tbuckley/cabot-search huggingface dataset:
Respiratory muscle activity in patients with COPD walking to exhaustion with and without pressure support
Authors: D. Kyroussis, M.I. Polkey, C-H. Hamnegard, G.H. Mills, M. Green, J. Moxham
Journal: European Respiratory Journal (2000)

The function of the diaphragm and other respiratory muscles during exercise in chronic obstructive pulmonary disease (COPD) remains controversial and few data exist regarding respiratory muscle pressure generation in this situation. The inspiratory pressure/time products of the oesophageal and transdiaphragmatic pressure, and the expiratory gastric pressure/time product during exhaustive treadmill walking in 12 patients with severe COPD are reported. The effect of noninvasive positive pressure ventilation during treadmill exercise was also examined in a subgroup of patients (n=6). During free walking, the inspiratory pressure/time products rose early in the walk and then remained level until the patients were forced to stop because of intolerable dyspnoea. In contrast, the expiratory gastric pressure/time product increased progressively throughout the walk. When patients walked the same distance assisted by noninvasive positive pressure ventilation, a substantial reduction was observed in the inspiratory and expiratory pressure/time products throughout the walk. When patients walked with positive pressure ventilation for as long as they could, the pressure/time products observed at exercise cessation were lower than those observed during exercise cessation after free walking. It is concluded that, in severe chronic obstructive pulmonary disease, inspiratory muscle pressure generation does not increase to meet the demands imposed by exhaustive exercise, whereas expiratory muscle pressure generation rises progressively. Inspiratory pressure support was shown to substantially unload all components of the respiratory muscle pump.
Lower Progression Rate of End-Stage Renal Disease in Patients with Peripheral Arterial Disease Using Statins or Angiotensin-Converting Enzyme Inhibitors
Authors: Harm H.H. Feringa, Stefanos E. Karagiannis, Michel Chonchol, Radosav Vidakovic, Peter G. Noordzij, Abdou Elhendy, Ron T. van Domburg, Gijs Welten, Olaf Schouten, Jeroen J. Bax, Tomas Berl, Don Poldermans
Journal: Journal of the American Society of Nephrology (2007)

Patients with peripheral arterial disease (PAD) are at increased risk for ESRD and cardiovascular events. The primary objective was to assess the association between ankle-brachial index (ABI) values and renal outcome. The secondary objective was to evaluate whether statins and angiotensin-converting enzyme inhibitors (ACEI) are associated with improved renal and cardiovascular outcome in patients with PAD. In a prospective observational cohort study of 1940 consecutive patients with PAD, ABI was measured and chronic statin and ACEI therapy was noted at baseline. Serial creatinine concentrations were obtained at baseline, 6 mo, and every year after enrollment. End points were ESRD, all-cause mortality, and cardiac events during a median follow-up period of 8 yr. Baseline estimated GFR <60 ml/min per 1.73 m(2) was assessed in 27% of patients. ESRD, all-cause mortality, and cardiac events occurred in 10, 46, and 31% of patients, respectively. In multivariate analysis, a lower baseline ABI was significantly associated with a higher progression rate of ESRD (hazard ratio [HR] per 0.10 decrease 1.34; 95% confidence interval [CI] 1.21 to 1.49). Chronic use of statins and ACEI were significantly associated with lower ESRD (HR 0.41 [95% CI 0.28 to 0.63] and 0.74 [95% CI 0.54 to 0.98], respectively), mortality (HR 0.66; [95% CI 0.55 to 0.82] and 0.84 [95% CI 78 to 0.95], respectively), and cardiac events (HR 0.71 [95% CI 0.56 to 0.91] and 0.81 [95% CI 0.68 to 0.96], respectively). In patients with PAD, low ABI values independently predict the onset of ESRD. Less progression toward ESRD and improved cardiovascular outcome was observed among patients who were on long-term statins and ACEI.
Bronchoscopy in patients with suspected PCP: supine or sitting?
Authors: P Vijayanand
Journal: Thorax (2003)

We read with interest the case report by Newton et al 1 describing platypnoea and orthodeoxia in a patient with pneumocystis pneumonia (PCP). We would like to add our own experience and question whether the observation has an important clinical implication.

