tbuckley/cabot-search huggingface dataset:
What has happened to charity?
Authors: Mark Aitken
Journal: Journal of the Royal Society of Medicine (2009)

Before 1948, hospital healthcare was funded by a mixture of voluntary charitable donations and compulsory local taxation. After 1948, this became compulsory national taxation. Initially the delivery of hospital healthcare differed very little from what had previously been available except that gratitude for charity gradually became replaced by a demand for service. Before 1948, members of hospital management boards were drawn from the local population and included substantial numbers of doctors. Most of these members were unpaid and freely gave their time1 just as others gave money to support the hospital's functions.

Today those boards have been replaced by highly-paid management executives who decide what is best for the local population without having to abide by the advice of the medical profession or even consult the representatives of the local community.2 The meaning of charity has become corrupted. Even the General Medical Council masquerades as a registered charity and yet it is funded by compulsory donations from the medical profession. Just as charity has become corrupted so has healthcare management become corrupt. The revelations of the way in which a certain private healthcare provider appears to have charged the NHS in Scotland millions of pounds for services which were not delivered3 is like a charity giving food aid to an African dictator who then fills the breadbaskets of his own cronies and leaves the general population starving. We would be outraged by the latter but just a little annoyed by the former even though that funding had been raised by public, albeit compulsory, donations.

In the current NHS climate governance has replaced conscience, accountability is just about money management and charity has been thrown out with Nye Bevan and his bathwater. The compassionate disbursement of compulsorily donated charitable funds and charity in its true sense need to be revived.
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis
Authors: Karoline Kollmann, Gerwin Heller, Christine Schneckenleithner, Wolfgang Warsch, Ruth Scheicher, Rene G. Ott, Markus Schäfer, Sabine Fajmann, Michaela Schlederer, Ana-Iris Schiefer, Ursula Reichart, Matthias Mayerhofer, Christoph Hoeller, Sabine Zöchbauer-Müller, Dontscho Kerjaschki, Christoph Bock, Lukas Kenner, Gerald Hoefler, Michael Freissmuth, Anthony R. Green, Richard Moriggl, Meinrad Busslinger, Marcos Malumbres, Veronika Sexl
Journal: Cancer Cell (2013)

In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a.
Gene expression profiles of idiopathic interstitial pneumonias: Identification of disease-specific diagnostic markers and molecular therapeutic targets
Authors: Nobuhisa Ishikawa, Noboru Hattori, Masaya Taniwaki, Yasushi Horimasu, Tomoyo Matsuda, Nobuoki Kohno
Journal: European Respiratory Journal (2012)

Introduction:  Idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) are characterized by alveolar epithelial damage and inflammatory responses that lead to fibroblast proliferation and, ultimately, to loss of normal pulmonary architecture and function. Differential diagnosis between IPF and NSIP may be difficult. The molecular mechanisms underlying idiopathic interstitial pneumonias (IIPs) remain unclear.   Aims:  This study aimed to elucidate the mechanisms underlying IIPs and identify disease-specific diagnostic markers and molecular therapeutic targets.   Methods:  The study included 12 patients with IIPs (IPF, 7 patients; NSIP, 5 patients). RNA was extracted from frozen lung specimens from the study population and was profiled using Illumina Human WG-6 v3 BeadChips. Gene ontology functional annotations were investigated in the genes upregulated in IIPs.   Results:  Evaluation of 48,000 transcripts in the expression profiles helped identify 1594 transcripts that were commonly upregulated in lung tissues from IIP patients compared to those from normal control subjects. The transcriptional profiles of IPF and NSIP were unexpectedly similar. Lungs with IIP were characterized by increased expression of transcripts associated with cell cycle, ABC transpoters and p53 signaling pathways, such as  MDM2 ,  RBL1, RAD21 ,  CFTR  and  BAX .   Conclusion:  The current data provide valuable information on the molecular mechanism underlying pulmonary fibrosis in IIP patients. Additionally, several potentially promising and novel diagnostic biomarkers as well as therapeutic targets have been identified for IIPs.
Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer's disease
Authors: Justin Paul, Sidney Strickland, Jerry P. Melchor
Journal: The Journal of Experimental Medicine (2007)

