tbuckley/cabot-search huggingface dataset:
Eosinophil cationic protein is not only a distinctive eosinophil proteinAuthors' reply
Authors: J Monteseirin, A Vega
Journal: Thorax (2007)

Eosinophil cationic protein is not only a distinctive eosinophil proteinWe read with interest the article by Qiu et al (Thorax 2007;62:475-82).In this paper, neutrophils and eosinophils were identified using mouse anti-human neutrophil elastase and anti-eosinophil cationic protein (ECP), both monoclonal antibodies (mAbs).mAbs against ECP have been used to detect total eosinophils, but immunostaining techniques evidenced that the number of ECP + cells was higher than the number of eosinophils. 1 Recent studies show that ECP is not only a distinctive eosinophil protein, but has been found in neutrophils. [1]][3] In this regard, it has been reported that these cells can take up ECP from the bloodstream after phagocytosis and store it, but not synthesize it. 3In agreement with these reports, our recently published results 4 indicate that in resting (unstimulated) neutrophils, no ECP mRNA was detected, and only a small amount of intracellular or released protein was found.However, after cellular stimulation, ECP was synthesised.This was verified by several lines of evidence: (1) after neutrophil stimulation, bands of PCR product corresponding to ECP mRNA were detected; (2) de novo biosynthesis protein was detected by S 35 radiolabelling; (3) an increase in intracellular ECP protein was observed by flow cytometry, fluorescence microscopy and western blotting; and (4) accompanying ECP release was detected by ELISA.Our results are exclusively due to neutrophils and cannot be ascribed to possible contamination by eosinophils for several reasons: (1) both cells types had a different course of ECP release.Eosinophils released ECP after 30 min of cell stimulation; neutrophils only released protein after 3-18 h;(2) PAF failed to induce ECP release by eosinophils whereas it induced ECP release by neutrophils; (3) lipopolysaccharide induced ECP release from eosinophils but not from neutrophils; (4) allergen, anti-IgE, anti-FceRI and anti-galectin-3 dependent ECP production was observed in neutrophils but not in eosinophils; (5) CD66b is a specific marker for neutrophils and we found that these cells (CD66b + ) do in fact highly express ECP; (7) Charcot Leyden Crystal protein is a marker of eosinophils and basophils but not of neutrophils and we did not find its transcript in our neutrophil preparation.Collectively, these results suggest that caution should be exercised in the interpretation of immunohistochemistry when antibodies to ECP are used as specific markers for eosinophils, especially in endobronchial biopsy specimens from patients with severe exacerbation of asthma in which an accumulation of activated cells exist.
Short term effects of tobacco smoking on exhaled breath temperature
Authors: Tanya Kralimarkova, Diana Hristova, Ryan Kadavil, Jasmine John, Jacquilin Sabu, Vasil Dimitrov, Todor Popov
Journal: European Respiratory Journal (2014)

Background: Exhaled breath temperature (EBT) has been demonstrated to be an integral indicator of both inflammation and remodeling in the airways. We have shown that EBT in smokers drops over time proportionally to the cumulative load of tobacco smoking (in pack years). However, more insight is needed for mechanisms of action of daily smoking on the airways wall. The aim of this study was to explore the short term influence of smoking on EBT.

Methods: We compared baseline EBT measured in the morning in 41 smokers without overt signs of COPD, mean age 35±20 (standard deviation, SD) years, 16 males, and in 38 non-smokers (37±14 years, 13 males. We also measured EBT in the smokers before and 15 minutes after smoking the first cigarette for the day. In a separate experiment we compared EBT at 8 a.m. and 1 p.m. in 63 subjects: 25 smokers, 40±16 years, 11 males, and 38 non-smokers , 40±16 years, 13 males. The devices we used were hand-held breath thermometers (X-Halo, Delmedica Investments LTD Singapore).

