tbuckley/cabot-search huggingface dataset:
Development of phospholipase A2 and lysophosphatidylcholine metabolising enzyme activities in the neonatal rat intestine.
Authors: C Tagesson, E Telemo, G Ekstrom, B Westrom
Journal: Gut (1987)

We have studied the development of phospholipase A2 (PLA2) and lysophosphatidylcholine (lysoPC)-metabolising enzyme activities in the neonatal rat intestine and its relation to the intestinal permeability of macromolecules. The permeability was determined by feeding young rats a mixture of bovine serum albumin, bovine immunoglobulin G and fluorescein-isothiocyanate-conjugated dextran 70,000, and analysing the serum concentrations after six hours. The animals were then killed and the intestinal mucosa was homogenised and assessed for PLA2 and lysoPC-metabolising enzyme activities. The intestine was 9open9 to the macromolecules in 14 day old animals, but 9closed9 in 22 and 32 day old animals and in 14 day old rats treated with cortisone acetate on day 10, 11, and 12 postpartum. The activity of PLA2 (at pH 6 and 2 mM Ca2+) was higher in 32, 22, and cortisone treated 14 day old animals, than in untreated, 14 day old animals. Incubation of 14C-acyl-lysoPC with mucosa from 14 day old rats did not change the radioactivity pattern as shown by thin layer chromatography, whereas after incubation with mucosa from 22 or 32 day old animals all the radiolabel was found in free 14C-fatty acid and in 14C-phosphatidylcholine. These findings indicate that mucosal PLA2 activity increases during intestinal maturation and that the mucosa acquires the ability to acylate and deacylate lysoPC when it is 9closed9 to macromolecules.
Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines
Authors: David C. Tscharke, Gunasegaran Karupiah, Jie Zhou, Tara Palmore, Kari R. Irvine, S.M. Mansour Haeryfar, Shanicka Williams, John Sidney, Alessandro Sette, Jack R. Bennink, Jonathan W. Yewdell
Journal: The Journal of Experimental Medicine (2004)

The large size of poxvirus genomes has stymied attempts to identify determinants recognized by CD8+ T cells and greatly impeded development of mouse smallpox vaccination models. Here, we use a vaccinia virus (VACV) expression library containing each of the predicted 258 open reading frames to identify five peptide determinants that account for approximately half of the VACV-specific CD8+ T cell response in C57BL/6 mice. We show that the primary immunodominance hierarchy is greatly affected by the route of VACV infection and the poxvirus strain used. Modified vaccinia virus ankara (MVA), a candidate replacement smallpox vaccine, failed to induce responses to two of the defined determinants. This could not be predicted by genomic comparison of viruses and is not due strictly to limited MVA replication in mice. Several determinants are immunogenic in cowpox and ectromelia (mousepox) virus infections, and immunization with the immunodominant determinant provided significant protection against lethal mousepox. These findings have important implications for understanding poxvirus immunity in animal models and bench-marking immune responses to poxvirus vaccines in humans.
Feasibility of Shortening Respiratory Isolation with a Single Sputum Nucleic Acid Amplification Test
Authors: Michael Campos, Andrew Quartin, Eliana Mendes, Alexandre Abreu, Samuel Gurevich, Luis Echarte, Tanira Ferreira, Timothy Cleary, Elena Hollender, David Ashkin
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Serial smear analysis to guide respiratory isolation (RI) of patients with suspected tuberculosis (TB), the majority of whom will be found not to have TB, leads to expensive and unnecessary isolation, and may potentially result in decreased vigilance of subjects with respiratory compromise.To compare the performance of a single first-sputum, Mycobacterium tuberculosis-specific nucleic acid amplification (NAA) test with three sputum smears for assessing the need for RI.Prospective evaluation of 493 patients with suspected TB (74% HIV positive) admitted to RI in a major county hospital in the United States, who had at least three sputum smears and material available from the first sample for additional NAA testing.Accuracy of the first sputum NAA result and serial smears for identifying patients with potentially infectious TB who truly require RI was determined. Forty-six patients (9.3%) had TB confirmed by culture. First-sputum NAA test detected all patients with TB who had a positive smear (n = 35), even when the first of the three specimens was smear negative. In addition, when compared with serial smears, the first-sputum NAA had a higher sensitivity (0.87; 95% confidence interval [CI], 0.74-0.95) and specificity (1.0) in the detection of subjects with positive M. tuberculosis cultures (smear sensitivity, 0.76; 95% CI, 0.61-0.87; and specificity, 0.96; 95% CI, 0.94-0.98).A single first-sputum NAA testing can rapidly and accurately identify the subset of patients with suspected TB who require RI according to serial sputum smears. Its potential use to shorten RI time does not preclude the need to obtain subsequent specimens for culture.
Viral Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Authors: Sharon Chao Wootton, Dong Soon Kim, Yasuhiro Kondoh, Eunice Chen, Joyce S. Lee, Jin Woo Song, Jin Won Huh, Hiroyuki Taniguchi, Charles Chiu, Homer Boushey, Lisa H. Lancaster, Paul J. Wolters, Joseph DeRisi, Don Ganem, Harold R. Collard
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Idiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation.To use unbiased genomics-based discovery methods to define the role of viruses in acute exacerbation of idiopathic pulmonary fibrosis.Bronchoalveolar lavage and serum from patients with acute exacerbation of idiopathic pulmonary fibrosis, stable disease, and acute lung injury were tested for viral nucleic acid using multiplex polymerase chain reaction, pan-viral microarray, and high-throughput cDNA sequencing.Four of forty-three patients with acute exacerbation of idiopathic pulmonary fibrosis had evidence of common respiratory viral infection (parainfluenza [n = 1], rhinovirus [n = 2], coronavirus [n = 1]); no viruses were detected in the bronchoalveolar lavage from stable patients. Pan-viral microarrays revealed additional evidence of viral infection (herpes simplex virus [n = 1], Epstein-Barr virus [n = 2], and torque teno virus [TTV] [n = 12]) in patients with acute exacerbation. TTV infection was significantly more common in patients with acute exacerbation than stable controls (P = 0.0003), but present in a similar percentage of acute lung injury controls. Deep sequencing of a subset of acute exacerbation cases confirmed the presence of TTV but did not identify additional viruses.Viral infection was not detected in most cases of acute exacerbation of idiopathic pulmonary fibrosis. TTV was present in a significant minority of cases, and cases of acute lung injury; the clinical significance of this finding remains to be determined.
Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia
Authors: Tiziana Cotechini, Maria Komisarenko, Arissa Sperou, Shannyn Macdonald-Goodfellow, Michael A. Adams, Charles H. Graham
Journal: The Journal of Experimental Medicine (2014)

Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5–16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications.
Smad-Binding Defective Mutant of Transforming Growth Factor β Type I Receptor Enhances Tumorigenesis but Suppresses Metastasis of Breast Cancer Cell Lines
Authors: Fang Tian, Stacey DaCosta Byfield, W. Tony Parks, Christina H. Stuelten, Deepa Nemani, Ying E. Zhang, Anita B. Roberts
Journal: Cancer Research (2004)

Abstract The role of transforming growth factor β (TGF-β) in carcinogenesis is complex, with tumor suppressor and pro-oncogenic activities depending on the particular tumor cell and its stage in malignant progression. We previously have demonstrated in breast cancer cell lines that Smad2/3 signaling played a dominant role in mediating tumor suppressor effects on well-differentiated breast cancer cell lines grown as xenografts and prometastatic effects on a more invasive, metastatic cell line. Our present data based on selective interference with activation of endogenous Smad2 and Smad3 by stable expression of a mutant form of the TGF-β type I receptor (RImL45) unable to bind Smad2/3 but with a functional kinase again show that reduction in Smad2/3 signaling by expression of RImL45 enhanced the malignancy of xenografted tumors of the well-differentiated MCF10A-derived tumor cell line MCF10CA1h, resulting in formation of larger tumors with a higher proliferative index and more malignant histologic features. In contrast, expression of RImL45 in the more aggressive MCF10CA1a cell line strongly suppressed formation of lung metastases following tail vein injection. These results suggest a causal, dominant role for the endogenous Smad2/3 signaling pathway in the tumor suppressor and prometastatic activities of TGF-β in these cells. Using an in vitro assay, we further show that non-Smad signaling pathways, including p38 and c-Jun NH2-terminal kinase, cooperate with TGF-β/Smads in enhancing migration of metastatic MCF10CA1a cells, but that, although necessary for migration, these other pathways are not sufficient for metastasis.
High prevalence of retinoblastoma protein loss in triple-negative breast cancers and its association with a good prognosis in patients treated with adjuvant chemotherapy
Authors: D. Treré, E. Brighenti, G. Donati, C. Ceccarelli, D. Santini, M. Taffurelli, L. Montanaro, M. Derenzini
Journal: Annals of Oncology (2009)
Response to imatinib plus sirolimus in advanced chordoma
Authors: S. Stacchiotti, A. Marrari, E. Tamborini, E. Palassini, E. Virdis, A. Messina, F. Crippa, C. Morosi, A. Gronchi, S. Pilotti, P.G. Casali
Journal: Annals of Oncology (2009)
Neonatal Exposure to Brominated Flame Retardant BDE-47 Reduces Long-Term Potentiation and Postsynaptic Protein Levels in Mouse Hippocampus
Authors: Milou M.L. Dingemans, Geert M.J. Ramakers, Fabrizio Gardoni, Regina G.D.M. van Kleef, Åke Bergman, Monica Di Luca, Martin van den Berg, Remco H.S. Westerink, Henk P.M. Vijverberg
Journal: Environmental Health Perspectives (2007)

