tbuckley/cabot-search huggingface dataset:
Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium
Authors: Volker Schächinger, Alexandra Aicher, Natascha Döbert, Rainer Röver, Jürgen Diener, Stephan Fichtlscherer, Birgit Assmus, Florian H. Seeger, Christian Menzel, Winfried Brenner, Stefanie Dimmeler, Andreas M. Zeiher
Journal: Circulation (2008)

Background— Clinical trials indicate a beneficial effect of intracoronary infusion of progenitor cells on myocardial function in patients with ischemic heart disease. The extent and potential determinants of proangiogenic progenitor cell homing into the damaged myocardium after intracoronary infusion and the underlying mechanisms are still unknown. Method and Results— Circulating proangiogenic progenitor cells isolated from peripheral blood and cultivated for 3 days were labeled with radioactive indium oxine ( 111 In-oxine). Radiolabeled proangiogenic progenitor cells (7.6±3.0 MBq, mean±SD) were administered to patients with previous myocardial infarction and a revascularized infarct vessel at various stages after infarction (5 days to 17 years). Viability of the infarcted myocardium was determined by 18 F-fluorodeoxyglucose–positron emission tomography and microcirculatory function by intracoronary Doppler measurements. One hour after application of progenitor cells, a mean of 6.9±4.7% (range, 1% to 19%; n=17) of total radioactivity was detected in the heart, which declined to 2±1% after 3 to 4 days. Average activity within the first 24 hours was highest among patients with acute myocardial infarction (≤14 days; 6.3±2.9%; n=8) and progressively decreased in patients treated in an intermediate phase (&gt;14 days to 1 year; 4.5±3.2%; n=4) or a chronic stage (infarct age &gt;1 year; 2.5±1.6%; n=5). Low viability of the infarcted myocardium and reduced coronary flow reserve were significant ( P &lt;0.05) predictors of proangiogenic progenitor cell homing. Conclusions— In patients after myocardial infarction undergoing intracoronary infusion of 111 In-oxine–labeled proangiogenic progenitor cells, a substantial amount of radioactivity is detected for several days in the heart, indicating homing of progenitor cells to the myocardium. The amount of proangiogenic progenitor cells retained in the heart decreased progressively with time after the acute myocardial infarction. Proangiogenic progenitor cells preferentially home to extensive acute myocardial infarcts characterized by low viability and reduced coronary flow reserve.
Units of management in reorganised NHS: what choice for senior medical staff?
Authors: R. Dyson
Journal: BMJ (1982)

