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)

A method for obtaining luminescent sera, consisting in isolation of pure antigens G, A, M from human gamma-globulin and blood serum from patients with myeloma disease is suggested. A native antiserum was obtained by immunization of rabbits with water-insoluble polycondensate of antigens "sewn" with glutaric aldehyde. Adsorption of antisera as well as specific antigens was carried out with antigen- and antibodyimmunosorbent, the latter being obtained with the help of both glutaric aldehyde and sefarose 4B treated with cyanogen bromide. The sera had a specific titre in the precipitation reaction against their own antigens 1:32 and were highly specific. A globulin fraction was obtained by sedimentation with polyethylene-glycol. Marking of the specific protein with fluoresceine isothiocyanate was carried out using the dialysis method with subsequent purification on sefadex and DEAE-cellulose. The application of the abovementioned sera made it possible to ascertain the character of distribution of deposits of immunoglobulins in glomeruli in systemic lupus erythematodes, glomerulonephritis and in the cells of the synovial fluid sediment in rhematoid arthritis.
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PMID:[Utilization of luminescent monospecific sera against human immunoglobulins G, A and M for diagnostic purposes]. 110 50

To study the role of free radical formation on the impairment of pulmonary function seen with general anesthesia, we measured the hydrogen peroxide (H2O2) concentration in the exhaled breath condensate of 27 patients. Patients were divided into three study groups: a healthy patient group (group 1, n = 15) consisting of ASA physical status 1 and 2 patients undergoing elective noncardiothoracic surgery; a specific anesthetic event group (group 2, n = 6) composed of patients undergoing cardiopulmonary bypass (CPB); and a positive control group (group 3, n = 6) consisting of patients with the adult respiratory distress syndrome (ARDS). The exhaled breath condensate was collected by diverting exhaled breath through a glass condensation coil submerged in an ice/salt water bath. The exhaled breath condensate samples were then assayed using a spectrophotometric method. In group 1, samples were collected before and after the induction of general anesthesia with intravenous drugs, and before and after the administration of the inhalational anesthetics isoflurane (1.5%) (n = 7) or N2O (70%) (n = 8). In group 2, samples were collected pre- and post-CPB, and in group 3, when specific diagnostic criteria for ARDS were met. There was no significantly detectable H2O2 (not significantly different from zero) in any of the samples from the group 1 patients. Similarly, group 2 patients had exhaled breath H2O2 concentrations near zero except for one patient who was positive for the lupus anticoagulant. Group 3 patients had a mean (+/- SE) exhaled breath H2O2 concentration of 0.55 (+/- 0.08) microM, which was significantly greater than zero (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:General anesthesia and exhaled breath hydrogen peroxide. 157 37

Criteria for the recognition of systemic lupus erythematosus (SLE) were applied to 362 subjects exposed to trichloroethylene, trichloroethane, inorganic chromium, and other chemicals in water obtained from wells in an industrially contaminated aquifer in Tucson, Arizona. Their antinuclear autoantibodies were measured by fluorescence (FANA) in serum. Ten patients with clinical SLE and/or other collagen-vascular diseases were considered separately. Results were compared to an Arizona control group, to published series, and to laboratory controls. Frequencies of each of 10 ARA symptoms were higher in exposed subjects than in any comparison group except those with clinical SLE. The number of subjects than in any comparison group except those with clinical SLE. The number of subjects with 4 or more symptoms was 2.3 times higher compared to referent women and men. FANA titers greater than 1:80 was approximately 2.3 times higher in women but equally frequent in men as in laboratory controls. ARA score and FANA rank were correlated with a coefficient (cc) of .1251, r2 = .0205 (p less than 0.036) in women and this correlation was almost statistically significant in men cc = .1282, r2 = .0253 (p less than 0.059). In control men and women neither correlation was significant. Long-term low-dose exposure to TCE and other chemicals in contaminated well water significantly increased symptoms of lupus erythematosus as perceived by the ARA score and the increased FANA titers.
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PMID:Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water. 174 91

We studied the effects of difluoromethylornithine (DFMO), an experimental drug that inhibits the biosynthesis of natural polyamines, on anti-DNA antibody production, immunoglobulin synthesis, proteinuria, and blood urea nitrogen (BUN) in lupus-prone female NZB/W mice. Administration of 1% of the drug in drinking water reduced anti-DNA antibody levels by about 80% of that of untreated mice of the same strain. There was a reduction of IgG and IgA levels in older DFMO treated mice, whereas IgM level was not affected. Proteinuria and BUN were also significantly reduced in treated mice. Moreover, DFMO treatment reduced the concentration of putrescine and spermidine in spleen cells. Our results suggest that polyamine biosynthesis inhibition by DFMO may provide a new approach to the treatment of lupus.
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PMID:Difluoromethylornithine therapy of female NZB/W mice. 202 14