Cerebrovascular dysfunction contributes to the pathology and progression of Alzheimer's disease (AD), but the mechanisms are not completely understood. Using transgenic mouse models of AD (TgCRND8, PDAPP, and Tg2576), we evaluated blood–brain barrier damage and the role of fibrin and fibrinolysis in the progression of amyloid-β pathology. These mouse models showed age-dependent fibrin deposition coincident with areas of blood–brain barrier permeability as demonstrated by Evans blue extravasation. Three lines of evidence suggest that fibrin contributes to the pathology. First, AD mice with only one functional plasminogen gene, and therefore with reduced fibrinolysis, have increased neurovascular damage relative to AD mice. Conversely, AD mice with only one functional fibrinogen gene have decreased blood–brain barrier damage. Second, treatment of AD mice with the plasmin inhibitor tranexamic acid aggravated pathology, whereas removal of fibrinogen from the circulation of AD mice with ancrod treatment attenuated measures of neuroinflammation and vascular pathology. Third, pretreatment with ancrod reduced the increased pathology from plasmin inhibition. These results suggest that fibrin is a mediator of inflammation and may impede the reparative process for neurovascular damage in AD. Fibrin and the mechanisms involved in its accumulation and clearance may present novel therapeutic targets in slowing the progression of AD.
A CASE OF RUPTURE OF THE KIDNEY FROM SLIGHT TRAUMA
Authors: J. L. Atkinson
Journal: BMJ (1914)

Jackson's pericolic mnembrane, on the ether hand, may give rise to svmptoms simulating chr(onic appendicitis.This occasional membrane is a congenital abnormality, and takes oriain from the primitive riglht lateral process of the great omentum.Wllen only a limited band persists as a relic of the membrane, constriction of the ascending colon may result, tlhouglh often the symptoms resembling chronic appendicitis are due to an associated abnormal mobility of the proximal colon.
<i>TGFBR1</i>*6A and Cancer: A Meta-Analysis of 12 Case-Control Studies
Authors: Boris Pasche, Virginia Kaklamani, Nanjiang Hou, Taya Young, Alfred Rademaker, Paolo Peterlongo, Nathan Ellis, Kenneth Offit, Trinidad Caldes, Michael Reiss, Tongzhang Zheng
Journal: Journal of Clinical Oncology (2004)
Determining the optimal newborn screening protocol for cystic fibrosis
Authors: Kevin W Southern
Journal: Thorax (2012)

There is more published research examining newborn screening (NBS) for cystic fibrosis (CF) than for any other condition. Overall, the evidence for clinical benefit supports this strategy in an appropriate population with accessible healthcare provision. However, the evidence base is not as strong as one might expect, and this highlights the importance of ensuring that CF NBS programmes are designed and implemented in a rigorous and thoughtful manner that minimises potential distress for families.
Allergic bronchopulmonary fungal disease without clinical asthma.
Authors: J J Glancy, J L Elder, R McAleer
Journal: Thorax (1981)

During a retrospective survey of patients with pulmonary shadows and blood eosinophilia between the years 1965 and 1980, 42 patients were found with allergic bronchopulmonary fungal disease. Eleven of these had no clinical evidence of asthma. Three of these 11 had hypersensitivity to fungi other than Aspergillus sp. In the absence of asthma there was some difficulty in making a diagnosis, particularly where collapse of the upper lobe occurred in middle-aged or elderly patients and bronchogenic carcinoma was presumed responsible. We suggest that the term allergic bronchopulmonary aspergillosis be replaced by allergic bronchopulmonary fungal disease, the diagnosis be considered in patients with lung disease and blood eosinophilia even in the absence of asthma, and a wider range of fungal allergens be used for skin and precipitin tests.
S51 Thioredoxin modifies MIF release from human monocytes following stimulation with LTA and LPS
Authors: S. K. Leaver, G. J. Quinlan, T. W. Evans, A. Burke-Gaffney
Journal: Thorax (2010)

