tbuckley/cabot-search huggingface dataset:
Blood shifts between trunk and extremities during exercise depend on respiratory muscle action
Authors: Barbara Uva, Dario Bovio, Andrea Aliverti
Journal: European Respiratory Journal (2013)

We recently found (Aliverti, JApplPhysiol, 2010) that during quiet breathing (QB) at rest a small quantity of blood is shifted from the splanchnic vascular bed to the extremities by increasing abdominal pressure (Pab) with diaphragmatic descent. To study if and how blood is displaced to/from the thorax also during exercise, when abdominal muscles contribute to generate Pab variations, in 11 healthy subjects (8M, 3F, 25±7yrs, 70±11kg, 1.78±0.1m) changes in body volume (Vb) and trunk volume (Vtr) were measured simultaneously by whole body and optoelectronic plethysmography, respectively. The volume of blood shifts between the thorax and extremities (Vbs) was obtained as ΔVtr-ΔVb during QB at rest and 3 different types of submaximal constant exercise (ankle flexion against a resistance): spontaneous (SE), rib cage (RCE, voluntary emphasized inspiratory rib cage breathing) and abdominal (ABE, voluntary active abdominal expiration breathing) exercise.

At rest, within breath tidal Vbs averaged 126±94ml. During SE, RCE and ABE it averaged 338±108ml, 420±260ml, 457±207ml, respectively(p<0.001 vs rest). During SE and RCE blood was displaced from the extremities into the thorax (190±313 and 584±508ml, respectively), while during ABE it was displaced from the thorax to the extremities (223±166ml). Oxygen consumption was 3.5±0.5, 17.5±3, 14.9±3 and 14.4±3ml/Kg*min-1, respectively during rest, SE, RCE and ABE.

Our results suggest that even during low levels of exercise significant blood shifts occur from the thorax to the extremities and viceversa. The direction and amount of blood displacement depend on the relative predominance of the action of diaphragm, rib cage and abdominal muscles.
Multiorgan Nuclear Factor Kappa B Activation in a Transgenic Mouse Model of Systemic Inflammation
Authors: TIMOTHY S. BLACKWELL, FIONA E. YULL, CHIH-LI CHEN, ANNAPURNA VENKATAKRISHNAN, THOMAS R. BLACKWELL, DONNA J. HICKS, LISA H. LANCASTER, JOHN W. CHRISTMAN, LAWRENCE D. KERR
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We utilized a line of transgenic mice expressing Photinus luciferase complementary DNA (cDNA) under the control of a nuclear factor kappa B (NF- κ B)-dependent promoter (from the 5 ′ human immunodeficiency virus-1 [HIV-1] long terminal repeat) to examine the role of NF- κ B activation in the pathogenesis of systemic inflammation induced by bacterial endotoxin (lipopolysaccharide [LPS]). After intraperitoneal injection of E. coli LPS, these mice displayed a time- and dose-dependent, organ-specific pattern of luciferase expression, showing that NF- κ B-dependent gene transcription is transiently activated in multiple organs by systemic LPS administration. Luciferase expression in liver could be specifically blocked by intravenous administration of replication-deficient adenoviral vectors expressing a dominant inhibitor of NF- κ B (I κ B- α DN), confirming that luciferase gene expression is a surrogate marker for NF- κ B activation in this line of mice. After treatment with intraperitoneal LPS, the mice were found to have increased lung tissue messenger RNA (mRNA) expression of a variety of cytokines that are thought to be NF- κ B-dependent, as well as elevated serum concentrations of presumed NF- κ B-dependent cytokines. In lung tissue homogenates, a close correlation was identified between luciferase activity and KC levels. These studies show that systemic treatment with LPS orchestrates a multiorgan NF- κ B-dependent response that likely regulates the pathobiology of systemic inflammation.
A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial
Authors: Tiia Ngandu, Jenni Lehtisalo, Alina Solomon, Esko Levälahti, Satu Ahtiluoto, Riitta Antikainen, Lars Bäckman, Tuomo Hänninen, Antti Jula, Tiina Laatikainen, Jaana Lindström, Francesca Mangialasche, Teemu Paajanen, Satu Pajala, Markku Peltonen, Rainer Rauramaa, Anna Stigsdotter-Neely, Timo Strandberg, Jaakko Tuomilehto, Hilkka Soininen, Miia Kivipelto
Journal: The Lancet (2015)
Effect of anti-lymphocyte induction therapy on renal allograft survival
Authors: L A Szczech, J A Berlin, S Aradhye, R A Grossman, H I Feldman
Journal: Journal of the American Society of Nephrology (1997)

