tbuckley/cabot-search huggingface dataset:
Abstract 4912: Systematic, comparative network analysis on non-small cell lung cancer
Authors: Serene Wong, Max Kotlyar, Dan Strumpf, Nick Cercone, Frances A. Shepherd, Ming-Sound Tsao, Igor Jurisica
Journal: Cancer Research (2012)

Abstract BACKGROUND: Most cancers lack any effective early disease markers, prognostic and predictive signatures. We fail treating cancer due to multiple ways cancer initiates and develops treatment resistance. While drug modes of action are complex and poorly understood, using Comparative Toxicogenomics Database is an effective way to identify drug combinations. Integrating signatures with deregulated network information may lead to identifying novel treatment option for individual patients. APPROACH: A systematic graph analysis was used to extract network structure differences between normal and tumor patient samples in non-small cell lung cancer. Three gene expression datasets with 27 squamous cell carcinoma, 129 adenocarcinoma, 20 large cell carcinoma and 141 normal samples, and 18 prognostic non-small cell lung cancer gene signatures were used to construct normal and tumor co-expression graphs. RESULTS: We enumerated all 5-node graphlets in normal and tumor graphs, and separated them into 3 categories: unique for normal graph, unique for tumor graph, or present in both. We further focused on subgraphs with the same membership across all 3 datasets and unique to tumor graph. Using gene enrichment analysis with a hypergeometric test we identified 9 subgraphs significantly enriched in the term “regulation of lymphocyte activation” (p&amp;lt;0.05), and genes related to chemokine receptors (CCR2, CCR7), interleukin (IL16), interleukin receptor (IL7R), interferon regulatory factor (IRF4), and T cells or B cells (PTPRCAP, SH2D1A, LCK, BTK, MS4A1). Importantly, this analysis identified protein interaction deregulated in tumors. Using the Comparative Toxicogenomics Database, we identified putative compounds that may “repair” the wiring of these subnetworks in tumor samples. 7 out of 7 identified compounds for the significantly up-regulated genes (p&amp;lt;0.05), and 20 out of 25 significantly down-regulated genes (p&amp;lt;0.05) are associated with non-small cell lung cancer. The other 5 identified compounds are known for other types of cancer or neoplasms, including lung neoplasms. Importantly, 13/38 edges have known/predicted protein interaction evidence, with a high prediction scores &amp;gt;0.9 (11 interactions) and 0.8 (2 interactions). CONCLUSIONS: Systematic integration and network analysis of non-small cell lung signatures identifies potential treatment options and insights to the difference in the underlying wiring related to immune system, an emerging hallmark of cancer. 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 4912. doi:1538-7445.AM2012-4912
Treatment Tolerance and Efficacy in Geriatric Oncology: A Systematic Review of Phase III Randomized Trials Conducted by Five National Cancer Institute–Sponsored Cooperative Groups
Authors: Ambuj Kumar, Heloisa P. Soares, Lodovico Balducci, Benjamin Djulbegovic
Journal: Journal of Clinical Oncology (2007)

Elderly patients share the majority of the disease burden in cancer. Although 61% of new cancer cases occur among elderly, they comprise only 25% of the patients enrolled onto randomized clinical trials (RCTs). A systematic review to assess the accurate participation of elderly patients in RCTs has not been performed.We reviewed all consecutively completed phase III RCTs conducted by five National Cancer Institute-sponsored cooperative groups. Published papers and study protocols were used for data extraction. We used a cutoff age of 65 years to define elderly patients. For trials that did not exclusively enroll elderly, data were extracted on number of participants 65 years of age. Outcome between the innovative and the standard treatment was compared.Of 345 studies, only one trial exclusively enrolled elderly patients (0.28%); 57% of the trials (n = 197) had no stratification by age, and 12% of the studies had a stratification age 65 years (n = 42). Overall survival in the trial exclusively enrolling elderly favored the newer treatments (hazard ratio [HR], 0.69; 95% CI, 0.47 to 1.02; P = .06). Additionally, in trials enrolling more than 40% of elderly, survival and event-free survival favored the innovative treatments (HR for survival, 0.91; 95% CI, 0.84 to 0.99; P = .03; HR for event-free survival, 0.85; 95% CI, 0.72 to 1.01; P = .07). Treatment-related mortality was similar in both the innovative and standard treatment groups (HR, 0.91; 95% CI, 0.47 to 1.78; P = .8).Our data indicate that enrollment of elderly in experimental RCTs is not associated with increased harm to this patient population. Increased participation of elderly may help in finding new treatments that are clinically applicable specifically to this cohort of patients.
Philip Montagu D'Arcy Hart (1900-2006)
Authors: E. Tansey
Journal: Journal of the Royal Society of Medicine (2006)

