tbuckley/cabot-search huggingface dataset:
The effect of cardiac disease on hemoglobin-oxygen binding
Authors: R. D. Woodson, J. D. Torrance, S. D. Shappell, C. Lenfant
Journal: Journal of Clinical Investigation (1970)

The relation between degree of cardiac functional impairment and changes in hemoglobin-oxygen affinity and 2,3-diphosphoglycerate (2,3-DPG) has been studied in 39 patients with noncyanotic heart disease. A progressive decline in hemoglobin-oxygen affinity was found with worsening cardiac function as assessed by cardiac index, arteriovenous oxygen (A-V O(2)) difference, and cardiac symptoms; this alteration in hemoglobin-oxygen binding represents a significant mechanism for adaptation to the limited oxygen supply imposed by the cardiac lesion. The highly significant correlation of mixed venous blood oxygen saturation (S[unk]V(VO2)) with 2,3-DPG and the position of the oxygen dissociation curve suggests that the level of deoxygenated hemoglobin is an important in vivo regulator of hemoglobin-oxygen affinity.
The Efficacy of Afamelanotide and Narrowband UV-B Phototherapy for Repigmentation of Vitiligo
Authors: Pearl E. Grimes, Iltefat Hamzavi, Mark Lebwohl, Jean Paul Ortonne, Henry W. Lim
Journal: JAMA Dermatology (2012)

Vitiligo is characterized by depigmented patches of skin due to loss of cutaneous melanocytes. Many recent studies have demonstrated defects in the melanocortin system in patients with vitiligo, including decreased circulating and lesional skin levels of α-melanocyte-stimulating hormone (α-MSH). Afamelanotide is a potent and longer-lasting synthetic analogue of naturally occurring α-MSH.We describe the preliminary results of 4 patients with generalized vitiligo who developed repigmentation using afamelanotide in combination with narrowband UV-B (NB-UV-B) phototherapy. Patients were treated 3 times weekly with NB-UV-B and starting in the second month received a series of 4 monthly implants containing 16 mg of afamelanotide. Afamelanotide induced faster and deeper repigmentation in each case. All patients experienced follicular and confluent areas of repigmentation within 2 days to 4 weeks after the initial implant, which progressed significantly throughout treatment. All patients experienced diffuse hyperpigmentation.We propose that afamelanotide represents a novel and potentially effective treatment for vitiligo. The combined therapy of NB-UV-B and afamelanotide appears to promote melanoblast differentiation, proliferation, and eumelanogenesis. Further studies are necessary to confirm these observations.
Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk
Authors: Rajiv Chowdhury, Samantha Warnakula, Setor Kunutsor, Francesca Crowe, Heather A. Ward, Laura Johnson, Oscar H. Franco, Adam S. Butterworth, Nita G. Forouhi, Simon G. Thompson, Kay-Tee Khaw, Dariush Mozaffarian, John Danesh, Emanuele Di Angelantonio
Journal: Annals of Internal Medicine (2014)

