tbuckley/cabot-search huggingface dataset:
Abstract 508: Signal transduction and activator of transcription (STAT) 3 is necessary for environment-mediated drug resistance
Authors: Tasnim Ara, Rie Nakata, Hiroyuki Shimada, Ralf Buettner, Robert C. Seeger, Hua Yu, Richard Jove, Yves A. DeClerck
Journal: Cancer Research (2011)

Abstract There is recent evidence that STAT3 plays a pivotal and central role in controlling inflammatory pathways that promote malignant transformation and progression, including the ability of tumor cells to escape drug-induced apoptosis. Using neuroblastoma as a model, our laboratory had previously demonstrated that bone marrow mesenchymal stem cells through their production of interleukin-6 are a source of environment-mediated drug resistance. Here we have examined the role of STAT3, a downstream target of IL-6, in this effect. We first demonstrate that in contrast to many other cancers, STAT3 is not constitutively active in most neuroblastoma cells. However, it is rapidly phosphorylated after 15 minutes of exposure to IL-6 and its soluble receptor (sIL6-R). Activation of STAT3 is associated with its nuclear translocation and DNA binding. Treatment of CHLA-255 and SK-N-SH neuroblastoma cells with IL-6 increases their resistance to Etoposide and Melphalan in a dose-dependent manner. IL-6 inhibits the release of cytochrome C from the mitochondria and upregulates several pro-survival factors like Bcl-XL, XIAP and survivin without affecting the expression of Bax and Bad. The protective effect of IL-6 on drug-induced apoptosis is significantly inhibited in the presence of the STAT3 inhibitor Stattic (2.5 μM) or upon downregulation of STAT3 by siRNA, indicating that STAT3 is necessary for drug resistance. We also show that sIL-6R, produced by monocytes, enhances STAT3 activation and promotes drug resistance. In vivo, IL-6 and sIL-6R increase STAT3 activation in CHLA-255 neuroblastoma cells and their proliferation. Finally we observed elevated expression of phosphoSTAT3 in bone marrow samples of patients with metastatic neuroblastoma cells. Altogether, the data demonstrate that in neuroblastoma STAT3 activation by IL-6 in the tumor microenvironment plays a key role in environment-mediated drug resistance. 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 508. doi:10.1158/1538-7445.AM2011-508
Release the Hounds! Activating the T-Cell Response to Cancer
Authors: Mario Sznol, Dan L. Longo
Journal: New England Journal of Medicine (2014)

Among the many subterfuges that cancer cells deploy to limit detection by host immune defenses, activation of so-called immune checkpoints is one that may be exploitable in activating a counterattack. Many complex multicellular regulatory events are involved in keeping the immune system from overreacting to a stimulus or mistaking a component of oneself for a dangerous invader. One such event that regulates inflammatory responses in the tissues involves the programmed death 1 (PD-1) pathway. One or both of the PD-1 ligands, PD-L1 and PD-L2, which are expressed on cells in the tissues, bind to PD-1 receptors on T cells and . . .
Case 23-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, D.H. Spodick, J.F. Southern
Journal: New England Journal of Medicine (1992)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 23-1992 — A 55-Year-Old Man with Recurrent Pericardial and Pleural Effusions after Aortic-Valve Replacement
JOURNALISM DEVOTED TO THE PROMOTION AND CONCENTRATION OF MEDICAL AND SURGICAL SCIENCE.
Authors: Henry O. Marcy
Journal: JAMA (1883)

Read to the American Association of Medical Editors, June 5th, 1883. It is scarcely more than two decades since the late surgeon George A. Otis, whose great work, “The Surgical History of the War of the Rebellion,” has won for its author imperishable honor, advised us as his pupil even at the beginning of medical study, to devote a certain portion of each day in the discharge of the duties of curator of a natural history collection. This he did with the statement that the medical man needed a side issue for his superfluous energies. The late Dr. A. A. Gould, of Boston, who was one of the wisest clinical instructors, it has been our fortune tune to meet and ever in demand at the bed-side of the rich and the poor alike, found time in the midst of his busy career to give attention to natural science, with certain
Invited commentary: Commentary on Viewpoint article by A H Henderson, M J Lewis, A M Shah, and J A Smith (April, pages 305-8)
Authors: R. M J PALMER, R. E A SMITH
Journal: Cardiovascular Research (1992)

Journal Article Invited commentary: Commentary on Viewpoint article by A H Henderson, M J Lewis, A M Shah, and J A Smith (April, pages 305-8) Get access RICHARD M J PALMER, RICHARD M J PALMER Search for other works by this author on: Oxford Academic PubMed Google Scholar RUSSELL E A SMITH RUSSELL E A SMITH Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 6, June 1992, Page 638, https://doi.org/10.1093/cvr/26.6.638 Published: 01 June 1992
Abstract 2880: Dasatinib induces apoptosis in head and neck squamous cell carcinoma cells through down-regulation of epidermal growth factor receptor (EGFR) <i>in vitro</i> and <i>in vivo</i>
Authors: Yu-Chin Lin, Meng-Hsuan Wu, Tzu-Tang Wei, Shu-Hui Chung, Kuen-Feng Chen, Ann-Lii Cheng, Ching-Chow Chen
Journal: Cancer Research (2012)