Philip D'Arcy Hart was born in 1900 into a family prominent in politics and finance. His grandfather was first Baron Swaythling, founder of the banking firm Samuel Montagu and Liberal MP for the Whitechapel Division of Tower Hamlets, London. In 1941, Philip married Ruth Meyer, later a medical gynaecologist. The author and editors are grateful to Philip and Ruth D'Arcy Hart for confirming, at a meeting with Iain Chalmers on 25 August 2004, the accuracy of the account that follows.
Nonequality of brand name thyroxine preparations
Authors: J. M. Jacobson
Journal: JAMA (1980)

To the Editor.—  Despite widespread use of oral sodium levothyroxine preparations, there are few data available comparing efficacy of different brand name oral preparations. We studied ultimate bioavailability of thyroid hormone in two preparations, Letter and Synthroid 100-μg thyroxine tablets.  Ten patients (three men and seven women) requiring treatment with thyroid hormone volunteered for the study. One had diffuse goiter, three had hypothyroidism, and six had thyroid nodules. Each was treated for one month with an appropriate dose of Letter (lot No. 7913416) dispensed as the 100-μg tablet and then for a second month with a numerically equivalent dose of Synthroid (lot No. ZD1678) dispensed as the 100-μg tablet. After each treatment interval, blood was drawn for determination of the serum thyroxine (T 4 ) level (normal, 5.5 to 12.0 μg/dL), 1 serum triiodothyronine (T 3 ) level (normal, 84 to 220 ng/dL), 2 triiodothyronine resin uptake (RT 3 U) (normal, 25%
Tolerance Induced by Parity in Mice Incompatible at the &lt;italic&gt;H-2&lt;/italic&gt; Locus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Edward J. Breyere, Morris K. Barrett
Journal: JNCI Journal of the National Cancer Institute (1961)

BALB/c (H-2d) female mice were divided into 3 groups and mated to males of the following strains to produce from 1 to 8 Utters: C3H (H-2k), DBA/2 (H-2d), and BALB/c. A fourth group was retained as virgins. After the parous females had their last litter, all 4 groups were challenged with plasma-cell tumor SS (70429), of C3H origin. The tumor grew in 59 percent of females parous by C3H males, in less than 1 percent of those parous by BALB/c males, and in none of the others. These findings are presented as evidence that tolerance in an apparently H-2 incompatible system can be induced by strain-specific matings. As in previous studies, tolerance appeared to increase with multiparity. Approximately half the tumors in specifically parous females grew in the form of a ring, a phenomenon apparently peculiar to this situation.
Bronchial Carcinoid Tumor and Hypercalcemia
Authors: E. SARFATI
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 March 1987Bronchial Carcinoid Tumor and HypercalcemiaE. SARFATI, A. LAVERGNE, D. GOSSOT, D. FISCHER, C. DUBOSTE. SARFATISearch for more papers by this author, A. LAVERGNESearch for more papers by this author, D. GOSSOTSearch for more papers by this author, D. FISCHERSearch for more papers by this author, C. DUBOSTSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-106-3-476_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We report a case of bronchial carcinoid tumor concomitant with hypercalcemia in which the hypercalcemia disappeared after excision of the lesion.A 64-year-old man was admitted to our department because of persistent hypercalcemia after an unsuccessful cervicotomy for suspected primary hyperparathyroidism. Two years ago, his serum calcium level was normal, and a chest radiograph of the right lung showed a small opacity that was disregarded Three months before admission, the patient had progressive and severe asthenia. Clinical findings were normal. A chest radiograph showed a high-density nodule in the right lung. Blood chemistry tests revealed hypercalcemia, 155...References1. HURTBATES RM. Carcinoid tumors of the bronchus: 33 years experience. Thorax. 1984;39:617-23. CrossrefMedlineGoogle Scholar2. MCCAUGHANMARTINIBAINS BNM. Bronchial carcinoid-review of 124 cases. J Thorac Cardiovasc Surg. 1985;89:8-17. CrossrefMedlineGoogle Scholar3. MAXLAWRENCE MP. Ectopic secretion of parathyroid hormone. Surg. Gynecol Obstet. 1980;150:411-8. MedlineGoogle Scholar4. SANOSAITOYAMASAKI THR. Immunoreactive somatostatin and calcitonin in pulmonary neuroendocrine tumor. Cancer. 1986;57:64-8. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: E. SARFATI; A. LAVERGNE; D. GOSSOT; D. FISCHER; C. DUBOSTAffiliations: Hôpital Saint-Louis 75010 Paris France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byWhat Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the LiteratureCase Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers 1 March 1987Volume 106, Issue 3Page: 476-477KeywordsBlood chemistryCalciumCarcinoid tumorHypercalcemiaHyperparathyroidismLesionsLungsPatient advocacyThorax ePublished: 1 December 2008 Issue Published: 1 March 1987 PDF downloadLoading ...
Histological response and antigen transmission in the lymph nodes of athymic nu/nu mice inoculated with Crohn's disease tissue filtrates.
Authors: J F Collins, R G Strickland, E L Kekahbah, M H Arthur, F Naeim, G L Gitnick
Journal: Gut (1988)