Results: Baseline morning EBT was higher in smokers than in non-smokers: 34,38 (mean) ±0.08 (s.e.m.) °C vs. 33,94±0.16°C, P = 0.015. After the first cigarette for the day, EBT of smokers increased from 34.38±0.08°C to 34,57±0.08°C, P = 0.004. While EBT in non-smokers decreased in the course of the day, EBT of smokers increased: between groups difference was 0.42±0.07°C, P=0.02. No gender differences were outlined.

Conclusions: Smokers without overt COPD have higher baseline EBT than age matched non-smokers; smoking their first cigarette for the day increases EBT. In addition, smoking is associated with a different circadian pattern of EBT during the day. Smoking sustains airway inflammation on a daily basis.
Race, Breast Cancer Subtypes, and Survival in the Carolina Breast Cancer Study
Authors: Lisa A. Carey, Charles M. Perou, Chad A. Livasy, Lynn G. Dressler, David Cowan, Kathleen Conway, Gamze Karaca, Melissa A. Troester, Chiu Kit Tse, Sharon Edmiston, Sandra L. Deming, Joseph Geradts, Maggie C. U. Cheang, Torsten O. Nielsen, Patricia G. Moorman, H. Shelton Earp, Robert C. Millikan
Journal: JAMA (2006)

A HETEROGeneous disease composed of a growing number of recognized biological subtypes.The prognostic and etiologic importance of this diversity is complicated by many factors, including the observation that differences in clinical outcomes often correlate with race.Age-adjusted mortality in the United States from breast cancer in white women is 28.3 deaths per 100 000 compared with 36.4 deaths per 100 000 in African American women. 1 This disparity is particularly pronounced among women younger than 50 years, in whom mortality is 77% higher among African American women compared with white women (11.0 vs 6.3 deaths per 100 000).Breast cancer in African American women has been characterized by higher grade, 2,3 later
Sleep {middle dot} 6: Obstructive sleep apnoea/hypopnoea syndrome and hypertension
Authors: G V Robinson
Journal: Thorax (2004)

Abstract The use of CPAP to control excessive daytime sleepiness in OSAHS probably also produces a substantial reduction in vascular risk. This is reviewed with particular reference to hypertension. AHI, apnoea/hypopnoea indexBMI, body mass indexCPAP, continuous positive airway pressureOSAHS, obstructive sleep apnoea/hypopnoea syndromeobstructive sleep apnoea/hypopnoea syndromehypertension
Expression of<i>SLC22A1</i>variants may affect the response of hepatocellular carcinoma and cholangiocarcinoma to sorafenib
Authors: Elisa Herraez, Elisa Lozano, Rocio I.R. Macias, Javier Vaquero, Luis Bujanda, Jesus M. Banales, Jose J.G. Marin, Oscar Briz
Journal: Hepatology (2013)

Reduced drug uptake is an important mechanism of chemoresistance. Down-regulation of SLC22A1 encoding the organic cation transporter-1 (OCT1) may affect the response of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CGC) to sorafenib, a cationic drug. Here we investigated whether SLC22A1 variants may contribute to sorafenib chemoresistance. Complete sequencing and selective variant identification were carried out to detect single nucleotide polymorphisms (SNPs) in SLC22A1 complementary DNA (cDNA). In HCC and CGC biopsies, in addition to previously described variants, two novel alternative spliced variants and three SNPs were identified. To study their functional consequences, these variants were mimicked by directed mutagenesis and expressed in HCC (Alexander and SK-Hep-1) and CGC (TFK1) cells. The two novel described variants, R61S fs*10 and C88A fs*16, encoded truncated proteins unable to reach the plasma membrane. Both variants abolished OCT1-mediated uptake of tetraethylammonium, a typical OCT1 substrate, and were not able to induce sorafenib sensitivity. In cells expressing functional OCT1 variants, OCT1 inhibition with quinine prevented sorafenib-induced toxicity. Expression of OCT1 variants in Xenopus laevis oocytes and determination of quinine-sensitive sorafenib uptake by high-performance liquid chromatography-dual mass spectrometry confirmed that OCT1 is able to transport sorafenib and that R61S fs*10 and C88A fs*16 abolish this ability. Screening of these SNPs in 23 HCC and 15 CGC biopsies revealed that R61S fs*10 was present in both HCC (17%) and CGC (13%), whereas C88A fs*16 was only found in HCC (17%). Considering all SLC22A1 variants, at least one inactivating SNP was found in 48% HCC and 40% CGC. Conclusion : Development of HCC and CGC is accompanied by the appearance of aberrant OCT1 variants that, together with decreased OCT1 expression, may dramatically affect the ability of sorafenib to reach active intracellular concentrations in these tumors. (Hepatology 2013;53:1065–1073)
Autologous skin transplantation for widespread cutaneous necrosis in secondary antiphospholipid syndrome
Authors: C Fiehn
Journal: Annals of the Rheumatic Diseases (2001)

