Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Commercial 14C-labeled KB cell DNA, widely used to assay sera for anti-DNA antibodies, was chromatographed on benzoylated-naphthoylated-DEAE-cellulose (BNDC) and on hydroxyapatite (HAP). On BNDC, only 25% of the 14C label eluted with 1 M NaC1 (KB fraction I) characteristic of ds-DNA. Fifty-five percent of the label eluted with 50% formamide-1 M NaC1 (KB fraction II) characteristic of ss or denatured DNA. On HAP, however, none of the 14C label eluted with 0.2 M phosphate buffer as anticipated for ss-DNA, but, rather, all of the 14C label eluted with 0.4 M phosphate, characteristic of ds-DNA. after pretreatment with S1 endonuclease of Aspergillus oryzae, which selectively digests ss regions, however, 42% of the 14C label was lost from the 0.4 M phosphate peak. These results indicated that more than half of this 14C-KB-cell DNA preparation was ds-DNA with ss regions which was undetectable by HAP chromatography. 3H-ds-DNA and circular 3H-ss-DNA prepared from T7 and phiX174 bacteriophage, respectively, were found to be chromatographically pure on both BNDC and HAP. None of 10 non-SLE sera (rheumatoid arthritis 3, mixed connective tissue disease 4, scleroderma 1, ulcerative colitis 1, and pulmonary fibrosis with chronic active hepatitis 1), previously believed to contain anti-ds-DNA antibodies on the basis of KB cell DNA testing and detectable antibodies against KB fraction 1 or T7 DNA: all of 10 KB cell DNA positive SLE sera had antibodies against both. Additionally, none of the 10 non-SLE sera had antibodies against KB cell DNA when retested with DNA that had been pretreated with S1 endonuclease. Seven of these 10, however, as well as all 10 SLE sera, had antibodies against phiX174 DNA, KB fraction II DNA and alkali-denatured T7 DNA. The data support the conclusions that 1) false positive tests for anti-ds-DNA antibodies can result from contamination of ds-DNA with ds-DNA having ss regions, and 2) non-SLE sera do not contain antibodies specific for ds-DNA at levels comparable to those found in SLE sera but rather contain high levels of antibodies reacting with ss regions or mixed DNA.
 ...
PMID:Characterization of DNA used to assay sera for anti-DNA antibodies; determination of the specificities of anti-DNA antibodies in SLE and non-SLE rheumatic disease states. 30 90

A human monoclonal IgM k anti-DNA antibody, designated 2F7, was prepared by somatic hybridization of peripheral blood lymphocytes from a lupus patient with a human-mouse heterohybridoma cell line, K6H6/B5. 2F7 was tested for its antigen binding and idiotypic specificity by direct binding and inhibition enzyme-linked immunosorbent assays. 2F7 had a high binding activity to single-stranded DNA (ssDNA) but not to double-stranded DNA. It cross-reacted with single-stranded homopolymers with pyrimidine bases and double-stranded polynucleotides containing those homopolymers, suggesting that 2F7 recognizes a conformational determinant made up of both deoxyribose-phosphate backbone and specific nucleotide base. 2F7 did not cross-react with eight structurally unrelated self-antigens. Dissociation constant (Kd) of 2F7 for sonicated ssDNA was approximately 4.5 x 10(-9) M, indicating its relatively high affinity. Idiotypic characterization with rabbit anti-idiotype raised against 2F7 suggested that 2F7 expressed an idiotype at or near its antigen-binding sites that was not detected in sera from 20 unrelated lupus patients, 10 lupus family members and 10 normal individuals. These results suggest that certain IgM class anti-DNA antibodies in human systemic lupus erythematosus may arise by antigen stimulation and not simply by polyclonal B-cell activation.
Lupus 1992 Dec
PMID:Lupus-derived human monoclonal IgM anti-DNA antibody displays monospecificity, high affinity and private idiotype specificity. 130 4

In order to investigate the possibility that autoantibodies to thrombomodulin (TM) may exist in patients with the lupus anticoagulant (LA) and perhaps be implicated in the pathogenesis of recurrent thrombosis seen in such patients, we developed an enzyme-immunoassay to screen serum samples for anti-human TM activity. The major technical problem encountered in developing this assay was to reduce the non-specific binding of serum components from both the LA positive and the negative population. Considerable reduction of non-specific binding was achieved by use of a phosphate/citrate buffer at pH 8.0 and the use of an optimal sample dilution of 1/40. In addition, samples were always tested in parallel in blank wells and results are expressed as an OD ratio. Samples from 113 patients with the LA were assayed and compared to 78 patients referred for LA testing but found to be negative. The mean OD values for the LA positive patients (+/- SD) was 1.36 (0.44) with a range of 0.78-2.57. This was virtually identical to the values for the LA negative population (1.38 +/- 0.40, range 0.76-2.77). The results of this study indicate that there is no evidence for the presence of a significant autoantibody activity to TM in patients with the LA when compared to LA negative patients. If such autoantibodies do exist their frequency must be quite low.
 ...
PMID:Autoantibodies to thrombomodulin: development of an enzyme immunoassay and a survey of their frequency in patients with the lupus anticoagulant. 132 78

