tbuckley/cabot-search huggingface dataset:
Tumour necrosis factor gene polymorphisms as severity markers in rheumatoid arthritis
Authors: C. L Verweij
Journal: Annals of the Rheumatic Diseases (1999)

A large number of diseases are multifactorial whereby both environmental and genetic factors contribute to the aetiology and/or clinical severity.The genetics of many of these diseases is complex, involving multiple genes, and Mendelian patterns of inheritance do not apply.2][3] The mode of segregation in the population is best explained by a polygenic background influenced by the right environmental stimulus.Estimates suggest that at least 10 diVerent genetic regions may be linked to susceptibility to RA. 4 As a consequence, variability in the contribution of genetic factors involved in disease may be related to variability in clinical presentation with a spectrum ranging from mild to severe disease.6][7] Parametric linkage analysis suggests that HLA may contribute up to 30% of overall inherited susceptibility in RA. 8 However, despite intense research eVorts the functional basis of disease associated HLA alleles in RA is still not understood.In the hunt for additional genetic factors that contribute to RA two approaches have been taken.Firstly, genome wide screening in large multicase family registries is carried out to define genetic regions that co-segregate with disease more frequently than is expected.Secondly, candidate genes may be defined on the basis of their role in the pathophysiology of the disease.Association studies in aVected and unaVected persons are used to define disease susceptibility genes.Subsequent disease stratification studies may help to define genetic markers that are associated with specific clinical manifestations.As far as RA is concerned, these analyses may be complicated as a consequence of genetic heterogeneity, incomplete penetrance and gene interactions.
AML1-ETO Decreases ETO-2 (MTG16) Interactions with Nuclear Receptor Corepressor, an Effect That Impairs Granulocyte Differentiation
Authors: Vinzon Ibañez, Arun Sharma, Silvia Buonamici, Amit Verma, Sudhakar Kalakonda, Jianxiang Wang, ShriHari Kadkol, Yogen Saunthararajah
Journal: Cancer Research (2004)

Abstract The t(8;21) chromosome abnormality in acute myeloid leukemia targets the AML1 and ETO genes to produce the leukemia fusion protein AML1-ETO. Another member of the ETO family, ETO-2/MTG16, is highly expressed in murine and human hematopoietic cells, bears &amp;gt;75% homology to ETO, and like ETO, contains a conserved MYND domain that interacts with the nuclear receptor corepressor (N-CoR). AML1-ETO prevents granulocyte but not macrophage differentiation of murine 32Dcl3 granulocyte/macrophage progenitors. One possible mechanism is recruitment of N-CoR to aberrantly repress AML1 target genes. We wished to examine another mechanism by which AML1-ETO might impair granulocyte differentiation. We demonstrate that AML1-ETO decreases interactions between ETO-2 and N-CoR. Furthermore, overexpression of ETO-2 relieves AML1-ETO-induced granulocyte differentiation arrest. This suggests that decreased interactions between ETO-2 and N-CoR may contribute to granulocyte differentiation impairment. The MYND domain coimmunoprecipitates with N-CoR and inhibits interactions between ETO-2 and N-CoR, presumably by occupying the ETO-2 binding site on N-CoR. This inhibition of ETO-2 interactions with N-CoR is specific because the MYND domain does not inhibit retinoic acid receptor interactions with N-CoR. To examine the effect of decreasing interactions between ETO-2 and N-CoR in hematopoietic cells, without effects of AML1-ETO such as direct repression of AML1 target genes, the MYND domain was expressed in 32Dcl3 and human CD34+ cells. The MYND domain prevented granulocyte but not macrophage differentiation of both 32Dcl3 and human CD34+ cells, recapitulating this effect of AML1-ETO. In conclusion, decreasing interactions between ETO-2 and N-CoR, an effect of AML1-ETO, inhibits granulocyte differentiation.
Shared Genetic Etiology Between Eoe and Other Allergic Diseases
Authors: Leah Claire Kottyan, Joelle A. Rothenberg, Rahul J. D'Mello, Thomas T. Quan, Joseph D. Sherrill, Benjamin P. Davis, Mirna Chehade, Robert A. Wood, Robbie D. Pesek, Brian P. Vickery, David M. Fleischer, Robert W. Lindblad, Hugh A. Sampson, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2015)
Measurement of bronchial reactivity: a question of interpretation.
Authors: A E Tattersfield
Journal: Thorax (1981)

