tbuckley/cabot-search huggingface dataset:
KATP channel opening accelerates and stabilizes rotors in a swine heart model of ventricular fibrillation
Authors: Jorge G. Quintanilla, Javier Moreno, Tamara Archondo, Ashley Chin, Nicasio Pérez-Castellano, Elena Usandizaga, María Jesús García-Torrent, Roberto Molina-Morúa, Pablo González, Cruz Rodríguez-Bobada, Carlos Macaya, Julián Pérez-Villacastín
Journal: Cardiovascular Research (2013)

The mechanisms underlying ventricular fibrillation (VF) are still disputed. Recent studies have highlighted the role of KATP-channels. We hypothesized that, under certain conditions, VF can be driven by stable and epicardially detectable rotors in large hearts. To test our hypothesis, we used a swine model of accelerated VF by opening KATP-channels with cromakalim. Optical mapping, spectral analysis, and phase singularity tracking were performed in eight perfused swine hearts during VF. Pseudo-bipolar electrograms were computed. KATP-channel opening almost doubled the maximum dominant frequency (14.3 ± 2.2 vs. 26.5 ± 2.8 Hz, P < 0.001) and increased the maximum regularity index (0.82 ± 0.05 vs. 0.94 ± 0.04, P < 0.001), the density of rotors (2.0 ± 1.4 vs. 16.0 ± 7.0 rotors/cm2×s, P < 0.001), and their maximum lifespans (medians: 368 vs. ≥3410 ms, P < 0.001). Persistent rotors (≥1 movie = 3410 ms) were found in all hearts after cromakalim (mostly coinciding with the fastest and highest organized areas), but they were not epicardially visible at baseline VF. A 'beat phenomenon' ruled by inter-domain frequency gradients was observed in all hearts after cromakalim. Acceleration of VF did not reveal any significant regional preponderance. Complex fractionated electrograms were not found in areas near persistent rotors. Upon KATP-channel opening, VF consisted of rapid and highly organized domains mainly due to stationary rotors, surrounded by poorly organized areas. A 'beat phenomenon' due to the quasi-periodic onset of drifting rotors was observed. These findings demonstrate the feasibility of a VF driven by stable rotors in hearts whose size is similar to the human heart. Our model also showed that complex fractionation does not seem to localize stationary rotors.
A network module-based method for identifying cancer prognostic signatures
Authors: Guanming Wu, Lincoln Stein
Journal: Genome biology (2012)

Discovering robust prognostic gene signatures as biomarkers using genomics data can be challenging. We have developed a simple but efficient method for discovering prognostic biomarkers in cancer gene expression data sets using modules derived from a highly reliable gene functional interaction network. When applied to breast cancer, we discover a novel 31-gene signature associated with patient survival. The signature replicates across 5 independent gene expression studies, and outperforms 48 published gene signatures. When applied to ovarian cancer, the algorithm identifies a 75-gene signature associated with patient survival. A Cytoscape plugin implementation of the signature discovery method is available at http://wiki.reactome.org/index.php/Reactome_FI_Cytoscape_Plugin
Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria
Authors: Piero Ruggenenti, Annalisa Perna, Giulia Gherardi, Giovanni Garini, Carmine Zoccali, Maurizio Salvadori, Francesco Scolari, Francesco Paolo Schena, Giuseppe Remuzzi
Journal: The Lancet (1999)
Evidence that the Root of the Tree of Life Is Not within the Archaea
Authors: Ryan G. Skophammer, Craig W. Herbold, Maria C. Rivera, Jacqueline A. Servin, James A. Lake
Journal: Molecular Biology and Evolution (2006)

The Archaea occupy uncommon and extreme habitats around the world. They manufacture unusual compounds, utilize novel metabolic pathways, and contain many unique genes. Many suspect, due to their novel properties, that the root of the tree of life may be within the Archaea, although there is little direct evidence for this root. Here, using gene insertions and deletions found within protein synthesis factors present in all prokaryotes and eukaryotes, we present statistically significant evidence that the root of life is outside the Archaea.
Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy
Authors: K. G. Pringle, K. L. Kind, A. N. Sferruzzi-Perri, J. G. Thompson, C. T. Roberts
Journal: Human Reproduction Update (2009)

