tbuckley/cabot-search huggingface dataset:
Respiratory virus induction of alpha‐, beta‐ and lambda‐interferons in bronchial epithelial cells and peripheral blood mononuclear cells
Authors: M. R. Khaitov, V. Laza‐Stanca, M. R. Edwards, R. P. Walton, G. Rohde, M. Contoli, A. Papi, L. A. Stanciu, S. V. Kotenko, S. L. Johnston
Journal: Allergy (2009)

Respiratory viruses, predominantly rhinoviruses are the major cause of asthma exacerbations. Impaired production of interferon-beta in rhinovirus infected bronchial epithelial cells (BECs) and of the newly discovered interferon-lambdas in both BECs and bronchoalveolar lavage cells, is implicated in asthma exacerbation pathogenesis. Thus replacement of deficient interferon is a candidate new therapy for asthma exacerbations. Rhinoviruses and other respiratory viruses infect both BECs and macrophages, but their relative capacities for alpha-, beta- and lambda-interferon production are unknown.To provide guidance regarding which interferon type is the best candidate for development for treatment/prevention of asthma exacerbations we investigated respiratory virus induction of alpha-, beta- and lambda-interferons in BECs and peripheral blood mononuclear cells (PBMCs) by reverse transferase-polymerase chain reaction and enzyme-linked immunosorbent assay.Rhinovirus infection of BEAS-2B BECs induced interferon-alpha mRNA expression transiently at 8 h and interferon-beta later at 24 h while induction of interferon-lambda was strongly induced at both time points. At 24 h, interferon-alpha protein was not detected, interferon-beta was weakly induced while interferon-lambda was strongly induced. Similar patterns of mRNA induction were observed in primary BECs, in response to both rhinovirus and influenza A virus infection, though protein levels were below assay detection limits. In PBMCs interferon-alpha, interferon-beta and interferon-lambda mRNAs were all strongly induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon-alpha>-beta>-lambda. Thus respiratory viruses induced expression of alpha-, beta- and lambda-interferons in BECs and PBMCs. In PBMCs interferon-alpha>-beta>-lambda while in BECs, interferon-lambda>-beta>-alpha.We conclude that interferon-lambdas are likely the principal interferons produced during innate responses to respiratory viruses in BECs and interferon-alphas in PBMCs, while interferon-beta is produced by both cell types.
Effect of obstructive sleep apnoea on severity and short-term prognosis of acute coronary syndrome
Authors: Ferran Barbé, Alicia Sánchez-de-la-Torre, Jorge Abad, Joaquin Durán-Cantolla, Olga Mediano, Jose Amilibia, Maria José Masdeu, Marina Florés, Antonia Barceló, Mónica de la Peña, Albina Aldomá, Fernando Worner, Joan Valls, Gerard Castellà, Manuel Sánchez-de-la-Torre
Journal: European Respiratory Journal (2015)

The goal of this study was to evaluate the influence of obstructive sleep apnoea on the severity and short-term prognosis of patients admitted for acute coronary syndrome. Obstructive sleep apnoea was defined as an apnoea–hypopnoea index (AHI) &gt;15 h −1 . We evaluated the acute coronary syndrome severity (ejection fraction, Killip class, number of diseased vessels, and plasma peak troponin) and short-term prognosis (length of hospitalisation, complications and mortality). We included 213 patients with obstructive sleep apnoea (mean± sd AHI 30±14 h −1 , 61±10 years, 80% males) and 218 controls (AHI 6±4 h −1 , 57±12 years, 82% males). Patients with obstructive sleep apnoea exhibited a higher prevalence of systemic hypertension (55% versus 37%, p&lt;0.001), higher body mass index (29±4 kg·m −2 versus 26±4 kg·m −2 , p&lt;0.001), and lower percentage of smokers (61% versus 71%, p=0.04). After adjusting for smoking, age, body mass index and hypertension, the plasma peak troponin levels were significantly elevated in the obstructive sleep apnoea group (831±908 ng·L −1 versus 987±884 ng·L −1 , p=0.03) and higher AHI severity was associated with an increased number of diseased vessels (p=0.04). The mean length of stay in the coronary care unit was higher in the obstructive sleep apnoea group (p=0.03). This study indicates that obstructive sleep apnoea is related to an increase in the peak plasma troponin levels, number of diseased vessels, and length of stay in the coronary care unit.
Smoking cessation: evidence based recommendations for the healthcare system
Authors: M. Raw, A. McNeill, R. West
Journal: BMJ (1999)