<h3>Rationale</h3> Thioredoxin (Trx) is a 12-kDa ubiquitous redox-active thiol (-SH) protein. Plasma levels of Trx are raised in numerous medical and surgical conditions associated with oxidative stress and inflammation such as sepsis (Burke-Gaffney 2005). Trx is thought to have an anti-inflammatory role, at least when released into the circulation. By contrast macrophage migration inhibitory factor (MIF) is regarded as a pivotal pro-inflammatory protein. Indeed co-injection of MIF and <i>E. coli</i> enhanced lethality, whereas, anti-MIF monoclonal antibodies conferred protection against murine caecal ligation and puncture and administration of <i>E. coli</i> (Calandra 2000). We have previously reported a positive correlation between Trx and MIF in adults with SIRS/sepsis. (Leaver 2009) Furthermore Trx was shown to inhibit the secretion of MIF in THP-1 cells (Tamaki 2006). The aim of this study was to determine the effect of exogenous Trx on the release of MIF and for comparison IL-8 and IL-10 from primary human monocytes at baseline and following stimulation with lipoteichoic acid (LTA) or lipopolysaccharide (LPS). <h3>Methods</h3> Monocytes were extracted from whole blood of healthy volunteers using Percoll gradients and MACS columns. Monocytes (1×10<sup>6</sup> cells/ml) were pre-incubated with Trx (0.1–10 000 nM) for 24 h followed by treatment (24 h) with medium alone, LPS 1 μg/ml, LTA 10μg/ml. MIF, IL-8 and IL-10 concentrations in cell supernatants were determined by ELISA. <h3>Results</h3> Following incubation with Trx there was no significant change in MIF release from monocytes. By contrast, LPS and LTA significantly (p&lt;0.01) induced MIF from base line. When monocytes were treated with LPS (Abstract S51 Figure 1) or LTA following pre-incubation with Trx, MIF release was significantly less than the theoretical additive effects of the two treatments alone. By contrast, although Trx significantly induced IL-8 and IL-10, Trx did not modulate LPS or LTA induced cytokine release. <h3>Conclusion</h3> Trx reduced MIF release following stimulation with LPS and LTA. Extracellular Trx exerts an anti-inflammatory effect in this model. The Trx/MIF axis should be explored as a potential route for therapeutic intervention in patients with sepsis.
The Challenge of Connecting the Dots in the B.R.A.I.N.
Authors: Anna Devor, Peter A. Bandettini, David A. Boas, James M. Bower, Richard B. Buxton, Lawrence B. Cohen, Anders M. Dale, Gaute T. Einevoll, Peter T. Fox, Maria Angela Franceschini, Karl J. Friston, James G. Fujimoto, Mark A. Geyer, Joel H. Greenberg, Eric Halgren, Matti S. Hämäläinen, Fritjof Helmchen, Bradley T. Hyman, Alan Jasanoff, Terry L. Jernigan, Lewis L. Judd, Seong-Gi Kim, David Kleinfeld, Nancy J. Kopell, Marta Kutas, Kenneth K. Kwong, Matthew E. Larkum, Eng H. Lo, Pierre J. Magistretti, Joseph B. Mandeville, Eliezer Masliah, Partha P. Mitra, William C. Mobley, Michael A. Moskowitz, Axel Nimmerjahn, John H. Reynolds, Bruce R. Rosen, Brian M. Salzberg, Chris B. Schaffer, Gabriel A. Silva, Peter T.C. So, Nicholas C. Spitzer, Roger B. Tootell, David C. Van Essen, Wim Vanduffel, Sergei A. Vinogradov, Lawrence L. Wald, Lihong V. Wang, Bruno Weber, Arjun G. Yodh
Journal: Neuron (2013)
Gastric motility and emptying in normal and post-vagotomy subjects.
Authors: H J Sheiner, M F Quinlan, I J Thompson
Journal: Gut (1980)