Lymph node histology and antigen transmission in the nu/nu mouse in response to animal inoculation with Crohn9s disease tissue filtrates were re-evaluated. We found that a hyperplastic lymph node response in nu/nu mice occurred with Crohn9s disease (CD), ulcerative colitis (UC), or other intestinal disease (OID) tissue inoculations. In addition, antigen transmission to lymph nodes as detected by indirect immunofluorescence using CD sera was observed in all inoculation groups. The immunofluorescent reaction also occurred independently of lymph node histology. Thus, we confirm that CD sera recognize an antigen(s) expressed in lymph nodes of athymic mice inoculated with CD tissue filtrates. The antibody (or antibodies) in CD sera was not specific for this 9CD antigen or antigens9, however, as tested in the nu/nu mouse system, because the CD sera antibodies also recognised antigens in UC inoculated and OID inoculated animals.
Increased Plasma Apolipoprotein(a) Levels in IDDM Patients With Diabetic Nephropathy
Authors: Lise Tarnow, Peter Rossing, Flemming S Nielsen, Birgitte V Hansen, Jørn Dyerberg, Hans-Henrik Parving
Journal: Diabetes Care (1996)

OBJECTIVE The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a) [apo(a)] in particular to CVD in nephropathic patients with IDDM. RESEARCH DESIGN AND METHODS We investigated 199 IDDM patients with diabetic nephropathy and 192 normoalbuminuric IDDM patients matched for sex, age, diabetes duration, and BMI. RESULTS The prevalence of CVD was 30 and 12% in patients with and without nephropathy, respectively (P &amp;lt; 0.001). The level of apo(a) was significantly higher in patients with nephropathy, 189 (20–2,350) U/l as compared with the normoalbuminuric group, 103 (20–1,940) U/l (P &amp;lt; 0.005). The prevalence of plasma apo(a) &amp;gt; 300 U/l (at-risk level for cardiovascular pathogenicity) was 38% (31–45) vs. 22% (16–28) in patients with and without nephropathy, respectively (P &amp;lt; 0.0005). In nephropathic patients, the prevalence of plasma apo(a) &amp;gt; 300 U/l was raised in patients with CVD (48%, 36–61%) as compared with patients without (34%, 26–42%) (P = 0.05). Furthermore, the serum concentrations of the following apolipoproteins and lipids were higher in patients with nephropathy as compared with normoalbuminuric patients: apoB 1.33 ± 0.37 vs. 1.06 ± 0.26 g/l; total cholesterol 5.6 ± 1.2 vs. 4.8 ± 0.9 mmol/l; and triglycerides 1.22 (0.31–9.87) vs. 0.77 (0.28–3.05) mmol/l, P &amp;lt; 0.0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration &amp;gt; 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03–3.36) (P &amp;lt; 0.05). CONCLUSIONS Dyslipidemia and raised plasma concentrations of apo(a), particularly &amp;gt; 300 U/l, may contribute to the enhanced morbidity and mortality from CVD characteristically observed in IDDM patients with diabetic nephropathy.
Laryngeal Sarcoidosis Detected by FDG Positron Emission Tomography
Authors: Kyoichi Kaira, Tamotsu Ishizuka, Noriko Yanagitani, Noriaki Sunaga, Takeshi Hisada, Masatomo Mori
Journal: Clinical Nuclear Medicine (2008)

