tbuckley/cabot-search huggingface dataset:
Contralateral differences among biomarkers determined by a modified nasal lavage technique after unilateral antigen challenge
Authors: J.‐Å. Wihl, C. R. Baumgarten, G. Petersson
Journal: Allergy (1995)

The concentration of biomarkers from vessels and inflammatory cells in nasal lavage fluid reflects the degree of hyperresponsiveness in patients with allergic rhinitis. The lavage has usually been performed of both nasal cavities together after prewashings and administration of decongestants. To improve the technique, we introduced a modification involving lavage of the nasal cavities separately without any prewashings or decongestants. We challenged 20 rhinitic subjects sensitive to timothy unilaterally with timothy extract. In nasal lavages performed before, immediately after, and 6 h after the challenge, we determined the concentrations of albumin, histamine, bradykinin, TAME (TV‐α‐tosyl‐L‐arginine methyl ester)‐esterase, and leukotriene C 4 (LTC 4 ). In eight subjects, the procedure was repeated 1 and 2 weeks later. After the challenge, albumin, bradykinin, TAME‐esterase, and LTC 4 in the nasal lavage fluid increased on the ipsilateral side but not on the Contralateral side. Histamine did not increase after antigen challenge. After 6 h, the biomarkers were not increased. The concentrations of biomarkers did not differ between sides before the challenge and not between visits. Thus, the modified nasal lavage technique is reliable and improved compared to previous methods because it involves reproducible determinations of different biomarkers, and it is simple and easy to perform.
Reducing ischaemia/reperfusion injury through -opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling
Authors: M.-H. Huang, V. Nguyen, Y. Wu, S. Rastogi, C. Y. Lui, Y. Birnbaum, H.-Q. Wang, D. L. Ware, M. Chauhan, N. Garg, K.-K. Poh, L. Ye, A. R. Omar, H.-C. Tan, B. F. Uretsky, K. Fujise
Journal: Cardiovascular Research (2009)

The purpose of this study was to determine whether intrinsic cardiac adrenergic (ICA) cells release calcitonin gene-related peptide (CGRP), exerting synergistic adrenopeptidergic cardioprotection. In situ hybridization coupled with immunostaining demonstrated that ICA cells exclusively expressed CGRP mRNA and co-expressed CGRP and δ-opioid receptor in human and rat left ventricular (LV) myocardium. Radioimmunoassay detected constitutive CGRP release from ICA cells in human and rat hearts. The δ-opioid agonist [D-Pen25]-enkephalin (DPDPE) increased CGRP release from ICA cells in denervated rat heart. In an ischaemia/reperfusion rat model, pre-ischaemic treatment with DPDPE reduced infarct size (IS) by 51 ± 16% (P < 0.01). Co-infusion of β2-adrenergic receptor (β2-AR) and CGRP receptor (CGRP-R) antagonists increased IS by 62 ± 23% (P < 0.01) compared with saline and abolished DPDPE-initiated IS reduction. Pre-treatment of ICA cell–myocyte co-culture with the β2-AR/CGRP-R antagonists increased myocyte death rate by 24 ± 4% (P < 0.01) and abolished DPDPE-initiated myocyte protection against hypoxia/reoxygenation (re-O2). In the ICA cell-depleted myocyte culture, DPDPE did not confer myocyte protection. Supplementing ICA cell-depleted myocyte culture with β2-AR/CGRP-R agonists reduced hypoxia/re-O2-induced myocyte death by 24 ± 5% (P < 0.01), simulating endogenous neurohormonal effects of ICA cells. Western blot analysis showed that DPDPE markedly increased phosphorylated myocardial Akt levels. This effect was abolished in the presence of β2-AR/CGRP-R blockade. Terminal dUTP nick-end labelling staining analysis of the LV infarct zone demonstrated that DPDPE reduced myocyte apoptosis by 58 ± 19% (P < 0.05), an effect that was eliminated in the presence of β2-AR/CGRP-R blockade. Finally, echocardiography showed that DPDPE increased LV contractility in a manner dependent on β-AR/CGRP-R stimulation. ICA cells constitute a δ-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through β2-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic pathway during ischaemia/reperfusion.
P482Tyrosine phosphorylation is important in Hic-5 subcellular localisation in Src -/- mouse embryonic fibroblasts
Authors: M Pieri, J Ohanian, V Ohanian
Journal: Cardiovascular Research (2014)

