tbuckley/cabot-search huggingface dataset:
Atropine inhibits gastric distension and pharyngeal receptor mediated lower oesophageal sphincter relaxation
Authors: R K Mittal, C Chiareli, J Liu, R H Holloway, W Dixon
Journal: Gut (1997)

Background —Atropine decreases the frequency of transient lower oesophageal sphincter relaxation (TLOSR) through an unknown mechanism. Gastric distension and pharyngeal receptor excitation are two possible sources for the afferent stimulus responsible for TLOSR. Aims —To determine whether atropine affects gastric distension induced TLOSR and pharyngeal receptor mediated lower oesophageal sphincter (LOS) relaxation. Methods —Oesophageal manometry and pH recordings were performed in 10 healthy volunteers on two separate days in the postprandial setting, following either atropine (15 μg/kg intravenous bolus and 4 μg/kg/h as a maintenance dose) or placebo. Pharyngeal receptor mediated LOS relaxation was studied in nine subjects by rapid injection of minute amounts of water (0.05, 0.1, 0.2, 0.3, and 0.4 ml) in the pharynx before and after atropine. Gastric distension mediated TLOSR was studied in eight subjects by insufflating the stomach with 300, 600 and 900 ml of CO 2 before and after atropine. Results —Atropine reduced the frequency of spontaneous gastro-oesophageal reflux and TLOSR compared with placebo (p&lt;0.05). Pharyngeal stimulation resulted in bolus volume dependent LOS relaxation. Atropine decreased the frequency and amplitude of pharyngeal receptor mediated LOS relaxation at bolus volumes of 0.05, 0.1, and 0.2 ml. Gastric distension resulted in intermittent episodes of TLOSR. The frequency of gastric distension induced TLOSR was significantly decreased by atropine. Conclusion— (1) Atropine reduces the frequency of spontaneous reflux and TLOSR in normal subjects; and (2) gastric distension induced TLOSR and pharyngeal receptor mediated LOS relaxation is inhibited by atropine.
Evolution and Architecture of the Inner Membrane Complex in Asexual and Sexual Stages of the Malaria Parasite
Authors: M. Kono, S. Herrmann, N. B. Loughran, A. Cabrera, K. Engelberg, C. Lehmann, D. Sinha, B. Prinz, U. Ruch, V. Heussler, T. Spielmann, J. Parkinson, T. W. Gilberger
Journal: Molecular Biology and Evolution (2012)

The inner membrane complex (IMC) is a unifying morphological feature of all alveolate organisms. It consists of flattened vesicles underlying the plasma membrane and is interconnected with the cytoskeleton. Depending on the ecological niche of the organisms, the function of the IMC ranges from a fundamental role as reinforcement system to more specialized roles in motility and cytokinesis. In this article, we present a comprehensive evolutionary analysis of IMC components, which exemplifies the adaptive nature of the IMCs' protein composition. Focusing on eight structurally distinct proteins in the most prominent "genus" of the Alveolata—the malaria parasite Plasmodium—we demonstrate that the level of conservation is reflected in phenotypic characteristics, accentuated in differential spatial–temporal patterns of these proteins in the motile stages of the parasite's life cycle. Colocalization studies with the centromere and the spindle apparatus reveal their discriminative biogenesis. We also reveal that the IMC is an essential structural compartment for the development of the sexual stages of Plasmodium, as it seems to drive the morphological changes of the parasite during the long and multistaged process of sexual differentiation. We further found a Plasmodium-specific IMC membrane matrix protein that highlights transversal structures in gametocytes, which could represent a genus-specific structural innovation required by Plasmodium. We conclude that the IMC has an additional role during sexual development supporting morphogenesis of the cell, which in addition to its functions in the asexual stages highlights the multifunctional nature of the IMC in the Plasmodium life cycle.
Interleukin 4 induces selective production of interleukin 6 from normal human B lymphocytes.
Authors: E B Smeland, H K Blomhoff, S Funderud, M R Shalaby, T Espevik
Journal: The Journal of Experimental Medicine (1989)

