tbuckley/cabot-search huggingface dataset:
TGF-β upregulates miR-181a expression to promote breast cancer metastasis
Authors: Molly A. Taylor, Khalid Sossey-Alaoui, Cheryl L. Thompson, David Danielpour, William P. Schiemann
Journal: Journal of Clinical Investigation (2012)

Late-stage breast cancer metastasis is driven by dysregulated TGF-β signaling, but the underlying molecular mechanisms have not been fully elucidated. We attempted to recapitulate tumor and metastatic microenvironments via the use of biomechanically compliant or rigid 3D organotypic cultures and combined them with global microRNA (miR) profiling analyses to identify miRs that were upregulated in metastatic breast cancer cells by TGF-β. Here we establish miR-181a as a TGF-β–regulated "metastamir" that enhanced the metastatic potential of breast cancers by promoting epithelial-mesenchymal transition, migratory, and invasive phenotypes. Mechanistically, inactivation of miR-181a elevated the expression of the proapoptotic molecule Bim, which sensitized metastatic cells to anoikis. Along these lines, miR-181a expression was essential in driving pulmonary micrometastatic outgrowth and enhancing the lethality of late-stage mammary tumors in mice. Finally, miR-181a expression was dramatically and selectively upregulated in metastatic breast tumors, particularly triple-negative breast cancers, and was highly predictive for decreased overall survival in human breast cancer patients. Collectively, our findings strongly implicate miR-181a as a predictive biomarker for breast cancer metastasis and patient survival, and consequently, as a potential therapeutic target in metastatic breast cancer.
Reaching the world's poorest communities is key to achieving MDGs
Authors: P. Moszynski
Journal: BMJ (2010)

Further progress towards the millennium development goals (MDGs) requires much greater focus on the poorest and most marginalised communities, says research published by Unicef and Save the Children ahead of the Millennium Summit in New York later this month.

Unicef’s annual Progress for Children report indicates that, in the push to meet the development goals by their 2015 target, the very poor are falling further and further behind. Mortality rates for children under five are, on average, more than twice as high for the poorest 20% of households as for the richest 20%. And the poorest children are twice as likely to be underweight.

The report finds that although most developing countries are …
Environmental and Familial Contributions to Insulin Levels and Change in Insulin Levels in Middle-aged Women
Authors: Rena R. Wing
Journal: JAMA (1992)

To examine familial and environmental variables associated with elevated insulin levels and changes in insulin levels in healthy, premenopausal women.A population-based sample of 518 women (aged 42 to 50 years) completed baseline assessments of weight, cardiovascular risk factors, exercise behaviors, and glucose and insulin levels (fasting and 2 hours after a glucose load); 495 of the women were reevaluated after 3 years.Plasma insulin levels were related to weight, activity level, race, body fat distribution, and weight gain since age 20 years. Parental history of either diabetes or hypertension was also related to elevated insulin levels, independent of body mass index, with the highest insulin levels occurring in those women with a parental history of both diseases. Increases in plasma insulin levels over the years of follow-up were related to weight gain.This study suggests that importance of using family history to identify women who may have elevated insulin levels and of intervening to prevent weight gain during middle age.
Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model
Authors: Ida Hilden, Brian Lauritzen, Brit Binow Sørensen, Jes Thorn Clausen, Christina Jespersgaard, Berit Olsen Krogh, Andrew Neil Bowler, Jens Breinholt, Albrecht Gruhler, L. Anders Svensson, Helle Heibroch Petersen, Lars Christian Petersen, Kristoffer W. Balling, Lene Hansen, Mette Brunsgaard Hermit, Thomas Egebjerg, Birgitte Friederichsen, Mirella Ezban, Søren Erik Bjørn
Journal: Blood (2012)
Viruses and the aetiology of diabetes: a study in identical twins.
Authors: P G Nelson, D A Pyke, D R Gamble
Journal: BMJ (1975)

