tbuckley/cabot-search huggingface dataset:
The Beta Agonist Lung Injury Trial Prevention. A Randomized Controlled Trial
Authors: Gavin D. Perkins, Simon Gates, Daniel Park, Fang Gao, Chris Knox, Ben Holloway, Daniel F. McAuley, James Ryan, Joseph Marzouk, Matthew W. Cooke, Sarah E. Lamb, David R. Thickett
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Experimental studies suggest that pretreatment with β-agonists might prevent acute lung injury (ALI).Objectives: To determine if in adult patients undergoing elective esophagectomy, perioperative treatment with inhaled β-agonists effects the development of early ALI.Methods: We conducted a randomized placebo-controlled trial in 12 UK centers (2008–2011). Adult patients undergoing elective esophagectomy were allocated to prerandomized, sequentially numbered treatment packs containing inhaled salmeterol (100 μg twice daily) or a matching placebo. Patients, clinicians, and researchers were masked to treatment allocation. The primary outcome was development of ALI within 72 hours of surgery. Secondary outcomes were ALI within 28 days, organ failure, adverse events, survival, and health-related quality of life. An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury.Measurements and Main Results: A total of 179 patients were randomized to salmeterol and 183 to placebo. Baseline characteristics were similar. Treatment with salmeterol did not prevent early lung injury (32 [19.2%] of 168 vs. 27 [16.0%] of 170; odds ratio [OR], 1.25; 95% confidence interval [CI], 0.71–2.22). There was no difference in organ failure, survival, or health-related quality of life. Adverse events were less frequent in the salmeterol group (55 vs. 70; OR, 0.63; 95% CI, 0.39–0.99), predominantly because of a lower number of pneumonia (7 vs. 17; OR, 0.39; 95% CI, 0.16–0.96). Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury.Conclusion: Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI.Clinical trial registered with International Standard Randomized Controlled Trial Register (ISRCTN47481946) and European Union database of randomized Controlled Trials (EudraCT 2007-004096-19).
Adaptation of a Diverse Simian Immunodeficiency Virus Population to a New Host Is Revealed through a Systematic Approach to Identify Amino Acid Sites under Selection
Authors: T. H. Vanderford, L. J. Demma, M. B. Feinberg, S. I. Staprans, J. M. Logsdon
Journal: Molecular Biology and Evolution (2006)

Simian immunodeficiency viruses (SIV) have had considerable success at crossing species barriers; both human immunodeficiency virus (HIV)-1 and HIV-2 have been transmitted on multiple occasions from SIV-infected natural host species.However, the precise evolutionary and ecological mechanisms characterizing a successful cross-species transmission event remain to be elucidated.Here, in addition to expanding and clarifying our previous description of the adaptation of a diverse, naturally occurring SIVsm inoculum to a new rhesus macaque host, we present an analytical framework for understanding the selective forces driving viral adaptation to a new host.A preliminary analysis of large-scale changes in virus population structure revealed that viruses replicating in the macaques were subject to increasing levels of selection through day 70 postinfection (p.i.), whereas contemporaneous viruses in the mangabeys remained similar to the source inoculum.Three different site-by-site methods were employed to identify the amino acid sites responsible for this macaque-specific selection.Of 124 amino acid sites analyzed, 3 codons in V2, a 2-amino acid shift in an N-linked glycosylation site, and variation at 2 sites in the highly charged region were consistently evolving under either directional or diversifying selection at days 40 and 70 p.i.This strong macaque-specific selection on the V2 loop underscores the importance of this region in the adaptation of SIVsm to rhesus macaques.Due to the extreme viral diversity already extant in the naturally occurring viral inoculum, we employed a broad range of phylogenetic and numerical tools in order to distinguish the signatures of past episodes of selection in viral sequences from more recent selection pressures.
Shear stress sustains atheroprotective endothelial KLF2 expression more potently than statins through mRNA stabilization
Authors: J VANTHIENEN, J FLEDDERUS, R DEKKER, J ROHLENA, G VANIJZENDOORN, N KOOTSTRA, H PANNEKOEK, A HORREVOETS
Journal: Cardiovascular Research (2006)

