tbuckley/cabot-search huggingface dataset:
Labour will cap private providers' profits on NHS work at 5%
Authors: A. O'Dowd
Journal: BMJ (2015)

The Labour Party has promised to cap profits at 5% on outsourced healthcare contracts worth over £500 000 (€680 000; $740 000), as part of its newly launched general election campaign.

Doctors’ leaders have, however, reacted to the proposal with scepticism, saying that it could be unworkable in practice and that it might be another “sticking plaster solution” that did not go far enough.

Labour’s leader, Ed Miliband, launched his party’s election campaign on 27 March in a speech given in London, in which he said that Labour would guarantee that local health services would no longer be threatened by marketisation and privatisation and that there would be extra investment for the NHS.

Labour’s proposals include the plan to …
CN-08 * THERAPEUTIC CONCENTRATION OF TEMOZOLOMIDE DO NOT IMPAIR THE FUNCTION OF HUMAN DENDRITIC CELL SUBSETS
Authors: R. Iwata, A. Asai, T. Ito, H. Oshige, K. Yoshimura, M. Nonaka
Journal: Neuro-Oncology (2014)

In humans, CD11c+ myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) represent two major subsets of DCs. They play distinct roles in innate and adaptive anti-tumor immunity by their expression of specialized cytokines and molecules. In addition, monocytes-derived DCs (moDCs) as in vitro-made myeloid DCs are commonly used as DC-vaccine therapy for several malignancies. However, the efficacy of DC-vaccine monotherapy has been reported to be limited, and therefore, combination use of appropriate chemotherapy would be required for the treatment strategy of immunotherapy. Because anti-tumor reagents generally have an activity to kill hematopoietic cells or inhibit lymphocyte functions, congeniality of anti-tumor reagents and DCs is important for the effective combination therapy. Temozolomide (TMZ) is an oral alkylating agent with established anti-tumor activity in patients with glioblastoma. In this study, we focused on the TMZ function and explored its influence on human DC subsets, including blood CD11c+ mDCs, pDCs, and moDCs. We found that over 300 mM of TMZ killed the DC subsets but that there were no killing effect at in vivo clinical concentration of less than 100 mM TMZ. Up to 100 mM TMZ did not affect IFN-a production from pDCs and IL-12 production from blood mDCs and moDCs and their expression of surface B7 and TNF superfamilies in response to various TLR ligands. In addition, TMZ did not inhibit moDC-mediated T cell responses. Thus, TMZ can elicit anti-tumor activity without affecting DC-mediated immune responses. Our present findings suggest that TMZ is a potential anti-tumor reagent suitable for the combination use with DC-vaccine therapy.
There Are Just Not Enough Hours in the Day
Authors: Julie Ann Freischlag
Journal: JAMA Surgery (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Regulation of gene expression by dietary Ca2+ in kidneys of 25-hydroxyvitamin D3-1α-hydroxylase knockout mice
Authors: Joost G.J. Hoenderop, Helena Chon, Dimitra Gkika, Hans A.R. Bluyssen, Frank C.P. Holstege, Rene St-Arnaud, Branko Braam, Rene J.M. Bindels
Journal: Kidney International (2004)
The Constitutive Function of Native TRPC3 Channels Modulates Vascular Cell Adhesion Molecule-1 Expression in Coronary Endothelial Cells Through Nuclear Factor κB Signaling
Authors: Kathryn Smedlund, Jean-Yves Tano, Guillermo Vazquez
Journal: Circulation Research (2010)

