tbuckley/cabot-search huggingface dataset:
Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma
Authors: H. Gono, K. Fujimoto, S. Kawakami, K. Kubo
Journal: European Respiratory Journal (2003)

The aim of this study was to examine the relationship between the structural changes in large and small airways in asymptomatic asthmatics quantified by high-resolution computed tomography (HRCT) and airflow obstruction. The bronchial wall thickness at the trunk of the apical bronchus (B1) of the right upper lobe was used for assessment of the large airways. Air trapping, evaluated by the ratio of the average CT‐determined values for the bilateral upper and lower lung segments at full expiration to that at full inspiration (E/I ratio), was used for assessment of the small airways. Measurements were obtained with a helical HRCT in 24 asymptomatic asthmatics followed by optimal treatment with inhaled and/or oral corticosteroids for &gt;6 months. Prior (20–30 min) to the HRCT examination, all patients were given an inhaled bronchodilator. The ratio of airway wall thickness to outer diameter (T/D) and the percentage wall area (WA%) at the B1 bronchus and the E/I ratio were significantly greater for the 14 asthmatics with deficient reversible airflow obstruction (forced expiratory volume in one second (FEV 1 ) &lt;80% prediced or FEV 1 /forced vital capacity &lt;70% after bronchodilator inhalation) than for the 10 asthmatics with normal spirometry and seven normal subjects. T/D, WA%, and E/I ratio showed significant negative correlations with FEV 1 % pred after bronchodilator inhalation. The E/I ratio also showed significant positive correlations with T/D, WA%, and residual volume/total lung capacity. These findings suggest that, in spite of optimal treatment, structural changes in both large and small airways may simultaneously occur in asthmatics with deficient reversible airflow obstruction.
Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines
Authors: Cornel Joseph Phillip, Shadia Zaman, Shujun Shentu, Kumudha Balakrishnan, Jiexin Zhang, Veera Baladandayuthapani, Pietro Taverna, Sanjeev Redkar, Michael Wang, Christine Marie Stellrecht, Varsha Gandhi
Journal: Journal of Hematology & Oncology (2013)

MET is a receptor tyrosine kinase that is activated by the ligand HGF and this pathway promotes cell survival, migration, and motility. In accordance with its oncogenic role, MET is constitutively active, mutated, or over-expressed in many cancers. Corollary to its impact, inhibition of MET kinase activity causes reduction of the downstream signaling and demise of cells. In myeloma, a B-cell plasma malignancy, MET is neither mutated nor over-expressed, however, HGF is increased in plasma or serum obtained from myeloma patients and this was associated with poor prognosis. The small-molecule, amuvatinib, inhibits MET receptor tyrosine kinase. Based on this background, we hypothesized that targeting the HGF/MET signaling pathway is a rational approach to myeloma therapy and that myeloma cells would be sensitive to amuvatinib.
Hunting for histamine's source
Authors: Ruth Williams
Journal: The Journal of Experimental Medicine (2006)

For asthma sufferers, contracting a lung infection can mean hospitalization, but it has never been clear how bugs exacerbate allergic conditions. Xu et al. (page 2907) now show that the major allergic inflammatory mediator—histamine—is also produced in response to infection. But it comes from an unexpected source.






Figure 1

Rising numbers of neutrophils (left) in the infected lung are the cause of rising histamine (right).




Mast cells together with basophils are considered the major producers of histamine. Because bacterial infection of the lung can lead to asthma attacks more severe than those caused by allergens, Caughey's group hypothesized that histamine might be produced in response to infection and, if indeed it were, that mast cells were likely to be the source.

The team found that, approximately one week after infection with Mycoplasma pulmonis bacteria, histamine levels in the lungs of the mice had risen dramatically. However, this increase was observed even if the mice had no mast cells. The team noticed that the rising level of histamine paralleled an increase in the number of neutrophils in the lung. Considering the possibility that these cells might be the source of the histamine, the team depleted neutrophils in the mast cell-deficient mice and, sure enough, observed a concurrent drop in the level of infection-induced histamine.

Although neutrophils have previously been reported to produce histamine, their contribution was thought to be small. The vast amount of histamine they produce in response to lung infection—an approximately 50-fold induction—was therefore a surprise, says research leader, Caughey.