The effects of proximal gastric vagotomy (PGV) and vagotomy with pyloroplasty (V and P) on gastric motility were studied using a solid meal labelled with a radiopharmaceutical agent. In having on-line computer facilities it was possible not only to record the rate of emptying but also to analyse the relative roles of the fundus and the antrum within the overall framework of gastric emptying. In normal subjects the fundus filled and then emptied in an almost linear pattern. The antrum, however, did not completely fill until well after the meal was eaten and thereafter appeared to maintain a constant volume during the study. The redistribution of contents between fundus and antrum was reflected in the total stomach emptying curve as a delay, or lag phase before gastric emptying commenced. After both types of vagotomy fundic filling was delayed, representing a slower eating time, which was presumably due to early satiety. Antral filling and volume was disturbed only after V and P, which was also reflected by a loss of the lag phase seen on the total stomach curve. PGV retained antral function but there was significant delay in the redistribution of contents between fundus and antrum, though this did not have clinical significance. The rate of emptying was unaffected by either operation. It was concluded PGV did maintain antral function and a more normal pattern of emptying compared with V and P. After V and P the changes in antral function were considerable and these changes are probably associated with some of the complications resulting from this operation.
MCIP1 Overexpression Suppresses Left Ventricular Remodeling and Sustains Cardiac Function After Myocardial Infarction
Authors: Eva van Rooij, Pieter A. Doevendans, Harry J.G.M. Crijns, Sylvia Heeneman, Daniel J. Lips, Marc van Bilsen, R. Sanders Williams, Eric N. Olson, Rhonda Bassel-Duby, Beverly A. Rothermel, Leon J. De Windt
Journal: Circulation Research (2004)

Pathological remodeling of the left ventricle (LV) after myocardial infarction (MI) is a major cause of heart failure. Although cardiac hypertrophy after increased loading conditions has been recognized as a clinical risk factor for human heart failure, it is unknown whether post-MI hypertrophic remodeling of the myocardium is beneficial for cardiac function over time, nor which regulatory pathways play a crucial role in this process. To address these questions, transgenic (TG) mice engineered to overexpress modulatory calcineurin-interacting protein-1 (MCIP1) in the myocardium were used to achieve cardiac-specific inhibition of calcineurin activation. MCIP1-TG mice and their wild-type (WT) littermates, were subjected to MI and analyzed 4 weeks later. At 4 weeks after MI, calcineurin was activated in the LV of WT mice, which was significantly reduced in MCIP1-TG mice. WT mice displayed a 78% increase in LV mass after MI, which was reduced by 38% in MCIP1-TG mice. Echocardiography indicated marked LV dilation and loss of systolic function in WT-MI mice, whereas TG-MI mice displayed a remarkable preservation of LV geometry and contractility, a pronounced reduction in myofiber hypertrophy, collagen deposition, and beta-MHC expression compared with WT-MI mice. Together, these results reveal a protective role for MCIP1 in the post-MI heart and suggest that calcineurin is a crucial regulator of postinfarction-induced pathological LV remodeling. The improvement in functional, structural, and molecular abnormalities in MCIP1-TG mice challenges the adaptive value of post-MI hypertrophy of the remote myocardium. The full text of this article is available online at http://circres.ahajournals.org.
Primary Lymphoma of the Liver: Clinical–Pathological Features and Relationship With Hcv Infection in French Patients
Authors: Jean-Pierre Bronowicki, Catherine Bineau, Pierre Feugier, Olivier Hermine, Nicole Brousse, Frédéric Oberti, Marie-Christine Rousselet, Sébastien Dharancy, Philippe Gaulard, Jean-François Flejou, Dominique Cazals-Hatem, Eric Labouyrie
Journal: Hepatology (2003)

Primary lymphoma of the liver (PLL) is rare. In some cases, the hepatic lymphoma has been diagnosed in patients who were infected by the hepatitis C virus (HCV). It has been suggested that HCV plays a role in the pathogenesis of lymphoma. The aim of our multicentric retrospective study was to assess the characteristics of PLL and to determine the prevalence of HCV infection in PLL. Thirty-one immunocompetent patients (anti-human immunodeficiency virus, anti-human T-cell leukemia/lymphoma virus negative, no history of allograft) with PLL fulfilled the entire selection criteria. The liver biopsy specimens were reassessed by the same pathologist. The non-Hodgkin's lymphomas were classified according to the World Health Organization classification. Blood samples were tested in 28 patients for antibodies to HCV, and HCV RNA was detected by reverse transcription polymerase chain reaction. In the majority of cases, the clinical, biologic, and radiologic data were nonspecific. Twenty-seven of 31 patients presented a B-cell lymphoma corresponding to the centroblastic morphologic variant of a diffuse, large B-cell lymphoma (22 cases), a Burkitt's lymphoma (1 case), an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (3 cases), and unclassified, small B-cell lymphoma (1 case). The 4 other cases were T-cell lymphomas. The prevalence of HCV infection was 21% (6 of 28 cases). All of these patients were positive for HCV RNA by polymerase chain reaction in blood. Most of the HCV-infected patients presented a high-grade, B-cell type lymphoma. In conclusion, our study confirms the rarity of PLL and demonstrates an increased prevalence of HCV infection.
Clinical Response to Crizotinib Retreatment After Acquisition of Drug Resistance
Authors: Hiromichi Matsuoka, Takayasu Kurata, Isamu Okamoto, Hiroyasu Kaneda, Kaoru Tanaka, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2013)

