tbuckley/cabot-search huggingface dataset:
Interleukin-1R antagonist gene and pre-natal smoke exposure are associated with childhood asthma
Authors: R. A. Ramadas, A. Sadeghnejad, W. Karmaus, S. H. Arshad, S. Matthews, M. Huebner, D-Y. Kim, S. L. Ewart
Journal: European Respiratory Journal (2006)

The interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory cytokine. In the present study, association of the human <i>IL1RN</i> gene polymorphisms with asthma, bronchial hyperresponsiveness and forced expiratory volume in one second/forced vital capacity ratio was tested and the data was stratified by environmental tobacco smoke exposure in order to investigate a gene-smoking interaction. In an unselected subset (n = 921) of the Isle of Wight birth (UK) cohort, which has previously been evaluated for asthma and related manifestations at ages 1, 2, 4 and 10 yrs, three <i>IL1RN</i> single nucleotide polymorphisms (SNP) were genotyped. Logistic regression and repeated measurement models for tests of association using a representative SNP rs2234678 were used, as all SNPs tested were in strong linkage disequilibrium. In the overall analysis, the SNP rs2234678 was not associated with asthma. However, in the stratum with maternal smoking during pregnancy the rs2234678 GG genotype significantly increased the relative risk of asthma in children, both in analyses of repeated asthma occurrences and persistent asthma. In conclusion, the present results show that in the first decade of life, the gene–environment interaction of the interleukin-1 receptor antagonist gene polymorphism rs2234678 and maternal smoking during pregnancy increased the risk for childhood asthma.
Role for Sulfatides in Platelet Aggregation
Authors: Michael Merten, Perumal Thiagarajan
Journal: Circulation (2001)

Background — Sulfatides are sulfated glycosphingolipids present on the surface of oligodendrocytes, renal tubular cells, and certain tumor cells. They appear to be involved in nerve conduction and cell adhesion, but their precise physiological function is not known. Methods and Results — Here, we show a novel role for sulfatides as a major ligand for P-selectin in platelet adhesion and aggregation. Sulfatides are expressed on the platelet surface, and platelets expressing sulfatides adhere to P-selectin. Both sulfatide micelles and sulfatide-binding recombinant malaria circumsporozoite protein (MCSP) inhibit this adhesion. In parallel, platelets and CHO cells expressing P-selectin adhere to sulfatides, and anti-P-selectin antibodies inhibit this adhesion. Furthermore, both anti-P-selectin antibodies and sulfatide antagonist MCSP significantly reverse platelet aggregation induced by ADP, collagen, or thrombin receptor-activating peptide, suggesting that sulfatide-P-selectin interactions are necessary for the formation of stable platelet aggregates. Conclusions — These results show that sulfatide interactions with P-selectin are important in platelet adhesion and platelet aggregation. The sulfatide interactions with P-selectin stabilize platelet aggregates, representing a new mechanism of platelet aggregation that may play a significant role in hemostasis and thrombosis.
Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin II-B–depleted mice
Authors: Deniz Üren, Hweung-Kon Hwang, Yoshinobu Hara, Kazuyo Takeda, Sachiyo Kawamoto, Antonella N. Tullio, Zu-Xi Yu, Victor J. Ferrans, Nancy Tresser, Alexander Grinberg, Yvette A. Preston, Robert S. Adelstein
Journal: Journal of Clinical Investigation (2000)

Complete ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice resulted in cardiac and brain defects that were lethal during embryonic development or on the day of birth. In this paper, we report on the generation of mice with decreased amounts of NMHC-B. First, we generated BΔI/BΔI mice by replacing a neural-specific alternative exon with the PGK-Neo cassette. This resulted in decreased amounts of NMHC-B in all tissues, including a decrease of 88% in the heart and 65% in the brain compared with B+/B+ tissues. BΔI/BΔI mice developed cardiac myocyte hypertrophy between 7 months and 11 months of age, at which time they reexpressed the cardiac β-MHC. Serial sections of BΔI/BΔI brains showed abnormalities in neural cell migration and adhesion in the ventricular wall. Crossing BΔI/BΔI with B+/B– mice generated BΔI/B– mice, which showed a further decrease of approximately 55% in NMHC-B in the heart and brain compared with BΔI/BΔI mice. Five of 8 BΔI/B– mice were born with a membranous ventricular septal defect. Moreover, 5 of 5 BΔI/B– mice developed myocyte hypertrophy by 1 month; BΔI/B– mice also reexpressed the cardiac β-MHC. More than 60% of BΔI/B– mice developed overt hydrocephalus and showed more severe defects in neural cell migration and adhesion than did BΔI/BΔI mice. These data on BΔI/BΔI and BΔI/B– mice demonstrate a gene dosage effect of the amount of NMHC-B on the severity and time of onset of the defects in the heart and brain.
Azithromycin prophylaxis against a chloroquine-resistant strain of Plasmodium falciparum
Authors: A Kuschner, D.G Heppner, Bt Wellde, T Hall, I Schneider, W.R Ballou, J.C Sadoff, D.N Taylor, S.L Andersen, B Schuster, G Foulds
Journal: The Lancet (1994)
Demonstration by Pressor and Steroidogenic Assays of Increased Renin in Lymph of Dogs with Secondary Hyperaldosteronism
Authors: JAMES T. HIGGINS, JAMES O. DAVIS, JOHN URQUHART
Journal: Circulation Research (1964)

