tbuckley/cabot-search huggingface dataset:
Prostaglandins and the induction of food sensitive enteropathy
Authors: A McI MOWAT
Journal: Gut (2000)

Intestinal inflammatory diseases are mediated by dysregulated immune responses to undefined luminal antigens.Feeding hen egg-white lysozyme to mice expressing a transgenic T-cell receptor that recognizes hen egg-white lysozyme peptide 46-61 resulted in no intestinal pathology; however, simultaneous administration of cyclooxygenase-2 inhibitors and dietary hen egg-white lysozyme resulted in increased proliferation of lamina propria mononuclear cells and crypt epithelial cells, crypt expansion and villus blunting.Lamina propria mononuclear cells produce high levels of cyclooxygenase-2-dependent arachidonic acid metabolites, which act as immunomodulators in the immune response to dietary antigen.These findings establish that cyclooxygenase-2dependent arachidonic acid metabolites are essential in the development and maintenance of intestinal immune homeostasis.
Unable to see the wood for the trees
Authors: O. Elkayam, M. Yaron, M. Tishler, D. Caspi
Journal: Annals of the Rheumatic Diseases (1998)

Case historyA 48 year old man with 17 year history of primary Sjögren syndrome (pSS) presented with a sudden swelling of the left lower limb without pain, fever or any other symptom.The diagnosis of pSS was based on xerophthalmia, xerostomia, and swelling of the parotid glands in the presence of positive antinuclear antibodies (ANA), rheumatoid factor (RF), anti-Ro ( 85 IU ELISA, normal range <25 IU ), anti-La (37 IU ELISA, normal range < 25 IU), and typical pathological findings in a minor salivary gland biopsy specimen.During 17 years, the clinical course was characterised by recurrent swelling of the parotid glands without evidence of extraglandular disease or significant changes in his laboratory profile.On admission, diVuse non-tender swelling of the whole limb was observed without lymphadenopathy.The rest of the physical examination was normal.He was admitted to hospital with suspected deep vein thrombosis (DVT) and treatment with intravenous heparin was started.An ultrasound Doppler examination up to the left inguinal area could not confirm DVT, but in view of the suggestive clinical picture, intravenous heparin was continued.Table 1 summarises laboratory tests on admission.A chest radiograph was normal.Two days after admission, the patient became anuric with progressive dyspnoea.Physical examination was suggestive of pleural eVusion, confirmed on chest radiograph and thoracocentesis, which revealed a transudate without malignant cells.Electrocardiogram was normal.Central vein pressure was found to be high (24 mm Hg).Blood tests showed renal deterioration with blood urea nitrogen 83 mg/dl and serum creatinine of 4.3 mg/dl.
Lack of association between the interferon-α signature and longitudinal changes in disease activity in systemic lupus erythematosus
Authors: C Landolt-Marticorena, G Bonventi, A Lubovich, C Ferguson, T Unnithan, J Su, D D Gladman, M Urowitz, P R Fortin, J Wither
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To study the longitudinal expression of interferon (IFN)-inducible genes in systemic lupus erythematosus (SLE) and determine their suitability as disease biomarkers. <h3>Methods:</h3> RNA was isolated from the peripheral blood of 94 patients with SLE and 11 controls and reverse transcribed into cDNA. The expression levels of five IFN-responsive genes (<i>LY6E, OAS1, IFIT1, ISG15</i> and <i>MX1</i>) were determined by quantitative PCR, normalised to <i>GAPDH</i> and summed to generate a global IFN score. Patients were followed longitudinally for a period of 3–12 months, and the association between disease activity, as measured by the SLE disease activity index (SLEDAI-2K), and other clinical and laboratory variables was examined. <h3>Results:</h3> The expression of all five IFN-responsive genes was significantly higher in patients with SLE than in controls. The expression of <i>LY6E</i>, <i>OAS1</i>, <i>IFIT1</i> and the global IFN score was associated with high disease activity. The global IFN score was also associated with active renal disease, a decreased C3, and the presence of anti-dsDNA or anti-RNA binding protein antibodies at a single point in time. However, there was a poor correlation between changes in this score and changes in disease activity, C3 or anti-dsDNA antibody levels in patients followed longitudinally. In most patients the levels of IFN-induced gene expression remained relatively stable over 3–12 months despite marked changes in disease activity. Nevertheless, in patients with low/moderate disease activity, those with high IFN scores had a more recent history of sustained high disease activity. <h3>Conclusion:</h3> The findings indicate that IFN-induced gene expression has limited clinical utility as a biomarker of acute changes in disease activity.
RENAL FUNCTION, ELECTROLYTE EXCRETION AND BODY FLUIDS IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY BEFORE AND AFTER SODIUM DEPRIVATION 12
Authors: James F. Nickel, Preston B. Lowrance, Edgar Leifer, Stanley E. Bradley
Journal: Journal of Clinical Investigation (1953)

