tbuckley/cabot-search huggingface dataset:
AXL Inhibition Sensitizes Mesenchymal Cancer Cells to Antimitotic Drugs
Authors: Catherine Wilson, Xiaofen Ye, Thinh Pham, Eva Lin, Sara Chan, Erin McNamara, Richard M. Neve, Lisa Belmont, Hartmut Koeppen, Robert L. Yauch, Avi Ashkenazi, Jeff Settleman
Journal: Cancer Research (2014)

Molecularly targeted drug therapies have revolutionized cancer treatment; however, resistance remains a major limitation to their overall efficacy. Epithelial-to-mesenchymal transition (EMT) has been linked to acquired resistance to tyrosine kinase inhibitors (TKI), independent of mutational resistance mechanisms. AXL is a receptor tyrosine kinase associated with EMT that has been implicated in drug resistance and has emerged as a candidate therapeutic target. Across 643 human cancer cell lines that were analyzed, elevated AXL was strongly associated with a mesenchymal phenotype, particularly in triple-negative breast cancer and non-small cell lung cancer. In an unbiased screen of small-molecule inhibitors of cancer-relevant processes, we discovered that AXL inhibition was specifically synergistic with antimitotic agents in killing cancer cells that had undergone EMT and demonstrated associated TKI resistance. However, we did not find that AXL inhibition alone could overcome acquired resistance to EGFR TKIs in the EMT setting, as previously reported. These findings reveal a novel cotreatment strategy for tumors displaying mesenchymal features that otherwise render them treatment refractory.
Erythropoietin regulates intestinal iron absorption in a rat model of chronic renal failure
Authors: Surjit K. Srai, Bomee Chung, Joanne Marks, Katayoun Pourvali, Nita Solanky, Chiara Rapisarda, Timothy B. Chaston, Rumeza Hanif, Robert J. Unwin, Edward S. Debnam, Paul A. Sharp
Journal: Kidney International (2010)
Haemodynamic effects of salbutamol in patients with acute myocardial infarction and severe left ventricular dysfunction.
Authors: A D Timmis, S K Strak, D A Chamberlain
Journal: BMJ (1979)

The haemodynamic effects of salbutamol infusions at rates of 10,20, and 40 micrograms/min were measured in 11 patients with acute myocardial infarction complicated by left ventricular failure. Four patients also had cardiogenic shock. Consistent increases were observed in cardiac outputs at all doses (up to 56% at 40 micrograms/min), while the mean systemic arterial pressure fell slightly (average 5 mm Hg), implying a reduction in peripheral vascular resistance. Changes in right atrial pressure and indirect left atrial pressure (measured as pulmonary artery end-diastolic pressure) were small and not significant. Analysis of data from individual patients showed that the greatest increment in cardiac output was reached at 10 micrograms/min in two cases, 20 microgram/min in three, and 40 micrograms/min in the remaining six. Heart rate at these doses increased by an average of only 10 beats/min. Salbutamol failed to reduce left ventricular filling pressure and cannot be recommended for the treatment of pulmonary oedema in acute myocardial infarction. The increase in cardiac output, however, was considerable, so that the drug may be important in the management of low-output states. This action is probably a result of peripheral arteriolar dilatation (itself a result of beta 2-adrenoreceptor stimulation) and is achieved with little alteration in the principal determinants of myocardial oxygen requirement.
844. A Single Vector-Dependent, Doxycycline- Regulatable, Lung Cancer Specific Oncolytic Adenovirus
Authors: Isaac Sipo, Almudena Hurtado Pico, Judith Wildner, Lennart Suckau, Sandra Pinkert, Stefan Weger, Wolfgang Poller, Henry Fechner
Journal: Molecular Therapy (2006)

Tight regulation of oncolytic adenoviruses (oAdV) represents an important requirement for their safe application. We have developed a new doxycycline (Dox)-dependent oAdV with a bidirectional expression cassette, which drives the expression of the reverse tetracycline-controlled transactivator (rtTAs-M2) from a lung tumor-specific promoter and, in the opposite direction, the expression of the adenoviral E1A gene from a second generation tetO7 sequence linked to an isolated TATA box. In H441 lung cancer cells, this oAdV showed a strictly Dox-dependent E1A expression, adenoviral replication, cell killing activity and a 450-fold induction of progeny virus production. Furthermore, the virus could be shut off again by withdrawal of Dox and, in contrast to an oAdV expressing E1A directly from the SP-B promoter, did not replicate in non-target HeLa cells. In contrast, when the isolated TATA box in the E1A expression cassette was replaced by a CMV minimal promoter, the corresponding oAdV already expressed significant amounts of E1A in the absence of the inducer. These were sufficient to prevent any Dox-dependent regulation of adenoviral replication. These results underline the importance of non-leaky E1A expression for preventing undesirable oAdV replication and demonstrate, for the first time, Dox-dependent oAdV replication from a single adenoviral vector genome.
Opposing roles of IL‐17A and IL‐25 in the regulation of TSLP production in human nasal epithelial cells
Authors: G. Xu, L. Zhang, D. Y. Wang, R. Xu, Z. Liu, D. M. Han, X. D. Wang, K. J. Zuo, H. B. Li
Journal: Allergy (2009)