Purpose: The actin cytoskeleton is a dynamic structure regulated by actin regulatory proteins, an example of which is Hic-5 (hydrogen peroxide-inducible clone 5). Hic-5 is an adaptor protein regulated by tyrosine phosphorylation, which has been shown to affect cytoskeletal organisation in rat mesenteric small arteries and fibroblasts, but the cellular mechanisms involved are unclear. The aims of this study were to analyse Hic-5 tyrosine phosphorylation and determine its effect on Hic-5 subcellular localisation in Src null mouse embryonic fibroblasts (Src -/- MEFs), which were used as a model system for further work that will be carried out in rat vascular smooth muscle cells. Methods: Src -/- MEFs were transfected with yellow fluorescent protein (YFP)-tagged Hic-5 or Y60F-Hic-5 (a mutant form of Hic-5 in which Tyr-60 has been mutated to phenylalanine) ± v-Src. Following transfections, wild type and mutant Hic-5 were purified by GFP-trap, and tyrosine phosphorylation was analysed by western blotting and mass spectrometry. Localisation of wild type and mutant Hic-5 in the presence and absence of v-Src in Src -/- MEFs was determined by immunofluorescence. Results: There was minimal tyrosine phosphorylation of Y60F-Hic-5-YFP compared to wild type Hic-5-YFP in Src -/- MEFs in the presence of v-Src (p≤0.05, n=3). Tyrosine-60 was identified as a phosphorylated residue using mass spectrometry. Importantly, immunofluorescence experiments have shown wild type Hic-5-YFP being relocalised from the cytoplasm to focal adhesions of these cells in the presence of v-Src, whereas Y60F-Hic-5-YFP remained mostly in the cytoplasm under the same conditions. Conclusion: Hic-5 phosphorylation on Tyr-60 is Src-dependent and is important in determining subcellular localisation of Hic-5 in Src -/- MEFs. Taking into consideration that Hic-5 has been previously shown to be tyrosine-phosphorylated in response to noradrenaline in rat mesenteric small arteries with associated remodelling of the actin cytoskeleton, our results have implications for the importance of Hic-5 tyrosine phosphorylation in focal adhesion signalling in vascular smooth muscle cells.
A phase II study of 5‐day intravenous azacitidine in patients with myelodysplastic syndromes
Authors: Mike G. Martin, Richard A. Walgren, Elizabeth Procknow, Geoffrey L. Uy, Keith Stockerl‐Goldstein, Amanda F. Cashen, Peter Westervelt, Camille N. Abboud, Frederieke Kreisel, Kristan Augustin, John F. DiPersio, Ravi Vij
Journal: American Journal of Hematology (2009)