L'azotemie par manque de sel is a descriptive phrase coined by Blum, Graber, and van Caulaert (1, 2) to describe the azotemia and hypochloremia which developed in certain diabetic patients main- tained on low salt diets immediately after recovery from coma.When sodium chloride was adminis- tered to these patients the plasma chloride con- centration increased and nitrogen retention dimin- ished or cleared.Pre-existing renal disease, anuria, or acidosis per se were not contributory factors.Blum and his associates (2) concluded that the development of azotemia was a compensa- tory response to decreased molecular concentra- tion and osmotic activity of the blood.This view
Diabetic Peripheral Neuropathy Compromises Balance During Daily Activities
Authors: Steven J. Brown, Joseph C. Handsaker, Frank L. Bowling, Andrew J.M. Boulton, Neil D. Reeves
Journal: Diabetes Care (2015)

OBJECTIVE Patients with diabetes with peripheral neuropathy have a well-recognized increased risk of falls that may result in hospitalization. Therefore this study aimed to assess balance during the dynamic daily activities of walking on level ground and stair negotiation, where falls are most likely to occur. RESEARCH DESIGN AND METHODS Gait analysis during level walking and stair negotiation was performed in 22 patients with diabetic neuropathy (DPN), 39 patients with diabetes without neuropathy (D), and 28 nondiabetic control subjects (C) using a motion analysis system and embedded force plates in a staircase and level walkway. Balance was assessed by measuring the separation between the body center of mass and center of pressure during level walking, stair ascent, and stair descent. RESULTS DPN patients demonstrated greater (P &amp;lt; 0.05) maximum and range of separations of their center of mass from their center of pressure in the medial-lateral plane during stair descent, stair ascent, and level walking compared with the C group, as well as increased (P &amp;lt; 0.05) mean separation during level walking and stair ascent. The same group also demonstrated greater (P &amp;lt; 0.05) maximum anterior separations (toward the staircase) during stair ascent. No differences were observed in D patients. CONCLUSIONS Greater separations of the center of mass from the center of pressure present a greater challenge to balance. Therefore, the higher medial-lateral separations found in patients with DPN will require greater muscular demands to control upright posture. This may contribute to explaining why patients with DPN are more likely to fall, with the higher separations placing them at a higher risk of experiencing a sideways fall than nondiabetic control subjects.
Transcriptional analysis of highly syntenic regions between Medicago truncatula and Glycine max using tiling microarrays
Authors: Lei Li, Hang He, Juan Zhang, Xiangfeng Wang, Sulan Bai, Viktor Stolc, Waraporn Tongprasit, Nevin D Young, Oliver Yu, Xing-Wang Deng
Journal: Genome biology (2008)

