Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-liver microsomes (anti-LM) autoantibodies in patients with dihydralazine-induced hepatitis were found to react specifically with cytochrome P4501A2 (P4501A2) but not with P4501A1 expressed in yeast and bacteria. These results were confirmed by immunoinhibition of methoxyresorufin-O-demethylase activity (supported by the P4501A subfamily); anti-LM antibodies more strongly inhibited this activity in yeast expressing P4501A2 than in yeast expressing P4501A1. Anti-LM were shown to be specific to the disease; in three cases, these autoantibodies were present at high titers during disease, whereas the titers decreased upon recovery and became undetectable a few months after recovery. Thus, there exists a time-dependent relationship between the disease and the autoantibodies, which does not prove that the autoantibodies are causative of the hepatitis; they might only be a marker. The inductive capacity of dihydralazine toward P450 was also studied. In rats treated in vivo and in human hepatocytes treated in vitro with dihydralazine, a 2-fold increase in P4501A2- and P4501A-supported monooxygenase activities was found. The levels of the other P450 isoforms tested were unchanged during treatment, both in vivo in rats and in vitro in cultures of human hepatocytes. In human hepatocytes, dihydralazine produced a dose-dependent increase in the level of P4501A up to 0.1 mM; induction of P4501A was less strong at 0.2 mM and disappeared at 0.5 mM. The same treatment did not change the level of P4503A4, taken as control. The strong heterogeneity in the expression of P4501A enzymes in human liver and the capacity of these enzymes for induction by dihydralazine and by other compounds might be predisposing factors in this autoimmune disease.
Mol Pharmacol 1992 Aug
PMID:Anti-liver microsomes autoantibodies and dihydralazine-induced hepatitis: specificity of autoantibodies and inductive capacity of the drug. 151 26

The immune response of males and females is not identical but instead has been shown to be dimorphic in its nature, with females generally demonstrating a greater overall response than males. This dimorphism extends to both the humoral and cell mediated systems and appears to be mechanistically based on the differences in type and concentration of sex steroids in males vs females. Furthermore, growth hormone and prolactin secretions which are different in males and females may also be partly responsible for the observed dimorphism. Because autoimmune disease results from a pathological perturbation of normal immune function, it follows that expression of these diseases will also demonstrate a dimorphic pattern. Examples of this autoimmune dimorphism include (but are not limited to) lupus, rheumatoid arthritis and multiple sclerosis with the two former more prevalent in females than males and the latter more severe during pregnancy. To explain autoimmune dimorphism it therefore becomes necessary firstly to describe the cellular and hormonal interactions found in normal immune regulation and thereafter extrapolate these to autoimmune phenomena.
J Steroid Biochem Mol Biol 1991
PMID:Sex steroid regulation of autoimmunity. 195 63

Autoantibodies against U3 small nuclear ribonucleoprotein are associated with scleroderma autoimmune disease. They were shown to react with fibrillarin, a 34- to 36-kilodalton protein that has been detected in all eukaryotes tested from humans to yeasts. We isolated a 1.6-kilobase cDNA encoding fibrillarin from a Xenopus laevis cDNA library. The protein contains a 79-residue-long Gly-Arg-rich domain in its N-terminal region and a putative RNA-binding domain with ribonucleoprotein consensus sequence in its central portion. This is the first report of cloning of fibrillarin, and the deduced protein sequence is in agreement with the involvement of the protein in a ribonucleoprotein particle.
Mol Cell Biol 1990 Jan
PMID:Molecular cloning of Xenopus fibrillarin, a conserved U3 small nuclear ribonucleoprotein recognized by antisera from humans with autoimmune disease. 213 67

Reversal of autoimmune disease with monoclonal antibodies to polymorphic determinants associated with class II gene products of the major histocompatibility complex (MHC) and to T-cell receptor variable region segments has been demonstrated in animal models. Recent studies have shown that it is also possible to use mutant peptides to block recognition of self-antigen associated with MHC by T-cells that mediate autoimmune disease. These mutant peptides have been used to prevent the model autoimmune condition experimental allergic encephalomyelitis. The possibility of extending these approaches to human disease is discussed.
Mol Biol Med 1990 Aug
PMID:Development of antigen-specific therapies for autoimmune disease. 223 45