Abstract The approved 7‐day schedule of subcutaneous azacitidine for myelodysplastic syndrome is associated with injection site reactions and bruising and may be inconvenient because of the need for weekend doses. Although pharmacokinetic data with IV azacitidine suggests equivalence, there are no efficacy data published. Patients with all myelodysplastic syndromes (MDS) FAB subtypes were enrolled and received 75 mg/m 2 /d of azacitidine by 20‐min intravenous infusion for 5 days in every 28 days. Global methylation studies were performed at baseline and prior to Cycle 3. Twenty‐five patients were enrolled and 22 were evaluable. Median age was 69.5 years; 9 (41%) patients had lower‐risk disease (IPSS Low or Int‐1) and 13 (59%) had higher‐risk disease (IPSS Int‐2 or High). Twenty‐seven percent of patients responded (5 CRs and 1 PR). The median time to response was 108 days. The median PFS was 339 days (11.3 months), the median OS was 444 days (14.8 months) and the median duration of response (DOR) was 450 days (15.0 months). Global methylation studies suggest a greater degree of demethylation in responders. This regimen appeared to offer a PR + CR rate and median DOR somewhat similar to what has been reported with the 7‐day subcutaneous regimen; however, OS was shorter. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.
Human cytomegalovirus elicits fetal γδ T cell responses in utero
Authors: David Vermijlen, Margreet Brouwer, Catherine Donner, Corinne Liesnard, Marie Tackoen, Michel Van Rysselberge, Nicolas Twité, Michel Goldman, Arnaud Marchant, Fabienne Willems
Journal: The Journal of Experimental Medicine (2010)

The fetus and infant are highly susceptible to viral infections. Several viruses, including human cytomegalovirus (CMV), cause more severe disease in early life compared with later life. It is generally accepted that this is a result of the immaturity of the immune system. gammadelta T cells are unconventional T cells that can react rapidly upon activation and show major histocompatibility complex-unrestricted activity. We show that upon CMV infection in utero, fetal gammadelta T cells expand and become differentiated. The expansion was restricted to Vgamma9-negative gammadelta T cells, irrespective of their Vdelta chain expression. Differentiated gammadelta T cells expressed high levels of IFN-gamma, transcription factors T-bet and eomes, natural killer receptors, and cytotoxic mediators. CMV infection induced a striking enrichment of a public Vgamma8Vdelta1-TCR, containing the germline-encoded complementary-determining-region-3 (CDR3) delta1-CALGELGDDKLIF/CDR3gamma8-CATWDTTGWFKIF. Public Vgamma8Vdelta1-TCR-expressing cell clones produced IFN-gamma upon coincubation with CMV-infected target cells in a TCR/CD3-dependent manner and showed antiviral activity. Differentiated gammadelta T cells and public Vgamma8Vdelta1-TCR were detected as early as after 21 wk of gestation. Our results indicate that functional fetal gammadelta T cell responses can be generated during development in utero and suggest that this T cell subset could participate in antiviral defense in early life.
AMYL NITRITE MAY ALTER T LYMPHOCYTES IN HOMOSEXUAL MEN
Authors: JamesJ. Goedert, WilliamC. Wallen, DeanL. Mann, DouglasM. Strong, CarolynY. Neuland, MarkH. Greene, Christine Murray, JosephF. Fraumeni, WilliamA. Blattner
Journal: The Lancet (1982)
Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy.
Authors: P J Counihan, M P Frenneaux, D J Webb, W J McKenna
Journal: Circulation (1991)

Exercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads.To enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n = 6) or an abrupt decrease in systolic blood pressure (20-60 mm Hg) from the peak value (n = 32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p less than 0.001).The relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy.
Quality of care and mortality are worse in chronic kidney disease patients living in remote areas
Authors: Diana Rucker, Brenda R. Hemmelgarn, Meng Lin, Braden J. Manns, Scott W. Klarenbach, Bharati Ayyalasomayajula, Matthew T. James, Aminu Bello, Deb Gordon, Kailash K. Jindal, Marcello Tonelli
Journal: Kidney International (2010)
OP19 * SERUM SPECTROSCOPY OF BRIAN TUMOURS: A RAPID AND ACCURATE DIAGNOSTIC TOOL
Authors: J. R. Hands, K. M. Ashton, A. Brodbelt, C. Davis, T. P. Dawson, M. D. Jenkinson, R. W. Lea, C. Walker, G. Clemens, M. J. Baker
Journal: Neuro-Oncology (2014)