Induction immunosuppression with antilymphocyte antibodies has not been shown to improve cadaveric kidney allograft survival in randomized, controlled trials despite widespread use. This meta-analysis of randomized, controlled trials assessed the effectiveness of induction therapy in prolonging allograft survival. Studies of induction therapy were identified in Medline (1986 through 1996), using the terms "monoclonal antibodies" or "antilymphocyte serum," and "kidney transplantation," "human," and "clinical trial." Bibliographies, pharmaceutical manufacturers, the United Network for Organ Sharing, National Institutes of Health, and study authors were also consulted. Seven of 247 identified studies met the following inclusion criteria: (1) an adult study population; (2) assessment of antilymphocyte antibodies in the immediate posttransplant period; (3) a control arm of cyclosporine, azathioprine, and prednisone in the immediate posttransplant period; and (4) presentation of survival data. Two readers independently extracted protocol and survival data from each study. Summary odds ratios (fixed and random effects) and a rate ratio from proportional hazards regression at 2 yr were estimated to examine the effect of induction therapy on allograft survival. The summary odds ratios were both 0.66 (confidence interval [CI], 0.45 to 0.96; P = 0.03), and the rate ratio was 0.69 (CI, 0.49 to 0.97; P = 0.03), indicating a beneficial effect of induction therapy on allograft survival. Allograft survival was 85.6% (CI, 82.1 to 89.1%) in the induction therapy group and 79.6% (CI, 75.6 to 83.6%) in the conventional therapy group. These results were stable in a sensitivity analysis based on study quality. Allograft survival was prolonged with induction therapy compared with conventional immunosuppression. These data indicate a potential role for the routine use of induction therapy in renal transplantation to optimize the survival of cadaveric allografts.
ZNF217 confers resistance to the pro-apoptotic signals of paclitaxel and aberrant expression of Aurora-A in breast cancer cells
Authors: Aurélie Thollet, Julie A Vendrell, Léa Payen, Sandra E Ghayad, Sabrina Ben Larbi, Evelyne Grisard, Colin Collins, Marie Villedieu, Pascale A Cohen
Journal: Molecular Cancer (2010)

Abstract Background ZNF217 is a candidate oncogene located at 20q13, a chromosomal region frequently amplified in breast cancers. The precise mechanisms involved in ZNF217 pro-survival function are currently unknown, and utmost importance is given to deciphering the role of ZNF217 in cancer therapy response. Results We provide evidence that stable overexpression of ZNF217 in MDA-MB-231 breast cancer cells conferred resistance to paclitaxel, stimulated cell proliferation in vitro associated with aberrant expression of several cyclins, and increased tumor growth in mouse xenograft models. Conversely, siRNA-mediated silencing of ZNF217 expression in MCF7 breast cancer cells, which possess high endogenous levels of ZNF217, led to decreased cell proliferation and increased sensitivity to paclitaxel. The paclitaxel resistance developed by ZNF217-overexpressing MDA-MB-231 cells was not mediated by the ABCB1/PgP transporter. However, ZNF217 was able to counteract the apoptotic signals mediated by paclitaxel as a consequence of alterations in the intrinsic apoptotic pathway through constitutive deregulation of the balance of Bcl-2 family proteins. Interestingly, ZNF217 expression levels were correlated with the oncogenic kinase Aurora-A expression levels, as ZNF217 overexpression led to increased expression of the Aurora-A protein, whereas ZNF217 silencing was associated with low Aurora-A expression levels. We showed that a potent Aurora-A kinase inhibitor was able to reverse paclitaxel resistance in the ZNF217-overexpressing cells. Conclusion Altogether, these data suggest that ZNF217 might play an important role in breast neoplastic progression and chemoresistance, and that Aurora-A might be involved in ZNF217-mediated effects.
Mucus, pepsin, and peptic ulcer.
Authors: C W Venables
Journal: Gut (1986)