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of cellular polyamines, putrescine, spermidine and spermine. Difluoromethylornithine (DFMO) is an irreversible inhibitor of ODC and thereby depletes putrescine and spermidine levels in vivo and in vitro. Previous studies in lupus-prone MRL-lpr/lpr mice treated with 1% DFMO in drinking water have been associated with improved lifespan, and reduced anti-DNA antibody production, lymphadenopathy, and splenic polyamine levels. Since glomerulonephritis is a major cause of morbidity and mortality in lupus, we studied the effect of DFMO on renal histology of MRL-lpr/lpr mice. Female BALB/c and MRL-(+)/+ mice were used as controls. Dose response studies revealed that 1.5% DFMO in drinking water had maximum therapeutic efficacy and produced a significant 79% increase in the median lifespan of a group of 20 mice compared to an equal number of controls (P less than 0.001). Renal histologic studies were performed on kidney sections from four to five mice each from DFMO-treated and untreated groups at 12, 16, 20, 24 and 29 weeks of age. Sections were read blinded to duration and treatment and scored by four major histologic criteria (glomerulonephritis, interstitial inflammation, perivascular inflammation, and vasculitis) and showed significant reduction in all these parameters in DFMO-treated mice when compared to age- and sex-matched untreated mice of the same strain. DFMO treatment had no significant effect on pulmonary histologic findings on these mice. DFMO treatment reduced ODC activity and polyamine concentrations in treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Successful treatment of lupus nephritis in MRL-lpr/lpr mice by inhibiting ornithine decarboxylase. 206 4

We conducted a series of experiments to examine the efficacy of Telazol (TEL) for immobilization of captive gray wolves (Canis lupus). Ten wolves were immobilized with either 5 or 10 mg/kg TEL. There was no difference in induction time (6.5 +/- 0.8 versus 5.8 +/- 1.2 min; P = 0.63) between the two doses, but the time to initial arousal was longer for the higher dose (P = 0.0008). Wolves were again immobilized with 10 mg/kg TEL and upon initial arousal were given additional doses of either 5.0 mg/kg TEL or 2.5 mg/kg ketamine (KET) to maintain immobilization. Wolves given boosters of TEL had longer second recovery times than wolves given KET (P = 0.01). There were no differences in induction times or arousal times for wolves immobilized with TEL that had been reconstituted with sterile water and stored at 20 C for 30 days (P greater than or equal to 0.11) or 60 days (P greater than or equal to 0.27) when compared to immobilization times using fresh solution. Induction times for wolves given TEL reconstituted with water and propylene glycol and stored for 60 days at -9 C were longer (P less than 0.05) than such times for wolves given standard TEL, but time to initial arousal was unchanged (P greater than or equal to 0.44). There were no differences in heart rates (P = 0.36), blood pressures (P = 0.32), respiratory rates (P = 0.91), and rectal temperatures (P = 0.62) between the two TEL doses. Telazol was shown to be an effective and safe immobilizing agent for gray wolves.
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PMID:Physiological and behavioral responses of gray wolves (Canis lupus) to immobilization with tiletamine and zolazepam. 230 5

The antifreeze protein genes of the wolffish (Anarhichas lupus) constitute a large multigene family of 80 to 85 copies, which can be classified into two sets. One-third of the genes were linked but irregularly spaced. The other two-thirds were organized as 8-kilobase-pair (kbp) tandem direct repeats that each contained two genes in inverted orientation; DNA sequence analysis suggests that both genes are functional. Except for a single region specific to each gene, the genes and their immediate flanking sequences were 99.2% identical. This degree of identity ended soon after a putative transcription termination sequence; as the 3' ends of the genes were only 1.3 kbp apart, these sequences might confer mutual protection from interference by transcriptional runoff. A Southern blot of wolffish DNA restricted with enzymes that do not cut within the tandem repeats indicated that the repeats were clustered in groups of six or more. The organization of antifreeze protein genes in the wolffish was very similar to that in the unrelated winter flounder, which produces a completely different antifreeze. This similarity might reflect common dynamics by which their progenitors adapted to life in ice-laden sea water.
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PMID:Wolffish antifreeze protein genes are primarily organized as tandem repeats that each contain two genes in inverted orientation. 285 24