The new shadow district health authorities are now starting to consider seriously what pattern of units of management to adopt when replacing the post-1974 administrative sectors and nursing divisions. The guidelines were pub? lished in the DHSS's cir? cular HC(80)8 Health Service Development : Structure and Management. The timetable is very tight; while some regions aimed for the end of February most are seeking completion by the end of April. Many senior medical staff will probably have recently re? ceived, or will be about to Professor Roger Dyson is chairman receive, detailed and some designate of the North Staffordshire times quite radical proposals DHA* for change with deadlines so tight that if they draw breath they may miss their opportunity to contribute to the debate?a debate about decisions that could have important implications for the way in which they do their work. My aim is to outline some of the major issues and choices for medical staff and so help in securing a more effective medical con? tribution to the final decisions of the DHAs.
Distinctive clinical and dermoscopic features of BRAF V600K mutated melanomas
Authors: G. Ponti, M. Manfredini, A. Tomasi, G. Pellacani
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, The dermoscopic criteria associated with BRAF and NRAS mutation status in primary cutaneous melanoma have recently been analysed by Pozzobon et al.1 in an interesting study published in BJD. The authors found out that a peppering pattern was significantly increased among BRAF mutant melanoma, being present in 68% of their cases series, with an odds ratio of 1·68 (95% confidence interval 1·09–2·58, P =0·015).1 The intent of this letter is to underline the distinctive dermoscopic and clinical features of BRAF p.V600K melanoma (the second most common BRAF V600 mutation, detected in 5–30% of cases), which might be slightly different from the features of BRAF V600E melanoma. Although BRAF inhibitors are efficacious in melanomas with V600E and V600K mutations, the two tumour types should be considered distinct entities with slightly different age of onset and clinical behaviour.2 3 4 5 Recently published scientific studies reported that BRAF V600K melanomas are characterized by an older age of onset and an increased risk for brain and lung metastases, as well as a shorter time from diagnosis to metastasis and death.3 Other reports of patients with melanoma with BRAF V600K mutations recognized significant differences in sex, age, primary melanoma location, interval from the time of initial melanoma diagnosis to diagnosis of stage IV disease, and overall survival after the diagnosis of stage IV disease. V600K mutation was significantly associated with older age, male sex, head and neck primary melanoma site, higher degree of chronic sun damage and short overall survival from the time of diagnosis of stage IV disease.3 4 5
Analysis of the Kveim-Siltzbach Test Reagent for Bacterial DNA
Authors: ELVIRA RICHTER, Y. P. KATARIA, G. ZISSEL, J. HOMOLKA, M. SCHLAAK, J. MÜLLER-QUERNHEIM
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The sarcoid spleen–derived reagent for the Kveim-Siltzbach test (KST) elicits a sarcoid-specific, granulomatous, cutaneous response used to establish the diagnosis of sarcoidosis. In the context of the ongoing discussion of a bacterial cause of sarcoidosis we asked the question whether bacterial DNA could be found in the KST reagent. For this purpose two different KST reagents, an identical preparation from a normal spleen, and a native sarcoid spleen were analyzed by polymerase chain reaction (PCR) employing universal primers detecting conserved DNA sequences coding for bacterial ribosomal 16S RNA. Neither KST reagents, the control preparation, nor the spleen yielded a positive signal, indicating that the preparations are free of bacterial contamination. Because the KST reagent elicits granuloma, these results do not support the hypothesis of a bacterial cause of sarcoid granuloma.
Voting for Guy's and Lewisham Hospitals to become a self governing trust
Authors: J S Cameron, R Grahame, J Jarrett, H Keen, M Laurence, R Lewis, B Rosen
Journal: BMJ (1991)

breast screening we have found a difference in the ability to trace Asian and non-Asian women.In a study in central Manchester we were unable to gain access at their address for only six of 93 Asian non- attenders compared with 26% of 103 non-Asian women.Bv gaining some information from other occupiers we established that half of the Asian women were no longer resident at the address on the invitation.Though this was the main reason for non-attendance among Asian women, it could only be estimated to be the reason for 26-54% of the non-Asian women.Our impression was of two different types of response: when we followed up non-Asian women access was more difficult and it was harder to gather information from other occupiers or neigh- bours, whereas more of the Asian community were available and were more helpful.Furthermore, the outcome of personal visits to non-attenders was more successful among Asian women: of the Asian women contacted and offered additional appointments, 70% subsequently attended for screening whereas only 36% of non-Asian women did so.In terms of the effectiveness of personal visits on the overall uptake of screening attendance for breast screening by Asian women increased by 9%.
Transcript imaging of the development of human T helper cells using oligonucleotide arrays
Authors: Lars Rogge, Elisabetta Bianchi, Mauro Biffi, Elisa Bono, Sheng-Yung P. Chang, Heather Alexander, Chris Santini, Giuliana Ferrari, Luigi Sinigaglia, Monika Seiler, Martin Neeb, Jan Mous, Francesco Sinigaglia, Ulrich Certa
Journal: Nature Genetics (2000)
Tofacitinib or Adalimumab versus Placebo in Rheumatoid Arthritis
Authors: Ronald F. van Vollenhoven, Roy Fleischmann, Stanley Cohen, Eun Bong Lee, Juan A. García Meijide, Sylke Wagner, Sarka Forejtova, Samuel H. Zwillich, David Gruben, Tamas Koncz, Gene V. Wallenstein, Sriram Krishnaswami, John D. Bradley, Bethanie Wilkinson
Journal: New England Journal of Medicine (2012)

Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis.In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity).At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P<0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts.In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.gov number, NCT00853385.).
A NEW PIPET CLEANER
Authors: F. W. Hartman
Journal: JAMA (1924)

The necessity of cleaning dozens of pipets daily is one of the problems of the central laboratory scheme. Suction alone is variable, and at best is often not of sufficient force. The combination of pressure and suction seemed logical, but difficulty was encountered in holding the pipets while pressure was applied. This was finally overcome by drawing a half inch pressure tube with walls three-eighths inch in thickness (<i>B</i>) within a nickeled brass pipe (<i>A</i>) into which eight one-fourth inch holes have been bored at one inch intervals. Now the tubing was perforated with a one-eighth inch cork borer corresponding to the holes in the brass pipe. The pipet inserted into these holes is held firmly and clasped more tightly when pressure is turned on. Within the rubber tube a brass plunger valve is fitted, allowing from one to eight pipets to be cleaned at a time. Into the opposite
A novel real-time RT-PCR assay for quantification of OTT-MAL fusion transcript reliable for diagnosis of t(1;22) and minimal residual disease (MRD) detection
Authors: P Ballerini, A Blaise, T Mercher, B Pellegrino, C Perot, J van den Akker, E Gatbois, M Adam, L Douay, R Berger, O Bernard, J Landman-Parker
Journal: Leukemia (2003)
Peroxisome proliferator–activated receptor-α−/− mice show enhanced hepatocyte proliferation in response to the hepatomitogen 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene, a ligand of constitutive androstane receptor
Authors: Amedeo Columbano, Giovanna M. Ledda-Columbano, Monica Pibiri, Danilo Concas, Janardan K. Reddy, Sambasiva M. Rao
Journal: Hepatology (2001)

Previously, we have suggested that liver cell proliferation induced by certain mitogens is dependent on their binding and activation of nuclear receptors of the steroid/thyroid superfamily. More recently, it was shown that absence of the nuclear receptors peroxisome proliferator-activated receptor–α (PPARα) and constitutive androstane receptor (CAR) completely abolishes the proliferative response of hepatocytes to the mitogenic stimulus exerted by their specific ligands, peroxisome proliferators (PPs) and 1,4–bis[2–(3,5–dichloropyridyloxy)] benzene (TCPOBOP), respectively. Here we show that deletion of the PPARα gene accelerates and enhances the proliferative response evoked by the xenobiotic 1,4–bis[2–(3,5–dichloropyridyloxy)] benzene (TCPOBOP), a powerful mouse–liver mitogen and a ligand of the nuclear receptor CAR. Indeed, the number of hepatocytes entering S phase 24 hours after mitogen treatment was much greater in PPARα -/- mice compared with that of wild type mice (labeling indices 21.4% and 7.5%, respectively). Labeling index of hepatocytes from PPARα -/- mice was found to be higher than that of wild type mice up to 36 hours after treatment, indicating that lack of PPARα not only accelerated but also enhanced the overall proliferative response of the liver. The accelerated entry into S phase observed in hepatocytes from PPARα -/- mice was associated with a very rapid induction of cyclin D1. No major differences between TCPOBOP–treated PPARα -/- and wild type mice were observed in the expression of the 2 inhibitors of cyclin/CDKs complexes, p27 and p21. The results suggest that PPARα may play a role in modulating CAR–signaling pathways in the cell, in particular those leading to hepatocyte proliferation.
JAK-STAT Blockade Inhibits Tumor Initiation and Clonogenic Recovery of Prostate Cancer Stem-like Cells
Authors: Paula Kroon, Paul A. Berry, Michael J. Stower, Greta Rodrigues, Vincent M. Mann, Matthew Simms, Deepak Bhasin, Somsundaram Chettiar, Chenglong Li, Pui-Kai Li, Norman J. Maitland, Anne T. Collins
Journal: Cancer Research (2013)

