tbuckley/cabot-search huggingface dataset:
Acute dose- and time-dependent effects of budesonide on airway blood flow in asthma
Authors: Eliana Mendes, Patricia Rebolledo, Johana Arana, Michael Campos, Adam Wanner
Journal: European Respiratory Journal (2012)

Inhaled corticosteroids (ICS) have been shown to decrease airway blood flow (Qaw) via a non-genomic action on airway vascular smooth muscle contraction. We have previously shown a dose-dependent decrease in Qaw with a single inhalation of 360, 720 and 1440 µg budesonide (BUD) in moderate-to-severe asthmatics where Qaw decreased transiently from 12 to 21% after all doses (p  Objective: Here, we have investigated the effects of repetitive BUD inhalations on Qaw in moderate-to-severe asthma patients on regular ICS use.  Methods: The 18 subjects enrolled were told to abstain from ICS for at least 36 h before the experiment. Inhalation of 720 μg BUD was given 4 times, separated by 30 min. Qaw, FEV1, blood pressure, heart rate and oxygen saturation were measured before each inhalation and 30, 90, 150, 210 and 270 min after the last dose. A soluble, inert gas-uptake method was used to measure Qaw.  Results: Baseline mean Qaw was 61.33 ± 3.15 µL/min (per mL of lung anatomical dead space) and FEV1 2.3 ± 0.3 L. Numerically, mean Qaw progressively decreased after each BUD inhalation. At 30 min after the last dose, mean Qaw was 28% below baseline (p  Conclusions: In moderate-to-severe asthma patients on regular ICS use, repeated inhalations of high BUD dose have a cumulative acute vasoconstrictive effect in the airway suggesting an acute non-genomic action that increases vasomotor tone. This effect could decrease airway obstruction and the vascular clearance of concomitantly inhaled bronchodilators from the airway.
Protoporphyrin IX formation after topical application of methyl aminolaevulinate and BF-200 aminolaevulinic acid declines with age
Authors: C.V. Nissen, P.A. Philipsen, H.C. Wulf
Journal: British Journal of Dermatology (2015)

Journal Article Protoporphyrin IX formation after topical application of methyl aminolaevulinate and BF‐200 aminolaevulinic acid declines with age Get access C.V. Nissen, C.V. Nissen Department of Dermatology Bispebjerg Hospital University of Copenhagen Bispebjerg Bakke 23 DK‐2400 Copenhagen NV Denmark Correspondence Christoffer V. Nissen. E‐mail: christoffer.valdemar.nissen@regionh.dk Search for other works by this author on: Oxford Academic Google Scholar P.A. Philipsen, P.A. Philipsen Department of Dermatology Bispebjerg Hospital University of Copenhagen Bispebjerg Bakke 23 DK‐2400 Copenhagen NV Denmark Search for other works by this author on: Oxford Academic Google Scholar H.C. Wulf H.C. Wulf Department of Dermatology Bispebjerg Hospital University of Copenhagen Bispebjerg Bakke 23 DK‐2400 Copenhagen NV Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 3, 1 September 2015, Pages 760–766, https://doi.org/10.1111/bjd.13923 Published: 01 September 2015
Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2013)

Chinese translation Description: New U.S. Preventive Services Task Force (USPSTF) recommendation statement on vitamin D and calcium supplementation to prevent fractures in adults. Methods: The USPSTF commissioned 2 systematic evidence reviews and a meta-analysis on vitamin D supplementation with or without calcium to assess the effects of supplementation on bone health outcomes in community-dwelling adults, the association of vitamin D and calcium levels with bone health outcomes, and the adverse effects of supplementation. Population: These recommendations apply to noninstitutionalized or community-dwelling asymptomatic adults without a history of fractures. This recommendation does not apply to the treatment of persons with osteoporosis or vitamin D deficiency. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with greater than 400 IU of vitamin D3 and greater than 1000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (I statement) The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D3 and 1000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (D recommendation)
Dual Targeting of Protein Degradation Pathways with the Selective HDAC6 Inhibitor ACY-1215 and Bortezomib Is Synergistic in Lymphoma
Authors: Jennifer E. Amengual, Paul Johannet, Maximilian Lombardo, Kelly Zullo, Daniela Hoehn, Govind Bhagat, Luigi Scotto, Xavier Jirau-Serrano, Dejan Radeski, Jennifer Heinen, Hongfeng Jiang, Serge Cremers, Yuan Zhang, Simon Jones, Owen A. O'Connor
Journal: Clinical Cancer Research (2015)

