tbuckley/cabot-search huggingface dataset:
Abstract 1861: EPHB4 as a potential therapeutic target for esophageal cancer
Authors: Rifat Hasina, Karun Mutreja, Ichiro Kawada, Rajani Kanteti, Qudsia Arif, Ren Liu, Xiuqing Li, Yue Zhou, Elizabeth Hyjek, Mark W. Lingen, Jeffery Mueller, Irving Waxman, Victoria Villaflor, Mark Ferguson, Everett E. Vokes, Parkash Gill, Ravi Salgia
Journal: Cancer Research (2012)

Abstract Despite substantial improvements in screening, diagnosis, and treatment of esophageal cancer, the prognosis of this disease remains bleak. Survival at 5 years for all esophageal cancer patients taken together, with amenable treatments and with or without surgery ranges from 5-20% (Cancer Facts and Figures. American Cancer Society 2011). Although a multidisciplinary approach to include surgery, radiation, and chemotherapy, alone or in combination, attempts to improve the survival of this aggressive disease, these statistics underscore the continued need for attention to this disease and for identification of new targets in its treatment. We have been studying the role of receptor tyrosine kinases (RTKs) in cancer, particularly the EphB4 receptor, which has become increasingly associated with the pathobiology of adult cancers over the past several years. It has been shown to be aberrantly expressed and/or to play an oncogenic role in cancers of the breast, bladder, ovary, uterus, colon, head and neck, and prostate through its effects on cellular motility, growth, and migration, as well as on tumors’ ability to induce neoangiogenesis. To date, its role and potential as a target for therapy in different cancers have not been thoroughly investigated and remain poorly understood. Targeted inactivation of EphB4 and its ligand Ephrin-B2 have demonstrated that both are essential for angiogenic remodeling and embryonic survival (Adams and Klein 2000; Kim, Hu et al. 2008). In this report, we determine that EphB4 is overexpressed, has increased gene copy number and is involved in enhanced motility and migration in esophageal cancer. Archival patient samples consisting of 93 squamous cell carcinoma, 100 adenocarcinoma and 25 adjacent normal control samples as well as four adenocarcinoma and nine squamous cell carcinoma cell lines were used for the studies. Extensive mouse modeling of esophageal cancer was also used. We have reported that there is consistently higher expression of EphB4 in both squamous and adenocarcinoma compared to adjacent normal tissue with a statistically significant correlation between EphB4 expression and higher grades of squamous cell carcinoma. In a chemically induced esophageal squamous cell carcinoma model in mice, EphB4 was found overexpressed compared to normal controls. This study identifies EphB4 to be an important pathway in esophageal neoplastic lesions. It would now be useful to bring this to clinical fruition. 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 1861. doi:1538-7445.AM2012-1861
An NLRP3 inflammasome–triggered Th2-biased adaptive immune response promotes leishmaniasis
Authors: Prajwal Gurung, Rajendra Karki, Peter Vogel, Makiko Watanabe, Mark Bix, Mohamed Lamkanfi, Thirumala-Devi Kanneganti
Journal: Journal of Clinical Investigation (2015)

Leishmaniasis is a major tropical disease that can present with cutaneous, mucocutaneous, or visceral manifestation and affects millions of individuals, causing substantial morbidity and mortality in third-world countries. The development of a Th1-adaptive immune response is associated with resistance to developing Leishmania major (L. major) infection. Inflammasomes are key components of the innate immune system that contribute to host defense against bacterial and viral pathogens; however, their role in regulating adaptive immunity during infection with protozoan parasites is less studied. Here, we demonstrated that the NLRP3 inflammasome balances Th1/Th2 responses during leishmaniasis. Mice lacking the inflammasome components NLRP3, ASC, or caspase 1 on a Leishmania-susceptible BALB/c background exhibited defective IL-1β and IL-18 production at the infection site and were resistant to cutaneous L. major infection. Moreover, we determined that production of IL-18 propagates disease in susceptible BALB/c mice by promoting the Th2 cytokine IL-4, and neutralization of IL-18 in these animals reduced L. major titers and footpad swelling. In conclusion, our results indicate that activation of the NLRP3 inflammasome is detrimental during leishmaniasis and suggest that IL-18 neutralization has potential as a therapeutic strategy to treat leishmaniasis patients.
The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer
Authors: Marcus Schmidt, Daniel Böhm, Christian von Törne, Eric Steiner, Alexander Puhl, Henryk Pilch, Hans-Anton Lehr, Jan G. Hengstler, Heinz Kölbl, Mathias Gehrmann
Journal: Cancer Research (2008)

