tbuckley/cabot-search huggingface dataset:
Adrenal Medullary Secretion During Hypoxia, Bleeding, and Rapid Intravenous Infusion
Authors: NOBLE O. FOWLER, RALPH SHABETAI, JOHN C. HOLMES
Journal: Circulation Research (1961)

This study reports the effect of hypoxia, of lowering blood pressure by bleeding, and of rapid infusion upon adrenal secretion in anesthetized dogs. Adrenal norepinephrine-like substances (NEL) were measured in adrenal venous blood by means of a bio-assay method, using the rabbit aortic strip. In 10 of 11 dogs breathing 7.1 per cent O 2 in N 2 , the left adrenal NEL output was augmented 1.5 to 6.6 times control levels. The increased adrenal medullary secretion during hypoxia was not dependent upon a fall in systemic arterial blood pressure and was not associated with an increase of 17-hydroxycorticosteroid output. In five dogs bled to a blood pressure of 80 to 90 mm. Hg, left adrenal NEL output was augmented 2.9 to 7.4 times control levels. In 11 animals in which the blood pressure was lowered to 40 to 50 mm. Hg by bleeding, left adrenal NEL output was augmented 1.8 to 17 times control levels. Seven dogs were made anemic and hypervolemic by rapid infusion of 1,125 to 1,900 ml. normal saline or Krebs' solution. Cardiac outputs were increased more than 200 per cent in six, and considerable dilution anemia was produced. However, left adrenal NEL outputs fell to values ranging from 14 to 50 per cent of control. During rapid infusions, output of adrenal 17-OHCS increased 18.5 to 92 per cent. It is concluded that increased adrenal medullary secretion did not participate in the increase of cardiac output observed in these seven animals.
A fresh look at D-dimer in suspected pulmonary embolism
Authors: A C MILLER
Journal: Thorax (1998)

Newer imaging approaches in suspected pulmonary embolism (PE) such as the PISA-PED perfusion lung scanning criteria,1spiral computed tomography,2 and leg vein ultrasound3 are attracting widespread interest. Attempts are being made to clarify and rationalise clinical diagnosis,4 and the use of low molecular weight heparin in PE5 is increasing. However, it is often forgotten that clinical suspicion of PE turns out to be incorrect in five out of every six patients properly investigated.6 7 Since in most district general hospitals imaging tests for suspected PE cannot usually be arranged immediately, such patients have to be admitted and heparin started while awaiting an isotope lung scan which often fails to give an unequivocal answer. All this is costly in time and resources and engenders considerable anxiety in the patient.

A simple cheap and accurate test to exclude PE that is also available out of hours would be of great interest to general physicians. Hopes for plasma d-dimer seemed not to have been …
Adaptive Evolution in Rodent Seminal Vesicle Secretion Proteins
Authors: R. C. Karn, N. L. Clark, E. D. Nguyen, W. J. Swanson
Journal: Molecular Biology and Evolution (2008)