A 29 year old patient who had been born and raised in Zambia presented 10 months after arrival in the UK with …
Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux
Authors: R. N Patterson, B. T Johnston, J. E S Ardill, L. G Heaney, L. P A McGarvey
Journal: Thorax (2007)

Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally-mediated oesophageal-tracheobronchial reflex with airway sensory nerve activation and tachykinin release.To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux.Thirty-two patients with airways disease (16 with mild asthma and 16 non-asthmatic subjects with chronic cough) underwent 24 h oesophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH<4 of >4.9% at the distal probe). All subjects underwent sputum induction. Differential cell counts and concentrations of substance P (SP), neurokinin A (NKA), albumin and alpha2-macroglobulin were determined.SP and NKA levels were significantly higher in patients with reflux than in those without (SP: 1434 (680) pg/ml vs 906 (593) pg/ml, p=0.026; NKA: 81 (33) pg/ml vs 52 (36) pg/ml, p=0.03). Significantly higher tachykinin levels were also found in asthmatic patients with reflux than in asthmatic patients without reflux (SP: 1508 (781) pg/ml vs 737 (512) pg/ml, p=0.035; NKA: median (interquartile range 108 (85-120) pg/ml vs 75 (2-98) pg/ml, p=0.02). In patients with asthma there was a significant positive correlation between distal oesophageal acid exposure and SP levels (r=0.59, p=0.01) and NKA levels (r=0.56, p=0.02). Non-significant increases in SP and NKA were measured in patients with cough with reflux (SP: 1534.71 (711) pg/ml vs 1089 (606) pg/ml, p=0.20; NKA: 56 (43) pg/ml vs 49 (17) pg/ml, p=0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups.This study demonstrates increased airway tachykinin levels in patients with asthma and cough patients with coexistent acid reflux. This suggests airway sensory nerve activation in this population.
Generalized pustular psoriasis associated with chronic renal failure
Authors: Julian Verbov
Journal: British Journal of Dermatology (1976)

Journal Article Generalized pustular psoriasis associated with chronic renal failure Get access Julian Verbov Julian Verbov Broadgreen Hospital, Liverpool L14 3LB Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue 1, 1 January 1976, Page 105, https://doi.org/10.1111/j.1365-2133.1976.tb04351.x Published: 01 January 1976
The Cytoskeleton Protein Filamin-A Is Required for an Efficient Recombinational DNA Double Strand Break Repair
Authors: Jingyin Yue, Qin Wang, Huimei Lu, Mark Brenneman, Feiyue Fan, Zhiyuan Shen
Journal: Cancer Research (2009)

The human actin-binding protein filamin-A (also known as ABP-280) cross-links actin into a dynamic three-dimensional structure. It interacts with >45 proteins of diverse functions, serving as the scaffold in various signaling networks. BRCA2 is a protein that regulates RAD51-dependent recombinational repair of DNA double strand breaks (DSB). Proximate to the COOH terminus of the BRCA2 protein, a conserved and DNA binding domain (BRCA2-DBD) interacts with filamin-A and BCCIP. In this study, we sought to test the hypothesis that filamin-A influences homologous recombinational repair of DSB and the maintenance of genomic stability. We used three pairs of cell lines with normal and reduced filamin-A expression, including breast cancer and melanoma cells. We found that lack or reduction of filamin-A sensitizes cells to ionizing radiation, slows the removal of DNA damage-induced gammaH2AX nuclear foci, reduces RAD51 nuclear focus formation and recruitment to chromatin in response to irradiation, and results in a 2-fold reduction of homologous recombinational repair of DSB. Furthermore, filamin-A-deficient cells have increased frequencies of micronucleus formation after irradiation. Our data illustrate the importance of the cytoskeleton structure in supporting the homologous recombinational DNA repair machinery and genome integrity, and further implicate a potential of filamin-A as a marker for prognosis in DNA damage-based cancer therapy.
The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis
Authors: Mitchell M. Levy, R. Phillip Dellinger, Sean R. Townsend, Walter T. Linde-Zwirble, John C. Marshall, Julian Bion, Christa Schorr, Antonio Artigas, Graham Ramsay, Richard Beale, Margaret M. Parker, Herwig Gerlach, Konrad Reinhart, Eliezer Silva, Maurene Harvey, Susan Regan, Derek C. Angus
Journal: Intensive Care Medicine (2010)