The team now plans to see whether other bacteria induce a similar increase in the production of histamine, and whether high histamine levels are also a feature of human lung infections. If so, Caughey suggests that antihistamines, not generally considered in the treatment of infection, deserve a second look.
Quantitative assessment of the value of spirometry.
Authors: N J Russell, N J Crichton, P A Emerson, A D Morgan
Journal: Thorax (1986)

To determine the value of simple spirometric measurements in the diagnostic assessment of breathless patients, doctors requesting such tests were asked to predict the likely ventilatory abnormality, expressing these pretest predictions as probabilities. Comparison of these pretest predictions with the test results allowed an analysis of the doctors' ability to identify lung function abnormalities and an assessment of the diagnostic usefulness of the test. Predictions and spirometric measurements were made in 123 patients. Doctors expressed preference for a particular spirometric category in 112 cases, of which 13 were predicted to have a restrictive defect, 77 were predicted to have an obstructive defect, and 22 were predicted to be normal. Spirometry showed that nine patients had a restrictive defect, 79 had an obstructive defect, and 24 had normal indices. The study showed that 61% of the tests gave a result that doctors predicted as being unlikely. The study also showed that doctors had difficulty in identifying the reversibility of airflow obstruction in patients in whom they correctly predicted obstruction. Spirometry fulfils a useful role in the diagnosis of breathless patients.
Role of adenosine in local control of intestinal circulation in the dog.
Authors: H J Granger, C P Norris
Journal: Circulation Research (1980)

Adenosine, a purine nucleoside and powerful vasodilator, may be the chemical messenger elaborated by the intestinal cells to signal local adjustments of vascular tone.Close intra-arterial infusion of adenosine into the superior mesenteric artery elicited a 2.5-fold increase in intestinal blood flow at a calculated plasma concentration of 10~e Af, and the half-maximal response occurred at 10"' in.These values are similar to those reported for effects of adenosine on coronary blood flow.In the fasted dog, inhibition of the interaction between adenosine and the vasculature with theophylline did not alter prevailing blood flow, flow autoregulation, or postprandial hyperemia.Moreover, inhibition of parenchymal reuptake of adenosine by 10~5 M dipyridimole did not cause a decrease in vascular resistance of the empty intestine.Thus, in the inactive intestine, adenosine does not appear to be present in sufficient concentration to contribute to the prevailing vascular tone.Furthermore, under these conditions, the nucleoside does not appear to participate in local microvascular responses to mild stresses such as reduction of perfusion pressure or moderate increases in O 2 demand.By contrast, theophylline did shorten the duration of reactive hyperemia in the intestine of fasted dogs by 50%, suggesting that adenosine accumulates to vasoactive levels in the fasted state if the stress is severe.In the fed state, theophylline reduced the high degree of flow autoregulation usually observed in the hyperfunctional state.In addition, dipyridimole caused a 20% increase in intestinal blood flow of fed animals.Thus, the contribution of adenosine to local vasoregulation in intestine appears to increase as O 2 demand rises.
The value of plants used in traditional medicine for drug discovery.
Authors: D S Fabricant, N R Farnsworth
Journal: Environmental Health Perspectives (2001)

In this review we describe and discuss several approaches to selecting higher plants as candidates for drug development with the greatest possibility of success. We emphasize the role of information derived from various systems of traditional medicine (ethnomedicine) and its utility for drug discovery purposes. We have identified 122 compounds of defined structure, obtained from only 94 species of plants, that are used globally as drugs and demonstrate that 80% of these have had an ethnomedical use identical or related to the current use of the active elements of the plant. We identify and discuss advantages and disadvantages of using plants as starting points for drug development, specifically those used in traditional medicine.
Effect of Olanzapine on Body Composition and Energy Expenditure in Adults With First-Episode Psychosis
Authors: Karen A. Graham, Diana O. Perkins, Lloyd J. Edwards, Robert C. Barrier, Jeffrey A. Lieberman, Joyce B. Harp
Journal: American Journal of Psychiatry (2004)

