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)

Proteins from U1 and U2 small nuclear ribonucleoprotein (snRNP) particles, which are common targets of autoantibodies found in some rheumatic diseases, were analysed for the presence of glycans. A glycan detection assay revealed that the U1-specific proteins 68K and A and the U2-specific protein B" are glycosylated. However, none of the Sm proteins, which are common to all the major snRNP particles, showed a detectable level of glycosylation. With the use of specific lectins, an analysis of the particular carbohydrate(s) attached to the U1 snRNP 68K protein demonstrated the presence of at least one N-linked oligosaccharide chain. Lectin detection of galactose, glucose, mannose and N-acetylglucosamine on 68K was confirmed by chemical analysis of the carbohydrates. The glycopeptide nature of these antigens may be important for understanding the role of autoantigens in the pathogenesis of autoimmune disorder.
Lupus 1992 Feb
PMID:Small nuclear ribonucleoprotein particles contain glycoproteins recognized by rheumatic disease-associated autoantibodies. 130 63

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.
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PMID:Sulfated glycolipids are the platelet autoantigens for human platelet-binding monoclonal anti-DNA autoantibodies. 186 60

Quantitative electron microscope autoradiography has been used to define the macromolecular composition of the interferon-induced human lupus-type inclusions (LI) in the human B lymphoblastoid cell line, Daudi. LI were first apparent in Daudi cell cultures 12 h after the addition of 100 units/ml of the purified recombinant human leukocyte interferon, IFLrA. Radiolabels were added at this time and allowed to incorporate over the following 12 h during which an estimated greater than 99% of the LI material present at 24 h was formed. The LI-incorporated radiolabels were present only during this discrete 12-h period after the interferon activation of LI cell pathways in order to detect LIs de novo synthesized macromolecular components. The estimate relative specific activities of the LI-incorporated radiolabels were: choline at 4.042, mannose at 2.631, uridine at 0.664, glucosamine at 0.578, and amino acids at 0.477. With thymidine the estimated LI specific activity was 0.000. LI isolated from whole cells retained the tubular elements and the interwoven membrane network. These results provide direct evidence that the interferon-induced Daudi cell LI are de novo synthesized complexes of ribonucleoprotein and membrane.
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PMID:Evidence that the interferon-induced Daudi cell human lupus inclusions are de novo synthesized complexes of ribonucleoprotein and membrane. 278 94

Captive gray wolves (Canis lupus) were given 2.2 mg/kg xylazine hydrochloride intramuscularly resulting in profound sedation in 9.1 +/- 0.6 min (mean +/- SE). Heart rate was 42.0 +/- 1.0 beats per minute and respiratory rate was 20.1 +/- 1.6 respirations per minute during sedation. A variety of manipulations could be performed on sedated animals in relative safety. Thirty min after xylazine administration, the animals were given either 0.15 mg/kg yohimbine hydrochloride or 5% dextrose solution intravenously causing recovery in 5.3 +/- 1.0 and 97.1 +/- 14.0 min, respectively (P less than 0.001).
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PMID:Use of xylazine sedation with yohimbine antagonism in captive gray wolves. 319 66

The remarkable history of the 1951 pp 66 year old woman with gastric adenocarcinoma is reviewed. After subtotal gastrectomy she survived for 22 years without any metastases. Presumably the artificially induced high titer IgG, anti-P1 proved to be cytotoxic in two stages: (1) binding of anti-P1 to the terminal fifth sugar, galactose, and (2) the action of cellular immunity in the form of killer T derived lymphocytes containing receptors for IgG molecules. An identical mechanism may be operative in inducing abortions in the pp pregnant woman with a P1 fetus. P1 illegitimate glycolipid (GL) red cell antigen and Forssman (Fs) tissue in adenocarcinoma suggest the self-nonself concept because these are genetically foreign to the host. This concept applies also to numerous "autoimmune" diseases such as RA, lupus, glomerulonephritis, Coombs positive hemolytic anemia and other diseases with immune complexes (ICs) of 20--22 Svedberg units deposited as lesions with tissue damage. In the presence of the GL antigens (ABO, P, Fs), the normal serum contains antibodies for the missing antigen(s). The predicted anti-Fs was present in about 80% of normal employees of ages 18--70. In cancer sera the incidence was 35--40%. On testing normal sera by age in terms of decades anti-Fs was present in 93% in the youngest, and only 55% in the oldest group. This may be associated with the gradual loss of protein synthesis with aging and/or the accumulation of soluble ICs which bind the C1q portion of the C added to the test mixture of heat-inactivated serum (1 : 8) g.p. C (1 : 30) and srbc. In "autoimmune" diseases there is an active immune response to viral or bacterial infections or infestations or drugs which attach to rbc and/or tissue cell membranes. This results in the deposition in selected organs of ICs of 20--22 S units with lesions and tissue damage. For therapy plasma (from young donors) exchange has been recommended to compensate for the loss of IgG antibodies and C.
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PMID:The self-nonself concept as a basis for immune complex to replace "autoimmune diseases". 616 23

