tbuckley/cabot-search huggingface dataset:
Does Nitric Oxide Mediate the Vasodilator Activity of Nitroglycerin?
Authors: Andrei L. Kleschyov, Matthias Oelze, Andreas Daiber, Yale Huang, Hanke Mollnau, Eberhard Schulz, Karsten Sydow, Birgit Fichtlscherer, Alexander Mülsch, Thomas Münzel
Journal: Circulation Research (2003)

Nitroglycerin (glyceryl trinitrate, GTN) relaxes blood vessels primarily via activation of the soluble guanylyl cyclase (sGC)/cGMP/cGMP-dependent protein kinase (cGK-I) pathway. Although the precise mechanism of sGC activation by GTN in the vascular wall is unknown, the mediatory role of nitric oxide (NO) has been postulated. We tested the GTN/NO hypothesis in different types of isolated rat and rabbit blood vessels using two novel approaches: (1) EPR spin trapping using colloid Fe(DETC)2 and (2) analysis of cGK-I-dependent phosphorylation of the vasodilator-stimulated phosphoprotein at Ser239 (P-VASP). For comparison, another organic nitrate, isosorbide dinitrate (ISDN), and endothelium-dependent vasodilator, calcium ionophore A23187, were tested. We found a marked discrepancy between GTN's strong vasoactivity (vasodilation and augmentation of P-VASP) and its poor NO donor properties. In aortas precontracted with phenylephrine, GTN, ISDN, and A23187 induced nearly full relaxations (>80%) and doubling of vascular P-VASP content at concentrations of 100 nmol/L, 100 micromol/L, and 1 micromol/L, respectively. GTN applied in vasorelaxant concentrations (10 to 1000 nmol/L) did not significantly increase the basal vascular NO production, in contrast to ISDN and A23187. The absence of GTN-derived NO was confirmed in rabbit vena cava and renal artery. A significant increase in vascular NO formation was observed only at suprapharmacological GTN concentrations (>10 micromol/L). The concentration dependency of NO formation from GTN was comparable to that of ISDN, although the latter exhibits 100-folds lower vasorelaxant potency. We conclude that GTN activates the sGC/cGMP/cGK-I pathway and induces vasorelaxation without intermediacy of the free radical NO. The full text of this article is available online at http://www.circresaha.org.
Physician Reporting of Adverse Drug Reactions
Authors: H. Denman Scott
Journal: JAMA (1990)

The Food and Drug Administration, Rockville, Md, contracted with the Rhode Island Department of Health, Providence, to conduct a project to increase reporting of suspected adverse drug reactions through physician education. Voluntary reporting, an important part of postmarketing surveillance that signals potential problems with marketed drugs, historically has been underused by physicians. After 2 years, there was a more than 17-fold increase in reports submitted directly from Rhode Island compared with the yearly average before initiation of the project. Increases in the total numbers of reports were paralleled by significant increases in the numbers of reports of severe reactions. Similar increases were not experienced nationally. Physicians in Rhode Island were surveyed before and 2 years after interventions began to determine changes in knowledge and attitudes about reporting of adverse drug reactions. Significant gains in knowledge and positive attitudes toward the reporting system occurred. We conclude that physicians can be stimulated to increase their reporting of suspected reactions, thereby improving the viability of the federal reporting system.
Fragrance allergy increases with age
Authors: W. Uter, A. Schnuch
Journal: British Journal of Dermatology (2004)

Journal Article Fragrance allergy increases with age Get access W. Uter, W. Uter Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen‐Nürnberg, and *Information Network of Departments of Dermatology [http://www.ivdk.org, University of Göttingen, Germany E‐mail: Wolfgang.Uter@rzmail.uni‐erlangen.de Search for other works by this author on: Oxford Academic Google Scholar A. Schnuch A. Schnuch Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen‐Nürnberg, and *Information Network of Departments of Dermatology [http://www.ivdk.org, University of Göttingen, Germany E‐mail: Wolfgang.Uter@rzmail.uni‐erlangen.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 6, 1 June 2004, Pages 1218–1220, https://doi.org/10.1111/j.1365-2133.2004.05968.x Published: 01 June 2004
Clonal BRAF Mutations in Melanocytic Nevi and Initiating Role of BRAF in Melanocytic Neoplasia
Authors: Iwei Yeh, Andreas von Deimling, Boris C. Bastian
Journal: JNCI Journal of the National Cancer Institute (2013)