Cutaneous involvement in primary and secondary antiphospholipid syndrome often is a therapeutical dilemma.Here we describe a case of widespread cutaneous necrosis due to thrombosis of the microvasculature, and cutaneous vasculitis in secondary antiphospholipid syndrome in a patient with systemic lupus erythematosus.Autologous skin transplantation was able to cover the skin defects but was only successful in the presence of immunosuppressive treatment with glucocorticoids and cyclosporin A.
Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants
Authors: Jan ter Meulen, Edward N van den Brink, Leo L. M Poon, Wilfred E Marissen, Cynthia S. W Leung, Freek Cox, Chung Y Cheung, Arjen Q Bakker, Johannes A Bogaards, Els van Deventer, Wolfgang Preiser, Hans Wilhelm Doerr, Vincent T Chow, John de Kruif, Joseph S. M Peiris, Jaap Goudsmit
Journal: PLoS Medicine (2006)

Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties.Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318-510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one.The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.
Gene replacement therapy in the CNS: A view from the retina
Authors: Gail M. Seigel
Journal: Behavioral and Brain Sciences (1995)

Abstract Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles.
Horizontal Transfer and Selection in the Evolution of P Elements
Authors: J C Silva, M G Kidwell
Journal: Molecular Biology and Evolution (2000)

The roles of selection and horizontal transfer in the evolution of the canonical subfamily of P elements were studied in the saltans and willistoni species groups of the genus Drosophila (subgenus Sophophora). We estimate that the common ancestor of the canonical P subfamily dates back 2–3 Myr at the most, despite the much older age (more than 40 Myr) of the P family as a whole. The evolution of the canonical P subfamily is characterized by weak selection at nonsynonymous sites. These sites have evolved at three quarters the rate of synonymous sites, in which no selective constraints were detected. Their recent horizontal transfer best explains the high degree of similarity among canonical P elements from the saltans and willistoni species groups. These results are consistent with a model of P-element evolution in which selective constraints are imposed at the time of horizontal transfer. Furthermore, it is estimated that the spread and diversification of the canonical subfamily involved a minimum of 11 horizontal transfer events among the 18 species surveyed within the past 3 Myr. The presence of multiple P subfamilies in the saltans and willistoni species groups is likely to be the result of multiple invasions that have previously swept through these taxa in a succession of horizontal transfer events. These results suggest that horizontal transfer among eukaryotes might be more common than anticipated.
Interferon-g or azathioprine plus corticosteroids do not alter the expression of apoptotic markers in alveolar macrophages of patients with IPF
Authors: Fotios Drakopanagiotakis, Areti Xyfteri, Evangelos Tsiambas, George Vilaras, Andreas Karameris, Constantina Tsakanika, Vlasis Polychronopoulos, Demosthenes Bouros
Journal: European Respiratory Journal (2011)