Sera were collected from 49 pairs of identical twins, 27 of whom were discordant (only one twin affected) and 22 concordant (both diabetic) for insulin-dependent diabetes. All were tested for antibodies to mumps, cytomegalovirus, rubella, Coxsackie virus types B1-5, and Mycoplasma pneumoniae. The diabetic co-twins had no more antibodies to any of the viruses than the non-diabetic co-twins of the discordant pairs. Antibodies to Coxsackie B2, rubella virus, and M pneumoniae were found more often in the discordant than in the concordant twins. In 30 of the 71 diabetic twins symptoms began when they were aged 4-6 years or 10-15 years. More concordant than discordant twins were diagnosed during the months January to March. Hence there was no direct evidence of a virus aetiology of juvenile onset diabetes in these twins, and the difference in antibody titres between the concordant and discordant twins was in keeping with a genetic difference between them. The age and time of onset suggested that environmental factors may be important in causing diabetes in the twins.
Mesantoin and Pulmonary Changes
Authors: THOMAS E. GOFFMAN
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 February 1982Mesantoin and Pulmonary ChangesTHOMAS E. GOFFMAN, M.D., BARRY S. DICICCO, M.D., EDWARD TSOU, M.D.THOMAS E. GOFFMAN, M.D.Search for more papers by this author, BARRY S. DICICCO, M.D.Search for more papers by this author, EDWARD TSOU, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-2-254_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Pulmonary involvement has recently been reported in phenytoin hypersensitivity reactions (1). We would like to add mephenytoin, a hydantoin derivative, as a probable source of a similiar hypersensitivity reaction with a pulmonary component.A 20-year-old white woman with a long history of a seizure disorder was placed on mephenytoin after failure to respond to primidone. Phenytoin had been discontinued several years before because of severe gingival hyperplasia and hirsutism. The patient presented to our hospital, 3 weeks after mephenytoin therapy was started, with a diffuse macular rash, hepatosplenomegaly, generalized adenopathy, mild elevation of serum transaminase, eosinophilia, fevers...Reference1. MICHAELRUDIN JM. Acute pulmonary disease caused by phenytoin. Ann Intern Med. 1981;95:452-4. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: THOMAS E. GOFFMAN, M.D.; BARRY S. DICICCO, M.D.; EDWARD TSOU, M.D.Affiliations: Georgetown University Hospital Washington, D.C. 20007 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1982Volume 96, Issue 2Page: 254-255KeywordsAminotransferasesEosinophiliaEpilepsyFeversHepatosplenomegalyHypersensitivityHyperthermiaRashes ePublished: 1 December 2008 Issue Published: 1 February 1982 PDF downloadLoading ...
Hepatitis C pharmacogenetics: State of the art in 2010
Authors: Nezam H. Afdhal, John G. McHutchison, Stefan Zeuzem, Alessandra Mangia, Jean-Michel Pawlotsky, Jeffrey S. Murray, Kevin V. Shianna, Yasuhito Tanaka, David L. Thomas, David R. Booth, David B. Goldstein
Journal: Hepatology (2010)

In 2009, a correlated set of polymorphisms in the region of the interleukin-28B ( IL28B ) gene were associated with clearance of genotype 1 hepatitis C virus (HCV) in patients treated with pegylated interferon-alfa and ribavirin. The same polymorphisms were subsequently associated with spontaneous clearance of HCV in untreated patients. The link between IL28B genotype and HCV clearance may impact decisions regarding initiation of current therapy, the design and interpretation of clinical studies, the economics of treatment, and the process of regulatory approval for new anti-HCV therapeutic agents. (Hepatology 2011)
Diagnosis and management of the solitary pulmonary nodule
Authors: G. Weir, S. Kos, J. Burrill, P. Salat, S. Ho, D. Liu
Journal: BMJ (2011)