BRAFV600E mutations are frequent in melanomas originating from intermittently sun-exposed skin and also in common acquired melanocytic nevi, suggesting that BRAF mutation is an early event in melanocytic neoplasia. All neoplastic melanocytes within such a nevus would be expected to carry the BRAF mutation, and thus we evaluated the frequency of cells with BRAFV600E mutations within acquired nevi by droplet digital polymerase chain reaction. In BRAF-mutant nevi the number of BRAF mutant alleles equaled the number of wild-type (WT) alleles in the neoplastic cell population, consistent with a fully clonal heterozygous BRAF mutation. The allelic ratio of BRAFV600E to BRAFWT in the eight VE1-positive nevi, adjusted for degree of stromal contamination, ranged from 0.84 to 1.12 with an average ratio of 1.01. This was confirmed by immunohistochemistry with an antibody specific for BRAFV600E, which uniformly labeled the neoplastic cells without any evidence of heterogeneity. We found BRAFV600E mutations in the melanocytic nevi to be fully clonal, strongly suggesting that BRAF-activating mutations typically are early initiating events in melanocytic neoplasia.
Delay in medical attention to hand eczema: a follow-up study
Authors: M. Hald, T. Agner, J. Blands, J.D. Johansen
Journal: British Journal of Dermatology (2009)

Journal Article Delay in medical attention to hand eczema: a follow‐up study Get access M. Hald, M. Hald National Allergy Research Centre and Marianne Hald. E‐mail: marhal02@geh.regionh.dk Search for other works by this author on: Oxford Academic Google Scholar T. Agner, T. Agner Department of Dermato‐allergology, Gentofte Hospital, University of Copenhagen, Niels Andersens vej 65, 2900 Hellerup, Denmark Search for other works by this author on: Oxford Academic Google Scholar J. Blands, J. Blands National Board of Health, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar J.D. Johansen, J.D. Johansen National Allergy Research Centre and Search for other works by this author on: Oxford Academic Google Scholar on behalf of the Danish Contact Dermatitis Group on behalf of the Danish Contact Dermatitis Group Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 6, 1 December 2009, Pages 1294–1300, https://doi.org/10.1111/j.1365-2133.2009.09402.x Published: 01 December 2009
The kinetics of allergen-induced transcription of messenger RNA for monocyte chemotactic protein-3 and RANTES in the skin of human atopic subjects: relationship to eosinophil, T cell, and macrophage recruitment.
Authors: S Ying, L Taborda-Barata, Q Meng, M Humbert, A B Kay
Journal: The Journal of Experimental Medicine (1995)

The C-C chemokines RANTES and monocyte chemotactic protein-3 (MCP-3) are potent chemoattractants in vitro for eosinophils and other cell types associated with allergic reactions. We tested the hypothesis that the allergen-induced infiltration of eosinophils, T cells, and macrophages in the skin of atopic subjects is accompanied by the appearance of mRNA+ cells for RANTES and MCP-3. Cryostat sections were obtained from skin biopsies from six subjects 6, 24, and 48 h after allergen challenge. Tissue was processed for immunocytochemistry (ICC) and for in situ hybridization using 35S-labeled riboprobes for RANTES and MCP-3. In contrast to diluent controls, allergen provoked a significant increase in mRNA+ cells for MCP-3, which peaked at 6 h and progressively declined at 24 and 48 h. This paralleled the kinetics of total (major basic protein positive [MBP]+) and activated (cleaved form of eosinophil cationic protein [EG2]+) eosinophil infiltration. The allergen-induced expression of cells mRNA+ for RANTES was also clearly demonstrable at 6 h. However, the numbers were maximal at 24 h and declined slightly at the 48-h time point. The number of mRNA+ cells for RANTES paralleled the kinetics of infiltration of CD3+, CD4+, and CD8+ T cells whereas the number of CD68+ macrophages was still increasing at 48 h. These data support the view that MCP-3 is involved in the regulation of the early eosinophil response to specific allergen, whereas RANTES may have more relevance to the later accumulation of T cells and macrophages.
Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics
Authors: F. Mitsunobu, T. Mifune, Y. Hosaki, K. Ashida, H. Tsugeno, M. Okamoto, S. Harada, S. Takata, Y Tanizaki, M Harada
Journal: European Respiratory Journal (2000)