Increasing environmental levels of brominated flame retardants raise concern about possible adverse effects, particularly through early developmental exposure.The objective of this research was to investigate neurodevelopmental mechanisms underlying previously observed behavioral impairments observed after neonatal exposure to polybrominated diphenyl ethers (PBDEs).C57Bl/6 mice received a single oral dose of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on postnatal day (PND) 10 (i.e., during the brain growth spurt). On PND17-19, effects on synaptic plasticity, levels of postsynaptic proteins involved in long-term potentiation (LTP), and vesicular release mechanisms were studied ex vivo. We investigated possible acute in vitro effects of BDE-47 on vesicular catecholamine release and intracellular Ca(2+) in rat pheochromocytoma (PC12) cells.Field-excitatory postsynaptic potential (f-EPSP) recordings in the hippocampal CA1 area demonstrated reduced LTP after exposure to 6.8 mg (14 micromol)/kg body weight (bw) BDE-47, whereas paired-pulse facilitation was not affected. Western blotting of proteins in the postsynaptic, triton-insoluble fraction of hippocampal tissue revealed a reduction of glutamate receptor subunits NR2B and GluR1 and autophosphorylated-active Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII), whereas other proteins tested appeared unaffected. Amperometric recordings in chromaffin cells from mice exposed to 68 mg (140 micromol)/kg bw BDE-47 did not reveal changes in catecholamine release parameters. Modest effects on vesicular release and intracellular Ca(2+) in PC12 cells were seen following acute exposure to 20 microM BDE-47. The combined results suggest a post-synaptic mechanism in vivo.Early neonatal exposure to a single high dose of BDE-47 causes a reduction of LTP together with changes in postsynaptic proteins involved in synaptic plasticity in the mouse hippocampus.
Effects of a medical emergency team on reduction of incidence of and mortality from unexpected cardiac arrests in hospital: preliminary study
Authors: M. D Buist
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether earlier clinical intervention by a medical emergency team prompted by clinical instability in a patient could reduce the incidence of and mortality from unexpected cardiac arrest in hospital. <b>Design:</b> A non-randomised, population based study before (1996) and after (1999) introduction of the medical emergency team. <b>Setting:</b> 300 bed tertiary referral teaching hospital. <b>Participants:</b> All patients admitted to the hospital in 1996 (n=19 317) and 1999 (n=22 847). <b>Interventions:</b> Medical emergency team (two doctors and one senior intensive care nurse) attended clinically unstable patients immediately with resuscitation drugs, fluid, and equipment. Response activated by the bedside nurse or doctor according to predefined criteria. <b>Main outcome measures:</b> Incidence and outcome of unexpected cardiac arrest. <b>Results:</b> The incidence of unexpected cardiac arrest was 3.77 per 1000 hospital admissions (73 cases) in 1996 (before intervention) and 2.05 per 1000 admissions (47 cases) in 1999 (after intervention), with mortality being 77% (56 patients) and 55% (26 patients), respectively. After adjustment for case mix the intervention was associated with a 50% reduction in the incidence of unexpected cardiac arrest (odds ratio 0.50, 95% confidence interval 0.35 to 0.73). <b>Conclusions:</b> In clinically unstable inpatients early intervention by a medical emergency team significantly reduces the incidence of and mortality from unexpected cardiac arrest in hospital. <h3>What is already known on this topic</h3> In most studies mortality from unexpected cardiac arrest in hospital exceeds 50% Such events are usually preceded by signs of clinical deterioration in the hours before cardiac arrest <h3>What this paper adds</h3> Early intervention by a medical emergency team significantly reduced the incidence of and mortality from unexpected cardiac arrest in hospital
The importance of patient participation in measuring rheumatoid arthritis flares
Authors: Clifton O Bingham, Rieke Alten, Maarten P de Wit
Journal: Annals of the Rheumatic Diseases (2012)

Rheumatoid arthritis (RA) patients and their healthcare providers frequently use the term ‘flare’ to describe periods of worsening disease activity. The term is not well defined and reflects a continuum of clinical experiences that is highly dependent on individual contextual factors.1,–,5 What constitutes a flare for one patient may not be the same as for another; what patients describe as a flare may be quite different from what a clinician considers significant; and the level at which symptoms become unmanageable may also vary from patient to patient and even in the same patient over time depending on disease activity, treatment effects and coping strategies. And while ‘flare’ is a commonly used term in English, it is not necessarily easily translated into other languages.2 With advances in RA treatment and improved outcomes, a careful study of the manifestations of flare is needed to identify patient-relevant elements that may encompass features beyond our current core set of outcome measures.