Pan-class histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform-selective HDAC inhibitors are emerging as potentially more targeted agents. HDAC6 is a class IIb deacetylase that facilitates misfolded protein transport to the aggresome for degradation. We investigated the mechanism and therapeutic impact of the selective HDAC6 inhibitor ACY-1215 alone and in combination with bortezomib in preclinical models of lymphoma.Concentration-effect relationships were defined for ACY-1215 across 16 lymphoma cell lines and for synergy with bortezomib. Mechanism was interrogated by immunoblot and flow cytometry. An in vivo xenograft model of DLBCL was used to confirm in vitro findings. A collection of primary lymphoma samples were surveyed for markers of the unfolded protein response (UPR).Concentration-effect relationships defined maximal cytotoxicity at 48 hours with IC50 values ranging from 0.9 to 4.7 μmol/L. Strong synergy was observed in combination with bortezomib. Treatment with ACY-1215 led to inhibition of the aggresome evidenced by acetylated α-tubulin and accumulated polyubiquitinated proteins and upregulation of the UPR. All pharmacodynamic effects were enhanced with the addition of bortezomib. Findings were validated in vivo where mice treated with the combination demonstrated significant tumor growth delay and prolonged overall survival. Evaluation of a collection of primary lymphoma samples for markers of the UPR revealed increased HDAC6, GRP78, and XBP-1 expression as compared with reactive lymphoid tissue.These data are the first results to demonstrate that dual targeting of protein degradation pathways represents an innovative and rational approach for the treatment of lymphoma.
Systematic review and meta-analysis of ethnic differences in risks of adverse reactions to drugs used in cardiovascular medicine
Authors: Sarah E McDowell, Jamie J Coleman, R E Ferner
Journal: BMJ (2006)

To review the evidence for ethnic differences in susceptibility to adverse drug reactions (ADRs) to cardiovascular drugs.Systematic review and meta-analysis.We searched Medline and Embase to March 2005. Reference lists of identified articles were hand searched for further relevant articles.Studies were eligible for inclusion if they included at least two ethnic groups and one or more ADRs. We excluded case reports and case series.564 studies contained some description of ethnicity and an ADR, and 132 of them related to cardiovascular therapies. Twenty four studies provided data for ADRs for at least two ethnic groups and were therefore eligible for inclusion. In pooled analyses the relative risk of angio-oedema from angiotensin converting enzyme (ACE) inhibitors in black compared with non-black patients was 3.0 (95% confidence interval 2.5 to 3.7); the relative risk of cough from ACE inhibitors was 2.7 (1.6 to 4.5) in East Asian compared with white patients; and the relative risk of intracranial haemorrhage with thrombolytic therapy was 1.5 (1.2 to 1.9) in black compared with non-black patients.Patients from different ethnic groups have different risks for important ADRs to cardiovascular drugs. Ethnic group may therefore be one determinant of harms of a given treatment in the individual patient, either because it acts as a surrogate measure of genetic make up or because cultural factors alter the risk. Data are sparse, and regulators should consider asking for better data before licensing.
Studies of Two Subpopulations of Human Lymphocytes Differing in Responsiveness to Concanavalin A
Authors: David Boldt, Sister Ann Marie Skinner, Stuart Kornfeld
Journal: Journal of Clinical Investigation (1972)

