Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Main components of kinin system, the arginine-esterase activity and proteinase inhibitors were estimated in blood serum of patients with nephrotic syndrome of various etiology (glomerulonephritis, amyloidosis, systemic lupus erythematous) and also in patients with latent nephritis and in healthy donors. Content of all the kinin system components (kallikreinogen, kininogen and kininase 1) proved to be increased in all the forms of nephropathy studied. Free kallikrein was found in blood serum of patients with nephrotic syndrome as distinct from healthy persons and patients with latent nephritis. The arginine-esterase activity, which shows the level of trypsin-like proteinases, was altered dissimilarly, depending on the nephrotic syndrome etiology: it was maximally increased in nephrotic syndrome of amyloid genesis and decreased in patient with systemic lupus erythematosus. High content of kallikrein and kininase I with simultaneous decrease in kininogen was typical for patients with severe form of nephrotic syndrome. Impairment of kidney in nephrotic syndrome was also characterized by an increase in alpha1-antitrypsin and in the total antitryptic activity, which reached the maximal value in nephrotic syndrome of the I degree and decreased at the II degree of the disease. In nephrotic syndrome content of alpha2-macroglobulin was maximally increased at the II degree of nephrotic syndrome and decreased in severe form of the disease. The primary alteration in content of proteinase inhibitors and high level of kinin system components were assumed to determine the conditions for activation of kinin system in blood serum and to impair the nephrotic syndrome pathogenesis, which was complicated by systemic manifestations. High content of kinin system components was apparently determined by the increased synthesis in liver tissue in response to inflammation and massive proteinuria; kininase I and alpha2-macrolgobulin, as proteins with high molecular weight, were likely to be selectively retained in blood circulation when the capillary penetration was increased.
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PMID:[State of the kinin system and level of serum proteinase inhibitors in latent nephritis and the nephrotic syndrome of different etiology]. 7 Jan 11

We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations.
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PMID:A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene. 151 80

SK&F 105685 (N,N-Dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine+ ++ dihydrochloride) is a novel azaspirane with beneficial activity in animal models of autoimmune diseases such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis in the Lewis rat and lupus-like disease in the MRL mouse. The effect of SK&F 105685 on the proliferation of rat lymphoid cells was examined in vitro. The compound inhibited the proliferative response of spleen, thymus and lymph node cells to the mitogen concanavalin A (Con A) in a dose-dependent manner but had little or no effect on the mitogenic response of peripheral blood lymphocytes. Although less potent than cyclosporin A, SK&F 105685 was able to inhibit the proliferation of spleen cells stimulated with PMA and ionomycin or the mitogens phytohemagglutinin (PHA), Con A and pokeweed mitogen (PWM). Relatively early event(s) in cell proliferation were affected by SK&F 105685 since delaying addition of the drug by 24 to 48 hours after Con A stimulation of rat spleen cells resulted in reduced levels of suppression. The mode of action of SK&F 105685 appeared to differ from that of cyclosporin A or rapamycin. Unlike cyclosporin A, SK&F 105685 did not affect IL-2 production by Con A-stimulated spleen cells or the IL-2-producing Jurkat cell line, but, like rapamycin, the compound significantly reduced the IL-2-induced proliferation of rat ConA blasts. These results suggest that inhibition of lymphocyte proliferation by SK&F 105685 may require the activity of an intermediate effector cell(s) present in susceptible populations such as cells from the spleen, thymus, lymph nodes and Con A blast preparations but absent or present in low numbers in resistant populations such as peripheral blood cells. Indomethacin and NG-monomethyl-L-arginine (NGMMA), a competitive inhibitor of nitric oxide synthase, were both unable to relieve SK&F 105685-induced suppression of splenic Con A responses thereby ruling out a role for the production of prostaglandins or nitric oxide by macrophages as an intermediate in drug-mediated suppression. In summary, SK&F 105685 was unable to inhibit lymphoproliferative responses by a mechanism distinct from that of cyclosporin A or rapamycin and which appears to involve regulation of cellular interactions rather than a direct effect on responding lymphocytes.
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PMID:Inhibition of lymphoproliferative responses by SK&F 105685, a novel anti-arthritic agent. 166 43