The scintigraphic semeiotics was investigated of involvement of osteoarticular system in rheumatoid polyarthritis in 186 patients (79 of them suffered of rheumatoid arthritis, 62 of systemic lupus erythematosus, 34 of systemic scleroderma, 11 of dermatomyositis). Roentgenological examination was supplemented by consecutive local scintigraphy of axial skeleton and peripheral joint by of gamma rays with labeled 99mTc phosphate complexes. Isoactive zones with subsequent quantitative evaluation of the information were obtained as a result of computerized processing of the scintigraphic images of the joints. The results were compared with those obtained in patients with rheumatoid arthritis. It was established that inspite of the similarity of the scintigraphic manifestations, each of them has its regularities due to differences of the pathomorphological processes in the joints.
 ...
PMID:[The importance of osteoscintigraphy for the early detection of rheumatic joint lesions]. 141 80

Antibodies reactive with native double stranded DNA are characteristic of the chronic inflammatory disease systemic lupus erythematosus. Native DNA is however, a poor immunogen and the mechanism of anti-DNA antibody production is incompletely understood. Modification of DNA can increase its immunogenicity and in inflammatory disease states reactive oxygen species produced from phagocytic cells have been shown to thus modify DNA. In this study, monoclonal antibodies produced spontaneously by two mice strains with lupus-like disease were used in a competition ELISA to monitor changes to DNA induced by reactive oxygen species. Different procedures for reactive oxygen species generation were found to cause distinct and characteristic changes to DNA involving modifications of base residues, the sugar-phosphate backbone and the gross conformational structure of double-stranded DNA. In view of this, it may be possible to use these antibodies further to probe DNA and infer the source and nature of the reactive oxygen species it has been exposed to, particularly in vivo.
 ...
PMID:Probing molecular changes induced in DNA by reactive oxygen species with monoclonal antibodies. 148

We studied the in vitro effect of human intravenous immunoglobulin (IVIg) on the lupus anticoagulant (LA) activity present in sera of 11 patients. LA potency was determined in all the cases and a fixed dilution of each serum was chosen to perform the dose-dependent neutralization experiments. For each patient, the dilute serum was incubated for 3 h at 37 degrees C with phosphate buffer saline (PBS) alone or containing IVIg at final concentrations of 0 to 50 mg/ml. Aliquots of the incubation mixtures were added to equal volumes of normal plasma and APTTs were performed. IVIg partially neutralized the LA activity present in 10 out of 11 patients sera. These neutralizations showed an IVIg dose-dependent behaviour. Statistically significant neutralizations were observed at least at one molar ratio (MR = [IVIg]/patient's [IgG] or [IgM]). In every case, a particular MR was found in which the neutralization was maximal (N%max). The N%max ranged from 33.6% to 79.5%. Eight patients showed maximal LA neutralization at MR ranging from 8.9 to 56.8. In one patient with drug-induced LA and another exhibiting LA cofactor effect, MRs were more elevated. We found poor negative correlation between N%max and LA potency (r = -0.46) or N%max and MR of N%max (r = 0.47), although no statistic significance was reached. However, there was good agreement between LA potency and MR of N%max (r = 0.98, p less than 0.001). We have shown that IVIg may neutralize LA activity in vitro. In view of these results, we believe that IVIg should be considered as an alternative therapy in patients with LA-related clinical complications.
 ...
PMID:Neutralization of lupus anticoagulant activity by human immunoglobulin "in vitro". 152 98

Antiphospholipid antibodies (aPL), prevalent in sera of patients with systemic lupus erythematosus (SLE), have been linked to thrombosis, thrombocytopenia, recurrent miscarriages, neurological disorders and ischemic heart disease. Most evidence suggests that phosphodiester-linked phosphate groups are the reactive epitope of cardiolipin (CL) in binding to aPL. Little attention has been given to the acyl moiety. To address this problem we have evaluated the ELISA binding of 12 highly positive IgG anticardiolipin antibody-positive SLE sera to: bovine CL (86.1% 18:2n-6), monolyso CL (MLCL; bovine CL minus 1 fatty acid), dilyso CL (DLCL; minus 2 fatty acids), tetraoleoyl CL (TOCL), myristoyl CL (MCL) and E. coli CL. The reductions in binding of the IgG aPL antibodies relative to bovine CL were as follows: DLCL 83%; MLCL 70.7%; MCL 58%; and TOCL 14% (P less than 0.05). These data suggest that the number of acyl chains and the unsaturation of the acyl chain of CL may be important determinants in the binding to aPL present in SLE sera. To investigate the nutritional relevance of this finding, we examined the incorporation of several dietary fatty acid classes into the CL pool of mice. Mice were fed diets containing n-6 (safflower oil), n-9 (olive oil) or n-3 fatty acids as either 18:3n-3 (linseed oil) or 20:5n-3/22:6n-3 (fish oil) for a 5 month period. The feeding of fish oil and olive oil resulted in replacement of a substantial portion of 18:2n-6 with 22:6n-3 or 18:1n-9, respectively. These results suggest that there may be therapeutic value in modifying the CL acyl composition by nutritional means with respect to binding to pathogenic aPL.
 ...
PMID:Implications of modifying cardiolipin acyl composition by diet. 1. Cardiolipin acyl chain is an important determinant in the binding to antiphospholipid antibodies in SLE sera. 162 34