In the first trimester the extravillous cytotrophoblast cells occlude the uterine spiral arterioles creating a low oxygen environment early in pregnancy, which is essential for pregnancy success. Paradoxically, shallow trophoblast invasion and defective vascular remodelling of the uterine spiral arteries in the first trimester may result in impaired placental perfusion and chronic placental ischemia and hypoxia later in gestation leading to adverse pregnancy outcomes. The hypoxia inducible factors (HIFs) are key mediators of the response to low oxygen. We aimed to elucidate mechanisms of regulation of HIFs and the role these may play in the control of placental differentiation, growth and function in both normal and pathological pregnancies. The Pubmed database was consulted for identification of the most relevant published articles. Search terms used were oxygen, placenta, trophoblast, pregnancy, HIF and hypoxia. The HIFs are able to function throughout all aspects of normal and abnormal placental differentiation, growth and function; during the first trimester (physiologically low oxygen), during mid-late gestation (where there is adequate supply of blood and oxygen to the placenta) and in pathological pregnancies complicated by placental hypoxia/ischemia. During normal pregnancy HIFs may respond to complex alterations in oxygen, hormones, cytokines and growth factors to regulate placental invasion, differentiation, transport and vascularization. In the ever-changing environment created during pregnancy, the HIFs appear to act as key mediators of placental development and function and thereby are likely to be important contributors to both normal and adverse pregnancy outcomes.
Subclinical gut inflammation in spondyloarthropathy patients is associated with upregulation of the E-cadherin/catenin complex
Authors: P Demetter
Journal: Annals of the Rheumatic Diseases (2000)

OBJECTIVE Previously an upregulation of E-cadherin and its associated molecules α-catenin, β-catenin and plakoglobin has been demonstrated in clinically overt inflammatory bowel disease (IBD). The aim of this study was to investigate the expression of the E-cadherin/catenin complex in subclinically inflamed bowel mucosa from spondyloarthropathy (SpA) patients. METHODS Ileal and colonic biopsy specimens from 19 SpA patients with subclinical inflammatory gut lesions and from seven controls were stained with monoclonal antibodies against E-cadherin, β-catenin and plakoglobin and a polyclonal antibody against α-catenin. E-cadherin mRNA was detected using a riboprobe. Inflammation was histologically classified into acute, chronic active and chronic quiescent forms. RESULTS In acute and chronic active bowel inflammation of SpA patients, upregulation of the E-cadherin/catenin glycoprotein complex could be observed. Chronic lesions in a quiescent state did not show such an upregulation. Furthermore, chronic inflammation was associated with an increase in E-cadherin mRNA. CONCLUSIONS As some of the SpA patients with subclinical gut inflammation develop IBD, upregulation of the E-cadherin/catenin complex in inflamed bowel mucosa from SpA patients may point to early cellular changes in the development of IBD. However, at present it cannot be excluded that increased E-cadherin/catenin complex expression is a bystander phenomenon of active inflammation.
LV Thrombus Detection by Routine Echocardiography
Authors: Jonathan W. Weinsaft, Han W. Kim, Anna Lisa Crowley, Igor Klem, Chetan Shenoy, Lowie Van Assche, Rhoda Brosnan, Dipan J. Shah, Eric J. Velazquez, Michele Parker, Robert M. Judd, Raymond J. Kim
Journal: JACC. Cardiovascular imaging (2011)
The Disclosure Dilemma — Large-Scale Adverse Events
Authors: Denise M. Dudzinski, Philip C. Hébert, Mary Beth Foglia, Thomas H. Gallagher
Journal: New England Journal of Medicine (2010)

Some adverse events such as a failure to disinfect medical equipment have the potential to harm many patients. The authors argue that medical institutions should develop policies for addressing large-scale adverse events and should routinely disclose these events to patients, even when the risk of harm is very low.
Myeloid leukemic progenitor cells can be specifically targeted by minor histocompatibility antigen LRH-1–reactive cytotoxic T cells
Authors: Wieger J. Norde, Ingrid M. Overes, Frans Maas, Hanny Fredrix, Johanna C. M. Vos, Michel G. D. Kester, Robbert van der Voort, Inge Jedema, J. H. Frederik Falkenburg, Anton V. Schattenberg, Theo M. de Witte, Harry Dolstra
Journal: Blood (2008)
Neuromorphic Analogue VLSI
Authors: R Douglas, M Mahowald, C Mead
Journal: Annual Review of Neuroscience (1995)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Patterns of Codon Usage Bias in Silene latifolia
Authors: S. Qiu, R. Bergero, K. Zeng, D. Charlesworth
Journal: Molecular Biology and Evolution (2010)

