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Sample records for experimental glomerulonephritis induced

  1. Experimental proliferative glomerulonephritis in the cat.

    PubMed

    Bishop, S A; Stokes, C R; Lucke, V M

    1992-01-01

    A model of chronic serum sickness was used to induce immune-complex glomerulonephritis in seven experimental cats, by daily intravenous inoculation of an increasing dose (5 to 35 mg) of human serum albumin (HSA). At week four, two of the seven animals developed anterior uveitis. At week 23, two different animals developed the subcutaneous oedema characteristic of the nephrotic syndrome (NS), whilst the other five cats appeared clinically normal. The kidneys were examined at necropsy by light microscopy and by transmission electron microscopy. The glomeruli of four animals (three with both proteinuria and uraemia, and one with proteinuria only) showed morphological changes under light microscopy. The abnormalities suggested that a diffuse mesangial proliferative glomerulonephritis (GN) had been induced in three cats and diffuse membranoproliferative GN induced in another. Ultrastructural studies revealed electron-dense deposits (immune-complexes) in six of the seven cats. Two cats without glomerular abnormalities by light microscopy had mesangial deposits and three cats with mesangial proliferative GN had deposits at mesangial, subendothelial and/or subepithelial sites. The single cat with membranoproliferative GN had deposits at mesangial, subendothelial, subepithelial and intramembranous sites. Immunohistological examination (peroxidase-antiperoxidase technique) showed that HSA and immunoglobulin (IgG and IgM) were deposited in the glomeruli of these cats. Deposits were the most dense in cats with more severe renal lesions. Deposits of IgM were most abundant. An extensive cellular infiltrate, comprising macrophages, neutrophils and plasma cells, was observed only in the four animals which showed abnormalities in glomerular ultrastructure. The disease induced in these cats thus appears to differ from the membranous nephropathy previously described in the cat and bears a close resemblance to immune complex (IC) disease in man. In view of the relatively few specific

  2. Mucosal Tolerance Induced by an Immunodominant Peptide from Rat α3(IV)NC1 in Established Experimental Autoimmune Glomerulonephritis

    PubMed Central

    Reynolds, John; Abbott, Danielle S.; Karegli, Julieta; Evans, David J.; Pusey, Charles D.

    2009-01-01

    Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the α 3 chain of type IV collagen, α3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat α3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 μg had no effect, a dose of 1000 μg resulted in a moderate reduction in EAG severity, and a dose of 3000 μg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of α3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture’s disease and other autoimmune disorders. PMID:19406992

  3. Glomerulonephritis

    MedlinePlus

    ... that suppress the immune system A procedure called plasmapheresis may sometimes be used for glomerulonephritis caused by ... Saunders; 2012:chap 32. Cattran DC, Reigh HN. Overview of therapy for glomerular disease. In: Taal MW, ...

  4. Th1 and Th17 Cells Induce Proliferative Glomerulonephritis

    PubMed Central

    Summers, Shaun A.; Steinmetz, Oliver M.; Li, Ming; Kausman, Joshua Y.; Semple, Timothy; Edgtton, Kristy L.; Borza, Dorin-Bogdan; Braley, Hal; Holdsworth, Stephen R.

    2009-01-01

    Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1−/− mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against α3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 ± 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies. PMID:19820122

  5. Th1 and Th17 cells induce proliferative glomerulonephritis.

    PubMed

    Summers, Shaun A; Steinmetz, Oliver M; Li, Ming; Kausman, Joshua Y; Semple, Timothy; Edgtton, Kristy L; Borza, Dorin-Bogdan; Braley, Hal; Holdsworth, Stephen R; Kitching, A Richard

    2009-12-01

    Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1(-/-) mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against alpha3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 +/- 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies. PMID:19820122

  6. Mesangial Localization of Immune Complexes in Experimental Canine Adenovirus Glomerulonephritis

    PubMed Central

    Wright, N. G.; Morrison, W. I.; Thompson, H.; Cornwell, H. J. C.

    1974-01-01

    Each of a group of 14 dogs was infected experimentally by an intravenous dose of canine adenovirus calculated to allow survival until the initial stages of antibody production; the kidneys of infected dogs were examined during the period of 4-14 days after administration of virus. Proliferative glomerulonephritis with localization of IgG, C3 and viral antigen in mesangial regions was demonstrated. With the electron microscope, electron dense deposits were found scattered throughout the mesangium. There was proliferation of mesangial cells, infiltration into the glomerular tuft of polymorphonuclear leucocytes and, in some cases, focal glomerular necrosis with intracapsular and tubular haemorrhage. By means of an indirect immunofluorescence test, anti-viral antibody was detected in kidney eluates; anti-kidney antibody was not present. ImagesFigs. 5-8Figs. 9-10Figs. 1-4 PMID:4375485

  7. Membranoproliferative glomerulonephritis

    MedlinePlus

    Membranoproliferative GN I; Membranoproliferative GN II; Mesangiocapillary glomerulonephritis; Membranoproliferative glomerulonephritis; Lobular GN; Glomerulonephritis - membranoproliferative; MPGN type I; MPGN type ...

  8. Glomerulonephritis-induced changes in kidney gene expression in rats

    PubMed Central

    Pavkovic, Mira; Riefke, Björn; Frisk, Anna-Lena; Gröticke, Ina; Ellinger-Ziegelbauer, Heidrun

    2015-01-01

    We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans (Pusey, 2003[2]). Male Wistar Kyoto (WKY) and Sprague–Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. To obtain insight into molecular processes during GN pathogenesis, mRNA expression was investigated in WKY and SD kidneys using Affymetrix's GeneChip Rat genome 230_2.0 arrays (GSE64265). The immunopathological processes during GN are still not fully understood and likely involve both innate and adaptive immunity. In the present study, several hundred mRNAs were found deregulated, which functionally were mostly associated with inflammation and regeneration. The β-chain of the major histocompatibility complex class II RT1.B (Rt1-Bb) and complement component 6 (C6) were identified as two mRNAs differentially expressed between WKY and SD rat strains which could be related to known different susceptibilities to NTS of different rat strains; both were increased in WKY and decreased in SD rats (Pavkovic et al., 2015 [1]). Increased Rt1-Bb expression in WKY rats could indicate a stronger and more persistent cellular reaction of the adaptive immune system in this strain, in line with findings indicating adaptive immune reactions during GN. The complement cascade is also known to be essential for GN development, especially terminal cascade products like C6. PMID:26697341

  9. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

    PubMed

    Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

    2009-11-01

    Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required. PMID:19524415

  10. P2X7 Deficiency Attenuates Renal Injury in Experimental Glomerulonephritis

    PubMed Central

    Taylor, Simon R.J.; Turner, Clare M.; Elliott, James I.; McDaid, John; Hewitt, Reiko; Smith, Jennifer; Pickering, Matthew C.; Whitehouse, Darren L.; Cook, H. Terence; Burnstock, Geoffrey; Pusey, Charles D.; Unwin, Robert J.; Tam, Frederick W.K.

    2009-01-01

    The P2X7 receptor is a ligand-gated cation channel that is normally expressed by a variety of immune cells, including macrophages and lymphocytes. Because it leads to membrane blebbing, release of IL-1β, and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of inflammatory diseases. Although the P2X7 receptor is usually not detectable in normal renal tissue, we previously reported increased expression of both mRNA and protein in mesangial cells and macrophages infiltrating the glomeruli in animal models of antibody-mediated glomerulonephritis. In this study, we used P2X7-knockout mice in the same experimental model of glomerulonephritis and found that P2X7 deficiency was significantly renoprotective compared with wild-type controls, evidenced by better renal function, a striking reduction in proteinuria, and decreased histologic glomerular injury. In addition, the selective P2X7 antagonist A-438079 prevented the development of antibody-mediated glomerulonephritis in rats. These results support a proinflammatory role for P2X7 in immune-mediated renal injury and suggest that the P2X7 receptor is a potential therapeutic target. PMID:19389853

  11. Experimental glomerulonephritis in the isolated perfused rat kidney.

    PubMed Central

    Couser, W G; Steinmuller, D R; Stilmant, M M; Salant, D J; Lowenstein, L M

    1978-01-01

    The development of immune deposits on the subepithelial surface of the glomerular capillary wall was studied in isolated rat kidneys perfused at controlled perfusion pressure, pH, temperature, and flow rates with recirculating oxygenated perfusate containing bovine serum albumin (BSA) in buffer and sheep antibody to rat proximal tubular epithelial cell brush border antigen (Fx1A). Control kidney were perfused with equal concentrations of non-antibody immunoglobulin (Ig)G. Renal function was monitored by measuring inulin clearance, sodium reabsorption, and urine flow as well as BSA excretion and fractional clearance. Perfused kidneys were studied by light, immunofluorescence, and electron microscopy. All kidneys perfused with anti-Fx1A developed diffuse, finely granular deposits of IgG along the glomerular capillary wall by immunofluorescence. Electron microscopy revealed these deposits to be localized exclusively in the subepithelial space and slit pores. Similar deposits were produced in a nonrecirculating perfusion system, thereby excluding the formation of immune complexes in the perfusate caused by renal release of tubular antigen. Control kidneys perfused with nonantibody IgG did not develop glomerular immune deposits. Renal function and BSA excretion were the same in experimental and control kidneys. Glomerular deposits in antibody perfused kidneys were indistinguishable from deposits in rats injected with anti-Fx1A or immunized with Fx1A to produce autologous immune complex nephropathy. These studies demonstrate that subepithelial immune deposits can be produced in the isolated rat kidney by perfusion with specific antibody to Fx1A in the absence of circulating immune complexes. In this model deposits result from in situ complex formation rather than circulating immune complex deposition. Images PMID:372233

  12. Treatment of experimental mesangioproliferative glomerulonephritis with non-anticoagulant heparin: therapeutic efficacy and safety.

    PubMed

    Burg, M; Ostendorf, T; Mooney, A; Koch, K M; Floege, J

    1997-04-01

    Treatment with conventional heparin is effective in experimental mesangioproliferative glomerulonephritis. However, the long-term effects and safety of this therapy, in particular in the presence of mesangiolysis, have not been assessed. In addition, this therapy has been hampered by bleeding complications. In the present study, therefore, we investigated the long-term effects of a short course of non-anticoagulant (NA) heparin treatment in the anti-Thy 1.1 mesangioproliferative glomerulonephritis, in which early immune-mediated mesangiolysis subsequently leads to mesangial hyperproliferation. Rats received continuous ip NA-heparin or vehicle during the active mesangioproliferative phase (Days 2 to 9; early treatment) or during the early resolution phase (Days 10 to 17; late treatment). Whereas NA-heparin in the early treatment group did not affect the glomerular macrophage, lymphocyte, or platelet influx, it did lead to significantly decreased glomerular cellularity, mesangial cell proliferation, alpha-smooth muscle actin, desmin expression (ie, markers of activated mesangial cells), and matrix accumulation as well as to persistent mesangiolytic lesions including microaneurysms. Despite this latter finding, at Day 120, NA-heparin-treated rats of the early treatment group showed significantly better renal function and less proteinuria and glomerulosclerosis than vehicle-infused rats. In contrast, late therapy with NA-heparin neither accelerated resolution of the nephritis or otherwise affected the course of the disease. We conclude that transient NA-heparin therapy is effective in mesangioproliferative glomerulonephritis, both acutely and long term, when it is initiated during the active phase of the disease. Also, NA-heparin therapy is safe even in glomerular diseases accompanied by mesangiolysis. PMID:9111513

  13. Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis.

    PubMed

    Bishop, S A; Bailey, M; Lucke, V M; Stokes, C R

    1992-07-01

    An experimental model of proliferative glomerulonephritis (GN) in the cat, which closely resembles human proliferative forms of GN, has been used to study the role of antibody and antibody affinity in the development of immune complex-mediated renal disease. The serum IgG and IgM antibody response to antigen, average antibody affinity (avidity) and affinity heterogeneity of the IgG and IgM populations was assessed at varying times after commencement of chronic immunization with the antigen, human serum albumin (HSA), by enzyme immunoassay. Cats could be classified according to whether they were "low", "intermediate" or "high" IgG responders, by quantification of serum IgG values. Cats with the lowest serum IgG values failed to develop glomerulonephritis. However, there was no relationship between actual IgG values and the severity of the induced disease. In contrast to IgG, there was no division of cats into low or high IgM anti-HSA responders. Again, cats with the lowest IgM values failed to develop GN, but, more interestingly, a late, marked increase in serum IgM anti-HSA occurred only in cats that developed clinical signs of GN (anterior uveitis and nephrotic syndrome). Maturation of average, functional IgG affinity (avidity) for HSA following chronic immunization was clearly demonstrated for all cats. At the end of the experiment, all cats had IgG of high affinity for HSA and the average affinity heterogeneity of the IgG populations was less than in measurements taken earlier. Values of IgG affinity at the end of the experiment were very similar both in cats which developed GN and in those which remained clinically, biochemically and pathologically normal. In contrast to IgG antibody, some cats developed IgM of increased affinity, whilst others produced antibody of reduced affinity, following chronic immunization. There was no correlation between the development of disease and the production of either low or high affinity IgM antibody. Data indicated that an

  14. Hepatitis E Virus-Induced Cryoglobulinemic Glomerulonephritis in a Nonimmunocompromised Person.

    PubMed

    Guinault, Damien; Ribes, David; Delas, Audrey; Milongo, David; Abravanel, Florence; Puissant-Lubrano, Bénédicte; Izopet, Jacques; Kamar, Nassim

    2016-04-01

    Hepatitis E virus (HEV)-related kidney disease and symptomatic cryoglobulinemia have been observed in solid-organ transplant recipients. However, HEV RNA in the cryoprecipitate has not yet been assessed. We report what to our knowledge is the first documented case of autochthonous HEV-induced cryoglobulinemic crescentic and membranoproliferative glomerulonephritis in an immunocompetent man with no notable medical history. He presented with edema, hypertension, increased serum creatinine level, and nephrotic syndrome. Type II cryoglobulinemia with monoclonal immunoglobulin G (IgG) κ light chain was detected. Anti-HEV IgG and IgM, as well as HEV RNA, were detected in serum and cryoprecipitate. Histologic analysis of a kidney biopsy specimen revealed features of crescentic and membranoproliferative glomerulonephritis. After HEV clearance, kidney and liver parameters improved and HEV RNA and cryoglobulinemia were undetectable. Hence, we conclude that HEV can cause severe kidney disease and should be considered in cases of unexplained glomerular disease. PMID:26682764

  15. The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis.

    PubMed

    Ooi, Joshua D; Chang, Janet; Hickey, Michael J; Borza, Dorin-Bogdan; Fugger, Lars; Holdsworth, Stephen R; Kitching, A Richard

    2012-09-25

    Microscopic polyangiitis is an autoimmune small-vessel vasculitis that often manifests as focal and necrotizing glomerulonephritis and renal failure. Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a role in this disease, but the role of autoreactive MPO-specific CD4(+) T cells is uncertain. By screening overlapping peptides of 20 amino acids spanning the MPO molecule, we identified an immunodominant MPO CD4(+) T-cell epitope (MPO(409-428)). Immunizing C57BL/6 mice with MPO(409-428) induced focal necrotizing glomerulonephritis similar to that seen after whole MPO immunization, when MPO was deposited in glomeruli. Transfer of an MPO(409-428)-specific CD4(+) T-cell clone to Rag1(-/-) mice induced focal necrotizing glomerulonephritis when glomerular MPO deposition was induced either by passive transfer of MPO-ANCA and LPS or by planting MPO(409-428) conjugated to a murine antiglomerular basement membrane mAb. MPO(409-428) also induced biologically active anti-MPO Abs in mice. The MPO(409-428) epitope has a minimum immunogenic core region of 11 amino acids, MPO(415-426), with several critical residues. ANCA-activated neutrophils not only induce injury but lodged the autoantigen MPO in glomeruli, allowing autoreactive anti-MPO CD4(+) cells to induce delayed type hypersensitivity-like necrotizing glomerular lesions. These studies identify an immunodominant MPO T-cell epitope and redefine how effector responses can induce injury in MPO-ANCA-associated microscopic polyangiitis. PMID:22955884

  16. Hydralazine-induced pauci-immune glomerulonephritis: intriguing case series with misleading diagnoses

    PubMed Central

    Babar, Faizan; Posner, Jeffery N.; Obah, Eugene A.