Rationale : Upregulation of endothelial vascular cell adhesion molecule (VCAM)-1 and the subsequent increase in monocyte recruitment constitute critical events in atherogenesis. We have recently shown that in human coronary artery endothelial cells (HCAECs) regulated expression of VCAM-1 depends, to a significant extent, on expression and function of the Ca 2+ -permeable channel transient receptor potential canonical (TRPC)3, regardless of the ability of the stimulatory signal to induce regulated Ca 2+ influx, leading to the hypothesis that TRPC3 constitutive, rather than regulated function, contributes to the underlying signaling mechanism. Objective : The present studies addressed this important question and gathered mechanistic insight on the signaling coupling constitutive TRPC3 function to VCAM-1 expression. Methods and Results : In HCAECs, maneuvers that prevent Ca 2+ influx or knockdown of TRPC3 markedly reduced tumor necrosis factor (TNF)α-induced VCAM-1 and monocyte adhesion. TNFα also induced TRPC3 expression and TRPC3-mediated constitutive cation influx and currents. Stable (HEK293 cells) or transient (HCAECs) overexpression of TRPC3 enhanced TNFα-induced VCAM-1 compared to wild-type cells. IκBα phosphorylation/degradation was reduced by TRPC3 knockdown and increased by channel overexpression. Inhibition of calmodulin completely prevented nuclear factor κB activation, whereas blocking calmodulin-dependent kinases or NADPH oxidases rendered partial inhibition. Conclusions : Our findings indicate that in HCAECs expression of VCAM-1 and monocyte adhesion depend, to a significant extent, on TRPC3 constitutive function through a signaling mechanism that requires constitutive TRPC3-mediated Ca 2+ influx for proper activation of nuclear factor κB, presumably through Ca 2+ -dependent activation of the calmodulin/calmodulin-dependent kinase axis.
Does This Adult Patient Have Early HIV Infection?
Authors: Evan Wood, Thomas Kerr, Greg Rowell, Julio S. G. Montaner, Peter Phillips, P. Todd Korthuis, David L. Simel
Journal: JAMA (2014)

Timely identification of human immunodeficiency virus (HIV) infection in adults can contribute to reduced mortality and likelihood of further HIV transmission. During the first 6 months after infection, known as early HIV infection, patients often report a well-described constellation of symptoms and signs. However, the literature examining utility of the clinical examination in identifying early infection has not been systematically assessed.To assess the accuracy of symptoms and signs in identifying early HIV infection among adults.We searched MEDLINE and EMBASE (1981-May, 2014) for articles investigating symptoms and signs of early HIV infection in adults and searched reference lists of retrieved articles.We retained original studies that compared symptoms and signs among patients with early HIV infection in comparison to HIV-negative individuals.Data were extracted and used to calculate sensitivity, specificity, and likelihood ratios (LRs), and meta-analysis was used to calculate summary LRs.Of 1356 studies, 16 studies included data that were eligible for meta-analysis and included a total of 24,745 patients and 1253 cases of early HIV infection. Symptoms that increased the likelihood of early HIV infection the most included genital ulcers (LR, 5.4; 95% CI, 2.5-12), weight loss (LR, 4.7; 95% CI, 2.1-7.2), vomiting (LR, 4.6; 95% CI, 2.5-8.0), and swollen lymph nodes (LR, 4.6; 95% CI, 1.3-8.0). No symptoms had an LR that was 0.5 or lower, but the absence of recent fever (LR, 0.74; 95% CI, 0.64-0.84) slightly decreased the likelihood of early HIV infection. The presence of lymphadenopathy on physical examination was the most useful sign (LR, 3.1; 95% CI, 1.0-5.2). No sign had an LR of 0.5 or less, but the absence of lymphadenopathy slightly decreased the likelihood of early HIV infection (LR, 0.70, 95% CI, 0.49-0.92). Using data from studies that considered combinations of findings (range of possible findings, 4-17), the summary LR for individuals with 0 findings was 0.47 (95% CI, 0.38-0.58).The limited utility of the clinical examination to detect or rule out early HIV infection highlights the importance of routine testing for HIV infection among adults.
Cholestasis Induced by Estradiol-17β-D-Glucuronide: Mechanisms and Prevention by Sodium Taurocholate†
Authors: Luigi E. Adinolfi, Riccardo Utili, Giovanni B. Gaeta, Charles O. Abernathy, Hyman J. Zimmerman
Journal: Hepatology (1984)