Background: Guidelines advocate changes in fatty acid consumption to promote cardiovascular health. Purpose: To summarize evidence about associations between fatty acids and coronary disease. Data Sources: MEDLINE, Science Citation Index, and Cochrane Central Register of Controlled Trials through July 2013. Study Selection: Prospective, observational studies and randomized, controlled trials. Data Extraction: Investigators extracted data about study characteristics and assessed study biases. Data Synthesis: There were 32 observational studies (512 420 participants) of fatty acids from dietary intake; 17 observational studies (25 721 participants) of fatty acid biomarkers; and 27 randomized, controlled trials (105 085 participants) of fatty acid supplementation. In observational studies, relative risks for coronary disease were 1.03 (95% CI, 0.98 to 1.07) for saturated, 1.00 (CI, 0.91 to 1.10) for monounsaturated, 0.87 (CI, 0.78 to 0.97) for long-chain ω-3 polyunsaturated, 0.98 (CI, 0.90 to 1.06) for ω-6 polyunsaturated, and 1.16 (CI, 1.06 to 1.27) for trans fatty acids when the top and bottom thirds of baseline dietary fatty acid intake were compared. Corresponding estimates for circulating fatty acids were 1.06 (CI, 0.86 to 1.30), 1.06 (CI, 0.97 to 1.17), 0.84 (CI, 0.63 to 1.11), 0.94 (CI, 0.84 to 1.06), and 1.05 (CI, 0.76 to 1.44), respectively. There was heterogeneity of the associations among individual circulating fatty acids and coronary disease. In randomized, controlled trials, relative risks for coronary disease were 0.97 (CI, 0.69 to 1.36) for α-linolenic, 0.94 (CI, 0.86 to 1.03) for long-chain ω-3 polyunsaturated, and 0.86 (CI, 0.69 to 1.07) for ω-6 polyunsaturated fatty acid supplementations. Limitation: Potential biases from preferential publication and selective reporting. Conclusion: Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats. Primary Funding Source: British Heart Foundation, Medical Research Council, Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.
Intracellular Calcium and Vulnerability to Fibrillation and Defibrillation in Langendorff-Perfused Rabbit Ventricles
Authors: Gyo-Seung Hwang, Hideki Hayashi, Liang Tang, Masahiro Ogawa, Heidy Hernandez, Alex Y. Tan, Hongmei Li, Hrayr S. Karagueuzian, James N. Weiss, Shien-Fong Lin, Peng-Sheng Chen
Journal: Circulation (2006)

The role of intracellular calcium (Ca(i)) in defibrillation and vulnerability is unclear.We simultaneously mapped epicardial membrane potential and Ca(i) during shock on T-wave episodes (n=104) and attempted defibrillation episodes (n=173) in 17 Langendorff-perfused rabbit ventricles. Unsuccessful and type B successful defibrillation shocks were followed by heterogeneous distribution of Ca(i), including regions of low Ca(i) surrounded by elevated Ca(i) ("Ca(i) sinkholes") 31+/-12 ms after shock. The first postshock activation then originated from the Ca(i) sinkhole 53+/-14 ms after the shock. No sinkholes were present in type A successful defibrillation. A Ca(i) sinkhole also was present 39+/-32 ms after a shock on T that induced ventricular fibrillation, followed 22+/-15 ms later by propagated wave fronts that arose from the same site. This wave propagated to form a spiral wave and initiated ventricular fibrillation. Thapsigargin and ryanodine significantly decreased the upper limit of vulnerability and defibrillation threshold. We studied an additional 7 rabbits after left ventricular endocardial cryoablation, resulting in a thin layer of surviving epicardium. Ca(i) sinkholes occurred 31+/-12 ms after the shock, followed in 19+/-7 ms by first postshock activation in 63 episodes of unsuccessful defibrillation. At the Ca(i) sinkhole, the rise of Ca(i) preceded the rise of epicardial membrane potential in 5 episodes.There is a heterogeneous postshock distribution of Ca(i). The first postshock activation always occurs from a Ca(i) sinkhole. The Ca(i) prefluorescence at the first postshock early site suggests that reverse excitation-contraction coupling might be responsible for the initiation of postshock activations that lead to ventricular fibrillation.
Longer treatment time and slower ultrafiltration in hemodialysis: Associations with reduced mortality in the DOPPS
Authors: R. Saran, J.L. Bragg-Gresham, N.W. Levin, Z.J. Twardowski, V. Wizemann, A. Saito, N. Kimata, B.W. Gillespie, C. Combe, J. Bommer, T. Akiba, D.L. Mapes, E.W. Young, F.K. Port
Journal: Kidney International (2006)
Observations on the Natural History of Varicosity of Pulmonary Veins
Authors: FLORENCIO A. HIPONA, AHMED JAMSHIDI
Journal: Circulation (1967)

Pulmonary vein varix was diagnosed by roentgen studies in three patients. One showed enlargement of the lesion in 7 years with progression of heart disease and regression of the varix after correction of the mitral insufficiency. The other two patients without associated heart disease demonstrated no change in the varicosity of the pulmonary vein after 4 and 15 years.
Limitations of Remotely Sensed Aerosol as a Spatial Proxy for Fine Particulate Matter
Authors: Christopher J. Paciorek, Yang Liu
Journal: Environmental Health Perspectives (2009)

