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Moinuddin

Publications and source records attributed to Moinuddin.

11 recordsLinked to original sources
PubMed2006

Peroxynitrite-modified DNA: a better antigen for systemic lupus erythematosus anti-DNA autoantibodies.

Native human DNA was modified by ONOO- (peroxynitrite), generated by the synergistic action of sodium nitroprusside [Na2Fe(CN)5NO], an NO donor, and pyrogallol, a superoxide donor. The modifications were analysed by UV absorption characteristics, fluorescence emission transitions, nuclease S1 digestibility and melting-temperature studies. Modified DNA was found to be highly immunogenic, inducing high-titre immunogen-specific antibodies in experimental animals. A maximum of 85% inhibition of the antibody binding was observed in competition ELISA with immunogen as inhibitor. SLE (systemic lupus erythematosus) anti-DNA autoantibodies recognized modified DNA as a better antigen than the native analogue. Modification of native DNA by ONOO-, forming neo-epitopes on the molecule, may be one of the factors for the induction of the autoimmune response seen in SLE.

Animals↗
PubMed2005

Immunological studies on peroxynitrite modified human DNA.

Peroxynitrite (ONOO(-)) is a strong and potent oxidizing and nitrating agent, formed by rapid reaction of two highly reactive, nitric oxide and superoxide anion. The action of peroxynitrite generated by synergistic action of diethylamine NONOate (a nitric oxide donor) and 1,4-hydroquinone (a superoxide donor), on human placental DNA was monitored by ultraviolet and fluorescence spectroscopy, melting temperature studies, S1 nuclease digestibility and alkaline agarose electrophoresis. The peroxynitrite modified human DNA (ONOO(-)-DNA) was found to be highly immunogenic in rabbits inducing high titre immunogen specific antibodies. However, the induced antibodies exhibited appreciable cross-reactivity with various polynucleotides and nucleic acids. The data demonstrate that the antibodies, though cross-reactive, preferentially bind ONOO(-)-modified epitopes on DNA. Visual detection of immune complex formation with native and ONOO(-)-DNA reiterated preferential binding with modified human DNA. DNA modified by ONOO(-) presents unique epitopes which may be one of the factors for the induction of autoantibodies in cancer patients.

Animals↗
PubMed2005

Acquired antigenicity of DNA after modification with peroxynitrite.

There are many contaminants affecting human beings, the most important being the metabolites of gases in air around us or certain deleterious by products from metabolic activity. They are reactive species of nitrogen, oxygen and their derivatives. Nitrogen is taken into body as nitrates, nitrites, peptides, proteins, etc. and its metabolites include higher oxides of nitrogen and peroxynitrite. Although NO is a free radical, it is probably insufficiently reactive to attack DNA directly. By contrast its derivatives N2O3, HNO2, ONOO- can nitrate, deaminate, cause strand breaks in DNA leading to serious consequences including mutations. The study exploits this property of ONOO-, such that on modification DNA which in its native form is non-immunogenic acquires the ability to elicit immune response in experimental animals. The extent of modifications, characterization of induced antibodies along with antigen-antibody interactions are studied and analyzed through different techniques.

Animals↗
PubMed2003

Hydroxyl radical modification of polyguanylic acid: role of modified guanine in circulating SLE anti-DNA autoantibodies.

The hydroxyl radical generated by UV irradiation of hydrogen peroxide cause an extensive damage to guanine residues of ribohomopolymer, polyguanylic acid, poly (G) as investigated by spectrophotometric measurements, agarose gel electrophoresis, Sephadex G-200 gel filtration and DEAE Sephadex A-25 column chromatography. Native and ROS-poly (G) were highly immunogenic inducing high titre antibodies in rabbits. The antibodies showed wide range of cross reactivity with various synthetic polynucleotides exhibiting B-, A-, and allied conformations. The diverse antigen binding characteristics of the induced antibodies resembles to those of naturally occurring lupus anti-DNA autoantibodies. Sera from various SLE patients showed preferential binding to ROS-poly (G) than native poly (G), indicating that oxidatively modified guanine residues are better recognised. The significance of these findings in the induction of SLE anti-DNA autoantibodies by oxygen free radicals modified guanine residues in DNA has been discussed.

