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)

The aim of this study was to assess the skeletal metabolism in a murine model of systemic lupus erythematosus (SLE). MRL/n and MRL/l mice (respectively representing a benign and a malignant form of the disease) were observed from 1.5 to 6.5 months of life. The monthly follow-up included: biochemical and histomorphometrical studies of the femoral bone, serum biochemistry, immunoglobulins and osteocalcin, and histological evaluation of the kidney tissue. The results showed a higher femoral weight (+11.5%), calcium (+4.4%) and protein bone content (+11.4%) and a significantly higher (+77%) phosphorus bone content in the MRL/n group; significantly lower (-48.9%) bone alkaline phosphatase enzymatic activity, lower bone alkaline/acid phosphatase enzymatic activities ratio (-40.8%) and lower (-38.4%) serum osteocalcin values in the MRL/l group (which might suggest reduced bone formation in these animals); markedly smaller trabecular bone volume (BV/TV) in the femoral head (-36.2%) and femoral neck (-39.8%), and smaller cortical and femoral areas in the mid-femoral shaft (-38.8% and -38.1% respectively) in the MRL/l group; higher serum immunoglobulins, increased serum blood urea nitrogen (BUN) and creatinine and a higher index of activity in the kidney histology in the MRL/l group, indicating increased activity of the disease in this substrain. The MRL mice, through their two substrains, may serve as a valuable laboratory animal model for study of the skeletal changes in SLE and of the influence of the disease activity on the skeletal metabolism.
Lupus 2001
PMID:Osteoporosis in murine systemic lupus erythematosus--a laboratory model. 1143 79

Sairei-to, one of the Japanese-Chinese herbal medicines has been used for the treatment of various diseases, especially collagen disease and edema in nephrotic syndrome. However, the mechanism of the therapeutic effects remains uncertain. Therefore, we investigated the immunological changes of skin, kidney, spleen cells and serum in autoimmune-prone MRL/lpr, MRL/n and C57BL/6J mice treated with Sairei-to. In MRL/lpr mice treated with Sairei-to, the improvement of proteinuria, reduction in the number of hematoxylin bodies in kidney, and reduced serum levels of blood urea nitrogen were observed. These results indicate that Sairei-to can improve or inhibit the progression of lupus nephritis. The proportion of CD19 and the serum levels of IgG1, which is one of the pathogenesis of lupus dermatoses and lupus nephritis, were significantly reduced in Sairei-to-treated MRL/lpr mice. Therefore, it is suspected that the B cell function was suppressed by Sairei-to. In addition, CD4/8 ratio in spleen cells and the degree of lymphoproliferation in MRL/lpr mice also decreased. Interestingly, IL-4 producing spleen cells were increased significantly by ELISPOT assay, and IFN-gamma mRNA expressions were reduced in Sairei-to-treated MRL/lpr mice. Regarding the Th balance, an imbalance towards Th1 predominance may play a significant role in MRL/lpr mice, and the Th1 axis was suppressed and the Th2 axis became predominant in Sairei-to-treated MRL/lpr mice. On the other hand, Th2 cell type immunoglobulins (IgG1) were suppressed. These results suggested that Sairei-to is potential for impairing shifted Th1/Th2 balance and hypergammaglobulinemia resulting in therapeutic effects.
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PMID:Unique therapeutic effects of the Japanese-Chinese herbal medicine, Sairei-to, on Th1/Th2 cytokines balance of the autoimmunity of MRL/lpr mice. 1191 7