Interleukin (IL)-6 overexpression and constitutive STAT3 activation occur in many cancers, including prostate cancer. However, their contribution to prostate stem and progenitor cells has not been explored. In this study, we show that stem-like cells from patients with prostate cancer secrete higher levels of IL-6 than their counterparts in non-neoplastic prostate. Tumor grade did not influence the levels of expression or secretion. Stem-like and progenitor cells expressed the IL-6 receptor gp80 with concomitant expression of pSTAT3. Blockade of activated STAT3, by either anti-IL-6 antibody siltuximab (CNTO 328) or LLL12, a specific pSTAT3 inhibitor, suppressed the clonogenicity of the stem-like cells in patients with high-grade disease. In a murine xenograft model used to determine the in vivo effects of pSTAT3 suppression, LLL12 treatment effectively abolished outgrowth of a patient-derived castrate-resistant tumor. Our results indicate that the most primitive cells in prostate cancer require pSTAT3 for survival, rationalizing STAT3 as a therapeutic target to treat advanced prostate cancer.
Review of lipid-lowering clinical trials in relation to observational epidemiologic studies.
Authors: H A Tyroler
Journal: Circulation (1987)

A review of the experimental clinical trials and observational cohort evidence relating serum cholesterol level and its reduction to risks of coronary heart disease (CHD) discloses strong similarities among the quantitative and qualitative relationships found in these studies. Not only are the risk functions similar, but the percent reduction observed is the same as that predicted from the population experience and is proportional to the degree of cholesterol lowering. Furthermore, the risk function is continuous from the highest to the lowest serum cholesterol levels studied. These findings confirm the lipid hypothesis and indicate that lowering serum cholesterol reduces CHD risk. The understanding and control of CHD requires a dual approach: (1) identification and treatment of high-risk individuals, and (2) modification of environmental and behavioral determinants to achieve more favorable distributions of serum cholesterol in populations.
Case 63-1962
Authors: Earle M. Chapman, Robert E. Scully
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A forty-seven-year-old man was admitted to the hospital because of weakness and malaise.Four years previously intermittent crampy pain with paresthesias began in the ankles and successively involved the posterior portions of the calves and the anterior and posterior portions of the thighs.The pain was produced by exercise and immediately relieved by rest, and he noticed that the symptoms seemed more severe when he was emotionally upset. One year before entry paresthesias developed in the arms and hands, especially in the fingers of the left hand, which he described as numb, as if . . .
Venous leg ulcers.
Authors: D J Paynton
Journal: BMJ (1993)

ance of immunological tolerance to these natural compounds.'Under conditions of autoimmunity, such as experimentally induced immune mediated demyelination of the peripheral nerves, injections of pure gangliosides do not result in the induction of antibodies to gangliosides and do not worsen the course of the disease.7A neurological syndrome induced in rabbits by injecting gangliosides derived from brain reported by Nagai et at could not be reproduced and could be explained as resulting from contamination of the ganglioside preparation by myelin proteins.Antibodies reactive with gangliosides recognise the carbohydrate portion of the molecule.These carbohydrate epitopes are not uniquely expressed on gangliosides but are also present on glyco- proteins and bacterial cell walls.9Controlled studies in humans have proved that the prolonged administration of Gmi in healthy individuals as well as in patients with neurological diseases does not modify the pattern of antibody crossreactivity to glycoconjugates.'°In conclusion, all available data are consistent with the lack of immunogenicity of brain-derived gangliosides if purity is guaranteed.Thus, their use for therapeutic purpose should not be restricted by the present immunological knowledge.
Cowden disease.
Authors: JOSEPH W. BURNETT, RONALD GOLDNER, GARY J. CALTON
Journal: British Journal of Dermatology (1975)

Two patients with Cowden disease, a syndrome consisting of cutaneous papules and nodules on the face, oral mucous membranes and dorsal aspects of the forearms and hands in association with tumours of the thyroid gland, breasts, gastro-intestinal tract, and female reproductive tract, are reported. This disease is important to the physician because recognition of these cutaneous lesions may allow early diagnosis of internal neoplasia.
Body Weight and Longevity
Authors: John W. Beasley
Journal: JAMA (1987)

