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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/28642294/mhc-class-ii-invariant-chain-peptide-or-gamma-delta-t-cell-depletion-ameliorates-experimental-preeclampsia
#1
Piyali Chatterjee, Valorie L Chiasson, Geetha Seerangan, Eugene De Guzman, Moheb Milad, Kelsey R Bounds, Olga Gasheva, Richard P Tobin, Mohamad Hatahet, Shelley Kopriva, Kathleen A Jones, M Karen Newell-Rogers, Brett Mitchell
Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia; however, the molecular mechanisms involved are unknown.  We tested the hypothesis that Toll-like receptor activation induces MHC class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause preeclampsia-like features in mice.  Treatment with VG1177, a competitive antagonist peptide for CLIP in the groove of MHC class II, was able to both prevent and treat preeclampsia-like features in mice...
June 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28634189/reduced-platelet-count-but-no-major-platelet-function-abnormalities-are-associated-with-loss-of-function-atp-binding-cassette-1-abca1-gene-mutations
#2
Pietro Minuz, Alessandra Meneguzzi, Eti Alessandra Femia, Cristiano Fava, Stefano Calabria, Mariangela Scavone, Donatella Benati, Giovanni Poli, Carlo Zancanaro, Sebastiano Calandra, Tiziano Lucchi, Marco Cattaneo
Loss of function mutations of the the ATP-binding cassette-1 (ABCA1) gene are the cause of Tangier disease (TD) in homozygous subjects and familial HDL deficiency (FHD) in heterozygous subjects. These disorders are characterized by reduced plasma HDL-cholesterol and altered efflux of cholesterol from cells. Previous studies in TD patients and ABCA1(-/-) murine models reported defects in platelet count, morphology and function, but the issue is still controversial. We analysed three subjects with low to very low HDL cholesterol levels due to loss of function mutations of the ABCA1 gene...
June 20, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28620012/metabolic-disturbances-of-non-alcoholic-fatty-liver-resemble-the-alterations-typical-for-type-2-diabetes
#3
Bram Brouwers, Vera B Schrauwen-Hinderling, Tomas Jelenik, Anne Gemmink, Bas Havekes, Yvonne Bruls, Dennis Dahlmans, Michael Roden, Matthijs K C Hesselink, Patrick Schrauwen
Non-alcoholic fatty liver (NAFL) is an independent risk factor for the development of type 2 diabetes (T2DM). We examined metabolic perturbations in people with NAFL, patients with T2DM and people with normal intrahepatic lipid (IHL) (CON). A 2-step (10mU/m(2)/min, 40mU/m(2)/min) hyperinsulinemic-euglycemic clamp was performed in 11 NAFL, 13 T2DM and 11 CON, all matched for BMI and aerobic fitness. IHL was measured using proton magnetic resonance spectroscopy. Because of high IHL variability in T2DM patients, this group was separated into a high IHL (IHL≥5...
June 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28620011/dietary-restriction-but-not-angiotensin-ii-type-1-receptor-blockade-improves-dna-damage-related-vasodilator-dysfunction%C3%A2-in-rapidly-aging-ercc1-%C3%AE-mice
#4
Haiyan Wu, Bibi S van Thiel, Paula Katherine Bautista-Nino, Erwin Reiling, Matej Durik, Frank P J Leijten, Yanto Ridwan, Renata M C Brandt, Harry van Steeg, Martijn E T Dollé, Wilbert P Vermeij, Jan H J Hoeijmakers, Jeroen Essers, Ingrid van der Pluijm, A H Jan Danser, Anton J M Roks
DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1(∆/-) mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system ...
June 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28611236/quantification-of-circulating-gdf-11-and-%C3%AE-2-mg-in-aged-patients-with-age-related-impairment-in-cognitive-function
#5
Rungong Yang, Shuhong Fu, Liang Zhao, Bei Zhen, Ling Ye, Xiaolu Niu, Xiaoxia Li, Pumin Zhang, Jie Bai
GDF-11 has been implicated in reverse effects of aging on the central nervous system of humans. β2-MG has been reported to negatively regulate cognitive. However, there is a lot of controversy about the role of GDF-11 and β2-MG in ageing and cognitive regulation. Objective: To examine the involvement of GDF-11 and β2-MG in the aging process and cognitive dysfunction. Methods: A total of 51 healthy subjects and 41 elderly patients with different degrees of age-related cognitive impairment participated in the study...
June 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28611235/improvement-in-exercise-duration-lung-function-and-well-being-in-g551d-cystic-fibrosis-patients-a-double-blind-placebo-controlled-randomised-cross-over-study-with-ivacaftor
#6
Dominic T Keating, Deirdre Edgeworth, Matthew Ellis, Brenda Button, Elyssa Williams, Denise Clark, Audrey Tierney, Stephane Heritier, Anastase Kotsimbos, John Wilson
G551D , a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in cystic fibrosis (CF) is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%Δ) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, BMI, sweat chloride, and disease specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore))...