Abstract Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation-associated genes. In multivariate Cox regression analysis, the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort [hazard ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40–3.46]. The B-cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR, 0.66; 95% CI, 0.46–0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high-grade tumors (n = 286; HR, 0.78; 95% CI, 0.62–0.98) and a second validation cohort enriched for younger patients (n = 302; HR, 0.83; 95% CI, 0.7–0.97). Thus, we could show in three cohorts of untreated, node-negative breast cancer patients that the humoral immune system plays a pivotal role in metastasis-free survival of carcinomas of the breast. [Cancer Res 2008;68(13):5405–13]
Direct activation of STING in the tumor microenvironment with synthetic cyclic dinucleotide derivatives leads to potent and systemic tumor-specific immunity
Authors: Leticia Corrales, Laura Hix Glickman, Sarah M McWhirter, David B Kanne, Kelsey E Sivick, Edward Lemmens, Justin J Leong, Ken Metchette, Thomas W Dubensky, Thomas Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2014)

Aim: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (≥50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments9 medical records and radiation charts. Results: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). Conclusion: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.
Pegylated interferon alpha 2b (PEG IFN) plus ribavirin (R) for treatment of chronic hepatitis C: optimization of ribavirin dose
Authors: M. Manns, J.G. Mc Hutchison, S. Gordorn, V. Rustgi, M.V. Lee, M.L. Ling, M. Cohard, J.K. Albrecht
Journal: Journal of Hepatology (2001)
Actions of extracellular chloride ion substitution on contractility of isolated ventricular myocardium
Authors: C H Fry, H Griffiths, S K Hall
Journal: Cardiovascular Research (1993)

Journal Article Actions of extracellular chloride ion substitution on contractility of isolated ventricular myocardium Get access C H Fry, C H Fry Department of Physiology, UMDS, St Thomas' Campus, Lambeth Palace Road, London SE1 7EH, United Kingdom: C H Fry, H Griffiths, S K Hall. Correspondence to Dr Fry. Search for other works by this author on: Oxford Academic PubMed Google Scholar H Griffiths, H Griffiths Department of Physiology, UMDS, St Thomas' Campus, Lambeth Palace Road, London SE1 7EH, United Kingdom: C H Fry, H Griffiths, S K Hall. Search for other works by this author on: Oxford Academic PubMed Google Scholar S K Hall S K Hall Department of Physiology, UMDS, St Thomas' Campus, Lambeth Palace Road, London SE1 7EH, United Kingdom: C H Fry, H Griffiths, S K Hall. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 5, May 1993, Pages 856–860, https://doi.org/10.1093/cvr/27.5.856 Published: 01 May 1993 Article history Received: 24 August 1992 Accepted: 03 November 1992 Published: 01 May 1993
"Left Heart Failure" and Atrial Septal Defects.
Authors: Hans H. Hecht
Journal: Annals of Internal Medicine (1965)

s1 May 1965"Left Heart Failure" and Atrial Septal Defects.Hans H. Hecht, M.D., F.A.C.P., Gerasim Tikoff, M.D., Alexander M. Schmidt, M.D., Hiroshi Kuida, M.D.Hans H. Hecht, M.D., F.A.C.P.Search for more papers by this author, Gerasim Tikoff, M.D.Search for more papers by this author, Alexander M. Schmidt, M.D.Search for more papers by this author, Hiroshi Kuida, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1071_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptComplete clinical, laboratory, and repeated hemodynamic studies were carried out on 38 cases of large atrial septal defect of the secundum type ranging in age from 1 to 71 (mean, 38.6 years). The following observations were made:(1) Heart failure due to right ventricular overload is characterized in this entity by maintenance of normal atrial and normal end ventricular diastolic pressures, decreased right ventricular forward stroke volume, and decrease in left to right, and appearance of right to left shunt.(2) An elevation of common atrial pressure (in the absence of concomitant mitral stenosis) apparently signals left ventricular failure and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Hans H. Hecht, M.D., F.A.C.P.; Gerasim Tikoff, M.D.; Alexander M. Schmidt, M.D.; Hiroshi Kuida, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1071-1071KeywordsAtrial septal defectBlood pressureClinical laboratoriesHeart failureHemodynamicsMitral stenosisStroke ePublished: 1 December 2008 Issue Published: 1 May 1965 PDF downloadLoading ...
Penicillin in Infants Weighing Two Kilograms or Less with Early-Onset Group B Streptococcal Disease
Authors: Suma P. Pyati, Rosita S. Pildes, Norman M. Jacobs, Rajam S. Ramamurthy, Tsu F. Yeh, Devyani S. Raval, Lawrence D. Lilien, P. Amma, William I. Metzger
Journal: New England Journal of Medicine (1983)