BackgroundRecent research highlights the promise of remotely sensed aerosol optical depth (AOD) as a proxy for ground-level particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5). Particular interest lies in estimating spatial heterogeneity using AOD, with important application to estimating pollution exposure for public health purposes. Given the correlations reported between AOD and PM2.5, it is tempting to interpret the spatial patterns in AOD as reflecting patterns in PM2.5.ObjectivesWe evaluated the degree to which AOD can help predict long-term average PM2.5 concentrations for use in chronic health studies.MethodsWe calculated correlations of AOD and PM2.5 at various temporal aggregations in the eastern United States in 2004 and used statistical models to assess the relationship between AOD and PM2.5 and the potential for improving predictions of PM2.5 in a subregion, the mid-Atlantic.ResultsWe found only limited spatial associations of AOD from three satellite retrievals with daily and yearly PM2.5. The statistical modeling shows that monthly average AOD poorly reflects spatial patterns in PM2.5 because of systematic, spatially correlated discrepancies between AOD and PM2.5. Furthermore, when we included AOD as a predictor of monthly PM2.5 in a statistical prediction model, AOD provided little additional information in a model that already accounts for land use, emission sources, meteorology, and regional variability.ConclusionsThese results suggest caution in using spatial variation in currently available AOD to stand in for spatial variation in ground-level PM2.5 in epidemiologic analyses and indicate that when PM2.5 monitoring is available, careful statistical modeling outperforms the use of AOD.
Mouse model of enlarged vestibular aqueducts defines temporal requirement of Slc26a4 expression for hearing acquisition
Authors: Byung Yoon Choi, Hyoung-Mi Kim, Taku Ito, Kyu-Yup Lee, Xiangming Li, Kelly Monahan, Yaqing Wen, Elizabeth Wilson, Kiyoto Kurima, Thomas L. Saunders, Ronald S. Petralia, Philine Wangemann, Thomas B. Friedman, Andrew J. Griffith
Journal: Journal of Clinical Investigation (2011)

Mutations in human SLC26A4 are a common cause of hearing loss associated with enlarged vestibular aqueducts (EVA). SLC26A4 encodes pendrin, an anion-base exchanger expressed in inner ear epithelial cells that secretes HCO3– into endolymph. Studies of Slc26a4-null mice indicate that pendrin is essential for inner ear development, but have not revealed whether pendrin is specifically necessary for homeostasis. Slc26a4-null mice are profoundly deaf, with severe inner ear malformations and degenerative changes that do not model the less severe human phenotype. Here, we describe studies in which we generated a binary transgenic mouse line in which Slc26a4 expression could be induced with doxycycline. The transgenes were crossed onto the Slc26a4-null background so that all functional pendrin was derived from the transgenes. Varying the temporal expression of Slc26a4 revealed that E16.5 to P2 was the critical interval in which pendrin was required for acquisition of normal hearing. Lack of pendrin during this period led to endolymphatic acidification, loss of the endocochlear potential, and failure to acquire normal hearing. Doxycycline initiation at E18.5 or discontinuation at E17.5 resulted in partial hearing loss approximating the human EVA auditory phenotype. These data collectively provide mechanistic insight into hearing loss caused by SLC26A4 mutations and establish a model for further studies of EVA-associated hearing loss.
Gene expression in actinic keratoses: pharmacological modulation by imiquimod
Authors: B. Lysa, U. Tartler, R. Wolf, P. Arenberger, B. Benninghoff, T. Ruzicka, U.R. Hengge, M. Walz
Journal: British Journal of Dermatology (2004)