A 21-year-old woman presented with bilateral optic neuritis, combined with central retinal vein occlusion. General physical examination and neurologic consultation revealed no other findings. Laboratory investigation yielded an elevated erythrocyte sedimentation rate, positive LE preparation, elevated ANA titer, and elevated blood urea nitrogen and creatinine levels. Diagnosis of systemic lupus erythematosus (SLE) was made. Renal failure developed quickly and she was treated with hemodialysis, transfusion and subsequently systemic corticosteroid. Anti-phospholipid antibody was positive to lupus anti-coagulant and the titer was normalized after 2-month steroid therapy at which time the visual outcome differed between the eyes. The right eye showed improvement in visual acuity and visual field, but the left eye was not improved and retained a central scotoma. SLE needs to be considered in young women with optic neuritis when other causes of optic neuritis have been excluded, and serologic tests including anti-phospholipid antibody should be conducted.
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PMID:Bilateral optic neuritis as first manifestation of systemic lupus erythematosus. 1216 19

The present study extended our previous observation that interferon (IFN)-gamma may be responsible for the active disease that develops in NZB x NZWF1 mice and serves as a model for human systemic lupus erythematosus. Treatments with cytokine-encoding plasmids were delivered intraperitoneally every 4 weeks, starting at 3 months of age (i.e. before the onset of lupus). In comparison with the control plasmid and the IL-4-encoding plasmid, the IFN-gamma-encoding plasmid promoted increased blood urea nitrogen values and reduced the survival rate, and these changes were accompanied by the development of anti-nuclear antibody. There were no differences, however, between treatment with control plasmids and treatment with IL-4-encoding plasmids in terms of the development of lupus. The findings clearly indicated that IFN-gamma but not IL-4 contributed to the development of lupus in the NZB x NZWF1 mice.
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PMID:Promotion of lupus in NZB x NZWF1 mice by plasmids encoding interferon (IFN)-gamma but not by those encoding interleukin (IL)-4. 1235 39

It has been repeatedly shown that the heavy metal mercury can induce or exacerbate lupus like autoimmunity in susceptible strains of rats and mice. A hallmark of such autoimmune induction is the accompaniment of an immune shift, in which there is usually an initial skewing toward a Th2-like immune environment. Another heavy metal, lead (Pb), has also been found to induce a Th2 shift in mice. However, exposure of normal mouse strains to Pb does not appear to induce autoimmunity. In order to investigate whether mice genetically predisposed to murine systemic lupus erythematosus (SLE) are susceptible to a Pb-induced exacerbation of lupus, males and females of four New Zealand mixed (NZM) mouse strains, along with BALB/c and C57Bl/6 controls, were administered three 100-microliter intraperitoneal injections of either 1.31 mM lead or sodium acetate per week for 3 wk. The four NZM strains chosen, NZM391, NZM2328, NZM88, and NZM2758, have differential genetic penetrance for SLE with variances in certain manifestations of the disease, but all of these strains naturally develop glomerulonephritis and produce high titers of anti-nuclear autoantibodies. The mice were prebled for baseline values and were bled directly after the injection period (d 1) and monthly thereafter for 5 mo. Sera were assessed for anti-double-stranded DNA titers, urea nitrogen levels, and creatine kinase activity, as well as four total immunoglobulin (Ig) G2a and IgG1 levels. Mortality and morbidity of the mice were also recorded. All NZM strains showed an acute, non-gender-based, susceptibility to Pb at d 1, but the control strains were unaffected. Over time, it became apparent that the strains diverged: The NZM391 strain showed gender-independent susceptibility to Pb enhancement of lupus manifestations and mortality; the NZM2328 strain exhibited gender-independent Pb susceptibility to manifestations, although only females had increased mortality; the NZM2758 strain exhibited non-gender-based elevations in urea nitrogen and creatine kinase activity levels; and the NZM88 strain displayed male susceptibility to anti-DNA and life span. Surprisingly, Pb increased the longevity of NZM88 and NZM2758 females. These results indicate that Pb indeed can exacerbate SLE in lupus-prone mice; however, even among lupus-prone strains, genetic differences determine the degree of exacerbation. Using the known phenotype and genetic differences, one can identify and characterize possible traits and loci associated with Pb susceptibility.
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PMID:Susceptibility of lupus-prone NZM mouse strains to lead exacerbation of systemic lupus erythematosus symptoms. 1282 36