Early intensive treatment strategies that include combinations of non-biological and biological disease-modifying antirheumatic drugs are used to reach a treatment goal of remission or a very low disease activity state.6,–,10 By moving more patients to states of low disease activity, we now face new questions in clinical practice, namely how to taper therapy to maintain efficacy, to improve longer-term safety and potentially to lower costs. There is a limited evidence base from clinical practice and clinical trials to guide such decisions, partly because there is no standardised measure to assess significant disease worsening, or flare. By convention, an inversion of improvement criteria (driven predominantly by physician-assessed variables) has often been adopted,11 12 with an assumption that the magnitude of relevant change for worsening and improvement will be similar, although studies suggest …
Gastroschisis: one year outcomes from national cohort study
Authors: T. J. Bradnock, S. Marven, A. Owen, P. Johnson, J. J. Kurinczuk, P. Spark, E. S. Draper, M. Knight
Journal: BMJ (2011)

In September 2017 we called together individuals from across the city, who are currently delivering or receiving end of life care services. Discussion ensued about how services could be improved. All agreed to collaborate to develop a more coordinated approach. The working party membership developed a clear vision and associated mission statements, as well as an outline plan for a new system wide model of coordinated care delivery. <h3>Vision</h3> To create a better experience at the end of life (EOL) for everyone in Birmingham and Solihull. <h3>Mission statements</h3> By bringing together providers with a common purpose, to shape EOL service development and improvement we will: Create a central coordination system for all EOL services that will ensure: Early identification of those in need of end of life care Improved patient–centred care, designed according to individuals' priorities, including promoting choice of place of care and reducing inappropriate hospital admissions Equitable access to services Fewer gaps in care provision Increased information sharing to enhance patient safety. Promote a compassionate community ethos, working with the diverse communities in BSOL to design and deliver end of life care Ensure end of life education is delivered in a coordinated way, to best enable everyone to care Collaborate to design services that are delivered efficiently and are sustainable by sharing intelligence, eliminating duplication of provision and holding each other to account Evaluate evidence concerning new models of care critically to inform the activities of the Working Group Undertake evaluation research to determine the impact of the new BSOL end of life care system/model. <h3>Achievements</h3> The Vision and mission statements have been integrated into a re-draft of the Birmingham and Solihull Sustainability and Transformation Partnership Strategy, as new priorities for end of life care. The working party will be represented at an STP EOLC oversight group, which will drive the implementation of these priorities and will report into the STP portfolio board.
Pulmonary fibrosis: rate of disease progression as a trigger for referral for lung transplantation
Authors: L. S Mackay, R. L Anderson, G. Parry, J. Lordan, P. A Corris, A. J Fisher
Journal: Thorax (2007)

<h3>Background:</h3> Lung transplantation is the only treatment modality that provides a survival advantage in pulmonary fibrosis, but many patients deemed suitable will die awaiting lung transplantation. While donor organ shortage undoubtedly contributes to this, late referral to the transplant centre may also play a role. This study investigates factors influencing the chance of patients with pulmonary fibrosis reaching lung transplantation. <h3>Methods:</h3> A single-centre retrospective review of patient demographic data, assessment investigations and subsequent clinical outcomes was performed for patients with pulmonary fibrosis assessed for lung transplantation over a 5-year period. <h3>Results:</h3> Between March 1999 and March 2004, 129 patients with pulmonary fibrosis underwent formal transplant assessment. Sixty-nine were accepted and listed for lung transplantation. Of these, 17 were transplanted, 37 died while waiting, 4 were removed from the list and 11 were still waiting at the conclusion of the study. The median waiting time on the list for those transplanted was 103 days (range 6–904) compared with 125 days (range 2–547) for those who died while on the list (p = 0.65). There was no significant difference in age, spirometry, total lung capacity, gas transfer measures or 6 min walk distance between those who died waiting and those transplanted. However, time from onset of symptoms to transplant assessment was significantly shorter in those who died on the waiting list (median 29 months (range 2–120)) than in those transplanted (median 46 months (range 6–204), p = 0.037). <h3>Conclusion:</h3> Patients with pulmonary fibrosis who died awaiting transplantation had similar disease severity at assessment as those who achieved transplantation. However, the interval between symptom onset and transplant referral was significantly shorter in those who died while on the waiting list, suggesting they had more rapidly progressive disease. The rate of disease progression appears to be a more sensitive indicator for transplantation referral than any single physiological measure of disease severity and should act as an important trigger for early transplant referral.