Measurement of bronchial reactivity: a question of interpretation Non-specific bronchial hyperreactivity is well recognised in asthma although the underlying mechanism is poorly understood.Reproducible results can now be obtained both for exercise and for a variety of inhalation challenge tests but inter- pretation of the results remains controversial and poses the main challenge to work in this area.This editorial discusses some aspects of interpretation with particular reference to studies of broncho- dilating and bronchoconstricting agents.There are three main reasons for wanting to measure non-specific bronchial responsiveness.First, the expectation that further understanding of bronchial reactivity will help to unravel the cause of asthma; clearly if the cause of bronchial hyperreactivity was known our understanding of asthma would be greatly increased.Second, if a bronchial challenge test provided a useful model of asthma, drugs could be tested under reasonably controlled conditions.This approach has been of limited value since the effectiveness of a drug in blocking an acute bronchial challenge has not correlated particularly well with its effectiveness in clinical practice, as shown for example by a comparison of sodium cromoglycate with steroids.Finally, and more controversial, is the use of bronchial reactivity test- ing in the routine diagnosis, assessment, and management of asthma.In man, bronchial reactivity is measured as the airway response to a standard stimulus, usually exercise or an inhalation challenge.With the latter increasing doses of stimulus allow a dose-response relationship to be obtained.This approach is analogous to measuring the change in length or tension of a strip of bronchial smooth muscle in response to a stimulus, but unfortunately, in intact man, both the stimulus and the measurement are quantified much less easily.The inhaled broncho- constricting stimuli include histamine, methacholine, prostaglandin F2a, and cold air given with different nebulisers, nebulised volumes, particle size, and inhalation techniques, all of which affect both the site and amount of stimulus deposited in the air- ways.t 2 The amount of drug actually entering
Evolution of the Cichlid Visual Palette through Ontogenetic Subfunctionalization of the Opsin Gene Arrays
Authors: Tyrone C. Spady, Juliet W. L. Parry, Phyllis R. Robinson, David M. Hunt, James K. Bowmaker, Karen L. Carleton
Journal: Molecular Biology and Evolution (2006)

The evolution of cone opsin genes is characterized by a dynamic process of gene birth and death through gene duplication and loss. However, the forces governing the retention and death of opsin genes are poorly understood. African cichlid fishes have a range of ecologies, differing in habitat and foraging style, which make them ideal for examining the selective forces acting on the opsin gene family. In this work, we present data on the riverine cichlid, Oreochromis niloticus, which is an ancestral outgroup to the cichlid adaptive radiations in the Great African lakes. We identify 7 cone opsin genes with several instances of gene duplication. We also characterize the spectral sensitivities of these genes through reconstitution of visual pigments. Peak absorbances demonstrate that each tilapia cone opsin gene codes for a spectrally distinct visual pigment: SWS1 (360 nm), SWS2b (423 nm), SWS2a (456 nm), Rh2b (472 nm), Rh2a β (518 nm), Rh2a α (528 nm), and LWS (561 nm). Furthermore, quantitative reverse transcription polymerase chain reaction at 3 ontogenetic time points demonstrates that although only 4 genes (SWS2a, Rh2a α and β, and LWS) are expressed in adults, mRNAs for the other genes are all expressed during ontogeny. Therefore, subfunctionalization through differential ontogenetic expression may be a key mechanism for preservation of opsin genes. The distinct peak absorbances of these preserved opsin genes provide a palette from which selection creates the diverse visual sensitivities found among the cichlid species of the lacustrine adaptive radiations.
Bronchodilator delivery with metered-dose inhalers in mechanically-ventilated patients
Authors: R Dhand, MJ Tobin
Journal: European Respiratory Journal (1996)

Metered-dose inhalers (MDIs) provide several advantages over nebulizers, including ease of administration, decreased cost, reliability of dosing, and freedom from contamination. However, this method of aerosol delivery has been considered ineffective in mechanically-ventilated patients because most of the aerosol deposits in the endotracheal tube and ventilator circuit. A smaller amount of aerosol from a MDI is deposited in the lower respiratory tract of mechanically-ventilated patients than in ambulatory patients, although recent studies show that a significant bronchodilator effect can still be achieved. When employed optimally, significant bronchodilation occurs with as little as 4 puffs of a sympathomimetic aerosol. Multiple factors influence the efficacy of MDIs in mechanically-ventilated patients. The method of connecting the MDI canister to the ventilator circuit has a marked effect on aerosol delivery, and other factors include the timing of MDI actuation, ventilator mode, tidal volume, circuit humidity, and duty cycle. With a proper technique of administration, a MDI serves as an effective, convenient, and safe method for delivering bronchodilator aerosols in mechanically-ventilated patients.
S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction
Authors: T. Sigsgaard, I. Brandslund, O. Omland, C. Hjort, E.D. Lund, O.F. Pedersen, M.r Miller
Journal: European Respiratory Journal (2000)

Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.
Insurance problems among patients with ankylosing spondylitis
Authors: A Boonen
Journal: Annals of the Rheumatic Diseases (2003)

