Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human TNF alpha locus locates between HLA-B and DR region on the short arm of chromosome 6. The 5.5 kb and 10.5 kb of TNF alpha restriction fragment length polymorphic (RFLP) bands were identified by Southern hybridization using a restriction enzyme, NcoI. The frequencies of those bands were not different among patients with systemic lupus erythematosus (SLE), those with rheumatoid arthritis and normal controls. In the lupus patients, proteinuria was more frequent in the patients with the 5.5 kb RFLP band (19/39: 48.7%) than those without 5.5 kb band (7/35: 20%) (p less than 0.05). Furthermore, this band was strongly associated with the haplotype HLA B44-DRw13-DQw1. In order to investigate the association between this gene polymorphism and the production of TNF alpha, peripheral blood mononuclear cells from patients with SLE and normal controls were cultured for 24 hours with lipopolysaccharide and concanavalin A and the amount of TNF alpha in the supernatant was measured by enzyme linked immunosorbent assay. The TNF alpha production of lupus patients was not statistically different from that of normal controls. The production of TNF alpha was not related to 5.5 kb RFLP band, but in the patients with SLE, the mean value of TNF alpha in patients with the 5.5 kb RFLP band tended to be higher than those without the band. Lupus patients were divided into two groups by the production of TNF alpha i.e. low TNF alpha inducibility group and high TNF alpha inducibility group. Patients with proteinuria were more frequent in patients of the high TNF alpha inducibility group than those of low TNF alpha inducibility group (p less than 0.05). There were four patients with HLA B44-DRw13-DQw1 who had the 5.5 kb RFLP band and three of them belonged to the high TNF alpha inducibility group with nephrosis. These data suggest that TNF alpha and HLA are possibly associated with the severity of lupus nephritis.
 ...
PMID:[Tumor necrosis factor alpha in systemic lupus erythematosus: evaluation by restriction fragment length polymorphism and production by peripheral blood mononuclear cells]. 135 65

Pre-B cell lines proliferating for several months on stromal cells in the presence of interleukin 7 (IL-7) were established from fetal liver of (NZB x NZW)F1 mice. They express the B lineage-specific markers PB76, B220, and VpreB, but do not express surface immunoglobulin (sIg). Upon removal of IL-7 from the culture, they differentiate to sIg+ B cells that can then be stimulated by lipopolysaccharide to become IgM-secreting cells. Transfer of these pre-B cell lines into SCID mice leads to hypergammaglobulinemia of IgM (600-900 micrograms/ml), IgG2a (1-3 mg/ml), and IgG3 (300-500 micrograms/ml) for the next 3-5 mo. The spleen appears populated with (NZB x NZW)F1-derived pre-B cells, few B cells, and many IgM and/or IgG-producing plasma cells. In contrast, SCID mice populated with pre-B cell lines of normal (C57BL/6 x DBA/2)F1 mouse fetal liver develop normal levels of serum IgM (approximately 100-300 micrograms/ml), almost no detectable levels of IgG, and no plasma cell hyperplasia. The (NZB x NZW)F1 pre-B cell-populated SCID mice contain elevated serum titers of IgG antinuclear autoantibodies, but no retroviral gp70-specific nor erythrocyte-specific autoantibodies. Up to 20% of the SCID mice develop proteinuria as a consequence of IgG deposits in the kidney glomeruli during a 7-mo period of observation. All signs of autoimmune disease seen in these mice are independent of the sex of the SCID host. This experimental system provides a distinction between the disease-determining (NZB x NZW)F1 genes, which are expressed in the B lymphocyte lineage and cause the development of the disease, from those expressed in other cell lineages which only modulate its progression.
 ...
PMID:Development of autoimmune disease in SCID mice populated with long-term "in vitro" proliferating (NZB x NZW)F1 pre-B cells. 140 80