We have previously identified two BCGF II-like factors which can be distinguished by their differential reactivity in several murine BCGF II assays. Prototype sources of these two factors are a partially purified preparation derived from PHA-P-stimulated human peripheral blood T lymphocytes (designated human BCGF), and supernatant from antigen-stimulated D10.G4.1 murine T cells (designated D10 sup). Extending the characterization of these two factors, we show here that human BCGF and D10 sup both cause tritiated thymidine ([3H]TdR) incorporation and IgM secretion by T cell-depleted, in vivo-activated, large murine B cells. In contrast, only the human BCGF consistently induced proliferation and IgM secretion by T cell-depleted, small murine B cells. When simultaneously added to cultures, D10 sup and human BCGF synergized to produce optimal IgM secretion by large murine B cells and murine BCL1 B lymphoma cells. The same factors were tested in an IgM-specific plaque assay, and a similar synergistic response was observed for the large B cells, but not for the BCL1 cells. The combination of factors also produced maximal [3H]TdR incorporation by large murine B cells. In contrast, the addition of human BCGF totally abrogated D10 sup-induced BCL1 proliferation. Together, these data suggest that the synergies observed in IgM secretion result from an increased production of plaque-forming cells (PFC) in cultures of large B cells and an increase in IgM production per responding cell in BCL1 cells. Kinetic analysis of the time of action of the two BCGF II-like lymphokines in the induction of the PFC response by large B cells indicated that human BCGF was required within the first 24 hr of a 4-day culture period, while D10 sup could be added as late as the final 15 hr without significant diminution of the response. In summary, these data provide further support for the existence of two distinct B cell stimulatory factors which cause growth and differentiation of activated B cells, and indicate that these two factors synergize to produce optimal Ig secretion. For ease of discussion, the activity in the human BCGF preparation is referred to as BCGF IIA, and the activity in D10 sup is referred to as BCGF IIB.
Methicillin-resistant <i>Staphylococcus aureus</i>: Colonization and Infection in a Long-term Care Facility
Authors: Suzanne F. Bradley, Margaret S. Terpenning, Mary A. Ramsey, Lidija T. Zarins, Karen A. Jorgensen, William S. Sottile, Dennis R. Schaberg, Carol A. Kauffman
Journal: Annals of Internal Medicine (1991)

▪Objective: To assess methicillin-resistant Staphylococcus aureus (MRSA) colonization, transmission, and infection over a 1-year period in a long-term care facility with endemic MRSA. ▪Design: Monthly surveillance for MRSA colonization of nares, perineum, rectum, and wounds. ▪Setting: Long-term care facility attached to an acute care Veterans Affairs medical center. ▪Patients: All 341 patients in the facility had monthly surveillance cultures for 1 year. ▪Outcome Measurements: Colonization and infection with MRSA. ▪Main Results: The monthly MRSA colonization rate was 23% ± 1.0%; colonization occurred most commonly in the nares and wounds. Poor functional status was associated with MRSA colonization. Most patients (65%) never acquired MRSA; 25% of patients were already colonized at admission to the facility or at the start of the study, and only 10% of newly admitted patients acquired MRSA while in the facility. These latter patients acquired several different strains in a pattern of acquisition similar to that generally seen within the facility. In the course of 1 year, only nine patients who acquired MRSA had a roommate with the same phage type; no clustering was evident, and none of these patients developed infection. Nine other patients (3%) developed MRSA infection; five of these patients required hospitalization, but none died as a result of infection. ▪Conclusions: In the long-term care facility in which our study took place, MRSA was endemic, and the infection rate was low. In such settings, the cost effectiveness of aggressive management of MRSA (widespread screening for MRSA and eradication with antimicrobial agents) needs to be assessed.
Doped East German athletes to receive compensation
Authors: A. Tuffs
Journal: BMJ (2002)

Athletes from former East Germany who were given performance enhancing drugs for many years and who consequently experienced longstanding health problems will receive payments of several thousand euros, the German federal parliament decided on 13 June.

A special law has been passed which sets up a compensation fund of about €2m (£1.3m; $1.9m). The fund is meant to be supplemented …
Targeting the NF-κB signaling pathway in Notch1-induced T-cell leukemia
Authors: Tomas Vilimas, Joaquina Mascarenhas, Teresa Palomero, Malay Mandal, Silvia Buonamici, Fanyong Meng, Benjamín Thompson, Christina Spaulding, Sami Macaroun, Maria-Luisa Alegre, Barbara L Kee, Adolfo Ferrando, Lucio Miele, Iannis Aifantis
Journal: Nature Medicine (2006)
UK spending on healthcare lowest of G7 countries
Authors: G. Iacobucci
Journal: BMJ (2014)

