tbuckley/cabot-search huggingface dataset:
Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis.
Authors: A E Koch, S L Kunkel, L A Harlow, D D Mazarakis, G K Haines, M D Burdick, R M Pope, R M Strieter
Journal: Journal of Clinical Investigation (1994)

We have shown that human macrophages (m phi s) play an important role in the elaboration of chemotactic cytokines in rheumatoid arthritis (RA) (Koch, A. E., S. L. Kunkel, J. C. Burrows, H. L. Evanoff, G. K. Haines, R. M. Pope, and R. M. Strieter. 1991. J. Immunol. 147:2187; Koch, A. E., S. L. Kunkel, L. A. Harlow, B. Johnson, H. L. Evanoff, G. K. Haines, M. D. Burdick, R. M. Pope, and R. M. Strieter. 1992. J. Clin. Invest. 90:772; Koch, A. E., P. J. Polverini, S. L. Kunkel, L. A. Harlow, L. A. DiPietro, V. M. Elner, S. G. Elner, and R. M. Strieter. 1992. Science (Wash. DC). 258:1798). Recently, m phi inflammatory protein-1 (MIP-1 alpha), a cytokine with chemotactic activity for m phi s and neutrophils (PMNs), has been described. We have examined the production of MIP-1 alpha using sera, synovial fluid (SF), and synovial tissue (ST) from 63 arthritic patients. MIP-1 alpha was higher in RA SF (mean, 29 +/- 8 ng/ml [SE]) compared with other forms of arthritis (2.8 +/- 1.7), or osteoarthritis (0.7 +/- 0.4; P < 0.05). RA SF MIP-1 alpha was greater than that found in either RA or normal peripheral blood (PB) (P < 0.05). Anti-MIP-1 alpha neutralized 36 +/- 3% (mean +/- SE) of the chemotactic activity for m phi s, but not PMNs, found in RA SFs. RA SF and PB mononuclear cells produced antigenic MIP-1 alpha. Mononuclear cell MIP-1 alpha production was augmented with phytohemagglutinin or LPS. Isolated RA ST fibroblast production of antigenic MIP-1 alpha was augmented upon incubation of cells with LPS, and to a lesser extent with tumor necrosis factor-alpha. Isolated RA ST m phi s expressed constitutive MIP-1 alpha mRNA and antigenic MIP-1 alpha. Using ST immunohistochemistry, MIP-1 alpha+ cells from RA compared with normal were predominantly m phi s and lining cells (P < 0.05). These results suggest that MIP-1 alpha plays a role in the selective recruitment of m phi s in synovial inflammation associated with RA.
Germany's "demographic storm" will see nursing care costs rise to 41.6bn by 2060
Authors: N. Stafford
Journal: BMJ (2012)

With one of the lowest birth rates in the world, Germany was not prepared to cope with the massive demands that its health system will face during the next 50 years from a rapidly aging population, concludes a new study.

The first wave of Germany’s baby boom generation, generally considered those born between 1955 and 1967, will reach retirement in 2020, says the study, from the Fritz Beske Institute of Health System Research in Kiel.1 From that point on, the demands on the health system will rapidly accelerate, reaching a peak in 2040. But high demands on the system …
Action of the Ovarian Hormones on Uterine Muscle
Authors: G. W. Corner, A. Csapo
Journal: BMJ (1953)