In this paper we have shown that extensively purified human B lymphocytes respond to IL-4 treatment with a marked production of IL-6. Addition of anti-mu potentiated the effect of IL-4 on IL-6 production. Other cytokines tested like TNF-alpha and-beta, IFN-gamma, IL-1, IL-2, and IL-5 did not induce IL-6 secretion when given to resting B cells. Although B cells generally also produced TNF-alpha and TNF-beta upon stimulation, IL-4 did not induce TNF secretion and seemingly had a specific effect on IL-6 production.
Evidence of a Genetic Relationship Between Susceptibility to 3-Methylcholanthrene-Induced Subcutaneous Tumors and Inducibility of Aryl Hydrocarbon Hydroxylase2
Authors: Richard E. Kouri, Harry Ratrie, Carrie E. Whitmire
Journal: JNCI Journal of the National Cancer Institute (1973)

We found a close correlation between susceptibility to 3-methylcholanthrene (MCA)induced subcutaneous tumors and the genetically mediated presence of aryl hydrocarbon hydoxylase (AHH) induction. In a genetic system where AHH inducibility segregated as a single autosomal dominant genel mice carrying the Ahb (or inducible) allele were 5–10 times more sensitive to MCA tumorigenesis than were their non inducible (Ahd/Ahd) littermates. In backcross animals [(C57BL/6×DBA/2)×DBA/2], 10 of 12 (83%) mice with tumors were AHH inducible. This was statistically significant (P<0.025) (the expected response was 50%) and clearly indicated a relationship between this enzyme system and MCA carcinogenesis.
Phase II Study of Cediranib in Patients with Advanced Gastrointestinal Stromal Tumors or Soft-Tissue Sarcoma
Authors: Ian Judson, Michelle Scurr, Kate Gardner, Elizabeth Barquin, Marcelo Marotti, Barbara Collins, Helen Young, Juliane M. Jürgensmeier, Michael Leahy
Journal: Clinical Cancer Research (2014)

Cediranib is a potent VEGF signaling inhibitor with activity against all three VEGF receptors and KIT. This phase II study evaluated the antitumor activity of cediranib in patients with metastatic gastrointestinal stromal tumor (GIST) resistant/intolerant to imatinib, or metastatic soft-tissue sarcomas (STS; ClinicalTrials.gov, NCT00385203).Patients received cediranib 45 mg/day. Primary objective was to determine the antitumor activity of cediranib according to changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET) tumor uptake in patients with GIST using maximum standardized uptake values (SUVmax). Secondary objectives included objective tumor response and tolerability in patients with GIST/STS.Thirty-four of 36 enrolled patients were treated (GIST n = 24; STS n = 10). At day 29, five patients had confirmed decreases in SUVmax (≥10% from day 8) and two had confirmed partial metabolic responses (≥25% decrease), but arithmetic mean percentage changes in SUVmax, averaged across the cohort, were not significant at day 8 [6.8%; 95% confidence interval (CI), 19.95-33.54) or day 29 (4.6%; 95% CI, 8.05-17.34). Eleven patients with GIST achieved a best objective tumor response of stable disease; eight achieved stable disease ≥16 weeks. In patients with STS, four of six with alveolar soft-part sarcoma (ASPS) achieved confirmed and durable partial responses. The commonest adverse events were diarrhea (85%), fatigue (74%), and hypertension (68%).In patients progressing on imatinib/sunitinib, cediranib 45 mg/day demonstrated evidence of activity by (18)FDG-PET, but did not reduce average SUVmax. Evidence of antitumor activity was seen in ASPS.
Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL
Authors: Bing He, Weifeng Xu, Paul A. Santini, Alexandros D. Polydorides, April Chiu, Jeannelyn Estrella, Meimei Shan, Amy Chadburn, Vincenzo Villanacci, Alessandro Plebani, Daniel M. Knowles, Maria Rescigno, Andrea Cerutti
Journal: Immunity (2007)
Virus Expression and Immunoprophylaxis of a Murine Lymphoma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: I Sekine, D L Vredevoe, E F Hays
Journal: JNCI Journal of the National Cancer Institute (1975)