Patterns of codon usage bias (CUB) convey useful information about the selection on synonymous codons induced by gene expression and contribute to an understanding of substitution patterns observed at synonymous sites. They can also be informative about the distinctive evolutionary properties of sex chromosomes such as genetic degeneration of the Y chromosome, dosage compensation, and hemizygosity of the X chromosome in males, which can affect the selection on codon usage. Here, we study CUB in Silene latifolia, a species of interest for studying the early stages of sex chromosome evolution. We have obtained a large expressed sequence tag data set containing more than 1,608 sequence fragments by 454 sequencing. Using three different methods, we conservatively define 21 preferred codons. Interestingly, the preferred codons in S. latifolia are almost identical to those in Arabidopsis thaliana, despite their long divergence time (we estimate average nonsynonymous site divergence to be 0.216, and synonymous sites are saturated). The agreement suggests that the nature of selection on codon usage has not changed significantly during the long evolutionary time separating the two species. As in many other organisms, the frequency of preferred codons is negatively correlated with protein length. For the 43 genes with both exon and intron sequences, we find a positive correlation between gene expression levels and GC content at third codon positions, but a strong negative correlation between expression and intron GC content, suggesting that the CUB we detect in S. latifolia is more likely to be due to natural selection than to mutational bias. Using polymorphism data, we detect evidence of ongoing natural selection on CUB, but we find little support for effects of biased gene conversion. An analysis of ten sex-linked genes reveals that the X chromosome has experienced significantly more unpreferred to preferred than preferred to unpreferred substitutions, suggesting that it may be evolving higher CUB. In contrast, numbers of substitutions between preferred and unpreferred codons are similar in both directions in the Y-linked genes, contrary to the expectation of genetic degeneration.
Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus
Authors: Peter Libby, David M. Nathan, Kristin Abraham, John D. Brunzell, Judith E. Fradkin, Steven M. Haffner, Willa Hsueh, Marian Rewers, B. Tibor Roberts, Peter J. Savage, Sonia Skarlatos, Momtaz Wassef, Cristina Rabadan-Diehl
Journal: Circulation (2005)
The Insertion/Deletion Polymorphism of the ACE Gene Is Related to Insulin Sensitivity in Overweight Women
Authors: Alice S. Ryan, Barbara J. Nicklas, Dora M. Berman, Robert E. Ferrell
Journal: Diabetes Care (2001)

OBJECTIVE—The ACE insertion/deletion (I/D) polymorphism has been identified as a genetic risk factor for coronary heart disease (CHD). The deletion (D) allele of the ACE gene may be associated with higher insulin sensitivity. Individuals who are homozygous for the DD allele have higher ACE levels and possibly more angiotensin II, which, when infused exogenously, causes an increase in insulin sensitivity. The purpose of this study was to investigate the association of the I/D polymorphism of the ACE gene with insulin sensitivity and CHD risk factors. RESEARCH DESIGN AND METHODS—The study included 66 women (ages 57 ± 1 years) who were overweight or obese (means ± SEM, BMI = 33 ± 1 kg/m2) and sedentary (Vo2max = 19.6 ± 0.4 ml · kg–1 · min1). Total body fat mass and percent fat were determined by dual-energy X-ray absorptiometry, and abdominal fat was by computed tomography. Insulin sensitivity was measured during the last 30 min of 3-h hyperinsulinemic-euglycemic clamps (40 mU · m−2 · min−1). Comparisons were made among women with the II (n = 9), ID (n = 36), and DD (n = 21) genotypes. RESULTS—Age, percent body fat, waist-to-hip ratio, visceral and subcutaneous abdominal fat areas, plasma lipid levels, and systolic and diastolic blood pressures did not differ by ACE genotype. Fasting glucose and 2-h glucose levels were similar among genotypes, but fasting plasma insulin levels were lower in DD women than in ID women (P &amp;lt; 0.05). Glucose utilization was higher in women with the DD genotype than in women with the II genotype (53.1 ± 3.9 vs. 36.0 ± 3.8 μmol · kg−1 FFM · min−1, P = 0.01) and was higher in ID women than in II women (48.5 ± 2.5 μmol · kg−1 FFM · min−1, P = 0.04). CONCLUSIONS—These data suggest that the I/D polymorphism is not associated with risk factors for CHD in overweight sedentary women; however, women who are homozygous for the D allele of the ACE gene are more insulin sensitive, whereas women who are homozygous for the I allele of the ACE gene have greater insulin resistance and potential risk for type 2 diabetes.
Sequential Evolution of a Symbiont Inferred From the Host: Wolbachia and Drosophila simulans
Authors: J. W. O. Ballard
Journal: Molecular Biology and Evolution (2003)