Estradiol-17β-D-glucuronide (E-17G), a metabolite of natural estrogen, is a potent cholestatic agent in vivo. We, therefore, studied the mechanisms of E-17G cholestasis using in vitro perfused rat liver system. Furthermore, since it has been postulated that sodium taurocholate (TC) may interfere with either uptake or biliary excretion of other steroid agents, we tested whether E-17G cholestasis could be modified by TC administration. During a constant infusion of TC at a physiological rate (0.50 μ mole per min), a dose-dependent decrease of bile flow was observed after E-17G addition from 1.5 to 5 x 10 −5 M . E-17G decreased bile acid excretory rate but not bile acid concentration in bile. In separate experiments, TC was infused at different rates (0, 0.25, 0.50, and 0.75 μ mole per min) into the perfusate over the entire experimental period, and E-17G was added at 1.75 x 10 −5 M . In this setting, E-17G cholestasis was diminished by increasing TC infusion rate and was prevented by TC at 0.75 μ mole per min. Infusion of sodium dehydrocholate (0.75 μ mole per min), a nonmicelle-forming bile acid, did not prevent E-17G cholestasis. During E-17G cholestasis, an increased biliary permeability to 14 C-sucrose was observed. This effect was also prevented by TC, but not by sodium dehydrocholate which was infused at 0.75 μ mole per min. The perfusate disappearance curves of 3 H-E-17G at the different TC infusion rates showed no changes in the initial uptake phase, but a profound dose-dependent difference in the excretory phase. The amount of E-17G left in perfusate at the end of experiments was 34% when no TC was infused and decreased to 28%; 22 and 7% at 0.25; 0.50 and 0.75 nmole per min TC rate, respectively. Measurement of 3 H-E-17G excreted in bile as well as its biliary concentration in the four TC groups showed that TC significantly increased E-17G excretion. Small amounts of E-17G were recovered in liver plasma membranes. However, these amounts were directly proportional to changes of bile flow induced by estrogen at different TC infusion rates. In these same liver membrane preparations, neither Na + ,K + − nor Mg ++ −ATPases were altered. The data suggest that alterations of canalicular membrane permeability may be critical in the development of E-17G cholestasis. Prevention of E-17G cholestasis by TC infusion may occur through increased micellar solubilization and facilitated biliary excretion of the estrogen thus avoiding its membrane-altering action.
Telephone Care Management To Improve Cancer Screening among Low-Income Women
Authors: Allen J. Dietrich, Jonathan N. Tobin, Andrea Cassells, Christina M. Robinson, Mary Ann Greene, Carol Hill Sox, Michael L. Beach, Katherine N. DuHamel, Richard G. Younge
Journal: Annals of Internal Medicine (2006)

Background: Minority and low-income women receive fewer cancer screenings than other women. Objective: To evaluate the effect of a telephone support intervention to increase rates of breast, cervical, and colorectal cancer screening among minority and low-income women. Design: Randomized, controlled trial conducted between November 2001 and April 2004. Setting: 11 community and migrant health centers in New York City. Patients: 1413 women who were overdue for cancer screening. Intervention: Over 18 months, women assigned to the intervention group received an average of 4 calls from prevention care managers and women assigned to the control group received usual care. Follow-up data were available for 99% of women, and 91% of the intervention group received at least 1 call. Measurements: Medical record documentation of mammography, Papanicolaou testing, and colorectal cancer screening according to U.S. Preventive Services Task Force recommendations. Results: The proportion of women who had mammography increased from 0.58 to 0.68 with the intervention and decreased from 0.60 to 0.58 with usual care; the proportion who had Papanicolaou testing increased from 0.71 to 0.78 with the intervention and was unchanged with usual care; and the proportion who had colorectal screening increased from 0.39 to 0.63 with the intervention and from 0.39 to 0.50 with usual care. The difference in the change in screening rates between groups was 0.12 for mammography (95% CI, 0.06 to 0.19), 0.07 for Papanicolaou testing (CI, 0.01 to 0.12), and 0.13 for colorectal screening (CI, 0.07 to 0.19). The proportion of women who were up to date for 3 tests increased from 0.21 to 0.43 with the intervention. Limitations: Participants were from 1 city and had access to a regular source of care. Medical records may not have captured all cancer screenings. Conclusions: Telephone support can improve cancer screening rates among women who visit community and migrant health centers. The intervention seems to be well suited to health plans, large medical groups, and other organizations that seek to increase cancer screening rates and to address disparities in care.
CHANGES IN THE TISSUE SURROUNDING A GROWING TUMOR AND THE SIGNIFICANCE OF THE "PRECANCEROUS STATE."
Authors: Isaac Levin
Journal: The Journal of Experimental Medicine (1912)