CBA mice tested with a rapidly lethal transplanted lymphoma could survive challenge when pretreated with allogeneic lymphoma cells or other material expressing murine leukemia virus (MuLV). Protection resulted when recipients were given injections of AKR and C3H transplanted lymphomas or selected normal AKR and SJL tissues, filtrates of which give positive assays for MuLV by in vitro and/or in vivo tests. There was no protection when recipients were given injections of C3H lymphomas or C3H normal tissues that failed to have positive assays for virus.
Noninvasive Ventilation with Helium–Oxygen in Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: SAMIR JABER, REDOUANE FODIL, ANNALISA CARLUCCI, MOHAMED BOUSSARSAR, JÉRÔME PIGEOT, FRANÇOIS LEMAIRE, ALAIN HARF, FRÉDÉRIC LOFASO, DANIEL ISABEY, LAURENT BROCHARD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The use of helium–oxygen (HeO2) was tested in combination with noninvasive ventilation (NIV) in 10 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Effort to breathe as assessed by the respiratory muscle pressure-time index (PTI), work of breathing (WOB), and gas exchange were the main endpoints. Results of NIV-HeO2 were compared with those obtained with standard NIV (AirO2), at two levels of pressure-support ventilation (PSV), 9 ± 2 cm H2O and 18 ± 3 cm H2O. Significant reductions in PTI were observed between HeO2 and AirO2 at both the low PSV level (n = 9; 160 ± 58 versus 198 ± 78 cm H2O/s/ min; p < 0.05) and the high PSV level (n = 10; 100 ± 45 versus 150 ± 82 cm H2O/s/min; p < 0.01). WOB also differed significantly between HeO2 and AirO2 (7.8 ± 4.1 versus 10.9 ± 6.1 J/min at the low PSV level, p < 0.05; and 5.7 ± 3.3 versus 9.2 ± 5. J/min, p < 0.01 at the high PSV level). HeO2 reduced PaCO2 at both the low PSV level (61 ± 13 versus 64 ± 15 mm Hg; p < 0.05) and the high PSV level (56 ± 13 versus 58 ± 14 mm Hg; p < 0.05), without significantly changing breathing pattern or oxygenation. We conclude that use of HeO2 during NIV markedly enhances the ability of NIV to reduce patient effort and to improve gas exchange.
Effect of indacaterol, a novel long-acting β<sub>2</sub>-agonist, on isolated human bronchi
Authors: E. Naline, A. Trifilieff, R. A. Fairhurst, C. Advenier, M. Molimard
Journal: European Respiratory Journal (2006)

Indacaterol is a novel β 2 -adrenoceptor agonist in development for the once-daily treatment of asthma and chronic obstructive pulmonary disease. The present study evaluated the relaxant effect of indacaterol on isolated human bronchi obtained from lungs of patients undergoing surgery for lung carcinoma. Potency (-logEC 50 ), maximal relaxant effect (E max ) and onset of action were determined at resting tone. Duration of action was determined against cholinergic neural contraction induced by electrical field stimulation (EFS). At resting tone, -logEC 50 and E max values were 8.82±0.41 and 77±5% for indacaterol, 9.84±0.22 and 94±1% for formoterol, 8.36±0.16 and 74±4% for salmeterol, and 8.43±0.22 and 84±4% for salbutamol, respectively. In contrast to salmeterol, indacaterol did not antagonise the isoprenaline response. Indacaterol's onset of action (7.8±0.7 min) was not significantly different from that of formoterol (5.8±0.7 min) or salbutamol (11.0±4.0 min), but it was significantly faster than that of salmeterol (19.4±4.3 min). EFS-induced contractions were inhibited with -logIC 50 values of 6.96±0.13 (indacaterol), 8.96±0.18 (formoterol), 7.18±0.34 (salmeterol) and 6.39±0.26 (salbutamol). Duration of action was &gt;12 h for indacaterol and salmeterol, and 35.3±8.8 and 14.6±3.7 min for formoterol and salbutamol, respectively. In isolated human bronchi, indacaterol behaved as a long-acting β 2 -adrenoceptor agonist with high intrinsic efficacy and fast onset of action.
Error in Characterization of Treg Cells in the Article by Soloski and Chrest (Arthritis Rheum, May 2013)
Authors: Mark J. Soloski, Francis J. Chrest
Journal: Arthritis & Rheumatology (2014)

In the article by Soloski and Chrest in the May 2013 issue of Arthritis & Rheumatism (pages 1148–1156), the statement “In addition, natural Treg cells can be defined as CD4+CD137lowCD25+FoxP3+ (14)” (page 1151) contained an error. It should correctly read “In addition, natural Treg cells can be defined as CD4+CD127lowCD25+FoxP3+ (14).” Similarly, in the second column of Table 1, the specific marker for CD4+ natural Treg cells was shown as “CD137lowCD25+/FoxP3+”; this should correctly read “CD127lowCD25+FoxP3+.”
Effects of 50- or 60-hertz, 100 microT magnetic field exposure in the DMBA mammary cancer model in Sprague-Dawley rats: possible explanations for different results from two laboratories.
Authors: L E Anderson, J E Morris, L B Sasser, W Löscher
Journal: Environmental Health Perspectives (2000)