The importance of IL-17A, IL-17F, and IL-25 in allergic rhinitis (AR), as well as their possible role in regulation on thymic stromal lymphopoietin (TSLP) production in nasal epithelial cells, is not well understood.To determine the possible regulation of IL-17A, IL-17F, and IL-25 on TSLP production in the initiation of allergic responses.The levels of IL-17A, IL-17F, IL-25, and TSLP in nasal lavages of patients with AR were measured using an enzyme-linked immunosorbent assay (ELISA) and compared with that in normal controls. Then, primary human nasal epithelial cells (HNECs) were stimulated with dsRNA (0-75 microg/ml), as well as IL-17A (100 ng/ml), IL-17F (100 ng/ml), and IL-25(100 ng/ml). The mRNA expression of IL-17A, IL-17F, IL-25, TSLP, as well as the chemokines CCL20, IL-8, and eotaxin was analyzed using quantitative real-time PCR, and their protein levels in the supernatants of cultured HNECs were determined by ELISA.Both TSLP and IL-17 cytokines are significantly elevated in patients with AR. dsRNA was found to increase the production of IL-17F, IL-25, TSLP, CCL20, and IL-8 in HNECs. Furthermore, IL-25 significantly enhanced dsRNA-induced TSLP production in primary HNECs and was dominant to the inhibitory effect of IL-17A on TSLP regulation.Our study provides the first evidence that both IL-17F and IL-25 can be induced by dsRNA in HNECs. Despite of the opposing effects of IL-17A and IL-25 on TSLP regulation in HNECs, IL-25 was dominant to IL-17A, providing a plausible explanation for the simultaneous upregulation of IL-17 cytokines and TSLP in patients with AR.
Some Notes on Abdominal Injuries
Authors: G. G. Turner
Journal: BMJ (1940)

Recent discussions on problems connected with abdominal injuries, and the paper by Ambrose Lockwood in the British Medical Journal of March 9, have all stressed the importance of keeping resection of the injured intestine in reserve, and the young surgeon, without much experi- ence of abdominal work, is urged to look upon repair by suture rather than resection as -the first line of defence.Yet little has been said about this matter of repair, and of the diagrams which I have recently seen Fig. 1 portrays FIG.1.-Small wounds in bowel suitable for closure by simple suture (A.L. Lockwood).
Acute lung injury/Airway
Authors: L. Bindl, G. Kühl, P. Lasch, None Appel, J. Möller, J. Hammer, A. Numa, C. J. L. Newth, M. J. Peters, K. Kiff, B. McErlean, R. Yates, D. J. Hatch, R. C. Tasker, A. Martínez-Azagra, J. Casado Flores, N. González Bravo, E. Mora, J. García Pérez, H. J. Feickert, Ch. Kayser, M. Sasse, J. Fackler, C. Steinhart, D. Nichols, D. Bohm, M. Heulitt, T. Green, L. Martin, K. Newth, M. Klein, J. Ware, Mayer Sagy, Mehdi Poustchi-Amin, Laura Nimkoff, Peter Silver, Mark Shikowitz, John C. Leonidas
Journal: Intensive Care Medicine (1996)
A Case of Idiopathic Dilatation of the Colon
Authors: W. Leggett
Journal: BMJ (1911)

