tbuckley/cabot-search huggingface dataset:
Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions via MKK6 activation
Authors: René Köffel, Anastasia Meshcheryakova, Joanna Warszawska, Annika Hennig, Karin Wagner, Almut Jörgl, Daniela Gubi, Doris Moser, Anastasiya Hladik, Ulrike Hoffmann, Michael B. Fischer, Wim van den Berg, Marije Koenders, Clemens Scheinecker, Bernhard Gesslbauer, Sylvia Knapp, Herbert Strobl
Journal: Blood (2014)
Abstract LB-305: Why two are better than one: Suppression of carcinoma cell growth <i>in vitro</i> and in human HGF/SF transgenic SCID by inhibitors of MET (SGX523) and EGFR (erlotinib)
Authors: Yu-Wen Zhang, Ben Staal, Curt Essenburg, Yanli Su, Liang Kang, Rich West, Dafna Kaufman, Tom DeKoning, Bryn Eagleson, Sean Buchanan, George Vande Woude
Journal: Cancer Research (2010)

Abstract The signaling cascade originating from hepatocyte growth factor/scatter factor (HGF/SF)-MET ligand-receptor pair is frequently observed in a broad spectrum of human cancers. Inappropriate activation of this pathway has been shown to occur via: paracrine/autocrine activation; by amplification or mutation in the MET gene; or through ligand independent mechanisms (www.vai.org/met). Various MET drugs targeting this pathway are under development and in need of relevant in vivo tumor models to allow assessment of drug efficacy alone or in combination against human MET expressing tumors. Conventional mouse models post a significant limitation on fulfilling such demand as mouse HGF/SF has low affinity/activity on the human MET. Such limitations are abrogated in human HGF/SF transgenic SCIDs (designated hHGFtg-SCID), which, unlike its non-transgenic littermates, produce human HGF/SF to allow human MET signaling on cells of human cancer xenografts. Here, we show that the hHGFtg-SCID mouse significantly enhances tumor xenograft growth of many MET-expressing human carcinoma cell lines including lung, breast, kidney, colon, gastric and pancreatic cancers. Using the hHGFtg-SCID mouse model systems, we demonstrated that SGX523, a MET small molecule kinase inhibitor which suppressed MET phosphorylation and downstream signaling activation in vitro, partially inhibits the growth of xenografts derived from NCI-H596 lung cancer cells, HCC1954 breast cancer cells and HPAF II pancreatic cancer cells. Furthermore, we found that the partial tumor growth inhibition by SGX523 was significantly enhanced by co-administration of erlotinib, the EGFR small molecule kinase inhibitor. In vitro, erlotinib also enhanced SGX523 inhibitory activity in cell proliferation and G1/S cell cycle progression assays. Our data suggest that the hHGFtg-SCID mouse is a valuable system for evaluating MET drugs, and simultaneously targeting MET and EGFR pathways may provide a better treatment for cancers harboring inappropriate activation of both pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-305.
Book Review Death in Childbirth: An International Study of Maternal Care and Maternal Mortality 1800-1950 By Irvine Loudon. 622 pp. Oxford, England, Clarendon Press, 1993. $95. (Distributed in the U.S. by Oxford University Press, New York.) 0-19-822997-6
Authors: Charlotte G. Borst
Journal: New England Journal of Medicine (1993)
Vital Staining of Cardiac Myocytes During Embryonic Stem Cell Cardiogenesis In Vitro
Authors: Joseph M. Metzger, Wan-In Lin, Linda C. Samuelson
Journal: Circulation Research (1996)