Fluorodeoxyglucose positron emission tomography (FDG PET) has been widely used in the assessment of malignancy. However, FDG is not tumor-specific and may be taken up by nonmalignant conditions such as sarcoidosis. Sarcoidosis is a systemic disease and extrapulmonary lesions are also present. However, laryngeal sarcoidosis is a rare manifestation of extrapulmonary sarcoidosis. A 60-year-old man with a history of previous sarcoidosis presented with hoarseness. PET imaging demonstrated increased FDG uptake in the larynx. The histologic examination revealed laryngeal sarcoidosis. We report a case of laryngeal sarcoidosis and emphasize the role of FDG PET.
Case of Muco-Enteritis, with Abscess at Umbilicus: Relieved by Profuse Serous Discharge from a Spontaneous Opening of the Umbilicus by Ulceration, Followed by Prolonged Suppuration, Repeated Haemorrhage, and Stercoraceous Vomiting
Authors: A. Knox
Journal: BMJ (1850)

nMoral and mental quietude is most desirable, but here ain not iactivit.According to the natural dispositions, various degres of mental occupation and social intercourse are necessary; and so strongly is the action, and thence the structure of the heart, influenced by mete physical causes, that there is no morbific circumstance more pernicious than violent mental passions, and no medicine, in chronic cases, so salutary as the calm enjoyment of agreeable social relations, and of amusing intellectual pursuits.We speak practicaUy not less than poeticaUy, when we place these passions in the human heart; and as we hear of many a whole heart rent and broken with grief and trouble, or burst with unbridled passion, we may well judge what havoc these feelings may cause in a heart already unsound.It is not often ours to "minister to a mind diseased, or cleanse the stuffed bosom of that perilous stuff that weighs upon the heart;" but we may often enlist the patient's understanding and well-grounded fears on our own side, when we counsel him sobriety in his sorrow, and calmness in his care: on us may devolve the privilege and responsibility (and in no case does the conscientious physician, with his best exertions, more need Divine help to direct his judgment aright) of advising and deciding with regard to important changes in the relations and occupations of his future life."
Lung volume reduction surgery in chronic obstructive pulmonary disease.
Authors: L Davies, P M Calverley
Journal: Thorax (1996)

We undertook surgical bilateral lung volume reduction in 20 patients with severe chronic obstructive pulmonary disease to relieve thoracic distention and improve respiratory mechanics.The operation, done through median sternotomy, involves excision of 20% to 30% of the volume of each lung.The most affected portions are excised with the use of a linear stapling device fitted with strips of bovine pericardium attached to both the anvil and the cartridge, to buttress the staple lines and eliminate air leakage through the staple holes.Preoperative and postoperative assessment of results has included grading of dyspnoea and quality of life, exercise performance, and objective measurements of lung function by spirometry and plethysmography.There has been no early or late mortality and no requirement for immediate postoperative ventilatory assistance.Follow-up ranges from 1 to 15 months (mean 6.4 months).The mean forced expiratory volume in 1 second has improved by 82% and the reduction in total lung capacity, residual volume, and trapped gas has been highly significant.These changes have been associated with marked relief of dyspnoea and improvement in exercise tolerance and quality of life.Although the follow-up period is short, these preliminary results suggest that bilateral surgical volume reduction may be of significant value for selected patients with severe chronic obstructive pulmonary disease.(
Mutation of C/EBPα predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen
Authors: Marie S. Hasemann, Inge Damgaard, Mikkel B. Schuster, Kim Theilgaard-Mönch, Annette B. Sørensen, Alan Mršić, Thijs Krugers, Bauke Ylstra, Finn S. Pedersen, Claus Nerlov, Bo T. Porse
Journal: Blood (2008)
Elastosis and Fragmentation of Fibers of the Elastic System in Fatal Asthma
Authors: THAIS MAUAD, ANA CAROLINA GALTAROSSA XAVIER, PAULO HILÁRIO NASCIMENTO SALDIVA, MARISA DOLHNIKOFF
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Fibers of the elastic system (FES) are important in regulating airway patency and lung elastic recoil. Their possible role in modulating bronchoconstriction is not fully understood. Chronic inflammation and mechanical stretching present in asthma could lead to conformational alterations in the FES, participating in the mechanism of airway remodeling observed in this disease. In airway mucosa, two layers of FES are discernible: one superficial network, attached to the basement membrane, and a deeper network, lying close to the airway smooth muscle. Using image analysis and conventional morphometry, we analyzed airway content of FES in central and peripheral airways in 31 cases of fatal asthma and in 10 control lungs. Slides were stained using the oxidized resorcin-fuchsin method. Optical analysis revealed fragmentation of the FES in the superficial network of central asthmatic airways. Morphometry showed the presence of elastosis in central asthmatic airways when the entire thickness of the mucosa was considered. In the superficial network elastic fiber content was significantly decreased. These results indicate that FES participate in airway remodeling in asthma. We also suggest that disrupture of fiber attachments at the basement membrane in the superficial layer could impair the mechanism of airway recoil in asthmatic patients.
Access to Health Care for the Rural Elderly
Authors: Thomas C. Rosenthal
Journal: JAMA (2000)