Autoimmune diseases are characterized by spontaneously occurring autoantibodies which have proven to be useful reagents for the characterization of specific nuclear proteins. Using a monoclonal autoantibody (72B9) derived from a murine lupus strain, we have cloned a cDNA from the human T-cell line MOLT-4, which encodes nuclear lamin B. The identity of the encoded protein as lamin B was established by both biochemical and immunological criteria. Inspection of the deduced amino acid sequence of lamin B revealed the presence in coil 1B of the alpha-helical domain of a leucine heptad repeat region. Analysis of mRNA in HL60 and MOLT-4 cells, which express only lamin B, or HeLa cells, which express all three major lamins (A, B, and C), together with the comigration of in vitro-translated product with isolated HeLa cell lamin B by two-dimensional gel electrophoresis, suggests that a single lamin B is expressed in mammalian somatic cells. In vitro translation with the cDNA clone revealed an EDTA-sensitive posttranslational modification which resulted in an increase in the apparent molecular weight to that equivalent to the native in vivo-synthesized lamin B protein. This in vitro modification included incorporation of a product of mevalonolactone and required an intact carboxy terminus.
Mol Cell Biol 1990 May
PMID:In vitro posttranslational modification of lamin B cloned from a human T-cell line. 232 50

We have previously demonstrated that recombinant gamma-interferon (gamma IF) inhibits thyroid cell proliferation in vitro. We now demonstrate differential regulation of thyroid cell genes by recombinant gamma IF, as evidenced by data obtained measuring thyroglobulin (Tg) mRNA and MHC class II alpha-chain mRNA transcripts. Using the rat thyroid cell clone 1B-6, derived from FRTL-5 cells, gamma IF markedly increases MHC class II (RT1.D) alpha-chain transcripts in proliferating cells. Simultaneously, Tg mRNA transcript levels are markedly inhibited, even in the presence of TSH and insulin-like growth factor I (as insulin), known stimulators of Tg mRNA. Similar data were obtained for both FRTL-5 and FRTL parent cell lines. Furthermore, using probes to the 5' region of the rat Tg gene we recognized not just a 9.0-kilobase (kb) mRNA, but also an additional 1.1-kb message in all proliferating thyroid cell cultures, suggesting truncation or alternative splicing of the Tg mRNA. Both the 9.0- and 1.1-kb mRNAs were inhibited by gamma IF. These data add further complexity to the cytokine regulation of thyroid cell gene expression and advise caution in making the assumption that thyroid cells may be efficient thyroid antigen-presenting cells in thyroid autoimmune disease.
Mol Endocrinol 1989 May
PMID:Differential cytokine regulation of MHC class II and thyroglobin mRNAs in rat thyroid cells. 250 13

Of 79 hybridomas derived from stimulated or unstimulated autoimmune disease prone mouse strains, secreting autoantibodies of various specificities more than 65% use V genes from five Vk families, namely, Vk1, Vk4, Vk8, Vk10 and Vk19. Restriction fragment length polymorphism (RFLP) analysis of genomic DNAs from autoimmune prone mouse strains, tight skin, NZB and SJL show marked differences in the polymorphism of the Vk1, Vk10 and Vk19 gene families.
Mol Immunol 1988 Feb
PMID:Biased usage of certain Vk gene families by autoantibodies and their polymorphism in autoimmune mice. 289 24