    2016-01-01

    Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects. PMID:27124161

  17. Characterization of feline glomerulonephritis associated with viral-induced hematopoietic neoplasms.

    PubMed

    Glick, A D; Horn, R G; Holscher, M

    1978-08-01

    Light, electron, and immunofluorescence microscopy on tissues from 63 domestic cats revealed that glomerulonephritis occurred in almost one third of cats with hematopoietic neoplasms of the type linked with feline leukemia virus (FeLV). Glomerular lesions were of the immune complex type with subepithelial, subendothelial, and mesangial dense deposits and reticular aggregates, similar to the nephropathy associated with systemic lupus erythematosus in humans. Evidence that the glomerular lesions may be viral-induced raises the possibility of similar pathogenetic mechanisms in human disease. PMID:677265

  18. Genetic factors influence level of proteinuria in cationic antigen-induced immune complex glomerulonephritis in the rat.

    PubMed Central

    Kato, A; Thaiss, F; Oite, T; Günther, E; Batsford, S; Vogt, A

    1985-01-01

    The influence of genetic factors on the susceptibility of the rat to cationic antigen-induced in situ immune complex glomerulonephritis was investigated. The levels of proteinuria developing in 11 inbred strains of rats differing in MHC and in genetic background varied markedly. Susceptibility was not MHC associated but resided in the genetic background. PMID:3159528

  19. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo.

    PubMed

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E; Borza, Dorin-Bogdan

    2010-09-15

    The noncollagenous (NC1) domains of alpha3alpha4alpha5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport posttransplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of alpha3alpha4alpha5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM Abs. Alport alloantibodies, which bound to native murine alpha3alpha4alpha5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b(-/-) mice susceptible to Ab-mediated inflammation. Goodpasture autoantibodies, which bound to murine alpha3NC1 monomer and dimer subunits but not to native alpha3alpha4alpha5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 crosslinks, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked alpha3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys, a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of alpha3alpha4alpha5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by posttranslational modifications of an autoantigen. PMID:20709951

  20. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: Protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo 1

    PubMed Central

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E.; Borza, Dorin-Bogdan

    2010-01-01

    The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport post-transplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM antibodies. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to antibody-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 cross-links, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys—a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by post-translational modifications of an autoantigen. PMID:20709951

  1. Hydrogen Peroxide–Inducible Clone-5 Regulates Mesangial Cell Proliferation in Proliferative Glomerulonephritis in Mice

    PubMed Central

    Jamba, Ariunbold; Kondo, Shuji; Urushihara, Maki; Nagai, Takashi; Kim-Kaneyama, Joo-ri; Miyazaki, Akira; Kagami, Shoji

    2015-01-01

    Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein. We previously demonstrated that Hic-5 was localized in mesangial cells and its expression was associated with glomerular cell proliferation and matrix expansion in human and rat glomerulonephritis (GN). In the present study, we first assessed the role of Hic-5 in mesangioproliferative GN by injecting Habu venom into heminephrectomized wild type (Hic-5+/+) and Hic-5-deficient (Hic-5-/-) mice. Hic-5+/+ GN mice exhibited glomerular cell proliferation on day 7. Surprisingly, glomerular cell number and Ki-67-positive cells in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7, although the number of glomerular apoptotic cells and the expression of growth factors (platelet-derived growth factor-BB and TGF-β1) and their receptors were similarly increased in both Hic-5+/+ and Hic-5-/- GN mice. In culture experiments, proliferation assays showed that platelet-derived growth factor-BB and TGF-β1 enhanced the proliferation of Hic-5-/- mesangial cells compared with Hic-5+/+ mesangial cells. In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21. The present results suggest that Hic-5 might regulate mesangial cell proliferation in proliferative GN in mice. In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis. PMID:25835392

  2. Influenza vaccination induced leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis.

    PubMed

    Yanai-Berar, N; Ben-Itzhak, O; Gree, J; Nakhoul, F

    2002-09-01

    Influenza vaccination is a widely accepted practice, particularly among the elderly and high-risk individuals. Minor and transitory side effects following the vaccination are common, while systemic complications are infrequently reported. We describe here a case of a patient who presented to the emergency room with arthralgia, myalgias and purpura, following influenza vaccination. Necrotizing vasculitis associated with pauci-immune glomerulonephritis was observed on kidney biopsy. With increasing use of influenza vaccination, attention should be drawn to the possible expression of systemic adverse effects such as vasculitis and glomerulonephritis. PMID:12356192

  3. Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

    PubMed Central

    Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.

    2016-01-01

    Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429

  4. Plasma and urine biochemical changes in cats with experimental immune complex glomerulonephritis.

    PubMed

    Bishop, S A; Lucke, V M; Stokes, C R; Gruffydd-Jones, T J

    1991-01-01

    Biochemical changes in plasma and urine were monitored in six cats before and during the induction of immune complex-mediated glomerulonephritis (ICGN) by daily intravenous administration of human serum albumin (HSA). The earliest indication of renal dysfunction in the cats was hypoalbuminaemia, which occurred as early as 13 weeks before cats developed clinical signs of renal disease. Proteinuria occurred 2 to 3 weeks before clinical disease, but was sensitive in predicting renal pathology in two cats that did not develop clinical signs of disease. In addition, increased activities of several urinary enzymes were detected in affected cats, with measurement of N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transferase providing the earliest and most sensitive indication of renal damage. These plasma and urine measurements correlated more closely with the renal pathology, observed at postmortem, than clinical assessment of disease. It was concluded that ICGN in the cat could be diagnosed earliest by measurement of plasma protein concentration, whilst disease progress could be effectively monitored by including assays to measure urine protein and urine enzymes. PMID:1826913

  5. Acute glomerulonephritis.

    PubMed

    Yoshizawa, N

    2000-09-01

    Acute glomerulonephritis (AGN) is a representative disease of acute nephritic syndrome characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. The prototype of AGN is acute poststreptococcal glomerulonephritis (APSGN). "Nephritogenic streptococci" are defined as organisms that are cultured from a patient who develops AGN. Although only a limited number of M-types of streptococci have been recognized as "nephritogenic streptococci", all M-types of streptococci may have nephritogenic potential because the genes for major putative nephritogenic antigens such as SPEB and NAPIr are found to be present in all group A streptococci thus far examined. Pathogenic mechanisms for APSGN involving both humoral and cell-mediated immunity have been recently proposed. The role of humoral immunity is presumed to be mediated by the in situ formation of nephritogenic streptococcal antigen-antibody complexes and circulating immune complexes. While in the cellular immune component a role for delayed-type hypersensitivity has been suggested to contribute to the pathogenesis of APSGN. PMID:10969898

  6. Embryonic fibronectin isoforms are synthesized in crescents in experimental autoimmune glomerulonephritis.

    PubMed Central

    Nickeleit, V.; Zagachin, L.; Nishikawa, K.; Peters, J. H.; Hynes, R. O.; Colvin, R. B.

    1995-01-01

    Crescents are a severe and stereotyped glomerular response to injury that occur in several forms of glomerulonephritis that progress to renal failure. The key pathogenetic step that leads to glomerular scarring in unknown, but fibronectin (FN), the clotting system, macrophages, and proliferating parietal epithelial cells are known to participate. This study was designed to determine whether FN is synthesized locally, and in what molecular isoform, and whether cytokines known to promote FN synthesis are present in the crescent. Rats immunized with bovine glomerular basement membrane develop cellular crescents by 14 days and fibrous crescents and glomerulosclerosis by 35 days. In situ hybridization was performed with oligonucleotides specific for sequences common to all FN isoforms (total FN) or sequences specific for the alternatively spliced segments (EIIIA, EIIIB, and V). Throughout the time period (14, 21, and 35 days) all crescents and glomerular tufts contained cells with strong ISH signals for total and V+ mRNA, with the strongest signals present in large cellular crescents at day 21. In contrast, EIIIA+ and EIIIB+ mRNAs showed maximal abundance within sclerosing crescents at 35 days. Protein deposition of EIIIA+, EIIIB+, and V+ FN isoforms was confirmed by immunofluorescence with segment-specific FN antibodies. Transforming growth factor-beta and interleukin-1 beta, both known to promote FN synthesis, were found in cellular crescents (days 14 and 21) and were still present, but greatly diminished, in the sclerotic phase (day 35). In summary, EIIIA-, EIIIB-, and V+ FN mRNA plasma isoforms predominate in cellular crescents, whereas in the fibrosing stage, mainly the oncofetal EIIIA+, EIIIB+, and V+ isoforms are synthesized and accumulate. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7573372

  7. Experimental immune complex glomerulonephritis and the nephrotic syndrome in cats immunised with cationised bovine serum albumin.

    PubMed

    Nash, A S; Mohammed, N A; Wright, N G

    1990-11-01

    Membranous nephropathy was induced in four cats by repeated intravenous injections of 120 mg cationic bovine serum albumin (BSA, pI 9.5). All four cats developed diffuse granular deposits of IgG and C3 along the glomerular capillary walls as early as five weeks which persisted until the end of the experiment at 17 weeks. Ultrastructural studies revealed many subepithelial electron dense deposits. Two cats developed severe proteinuria and the nephrotic syndrome characterised by hypoalbuminaemia and oedema. An additional four cats received repeated injections of unmodified native BSA (pI 4.5) and remained basically normal. This is the first report of membranous nephropathy and the nephrotic syndrome in an experimental animal model which, unlike other animal models, is subject to the spontaneously occurring disease. PMID:2148430

  8. Membranous glomerulonephritis and cellular crescents induced by levamisole-adulterated cocaine abuse: a case report

    PubMed Central

    Moll-Guillen, Jose-Luis; Espí-Reig, Jordi; Blanes-Julia, Marino; García-Martínez, Ana-María; Pujol-Marco, Conrad; Hernández-Jaras, Julio

    2015-01-01

    Levamisole is illicitly employed as a cocaine adulterant. The consumption of levamisole-adulterated cocaine can provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated syndromes. Patients carrying an HLAB27 allele are known to be at higher risk of developing agranulocytosis when treated with levamisole. Likewise, patients with ANCA-associated vasculitis (AAV) and internal organ involvement have typically been exposed to offending agents for prolonged periods of time, often on the order of years. Here, we report an unusual case of a patient in which kidney biopsy showed membranous glomerulonephritis with cellular crescents associated with levamisole-contaminated cocaine use. PMID:26605317

  9. Interleukin-1 receptor antagonist ameliorates experimental anti-glomerular basement membrane antibody-associated glomerulonephritis.

    PubMed Central

    Tang, W W; Feng, L; Vannice, J L; Wilson, C B

    1994-01-01

    The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in

  10. Adalimumab (TNFα Inhibitor) Therapy Exacerbates IgA Glomerulonephritis Acute Renal Injury and Induces Lupus Autoantibodies in a Psoriasis Patient

    PubMed Central

    Wei, S. S.; Sinniah, R.

    2013-01-01

    Adalimumab (Humira) is a tumour necrosis factor α (TNFα) inhibitor that is approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ankylosing spondylitis, and juvenile idiopathic arthritis (Sullivan and Preda (2009), Klinkhoff (2004), and Medicare Australia). Use of TNFα inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, and sarcoidosis or sarcoid-like granulomas) (Ramos-Casals et al. (2010)). We report a patient with extensive psoriasis presenting with renal failure and seropositive lupus markers without classical lupus nephritis after 18 months treatment with adalimumab. He has renal biopsy proven IgA nephritis instead. Renal biopsy is the key diagnostic tool in patients presenting with adalimumab induced nephritis and renal failure. He made a remarkable recovery after adalimumab cessation and steroid treatment. To our knowledge, this is a unique case of a psoriasis patient presenting with seropositive lupus markers without classical lupus nephritis renal failure and had renal biopsy proven IgA glomerulonephritis after receiving adalimumab. PMID:24558628

  11. [Glomerulonephritis in dogs and cats].

    PubMed

    Reinacher, M; Frese, K

    1991-04-01

    Immunohistology and special staining of plastic sections allow diagnosis and differentiation of subtypes of glomerulonephritis in dogs. Frequency and clinical importance of these forms of glomerulonephritis vary significantly. In cats, glomerulonephritis occurs frequently in FIV-positive cats but is rare in animals suffering from persistent FeLV infection or FIP. PMID:2068715

  12. Factor VIII and glomerulonephritis.

    PubMed

    Ekberg, M; Nilsson, I M

    1975-05-17

    To find out if determination of factor VIII,which most probably is synthetised in the intima of blood-vessesls, is of value for predicting the severity of vessel damge in glomerulonephritis, factor-VIII activity, factor-VIII-related antigen, and glomerular filtration-ratewere esto,ated om 85 patients with early glomerulonephritis on admission, and in 70 of these at follow-up for up to 4 years. The levels of factor-VIII activity and factor-VIII-related antigen on admission were normal in those patients who recovered. Where renal function was impaired on admission or becaome so during follow-up, factor VIII was high. Determination of factor VIII might thus be of prognostic value in early glomerulonephritis. PMID:49471

  13. Zhen-wu-tang attenuates cationic bovine serum albumin-induced inflammatory response in membranous glomerulonephritis rat through inhibiting AGEs/RAGE/NF-κB pathway activation.