Abstract Mouse embryonic stem (ES) cells differentiate in vitro into a variety of cell types, including spontaneously contracting cardiac myocytes. The primary aim of this work was to use vital stain techniques for real-time detection of developing cardiac myocytes in ES cell differentiation cultures. The −440 to +6 human cardiac α-actin promoter was used to direct expression of the Escherichia coli reporter gene lacZ (pHCActlacZ) into ES cell–derived cardiac myocytes during cardiogenesis in vitro. Undifferentiated ES cells were electroporated with HCActlacZ together with a plasmid containing the neomycin gene under the direction of the phosphoglycerate kinase promoter, and stable transformants were selected in G418. Individual clones were screened for activation of lacZ gene expression in cardiac myocytes developing in vitro. Results showed that expression of the HCActlacZ reporter construct was activated very early during the ES cell differentiation program, at a time point before the appearance of spontaneous contractile activity. The earliest detection was at day 6 of differentiation, when ≈25% of the differentiation cultures expressed the reporter construct, with expression increasing to ≈70% at day 9 and continuing throughout the duration of spontaneous contractile activity exhibited by the ES cell–derived cardiac myocytes. Indirect immunofluorescence assays provide evidence that expression was restricted to the cardiac myocytes in culture. In the present study, we show vital staining of transgene expression in living cardiac myocytes using lipophilic fluorogenic β-galactopyranoside substrates for real-time detection of the reporter gene during continuous contraction of the ES cell myocytes in vitro. The vital stain approach used in the present study will permit the identification of differentiating ES cells that are committed to the cardiac lineage for analysis of gene expression at early time points of ES cell cardiogenesis and, in addition, will aid in selecting genetically modified ES cell cardiac myocytes for use in functional studies.
FREQUENCY OF RISK FACTORS FOR ISCHÆMIC HEART-DISEASE IN A HEALTHY BRITISH POPULATION
Authors: B. Lewis, I.D.P. Wootton, D.M. Krikler, A. February, A. Chait, C.M. Oakley, G. Sigurdsson, B. Maurer, J. Birkhead
Journal: The Lancet (1974)
T5 Opg Regulates Pulmonary Arterial Smooth Muscle Cell Proliferation And The Expression Of Pah-associated Genes Via Fas
Authors: S. Dawson, J. Pickworth, A. Rothman, J. Iremonger, N. Arnold, S. Francis, A. Lawrie
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive pulmonary vascular remodelling, a key component of which is the proliferation and migration of pulmonary arterial smooth muscle cells (PA-SMCs). Although current therapies are good at alleviating symptoms, they do not reverse the underlying pulmonary vascular remodelling. We have previously demonstrated that the secreted glycoprotein, osteoprotegerin (OPG, TNFRSF11B), is elevated within pulmonary vascular lesions and serum from idiopathic PAH (IPAH) patients and induces PA-SMC proliferation and migration <i>in vitro</i>. Furthermore, genetic deletion or antibody blockade of OPG can prevent and reverse disease in pre-clinical animal models. However, how OPG signals to mediate PA-SMC phenotype remains unclear. We therefore aimed to characterise the OPG signalling cascade in PA-SMCs, and identify the receptor through which this is mediated. <h3>Methods</h3> PA-SMCs were stimulated with 0.2% FCS and OPG (50 ng/ml) for 10 and 60 min. Phosphorylation targets were identified by Kinex antibody microarray (Kinexus, Canada). An RNA expression microarray (Agilent) was performed on PA-SMCs following 6-hour OPG stimulation. OPG binding partners were identified following reverse transfection of HEK293 cells with 2054 human membrane proteins (Retrogenix, Sheffield, UK). Interactions were confirmed in PA-SMCs by co-immunoprecipitation. PA-SMCs were pre-treated with Fas neutralising antibody (1500 ng/ml), TRAIL antibody (1500 ng/ml) or both antibodies, 30 min before OPG stimulation. Proliferation was assessed after 72 h. <h3>Results</h3> OPG induced significant activation of CDK4 and CDK5, HSP27 and ERK1/2, and significant decrease in phospho-mTOR. OPG significantly altered the expression of 57 PAH-associated genes, including TRAIL. Four novel OPG interactions with IL1RAcP, Fas, TMPRSS11D and GAP43 were identified and we confirmed OPG interaction with IL1RAcP and Fas in PA-SMC. Fas RNA expression was elevated in IPAH PA-SMCs and protein expression was elevated in the right ventricle and pulmonary artery from IPAH patients. Fas blockade reduced OPG-induced proliferation by ~40%, which was further reduced by simultaneous TRAIL blockade. Fas blockade also prevented OPG-induced PDGFRA and TNC RNA expression. <h3>Conclusions</h3> These studies begin to reveal the intracellular signalling mechanisms and receptor through which OPG induces PA-SMC proliferation, further highlighting the therapeutic potential of targeting OPG in PAH.
Glycemic Control in Early IDDM
Authors: Catherine Allen, Daniel J Zaccaro, Mari Palta, Ronald Klein, Stephen C Duck, Donn J D'Alessio
Journal: Diabetes Care (1992)