Proteins involved in reproductive fitness have evolved unusually rapidly across diverse groups of organisms. These reproductive proteins show unusually high rates of amino acid substitutions, suggesting that the proteins have been subject to positive selection. We sought to identify seminal fluid proteins experiencing adaptive evolution because such proteins are often involved in sperm competition, host immunity to pathogens, and manipulation of female reproductive physiology and behavior. We performed an evolutionary screen of the mouse prostate transcriptome for genes with elevated evolutionary rates between mouse and rat. We observed that secreted rodent prostate proteins evolve approximately twice as fast as nonsecreted proteins, remarkably similar to findings in the primate prostate and in the Drosophila male accessory gland. Our screen led us to identify and characterize a group of seminal vesicle secretion (Svs) proteins and to show that the gene Svs7 is evolving very rapidly, with many amino acid sites under positive selection. Another gene in this group, Svs5, showed evidence of branch-specific selection in the rat. We also found that Svs7 is under selection in primates and, by using three-dimensional models, demonstrated that the same regions have been under selection in both groups. Svs7 has been identified as mouse caltrin, a protein involved in sperm capacitation, the process responsible for the timing of changes in sperm activity and behavior, following ejaculation. We propose that the most likely explanation of the adaptive evolution of Svs7 that we have observed in rodents and primates stems from an important function in sperm competition.
Gene expression profiling of pediatric acute myelogenous leukemia
Authors: Mary E. Ross, Rami Mahfouz, Mihaela Onciu, Hsi-Che Liu, Xiaodong Zhou, Guangchun Song, Sheila A. Shurtleff, Stanley Pounds, Cheng Cheng, Jing Ma, Raul C. Ribeiro, Jeffrey E. Rubnitz, Kevin Girtman, W. Kent Williams, Susana C. Raimondi, Der-Cherng Liang, Lee-Yung Shih, Ching-Hon Pui, James R. Downing
Journal: Blood (2004)
Autoimmunity in a Phase I Trial of a Fully Human Anti-Cytotoxic T-Lymphocyte Antigen-4 Monoclonal Antibody With Multiple Melanoma Peptides and Montanide ISA 51 for Patients With Resected Stages III and IV Melanoma
Authors: Kristin Sanderson, Ronald Scotland, Peter Lee, Dongxin Liu, Susan Groshen, Jolie Snively, Shirley Sian, Geoffrey Nichol, Thomas Davis, Tibor Keler, Michael Yellin, Jeffrey Weber
Journal: Journal of Clinical Oncology (2004)

Nineteen patients with high-risk resected stage III and IV melanoma were immunized with three tumor antigen epitope peptides from gp100, MART-1, and tyrosinase emulsified with adjuvant Montanide ISA 51 and received a fully human anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody MDX-010. Each of three cohorts received escalating doses of antibody with vaccine primarily to evaluate the toxicities and maximum-tolerated dose (MTD) of MDX-010 with vaccine. MDX-010 pharmacokinetics and immune responses were secondary end points.Peptide immunizations with MDX-010 were administered every 4 weeks for 6 months and then every 12 weeks for 6 months. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was performed before treatment and after the sixth vaccination. Patients were observed until relapse.Grade 3 gastrointestinal (GI) toxicity (diarrhea or abdominal pain) was observed in three patients in the highest dose cohort and one in the middle dose cohort who seemed to be autoimmune. That defined the MTD with vaccine on this schedule at 1 mg/kg. Of eight patients with evidence of autoimmunity, three have experienced disease relapse. Of 11 patients without autoimmune symptoms, nine have experienced disease relapse. Significant immune responses were measured by tetramer and enzyme-linked immunospot assays against gp100 and MART-1.Dose-related autoimmune adverse events, predominantly skin and GI toxicities, were reversible. Patients mounted an antigen-specific immune response to a peptide vaccine when combined with a human anti-CTLA-4 antibody.
Higher plantar pressure on the medial side in four soccer-related movements
Authors: Pui-lam Wong, Karim Chamari, De Wei Mao, Ulrik Wisløff, Youlian Hong
Journal: British Journal of Sports Medicine (2006)

Objective: To measure the plantar pressure in four soccer-related movements in 15 male soccer players (mean (SD) age 20.9 (1.3) years, height 173 (4) cm, weight 61.7 (3.6) kg). Design: : To record plantar pressure distribution, the players wore soccer boots with 12 circular studs and with an insole pressure recorder device equipped with 99 sensors. Plantar pressure was recorded in five successful trials in each of the four soccer-related movements: running, sideward cutting, 45° cutting and landing from a vertical jump. Each footprint was divided into 10 recorded areas for analysis. Results: : Compared with running at 3.3 m/s, maximal speed sideward cutting and 45° cutting induced higher peak pressure (p&lt;0.05) under the second toe, medial forefoot, medial arch and medial heel. The peak pressure of the maximal jump landing was lower under the medial forefoot and lateral forefoot as compared with running (p&lt;0.05). The pressure–time integral showed that sideward cutting and 45° cutting induced higher pressures (p&lt;0.05) than running for all recorded areas, except for the lateral forefoot and the lateral arch. In all the four soccer-related movements, a higher pressure was found on the medial side of the plantar surface as compared with the lateral side. Conclusions: : These data suggest that the medial side of the plantar surface may be more prone to injuries, and that foot orthosis adoption, improved soccer boot design and specific muscle training could be considered to reduce pressure and the subsequent risk of injury.
On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets.
Authors: J Forman
Journal: The Journal of Experimental Medicine (1975)