We have identified two populations of human lymphocytes differing in responsiveness to the plant mitogen concanavalin A (Con-A). When peripheral blood lymphocytes are passed through a nylon column a population of lymphocytes highly responsive to Con-A adheres to the fibers while a second population of cells relatively unresponsive to Con-A emerges from the column. The untreated peripheral blood lymphocytes are termed "unfiltered" cells while the lymphocytes which pass through the column are termed "filtered" cells. Under standard assay conditions the Con-A-stimulated DNA synthesis is 6.5-fold greater, and the percentage blast formation is four-to fivefold greater in the unfiltered than in the filtered population. Mixing unfiltered with filtered cells fails to induce responsiveness in the latter indicating that a "helper" cell is not involved. The failure of filtered cells to respond to Con-A is specific for that mitogen since both populations respond nearly equally to erythroagglutinating phytohemagglutinin (E-PHA) and the poke weed mitogen (PWM). Binding studies with Con-A-(131)I demonstrate that the unfiltered population possesses approximately three times as many Con-A receptor sites per cell as the filtered cells, although both cell populations bind the mitogen with the same affinity (apparent association constant [K] of 1.67 x 10(6)m(-1)). The relationship between Con-A binding and lymphocyte activation was determined by measuring the effect on DNA synthesis of incubating the two lymphocyte populations with increasing amounts of Con-A. The concentration of Con-A required for half-maximal stimulation of DNA synthesis was 5-14 times greater for the filtered cells. However in the presence of very high Con-A concentrations the filtered cells achieved a maximal rate of DNA synthesis approaching that of the unfiltered population. These data implicate the decreased number of Con-A receptor sites on the filtered cells in their failure to respond to low concentrations of Con-A. A crucial event in the activation of lymphocytes by plant mitogens may be the binding of a critical number of the mitogen molecules to the cell surface.
Response to Comment on: Cohen et al. Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity. Diabetes Care 2012;35:1420–1428
Authors: David E. Cummings, Ricardo V. Cohen
Journal: Diabetes Care (2013)

We thank Dr. Kral for his thoughtful comments on our article regarding the use of Roux-en-Y gastric bypass surgery (RYGB) to treat type 2 diabetes (T2DM), and we would like to respond and add to his comments (1).

Although the 1991 National Institutes of Health (NIH) guidelines were thoughtfully constructed and have been highly valuable, we agree that they were not originally intended as stringent dictums governing bariatric surgery. The NIH itself posts the following concession atop their related website (http://consensus.nih.gov/1991/1991gisurgeryobesity084html.htm). “This statement is more than 5 years old and is provided solely for historical purposes… . Some of the material is likely to be out of date, and at worst simply wrong.”

Nevertheless, no updated NIH guidelines have since been rendered, and the 1991 recommendations have had enormous impact. American …
Interleukin-17 expression in the urticarial rash of familial cold autoinflammatory syndrome: a case report
Authors: A. Yamauchi, H. Iwata, H. Ohnishi, T. Teramoto, N. Kondo, M. Seishima
Journal: British Journal of Dermatology (2010)

Journal Article Interleukin‐17 expression in the urticarial rash of familial cold autoinflammatory syndrome: a case report Get access A. Yamauchi, A. Yamauchi Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar H. Iwata, H. Iwata Departments of Dermatology Correspondence: Hiroaki Iwata. E‐mail: hiriwata0927@yahoo.co.jp Search for other works by this author on: Oxford Academic Google Scholar H. Ohnishi, H. Ohnishi Pediatrics, Graduate School of Medicine, Gifu University, 1‐1 Yanagido, Gifu City 501‐1194, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Teramoto, T. Teramoto Pediatrics, Graduate School of Medicine, Gifu University, 1‐1 Yanagido, Gifu City 501‐1194, Japan Search for other works by this author on: Oxford Academic Google Scholar N. Kondo, N. Kondo Pediatrics, Graduate School of Medicine, Gifu University, 1‐1 Yanagido, Gifu City 501‐1194, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Seishima M. Seishima Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 6, 1 December 2010, Pages 1351–1353, https://doi.org/10.1111/j.1365-2133.2010.09978.x Published: 01 December 2010
EFFECT OF COLCHICINE AND VINBLASTINE ON THE TOPOGRAPHICAL SEPARATION OF MEMBRANE FUNCTIONS
Authors: Thomas E. Ukena, Richard D. Berlin
Journal: The Journal of Experimental Medicine (1972)