The Surviving Sepsis Campaign (SSC or "the Campaign") developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes.A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the US, Europe, and South America. Elements of the guidelines were "bundled" into two sets of targets to be completed within 6 h and within 24 h. An analysis was conducted on data submitted from January 2005 through March 2008.Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (P<0.0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 years (P = 0.008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (P = 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.5-8.4%).The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.
SENP1-mediated GATA1 deSUMOylation is critical for definitive erythropoiesis
Authors: Luyang Yu, Weidong Ji, Haifeng Zhang, Matthew J. Renda, Yun He, Sharon Lin, Ee-chun Cheng, Hong Chen, Diane S. Krause, Wang Min
Journal: The Journal of Experimental Medicine (2010)

Small ubiquitin-like modifier (SUMO) modification of proteins (SUMOylation) and deSUMOylation have emerged as important regulatory mechanisms for protein function. SENP1 (SUMO-specific protease) deconjugates SUMOs from modified proteins. We have created SENP1 knockout (KO) mice based on a Cre–loxP system. Global deletion of SENP1 (SENP1 KO) causes anemia and embryonic lethality between embryonic day 13.5 and postnatal day 1, correlating with erythropoiesis defects in the fetal liver. Bone marrow transplantation of SENP1 KO fetal liver cells to irradiated adult recipients confers erythropoiesis defects. Protein analyses show that the GATA1 and GATA1-dependent genes are down-regulated in fetal liver of SENP1 KO mice. This down-regulation correlates with accumulation of a SUMOylated form of GATA1. We further show that SENP1 can directly deSUMOylate GATA1, regulating GATA1-dependent gene expression and erythropoiesis by in vitro assays. Moreover, we demonstrate that GATA1 SUMOylation alters its DNA binding, reducing its recruitment to the GATA1-responsive gene promoter. Collectively, we conclude that SENP1 promotes GATA1 activation and subsequent erythropoiesis by deSUMOylating GATA1.
The GINA Asthma Challenge: reducing asthma hospitalisations
Authors: J.M. FitzGerald, E. Bateman, S. Hurd, L-P. Boulet, T. Haahtela, A.A. Cruz, M.L. Levy
Journal: European Respiratory Journal (2011)

For several decades, global health agendas have been dominated by the burden of endemic infections, such as malaria, and epidemics caused by respiratory viruses, HIV and the resurgence of tuberculosis (TB). Recently, under the leadership of the World Health Organization (WHO) and other agencies [1], attention has been directed towards the growing morbidity and mortality attributable to chronic diseases (which are predominantly cardiovascular, respiratory, metabolic or neoplastic in nature), as well as the fact that in many countries the strategies and resources to address these major public health challenges are either nonexistent or rudimentary [2]. In 2005, it was estimated that 35 million of all worldwide deaths were attributable to chronic diseases. This is twice the number of deaths caused by all infectious diseases, including HIV, TB and malaria, along with malnutrition and perinatal mortality [3]. The burden is not only in human suffering, but it also represents a significant economic burden on societies and health systems; estimates are that a majority of this future burden will occur in developing, rather than developed, countries. In response to these realities, the United Nations (UN) General Assembly has recently adopted a resolution that calls upon nations to address the increasing burden of premature deaths from noncommunicable diseases [4]. Moreover, in May 2010, the Assembly …
Resistance of Glioblastoma-Initiating Cells to Radiation Mediated by the Tumor Microenvironment Can Be Abolished by Inhibiting Transforming Growth Factor-β
Authors: Matthew E. Hardee, Ariel E. Marciscano, Christina M. Medina-Ramirez, David Zagzag, Ashwatha Narayana, Scott M. Lonning, Mary Helen Barcellos-Hoff
Journal: Cancer Research (2012)