Thoracic duct lymph from normal dogs and from dogs with hyperaldosteronism secondary to thoracic inferior vena caval constriction was assayed for renin. After acidification, dialysis and incubation, lymph from animals with caval constriction showed more angiotensin-like material than lymph of normal dogs when assayed for both pressor and aldosterone-stimulating activities. Nephrectomy was followed by a marked decrease or disappearance of renin activity from lymph. Lymph from dogs with renal venous hypertension secondary to abdominal vena caval constriction did not show increased renin content. Dual assay makes detection of angiotensin II more specific and the findings indicate that increased amounts of renin are released from the kidney into lymph of dogs with experimental secondary hyperaldosteronism.
Uniform Format for Disclosure of Competing Interests in ICMJE Journals
Authors: Jeffrey M. Drazen, Martin B. Van Der Weyden, Peush Sahni, Jacob Rosenberg, Ana Marusic, Christine Laine, Sheldon Kotzin, Richard Horton, Paul C. Hébert, Charlotte Haug, Fiona Godlee, Frank A. Frizelle, Peter W. de Leeuw, Catherine D. DeAngelis
Journal: JAMA (2009)

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Interocular Asymmetries in Axial Length and Refractive Error in 4 Cohorts
Authors: Omar A. Mahroo, Cathy Williams, Pirro G. Hysi, Katie M. Williams, Obeda Kailani, Juliet Thompson, Phillippa M. Cumberland, Jeremy A. Guggenheim, Jugnoo S. Rahi, Richard A. Harrad, Christopher J. Hammond
Journal: Ophthalmology (2014)
Risk adjusted benchmarking of abdominoperineal excision for rectal adenocarcinoma in the context of the Belgian PROCARE improvement project
Authors: Freddy Penninckx, Steffen Fieuws, Koen Beirens, Pieter Demetter, Wim Ceelen, Alex Kartheuser, Gaetan Molle, Jean Van de Stadt, Koen Vindevoghel, Elizabeth Van Eycken
Journal: Gut (2012)