Leukotrienes (LTs) are pro-inflammatory mediators that contribute to the pathophysiological features of asthma. The relationship between the amounts of LTB4 and LTC4 produced by the leukocytes of asthmatic patients on the one hand and immunoglobulin E (IgE)-mediated allergy, asthma exacerbations and bronchial hyperresponsiveness was studied. Leukocytes were obtained from peripheral blood drawn from 29 atopic and 27 nonatopic asthmatics during exacerbations and clinically controlled periods, as well as from 20 control individuals. The leukocytes were stimulated with calcium ionophore A23187 to induce LTB4 and LTC4 production. Allergy was assessed by means of specific serum IgE or by positive skin tests, whereas bronchial hyperresponsiveness was measured by methacholine challenge. The leukocytes of the asthmatics generated significantly more LTB4 (p<0.05) and LTC4 (p<0.01) than those of controls. The leukocytes of patients with atopic asthma generated significantly more LTC4 than those of patients with nonatopic asthma (p<0.01). Significantly more LTC4 was produced by leukocytes obtained during exacerbations, than by those obtained during clinically controlled periods (p<0.01). In addition, there was a significant correlation between LTB4 generation by leukocytes and the degree of bronchial hyperresponsiveness to methacholine (r=-0.792, p<0.0001). These results suggest that leukotriene C4 production by leukocytes is associated with immunoglobulin E-mediated allergy and asthma exacerbations, and further that generation of leukotriene B4 is closely related to bronchial hyperresponsiveness in patients with asthma.
Diffusible component from the spore surface of the fungus Aspergillus fumigatus which inhibits the macrophage oxidative burst is distinct from gliotoxin and other hyphal toxins
Authors: C. G. Mitchell, J. Slight, K. Donaldson
Journal: Thorax (1997)

The fungus Aspergillus fumigatus, whose spores are present ubiquitously in the air, causes a range of diseases in the human lung. A small molecular weight (< 10 kD) heat stable toxin released from the spores of clinical and environmental isolates of A fumigatus within minutes of deposition in aqueous solution has previously been described. A key effect of the toxin was to inhibit the oxidative burst of macrophages as measured by superoxide anion release. It was hypothesised that the toxin was one of the commonly found A fumigatus hyphal toxins such as gliotoxin. This inhibitor may be an important factor which allows the fungus to colonise the lung.The spore derived inhibitor was shown to inhibit the respiratory burst of rat alveolar macrophages, as measured by the generation of superoxide anion. Samples of the spore diffusate were subject to reversed phase high performance liquid chromatography (HPLC), thin layer chromatography (TLC), high performance thin layer chromatography (HPTLC), or organic extraction followed by TLC or HPLC to identify the presence of gliotoxin, fumagillin, helvolic acid, fumigaclavine-C, and aurasperone-C. Commercially obtained preparations of the toxins gliotoxin, fumagillin and helvolic acid and extracts enriched for fumigaclavine-C and aurasperone-C were used as internal and external standards and in the respiratory burst measurements.Gliotoxin, fumagillin, helvolic acid, fumigaclavine-C, and aurasperone-C were not detected in spore derived diffusate using PHLC or TLC. Using extraction procedures with solvents known to extract gliotoxin from A fumigatus culture supernatants, no gliotoxin was detected in the spore derived diffusate. Commercial gliotoxin, fumagillin, and helvolic acid or extracts enriched for fumigaclavine-C and aurasperone-C did not inhibit the oxidative burst of macrophages.The hypothesis that the spore derived toxin is one of the toxins derived from hyphae such as gliotoxin, helvolic acid, fumagillin, fumigaclavine-C, or aurasperone-C is not proved. The spore toxin may exert its effect through its ability to diffuse rapidly into the lung lining fluid, diminish the macrophage oxidative burst, and play a part in allowing A fumigatus to persist in the lung and manifest its well known pathogenic effects.
Mutations in Apc and p53 Synergize to Promote Mammary Neoplasia
Authors: Valérie Méniel, Trevor Hay, Anthony Douglas-Jones, Owen J. Sansom, Alan R. Clarke
Journal: Cancer Research (2005)