<h3>To the Editor.—</h3> The article by Manson et al<sup>1</sup>entitled "Body Weight and Longevity" represents a worthwhile attempt to eliminate confounding variables in the examination of the relationship between body weight and longevity. Unfortunately, three additional variables that probably should have been looked at have not been. They are (1) physical activity, (2) social status, and (3) diet. Physical inactivity is positively correlated both with greater body weight and with mortality. Therefore, investigations of the relationship between body weight and longevity should include assessments of physical activity. Unfortunately, this is obviously extremely difficult to measure, but again, the failure to look at this variable weakens the establishment of a possible causal relationship between body weight and increased mortality. The second variable, that of social status, should also be examined since persons in the United States with a lower social status also have higher mortality. Lower social status is also
Cyclooxygenase-2-Dependent Activation of Signal Transducer and Activator of Transcription 3 by Interleukin-6 in Non–Small Cell Lung Cancer
Authors: Harnisha Dalwadi, Kostyantyn Krysan, Nathalie Heuze-Vourc'h, Mariam Dohadwala, David Elashoff, Sherven Sharma, Nicholas Cacalano, Alan Lichtenstein, Steven Dubinett
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cyclooxygenase-2 (COX-2), phosphorylated signal transducers and activators of transcription 3 (STAT3), and interleukin-6 (IL-6) are elevated in non–small cell lung cancer (NSCLC). These molecules affect numerous cellular pathways, including angiogenesis and apoptosis resistance, and, therefore, may act in concert in NSCLC. Experimental Design: We examined IL-6 and phosphorylated STAT3 in COX-2-overexpressing [COX-2 sense-oriented (COX-2-S)] NSCLC cells and control cells. The effect of IL-6, STAT3, phosphatidylinositol 3-kinase, and mitogen-activated protein/extracellular signal-regulated kinase kinase on vascular endothelial growth factor (VEGF) production and apoptosis resistance was assessed in COX-2-overexpresing cells. Results: We report that NSCLC cells overexpressing COX-2 (COX-2-S) have increased IL-6 and phosphorylated STAT3 expression compared with control cells. IL-6 induced expression of VEGF in NSCLC cells. Moreover, blocking IL-6, mitogen-activated protein/extracellular signal-regulated kinase kinase, or phosphatidylinositol 3-kinase decreased VEGF production in COX-2-S cells. The addition of IL-6 to NSCLC cells resulted in increased apoptosis resistance. Furthermore, the inhibition of STAT3 or IL-6 induced apoptosis and reduced survivin expression, a member of the inhibitor of apoptosis protein family in COX-2-S cells. Conclusions: Overall, these findings suggest a novel pathway in which COX-2 activates STAT3 by inducing IL-6 expression. This pathway could contribute to tumor formation by promoting survivin-dependent apoptosis resistance and VEGF production. These findings provide a rationale for the future development of STAT3, IL-6, and/or COX-2-targeted therapies for the treatment of lung cancer.
Specialists or Generalists
Authors: Roger A. Rosenblatt
Journal: JAMA (1992)

One of the enduring debates in American medical policy is whether the United States should build its medical care system on a foundation of medical generalists or rely instead on more narrowly defined specialists.<sup>1,2</sup>For the most part, we have taken the latter road.<sup>3</sup>Despite 21 years of federal programs designed to increase the production of primary care physicians, most physicians select specialty careers, a trend that has accelerated with declining match rates in primary care fields in recent years.<sup>4</sup> Although the debate has been both loud and long, the evidence available to resolve this issue rationally has been somewhat meager and frequently flawed. It is very difficult to determine exactly what physicians do, much less how much it costs or how profound its impact. Answering these questions is difficult, methodologically treacherous, and enormously expensive. Unlike a population of laboratory animals, physicians are reluctant and often fractious