Editorial by Coleman et al 

This article summarises the new Smoking Cessation Guidelines for Health Professionals, published in full in Thorax ,1 along with guidance on the cost effectiveness of interventions for smoking cessation.2 The purpose of the guidelines is to recommend and promote the integration of effective and cost effective interventions into routine clinical care throughout the healthcare system, and they are aimed at health commissioners, managers, and clinicians. They are the first professionally endorsed, evidence and consensus based guidelines on smoking cessation for the English healthcare system.

At the time of going to press the full guidelines have been endorsed by more than 20organisations (see box).

### Summary points

### Professional endorsement

Each …
Viruses Affecting Man and Animals
Authors: Edwin D. Kilbourne
Journal: JAMA (1972)

The problem intrinsic to a multipleauthored text are enhanced when such a publication is merely a compilation of symposium papers. The present book does not escape these problems although the quality of many of the chapters is high. The range of the topics is suggested by the program headings: Viral Biology; Virus-Cell Interaction; Viral Oncology; Viral Immunology; Viral Epidemiology and Epizootiology, and Prevention and Control of Virus Diseases. Of necessity, the representation of individual papers under these categories is somewhat uneven and the inclusion of an epidemiologic paper on "Live Influenza Vaccines" under "Viral Immunology" is certainly forced. Seven of the 29 chapters are concerned with interferon, which perhaps indicates some imbalance in the initial selection of topics and speakers. A similar lack of editorial constraint is reflected in the inclusion in the volume of a five-page primary presentation of data (Becher and Olschevsky on the molecular composition of herpes
Qualitative and quantitative analysis of glucosinolates and nucleosides in Radix Isatidis by HPLC and liquid chromatography tandem mass spectrometry
Authors: Xiuming Wang, Yuanyuan Xie, Xiaomei Hu, Youkang Li, Ping Hu, Yiming Wang, Qionglin Liang, Guoan Luo
Journal: Acta Pharmaceutica Sinica B (2013)

Multi-component fingerprinting and quantitation of the glucosinolates and nucleosides in samples of Radix Isatidis have been carried out using high-performance liquid chromatography with diode-array detection and electrospray ionization tandem mass spectrometry (HPLC–DAD–ESI/MS). Five nucleosides together with one glucosinolate were identified by comparing retention times, ultraviolet spectra, mass spectra and/or empirical molecular formulae of reference compounds. Quantitation of these six compounds was carried out simultaneously by HPLC on a Phenomenex Luna C18 column using gradient elution with methanol and water and detection at 254 nm. All calibration curves were linear (r>0.9994) within test ranges. Limits of detection and quantitation were 0.33 ng and 2.50 ng on column, respectively. Intra- and inter-day precision (as relative standard deviation) for all analytes was <2.19% with recoveries in the range 99.6%–101.8% at three concentration levels. The validated method was successfully applied to fingerprinting and assay of 25 batches of Radix Isatidis sourced from different geographical regions of China. The method is simple and reliable and has potential value in the quality control of Radix Isatidis.
Dendritic cells: potential triggers of autoimmunity and targets for therapy
Authors: J A Hardin
Journal: Annals of the Rheumatic Diseases (2005)

Dendritic cells (DCs) are often referred to as the body’s sentinels, constantly guarding against pathogens.1–3 In this role they are the antigen presenting cell that primes naive T cells in vivo.4 DCs also help maintain tolerance to “self” substances through multiple mechanisms that include T cell deletion and anergy as well as the generation of regulatory T cells.5–7 This dual role in regulating both immune responses and immune tolerance suggests that DCs are likely to have a role in autoimmune diseases such as lupus. The possibilities include presentation of “self” antigens as immunogens, a failure to delete autoreactive T cells, overproduction of inflammatory cytokines, and inadequate induction of regulatory T cells. As noted below, insights into these pathogenetic mechanisms in lupus are beginning to emerge. It is also clear that at least some of these activities of DCs can be manipulated through pharmacological agents.8,9