OBJECTIVE A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. RESEARCH DESIGN AND METHODS Unselected cases with IDDM, who were &amp;lt; 30 yr of age, were identified at diagnosis from a 28-county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. RESULTS In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P &amp;lt; 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P &amp;gt; 0.10). Adolescent males (10–19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P &amp;lt; 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children &amp;lt; 10 yr of age (P &amp;lt; 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. CONCLUSIONS These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self-management.
Reasons for longer hospital waiting times need to be understood, says Nuffield Trust
Authors: G. Iacobucci
Journal: BMJ (2015)

NHS hospitals will continue to struggle to meet waiting time targets in the future because of systemic problems in the health service, a new analysis from the Nuffield Trust claims.1

The healthcare think tank said that, although previous dips in national performance against targets had been attributed to failings at a handful of low performing hospital trusts, some measures had deteriorated markedly at hospitals over the past year, across the performance spectrum. The trust warned of “no quick fixes” to reverse the trend and said that the NHS should be prepared for further breaches.

The analysis was presented in a new policy briefing from the Nuffield Trust that assessed how all 156 hospital trusts in England have …
Effectiveness of Coronary Artery Bypass Grafting With or Without Cardiopulmonary Bypass in Overweight Patients
Authors: Raimondo Ascione, Barnaby C. Reeves, Karen Rees, Gianni D. Angelini
Journal: Circulation (2002)

Background— Off-pump coronary artery bypass surgery has been demonstrated to reduce morbidity in elective patients. However, high-risk patients might benefit the most from this surgical procedure. Our goal was to investigate the effectiveness of on-pump and off-pump coronary artery bypass surgery on early clinical outcome in a consecutive series of overweight patients. Methods and Results— From April 1996 to April 2001, data on 4321 patients undergoing coronary surgery (mortality 1.4%) were prospectively entered into the Patient Analysis and Tracking System. Data were extracted for all patients with a body mass index ≥25 kg/m 2 . A risk-adjusted analysis was performed to assess the effect of surgical technique in the whole overweight cohort. 2844 patients were identified (2261 male, median age 63, interquartile range 56 to 68). Patients undergoing on-pump surgery (2170, 76.3%) were less likely than those undergoing off-pump surgery to have hypercholesterolemia or left main stem disease and were, on average, less obese. However, they were more likely to have unstable angina and to have had a previous myocardial infarction, and they had more extensive coronary disease and received more grafts (all P &lt;0.05). Unadjusted analyses, taking account only of consultant team, showed significant benefits of off-pump surgery in terms of hospital deaths, arrhythmias, inotropic use, use of intra-aortic balloon pump, blood loss, transfusion requirement, postoperative hemoglobin, chest infections, neurological complications, intensive care unit and hospital stay (all P &lt;0.05). After adjustment for confounding prognostic factors, the benefits of off-pump surgery were still significant for death in hospital, transfusion requirement, postoperative hemoglobin, neurological complications, intensive care unit and hospital stay (ORs 0.35 to 0.79, P &lt;0.05). Conclusions— These results suggest that off-pump surgery is safe and effective and is associated with a reduced in-hospital mortality and morbidity in overweight patients when compared with conventional coronary surgery with cardiopulmonary bypass and cardioplegic arrest.
Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis.
Authors: H Koyama, K Nishimura, T Mio, A Ikeda, N Sugiura, T Izumi
Journal: Thorax (1994)

BACKGROUND--Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. METHODS--Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. RESULTS--Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). CONCLUSIONS--The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.
No Smallpox in Uniontown.
Authors: Jacob S. Hackney
Journal: JAMA (1899)

Uniontown, Pa., May 6, 1899. <h3>To the Editor:</h3> —Under the caption of "Medical News," in the Journal of May 6, you state Uniontown has eight cases of smallpox and that the government has ordered all mail fumigated, and that the freight and traffic business has been suspended. I have been practicing medicine at this place for the past fifteen years and during all that time this is the first that I have ever heard that we had any smallpox. Allow me to correct your statement and say that there is not and has not been any smallpox at this place for the past twenty years. Very respectfully, [The correspondent who furnished us the item referred to will not repeat the offence.—Ed.]
Rationale for Total Pancreatectomy for Carcinoma of the Pancreatic Head
Authors: John J. Collins, John E. Craighead, John R. Brooks
Journal: New England Journal of Medicine (1966)