Legumes are the third largest family of flowering plants and are unique among crop species in their ability to fix atmospheric nitrogen. As a result of recent genome sequencing efforts, legumes are now one of a few plant families with extensive genomic and transcriptomic data available in multiple species. The unprecedented complexity and impending completeness of these data create opportunities for new approaches to discovery.We report here a transcriptional analysis in six different organ types of syntenic regions totaling approximately 1 Mb between the legume plants barrel medic (Medicago truncatula) and soybean (Glycine max) using oligonucleotide tiling microarrays. This analysis detected transcription of over 80% of the predicted genes in both species. We also identified 499 and 660 transcriptionally active regions from barrel medic and soybean, respectively, over half of which locate outside of the predicted exons. We used the tiling array data to detect differential gene expression in the six examined organ types and found several genes that are preferentially expressed in the nodule. Further investigation revealed that some collinear genes exhibit different expression patterns between the two species.These results demonstrate the utility of genome tiling microarrays in generating transcriptomic data to complement computational annotation of the newly available legume genome sequences. The tiling microarray data was further used to quantify gene expression levels in multiple organ types of two related legume species. Further development of this method should provide a new approach to comparative genomics aimed at elucidating genome organization and transcriptional regulation.
The Effect of β-Adrenergic and Peroxisome Proliferator–Activated Receptor-γ Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue
Authors: Iwona Bogacka, Thomas W. Gettys, Lilian de Jonge, Tuong Nguyen, Jana M. Smith, Hui Xie, Frank Greenway, Steven R. Smith
Journal: Diabetes Care (2007)

OBJECTIVE—The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. This study was conducted to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in nondiabetic subjects. RESEARCH DESIGN AND METHODS—A total of 57 women and men were randomized into four groups: 1) placebo/placebo (PP), 2) ephedrine HCl (25 mg, 3 times daily) plus caffeine (200 mg, 3 times daily)/placebo (ECP), 3) placebo/pioglitazone (45 mg) (PPio), and 4) ephedrine plus caffeine/pioglitazone (ECPio) for 16 weeks. Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression. RESULTS—Body fat decreased by 6.0 and 4.6% in the ECP and ECPio groups, respectively, while remaining unchanged in the PPio and PP groups. Triglyceride levels decreased by −7.7, −24, −15.2, and −41 mg/dl after 16 weeks treatment in the PP, PPio, ECP, and ECPio groups, respectively. This indicates that pioglitazone groups with or without EC (ephedrine HCl plus caffeine) decreased triglycerides, and EC groups with or without pioglitazone decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in the ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl CoA dehydrogenase, and malonyl-CoA decarboxylase increased with PPio and ECPio. Stearoyl-CoA desaturase decreased with ECP. CONCLUSIONS—Combined activation of peroxisome proliferator–activated receptor-γ and β-adrenergic receptors has beneficial effects on body weight, plasma triglycerides, and lipid metabolism in subcutaneous fat by increasing the expression of genes required for fatty acid catabolism.
OUTCOMES AFTER TRANSFEMORAL TAVR FROM THE NON–RANDOMIZED CONTINUED ACCESS REGISTRY OF THE PARTNER TRIAL
Authors: Susheel K. Kodali, E. Murat Tuzcu, Charanjit Rihal, William Fearon, Vasilis Babaliaros, Alan Zajarias, Howard Herrmann, Mathew Williams, David L. Brown, Michael Mack, Paul Teirstein, Brian Whisenant, Raj Makkar, Samir Kapadia, Martin Leon
Journal: Journal of the American College of Cardiology (2013)
A Bax-Mediated Mechanism for Obatoclax-Induced Apoptosis of Cholangiocarcinoma Cells
Authors: Rory L. Smoot, Boris R.A. Blechacz, Nathan W. Werneburg, Steve F. Bronk, Frank A. Sinicrope, Alphonse E. Sirica, Gregory J. Gores
Journal: Cancer Research (2010)

Apoptosis induction by BH3 mimetics is a therapeutic strategy for human cancer. These mimetics exert single-agent activity in cells "primed" for cell death. Primed cells are dependent upon antiapoptotic Bcl-2 proteins for survival and are characterized by the ability of the BH3 mimetic to induce cytochrome c release from their isolated mitochondria. Our aim was to examine the single-agent activity of obatoclax, a BH3 mimetic in cholangiocarcinoma cell lines. In clonogenic assays, inhibition of colony formation was observed by obatoclax treatment. Despite single-agent activity by obatoclax, the mitochondria from these cells did not release cytochrome c after incubation with this BH3 mimetic. However, immunofluorescence and cell fractionation studies identified Bax activation and translocation to mitochondria after treatment with obatoclax. shRNA targeted knockdown of Bax doubled the IC50 for obatoclax but did not abrogate its cytotoxicity, whereas knockdown of Bak did not alter the IC50. In a cell-free system, obatoclax induced an activating conformational change of Bax, which was attenuated by a site-directed mutagenesis of a previously identified protein activation site. Finally, the drug also elicited a significant in vivo response in a rodent model of this disease. In conclusion, single-agent obatoclax treatment results in Bax activation, which contributes, in part, to cell death in cholangiocarcinoma cells. These data indicate that BH3 mimetics may also function as direct activators of Bax and induce cytotoxicity in cells not otherwise primed for cell death.
Convergence of biological and psychological perspectives on cognitive coordination in schizophrenia
Authors: William A. Phillips, Steven M. Silverstein
Journal: Behavioral and Brain Sciences (2003)