IDIOPATHIC DILATATION OF COLON.[TH BDIJo 77 incision was employed with no cross division of muscle or aponeurotic fibres.And, lastly, that while the number of cases is possibly too few to admit of a very positive state.ment-9 in all-where the incision had to be carried either upwards or downwards, it seems probable that downward extension is more likely to be followed by a bulging cicatrix than upward.CONCLUSIONS. 1.That, where proper precautions are taken to protect the general peritoneal cavity, this method of operating admits of every abscess being opened and every appendix sought for and removed with perfect safety.Cases of Uncomplicated Appendical Abscess Treated with Pure Carbolic Acid and Iodoform.
Catheter interventional septal abiation for hypertrophic obstructive cardiomyopathy: an analysis of the follow-up data from the registry of the german society of cardiology
Authors: Lothar Faber, Hubert Seggewiss, H. Kuhn, F. Gietzen, P. Boekstegers, Ludger Seipel, Ulrich Gleichmann, Dieter Horstkotte
Journal: Journal of the American College of Cardiology (2002)
DIFFUSE INTERSTITIAL MYOCARDIAL FIBROSIS DETECTED BY T1 MAPPING IS INCREASED IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS AND CORRELATES WITH LEFT VENTRICULAR SYSTOLIC AND DIASTOLIC DYSFUNCTION
Authors: Carlos G. Santos-Gallego, Torsten Vahl, Georg Goliasch, Eduardo Pozo, Pablo Pazos, Sarayu Ramachandran, Partho Sengupta, Jagat Narula, Valentin Fuster, Juan Jose Badimon, Javier Sanz
Journal: Journal of the American College of Cardiology (2013)
The Psychiatric Consultation
Authors: Samuel Friedman
Journal: JAMA (1968)

Eighteen coauthors contribute 215 pages of text, a method which readily invokes repetitiveness and, on occasion, contrary views. Thus, Aldrich regards the first year of psychiatric resident training as an appropriate period for the consultation service, while Schwab recommends the second year. My experience indicates that the first year resident lacks the necessary knowledge and ease in the field to perform a helpful or meaningful consultation. Consultations with the clergy, courts, industry, school, college, and government, welfare, or community agencies constitute some of the significant chapters. Although each of these areas presents some particular problems, the necessity of such fragmentation of discussion seems somewhat dubious. The material on education and training in psychiatric consultation emphasizes the uniqueness of this function and implies that many psychiatrists, though well trained in diagnosis and therapy, may be deficient in this specific skill. Do I hear any protests? Pollack's material on "Psychiatric Consultation for
Effect of Lymphatic Mapping on the New Tumor-Node-Metastasis Classification for Colorectal Cancer
Authors: Anton J. Bilchik, Dean T. Nora, Leslie H. Sobin, Roderick R. Turner, Steven Trocha, David Krasne, Donald L. Morton
Journal: Journal of Clinical Oncology (2003)

Sensitive detection methods and accurate reporting are necessary to determine the prognostic significance of micrometastases (MM) and isolated tumor cells (ITCs) in lymph nodes that drain colorectal cancers (CRCs). This study examined the role of lymphatic mapping (LM) in the application of the new tumor-node-metastasis (TNM) classification for MM and ITC.All patients at the John Wayne Cancer Institute underwent LM immediately before standard resection of primary CRC between 1996 and 2001. Sentinel nodes (SNs) were identified using blue dye and/or radiotracer and were examined by hematoxylin-eosin (H&E) staining, cytokeratin immunohistochemistry, and multilevel sectioning. The comparison group comprised 370 patients whose primary CRCs were resected without LM during the same period at the same institution.LM was successfully performed in 115 of 120 (96%) patients and correctly predicted the tumor status of the nodal basin in 110 of 115 (96%) patients. Thirty-seven patients (32%) were lymph node-positive by H&E, ITC and MM were found in 23 patients (29.4%) whose lymph nodes were negative by H&E. Tumor deposits were found in the SN only in 29 patients (50%). Nodal involvement was identified for 14.3%, 30%, 74.6%, and 83.3% of T1, T2, T3, and T4 tumors, respectively, in the study group, and for 6.8%, 8.5%, 49.3%, and 41.8% of T1, T2, T3, and T4 tumors, respectively, in the comparison group. The study group had a higher percentage of nodal metastases (53% v 36%; P <.01) and a higher incidence of MM and ITC (29.4% v 1.9%; P <.0001). The mean number of lymph nodes found in the study group (14) was also significantly more than the number found in the comparison group (10; P <.00001).Conventional examination of lymph nodes for CRC is inadequate for the detection of MM and ITC as described in the new TNM classification. Thus, LM and focused SN analysis should be considered to fully stage CRC.
Accuracy of an ultrasound Doppler servo method for noninvasive determination of instantaneous and mean arterial blood pressure.
Authors: R Aaslid, A O Brubakk
Journal: Circulation (1981)