This study aims to unravel the biogeography of a model symbiont/host system by exploiting the prediction that a symbiont will leave a signature of infection on the host. Specifically, a global sample of 1,442 Drosophila simulans from 33 countries and 64 sampling localities was employed to infer the phylogeography of the maternally inherited alpha-proteobacteria Wolbachia. Phylogenetic analyses, from three symbiont genes and 24 mtDNA genomes (excluding the A + T–rich region), showed that each of four Wolbachia strains infected D. simulans once. The global distribution and abundance of the Wolbachia strains and the three mtDNA haplogroups (D. simulanssiI, siII and siIII) was then determined. Finally, network analyses of variable regions within siI (584 bp from seven additional lines) and siII (1,701 bp from 383 lines) facilitated a detailed biogeographic discussion. There is little variation in siIII and the haplogroup is restricted in its distribution. These data show how the history of an infection can be mapped by combining data from the symbiont and the host. They say little about the organismal history of the host because the mtDNA genome is a biased representation of the whole genome.
The expression of cannabinoid receptor 1 is significantly increased in atopic patients
Authors: Mar Martín-Fontecha, Thomas Eiwegger, Tuomas Jartti, Ainoa Rueda-Zubiaurre, Kerstin Tiringer, Jefim Stepanow, Tuomo Puhakka, Beate Rückert, Silvia Ortega-Gutiérrez, María L. López-Rodríguez, Mübeccel Akdis, Cezmi A. Akdis, Oscar Palomares
Journal: Journal of Allergy and Clinical Immunology (2014)
Effect of corticosteroid therapy on bromsulphthalein excretion in active chronic hepatitis.
Authors: G C Cook, M Velasco, S Sherlock
Journal: Gut (1968)

METHODSBromsulphthalein (BSP) disappearance curves were performed after an overnight fast following the intraven- ous injection of 5.0 mg BSP per kg body weight.Venous blood was taken from the opposite arm at three, eight, 12, 20, 30, and 45 minutes after injection of BSP.Plasma BSP was estimated on the same day by a method based on that of Seligson, Marino, and Dodson (1957).To 3.5 ml alkaline buffer (pH 10-6) (12.2 g Na2 HPO4.7O, 1.77 g Na3PO4H2O, and 3.20 g of sodium p-toluene sulphonate, made up to 500 ml with distilled water), 0.5 ml plasma was added and the colour estimated with a Unicam spectrophotometer at 580 mu.After the 270 on July 13,
The K veim response: still useful, still a puzzle.
Authors: C S Munro, D N Mitchell
Journal: Thorax (1987)

The Kveim response: still useful, still a puzzle A skin test using sarcoid tissue to demonstrate cuta- neous reactivity in individuals with probable sarcoid- osis was described in 1935 by Williams and Nick- erson,' but they did not report the histology of the responses.In 1941 Ansgar Kveim,2 an Oslo der- matologist, published a complete description of the test that now bears his name.He noted that in subjects with sarcoidosis intradermal injection of a crude homogenate of sarcoid tissue produced, over several weeks, papules which on histological examination contained epithelioid cell granulomas exactly like those of the disorder.Reactions in control subjects, including some with tuberculosis, were negative.Sub- sequent investigators, notably Putkonen,3 Danbolt,4 and Nelson,5 6 used crude ("conventional") sus-
Preferential binding of lysozyme to elastic fibres in pulmonary emphysema
Authors: B. Shteyngart, S. Chaiwiriyakul, J. Wong, J. O Cantor
Journal: Thorax (1998)