We examined the effect of a fish oil-enriched diet on the development of experimental membranous nephropathy in the rat induced by administration of cationic bovine gamma globulin (CBGG). Rats were placed on a fish oil-enriched diet and control rats received a diet containing an equivalent amount of beef tallow. After 6 weeks on either diet, rats were pre-immunized and injected with CBGG. Proteinuria was significantly reduced in the fish oil-fed group as compared to the control group (160 +/- 40 mg/24 hours, n = 15, versus 280 +/- 36 mg/24 hours, n = 17, p less than 0.02). Glomerular filtration rate was also significantly higher in the fish oil-fed rats than in controls (0.91 +/- 0.07 ml/minute, n = 11, versus 0.60 +/- 0.05 ml/minute, n = 10, p less than 0.005). Glomerular production of prostaglandin E2 and thromboxane B2 the stable product of thromboxane A2, were inhibited by 68% and 70%, respectively, by the fish oil-enriched diet (n = 8, p less than 0.01 versus control). Glomerular leukotriene B4 was also inhibited by 50% in the fish oil-treated rats (n = 6, p less than 0.01), but inhibition of leukotriene B4 by the specific inhibitor L-663,536 in control rats did not ameliorate proteinuria. There was no difference in the amount of distribution of glomerular immune deposits as demonstrated by immunofluorescence and electron microscopy between the experimental and control groups. Moreover, comparable amounts of glomerular IgG deposits were present in the two groups. The specific immune response, assessed by measuring anti-BGG antibody levels, was not different between the two dietary groups, while more than 85% suppression of the splenic T- and B-cell mitogenic response to concanavalin-A and lipopolysaccharide was noted in rats fed the fish oil-enriched diet. We conclude that a fish oil-enriched diet reduces proteinuria and preserves the glomerular filtration rate in rats with CBGG-induced membranous nephropathy. Its mechanism of action remains to be established.
 ...
PMID:Effects of dietary fish oil on the induction of experimental membranous nephropathy in the rat. 170 5

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. A concomitance between enhanced I-a display by resident glomerular macrophages, IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis.
 ...
PMID:IL-1-like production in adriamycin-induced nephrotic syndrome in the rat. 173 26

Systemic lupus erythematosus is a multifactorial systemic disease in which genetic, immunologic, hormonal, and environmental factors may contribute to disease pathogenesis. Bacterial products (eg, bacterial lipopolysaccharide [LPS]) induce a lupuslike disease in normal mice and trigger an early and accelerated form of lupus nephritis in NZB/W mice. To investigate whether the mechanism by which LPS accelerates nephritis in the NZB/W mice involves interference with processing of immune complexes (IC), we administered LPS to NZB/W mice for 5 weeks and probed the kinetics of removal, liver uptake, and organ localization of a subsaturating dose of radiolabeled IC (2.5 mg of bovine serum albumin-antibovine serum albumin). Control NZB/W mice received vehicle (saline) alone. In NZB/W exposed to LPS, features of polyclonal B-cell activation (PBA) were enhanced, anti-DNA antibodies were raised, and a proliferative glomerulonephritis developed that was associated with renal insufficiency and substantial proteinuria. This LPS-accelerated nephritis could not be attributed to altered complement concentration, to altered blood cell carrier function, to delayed removal of pathogenic (large-sized) ICs from the circulation, to impaired liver uptake of ICs, or to enhanced localization of ICs in kidney. The findings indicate that transformation of nephritis is probably the result of LPS-induced PBA, that defective processing of pathogenic IC is not a contributory factor to nephritis, and that mechanisms other than passive renal localization of circulating ICs must be operative.
 ...
PMID:Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice. 222 Oct 21

