic processes may also be associated with severe thrombocytosis, usually because of increased platelet production [2, 3]. Our patient's platelet counts were normal, about 250 000 ...References1. Bithell TC. Thrombocytosis. In: Lee GR, Bithell TC, Foerster J, Athens J, Lukens J, eds. Wintrobe's Clinical Hematology. 9th ed. Philadelphia: Lea & Febiger; 1993:1390-6. Google Scholar2. Marchasin S, Wallerstein R, Aggeler P. Variations of the platelet count in disease. Cal Med. 1964; 101:95-100. Google Scholar3. Levin J, Conley C. Thrombocytosis associated with malignant disease. Arch Intern Med. 1964; 114:497-500. Google Scholar Author, Article, and Disclosure InformationAffiliations: Duke University Medical Center, Durham, NC 27710 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByA Review and Assessment of Drug-Induced ThrombocytosisLow molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis 1 May 1997Volume 126, Issue 9Page: 742-743KeywordsChemotherapyDrug therapyPartial thromboplastin timePlateletsProgressive diseasesProthrombin timeResearch laboratoriesSplenectomySurgeryThrombocytosis Issue Published: 1 May 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
FRI0358 Short Term Prognosis of A Prospectively Followed Cohort of Unselected Adult IGA Vasculitis Cases – A Single Rheumatology Centre Experience
Authors: J. Ostrovršnik, A. Hočevar, Ž. Rotar, M. Tomšič
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The acute phase of adult IgA vasculitis (IgAV) is well characterized. Data of even short-term prognosis of adult IgAV is scarce, mostly retrospective and usually limited to patients with significant renal disease. <h3>Objectives</h3> Our aim was to examine the short-term prognosis in a cohort of unselected adult IgAV cases. <h3>Methods</h3> We analysed medical records of newly diagnosed, histologically proven cases of IgAV at our department of rheumatology between 1 January 2010 and 30 June 2015, that were followed until 31 December 2015. <h3>Results</h3> We identified 139 IgAV cases during the observation period. The clinical characteristics at presentation and the initial treatment are shown in Table 1. During the acute phase of the disease 3/139 patients died (2 due to active vasculitis, 1 due to generalized CMV infection and heart failure). Twenty patients were lost to follow-up. The clinical characteristics of the remaining 116 patients who were followed for a median 8.9 (IQR 5.5 – 22.7) months at follow-up are shown in Table 2. During the follow-up new malignancy was diagnosed in 6/116 (5.2%) patients and 8/116 (6.9%) patients died. All deaths were due to causes unrelated to IgAV. <h3>Conclusions</h3> Contrary to the experience in children, IgAV in adults does not seem to be a benign disease even in the short-term. Admittedly, it is impossible to conclude whether this is due to the nature of the adult IgAV or because adults have more comorbidities than children. <h3>Disclosure of Interest</h3> None declared