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is a worldwide disease with aggressive course and dismal outcome. Dasatinib, a bcr-abl inhibitor, has been approved clinically for the treatment of chronic myeloid leukemia and demonstrated to be effective against solid tumors in vitro through Src inhibition. Here, we disclose that dasatinib induced apoptosis of HNSCC cells in vitro and in vivo through down-regulation of EGFR. Methods: HNSCC cells, including Ca9-22, FaDu, HSC3, SAS, SCC-25, and UMSCC1 were treated with dasatinib. Cell viability, apoptosis, and underlying signal transduction were evaluated. Results: Dasatinib exhibited differential sensitivities against HNSCC cells. The growth inhibition and apoptosis were correlated with its inhibition on Akt, Erk, and bcl-2, but irrespective of Src inhibition. Accordingly, we found that down-regulation of epidermal growth factor receptor (EGFR) was a determinant of dasatinib sensitivity. Dasatinib inhibited EGFR through lysosome degradation. Increased EGFR activation by ligand administration rescued cells from dasatinib-induced apoptosis, whereas inhibition of EGFR enhanced its apoptotic effect. Estrogen receptor (ER) was demonstrated to play a role in bcl-2 expression, and dasatinib inhibited ER at pre-translational level. ER worked in concert with EGFR to regulate dasatinib-induced apoptosis. Furthermore, xenograft model showed that dasatinib inhibited HSC3 tumor growth through in vivo down-regulation of EGFR and ER. Conclusion: Down-regulation of EGFR is a novel mechanism responsible for dasatinib-induced apoptosis in HNSCC. 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 2880. doi:1538-7445.AM2012-2880
Immunostimulatory Sequences Regulate Interferon-inducible Genes but not Allergic Airway Responses
Authors: Gail M. Gauvreau, Edith M. Hessel, Louis-Philippe Boulet, Robert L. Coffman, Paul M. O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

1018 ISS is a synthetic oligonucleotide containing immunostimulatory CpG motifs. In animal studies, 1018 ISS effectively inhibited Th2-mediated lung inflammation, including eosinophil infiltration, and airway hyperresponsiveness.To evaluate whether 1018 ISS has activity in subjects with allergic asthma.Forty subjects (n = 21, 1018 ISS; n = 19, placebo) were enrolled in a randomized, double-blind, placebo-controlled, parallel-group study to examine safety, pharmacologic activity, and efficacy of 1018 ISS on allergen-induced airway responses. Subjects received 36 mg of 1018 ISS or placebo by nebulization weekly for 4 wk.Allergen inhalation challenge was performed 24 h after the 2nd and 4th doses to measure the early and late fall in FEV(1). Sputum cells and peripheral blood mononuclear cells were collected before and after dosing, and gene expression was measured by quantitative polymerase chain reaction.Treatment with 1018 ISS significantly increased expression of interferon (IFN)-gamma and IFN-inducible genes, such as IFN-gamma-inducible 10 kD protein (IP10), monokine induced by IFN-gamma (MIG), IFN-stimulated gene (ISG)-54, monocyte chemotactic protein (MCP)-1, and MCP-2 from cells collected postdose (p < 0.05). There was no attenuation of the early or late decrease in FEV(1) after 1018 ISS compared with placebo, nor a reduction in allergen-induced sputum eosinophils or Th2-related gene expression measured in sputum cells.This study demonstrated that 1018 ISS is safe and pharmacologically active in the respiratory tract of asthmatics but, at this dose regimen, did not inhibit a fall in FEV(1) or other key features of the response to inhaled allergen challenge. This suggests that induction of IFN and IFN-inducible genes alone is not sufficient to inhibit allergen-induced responses in asthmatic subjects.
Minor histocompatibility antigen-specific T cells with multiple distinct specificities can be isolated by direct cloning of IFNγ-secreting T cells from patients with relapsed leukemia responding to donor lymphocyte infusion
Authors: F M Kloosterboer, S A P van Luxemburg-Heijs, R A van Soest, H M van Egmond, A M Barbui, M P W Strijbosch, R Willemze, J H F Falkenburg
Journal: Leukemia (2004)
Laparoscopic Microwave Coagulation Therapy for Hepatocellular Carcinoma
Authors: None Seki, None Sakaguchi, None Kadoya, None Morikawa, None Habu, None Nishiguchi, None Shiomi, None Kitada, None Kuroki
Journal: Endoscopy (2000)