In 1907 Sir Henry Dale reported from his laboratory at Herne Hill the curious discovery that the uterus of the cat does not always react in the same way when its muscular tissue is stimulated through the hypogastric nerves or by intravenous injection of adrenaline.If the cat is not pregnant these stimuli cause relaxation of the uterus, but if she is pregnant they cause contraction.Before Dale's paper was printed Professor A. R. Cushny (1907) made identically the same observation at Univer- sity College and' reported it to the Physiological Society.Although it probably did not occur to either of these eminent pharmacologists that the reversal of muscular response which they had noticed was caused by action of the ovary, and although in fact " pregnancy reversal" still awaits detailed explanation, it was this observation that opened the way to study of the relation between the ovary and the behaviour of the uterine muscle.In that same year the Heidelberg gynaecologist Erwin Kehrer (1907) was making his pioneer studies of uterine muscle in vitro, in which he applied the then very recent discovery of Rudolf Magnus that 'strips of involuntary muscle cut from the intestine will long remain active if immersed in warm oxygenated physiological salt solu- tion.By attaching such a strip to a lever, the spon- taneous isotonic contractions of the muscle and its response to stimulation can be registered.This beauti- fully simple method began at once to be used in every pharmacological laboratory where oxytocic drugs were studied, Kehrer himself leading the way.In 1908, reporting his first studies on the action of ergot deri- vatives, he recommended the use of young virgin cats, for he had found that uterine tissue from adult animals taken during the breeding season was often less active and less predictable in its responses.This precautionary specification of the 'virgin uterus for tests of oxytocic drugs was written into all the pharmacopoeias of the world long before it could be understood in the light of endocrinology.In 1913 Max Stickel noticed that the movements of fhe rabbit's uterus in situ are greatly reduced by ablation of the ovaries, and a few years later (1919) Athias, of Lisbon, confirmed this fundamental obser- vation by in vitro experiments on guinea-pigs' uteri by
Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis
Authors: Fabio P. S. Santos, Hagop M. Kantarjian, Nitin Jain, Taghi Manshouri, Deborah A. Thomas, Guillermo Garcia-Manero, Debra Kennedy, Zeev Estrov, Jorge Cortes, Srdan Verstovsek
Journal: Blood (2009)
From an Exercise in Professional Etiquette to Society's Wish List? Review of American Medical Association,<i>Code of Medical Ethics: Current Opinions with Annotations</i>
Authors: Tom Meulenbergs
Journal: The American Journal of Bioethics (2004)

"From an Exercise in Professional Etiquette to Society's Wish List? Review of American Medical Association, Code of Medical Ethics: Current Opinions with Annotations ." , 4(2), pp. 69–70
Characteristics of binding of endothelin-1 and endothelin-3 to rat hearts. Developmental changes in mechanical responses and receptor subtypes.
Authors: T Ishikawa, L M Li, O Shinmi, S Kimura, M Yanagisawa, K Goto, T Masaki
Journal: Circulation Research (1991)

Endothelin-1 (ET-1) and endothelin-3 (ET-3) produced positive inotropic effects on electrically stimulated left atria and increased the frequency of spontaneously beating right atria of adult rats. The potency of the inotropic effect of ET-1 was greater than that of ET-3, but the potencies of the chronotropic effects of ET-1 and ET-3 were not significantly different. In the neonatal atria, ET-1 and ET-3 also induced positive inotropic and chronotropic responses. ET-1 and ET-3 showed weak or no cardiotonic effects on the adult ventricles, whereas they caused marked positive inotropy in the neonatal ventricles. The characteristics of binding sites for ET-1 and ET-3 were very similar between the atria and the ventricles of the rat neonate. Saturation and competition binding experiments have shown that neonatal cardiac membranes from both atria and ventricle have two distinct binding sites for endothelin, that is, a low-affinity and a high-affinity site. ET-1 was found to bind to the low-affinity sites with a significantly lower Kd than ET-3, whereas the estimated Kd values for ET-1 and ET-3 at the high affinity sites were similar. In contrast, the binding sites in adult atria were different from those of the ventricles: only a single binding site for both ET-1 and ET-3 was detected. Adult atrial membranes, on the other hand, had two distinct binding sites similar to those of neonatal membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 5029: Upregulation of miRNA27, miRNA125a and 125b in ERalpha-negative breast cancers
Authors: Tomasz P. Lehmann, Konstanty Korski, Matthew Ibbs, Jan Breborowicz, Sylwia Grodecka-Gazdecka, Robert Gryczka, Pawel Jagodzinski
Journal: Cancer Research (2012)

Abstract MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that post-transcriptionally inhibit gene expression. Many miRNAs have been implicated in the human breast cancer. We show here the correlation between breast cancer types characterized upon histological and immunohistochemical analysis and miRNA expression in 22 Polish patients. The group was divided into three categories: ERalpha-negative / ERalpha-positive, HER2-negative / HER2-positive and lymph node -negative / lymph node -positive (N-/N+) cases. Surgically removed tumors were congealed in liquid nitrogen and subsequently small RNA was extracted. We investigated the level of miR-17-5p, miR-27, miR-125a, miR-125b and miR-206 using real-time PCR TaqMan probes. Let-7 miRNA and U6 RNA were used as reference genes. We observed upregulation of the subsequent suppressor miRNAs miR-27, miR-125a and 125b in ERalpha-negative tumors (p&amp;lt;0.05). Comparison of expression of miR-17-5p, miR-27, miR-125a, miR-125b and miR-206 in N- and N+ samples did not reveal any significant differences. We also observed a tendency to lower level of expression of all investigated miRNAs in HER2-positive patients in comparison with HER2-negative. We concluded that miR-27, miR-125a and miR-125b may play an important role in the regulation of ER-alpha expression in breast cancer cells. They could also be regarded as surrogate markers of ER-alpha -negativity. However, the small number of patients included to the study warrants further investigation in the larger cohort of breast cancer patients. 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 5029. doi:1538-7445.AM2012-5029
Cancer patients rate London's hospitals the worst in England
Authors: I. Torjesen
Journal: BMJ (2012)