    PubMed

    Wu, Junbiao; Liu, Bihao; Liang, Chunling; Ouyang, Hui; Lin, Jin; Zhong, Yanchun; He, Yu; Zhou, Jie; Zhou, Yuan; Zhou, Jiuyao

    2016-04-01

    Zhen-wu-tang (ZWT), a traditional Chinese compound formula recorded in the Treatise on Febrile Diseases, has significant inhibitory effects on inflammatory damage and oxidative lesions in rats, but its mechanism of action remains unclear. The aim of the present study was to explore whether the anti-inflammatory and anti-oxidative effects of ZWT were mediated by the AGEs/RAGE/NF-κB signaling pathway in rats with cationic bovine serum albumin (C-BSA)-induced membranous glomerulonephritis (MGN). We found that ZWT significantly reduced the production of malondialdehyde (MDA), but enhanced the superoxide dismutase (SOD) activity. The ELISA results showed that ZWT not only reduced the serum levels of AGEs but also decreased the release of inflammatory mediators (TNF-α, IL-1β, and IL-6). Meanwhile, HE staining showed that pathological kidney injury was alleviated by ZWT. In addition, ZWT suppressed the expression of RAGE1 and NF-κB p65, as well as the nuclear translocation of NF-κB p65. The accumulation of AGEs, oxidative lesions and inflammation damage were reduced by an AGE inhibitor. Thus, the present study demonstrates that AGEs play a role in the pathogenesis of MGN and that AGE inhibition could reduce the inflammatory reactions and oxidative lesions in MGN. In general, ZWT attenuated MGN, in part, by inhibiting the AGEs/RAGE/NF-κB pathway. PMID:26851631

  14. Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis

    PubMed Central

    Kim, Kyung Min; Sung, Kyoung; Yang, Hea Koung; Kim, Seong Heon; Kim, Hye Young; Ban, Gil Ho; Park, Su Eun; Lee, Hyoung Doo

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID:27186222

  15. Hypercoagulation in glomerulonephritis.

    PubMed Central

    Salem, H H; Whitworth, J A; Koutts, J; Kincaid-Smith, P S; Firkin, B G

    1981-01-01

    The clotting values of 50 patients with glomerulonephritis were examined. Three different coagulation groups were recognised: those with normal clotting values (group 1); those with high concentrations of factor VIII but otherwise normal clotting results (group 2); and patients who showed the presence of an activator of the intrinsic coagulation pathway, indicated by the presence of a short activated partial thromboplastin time or the ability of patients' plasma to shorten control clotting time in mixing studies (group 3). Patients in group 2 either had a uniform rise in all three components of the factor VIII molecule or a disproportionately higher concentration of factor-VIII-related antigen. In contrast, the level of VIII clotting activity in patients in group 3 was always higher than concentrations of either VIIIAg or VIIIWF. A significantly high incidence of thrombotic complications was observed in patients with group 3 but in none of the patients in either group 1 or group 2. Impaired renal function was more common in patients in groups 2 and 3, with higher mean serum creatinine concentrations in those with group 3. Patients with glomerulonephritis who have a short partial thromboplastin time with kaolin or who shorten control clotting time form a subgroup in whom hypercoagulation could adversely affect the course of their disease. The value of antiplatelet or anticoagulant treatment in these patients needs to be explored. PMID:6788212

  16. Membranous glomerulonephritis associated with Mycobacterium shimoidei pulmonary infection

    PubMed Central

    Kanaji, Nobuhiro; Kushida, Yoshio; Bandoh, Shuji; Ishii, Tomoya; Haba, Reiji; Tadokoro, Akira; Watanabe, Naoki; Takahama, Takayuki; Kita, Nobuyuki; Dobashi, Hiroaki; Matsunaga, Takuya

    2013-01-01

    Patient: Male, 83 Final Diagnosis: Membranous glomerulonephritis Symptoms: Producting cough Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Rare disease Background: Membranous glomerulonephritis can occur secondarily from infectious diseases. There are no reports describing membranous glomerulonephritis caused by non-tuberculous mycobacterium infection. However, several cases with membranous glomerulonephritis due to Mycobacterium tuberculosis have been reported. Mycobacterium shimoidei is an uncommon pathogen, and less than 20 cases with this species have been reported. A therapeutic regimen for this infection has not been established yet. Case Report: An 83-year-old Japanese man presented with productive cough for 6 months. Computed tomography scan showed multiple cavities in the bilateral pulmonary fields. Acid-fast bacilli were evident in his sputum by Ziehl-Neelsen staining (Gaffky 3). PCR amplifications for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were all negative. Finally, Mycobacterium shimoidei was identified by rpoB sequencing and 16S rRNA sequencing. Urine examination showed a sub-nephrotic range of proteinuria and histology of the kidney showed membranous glomerulonephritis. Antimycobacterial treatment with clarithromycin, rifampicin, and ethambutol dramatically improved not only the pulmonary disease, but also the proteinuria. Conclusions: To the best of our knowledge, the presented case is the first report showing non-tuberculous mycobacterium-induced secondary membranous glomerulonephritis. A combination with clarithromycin, ethambutol, and rifampicin might be effective for treatment of Mycobacterium shimoidei infection. PMID:24367720

  17. Hypertension in Chronic Glomerulonephritis.

    PubMed

    Ihm, Chun-Gyoo

    2015-12-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  18. Comparative pathology of glomerulonephritis in animals.

    PubMed

    Slauson, D O; Lewis, R M

    1979-03-01

    Glomerulonephritis constitutes an important category of renal diseases in animals and has been recognized with increasing frequency in the last decade. We report here the comparative morphologic aspects of glomerulonephritis as a naturally occurring disease of animals. We briefly review the immunopathogenesis of glomerulonephritis. The morphology of renal lesions occurring in glomerulonephritis in dogs, cats, cattle, sheep, horses and swine has been reviewed with emphasis on the range and specificity of various glomerular lesions and on the comparison of lesions between various species. A distinction was made between glomerulonephritis as a primary disease entity and glomerulonephritis associated with other disease processes. Primary idiopathic glomerulonephritis occurred in all species but was most commonly recognized as a clinically important disease in dogs and cats. Glomerulonephritis also occurred in association with other diseases such as equine infectious anemia, chronic hog cholera, canine pyometra, dirofilariasis, feline leukemia virus infection and canine systemic lupus erythematosus. PMID:442447

  19. Membranoproliferative glomerulonephritis with essential cryoglobulinemia

    PubMed Central

    Satish, S.; Rajesh, R.; George, K.; Elango, E. M.; Unni, V. N.

    2008-01-01

    Cryoglobulinemia is an uncommon cause of renal disease and often occurs in patients with hepatitis C virus (HCV) infection. We report a case of membranoproliferative glomerulonephritis in a patient with cryoglobulinemia, which was not associated with HCV infection or any identifiable etiology. PMID:20142909

  20. Staphylococcus-related glomerulonephritis and poststreptococcal glomerulonephritis: why defining "post" is important in understanding and treating infection-related glomerulonephritis.

    PubMed

    Glassock, Richard J; Alvarado, Anthony; Prosek, Jason; Hebert, Courtney; Parikh, Samir; Satoskar, Anjali; Nadasdy, Tibor; Forman, John; Rovin, Brad; Hebert, Lee A

    2015-06-01

    A spate of recent publications describes a newly recognized form of glomerulonephritis associated with active staphylococcal infection. The key kidney biopsy findings, glomerular immunoglobulin A (IgA) deposits dominant or codominant with IgG deposits, resemble those of IgA nephritis. Many authors describe this condition as "postinfectious" and have termed it "poststaphylococcal glomerulonephritis." However, viewed through the prism of poststreptococcal glomerulonephritis, the prefix "post" in poststaphylococcal glomerulonephritis is historically incorrect, illogical, and misleading with regard to choosing therapy. There are numerous reports describing the use of high-dose steroids to treat poststaphylococcal glomerulonephritis. The decision to use steroid therapy suggests that the treating physician believed that the dominant problem was a postinfectious glomerulonephritis, not the infection itself. Unfortunately, steroid therapy in staphylococcus-related glomerulonephritis can precipitate severe staphylococcal sepsis and even death and provides no observable benefits. Poststreptococcal glomerulonephritis is an authentic postinfectious glomerulonephritis; poststaphylococcal glomerulonephritis is not. Making this distinction is important from the perspective of history, pathogenesis, and clinical management. PMID:25890425

  1. Pauci-Immune Crescentic Glomerulonephritis: An ANCA-Associated Vasculitis

    PubMed Central

    Syed, Rafeel; Rehman, Amina; Valecha, Gautam; El-Sayegh, Suzanne

    2015-01-01

    Rapidly progressive glomerulonephritis (RPGN) is a syndrome signified by a precipitous loss of renal function, with features of glomerulonephritis including dysmorphic erythrocyturia and glomerular proteinuria. RPGN is associated with extensive crescent formation, and, thus, the clinical term RPGN is often used interchangeably with the pathologic term crescentic glomerulonephritis (CGN). From an immunopathologic standpoint, primary RPGN is divided into pauci-immune GN (PICG), anti-GBM GN, and immune complex GN. PICG, the most common etiology of primary RPGN, refers to a necrotizing glomerulonephritis with few or no immune deposits by immunofluorescence (IF) or electron microscopy (EM). In most patients, pauci-immune CGN is a component of a systemic small vessel vasculitis such as granulomatosis with polyangiitis (GPA). Approximately 90% of patients with PICG have circulating ANCA antibodies, leading to the nomenclature ANCA-associated vasculitis (AAV). Recent research has identified several other antibodies associated with PICG, which is now understood to be a complex spectrum of disease with considerable overlap in terms of clinical phenotype and outcomes. In addition, several genetic and environmental factors have recently been implicated in the pathogenesis of this disorder. With new prognostic classifications, enhanced understanding of immunopathologic mechanisms, and novel treatment paradigms, clinical and experimental interest in PICG remains high. PMID:26688808

  2. Autoimmune lymphoproliferative syndrome presenting with glomerulonephritis.

    PubMed

    Kanegane, Hirokazu; Vilela, Maria Marluce dos Santos; Wang, Yue; Futatani, Takeshi; Matsukura, Hiroyoshi; Miyawaki, Toshio

    2003-05-01

    Autoimmune lymphoproliferative syndrome (ALPS) is characterized clinically by chronic non-malignant lymphoproliferation and autoimmunity and is caused by a genetic defect in programmed cell death (apoptosis). Most patients with ALPS have heterozygous mutations in the Fas gene. We describe an 11-year-old Brazilian boy with hepatosplenomegaly, lymphadenopathy, hemolytic anemia, and hypergammaglobulinemia since early infancy. T cell lines from the patient were defective in Fas-mediated apoptosis. He was diagnosed as having ALPS and found to have a novel Fas gene mutation (IVS4+1G>A). In addition, he presented with glomerulonephritis in infancy. An aunt and uncle who had the same Fas mutations also had histories of glomerulonephritis. Although glomerulonephritis is common in Fas-deficient mice, it is infrequent in human ALPS. Corticosteroid therapy ameliorated the glomerulonephritis in our patient, as well as his lymphoproliferation, anemia, and hypergammaglobulinemia. This study suggests that glomerulonephritis is one of the characteristic features of ALPS. PMID:12736807

  3. Crescentic glomerulonephritis in a child with Heiner syndrome.

    PubMed

    Yavuz, Sevgi; Karabay-Bayazıt, Aysun; Yılmaz, Mustafa; Gönlüşen, Gülfiliz; Anarat, Ali

    2014-01-01

    Heiner syndrome is a food-induced pulmonary hypersensitivity disease that predominantly affects infants. Chronic respiratory symptoms with pulmonary infiltrates on radiography, positive milk precipitins and resolution of findings upon removal of cow's milk constitute the main features. Severe cases may present with pulmonary hemosiderosis. Few renal manifestations associated with this syndrome have been reported so far. Here we report the first case of Heiner syndrome complicated by crescentic glomerulonephritis after 5 years of follow-up. PMID:26388600

  4. Membranous glomerulonephritis: a morphometric study.

    PubMed

    Paraskevakou, H; Kavantzas, N; Pavlopoulos, P M; Voudiklari, S; Zerefos, N; Papagalanis, N; Davaris, P

    2000-01-01

    Archival material from 45 renal biopsies with a diagnosis of idiopathic membranous glomerulonephritis (MGN) were studied by computer-aided image analysis in order to evaluate the prognostic significance of glomerular and interstitial morphometry in MGN. The control group consisted of thirty seven normal renal biopsy specimens. The surface area, the perimeter, the major axis length and the shape factor of renal glomeruli as well as the percentage of the interstitial fibrosis were measured. All the morphometric parameters related to the size of glomeruli had significantly higher values in the patient group (p = 0.000 for all the parameters). However, no significant difference of the glomerular size between different stages of MGN was observed. In contrast, the percentage of interstitial fibrosis increased as the MGN stage rose (median values: 10.3% in stage 1, 14.2% in stage II, 26.9% in stage III, 28.9% in stage IV and 34.2% in stage V, Kruskal-Wallis ANOVA H = 37.645, p = 0.000). In the multivariate analysis the percentage of interstitial fibrosis was the only independent prognostic factor (p = 0.013). Our findings suggest that, in membraneous glomerulonephritis, the interstitial fibrosis increases as the MGN stage progresses, while the size of renal glomeruli has increased at a very early stage of the disease. This fact may indicate that interstitial fibrosis, not glomerular lesions, is mainly responsible for the reduction of renal function. PMID:10729917

  5. Glomerulonephritis

    MedlinePlus

    ... seen, including: Nerve inflammation (polyneuropathy) Signs of fluid overload, including abnormal heart and lung sounds Swelling ( edema ) ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  6. Gastric Syphilis and Membranous Glomerulonephritis.

    PubMed

    Roh, Min; Sohn, Joo Hyun; Kim, Tae Yeob; Kim, Sung Jong; Kim, Ji Soong; Chung, Sung Jun; Pyo, Ju Yeon; Oh, Young-Ha

    2015-05-01

    Syphilis is a chronic systemic infectious disease caused by the bacterium Treponema pallidum. Gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis, but the co-occurrence of these two complications in the same patient is extremely rare. Thus, because of their nonspecific presentation, suspicion of gastric syphilis (GS) and nephrotic syndrome is essential for diagnosis. Patients should be investigated thoroughly and a diagnosis made based on clinical, endoscopic, and histological findings, in order to initiate appropriate therapy. We report of a 34-year-old male patient with a history of epigastric pain and a diagnosis of GS and syphilis-associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy, who was treated successfully with penicillin G benzathine. This case report provides information on the typical features of GS that should help raise awareness of this rare disease entity among clinicians, resulting in earlier diagnosis and administration of appropriate therapy. PMID:26064828

  7. Gastric Syphilis and Membranous Glomerulonephritis

    PubMed Central

    Roh, Min; Kim, Tae Yeob; Kim, Sung Jong; Kim, Ji Soong; Chung, Sung Jun; Pyo, Ju Yeon; Oh, Young-Ha

    2015-01-01

    Syphilis is a chronic systemic infectious disease caused by the bacterium Treponema pallidum. Gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis, but the co-occurrence of these two complications in the same patient is extremely rare. Thus, because of their nonspecific presentation, suspicion of gastric syphilis (GS) and nephrotic syndrome is essential for diagnosis. Patients should be investigated thoroughly and a diagnosis made based on clinical, endoscopic, and histological findings, in order to initiate appropriate therapy. We report of a 34-year-old male patient with a history of epigastric pain and a diagnosis of GS and syphilis-associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy, who was treated successfully with penicillin G benzathine. This case report provides information on the typical features of GS that should help raise awareness of this rare disease entity among clinicians, resulting in earlier diagnosis and administration of appropriate therapy. PMID:26064828

  8. Neutrophils: game changers in glomerulonephritis?

    PubMed Central

    Mayadas, Tanya N.; Rosetti, Florencia; Ernandez, Thomas; Sethi, Sanjeev

    2010-01-01

    Glomerulonephritides represent a diverse array of diseases that have in common immune cell-mediated effector mechanisms that cause organ damage. The contribution of neutrophils to the pathogenesis of proliferative glomerulonephritis (GN) is not well recognized. Most equate neutrophils with killing pathogens and causing collateral tissue damage during acute inflammation. However, these phagocytes are endowed with additional characteristics that have been traditionally reserved for cells of the adaptive immune system. They communicate with other cells, exhibit plasticity in their responses and have the potential to coordinate and inform the subsequent immune response, thus countering the notion that they arrive, destroy and then disappear. Therefore, neutrophils, which are the first to arrive at a site of inflammation, are potential game changers in GN. PMID:20667782