Patients with systemic lupus erythematosus experience clinical exacerbation during superimposed bacterial infection. Previous studies in mice indicated that heightened immune phenomena during exposure to bacterial lipopolysaccharide (LPS) appear to be related, in part, to polyclonal B cell activation, to abnormal disposal of immune complexes (IC), and to increased localization of IC in tissues. To investigate whether such effects were reversible, we administered bacterial LPS to C57BL/6 mice for 5 weeks. Control mice received vehicle alone. We then discontinued LPS, and 6 weeks later LPS and control mice were challenged with a subsaturating dose of radiolabeled IC; the removal of IC from the circulation, their localization in the liver, spleen, and kidney were determined. In comparison to values in control mice, in mice previously exposed to LPS, serologic features of polyclonal B cell activation persisted; liver uptake of pathogenic IC (greater than Ag2Ab2) was normal, but removal of small size IC (less than or equal to Ag2Ab2) from the circulation was delayed; localization of IC in the kidneys was enhanced, and pathologic proteinuria developed. The effects of repeated exposure to bacterial LPS are partially reversible, but they last long after LPS is discontinued and may contribute to altered disposal of IC, enhanced organ localization of IC, and organ dysfunction.
 ...
PMID:Defective disposal of immune complexes and polyclonal B cell activation persist long after exposure to bacterial lipopolysaccharide in mice. 281 Dec 99

We investigated the relationship between the increased cell diameter of Lyt-2+ T cells and the development of autoimmune disease in aging NZB and NZB X NZW F1 hybrid (BW) mice. Individual animals were analyzed for Lyt-2+ T cell size (by narrow-angle forward light scatter), anti-erythrocyte autoantibodies, anemia, proteinuria, and splenomegaly. The peak light scatter of the Lyt-2+ T cells correlated with the level of anti-erythrocyte autoantibodies and severity of hemolytic anemia, but not with proteinuria or splenomegaly. The cell size of this T cell subset did not increase in old BW or in NZB mice homozygous for the xid gene (NZB.xid). The in vivo administration of bacterial lipopolysaccharide to young NZB mice did not stimulate the enlargement of Lyt-2+ T cells. Ly-2+ T cells from old NZB mice could be stimulated by concanavalin A (Con A) to express interleukin 2 (IL 2) receptors and to synthesize DNA in vitro. However, in vivo administration of Con A to old NZB mice did not induce the expression of IL 2 receptors on Lyt-2+ T cells. Further, in vivo T suppressor function was impaired in old NZB mice with enlarged Lyt-2+ T cells. Thus, the enlargement of Lyt-2+ T cells in old NZB mice appears related to impaired T cell function in vivo and is associated with the development of anti-erythrocyte autoantibodies and autoimmune hemolytic anemia.
 ...
PMID:Enlargement of Lyt-2-positive T cells is associated with functional impairment and autoimmune hemolytic anemia in New Zealand Black mice. 392 48

We investigated the pathogenesis of increased glomerular permeability in Balb/c mice after 5 weeks of administration of a polyclonal B cell activator (bacterial lipopolysaccharide). The glomerular transfer of anionic ferritin across the capillary walls and the urinary excretion of serum albumin served as probes of glomerular permeability; anionic groups of the glomerular basement membrane were assessed by the binding of cationized ferritin, and glomeruli were studied by light, immunofluorescence, and electron microscopy. The mice developed circulating immune complexes, proteinuria, and a proliferative glomerulonephritis, with mesangial and capillary loop deposits of immunoreactants. Increased transfer of anionic ferritin molecules occurred across capillary walls with and without demonstrable electron-dense deposits; detachments of visceral epithelium were not seen, and epithelial transport of anionic ferritin was negligible. Loss of anionic groups was extensive in glomerular capillary loops with and without associated electron-dense deposits. The findings indicate that an increase in glomerular permeability may precede the deposition of immunoreactants in the capillary wall; that filtration of macromolecules can occur across capillary walls with or without demonstrable immune deposits; and that loss of anionic groups of the glomerular basement membrane and enhanced filtration of macromolecules can occur in the absence of focal detachments of the visceral epithelium.
 ...
PMID:Altered glomerular permeability in the early phase of immune complex nephritis. 622 69