In a retrospective questionnaire survey, 129 Dutch patients with ankylosing spondylitis (AS) were asked if they had had difficulties in arranging a medical insurance, an additional work disability insurance, or a life assurance. Patients who had arranged the insurance after diagnosis were compared with those who had arranged the insurance before diagnosis. A restraint in arranging the insurance was defined …
A phase I–II study of weekly cisplatin and gemcitabine with concurrent radiotherapy in locally advanced cervical carcinoma
Authors: J.J. Zarbá, A.V. Jaremtchuk, P. Gonzalez Jazey, M. Keropian, R. Castagnino, C. Mina, G. Arroyo
Journal: Annals of Oncology (2003)
Lung function in awake healthy infants: the first five days of life
Authors: KC Lodrup-Carlsen, KH Carlsen
Journal: European Respiratory Journal (1993)

Our main aim was to determine an appropriate time for lung function measurements in infants, prior to environmental influences upon their respiratory tract. Tidal flow-volume loops, respiratory system compliance (Crs) and resistance (Rrs) (single breath passive occlusion technique) were measured in 24 healthy, awake awake infants, at one hour and on the following four days of life to investigate variability and reproducibility over time. Possible differences in lung function were sought between the 12 vaginally-delivered and 12 Caesarean section-delivered infants. Tidal volumes increased each day, but significantly so only from Day 0 to Day 1. The expiratory flow-time ratios (time to reach peak expiratory flow to total expiratory time (Tme/Te) and tidal expiratory flow at 75% to peak flow (TEF25/PTEF)) and expiratory flow-volume ratio (volume to reach peak expiratory flow to total expiratory volume (Vme/Ve)) were significantly smaller on Day 1 than Day 0, but did not change significantly thereafter. Crs and Rrs were lower on Day 0 than later. Intra-individual variation remained stable for tidal flow-volume parameters throughout the study, but was significantly higher during Day 0 and Day 1 for Crs and Rrs. There were no significant differences related to mode of delivery of the infant. We conclude that, for epidemiological purposes, tidal lung function parameters may be measured from Day 2 to Day 4, and that they are not influenced by mode of delivery of the infant.
Brief Report: The Ability of the 2013 American College of Cardiology/American Heart Association Cardiovascular Risk Score to Identify Rheumatoid Arthritis Patients With High Coronary Artery Calcification Scores
Authors: Vivian K. Kawai, Cecilia P. Chung, Joseph F. Solus, Annette Oeser, Paolo Raggi, C. Michael Stein
Journal: Arthritis & Rheumatology (2014)

Objective Patients with rheumatoid arthritis (RA) have increased risk of atherosclerotic cardiovascular disease that is underestimated by the Framingham Risk Score (FRS). We undertook this study to test the hypothesis that the 2013 American College of Cardiology/American Heart Association (ACC/AHA) 10‐year risk score would perform better than the FRS and the Reynolds Risk Score (RRS) in identifying RA patients known to have elevated cardiovascular risk based on high coronary artery calcification (CAC) scores. Methods Among 98 RA patients eligible for risk stratification using the ACC/AHA risk score, we identified 34 patients with high CAC (defined as ≥300 Agatston units or ≥75th percentile of expected coronary artery calcium for age, sex, and ethnicity) and compared the ability of the 10‐year FRS, RRS, and ACC/AHA risk scores to correctly assign these patients to an elevated risk category. Results All 3 risk scores were higher in patients with high CAC ( P &lt; 0.05). The percentage of patients with high CAC correctly assigned to the elevated risk category was similar among the 3 scores (FRS 32%, RRS 32%, ACC/AHA risk score 41%) ( P = 0.223). The C statistics for the FRS, RRS, and ACC/AHA risk score predicting the presence of high CAC were 0.65, 0.66, and 0.65, respectively. Conclusion The ACC/AHA 10‐year risk score does not offer any advantage compared to the traditional FRS and RRS in the identification of RA patients with elevated risk as determined by high CAC. The ACC/AHA risk score assigned almost 60% of patients with high CAC to a low risk category. Risk scores and standard risk prediction models used in the general population do not adequately identify many RA patients with elevated cardiovascular risk.
In vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells
Authors: Brienne A. McKenzie, Franz J. Zemp, Alexandra Pisklakova, Aru Narendran, Grant McFadden, Xueqing Lun, Rajappa S. Kenchappa, Ebba U. Kurz, Peter A. Forsyth
Journal: Neuro-Oncology (2015)

