tbuckley/cabot-search huggingface dataset:
A Three-Gene Assay for Monitoring Immune Quiescence in Kidney Transplantation
Authors: Silke Roedder, Li Li, Michael N. Alonso, Szu-Chuan Hsieh, Minh Thien Vu, Hong Dai, Tara K. Sigdel, Ian Bostock, Camila Macedo, Diana Metes, Adrianna Zeevi, Ron Shapiro, Oscar Salvatierra, John Scandling, Josefina Alberu, Edgar Engleman, Minnie M. Sarwal
Journal: Journal of the American Society of Nephrology (2014)

Organ transplant recipients face life-long immunosuppression and consequently are at high risk of comorbidities. Occasionally, kidney transplant recipients develop a state of targeted immune quiescence (operational tolerance) against an HLA-mismatched graft, allowing them to withdraw all immunosuppression and retain stable graft function while resuming immune responses to third-party antigens. Methods to better understand and monitor this state of alloimmune quiescence by transcriptional profiling may reveal a gene signature that identifies patients for whom immunosuppression could be titrated to reduce patient and graft morbidities. Therefore, we investigated 571 unique peripheral blood samples from 348 HLA-mismatched renal transplant recipients and 101 nontransplant controls in a four-stage study including microarray, quantitative PCR, and flow cytometry analyses. We report a refined and highly validated (area under the curve, 0.95; 95% confidence interval, 0.92 to 0.97) peripheral blood three-gene assay (KLF6, BNC2, CYP1B1) to detect the state of operational tolerance by quantitative PCR. The frequency of predicted alloimmune quiescence in stable renal transplant patients receiving long-term immunosuppression (n=150) was 7.3% by the three-gene assay. Targeted cell sorting of peripheral blood from operationally tolerant patients showed a significant shift in the ratio of circulating monocyte-derived dendritic cells with significantly different expression of the genes constituting the three-gene assay. Our results suggest that incorporation of patient screening by specific cellular and gene expression assays may support the safety of drug minimization trials and protocols.
THE AREA UNDER THE STRAIN CURVE PROVIDES EARLY PREDICTION OF INFARCT SIZE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Bjørnar Grenne, Christian Eek, Benthe Sjøli, Thomas Dahlslett, Per K. Hol, Stein Ørn, Helge Skulstad, Otto A. Smiseth, Thor Edvardsen, Harald Brunvand
Journal: Journal of the American College of Cardiology (2011)
Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila.
Authors: T F Byrd, M A Horwitz
Journal: Journal of Clinical Investigation (1991)

We have been exploring the role of iron in the pathogenesis of the intracellular bacterial pathogen Legionella pneumophila. In previous studies, we have demonstrated that L. pneumophila intracellular multiplication in human monocytes is iron dependent and that IFN gamma-activated monocytes inhibit L. pneumophila intracellular multiplication by limiting the availability of iron. In this study, we have investigated the effect on L. pneumophila intracellular multiplication of lactoferrin, an iron-binding protein which is internalized via specific receptors on monocytes, and of nonphysiologic iron chelates which enter monocytes by a receptor-independent route. Apolactoferrin completely inhibited L. pneumophila multiplication in nonactivated monocytes, and enhanced the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication. In contrast, iron-saturated lactoferrin had no effect on the already rapid rate of L. pneumophila multiplication in nonactivated monocytes. Moreover, it reversed the capacity of activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron from the lactoferrin-lactoferrin receptor pathway. The capacity of iron-lactoferrin to reverse monocyte activation was dependent upon its percent iron saturation and not just its total iron content. Similarly, the nonphysiologic iron chelates ferric nitrilotriacetate and ferric ammonium citrate completely reverse and ferric pyrophosphate partially reversed the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron derived from nonphysiologic iron chelates internalized by monocytes independently of the transferrin and lactoferrin endocytic pathways. This study suggests that at sites of inflammation, lactoferrin may inhibit or promote L. pneumophila intracellular multiplication in mononuclear phagocytes depending upon its degree of iron saturation. In addition, this study suggests a potential role for PMN in host defense against L. pneumophila--providing apolactoferrin to infected monocytes--and it supports the concept that PMN and monocytes may cooperate in host defense against intracellular parasites and other pathogens.
Comparative proteome profile during the early period of small-for-size liver transplantation in rats revealed the protective role of Prdx5
Authors: Jindao Wu, Qiyun Tang, Jian Shen, Aihua Yao, Fuqiang Wang, Liyong Pu, Yue Yu, Xiangcheng Li, Guoqiang Li, Feng Zhang, Beicheng Sun, Lianbao Kong, Donghua Li, Yewei Zhang, Xuejiang Guo, Xuehao Wang
Journal: Journal of Hepatology (2010)
Surveillance of Antibiotic Prescribing in Office Practice
Authors: WILLIAM SCHAFFNER
Journal: Annals of Internal Medicine (1978)