F1 hybrid offspring of New Zealand Black mothers and New Zealand White fathers [(NZB X NZW)F1] female mice develop antibodies to single-stranded (ss) and native DNA, immune complex glomerulonephritis, massive proteinuria, and premature death with renal failure. By a series of matings, congenic (NZB X NZW)F1 . xid/xid mice were prepared. These mice were different from (NZB X NZW)F1 mice in having the X chromosome-linked immune deficiency gene, xid, in homozygous form. Such congenic (NZB X NZW)F1 . xid/xid females failed to develop antibodies to single-stranded or native DNA. They also failed to develop fatal renal disease as measured by proteinuria, glomerular histology, glomerular immunofluorescence, and survival. To control for unknown genetic factors, studies were performed with littermates that were derived by mating NZB . xid/+ females with NZW . xid/Y males such that the resulting offspring were either (NZB X NZW)F1 . xid/xid (and therefore "defective") or (NZB X NZW)F1 . xid/+ [phenotypically like (NZB X NZW)F1]. In these and in additional studies, mice were housed in the same cages and identified by ear tagging so as to avoid possible environmental variations from cage to cage. In these studies, xid/xid mice failed to develop the characteristic signs of autoimmunity, whereas the controls did. Similar results were also obtained with (NZW X NZB)F1 xid/xid mice compared with (NZW X NZB)F1 xid/+ mice. The effect of xid/xid upon (NZB X NZW)F1 mice was further investigated by assessing responses to immunization and polyclonal B cell activation in vivo. The xid/xid mice failed to produce anti-ssDNA following immunization with ssDNA complexed to a protein carrier in fluid form or even emulsified in adjuvant. Finally, the xid/xid mice failed to produce antiDNA in response to multiple injections of the polyclonal activator, bacterial lipopolysaccharide (LPS), or the polyclonal activator, polyribose inosinic acid . polyribose cytidylic acid. However, the xid/xid mice were neither generally hyporesponsive nor unable to recognize LPS because they made normal antibody responses following immunization with LPS to which multiple trinitrophenyl groups were chemically attached. We conclude from these studies that xid/xid, which is known to cause the deletion of a B cell subset, has a profound affect upon (NZB X NZW)F1 mice, rendering them insusceptible to the naturally occurring autoimmune disease characteristic of (NZB X NZW)F1 mice, and preventing them from producing antibodies to DNA despite purposeful immunization and polyclonal B cell activation. These results force a reevaluation of previous concepts regarding the mechanisms by which xid/xid might interfere with the development of autoimmunity, and a consideration of therapeutic implications.
 ...
PMID:Ability of the xid gene to prevent autoimmunity in (NZB X NZW)F1 mice during the course of their natural history, after polyclonal stimulation, or following immunization with DNA. 698 Sep

We investigated the effect of the potent immunosuppressive agent, FK506, on experimental glomerular thrombosis in rats by combined injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS). Either FK506 or placebo was administered intramuscularly three hours prior to injection of NTS that was followed one hour later by LPS. Rats were killed five hours after the LPS injection. Compared with placebo, FK506 pretreatment significantly reduced thrombosis formation, in a dose-dependent manner. FK506 also reduced proteinuria and the rise of serum creatinine level. Early infiltration of polymorphonuclear leukocytes into the glomeruli after LPS injection was significantly suppressed in the FK506 group compared with the placebo group. We also measured serum tumor necrosis factor (TNF) activity by using an L929 fibroblast cytotoxicity assay. Peak serum TNF activity was observed one hour after LPS injection, and FK506 significantly suppressed the elevation. Thrombosis was also developed in athymic nude rats, suggesting thrombosis formation is T cell independent. These data suggest that the FK506 has inhibitory effects on non-lymphocytes and possesses an anti-inflammatory effect in vivo.
 ...
PMID:FK506 inhibits renal glomerular thrombosis induced in rats by nephrotoxic serum and lipopolysaccharide. 752 50


1 2 3 4 5 6 7 8 9 10 Next >>