Background and Study Aims: Several different effective forms of treatment are available, singly or in combination, for patients with hepatocellular carcinoma (HCC). These include surgical resection, transcatheter arterial embolization, percutaneous ethanol injection, and percutaneous microwave coagulation therapy. In this study, we carried out laparoscopic microwave coagulation therapy (LMCT), using laparoscopic microwave electrodes to treat HCC.
Teaching Medicine as a Human Experience: A Patient-Doctor Relationship Course for Faculty and First-Year Medical Students
Authors: William T. Branch, Ronald A. Arky, Beverly Woo, John D. Stoeckle, Donald B. Levy, William C. Taylor
Journal: Annals of Internal Medicine (1991)

We developed a required, longitudinal course for first-year medical students that addressed the patient-doctor relationship. Our course linked understanding patients' experiences and perspectives on illness with listening to, talking with, and establishing a rapport with patients while obtaining their medical histories. Learning was enhanced by use of an interdisciplinary faculty and by small-group continuity and faculty mentoring. Our curriculum adapted problem-based, self-directed educational methods to convey medical humanism. We focused on bedside interviewing as the means for exploring patients' social, emotional, and ethical concerns.
A STUDY OF THE MECHANISM OF RECOVERY FROM EXPERIMENTAL PNEUMOCOCCUS INFECTION
Authors: Oswald H. Robertson, Shutai T. Woo, Sheo Nan Cheer, Li Pin King
Journal: The Journal of Experimental Medicine (1928)

A study was made of the blood of cats and rabbits during experimental pneumococcus infection with a view to ascertaining the relationship of acquired immune properties to the mechanism of recovery. Observations were directed chiefly towards the detection of pneumococcidal promoting substances, but the other manifestations of anti-pneumococcus reaction were studied as well. It was found constantly that the serum of animals recovering from infection possessed the power to promote the destruction of highly virulent pneumococci in rabbit serum-leucocyte mixtures which mixtures of themselves have no growth inhibitory action. Furthermore, the presence of this serum immunity was associated with a marked increase in acquired resistance to the pneumococcus. In cats which were studied in the most detail the pneumococcidal promoting power of the serum as well as the opsonic, agglutinative, and mouse protective activities became demonstrable at the time of recovery and their appearance in the serum always marked the termination of blood invasion. These immune reactions were found to be type-specific. The animals which succumbed failed to develop detectable serum immune properties and showed persistent blood invasion. The degree of leucocytosis did not appear to bear any constant relation to the outcome of the disease. The significance of these findings is discussed.
Five Cases of So-Called Blackwater Fever
Authors: H. M. Dowler
Journal: BMJ (1899)

LJULY I5, .i899.ally ceased to cry and toss about, lher expressionl was one of extreme relief, and before I had finished she was sound asleep.Slhe slept sounldly for two lhours, and there was no return of the symptoms on waking.In the mornling the temperature was normal.She was kept in bed for three days and under observation till August izth, and had no return of the fever.The arsenic and quinine mixture wliclh she had been taking before were continued.CASE x.-A.1I., aged 31, was sufferinor from malarial fever aggravated by neglect and exposure to the sun.Tier mother stated that she was subject to ague, and had had fever for two days.She had not been kept in bed, and she would not take any medicine.I was called in at ii P.M. on August 26th, I896, and found the child quite delirious.The tempera- ture taken in the groin was x05.40 F., but probably nearer 1070 in the mouth.I rubbed in inxx of creosote at once and the effect was almost instantaneous; the delirium ceased rapidly, she became conscious, then was very irritable for a few minutes, and in a few minutes more was quite comfortable and quiet.In half an hour the temperature had fallen 3 degrees.She slept soundly for two hours, and fairly well for the rest of the night.On August 27th, z896, at 7 A.M. the temper-ature was ooo0 F., but rose to 1050 at IO A.M., with internal strabismus and commencing convul- sions.The inunction of creosote (inxx) repeated gave immediate relief.Some creosote and oil were prescribed inl mxx doses.to be rubbed in if the temperature rose again over 2030, but the mother, becoming impatient, rubbed it in five or six times in the course of the next twenty-four hours.This indiscretion, however, was followed by no bad results.The tempera- ture fell to normal on the morning of August 29th, without,any other treament.There was no recurrence.
Genome-Wide Association Study of Short-Acting β<sub>2</sub>-Agonists. A Novel Genome-Wide Significant Locus on Chromosome 2 near <i>ASB3</i>
Authors: Elliot Israel, Jessica Lasky-Su, Amy Markezich, Amy Damask, Stanley J. Szefler, Brooke Schuemann, Barbara Klanderman, Jody Sylvia, Shamsah Kazani, Rongling Wu, Fernando Martinez, Homer A. Boushey, Vernon M. Chinchilli, Dave Mauger, Scott T. Weiss, Kelan G. Tantisira
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