The topographical separation of membrane functions into phagocytic and transport areas, inferred from physiological studies, is not demonstrable in cells treated with colchicine and vinblastine, alkaloids which bind to microtubular proteins.
Tumor Grade Is Associated With Venous Thromboembolism in Patients With Cancer: Results From the Vienna Cancer and Thrombosis Study
Authors: Jonas Ahlbrecht, Boris Dickmann, Cihan Ay, Daniela Dunkler, Johannes Thaler, Manuela Schmidinger, Peter Quehenberger, Andrea Haitel, Christoph Zielinski, Ingrid Pabinger
Journal: Journal of Clinical Oncology (2012)

Purpose Patients with cancer are at risk of venous thromboembolism (VTE). Tumor-related factors could help estimate patients' individual risk for VTE. Currently, only scarce information on the association between tumor grade and VTE is available. We thus evaluated the role of tumor grade and its association with VTE. Patients and Methods The Vienna Cancer and Thrombosis Study is a prospective, observational cohort study including patients with newly diagnosed cancer or progression of disease after remission. Study end point is the occurrence of symptomatic VTE. Results Seven hundred forty-seven patients with solid tumors received follow-up for a median of 526 days. VTE occurred in 52 patients (7.0%). At study inclusion, 468 patients had low-grade tumors (G1 and G2) and 279 had high-grade tumors (G3 and G4). In multivariable Cox regression analysis including tumor grade, tumor histology, tumor sites, stage, sex, and age, patients with high-grade tumors had a significantly higher risk of VTE compared with those with low-grade tumors (hazard ratio, 2.0; 95% CI, 1.1 to 3.5; P = .015). The cumulative probability of developing VTE after 6 months was higher in patients with high-grade tumors than in those with low-grade tumors (8.2% v 4.0%; log-rank test P = .037). Patients with high-grade tumors had higher D-dimer levels (P = .008) and leukocyte counts (P &lt; .001), and lower hemoglobin levels (P = .008). Conclusion The tumor grade may help identify patients with cancer who are at high risk of VTE. The association of tumor grade with recently identified biomarkers indicates a link between tumor differentiation and pathogenesis of cancer-associated VTE.
Neural Mechanisms Underlying 5-HTTLPR-Related Sensitivity to Acute Stress
Authors: Emily M. Drabant, Wiveka Ramel, Michael D. Edge, Luke W. Hyde, Janice R. Kuo, Philippe R. Goldin, Ahmad R. Hariri, James J. Gross
Journal: American Journal of Psychiatry (2012)

Many studies have shown that 5-HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology. However, the specific neural mechanisms through which this gene-by-environment interaction confers risk remain largely unknown, and no study to date has directly examined the modulatory effects of 5-HTTLPR on corticolimbic circuit responses during exposure to acute stress.An acute laboratory stressor was administered to 51 healthy women during blood-oxygen-level-dependent functional magnetic resonance imaging. In this task, participants were threatened with electric shocks of uncertain intensity, which were unpredictably delivered to the wrist after a long anticipatory cue period of unpredictable duration.Relative to women carrying the L allele, those with the SS genotype showed enhanced activation during threat anticipation in a network of regions, including the amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate cortex, and medial prefrontal cortex. Individuals with the SS genotype also displayed enhanced positive coupling between medial prefrontal cortex activation and anxiety experience, whereas enhanced negative coupling between insula activation and perceived success at regulating anxiety was observed in individuals carrying the L allele.These findings suggest that during stress exposure, neural systems that enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat may be engaged preferentially in individuals with the SS genotype. This may be one mechanism underlying the risk for psychopathology conferred by the S allele upon exposure to life stressors.
T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions.
Authors: K W Wucherpfennig, J Newcombe, H Li, C Keddy, M L Cuzner, D A Hafler
Journal: The Journal of Experimental Medicine (1992)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune etiology. A recent study has suggested the presence of a restricted T cell receptor (TCR) V alpha repertoire in MS lesions. The presence of such a restricted TCR repertoire at the site of inflammation would have important consequences for the pathogenesis and the ultimate treatment of MS. To further characterize the TCR V alpha and V beta repertoire in MS plaque tissue, we examined a series of 26 histologically well-characterized central nervous system (CNS) tissue specimens from six MS patients as well as samples from five normal postmortem cases and a case of subacute sclerosing panencephalitis. RNA was extracted from frozen sections and cDNAs were amplified by polymerase chain reaction using primers for TCR V alpha (V alpha 1-18) and V beta (V beta 1-19) gene families. This analysis demonstrated a broad TCR V alpha-V beta repertoire in active lesions, while fewer TCR V genes were detected in chronic plaques and control samples. Even though a large number of TCR V alpha and V beta gene segments were present in the majority of active lesions, there were clear differences in the TCR repertoire between plaques from the same case, suggesting that local events influence the TCR repertoire at the level of T cell recruitment or T cell expansion. Examination of cytokine mRNAs demonstrated that IL-1 mRNA was present in the majority of acute and subacute plaques, while IL-2 and IL-4 mRNA were detected in only a few acute lesions. These data demonstrate that the TCR repertoire in MS plaques is polyclonal. However, autoreactive alpha/beta T cells thought to be critical in the initiation of the inflammatory process probably represent a minor fraction of T cells in active MS plaques and may use a limited number of TCR V gene segments for recognition of the autoantigen.
A mild type of Hb S‐β<sup>+</sup>‐thalassemia [‐92(C→T)] in a sicilian family
Authors: V. Divoky, E. Baysal, G. Schiliro, S. P. Dibenedetto, T. H. J. Huisman
Journal: American Journal of Hematology (1993)