  9. Skimmin, a Coumarin from Hydrangea paniculata, Slows down the Progression of Membranous Glomerulonephritis by Anti-Inflammatory Effects and Inhibiting Immune Complex Deposition

    PubMed Central

    Xin, Hongqi; Li, Yan; Zhang, Dongming; Shi, Jing; Yang, Jingzhi

    2013-01-01

    Skimmin is one of the major pharmacologically active molecules present in Hydrangea paniculata, a medical herb used in the traditional Chinese medicine as an anti-inflammatory agent. In the current study, we attempted to investigate its renoprotective activity and underlying mechanisms in a rat model of membranous glomerulonephritis induced by cationic bovine serum albumin (c-BSA). Sprague-Dawley (SD) rats were divided into five groups, including normal control, model control, Mycophenolate Mofetil-treated group, and two skimming-treated groups (15 mg/kg and 30 mg/kg). Our research showed that treatment with skimmin significantly reduced the levels of blood urea nitrogen (BUN), urinary albumin excretion (UAE), and serum creatinine (Scr) as compared with model control after experimental induction of membranous glomerulonephritis (P < 0.01). Moreover, glomerular hypercellularity, tubulointerstitial injury, and glomerular deposition of IgG were less intense after skimmin treatment. By immunochemistry analysis, we demonstrated that skimmin could significantly inhibit interleukin-1β (IL1β) and IL-6 expression (P < 0.05), reduce the loss of nephrin and podocin, and suppress the infiltration of renal interstitium by CD3-positive T cell and CD20-positive B cell. These results suggest that treatment with skimmin can significantly improve renal function and suppress the IgG deposition as well as the development of glomerular lesions in a rat model of membranous glomerulonephritis. PMID:23990847

  10. Recurrent Glomerulonephritis after Renal Transplantation: An Unsolved Problem

    PubMed Central

    Golgert, William A.; Appel, Gerald B.; Hariharan, Sundaram

    2008-01-01

    Background and objectives: Despite advances in prevention of acute rejection and improved short- and long-term kidney graft survival, recurrent glomerulonephritis remains problematic and poorly characterized. This study analyzed prevalence and outcome of recurrent glomerulonephritis from various registries. Design, setting, participants, & measurements: Definition, classification, and limitations in evaluating epidemiology of native and recurrent glomerulonephritis are discussed. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed. Results: Analysis of data from transplant registries revealed that glomerulonephritis is an important cause of end-stage renal disease in white and pediatric recipients; however, glomerulonephritis as the cause of end-stage renal disease is not characterized well in black recipients, and many of them are perhaps labeled to have hypertensive nephrosclerosis as the cause of renal disease without renal biopsy. A systematic approach toward urinalysis after transplantation and utility of immunofluorescence and electron microscopic examination of renal biopsy tissues will identify the true prevalence of recurrent glomerulonephritis. Data on recurrent glomerulonephritis should be compiled by either using registry analysis or pooling data from multiple centers. This will provide true data on prevalence and outcome and could potentially initiate translational research studies. Conclusions: The understanding of the pathogenesis of recurrent glomerulonephritis is critical to optimize prevention as well as to treat individual recurrent glomerulonephritis, which can enhance long-term graft survival. PMID:18272827

  11. Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis

    PubMed Central

    Vanikar, A.V.; Patel, R.D.; Suthar, K. S.; Trivedi, H. L.

    2016-01-01

    Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB. PMID:26894074

  12. Effect of cyclosporin on immune complex deposition in murine glomerulonephritis.

    PubMed Central

    Quinn, D G; Fennell, J S; Sheils, O; Gaffney, E F; Feighery, C F

    1991-01-01

    Chronic glomerulonephritis (GN) was induced in N/M mice by daily injections of human serum albumin (HSA). The glomerular lesion was similar to that observed in human membranous GN and was characterized by intense mesangial and capillary loop immunofluorescent staining for HSA, IgG and C3. Electron microscopic examination revealed numerous electron-dense deposits in the mesangium and along the subepithelial side of the glomerular basement membrane, the latter deposits being associated with membranous spikes. Chronically injected mice that had been treated with cyclosporin (CsA) from Day 1 had different patterns of immune complex deposition. Mesangial deposition was apparently unaltered but no subepithelial deposits or spikes were evident. In addition, only two out of 21 HSA-injected mice which began CsA treatment on Day 21 had subepithelial deposits. There was no significant difference in serum levels of HSA-specific IgG between the three groups of mice. CsA treatment would therefore appear to ameliorate the immunopathology of antigen-induced glomerulonephritis in this model without affecting serum antibody levels, and may be of therapeutic value in the treatment of human membranous GN. Images Figure 1 Figure 2 Figure 3 PMID:1828056

  13. Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis.

    PubMed

    Grove, P; Neale, P H; Peck, M; Schiller, B; Haas, M

    1998-01-01

    We report here a case of fibrillary glomerulonephritis arising in a 43-year-old man with a polyclonal gammopathy, who presented with progressive renal insufficiency, microscopic hematuria, and mild proteinuria (0.7 g/d). Ultrastructural studies showed deposits of randomly oriented fibrils in the glomerular mesangium and adjacent portions of some glomerular basement membranes, with a mean fibril thickness of 14.3 nm, highly consistent with fibrillary glomerulonephritis. The Congo red stain was negative on histologic sections. Immunofluorescence studies revealed strong mesangial and focal glomerular capillary staining for immunoglobulin (Ig) G, complement (C) 3, and kappa light chains, with minimal staining for IgA, IgM, C1q, or lambda light chains. The IgG present was entirely of the IgG1 subclass. This case is quite unusual for fibrillary glomerulonephritis, which typically presents with polyclonal IgG deposits and IgG4 as the dominant IgG subclass present. Monoclonal deposits are more frequently associated with immunotactoid glomerulopathy, characterized ultrastructurally by microtubule-like structures 30 to 50 nmn thick, often in parallel arrays. The present case illustrates that although fibrillary glomerulonephritis and immunotactoid glomerulopathy might be distinguishable on ultrastructural grounds, there is overlap between these two entities with respect to the potential composition of the glomerular deposits present. PMID:9556416

  14. Update on endocarditis-associated glomerulonephritis.

    PubMed

    Boils, Christie L; Nasr, Samih H; Walker, Patrick D; Couser, William G; Larsen, Christopher P

    2015-06-01

    Glomerulonephritis (GN) due to infective endocarditis (IE) is well documented, but most available data are based on old autopsy series. To update information, we now present the largest biopsy-based clinicopathologic series on IE-associated GN. The study group included 49 patients (male-to-female ratio of 3.5:1) with a mean age of 48 years. The most common presenting feature was acute kidney injury. Over half of the patients had no known prior cardiac abnormality. However, the most common comorbidities were cardiac valve disease (30%), intravenous drug use (29%), hepatitis C (20%), and diabetes (18%). The cardiac valve infected was tricuspid in 43%, mitral in 33%, and aortic in 29% of patients. The two most common infective bacteria were Staphylococcus (53%) and Streptococcus (23%). Hypocomplementemia was found in 56% of patients tested and ANCA antibody in 28%. The most common biopsy finding was necrotizing and crescentic GN (53%), followed by endocapillary proliferative GN (37%). C3 deposition was prominent in all cases, whereas IgG deposition was seen in <30% of cases. Most patients had immune deposits detectable by electron microscopy. Thus, IE-associated GN most commonly presents with AKI and complicates staphylococcal tricuspid valve infection. Contrary to infection-associated glomerulonephritis in general, the most common pattern of glomerular injury in IE-associated glomerulonephritis was necrotizing and crescentic glomerulonephritis. PMID:25607109

  15. Noncongophilic fibrillary glomerulonephritis in a cat.

    PubMed

    Cavana, P; Capucchio, M T; Bovero, A; Ripanti, D; Catalano, D; Scaglione, F E; Miller, J; Blunden, T; Farca, A M

    2008-05-01

    This report describes an uncommon case of nonamyloidotic fibrillary glomerulonephritis. A 5-year-old female European cat was presented with nephrotic syndrome. Serum biochemistry and urinalysis revealed a mild increase in cholesterol, low total protein, severe hypoalbuminemia, and high proteinuria with a high protein-to-creatinine ratio. An histologic examination revealed an interstitial nephritis and a diffuse glomerulonephritis, with multifocal thickening of the Bowman's capsule. Transmission electron microscopy showed widespread fibrillary deposits in the glomerular basement membrane and in the mesangium. These fibrils ranged between 18 and 26 nm in diameter and were Congo red negative, which allowed their differentiation from amyloid. Immunohistochemistry demonstrated expression for immunoglobulin M (IgM) and immunoglobulin G (IgG) within the mesangium. Renal deposits of Congo red-negative amyloid-like fibrils have been described in humans, horses, monkeys, and dogs. This is the first report of noncongophilic fibrillary glomerulopathy in a cat. PMID:18487491

  16. Atypical membranoproliferative glomerulonephritis in a cat.

    PubMed

    Inoue, K; Kami-ie, J; Ohtake, S; Wakui, S; Machida, S; Shirota, K

    2001-07-01

    Membranoproliferative glomerulonephritis was observed in a 2-year-old male Japanese domestic cat with clinical renal failure. In the glomeruli, moderate mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls were prominent. In addition, frequent duplication of the capillary walls, splitting, and spike formation were observed in the glomerular basement membrane. Granular cat IgG and complement component deposition were detected globally along the glomerular capillary walls and in the mesangium. Transmission electron microscopy revealed dense deposits in the subendothelial and subepithelial regions and the mesangium. Mesangial interposition was also observed. These glomerular lesions are also found in humans with membranoproliferative glomerulonephritis type III, which has not been reported in animals. PMID:11467485

  17. Proliferative glomerulonephritis with monoclonal immunoglobulin in renal allografts

    PubMed Central

    Al-Rabadi, Laith; Francis, Jean M.; Henderson, Joel; Ghai, Sandeep

    2015-01-01

    Glomerulopathy due to dysproteinemia can have a wide spectrum of pathologic and clinical features based on specific characteristics of the abnormal protein and the response induced within the parenchymal tissue. Monoclonal immunoglobulin G (IgG) deposition can manifest as a different glomerular disease. Proliferative glomerulonephritis (GN) with monoclonal IgG deposits (PGNMID) is a unique entity mimicking immune complex GN that does not conform to any of those subtypes. IgG monoclonal granular deposition in the glomeruli with a pattern similar to immune complex disease suggested by C3 and C1q deposition should prompt consideration of PGNMID. Literature is scarce in terms of recurrence of disease in renal allografts. In this article we present the clinical–pathologic features of three cases of PGNMID in the renal allograft showing the variable course and manifestation of the disease. PMID:26613031

  18. Cordyceps militaris fruit body extract ameliorates membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

    PubMed

    Song, Jingjing; Wang, Yingwu; Liu, Chungang; Huang, Yan; He, Liying; Cai, Xueying; Lu, Jiahui; Liu, Yan; Wang, Di

    2016-04-01

    Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent. PMID:27008597

  19. Post-infectious glomerulonephritis following infective endocarditis: Amenable to immunosuppression

    PubMed Central

    Mantan, M.; Sethi, G. R.; Batra, V. V.

    2013-01-01

    Glomerulonephritis develops in about 20% patients with infective endocarditis (IE), but is mostly asymptomatic. Heavy proteinuria or derangement of kidney functions is uncommon. We report here a child with IE and proliferative glomerulonephritis who manifested as significant proteinuria that recovered on treatment with immunosupressants. PMID:24049276

  20. Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits

    PubMed Central

    Larsen, Christopher P; Messias, Nidia C; Walker, Patrick D; Fidler, Mary E; Cornell, Lynn D; Hernandez, Loren H; Alexander, Mariam P; Sethi, Sanjeev; Nasr, Samih H

    2015-01-01

    The diagnosis of membranoproliferative glomerulonephritis (MPGN) has recently undergone change from an electron microscopy-based classification scheme to one based largely on immunofluorescence findings. This change is due to the recognition that many of these cases are driven by abnormalities of the alternative complement cascade, resulting in the concept of C3 glomerulopathy. Here we reviewed our case files to identify those with an MPGN pattern that show false negative staining for monoclonal immunoglobulins by routine immunofluorescence. Monoclonal immunoglobulin deposits were unmasked by performing immunofluorescence on formalin-fixed paraffin embedded tissue after protease digestion. Clinico-pathological details of 16 such cases with a mean serum creatinine of 2.7 mg/dl and mean 24 h proteinuria of 7.1 g were then determined. Hypocomplementemia was present in two-thirds of patients. Fourteen patients had a paraprotein on serum immunofixation, all of which matched the biopsy immunofluorescence staining pattern. Bone marrow biopsy showed plasma cell dyscrasia or B-cell lymphoproliferative disorder in 13 patients. Ten of these patients had findings on biopsy most consistent with C3 glomerulonephritis prior to performing paraffin immunofluorescence. Thus a high index of suspicion is necessary to avoid misdiagnosis in these cases, as many would have been mistakenly diagnosed as C3 glomerulopathy or unclassified MPGN if paraffin immunofluorescence was not performed. PMID:26154922

  1. [Immune complex glomerulonephritis associated with pulmonary tuberculosis].

    PubMed

    Villar, I; Hernández, E; Cozzi, J; Paletta, C; Mathurín, S

    1994-01-01

    A 32 year old man was admitted for dyspnea, hemoptysis, macroscopic hematuria, hypertension (140/100), peripheral edema and hemodynamic decompensation. Lung Xrays revealed pulmonary edema and a cavity in the left apex. Laboratory determinations revealed an altered renal function with increased creatinine and urea levels and nephrotic syndrome. There was leucocyturia, hematuria and cylindruria. The sputum showed a large number of acid-fast bacilli. The patient began anti-tuberculosis treatment with three drugs (isoniacid, rifampicin, pirazinamide). On ultrasonography, both kidneys revealed ecogenic lesions with size, shape and cortico-medular relationship preserved. The patient persisted with altered renal function, steady levels of urea nitrogen, creatinine and potassium, preserved diuresis and hypertension. Bidimensional echocardiogram: LVDD 55 mm, hypoquinetic septum, pericardic effusion, thickened pericardium, pleural effusion, shortening fraction decreased. He received treatment for this congestive cardiac failure and hypertension with enalapril, nifedipine and fursemide. A percutaneous renal biopsy was performed with anatomopathologic diagnosis of diffuse encocapillar proliferative glomerulonephritis with crescents (15%) and total glomerular sclerosis (33%). Immunofluorescence: positive, immune-complexes with IgM and C3. The patient gradually recovered his normal renal function, improved his pleural effusions and normalized his cardiac function. He was discharged in good clinical condition on the 69th day of anti-tuberculosis treatment. An association between pulmonary tuberculosis and glomerulonephritis is discussed. It is proposed that renal lesions might be the consequence of the tuberculosis due to the sedimentation of circulating immune-complexes. PMID:7854090

  2. CCR6 Recruits Regulatory T Cells and Th17 Cells to the Kidney in Glomerulonephritis

    PubMed Central

    Turner, Jan-Eric; Paust, Hans-Joachim; Steinmetz, Oliver M.; Peters, Anett; Riedel, Jan-Hendrik; Erhardt, Annette; Wegscheid, Claudia; Velden, Joachim; Fehr, Susanne; Mittrücker, Hans-Willi; Tiegs, Gisa; Stahl, Rolf A.K.