Weight gain is a commonly observed adverse effect of atypical antipsychotic medications, but associated changes in energy balance and body composition are not well defined. The authors report here the effect of olanzapine on body weight, body composition, resting energy expenditure, and substrate oxidation as well as leptin, insulin, glucose, and lipid levels in a group of outpatient volunteers with first-episode psychosis.Nine adults (six men and three women) experiencing their first psychotic episode who had no previous history of antipsychotic drug therapy began a regimen of olanzapine and were studied within 7 weeks and approximately 12 weeks after olanzapine initiation.After approximately 12 weeks of olanzapine therapy, the median increase in body weight was 4.7 kg, a significant increase of 7.3% from first observation. Body fat, measured by dual-energy x-ray absorptiometry, increased significantly, with a propensity for central fat deposition. Lean body mass and bone mineral content did not change. Resting energy expenditure, measured by indirect calorimetry, did not change. Respiratory quotient significantly increased 0.12 with olanzapine and was greatest in those who gained >5% of their initial weight. Fasting insulin, C-peptide, and triglyceride levels significantly increased, but there were no changes in glucose levels; total, high density lipoprotein, or low density lipoprotein cholesterol levels; or leptin levels.Olanzapine appears to have induced an increase in central body fat deposition, insulin, and triglyceride levels, suggesting the possible development of insulin resistance. The decrease in fat oxidation may be secondary or predispose patients to olanzapine-induced weight gain.
Cellular origin and procoagulant properties of microparticles in meningococcal sepsis
Authors: Rienk Nieuwland, René J. Berckmans, Sarah McGregor, Anita N. Böing, Fred P. H. Th. M. Romijn, Rudi G. J. Westendorp, C. Erik Hack, Augueste Sturk
Journal: Blood (2000)
Disorders of the Respiratory System
Authors: Reginald E. Greene
Journal: JAMA (1981)

This is a short book that has been designed primarily for medical students as an introduction to respiratory disorders. It is heavily weighted toward physiological considerations, to which almost one half of the text is devoted. The physiological topics are sometimes presented in an individualistic and imaginative manner, but often in more detail and complexity than is suitable for medical students (or medical practitioners). The authors indicate that some sections may be of little interest to the individual reader and too sophisticated and complex to be grasped on first reading; this is true. The writing style makes the reading somewhat tedious. The nuances produced by transatlantic differences in language play no role in this. However, the style seems to be more appropriate as verbal lecture material than as written word. The major limitation of the book is its application to clinical use. Little space is left to the clinical entities,
Jaundice in a chronic hepatitis B carrier
Authors: R Noun, S Zeidan, C Ghorra, S Slaba, L Menassa-Moussa, R Sayegh
Journal: Gut (2007)

Figure 1 Cholangiogram through the ERCP catheter inserted into the common bile duct up to the junction with the cystic duct.There is aneurysmal dilation of the main hepatic duct containing a filling defect with dilated right intrahepatic ducts.The left intrahepatic duct is not visualised.Nodular regenerative hyperplasia and azathioprine 1409 www.gutjnl.com
A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision
Authors: Claudia Benz, Conrad C. Bleul
Journal: The Journal of Experimental Medicine (2005)

Hematopoietic precursors continuously colonize the thymus where they give rise mainly to T cells, but also to B and dendritic cells. The lineage relationship between these three cell types is unclear, and it remains to be determined if precursors in the thymus are multipotent, oligopotent, or lineage restricted. Resolution of this question necessitates the determination of the clonal differentiation potential of the most immature precursors in the thymus. Using a CC chemokine receptor 9–enhanced green fluorescent protein knock-in allele like a surface marker of unknown function, we identify a multipotent precursor present in bone marrow, blood, and thymus. Single cells of this precursor give rise to T, B, and dendritic cells. A more differentiated stage of this multipotent precursor in the thymus has lost the capacity to generate B but not T, dendritic, and myeloid cells. Thus, the newly identified precursor maps to the branching point of the T versus B lineage decision in the hematopoietic lineage hierarchy.
Effects of chronic cigarette smoke exposure on lung inflammation in ovalbumin-sensitized mice
Authors: Thayse Regina Brüggemann, Paula Fernandes, Jessica Marques Saez Oliveira, Beatriz Mangueira Saraiva-Romanholo, Milton Arruda Martins, Fernanda Magalhaes Arantes-Costa
Journal: European Respiratory Journal (2014)