Selenium is a trace mineral and a required nutrient for animals and humans. Selenium intake appears to be inversely correlated with the risk of developing cancer. Since immunological effects of selenium have been described we studied the capacity of selenium to modify the lupus-like disease of NZB/NZW female mice. Our data indicate that selenium supplementation (sodium selenite 4 parts per million in the drinking water) significantly improves survival in these autoimmune mice: mean survival 55.6 +/- 4.6 weeks (mean +/- s.e.) for treated mice versus 36.1 +/- 1.9 weeks for controls (P less than 0.04). Additionally, selenium supplemented mice had significantly higher natural killer cell activity (P less than 0.001). However, no obvious effects of selenium supplementation on autoantibody production were observed.
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PMID:Improved survival in murine lupus as the result of selenium supplementation. 326 35

A/J mice are proposed as a model of the human lupus diathesis since we previously determined that they express a slow acetyltor phenotype while others showed them to have a predisposition to develop spontaneous and drug-induced antinuclear antibodies. A/J mice were mated with C57BL/6J mice, a rapid acetylator phenotype which is relatively resistant to spontaneous and drug-induced antinuclear antibodies, to assess the importance of slow acetylator status as a component of the lupus diathesis. Procainamide, a potent inducer of antinuclear antibodies, was acetylated to a lesser degree by A/J mice than by C57BL/6J mice. This difference, detectable by in vitro assay but not by urinary levels of acetylated drug, represents a genetic polymorphism which can be detected in F2 and backcross progency of these two strains. We confirmed that A/J mice have a higher incidence of spontaneous antinuclear antibodies than C57BL/6J mice and that in A/J mice these antibodies can be induced by oral procainamide (6 g/l of drinking water for 37 weeks); procainamide tended to suppress antinuclear antibody formation in C57BL/6J mice, however. Rapid and slow acetylators among F2 and backcross populations were identified by a test for N-acetyltransferase activity in blood hemolysates. These two groups together with their respective rapid and slow acetylator parents were compared in respect to incidence of antinuclear antibodies. Slow acetylator phenotypes among F2 and backcross mice were predisposed to high titers of antinuclear antibodies like the slow acetyltor A/J strain. However, long-term exposure to procainamide suppressed antinuclear antibody formation as was found in the rapid acetylator C57BL/6J strain. Thus, the ability to N-acetylate procainamide is not the sole factor controlling the ability of this drug to induce antinuclear antibodies.
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PMID:Antinuclear antibodies related to acetylator phenotype in mice. 697 Aug 9

The lymphoproliferative lpr gene confers a lupus-like disease with lymphadenopathy, antinuclear antibody production, and glomerulonephritis in MRL-lpr/lpr mice. Upregulation of ornithine decarboxylase (ODC) activity and polyamine levels have been observed in the kidney and lymphoid organs of this strain. Inhibition of ODC with 0.5-1.5% (w/v) difluoromethylornithine (DFMO) in drinking water prolonged life-span and ameliorated renal disease. Glomerulonephritis is a major cause of morbidity and mortality in human and murine lupus. In order to elucidate the mechanism(s) of ODC regulation in lupus nephritis, we characterized ODC at the protein and mRNA levels in 3 strains of autoimmune mice with the lpr genetic background (MRL-lpr/lpr, C3H-lpr/lpr and C57BL/6J-lpr/lpr) using Western blotting, enzyme kinetics, turnover rate measurements, Northern blot hybridization, and reverse transcription-polymerase chain reaction (RT-PCR). Normal BALB/c mice were used as a control. We found that ODC activity in the kidney of lpr strains was 4- to 6-fold higher than that of BALB/c mice. The intensity of the major ODC protein band at 54 kD in Western blot was 4-fold higher in MRL-lpr/lpr and C3H-lpr/lpr kidney compared to that of BALB/c kidney. Putrescine levels were 2- to 4-fold higher in kidney of lpr strains than that of BALB/c and DFMO-treated MRL-lpr/lpr mice. DFMO treatment significantly reduced ODC activity and polyamine levels. The half-life of ODC enzyme in MRL-lpr/lpr, C3H-lpr/lpr, B6-lpr/lpr and BALB/c mouse kidneys was 15, 5, 8 and 23 min, respectively. There was no significant difference in the Km values of different strains, whereas Vmax values differed significantly. There was no difference in the level of SAMDC, another enzyme involved in the polyamine biosynthetic pathway, in various strain. Steady-state levels of ODC mRNA were lower in lpr strains compared to that of BALB/c mouse. Our results suggest that the basis for up-regulation of ODC is not at the transcriptional level, but may involve post-transcriptional modification(s) in lpr strains. The link between aberrant regulation of ODC and the immunopathogenesis of murine lupus nephritis indicates novel targets for lupus therapy.
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PMID:Regulation of ornithine decarboxylase in the kidney of autoimmune mice with the lpr gene. 757 52


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