<h3>Objective</h3> The abdominoperineal excision (APE) rate, a quality of care indicator in rectal cancer surgery, has been criticised if not adjusted for confounding factors. This study evaluates variability in APE rate between centres participating in PROCARE, a Belgian improvement initiative, before and after risk adjustment. It also explores the effect of merging the Hartmann resections (HR) rate with that of APE on benchmarking. <h3>Design</h3> Data of 3197 patients who underwent elective radical resection for invasive rectal adenocarcinoma up to 15 cm were registered between January 2006 and March 2011 by 59 centres, each with at least 10 patients in the registry. Variability of APE or merged APE/HR rates between centres was analysed before and after adjustment for gender, age, ASA score (3 or more), tumour level (rectal third), depth of tumour invasion (cT4) and preoperative incontinence. <h3>Results</h3> The overall APE rate was 21.1% (95% CI 19.7 to 22.5%). Significant variation of the APE rate was observed before and after risk adjustment (p&lt;0.0001). For cancers in the lower rectal third, the overall APE rate increased to 45.8% (95% CI 43.1 to 48.5%). Also, variation between centres increased. Risk adjustment influenced the identification of outliers. HR was performed in only 2.6% of patients. However, merging of risk adjusted APE and HR rates identified other centres with outlying definitive colostomy rates than APE rate alone. <h3>Conclusion</h3> Significant variation of the APE rate was observed. Adjustment for confounding factors as well as merging HR with APE rates were found to be important for the assessment of performances.
Protein Kinase C Activation Downregulates Human Organic Anion Transporter 1-Mediated Transport through Carrier Internalization
Authors: Natascha A. Wolff, Karen Thies, Nicola Kuhnke, Glen Reid, Björn Friedrich, Florian Lang, Gerhard Burckhardt
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Organic anion transport in intact renal proximal tubule cells in animal model systems is downregulated by treatments that activate protein kinase C (PKC). How this downregulation is achieved is not yet known. Stimulation of PKC with sn-1,2-dioctanoylglycerol resulted in strong inhibition of p-aminohippurate transport mediated by the cloned human organic anion transporter 1 (hOAT1) expressed in Xenopus oocytes and HEK293 cells, as well as hOAT1 internalization in both expression systems. The sn-1,2-dioctanoylglycerol-induced transport inhibition was partially prevented by staurosporine. It was independent of the conserved canonical PKC consensus sites in hOAT1, however, and was unaffected by agents that destabilize actin filaments or microtubules, which altered baseline hOAT1-mediated p-aminohippurate uptake activity in oocytes. It is concluded that PKC-induced hOAT1 downregulation is achieved through carrier retrieval from the cell membrane and does not involve phosphorylation of the predicted classic hOAT1 PKC consensus sites. E-mail: [email protected]
Sevelamer Controls Parathyroid Hormone–Induced Bone Disease as Efficiently as Calcium Carbonate without Increasing Serum Calcium Levels during Therapy with Active Vitamin D Sterols
Authors: Isidro B. Salusky, William G. Goodman, Shobha Sahney, Barbara Gales, Ashley Perilloux, He-Jing Wang, Robert M. Elashoff, Harald Ju[Combining Diaeresis]ppner
Journal: Journal of the American Society of Nephrology (2005)

Little is known about the impact of various phosphate binders on the skeletal lesions of secondary hyperparathyroidism (2 degrees HPT). The effects of calcium carbonate (CaCO3) and sevelamer were compared in pediatric peritoneal dialysis patients with bone biopsy-proven 2 degrees HPT. Twenty-nine patients were randomly assigned to CaCO3 (n = 14) or sevelamer (n = 15), concomitant with either intermittent doses of oral calcitriol or doxercalciferol for 8 mo, when bone biopsies were repeated. Serum phosphorus, calcium, parathyroid hormone (PTH), and alkaline phosphatase were measured monthly. The skeletal lesions of 2 degrees HPT improved with both binders, and bone formation rates reached the normal range in approximately 75% of the patients. Overall, serum phosphorus levels were 5.5 +/- 0.1 and 5.6 +/- 0.3 mg/dl (NS) with CaCO3 and sevelamer, respectively. Serum calcium levels and the Ca x P ion product increased with CaCO3; in contrast, values remained unchanged with sevelamer (9.6 +/- 01 versus 8.9 +/- 0.2 mg/dl; P < 0.001, respectively). Hypercalcemic episodes (>10.2 mg/dl) occurred more frequently with CaCO3 (P < 0.01). Baseline PTH levels were 980 +/- 112 and 975 +/- 174 pg/ml (NS); these values decreased to 369 +/- 92 (P < 0.01) and 562 +/- 164 pg/ml (P < 0.01) in the CaCO3 and the sevelamer groups, respectively (NS between groups). Serum alkaline phosphatase levels also diminished in both groups (P < 0.01). Thus, treatment with either CaCO3 or sevelamer resulted in equivalent control of the biochemical and skeletal lesions of 2 degrees HPT. Sevelamer, however, maintained serum calcium concentrations closer to the lower end of the normal physiologic range, thereby increasing the safety of treatment with active vitamin D sterols.
Influence of sampling interval on the evaluation of nocturnal blood pressure in subjects with and without obstructive sleep apnoea
Authors: O. Marrone, S. Romano, G. Insalaco, M.R. Bonsignore, A Salvaggio, G Bonsignore
Journal: European Respiratory Journal (2000)