Animals↗
PubMed1998

Binding of naturally occurring anti-DNA antibodies to estradiol.

Binding of naturally occurring human anti-DNA autoantibodies to beta-estradiol and native DNA has been investigated. Sera from seven SLE patients were tested for their reactivity with beta-estradiol and native calf thymus DNA. Solid Phase enzyme immunoassay was performed using both colorigenic and fluorogenic substrates. The results show enhanced binding of human anti-DNA autoantibodies to beta-estradiol as compared to native DNA. This was further substantiated by increased binding of affinity purified SLE IgG to beta-estradiol. These results suggest a role for female sex hormone in the etiopathogenesis of SLE and are significant vis-a-vis female predominance of SLE.

Antibodies, Antinuclear↗
PubMed1998

SLE autoantibodies binding to native calf thymus DNA brominated in high salt.

Native calf thymus DNA was brominated in high salt to achieve B-->Z conformational transition. Ultraviolet and circular dichroism spectroscopic studies point towards the conformational modification of the native DNA. Specific binding of the monoclonal anti-Z-DNA antibody (Z-22) to the DNA brominated in high salt further confirmed the B-->Z conformational isomerization of native DNA. The role of Z-DNA in the etiopathogenesis of systemic lupus erythematosus has been investigated in the light of the binding of naturally occurring human anti-DNA autoantibodies to the induced Z-DNA.

Animals↗
PubMed1998

Effect of dialysis on bleeding time in chronic renal failure.

Renal failure is associated with severe haemorrhagic complications. Platelets play an important role in coagulation and their dysfunction may be responsible for the bleeding tendency in these patients. Sixty patients with advanced renal failure were investigated for bleeding tendency due to platelet dysfunction. The pre-dialysis platelet count was 46 to 325 x 10(9)/L) (mean 166 x 10(9)/L). Post-dialysis platelet count was 60 to 310 x 10(9)/L, (mean 172 x 10(9)/L) Pre-dialysis mean bleeding time (BT) was 4.95 +/- 0.27 minutes (range 1.30 to 20 minutes). Thirty-three patients (55%) had prolonged BT before dialysis. Mean BT in all patients after dialysis was 2.46 +/- 0.24 minutes (range 1.15 to 10 minutes). BT was corrected in 27 (81.8%) out of 33 patients with prolonged BT before dialysis. In 6 patients (10%) it remained prolonged. This improvement in BT after dialysis was statistically significant (p value < 0.001). Both peritoneal and hemodialysis resulted in significant improvement in bleeding time.

Adolescent↗
PubMed1997

Binding characteristics of SLE anti-DNA autoantibodies to modified DNA analogues.

Native calf thymus DNA was modified with furocoumarins and reactive oxygen species (ROS). The modifications were probed by UV & Fluorescence spectroscopy, thermal denaturation and hydroxyapatite chromatography. In CD spectroscopy changes in the ellipticity of the DNA molecule were observed as a result of modification. The binding specificity of naturally occurring anti-DNA antibodies with modified DNA molecules was assessed by ELISA and quantitative precipitin titration. The affinity of anti-DNA antibodies for modified conformers was found to be quite high.

Antibodies, Antinuclear↗
PubMed1994

SLE anti-DNA autoantibodies binding estradiol-albumin-DNA conjugate.

The present study was designed to study the possible role of the female sex hormone, estradiol in conjugation with DNA, in the pathogenesis of systemic lupus erythematosus (SLE). Calf thymus DNA fragments (average size 200 bp) were covalently linked to estradiol-albumin (E2-BSA) by treatment with glutaraldehyde. The conjugate was separated from free DNA by gel exclusion chromatography. It was characterized by UV spectroscopy and thermal denaturation studies. The conjugate (E2-BSA-DNA) induced high titer antibodies which were highly specific towards their immunogen. These antibodies also recognize estradiol-albumin and beta-estradiol but not native DNA (B-form), brominated DNA (Z-form) or poly(rG).poly(dC) (A-form). The E2-BSA-DNA conjugate showed significant binding with SLE sera known to have a high level of anti-native DNA antibodies. The results indicated the recognition of unique conformation of estradiol-BSA-DNA conjugate by naturally occurring SLE anti-DNA autoantibodies.

Animals↗