Introduction:  Pathologic apoptosis is described in IPF. Macrophage activation is implicated in the pathogenesis of fibrotic lung diseases. The apoptotic profile of alveolar macrophages (AM) in IPF is unclear.   Aim:  To examine the expression of apoptotic proteins in AM of patients with IPF after therapeutic intervention.   Methods:  Twenty newly diagnosed IPF patients were randomised in group A treated by a combination of interferonγ-1b and prednisolone and group B treated by azathioprine and prednisolone. Groups were compared regarding clinical deterioration, lung function, and bronchoalveolar lavage (BAL) apoptosis markers.  We analyzed by immunohistochemistry, the expression of the anti- apoptotic markers bcl-2 and the pro-apoptotic markers bax, fas, fas ligand in AM obtained from BAL before and after treatment. We measured apoptosis by TUNEL.  Immunohistochemistry results were evaluated with a digital image analysis assay.   Results:  No difference was observed regarding age, gender, smoking habit between the two groups of IPF patients. The patients of both groups had similar FEV1, FVC and DLCO values at entry and after six months of treatment.  We found no difference in the expression of apoptotic markers in AMs before and after treatment between groups. We found no correlation between clinical and functional parameters and change in apoptotic markers.   Conclusions:  We specifically examined the expression of apoptotic markers in AMs of patients with IPF and we report that different treatment options do not affect the expression of these markers in IPF. These results may be related to the ineffectiveness of pharmacological therapies for IPF.
Chronic non-cancer pain and opioid dependence
Authors: C. Littlejohn, A. Baldacchino, J. Bannister
Journal: Journal of the Royal Society of Medicine (2004)

There are four main questions to address on the subject of chronic non-cancer pain and opioid addiction. Are opioids effective in the treatment of such pain? If so, do the risks of iatrogenic addiction outweigh the benefits? To what extent do patients with primary opioid addiction experience chronic pain? How should this pain be treated?

We review the subject from a UK perspective. Most of the published work comes from the USA, where addiction tends to be viewed primarily as a neurobiological disease or disorder, albeit one that can be influenced by environmental factors.1 UK workers are less inclined to privilege the biological over the psychosocial—readier to accept that people can make heavy use of drugs without being addicted, that the heavy use of drugs can be a choice rather than 'loss of control', and that many people can modify their drug consumption without help.2 Indeed, there are those who see addicts' descriptions of their 'compulsive behaviours' as an artifact of the social and legal prohibitions on the use of drugs (i.e. that the claim 'I only take drugs because I am addicted' is merely a post-hoc rationalization).3 Even in the treatment of pain, the prescription of opioid analgesics has waxed and waned according to the fashion of the moment.

The term addiction is ubiquitous in the published work but is no longer found in either of the contemporary diagnostic manuals, the Diagnostic and Statistical Manual of Mental Disorders (DSM)4 or the International Classification of Diseases (ICD).5 We use it here because it retains ideas about 'loss of control' and chaotic drug use despite adverse physical, mental and social consequences.
Workplace Wellness Recognition for Optimizing Workplace Health
Authors: Gregg C. Fonarow, Chris Calitz, Ross Arena, Catherine Baase, Fikry W. Isaac, Donald Lloyd-Jones, Eric D. Peterson, Nico Pronk, Eduardo Sanchez, Paul E. Terry, Kevin G. Volpp, Elliott M. Antman
Journal: Circulation (2015)