Hospital trusts in London have been ranked bottom in a league table rating cancer patients’ experience, issued by Macmillan Cancer Support. Trusts in the north of England have come out top.1

Nine London trusts featured in the bottom 10, meaning that patients who were treated there were the least satisfied with their care, and not a single trust in the capital made it into the top 10 trusts that patients rated the best.

Patients considered Imperial College Healthcare NHS Trust to be the worst trust in England, rating it bottom for the second year running.

Macmillan Cancer Support developed the league table using data …
Ecological analysis of collectivity of alcohol consumption in England: importance of average drinker
Authors: H. Colhoun, Y. Ben-Shlomo, W. Dong, L. Bost, M. Marmot
Journal: BMJ (1997)

Voltage-gated sodium (Na<sub>v</sub>) channel inhibitors are used clinically as analgesics and local anesthetics. However, the absence of Na<sub>v</sub> channel isoform selectivity of current treatment options can result in adverse cardiac and central nervous system side effects, limiting their therapeutic utility. Human hereditary gain- or loss-of-pain disorders have demonstrated an essential role of Na<sub>v</sub>1.7 sodium channels in the sensation of pain, thus making this channel an attractive target for new pain therapies. We have previously identified a novel, state-dependent human Na<sub>v</sub>1.7 selective inhibitor (PF-05089771, IC<sub>50</sub> = 11 nM) that interacts with the voltage-sensor domain (VSD) of Domain IV. We have further characterized the state-dependent interaction of PF-05089771 by systematically varying the voltage, frequency and duration of conditioning prepulses to provide access to closed, open and fast- or slow-inactivated states. The current study demonstrates that PF-05089771 exhibits a slow onset of block that is depolarization- and concentration-dependent, with a similarly slow recovery from block. Furthermore, the onset of block by PF-05089771 develops with similar rates using protocols that bias channels into predominantly fast- or slow-inactivated states, suggesting that channel inhibition is less dependent on the availability of a particular inactivated state than the relative time that the channel is depolarized. Taken together, the inhibitory profile of PF-05089771 suggests that a conformational change in the Domain IV-VSD following depolarization is necessary and sufficient to reveal a high affinity binding site with which PF-05089771 interacts, stabilizing the channel in a non-conducting conformation from which recovery is slow.
Antiarrhythmic Drugs: a Possible Cause of Out-of-Hospital Cardiac Arrest
Authors: Jeremy N. Ruskin, Brian McGovern, Hasan Garan, John P. DiMarco, Elizabeth Kelly
Journal: New England Journal of Medicine (1983)

SUDDEN cardiac death accounts for approximately two thirds of the 600,000 annual deaths that are attributable to cardiac disease in the United States. Most of these deaths are instantaneous, occurring within seconds or minutes, and where documented, the terminal event has in most cases been a ventricular tachyarrhythmia.1 2 3 4 Earlier studies have documented the high rate of recurrence of ventricular fibrillation and sudden death in patients with ventricular tachyarrhythmia regardless of empirical antiarrhythmic drug therapy.2 , 5 , 6 In fact, between 30 and 60 per cent of patients who are resuscitated after out-of-hospital cardiac arrest are found to have been taking antiarrhythmic drugs at . . .
When and Whom To Screen
Authors: Thomas E. Lindow
Journal: Annals of Internal Medicine (1993)