Autoimmune New Zealand white (NZW) mice contribute to (New Zealand black x New Zealand white)F1 mice 1 or more major histocompatibility complex-linked genes that strongly correlate with susceptibility to murine lupus. The NZW class II major histocompatibility complex genes, I-E alpha and I-E beta, were cloned and sequenced and found to differ from normal B10.PL (H-2u) mice by 3 amino acids in the first domain of the I-E beta subunit. Of these differences, the arginine at position 72 of NZW mice could be an important disease determinant since it lies in a predicted antigen-binding cleft.
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PMID:Sequence of I-E genes from autoimmune New Zealand white mice. 210 15

A detailed analysis of variable region sequences, derived from monoclonal lupus anti-DNA autoantibodies has led to several conclusions with respect to the etiology and pathogenesis of systemic lupus erythematosus (SLE). It was found that the gene elements which are expressed in anti-DNA heavy and light chains are present in the germ lines of normal and diseased animals. However, several VH gene segments are not normally expressed in antibodies to external antigens and may, therefore, be excluded by the regulatory mechanism of self-tolerance. The presence of somatic point mutations, which may serve to change antigenic specificity as well as to increase affinity, indicates that an antigen (DNA)-driven mechanism rather than a polyclonal activation is responsible for the autoimmune response in SLE. An additional unique motif of anti-DNA heavy chains was found to consist of an arginine-rich basic peptide in the third complementarity-determining (hypervariable) region. These data have enabled us to build a computer model of the anti-DNA binding site and to design specific inhibitors of the autoimmune reaction.
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PMID:[Genetic origins of anti-DNA autoantibodies]. 236 8

The V region sequences of two anti-DNA (A52, D42) and two anti-RNA (D44, D444) autoantibodies, derived from lupus prone NZB/NZW F1 female mice, were determined by mRNA sequencing. The sequences had the following features: 1) there was no clear sequence relationship between anti-DNA and anti-RNA antibodies; 2) there were no major similarities between any of the L chain sequences and each VL gene segment belonged to a different mouse VK subgroup; 3) the H chains of the two anti-RNA antibodies showed closely related sequences of VH gene segments and very similar third complementarity determining regions (CDR3); 4) the H chains of the two anti-DNA antibodies had VH segments belonging to different VH gene families but had a unique and similar combination of D segments and junctional sequences, suggesting a common recognition element for Ag and/or for idiotypic regulation in the H chain CDR3; and 5) the VH gene segment of one anti-DNA antibody (D42) was found to be very similar to the VH gene segment of a CBA mouse hybridoma antibody (6G6) which binds to the environmental Ag phosphocholine. The three-dimensional structure of the Fv-region of the anti-DNA antibody (D42) was modeled by computer and a stretch of poly(dT), ssDNA was docked to a cleft in the antibody combining site, formed by the three H chain CDR and by CDR1 and CDR3 of the L chain. The cleft is characterized by a preponderance of arginine and tyrosine residues, lining both the walls and base of the cleft.
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PMID:V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice. 245 27

A 47-year-old man with Graves' disease suffered from a feeling of hunger and sweating in the night, polyarthralgia and fever one month after the start of treatment with methimazole. The above symptoms were ascribed to the side effects of methimazole; insulin autoimmune syndrome and lupus-like syndrome. The change in the antithyroid drug to propylthiouracil caused an amelioration of the symptoms. In addition to an anti-insulin antibody with a high binding capacity, hyperglucagonemia (260 pg/ml with a plasma glucose level of 61 mg/dl) was observed, which returned to normal in parallel with the decrease in the insulin binding capacity of the plasma one month after beginning the treatment with propylthiouracil. A normal decrease in the plasma glucagon level due to exogenous insulin (2 mU/kg/min) was observed with the euglycemic clamp. However, the plasma glucagon level was not suppressed by the oral glucose loading and elicited a poor response to the arginine infusion. Taking previous reports into account, this basal hyperglucagonemia seems to be a characteristic finding in the insulin autoimmune syndrome, while a sluggish response of glucagon to oral glucose or arginine infusion might be ascribed to hyperthyroidism. This is the first case report concerning a kinetical study of the glucagon secretion in insulin autoimmune syndrome with Graves' disease.
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PMID:Hyperglucagonemia of insulin autoimmune syndrome induced by methimazole in a patient with Graves' disease. 265 8

