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Anisur Rahman

Publications and source records attributed to Anisur Rahman.

25 records · Page 2Linked to original sources
PubMed2003

Cytokines in systemic lupus erythematosus, London, UK.

The meeting consisted of 11 talks that illustrated the complexity of the pathogenetic mechanisms underlying systemic lupus erythematosus and aimed to identify ways in which cytokine modulation might affect those mechanisms. The evidence relating to the involvement of tumour necrosis factor-alpha, interleukin-10 and BLyS in this disease was discussed in particular detail. A final discussion explored the possible ways in which cytokine modulation might lead to new methods of treating systemic lupus erythematosus in the future.

Animals↗
PubMed2003

Relative importance of different human aPL derived heavy and light chains in the binding of aPL to cardiolipin.

INTRODUCTION: Previous studies have suggested the importance of somatic mutations and arginine, asparagine and lysine residues in the complementarity determining regions (CDRs) of antiphospholipid antibodies (aPL) implicated in the pathogenesis of the antiphospholipid antibody syndrome. The relative contributions of the heavy and light chains of aPL in binding to cardiolipin (CL) were assessed by pairing the heavy and light chains of two IgG, beta(2)GPI dependent aPL (IS4 and CL24) with different partner chains from other IgG, beta(2)GPI independent aPL (UK4) and anti-DNA antibodies (B3 and 33H11). METHODS: Four heavy (V(H)) and five light (V(L)) chain variable sequences from three aPL and two anti-DNA antibodies were cloned into expression vectors containing appropriate gamma(1), lambda or kappa constant region cDNA. Paired combinations of heavy and light chain expression plasmids were transfected into COS-7 cells allowing transient expression of whole IgG molecules, which were harvested and tested for the ability to bind CL and DNA by enzyme-linked immunosorbant assay (ELISA). RESULTS: Whole IgG was produced from 19 heavy/light chain combinations. IS4V(H) was dominant in conferring the ability to bind CL with four of the five V(L) tested. The identity of the V(L) region paired with IS4V(H) was important in determining the strength of binding to CL. IS4V(H) contains multiple arginine residues in CDR3, which may have accumulated due to antigen driven selection. It is likely that these arginine residues may interact with CL. The combination B3V(H)/B3V(L) also bound CL, but none of the other 14 combinations showed any binding in this assay. CONCLUSION: Whole IgG molecules capable of binding CL were produced by in vitro expression in COS-7 cells. Arginine residues play important roles in binding to CL and double-stranded DNA. However, different patterns of mutation to arginine are associated with binding to each of these antigens.

Amino Acid Sequence↗
PubMed2003

A systematic analysis of sequences of human antiphospholipid and anti-beta2-glycoprotein I antibodies: the importance of somatic mutations and certain sequence motifs.

OBJECTIVE: Previous studies have suggested the importance of somatic mutations and certain residues in the complementarity determining regions (CDRs) of antiphospholipid antibodies (aPL) implicated in the pathogenesis of antiphospholipid antibody syndrome (APS). The authors tested this hypothesis by carrying out a systematic analysis of all published aPL sequences. METHODS: Each aPL variable region sequence was aligned to the closest germline counterpart in the VBASE Sequence Directory by using DNAPLOT software, allowing analysis of nucleotide homology and distribution of somatic mutations. The probability that this distribution arose as a result of antigen-driven accumulation of replacement mutations in the CDRs was tested statistically. RESULTS: There was no preferential gene or family use in the 36 aPL sequences identified. Immunoglobulin (Ig) M aPL had few somatic mutations compared with IgG. Of the IgG aPL, 9 of 14 showed evidence of antigen-driven accumulation of replacement mutations in the CDRs. Multinomial analysis allowed a clearer statistical identification of sequences that had been subject to antigen drive. The more specific IgM aPL and some IgG aPL displayed an accumulation of arginine, asparagine, and lysine residues in CDRs. CONCLUSIONS: High-specificity binding in IgG aPL, but not in more specific IgM aPL, is conferred by antigen-driven somatic mutation. This may in part be caused by an accumulation of arginine, asparagine, and lysine residues in the CDRs, which are germlines encoded in the more specific IgM aPL, but often arise because of somatic mutation in IgG aPL. RELEVANCE: An understanding of the role of arginine, asparagine, and lysine residues in the binding of pathogenic aPL to phospholipids, and to beta(2)-glycoprotein I, may eventually help in the development of drugs to interfere with those interactions, and thereby improve the treatment of antiphospholipid antibody syndrome.

Amino Acid Sequence↗
PubMed2002

Comparison of single-dose azithromycin and 12-dose, 3-day erythromycin for childhood cholera: a randomised, double-blind trial.

BACKGROUND: Cholera is a major public-health problem, with children most affected. However, effective single-dose antimicrobial regimens have been identified only for adults. Our aim was to compare the efficacy of azithromycin and erythromycin regimens in the treatment of children. METHODS: We did a double-blind, randomised study of 128 severely dehydrated children (age 1-15 years) with cholera, treated at one of two treatment centres in Bangladesh in 1999. Children were assigned single-dose azithromycin (20 mg/kg bodyweight, maximum individual dose 1 g; n=65) or 12.5 mg/kg erythromycin (maximum dose 500 mg; n=63) every 6 h for 3 days. Patients stayed in hospital for 5 days. We measured fluid balance every 6 h, and obtained a rectal swab or stool sample for culture daily. Our primary outcome measures were clinical success of treatment-ie, cessation of watery diarrhoea within 48 h-and bacteriological success-ie, absence of Vibrio cholerae O1 or O139 from cultures of stool or rectal swab samples after study day 2. Analysis was per protocol. FINDINGS: Two children in both groups withdrew from the study, and we excluded one child in the erythromycin group. Treatment was clinically successful in 48 (76%) patients who received azithromycin and 39 (65%) who received erythromycin (difference 11%, 95% CI -5 to 27, p=0.244); and bacteriologically successful in 45 (71%) and 49 (82%) patients, respectively (10%, -5 to 25, p=0.261). Patients treated with azithromycin had a shorter duration of diarrhoea (median 24 h vs 42 h; difference 12 h, 0-18 h, p=0.019) and fewer episodes of vomiting (1 vs 4; difference 1 episode, 0-3 episodes, p=0.023). INTERPRETATION: Single-dose azithromycin is as effective for treatment of cholera in children as standard erythromycin therapy, but is associated with less vomiting.

Adolescent↗
PubMed2002

Molecular and genetic characterizations of five pathogenic and two non-pathogenic monoclonal antiphospholipid antibodies.

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by thrombosis, recurrent fetal loss and thrombocytopenia. Antiphospholipid antibodies, detected by enzyme-linked immunoabsorbent assays (aCL) and/or in vitro blood clotting assays (LAC) are strongly associated with APS. Both the molecular structures used by pathogenic antiphospholipid antibodies and the genetic mechanisms leading to their production are unknown. We describe here the variable region genes of seven IgG antiphospholipid antibodies derived from two APS patients. Of these, five are pathogenic as defined in a mouse model of thrombosis and two are not. Analyses of the expressed variable region genes show no preferential V gene usage. However, similar to anti-DNA antibodies, pathogenic antiphospholipid antibodies contain an increased number of arginine residues in the third complimentarity-determining region (CDR3) of their H chains. The increased accumulation of arginine residues in the V(H) CDR3 may act to enhance antigen binding, promote disease and point to the importance of the H chain in the pathogenic potential of certain antiphospholipid antibodies.

Adolescent↗