Abstract The concept of locally specialized functions dominates research on higher brain function and its disorders. Locally specialized functions must be complemented by processes that coordinate those functions, however, and impairment of coordinating processes may be central to some psychotic conditions. Evidence for processes that coordinate activity is provided by neurobiological and psychological studies of contextual disambiguation and dynamic grouping. Mechanisms by which this important class of cognitive functions could be achieved include those long-range connections within and between cortical regions that activate synaptic channels via NMDA-receptors, and which control gain through their voltage-dependent mode of operation. An impairment of these mechanisms is central to PCP-psychosis, and the cognitive capabilities that they could provide are impaired in some forms of schizophrenia. We conclude that impaired cognitive coordination due to reduced ion flow through NMDA-channels is involved in schizophrenia, and we suggest that it may also be involved in other disorders. This perspective suggests several ways in which further research could enhance our understanding of cognitive coordination, its neural basis, and its relevance to psychopathology.
Progressive Transforming Growth Factor β1–induced Lung Fibrosis Is Blocked by an Orally Active ALK5 Kinase Inhibitor
Authors: Philippe Bonniaud, Peter J. Margetts, Martin Kolb, Jane Ann Schroeder, Ann M. Kapoun, Debby Damm, Alison Murphy, Sarvajit Chakravarty, Sundeep Dugar, Linda Higgins, Andrew A. Protter, Jack Gauldie
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Pulmonary fibrosis is characterized by chronic scar formation and deposition of extracellular matrix, resulting in impaired lung function and respiratory failure. Idiopathic pulmonary fibrosis (IPF) is associated with pronounced morbidity and mortality and responds poorly to known therapeutic interventions; there are no known drugs that effectively block or reverse progressive fibrosis. Transforming growth factor beta (TGF-beta) is known to mediate extracellular matrix gene regulation and appears to be a major player in both the initiation and progression of IPF. TGF-beta mediates its biological effects through members of a family of activin receptor-like kinases (ALK). We have used a gene transfer model of progressive TGF-beta1-induced pulmonary fibrosis in rats to study a newly described orally active small molecular weight drug that is a potent and selective inhibitor of the kinase activity of ALK5, the specific TGF-beta receptor. We show that the drug inhibits the induction of fibrosis when administered at the time of initiation of fibrogenesis and, most important, blocks progressive fibrosis when administered transiently to animals with established fibrosis. These data show promise of the development of an effective therapeutic intervention for IPF and that inhibition of chronic progressive fibrosis may be achieved by blocking TGF-beta receptor activation.
A Practical Solution for Dyspareunia in Breast Cancer Survivors: A Randomized Controlled Trial
Authors: Martha F. Goetsch, Jeong Y. Lim, Aaron B. Caughey
Journal: Journal of Clinical Oncology (2015)