Letters1 December 1993When and Whom To ScreenThomas E. Lindow, MDThomas E. Lindow, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-11-199312010-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Schapira and colleagues [1] noted that screening with the combination of CA 125 and ultrasound prolongs life by less than a day per woman screened. Pauker [2] pointed out that such screening prolongs the lives of those found to have preclinical cancer by 11.6 years each. Nevertheless, he goes on to say, such (screening) programs cannot be recommended as public policy [2].Why do they disregard an astounding 11.6-year prolongation of life and concentrate instead on the misleading less-than-1-day statistic?A woman does not need a scientific study to tell her that a clean bill of health ...References1. Schapira MM, Matchar DB, Young MJ. The effectiveness of ovarian cancer screening: a decision analysis model. Ann Intern Med. 1993; 118:838-43. Google Scholar2. Pauker SG. Deciding about screening. Ann Intern Med. 1993; 118: 901-2. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHow Changes in Health Care Practices, Systems, and Research Challenge the Practice of Informed Consent 1 December 1993Volume 119, Issue 11Page: 1150-1152KeywordsCancer screeningLaparotomyLife expectancyOvarian cancer screeningPublic policyUltrasound imaging ePublished: 15 August 2000 Issue Published: 1 December 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hats for the newborn infant.
Authors: D M Chaput de Saintonge, K W Cross, M K Shathorn, S R Lewis, J K Stothers
Journal: BMJ (1979)

The efficacy of a Gamgee-lined hat in reducing the rate of fall in rectal temperature of infants during the first 30 minutes of life was studied. The trial, which included 211 infants, was randomised, prospective, and controlled. One hundred and seven infants were exposed to overhead radiantheaters. Of these, only 30 had normal deliveries, so the analysis was confined to the infants who were not subjected to radiant heat, and in this group no conclusions were drawn about the efficacy of a hat or a radiant heater. In the 104 infants not subjected to radiant heat, body weight, initial rectal temperature, the application of hat, the environmental temperature, and the duration of exposure while naked were all found to influence measureably the rate of fall in rectal temperature during the first 30 minutes. Gamgee-lined hats should be routinely used to minimise heat loss, especially in small infants exposed at birth, during surgical operations, and during investigations necessitating prolonged exposure.
A susceptibility gene for kidney disease in an obese mouse model of type II diabetes maps to chromosome 8
Authors: Streamson Chua, Yifu Li, Shun Mei Liu, Ruijie Liu, Ka Tak Chan, Jeremiah Martino, Zongyu Zheng, Katalin Susztak, Vivette D. D'Agati, Ali G. Gharavi
Journal: Kidney International (2010)
Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma
Authors: Yvette L. Kasamon, Heather A. Jacene, Christopher D. Gocke, Lode J. Swinnen, Douglas E. Gladstone, Brandy Perkins, Brian K. Link, Leslie L. Popplewell, Thomas M. Habermann, Joseph M. Herman, William H. Matsui, Richard J. Jones, Richard F. Ambinder
Journal: Blood (2012)
Bristol inquiry into baby deaths to move into new phase
Authors: C. Dyer
Journal: BMJ (2000)

The inquiry into children's heart surgery services at Bristol will move into a new phase in the new year, looking at the wider issues that the saga has thrown up for the health service as a whole, such as the determinants of performance and professional and managerial culture.

Just before the inquiry adjourned for Christmas, the chairman, Professor Ian Kennedy, announced that his panel would produce a special report on the issue of retention of organs after postmortem examination, at the request of the chief medical officer for England, Professor Liam Donaldson.

The revelation that for years doctors at Bristol Royal Infirmary and other British hospitals had been retaining children's organs without their parents' knowledge provoked …
Cytogenetic Studies and Their Clinical Correlates in Adults with Acute Leukemia
Authors: JACQUELINE S. HART
Journal: Annals of Internal Medicine (1971)

Cytogenetic studies were performed in 95 adults with acute leukemia, 39 (41%) of whom had abnormal karyotypes in their leukemic cells. The karyotypes were grouped according to the Denver-Chicago classification, and abnormalities were correlated with clinical variables. The frequency and quality of abnormality was not influenced by age, morphologic type of leukemia, or prior treatment. The frequency of abnormal karyotypes was increased in patients with increasing leukocytosis. Hypodiploidy adversely affected response to treatment and survival. D or E group chromosome deletions were associated with a decreased response to treatment and survival, whereas patients with extra D or E chromosomes had an improved prognosis. The overall distribution of chromosomal abnormalities in the leukemic cells deviated significantly from the expected for random distribution. D+, E+, and G- abnormalities were significantly more frequent than expected. Patients with marrow leukemic cell aneuploidy showed a loss of their abnormality during complete remission and recurrence at the time of relapse. The evidence suggested that chromosomal aberrations occur with increasing frequency as patients approach death.
Vav1 Is a Component of Transcriptionally Active Complexes
Authors: Martin Houlard, Ramachandran Arudchandran, Fabienne Regnier-Ricard, Antonia Germani, Sylvie Gisselbrecht, Ulrich Blank, Juan Rivera, Nadine Varin-Blank
Journal: The Journal of Experimental Medicine (2002)