Catalytically active antibodies (abzymes) hydrolyzing proteins, polysaccharides, ATP, DNA, and RNA have been detected in the sera of patients with various autoimmune and some viral diseases, but abzymes from the sera of animals are practically unstudied. The development of lupus-like autoimmune disease of MRL/MpJ-lpr mice is an experimental model for study of autoimmune pathologies and immunopathogenesis. In this work, homogeneous IgG preparations were isolated from the sera of MRL/MpJ-lpr mice. These antibodies (Abs), their Fab-fragments, and isolated light chains were shown to possess catalytic activity in DNA hydrolysis, whereas Abs from the sera of control healthy mice did not hydrolyze DNA. The data demonstrate that DNA hydrolyzing activity is an intrinsic property of Abs from MRL/MpJ-lpr mice. It was shown that various markers of autoimmune pathologies (level of total protein concentration in urea (proteinuria), Abs titers to native and denatured DNA, and DNA-hydrolyzing activity of IgG) increased in animals with aging, but they noticeably increased (2-22 times) only after appearance of obvious indicators of pathology independently of age. The highest increase in proteinuria (25-fold), anti-DNA Abs titers (12-19-fold), and abzyme activity (120-fold) was found in mice after their immunization with DNA-protein complex.
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PMID:DNA-hydrolyzing antibodies from sera of autoimmune-prone MRL/MpJ-lpr mice. 1461 78

To investigate whether green tea has inhibitory effects on the development of autoimmune disease (AID), one-month-old MRL-Faslprcg/Faslprcg mice were fed diets containing 2% green tea powder (GTP) for 3 months. At the end of GTP feeding, the weights of body, subcutaneous (s.c.) and intraperitoneal (i.p.) lymph nodes (LN), kidneys, spleen and intraperitoneal adipose tissue (IPAT), serological abnormalities and renal lesions were compared between GTP-fed and control mice. SCLN, IPLN, kidneys and IPAT weights in both sexes, spleen weight in males and body weight increase in males were significantly lower in GTP-fed mice. Particularly, LN hyperplasia and fatty accumulation were markedly reduced by GTP. Serum levels of anti-DNA antibodies and immune complexes (IC) were significantly lowered and proteinuria and blood urea nitrogen tended to be improved by GTP. The incidence of serious glomerulonephritis was significantly lower and nephric vasculitis was almost completely prevented in GTP-fed mice. Moreover, the survival of mice was significantly prolonged by GTP feeding for 6 months. These results indicate that the progression of lupus-like syndrome including glomerulonephritis was significantly delayed by reduced production of autoantibodies and IC in GTP-fed MRL-Faslprcg/Faslprcg mice, which led to the prolonged survival.
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PMID:Inhibitory effects of autoimmune disease by green tea in MRL-Faslprcg/Faslprcg mice. 1475 19

The dietary supplement and adrenergic receptor agonist ephedrine has been a controversial topic as its safety has been questioned. Beta-adrenergic receptor (beta-AR) activation causes immunomodulation, which may contribute to promotion of autoimmune pathology. This report investigated the ability of ephedrine to exacerbate processes associated with autoimmune disease in a lupus-prone mouse model. To mimic human supplementation, ephedrine was administered to NZM391 (lupus-prone) and BALB/c (nonlupus prone) mice orally twice a day for three months at a dose of 50 and 100 microg/day. Some ephedrine-treated NZM391 mice also were preadministered the beta-AR antagonist propranolol to investigate beta-AR involvement. Mice were bled monthly, and sera were assayed for a variety of lupus manifestations and immunological measurements. In NZM391 males and females, both doses of ephedrine significantly increased lupus manifestations, including IgG production and organ-directed autoantibody titers, and significantly lowered the ratio of IgG2a/IgG1 compared to controls. Ephedrine significantly decreased female lifespan and significantly increased circulating populations of plasma cells (CD38(hi) CD19(lo) cytoplasmic IgG+) and CD40+ B1a cells, while preventing an age-related decrease in the B1a cell population expressing a high level of CD5. While ephedrine induced gender-specific immunomodulation in BALB/c mice, increases in the lupus manifestations of anti-dsDNA titers and serum urea nitrogen were not detected. Preadministration of propranolol decreased lupus manifestations and serum levels of IgG and IgE in ephedrine-treated mice, but did not block the shift towards IgG1 production. These findings indicate that ephedrine via beta-AR can exacerbate lupus symptoms in NZM391 mice and that blockade of the beta-ARs on B cells, and not T cells, apparently was of greater importance as the inhibition of lupus symptoms corresponded to an inhibition of immunoglobulin levels, not a change of Th1/Th2 balance.
Lupus 2005
PMID:The dietary supplement ephedrine induces beta-adrenergic mediated exacerbation of systemic lupus erythematosus in NZM391 mice. 1586 16