It has been thought for a long time that regulatory T cells are related to the pathogenesis of lupus.10,11 Now, at the forefront of this consideration is the possibility that DCs play a critical role in balancing the array of autoreactive T cells with a corresponding set of regulatory T cells.12 It is clear that immature DCs induce deletional tolerance of autoreactive T cells in the periphery.13–15 However, the original concept that immature DCs are responsible for tolerance and mature DCs induce immune responses has given way to a more complex scenario in which DCs in different states of maturation are able to induce CD4+CD25+ regulatory T cells.16,17 In this paper, my aim is to consider the possibility that the maturation of DCs might be manipulated in such a way as to either enhance regulatory T cell generation or diminish priming of …
Clinical Use of Viable Frozen Human Skin
Authors: Ronald B. Berggren
Journal: JAMA (1965)

After a method for the successful freezing and storing of viable skin was developed in the laboratory, it was applied to human skin grafts. Split-thickness skin was prepared by soaking in 10% dimethyl sulfoxide (DMSO) and frozen in dry ice. It was then stored at liquid nitrogen temperatures (—196 C) for periods up to 608 days. The grafts were used in various clinical situations. The success of the grafts was directly related to the status of the recipient bed and showed no relation to the time of storage. The grafts have been used in 26 cases as autografts and 12 cases as homografts.
Haloperidol and Limb Deformity
Authors: James W. Hanson
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The continuing possibility that a potent new teratogen will come into general use in the guise of a safe and effective drug has prompted us to view with concern all reports of drug-associated malformations. Last winter we learned of the case reported in this issue ofThe Journal(p 62) of a child born with limb-reduction deformities, whose mother had taken haloperidol and other drugs early in pregnancy. In an attempt to clarify any possible relationship between this drug and other cases of reduction deformities, we reviewed the prenatal drug-exposure histories of children with similar defects born in Metropolitan Atlanta in the past four years. Haloperidol has been used in the treatment of a variety of psychoses and psychotic reactions in Europe since 1958 and in the United States since 1967. Little information on the teratogenic potential of haloperidol is available from the literature. Experiments in several
221 A MURINE AND HUMAN STUDY DEMONSTRATING THE ROLE OF PLGF IN HEPATOCELLULAR CARCINOMA
Authors: F. Heindryckx, S. Coulon, L. Crapè, G. Cornelis, L. Libbrecht, A. Geerts, I. Colle, H. Van Vlierberghe
Journal: Journal of Hepatology (2011)
Age-related changes in musculoskeletal mass between black and white women
Authors: James A. Gasperino, Jack Wang, Richard N. Pierson, Steven B. Heymsfield
Journal: Metabolism (1995)

Earlier studies from our laboratory indicated that matched black and white women differ significantly in total body potassium (TBK), total body bone density (TBD), and total body bone mineral (TBBM). The aim of this investigation was to examine absolute levels and the kinetics of age-related changes in TBK, TBD, TBBM, and percent body fat in a cross-sectional cohort of 34 matched pairs (age +/- 4 years, weight +/- 2 kg, and height +/- 4 cm) of black and white healthy non-obese women. Black and white women had a similar percentage of body weight as fat, although adipose tissue distribution (ie, waist to hip circumference ratio [WHR]) differed significantly (P < .0007) between the two groups (WHR, mean +/- SD: black, 0.837 +/- 0.062; white, 0.788 +/- 0.043). TBBM and TBD were significantly (P < .0001) higher in young black women, and ethnic differences in total bone mineral mass persisted at all ages. TBK (P = 0.0482) and appendicular skeletal muscle mass (P < .0001) were higher in young black women; however, by ages 60 to 70 years, the two groups had similar TBK. Both groups of women lost musculoskeletal mass (ie, TBK and TBBM) and gained fat mass at similar rates. The results of this study suggest that black women have a greater appendicular muscle and skeletal mass, as well as upper-body fat distribution, than white women. These differences are independent of body weight, height, or percent fat, and the ethnic skeletal differences persist throughout the adult life span. The higher appendicular muscle mass, skeletal mass, and upper-body fat distribution suggest that black women may have greater androgenic activity than white women.
Relation of neurohumoral activation to clinical variables and degree of ventricular dysfunction: A report from the registry of studies of left ventricular dysfunction
Authors: Claude R. Benedict, David E. Johnstone, Debra H. Weiner, Martial G. Bourassa, Vera Bittner, Richard Kay, Philip Kirlin, Barry Greenberg, Robert M. Kohn, John M. Nicklas, Kevin McIntyre, Miguel A. Quinones, Salim Yusuf
Journal: Journal of the American College of Cardiology (1994)
Refsum's disease: characterization of the enzyme defect in cell culture
Authors: James H. Herndon, Daniel Steinberg, B. William Uhlendorf, Henry M. Fales
Journal: Journal of Clinical Investigation (1969)