A new noninvasive method for determining arterial blood pressure is presented. Using a fast servo system, the pressure in the arm cuff is controlled so that the flow is maintained at a low value. Transcutaneous ultrasound Doppler techniques are used to detect flow to the artery. Comparison with invasive pressure measurements demonstrated that the servo method reproduced beat-to-beat variations in arterial blood pressure faithfully. Mean arterial blood pressure was determined from the noninvasive recordings using the same mathematically valid procedure as was used for the invasive recordings. The deviation between the invasive and the noninvasive determinations of this measurement was -0.6 +/- 2.2 mm Hg (mean +/- SD) in 23 subjects.
The isolated perfused lung.
Authors: R W Niemeier
Journal: Environmental Health Perspectives (1984)

The unique nonrespiratory functions of the lungs have become more apparent in recent years. The isolated perfused lung model offers many advantages over other methods for the study of pulmonary metabolism, xenobiotic disposition and the influence of interactions among agents of different physical forms. Detailed descriptions of the experimental preparation are elements in evaluating and comparing data from various sources but these are frequently neglected. A discussion and critique of the following elements are provided in this review in order to elucidate the typical problems one might encounter in evaluating data: perfusate type, perfusion method, construction materials, ventilation method, temperature control, surgical procedure, microbiological contamination and evaluation criteria of the preparation. Examples are given where the IPL method has been applied and suggestions are made for future research efforts.
NOTES ON A CASE OF CONGENITAL HEART DISEASE WITH CYANOTIC EPISODES 12
Authors: W. F. Hamilton, J. A. Winslow, W. F. Hamilton
Journal: Journal of Clinical Investigation (1950)

Recent papers on cyanotic congenital heart disease (1-8) contain references to patients that suddenly become cyanotic, lose consciousness, and suffer dyspnea or other signs of cardio-respiratory distress.When such episodes are the result of exercise or of other factors which give rise to an increase in oxidations there might be some decrease in arterial saturation, even though the intracardiac shunt remains constant in the relative amount of venous blood which mixes into the arterial stream.If we imagine a case with large intracardiac shunt in which blood in the pulmonary vein is 100% saturated and two-thirds of the arterial stream is venous blood, and if we were to assume further the resting mixed venous saturation to be 50%o, we would have an arterial saturation of 67%o.
Cardiovascular benefits of incretins
Authors: A. H. Barnett, P. O'Hare
Journal: BMJ (2013)

Cohen and colleagues make no mention of the evidence that treatment of type 2 diabetes with increasingly larger doses of sulfonylureas and insulin is not without serious risk from hypoglycaemia, weight gain, and possibly increased cardiovascular risk.1 A balanced account of this is needed in any review of incretins.

There have been concerns that such treatments, or the hypoglycaemia and weight gain they produce, explain failure to reduce cardiovascular disease despite tightening glycaemic control. Large meta-analyses of sulfonylureas suggest that they may increase cardiovascular risk.2 3 By contrast, a large meta-analysis of dipeptidyl peptidase 4 inhibitors suggests significant cardiovascular benefit.4 …
ANTIGEN-SPECIFIC SYNERGISM IN THE IMMUNE RESPONSE OF IRRADIATED MICE GIVEN MARROW CELLS AND PERITONEAL CAVITY CELLS OR EXTRACTS
Authors: James C. Kennedy, Perry E. Treadwell, Edwin S. Lennox
Journal: The Journal of Experimental Medicine (1970)

A synergistic immune response to foreign erythrocytes may be induced in heavily irradiated mice injected with a mixture of isologous cells obtained from marrow and from the peritoneal cavity. Under appropriate conditions, homologous or heterologous peritoneal cavity cells, heat-killed cells, or cellfree extracts made from such cells are also effective. The activity of the peritoneal cavity cells or extracts is antigen-specific, in the sense that cells or extracts obtained from animals previously immunized with the test antigen produce much stronger synergistic effects than do cells from animals immunized with some other antigen; however, the peritoneal cavity cells or extracts are not immunogenic when tested in primed animals. The marrow cells, demonstrated to contain precursors of the antibody-forming cells produced during this synergistic immune response, also show a form of antigen-specificity.
The Dye Dilution Method for Describing the Central Circulation
Authors: ELLIOT V. NEWMAN, MARGARET MERRELL, ABRAHAM GENECIN, CARLOS MONGE, WILLIAM R. MILNOR, WILLIAM P. MCKEEVER
Journal: Circulation (1951)

In addition to providing accurate measurement of circulation times and cardiac output, the dye dilution curves may reveal the size and location of the volumes of blood with which the dye is mixed in the central circulatory system. A trivalent approach to the analysis of these curves is presented by a combination of theoretic analysis, mechanical system experimentation and clinical observation.
The Trauma of Athletics
Authors: Augustus Thorndike
Journal: New England Journal of Medicine (1952)