Lysozyme is increased in inflammatory reactions and is a component of the extracellular matrix, but its possible role in lung diseases such as emphysema and interstitial fibrosis has not been investigated.To characterise differences in lysozyme content among normal, emphysematous, and fibrotic human lungs, tissue sections obtained from necropsy specimens were immunostained with rabbit polyclonal anti-human lysozyme antibody using the labelled streptavidin-biotin peroxidase method. The immunostained sections were evaluated semi-quantitatively (grading the degree of immunostaining on a scale of 0-4). To determine if degradation of the extracellular matrix affects lysozyme binding, hyaluronidase-treated normal lung tissues were incubated with egg white lysozyme, immunostained with the lysozyme antibody, which crossreacts with egg white lysozyme, and evaluated for degree of staining.Lysozyme immunostaining was significantly increased in lungs with pulmonary emphysema compared with normal or fibrotic tissues (3.4 versus 1.6 and 1.9, respectively; p < 0.05) and was preferentially associated with interstitial elastic fibres. Hyaluronidase-treated lung tissues incubated with lysozyme showed increased immunostaining for this protein compared with untreated controls (1.9 versus 1.2; p < 0.05).The results suggest that damage to elastic fibres and/or the surrounding extracellular matrix increases lysozyme binding. It is hypothesised that attachment of lysozyme to elastic fibres may interfere with their repair and possibly enhance the progression of pulmonary emphysema.
Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome
Authors: Csaba Galambos, Hara Levy, Carolyn L. Cannon, Sara O. Vargas, Lynne M. Reid, Robert Cleveland, Robert Lindeman, Daphne E. deMello, Susan E. Wert, Jeffrey A. Whitsett, Antonio R. Perez-Atayde, Harry Kozakewich
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12–21.3 haploid deletion encompassing the TTF-1 gene locus who had cerebral dysgenesis, thyroidal dysfunction, and respiratory insufficiency. The clinical course was notable for mild hyaline membrane disease, continuous ventilatory support, and symmetrically distributed pulmonary cysts by imaging. He developed pneumonia and respiratory failure and died at 8 months. Pathologically, the lungs had grossly visible emphysematous changes with "cysts" up to 2 mm in diameter. The airway generations and radial alveolar count were diminished. In addition to acute bacterial pneumonia, there was focally alveolar septal fibrosis, pneumocyte hypertrophy, and clusters of airspace macrophages. Ultrastructurally, type II pneumocytes had numerous lamellar bodies, and alveolar spaces contained fragments of type II pneumocytes and extruded lamellar bodies. Although immunoreactivity for surfactant protein SP-A and ABCA3 was diminished, that for SP-B and proSP-C was robust, although irregularly distributed, corresponding to the distribution of type II pneumocytes. Immunoreactivity for TTF-1 protein was readily detected. In summation, we document abnormal airway and alveolar morphogenesis and altered expression of surfactant-associated proteins, which may explain the respiratory difficulties encountered in TTF-1 haploinsufficiency. These findings are consistent with experimental evidence documenting the important role of TTF-1 in pulmonary morphogenesis and surfactant metabolism.
Free radicals in antigen formation: reduction of contact allergic response to hydroperoxides by epidermal treatment with antioxidants
Authors: E. Gafvert, J.L.G. Nilsson, G. Hagelthorn, A-T. Karlberg
Journal: British Journal of Dermatology (2002)

Summary Background For patients with allergic contact dermatitis, the main therapy is anti-inflammatory steroids, a non-specific and symptomatic treatment. In contact allergy, the antigen formation is considered to be the binding of a chemical (hapten) to a biological macromolecule, e.g. a protein. Limonene-2-hydroperoxide (Lim-OOH) is a hapten with a known allergenic effect. It is likely to bind to proteins in the skin via a radical mechanism. It might be possible to inhibit the allergic reaction by epidermal application of substances that can trap free radicals, e.g. antioxidants such as ascorbic acid or α-tocopherol, prior to the application of the hapten. Objectives To study the influence of antioxidants on the allergenic effect of Lim-OOH in sensitization experiments on guinea pigs. Methods Pretreatment with the antioxidants was performed before induction to study the effect on sensitization as well as before challenge testing to study the effect on elicitation. Results A reduction in the response rate was found both at sensitization and at elicitation. The antioxidants had no effect on cobalt allergy or on the allergenic effect of haptens that form antigens via nucleophilic–electrophilic reactions. No reduction of the effect was seen for irritants. Conclusions The protective effect of antioxidants in elicitation could be of practical therapeutic value, as it indicates a possibility for the treatment of patients who have become sensitized to haptens that form full antigens via a radical mechanism.
Cell Type-Specific Involvement of RIG-I in Antiviral Response
Authors: Hiroki Kato, Shintaro Sato, Mitsutoshi Yoneyama, Masahiro Yamamoto, Satoshi Uematsu, Kosuke Matsui, Tohru Tsujimura, Kiyoshi Takeda, Takashi Fujita, Osamu Takeuchi, Shizuo Akira
Journal: Immunity (2005)