Spleen cells cultured with syngeneic trinitrophenyl (TNP)-modified stimulator cells display a cytotoxic effect against syngeneic TNP-modified targets, but not against modified targets from unrelated H-2 haplotypes. Targets that share the K and I region of the H-2 complex with the stimulator (or effector) cell are lysed to the same extent as the specific targets, while targets that share the I region only are not. When only the D region is shared, a weak cytotoxic effect is observed. Therefore, the stimulator (or effector) and target cell must share the K or D but not the I region of the H-2 complex in order for optimal cytotoxicity to occur. Spleen cells sensitized to irradiated TNP-modified H-2-allogeneic cells are cytotoxic to these specific cells. Coculture of F1 hybrid cells with irradiated TNP-modified parental cells result in a cytotoxic effect against only those specific parental cells and not TNP-modified cells from the other parent. The cytotoxic effect of the F1 effector cells in the cell-mediated lympholysis test is blocked by the addition of unlabeled TNP-modified targets that are H-2 syngeneic with the sensitizing parental strain, but not H-2 syngeneic with the other parental strain. These data demonstrate that the specificity of the effector cell in this syngeneic cytotoxicity system is directed against altered self H-2-controlled-gene products, rather than a requirement for sharing of histocompatibility genes between effector and target cell in order for lysis to occur. The role of H-2 antigens in determining the sensitivity of a target cell to T-cell-mediated lysis is discussed.
Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial
Authors: Guy G Brusselle, Christine VanderStichele, Paul Jordens, René Deman, Hans Slabbynck, Veerle Ringoet, Geert Verleden, Ingel K Demedts, Katia Verhamme, Anja Delporte, Bénédicte Demeyere, Geert Claeys, Jerina Boelens, Elizaveta Padalko, Johny Verschakelen, Georges Van Maele, Ellen Deschepper, Guy F P Joos
Journal: Thorax (2013)

<h3>Background</h3> Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. <h3>Methods</h3> We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β<sub>2</sub> agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). <h3>Results</h3> The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. <h3>Conclusions</h3> Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. <h3>ClinicalTrials.gov number</h3> NCT00760838.
A requirement for membrane-associated phospholipase A2 in platelet cytotoxicity activated by receptors for immunoglobulin G and complement.
Authors: D E Symer, W A Paznekas, H S Shin
Journal: The Journal of Experimental Medicine (1993)

Platelets are potent antibody- and complement-dependent cytotoxic effector cells. We showed previously that a single platelet can lyse a target cell sensitized with immunoglobulin G (IgG) and complement components up to C3 (C integral of 3b denotes the target cell-bound fragment of complement up to C3; the precise nature of the bound C3 fragment has not been established), and that the complete cytotoxic system capable of specific recognition and lysis resides in platelet membranes. To define the components of platelet membranes required for cytotoxicity, a set of inhibitors of phospholipase A2 (PLA2) that act by different chemical mechanisms was tested. The lytic reaction is blocked at appropriate concentrations of bromophenacylbromide, mepacrine, and manoalide. When platelets are treated with bromophenacylbromide, inhibition of cytolytic activity and that of PLA2 enzymatic activity occur in parallel. Platelets release arachidonate when incubated with target cells bearing IgG and C integral of 3b, confirming that Fc gamma R and complement receptor trigger both PLA2 action and efficient lysis. Inhibition by thimerosal of a reverse reaction, i.e., reacylation catalyzed by acyltransferase, causes increased target cell lysis, presumably by increasing the products of PLA2 action. Platelet cytotoxicity is increased when platelets are pretreated with some products of PLA2: exogenous lysophospholipids and not free arachidonic acid increase cytotoxicity. Electron microscopy suggests that platelets and target cells may fuse, possibly as a result of the formation of lysophospholipids which are well-known membrane fusogens. Fixation with paraformaldehyde does not affect platelet cytotoxicity, suggesting that the complete cytotoxic system resides as a preformed complex in platelet membranes. The results indicate that platelet membrane-associated PLA2, together with receptors for Fc and complement, are required for platelet cytotoxicity.
An antiproliferative BMP-2/PPARγ/apoE axis in human and murine SMCs and its role in pulmonary hypertension
Authors: Georg Hansmann, Vinicio A. de Jesus Perez, Tero-Pekka Alastalo, Cristina M. Alvira, Christophe Guignabert, Janine M. Bekker, Stefan Schellong, Takashi Urashima, Lingli Wang, Nicholas W. Morrell, Marlene Rabinovitch
Journal: Journal of Clinical Investigation (2008)