Signaling of the C3a anaphylatoxin through its G protein-coupled receptor, C3aR, is relevant in a variety of inflammatory diseases, but its role in lupus nephritis is undefined. In this study, we show that expression of C3aR was significantly increased in prediseased and diseased kidneys of MRL/lpr lupus mice compared with MRL/+ controls. To investigate the role of C3aR in experimental lupus, a small molecule antagonist of C3aR (C3aRa) was administered continuously to MRL/lpr mice from 13 to 19 wk of age. All 13 C3aRa-treated mice survived during the 6-wk treatment compared with 9 of 14 (64.3%) control animals given vehicle (p = 0.019). Relative to controls, C3aRa-treated animals were protected from renal disease as measured by albuminuria (p = 0.040) and blood urea nitrogen (p = 0.021). In addition, there were fewer neutrophils, monocytes, and apoptotic cells in the kidneys of C3aRa-treated mice. C3aRa treatment also led to reduced renal IL-1beta and RANTES mRNA and phosphorylated phosphatase and tensin homologue deleted on chromosome 10 protein, whereas the mass of phosphorylated protein kinase B/Akt was increased by C3aRa. Thus, C3aR antagonism significantly reduces renal disease in MRL/lpr mice, which further translates into prolonged survival. These data illustrate that C3aR is relevant in experimental lupus nephritis and may be a target for therapeutic intervention in the human disease.
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PMID:Signaling through up-regulated C3a receptor is key to the development of experimental lupus nephritis. 1603 39

Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene which encodes the receptor for nerve growth factor (NGF). We report the clinical course in three sibs with CIPA and proven NTRK1 gene mutations with a follow-up over a 25-year period in one of them. They had the characteristic clinical features of an abnormally high pain threshold, and mental retardation; in addition their clinical course was marked by the occurrence of early onset renal disease with recurrent microhematuria and proteinuria and frequent observations of increased serum creatinine and blood urea levels. Light microscopy study of a renal biopsy performed in one of them at age of 20 months showed focal glomerulosclerosis, interstitial fibrosis and tubular atrophy. This patient and his younger brother died because of renal failure at the age of 25 years and 14 years, respectively. The sister still alive showed renal impairment and deep venous thrombosis associated with lupus anticoagulant activity, decrease of circulating autoreactive CD5 (+) B lymphocytes and increased urinary levels of IgG and kappa and lambda light chains, suggesting a possible defect in regulation of B-lymphocyte function. In the light of the NGF-related molecular defect, the extraneurological tissue involvement in CIPA might in part reflect dysregulation of immune mechanisms which possibly brings about a chronic inflammatory response. This, in turn, could result in renal disease which should be mentioned among the life-threatening complications associated with this disorder.
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PMID:Congenital insensitivity to pain with Anhidrosis (NTRK1 mutation) and early onset renal disease: clinical report on three sibs with a 25-year follow-up in one of them. 1613 53


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