<h3>Abstract</h3> Yeast secrete ATP in response to glucose, a property with previously unknown functional consequence. In this report, we show that extracellular ATP is a signal for growth of surrounding cells. The ATP signaling behavior was serendipitously uncovered by finding reduced toxicity of an inducible, dominant-lethal form of alpha tubulin (tub1-828); lethality was dramatically reduced in cultures grown at high, compared to low cell density. Reduced cell death at high cell density occurred because the mutant tubulin’s deleterious effect of mitosis was reduced such that the rate of chromosome loss/cell division was lower (18-fold) in cultures inoculated with a high density (75,000/ml) compared to a low density (1,000/ml) of cells. The sparing effect of growth at high cell density could be replicated by co-culturing a low number of cells (3440/5 ml) that expressed tub1-828, with a high number of cells (2.3 E6/5 ml) that did not express the mutant protein. In this condition toxicity was reduced at high cell density apparently because it produced a sufficient concentration of a secreted growth substance, such that the mutant protein was rapidly diluted by synthesis of wild-type alpha tubulin (TUB1). Enhanced growth at high cell density was confirmed by fluorescence-activated cell sorting (FACS) analysis after DNA staining, which showed that the rate of the G1-G2 transition was faster for cells at high density. ATP replaced the need for high cell density for resistance to tub1-828, and stimulated the transition from G1 to G2 in cells at low density. This newly discovered quorum sensing response in yeast, mediated by ATP, indicates that yeast decision-making is not entirely autonomous.
Relationship between HBV-specific DNA polymerase and HBe antigen/antibody system in chronic HBV infection: factors determining selection of patients and outcome of antiviral therapy.
Authors: A Craxi, I V Weller, M F Bassendine, M J Fowler, J Monjardino, H C Thomas, S Sherlock
Journal: Gut (1983)

The sera of 23% of HBe antigen positive patients with chronic hepatitis are HBV-DNA polymerase negative. These patients are probably undergoing spontaneous seroconversion from a state of high to low viral replication and do not require antiviral therapy. In chronic HBV infection rapid changes in viral replication as a result of antiviral therapy are reflected by changes in HBV-DNA and HBV-DNA polymerase but not by changes in HBe antigen concentrations. Disappearance of HBe antigen from serum may be delayed for 180 days after permanent inhibition of HBV replication with adenine arabinoside or its monophosphate derivative.
Prostate Cancer–Specific Survival in Elderly Patients
Authors: Michael Froehner
Journal: Journal of Clinical Oncology (2011)

In a recent analysis of an impressive data set, Bechis et al 1 investigated the impact of age on prostate cancer treatment and survival.The authors found that elderly men with high-risk disease who were receiving local therapy had a roughly halved riskadjusted mortality and concluded that underuse of curative local therapy may partially explain this difference. 1This is indeed possible.There could, however, be biases that render an interpretation of the data more difficult.It is conceivable that elderly men with high-risk disease were preferably selected for curative treatment if they were healthy and harbored less-advanced disease.Such selection could even have occurred within the same Cancer of the Prostate Risk Assessment 2 classes.Their conservatively treated counterparts could be expected to have a selection-related poorer survival both as a result of cancer progression and competing mortality.When dying from noncancer causes (for instance, cardiovascular disease or sepsis), conservatively treated patients with advanced prostate cancer might additionally be susceptible to an attribution bias. 3Advanced prostate cancer might, quite correctly, be considered a contributing cause of death in these patients.In this way, life-shortening comorbidity might translate into increased prostate-cancer mortality rates in frail elderly patients.It is questionable whether these biases may reliably be eliminated by statistical risk adjustment.Therefore, the observations of this study 1 are rather hypothesis generating and underline the importance of investigating treatment options in elderly patients with prostate cancer in randomized trials.
Preservation of Ventricular Function by Adrenergic Influences during Metabolic Acidosis in the Cat
Authors: JOSE M. ROCAMORA, S. EVANS DOWNING
Journal: Circulation Research (1969)