Using fiscal and administrative data routinely collected by the Tennessee Medicaid program, we conducted epidemiologic analyses of physicians' prescribing of selected antibiotics in office practice. This research has defined several subgroups of physicians who regularly malprescribed chloramphenicol or tetracyclines (to children less than 8 years old). After special educational mailings to all physicians, prescribing of these antimicrobial drugs diminished. Similar analyses could enable the profession to design specific remedial educational interventions, target them at physicians needing contemporary information, and assess their impact by monitoring subsequent prescribing. Such a program might diminish inappropriate drug use, reduce adverse drug reactions, help contain medical care costs, and produce better educated physicians.
The Diffuse Vascular Lesion of So-Called "Thrombotic Thrombocytopenic Purpura"
Authors: HAROLD W. MARCH
Journal: Circulation (1954)

"Thrombotic thrombocytopenic purpura" is a thrombocytopenic, hemolytic disease with occlusive mounds in the arterioles and capillaries. These mounds have been popularly supposed to represent bland platelet thrombi. In recent years observations have been forthcoming in favor of a primary vascular lesion as the anatomic basis of the disease. This paper places special emphasis on the latter proposition, and pathologic material is presented to demonstrate how such a lesion probably evolves.
Government will not back down over free personal care for all elderly people
Authors: Madeleine Brettingham
Journal: BMJ (2005)

The UK's minister for community care, Stephen Ladyman, has insisted that the government will not extend free personal care to all elderly people in England and Wales. The remarks were made at a meeting of the House of Commons select committee on health, as part of its investigation into the current state of continuing care in the NHS.

Dr Ladyman said that people demanding a move towards the Scottish system, which provides subsidised places in nursing homes and free personal care for everyone aged over 65, as recommended for all elderly people by the Royal Commission on Long Term Care ( BMJ 2000;321:317), were guilty of a “callous misinterpretation of …
Creatine kinase release not associated with myocardial necrosis after short periods of coronary artery occlusion in conscious baboons
Authors: Guy R. Heyndrickx, Jun Amano, Twila Kenna, John T. Fallon, Thomas A. Patrick, W. Thomas Manders, Geoffrey G. Rogers, Clive Rosendorff, Stephen F. Vatner
Journal: Journal of the American College of Cardiology (1985)
Graduate entry programmes in medicine
Authors: Linda Hutchinson, Patricia Hughes, Peter McCrorie
Journal: BMJ (2002)

There are currently four graduate entry schemes into UK medical school based at Oxford, Cambridge, Leicester and Warwick, and St George9s Hospital, London. Career focus asked pioneers of the scheme at St George9s--<b>Linda Hutchinson</b>, <b>Patricia Hughes</b>, and <b>Peter McCrorie</b>--discuss their experience
Sex hormones and skin collagen content in postmenopausal women.
Authors: M Brincat, C F Moniz, J W Studd, A J Darby, A Magos, D Cooper
Journal: BMJ (1983)

Skin biopsy specimens were taken from 29 postmenopausal women who had not been given hormone replacement therapy and from 26 women who had been treated with oestrogen and testosterone implants for two to 10 years. The mean hydroxyproline content and therefore the mean collagen content in the skin was found to be 48% greater in the treated than the untreated women, who were matched for age. This difference was significant (p less than 0.01). The implication of this finding is that oestrogen or testosterone, or both, prevents the decrease in skin collagen content that occurs with aging and protects skin in the same way as it protects bone in postmenopausal women.
False-negative Results in Brain Scanning
Authors: E. H. Burrows
Journal: BMJ (1972)

There were 118 false-negative results in a series of 847 cases of proved intracranial lesions subjected to brain scanning. In patients with neoplasms false-negative results are much more likely if the site of the tumour is infratentorial or mediobasal. In patients with stroke the incidence of false-negative results depends on the stroke-scan interval.
THE TREATMENT OF CHRONIC DUODENAL ULCER
Authors: E. C. Hort
Journal: BMJ (1910)

