tbuckley/cabot-search huggingface dataset:
Pressure-Volume Correlates of Left Ventricular Oxygen Consumption in the Hypervolemic Dog
Authors: ELLIS L. ROLETT, PETER M. YURCHAK, WILLIAM B. HOOD, RICHARD GORLIN
Journal: Circulation Research (1965)

Volume changes in the intact functioning canine left ventricle were induced by whole blood infusion and were measured by the thermodilution technic. Multiple regression analyses were performed to detect significant correlations between hemodynamic variables and left ventricular oxygen consumption. Hemodynamic variables, in addition to the pressure-time integral, ventricular volume, and ventricular work, included estimates of myocardial stress, force, and shortening. The most significant individual correlates of oxygen consumption were the pressure-time integral ( r =0.91) and ventricular end systolic volume ( r =0.81), whereas the interaction of volume with pressure-time, thus approximating wall stress and force, was the most significant variable overall (r=0.93). A number of multiple linear regression models were tested for the prediction of ventricular oxygen consumption. The equation (model E) with the greatest multiple regression coefficient (R=0.947) included heart rate, pressure-time per beat, pressure-time per minute, end systolic volume, and (end systolic volume) 2/3 as independent variables. A less elaborate regression equation including only pressure-time per minute and end systolic volume as independent variables was, however, nearly as accurate as model E in the prediction of oxygen consumption. The addition of estimates of left ventricular work and shortening to these regression models did not further improve the ability to predict oxygen consumption accurately. The relationships between these hemodynamic variables and ventricular oxygen consumption were not altered by pericardiotomy or catecholamine depletion. In the hypervolumic heart acute ventricular dilatation did not occur following pericardiotomy. The results of this study confirm the postulate that an increase in ventricular volume, as well as pressure, will be accompanied by an increase in ventricular oxygen consumption. This in turn implies a relationship between the wall stress or force generated by the myocardium and the energy requirement of contraction.
MMTV Env encodes an ITAM responsible for transformation of mammary epithelial cells in three-dimensional culture
Authors: Elad Katz, Mohamed H. Lareef, John C. Rassa, Shannon M. Grande, Leslie B. King, Jose Russo, Susan R. Ross, John G. Monroe
Journal: The Journal of Experimental Medicine (2005)

Expression of immunoreceptor tyrosine-based activation motif (ITAM)-containing signaling proteins is normally restricted to hematopoietic tissues. The basal activity of ITAM-containing proteins is mediated through negative regulation by coreceptors restricted to hematopoietic tissues. We have identified an ITAM signaling domain encoded within the env gene of murine mammary tumor virus (MMTV). Three-dimensional structures derived in vitro from murine cells stably transfected with MMTV env display a depolarized morphology in comparison with control mammary epithelial cells. This effect is abolished by Y&amp;gt;F substitution within the Env ITAM, as well as inhibitors of Syk and Src protein tyrosine kinases. Env-expressing cells bear hallmarks of cell transformation such as sensitivity to apoptosis induced by tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) or TNFα, as well as down-regulation of E-cadherin and Keratin-18. Human normal mammary epithelial cells expressing MMTV Env also develop transformed phenotype, as typified by growth in soft agar and Matrigel invasion. These disruptions are abrogated by Y&amp;gt;F substitutions. We conclude that ITAM-dependent signals are generated through MMTV Env and trigger early hallmarks of transformation of mouse and human mammary epithelial cells. Therefore, these data suggest a heretofore unappreciated potential mechanism for the initiation of breast cancer and identify MMTV Env and ITAM-containing proteins in human breast tumors as probable oncoproteins.
Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids.
Authors: G E Packe, J G Douglas, A F McDonald, S P Robins, D M Reid
Journal: Thorax (1992)