Introduction: Several studies have identified smoking as a risk factor for development of asthma, but others have failed to find such an association. Objective: To compare the effects of long cigarette smoke exposure once or twice a day in a model of chronic allergic pulmonary inflammation. Methods: Balb/c mice were sensitized with ovalbumin (OVA) and alum and challenged with an aerosol of OVA. The cigarette smoke groups were exposed to cigarette smoke once or twice a day for thirty consecutive days. Control groups (SAL) received alum only. Twenty-four hours after the last challenge, we evaluated the lung responsiveness, lung inflammation and the production of cytokines and OVA-specific antibodies (IgG1, IgG2a and IgE). Results: OVA-sensitized mice showed increased responsiveness, lung eosinophilia and elevated production of cytokines (IL-4, -5, -10, TSLP) in lung as well as great production IgG1, IgG2a and IgE anti-OVA. The co-exposure of sensitized mice to chronic cigarette smoke once a day decreased the numbers of eosinophils and neutrophils in airways and increased IL-10, IL-13 and TSLP. While twice a day of co-exposure to cigarette smoke decreased IgE production and eosinophil influx in airway. However, these mice showed an increase in the production of IL-10. Comparing both protocols of co-exposition, OVA group co-exposed twice a day to cigarette smoke showed a decreased of IL-13, TSLP, IL-10 when compared to OVA group co-exposed only once a day. Conclusion: Co-exposition of chronic cigarette smoke once and twice a day regulates lung inflammation by increasing regulatory cytokine IL-10 while twice a day also decreased IgE level.
British Association of Dermatologists’ guidelines for the safe and effective prescribing of azathioprine 2011
Authors: S.J. Meggitt, A.V. Anstey, M.F. Mohd Mustapa, N.J. Reynolds, S. Wakelin, M.J. Tidman, L.C. Fuller, J. McLelland, J. Lear, J. Hughes, A.J. McDonagh, S. Punjabi, N. Morar, D.A. Buckley, I. Nasr, P. Maycock, S. Amin, S.E. Hulley, S.E. Haveron
Journal: British Journal of Dermatology (2011)

Department of Dermatology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, U.K. *Department of Dermatology, Royal Gwent Hospital, Cardiff Road, Newport, Gwent NP20 2UB, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, U.K. §Department of Dermatology, St Mary’s Hospital, Imperial College Healthcare Trust, Praed Street, London W2 1NY, U.K.
Evidence for complex system integration and dynamic neural regulation of skeletal muscle recruitment during exercise in humans
Authors: A St Clair Gibson, T D Noakes
Journal: British Journal of Sports Medicine (2004)

A model is proposed in which the development of physical exhaustion is a relative rather than an absolute event and the sensation of fatigue is the sensory representation of the underlying neural integrative processes. Furthermore, activity is controlled as part of a pacing strategy involving active neural calculations in a “governor” region of the brain, which integrates internal sensory signals and information from the environment to produce a homoeostatically acceptable exercise intensity. The end point of the exercise bout is the controlling variable. This is an example of a complex, non-linear, dynamic system in which physiological systems interact to regulate activity before, during, and after the exercise bout.
Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma Suspect Eyes
Authors: Atsuya Miki, Felipe A. Medeiros, Robert N. Weinreb, Sonia Jain, Feng He, Lucie Sharpsten, Naira Khachatryan, Na'ama Hammel, Jeffrey M. Liebmann, Christopher A. Girkin, Pamela A. Sample, Linda M. Zangwill
Journal: Ophthalmology (2014)
T-Lymphokine–Activated Killer Cell–Originated Protein Kinase Functions as a Positive Regulator of c-Jun-NH2-Kinase 1 Signaling and H-Ras–Induced Cell Transformation
Authors: Sang-Muk Oh, Feng Zhu, Yong-Yeon Cho, Ki Won Lee, Bong Seok Kang, Hong-Gyum Kim, Tatyana Zykova, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2007)

Abstract T-lymphokine–activated killer cell–originated protein kinase (TOPK) is overexpressed in highly proliferating tumors such as leukemias and myelomas, and seems to play a key role in tumorigenesis or metastasis. However, the precise role and regulatory mechanism explaining the effects of TOPK on tumor cells still remain elusive. Here, we reported that TOPK regulates UVB-induced c-Jun-NH2-kinase 1 (JNK1) activity, and is essential for H-Ras–induced activator protein-1 activity and cell transformation. We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo. Moreover, UVB-induced JNK1 activity was greatly augmented in mouse epidermal JB6 Cl41 cells that stably expressed TOPK cDNA. On the other hand, JNK1 activity was markedly attenuated by stable expression of small interfering RNA against TOPK in malignant melanoma RPMI 7951 cells. Interestingly, TOPK interacted with JNK-interacting protein 1 and caused an elevation of JNK-interacting protein 1 scaffolding activity, thereby enhancing JNK1 activity. Furthermore, JNK1 was required for TOPK-mediated activator protein-1 transcriptional activity and transformed foci induced by UVB or H-Ras. Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras. These studies might also provide a novel molecular mechanism for the role of TOPK in UVB-mediated skin carcinogenesis. [Cancer Res 2007;67(11):5186–94]
Genome Reduction by Deletion of Paralogs in the Marine Cyanobacterium Prochlorococcus
Authors: H. Luo, R. Friedman, J. Tang, A. L. Hughes
Journal: Molecular Biology and Evolution (2011)