The workplace is an important setting for promoting cardiovascular health and cardiovascular disease and stroke prevention in the United States. Well-designed, comprehensive workplace wellness programs have the potential to improve cardiovascular health and to reduce mortality, morbidity, and disability resulting from cardiovascular disease and stroke. Nevertheless, widespread implementation of comprehensive workplace wellness programs is lacking, and program composition and quality vary. Several organizations provide worksite wellness recognition programs; however, there is variation in recognition criteria, and they do not specifically focus on cardiovascular disease and stroke prevention. Although there is limited evidence to suggest that company performance on employer health management scorecards is associated with favorable healthcare cost trends, these data are not currently robust, and further evaluation is needed. As a recognized national leader in evidence-based guidelines, care systems, and quality programs, the American Heart Association/American Stroke Association is uniquely positioned and committed to promoting the adoption of comprehensive workplace wellness programs, as well as improving program quality and workforce health outcomes. As part of its commitment to improve the cardiovascular health of all Americans, the American Heart Association/American Stroke Association will promote science-based best practices for comprehensive workplace wellness programs and establish benchmarks for a national workplace wellness recognition program to assist employers in applying the best systems and strategies for optimal programming. The recognition program will integrate identification of a workplace culture of health and achievement of rigorous standards for cardiovascular health based on Life's Simple 7 metrics. In addition, the American Heart Association/American Stroke Association will develop resources that assist employers in meeting these rigorous standards, facilitating access to high-quality comprehensive workplace wellness programs for both employees and dependents, and fostering innovation and additional research.
Cold Air Challenge at Age 6 and Subsequent Incidence of Asthma
Authors: ENRICO LOMBARDI, WAYNE J. MORGAN, ANNE L. WRIGHT, RENATO T. STEIN, CATHARINE J. HOLBERG, FERNANDO D. MARTINEZ
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The aim of this study was to assess the relation between bronchial hyperresponsiveness to dry, cold air at age 6 and the subsequent incidence of asthma. The cumulative incidence of newly diagnosed asthma between ages 6 and 11 among 360 children included in this study was 12.0%. Survival analysis showed that hyperresponsiveness to cold air at age 6 was associated with an increased risk of developing subsequent asthma (hazard ratio = 2.6, 95% CI = 1.2–5.4; p = 0.01). However, after adjusting for potential confounders, only mild wheezing at age 6 (adjusted hazard ratio = 7.5, 95% CI = 3.6– 15.9; p < 0.001) and skin test reactivity to allergens at age 6 (adjusted hazard ratio = 3.6, 95% CI = 1.5–8.5; p < 0.01), but not hyperresponsiveness to cold air (adjusted hazard ratio = 0.9, 95% CI = 0.4 –2.2; p = 0.8), remained significant predictors of subsequent development of asthma. These findings were substantially confirmed after stratifying for wheezing illnesses before age 3. We conclude that hyperresponsiveness to cold air at age 6 was associated with subsequent development of a diagnosis of asthma but this effect was not independent of atopy and mild wheezing at age 6.
Inducible Nitric Oxide Synthase Deficiency Protects the Heart From Systolic Overload–Induced Ventricular Hypertrophy and Congestive Heart Failure
Authors: Ping Zhang, Xin Xu, Xinli Hu, Elza D. van Deel, Guangshuo Zhu, Yingjie Chen
Journal: Circulation Research (2007)

Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic constriction (TAC) resulted in myocardial iNOS expression, cardiac hypertrophy, ventricular dilation and dysfunction, and fibrosis, whereas iNOS-deficient mice displayed much less hypertrophy, dilation, fibrosis, and dysfunction. Consistent with these findings, TAC resulted in marked increases of myocardial atrial natriuretic peptide 4-hydroxy-2-nonenal (a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) in wild-type mice but not in iNOS-deficient mice. In response to TAC, myocardial endothelial NO synthase and iNOS was expressed as both monomer and dimer in wild-type mice, and this was associated with increased reactive oxygen species production, suggesting that iNOS monomer was a source for the increased oxidative stress. Moreover, systolic overload-induced Akt, mammalian target of rapamycin, and ribosomal protein S6 activation was significantly attenuated in iNOS-deficient mice. Furthermore, selective iNOS inhibition with 1400W (6 mg/kg per hour) significantly attenuated TAC induced myocardial hypertrophy and pulmonary congestion. These data implicate iNOS in the maladaptative response to systolic overload and suggest that selective iNOS inhibition or attenuation of iNOS monomer content might be effective for treatment of systolic overload-induced cardiac dysfunction.