BACKGROUND: Asthmatic patients taking low to moderate doses of inhaled topical corticosteroids have been shown to have lower bone density than those taking bronchodilators only. There is little information on bone density in asthmatic patients taking high dose inhaled corticosteroids. METHODS: Bone mass was studied in three age matched groups of asthmatic patients. These comprised: 17 asthmatic patients who had never taken inhaled or systemic corticosteroids (group 1); 20 patients who had taken beclomethasone diproprionate in a dosage of 1000-2000 micrograms daily for at least a year, who had also received courses of systemic corticosteroids in the past (group 2); and 20 patients who were taking both high dose inhaled corticosteroids and regular low dose prednisolone, at a median dose of 7 mg daily (group 3). Vertebral bone density was measured by quantitative computed tomography. Biochemical indices of bone formation and resorption were also measured. RESULTS: Mean bone density in group 2 (127.5(22.6) mg/ml) was similar to that in group 3 (114.5 (36.0) mg/ml). Bone density was significantly lower in both of these groups than in group 1 (160.4 (27.4) mg/ml). There were no significant differences between groups for any of the markers of bone formation and resorption. CONCLUSIONS: Asthmatic patients receiving high dose inhaled beclomethasone and intermittent courses of systemic corticosteroids have reduced vertebral bone density. The bone loss is similar in degree to that seen in patients taking high dose inhaled topical corticosteroids and continuous low dose systemic corticosteroids.
Growth factor delivery methods in the management of sports injuries: the state of play
Authors: L Creaney, B Hamilton
Journal: British Journal of Sports Medicine (2007)

In recent years there have been rapid developments in the use of growth factors for accelerated healing of injury. Growth factors have been used in maxillo-facial and plastic surgery with success and the technology is now being developed for orthopaedics and sports medicine applications. Growth factors mediate the biological processes necessary for repair of soft tissues such as muscle, tendon and ligament following acute traumatic or overuse injury, and animal studies have demonstrated clear benefits in terms of accelerated healing. There are various ways of delivering higher doses of growth factors to injured tissue, but each has in common a reliance on release of growth factors from blood platelets. Platelets contain growth factors in their α-granules (insulin-like growth factor-1, basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, vascular endothelial growth factor, transforming growth factor-β 1 ) and these are released upon injection at the site of an injury. Three commonly utilised techniques are known as platelet-rich plasma, autologous blood injections and autologous conditioned serum. Each of these techniques has been studied clinically in humans to a very limited degree so far, but results are promising in terms of earlier return to play following muscle and particularly tendon injury. The use of growth factors in sports medicine is restricted under the terms of the World Anti-Doping Agency (WADA) anti-doping code, particularly because of concerns regarding the insulin-like growth factor-1 content of such preparations, and the potential for abuse as performance-enhancing agents. The basic science and clinical trials related to the technology are reviewed, and the use of such agents in relation to the WADA code is discussed.
Mechanistic curiosity will not kill the Bayesian cat
Authors: Denny Borsboom, Eric-Jan Wagenmakers, Jan-Willem Romeijn
Journal: Behavioral and Brain Sciences (2011)

Abstract Jones &amp; Love (J&amp;L) suggest that Bayesian approaches to the explanation of human behavior should be constrained by mechanistic theories. We argue that their proposal misconstrues the relation between process models, such as the Bayesian model, and mechanisms. While mechanistic theories can answer specific issues that arise from the study of processes, one cannot expect them to provide constraints in general.
Poor diagnostic value of colonic CD44v6 expression and serum concentrations of its soluble form in the differentiation of ulcerative colitis from Crohn’s disease
Authors: W Reinisch, K-H Heider, G Oberhuber, C Dejaco, M Müllner, G R Adolf, C Gasché
Journal: Gut (1998)