Refsum's disease (heredopathia atactica polyneuritiformis, HAP) is an inherited neurological disorder associated with storage of the branched-chain fatty acid, phytanic acid (3,7,11,15-tetramethylhexadecanoic acid). Cultured fibroblasts derived from skin biopsies of HAP patients did not contain elevated levels of phytanate, yet showed rates of phytanate-C-(14)C oxidation less than 3% of those seen in cells from control subjects. Cells of control subjects converted phytanate to alpha-hydroxyphytanate, to pristanate (the [n-1] homologue of phytanate) and to 4,8,12-trimethyltridecanoate, compounds previously identified as intermediates on the major pathway for phytanate metabolism in animals, providing the first direct evidence that this same oxidative pathway is operative in human cells. None of these breakdown products could be found after incubation of phytanate with HAP cells. Labeled alpha-hydroxyphytanate and labeled pristanate were oxidized at normal rates by HAP cells. Oxidation of the latter proceeded at normal rates both when added to the medium at very low tracer levels and at levels 100 times greater. Phytanate was incorporated into and released from lipid esters at normal rates by HAP cells. Elevated levels of free phytanate in the medium were no more toxic to HAP cells than to control cells over the 48- to 72-hr exposures involved in these studies, as evidenced by morphologic criteria and by ability to oxidize labeled palmitate. These findings are consistent with the hypothesis that the cells from HAP patients are deficient in a single enzyme involved in the alpha-hydroxylation of phytanate, while the enzymes involved in later steps are present at normal or near-normal levels.
Tthyd, a new thymocyte alloantigen linked to Igh-1. Implications for a switch mechanism for T cell antigen receptors.
Authors: F L Owen, G M Spurll, E Panageas
Journal: The Journal of Experimental Medicine (1982)

Tthyd is an alloantigen coded for by a gene(s) near the immunoglobulin locus on chromosome 12 in the mouse. This T cell-specific antigen may be the third member of a family of antigen receptors on T cells encoded by a cluster of genes in the IgT-C region. This antigen is preferentially expressed on thymocytes in contrast to Tindd or Tsud that are expressed on peripheral T cells. The hypothesis that T cell receptors undergo a switch in surface isotype upon maturation is discussed.
THE DIAGNOSIS OF GALL-STONE LODGED IN THE COMMON DUCT
Authors: WILLIAM FITCH CHENEY
Journal: JAMA (1913)

ILLINOISwas no tenderness over the right hypoehondrium or the epigastrium.This absence of objective evidence in gall-bladder cases is not uncommon; repeatedly in patients who have come to operation it has been a surprise to find the extent of pathologic change existing in and around the gaill-bladder, although before operation no abnormality could be made out.The laboratory evidence likewise showed only'the presence of jaundice, with moderate secondary anemia.The urine was very dark and contained bile; the feces were very light and Aes were slightly lacking in bile; the hemoglobin and red corpusc M reduced, while at the outset the count of white cells was normal, 7,200.Course.-The next indication was to watch the course of events for a time to see whether or not the patient's story was correct, for, so far, her statement constituted all the data on which we 'could depend for diagnosis.Fortunately, the incidents of the next few days were in exact accord with what
A model for the study of hepatitis C virus entry
Authors: Valérie Castet, Darius Moradpour
Journal: Hepatology (2003)

The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies.
Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.
Authors: S Pitkanen, B H Robinson
Journal: Journal of Clinical Investigation (1996)

