tbuckley/cabot-search huggingface dataset:
Platelet-derived growth factor is a potent biologic response modifier of T cells.
Authors: R A Daynes, T Dowell, B A Araneo
Journal: The Journal of Experimental Medicine (1991)

Freshly isolated lymph node (LN) cells cultured in serum-containing medium were restricted to produce primarily interleukin 2 (IL-2) subsequent to T cell activation. Only minimal amounts of IL-4, IL-5, or interferon gamma (IFN-gamma) were produced under these conditions. Similar populations of LN cells cultured in serum-free medium were able to produce a variety of lymphokines after T cell activation, with the relative quantities of each species being dependent upon the lymphoid organ source of the lymphocytes. A similar relationship in the patterns of lymphokines produced by activated T cell hybridomas maintained under serum-free conditions was also observed, whereas activation in serum-supplemented media resulted in a predominant restriction to the secretion of IL-2. Additional studies determined that the entity in serum responsible for restricting T cell function in vitro was platelet-derived growth factor (PDGF). The PDGF-BB isoform was established to be the most active in the regulation of T cell function, enhancing IL-2 while depressing the production of IL-4, IL-5, and IFN-gamma at concentrations below 1 ng/ml. PDGF-AB was also found to be quite active, however, this isoform of PDGF was incapable of influencing IFN-gamma production at the concentrations tested. PDGF-AA was very weakly active. It therefore appears that PDGF, acting primarily through a beta receptor subunit (either alpha/beta- or beta/beta-type receptors) is able to influence profoundly the behavior of T cells, with some of its modulatory effects exhibiting isoform specificity. This is reflected by an enhancement in the production of IL-2, while simultaneously depressing the secretion of IL-4, IL-5, and IFN-gamma (PDGF-BB only) after T cell activation. Kinetic studies, where cell supernatants were analyzed both 24 and 48 h after T cell activation, suggested that "desensitization" to PDGF influences can occur naturally in vitro. Those species of lymphokines that were inhibited by PDGF over the first 24 h after activation could be produced at normal levels over the subsequent 24-h period. Finally, lymphokines maintained in the presence of PDGF-BB for greater than 24 h before their activation lost sensitivity to this growth factor. These cells regained responsiveness to PDGF after an additional incubation period in PDGF-free medium. Collectively, our data imply that the pattern of T cell lymphokines produced, plus the kinetics of their production after activation, are being controlled by the potent serum growth factor PDGF.(ABSTRACT TRUNCATED AT 400 WORDS)
Linear Dimensions of the Upper Airway Structure during Development
Authors: RAANAN ARENS, JOSEPH M. McDONOUGH, AARON M. CORBIN, MARY ELIZABETH HERNANDEZ, GREG MAISLIN, RICHARD J. SCHWAB, ALLAN I. PACK
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The upper airway undergoes progressive changes during childhood. Using magnetic resonance imaging (MRI), we studied the growth relationships of the tissues surrounding the upper airway (bone and soft tissues) in 92 normal children (47% males; range, 1 to 11 yr) who underwent brain MRI. None had symptoms of sleep-disordered breathing or conditions that impacted on their upper airway. MRI was performed under sedation. Sequential T1-weighted spin echo sagittal and axial sections were obtained and analyzed on a computer. We measured lower face skeletal growth along the midsagittal and axial oropharyngeal planes. In the midsagittal plane the mental spine–clivus distance related linearly to age (r = 0.86, p < 0.001). Along this axis, the dimensions of tongue, soft palate, nasopharyngeal airway, and adenoid increased with age and maintained constant proportion to the mental spine–clivus distance. Similarly, a linear relationship was noted for mandibular growth measured along the intermandibular line on the axial plane and age (r = 0.78, p < 0.001). In addition, the intertonsillar, tonsils, parapharyngeal fat pads, and pterygoids widths maintained constant proportion to intermandibular width with age. We conclude that the lower face skeleton grows linearly along the sagittal and axial planes from the first to the eleventh year. Our data indicate that soft tissues, including tonsils and adenoid, surrounding the upper airway grow proportionally to the skeletal structures during the same time period.
Dissecting the role of CB1 receptors on chronic liver diseases
Authors: Ramon Bataller, Bin Gao
Journal: Gut (2012)