Abstract Hematological data are presented for an adult Sicilian patient with a mild Hb S‐β + ‐thalassemia caused by a C→T mutation at position −92 of the β promoter. This mutation was identified by sequencing of amplified DNA and was confirmed by dot‐blot analysis with specific probes. A comparison of levels of Hb S and Hb A in Hb S‐β‐thalassemia patients with different β‐thalassemia alleles showed great variations; the highest level of Hb A (45%) was recorded in the patient with Hb S‐β + ‐thalassemia [‐92(C→T)] and the lowest (∼13%) in patients with Hb S‐β + ‐thalassemia [IVS‐II‐745 (C→G)]. Clinical severity is directly related to the level of Hb A present. © 1993 Wiley‐Liss, Inc.
Signal Transducer and Activator of Transcription 3 Is Required for Myocardial Capillary Growth, Control of Interstitial Matrix Deposition, and Heart Protection From Ischemic Injury
Authors: Denise Hilfiker-Kleiner, Andres Hilfiker, Martin Fuchs, Karol Kaminski, Arnd Schaefer, Bernhard Schieffer, Anja Hillmer, Andreas Schmiedl, Zhaoping Ding, Edith Podewski, Eva Podewski, Valeria Poli, Michael D. Schneider, Rainer Schulz, Joon-Keun Park, Kai C. Wollert, Helmut Drexler
Journal: Circulation Research (2004)

The transcription factor signal transducer and activator of transcription 3 (STAT3) participates in a wide variety of physiological processes and directs seemingly contradictory responses such as proliferation and apoptosis. To elucidate its role in the heart, we generated mice harboring a cardiomyocyte-restricted knockout of STAT3 using Cre/loxP-mediated recombination. STAT3-deficient mice developed reduced myocardial capillary density and increased interstitial fibrosis within the first 4 postnatal months, followed by dilated cardiomyopathy with impaired cardiac function and premature death. Conditioned medium from STAT3-deficient cardiomyocytes inhibited endothelial cell proliferation and increased fibroblast proliferation, suggesting the presence of paracrine factors attenuating angiogenesis and promoting fibrosis in vitro. STAT3-deficient mice showed enhanced susceptibility to myocardial ischemia/reperfusion injury and infarction with increased cardiac apoptosis, increased infarct sizes, and reduced cardiac function and survival. Our study establishes a novel role for STAT3 in controlling paracrine circuits in the heart essential for postnatal capillary vasculature maintenance, interstitial matrix deposition balance, and protection from ischemic injury and heart failure.