    2010-01-01

    T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17–producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNγ-producing Th1 cells are CCR6−. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6−/− mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis. PMID:20299360

  3. Fibrillary glomerulonephritis masquerading as rapidly progressive glomerulonephritis with pseudo-linear glomerular basement membrane staining.

    PubMed

    El-Husseini, Amr; Aycinena, Juan-Carlos; George, Bennet; Jennings, Stuart; Cornea, Virgilius; Sawaya, B Peter

    2015-10-01

    Fibrillary glomerulonephritis (FGN) is a rare disorder with poor renal prognosis. It is a heterogeneous disease associated with significant risk of end-stage renal disease (ESRD). Its etiology and pathogenesis have not been clearly identified. We report a case of a patient presenting with hypertensive crisis, nephrotic range proteinuria, and rapidly progressive glomerulonephritis (RPGN). The kidney biopsy demonstrates crescentic GN on light microscopy (LM) and strong pseudo-linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G on immunofluorescence (IF), suggestive of anti-GBM disease. However, circulating anti-GBM antibodies were negative. Electron microscopy (EM) revealed fibrillary deposits in the GBM, confirming the diagnosis of FGN. Review of the literature revealed very few reported similar cases. It appears that severe hypertension and heavy proteinuria, while uncommon in anti-GBM disease, are consistent findings in RPGN form of FGN. PMID:26249548

  4. Rapidly progressive glomerulonephritis due to coexistent anti-glomerular basement membrane disease and fibrillary glomerulonephritis

    PubMed Central

    Cheungpasitporn, Wisit; Zacharek, Claudia C.; Fervenza, Fernando C.; Cornell, Lynn D.; Sethi, Sanjeev; Herrera Hernandez, Loren P.; Nasr, Samih H.; Alexander, Mariam P.

    2016-01-01

    Anti-glomerular basement membrane (anti-GBM) disease is a major cause of rapidly progressive glomerulonephritis (RPGN). On the other hand, fibrillary glomerulonephritis (GN) typically presents as proteinuria, hematuria and renal insufficiency, but rarely as RPGN. Without electron microscopy, the diagnosis of fibrillary GN can be missed. We report a 68-year-old white woman who presented with RPGN with kidney biopsy demonstrating diffuse crescentic GN on light microscopy. By immunofluorescence, there was bright linear staining of the GBMs and smudgy mesangial staining for immunoglobulin G, C3, and kappa and lambda light chain. Electron microscopy revealed fibrillary deposits in the GBM and mesangium. A serum test for anti-GBM antibody was positive. To our knowledge, this is the first report of coexistence of fibrillary GN in a patient with anti-GBM disease. Electron microscopy is critical to identify the coexistence of other GN in patients presenting with crescentic GN. PMID:26798468

  5. Cryoglobulinemic Glomerulonephritis as a Presentation of Atypical Post-Infectious Glomerulonephritis

    PubMed Central

    Boumitri, Christine; Haddad, Fady G.; Rondla, Chetana; El-Sayegh, Suzanne; El-Charabaty, Elie

    2016-01-01

    Post-infectious glomerulonephritis (PIGN) usually occurs within few days to weeks following an infection. Clinical presentation is variable, but in general, it is considered a benign entity with good prognosis. It rarely requires kidney biopsy to confirm the diagnosis. We present a case of a 55-year-old, previously healthy, male who presented for worsening shortness of breath, persistent cough, and right-sided pleuritic chest pain. Initial workup revealed a right exudative effusion with empyema. Hospital course was complicated by acute kidney injury requiring renal replacement therapy with a peak creatinine of 10.2 mg/dL from a baseline of 1.18 mg/dL. On kidney biopsy, findings were compatible with a diagnosis of cryoglobulinemic glomerulonephritis or an atypical form of PIGN. While a wide variety of histopathological findings on renal biopsies have been described to complement the usual diffuse proliferative glomerulonephritis pattern, cryoglobulinemic features with negative cryoglobulin have never been reported. Our case is unique not only by having an atypical histological presentation but also by meeting the criteria of atypical PIGN with persistent hypertension and microscopic hematuria. PMID:26668683

  6. Membranoproliferative glomerulonephritis in a young cat.

    PubMed

    Asano, Tomoko; Tsukamoto, Atsushi; Ohno, Koichi; Ogihara, Kikumi; Kamiie, Junichi; Shirota, Kinji

    2008-12-01

    A 9-month-old male Japanese domestic cat showed pleural effusion, ascites, azotemia, hypoproteinemia and severe proteinuria. Histopathology of the percutaneous renal biopsy specimen revealed that all glomeruli showed intense mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls, resulting in lobular accentuation of the glomerular tufts. Frequent duplication of the capillary walls was also observed. Immunostaining for alpha-smooth muscle actin distinctly revealed mesangial interposition. Diffuse global and linear deposition of C3 and IgG was observed mostly along the peripheral capillary loops. Electron microscopy confirmed frequent circumferential mesangial interposition and subendothelial dense-deposits in the glomerulus. The glomerular lesion was consistent with human membranoproliferative glomerulonephritis type I, and might be a rare case that developed at young age. PMID:19122409

  7. Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive Glomerulonephritis

    PubMed Central

    Araki, Makoto; Matsubara, Takeshi; Abe, Hideharu; Torikoshi, Kazuo; Mima, Akira; Iehara, Noriyuki; Fukatsu, Atsushi; Kita, Toru; Arai, Hidenori; Doi, Toshio

    2016-01-01

    Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis. PMID:27492138

  8. Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive Glomerulonephritis.

    PubMed

    Araki, Makoto; Matsubara, Takeshi; Abe, Hideharu; Torikoshi, Kazuo; Mima, Akira; Iehara, Noriyuki; Fukatsu, Atsushi; Kita, Toru; Arai, Hidenori; Doi, Toshio

    2016-01-01

    Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis. PMID:27492138

  9. A protective role for endothelial nitric oxide synthase in glomerulonephritis.

    PubMed

    Heeringa, Peter; Steenbergen, Eric; van Goor, Harry

    2002-03-01

    In acute glomerulonephritis (GN), increased nitric oxide (NO) production occurs, suggesting a pathophysiological role for NO in the disease process. Although NO potentially could have both toxic as well as protective effects, its exact role in the pathophysiology of GN is unclear and may depend on the NOS isoform generating NO. The protective effects of NO such as prevention of leukocyte and platelet activation and adhesion have been attributed to NO generated by endothelial nitric oxide synthase (eNOS). Evidence for a beneficial role for eNOS includes the demonstration of reduced eNOS expression in experimental models of GN as well as human biopsy specimens that is mostly likely due to endothelial cell necrosis. Reduced NO production in GN also may occur through reaction of NO with superoxide anions or the myeloperoxidase (MPO)/hypochlorous acid (HOCL) system. Further evidence has been provided by the observation that in several experimental models of GN, glomerular injury is exacerbated following treatment with non-selective NO inhibitors. Finally, the development of GN is severely aggravated in mice lacking a functional gene for eNOS as compared to wild-type mice, providing direct support for a protective role of eNOS-derived NO in acute GN. PMID:11849432

  10. Pathogenic mechanism of acute post-streptococcal glomerulonephritis.

    PubMed

    Nordstrand, A; Norgren, M; Holm, S E

    1999-01-01

    Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease. However, the pathogenic mechanism behind APSGN remains largely unknown. As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes. During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process. In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN. Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein. However, additional factors may be required for the development of the disease. PMID:10680980

  11. Murine Double Minute-2 Inhibition Ameliorates Established Crescentic Glomerulonephritis.

    PubMed

    Mulay, Shrikant R; Romoli, Simone; Desai, Jyaysi; Honarpisheh, Mohammad Mohsen; Kumar, Santhosh V; Anders, Hans-Joachim; Thomasova, Dana

    2016-06-01

    Rapidly progressive glomerulonephritis is characterized by glomerular necroinflammation and crescent formation. Its treatment includes unspecific and toxic agents; therefore, the identification of novel therapeutic targets is required. The E3-ubiquitin ligase murine double minute (MDM)-2 is a nonredundant element of NF-κB signaling and the negative regulator of tumor suppressor gene TP53-mediated cell cycle arrest and cell death. We hypothesized that the MDM2 would drive crescentic glomerulonephritis by NF-κB-dependent glomerular inflammation and by p53-dependent parietal epithelial cell hyperproliferation. Indeed, the pre-emptive MDM2 blockade by nutlin-3a ameliorated all aspects of crescentic glomerulonephritis. MDM2 inhibition had identical protective effects in Trp53-deficient mice, with the exception of crescent formation, which was not influenced by nutlin-3a treatment. In vitro experiments confirmed the contribution of MDM2 for induction of NF-κB-dependent cytokines in murine glomerular endothelial cells and for p53-dependent parietal epithelial cell proliferation. To evaluate MDM2 blockade as a potential therapeutic intervention in rapidly progressive glomerulonephritis, we treated mice with established glomerulonephritis with nutlin-3a. Delayed onset of nutlin-3a treatment was equally protective as the pre-emptive treatment in abrogating crescentic glomerulonephritis. Together, the pathogenic effects of MDM2 are twofold, that is, p53-independent NF-κB activation increasing intraglomerular inflammation and p53-dependent parietal epithelial cell hyperplasia and crescent formation. We therefore propose MDM2 blockade as a potential novel therapeutic strategy in rapidly progressive glomerulonephritis. PMID:27102769

  12. Haematuria on the Spanish Registry of Glomerulonephritis

    PubMed Central

    Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel

    2016-01-01

    Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria’s overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome. PMID:26818712

  13. Eculizumab and Recurrent C3 Glomerulonephritis

    PubMed Central

    Gurkan, Sevgi; Fyfe, Billie; Weiss, Lynne; Xiao, Xue; Zhang, Yuzhou; Smith, Richard J.

    2015-01-01

    Background and objectives Hyperactivity of the alternative complement pathway is the principle defect in the C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease. Design, setting, participants & measurements In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of Dense Deposit Disease (DDD) and allograft recurrence of C3 (C3GN) glomerulonephritis was treated with eculizumab every-other-week for 1 year. The patient had pathological evidence of C3GN and proteinuria >1 g/d at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 months and 12 months. Results Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, during therapy it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease. Conclusions Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of alternative pathway remained, showing that eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients. PMID:23689905

  14. siRNA-Based Therapy Ameliorates Glomerulonephritis

    PubMed Central

    Shimizu, Hideki; Hori, Yuichi; Kaname, Shinya; Yamada, Koei; Nishiyama, Nobuhiro; Matsumoto, Satoru; Miyata, Kanjiro; Oba, Makoto; Yamada, Akira; Kataoka, Kazunori

    2010-01-01

    RNA interference by short interfering RNAs (siRNAs) holds promise as a therapeutic strategy, but use of siRNAs in vivo remains limited. Here, we developed a system to target delivery of siRNAs to glomeruli via poly(ethylene glycol)-poly(l-lysine)-based vehicles. The siRNA/nanocarrier complex was approximately 10 to 20 nm in diameter, a size that would allow it to move across the fenestrated endothelium to access to the mesangium. After intraperitoneal injection of fluorescence-labeled siRNA/nanocarrier complexes, we detected siRNAs in the blood circulation for a prolonged time. Repeated intraperitoneal administration of a mitogen-activated protein kinase 1 (MAPK1) siRNA/nanocarrier complex suppressed glomerular MAPK1 mRNA and protein expression in a mouse model of glomerulonephritis; this improved kidney function, reduced proteinuria, and ameliorated glomerular sclerosis. Furthermore, this therapy reduced the expression of the profibrotic markers TGF-β1, plasminogen activator inhibitor-1, and fibronectin. In conclusion, we successfully silenced intraglomerular genes with siRNA using nanocarriers. This technique could aid the investigation of molecular mechanisms of renal disease and has potential as a molecular therapy of glomerular diseases. PMID:20203158

  15. Metabolic Syndrome in IgA Glomerulonephritis

    PubMed Central

    Kaartinen, Kati; Syrjänen, Jaana; Pörsti, Ilkka; Harmoinen, Aimo; Huhtala, Heini; Mustonen, Jukka

    2014-01-01

    Background/Aims Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney disease. This study examines the prevalence of MetS in subjects with IgA glomerulonephritis (IgAGN) and its impact on disease progression in a retrospective fashion. Patients and Methods Altogether, 174 subjects (104 males) were examined 11 years (first visit) after IgAGN diagnosis and again after 16 years (second visit; 144 subjects responded). Different glomerular filtration markers were utilized. The MetS criteria by Alberti et al. [Circulation 2009;120:1640-1645] were applied, in which the presence of any three of five risk factors (elevated waist circumference, triglycerides, glucose, existence of hypertension, or reduced high-density lipoprotein cholesterol) constitutes the diagnosis. Results The prevalence of MetS at the first visit was 39%, corresponding to that of the general Finnish population. In univariate analyses, MetS was significantly associated with the progression of IgAGN at the second visit. However, in multivariate analyses, the existence of MetS was not a significant prognostic determinant. Conclusion The number of subjects with MetS among IgAGN patients and the general population is equal in Finland. MetS does not seem to be an independent prognostic variable. PMID:25337083

  16. Partial lipodystrophy, C3 nephritic factor and clinically inapparent mesangiocapillary glomerulonephritis.

    PubMed

    Bennett, W M; Bardana, E J; Wuepper, K; Houghton, D; Border, W A; Götze, O; Schreiber, R

    1977-05-01

    A case of partial lipodystrophy with C3 nephritic factor was found to be associated with mesangiocapillary glomerulonephritis although all clinical parameters of renal function were normal. Diagnosis of mesangiocapillary glomerulonephritis required renal biopsy. Nephriti factor obtained from this patient was immunochemically related to nephritic factor isolated from the serum of patients with typical mesangiocapillary glomerulonephritis without partial lipodystrophy. PMID:860726

  17. Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate Restores Nrf2 Activity and Ameliorates Crescentic Glomerulonephritis

    PubMed Central

    Zhou, Jason K.; Peng, Ai; Vaziri, Nosratola D.; Mohan, Chandra; Xu, Yan; Zhou, Xin J.

    2015-01-01

    Crescentic glomerulonephritis (GN) is the most severe form of GN and is associated with significant morbidity and mortality despite aggressive immunotherapy with steroids, cytotoxic drugs, and plasmapheresis. We examined the therapeutic efficacy of the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG, 50 mg/kg BW/day x3weeks), a potent anti-inflammatory and anti-oxidant agent, on experimental crescentic GN induced in 129/svJ mice by administration of rabbit anti-mouse glomerular basement membrane sera. Routine histology and key molecules involved in inflammatory and redox signaling were studied. EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. The improvements in renal function and histology were accompanied by the restoration of Nrf2 signaling (which was impaired in vehicle-treated mice) as shown by increased nuclear translocation of Nrf2 and cytoplasmic glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione peroxidase. EGCG-treated mice also showed reduction in p-Akt, p-JNK, p-ERK1/2 and p-P38 as well as restoration of PPARγ and SIRT1 levels. Lower dose of EGCG (25 mg/kg BW/day x2 weeks) treatment also significantly decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. Thus, our data illustrate the efficacy of EGCG in reversing the progression of crescentic GN in mice by targeting multiple signaling and inflammatory pathways as well as countering oxidative stress. PMID:25785827

  18. Experimental Contact Lens to Prevent Glaucoma-Induced Blindness

    MedlinePlus

    ... Articles | Inside Life Science Home Page An Experimental Contact Lens to Prevent Glaucoma-Induced Blindness By Sharon Reynolds Posted January 23, 2014 An experimental contact lens design releases a glaucoma medicine at a ...