Blood pressure (BP) variability during sleep is high in obstructive sleep apnoea syndrome (OSAS). How BP sampling interval affects the estimate of mean nocturnal BP in OSAS and control subjects was investigated. Nine subjects with apnoea/hypopnoea index (AHI) <5 and 18 OSAS patients with AHI >30 underwent nocturnal polysomnography with beat-by-beat BP monitoring. Mean nocturnal BP was evaluated averaging: a) all systolic (Ps) and diastolic (Pd) BP values; b) Ps and Pd sampled every 5, 10, 15, 20, and 30 min. The sampling starting point was repeatedly shifted, and several mean BP estimates for each sampling interval were obtained. Differences (deltaPs and deltaPd) between means obtained by sampling BP and by averaging all BP values were calculated. In both groups deltaPs and deltaPd scatter increased as sampling interval increased; their variance was always higher in OSAS subjects (p<0.001). Over 95% of deltaPs and deltaPd were <5% of the beat-by-beat mean values at all sampling intervals in controls, but this occurred only at sampling intervals < or =10 min in OSAS subjects. To conclude, for each blood pressure sampling time, a larger number of inaccurate nocturnal mean blood pressure estimates are obtained in obstructive sleep apnoea syndrome than in control subjects. Obstructive sleep apnoea syndrome subjects require more frequent blood pressure measurements to obtain a similar accuracy in nocturnal blood pressure evaluation.
ENDOCRINE REVIEWS: A Peer-Reviewed Journal
Authors: Andres Negro-Vilar
Journal: Endocrine Reviews (1993)

Journal Article Endocrine Reviews: A Peer-Reviewed Journal Get access Andres Negro-Vilar, M.D., Ph.D. Andres Negro-Vilar, M.D., Ph.D. Search for other works by this author on: Oxford Academic Google Scholar Endocrine Reviews, Volume 14, Issue 3, 1 June 1993, Page 255, https://doi.org/10.1210/edrv-14-3-255 Published: 01 June 1993
Increased Fructose Concentrations in Blood and Urine in Patients With Diabetes
Authors: Takahiro Kawasaki, Hiroshi Akanuma, Toshikazu Yamanouchi
Journal: Diabetes Care (2002)

To investigate fructose metabolic changes in patients with diabetes.Serum and urinary fructose concentrations were determined in healthy subjects (n = 23) and in nondiabetic (n = 23) and diabetic patients (n = 26). Fructose was measured using our newly developed method, and (13)C(6)-fructose was used as the internal standard. After adding sample to a fixed amount of internal standard, ion-exchange resins and high-performance liquid chromatography pretreatments were performed. Then, the amount of fructose in the sample was measured by gas chromatography-mass spectrometry.Serum fructose concentrations in patients with diabetes (12.0 +/- 3.8 micromol/l) were significantly higher than those in healthy subjects (8.1 +/- 1.0 micromol/l, P < 0.001) and nondiabetic patients (7.7 +/- 1.6 micromol/l, P < 0.001), and daily urinary fructose excretion was significantly greater in patients with diabetes (127.8 +/- 106.7 micromol/day) than in nondiabetic patients (37.7 +/- 23.0 micromol/day, P < 0.001). In patients with diabetes (n = 20), serum fructose concentrations (8.6 +/- 1.8 micromol/l, P < 0.001) and daily urinary fructose excretion (63.4 +/- 63.8 micromol/day, P < 0.01) significantly decreased by week 2 after admission.The present results differed from those of previous studies in that we found that the serum and urinary fructose concentrations decreased rapidly, concomitant with an improvement in glycemia. Therefore, hyperglycemia was associated with increased serum and urinary fructose concentrations in patients with diabetes.
Subclavian vascular access stenosis in dialysis patients
Authors: D Hernández, F Díaz, M Rufino, V Lorenzo, T Pérez, A Rodríguez, E De Bonis, M Losada, J M González-Posada, A Torres
Journal: Journal of the American Society of Nephrology (1998)