The importance of the hematopoietic protooncogene Vav1 in immune cell function is widely recognized, although its regulatory mechanisms are not completely understood. Here, we examined whether Vav1 has a nuclear function, as past studies have reported its nuclear localization. Our findings provide a definitive demonstration of Vav1 nuclear localization in a receptor stimulation–dependent manner and reveal a critical role for the COOH-terminal Src homology 3 (SH3) domain and a nuclear localization sequence within the pleckstrin homology domain. Analysis of DNA-bound transcription factor complexes revealed nuclear Vav1 as an integral component of transcriptionally active nuclear factor of activated T cells (NFAT)- and nuclear factor (NF)κB-like complexes, and the COOH-terminal SH3 domain as being critical in their formation. Thus, we describe a novel nuclear role for Vav1 as a component and facilitator of NFAT and NFκB-like transcriptional activity.
T cell receptor and immunoglobulin gene rearrangements in acute myeloblastic leukemia.
Authors: G Y Cheng, M D Minden, B Toyonaga, T W Mak, E A McCulloch
Journal: The Journal of Experimental Medicine (1986)

The organization and expression of the beta chain of T cell antigen receptor gene (beta-TCR) and Ig H and L chain genes were analyzed by Southern blot technique in 24 patients with a diagnosis of acute myeloblastic leukemia (AML). Rearrangements of the beta-TCR genes were seen in DNA samples from 3 of the 24 patients. One of these three patients also showed rearrangement of the Ig H chain gene. RNA samples from all three patients expressed a beta-TCR gene transcript on dot blot analysis. However, on Northern blot analysis, one patient expressed an incomplete 1.0 kb transcript and no Ig H chain mRNA, despite a rearranged configuration. The karyotypes of two of these patients showed abnormalities involving chromosome 7. Rearrangements of T cell antigen receptor genes may occur in nonlymphoid malignancy, and is consistent with the concept of lineage infidelity in AML.
Obesity surgery---another unmet need
Authors: J. Baxter
Journal: BMJ (2000)

Obesity, defined as having a body mass index >30 kg/m2, is dramatically increasing in incidence in the Western world. For example, 20 years ago 5% of the population in the United Kingdom was obese; now 17% is.1 The annual healthcare costs arising directly from obesity are at least £2bn ($3bn) in the United Kingdom and £45bn ($68bn) in the United States. 2 3 Data from several sources have identified the increased morbidity and mortality associated with obesity.4 Most patients who are obese are treated with a combination of advice on diet and lifestyle and in some cases with drugs. However, for patients who have morbid obesity (body mass index >40), this conservative approach is doomed to failure.

If left untreated patients who are morbidly obese (1-2% of the population in the United Kingdom) have only a 1 in 7 chance of reaching their normal life expectancy. A Cochrane review in 1997 noted that good results had been obtained from surgery for obesity in these patients.5 Over the past decade both the National Institutes of Health in the United States and the Scottish Intercollegiate Guidelines Network have suggested that surgery is the most effective treatment for selected patients who are morbidly obese; both organisations have …
Passionate Kissing and Microlesions of the Oral Mucosa: Possible Role in AIDS Transmission
Authors: Marcello Piazza
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Kissing generally is considered protective sex.<sup>1</sup>We do not agree, since the oral mucosa is very fragile. In fact, hepatitis B infection may occur by the oral route through microlesions present in the oral mucosa (inapparent-parenteral route)<sup>2,3</sup>and not by the classic enteric route.<sup>4</sup> Since it is impossible to verify the presence of microlesions in the oral mucosa by inspection, we suggest that the presence of blood in saliva is indirect evidence of them. After encouraging preliminary results,<sup>5</sup>we have verified this phenomenon by carrying out the following experiment. <h3>Study. —</h3> Ninety healthy subjects (mean age, 25 years; range, 17 to 35 years) forming 45 heterosexual couples completed this study. Each subject was given six containers numbered 1 to 6 and was asked to collect saliva after carrying out the following three events in their normal way: immediately before and two or three