Several isolates of the marine cyanobacterial genus Prochlorococcus have smaller genome sizes than those of the closely related genus Synechococcus. In order to test whether loss of protein-coding genes has contributed to genome size reduction in Prochlorococcus, we reconstructed events of gene family evolution over a strongly supported phylogeny of 12 Prochlorococcus genomes and 9 Synechococcus genomes. Significantly, more events both of loss of paralogs within gene families and of loss of entire gene families occurred in Prochlorococcus than in Synechococcus. The number of nonancestral gene families in genomes of both genera was positively correlated with the extent of genomic islands (GIs), consistent with the hypothesis that horizontal gene transfer (HGT) is associated with GIs. However, even when only isolates with comparable extents of GIs were compared, significantly more events of gene family loss and of paralog loss were seen in Prochlorococcus than in Synechococcus, implying that HGT is not the primary reason for the genome size difference between the two genera.
Sleep apnoea is a common occurrence in females
Authors: Karl A. Franklin, Carin Sahlin, Hans Stenlund, Eva Lindberg
Journal: European Respiratory Journal (2012)

Obstructive sleep apnoea (OSA) is primarily regarded as a male disorder, presenting with snoring, daytime sleepiness and cardiovascular disease. We aimed to determine the frequency of sleep apnoea among females in the general population. We investigated 400 females from a population-based random sample of 10,000 females aged 20–70 yrs. They answered a questionnaire and performed overnight polysomnography. OSA (apnoea/hypopnoea index (AHI) ≥5) was found in 50% (95% CI 45–55%) of females aged 20–70 yrs. Sleep apnoea was related to age, obesity and hypertension, but not to daytime sleepiness. Severe sleep apnoea (AHI ≥30) was present in 14% (95% CI 8.1–21%) of females aged 55–70 yrs and in 31% (95% CI 12–50%) of obese females with a body mass index of ≥30 kg·m −2 aged 55–70 yrs. Sleep apnoea with daytime sleepiness and sleep apnoea with hypertension were observed as two different phenotypes of OSA. OSA occurs in 50% of females aged 20–70 yrs. 20% of females have moderate and 6% severe sleep apnoea. Sleep apnoea in females is related to age, obesity and hypertension, but not to daytime sleepiness. When searching for sleep apnoea in females, females with hypertension or obesity should be investigated.
THE ROLE OF COMPLEMENT AND COMPLEMENT RECEPTORS IN INDUCTION AND REGULATION OF IMMUNITY
Authors: Michael C. Carroll
Journal: Annual Review of Immunology (1998)

▪ Abstract Covalent attachment of activated complement C3 (C3d) to antigen links innate and adaptive immunity by targeting antigen to follicular dendritic cells (FDC) and B cells via specific receptors CD21 and CD35. Recent characterization of knockout mice deficient in complement components C3, C4, or the receptors CD21 and CD35 as well as biochemical studies of the CD21/CD19/Tapa-1 coreceptor on B cells have helped to elucidate the mechanism of complement regulation of both B-1 and B-2 lymphocytes. Interestingly, natural antibody of the adaptive immune system provides a major recognition role in activation of the complement system, which in turn enhances activation of antigen-specific B cells. Enhancement of the primary and secondary immune response to T-dependent antigens is mediated by coligation of the coreceptor and the B cell antigen receptor, which dramatically increases follicular retention and B cell survival within the germinal center. Most recent evidence suggests that complement also regulates elimination of self-reactive B cells, as breeding of mice that are deficient in C4 or CD21/CD35 with the lupus-prone strain of lpr mice demonstrates an exacerbation of disease due to an increase in autoantibodies.