An 82-year-old woman developed symptomatic reactive hypoglycemia in the same year she developed a lupus-like syndrome, probably secondary to the administration of procainamide or hydralazine. Reactive hypoglycemia was confirmed by an oral glucose tolerance test, in which plasma glucose decreased from a fasting level of 87 mg/dL to 32 mg/dL at 3 hours and 23 mg/dL at 4 hours, the last value being associated with loss of consciousness. The patient awoke after the intravenous administration of dextrose. Sensitivity to exogenous insulin was normal or increased. Attempts to measure plasma insulin levels led to the finding of anti-insulin antibodies in the patient's serum; these antibodies were of relatively low titer, were IgG, and not associated with antibodies to the insulin receptor. The patient had no history of exogenous insulin use. Her reactive hypoglycemia appeared due to the autoimmune insulin syndrome, which developed in association with drug-induced lupus erythematosus.
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PMID:Reactive hypoglycemia and insulin autoantibodies in drug-induced lupus erythematosus. 634 54

At its inception, morphological imaging, like magnetic resonance imaging (MRI), is often not useful in neuropsychiatric systemic lupus erythematosus (NPSLE), although the disease clinically shows cerebral symptoms. Functional imaging, like positron emission tomography (PET), may be a method that offers some advantages. We report a 53-year-old white man with decreased memory and visual disturbances who met four of the American Rheumatism Association (ARA) criteria for the classification of SLE. He was investigated before and after 3 months of therapy using PET and F-18-fluoro-2-deoxy-D-glucose (FDG). Treatment consisted of prednisone (25 mg/day, tapered to 10 mg/day) and cyclophosphamide (daily 100 mg for 3 weeks followed by a drug-free interval of 1 week). For the control group, 15 clinically and neurologically healthy volunteers (5 male, 10 female, aged 48 +/- 7 years) were investigated. All study participants additionally had a cranial MRI. In both controls and the SLE patient, cranial MRI was negative. However, the patient showed a significant hypometabolism in the region parieto-occipital on both sides and the parietal region on the right side before treatment. After treatment metabolism in these regions was within normal limits. Hence, FDG-PET could help to verify brain-onset of SLE earlier and may be a powerful tool for controlling SLE treatment.
Lupus 1998
PMID:Neuropsychiatric systemic lupus erythematosus before and after immunosuppressive treatment: a FDG PET study. 949 52

Neuropsychiatric systemic lupus erythematosus (SLE) is frequently associated with deficits in brain glucose metabolism, even if morphological imaging by magnetic resonance imaging (MRI) shows no abnormalities. In these patients it is unclear whether or not the changes of brain metabolism measured by F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may progress to lesions of cerebral structure. We describe a 20-year-old woman with SLE who presented with depression, headache and impairment of memory. Initially, a cranial MRI was negative, but FDG-PET revealed significant hypometabolism in the frontal and parieto-temporo-occipital regions on both sides as well as hypermetabolism in the nuclei caudati. Within two months the patient developed an acute confusional state, seizures, visual disturbances and cranial MRI became positive showing hyperintensities at the basal ganglia and the temporo-occipital regions. Focal cerebral symptoms responded to treatment with high dose corticosteroids and brain lesions in MRI disappeared. However, a second FDG-PET showed persistent hypometabolism at frontal regions in accordance with the persistence of subclinical depression. To our knowledge, this is the first SLE case report showing that functional brain lesions visualized by FDG-PET may be a risk factor for subsequent structural brain damage seen in MRI. Thus, FDG-PET may help to verify cerebral involvement of SLE earlier than MRI.
Lupus 2000
PMID:Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus. 1087 34

Bovine thrombin is used as an aid to hemostasis in medical and surgical procedures. At least 500,000 Americans are exposed to this therapeutic annually and reports suggest that exposure is associated with the development of autoreactive antibodies. To determine whether bovine thrombin can induce pathological autoimmunity we exposed nonautoimmune-prone galactose-alpha1-3-galactose-deficient mice to the two bovine thrombin preparations currently approved for use in the United States. We found that, like humans exposed to bovine thrombin, mice developed an immune response against the therapeutic and the xenogeneic carbohydrate galactose-alpha1-3-galactose, and some mice developed autoantibodies against clotting factors. Further, unexpectedly, a single exposure to this therapeutic also induced autoimmunity with features characteristic of systemic lupus erythematosus including antibodies against nuclear antigens, native DNA, double-stranded DNA, and cardiolipin. High levels of these autoantibodies correlated with glomerulonephritis in all mice evaluated. This autoimmune syndrome was detected in mice 15 weeks after a secondary exposure to bovine thrombin and female mice were found to develop the syndrome at a significantly greater frequency than males. Thus, these studies indicate that exposure to bovine thrombin preparations can induce a pathological systemic autoimmune syndrome with lupus-like serology.
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PMID:Exposure of mice to topical bovine thrombin induces systemic autoimmunity. 1265 31

The complement (C') cascade is an important part of the innate immunity. It acts through three major pathways: classical (CP), alternative (AP) and mannose-binding-lectin (MP). C' reduction is a key feature in systemic lupus erythematosus (SLE), for its pathogenesis and for disease relapse. The aims of our study are to correlate C' variations with disease activity and verify the presence of C' deficiencies. We tested for three C' pathways 52 sera from 20 patients affected by SLE. A significant correlation between the ECLAM score and the degree of activation of the CP (Mann-Whitney; P = 0.001) was recorded, while the correlation with anti-dsDNA antibodies did not reach statistical significance (Mann-Whitney; P > 0.05). In conclusion, the ELISA assay can be considered well suited for testing SLE samples. We detected a significant link between the phases of lupus activity and the reduction of the CP.
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PMID:Complement cascade in systemic lupus erythematosus: analyses of the three activation pathways. 1975 82


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