The term "renal osteodystrophy" is used to include skeletal disorders of patients with chronic renal failure: osteitis fibrosa, osteomalacia, osteosclerosis, osteoporosis and the frequently associated extraskeletal calcifications. It is the chronic glomerular disease with phosphate retention and resultant hyperphosphatemia on one hand and deficient 1,25 (OH)2 D3 and resultant hypocalcemia on the other to induce secondary hyperparathyroidism. The three most common causes of chronic renal failure in our patients are chronic glomerulonephritis, diabetic nephropathy, hypertensive nephropathy in decreasing frequency, polycystic renal disease occurs in five patients. Other miscellaneous causes include nephrotic syndrome, chronic pyelonephritis, systemic lupus erythematosus, periarteritis nodosa, interstitial nephritis and renal stones. The bone changes are similar in primary and secondary hyperparathyroidism and the incidence of brown tumor is about 3% in the former and 1.5 to 1.7% in the latter. We present one among the 94 dialyzed patients who has long-standing severe chronic renal failure from polycystic kidney disease and develops brown tumor in the mid ulna after 7 years on maintenance hemodialysis. The incidence of brown tumor in our series is about 1.1%. Because of increased longevity of the dialyzed patients, brown tumor from secondary hyperparathyroidism is now more commonly observed. Hyperphosphatemia with serum calcium-phosphate products exceeding plasma solubility of 60 to 75 mg/dl may induce soft tissue and vascular calcification. This explains the much higher incidence of soft tissue calcification in secondary than primary hyperparathyroidism; two of our patients with generalized Monckeberg's type arterial calcification and multiple periarticular calcifications in five patients have been observed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Renal osteodystrophy. 164 77

The human monoclonal autoantibody HF2-1/17, produced by a human-human hybridoma derived from lymphocytes of a lupus patient with thrombocytopenia, reacts with single stranded DNA and platelets. To determine the chemical nature of the autoantigen against which this antibody is directed on platelets, this platelet antigen was purified by the lipid extraction of sonicated platelets, DEAE-Sephadex chromatography, and high performance liquid chromatography. The purified glycolipids, a trace component in platelets, demonstrated high reactivity with the HF2-1/17 antibody using a competition enzyme-linked immunosorbent assay system or immunostaining of thin layer chromatograms. The purified glycolipids co-migrated with bovine sulfatides by thin layer chromatography. The purified glycolipids contain sulfate and galactose but not sialic acid or phosphate. Fast atom bombardment-mass spectrometry revealed these sulfatides to be sulfated monohexyl ceramides. The dominant species has a molecular weight of 794 while a minor form has a molecular weight of 812 due to an extra hydroxyl group and loss of a double bond. These results indicate that the platelet autoantigen against which the human monoclonal anti-DNA antibody is directed represents a family of novel monogalactosyl sulfatides.
 ...
PMID:Sulfated glycolipids are the platelet autoantigens for human platelet-binding monoclonal anti-DNA autoantibodies. 186 60

The INO4 gene product is believed to be a positive regulatory factor in a complex cascade of positive and negative factors that coordinates the synthesis of phospholipids in the yeast Saccharomyces cerevisiae. Mutations at the INO4 locus result in a decrease in phosphatidylcholine synthesis and an inability to derepress the structural genes for inositol-1-phosphate synthase and phosphatidylserine synthase. In the present study, the transcript encoding the INO4 gene product has been identified and a transcription map of the INO4 region has been constructed. An ino4 deletion mutant was constructed by in vitro gene disruption and the deletion mutant was shown to be viable but auxotrophic for inositol. The deletion mutant expressed repressed levels of inositol-1-phosphate synthase (INO1) mRNA and exhibited reduced phosphatidylcholine biosynthesis, a phenotype similar to previously characterized ino4 mutants. The INO4 gene has been mapped to chromosome 15 and is tightly linked to the SUF1 tRNA gene. Translation of the DNA sequence of the INO4 gene results in a very basic protein of molecular weight 17,378. Computer analysis of the INO4 protein sequence identified several potential phosphorylation sites as well as several regions that contained significant similarities with the lupus LA antigen and with the helix-loop-helix region of the Myc family of proteins.
 ...
PMID:The Saccharomyces cerevisiae INO4 gene encodes a small, highly basic protein required for derepression of phospholipid biosynthetic enzymes. 215 38


1 2 3 4 5 6 7 8 9 10 Next >>