An analysis of the results of the experiments reported in this investigation shows that the changes so frequently observed in tissues surrounding a growing tumor may be caused by different conditions. The development and growth of a malignant tumor depends upon a local interaction between tumor cells and organ cells. When the cells of a normal organ are capable of inhibiting tumor growth, then an impairment of the normal state of the parenchymatous cells of this particular organ is essential for the growth of the tumor. This "precancerous state" does not consist primarily of an inflammatory change in the adjacent connective tissue, as Ribbert and his followers maintain, but in a degeneration of the parenchymatous cells of the organ. If, in another instance, the cells of the normal organs are unable to inhibit the proliferation of the tumor cells, then no preparation of the cells of the organ for the tumor is necessary, i. e., no "precancerous state" is needed to enable the tumor to grow. On the other hand, the proliferating tumor cells injure normal cells, either mechanically or chemically, producing a condition that appears on superficial examination like that described as the "precancerous state." In reality, however, this condition is the resultant effect of the tumor growth and may be more correctly designated the "postcancerous state." In these conditions, then, von Hansemann's explanation of the phenomenon, and not Ribbert's, seems to be the correct one. Of still greater importance is the fact demonstrated in the last series of experiments; namely, that the general condition of resistance or immunity to cancer growth exerts a greater influence on the organism of the animal than any of the local conditions described above. The local resistance of a testicle to tumor growth in a generally susceptible animal may be overcome, but if an animal is made generally immune to the growth of cancer, neither the animal as a whole nor a single organ or tissue in it can be made susceptible to the growth of the tumor.
Sequences in both class II major histocompatibility complex alpha and beta chains contribute to the binding of the superantigen toxic shock syndrome toxin 1.
Authors: N S Braunstein, D A Weber, X C Wang, E O Long, D Karp
Journal: The Journal of Experimental Medicine (1992)

Class II major histocompatibility complex (MHC) molecules present peptides derived from processed antigen to antigen-specific CD4-positive T cells. In addition, class II molecules bind with high affinity another class of antigens, termed superantigens. T cell stimulation by superantigens depends almost exclusively on the V beta segment expressed by the T cell receptor (TCR). Mapping of the superantigen binding site on class II molecules should provide valuable information on how MHC and TCR molecules interact. Recombinant mouse I-A class II molecules expressed on transfected L cells were analyzed for their ability to bind the toxic shock syndrome toxin 1. Polymorphic residues in the alpha helices of both the alpha and beta chains of I-A contributed to quantitative toxin binding, suggesting that the toxin binds to either a combinatorial or a conformational site on class II MHC molecules.
<i>Streptococcus pneumoniae</i>-induced regulation of cyclooxygenase-2 in human lung tissue
Authors: Kolja V. Szymanski, Mario Toennies, Anne Becher, Diana Fatykhova, Philippe D. N'Guessan, Birgitt Gutbier, Frederick Klauschen, Frank Neuschaefer-Rube, Paul Schneider, Jens Rueckert, Jens Neudecker, Torsten T. Bauer, Klaus Dalhoff, Daniel Drömann, Achim D. Gruber, Olivia Kershaw, Bettina Temmesfeld-Wollbrueck, Norbert Suttorp, Stefan Hippenstiel, Andreas C. Hocke
Journal: European Respiratory Journal (2012)

The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue. Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites. In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid(4) receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E(2) related pro- and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection. Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E(2) formation in human lung tissue may play an important role in the early phase of pneumococcal infections.
Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: a population-based cohort
Authors: Bénédicte Leynaert, Jordi Sunyer, Raquel Garcia-Esteban, Cecilie Svanes, Deborah Jarvis, Isa Cerveri, Julia Dratva, Thorarinn Gislason, Joachim Heinrich, Christer Janson, Nino Kuenzli, Roberto de Marco, Ernst Omenaas, Chantal Raherison, Francisco Gómez Real, Matthias Wjst, Elisabeth Zemp, Mahmoud Zureik, Peter G J Burney, Josep M Anto, Françoise Neukirch
Journal: Thorax (2012)

<h3>Background</h3> Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. <h3>Methods</h3> Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8–10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. <h3>Results</h3> Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. <h3>Conclusions</h3> This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.
Systolic pressure--diameter relations in the normal conscious dog
Authors: F. MAHLER, J. W. COVELL, J. ROSS
Journal: Cardiovascular Research (1975)

Pressure--diameter loops were generated in normal, conscious dogs during left ventricular contraction by means of endocardial ultrasonic gauges and micromanometers. Studies were made in the control state, during volume and pressure loading, and during enhancement of contractility. The diameter at the end of ejection was linearly related to systolic pressure, and the pressure--diameter relation at end-ejection was not affected by changes in preload. However, this relation was substantially displaced by changes in inotropic state, suggesting that the instantaneous pressure--length plane produced by pressure loading is unique to a given level of contractility.