Brain tumor-initiating cells (BTICs) are stem-like cells hypothesized to form a disease reservoir that mediates tumor recurrence in high-grade gliomas. Oncolytic virotherapy uses replication-competent viruses to target and kill malignant cells and has been evaluated in clinic for glioma therapy with limited results. Myxoma virus (MyxV) is a safe and highly effective oncolytic virus (OV) in conventional glioma models but, as seen with other OVs, is only modestly effective for patient-derived BTICs. The objective of this study was to determine whether MyxV treatment against human BTICs could be improved by combining chemotherapeutics and virotherapy. A 73-compound library of drug candidates in clinical use or preclinical development was screened to identify compounds that sensitize human BTICs to MyxV treatment in vitro, and synergy was evaluated mathematically in lead compounds using Chou-Talalay analyses. The effects of combination therapy on viral gene expression and viral replication were also assessed. Eleven compounds that enhance MyxV efficacy were identified, and 6 were shown to synergize with the virus using Chou-Talalay analyses. Four of the synergistic compounds were shown to significantly increase viral gene expression, indicating a potential mechanism for synergy. Three highly synergistic compounds (axitinib, a VEGFR inhibitor; rofecoxib, a cyclooxygenase-2 inhibitor; and pemetrexed, a folate anti-metabolite) belong to classes of compounds that have not been previously shown to synergize with oncolytic viruses in vitro. This study has identified multiple novel drug candidates that synergistically improve MyxV efficacy in a preclinical BTIC glioma model.
Transforming growth factor-beta activity in sheep lung lymph during the development of pulmonary hypertension.
Authors: E A Perkett, R M Lyons, H L Moses, K L Brigham, B Meyrick
Journal: Journal of Clinical Investigation (1990)

Chronic pulmonary hypertension is associated with extensive structural remodeling of the pulmonary arterial bed. The structural changes in the arterial walls include increased production of extracellular matrix components and smooth muscle cell hypertrophy, changes that have been similarly induced by transforming growth factor-beta (TGF-beta) in culture. In the present study, experiments were performed to determine whether TGF-beta is present in sheep lung lymph, and whether TGF-beta levels were altered in an animal model of chronic pulmonary hypertension induced by continuous air embolization. Several standard biological assays for TGF-beta activity were used for these determinations including soft agar assays, inhibition of epithelial cell proliferation, and a TGF-beta-specific radioreceptor assay. In each case, control lung lymph contained high concentrations of TGF-beta (100 ng/ml) which required transient acidification for detection. Samples of lung lymph from hypertensive sheep showed a transient and early two- to threefold increase in concentrations of latent TGF-beta. This activity could be partially blocked by TGF-beta antibodies. These studies indicate that sheep lung lymph contains TGF-beta and that the level of TGF-beta increases early during the development of pulmonary hypertension. Thus, TGF-beta may contribute to the development of the structural changes in the pulmonary arteries that occur during the onset of chronic pulmonary hypertension.
How impact factors changed medical publishing—and science
Authors: Hannah Brown
Journal: BMJ (2007)

Hannah Brown investigates the use and abuse of journal rankings 

George Lundberg spent the early 1980s lamenting the loss of his journal's once great reputation. JAMA (the Journal of the American Medical Association ), which he had taken over in 1982, had been in decline since its peak of popularity in the 1960s. And a new set of rankings that pitted medical journals against each other on the basis of article citations now seemed to confirm that JAMA was a long way behind the best. To make his editorship successful, Dr Lundberg needed a recovery strategy.

So, while other medical journals continued to dismiss as an irrelevance their citation rankings—labelled “impact factor” by the data crunching company that devised and compiled the system—Dr Lundberg seized the opportunity to make them work in JAMA 's favour. Recognising that impact factors were derived from citations, Dr Lundberg reasoned that chasing high profile authors and institutions could help boost JAMA 's rank and, therefore, its reputation. He instructed his editorial team to seek out studies that had the potential to become staple references in other papers and try to woo the authors into submitting to JAMA . “We were looking for prestige,” Dr Lundberg recalls.

At the time the strategy was implemented, JAMA had a lot of ground to make up in the impact factor stakes. “When we started, JAMA and the BMJ were roughly similar at around four, the Lancet was higher, and NEJM [ New England Journal of Medicine ] and Annals [of Internal Medicine] were higher still,” Dr Lundberg explains. “But then JAMA started rising and it never stopped,” he says. Over several years, Dr Lundberg successfully raised the journal's impact factor to around 11, while those of the Annals of Internal Medicine and the BMJ rose only slightly in the …
Breast Cancer Survivors' Perceptions of Survivorship Care Options
Authors: Erica L. Mayer, Adrienne B. Gropper, Bridget A. Neville, Ann H. Partridge, Danielle B. Cameron, Eric P. Winer, Craig C. Earle
Journal: Journal of Clinical Oncology (2011)

As the number of breast cancer survivors increases, a durable model of comprehensive survivor care is needed, incorporating providers and/or visit types both within and outside of oncology. The objective of this study was to explore survivors' comfort with different clinician types or with a telephone/Internet-based virtual visit as components of survivorship care.