The transcription factor KLF2 is considered an important mediator of the anti-inflammatory and anti-thrombotic properties of the endothelium. KLF2 is absent from low-shear, atherosclerosis-prone sites of the vascular tree but is induced by HMG-CoA reductase inhibitors (statins) in vitro. We studied KLF2-dependent induction of important determinants of the atheroprotective status of the endothelium to determine whether pharmacological intervention, e.g. by statins, can potentially replace shear stress.Shear stress and statin effects in combination with TNF-alpha were determined in human umbilical vein endothelial cells by quantitative measurements of the steady-state levels and stability of mRNA for KLF2 and its downstream target genes thrombomodulin (TM) and endothelial nitric oxide synthase (eNOS).We demonstrate that prolonged shear stress has a potential that is superior to that of statins to induce the KLF2-dependent expression of eNOS and TM, especially in the presence of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). These effects can be attributed to the sustained stabilization of KLF2 mRNA by shear, leading to an increased KLF2 protein expression and concomitant strong induction of KLF2 downstream targets. The stabilization of KLF2 mRNA is demonstrated to be dependent on signaling involving phosphoinositide 3-kinase (PI3K).The stabilization of KLF2 steady-state levels, as induced by prolonged shear stress but not by statins, may be essential for sustaining the quiescent, atheroprotective status of the vascular endothelium under inflammatory conditions.
Visual Acuity, Optical Components, and Macular Abnormalities in Patients with a History of Retinopathy of Prematurity
Authors: Wei-Chi Wu, Rey-In Lin, Chia-Pang Shih, Nan-Kai Wang, Yen-Po Chen, An-Ning Chao, Kuan-Jen Chen, Tun-Lu Chen, Yih-Shiou Hwang, Chi-Chun Lai, Chung-Ying Huang, Shawn Tsai
Journal: Ophthalmology (2012)
Role of gp91phox-Containing NADPH Oxidase in Mediating the Effect of K Restriction on ROMK Channels and Renal K Excretion
Authors: Elisa Babilonia, Daohong Lin, Yan Zhang, Yuan Wei, Peng Yue, Wen-Hui Wang
Journal: Journal of the American Society of Nephrology (2007)

Previous study has demonstrated that superoxide and the related products are involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity in the cortical collecting duct (CCD). This study investigated the role of gp91(phox)-containing NADPH oxidase (NOXII) in mediating the effect of low K intake on renal K excretion and ROMK channel activity in gp91(-/-) mice. K depletion increased superoxide levels, phosphorylation of c-Jun, expression of c-Src, and tyrosine phosphorylation of ROMK in renal cortex and outer medulla in wild-type (WT) mice. In contrast, tempol treatment in WT mice abolished whereas deletion of gp91 significantly attenuated the effect of low K intake on superoxide production, c-Jun phosphorylation, c-Src expression, and tyrosine phosphorylation of ROMK. Patch-clamp experiments demonstrated that low K intake decreased mean product of channel number (N) and open probability (P) (NP(o)) of ROMK channels from 1.1 to 0.4 in the CCD. However, the effect of low K intake on ROMK channel activity was significantly attenuated in the CCD from gp91(-/-) mice and completely abolished by tempol treatment. Immunocytochemical staining also was used to examine the ROMK distribution in WT, gp91(-/-), and WT mice with tempol treatment in response to K restriction. K restriction decreased apical staining of ROMK in WT mice. In contrast, a sharp apical ROMK staining was observed in the tempol-treated WT or gp91(-/-) mice. Metabolic cage study further showed that urinary K loss is significantly higher in gp91(-/-) mice than in WT mice. It is concluded that superoxide anions play a key role in suppressing K secretion during K restriction and that NOXII is involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity.
Circadian Rhythm of Salivary Cortisol in Holocaust Survivors With and Without PTSD
Authors: Rachel Yehuda, Julia A. Golier, Shira Kaufman
Journal: American Journal of Psychiatry (2005)

The authors' goal was to determine whether cortisol circadian rhythm alterations observed in younger subjects with posttraumatic stress disorder (PTSD) are also present in geriatric trauma survivors with PTSD.Salivary cortisol levels were measured at six intervals from awakening until bedtime in 23 Holocaust survivors with PTSD, 19 Holocaust survivors without PTSD, and 25 subjects who had not been exposed to the Holocaust. Thirty-three of the subjects were men, and 34 were women.Cortisol levels were significantly lower at awakening, at 8:00 a.m., and at 8:00 p.m. in Holocaust survivors with PTSD than in nonexposed subjects, resulting in a flatter circadian rhythm, similar to what has been observed in aging but different from what has been reported in younger subjects with PTSD.These data provide evidence of differential neuroendocrine alterations in geriatric PTSD.
The Early Expansion and Evolutionary Dynamics of POU Class Genes
Authors: David A. Gold, Ruth D. Gates, David K. Jacobs
Journal: Molecular Biology and Evolution (2014)