ULCERS[JAN. 8, 1I9IO.glands, and 1 probably originated in the ducts; 4 were ductearcinomata; 1 duct papilloma; 2 acinous carcinoma; 1 adeno-carcinoma, and 1 was returned as sarcoma by one pathologist and carcinoma by another; 1 was colloid.In conclusion, my thanks are due to the medical men under whose care the patients have been, and to Mr. A. T. Longbotham, the Superintendent Registrar of Births and Deaths, without whose help I should not have been able to trace as many of the cases as I have done.REFERENCE.
Medical and Nursing Education and Training Opportunities to Improve Survivorship Care
Authors: Betty R. Ferrell, Rodger Winn
Journal: Journal of Clinical Oncology (2006)

Improving the quality of care for cancer survivors is contingent on having physicians, nurses, and other professionals with adequate training in survivorship care. Previous literature has documented the deficiencies in existing formal education programs regarding the complex needs of this growing population. Continuing education programs and basic curricula need to incorporate the expanding body of knowledge regarding the physiologic and psychosocial sequelae of survivorship. This article reviews the current status of survivorship education and provides direction for essential content in future education. Topics such as prevention of secondary cancers, long-term complications, rehabilitation services, quality-of-life issues, pain and symptom management, and treatment of recurrent cancer are critical competencies of education that should then become routine care for cancer survivors.
Swallowed dental reamer.
Authors: G. D. Vinden
Journal: BMJ (1968)

themselves to logical interpretation.Rather they perpetuate the need for empirical rules in interpretation.The electrocardiogram is recorded in two planes, the frontal and transverse.The frontal plane includes the six limb leads.There is disagreement about precise reference of these leads to the heart.Earlier hexaxial reference systems were based on an absolute acceptance of Einthoven's theories.It is now thought that these theories may not be accu- rate, and a corrected reference system has been introduced.! Whatever the theoretical considerations, in practice these six limb leads may be represented as viewing the heart from a series of approximate positions in the frontal plane.Uhley and Rosenblum' consider that it would be logical to display the limb leads in the order aVR, aVL, I, II, aVF, III.The chest leads describe an arc in the transverse plane.The two planes coincide in the area of V6, so that V. could also be included with the frontal plane leads.V. is usually intermediate in pattern between leads I and II, as would be expected from their points of reference.Thus the two planes may be combined in displaying the electro- cardiogram (see Fig.).When mounted in this way there is a gradual change of pattern from aVR, through aVL,, I, V6, II, aVF, to III, and similarly from VI-6.The electrical axis can be read at a glance.Ischaemic changes will be grouped together, so that, for example, a lateral infarction would give rise to abnormal tracings in leads mounted along the right-hand side of the paper.This presentation may simplify interpreta-
THE ALCOHOL QUESTION IN THE NAVY.WITH SUGGESTIONS AS TO ITS RESTRICTION.
Authors: P. A. LOVERING
Journal: JAMA (1907)

The remarks I shall make to you will be mainly confined to the problem as it affects the personnel of the Navy. After a service of over thirty years in all parts of the world, under the varying conditions of peace and war, I am convinced that the use of spirituous drinks should be discouraged and limited as far as possible, and yet I recognize that laws to prohibit their sale<i>in toto</i>can not be enforced and, as a rule, have proved of doubtful value. During my naval service the necessity for temperance has increased very greatly. As the huge floating machines of war have grown in force, they require more intelligent and skillful handling to keep them effective. There is no place on a man-of-war for one whose brains are dulled and whose hands are tremulous from drinking. Even those filling very subordinate positions may readily hazard the
Signaling via the IL-20 receptor inhibits cutaneous production of IL-1β and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus
Authors: Ian A Myles, Natalia M Fontecilla, Patricia A Valdez, Paul J Vithayathil, Shruti Naik, Yasmine Belkaid, Wenjun Ouyang, Sandip K Datta
Journal: Nature Immunology (2013)
GMC is to reconsider guidance on end of life care
Authors: C. Dyer
Journal: BMJ (2009)