Increased expression of CD44v6 on colonic crypt epithelial cells in ulcerative colitis has been suggested as a diagnostic tool to distinguish ulcerative colitis from colonic Crohn's disease.To investigate colonic CD44v6 expression and serum concentrations of soluble CD44v6 (sCD44v6) in patients with ulcerative colitis and Crohn's disease.Colonic biopsy samples were obtained from 16 patients with ulcerative colitis, 13 with ileocolonic Crohn's disease, and 10 undergoing polypectomy. Serum samples were obtained from 15 patients with active ulcerative colitis, 20 with active Crohn's disease, and 20 healthy donors. Colonic CD44v6 expression was evaluated immunohistochemically by monoclonal antibody 2F10 and the higher affinity monoclonal antibody VFF18. Serum sCD44v6 concentrations were measured by ELISA.2F10 stained colonic epithelium of inflamed ulcerative colitis and Crohn's disease samples in 80% and 40% of cases, respectively, and VFF18 in 95% and 87%, respectively. Both monoclonal antibodies displayed a sensitivity and specificity of 60% and 87% to differentiate ulcerative colitis from colonic Crohn's disease. Serum concentrations of sCD44v6 were lower in patients with ulcerative colitis (median 153 ng/ml; interquartile range (IQR) 122-211) compared with Crohn's disease (219; IQR 180-243) and healthy donors (221; IQR 197-241 (p = 0.002)). Its sensitivity and specificity to discriminate ulcerative colitis from Crohn's disease was 75% and 71%, respectively.Colonic CD44v6 and serum sCD44v6 concentrations do not facilitate reliable differential diagnosis between ulcerative colitis and Crohn's disease.
The role of maternal obesity in susceptibility to respiratory viral infection and exacerbation rate in pregnant women with asthma
Authors: Vanessa Murphy, Heather Powell, Peter Gibson
Journal: European Respiratory Journal (2014)

Obesity may be a risk factor for exacerbations of asthma, but the mechanisms of this effect in pregnancy are unknown.  The aim was to determine the influence of body mass index (BMI) on the risk of asthma exacerbations during pregnancy, and investigate the role of respiratory viral infection.  Women with asthma (n=164) participated in a prospective study of viral infection and asthma exacerbations during pregnancy. BMI recorded at baseline (17 weeks) was categorised as healthy weight (18.5-24.9), overweight (25-29.9) or obese (>30). Exacerbations requiring medical intervention were recorded. Asthma control (ACQ7), medication use, exhaled nitric oxide (FENO), lung function and common colds were assessed monthly. Additional visits were attended during colds and exacerbations. Nasal and throat swabs were collected during suspected infections and viruses determined by polymerase chain reaction (PCR).  Overweight or obese women had a higher prevalence of exacerbations during pregnancy (49.5%) than healthy weight women (25%, P=0.007). ACQ during exacerbation was higher in overweight/obese women (median 2.14) than in healthy weight women (1.69, P=0.025). FENO during first exacerbation 13.4 (median, IQR 8.2, 39.2) in the healthy weight group (n=8), 19.9 (9.5, 34.1) in the overweight group (n=22) and 8.8 (6, 20) in the obese group (n=27, P=0.1083). Overweight/obese women were more likely to have exacerbations associated with PCR positive respiratory viral infections (24.7%) than healthy weight women (8.3%, P=0.284).  Being overweight/obese confers a greater risk of asthma exacerbation during pregnancy, and may be due to increased susceptibility to viral infection.
More outsourcing of public services could save 22.6bn a year, says Confederation of British Industry
Authors: Z. Kmietowicz
Journal: BMJ (2012)

If the government overcame its lacklustre approach to competition and gave private and other independent providers the opportunity to run a much larger share of public services, it could realise savings of £22.6bn (€28bn; $37bn) or more a year, says a new report from the Confederation of British Industry.1

Pressure on all areas of public services resulting from changing demographics and a need to make savings means that “business as usual is not an option,” said John Cridland, director general of the CBI, at a press briefing to launch its report. The CBI represents 240 000 businesses in the United Kingdom.

Despite the publication of the white paper on open public services last July, the government has so far lacked the momentum to push the policy, said Cridland.