A 39-year-old Japanese male former smoker presented at our hospital with several months of history of an occasional dry cough.He was found to have stage IV (cT4, N2, M1b) adenocarcinoma of the lung with bone metastasis.He received six courses of first-line chemotherapy with cisplatin and pemetrexed.His best response was a partial response, and after 7 months of first-line treatment, he showed evidence of progressive disease, with an increase in the size and number of pulmonary metastases as well as pleural fluid accumulation (Fig 1A).Mutation analysis of biopsied tumor tissue revealed that the tumor was wild type for the epidermal growth factor receptor (EGFR) gene.However, fluorescent in situ hybridization analysis with breakapart probes for the anaplastic lymphoma kinase gene (ALK) revealed the presence of an ALK rearrangement.As a second-line treatment, therefore, crizotinib was administered orally at a dose of 250 mg twice per day.Marked tumor regression became apparent (Fig 1B), and this response persisted for 4 months.Given that crizotinib toxicities were mild and manageable, the drug was administered without pause or dose reduction.After this time, however, pulmonary metastases again developed, and crizotinib was discontinued.The patient was enrolled e322
An extravascular hydraulic system to control blood pressure by a feedback regulation of the venous return
Authors: D. A SIDERIS, P. E VARDAS, D. N CHRYSOS, S. T TOUMANIDIS, L. MICHALIS, S. D MOULOPOULOS
Journal: Cardiovascular Research (1987)

Journal Article An extravascular hydraulic system to control blood pressure by a feedback regulation of the venous return Get access DIMITRIS A SIDERIS, DIMITRIS A SIDERIS From the Department of Clinical Therapeutics, Medical Department of Athens University, Athens, Greece Address for correspondence and reprints: Dr Dimitris A Sideris, Department of Clinical Therapeutics, Alexandra Maternity Hospital, Vas Sofias and Kourou Street, GR-115 28 Athens, Greece. Search for other works by this author on: Oxford Academic PubMed Google Scholar PANAYOTIS E VARDAS, PANAYOTIS E VARDAS From the Department of Clinical Therapeutics, Medical Department of Athens University, Athens, Greece Search for other works by this author on: Oxford Academic PubMed Google Scholar DIMITRIS N CHRYSOS, DIMITRIS N CHRYSOS From the Department of Clinical Therapeutics, Medical Department of Athens University, Athens, Greece Search for other works by this author on: Oxford Academic PubMed Google Scholar SAVVAS T TOUMANIDIS, SAVVAS T TOUMANIDIS From the Department of Clinical Therapeutics, Medical Department of Athens University, Athens, Greece Search for other works by this author on: Oxford Academic PubMed Google Scholar LAMBROS MICHALIS, LAMBROS MICHALIS From the Department of Clinical Therapeutics, Medical Department of Athens University, Athens, Greece Search for other works by this author on: Oxford Academic PubMed Google Scholar SPYRIDON D MOULOPOULOS SPYRIDON D MOULOPOULOS From the Department of Clinical Therapeutics, Medical Department of Athens University, Athens, Greece Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 21, Issue 5, May 1987, Pages 337–341, https://doi.org/10.1093/cvr/21.5.337 Published: 01 May 1987 Article history Received: 14 May 1986 Accepted: 15 October 1986 Published: 01 May 1987
Toxicity and efficacy of conventional amphotericin B deoxycholate versus escalating doses of amphotericin B deoxycholate—fat emulsion in HIV-infected patients with oral candidosis
Authors: Pascal Chavanet, Claudine Clement, Michel Duong, Marielle Buisson, Philippe D'Athis, Monique Dumas, Alain Bonnin, Henri Portier
Journal: Clinical Microbiology and Infection (1997)