  19. Fundus changes in mesangiocapillary glomerulonephritis type II: vitreous fluorophotometry.

    PubMed Central

    Raines, M F; Duvall-Young, J; Short, C D

    1989-01-01

    We have described a complex abnormality of retinal pigment epithelium, Bruch's membrane, and choriocapillaris in mesangiocapillary glomerulonephritis (MCGN) type II. Patients with MCGN type II were examined by vitreous fluorophotometry which reveals that there is a breakdown of the blood retinal barrier (BRB) in those patients with the typical fundus lesions. The function of this barrier was calculated as a penetration ratio and was statistically greater in these patients when compared with a group of (a) normal persons, (b) patients with drusen, and (c) patients with other forms of glomerulonephritis. Images PMID:2605145

  20. The role of Th1 and Th17 cells in glomerulonephritis

    PubMed Central

    Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

    2015-01-01

    Context: T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Evidence Acquisitions: Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Results: Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Conclusions: Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis. PMID:25964886

  1. IL-17 Expression in the Time Course of Acute Anti-Thy1 Glomerulonephritis

    PubMed Central

    Loof, Tanja; Krämer, Stephanie; Gaedeke, Jens; Neumayer, Hans-Hellmut; Peters, Harm

    2016-01-01

    Background Interleukin-17 (IL-17) is a new pro-inflammatory cytokine involved in immune response and inflammatory disease. The main source of IL-17 is a subset of CD4+ T-helper cells, but is also secreted by non-immune cells. The present study analyzes expression of IL-17 in the time course of acute anti-thy1 glomerulonephritis and the role of IL-17 as a potential link between inflammation and fibrosis. Methods Anti-thy1 glomerulonephritis was induced into male Wistar rats by OX-7 antibody injection. After that, samples were taken on days 1, 5, 10 (matrix expansion phase), 15 and 20 (resolution phase). PBS-injected animals served as controls. Proteinuria and histological matrixes score served as the main markers for disease severity. In in vitro experiments, NRK-52E cells were used. For cytokine expressions, mRNA and protein levels were analyzed by utilizing RT-PCR, in situ hybridization and immunofluorescence. Results Highest IL-17 mRNA-expression (6.50-fold vs. con; p<0.05) was found on day 5 after induction of anti-thy1 glomerulonephritis along the maximum levels of proteinuria (113 ± 13 mg/d; p<0.001), histological glomerular-matrix accumulation (82%; p<0.001) and TGF-β1 (2.2-fold; p<0.05), IL-6 mRNA expression (36-fold; p<0.05). IL-17 protein expression co-localized with the endothelial cell marker PECAM in immunofluorescence. In NRK-52E cells, co-administration of TGF-β1 and IL-6 synergistically up-regulated IL-17 mRNA 4986-fold (p<0.001). Conclusions The pro-inflammatory cytokine IL-17 is up-regulated in endothelial cells during the time course of acute anti-thy1 glomerulonephritis. In vitro, NRK-52E cells secrete IL-17 under pro-fibrotic and pro-inflammatory conditions. PMID:27243813

  2. Experimental evaluation of earthquake induced relay chattering

    SciTech Connect

    Bandyopadhyay, K.; Hofmayer, C.; Shteyngart, S.

    1990-01-01

    An experimental evaluation of relay performance under vibratory environments is discussed in this paper. Single frequency excitation was used for most tests. Limited tests were performed with random multifrequency inputs. The capacity of each relay was established based on a two-millisecond chatter criterion. The experimental techniques are described and the effects of parameters in controlling the relay capacity levels are illustrated with test data. A wide variation of the capacity levels was observed due to the influence of parameters related to the design of the relay and nature of the input motion. 3 refs., 15 figs.

  3. Hydrocarbon exposure may cause glomerulonephritis and worsen renal function: evidence based on Hill's criteria for causality.

    PubMed

    Ravnskov, U

    2000-08-01

    Many observational and experimental studies point to hydrocarbon exposure as an important pathogenic factor in glomerulonephritis. The findings have made little impact on current concepts and patient care, possibly because the hypothesis of a direct causal effect of the exposure and the hypothesis that the exposure worsens renal function have not been considered separately. This review examines these two hypotheses using Hill's criteria for causality. The results from 14 cross-sectional, 18 case-control studies, two cohort studies, 15 experiments on laboratory animals and two on human beings together with many case reports satisfy all but one of Hill's criteria for both hypotheses. Of particular importance is the finding in the case-control and follow-up studies of an association between degree of exposure and stage of renal disease, and an inverse association between degree of exposure and renal function, indicating that the most important effect of hydrocarbon exposure is its effect on renal function. End-stage renal failure may be preventable in many patients with glomerulonephritis provided a possible exposure to toxic chemicals is discontinued. PMID:10924538

  4. An immune-complex glomerulonephritis of Chinook salmon, Oncorhynchus tshawytscha (Walbaum).

    PubMed

    Lumsden, J S; Russell, S; Huber, P; Wybourne, B A; Ostland, V E; Minamikawa, M; Ferguson, H W

    2008-12-01

    Chinook salmon from New Zealand were shown to have a generalized membranous glomerulonephritis that was most severe in large fish. Marked thickening of the glomerular basement membrane was the most consistent lesion, with the presence of an electron-dense deposit beneath the capillary endothelium.Severely affected glomeruli also had expansion of the mesangium and loss of capillaries,synechiae of the visceral and parietal epithelium and mild fibrosis of Bowmans capsule. Chinook salmon from British Columbia, Canada with bacterial kidney disease caused by Renibacterium salmoninarum had similar histological lesions. They also had thickened glomerular basement membranes that were recognized by rabbit antiserum to rainbow trout immunoglobulin. This was true only when frozen sections of kidney were used and not formalin-fixed tissue. An attempt to experimentally produce a glomerulopathy in rainbow trout by repeated immunization with killed R. salmoninarum was not successful. Case records from the Fish Pathology Laboratory at the University of Guelph over a 10-year period revealed that a range of species were diagnosed with glomerulopathies similar to those seen in Chinook salmon. The majority of these cases were determined to have chronic inflammatory disease. This report has identified the presence of immunoglobulin within thickened basement membranes of Chinook salmon with glomerulonephritis and supports the existence of type III hypersensitivity in fish. PMID:18752546

  5. Congenital syphilis and glomerulonephritis with evidence for immune pathogenesis

    PubMed Central

    Wiggelinkhuizen, J.; Kaschula, R. O. C.; Uys, C. J.; Kuijten, R. H.; Dale, J.

    1973-01-01

    In 3 infants with congenital syphilis the dominant clinical manifestation of syphilitic kidney disease was the nephrotic syndrome. Mesangioendothelial proliferation was present in 2 cases and mixed proliferative glomerulonephritis with crescent formation in the third. The severity of the clinical and histopathological abnormalities could be related to the apparent duration of the illness. In all 3 cases immune complex deposition could be shown within and along the epithelial aspect of the glomerular basement membrane on light, electron, and immunofluorescent microscopy. These features, together with a reduced total serum haemolytic complement, suggest an immune pathogenesis of the glomerulonephritis associated with early congenital syphilis. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:4267344

  6. Neural correlates of experimentally induced flow experiences.

    PubMed

    Ulrich, Martin; Keller, Johannes; Hoenig, Klaus; Waller, Christiane; Grön, Georg

    2014-02-01

    Flow refers to a positive, activity-associated, subjective experience under conditions of a perceived fit between skills and task demands. Using functional magnetic resonance perfusion imaging, we investigated the neural correlates of flow in a sample of 27 human subjects. Experimentally, in the flow condition participants worked on mental arithmetic tasks at challenging task difficulty which was automatically and continuously adjusted to individuals' skill level. Experimental settings of "boredom" and "overload" served as comparison conditions. The experience of flow was associated with relative increases in neural activity in the left anterior inferior frontal gyrus (IFG) and the left putamen. Relative decreases in neural activity were observed in the medial prefrontal cortex (MPFC) and the amygdala (AMY). Subjective ratings of the flow experience were significantly associated with changes in neural activity in the IFG, AMY, and, with trend towards significance, in the MPFC. We conclude that neural activity changes in these brain regions reflect psychological processes that map on the characteristic features of flow: coding of increased outcome probability (putamen), deeper sense of cognitive control (IFG), decreased self-referential processing (MPFC), and decreased negative arousal (AMY). PMID:23959200

  7. Autoantibodies to ribosomal P antigens with immune complex glomerulonephritis in SJL mice treated with pristane.

    PubMed

    Satoh, M; Hamilton, K J; Ajmani, A K; Dong, X; Wang, J; Kanwar, Y S; Reeves, W H

    1996-10-01

    BALB/c ByJ mice develop a lupus-like syndrome characterized by anti-nRNP/Sm and Su autoantibodies and immune complex glomerulonephritis after a single i.p. pristane injection. In contrast, mercuric chloride induces anti-fibrillarin Abs only in SJL and other H-2s mice, and not in BALB/c (H-2d) mice. In the present study, the specificities of autoantibodies induced by pristane and HgCl2 were compared in SJL and BALB/c mice to examine whether these strains are "programmed" to make different sets of autoantibodies in response to nonspecific immune stimulation. Unexpectedly, the predominant autoantibodies induced by pristane in SJL mice were neither those characteristic of HgCl2-treated SJL mice nor those associated with pristane-induced disease in BALB/c mice but, rather, anti-ribosomal P, another lupus-related specificity. The autoantibodies were strongly reactive with the C-terminal 22 amino acids of the ribosomal P2 protein, indicating that they exhibited similar fine specificities to anti-P Abs in human SLE and MRL/Ipr mice. Like BALB/c mice, pristane-treated SJL mice developed severe glomerulonephritis characterized by proteinuria, mesangial proliferation, and glomerular immune complex deposits. This is the first evidence that the induction of a lupus-like syndrome by pristane is not restricted to BALB/c mice. The predominance of anti-P Abs in SJL mice contrasts sharply with the predominance of anti-nRNP/Sm and Su, in pristane-treated BALB/c mice, even though the renal lesions were similar in both strains. The data suggest that H-2s does not program mice to produce anti-fibrillarin Abs in response to nonspecific immune stimulation, arguing that autoantibody induction by pristane involves Ag-specific mechanisms. PMID:8816434

  8. Properdin and C3 Proactivator: Alternate Pathway Components in Human Glomerulonephritis

    PubMed Central

    McLean, Robert H.; Michael, Alfred F.

    1973-01-01

    Serological and immunopathological studies of human glomerulonephritis have suggested that alternate pathways of activation of the third component of complement may be important in some forms of glomerulonephritis. We have investigated the role of two alternate pathway proteins, properdin and C3 proactivator, in 22 patients with chronic membranoproliferative glomerulonephritis, 21 patients with systemic lupus erythematosus, 20 patients with acute poststreptococcal glomerulonephritis, and 19 patients with other forms of renal disease. C3 (measured at β1A), properdin, and C3 proactivator were assayed by single radial immunodiffusion. In sera with low β1A (< 2 SD), mean properdin was most significantly decreased in patients with acute poststreptococcal glomerulonephritis but was also significantly decreased in chronic membranoproliferative glomerulonephritis and in untreated systemic lupus erythematosus. Properdin levels in other renal disease, acute glomerulonephritis, and chronic membranoproliferative glomerulonephritis with normal β1A levels were not significantly different from normal. A positive correlation between β1A and properdin levels in individual sera was present in all diseases except systemic lupus erythematosus. Serum C3 proactivator was markedly decreased in active systemic lupus erythematosus and there was a positive correlation between β1A and C3 proactivator levels in systemic lupus erythematosus and other renal diseases but not acute poststreptococcal glomerulonephritis. Properdin in fresh sera from four patients with systemic lupus erythematosus and five with chronic membranoproliferative glomerulonephritis showed increased migration toward the cathode on immunoelectrophoresis, suggesting in vivo change of the properdin molecule. The observation of reduced serum levels of properdin and C3 proactivator and altered electrophoretic migration of properdin in some patients with glomerulonephritis provide new evidence for participation of these

  9. Experimental and analytical investigation of flow through rocket pump inducer

    NASA Technical Reports Server (NTRS)

    Lakshminarayana, B.

    1974-01-01

    The characteristics of a rocket pump inducer are discussed. The effect of the pumping requirements on the blade configuration is analyzed. The effects of viscosity on blade design were determined by tests of a four bladed inducer operated in air at a flow coefficient of 0.065. The fluid properties were measured at the exit of the inducer using conventional and hot wire probes. The experimental results and the method of predicting the outlet tangential velocity and head rise are discussed.

  10. Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in children.

    PubMed

    Hattori, M; Kurayama, H; Koitabashi, Y

    2001-07-01

    Aretrospective investigation was conducted by members of the Japanese Society for Pediatric Nephrology from 1990 to 1997 to define the clinical features and outcome of antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis in children. Thirty-four ANCA-seropositive Japanese pediatric patients with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis were identified. Of these, 3 cases associated with Wegener's granulomatosis were excluded because of the small sample size. Among the 31 patients studied, 10 had a diagnosis of necrotizing crescentic glomerulonephritis alone and 21 had microscopic polyangiitis. Females predominated (87%), and the median age at onset was 12 yr. Twenty-six patients received treatment with cyclophosphamide and corticosteroids, and five patients received treatment with corticosteroids alone; 84% of patients achieved remission, and 39% of responders relapsed in a median of 24 mo. ANCA titers correlated with response to treatment and disease activity, with some exceptions. Patients were followed for a median of 42 mo (range, 3 to 96 mo). Nine of 31 patients (29.0%) progressed to end-stage renal disease, 6 (19.4%) had reduced renal function, and 15 (48.4%) had normal renal function at the last observation. One patient (3.2%) died from cytomegalovirus infection 3 mo after initiation of therapy. Life-table analysis showed 75% renal survival at 39 mo. Patients who subsequently developed end-stage renal disease (n = 9) had significantly higher average peak serum creatinine levels and more chronic pathologic lesions at diagnosis compared with patients with favorable renal outcome (n = 15). In conclusion, our clinical experience suggests that the clinical disease spectrum of ANCA-associated glomerulonephritis is similar in pediatric and adult patients, but there is a female predominance in children. PMID:11423578

  11. Cerebral venous thrombosis in a patient with acute postinfectious glomerulonephritis.

    PubMed

    Morkhandikar, S; Priyamvada, P S; Srinivas, B H; Parameswaran, S

    2016-01-01

    Thrombosis of the cerebral venous sinuses (CVT) is described in nephrotic syndrome. A 13-year-old girl was admitted with acute post-infectious glomerulonephritis (APIGN). Subsequently she developed recurrent seizures with focal neurological deficits. On evaluation, she was found to have CVT. To the best of our knowledge, this is the first report of CVT in APIGN. Identifying this complication is imperative, as timely diagnosis and treatment could be lifesaving. PMID:27194837

  12. Posterior segment findings in a patient with immunotactoid glomerulonephritis

    PubMed Central

    Gupta, Aditi; Prabhu, Rangarajan Venugopal; Patel, Amit K.; Sivaraj, Ramesh

    2015-01-01

    Purpose: To present a case with posterior segment findings in a patient with cloudy corneas secondary to immunotactoid glomerulonephritis (ITG). Methods: A 57-year-old female was known to have bilateral cloudy corneas diagnosed 12 years ago secondary to immunotactoid glomerulonephritis. Clinically, fundus examination was difficult to visualise due to the density of her corneal opacities. Results: B-scan ultrasound revealed significant retino-choroidal & non-inflammatory scleral thickening. The macula also showed signs of thickening in both eyes. Optical coherence tomography (OCT) showed thinning of the inner retinal layers and significant choroidal folds in both eyes. Electrodiagnostic tests (EDT) concluded loss of retinal ganglion cells with preservation of retinal function in both eyes. Conclusion: This case widens the spectrum of findings seen in patients diagnosed with Immunotactoid Glomerulonephritis and alerts us to undertake detailed posterior segment examination where possible. Ocular coherence tomography (OCT) and B-scan ultrasonography are important adjuvants to help assess the posterior segment in patients with corneal opacities secondary to ITG.

  13. Mast cell chymase in experimentally induced psoriasis.

    PubMed

    Suttle, Mireille-Maria; Harvima, Ilkka T

    2016-06-01

    Mast cell chymase can have a pro-inflammatory or an immunosuppressive function in psoriasis, but the outcome may depend on the level of chymase activity. Therefore, mast cells showing chymase activity (Chyact ) and immunoreactivity (Chyprot ) were studied during the Köbner reaction (0 days, 2 h, 1 day, 3 days and 7 days) of psoriasis induced by the tape-stripping technique. Also, the effect of recombinant human chymase (rh-chymase) or human LAD2 mast cells (LAD2) on the (3) H-thymidine uptake of psoriatic peripheral blood mononuclear cells (PBMC) or total T cells was studied. The Chyact /Chyprot ratio tended to be higher in all time-point biopsies in the Köbner-negative (n = 10) than -positive (n = 8) group (P = 0.073), although chymase activity decreased significantly at 2 h to 1 day only in the Köbner-negative group. rh-chymase (0.05-0.5 μg/mL) stimulated to a varying extent PBMC in eight out of nine cultures, but in all cultures 5 μg/mL rh-chymase turned the stimulation towards inhibition. The effect of rh-chymase on T cells varied from stimulation to inhibition, but in 11 of 15 cultures rh-chymase, at least at 5 μg/mL, produced a change to inhibition. In co-cultures, LAD2 inhibited PBMC in the absence of soybean trypsin inhibitor (SBTI). In the presence of SBTI, LAD2 stimulated PBMC in the majority of seven cultures. In summary, the psoriatic immunopathogenesis may be promoted at low, but controlled at high, activity status of chymase. PMID:26703925

  14. Experimental background due to particle induced gas desorption in RHIC

    SciTech Connect

    Zhang,S.Y.; Trbojevic, D.

    2008-08-10

    Beam-gas collision created experimental background, i.e., singles, has affected heavy ion and polarized proton operations in Relativistic Heavy Ion Collider at Brookhaven National Laboratory. The gas molecules in interaction region are mainly caused by the electron induced gas desorption. and the electrons are produced from the beam induced electron multipacting, or called electron cloud. The background has a dependence on the usual electron cloud related parameters, such as the bunch intensity, bunch spacing, and the solenoid field. With the RHIC upgrade plan, the experimental background may become a luminosity limiting factor. Mitigations are discussed.

  15. Experimentally induced otitis and audiogenic seizure in the mouse.

    PubMed

    Niaussat, M M

    1977-04-15

    Audiogenic seizures can be induced in genetically non-susceptible 17-day-old mice (Rb/3 strain) with various results. Priming only induces 9% of seizures, auditory insulation 3,8%, while experimental otitis leads to 79%. The hypothesis concerning disuse supersensitivity subsequent to acoustic deprivation was not confirmed by the experiment. However, modification of acoustic transmission at middle ear level induced by otitis or ear physical damage during the maturation period, exposes the upper nervous centers to intense stimulation to which the reaction is a recruiting response. PMID:862735

  16. Proliferative Glomerulonephritis with Monoclonal IgG Deposits

    PubMed Central

    Satoskar, Anjali; Markowitz, Glen S.; Valeri, Anthony M.; Appel, Gerald B.; Stokes, Michael B.; Nadasdy, Tibor; D'Agati, Vivette D.

    2009-01-01

    Dysproteinemias that result in monoclonal glomerular deposits of IgG are relatively uncommon. Here, we report the largest series of proliferative glomerulonephritis with monoclonal IgG deposits, a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. We retrospectively identified 37 patients, most of whom were white (81%), female (62%), or older than 50 yr (65%). At presentation, 49% had nephrotic syndrome, 68% had renal insufficiency, and 77% had hematuria. In 30% of the patients, we identified a monoclonal serum protein with the same heavy- and light-chain isotypes as the glomerular deposits (mostly IgG1 or IgG2), but only one patient had myeloma. Histologic patterns were predominantly membranoproliferative (57%) or endocapillary proliferative (35%) with membranous features. Electron microscopy revealed granular, nonorganized deposits, and immunofluorescence demonstrated glomerular deposits that stained for a single light-chain isotype and a single heavy-chain subtype, most commonly IgG3κ (53%). During an average of 30.3 mo of follow-up for 32 patients with available data, 38% had complete or partial recovery, 38% had persistent renal dysfunction, and 22% progressed to ESRD. Correlates of ESRD on univariate analysis were higher creatinine at biopsy, percentage of glomerulosclerosis, and degree of interstitial fibrosis but not immunomodulatory treatment or presence of a monoclonal spike. On multivariate analysis, higher percentage of glomerulosclerosis was the only independent predictor of ESRD. Only one patient lacking a monoclonal spike at presentation subsequently developed a monoclonal spike and no patient with a monoclonal spike at presentation subsequently developed a hematologic malignancy. We conclude that proliferative glomerulonephritis with monoclonal IgG deposits does not seem to be a precursor of myeloma in the vast majority of patients. PMID:19470674

  17. Monoclonal gammopathy associated membranous glomerulonephritis: A rare entity

    PubMed Central

    Gowda, K. K.; Joshi, K.; Ramachandran, R.; Nada, R.

    2015-01-01

    A 40-year-old male presented with nephrotic syndrome. Light microscopic analysis of the renal biopsy showed thickening of the glomerular capillary wall. Immunofluorescence examination revealed granular deposition of monoclonal immunoglobulin (Ig) G3-kappa and complement C3 along the glomerular basement membrane. Electron microscopy showed subepithelial electron dense deposits, thus confirming membranous glomerulonephritis (MGN) with monoclonal gammopathy. MGN with monoclonal gammopathy is an extremely rare but distinctive entity. This patient was treated with a combination of bortezomib, thalidomide and dexamethasone and showed partial remission of his nephrotic state and dysproteinemia. PMID:25684873

  18. Fibrillary glomerulonephritis associated with limited scleroderma: a case report.

    PubMed

    Nakhoul, Georges N; Simon, James F

    2016-04-01

    Fibrillary glomerulonephritis (GN) is a rare glomerular disorder that has been associated with monoclonal gammopathies, malignancies, chronic infections, and autoimmune disorders. We present the case of a 56-year-old woman with limited-type scleroderma and remote discoid lupus, evaluated for dipstick positive hematuria and preserved kidney function. Serologies were negative. Kidney biopsy revealed fibrillary GN. Her renal function and proteinuria remain stable 4 years after her initial diagnosis. This case is unusual both in its presentation and evolution, but mostly because it is the first reported case of fibrillary GN in association with limited type scleroderma. PMID:26709524

  19. The Epidermal Growth Factor Receptor Promotes Glomerular Injury and Renal Failure in Rapidly Progressive Crescentic Glomerulonephritis; the Identification of Possible Therapy

    PubMed Central

    Bollée, Guillaume; Flamant, Martin; Schordan, Sandra; Fligny, Cécile; Rumpel, Elisabeth; Milon, Marine; Schordan, Eric; Sabaa, Nathalie; Vandermeersch, Sophie; Galaup, Ariane; Rodenas, Anita; Casal, Ibrahim; Sunnarborg, Susan W; Salant, David J; Kopp, Jeffrey B.; Threadgill, David W; Quaggin, Susan E; Dussaule, Jean-Claude; Germain, Stéphane; Mesnard, Laurent; Endlich, Karlhans; Boucheix, Claude; Belenfant, Xavier; Callard, Patrice; Endlich, Nicole; Tharaux, Pierre-Louis

    2011-01-01

    Rapidly progressive glomerulonephritis (RPGN) is a clinical a morphological expression of severe glomerular injury. Glomerular injury manifests as a proliferative histological pattern (“crescents”) with accumulation of T cells and macrophages, and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the EGFR/ErbB1 receptor in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 days after the induction of experimental RPGN. This suggests that targeting the HB-EGF/EGFR pathway could also be beneficial for treatment of human RPGN. PMID:21946538

  20. Familial C4B Deficiency and Immune Complex Glomerulonephritis

    PubMed Central

    Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY

    2010-01-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617

  1. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease

    PubMed Central

    Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K.

    2016-01-01

    Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208

  2. Membranoproliferative glomerulonephritis: the role for laser microdissection and mass spectrometry.

    PubMed

    Jain, Deepika; Green, Jamie A; Bastacky, Sheldon; Theis, Jason D; Sethi, Sanjeev

    2014-02-01

    Monoclonal gammopathy is increasingly recognized as a common cause of membranoproliferative glomerulonephritis (MPGN); however, establishing this diagnosis can be challenging. We report the case of a 58-year-old asymptomatic woman who presented with proteinuria with protein excretion of 5,000mg/d, microscopic hematuria, and normal kidney function. Kidney biopsy was consistent with MPGN pattern of injury. Immunofluorescence studies were positive for nonspecific segmental immunoglobulin M (IgM) and C3 staining. Electron microscopy showed subendothelial, subepithelial, and mesangial electron-dense deposits. The workup excluded an infectious or autoimmune disease, but IgG κ monoclonal protein was detected in serum at a concentration of 0.4mg/dL. Because there was a mismatch between the serum monoclonal protein (IgG κ) and immunofluorescence staining pattern (nonspecific IgM, no light chain restriction), laser microdissection and mass spectrometry were performed on the kidney biopsy tissue. This identified the deposits as monoclonal IgG κ, thereby leading to the diagnosis of monoclonal gammopathy-associated MPGN. Our case emphasizes the importance of searching for an underlying cause of MPGN, reviews the technique of laser microdissection-mass spectrometry, and highlights its application as a pathology tool for the evaluation of monoclonal gammopathy-related glomerulonephritis. PMID:24145022

  3. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome

    PubMed Central

    Huang, Yan-Mei; Zhou, Hui-Rong; Zhang, Ling; Yang, Ke-Ke; Luo, Jiang-Xi; Zhao, Hai-Lu

    2016-01-01

    Abstract Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function. Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5–12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old. We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7–33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy. Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID:27368022

  4. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease.

    PubMed

    Yeturi, Supraja; Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K

    2016-01-01

    Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208

  5. Rituximab therapy for primary glomerulonephritis: Report on two cases

    PubMed Central

    Fabrizi, Fabrizio; Cresseri, Donata; Fogazzi, Giovanni B; Moroni, Gabriella; Passerini, Patrizia; Martin, Paul; Messa, Piergiorgio

    2015-01-01

    The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient (hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function (he became dialysis independent with serum creatinine going back to 1.6 mg/dL) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids. PMID:26301235

  6. PHARMACOLOGIC TREATMENT OF HYPERALGESIA EXPERIMENTALLY INDUCED BY NUCLEUS PULPOSUS

    PubMed Central

    de Souza Grava, André Luiz; Ferrari, Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido

    2015-01-01

    Objective: To evaluate the effect of anti-inflammatory drugs (dexamethasone, indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in contact with the L5 dorsal root ganglion (DRG). Methods: Thirty male Wistar rats of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was induced by means of a fragment of NP removed from the sacrococcygeal region that was placed in contact with the L5 dorsal root ganglion. The 30 animals were divided into experimental groups according to the drug used. The drugs were administered for two weeks after the surgical procedure to induce hyperalgesia. Mechanical and thermal hyperalgesia was evaluated using the paw pressure test, von Frey electronic test and Hargreaves test, over a seven-week period. Results: The greatest reduction of hyperalgesia was observed in the group of animals treated with morphine, followed by dexamethasone, indomethacin and atenolol. Reductions in hyperalgesia were observed after drug administration ceased, except for the group of animals treated with morphine, in which there was an increase in hyperalgesia after discontinuation of the treatment. Conclusion: Hyperalgesia induced by NP contact with the DRG can be reduced through administration of anti-inflammatory and analgesic drugs, but a greater reduction was observed with the administration of dexamethasone. PMID:27026966

  7. Elastase-induced pulmonary emphysema: insights from experimental models.

    PubMed

    Antunes, Mariana A; Rocco, Patricia R M

    2011-12-01

    Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema. PMID:22159348

  8. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-06-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12-20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  9. White-blue pyelocalyceal cyst with hydrotic glomerulonephritis

    PubMed Central

    Chaurasia, Jai Kumar; Soni, Mayank; Ahmed, Murad; Naim, Mohammed

    2013-01-01

    A 5-month-old male infant presented with a 15 day history of distension of abdomen. On clinical examination, a soft lump was palpable in the left lumbar region. Radiological findings suggested an enlarged non-functional left kidney with ureteropelvic adhesive obstruction. The left renal mass was excised and submitted for histopathological examination. The excised renal mass was cystic with its wall partly white and partly blue. Gross and histopathological findings were diagnostic of a white-blue pyelocalyceal cyst with hydrotic glomerulonephritis. This entity needs to be differentiated from a large number of other cystic diseases of the kidney. Intrauterine screening and diagnosis may be significant for a possible early intrauterine uro-laparoscopic recanalisation of the pyeloureteral obstruction to save the affected kidney. PMID:24347451

  10. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-01-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  11. Crescentic glomerulonephritis in a polar bear (Ursus maritimus).