In line with the possible relationship between electric power and breast cancer risk and the underlying melatonin hypothesis, 50-Hz magnetic field (MF) exposure at microtesla flux densities for either 13 or 27 weeks significantly increased the development and growth of mammary tumors in a series of experiments from Löscher's group in Germany. Löscher's group used the 7,12-dimethylbenz[a]anthracene (DMBA) model of breast cancer in Sprague-Dawley rats. The finding could not be replicated when a similar experimental protocol was used in a study conducted by Battelle in the United States. In the present paper, investigators from the two groups discuss differences between their studies that might explain the apparent discrepancies between the results. These differences include the use of different substrains of Sprague-Dawley rats (the U.S. rats were more susceptible to DMBA than the European rats), different sources for diet and DMBA, differences in environmental conditions, and differences in MF exposure metrics. Furthermore, the effects of MF exposure reported by Löscher's group, albeit significant, were weak. We also discuss the general problem of replicating such weak effects.
Grandparental investment: Past, present, and future
Authors: David A. Coall, Ralph Hertwig
Journal: Behavioral and Brain Sciences (2010)

Abstract What motivates grandparents to their altruism? We review answers from evolutionary theory, sociology, and economics. Sometimes in direct conflict with each other, these accounts of grandparental investment exist side-by-side, with little or no theoretical integration. They all account for some of the data, and none account for all of it. We call for a more comprehensive theoretical framework of grandparental investment that addresses its proximate and ultimate causes, and its variability due to lineage, values, norms, institutions (e.g., inheritance laws), and social welfare regimes. This framework needs to take into account that the demographic shift to low fecundity and mortality in economically developed countries has profoundly altered basic parameters of grandparental investment. We then turn to the possible impact of grandparental acts of altruism, and examine whether benefits of grandparental care in industrialized societies may manifest in terms of less tangible dimensions, such as the grandchildren's cognitive and verbal ability, mental health, and well-being. Although grandparents in industrialized societies continue to invest substantial amounts of time and money in their grandchildren, we find a paucity of studies investigating the influence that this investment has on grandchildren in low-risk family contexts. Under circumstances of duress – for example, teenage pregnancy or maternal depression – there is converging evidence that grandparents can provide support that helps to safeguard their children and grandchildren against adverse risks. We conclude by discussing the role that grandparents could play in what has been referred to as Europe's demographic suicide.
Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients
Authors: Nishi Gupta, Azeem Saleem, Barbara Kötz, Safiye Osman, Eric O. Aboagye, Robert Phillips, Clare Vernon, Harpreet Wasan, Terry Jones, Peter J. Hoskin, Patricia M. Price
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases. Experimental Design: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles. At the second positron emission tomography session, 60 mg/kg nicotinamide was given orally 2 to 3 hours before 10-minute carbogen inhalation. In the middle of carbogen treatment, [15O]H2O (to measure regional tissue perfusion) and then [18F]5-FU (to measure 5-FU tissue pharmacokinetics) were administered. Results: Regions of interest were drawn in 12 liver metastases, 6 spleens, 6 livers, and 12 kidneys. Nicotinamide and carbogen administration increased mean blood pO2 from 93 mm Hg (95% confidence interval, 79-198) to 278 mm Hg (95% confidence interval, 241-316; P = 0.031). Regional perfusion (mLblood/min/mLtissue) increased in metastases (mean change = 52%, range −32% to +261%, P = 0.024), but decreased in kidney (mean change = −42%, range −82% to −11%, P = 0.0005) and liver (mean change = −34%, range −43% to −26%, P = 0.031). 5-FU uptake at 3.75 minutes (m2/mL) increased in tumor (mean change = 40%, range −39% to +196%, P = 0.06) and decreased in kidney (mean change = −25%, range −71% to 12%, P = 0.043). 5-FU delivery measured as K1 increased in tumor (mean change = 74%, range −23% to +293%, P = 0.0039). No differences were seen in [18F]5-FU tumor exposure (net area under curve) and retention. Conclusion: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases. Despite an increase in perfusion and 5-FU delivery, the effects were not directly related and did not increase 5-FU retention or tissue exposure.
A Randomized Trial of a Single Dose of Oral Dexamethasone for Mild Croup
Authors: Candice L. Bjornson, Terry P. Klassen, Janielee Williamson, Rollin Brant, Craig Mitton, Amy Plint, Blake Bulloch, Lisa Evered, David W. Johnson
Journal: New England Journal of Medicine (2004)