THE results of surgical treatment of carcinoma of the head of the pancreas are disappointing. Only about 10 per cent of patients operated upon are considered candidates for removal of the neoplasm.1 Of these, fewer than 13 per cent can be expected to survive for five years or more.1 2 3 A review of our experience with 11 consecutive Whipple operations¶ performed for carcinoma of the head of the pancreas at the Peter Bent Brigham Hospital suggests that subtotal pancreatectomy does not remove all the primary tumor in a significant proportion of cases. Total pancreatectomy appears to offer more promise and results . . .
Evaluating Glioma Therapies: Modeling Treatments and Predicting Outcomes
Authors: S. Kirby, M. Brothers, W. Irish, R. Florell, D. Macdonald, C. Schold, G. Cairncross
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Evaluating Glioma Therapies: Modeling Treatments and Predicting Outcomes Get access Sarah Kirby, Sarah Kirby Departments of Clinical Neurological Sciences and Oncology, University of Western Ontario, and London Regional Cancer CentreLondon, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Brothers, Michael Brothers Department of Radiology, Duke University Medical CenterDurham, NC Search for other works by this author on: Oxford Academic PubMed Google Scholar William Irish, William Irish Pittsburgh Transplantation Unit, University of PittsburghPA Search for other works by this author on: Oxford Academic PubMed Google Scholar Randall Florell, Randall Florell Departments of Clinical Neurological Sciences and Oncology, University of Western Ontario, and London Regional Cancer CentreLondon, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar David Macdonald, David Macdonald Departments of Clinical Neurological Sciences and Oncology, University of Western Ontario, and London Regional Cancer CentreLondon, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Clifford Schold, Clifford Schold Department of Neurology, Southwestern Medical CenterDallas, TX Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory Cairncross Gregory Cairncross * Departments of Clinical Neurological Sciences and Oncology, University of Western Ontario, and London Regional Cancer CentreLondon, Ontario, Canada *Correspondence to : Gregory Cairncross, M.D., London Regional Cancer Centre, 790 Commissioners Rd., E., London, ON, Canada N6A 4L6. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 24, 20 December 1995, Pages 1884–1888, https://doi.org/10.1093/jnci/87.24.1884 Published: 20 December 1995 Article history Received: 18 June 1995 Revision received: 30 August 1995 Accepted: 20 September 1995 Published: 20 December 1995
Concurrent and Predictive Validity of the Personality Disorder Diagnosis in Adolescent Inpatients
Authors: Kenneth N. Levy, Daniel F. Becker, Carlos M. Grilo, Jonathan J.F. Mattanah, Kathleen E. Garnet, Donald M. Quinlan, William S. Edell, Thomas H. McGlashan
Journal: American Journal of Psychiatry (1999)

The authors investigated the concurrent and predictive validity of the DSM-III-R diagnosis of personality disorder in adolescents by means of baseline and follow-up assessments of inpatients treated at the Yale Psychiatric Institute.One hundred sixty-five hospitalized adolescents were reliably assessed by using a structured interview for personality disorder diagnoses as well as two measures of impairment and distress--the Global Assessment of Functioning Scale and the SCL-90-R. Two years after initial assessment, 101 subjects were independently reassessed with the same measures; their functioning was also assessed at this time.At baseline, adolescents with personality disorders were significantly more impaired than those without personality disorders. At follow-up, adolescents with a personality disorder diagnosis at baseline had used significantly more drugs and had required more inpatient treatment during the follow-up interval. Over time, the scores on the Global Assessment of Functioning Scale and SCL-90-R of adolescents diagnosed with a personality disorder at baseline became more similar to the scores of adolescents without a personality disorder.The diagnosis of personality disorder in adolescent inpatients has good concurrent validity; however, the predictive validity of the diagnosis is mixed.
Rape with Extreme Violence: The New Pathology in South Kivu, Democratic Republic of Congo
Authors: Denis Mukengere Mukwege, Cathy Nangini
Journal: PLoS Medicine (2009)

Cathy Nangini and Denis Mukwege describe their work at the Panzi Hospital in the Democratic Republic of Congo, which treats women victims of rape with extreme violence that are often perpetrated at the hands of armed groups.
Clinical Lectures on Mental Diseases.
Authors: Thomas Smith Clouston
Journal: JAMA (1904)

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