Alcoholic liver disease (ALD) is a major cause of liver-related morbidity and mortality worldwide.1 Although the most effective therapy for patients with ALD is alcohol cessation, targeted therapies are needed in patients with progressive disease and active drinking, and for those with life-threatening conditions such as alcoholic hepatitis. The development of such therapies is hampered by poor knowledge of the main disease drivers. During the last two decades, the cellular and molecular mechanisms of the hepatic wound-healing response to repeated exposure to alcohol have been partially delineated. ALD is characterised by steatosis, inflammatory infiltrate mainly composed of polymorphonuclear cells, hepatocellular injury and progressive fibrosis. The cellular and molecular basis includes paracrine stimulation by damaged hepatocytes, the innate immune system, oxidative stress and the resulting activation of non-parenchymal cells. Several inflammatory and fibrogenic mediators are released at the areas of tissue repair and perpetuate inflammation, leading to progressive fibrosis and organ failure. Among these mediators, a growing body of evidence indicates that endogenous cannabinoids have an important role in hepatic wound healing and represent promising druggable targets for therapy.2

The endocannabinoid system is composed of endocannabinoids (anandamide (AEA), 2-arachidonoyl glycerol (2-AG)), cannabinoid receptors (CB) (CB1 and CB2), and the enzymes involved in endocannabinoid biosynthesis and degradation.2 The degradation enzymes include fatty acid amide hydrolase and monoglyceride lipase for degradation of AEA and 2-AG, respectively. CB1 receptors are expressed at high …
Vasoconstrictor role for vasopressin in experimental heart failure in the rabbit.
Authors: L Arnolda, B P McGrath, M Cocks, C I Johnston
Journal: Journal of Clinical Investigation (1986)

Vasopressin's role as a vasoconstrictor in chronic heart failure, was examined in rabbits with adriamycin cardiomyopathic congestive heart failure. Chronic adriamycin treatment resulted in a decrease in cardiac output (829 +/- 38-610 +/- 36 ml/min, P less than 0.005) and blood pressure (83 +/- 2-76 +/- 3 mmHg, P less than 0.01), and an increase in peripheral resistance (8,377 +/- 381-10,170 +/- 657 dyn-s-cm-5, P less than 0.05). Plasma renin activity (4.7 +/- 0.6-10.9 +/- 2.8 ng angiotensin I/ml X h) and norepinephrine (0.7 +/- 0.1-1.3 +/- 0.2 pmol/ml, P less than 0.05) increased while plasma vasopressin levels did not change. Vasopressin infusion, however, produced significantly greater increases in peripheral resistance in animals with heart failure than in controls. Moreover, a specific vasopressin vascular antagonist reduced blood pressure (7 +/- 3%) and peripheral resistance (14 +/- 4%) and increased cardiac output (10 +/- 3%) in animals with heart failure but had no cardiovascular effects in normal rabbits. These results suggest that vascular sensitivity to vasopressin is increased in heart failure, and that it contributes significantly to the increased afterload in heart failure despite normal plasma levels. In this model of severe, chronic heart failure the sympathetic, renin-angiotensin, and vasopressin systems all appear to be activated.
Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth? A systematic review and meta-analysis
Authors: E.M. Kolibianakis, L. Kalogeropoulou, G. Griesinger, E.G. Papanikolaou, J. Papadimas, J. Bontis, B.C. Tarlatzis
Journal: Human Reproduction Update (2007)

The aim of this systematic review and meta-analysis was to assess whether the addition of recombinant luteinizing hormone (LH) increases live birth rate, among patients treated with follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) analogues for in vitro fertilization (IVF). Eligible studies were randomized controlled trials (RCTs) answering the research question that contained sufficient information to allow ascertainment of whether randomization was true and whether equality was present between the groups compared, regarding baseline demographic characteristics, gonadotrophin stimulation protocol, number of embryos transferred and luteal phase support administered. A literature search identified seven RCTs (701 patients) that provided the information of interest, among which five reported agonist and two antagonist cycles. The reported outcome measure, clinical pregnancy, was converted to live birth using published data in one study. No significant difference in the probability of live birth was present with or without rLH addition to FSH (odds ratio [OR]: 0.92, 95% confidence interval (CI): 0.65–1.31; P = 0.65). This finding remained stable in subgroup analyses that ordered the studies by dose of rLH added, the type of analogue used to inhibit premature LH surge, the time rLH was added during the follicular phase, the age of patients analysed, the presence of allocation concealment and by the way the information on live birth was retrieved. In conclusion, the available evidence does not support the hypothesis that the addition of recombinant LH increases the live birth rate in patients treated with FSH and GnRH analogues for IVF.
Role of sequence variations in the human ether-a-go-go-related gene (HERG, KCNH2) in the Brugada syndrome
Authors: A VERKERK, R WILDERS, E SCHULZEBAHR, L BEEKMAN, Z BHUIYAN, J BERTRAND, L ECKARDT, D LIN, M BORGGREFE, G BREITHARDT
Journal: Cardiovascular Research (2005)