The POU genes represent a diverse class of animal-specific transcription factors that play important roles in neurogenesis, pluripotency, and cell-type specification. Although previous attempts have been made to reconstruct the evolution of the POU class, these studies have been limited by a small number of representative taxa, and a lack of sequences from basally branching organisms. In this study, we performed comparative analyses on available genomes and sequences recovered through "gene fishing" to better resolve the topology of the POU gene tree. We then used ancestral state reconstruction to map the most likely changes in amino acid evolution for the conserved domains. Our work suggests that four of the six POU families evolved before the last common ancestor of living animals—doubling previous estimates—and were followed by extensive clade-specific gene loss. Amino acid changes are distributed unequally across the gene tree, consistent with a neofunctionalization model of protein evolution. We consider our results in the context of early animal evolution, and the role of POU5 genes in maintaining stem cell pluripotency.
Inflammation in Alcoholic Liver Disease
Authors: H. Joe Wang, Bin Gao, Samir Zakhari, Laura E. Nagy
Journal: Annual Review of Nutrition (2012)

Frank Burr Mallory's landmark observation in 1911 on the histopathology of alcoholic liver disease (ALD) was the first identification of a link between inflammation and ALD. In this review, we summarize recent advances regarding the origins and roles of various inflammatory components in ALD. Metabolism of ethanol generates a number of metabolites, including acetate, reactive oxygen species, acetaldehyde, and epigenetic changes, that can induce inflammatory responses. Alcohol and its metabolites can also initiate and aggravate inflammatory conditions by promoting gut leakiness of microbial products, by sensitizing immune cells to stimulation, and by activating innate immune pathways, such as complement. Chronic alcohol consumption also sensitizes nonimmune cells, e.g., hepatocytes, to inflammatory signals and impairs their ability to respond to protective signals. Based on these advances, a number of inflammatory targets have been identified with potential for therapeutic intervention in ALD, presenting new opportunities and challenges for translational research.
Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD
Authors: D. Banerjee, O.A. Khair, D. Honeybourne
Journal: European Respiratory Journal (2004)

Chronic obstructive pulmonary disease (COPD) is characterised by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status. The aim of this study was to determine the impact of sputum potentially pathogenic microorganisms (PPMs) on bronchial airway inflammation, health status and plasma fibrinogen levels in subjects with moderate-to-severe COPD during the clinical stable state. Sputum total cell and neutrophil counts, supernatant interleukin‐8, leukotriene B 4 , tumour necrosis factor‐α and neutrophil elastase levels, neutrophil chemotaxis and plasma fibrinogen levels were estimated. Health status was determined using the St George's Respiratory Questionnaire and the 36‐item Short-Form Health Survey questionnaire. Twenty-seven (40%) subjects had PPMs and 40 (60%) non‐PPMs in their sputum. Both groups were of similar age, body mass index, smoking history and lung function. The PPMs group showed significantly higher levels of interleukin‐8, leukotriene B 4 , tumour necrosis factor‐α, neutrophil elastase and increased neutrophil chemotaxis. They also exhibited worse health status and raised plasma fibrinogen levels compared to the non‐PPMs group. In conclusion, subjects with clinically stable moderate-to-severe chronic obstructive pulmonary disease who had potentially pathogenic microorganisms in their sputum demonstrated an exaggerated airway inflammatory response, poorer health status and increased plasma fibrinogen levels than those who had nonpotentially pathogenic microorganisms.
The Changing Drug Scene: 1970-1972
Authors: JOHN F. GREDEN, DONALD W. MORGAN, SINAI I. FRENKEL
Journal: American Journal of Psychiatry (1974)

Using the same questionnaire, the authors surveyed drug use at a military installation in 1970, 1971, and 1972. Oven the three years, the total percentage of respondents reporting previous drug use increased: the amount of use and number of current users also increased. For most drug types, the increases occurred between 1970 and 1971; heroin use, however, increased each year. The authors question the usefulness of specialized short-term drug treatment programs.
In vivo imaging of pulmonary alveolar proteinosis using confocal endomicroscopy
Authors: M. Salaun, F. Roussel, P.-A. Hauss, S. Lachkar, L. Thiberville
Journal: European Respiratory Journal (2010)

To the Editors:

Fibred confocal fluorescence microscopy (FCFM) is a new technology that can provide microscopic imaging of a living tissue through a 1-mm flexible fibreoptic miniprobe 1, 2. To image the alveolar structures in vivo , the miniprobe is advanced through the working channel of the bronchoscope down to the alveolar ducts and sacs. In nonsmoking subjects, the FCFM is able to image the peripheral elastin framework of the alveolar ducts 3. In active smokers, the technique also images fluorescent alveolar macrophages which contain tobacco tar 3. The technique has the potential to improve the in vivo diagnosis of peripheral lung diseases during bronchoscopy.

