P0078INVESTIGATION THE VARIANTS AT THE BINDING SITE OF INFLAMMATORY TRANSCRIPTION FACTOR IN PATIENTS WITH ESRD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
SUI-LUNG SU
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Disease Process ◽  
Binding Activity ◽  
Luciferase Reporter ◽  
Healthy Controls ◽  
Chip Assay ◽  
Potential Binding ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Inflammation is an important factor for enhancing the disease process from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates the expression of genes involved in inflammation. We investigated the potential association with the gene polymorphism of transcription factor binding site of NF-κB in ESRD patients. Method We used the Taiwan Biobank database, University of California, Santa Cruz, reference genome, chromatin immunoprecipitation sequencing database to find the SNPs at potential binding sites of NF-κB. In addition, we performed a case–control study and genotyped 847 patients with ESRD and 846 healthy controls at Tri-Service-General-Hospital from 2015 to 2016. Further we used ChIP-assay and Luciferase reporter assay to identify the binding activity at different genotype. Results Results of biometrics screening in the databases revealed 15 SNPs with the potential binding site of NF-κB. Genotype distributions of rs9395890 were significantly different in ESRD cases and healthy controls (P = 0.032). In the Dominant model, rs9395890 with T allele had a higher risk of ESRD (P = 0.032; odds ratio [OR] = 1.32, 95% confidence interval [CI] = 0.99–1.76). The ChIP assay reveals that around 1.49 times enrichment of NF-κB of the variant type TT when compared to that of the wild type GG in the rs9395890 (P<0.027; TT=3.20±0.16, GT=2.81±0.20, GG=1.71±0.18,) and the luciferase activity curve showed T allele was higher than G allele. Conclusion In conclusion, we demonstrate that rs9395890 may be associated with ESRD in the Taiwanese population.

scholarly journals Investigation of the variants at the binding site of inflammatory transcription factor NF-κB in patients with end-stage renal disease

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jia-Hwa Yang ◽  
Wei-Teing Chen ◽  
Meng-Chang Lee ◽  
Wen-Hui Fang ◽  
Yu-Juei Hsu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Renal Disease ◽  
Binding Site ◽  
End Stage Renal Disease ◽  
Stage Renal Disease ◽  
End Stage

Fibrin clot structure in patients with end-stage renal disease

2007 ◽  
Vol 98 (08) ◽  
pp. 339-345 ◽  
Author(s):  
Johannes Sidelmann ◽  
Mikkel Brabrand ◽  
Robert Pedersen ◽  
Jørgen Pedersen ◽  
Kim Esbensen ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Healthy Controls ◽  
Structure Characteristics ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Fibrin Structure ◽  
Plasma Markers ◽  
Fibrin Clots

SummaryFibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD).These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p<0.001), less compactable (p<0.001), and less susceptible to fibrinolysis (p<0.001) than clots from controls.The maximum rate of turbidity increase was also higher for the patients than controls (p<0.001), and scan-ning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p<0.001). Patients had higher plasma concentrations of fibrinogen, C-reative protein and interleukin 6 than controls.These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.

A single polypeptide possesses the binding and transcription activities of the adenovirus major late transcription factor

1986 ◽  
Vol 6 (12) ◽  
pp. 4723-4733
Author(s):  
L A Chodosh ◽  
R W Carthew ◽  
P A Sharp
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Binding Site ◽  
Rna Polymerase Ii ◽  
Sodium Dodecyl ◽  
Binding Activity ◽  
Affinity Column ◽  
Dna Binding Activity ◽  
Dna Fragment

A simple approach has been developed for the unambiguous identification and purification of sequence-specific DNA-binding proteins solely on the basis of their ability to bind selectively to their target sequences. Four independent methods were used to identify the promoter-specific RNA polymerase II transcription factor MLTF as a 46-kilodalton (kDa) polypeptide. First, a 46-kDa protein was specifically cross-linked by UV irradiation to a body-labeled DNA fragment containing the MLTF binding site. Second, MLTF sedimented through glycerol gradients at a rate corresponding to a protein of native molecular weight 45,000 to 50,000. Third, a 46-kDa protein was specifically retained on a biotin-streptavidin matrix only when the DNA fragment coupled to the matrix contained the MLTF binding site. Finally, proteins from the most highly purified fraction which were eluted and renatured from the 44- to 48-kDa region of a sodium dodecyl sulfate-polyacrylamide gel exhibited both binding and transcription-stimulatory activities. The DNA-binding activity was purified 100,000-fold by chromatography through three conventional columns plus a DNA affinity column. Purified MLTF was characterized with respect to the kinetic and thermodynamic properties of DNA binding. These parameters indicate a high degree of occupancy of MLTF binding sites in vivo.

scholarly journals Inflammatory and metabolic profiles of patients with end-stage renal disease: potential strategy for predictive, preventive, and personalized medicine

2021 ◽  
Author(s):  
Xiaoxin Ma ◽  
Yongli Wang ◽  
Hongyu Wu ◽  
Fei Li ◽  
Xiping Feng ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
End Stage Renal Disease ◽  
Healthy Controls ◽  
Preventive And Personalized Medicine ◽  
Hydroxyphenylacetic Acid ◽  
Potential Strategy ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
And Personalized Medicine

Abstract Objectives Few studies reported the periodontal disease-related metabolic profile of end-stage renal disease (ESRD) patients. The present study aimed to compare the inflammatory and metabolic differences between patients with ESRD and healthy controls, and to identify potential useful biomarkers for predictive, preventive, and personalized medicine (PPPM) in GCP and serum of ESRD patients.Methods Patients with ESRD (ESRD group; n = 52) and healthy controls (HC group; n = 44) were recruited. Clinical periodontal parameters were recorded. The differential metabolites in the GCF and serum were identified by liquid chromatography/mass spectrometry. Inflammatory markers including Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8) and C-reactive protein (CRP) were also assessed. Results In ESRD group, IL-8 and CRP were significantly higher in GCF, whereas IL-6 and CRP were significantly higher in serum, compared with HC group (all P < 0.05). In the case of GCF, taurine levels were positively correlated with IL-8 levels in both groups (all P < 0.05). In the case of serum, L-phenylalanine and p-hydroxyphenylacetic acid levels were positively correlated with CRP levels in both groups (all P < 0.05). Significant positive correlation was observed between pseudouridine and IL-6 levels only in ESRD group. Conclusions IL-8 and CRP were potential inflammatory makers. Metabolites of taurine in GCF as well as L-phenylalanine and p-hydroxyphenylacetic acid in serum were possible biomarkers that correlated with inflammatory cytokine. All these biomarkers may consider as a potential strategy for the prediction, diagnosis, prognosis, and management of personalized periodontal therapy in the population with ESRD.

Abstract P119: Association Between Inspiratory Muscle Strength and Sympathetic Cardiac Modulation and Baroreflex in Patients With End Stage Renal Disease Undergoing Hemodialysis

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Kátia B Scapini ◽  
Silvia B Souza ◽  
Valéria C Hong ◽  
Oscar A Moraes ◽  
Jacqueline F Machi ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Baroreflex Sensitivity ◽  
Frequency Component ◽  
Inspiratory Muscle ◽  
Healthy Controls ◽  
Vagal Modulation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Inspiratory Muscle Strength ◽  
Esrd Patients

Introduction: Patients with end-stage renal disease (ESRD) are susceptible to development of autonomic dysfunction and have metabolic and muscular changes which are associated with decreased functional capacity. Objectives: To evaluate respiratory muscle strength and cardiac autonomic modulation in ESRD patients undergoing hemodialysis. Methods: ESRD patients undergoing hemodialysis (n= 9, mean age 46.2±14.1 years) and healthy controls (n =7, mean age 44.6±14.6 years) were assessed. Non–invasive curves of blood pressure were recorded continuously (Finometer ®) for 10 minutes. The heart rate variability was estimated in the time and frequency domain. Inspiratory and expiratory maximal pressures (IPmax and EPmax) were quantified using a pressure transducer. Mann-Whitney and Spearman tests were used. The results were expressed as mean ± SD. Results: Regarding respiratory muscle strength, ESRD patients had lower inspiratory (IPmax: 79.1±25.0 vs 121.3±24.3cmH 2 O, p=0.03) and expiratory muscle strength (EPmax 92.8±23.1 vs 153.8±23.5cmH 2 O, p=0.01) then healthy controls. ESRD patients presented lower heart rate variability than healthy controls (SDNN: 19.2±4.0 vs 52.6±18.8ms, p=0.000) and lower RMSSD, an index of vagal modulation (11.8±5.2 vs 46.1±20.4ms, p=0.000). Regarding frequency domain indexes, ESRD patients presented higher low-frequency component (LFnu= 68.9±11.9 vs 47.3± 2.8, p=0.008), lower high-frequency component (HFnu= 31.1±11.9 vs 52.7±12.8, p=0.008) and higher sympathovagal balance (LF/HF: (LF/HF= 3.1±1.3 vs 1.1±0.5, p=0.005) when compared to controls. Furthermore baroreflex sensitivity was reduced in ESRD patients (alfa index: 3.6±1.6 vs 11.7±4.4ms/mmHg, p=0.002). In ESRD patients the IPmax was significantly associated with LF (r=-0.813, p=0.014) and with alfa index (r=-0.900, p=0.037). Conclusion: ESRD patients undergoing hemodialysis presented reduced inspiratory muscle strength, increased sympathetic modulation and reduced cardiac vagal modulation and impaired baroreflex sensitivity. In these patients inspiratory muscle strength was associated with sympathetic cardiac modulation and baroreflex.

scholarly journals Association between matrix Gla protein and ulcerative colitis according to DNA microarray data

2019 ◽  
Vol 8 (1) ◽  
pp. 66-75 ◽  
Author(s):  
Xu-Yang Dong ◽  
Mei-Xu Wu ◽  
Hui-Min Zhang ◽  
Hong Lyu ◽  
Jia-Ming Qian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Binding Site ◽  
Dna Microarray ◽  
Bioinformatics Analysis ◽  
Matrix Gla Protein ◽  
Luciferase Reporter ◽  
Upstream Region ◽  
Healthy Controls ◽  
Microarray Profiling

Abstract Background Matrix Gla protein (MGP) is a secreted protein contributed to the immunomodulatory functions of mesenchymal stromal cells. Microarray profiling found a significantly higher expression level of the extracellular matrix gene MGP in patients with ulcerative colitis (UC). However, little is known about the role of MGP in UC and its upstream signaling regulation. This study aimed to identify the expression of MGP in UC and its upstream regulator mechanism. Methods Colonic mucosa biopsies were obtained from patients with UC and healthy controls. DNA microarray profiling was used to explore underlying genes correlating with UC development. Mice were fed with water containing different concentrations of dextran sodium sulfate (DSS) to induce an experimental colitis model. Colonic tissues were collected and evaluated using immunohistochemistry, immunoblot, real-time polymerase chain reaction, and chromatin immunoprecipitation assay. Bioinformatics analysis was performed to identify candidate MGP gene-promoter sequence and transcription-initiation sites. Luciferase-reporter gene assay was conducted to examine the potential transcription factor of MGP gene expression. Results The expression of MGP was significantly increased in colonic tissues from UC patients and DSS-induced colitis models, and was positively correlated with disease severity. Bioinformatics analysis showed a conserved binding site for Egr-1 in the upstream region of human MGP gene. The significantly higher level of Egr-1 gene expression was found in UC patients than in healthy controls. The activity of luciferase was significantly enhanced in the Egr-1 expression plasmid co-transfected group than in the control group and was further inhibited when co-transfected with the Egr-1 binding-site mutated MGP promoter. Conclusions Up-regulated expression of MGP was found in UC patients and DSS-induced colitis. The expression of MGP can be regulated by Egr-1.

Immunodiagnosis and molecular validation of Toxoplasma gondii infection among patients with end-stage renal disease undergoing haemodialysis

Parasitology ◽  
2019 ◽  
Vol 146 (13) ◽  
pp. 1683-1689 ◽  
Author(s):  
Zahra Arab-Mazar ◽  
Shirzad Fallahi ◽  
Davood Yadegarynia ◽  
Amirreza Javadi Mamaghani ◽  
Seyyed Javad Seyyed Tabaei ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Blood Samples ◽  
Igm Antibodies ◽  
Stage Renal Disease ◽  
End Stage

AbstractInfection is a significant cause of morbidity and mortality in patients with chronic kidney disease, especially who were under dialysis due to their depressed immunity. Toxoplasma gondii is a ubiquitous parasite that causes severe manifestations in immunocompromised patients. This case-control study was conducted to the immunodiagnosis and molecular validation of T. gondii infection among patients with end-stage renal disease undergoing haemodialysis. The study population consisted of 260 haemodialysis patients and 259 healthy controls referred to the main dialysis centres of Tehran, Iran during 2016. Anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies were assessed using enzyme-linked immunosorbent assay. As well, the T. gondii genomic DNA in whole blood samples of IgM-positive patients and healthy controls was evaluated using GRA6-polymerase chain reaction (PCR) and SAG1-loop-mediated isothermal amplification (LAMP) assays. The anti-T. gondii IgG and IgM antibodies were detected in 175 (67.3%) and 18 (7%) of haemodialysis patients and 122 (47%) and 4 (1.5%) of controls, respectively. Two of the 18 blood samples from IgM-positive patients and none of the IgM-positive control subjects were positive by GRA6-PCR. Whereas, nine and two blood samples of IgM-positive patients and controls were positive for Toxoplasma DNA by a SAG1-LAMP technique respectively. The seropositivity of the Toxoplasma IgM antibody was significantly different between haemodialysis patients and healthy controls which was confirmed by PCR and LAMP. The higher prevalence of T. gondii infection in haemodialysis patients compared with the controls proposes that these patients can be a group at risk for toxoplasmosis and screening for toxoplasmosis before dialysis is necessary for the patients.

scholarly journals Comparison of aortic pressures and aortic elastic properties between patients with end-stage renal disease and healthy controls

2019 ◽  
Vol 11 (2) ◽  
pp. 77-83 ◽  
Author(s):  
Macit Kalçık ◽  
Mucahit Yetim ◽  
Tolga Doğan ◽  
İbrahim Doğan ◽  
Barış Eser ◽  
...  
Keyword(s):  
Elastic Properties ◽  
End Stage Renal Disease ◽  
Aortic Stiffness ◽  
Aortic Distensibility ◽  
Ascending Aorta ◽  
Stiffness Index ◽  
Healthy Controls ◽  
Aortic Compliance ◽  
Stage Renal Disease ◽  
End Stage

Background Current evidence indicates that vascular calcification plays an essential role in the development of cardiovascular diseases in end-stage renal disease (ESRD) patients. Arterial stiffness is a marker of increased cardiovascular risk in various populations. The aim of this study is to evaluate the elastic properties of ascending aorta in patients with ESRD. Methods This single-center study enrolled 96 patients (45 females, age: 57.2 ± 12.8 years) with ESRD and 96 healthy controls (52 females, age: 55.3 ± 10.1 years). Aortic pressures and aortic elastic parameters including aortic strain, aortic distensibility, aortic stiffness index, and aortic compliance were calculated using accepted formulae. Results The hemodynamic parameters including aortic pulse pressure, aortic mean pressure, aortic fractional pulse pressure, and aortic pulsatility index were significantly higher in patients with ESRD. Systolic and diastolic aortic diameters were similar between the groups. However, pulsatile aortic diameter change, aortic strain, aortic distensibility, and aortic compliance were significantly lower, whereas aortic stiffness index was significantly higher in ESRD group. Conclusions The results demonstrated that a significant difference was present in terms of aortic blood pressures between patients with ESRD and controls. In addition, the elastic properties of ascending aorta were decreased in patients with ESRD.

Calciphylaxis: Pathogenesis and Therapy

1998 ◽  
Vol 2 (4) ◽  
pp. 245-248 ◽  
Author(s):  
Richard L. Worth
Keyword(s):  
Clinical Manifestations ◽  
Disease Process ◽  
Skin Lesions ◽  
Corticosteroid Administration ◽  
Inappropriate Treatment ◽  
Important Diagnostic Tool ◽  
Subcutaneous Tissues ◽  
Recent Debate ◽  
Stage Renal Disease ◽  
End Stage

Background: Calciphylaxis is a rare, painful and debilitating disease in which calcification of the skin and subcutaneous tissues or of internal organs can lead to skin necrosis, discolouration, and other skin lesions. The typical patient has end-stage renal disease (ESRD) and hyperparathyroidism. Selye originally characterized this syndrome in rats and distinguished it from other syndromes of abnormal calcification by the following sequence: sensitizers, latent period, and challengers. There has been recent debate regarding misdiagnosis and failure to differentiate this category of patients even in clinical studies. Objective: In this article the clinical manifestations of calciphylaxis are described; the importance of distinguishing this condition from other calcification syndromes is explained; risk factors, sensitizers, and challenges are reviewed; treatments of choice are discussed; and the merits of parathyroidectomy are evaluated. Conclusion: It is important to consider calciphylaxis in a differential diagnosis of calcification syndromes and in treating patients with ESRD and hyperparathyroidism, because early diagnosis and treatment can interrrupt the progression of the disease process; the disease is painful and debilitating; and inappropriate treatment such as corticosteroid administration may aggravate the condition. Skin biopsy is an important diagnostic tool when the condition is suspected. Parathyroidectomy may be justified because the untreated disease itself has significant rates of morbidity and mortality and because this treatment occasionally leads to dramatic clinical improvement.

scholarly journals Activation of Hodgkin cells via the CD30 receptor induces autocrine secretion of interleukin-6 engaging the NF-kappabeta transcription factor

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2443-2449 ◽  
Author(s):  
HJ Gruss ◽  
D Ulrich ◽  
SK Dower ◽  
F Herrmann ◽  
MA Brach
Keyword(s):  
Monoclonal Antibody ◽  
Transcription Factor ◽  
Binding Site ◽  
Transcriptional Activation ◽  
Interleukin 6 ◽  
Growth Factor Receptor ◽  
Human Growth ◽  
Binding Activity ◽  
Cross Linking ◽  
Growth Hormone Gene

The CD30 surface molecule is a recently identified member of the tumor necrosis factor/nerve growth factor receptor superfamily. Within the cytoplasmic signal transducing domain, CD30 shares no significant homology to other members of this family. Signaling events engaged via CD30 are still unknown. We here identify the NF-kappabeta transcription factor as a target of the CD30-induced signal pathway in Hodgkin's disease (HD) cells. Exposure of HD cells to CD30 ligand induces release of interleukin-6 (IL-6) that can be duplicated by cross-linking HD- cells to an agonistic anti-CD30 specific monoclonal antibody (alphaCD30), but not by cross-linking to an isotype-identical irrelevant monoclonal antibody. Cross-linking of HD cells to alphaCD30 leads to enhanced accumulation of IL-6 mRNA in a time-dependent fashion resulting from transcriptional activation of the IL-6 promoter. Transient transfection assays using a series of deleted IL-6 promoter constructs linked to the human growth hormone gene as a reporter gene furthermore indicate that transcriptional activation of the IL-6 promoter requires the presence of an intact NF-kappabeta binding site. In addition, introduction of an NF-kappabeta binding site appeared to be sufficient to confer inducibility of an heterologous promoter on activation of CD30 in HD cells. Cross-linking of CD30 promotes rapid and transient binding activity of nuclear proteins to the NF-kappabeta recognition site of the IL-6 promoter. Supershift experiments using a series of monoclonal antibodies recognizing distinct members of the NF- kappaBeta transcription factor family furthermore indicate that in CD30 cross-linked HD cells p50, p65/Rel-A, and Rel-B are present, whereas the c-rel protein is not.

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