INTRODUCTION: The ability to diagnose brain tumours rapidly from serum would allow for rapid testing and decreased time to results providing a responsive diagnostic environment. ATR-FTIR (Attenuated Total Reflection - Fourier Transform Infrared Spectroscopy) generates a serum sample - fingerprint - since biomolecules exhibit different responses to different wavelengths of light. We have previously used ATR-FTIR to discriminate high grade brain cancer, low-grade brain cancer and normal serum to sensitivities and specificities on average of 93.75 and 96.53 % respectively. This paper reports the analysis of 429 patients. METHOD: 1 µl of serum was analysed in triplicate from 429 patients via ATR-FTIR. This dataset was analysed using pattern recognition algorithms for the following models 1) Cancer (n = 314) vs Non-cancer (n = 122), 2) Metastatic Brain Cancer (n = 192) vs Brain Cancer (n = 124) vs Non-Cancer (n = 122), 3) Organ of tumour origin, 4)High grade glioma (n = 52) vs low grade glioma (n = 24) vs meningioma (n = 47) 5) Subtype of Brain Cancer. RESULTS: ATR-FTIR spectroscopy was able to discriminate different groupings with high accuracy. The predicted range for each diagnostic layer was between 78.26 - 100.00 % sensitivity and specificity respectively. Interrogation of the loadings plots showed differences in Amide and lipid content of the serum. CONCLUSION: A robust reproducible method has been developed for the diagnosis of small volumes of serum. In addition multiple layers of diagnostic information can be provided from the same spectral dataset. ATR-FTIR has shown to be an excellent clinical tool for rapid diagnosis enabling a dynamic and responsive clinical environment. Future work will investigate spectroscopic changes during treatment.
Thromboembolism and mitral valve prolapse.
Authors: B Rubin
Journal: Circulation (1980)

EDITOR product of 2.6, and 81 of 83 patients by an LV mass index of 110 g/m2.This small difference is not statistically significant.All three ways of looking at their data show clearly that, contrary to the authors' conclusions, the h * R product is not a better predic- tor than LV mass of the occurrence of LVH on the ECG.Certainly, the factors responsible for the inscription of LVH on an ECG are complex, and further studies willbe necessary to delineate the potential contribution, if any, of the solid-angle theory to their un- derstanding.
Hemodynamic and clinical tachyphylaxis to prazosin-mediated afterload reduction in severe chronic congestive heart failure.
Authors: M Packer, J Meller, R Gorlin, M V Herman
Journal: Circulation (1979)

Sequential doses of 5 mg of oral prazosin hydrochloride were administered to eight patients with severe chronic congestive heart failure refractory to conventional therapy.Initial doses of the drug produced marked increases in cardiac index (+0.87I/min/m2) associated with substantial decreases in left ventricular filling pressure (-10.7 mm Hg), total systemic vascular resistance (2118 to 1154 dyn-sec-cm-5), and heart rate (89 to 76 beats/min).However, serial administration of the same dose at 12-24-hour intervals was accompanied by the rapid development of tachyphylaxis, such that the magnitude of hemodynamic effects with second doses was less than 50% of the magnitude of effects seen with first doses (p < 0.01), and third doses produced no overall significant hemodynamic responses.Diuresis with furosemide failed to restore the circulatory effects of prazosin, and the use of 10-mg doses improved cardiovascular performance to only a small extent.Only two of eight patients had sustained hemodynamic responses large enough to justify chronic oral ambulatory therapy.Administration of oral hydralazine caused hemodynamic improvement superior to even high-dose prazosin therapy (p < 0.02).THE BENEFICIAL HEMODYNAMIC and clinical effects of peripheral vasodilators in patients with severe heart failure are well established,' 5 but the search continues for a well-tolerated oral agent which is chronically effective for the therapeutic reduction of preload and afterload.Although nitrates are orally active, their duration of action is short, and they have minimal effects on cardiac output.6' 7The use of hydralazine results in marked increases in cardiac output (CO), significant reductions in left ventricular fill- ing pressure (LVFP),4 and amelioration of clinical symptoms,3 but is often accompanied by poorly tolerated adverse effects.8'9 Therefore, the recent demonstration of balanced preload and afterload reduction with prazosin'0' 1' has stimulated interest in its use in chronic ambulatory therapy.Prazosin exerts a peripheral vasodilator action by producing a-sympathetic blockade;21-6 some have proposed an additional direct smooth muscle relaxant effect mediated by increased intracellular levels of cyclic AMP due to drug-induced phosphodiesterase inhibition.'7Despite extensive experience in antihypertensive therapy, previous work with prazosin in heart failure has involved hemodynamic monitoring of only initial doses of the drug;10 as a result, the ability of maintenance therapy to produce sustained reduc- tion of preload and afterload has not been
Arteriovenous-shunt-mediated increase in venous return causes apparent right coronary arterial autoregulation
Authors: J. F Gaugl, A. G Williams, H F. Downey
Journal: Cardiovascular Research (1993)

