tbuckley/cabot-search huggingface dataset:
Eosinophilic inflammation: mechanisms regulating IL‐5 transcription in human T lymphocytes
Authors: J. Wang, I. G. Young
Journal: Allergy (2007)

Interleukin (IL)-5 is a key regulator of eosinophilia in allergic inflammation and parasite infections but the mechanisms regulating IL-5 expression in activated human T lymphocytes are poorly understood. From studies on mouse cells, the activation protein (AP)-1 and GATA-3 sites in the proximal promoter region appear to be important in IL-5 regulation but the significance of an adjacent Ets/nuclear factor of activated T cell (NFAT) site has been less clear.Interleukin-5 transcriptional activity was measured by transfection of reporter genes into the human HSB-2 cells and normal T lymphocytes. Expression vectors encoding transcription factors were used for transactivation studies and IL-5 expression measured using reporter genes and mRNA levels. Transcription factor binding was shown with chromatin immunoprecipitation (ChIP).HSB-2 cells showed high inducible expression of IL-5 mRNA. Mutation of reporter gene plasmids showed the Ets/NFAT site was of equal importance to the AP-1 and GATA-3 sites in regulating IL-5 transcription. Transactivation by Ets1 increased luciferase expression 15-fold, in the absence of stimulation, and AP-1 (c-Fos/c-Jun) and GATA-3 gave transactivations of 85-fold, and 100-fold, respectively. Synergistic interactions were demonstrated between Ets1, GATA-3 and AP-1. Dominant-negative AP-1 inhibited IL-5 transcription. Transactivation by GATA-3 and synergy between GATA-3, Ets1 and AP-1 were verified measuring IL-5 mRNA levels. Chromatin immunoprecipitation showed increased binding of Ets1 and GATA-3 to the IL-5 promoter after stimulation. The importance of the Ets1 site and of synergistic interactions between the three transcription factors were verified with primary human T cells.Ets1, GATA-3 and AP-1 synergize to regulate IL-5 transcription in human T cells.
Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.
Authors: J L Mansi, U Berger, D Easton, T McDonnell, W H Redding, J C Gazet, A McKinna, T J Powles, R C Coombes
Journal: BMJ (1987)

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28 months. Seventy five patients relapsed, 60 at distant sites. Of these 60 patients, 26 had micrometastases detected at presentation and 34 were free of micrometastases initially. The relapse free interval was significantly shorter for patients with micrometastases, and these patients had a shorter survival. Analysis of the sites of relapse showed that the test predicted bone metastases only. Thus 10 out of 19 patients (53%) who developed bone metastases at first relapse had micrometastases at presentation compared with only 41 out of 288 patients (14%) who remained free of bone metastases or relapsed in non-skeletal sites. The presence of micrometastases detected at the time of initial surgery in a patient with primary breast cancer is a useful predictor of early relapse in bone and may help in selecting patients for subsequent systemic treatment.
Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis.
Authors: M Seitz, B Dewald, N Gerber, M Baggiolini
Journal: Journal of Clinical Investigation (1991)

Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor-containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture.
Survey of the long term incidence of osteonecrosis of the hip and adverse medical events in rheumatoid arthritis after high dose intravenous methylprednisolone.
Authors: I A Williams, A D Mitchell, W Rothman, P Tallett, K Williams, P Pitt
Journal: Annals of the Rheumatic Diseases (1988)

A prospective, randomised, double blind, matched cohort survey using retrospective data was undertaken to assess the long term incidence of osteonecrosis of the hip and adverse medical effects occurring after intravenous pulsed methylprednisolone used in the treatment of rheumatoid arthritis over the period 1977-86. One hundred and forty three patients were matched for age, sex, duration and severity of the disease, erosive and serological status. Information was obtained by direct questioning and from hip x rays, the latter being read independently by two 9blind9 radiologists. Two definite cases of osteonecrosis were identified, one in both the treated and control groups and three possible cases (radiological disagreement) in the treated group. Adverse medical events, when analysed by systems, were similar in both groups. This study did not provide evidence of increased osteonecrosis of the hip or adverse medical events in the treated group compared with the control group.
Limited-Stage Small-Cell Lung Cancer: The Current Status of Combined-Modality Therapy
Authors: Mark A. Socinski, Jeffrey A. Bogart
Journal: Journal of Clinical Oncology (2007)

Limited-stage (LS) small-cell lung cancer (SCLC) remains a therapeutic challenge to medical and radiation oncologists. The treatment of LS-SCLC has evolved significantly over the last two decades with combined-modality therapy now the standard of care. The addition of thoracic radiotherapy (TRT) to standard chemotherapy has led to improvements in long-term survival in this population. However, many questions remain about the optimal way to deliver chemoradiotherapy. In a landmark trial, twice-daily TRT to a dose of 45 Gy increased 5-year survival by 10% compared with once-daily TRT administered to the same dose. This suggests that more intensive TRT regimens may lead to further survival gains, assuming they can be delivered safely in this setting. Strategies currently under investigation include higher total daily doses delivered once daily or novel concurrent boost techniques allowing more intensive treatments over shorter periods of time. Several trials and meta-analyses have evaluated the timing of TRT with chemotherapy, with the weight of evidence suggesting that early and concurrent TRT with chemotherapy is optimal. Novel cytotoxic chemotherapy combinations have failed thus far to provide an advantage over standard etoposide-cisplatin combinations. Prophylactic cranial irradiation in near or complete responders to induction chemoradiotherapy has also been shown to improve long-term survival rates. LS-SCLC has been a model cancer in terms of the potential benefit of combined chemoradiotherapy strategies in improving patient outcomes.
Abstract 5593: Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers
Authors: Ryohei Katayama, Alice T. Shaw, Tahsin M. Khan, Mari Mino-Kenudson, Anthony J. Iafrate, Jeffrey A. Engelman
Journal: Cancer Research (2012)

Abstract ALK fusion oncogenes represent a novel molecular target in a small subset of non-small cell lung cancers (NSCLC). The vast majority of patients with ALK-positive NSCLC are highly responsive to ALK tyrosine kinase inhibitor (TKI) therapy. However, these patients invariably relapse, typically within one year, due to the development of resistance. Herein, we report findings from the first series of patients with acquired resistance to the ALK TKI crizotinib. In approximately one-third of patients, we identified a diverse array of secondary mutations distributed throughout the ALK TK domain. We also identified aberrant activation of other kinases as alternative mechanisms of crizotinib resistance. Additionally, we generated laboratory models of acquired crizotinib resistance which closely recapitulate the diversity of resistance mechanisms observed in patients. Our results highlight the marked heterogeneity of TKI resistance mechanisms in ALK-positive NSCLC, and provide the rationale for pursuing combinatorial therapeutic strategies in patients who relapse on crizotinib. 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 5593. doi:1538-7445.AM2012-5593
Saving children's lives by vaccination.
Authors: D. Morley
Journal: BMJ (1989)

In accordance with a World Health Assembly resolution of 1974, all children of the world are to be immunized by the year 1990. Thus was the origin of world wide Expanded Program for Immunization (EPI). Currently, this program prevents 2 million deaths from measles, pertussis and neonatal tetanus, and 1/4 a million deaths from paralytic poliomyelitis each year. Nevertheless, nearly 3 million children die, 200,000 are paralyzed and 150,000 are blinded by diseases which are preventable by immunization. Measles alone kills 1.6 million children each year and vaccination against it reduces child mortality by 30%. Added to the problems of maintaining an effective cold chain, and provision of managerial guidance for the distribution of vaccines, is the fact that measles vaccine can only be administered at 9 months age or older. However, current work on vaccines is focused on the development of a high titer of a more immunogenic measles vaccine which can be administered at 6 months of age. In spite of further potential for improvement in existing vaccinations and the development of new vaccines, resources are limited for such advancement. This limitation is partly due to misallocation of monetary resources, where priority is given to armament projects, instead of directing the funds to programs that save lives.
A Post-Graduate Address ON HEART AND AORTA STRAIN AND "LYING-DOWN HEART."
Authors: E. M. Brockbank
Journal: BMJ (1925)

I HAVVE chosen the subject of heart strain because which has to be considered by medical men at time under a variety of aspects, in our in compensation claims.As I think strain may occasionally enter into the question included it, and will give my reasons for so later stage. Definition.By lheart strain I mean the sudden subjective signs of cardiac muscle failure which attributed to some unusual muscular effort, the effort was one which ought not to have result in a healthy person.The chief subjective symptoms of heart are over the region of the heart or behind the sternum, like, or simulating, true angina pectoris, and breath on slight exertion.The objective some dilatation of the heart with extension of dullness left, signs of valvular disease, feeble sounds rhytlhm, and a quick pulse rate with manifest breath on slight effort.
The Treatment of Recurrent Corneal Erosions
Authors: George J. Wyman
Journal: JAMA (1965)

ABSTRACT To the Editor:— In the Nov 8 issue (194:688, 1965) a question was asked about recurrent corneal erosions. I agree completely with Dr. Charles I. Thomas' answer, but, I think the most effective treatment was not mentioned.In a case such as this, if a local anesthetic is instilled and all the loose epithelium removed with a cotton applicator, followed by binocular bandaging for 48 hours, practically every one of these patients will be relieved permanently. I usually moisten the applicator with 1% tincture of iodine. I have never seen a bad result from this therapy and these eye cripples are returned to normality without the frequent recurrences that are otherwise common.
Ensuring Access to Health Care
Authors: John Kerry
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Role of Exercise Stress Testing and Safety Monitoring for Older Persons Starting an Exercise Program
Authors: Thomas M. Gill
Journal: JAMA (2000)

While the benefits of physical activity and exercise among older persons are becoming increasingly clear, the role of exercise stress testing and safety monitoring for older persons who want to start an exercise program is unclear. Current guidelines regarding exercise stress testing likely are not applicable to the majority of persons aged 75 years or older who are interested in restoring or enhancing their physical function through a program of physical activity and exercise. In addition to being expensive and of unproven benefit, the current policy of routine exercise stress testing potentially could deter many older persons from participating in an exercise program. Research is needed to investigate current physician practices, evaluate the risk of adverse cardiac events, determine the role of pharmacological stress testing, and measure and compare absolute and relative exercise intensities. To assist clinicians, we offer a set of recommendations regarding precautions that can be taken to minimize the risk of adverse cardiac events among previously sedentary older persons who do not have symptomatic cardiovascular disease and are interested in starting an exercise program. JAMA. 2000;284:342-349
EARLY REFERENCES TO PHYSICAL ALLERGY
Authors: Samuel M. Feinberg
Journal: JAMA (1934)

<h3>To the Editor.—</h3> Under current comment, September 29, you discussed the importance of physical allergy and mentioned a few old references. Although you make no claim that these are the oldest references on the subject, Dr. Richard L. Sutton Jr. in a communication, October 27, corrects you with the statement that earlier reports of physical allergy are available and he cites articles published in 1883, 1881 and 1875. The references which Dr. Sutton cites are still not the oldest. For example, Blachez (<i>Bull. Soc. méd. d. hôp. de Paris</i><b>3</b>:262, 1872) recounts an instance of angioneurotic swellings due to exposure to cold water and to cold air or to the eating of ice. Behier (<i>ibid.</i><b>3</b>:262, 1866) describes his own case of urticaria brought on by cold water. Bourdon (<i>ibid.</i><b>3</b>:259, 1866) tells of asthma due to cold.
Regional deposition of nebulized hypodense nonisotonic solutions in the human respiratory tract
Authors: HK Chan, PR Phipps, I Gonda, P Cook, R Fulton, I Young, G Bautovich
Journal: European Respiratory Journal (1994)

Deposition of nonisotonic therapeutic and diagnosis aerosols can cause changes in airway fluid composition and bronchoconstriction in sensitive subjects. "Hypodense" aerosols containing a relatively low concentration of droplets in the carrier air were used in the studies of regional deposition of radiolabelled nebulized solutions of hypo- and hypertonic saline, in order to investigate whether the number of droplets per volume of carrier can affect deposition. Solutions with and without 0.5% nedocromil sodium were nebulized in order to examine the effects of a potential modifier of the rates of heat and mass transfer. The deposition was quantified using penetration index (PI) calculated from images obtained by single photon emission computerized tomography (SPECT) in 11 healthy volunteers per study. There was an increase in the penetration index (10.9%, for the saline only; 15.5%, for the nedocromil study) of the hypotonic compared to the hypertonic aerosol, although the initial size distribution of both types of aerosols was very similar (mass median aerodynamic diameter (MMAD) 3.7 and 3.8 microns; geometric standard deviation (GSD) 1.8 and 1.5 for the hypo- and hypertonic aerosols, respectively). The present results confirm the effects of tonicity on deposition of aerosols found in a parallel study reported in this issue of the Journal. They also give support to the theory that, in addition to the concentration of the nebulized solutions, the number of droplets per volume of the carrier air is a factor affecting deposition of aqueous aerosols. The presence of 0.5% nedocromil sodium in the solutions did not appear to interfere with the processes of heat and water transfer in the airways.
Comparison of cholesterol and beta-sitosterol: effects on jejunal fluid secretion induced by oleate, and absorption from mixed micellar solutions.
Authors: T Slota, N A Kozlov, H V Ammon
Journal: Gut (1983)

Jejunal fluid secretion induced by perfusion with oleic acid can be reduced by the addition of cholesterol. The present study was performed to test the specificity of this effect by comparing the effects of cholesterol with that of a plant sterol, beta-sitosterol during perfusion of the jejunum in healthy volunteers. In addition, we compared the solubilities of cholesterol and beta-sitosterol in micellar solutions and their jejunal absorption rates. One millimolar beta-sitosterol was as effective as 1 mM cholesterol in reducing jejunal fluid secretion induced by 6 mM oleate (n = 7). In mixed micellar solutions consisting of 10 mM taurocholate and 6 mM oleate, solubility of beta-sitosterol is about one third of cholesterol solubility. When cholesterol was gradually replaced by beta-sitosterol in the incubation mixture, beta-sitosterol reduced cholesterol solubility to a greater extent than would be expected from an equimolar replacement of cholesterol by beta-sitosterol. Absorption of beta-sitosterol was limited by its solubility in mixed micellar solutions and both sterols were absorbed at equal rates as long as their solubility limits were not exceeded (n = 5).
Treatment of Patients
Authors: W. A. Bellamy
Journal: BMJ (1947)

Facelifts, tummy tucks and breast enlargements are no longer the privilege of the rich and the famous. Any woman can have all these and many more cosmetic surgical treatments, and an increasing number of women do. Are they having cosmetic surgery because they are duped by a male-dominated beauty system, or do they genuinely choose these operations themselves? Feminists (and others) give diametrically opposed answers to this question. At the heart of the controversy, or so I claim in this article, lies a conceptual problem about free choice; therefore, the only thing that can settle it is a conceptual analysis of “freedom”. After having briefly outlined the views of both sides of the debate, I offer such an analysis.
Spheroid formation of human thyroid cancer cells in an automated culturing system during the Shenzhou-8 Space mission
Authors: Jessica Pietsch, Xiao Ma, Markus Wehland, Ganna Aleshcheva, Achim Schwarzwälder, Jürgen Segerer, Maria Birlem, Astrid Horn, Johann Bauer, Manfred Infanger, Daniela Grimm
Journal: Biomaterials (2013)
Radiation Hazards from Hemodialysis Patients
Authors: STEVEN J. ROSANSKY
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 December 1985Radiation Hazards from Hemodialysis PatientsSTEVEN J. ROSANSKY, M.D., NICKOLAS A. DETORIE, Ph.D.STEVEN J. ROSANSKY, M.D.Search for more papers by this author, NICKOLAS A. DETORIE, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-6-961_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In a recent issue, the occupational hazards to hospital personnel were described, including the effects of radiation exposure (1). To our knowledge, the potential hazards from the "radioactive" patient to the hemodialysis personnel and to subsequent patients using the same hemodialysis machine have not been well described.Recently, a patient with acute renal failure (estimated glomerular filtration rate, 5 mL/min) had received 300 µCi of131I-iodohippurate before dialysis. To ascertain the extent of radiation hazard, we sampled the patient's arterial and venous blood every 30 minutes during dialysis. These blood samples were then measured for131I activity...Reference1. PATTERSON W, CRAVEN D, SCHWARTZ D, NARDELL E, KASMER J, and NOBLE J. Occupational hazards to hospital personnel. Ann Intern Med. 1985;102:658-80. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: STEVEN J. ROSANSKY, M.D.; NICKOLAS A. DETORIE, Ph.D.Affiliations: University of South Carolina School of Medicine Columbia, SC 29201 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRadiation Exposure from Radionuclide Use in Dialysis Patients 1 December 1985Volume 103, Issue 6_Part_1Page: 961-961KeywordsAcute renal failureBloodEstimated glomerular filtration rateMedical dialysisRadiation exposure ePublished: 1 December 2008 Issue Published: 1 December 1985 PDF downloadLoading ...