Melanoma is a tumor of continuously increasing incidence for which new methods of imaging and targeted therapy are widely sought. Radioiodinated methylene blue is a promising tracer, showing selective uptake in human pigmented melanoma cells. We performed <sup>131</sup>I-labeling of the tracer using 1% methylene blue injection United States Pharmacopeia (USP) and <sup>131</sup>I sodium iodide. For quality control, a Merck high performance liquid chromatography (HPLC) system was used. We developed a new HPLC procedure using 0.1% trifluoroacetic acid, 90% acetonitrile and 10% water as solvent for isocratic elution of the tracer and applied a TLC method using ITLC-SG strips and the same solvent. The stability of the preparation was studied for 15 min, 3 h and 6 h. In order to evaluate the potential relevance of <sup>131</sup>I-labeled methylene blue for melanoma detection, the in vitro uptake of <sup>131</sup>I-methylene blue was investigated in SK-MEL 28 and 518A2 melanoma cells. Time and a temperature influence on uptake of <sup>131</sup>I methylene blue by these two melanoma cells were investigated. The radiochemical purity obtained by the HPLC method was 99.97±0.08% (n=8), while that by the TLC method was 99.88±0.16% (n=8). This indicates the excellent agreement between these two methods. The stability was persistent over 6 h and amounted to 99.75% ±0.21% (n=8). The uptake of <sup>131</sup>I methylene blue was time and temperature dependent by both melanoma cells lines. The net cellular uptake on incubation at 37°C of <sup>131</sup>I methylene blue by SK-MEL 28 cells was high at 56.3-61.8% and that by 518A2-cells was 36.3-56.0% . Uptake by these cells was also investigated at 22°C. The uptake by both cell types was also high at this temperature, but lower than that at 37°C, amounting to 45.0-51.7% and 25.6-36.3%, respectively. Due to its easy handling and quite high uptake by melanoma cells, we expect that this tracer could be successfully used in routine application for melanoma imaging or eventual radiotherapy.
Book Review Altering American Consciousness: The History of Alcohol and Drug Use in the United States, 1800–2000 Edited by Sarah W. Tracy and Caroline Jean Acker. 414 pp. Amherst, University of Massachusetts Press, 2004. $70 (cloth); $26.95 (paper). 1-55849-424-3 (cloth); 1-55849-425-1 (paper).
Authors: Dwight B. Heath
Journal: New England Journal of Medicine (2004)
Abstract 1513: Mesenchymal stromal cells enhance the malignant potential of human colorectal cancer cells by inducing epithelial to mesenchymal transition-related phenomena
Authors: Valentina Mele, Manuele Giuseppe Muraro, Diego Calabrese, Chiara Giovenzana, Michael Heberer, Chiara Bocelli-Tyndall, Luigi Terracciano, Giulio Cesare Spagnoli, Giandomenica Iezzi
Journal: Cancer Research (2011)

Abstract Background: Mesenchymal stromal cells (MSCs) are recruited to primary and metastatic sites of several tumour types, including colorectal cancer (CRC), and might contribute to tumour progression. The actual role played by MSCs and the mechanisms underlying MSC-tumour interactions remain to be clarified. We investigated the effects of human bone-marrow-derived MSCs (BM-MSCs) on CRC, in vitro and in vivo. Material and methods: Human established CRC cell lines were cultured in the presence or absence of BM-MSCs, in direct contact or in transwell plates. After a five day culture, tumour cell proliferation was assessed by differential cell counts, surface molecule expression was analyzed by flow cytometry, and production of soluble factors in culture supernatants was measured by Raybio antibody array® and ELISA. Tumour cells, sorted upon co-culture by flow cytometry, were evaluated for the expression of epithelial to mesenchymal transition (EMT)-related genes by quantitative PCR and for in vitro invasiveness, by chemoinvasion assay. Furthermore, their tumorigenicity was assessed upon injection in NOD/SCID mice and developing tumours were analyzed by immunofluorescence. Results: MSCs significantly increased tumour cell proliferation and decreased CD44 expression, independently of cell-to-cell contact. Analysis of co-culture supernatants revealed higher amounts of IL-6, MCP-1, RANTES and Angiogenin, in comparison to supernatants derived from single cultures. Moreover increased expression of several EMT-related genes, including SNAI2, TWIST, N-Cadherin, was detected on CRC cells sorted upon co-culture as compared with controls. Importantly, CRC cells co-cultured with MSCs showed higher invasive behaviour in vitro, than CRC cells cultured alone. No significant changes were observed in tumorigenicity. However, tumours originated from tumour cells co-cultured with MSCs showed a significantly higher vessel density as compared to controls. Conclusions: MSCs reduce adhesiveness, induce expression of EMT-related genes and increase proliferation, invasiveness and angiogenic potential of CRC cells. These effects might contribute to CRC progression and spreading. 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 1513. doi:10.1158/1538-7445.AM2011-1513
Acute effects of amiodarone on ultrastructure and electrical activity of isolated guinea pig hearts
Authors: G. Stark, M. Windisch, E. M Haller, U. Stark, T. Pieber, E. Pilger, G. J Krejs, H. A Tritthart
Journal: Cardiovascular Research (1991)