We studied the effect of penicillin on early-onset Group B streptococcal disease over a 52-month period in neonates who were at high risk of infection. Shortly after birth, 1187 neonates weighing 2000 g or less had blood samples taken for cultures and were randomized into an early-treatment group (given intramuscular penicillin G within 60 minutes of birth) or a control group. The incidence of early-onset disease was 20 per 1000 live births (24 of 1187); the number of infants in the early-treatment group who had disease (10 of 589) was similar to that in the control group (14 of 598). The fatality rates were similar in both groups (6 of 10 vs. 8 of 14). Cultures from blood obtained with one hour of birth were positive in 21 of the 24 infants with disease; 22 of the 24 were symptomatic within four hours of birth. Thus, infection was well established before the first hour of postnatal life. At autopsy, gram-positive cocci were seen in lung sections of four infants in whom cultures of blood obtained after treatment had been sterile; this indicates that giving routine antibiotic therapy before culture samples are obtained can obscure bacteriologic diagnosis. We conclude that penicillin given at birth to neonates weighing 2000 g or less does not prevent early-onset streptococcal disease or reduce excess mortality associated with disease.
Validity of two kinematic systems for calculating force and power during squat jumps
Authors: B T Crewther, L P Kilduff, D Cunningham, C Cook, G-Z Yang
Journal: British Journal of Sports Medicine (2010)

Force and power are key exercise outputs in research and training practice. The direct acquisition of this kinetic data typically requires a force plate, which is not always practical and cost-effective, and generally limited to laboratory-based settings. Thus, kinematic systems (eg, linear position transducers, accelerometers) are becoming increasingly popular as tools for calculating force and power in situ during exercise. The aim was to assess the validity of a commercial linear position transducer and accelerometer for calculating force and power during squat jumps. Seven healthy males performed 2×single repetition squat jumps with four loads (20 kg, 40 kg, 60 kg and 80 kg). The squats were performed on top of a Kistler force plate. A commercial linear position transducer (Gymaware (GYM)) and accelerometer (Myotest (MYO)) were attached to the bar to assess concentric peak force (PF) and peak power (PP), based on the combined mass of the external load and each subject. Data were pooled across all loads for analysis. The PF and PP data from the GYM and MYO systems were strongly correlated with the force plate data (r=0.84-0.93, p&lt;0.001) and also with each other (r=0.90-0.97, p&lt;0.001). The mean PF and/or PP values calculated from the GYM and MYO systems were found to be 4.5%-6.5% higher than the measured values from the force plate (p&lt;0.01). The PF and PP data from the linear position transducer and accelerometer showed strong relative validity compared to the force plate, but some differences in absolute validity were noted. The two kinematic systems provide other benefits (eg, portability, ease of use, cost effectiveness) for assessing PF and PP during squat jumps or similar isoinertial exercises.
Tonsils, Apolipoproteins and Enzymes
Authors: Donald S. Fredrickson
Journal: New England Journal of Medicine (1972)

With this issue of the Journal the number of known examples of Tangier disease rises to a baker's dozen. It is useful to have an occasional reminder that a subnormal cholesterol concentration requires a closer look for any orange tonsillar remnants in the pharynx. There is reason to doubt, however, whether lack of clinical awareness holds the rate of discovery to about one case of Tangier disease per year. It is more probable that the prevalence of the mutant gene (or genes) responsible for the disorder is simply quite low. Each new case of a rare genetic disorder usually sheds . . .
Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis
Authors: Goutam Ghosh, Indira V. Subramanian, Neeta Adhikari, Xiaoxiao Zhang, Hemant P. Joshi, David Basi, Y.S. Chandrashekhar, Jennifer L. Hall, Sabita Roy, Yan Zeng, Sundaram Ramakrishnan
Journal: Journal of Clinical Investigation (2010)

Adaptive changes to oxygen availability are critical for cell survival and tissue homeostasis. Prolonged oxygen deprivation due to reduced blood flow to cardiac or peripheral tissues can lead to myocardial infarction and peripheral vascular disease, respectively. Mammalian cells respond to hypoxia by modulating oxygen-sensing transducers that stabilize the transcription factor hypoxia-inducible factor 1α (HIF-1α), which transactivates genes governing angiogenesis and metabolic pathways. Oxygen-dependent changes in HIF-1α levels are regulated by proline hydroxylation and proteasomal degradation. Here we provide evidence for what we believe is a novel mechanism regulating HIF-1α levels in isolated human ECs during hypoxia. Hypoxia differentially increased microRNA-424 (miR-424) levels in ECs. miR-424 targeted cullin 2 (CUL2), a scaffolding protein critical to the assembly of the ubiquitin ligase system, thereby stabilizing HIF-α isoforms. Hypoxia-induced miR-424 was regulated by PU.1-dependent transactivation. PU.1 levels were increased in hypoxic endothelium by RUNX-1 and C/EBPα. Furthermore, miR-424 promoted angiogenesis in vitro and in mice, which was blocked by a specific morpholino. The rodent homolog of human miR-424, mu-miR-322, was significantly upregulated in parallel with HIF-1α in experimental models of ischemia. These results suggest that miR-322/424 plays an important physiological role in post-ischemic vascular remodeling and angiogenesis.
Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells.
Authors: X Xu, S H Kang, O Heidenreich, M Okerholm, J J O'Shea, M I Nerenberg
Journal: Journal of Clinical Investigation (1995)