Dyspareunia is common in breast cancer survivors because of low estrogen. This study explored whether dyspareunia is introital pain, preventable with analgesic liquid.In a randomized, controlled, double-blind trial, estrogen-deficient breast cancer survivors with severe penetrative dyspareunia applied either saline or 4% aqueous lidocaine to the vulvar vestibule for 3 minutes before vaginal penetration. After a 1-month blinded trial of patient-assessed twice-per-week tampon insertion or intercourse, all patients received lidocaine for 2 months in an open-label trial. The primary outcome was patient-related assessment of penetration pain on a scale of zero to 10. Secondary outcomes were sexual distress (Female Sexual Distress Scale), sexual function (Sexual Function Questionnaire), and resumption of intercourse. Comparisons were made with the Mann-Whitney U and Wilcoxon signed rank test with significance set at P < .05.In all, 46 patients, screened to exclude those with pelvic muscle and organ pain, uniformly had clinical evidence of severe vulvovaginal atrophy, dyspareunia (median pain score, 8 of 10; interquartile range [IQR], 7 to 9), increased sexual distress scores (median, 30.5; IQR, 23 to 37; abnormal, > 11), and abnormal sexual function. Users of lidocaine reported less pain during intercourse in the blinded phase (median score of 1.0 compared with saline score of 5.3; P = .007). After open-label lidocaine use, 37 (90%) of 41 reported comfortable penetration. Sexual distress decreased (median score, 14; IQR, 3 to 20; P < .001), and sexual function improved in all but one domain. Of 20 prior abstainers from intercourse who completed the study, 17 (85%) had resumed comfortable penetrative intimacy. No partners reported penile numbness.Breast cancer survivors with menopausal dyspareunia can have comfortable intercourse after applying liquid lidocaine compresses to the vulvar vestibule before penetration.
Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial
Authors: Emiel Wouters, Dirkje Postma, B. Fokkens, Wim Hop, Jelle Prins, Albertus Kuipers, H. Pasma, C. A J Hensing, E. Creutzberg
Journal: Thorax (2005)

Guidelines recommend inhaled corticosteroids (ICS) as maintenance treatment for patients with chronic obstructive pulmonary disease (COPD) with a post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and frequent exacerbations, although they have only a small preventive effect on the accelerated decline in lung function. Combined treatment with ICS and long acting beta2 agonists (LABA) may provide benefit to the stability of COPD, but it is unknown if withdrawal of ICS will result in disease deterioration.The effects of 1 year withdrawal of the ICS fluticasone propionate (FP) after a 3 month run-in treatment period with FP combined with the LABA salmeterol (S) (500 microg FP + 50 microg S twice daily; SFC) were investigated in patients with COPD in a randomised, double blind study. 497 patients were enrolled from 39 centres throughout the Netherlands; 373 were randomised and 293 completed the study.The drop out rate after randomisation was similar in the two groups. Withdrawal of FP resulted in a sustained decrease in FEV1: mean (SE) change from baseline -4.4 (0.9)% (S) v -0.1 (0.9)% (SFC); adjusted difference 4.1 (95% CI 1.6 to 6.6) percentage points (p<0.001). Corresponding figures for the FEV1/FVC ratio were -3.7 (0.8)% (S) v 0.0 (0.8)% (SFC) (p = 0.002). The annual moderate to severe exacerbation rate was 1.6 and 1.3 in the S and SFC groups, respectively (adjusted rate ratio 1.2; 95% CI 0.9 to 1.5; p = 0.15). The mean annual incidence rate of mild exacerbations was 1.3 (S) v 0.6 (SFC), p = 0.020. An immediate and sustained increase in dyspnoea score (scale 0-4; mean difference between groups 0.17 (0.04), p<0.001) and in the percentage of disturbed nights (6 (2) percentage points, p<0.001) occurred after withdrawal of fluticasone.Withdrawal of FP in COPD patients using SFC resulted in acute and persistent deterioration in lung function and dyspnoea and in an increase in mild exacerbations and percentage of disturbed nights. This study clearly indicates a key role for ICS in the management of COPD as their discontinuation leads to disease deterioration, even under treatment with a LABA.
Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells
Authors: Bisrat G Debeb, Xiaomei Zhang, Savitri Krishnamurthy, Hui Gao, Evan Cohen, Li Li, Angel A Rodriguez, Melissa D Landis, Anthony Lucci, Naoto T Ueno, Fredika Robertson, Wei Xu, Lara Lacerda, Thomas A Buchholz, Massimo Cristofanilli, James M Reuben, Michael T Lewis, Wendy A Woodward
Journal: Molecular Cancer (2010)

Abstract Background Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells. Results 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including β-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres. Conclusions 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.