Actinic keratoses (AKs) are premalignant lesions that can progress into squamous cell carcinoma. Imiquimod, which belongs to the new class of immune-response modifiers, was recently shown to be effective in the treatment of AKs. The underlying mechanisms are not fully understood.To study the expression of individual genes in uninvolved skin and AKs before therapy and to elucidate the way in which the expression of these genes is influenced by imiquimod therapy.We treated 13 patients with AK with imiquimod and compared gene expression before, during (five patients) and after (eight patients) therapy with that in uninvolved skin. We analysed genes coding for inflammatory cytokines or their receptors, adhesion molecules, anti-apoptotic proteins, p53 and toll-like receptors (TLRs) by reverse-transcriptase polymerase chain reaction.Comparing uninvolved skin and untreated AK, we found significant differences in the expression of interleukin (IL)-6, hurpin, TLR7 and TLR8. During imiquimod therapy, we detected a further upregulation of interferon-alpha, IL-6, IL-10 receptor 1 and TLR7. In contrast, two anti-apoptotic genes, hurpin and HAX-1, were downregulated. We did not detect significant differences in gene expression for p53, tumour necrosis factor-alpha and alpha- and beta-catenins. Clinically, the upregulated expression of the proinflammatory cytokines correlated with the local inflammation induced by imiquimod.Our results indicate that specific differences in gene expression are detectable between AK and uninvolved skin. Imiquimod influenced the expression of most genes analysed in this study. This work extends previous findings on the effects of imiquimod on gene regulation in AKs.
MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors
Authors: Xi Liu, Lorenzo F. Sempere, Haoxu Ouyang, Vincent A. Memoli, Angeline S. Andrew, Yue Luo, Eugene Demidenko, Murray Korc, Wei Shi, Meir Preis, Konstantin H. Dragnev, Hua Li, James DiRenzo, Mads Bak, Sarah J. Freemantle, Sakari Kauppinen, Ethan Dmitrovsky
Journal: Journal of Clinical Investigation (2010)

MicroRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31-mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression.
Effect of Metabotropic Glutamate Receptor 3 Genotype on <i>N</i> -Acetylaspartate Measures in the Dorsolateral Prefrontal Cortex
Authors: Stefano Marenco, Sonya U. Steele, Michael F. Egan, Terry E. Goldberg, Richard E. Straub, Anjail Z. Sharrief, Daniel R. Weinberger
Journal: American Journal of Psychiatry (2006)

Objective: This study was carried out to confirm prior evidence of an effect of a single nucleotide polymorphism (SNP) in the metabotropic glutamate receptor 3 (GRM3) gene (a putative risk factor for schizophrenia) on measures of N -acetylaspartate in healthy comparison subjects. Method: Fifty-four carefully screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic resonance spectroscopic imaging (MRSI) at 3 T and selected neuropsychological testing. Results: The A/A genotype group exhibited a significant reduction of N -acetylaspartate/creatine levels in the right dorsolateral prefrontal cortex compared to the G carriers. A tendency in the same direction was seen in the left dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal cortex. Conclusions: These findings provide further evidence that GRM3 affects prefrontal function and that variation in GRM3, monitored by SNP rs6465084, affects GRM3 function.
A neuropsychology of deception and self-deception
Authors: Roger A. Drake
Journal: Behavioral and Brain Sciences (1995)

Abstract As more criminals are imprisoned, other individuals change their behavior to replace them, as predicted by the “floating niche” theory of strategic behavior. The physiological correlates of sociopathy suggest that research in cognitive neuroscience can lead toward a solution. Promising pathways include building upon current knowledge of self-deceit, the independence of positive and negative emotions, the lateralization of risk and caution, and the conditions promoting prosocial behavior.
Reduced beta-cell glucose transporter in new onset diabetic BB rats.
Authors: L Orci, R H Unger, M Ravazzola, A Ogawa, I Komiya, D Baetens, H F Lodish, B Thorens
Journal: Journal of Clinical Investigation (1990)