Serum and plasma from patients with active systemic lupus erythematosus contain a specific inhibitor of complement (C5)-derived chemotactic activity. We found that the inhibitor is antigenically related to the Bb fragment of complement factor B. Lupus plasma and purified inhibitor significantly reduced the chemotactic activity of zymosan-treated normal serum, an effect that was abolished by antibodies to factor B. Similar results were obtained when purified Bb was used. Neither purified inhibitor nor Bb inhibited the chemotactic activity of purified human C5a or C5a des Arg. As reported previously, the chemotactic activity of C5a des Arg was enhanced significantly by the addition of an anionic polypeptide (cochemotaxin) present in normal serum and plasma. Interestingly, both purified lupus inhibitor and Bb inhibited the chemotactic activity exhibited by mixtures of C5a des Arg and its cochemotaxin. This effect was due, most likely, to their ability to neutralize the enhancing effect of the cochemotaxin on the chemotactic activity of C5a des Arg. Immunoelectrophoresis and western blots revealed that the purified inhibitor reacted with anti-factor B and exhibited a similar charge and molecular weight as purified Bb.
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PMID:Specific inhibitor of complement (C5)-derived chemotactic activity in systemic lupus erythematosus related antigenically to the Bb fragment of human factor B. 364 93

The MRL mouse strain spontaneously produces antinuclear autoantibodies that recognize DNA and the small nuclear ribonucleoprotein (snRNP) antigens. The monoclonal antibody 2.73 was derived from the lupus prone MRL/n line and is reactive with the 70K protein of the U1 snRNP particle. The epitope recognized by 2.73 was characterized by peptide and inhibition ELISA analysis. Several arginine/aspartic acid (RD) repeats of varying lengths are found in the carboxyl terminus of the 70K protein and are responsible for immunoreactivity with 2.73. We investigated the contribution of charge and found that the immunoreactivity of 2.73 and the 70K protein is specific for the RD repeats. The presentation of the epitope may also contribute to the epitopes immunoreactivity with the 2.73 mouse monoclonal autoantibody.
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PMID:Immunochemical analysis of an arginine-rich systemic lupus erythematosus autoepitope. 750 33

Immunoreactivity of the arginine/aspartic acid (RD) repeats of the 70K protein of U1 small nuclear ribonucleoprotein (snRNP) was determined to be conformationally dependent. The monoclonal autoantibody 2.73, isolated from a lupus-prone MRL/n mouse model, is reactive with the RD repeat regions of U1 snRNP 70K protein. Immunochemical analysis of the antigenic determinants with use of chemically synthesized peptides characterized the 2.73 epitope as the RD repeat [Pelsue, S., et al. (1993) Autoimmunity, 15, 231-236] Analysis by circular dichroism (CD) and nuclear magnetic resonance spectroscopy indicates conformational preferences in the immunoreactive peptides. Computer analyses of CD spectra obtained on the RD-containing peptides predict beta-turns and beta-sheet to be the preferred conformations of the RD repeats. This structure was also predicted by the Chou-Fasman algorithm. The RD repeat is believed to be a conserved structural motif; however, the biological function is still unclear. Immunological and biochemical analysis of autoimmune antibodies and their respective antigenic determinants has helped to characterize the possible mechanisms that lead to autoimmune diseases. This is the first report of a conformationally dependent, linear epitope of an autoantibody.
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PMID:Immunoreactivity between a monoclonal lupus autoantibody and the arginine/aspartic acid repeats within the U1-snRNP 70K autoantigen is conformationally restricted. 752 19


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