Although metabolic acidemia reduces the contractility of cardiac muscle in isolated preparations, it does not do so to the same extent in intact animals or those with a functioning sympathoadrenal system. The present study was designed to determine if the resistance of the heart to acidemia is the consequence of concurrent adrenergic influences on the myocardium. The function of the cat's left ventricle was examined in a preparation that allowed control of aortic pressure, cardiac output, heart rate and temperature. The arterial blood pH, Po 2 , Pco 2 , and temperature were continuously measured. Acidemia was produced either endogenously by temporarily diminishing perfusion of peripheral tissues, or by infusion of 0.5N lactic acid. Studies were made before and after beta-receptor blockade with propranolol, 0.25 to 0.5 mg/kg iv or im. In eight control animals, reduction of pH from 7.34 to 7.08 failed to diminish contractility. In 14 animals with beta-receptor blockade, reduction of pH to 7.02 reduced contractility by about 25% ( P &lt;.001). Correction of the acidemia by infusion of tris(hydroxymethyl)aminomethane returned contractility to approximately 95% of control. Rapid reduction of pH transiently diminished contractility in control animals and severely depressed those with beta-receptor blockade. These data support the position that sympathoadrenal activity is necessary to preserve ventricular function in the presence of severe metabolic acidemia.
Uptake of <i>Leishmania major</i> by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity
Authors: Florian Woelbing, Susanna Lopez Kostka, Katharina Moelle, Yasmine Belkaid, Cord Sunderkoetter, Sjef Verbeek, Ari Waisman, Axel P. Nigg, Juergen Knop, Mark C. Udey, Esther von Stebut
Journal: The Journal of Experimental Medicine (2006)

Uptake of Leishmania major by dendritic cells (DCs) results in activation and interleukin (IL)-12 release. Infected DCs efficiently stimulate CD4− and CD8− T cells and vaccinate against leishmaniasis. In contrast, complement receptor 3–dependent phagocytosis of L. major by macrophages (MΦ) leads exclusively to MHC class II–restricted antigen presentation to primed, but not naive, T cells, and no IL-12 production. Herein, we demonstrate that uptake of L. major by DCs required parasite-reactive immunoglobulin (Ig)G and involved FcγRI and FcγRIII. In vivo, DC infiltration of L. major–infected skin lesions coincided with the appearance of antibodies in sera. Skin of infected B cell–deficient mice and Fcγ−/− mice contained fewer parasite-infected DCs in vivo. Infected B cell–deficient mice as well as Fcγ−/− mice (all on the C57BL/6 background) showed similarly increased disease susceptibility as assessed by lesion volumes and parasite burdens. The B cell–deficient mice displayed impaired T cell priming and dramatically reduced IFN-γ production, and these deficits were normalized by infection with IgG-opsonized parasites. These data demonstrate that DC and MΦ use different receptors to recognize and ingest L. major with different outcomes, and indicate that B cell–derived, parasite-reactive IgG and DC FcγRI and FcγRIII are essential for optimal development of protective immunity.
Cardiorespiratory effects of volume- and pressure-controlled ventilation at various I/E ratios in an acute lung injury model.
Authors: H Mang, R M Kacmarek, R Ritz, R S Wilson, W P Kimball
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Numerous approaches to the provision of mechanical ventilation during acute lung injury are currently available. Of these, pressure control inverse ratio ventilation has been considered superior to volume control ventilation with PEEP with respect to improving gas exchange and minimizing cardiovascular compromise. However, no study systematically compares volume-controlled (VC) and pressure-controlled (PC) ventilation while maintaining mean airway pressure (MAP) constant at varying I/E ratios. We studied the effect of VC and PC with PEEP at normal (1:2) and inverse I/E ratios (2:1 and 4:1) on gas exchange, lung mechanics, and hemodynamics in a sheep lung injury model. Severe lung injury was induced in 12 sheep with bilateral lung lavages using normal saline; prelavage PO2 230 +/- 50 mm Hg, PEEP 5 cm H2O and postlavage, pretreatment PO2 70 +/- 20 mm Hg, PEEP 10 cm H2O, both at FIO2 0.50. MAP was kept constant throughout the study at 25 +/- 2 cm H2O while ventilating all animals with a VT of 10 ml/kg and a rate of 20/min by randomized application of VC and PC with I/E ratios of 1:2, 2:1, and 4:1. Despite liberal fluid administration, all ventilatory modes depressed cardiac output compared with preinjury values. However, gas exchange and hemodynamics did not differ among ventilation modes or I/E ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
Surgical resection plus chemotherapy versus chemotherapy alone: comparison of two strategies to treat diffuse large B-cell gastric lymphoma
Authors: M. Binn, A. Ruskoné-Fourmestraux, E. Lepage, C. Haioun, A. Delmer, P. Aegerter, A. Lavergne, C. Guettier, J.-C. Delchier
Journal: Annals of Oncology (2003)
Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women
Authors: E. M. Kesson, G. M. Allardice, W. D. George, H. J. G. Burns, D. S. Morrison
Journal: BMJ (2012)