The development of a non-competitive, solid-phase radioimmunoassay for quantitating anti-actin antibody is described. Anti-actin antibody was captured on BSA-coated microspheres of polystyrene to which a synthetic peptide representing the fifteen amino acid N-terminus of human beta-actin was covalently attached. A rabbit antiserum against the actin peptide fragment was used as reference serum for the assay. Serums of 23 out of 28 (82%) patients with chronic active hepatitis, shown to have anti-actin antibodies (range 2-140 micrograms ml-1) by immunofluorescence and immunoblot assays, were used to validate the radioimmunoassay. Only 7 out of 130 (5%) control subjects exhibited anti-actin antibody serum concentrations above 14 micrograms ml-1 (range 2-20 micrograms ml-1), the 95% confidence interval. Anti-actin antibody serum concentrations were determined to be elevated in 28 out of 47 (60%) patients with juvenile rheumatoid arthritis (range 5-89 micrograms ml-1), 43 out of 64 (67%) patients with human immunodeficiency virus infection and AIDS (range 3-80 micrograms ml-1), and 17 out of 23 (74%) infants with Kawasaki Syndrome (range 7-138 micrograms ml-1). All of the differences observed between patient groups, either singly or collectively, and the control group are highly significant (P less than 0.001) as judged by chi-square analysis. Since all of these disease states contain elements of viral infection and autoimmune disease, it is possible that viral infection in these diseases triggers the production of anti-actin antibody, possibly by means of molecular mimicry in response to viral oncogenes or to abnormal expression of actin in host tissue. This radioimmunoassay for anti-actin antibodies may prove to be a useful tool for the detection and monitoring of certain forms of autoimmune disease.
Mol Cell Probes 1988 Dec
PMID:Radioimmunoassay for anti-actin antibody: application in viral and autoimmune diseases. 307 13

"Inappropriate" expression of class II major histocompatibility complex (MHC) molecules by target cells has been found in all organ-specific autoimmune diseases so far examined for the presence of this phenomenon. These glycoproteins may have a functional role as class II+ thyrocytes are able to present both small fragments of foreign antigens and autoantigens to helper T cells. Interferon gamma is a likely modulator of MHC class II expression in the thyroid but other signals like thyroid-stimulating hormone seem to influence its action. By contrast, it appears that lymphokines are not involved in inducing the inappropriate MHC class II expression observed in situ in the pancreatic beta cells of diabetics. These data suggest that regulation of MHC class II expression is different in thyroid follicular cells from pancreatic beta cells, and that similar differences may be found in other cell types involved in autoimmune disease, thus reinforcing the concept of heterogeneity in the pathogenesis of organ-specific autoimmune disorders.
Mol Biol Med 1986 Apr
PMID:Inappropriate major histocompatibility complex class II expression by thyroid follicular cells in thyroid autoimmune disease and by pancreatic beta cells in type I diabetes. 309 Apr

The acute-phase proteins, fibronectin (Fn) and serum amyloid P (SAP), are opsonins which by virtue of their adhesive properties may be involved in the glomerular nephritis associated with splenic lupus erythematosus (SLE). Because of their possible involvement in the pathophysiology of lupus, plasma Fn and SAP levels from three strains of autoimmune mice were measured over time to determine if Fn and SAP rose as the mice sickened and renal function degenerated. Baseline levels of Fn and SAP were measured when the mice were between 1.5 and 3 months of age. The characteristic rapid onset of autoimmune disease in MRL/1pr mice was accompanied by a two- to threefold increase in plasma Fn and SAP by Day 100. The B/W mice, which develop autoimmune disease more slowly, did not have a significant increase in plasma Fn and SAP until Day 240. The NZB mice, with the most delayed onset of disease, exhibited a modest but significant elevation of plasma Fn and SAP by Day 360. Histologic examination of the kidneys of B/W and NZB mice indicated that pathological abnormality of the glomeruli and tubules coincided with the elevation of plasma Fn and SAP levels. In contrast, blood samples taken over time from normal BALB/c mice did not possess abnormal levels of Fn or SAP. It appears that elevation of plasma Fn and SAP in the MRL/1 pr, B/W, and NZB mice is related to the onset and severity of autoimmune disease and the subsequent loss of renal function.
Exp Mol Pathol 1988 Dec
PMID:Elevation of plasma fibronectin and serum amyloid P in autoimmune NZB, B/W, and MRL/1pr mice. 319 16


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