Journal Article Arteriovenous-shunt-mediated increase in venous return causes apparent right coronary arterial autoregulation Get access John F Gaugl, John F Gaugl Department of Physiology, Texas College of Osteopathic Medicine, 3500 Camp Bowie Blvd, Fort Worth, Texas 76107, USA: J F Gaugl, A G Williams, H F Downey. Correspondence to Dr Gaugl. Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur G Williams, Jr, Arthur G Williams, Jr Department of Physiology, Texas College of Osteopathic Medicine, 3500 Camp Bowie Blvd, Fort Worth, Texas 76107, USA: J F Gaugl, A G Williams, H F Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar H Fred Downey H Fred Downey Department of Physiology, Texas College of Osteopathic Medicine, 3500 Camp Bowie Blvd, Fort Worth, Texas 76107, USA: J F Gaugl, A G Williams, H F Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 5, May 1993, Pages 748–752, https://doi.org/10.1093/cvr/27.5.748 Published: 01 May 1993 Article history Received: 29 June 1992 Accepted: 18 September 1992 Published: 01 May 1993
NICE accused of restricting treatment for eye patients
Authors: L. Eaton
Journal: BMJ (2002)

A row has broken out in the United Kingdom over the latest proposals from the government's National Institute for Clinical Evidence (NICE) to restrict NHS funded treatments to certain groups of patients.

The Royal National Institute of the Blind (RNIB) claims that NICE's latest recommendations on treatment for age related macular degeneration (the commonest cause of central vision loss in the Western world) would condemn several thousand people to have to choose between either paying privately for treatment or losing their sight.

NICE issued its appraisal consultation document on Monday and consultation is due …
OX40 signaling favors the induction of TH9 cells and airway inflammation
Authors: Xiang Xiao, Savithri Balasubramanian, Wentao Liu, Xiufeng Chu, Haibin Wang, Elizabeth J Taparowsky, Yang-Xin Fu, Yongwon Choi, Matthew C Walsh, Xian Chang Li
Journal: Nature Immunology (2012)
EXPOSURE TO THE DIABETIC INTRAUTERINE ENVIRONMENT IS ASSOCIATED WITH VENTRICULAR HYPERTROPHY IN EARLY &amp;amp; LATE INFANCY
Authors: Timothy Colen, Nee Scze Khoo, Paul Brooks, Yuka Yamamoto, Shelby Kutty, Venu Jain, Tiina Ojala, Najlaa AL Rajaa, Winnie Savard, Michael Stickland, Sandra Davidge, Lisa Hornberger
Journal: Journal of the American College of Cardiology (2012)
Fallout, radiation doses near Dounreay, and childhood leukaemia.
Authors: S C Darby, R Doll
Journal: BMJ (1987)

Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by an underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by an underestimate of the relative biological efficiency of high as compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to the dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other possible explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease, and exposure to some other, unidentified environmental agent. These findings weigh heavily against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated.