scholarly journals HLA-DRB1 Amino Acid Positions and Residues Associated with Antibody-positive Rheumatoid Arthritis in Black South Africans

2018 ◽  
Vol 46 (2) ◽  
pp. 138-144 ◽  
Author(s):  
Nimmisha Govind ◽  
Richard J. Reynolds ◽  
Bridget Hodkinson ◽  
Claudia Ickinger ◽  
Michele Ramsay ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Amino Acid ◽  
Regression Models ◽  
Amino Acid Residues ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Logistic Regression Models ◽  
South Africans ◽  
Black South Africans ◽  
Univariate Analyses

Objective.To investigate the association of specific amino acid positions, residues, and haplotypes of HLA-DRB1 in black South Africans with autoantibody-positive rheumatoid arthritis (RA).Methods.High-resolutionHLA-DRB1genotyping was performed in 266 black South Africans with autoantibody-positive RA and 362 ethnically and geographically matched controls. The alleles were converted to specific amino acid residues at polymorphic sites for downstream analyses. Logistic regression models were used to test whether variability at site, specific amino acid residues, and haplotypes (constructed from positions 11, 71, and 74) were associated with RA.Results.Of the 29 amino acid positions examined, positions 11, 13, and 33 (permutation p = 3.4e-26, 1.2e-27, and 2.1e-28, respectively) showed the strongest association with RA. Univariate analyses of individual amino acid residues showed valine at position 11 (OR 5.1, 95% CI 3.7–7.0) and histidine at position 13 (OR 6.1, 95% CI 4.2–8.6) conferred the highest risk. The valine containing haplotypes of position 11, 71, 74, V_K_A conferred the most risk (OR 4.52, 95% CI 2.68–7.61) and conversely the haplotype with serine at this position, S_K_R, conferred the most protection (OR 0.83, 95% CI 0.61–1.15).Conclusion.Autoantibody-positive RA in black South Africans is associated with histidine at position 13 and valine at position 11 of HLA-DRB1, and haplotypes with valine at position 11 conferred the highest risk; conversely, serine at position 11 conveyed protection.

scholarly journals Site-specific replacement of amino acid residues within the CD binding loop of rat oncomodulin.

1990 ◽  
Vol 265 (24) ◽  
pp. 14450-14456 ◽  
Author(s):  
W.A. Palmisano ◽  
C.L. Treviño ◽  
M.T. Henzl
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Site Specific ◽  
Binding Loop

Abstract P36: Lesional Perfusion and Permeability Are Diagnostic and Prognostic Biomarkers of Cavernous Angioma With Symptomatic Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Je Yeong Sone ◽  
Nicholas Hobson ◽  
Sharbel Romanos ◽  
Abhinav Srinath ◽  
Abdallah Shkoukani ◽  
...  
Keyword(s):  
Regression Models ◽  
Prognostic Biomarker ◽  
Information Criterion ◽  
Cavernous Angioma ◽  
Prognostic Biomarkers ◽  
Diagnostic Efficacy ◽  
Logistic Regression Models ◽  
Conventional Mri ◽  
Contrast Enhanced ◽  
Univariate Analyses

Introduction: Diagnosis of cavernous angioma with symptomatic hemorrhage (CASH) requires MRI evidence of lesional bleeding associated directly with attributable symptoms. However, hemorrhagic signs of CASH may become clinically silent on conventional MRI after 3 months. As CASH is likely to rebleed for several years, accurate diagnosis of CASH that bled more than 3 months prior is needed. Hypothesis: Perfusion and permeability derivations of dynamic contrast-enhanced quantitative perfusion (DCEQP) MRI can diagnose CASH and predict bleeding/growth in CAs. Methods: CAs of 205 consecutively enrolled patients scanned with DCEQP during clinical visits were classified as CASH that bled 3 - 12 months prior (N = 55) versus non-CASH (N = 658) or CA with (N = 23) versus without (N = 721) bleeding/growth within a year after MRI. Demographics and 13 perfusion and 13 permeability derivations of DCEQP were assessed via machine learning and univariate analyses. Logistic regression models ln ( P / 1 - P ) = Σ (β i x i ) + β 0 were selected as the best diagnostic and prognostic biomarkers by minimizing the Bayesian information criterion (BIC). Results: The best diagnostic biomarker of CASH that bled 3 - 12 months prior (BIC = 321.6, Figure A) showed 80% sensitivity and 82% specificity. Permeability derivations did not add diagnostic efficacy when combined with perfusion. The best prognostic biomarker of bleeding/growth (BIC = 201.5, Figure B) showed 77% sensitivity and 72% specificity. Conclusion: Perfusion imaging may diagnose CASH even after hemorrhagic signs disappear on conventional MRI. A combination of permeability and perfusion derivations may help predict bleeding/growth in CAs.

scholarly journals Genetic Diversity of the cagA gene of Helicobacter pylori strains from Sudanese Patients with Different Gastroduodenal Diseases

2019 ◽  
Author(s):  
Hadeel Gassim Hassan ◽  
Abeer Babiker Idris ◽  
Mohamed A. Hassan ◽  
Hisham N. Altayb ◽  
Kyakonye Yasin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Amino Acid ◽  
Novel Mutation ◽  
Amino Acid Residues ◽  
Specific Amino Acid ◽  
Gastrointestinal Malignancy ◽  
High Incidence ◽  
H Pylori ◽  
High Level ◽  
Chloride Method

AbstractBackgroundThere is an increase in the prevalence of Helicobacter pylori infection in Sudan, accompanied by a high incidence of upper gastrointestinal malignancy. The cytotoxin-associated gene cagA gene is a marker of a pathogenicity island (PAI) in H. pylori and plays a crucial role in determining the clinical outcome of Helicobacter infections.ObjectiveThis study aimed to determine the frequency and heterogeneity of the cagA gene of H. pylori and correlate the presence of cagA gene with clinical outcomes.Materials and methodsFifty endoscopy biopsies were collected from Fedail and Soba hospitals in Khartoum state. DNA was extracted using the Guanidine chloride method followed by PCR to amplify 16S rRNA and cagA gene of H. pylori using specific primers. DNA amplicons of cagA gene were purified and sequenced. Bioinformatics and statistical analysis were done to characterize and to test the association between cagA gene and gastric complications.ResultsCagA gene was detected in 20/37(54%) of the samples that were found positive for H. pylori. There was no association between endoscopy finding and the presence of the cagA gene (p = 0.225). Specific amino acid variations were found at seven loci related to strains from a patient with duodenitis, gastric ulcer, and gastric atrophy (R448H, T457K, S460L, IT463-464VA, D470E, A482Q, KNV490-491-492TKT) while mutations in cancerous strain were A439P, T457P, and H500Y.ConclusionDisease-specific variations of cagA of H. pylori strains, in the region of amino acid residues 428-510, were evident among Sudanese patients with different gastroduodenal diseases. A novel mutation (K458N) was detected in a patient with duodenitis, which affects the positive electrostatic surface of cagA. Phylogenetic analysis showed a high level of diversity of cagA from Sudanese H. pylori strains.

scholarly journals Site-specific amino acid alterations in Ca2+ binding domains in calmodulin impair activation of RBC Ca(2+)-ATPase

1992 ◽  
Vol 62 (1) ◽  
pp. 77-78 ◽  
Author(s):  
D. Kosk-Kosicka ◽  
T. Bzdega ◽  
A. Wawrzynow ◽  
D.M. Watterson ◽  
T.J. Lukas
Keyword(s):  
Amino Acid ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Binding Domains

A Mutation in the  Subunit of the Platelet Integrin IIbβ3 Identifies a Novel Region Important for Ligand Binding

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 918-924 ◽  
Author(s):  
Eileen Collins Tozer ◽  
Elizabeth K. Baker ◽  
Mark H. Ginsberg ◽  
Joseph C. Loftus
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Single Amino Acid ◽  
Chimeric Receptor ◽  
Amino Acid Residues ◽  
Genetic Approach ◽  
Specific Amino Acid ◽  
Transfected Cells ◽  
Binding Function ◽  
A Cell

Abstract An unbiased genetic approach was used to identify a specific amino acid residue in the IIb subunit important for the ligand binding function of the integrin IIbβ. Chemically mutagenized cells were selected by flow cytometry based on their inability to bind the ligand mimetic antibody PAC1 and a cell line containing a single amino acid substitution in IIb at position 224 (D→V) was identified. Although well expressed on the surface of transfected cells, IIbD224Vβ3 as well as IIbD224Aβ3 did not bind IIbβ3-specific ligands or a RGD peptide, a ligand shared in common with vβ3. Insertion of exon 5 of IIb, residues G193-W235, into the backbone of the v subunit did not enable the chimeric receptor to bind IIbβ3-specific ligands. However, the chimeric receptor was still capable of binding to a RGD affinity matrix. IIbD224 is not well conserved among other integrin  subunits and is located in a region of significant variability. In addition, amino acid D224 lies within a predicted loop of the recently proposed β-propeller model for integrin  subunits and is adjacent to a loop containing amino acid residues previously implicated in receptor function. These data support a role for this region in ligand binding function of the IIbβ3 receptor.

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