Herein we report the use of FCFM during bronchoscopy on a smoking patient presenting with diffuse alveolar and interstitial opacities on chest radiograph. The in vivo confocal fluorescence endomicroscopy in real-time showed the globular lipoproteinaceous material which is typical of pulmonary alveolar proteinosis (PAP). This diagnosis was confirmed by cytological analysis of the bronchoalveolar lavage (BAL) fluid, and by the presence of high levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) serum antibodies.

This is the first report of the in vivo confocal microscopic appearance of lipoproteinaceous material during bronchoscopy, which appears to be typical of PAP.

A 42-yr-old, 25 pack-yr, active smoking male presented with a 4-month history of increasing breathlessness on exertion and dry cough. He reported a history of heavy and short household plaster dust exposure preceding the onset of symptoms. The physical examination was unremarkable. The chest radiograph showed bilateral alveolar and interstitial opacities. A high-resolution computed …
Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies
Authors: Alexander Thompson, Pei Gao, Lia Orfei, Sarah Watson, Emanuele Di Angelantonio, Stephen Kaptoge, Christie Ballantyne, Christopher P Cannon, Michael Criqui, Mary Cushman, Albert Hofman, Chris Packard, Simon G Thompson, Rory Collins, John Danesh
Journal: The Lancet (2010)
Integrative Genomic and Proteomic Analyses Identify Targets for Lkb1-Deficient Metastatic Lung Tumors
Authors: Julian Carretero, Takeshi Shimamura, Klarisa Rikova, Autumn L. Jackson, Matthew D. Wilkerson, Christa L. Borgman, Matthew S. Buttarazzi, Benjamin A. Sanofsky, Kate L. McNamara, Kathleyn A. Brandstetter, Zandra E. Walton, Ting-Lei Gu, Jeffrey C. Silva, Katherine Crosby, Geoffrey I. Shapiro, Sauveur-Michel Maira, Hongbin Ji, Diego H. Castrillon, Carla F. Kim, Carlos García-Echeverría, Nabeel Bardeesy, Norman E. Sharpless, Neil D. Hayes, William Y. Kim, Jeffrey A. Engelman, Kwok-Kin Wong
Journal: Cancer Cell (2010)
Relationship of antibody affinity to onset of immune complex disease in New Zealand mice.
Authors: R E Petty, M W Steward
Journal: Annals of the Rheumatic Diseases (1977)

Affinity (KR) of antibody to human serum transferrin in New Zealand mice was measured by a globulin precipitation technique. KR was low in mice immunized early in life, increased with age of immunization up to 16-26 weeks, and then fell to low levels. KR in young and old NZB mice was increased by immunization with antigen in Freund9s complete adjuvant. The correlation between low affinity antibody production and susceptibility to immune complex disease is discussed.
Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma
Authors: M Bendandi, S Marillonnet, R Kandzia, F Thieme, A Nickstadt, S Herz, R Fröde, S Inogés, A Lòpez-Dìaz de Cerio, E Soria, H Villanueva, G Vancanneyt, A McCormick, D Tusé, J Lenz, J-E Butler-Ransohoff, V Klimyuk, Y Gleba
Journal: Annals of Oncology (2010)
Hypertrophic osteoarthropathy related to end stage cholestatic cirrhosis: reversal after liver transplantation.
Authors: J P Huaux, A Geubel, B Maldague, P Michielsen, B de Hemptinne, J B Otte, C N de Deuxchaisnes
Journal: Annals of the Rheumatic Diseases (1987)