Abstract The poor prognosis of glioblastoma (GBM) routinely treated with ionizing radiation (IR) has been attributed to the relative radioresistance of glioma-initiating cells (GIC). Other studies indicate that although GIC are sensitive, the response is mediated by undefined factors in the microenvironment. GBM produce abundant transforming growth factor-β (TGF-β), a pleotropic cytokine that promotes effective DNA damage response. Consistent with this, radiation sensitivity, as measured by clonogenic assay of cultured murine (GL261) and human (U251, U87MG) glioma cell lines, increased by approximately 25% when treated with LY364947, a small-molecule inhibitor of TGF-β type I receptor kinase, before irradiation. Mice bearing GL261 flank tumors treated with 1D11, a pan-isoform TGF-β neutralizing antibody, exhibited significantly increased tumor growth delay following IR. GL261 neurosphere cultures were used to evaluate GIC. LY364947 had no effect on the primary or secondary neurosphere-forming capacity. IR decreased primary neurosphere formation by 28%, but did not reduce secondary neurosphere formation. In contrast, LY364947 treatment before IR decreased primary neurosphere formation by 75% and secondary neurosphere formation by 68%. Notably, GL261 neurospheres produced 3.7-fold more TGF-β per cell compared with conventional culture, suggesting that TGF-β production by GIC promotes effective DNA damage response and self-renewal, which creates microenvironment-mediated resistance. Consistent with this, LY364947 treatment in irradiated GL261 neurosphere-derived cells decreased DNA damage responses, H2AX and p53 phosphorylation, and induction of self-renewal signals, Notch1 and CXCR4. These data motivate the use of TGF-β inhibitors with radiation to improve therapeutic response in patients with GBM. Cancer Res; 72(16); 4119–29. ©2012 AACR.
Volume Pressure Relationships of the Pulmonary-Left Heart Vascular Segment
Authors: ROBERT C. LITTLE
Journal: Circulation Research (1960)

Volume-pressure curves were determined for the living left heart vascular segment by injecting fluid into the left atrium during momentary cardiac asystole and measuring left atrial pressure. Such curves show 2 essentially linear relationships with a break at a low pressure level. It has been suggested that this break is due to closure of the pulmonary veins or the pulmonary-left atrial junction at low pressure levels. This closure prevents regurgitation into the pulmonary veins. Higher atrial pressures overcome this block and permit retrograde perfusion of the pulmonary pathways. This suggestion was tested by measuring left atrial and pulmonary vein pressure during the injection of blood into the atrium of the quiescent heart. The results are consistent with such a collapse of the veno-left atrial junction at low pressure levels.
Benzyl alcohol attenuates acetaminophen-induced acute liver injury in a Toll-like receptor-4-dependent pattern in mice
Authors: Changchun Cai, Hai Huang, Sean Whelan, Li Liu, Benjamin Kautza, Jason Luciano, Guoliang Wang, Guoqiang Chen, Sladjana Stratimirovic, Allan Tsung, Timothy R. Billiar, Brian S. Zuckerbraun
Journal: Hepatology (2014)

Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in industrialized countries. Understanding the mechanisms of APAP-induced liver injury as well as other forms of sterile liver injury is critical to improve the care of patients. Recent studies demonstrate that danger signaling and inflammasome activation play a role in APAP-induced injury. The aim of these investigations was to test the hypothesis that benzyl alcohol (BA) is a therapeutic agent that protects against APAP-induced liver injury by modulation of danger signaling. APAP-induced liver injury was dependent, in part, on Toll-like receptor (TLR)9 and receptor for advanced glycation endproducts (RAGE) signaling. BA limited liver injury over a dose range of 135-540 μg/g body weight or when delivered as a pre-, concurrent, or post-APAP therapeutic. Furthermore, BA abrogated APAP-induced cytokines and chemokines as well as high-mobility group box 1 release. Moreover, BA prevented APAP-induced inflammasome signaling as determined by interleukin (IL)-1β, IL-18, and caspase-1 cleavage in liver tissues. Interestingly, the protective effects of BA on limiting liver injury and inflammasome activation were dependent on TLR4 signaling, but not TLR2 or CD14. Cell-type–specific knockouts of TLR4 were utilized to further determine the protective mechanisms of BA. These studies found that TLR4 expression specifically in myeloid cells (LyzCre- tlr4 −/− ) were necessary for the protective effects of BA. Conclusion : BA protects against APAP-induced acute liver injury and reduced inflammasome activation in a TLR4-dependent manner. BA may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury. (Hepatology 2014;60:990–1002)
Spiral computed tomographic scanning of the chest with three dimensional imaging in the diagnosis and management of paediatric intrathoracic airway obstruction.
Authors: M. Sagy, M. Poustchi-Amin, L. Nimkoff, P. Silver, M. Shikowitz, J. C. Leonidas
Journal: Thorax (1996)