NK cells are the first line of defense against foreign cells, virally infected cells, and tumors. The mechanisms whereby NK cells accumulate in extralymphoid sites in response to pathogenic stimuli are not well understood. The L-selectin adhesion molecule (CD62L) plays a primary role in mediating the initial interaction of leukocytes with vascular endothelium, a crucial step in the extravasation of immune effector cells into tissues. In this report, we show L-selectin to be uniquely expressed on a subset of resting human NK cells (CD56<sup>bright</sup>). Notably, CD56<sup>bright</sup> NK cells expressed L-selectin at a higher density than all other peripheral blood leukocytes. NK activation by PMA, IL-2, IL-15, or TGF-β down-regulated L-selectin on the CD56<sup>bright</sup> subset, while increased L-selectin levels were observed in both the CD56<sup>bright</sup> and CD56<sup>dim</sup> NK subsets in response to IL-12, IL-10, or IFN-α. Moreover, CD56<sup>bright</sup> NK cells bound with high efficiency to physiologic L-selectin ligands on peripheral lymph node high endothelial venules (HEV). In sharp contrast, CD56<sup>dim</sup> NK cells adhered poorly to HEV and were predominantly L-selectin<sup>−</sup> or expressed L-selectin only at low density. In CD56<sup>bright</sup> cells and a subpopulation of CD56<sup>dim</sup> cells, L-selectin ligation by mAb cross-linking activated lymphocyte function-associated Ag 1 (LFA-1), a second adhesion molecule required for leukocyte extravasation. LFA-1 was expressed on both NK subsets, although its density was constitutively higher on CD56<sup>dim</sup> cells. Taken together, evidence of differential expression of L-selectin and LFA-1 on CD56<sup>bright</sup> and CD56<sup>dim</sup> NK subsets strongly suggests unique migratory properties and functions of these cells during the early immune response to foreign pathogens.
Inhibition of adherence of Neisseria gonorrhoeae by human genital secretions.
Authors: E C Tramont
Journal: Journal of Clinical Investigation (1977)

Local genital antibodies to the infecting strains of Neisseria gonorrhoeae were demonstrated by indirect immunofluorescence (binding antibody) and by their ability to inhibit the attachment of gonococci to epithelial cells (functional antibody). Both IgG and IgA classes of immunoglobulin were involved, and the IgA component were primarily of a secreting (11S) nature. The ability of local genital antibody to inhibit attachment appears to persist for at least a short period of time and to be relatively strain specific.
SUPPRESSION OF GROWTH OF BROWN-PEARCE TUMOR CELLS BY A SPECIFIC ANTIBODY
Authors: John G. Kidd
Journal: The Journal of Experimental Medicine (1946)

Experiments are reported in detail which show that an antibody which appears in the blood of certain rabbits implanted with the Brown-Pearce tumor or injected with cell-free extracts of it is capable of suppressing the growth of the tumor cells under a variety of experimental conditions, the effects of the antibody being wholly distinct from those of unknown factors that frequently bring about regression of the growth. The implications of the findings are discussed with particular reference to facts indicating that the distinctive cell constituent with which the antibody reacts may play a significant part in the proliferative activities of the Brown-Pearce tumor cell.
Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe <i>Acinetobacter lwoffii</i> F78
Authors: Melanie L. Conrad, Ruth Ferstl, René Teich, Stephanie Brand, Nicole Blümer, Ali Ö. Yildirim, Cecilia C. Patrascan, Anna Hanuszkiewicz, Shizuo Akira, Hermann Wagner, Otto Holst, Erika von Mutius, Petra I. Pfefferle, Carsten J. Kirschning, Holger Garn, Harald Renz
Journal: The Journal of Experimental Medicine (2009)

The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9−/− knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78–treated TLR2/3/4/7/9−/− homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78–exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.
Assessing methods-a feel for other things.
Authors: S M Gore
Journal: BMJ (1981)