The benefits of dexamethasone treatment for moderate-to-severe croup are well established. However, most children with croup have mild symptoms, and it is unknown whether they would derive the same degree of benefit from dexamethasone treatment as children with more severe disease.We conducted a double-blind trial at four pediatric emergency departments in which 720 children with mild croup were randomly assigned to receive one oral dose of either dexamethasone (0.6 mg per kilogram of body weight) or placebo. The children had mild croup, as defined by a score of < or =2 on the croup scoring system of Westley et al. The primary outcome was a return to a medical care provider for croup within seven days after treatment. The secondary outcome was the presence of ongoing symptoms of croup on days 1, 2, and 3 after treatment. Other outcomes included economic costs, hours of sleep lost by the child, and stress on the part of the parent in relation to the child's illness.Baseline clinical characteristics were similar in the two groups. Return to medical care was significantly lower in the dexamethasone group (7.3 percent vs. 15.3 percent, P<0.001). In the dexamethasone group, there was quicker resolution of croup symptoms (P=0.003), less lost sleep (P<0.001), and less stress on the part of the parent (P<0.001).For children with mild croup, dexamethasone is an effective treatment that results in consistent and small but important clinical and economic benefits. Although the long-term effects of this treatment are not known, our data support the use of dexamethasone in most, if not all, children with croup.
VEGF receptor switching in heart development and disease
Authors: R. Madonna, R. De Caterina
Journal: Cardiovascular Research (2009)

Vascular endothelial growth factor (VEGF), also known as VEGF-A to distinguish it from other isoforms (B–D) that are mainly involved in lymphangiogenesis, is an endothelial cell mitogen that has an essential role in both vasculogenesis and angiogenesis.1 VEGF regulates the development of endoderm-derived tissues, such as the vascular endothelium and the endocardium, by inducing multiple angiogenic cellular responses, including promotion of survival, migration, and differentiation, through the activation of Akt signalling in endothelial cells.2 VEGF exerts its biological actions by interacting with two main tyrosine kinase receptors, known as VEGFR-1 \[or FMS-like tyrosine kinase-1 (Flt-1)] and VEGFR-2 [alternative names: foetal liver kinase-1 and kinase insert domain receptor (KDR)\] ( Figure 1 ).3



Figure 1 
A schematic representation of the cardiomyocyte VEGF signalling pathway. Flt-1 and KDR are the two major VEGF receptors. In cardiomyocytes, VEGF drives cardiac hypertrophy or its regression, depending on the prevalent binding to KDR or Flt-1, respectively. Copper (Cu) supplementation determines a switch in the VEGF signalling pathway, increasing the ratio of Flt-1 to KDR. By this mechanism, copper induces regression of cardiomyocyte hypertrophy. VEGF, vascular endothelial growth factor; Flt-1, FMS-like tyrosine kinase-1; KDR, kinase insert domain receptor; PKG-1, cGMP-dependent protein kinase-1; Cu, copper; DAG, diacylglycerol; IP3, inositol trisphosphate; Sos, Son of Sevenless; Shc, Src-homology collagen protein; Grb-2, growth factor receptor-bound protein 2; MEK1/2, mitogen activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) kinase 1/2; PKC, protein kinase C; PLC-γ, phospholipase C-γ; PD98059 (PD) and UO126 are selective ERK1/2 inhibitors.



Intriguingly, based on work … 

*Corresponding author. Tel: +39 0871 41512; fax: +39 0871 402817. E-mail address : rdecater{at}ifc.cnr.it
Adjuvant Bisphosphonates and Breast Cancer Survival
Authors: Stephanie Strobl, Belgin Korkmaz, Yelena Devyatko, Michael Schuetz, Ruth Exner, Peter C. Dubsky, Raimund Jakesz, Michael Gnant
Journal: Annual Review of Medicine (2015)

Randomized trials have studied bisphosphonates in the adjuvant setting of early breast cancer to investigate their ability to prevent treatment-induced bone loss. Trial results have also suggested their potential to prevent disease recurrence and metastases. These trials are summarized in this review. A recent patient-level meta-analysis by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) finds convincing evidence that adjuvant antiresorptive treatments provide persistent benefits to breast cancer patients in low-estrogen situations and should be considered an important part of the treatment algorithm.