Mutations of Apc and p53 have both been implicated in human and murine mammary neoplasia. To investigate potential interactions between Apc and p53, we conditionally inactivated Apc in both the presence and the absence of functional p53. Apc deficiency on its own leads to the development of metaplasia but not neoplasia. We show here that these areas of metaplasia are characterized by elevated levels of both p53 and p21. In the additional absence of p53,there is rapid progression to neoplasia, with 44.4% of lymphoma-free mice developing a mammary tumor with earliest observed onset at pregnancy. To investigate the mechanism by which p53 deficiency accelerates neoplasia, we used the Rosa26R reporter strain as a marker of Cre-mediated recombination and show a role for p53 in the loss of Apc-deficient cells. This role seems limited to pregnancy and subsequent time points. We therefore show clear synergy between these two mutations in mammary gland neoplasia and present data to suggest that at least one mechanism for this acceleration is the p53-dependent loss of Apc-deficient cells.
Dietary Intake of Antioxidants and Risk of Age-Related Macular Degeneration
Authors: Redmer van Leeuwen
Journal: JAMA (2005)

ContextAge-related macular degeneration (AMD) is the most prevalent cause of irreversible blindness in developed countries. Recently, high-dose supplementation with beta carotene, vitamins C and E, and zinc was shown to slow the progression of AMD.ObjectiveTo investigate whether regular dietary intake of antioxidants is associated with a lower risk of incident AMD.DesignDietary intake was assessed at baseline in the Rotterdam Study (1990-1993) using a semiquantitative food frequency questionnaire. Incident AMD until final follow-up in 2004 was determined by grading fundus color transparencies in a masked way according to the International Classification and Grading System.SettingPopulation-based cohort of all inhabitants aged 55 years or older in a middle-class suburb of Rotterdam, the Netherlands.ParticipantsOf 5836 persons at risk of AMD at baseline, 4765 had reliable dietary data and 4170 participated in the follow-up.Main Outcome MeasureIncident AMD, defined as soft distinct drusen with pigment alterations, indistinct or reticular drusen, geographic atrophy, or choroidal neovascularization.ResultsIncident AMD occurred in 560 participants after a mean follow-up of 8.0 years (range, 0.3-13.9 years). Dietary intake of both vitamin E and zinc was inversely associated with incident AMD. The hazard ratio (HR) per standard deviation increase of intake for vitamin E was 0.92 (95% confidence interval [CI], 0.84-1.00) and for zinc was 0.91 (95% CI, 0.83-0.98). An above-median intake of all 4 nutrients, beta carotene, vitamin C, vitamin E, and zinc, was associated with a 35% reduced risk (HR, 0.65; 95% CI, 0.46-0.92) of AMD. Exclusion of supplement users did not affect the results.ConclusionIn this study, a high dietary intake of beta carotene, vitamins C and E, and zinc was associated with a substantially reduced risk of AMD in elderly persons.
Response to Comment on Grimaldi et al. Association of Obstructive Sleep Apnea in Rapid Eye Movement Sleep With Reduced Glycemic Control in Type 2 Diabetes: Therapeutic Implications. Diabetes Care 2014;37:355–363
Authors: Babak Mokhlesi, Daniela Grimaldi, Eve Van Cauter
Journal: Diabetes Care (2014)

We are grateful to Drs. Scarlata and Antonelli-Incalzi (1) for their interest in our recent publication in Diabetes Care (2). We respectfully have to disagree with their statement that our study focused on “how rapid eye movement (REM) sleep deprivation due to obstructive sleep apnea [OSA] affects glycemic control in type 2 diabetes.” Indeed, our study was a cross-sectional analysis and did not include an experimental paradigm of REM sleep deprivation. In fact, the median duration of REM sleep in our cohort was 20.3% of the total sleep time—well within the normal range (Supplementary Table 1 in ref. 2). The primary aim of our study was to estimate the impact of OSA in REM sleep and in non-REM sleep on glycemic control (as assessed by HbA1c) in patients with …
Peripheral T-cell lymphoma involving subcutaneous tissue
Authors: K-H. CHO, J-K. OH, C-W. KIM, D-S. HEO, S-T. KIM
Journal: British Journal of Dermatology (2006)