Two examples of non-linear regression functions are given, only one of which can be transformed to become a straight line.Weighted least squares is again mentioned, and the idea of plotting interval means as a guide to the form of a regression function is emphasised in a second example.Correlation coefficients make a useful contribution to pre- liminary data analysis only if supported by graphical methods.Authors are advised to report descriptively their initial im- pressions of complex data, giving the reader a useful background against which to see a final multivariate solution.Non-linear relationships (15) Transformation' of one or both variables sometimes induces a straight-line relationship.Find the cube root of 04125, of 1, of 8. What is the logarithm of 1, the square root of 4, the cube of 2, and the reciprocal of 2? -0 125 -0 5; 1 1; 8 --2 -log 1 0; 4 2; 23 8; 2-1'- 7 05 2 -not all regression functions are linear 4. 1-.1-E -o 0 -o 0 0 3. I04I 1 2 3 4 5 6 0-48 First draw water lead (/vmol/l) FIG 1-Scatter diagram for first-flush water.Conversion: SI to traditional units-Blood lead: 1 ,umol/l z 0-0483 ,ug/ 100 ml.
SAGE analysis demonstrates increased expression of TOSO contributing to Fas-mediated resistance in CLL
Authors: Rodrigo Proto-Siqueira, Rodrigo A. Panepucci, Francisco P. Careta, Abigail Lee, Andrew Clear, Kelly Morris, Carolyn Owen, Edgar G. Rizzatti, Wilson A. Silva, Roberto P. Falcão, Marco A. Zago, John G. Gribben
Journal: Blood (2008)
Deaths in children with acute appendicitis
Authors: H. G. Pledger, R. Buchan
Journal: BMJ (1969)

Two hundred and four children died of acute appendicitis in England and Wales in the five-year period 1963-7. The mortality rate in children less than 5 years old was eight times higher than that in those aged 5-14. It is suggested that diagnosis, intravenous therapy, treatment of convulsions and hyperpyrexia, and anaesthesia are fields where there is room for improvement in management. Moreover, there is a place for the wider use of national medical audits on the lines of the Confidential Enquiry into Maternal Deaths.
Modular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy
Authors: Scott Q. Harper, Michael A. Hauser, Christiana DelloRusso, Dongsheng Duan, Robert W. Crawford, Stephanie F. Phelps, Hollie A. Harper, Ann S. Robinson, John F. Engelhardt, Susan V. Brooks, Jeffrey S. Chamberlain
Journal: Nature Medicine (2002)
Optic Neuritis
Authors: Laura J. Balcer
Journal: New England Journal of Medicine (2006)

A 25-year-old woman presents with a one-week history of blurred vision in the left eye. One day before the onset of visual loss, she noted a dull ache in the left periorbital region and pain on eye movement. Her symptoms progressed for three days but have not worsened since. She has no history of other visual or neurologic symptoms. Examination reveals visual acuity of 20/40 in the left eye, reduced color perception, and a left afferent pupillary defect. There is no visible swelling of the optic disk or pallor of the optic nerve, and a neurologic examination is normal. How should she be evaluated and treated?
Granulocyte Transfusions: Where Now?
Authors: Donald J. Higby
Journal: New England Journal of Medicine (1981)

Although the article on prophylactic granulocyte transfusions in acute myelogenous leukemia by Strauss et al. in this issue of the Journal1 might be criticized — for the low number of granulocytes given per transfusion, for the inclusion of patients with fever, or for the probable differences in antimicrobial-therapy practice and remission-induction regimens among the participating institutions — it describes a carefully done study, with conclusions well supported by the data. These workers found no evidence of benefit and concluded that routine prophylactic transfusions of white cells are not justified.Although many investigators have come to believe that prophylactic granulocyte transfusions . . .
The Effectiveness of β-Blockers After Myocardial Infarction in Patients With Type 2 Diabetes
Authors: Charlotte G. McDonald, Sumit R. Majumdar, Jeffrey L. Mahon, Jeffrey A. Johnson
Journal: Diabetes Care (2006)

We thank Dr. Bell (1) for his interest in and insightful comments about our study. Dr. Bell proposes that the use of lower doses of cardioselective β-blockers could have reduced the effectiveness of this class of agents after myocardial infarction (MI) in diabetic subjects, a reasonable hypothesis. Another hypothesis is that short-acting cardioselective β-blockers lead to periods of withdrawal and decreased efficacy (2).

As in previous studies (3, 4), we assumed a class effect among …