He said that the government …
Incidence of Thyroid Cancer in Women in Relation to Previous Exposure to Radiation Therapy and History of Thyroid Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Anne M. McTiernan, Noel S. Weiss, Janet R. Daling
Journal: JNCI Journal of the National Cancer Institute (1984)

Female residents of 13 counties of Western Washington, in whom papillary, follicular, or mixed papillary-follicular thyroid carcinomas had been diagnosed between 1974 and 1979 were interviewed regarding their medical and reproductive histories and past exposure to radiation treatments. For comparison, a random sample of women from the same population was interviewed. Women who had received radiation treatments to the head or neck prior to 5 years before interview were 16.5 times (95% confidence interval = 8.1-33.5) more likely than unexposed women to develop cancer. The relative risk (RR) was highest for papillary cancer (19.4) but also was elevated substantially for follicular and mixed papillary-follicular tumors. Women first irradiated at age 19 years or younger had a much higher RR than did women irradiated at age 20 or older. Regardless of prior radiation exposure, women who ever had had a goiter were at increased risk of developing thyroid cancer. Women who had ever developed a goiter had 17 times the risk of developing follicular cancer and almost 7 times the risk of developing papillary cancer as compared with women who never had had a goiter. Risk of thyroid cancer was elevated even among women who had had a history of goiter many years prior to diagnosis. A history of thyroid nodules was also a risk factor for papillary and mixed thyroid cancer. Neither a history of hypothyroidism nor hyperthyroidism was found to increase the risk of thyroid cancer.
Transmission blocking immunity in Plasmodium vivax malaria: antibodies raised against a peptide block parasite development in the mosquito vector.
Authors: V A Snewin, S Premawansa, G M Kapilananda, L Ratnayaka, P V Udagama, D M Mattei, E Khouri, G Del Giudice, J S Peiris, K N Mendis, P H David
Journal: The Journal of Experimental Medicine (1995)

One approach towards the development of a vaccine against malaria is to immunize against the parasite sexual stages that mediate transmission of the parasite from man to mosquito. Antibodies against these stages, ingested with the blood meal, inhibit the parasite development in the mosquito vector, constituting "transmission blocking immunity." Most epitopes involved in transmission-blocking immunity depend on the tertiary conformational structure of surface antigens. However, one of the transmission-blocking monoclonal antibodies we have raised against Plasmodium vivax reacts with a linear epitope on both asexual stages and gametes. This monoclonal antibody (A12) is capable of totally blocking development of the parasite in the mosquito host when tested in membrane feeding assays with gametocytes from P. vivax-infected patients. Immune screening of a P. vivax lambda gt11 genomic expression library with A12 led to the isolation of a clone to which was mapped the six-amino acid epitope recognized by A12. Antisera raised in mice against a 12-mer synthetic peptide containing this epitope coupled to bovine serum albumin not only had high titers of antipeptide antibodies as measured by enzyme-linked immunosorbent assay, but in addition recognized the same 24- and 57-kD parasite components as A12 on Western blots and reacted with the parasite by immunofluorescence. When tested in membrane feeding assays, these antibodies have significant suppressive effects on parasite development in the mosquito.
Cardiac output measurement in children: comparison of the Ultrasound Cardiac Output Monitor with thermodilution cardiac output measurement
Authors: Walter Knirsch, Oliver Kretschmar, Maren Tomaske, Kathrina Stutz, Nicole Nagdyman, Christian Balmer, Achim Schmitz, Dominique Béttex, Felix Berger, Urs Bauersfeld, Markus Weiss
Journal: Intensive Care Medicine (2008)
Notch1 phenotype and clinical stage progression in non-small cell lung cancer
Authors: Dat Nguyen, Larry Rubinstein, Naoko Takebe, Lucio Miele, Joseph E Tomaszewski, Percy Ivy, James H Doroshow, Sherry X Yang
Journal: Journal of Hematology & Oncology (2015)

Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis.
Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT
Authors: A. D. Sawitzke, H. Shi, M. F. Finco, D. D. Dunlop, C. L. Harris, N. G. Singer, J. D. Bradley, D. Silver, C. G. Jackson, N. E. Lane, C. V. Oddis, F. Wolfe, J. Lisse, D. E. Furst, C. O. Bingham, D. J. Reda, R. W. Moskowitz, H. J. Williams, D. O. Clegg
Journal: Annals of the Rheumatic Diseases (2010)

Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited.
Copayment Levels and Medication Adherence
Authors: Niteesh K. Choudhry
Journal: Circulation (2009)

S tatins play a central role in cardiovascular risk reduction.Their benefit has been demonstrated for a broad spectrum of patients, ranging from those without known vascular disease 1 to those who have recently had a myocardial infarction 2 or have undergone coronary artery bypass surgery. 3ot surprisingly, statins are the most widely sold class of drugs in the United States, accounting for $18.4 billion in sales in 2007.
RT-PCR determination of maspin and mammaglobin B in peripheral blood of healthy donors and breast cancer patients
Authors: L. Mercatali, V. Valenti, D. Calistri, S. Calpona, G. Rosti, S. Folli, M. Gaudio, G.L. Frassineti, D. Amadori, E. Flamini
Journal: Annals of Oncology (2005)
Thoracic positron emission tomography using18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease
Authors: Martin R. Weihrauch, Daniel Re, Klemens Scheidhauer, Sascha Ansén, Markus Dietlein, Stefanie Bischoff, Heribert Bohlen, Jürgen Wolf, Harald Schicha, Volker Diehl, Hans Tesch
Journal: Blood (2001)
Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial
Authors: Cécile Le Péchoux, Ariane Dunant, Suresh Senan, Aaron Wolfson, Elisabeth Quoix, Corinne Faivre-Finn, Tudor Ciuleanu, Rodrigo Arriagada, Richard Jones, Rinus Wanders, Delphine Lerouge, Agnès Laplanche
Journal: The Lancet Oncology (2009)
Monitoring Caspase-3 Activation with a Multimodality Imaging Sensor in Living Subjects
Authors: Pritha Ray, Abhijit De, Manishkumar Patel, Sanjiv Sam Gambhir
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Capsase-3 plays an important role in chemotherapy-induced apoptosis in many cancers. Herein, we applied a multimodality reporter vector to monitor caspase-3 activation indirectly in live cells and tumors of living animals undergoing apoptosis. Experimental Design: A fusion protein (MTF) was constructed by combining three different reporter proteins, red fluorescent protein (mRFP1), firefly luciferase (FL), and HSV1-sr39 truncated thymidine kinase (TK), linked through a caspase-3 recognizable polypeptide linker. After cleavage by caspase-3, a significant gain in mRFP1, FL, and TK activity are observed by fluorescence-activated cell sorting and enzyme-based assays. A melanoma cell line (B16F10-mtf-hrl) stably expressing mtf (to measure caspase-3 activation) and hrl-IRES-gfp (to determine the decrease in a number of viable cells) vectors was generated to measure two independent molecular events upon treatment. Results: Upon induction with 8 μmol/L staurosporine, the fusion protein showed a 2.8-fold increase in FL (P = 0.03), a 1.5-fold increase in TK (P = not significant), and a 2-fold increase in mRFP1 (P = 0.05) activity in 293T cells. Bioluminescence and micropositron emission tomography imaging of the apoptotic B16F10-mtf-hrl tumors showed a 2-fold higher FL activity (897 versus 416) and a 2-fold higher TK activity (10.3 versus 3.87) than control tumors when normalized with RL activity. Using a similar normalization approach, the time kinetics of caspase-3 activation by two protein kinase-C inhibitors was noninvasively monitored in living mice. Conclusion: This multimodality caspase sensor vector could effectively and noninvasively monitor caspase-3 activation from single live cells to a multicellular tumor environment and, thus, would be a valuable tool for drug screening in preclinical models and future patient cell based therapy.