The peripheral T-cell lymphomas, presumably derived from various immunocompetent peripheral T-cell system components, form a heterogeneous group of non-Hodgkin's lymphomas. We describe two patients with peripheral T-cell lymphoma primarily involving subcutaneous tissue. They presented with multiple subcutaneous nodules. Skin biopsy specimens in both patients demonstrated a lobular subcutaneous infiltrate. The infiltrate consisted of small and medium-sized atypical lymphoid cells. Both patients had a protracted clinical course before they were diagnosed as having malignant lymphoma. We detected latent Epstein-Barr virus infection in the skin lesions of case 2. Latent Epstein-Barr virus infection might be related to the development of this variant of peripheral T-cell lymphoma.
Phase I study of daily times five topotecan and single injection of cisplatin in patients with previously untreated non-small-cell lung carcinoma
Authors: E. Raymond, H.A. Burris, E.K. Rowinsky, J.R. Eckardt, G. Rodriguez, L. Smith, G. Weiss, D.D. Von Hoff
Journal: Annals of Oncology (1997)
Cancer Stem Cells in Head and Neck Squamous Cell Cancer
Authors: Mark E.P. Prince, Laurie E. Ailles
Journal: Journal of Clinical Oncology (2008)

Appropriate treatment of head and neck squamous cell cancer (HNSCC) remains one of the most difficult challenges in head and neck oncology. Overall survival of patients with HNSCC remains at approximately 50% at 5 years. Surgical therapy can be mutilating and often has significant effects on swallowing, speech, and physical appearance. The addition of chemotherapy to radiation treatment has shown efficacy in organ preservation in some sites in the head and neck, but has resulted in limited improvement in survival rates. HNSCC resistance to chemotherapy has limited the usefulness of chemotherapy in the treatment of this disease. We have recently demonstrated that human head and neck squamous cell cancers contain a tumorigenic, so-called cancer stem cell, subpopulation of cells that can self-renew and produce differentiated cells that form the bulk of the tumor. These tumorigenic HNSCC cells have a distinct phenotype and can be identified by a surface marker. Current treatment for HNSCC regimens may selectively kill the differentiated cancer cells, producing tumor regression while sparing the cancer stem cells, leading to tumor regrowth and relapse. It is important for us to understand why HNSCC does not respond to chemotherapy and to identify new targeted treatments that can overcome resistance and improve patient outcomes. Further study of HNSCC stem cells will increase our knowledge of this devastating disease and allow us to develop novel treatments.
Molecular and cellular evolution of functional tertiary lymphoid structures in salivary glands of NOD mice
Authors: M Bombardieri, E Astorri, E Corsiero, S Gabba, F Barone, G Proctor, C Pitzalis
Journal: Annals of the Rheumatic Diseases (2010)

Tertiary lymphoid structures (TLSs) are common features of chronic inflammatory diseases including Sjogren's syndrome (SS). We recently showed that these ectopic structures acquire secondary lymphoid organs properties and are capable of supporting B cell activation and autoantibody production including expression of activation-induced cytidine deaminase (AID) and Ig class switching. Dissecting TLSs dynamics in humans is technically and ethically challenging. Thus, we used the NOD mouse, a spontaneous model of autoimmune sialoadenitis, to characterise the cellular and molecular basis of autoreactive B cell activation and …
Applications of ovarian tissue transplantation in experimental biology and medicine
Authors: E. Torrents
Journal: Human Reproduction Update (2003)

Nowadays, high-dose chemotherapy and radiotherapy treatments for cancer are more effective but can severely affect the ovarian follicular store, compromising the fertility of surviving young patients. A promising alternative to prevent fertility loss in these patients is the cryopreservation and transplantation of ovarian tissue. Slices of animal and human ovarian tissue have been shown to survive the cryopreservation process. After transplantation, follicular development and restoration of hormone secretion have been observed in animal and human studies. This review addresses recent developments on ovarian tissue transplantation in animals and humans. We also illustrate the indications and technical difficulties of the procedure and the ethical issues that should be considered.