Previous studies from our laboratories have suggested a defect in glucose transport in islets isolated from BB rats on the first day of overt diabetes. To quantitate by immunostaining the glucose transporter of beta-cells (GLUT-2) before and at the onset of autoimmune diabetes we employed an antibody to its COOH-terminal octapeptide. On the first day of overt diabetes, defined as the day the daily blood glucose first reached 200 mg/dl, the volume density ratio of GLUT-2-positive to insulin-positive beta-cells was only 0.48 +/- 0.06, compared to 0.91 +/- 0.02 in age-matched nondiabetic diabetes-resistant controls (P less than 0.001). In age-matched nondiabetic diabetes-prone rats, most of which would have become diabetic, the ratio was 0.85 +/- 0.02, also less than the controls (P less than 0.05). Protein A-gold labeling of GLUT-2 in beta-cells of day 1 diabetic rats revealed 2.17 +/- 0.16 gold particles per micrometer length of microvillar plasma membranes compared to 3.91 +/- 0.14 in controls (P less than 0.001) and 2.87 +/- 0.24 in the nondiabetic diabetes-prone rats (P less than 0.02). Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound beta-cell depletion of autoimmune diabetes.
Analysis of genes responding to ultraviolet B irradiation of HaCaT keratinocytes using a cDNA microarray
Authors: K.M. Lee, J.G. Lee, E.Y. Seo, W.H. Lee, Y.H. Nam, J.M. Yang, S.H. Kee, Y.J. Seo, J.K. Park, C.D. Kim, J.H. Lee
Journal: British Journal of Dermatology (2005)

Background Ultraviolet (UV) B irradiation causes many important biological changes in skin, which lead to pathophysiological alterations of the homeostatic environment. Objectives To gain more insight into the molecular events provoked by UVB irradiation, we performed cDNA microarray analysis. Methods Immortalized HaCaT keratinocytes were irradiated with a high cytotoxic dose of UVB (50 mJ cm−2), and total RNA was isolated. Fluorescently labelled probes were prepared by reverse transcription and were hybridized with cDNA microarray slides made using 840 cDNA clones. Results Time‐course cDNA microarray analysis revealed the global gene expression profile after UVB exposure. Of 840 genes tested, 192 genes showed changes in their expression levels at one or more of four time points. The genes were clustered into four groups according to their expression patterns in a self‐organizing maps analysis. Classification of these genes into nine functional categories revealed that UVB irradiation affected several biological processes. The genes that were first upregulated and then returned to normal levels included several genes related to the inhibition of cell growth and the proteasome pathway. Conversely, the expressions of many genes involved in the cytoskeleton, signal transduction, metabolism and transcription were first downregulated or unchanged and then upregulated later, reflecting the recovery of UVB‐damaged cellular activities. Conclusions These results demonstrate the complexity of the transcriptional profile of the UVB response, and provide a basis for the global characterization of UV‐regulated gene expression.
Exposure to hog barn dust alters airway epithelial ciliary beating
Authors: T. A. Wyatt, J. H. Sisson, S. G. Von Essen, J. A. Poole, D. J. Romberger
Journal: European Respiratory Journal (2008)

Swine confinement workers are at increased risk of airway diseases, including mucus membrane irritation syndrome, chronic rhinosinusitis and chronic bronchitis. Dust extracts from swine confinement facilities stimulate the production of pro-inflammatory cytokines in bronchial epithelial cells, including interleukin (IL)-8. As IL-8 is capable of blocking β-agonist-stimulated increases in cilia beating, which impacts on mucociliary clearance, it was hypothesised that hog barn-dust exposure might alter cilia responses to stimulation. To test this hypothesis, ciliated bovine bronchial epithelial cell cultures were exposed to hog barn-dust extract (HDE) and ciliary beat frequency (CBF) was assayed. An elevation in baseline CBF was observed. This effect appeared to be independent of endotoxin but dependent upon nitric oxide. HDE also stimulated nitric oxide production in bronchial epithelial cells; however, stimulation of cilia beating by a β-agonist did not occur in cells pre-exposed to HDE. These data demonstrate that hog barn dust can alter normal stimulation of cilia, suggesting a mechanism for the abrogation of stimulated increases in mucociliary clearance in response to inhaled dust exposure.
Activation of epidermal growth factor receptor mediates reperfusion arrhythmias in anaesthetized rats
Authors: Mei Feng, Ji-Zhou Xiang, Zhang-Yin Ming, Qin Fu, Rong Ma, Qiu-Fang Zhang, Yao-Yan Dun, Lei Yang, Hui Liu
Journal: Cardiovascular Research (2011)

AimsEpidermal growth factor receptor (EGFR) plays a critical role in the development and function of the heart. Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart. The present study was designed to investigate whether EGFR activation would mediate cardiac arrhythmias induced by reperfusion in anaesthetized rats.