Background: Brugada syndrome (BrS) is an inherited electrical disorder associated with a high incidence of sudden death. In a minority of patients, it has been linked to mutations in SCN5A, the gene encoding the pore-forming α-subunit of the cardiac Na+ channel. Other causally related genes still await identification. We evaluated the role of HERG (KCNH2), which encodes the α-subunit of the rapid delayed rectifier K+ channel (IKr), in BrS. Methods and results: In two unrelated SCN5A mutation-negative patients, different amino acid changes in the C-terminal domain of the HERG channel (G873S and N985S) were identified. Voltage-clamp experiments on transfected HEK-293 cells show that these changes increase IKr density and cause a negative shift of voltage-dependent inactivation, resulting in increased rectification. Action potential (AP) clamp experiments reveal increased transient HERG peak currents (Ipeak) during phase-0 and phase-1 of the ventricular AP, particularly at short cycle length. Computer simulations demonstrate that the increased Ipeak enhances the susceptibility to loss of the AP-dome typically in right ventricular subepicardial myocytes, thereby contributing to the BrS phenotype. Conclusion: Our study reveals a modulatory role of IKr in BrS. These findings may provide better understanding of BrS and have implications for diagnosis and therapy.
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of β-oxidation in insulin secretion
Authors: Peter T. Clayton, Simon Eaton, Albert Aynsley-Green, Mark Edginton, Khalid Hussain, Steve Krywawych, Vipan Datta, Helga E.M. Malingré, Ruud Berger, Inge E.T. van den Berg
Journal: Journal of Clinical Investigation (2001)

A female infant of nonconsanguineous Indian parents presented at 4 months with a hypoglycemic convulsion. Further episodes of hypoketotic hypoglycemia were associated with inappropriately elevated plasma insulin concentrations. However, unlike other children with hyperinsulinism, this patient had a persistently elevated blood spot hydroxybutyrylcarnitine concentration when fed, as well as when fasted. Measurement of the activity of L-3-hydroxyacyl-CoA dehydrogenase in cultured skin fibroblasts with acetoacetyl-CoA substrate showed reduced activity. In fibroblast mitochondria, the activity was less than 5% that of controls. Sequencing of the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) genomic DNA from the fibroblasts showed a homozygous mutation (C773T) changing proline to leucine at amino acid 258. Analysis of blood from the parents showed they were heterozygous for this mutation. Western blot studies showed undetectable levels of immunoreactive SCHAD protein in the child’s fibroblasts. Expression studies showed that the P258L enzyme had no catalytic activity. We conclude that C773T is a disease-causing SCHAD mutation. This is the first defect in fatty acid β-oxidation that has been associated with hyperinsulinism and raises interesting questions about the ways in which changes in fatty acid and ketone body metabolism modulate insulin secretion by the β cell. The patient’s hyperinsulinism was easily controlled with diazoxide and chlorothiazide.
Diagnostic imaging of lung cancer
Authors: N. Hollings, P. Shaw
Journal: European Respiratory Journal (2002)

Carcinoma of the bronchus is the most common malignancy in the Western world. It is also the leading cause of cancer-related death accounting for 32% of all cancer deaths in males and 25% in females 1. In the USA it causes more deaths than cancers of the colon, breast and prostate combined 2. Disappointingly, in a recent UK survey of improvements in cancer survival 3, carcinoma of the bronchus showed the smallest percentage reduction in the number of deaths avoided between 1981–1990 (0.2%). This compares badly with breast (11% reduction) and melanoma (32%). The overall 5‐yr survival for lung cancer diagnosed between 1986–1990 was only 5.3% (against 66% for breast and 76% for melanoma). It is on this background that the radiologist remains actively employed in the detection, diagnosis, staging and review of this common malignancy.
The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma
Authors: Siobhan V. Glavey, Salomon Manier, Alessandro Natoni, Antonio Sacco, Michele Moschetta, Michaela R. Reagan, Laura S. Murillo, Ilyas Sahin, Ping Wu, Yuji Mishima, Yu Zhang, Wenjing Zhang, Yong Zhang, Gareth Morgan, Lokesh Joshi, Aldo M. Roccaro, Irene M. Ghobrial, Michael E. O’Dwyer
Journal: Blood (2014)
Lyt-2-/Lyt 3- variants of a cloned cytolytic T cell line lack an antigen receptor functional in cytolysis.
Authors: D P Dialynas, M R Loken, A L Glasebrook, F W Fitch
Journal: The Journal of Experimental Medicine (1981)