BACKGROUND: The usefulness of spiral computed tomographic (CT) scans of the chest with three dimensional imaging (3D-CT) of intrathoracic structures in the diagnosis and management of paediatric intrathoracic airway obstruction was assessed. METHODS: A retrospective review was made of five consecutive cases (age range six months to four years) admitted to the paediatric intensive care unit and paediatric radiology division of a tertiary care children9s hospital with severe respiratory decompensation suspected of being caused by intrathoracic large airway obstruction. Under adequate sedation, the patients underwent high speed spiral CT scanning of the thorax. Non-ionic contrast solution was injected in two patients to demonstrate the anatomical relationship between the airway and the intrathoracic large vessels. Using computer software, three-dimensional images of intrathoracic structures were then reconstructed by the radiologist. RESULTS: In all five patients the imaging results were useful in directing the physician to the correct diagnosis and appropriate management. In one patient, who had undergone repair of tetralogy of Fallot with absent pulmonary valve, the 3D-CT image showed bilateral disruptions in the integrity of the tracheobronchial tree due to compression by a dilated pulmonary artery. This patient underwent pulmonary artery aneurysmorrhaphy and required continued home mechanical ventilation via tracheostomy. In three other patients with symptoms of lower airway obstruction the 3D-CT images showed significant stenosis in segments of the tracheobronchial tree in two of them, and subsequent bronchoscopy established a diagnosis of segmental bronchomalacia. These two patients required mechanical ventilation and distending pressure to relieve their bronchospasm. In another patient who had undergone surgical repair of intrathoracic tracheal stenosis three years prior to admission the 3D-CT scan ruled out restenosis as the reason for her acute respiratory decompensation. CONCLUSIONS: 3D-CT scanning is a useful additional diagnostic tool for intrathoracic airway obstruction in paediatric patients.
CONTACT SENSITIVITY IN THE MOUSE
Authors: G. L. Asherson, M. Zembala
Journal: The Journal of Experimental Medicine (1970)

Contact sensitivity skin reactions were produced in mice by immunization with 2-phenyl-4-ethoxymethylene oxazolone (oxazolone) and detected by the increase in ear thickness after challenging the ears with 2% oxazolone. These skin reactions can be transferred from immunized donors to irradiated recipients by peritoneal exudate cells induced by thioglycollate. The peritoneal exudate cells were separated into purified macrophage and purified lymphocyte populations. Both cell populations transferred skin reactions. However, their time course was different. The reactions produced by lymphocytes were greater at 24 hr than at 12 hr while the reactions produced by macrophages declined slightly between 12 and 24 hr. The working hypothesis was formed that the peritoneal lymphocytes conveyed a factor (presumptive cytophilic antibody) to peritoneal macrophages which enabled them to transfer ear reactions. Experiment showed that peritoneal and lymph node lymphocytes from sensitized donors within a Millipore chamber conveyed a factor to macrophages outside the chamber which enabled them to transfer ear reactions. In contrast, peritoneal macrophages (from sensitized donors) within the chamber and peritoneal lymphocytes outside the chamber were inactive. These findings suggested that there are three modes of immunological tissue damage: hypersensitivity mediated by lymphocytes (classical delayed hypersensitivity), hypersensitivity mediated by circulating antibody (classical immediate type hypersensitivity), and hypersensitivity mediated by macrophages which have passively acquired a factor (macrophage-mediated hypersensitivity).