A case is reported of hypertrophic osteoarthropathy with recovery after a liver graft in a young man with end stage cholestatic cirrhosis related to non-Wilsonian copper overload. To our knowledge this is the first case in the literature illustrating the curative role of liver grafting on hypertrophic osteoarthropathy associated with chronic cholestatic liver disease.
Association between salicylates and Reye's syndrome
Authors: R. W. Soller
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The report by Halpin et al inThe Journal(1982;248:687) presented conclusions on salicylate use in children with viral illnesses that are not founded on comprehensive appraisals of the "raw" data for potential biases—specifically protopathic and product confusion biases. With respect to protopathic bias, the Food and Drug Administration Reye's Syndrome (RS) Working Group, stated "the temporal relationship between the use of a drug and the occurrence of the event must be considered in order to eliminate the bias that may result in estimation of a measure of association," and "it was considered critical that the use of aspirin must have been before the onset of Reye's Syndrome to be considered true exposure" (unpublished data, May 1982). This principle, when violated, results in protopathic bias.<sup>1</sup> In this regard, of all recent RS surveys, only the second-year Ohio study by Halpin et al contains the critical data
Is it impolite to discuss cognitive differences between liberals and conservatives?
Authors: Gordon Hodson
Journal: Behavioral and Brain Sciences (2014)

Hibbing and colleagues argue convincingly that liberals and conservatives differ in reactivity to (negative) stimuli. Yet their analysis sidesteps evidence that cognitive ability differs as a function of ideology. Cognitive abilities, like cognitive preferences (e.g., structure needs), shape whether stimuli are psychologically threatening (prompting avoidance) or offer opportunity (prompting approach). Incorporation of these findings is critical despite any socially "delicate" implications.
Author's reply to Gill and colleagues
Authors: K. A. Harrison
Journal: BMJ (2011)

It has been known since the 1970s that training of traditional birth attendants when supported by effective healthcare delivery can help with some neonatal problems.1 Cochrane reviews, regarded as the best evidence available, support this.

However, the main thrust of my article related to the high rates of maternal mortality and obstetric fistulas in sub-Saharan Africa.2 …
Antioxidant Effect of Estrogen on Cytomegalovirus-Induced Gene Expression in Coronary Artery Smooth Muscle Cells
Authors: Edith Speir, Zu-Xi Yu, Kazuyo Takeda, Victor J. Ferrans, Richard O. Cannon
Journal: Circulation (2000)

Pathogens infecting the arterial wall with resultant inflammation may contribute to atherogenesis. Human coronary artery smooth muscle cells (SMCs) infected with human cytomegalovirus (CMV) demonstrate a rapid increase in reactive oxygen species (ROSs), with activation of genes involved in viral replication and inflammation. Because estrogen appears to have antioxidant properties, we wished to determine whether this hormone attenuates SMC responses to CMV infection.Using confocal microscopy and an intracellular fluorescent dye activated by ROSs, we found that 17beta-estradiol (0.1 to 10 nmol/L) and its stereoisomer 17alpha-estradiol (which has low affinity for the estrogen receptor) dose-dependently inhibited ROS generation in CMV-infected SMCs. These effects were not blocked by the estrogen receptor inhibitor ICI 182,780. 3-Methoxyestrone, which lacks the phenolic hydroxyl group, did not interfere with ROS generation. We found that 17beta-estradiol and 17alpha-estradiol, but not 3-methoxyestrone, prevented binding of nuclear factor (NF)-kappaB to DNA. Furthermore, in SMCs transfected with the reporter constructs 3XkappaB-CAT, MIEP-CAT, or ICAM-CAT, cotransfection with a CMV-IE72 expression plasmid caused promoter and CAT activation. Treatment with 17beta-estradiol and 17alpha-estradiol, but not 3-methoxyestrone, inhibited CAT activity and, in CMV-infected SMCs, prevented IE72 and ICAM-1 protein expression and cytopathic effects.These findings indicate that estrogen molecules with an A-ring hydroxyl group have estrogen receptor-independent anti-CMV effects at physiological concentrations by inhibiting ROS generation, NF-kappaB activation, NF-kappaB-dependent transcription, and viral replication. To the extent that chronic infection of the vascular wall with CMV contributes to atherogenesis, these antioxidant actions of estrogen may be of therapeutic importance.
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1935)

Intratracheal, intracloacal, and subcutaneous injection of living cultures of the fowl coryza bacillus had no demonstrable effect on the susceptibility of fowl to coryza. Intraperitoneal injection was irregularly followed by a definitely altered susceptibility. Growth of the specific bacillus was inhibited in the nasal tract of approximately 70 per cent of 25 birds which had received an earlier intraperitoneal injection.