β2-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable.To investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma.We performed a GWAS of acute bronchodilator response (BDR) to inhaled β2-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top 50 SNPs were carried forward to replication in a population of 444 individuals.The combined P value for four SNPs reached statistical genome-wide significance aftercorrecting for multiple comparisons. Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2.21 × 10(-10), 5.75 × 10(-8), 9.3 × 10(-8), and 3.95 × 10(-8), respectively. The significant variants all map to a novel genetic region on chromosome 2 near the ASB3 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population.These GWAS findings for BDR in subjects with asthma suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in asthma.
Thrombolysis in acute stroke
Authors: J. Bogousslavsky
Journal: BMJ (1996)

enough to have adequate statistical power: more than 1200 patients had to be identified over three years to obtain 620 who were able and willing to participate.The infusion protocol may also have helped to control plasma glucose more rapidly than protocols used in previous studies."4What relevance might the findings have to people without a history of diabetes who present with myocardial infarction and a plasma glucose concentration at admission of 8-11 mmol/l?There is evidence that mortality in hospital is increased in this group even when patients with a previous diagnosis of diabetes are excluded.4 17During the 1960s and 1970s, combined infusions of glucose, insulin, and potassium were widely used in the acute management of myocardial infarction even in non-diabetic patients, especially in Italy.In a small randomised study, this seemed to increase ejection fraction and to reduce pulmonary artery end diastolic pressure.'8Despite the wide confidence intervals for the size of effect, the Swedish trial is impressive evidence that rigorous control of plasma glucose by insulin infusion improves the long term outcome of myocardial infarction for patients with established diabetes or plasma glucose concentration greater than 11 mmol/l on admission.The possibility that glucose and insulin infusions could benefit patients with lesser degrees of hyperglycaemia is one worth investigating in future trials.
Osteoma of the Superior Maxilla: Epithelioma of the Tongue
Authors: H. T. Dreschfeld
Journal: BMJ (1894)

In conclusion, I beg to suggrest that the phase of disease pre- sented in this case, from its mode of evolution and subsequent behaviour-especially under treatment, and from its, general symptoms-indicates:1.An inflammatory process or dermatitis simulating psoriasis.2. That it owes its origin to the seborrhleic conditions of the ekin, especially the head.3. That it is DrobablV parasitic.
A simple multistage field test for the prediction of anaerobic capacity in female games players
Authors: S-M Cooper, J S Baker, Z E Eaton, N Matthews
Journal: British Journal of Sports Medicine (2004)

Objective: To establish the validity of a 15 m multistage shuttle run test (MSRT) as a predictor of anaerobic capacity (expressed as mean power output (MPO) from the 30 second Wingate anaerobic test (WAnT)) in female university standard games players. Methods: Data came from three phases using a total of 72 players (mean (SD) age 20.3 (1.5) years, body mass 64.9 (8.8) kg, and stature 1.67 (0.04) m). The repeatability of the MSRT was assessed in phase 1 by applying 95% limits of agreement (LoA) to the test and retest results from a random sample of 20 players. In phase 2, linear relations between MPO and performance on the MSRT were investigated in a random sample of 36 players. As a result, a calibration model (Y = a + bX) was developed and cross validated in phase 3, in which the remaining 36 players performed both the WAnT and the MSRT. Time (seconds) to volitional exhaustion/disqualification from the MSRT was substituted into the calibration model from which MPO was predicted. The agreement between MPO predicted and MPO measured from the WAnT was quantified using LoA. Results: Insignificant bias between repeat applications of the MSRT (mean diff (SD diff ) = 1.0 (3.5) seconds (4 (14) m), t = 1.23, p = 0.230) was found from phase 1. Data were homoscedastic ( r = 0.061, p = 0.799) with LoA ± 6.9 seconds (± 27 m). In phase 2 the strongest correlation was between MPO (W/kg 0.67 ) and time to volitional exhaustion/disqualification on the MSRT; r = 0.715 ( r 2 = 51.1%, p = 0.0005). As a result, the calibration model developed was: MPO (W/kg 0.67 ) = 12.5 + (0.2 × time (seconds)) with a standard error of prediction of 2.1 W/kg 0.67 . The cross validation in phase 3 showed insignificant bias between measured and predicted MPO (mean diff (SD diff ) = 0.3 (2.8) W/kg 0.67 , t = 0.75, p = 0.460). Data were homoscedastic ( r = 0.05, p = 0.774) with LoA ± 5.5 W/kg 0.67 . Conclusions: The MSRT requires minimal equipment and training of assessors, and it is easy to perform. In the population studied, it provides scores that are repeatable, and anaerobic capacity (MPO) can be successfully predicted from its performance. It would seem therefore to be a useful field based test for use by female games players, their coaches, and support scientists.