To investigate the role of Lyt-2 and Thy-1 in cytolysis, we have generated, by ethyl methanesulfonate mutagenesis and selection, variants of the cloned cytolytic T lymphocyte line L3 that specifically lack either Lyt-2 or Thy-1. An analysis of these variants indicates that neither Lyt-2 nor Lyt-3 is responsible for the lethal hit, but suggests that Lyt-2 and/or Lyt-3 are required for an antigen receptor functional in cytolysis. The data also suggest that the expression of Lyt-3 on the cell surface is not independent of the expression of Lyt-2. Finally the data indicate the Thy-1 plays no role in cytolysis.
Serotypes, genotypes and antimicrobial resistance patterns of human diarrhoeagenic Escherichia coli isolates circulating in southeastern China
Authors: Y. Chen, X. Chen, S. Zheng, F. Yu, H. Kong, Q. Yang, D. Cui, N. Chen, B. Lou, X. Li, L. Tian, X. Yang, G. Xie, Y. Dong, Z. Qin, D. Han, Y. Wang, W. Zhang, Y.-W. Tang, L. Li
Journal: Clinical Microbiology and Infection (2013)
Prevalence of dysfunctional breathing in patients treated for asthma in primary care: cross sectional survey
Authors: M Thomas, R K McKinley, E Freeman, C Foy
Journal: BMJ (2001)

<h3>abstract</h3> <b>Objectives:</b> To estimate the prevalence of dysfunctional breathing in adults with asthma treated in the community. <b>Design:</b> Postal questionnaire survey using Nijmegen questionnaire. <b>Setting:</b> One general practice with 7033 patients. <b>Participants:</b> All adult patients aged 17-65 with diagnosed asthma who were receiving treatment. <b>Main outcome measure:</b> Score23 on Nijmegen questionnaire. <b>Results:</b> 227/307 patients returned completed questionnaires; 219 (71.3%) questionnaires were suitable for analysis. 63 participants scored 23. Those scoring 23 were more likely to be female than male (46/132 (35%) <i>v</i> 17/87 (20%), P=0.016) and were younger (mean (SD) age 44.8 (14.7) <i>v</i> 49.0 (13.8, (P=0.05). Patients at different treatment steps of the British Thoracic Society asthma guidelines were affected equally. <b>Conclusions:</b> About a third of women and a fifth of men had scores suggestive of dysfunctional breathing. Although further studies are needed to confirm the validity of this screening tool and these findings, these prevalences suggest scope for therapeutic intervention and may explain the anecdotal success of the Buteyko method of treating asthma. <h3>What is already known on this topic</h3> Abnormal breathing patterns may cause characteristic symptoms and impair quality of life Effective interventions exist for dysfunctional breathing Dysfunctional breathing has been described in patients attending hospital respiratory clinics <h3>What this study adds</h3> 29% of adults treated for asthma in primary care had symptoms suggestive of dysfunctional breathing Affected patients were more likely to be female and younger, but no differences were found with severity of asthma Some patients with asthma may benefit from breathing therapy
The 2006 and 2011 GOLD classifications and five-years mortality in COPD
Authors: Marianne Aanerud, Per Bakke, Jon Hardie, Tomas Eagan
Journal: European Respiratory Journal (2013)