June 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28592554/urinary-glycated-uromodulin-in-diabetic-kidney-disease
#7
Chia-Chu Chang, Chen-Yu Chen, Ching-Hui Huang, Chia-Lin Wu, Hung-Ming Wu, Ping-Fang Chiu, Chew-Teng Kor, Ting-Huan Chen, Geen-Dong Chang, Cheng-Chin Kuo, Hui-Chin Wen, Chih-Yang Huang, Chung-Ho Chang
Advanced glycation end products (AGEs) form during oxidative stress, which is increased in diabetes mellitus (DM). Uromodulin is a protein with a renal protective effect, and may be subject to glycation. The implications of uromodulin glycation and AGEs in the urine are not understood. Here, immunoprecipitation and liquid chromatography-mass spectrometry identified glycated uromodulin (glcUMOD) in the urine of 62.5% of patients with diabetic kidney disease (DKD), 20.0% of patients with non-diabetic chronic kidney disease (CKD) but non-DM, and no DM patients with normal renal function or healthy control participants; a finding replicated in a larger cohort of 84 patients with CKD in a case-control study (35 with DM, 49 without)...
June 7, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28588103/mycobacteriumtuberculosis-rv3615c-is-a-highly-immunodominant-antigen-and-specifically-inducespotent-th1-type-immune-responses-in-tuberculosis-pleurisy
#8
Jiangping Li, Juan Shen, Suihua Lao, Xiaomin Li, Jie Liu, Changyou Wu
T-cell responses have been demonstrated essential for preventing M.tb infection. The Th1-cytokines produced by T cells, such as INF-γ, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity...
June 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28572401/abcb1-gene-polymorphism-associated-with-clinical-factors-can-predict-drug-resistant-tuberculosis
#9
Yasmin Pontual, Vanessa da Silveira Dos Santos Pacheco, Sergio Pereira Monteiro, Marcel S B Quintana, Marli Jane Martins Costa, Valeria Cavalcanti Rolla, Liane De Castro
Polymorphism in ABCB1 gene encoding P-glycoprotein, a transmembrane drug efflux pump, contributes to drug resistance and have been widely studied, however, their association with rifampicin and ethambutol resistance in tuberculosis patients are still unclear. Genotype/allele/haplotype frequencies in c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) were obtained from 212 patients, of these, 80 patients with rifampicin and/or ethambutol resistance were selected as case group and 132 control-group through the result of their culture and drugs sensitive test...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28566469/visceral-adipose-tissue-activated-macrophage-content-and-inflammatory-adipokine-secretion-is-higher-in-pre-eclampsia-than-in-healthy-pregnancy
#10
Shahzya Huda, FIona Jordan, JAck Bray, Gillian Love, Reba Payne, Naveed Sattar, Dilys J Freeman
Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined...
May 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28566468/smad7-protects-against-acute-kidney-injury-by-rescuing-tubular-epithelial-cells-from-the-g1-cell-cycle-arrest
#11
Sha Fu, Ying Tang, Xiao Ru Huang, Min Feng, Anping Xu, Hui Y Lan
Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored. Here we report that Smad7 protects against AKI by rescuing the G1 cell cycle arrest of tubular epithelial cells (TECs) in ischemia/reperfusion-induced AKI in mice in which Smad7 gene is disrupted or restored locally into the kidney. In Smad7 gene knockout (KO) mice, more severe renal impairment including higher levels of serum creatinine and massive tubular necrosis was developed at 48 h after AKI...
May 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28559425/fgf21-ameliorates-diabetic-cardiomyopathy-by-activating-the-ampk-paraoxonase-1-signaling-axis-in-mice
#12
Fan Wu, Baile Wang, Saisai Zhang, Lihua Shi, Yanfang Wang, Rongrong Xiong, Xuebo Pan, Fanghua Gong, Xiaokun Li, Zhuofeng Lin
Aims: The aim in present study is to explore the molecular mechanism of FGF21 against diabetic cardiomyopathy. Materials and methods: FGF21 deficient mice and wild type littermates were used to induce diabetic mice by treatment with streptozotocin/high-fat diet (STZ/HFD), and then evaluated the difference of diabetic cardiomyopathy between two types of mice. Otherwise, primary cultured cardiomyocytes were also used to explore the potential molecular mechanism of FGF21 against high glucose-induced cardiomyocyte injuries...
May 30, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28550144/exacerbation-of-oxygen-glucose-deprivation-induced-blood-brain-barrier-disruption-potential-pathogenic-role-of-interleukin-9-in-ischemic-stroke
#13
Sha Tan, Yilong Shan, Yuge Wang, Yinyao Lin, Siyuan Liao, Zhezhi Deng, Li Zhou, Wei Cai, Qin Zeng, Lei Zhang, Bingjun Zhang, Xuejiao Men, Haiyan Li, Xueqiang Hu, Changyou Wu, Lisheng Peng, Zhengqi Lu
Interleukin (IL) -9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke. We recruited 42 patients newly diagnosed with ischemic stroke and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3+CD4+IL-9+ and CD3+CD8+IL-9+ cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals...