SINCE the appearance in 1940 of progress reports on the isolated topic of athletic trauma,1 many publications have appeared concerning lesions and injuries of similar types but not necessarily incident to athletics. Advances have been made in the treatment of trauma, whether due to physical agents of industrial occupational hazards or to war. Much of the same pathology exists as the result of athletic trauma.At this time one questions whether true amateurism exists in college athletics, whether the game is played among amateur scholarship heroes for financial gain or for fun, whether the deaths from the sport of professional . . .
Response to Clark and Kupper
Authors: Ingo Haase
Journal: Journal of Clinical Investigation (2006)

I read with great interest the commentary by Clark and Kupper titled Misbehaving macrophages in the pathogenesis of psoriasis (1) regarding our recently published articles in the JCI (2, 3). I very much appreciate this instructive commentary, but I feel that it should be put in perspective, in particular for readers who are not specialists in the field of psoriasis. 

First, to date, only 2 of the 8 mouse models cited in the commentary have shown conclusively that T cells are required in order for the psoriasis-like skin phenotype to develop in the respective model. In these 2 models, elimination of human CD3+ T cells from transplanted skin of 3 psoriatic individuals (4) or depletion of CD4+ T cells from CD18 hypomorphic mice (5) led to an improvement of the phenotype. Three of the other mouse models have shown that injection of in vitro–activated T cells/CD4+ T cells into skin grafts (6, 7) or of MHC-mismatched CD4+ T lymphocytes into SCID mice (8) reproduces or produces a psoriasis-like skin phenotype. This indicates that T cells can be sufficient but does not prove that they are required for the development of the psoriasis-like changes in the skin. 

Second, not all psoriasis patients respond sufficiently to cyclosporine A treatment. The amenability of psoriasis to cyclosporine treatment is used as an argument in favor of a pathogenic function of T cells. Although cyclosporine A is one of the most efficient drugs in the treatment of psoriasis, trials and clinical experience indicate that a subset of patients does not sufficiently respond to this treatment. For example, a meta-analysis of 3 controlled studies in 597 patients with severe psoriasis (9) demonstrated that only about half of the patients achieved a 70% or better improvement of their skin symptoms with cyclosporine A. Moreover, cyclosporine A not only affects T cells but also affects many other cell types, e.g., monocytes/macrophages, in which it can inhibit the production of TNF-α (10), a cytokine with a known function in the development of psoriasis. 

Third, the T cell–depleting agent denileukin diftitox (ONTAK) has poor efficacy in the treatment of psoriasis. DAB389IL-2 is a fusion protein consisting of IL-2 fused to diphtheria toxin. It binds to cells expressing the high-affinity IL-2 receptor and causes their destruction. In a double-blind, placebo-controlled phase II multicenter trial in patients with psoriasis, the efficacy of DAB389IL-2 as compared with placebo was minimal, and no dose-response relationship could be established (11). 

Finally, although it is likely that T lymphocytes have important functions in the development of psoriasis, it seems too early to conclude upon their pathogenic role. While a contribution of T cells may be critical for the development of psoriasis in a number of cases, any generalization of this concept would be premature at present. Instead, it should be considered that pathogenic pathways leading to the multifaceted clinical picture of psoriasis could be heterogeneous and may not necessarily depend on 1 single cell type.
Medical Devices, Abbreviations, Acronyms, and Eponyms: A Pocket Guide
Authors: Frederick R. Olson
Journal: JAMA (1995)

<b>Radiologic Guide to Medical Devices and Foreign Bodies,</b>edited by Tim B. Hunter and David G. Bragg, 624 pp, with illus, $180, ISBN 0-8016-6574-4, St Louis, Mo, Mosby, 1994. Written as a ready reference of medical miscellany,<i>Medical Devices, Abbreviations, Acronyms, and Eponyms (MDAAE)</i>attempts to provide a smallformat reference to the obscurities of medical language encountered in daily practice. This leads to one of the major drawbacks, that is, a bias toward radiological usage and practice. For instance, organizations such as ACR, AAWR, ABR, and AHRA are in the glossary, but not ACOG, ACS, AAOM, and others. Central venous pressure catheter placement is illustrated, but other devices, such as cardiac pacemakers and Ilizarov devices, are not. Acronyms are a linguistic nightmare, transient in meaning, narrow in usage, and the most specific form of jargon. Their seductive economy of expression leads to a code of sorts, understood only within a