HTLV-1 infection causes an adult T cell leukemia in humans. The viral encoded protein tax, is thought to play an important role in oncogenesis. Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues. Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice. Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines. Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6. Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation. Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies. Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model.
ACETONE AS A DECOLORIZER IN GRAM'S STAINING METHOD
Authors: M. W. Lyon
Journal: JAMA (1920)

<h3>To the Editor:</h3> —With the increasing cost of alcohol and the difficulty of obtaining the pure substance, the following uses of acetone for alcohol may prove of interest. Available literature does not mention them, but they are so simple that acetone must have been used in this manner before. The current local price of medicated 95 per cent, alcohol is $1.60 per pint, and absolute alcohol cannot be purchased locally. In place of alcohol, acetone 50 cents per pint, kept dehydrated with calcium chlorid, has been used for tissue work not only for dehydrating preparatory to embedding in paraffin in the usual manner, but also for passing from xylene to water and hematoxylin and thence from water to xylene again in staining sections on slides. The results are very satisfactory, and with a small amount of eosin in the last acetone, counterstaining and dehydration are accomplished in one step. Gram's
Drug Therapy in Elderly Patients
Authors: VALERY A. PORTNOI
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 March 1982Drug Therapy in Elderly PatientsVALERY A. PORTNOI, M.D.VALERY A. PORTNOI, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-3-376_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The article on drug therapy in the elderly (1) is a comprehensive and stimulating essay on the state of the art; however, one additional comment or clarification may be of value. The article leaves an impression that the polypharmacy so frequently seen in drug therapy in the elderly is inevitable because of concurrent medical conditions requiring control by many medications. The article does not stress that most of the conditions are stable, at times self-limited, and can be controlled without drug therapy. We have recently reported the results of a study in which long-term (average, 2 years)...References1. OUSLANDER J. Drug therapy in the elderly. Ann Intern Med. 1981; 95:711-22. LinkGoogle Scholar2. PORTNOI V and PAWLSON L. Abuse of diuretic therapy in nursing homes. J Chron Dis. 1981;34:363-5. CrossrefMedlineGoogle Scholar3. BURR M, KING S, and DAVIES H: The effects of discontinuing long term diuretic therapy in the elderly. Aging-aging. 1977;6:38-45. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: VALERY A. PORTNOI, M.D.Affiliations: The George Washington University Medical Center Washington, DC 20037 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1982Volume 96, Issue 3Page: 376-376KeywordsDrug therapyElderlyMedical conditions ePublished: 1 December 2008 Issue Published: 1 March 1982 PDF downloadLoading ...
Thyroid and other organ-specific autoantibodies in healthy ceritenarians
Authors: S. Mariotti, G. Barbesino, P. Caturegli, T. Giacomelli, A. Pinchera, D. Monti, A. Cossarizza, C. Franceschi, P. Sansoni, G. Passeri, U. Fagiolo
Journal: The Lancet (1992)
210 TRANSARTERIAL CHEMOEMBOLIZATION OF UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC) WITH DRUG ELUTING BEADS (DEB-TACE)
Authors: N. Campo, P. Gazzo, E. Azzola, D. Ivaldi, S. Lupo, M. Magnolia, S. Milazzo, C. Rainisio, G. Barbera, R. Testa
Journal: Journal of Hepatology (2010)
Urban Health Services of the Future
Authors: Harold A. Rashkis
Journal: JAMA (1971)

While the terms "disease" and "health" have several dictionary definitions, for the purpose of developing a service delivery system it is necessary to create operationally useful formulations. Since the way health and disease are defined is at once a function of who is doing the defining and who is developing the delivery system, the definitions developed by the provider of services differ from those developed by the consumer, and both of these differ from the formulation of a third party such as a government agency or an insurer, it is accordingly necessary that the present frame of reference be stated: The universe under consideration contains the strivings of urban peoples to eliminate and prevent disease and to approach a state of health; it also contains the facilities available for meeting those ends and is oriented toward planning for the future. It is not too great an oversimplification to state that