Background: In 2011, the global initiative of chronic obstructive lung disease (GOLD) published new guidelines for chronic obstructive pulmonary disease (COPD). The severity classification from 2006 took respiratory failure into account, but the 2011 classification is based on spirometry alone. A new risk stratification based on symptoms and exacerbations in addition to spirometry was launched in 2011.  Aim: To compare how the GOLD 2006 and 2011 definitions of severity and the 2011 risk stratification were associated with mortality in COPD.  Methods: A cohort of 419 Norwegian COPD patients aged 40-75 was examined in 2006, assessing spirometry, arterial blood gases, exacerbation history, and dyspnoea. Survival status was assessed in 2011. Cox proportional hazard models adjusted for sex and age were used to analyse the association between mortality, the two GOLD classifications, and the GOLD 2011 risk groups.  Results: Median follow-up time was 5.12 years, during which 64 subjects died. Using the 2006 classification, subjects with stage III did not have significantly increased death risk compared to GOLD stage II. Using the 2011 definition, subjects in stage III had a 94% higher risk of death compared with stage II. Risk groups B-D all had over three fold increased risks of death compared to risk group A, with group C having the highest hazard ratio (confidence interval) of 6.0 (2.0, 17.7).  Conclusion: Respiratory failure in COPD seem to partially explain increased mortality in the 2011 GOLD stage III. Clinical variables added to spirometry in the risk stratification groups from the 2011 guidelines carry prognostic information, but the mortality risk does not increase gradually in risk groups B-D.
Regression of Atherosclerosis Induced by Liver-Directed Gene Transfer of Apolipoprotein A-I in Mice
Authors: Rajendra K. Tangirala, Kazuhisa Tsukamoto, Sam H. Chun, David Usher, Ellen Puré, Daniel J. Rader
Journal: Circulation (1999)

Background —The ability of apolipoprotein (apo)A-I to induce regression of preexisting atherosclerotic lesions has not been determined, and a mouse model of atherosclerosis regression has not yet been reported. Methods and Results —LDL receptor–deficient mice were fed a western-type diet for 5 weeks to induce atherosclerotic lesions. A second-generation recombinant adenovirus encoding human apoA-I or a control adenovirus were injected intravenously in order to express apoA-I in the liver. Three days after injection, total apoA-I levels in mice injected with the apoA-I–expressing adenovirus were 216±16.0 mg/dL, compared with 68.0±3.0 mg/dL in control virus–injected mice ( P &lt;0.001). HDL cholesterol levels in mice injected with the AdhapoA-I vector 7 days after injection were 189±21.0 mg/dL, compared with 123±8.0 mg/dL in control virus-injected mice ( P &lt;0.02). Total and non-HDL cholesterol levels did not differ between the 2 groups. Atherosclerotic lesion area was quantified by en face analysis of the aorta and cross-sectional analysis of the aortic root. Compared with baseline mice, atherosclerosis progressed in mice injected with the control adenovirus. In contrast, in mice expressing apoA-I compared with baseline mice, total en face aortic lesion area was reduced by 70% and aortic root lesion was reduced by 46%. Expression of apoA-I was associated with a significant reduction in the fraction of lesions occupied by macrophages and macrophage-derived foam cells. Conclusions —Liver-directed gene transfer of human apoA-I resulted in significant regression of preexisting atherosclerotic lesions in LDL receptor–deficient mice as assessed by 2 independent methods.
Inhibition of airway remodeling in IL-5–deficient mice
Authors: Jae Youn Cho, Marina Miller, Kwang Je Baek, Ji Won Han, Jyothi Nayar, Sook Young Lee, Kirsti McElwain, Shauna McElwain, Stephanie Friedman, David H. Broide
Journal: Journal of Clinical Investigation (2004)

To determine the role of IL-5 in airway remodeling, IL-5–deficient and WT mice were sensitized to OVA and challenged by repetitive administration of OVA for 3 months. IL-5–deficient mice had significantly less peribronchial fibrosis (total lung collagen content, peribronchial collagens III and V) and significantly less peribronchial smooth muscle (thickness of peribronchial smooth muscle layer, α-smooth muscle actin immunostaining) compared with WT mice challenged with OVA. WT mice had a significant increase in the number of peribronchial cells staining positive for major basic protein and TGF-β. In contrast, IL-5–deficient mice had a significant reduction in the number of peribronchial cells staining positive for major basic protein, which was paralleled by a similar reduction in the number of cells staining positive for TGF-β, suggesting that eosinophils are a significant source of TGF-β in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial αVβ6 integrin expression, as well as significantly higher levels of bioactive lung TGF-β in WT compared with IL-5–deficient mice. Increased airway epithelial expression of αVβ6 integrin may contribute to the increased activation of latent TGF-β. These results suggest an important role for IL-5, eosinophils, αVβ6, and TGF-β in airway remodeling.