Mitochondria were isolated from skin fibroblast cultures derived from healthy individuals (controls) and from a group patients with complex I (NADH-CoQ reductase) deficiency of the mitochondrial respiratory chain. The complex I deficient patients included those with fatal infantile lactic acidosis (FILA), cardiomyopathy with cataracts (CC), hepatopathy with tubulopathy (HT), Leigh's disease (LD), cataracts and developmental delay (CD), and lactic acidemia in the neonatal period followed by mild symptoms (MS). Production of superoxide radicals, on addition of NADH, were measured using the luminometric probe lucigenin with isolated fibroblast mitochondrial membranes. Superoxide production rates were highest with CD and decreased in the order CD >> MS > LD > control > HT > FILA = CC. The quantity of Mn-superoxide dismutase (MnSOD), as measured by ELISA techniques, however, was highest in CC and FILA and lowest in CD. Plots of MnSOD quantity versus superoxide production showed an inverse relationship for most conditions with complex I deficiency. We hypothesize that oxygen radical production is increased when complex I activity is compromised. However, the observed superoxide production rates are modulated by the variant induction of MnSOD which decreases the rates, sometimes below those seen in control fibroblast mitochondria. In turn, we show that the variant induction of MnSOD is most likely a function of the change in the redox state of the cell experienced rather than a result of the complex I defect per se.
Obstructive sleep apnoea can directly cause death
Authors: S Pearce
Journal: Thorax (2003)

A 52 year old woman was referred for investigation of daytime somnolence. She complained of heavy snoring, unrefreshing disturbed sleep, and had fallen asleep while driving. She had an Epworth score1 of 24/24, a history of hypertension controlled on losartan, had never smoked, and only took occasional alcohol. She had limited mobility as a result of her extreme obesity (168 kg) with a height of 1.58 m (BMI 67.3 kg/m2). Her chest was clinically clear (FEV1 1.8 l, FVC 2.3 l) and her …
Anti-TNF- therapy monitoring in chronic rheumatic diseases by cytometric profiling of peripheral blood cells
Authors: U. Schulte-Wrede, M. Steinbrich-Zollner, J. R. Grun, J. Sieper, A. Radbruch, A. Grutzkau
Journal: Annals of the Rheumatic Diseases (2011)

Ankylosing spondylitis (AS) is a chronic inflammatory disorder mainly affecting the axial skeleton and belongs to a group of rheumatic diseases known as spondyloarthritides. Anti-tumour necrosis factor (TNF)-α (tumour necrosis factor) biologicals, which aim to block the disease-associated proinflammatory activity of this cytokine, have been successfully applied for treatment of rheumatoid arthritis (RA) and AS as well. Unfortunately, only a subgroup of around 60% of patients is successfully responding to this treatment and up to now, there are no useful biomarkers available for predicting a beneficial clinical response to the cost-intensive TNF-α therapies. The aim of the present study was to monitor treatment of AS patients over time with a multiparametric approach, called cytometric profiling, which allows immunoscoping of hundreds of immunophenotypic parameters at the single cell level. Fifty different monoclonal antibodies were combined to 10 different staining cocktails, which allowed the detection of all major leucocyte populations and their activation state in a few millitres of peripheral blood. Protocols applied include seven colour stainings that will allow the detection of up to 12 parameters. This strategy combines the generation of hypothesis-based and hypothesis-generating knowledge. The huge amount of data generated per measurement made it necessary to develop appropriate bioinformatic solutions for data storage, data normalisation and retrieval of differentially expressed parameters. Here the authors present first preliminary data generated in a cohort of 10 AS patients 4, 8 and 12 weeks after starting treatment. Patterns of immunophenotypic parameters could be determined by bioinformatic tools originally applied to array-based transcriptome studies. The authors approach revealed cytometric signatures that indicate a successful treatment of patients. Neutrophils, monocytes and NK cells could identified as cellular sensitisers responding to TNF-α blockade. Altogether, this study demonstrates the value of our cytometric profiling approach to reveal patterns of parameters that generally possess higher predictive and diagnostic power than solitary ones. Moreover, this approach will help to disclose hitherto unknown disease-associated parameters, which may be helpful to identify new pathophysiology- and therapy-related mechanisms.