IN ADDITION TO THE USUAL CHALlenges of chronic disease and functional decline, the rural elderly also face geographic isolation. Sixty-one million people live in the rural United States, a number that exceeds the entire population of the United Kingdom, Spain, Italy, or France. Nearly 15% of the US rural population is aged 65 years or older. As they age, the rural elderly confront several barriers to obtaining medical care. To a far greater degree than their urban counterparts, rural primary care physicians are expected to provide urgent care, rehabilitation, outreach, and specialty care (in collaboration with distant urban specialists) for their patients. Health care outcomes for the rural elderly, as with other groups in the United States, are influenced more by social position, insurance status, clinician access, and economic status than by geography. When differences in outcomes between rural and urban health care have been demonstrated, they generally relate to an imbalance of volume, staff support, equipment, and choice. In this article, we examine practice patterns and describe social, policy, and research issues influencing care for the rural elderly.
Research Ethics Review in Humanitarian Contexts: The Experience of the Independent Ethics Review Board of Médecins Sans Frontières
Authors: Doris Schopper, Ross Upshur, Francine Matthys, Jerome Amir Singh, Sunita Sheel Bandewar, Aasim Ahmad, Els van Dongen
Journal: PLoS Medicine (2009)

Doris Schopper and colleagues describe the functioning of the Médecins Sans Frontières independent ethics review board and the framework used for ethics review, and discuss challenging ethical issues encountered by the board since its inception.
Stimulation by leukotriene D4 of increases in the cytosolic concentration of calcium in dimethylsulfoxide-differentiated HL-60 cells.
Authors: L Baud, E J Goetzl, C H Koo
Journal: Journal of Clinical Investigation (1987)

The C6-sulfidopeptide leukotrienes C4 (LTC4) and D4 (LTD4) evoked increases in the cytosolic concentration of intracellular calcium ([Ca+2]i) in dimethylsulfoxide-differentiated HL-60 cells, as assessed by the fluorescence of quin-2. The increases in [Ca+2]i reached a peak within 15-90 s, attained 50% of the maximum level at 1.2 nM LTD4 and 60 nM LTC4, were greater in maximal magnitude for LTD4 than LTC4, and subsided in 5-7 min. Flow cytometric evaluation of the LTD4-induced increases in [Ca+2]i, reflected in increases in the fluorescence of intracellular indo-1, revealed that a mean of 77% of differentiated HL-60 cells responded, as contrasted with lesser increases in only 50% of undifferentiated HL-60 cells. The capacity of pretreatment of HL-60 cells with LTD4 to prevent subsequent responses of [Ca+2]i to LTC4 and LTD4, and the finding that the serine-borate inhibitor of conversion of LTC4 to LTD4 suppressed concurrently both LTC4-induced rises in [Ca+2]i and increases in adherence to Sephadex G-25 indicated that the responses of HL-60 cells to LTC4 required conversion to LTD4. That pertussis toxin and a chemical antagonist of LTD4 reduced the [Ca+2]i response suggested a dependence on LTD4 receptors. The LTD4-induced increases in [Ca+2]i were dependent on extracellular calcium and diminished by lanthanum, but not affected by nifedipine nor associated with changes in membrane potential, as measured with the fluorescent probe 3,3'-dipentyloxacarbocyanine. Thus, the increase in [Ca+2]i in HL-60 cells, which is coupled to an increase in adherence, appears to involve LTD4 receptor-specific and voltage-independent calcium channels in the plasma membrane.