Loss-of-function mutations in bone morphogenetic protein receptor II (BMP-RII) are linked to pulmonary arterial hypertension (PAH); the ligand for BMP-RII, BMP-2, is a negative regulator of SMC growth. Here, we report an interplay between PPARgamma and its transcriptional target apoE downstream of BMP-2 signaling. BMP-2/BMP-RII signaling prevented PDGF-BB-induced proliferation of human and murine pulmonary artery SMCs (PASMCs) by decreasing nuclear phospho-ERK and inducing DNA binding of PPARgamma that is independent of Smad1/5/8 phosphorylation. Both BMP-2 and a PPARgamma agonist stimulated production and secretion of apoE by SMCs. Using a variety of methods, including short hairpin RNAi in human PASMCs, PAH patient-derived BMP-RII mutant PASMCs, a PPARgamma antagonist, and PASMCs isolated from PPARgamma- and apoE-deficient mice, we demonstrated that the antiproliferative effect of BMP-2 was BMP-RII, PPARgamma, and apoE dependent. Furthermore, we created mice with targeted deletion of PPARgamma in SMCs and showed that they spontaneously developed PAH, as indicated by elevated RV systolic pressure, RV hypertrophy, and increased muscularization of the distal pulmonary arteries. Thus, PPARgamma-mediated events could protect against PAH, and PPARgamma agonists may reverse PAH in patients with or without BMP-RII dysfunction.
Characterization of a Putative Founder Mutation that Accounts for the High Incidence of Cystinosis in Brittany
Authors: VASILIKI KALATZIS, STÉPHANIE CHERQUI, GENEVIÈVE JEAN, BÉATRICE CORDIER, PIERRE COCHAT, MICHEL BROYER, CORINNE ANTIGNAC
Journal: Journal of the American Society of Nephrology (2001)

Cystinosis is an autosomal recessive disorder, characterized by an accumulation of intralysosomal cystine, with an incidence of 1 in 100,000 to 200,000 live births. A higher incidence of cystinosis, 1 in 26,000 live births, has been reported in the western French province of Brittany. PCR amplification and sequencing has identified a 27-bp deletion starting 3 bp before the end of exon 8 and continuing into intron 8, 898-900+24del27, which has only been detected in families from this region. Reverse transcription—PCR amplification of RNA from an affected individual has shown that this mutation is indeed a splice-site mutation and results in the production of aberrant transcripts. These transcripts are predicted to either severely truncate cystinosin or alter its topology, thus accounting for the severe phenotype of these individuals. The mutation 898-900+24del27 has been identified in 7 of 18 alleles studied. This mutation is likely to be a founder mutation and would account for the higher incidence of cystinosis in Brittany.1
Pediatric Intensive Care
Journal: Thorax (1990)

of the New Zealand Department of Health's recommendations advising against the use of fenoterol in patients with severe asthma, Duovent was deleted from the protocol and ipratropium bromide (Atrovent) is available when a further nebulised bronchodilator is required.We acknowledge Drs P Rothwell and B Mahood for suggesting the use of such protocols, Dr H Leslie and the staff of the Wellington Hospital emergency department for their interest and cooperation, and the secretarial staff of the department of medicine.
Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression
Authors: Silvia Fischer, Sabine Gesierich, Barbara Griemert, Anne Schänzer, Till Acker, Hellmut G. Augustin, Anna-Karin Olsson, Klaus T. Preissner
Journal: Cancer Research (2013)