Study objective — The aim was to evaluate the effects of tissue concentration of amiodarone on ultrastructure and electrical activity in isolated spontaneously beating Langendorff perfused guinea pig hearts. Design — Group 1: The influence of 10 μM amiodarone over a period of 1 h in a non-recirculated perfusate on conduction intervals, heart rate, creatine kinase concentration in the coronary effluent, coronary flow, and drug accumulation was determined. Group 2: Ultrastructural changes after 30 min and 60 min perfusion with amiodarone were examined. Group 3: Cardiac refractoriness was evaluated following 30 min and 60 min of perfusion with amiodarone. Experimental preparations — Isolated hearts of guinea pigs (200-300 g) were used: group 1, n = 6 animals; group 2, n = 3 for each time span; and group 3, n = 6 for each time span. Measurements and main results — A steady state for the effects of amiodarone on atrioventricular and intraventricular conduction [+31(SEM 5)%, p<0.01; +47(12)%, p<0.01, respectively] and on heart rate [-30(9)%, p<0.01] was reached after 15 min, and on His bundle conduction [+38(17)%, p<0.01] after 30 min. QT duration was not affected throughout the duration of the experiment. Cardiac refractoriness was significantly prolonged following 30 min perfusion with 10 μM amiodarone, and was further significantly increased following 60 min perfusion. Amiodarone tissue concentration increased to 365(39) nmol·g−1 wet weight, and this was accompanied by an increase in creatine kinase concentration in the coronary effluent. Coronary flow stayed constant throughout the whole experiment. At the end of the experiment electron microscopic examination of the myocardium of the left ventricle showed accumulation, fusion, and vacuolisation of mitochondria, and perinuclear oedema. Conclusions — These observations suggest that amiodarone, as well as exerting acute electrophysiological effects, creates ultrastructural changes which probably contribute to its effectiveness in arrhythmias caused by scarred myocardium.
Assessing the Safety of a Replacement Chemical: Nongenomic Activity of Bisphenol S
Authors: Julia R. Barrett
Journal: Environmental Health Perspectives (2013)

Suspected links between bisphenol A (BPA) and adverse human health effects have spurred a search for replacement chemicals for use in common applications such as polycarbonate plastics, food can linings, and thermal papers.Bisphenol S (BPS) has been adopted for some uses.A new study now shows that low doses of BPS can disrupt nongenomic signaling pathways in cultured pituitary cells [EHP 121(3):352-358; Viñas andWatson].Nearly 93% of U.S. residents over age 6 carry measurable amounts of BPA in their bodies.The compound is suspected to contribute to the development of diseases such as diabetes, asthma, and cancer, and animal studies have shown it adversely affects reproduction.In contrast to genomic regulation, which involves receptors in the cell nucleus, nongenomic regulation involves receptors in the cell membrane.Since BPA can interact with cell-membrane estrogen receptors, researchers explored whether structurally similar BPS might likewise inf luence non genomic pathways.Treatments included various low doses of BPS alone and paired with estradiol, an endogenous estrogen.Measured responses included activation of ERK and JNK, mitogen-activated protein kinases involved in cell growth, proliferation, and apoptosis (programmed cell death); activation of caspases 8 and 9, enzymes that also are involved in apoptosis; and release of prolactin, a hormone that helps regulate hundreds of biological functions, including metabolism, reproduction, and lactation.
Damp and Rheumatism
Authors: W. S. C. Copeman, G. D. Kersley, R. E. Tunbridge, H. Osmond-Clarke, S. Davidson, J. C. R. Hindenach, O. Savage, E. Lewis-Faning, R. M. Mason, J. H. Kellgren, E. G. L. Bywaters, H. F. West, W. S. Tegner, G. R. Fearnley, J. J. R. Duthie, E. Fletcher
Journal: BMJ (1956)