<b>Objectives</b> To describe the effect of multidisciplinary care on survival in women treated for breast cancer. <b>Design</b> Retrospective, comparative, non-randomised, interventional cohort study. <b>Setting</b> NHS hospitals, health boards in the west of Scotland, UK. <b>Participants</b> 14 358 patients diagnosed with symptomatic invasive breast cancer between 1990 and 2000, residing in health board areas in the west of Scotland. 13 722 (95.6%) patients were eligible (excluding 16 diagnoses of inflammatory cancers and 620 diagnoses of breast cancer at death). <b>Intervention</b> In 1995, multidisciplinary team working was introduced in hospitals throughout one health board area (Greater Glasgow; intervention area), but not in other health board areas in the west of Scotland (non-intervention area). <b>Main outcome measures</b> Breast cancer specific mortality and all cause mortality. <b>Results</b> Before the introduction of multidisciplinary care (analysed time period January 1990 to September 1995), breast cancer mortality was 11% higher in the intervention area than in the non-intervention area (hazard ratio adjusted for year of incidence, age at diagnosis, and deprivation, 1.11; 95% confidence interval 1.00 to 1.20). After multidisciplinary care was introduced (time period October 1995 to December 2000), breast cancer mortality was 18% lower in the intervention area than in the non-intervention area (0.82, 0.74 to 0.91). All cause mortality did not differ significantly between populations in the earlier period, but was 11% lower in the intervention area than in the non-interventional area in the later period (0.89, 0.82 to 0.97). Interrupted time series analyses showed a significant improvement in breast cancer survival in the intervention area in 1996, compared with the expected survival in the same year had the pre-intervention trend continued (P=0.004). This improvement was maintained after the intervention was introduced. <b>Conclusion</b> Introduction of multidisciplinary care was associated with improved survival and reduced variation in survival among hospitals. Further analysis of clinical audit data for multidisciplinary care could identify which aspects of care are most associated with survival benefits.
Physiologically-Based Pharmacokinetics in Drug Development and Regulatory Science
Authors: Malcolm Rowland, Carl Peck, Geoffrey Tucker
Journal: The Annual Review of Pharmacology and Toxicology (2011)

The application of physiologically-based pharmacokinetic (PBPK) modeling is coming of age in drug development and regulation, reflecting significant advances over the past 10 years in the predictability of key pharmacokinetic (PK) parameters from human in vitro data and in the availability of dedicated software platforms and associated databases. Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation. The value of this capability in selecting and designing appropriate clinical studies, its implications for resource-sparing techniques, and a more holistic view of the application of PK across the preclinical/clinical divide are considered. Finally, some attention is given to the positioning of PBPK within the drug development and approval paradigm and its future application in truly personalized medicine.
Neural Stem Cells and the Origin of Gliomas
Authors: Nader Sanai, Arturo Alvarez-Buylla, Mitchel S Berger
Journal: New England Journal of Medicine (2005)

Little progress has been made in the treatment of gliomas during the past 25 years. One reason is our poor understanding of the cell of origin in these tumors and of the mechanisms that bring that cell into a malignant state. This review argues that gliomas arise from neural stem cells and discusses the clinical implications of this concept.
Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state
Authors: Silvia Buonamici, Emanuela Ottaviani, Nicoletta Testoni, Vittorio Montefusco, Giuseppe Visani, Francesca Bonifazi, Marilina Amabile, Carolina Terragna, Deborah Ruggeri, Pier Paolo Piccaluga, Alessandro Isidori, Michele Malagola, Michele Baccarani, Sante Tura, Giovanni Martinelli
Journal: Blood (2002)