Stenosis of the subclavian vein (SVS) after cannulation occurs in 15 to 50% of chronic hemodialysis patients, and impedes the placement of an arteriovenous fistula in the ipsilateral arm. Its natural history and pathogenic mechanisms are not well established. This study examined 42 consecutive chronic renal failure patients (28 men and 14 women; 46+/-19 yr) in whom subclavian catheters had been placed as the initial vascular access for hemodialysis. All patients underwent sequential venography studies: at baseline (24 to 48 h after removal of the catheter) and 1, 3, and 6 mo thereafter. Venograms were considered abnormal when there was evidence of unequivocal strictures (more than 30% narrowing), with or without collateral circulation. At baseline, 52.4% (n=22) of patients showed stenotic vein lesions (n=19) or total thrombosis (n=3), and identical lesions were also observed after 1 mo. Surprisingly, 10 of 22 patients with initial SVS (45.4%) showed spontaneous recanalization of venous lesions in the venographies performed 3 mo after removal. The patients with normal baseline venograms (n=20) showed no change during follow-up. Patients with definitive stenosis at 6 mo (n=12) had a higher number of inserted catheters (1.58+/-0.6 versus 1.2+/-0.48; P < 0.05), longer time in place (49.08+/-32.2 versus 29.03+/-26.6 d; P < 0.05), and higher number of dialysis sessions (21+/-13.8 versus 12.4+/-11.4; P < 0.05) than those without SVS or with spontaneous recanalization of venous lesions during follow-up. Furthermore, a higher number of catheter-related infections were observed in patients with definitive SVS (66.6% versus 33.3%; P < 0.05). In summary, SVS is observed in more than half of patients 24 to 48 h after catheter removal and 1 mo later. Even when recanalization occurs in many cases, a definitive stenosis is seen in 28% of patients by the third month. Thus, the creation of an ipsilateral vascular access is possible provided that venography is normal at this time. Finally, mechanical factors and catheter-related infections are the major risk factors for the development of late SVS.
The Regulation of Steroid Action by Sulfation and Desulfation
Authors: Jonathan W. Mueller, Lorna C. Gilligan, Jan Idkowiak, Wiebke Arlt, Paul A. Foster
Journal: Endocrine Reviews (2015)

Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined.
Muscle-specific PPARγ-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones
Authors: Andrew W. Norris, Lihong Chen, Simon J. Fisher, Ildiko Szanto, Michael Ristow, Alison C. Jozsi, Michael F. Hirshman, Evan D. Rosen, Laurie J. Goodyear, Frank J. Gonzalez, Bruce M. Spiegelman, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2003)

Activation of peroxisome proliferator-activated receptor γ (PPARγ) by thiazolidinediones (TZDs) improves insulin resistance by increasing insulin-stimulated glucose disposal in skeletal muscle. It remains debatable whether the effect of TZDs on muscle is direct or indirect via adipose tissue. We therefore generated mice with muscle-specific PPARγ knockout (MuPPARγKO) using Cre/loxP recombination. Interestingly, MuPPARγKO mice developed excess adiposity despite reduced dietary intake. Although insulin-stimulated glucose uptake in muscle was not impaired, MuPPARγKO mice had whole-body insulin resistance with a 36% reduction (P < 0.05) in the glucose infusion rate required to maintain euglycemia during hyperinsulinemic clamp, primarily due to dramatic impairment in hepatic insulin action. When placed on a high-fat diet, MuPPARγKO mice developed hyperinsulinemia and impaired glucose homeostasis identical to controls. Simultaneous treatment with TZD ameliorated these high fat–induced defects in MuPPARγKO mice to a degree identical to controls. There was also altered expression of several lipid metabolism genes in the muscle of MuPPARγKO mice. Thus, muscle PPARγ is not required for the antidiabetic effects of TZDs, but has a hitherto unsuspected role for maintenance of normal adiposity, whole-body insulin sensitivity, and hepatic insulin action. The tissue crosstalk mediating these effects is perhaps due to altered lipid metabolism in muscle.
An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients
Authors: G Mazzarella
Journal: Gut (2002)

<h3>Abstract</h3> In zebrafish telencephalon, radial glial cells (RGs) show a remarkable ability to regenerate damaged neural tissue by re-initiating cell proliferation to produce neural precursors to rebuild the lost neural circuit. However, it is not fully understood how RGs respond to brain damage to initiate this regenerative response. Here we applied single-cell transcriptomics to RGs in adult zebrafish telencephalon and identified five RG subtypes, which are classified into four quiescent RGs (qRGs) and one proliferating RG (pRG). The four qRGs differentially express distinct subsets of qRG markers, suggesting heterogeneity of qRG in zebrafish adult brain. Interestingly, one qRG subtype shows high expression of ribosomal proteins, and its fraction increases in response to brain damage. Consistently, the mTOR pathway is activated in RGs near the injury site. It was reported that inflammatory responses of brain-resident immune cells, microglia, are required for inducing regenerative responses of RGs in zebrafish. Genetical elimination of microglia not only suppressed the damage-induced regenerative response of RGs, but also decreased the fraction of the ribosomal expression-enriched qRGs. Our pseudo-time analysis suggests that putative dormant RGs produce ribosomal expression-enriched qRGs through activation of ribosomal genesis, as well as suppression of cholesterol biogenesis, and pRGs through activation of the JAK/STAT pathway. Our findings reveal heterogeneity of qRGs in adult zebrafish brain and their dynamic regenerative response to brain damage.