Extracellular RNA (eRNA) released from injured cells promotes tissue permeability, thrombosis, and inflammation in vitro and in vivo, and RNase1 pretreatment can reduce all these effects. In this study, we investigated the role of the eRNA/RNase1 system in tumor progression and metastasis. Under quiescent and stimulatory conditions, tumor cells released much higher levels of endogenous extracellular RNA (eRNA) than nontumor cells. In glioblastomas, eRNA was detected at higher levels in tumors than nontumor tissue. eRNA induced tumor cells to adhere to and migrate through human cerebral microvascular endothelial cells (HCMEC/D3), in a manner requiring activation of VEGF signaling. In addition, eRNA liberated TNF-α from macrophages in a manner requiring activation of the TNF-α-converting enzyme TACE. Accordingly, supernatants derived from eRNA-treated macrophages enhanced tumor cell adhesion to HCMEC/D3. TNF-α release evoked by eRNA relied upon signaling activation of mitogen-activated protein kinases and the NF-κB pathway. In subcutaneous xenograft models of human cancer, administration of RNase1 but not DNase decreased tumor volume and weight. Taken together, these results suggest that eRNA released from tumor cells has the capacity to promote tumor cell invasion through endothelial barriers by both direct and indirect mechanisms, including through a mechanism involving TNF-α release from tumor-infiltrating monocytes/macrophages. Our findings establish a crucial role for eRNA in driving tumor progression, and they suggest applications for extracellular RNase1 as an antiinvasive regimen for cancer treatment.
Incorporated sarcolemmal fish oil fatty acids shorten pig ventricular action potentials
Authors: A VERKERK, A VANGINNEKEN, G BERECKI, H DENRUIJTER, C SCHUMACHER, M VELDKAMP, A BAARTSCHEER, S CASINI, T OPTHOF, R HOVENIER
Journal: Cardiovascular Research (2006)

Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil reduce the risk of sudden death presumably by preventing life-threatening arrhythmias. Acutely administered omega3-PUFAs modulate the activity of several cardiac ion channels, but the chronic effects of a diet enriched with fish oil leading to omega3-PUFA-incorporation into the sarcolemma on membrane currents are unknown.Pigs received a diet either rich in omega3-PUFAs or in omega9-fatty acids for 8 weeks. Ventricular myocytes (VMs) were isolated and used for patch-clamp studies.omega3-VMs contained higher amounts of omega3-PUFAs and had a shorter action potential (AP) with a more negative plateau than control VM. In omega3 VMs, L-type Ca(2+) current (I(Ca,L)) and Na(+)-Ca(2+) exchange current (I(NCX)) were reduced by approximately 20% and 60%, respectively, and inward rectifier K(+) current (I(K1)) and slow delayed rectifier K(+) current (I(Ks)) were increased by approximately 50% and 70%, respectively, compared to control. Densities of rapid delayed rectifier K(+) current, Ca(2+)-activated Cl(-) current, and Na(+) current (I(Na)) were unchanged, although voltage-dependence of I(Na) inactivation was more negative in omega3 VMs.A fish oil diet increases omega3-PUFA content in the ventricular sarcolemma, decreases I(Ca,L) and I(NCX), and increases I(K1) and I(Ks), resulting in AP shortening. Incorporation of omega3-PUFAs in the sarcolemma may have consequences for arrhythmias independent of circulating omega3-PUFAs.
Restoring Airway Surface Liquid in Cystic Fibrosis
Authors: Felix Ratjen
Journal: New England Journal of Medicine (2006)

The current pathophysiological model of cystic fibrosis lung disease assumes that defective expression, trafficking, or function of the cystic fibrosis transmembrane regulator (CFTR) protein leads to impaired epithelial chloride secretion and sodium hyperabsorption. This process, in turn, results in the depletion of airway surface liquid and abnormal mucociliary transport. Retention of mucus is thought to favor bacterial overgrowth, which then triggers a cycle of repeated or chronic infections associated with intense neutrophilic airway inflammation.Defective mucociliary transport itself can cause airway inflammation, as has been shown in mice that have an overexpression of the beta subunit of the epithelial sodium . . .