May 26, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28539328/dynamic-response-toinitial-stage-blindnessin-visual-system-development
#14
Erping Long, Xiayin Zhang, Zhenzhen Liu, Xiaohang Wu, Xuhua Tan, Duoru Lin, Qianzhong Cao, Jingjing Chen, Zhuoling Lin, Dongni Wang, Xiaoyan Li, Jing Li, Jinghui Wang, Wangting Li, Haotian Lin, Weirong Chen, Yizhi Liu
Sensitive periods and experience-dependent plasticity have become core issues in visual system development. Converging evidence indicates that visual experience is an indispensable factor in establishing mature visual system circuitry during sensitive periods and the visual system exhibits substantial plasticity when facing deprivation. The mechanisms that underlie the environmental regulation of visual system development and plasticity are of great interest but need further exploration. Here, we investigated a unique sample of human infants who experienced initial stage blindness (beginning at birth and lasting 2 to 8 months) before the removal of bilateral cataracts...
May 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28536293/peroxisome-proliferator-activated-receptor-%C3%AE-agonism-attenuates-endotoxaemia-induced-muscle-protein-loss-and-lactate-accumulation-in%C3%A2-rats
#15
Hannah Crossland, Dumitru Constantin-Teodosiu, Sheila Gardiner, Paul Greenhaff
The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5±0.1 mg(.)kg(-1.)day(-1)) for two weeks before and during 24 h continuous intravenous infusion of LPS (15 μg(...
May 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#16
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28522681/endothelial-nox1-oxidase-assembly-in-human-pulmonary-arterial-hypertension-driver-of-gremlin1-mediated-proliferation
#17
Imad Al Ghouleh, Sanghamitra Sahoo, Daniel N Meijles, Jefferson H Amaral, Daniel S de Jesus, John Sembrat, Mauricio Rojas, Dmitry A Goncharov, Elena A Goncharova, Patrick J Pagano
Background: Pulmonary arterial hypertension (PAH) is a rapidly degenerating and devastating disease of increased pulmonary vessel resistance leading to right heart failure. Palliative modalities remain limited despite recent endeavors to investigate the mechanisms underlying increased pulmonary vascular resistance, i.e. aberrant vascular remodeling and occlusion. However, little is known of the molecular mechanisms responsible for endothelial proliferation, a root cause of PAH-associated vascular remodeling...
May 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28495910/oxidative-imbalance-and-kidney-damage-in-spontaneously-hypertensive-rats-activation-of-extrinsic-apoptotic-pathway
#18
Daniele La Russa, Elvira Brunelli, Daniela Pellegrino
In both humans and animals, essential hypertension acts as a risk factor for subclinical kidney damage and precedes renal dysfunction. Several lines of evidence indicate that hypertension and oxidative stress are closely related. The increase in vascular oxidative stress plays a key role in the pathophysiological consequences of hypertension, including kidney disease. Our study examined this issue in SHR, a reliable model of essential hypertension. We used SHR 20 weeks-old when hypertension is stably developed, vascular remodeling started, but kidney function is preserved...
May 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28495909/pulse-wave-velocity-is-associated-with-cognitive-impairment-in-hemodialysis-patients
#19
Susanne Angermann, Marcus Baumann, Siegfried Wassertheurer, Christopher Clemens Mayer, Dominik Steubl, Christine Hauser, Yana Suttmann, Anna-Lena Reichelt, Robin Satanovskij, Georg Lorenz, Moritz Lukas, Bernhard Haller, Uwe Heemann, Timo Grimmer, Christoph Schmaderer
BACKGROUND: Cognitive impairment in hemodialysis patients is common and associated with adverse outcomes. So far, the underlying pathogenesis remains unclear. Therefore, we examined the potential relationship between cognitive impairment and three different categories of risk factors with particular focus on arterial stiffness measured by Pulse Wave Velocity (PWV). METHODS: A total of 201 chronic hemodialysis patients underwent cognitive testing under standardized conditions using the Montreal Cognitive Assessment (MoCA)...
May 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28487470/discrepant-effects-of-heart-failure-on-electrophysiological%C3%A2-property-in-right-ventricular-outflow-tract-and-left-ventricular-outflow-tract-cardiomyocytes
#20
Yen-Yu Lu, Chen-Chuan Cheng, Chin-Feng Tsai, Yung Kuo Lin, Ting-I Lee, Yao-Chang Chen, Shih-Ann Chen, Yi Jen Chen
Ventricular arrhythmias commonly arise from the right and left ventricular outflow tracts (RVOT/LVOT) in patients without structural heart disease. Heart failure (HF) significantly increases the risk of ventricular arrhythmias. The regional differences and how HF affects the electrophysiological characteristics of RVOT and LVOT cardiomyocytes remain unclear. The whole-cell patch clamp technique was used to investigate the action potentials and ionic currents in isolated single RVOT and LVOT cardiomyocytes from control and rapid ventricular pacing-induced HF rabbit...
May 9, 2017: Clinical Science (1979-)
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