    PubMed

    Baba, Hiroshi; Kudo, Tomoo; Makino, Yoshinori; Mochizuki, Yasumasa; Takagi, Takayo; Une, Yumi

    2013-11-01

    Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman's capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits. PMID:23856758

  12. [Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

    PubMed

    Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

    2014-02-26

    Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist. PMID:24665657

  13. The nephrotic syndrome in a heifer due to glomerulonephritis.

    PubMed

    Wiseman, A; Spencer, A; Petrie, L

    1980-05-01

    An 18-month-old Friesian heifer, which was admitted in November with a history of weight loss, diarrhoea and submandibular oedema, was found to have an enlarged left kidney and a massive proteinuria. Laboratory investigations revealed that there was a marked hypoalbuminaemia and that the range and the proportions of the individual proteins in the urine were almost identical to those in the serum. Consequently, the nephrotic syndrome was diagnosed. On gross and histopathological examination of the kidneys, there was evidence of pyelonephritis. However, immunofluorescence studies revealed a striking diffuse deposition of immunoglobulin in a predominantly linear pattern along the glomerular basement membranes. Abnormalities of the basement membranes. Abnormalities of the basement membranes were seen on ultrastructural examination and evidence of a flomerular protein leak was detected but changes typical of immune-complex deposition were absent. The immunofluorescence findings suggested a diagnosis of glomerulonephritis mediated by antiglomerular basement membrane antibody. PMID:7414086

  14. Experimentally induced rodent models of type 2 diabetes.

    PubMed

    Islam, Md Shahidul; Wilson, Rachel Dorothy

    2012-01-01

    Diabetes is one of the major global public health problems and is gradually getting worse particularly in developing nations where 95% of patients are suffering from type 2 diabetes (T2D). Animal models in diabetes research are very common where rodents are the best choice of use due to being smaller in size, easy to handle, omnivorous in nature, and non-wild tranquil behavior. Normally rodent models are classified into two major classes namely: (1) genetic or spontaneously induced models and (2) non-genetic or experimentally induced models. Non-genetic models are more popular compared to genetic models due to lower cost, wider availability, easier to induce diabetes, and of course easier to maintain compared to genetic models. A number of non-genetic models have been developed in last three decades for diabetes research including adult alloxan/streptozotocin (STZ) models, partial pancreatectomy model, high-fat (HF) diet-fed models, fructose-fed models, HF diet-fed STZ models, nicotinamide-STZ models, monosodium-glutamate (MSG) induced models, and intrauterine growth retardation (IUGR) models. A T2D model should have the all major pathogenesis of the disease usually found in humans; however, none of the above-mentioned models are without limitations. This chapter comparatively evaluates most of the experimentally induced rodent models of T2D with their limitations, advantages, disadvantages, and criticality of development in order to help diabetes research groups to more appropriately select the animal models to work on their specific research question. PMID:22893406

  15. The effect of experimentally-induced subacromial pain on proprioception.

    PubMed

    Sole, Gisela; Osborne, Hamish; Wassinger, Craig

    2015-02-01

    Shoulder injuries may be associated with proprioceptive deficits, however, it is unknown whether these changes are due to the experience of pain, tissue damage, or a combination of these. The aim of this study was to investigate the effect of experimentally-induced sub-acromial pain on proprioceptive variables. Sub-acromial pain was induced via hypertonic saline injection in 20 healthy participants. Passive joint replication (PJR) and threshold to detection of movement direction (TTDMD) were assessed with a Biodex System 3 Pro isokinetic dynamometer for baseline control, experimental pain and recovery control conditions with a starting position of 60° shoulder abduction. The target angle for PJR was 60° external rotation, starting from 40°. TTDMD was tested from a position of 20° external rotation. Repeated measures ANOVAs were used to determine differences between PJR absolute and variable errors and TTDMD for the control and experimental conditions. Pain was elicited with a median 7 on the Numeric Pain Rating Scale. TTDMD was significantly decreased for the experimental pain condition compared to baseline and recovery conditions (≈30%, P = 0.003). No significant differences were found for absolute (P = 0.152) and variable (P = 0.514) error for PJR. Movement sense was enhanced for the experimental sub-acromial pain condition, which may reflect protective effects of the central nervous system in response to the pain. Where decreased passive proprioception is observed in shoulders with injuries, these may be due to a combination of peripheral tissue injury and neural adaptations that differ from those due to acute pain. PMID:25261091

  16. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease: The utility of routine staining with immunoglobulin light chains.

    PubMed

    Gowda, K K; Nada, R; Ramachandran, R; Joshi, K; Tewari, R; Kohli, H S; Jha, V; Gupta, K L

    2015-01-01

    Proliferative glomerulonephritis occurring as a consequence of monoclonal glomerular deposits of IgG is uncommon. It is a form of renal involvement in monoclonal gammopathy that mimics immune complex glomerulonephritis. Here, we report the first series of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) from the Indian subcontinent highlighting use of light chain immunofluorescence (IF) in routine renal biopsy interpretation. We retrieved 6 patients diagnosed as proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) out of 160 biopsies (3.7%) with membranoproliferative patterns over 5 1/2 years (2009-2014), one of whom had recurrence 6 months post-renal transplant. Four (67%) patients presented with rapidly progressive renal failure and two (33%) with nephrotic syndrome. None of these patients had overt multiple myeloma. The predominant histologic pattern was membranoproliferative with all the biopsies showing IgG3 Kappa deposits on IF. The deposits were primarily subendothelial on electron microscopy. PMID:26664209

  17. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease: The utility of routine staining with immunoglobulin light chains

    PubMed Central

    Gowda, K. K.; Nada, R.; Ramachandran, R.; Joshi, K.; Tewari, R.; Kohli, H. S.; Jha, V.; Gupta, K. L.

    2015-01-01

    Proliferative glomerulonephritis occurring as a consequence of monoclonal glomerular deposits of IgG is uncommon. It is a form of renal involvement in monoclonal gammopathy that mimics immune complex glomerulonephritis. Here, we report the first series of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) from the Indian subcontinent highlighting use of light chain immunofluorescence (IF) in routine renal biopsy interpretation. We retrieved 6 patients diagnosed as proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) out of 160 biopsies (3.7%) with membranoproliferative patterns over 5 1/2 years (2009–2014), one of whom had recurrence 6 months post-renal transplant. Four (67%) patients presented with rapidly progressive renal failure and two (33%) with nephrotic syndrome. None of these patients had overt multiple myeloma. The predominant histologic pattern was membranoproliferative with all the biopsies showing IgG3 Kappa deposits on IF. The deposits were primarily subendothelial on electron microscopy. PMID:26664209

  18. [Aplastic anemia combined with an autoimmune disease (eosinophilic fasciitis or glomerulonephritis)].

    PubMed

    Stebler, C; Tichelli, A; Gratwohl, A; Dazzi, H; Nissen, C; Steiger, U; Speck, B

    1991-06-01

    We describe 3 patients with aplastic anemia and an autoimmune disease. Two had eosinophilic fasciitis and 1 glomerulonephritis. In all patients both diseases were successfully treated by immunosuppressive therapy. Pathophysiological aspects of this association are discussed. PMID:1857945

  19. Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings.

    PubMed Central

    Duvall-Young, J; Short, C D; Raines, M F; Gokal, R; Lawler, W

    1989-01-01

    Previously we have demonstrated a deposit in Bruch's membrane in a single case of mesangiocapillary glomerulonephritis type II. We studied a group of patients with this disease and described extensive clinical and fluorescein angiographic abnormalities, which were in marked contrast to the findings in a group of patients with other forms of glomerulonephritis. This finding contributes to our understanding of the pathophysiology of the complex of the retinal pigment epithelium, Bruch's membrane, and choriocapillaris. Images PMID:2605144

  20. Necrotizing ANCA-Positive Glomerulonephritis Secondary to Culture-Negative Endocarditis

    PubMed Central

    Van Haare Heijmeijer, Sophie; Wilmes, Dunja; Aydin, Selda; Clerckx, Caroline; Labriola, Laura

    2015-01-01

    Infective endocarditis (IE) and small-vessel vasculitis may have similar clinical features, including glomerulonephritis. Furthermore the association between IE and ANCA positivity is well documented, making differential diagnosis between IE- and ANCA-associated vasculitis particularly difficult, especially in case of culture-negative IE. We report on one patient with glomerulonephritis secondary to culture-negative IE caused by Bartonella henselae which illustrates this diagnostic difficulty. PMID:26819786

  1. Immediate effects of chocolate on experimentally induced mood states.

    PubMed

    Macht, Michael; Mueller, Jochen

    2007-11-01

    In this work two hypotheses were tested: (1) that eating a piece of chocolate immediately affects negative, but not positive or neutral mood, and (2) that this effect is due to palatability. Experiment 1 (48 normal-weight and healthy women and men) examined the effects of eating a piece of chocolate and drinking water on negative, positive and neutral mood states induced by film clips. Eating chocolate reduced negative mood compared to drinking water, whereas no or only marginal effects were found on neutral and positive moods. Experiment 2 (113 normal-weight and healthy women and men) compared effects of eating palatable and unpalatable chocolate on negative mood, and examined the duration of chocolate-induced mood change. Negative mood was improved after eating palatable chocolate as compared to unpalatable chocolate or nothing. This effect was short lived, i.e., it disappeared after 3 min. In both experiments, chocolate-induced mood improvement was associated with emotional eating. The present studies demonstrate that eating a small amount of sweet food improves an experimentally induced negative mood state immediately and selectively and that this effect of chocolate is due to palatability. It is hypothesized that immediate mood effects of palatable food contribute to the habit of eating to cope with stress. PMID:17597253

  2. Ichnocarpus frutescens Ameliorates Experimentally Induced Convulsion in Rats

    PubMed Central

    Singh, Narendra Kumar; Laloo, Damiki; Garabadu, Debapriya; Singh, Tryambak Deo; Singh, Virendra Pratap

    2014-01-01

    The present study was carried out to evaluate the anticonvulsant activity and probable mechanism of action of the methanol root extract from I. frutescens (MEIF) using different experimental animal models. Anticonvulsant activity of the single dose of MEIF (100, 200, and 400 mg/kg, p.o.) was evaluated in maximal electroshock- (MES-), pentylenetetrazole- (PTZ-), and isoniazid- (INH-) induced convulsions models in rats. The levels of γ-amino butyric acid (GABA), glutamate, GABA-transaminase (GABA-T) activity and oxidative stress markers were measured in pretreated rat's brain homogenate to corroborate the mechanism of observed anticonvulsant activity. MEIF (200–400 mg/kg, p.o.) protected the animals in all the behavioral models used. Pretreatment of MEIF (200–400 mg/kg, p.o.) and diazepam (1.0 mg/kg, i.p.) to the animals in INH-induced convulsion model showed 100% and 80% protection, respectively, as well as significant restoration of GABA and glutamate level in the rat's brain. MEIF and vigabatrin (50 mg/kg, i.p.) reduced the PTZ-induced increase in the activity of GABA-T (46%) in the brain. Further, MEIF reversed the PTZ-induced increase in lipid peroxidase (LPO) and decrease in reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. The findings of this study validate the anticonvulsant activity of I. frutescens. PMID:27379268

  3. [Hypertension and primary glomerulonephritis in adults. A study of 302 cases].

    PubMed

    Seba, A; Rayane, T; Kaci, L; Haddoum, F; Benabadji, M

    1997-08-01

    The purpose of the present work was to show the place of hypertension in primary glomerulonephritis in adults. Hypertension was defined as diastolic blood pressure above 90 mmHg and renal insufficiency as serum creatinine above 135 mc mol/L. Secondary glomerulonephritis was excluded. The study was performed in 302 patients with primary glomerulonephritis biopsied between March 1994 and March 1996. They were 183 males and 119 females, aged from 16 to 63 years (mean: 29.8 years). The incidence of hypertension at the time of admission was 46.6%: 141/302 cases. The only consideration of prolonged hypertension (excluded transient hypertension of acute nephritic syndrome) shows an incidence of 31.4%: 95/302 cases (table). Frequency of hypertension (HT) in different types of primary glomerulonephritis (GN): [table: see text] The histological types observed in these cases of hypertension were represented essentially by the proliferative lesions: 73% (72/95 cases) who were grouped mainly in proliferative glomerulonephritis postinfectious and IgA nephropathy. No proliferative lesions: 24% (23/95 cases) were especially represented by focal segmental sclerosis. Renal insufficiency noted in 69 cases on 95 hypertensions was probably the result of the parallel evolution of hypertension renal lesions and those belonging to these histologic types. In conclusion, this study shows a narrow correlation between the hypertension and proliferative glomerulonephritis in our young adults population. PMID:9404432

  4. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

    PubMed

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-05-10

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  5. Experimental analysis of radiation- and streaming-induced microparticle acoustophoresis

    NASA Astrophysics Data System (ADS)

    Rossi, Massimiliano; Marin, Alvaro; Kähler, Christian J.; Augustsson, Per; Laurell, Thomas; Muller, Peter B.; Barnkob, Rune; Bruus, Henrik

    2012-11-01

    We present an experimental analysis of the acoustophoretic motion of microparticles suspended in a liquid-filled acoustofluidic microchannel. This analysis intends to provide an experimental validation and support to very recent numerical and analytical models of radiation- and streaming-induced microparticle acoustophoresis (see Muller et al., Lab Chip 12, in press, 2012). For the experiments, we used a suspension of water and spherical polystyrene particles in a straight microchannel with rectangular cross section, actuated in its 1.94-MHz resonance by means of a piezoelectric transducer. The particles were labeled with a fluorescent dye and their motion was observed using an epifluorescent microscope. For the analysis, the Astigmatism Particle Tracking Velocimetry (APTV) technique was used to measure the three-dimensional trajectories and velocities of the particles with high precision and resolution (Cierpka et al., Meas Sci Technol 22, 2011). The experiments were performed for different particle sizes, ranging from 0.5- μm particles, dominated by the Stokes drag force induced by the acoustic streaming of the flow, to 5- μm particles, dominated by the acoustic radiation force. The results agree well with the analytical and numerical predictions.

  6. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

    PubMed Central

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-01-01

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  7. The influence of experimentally induced pain on shoulder muscle activity.

    PubMed

    Diederichsen, Louise Pyndt; Winther, Annika; Dyhre-Poulsen, Poul; Krogsgaard, Michael R; Nørregaard, Jesper

    2009-04-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0 degrees -105 degrees) at a speed of approximately 120 degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load

  8. In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

    1993-04-01

    The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

  9. Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy.

    PubMed

    Ariza, L; Pagès, G; García-Lareu, B; Cobianchi, S; Otaegui, P J; Ruberte, J; Chillón, M; Navarro, X; Bosch, A

    2014-08-22

    Animal models of diabetes do not reach the severity of human diabetic neuropathy but relatively mild neurophysiological deficits and minor morphometric changes. The lack of degenerative neuropathy in diabetic rodent models seems to be a consequence of the shorter length of the axons or the shorter animal life span. Diabetes-induced demyelination needs many weeks or even months before it can be evident by morphometrical analysis. In mice myelination of the peripheral nervous system starts at the prenatal period and it is complete several days after birth. Here we induced experimental diabetes to neonatal mice and we evaluated its effect on the peripheral nerve 4 and 8 weeks after diabetes induction. Neurophysiological values showed a decline in sensory nerve conduction velocity at both time-points. Morphometrical analysis of the tibial nerve demonstrated a decrease in the number of myelinated fibers, fiber size and myelin thickness at both time-points studied. Moreover, aldose reductase and poly(ADP-ribose) polymerase activities were increased even if the amount of the enzyme was not affected. Thus, type 1 diabetes in newborn mice induces early peripheral neuropathy and may be a good model to assay pharmacological or gene therapy strategies to treat diabetic neuropathy. PMID:24846610

  10. Expression of alternatively spliced fibronectin variants during remodeling in proliferative glomerulonephritis.

    PubMed Central

    Barnes, J. L.; Torres, E. S.; Mitchell, R. J.; Peters, J. H.

    1995-01-01

    Fibronectin (Fn) plays an important role in tissue remodeling during embryogenesis, wound repair, and vascular disease, and is thought to regulate cellular processes such as cell adhesion, migration, proliferation, and differentiation through specialized domains within the molecule. In addition, Fn can be alternatively spliced at three regions: extradomains EIIIA, EIIIB, and a variable segment V, potentially giving rise to functionally distinct variants of the molecule. We have previously shown a sequential expression of cellular Fn first by platelets, followed by macrophages, then mesangial cells in habu snake venom-induced proliferative glomerulonephritis (Am J Pathol 145: 585-597, 1994). These studies examined the cellular sources and glomerular localization of Fn in general but did not distinguish between the various alternatively spliced isoforms. In this study, we examine by in situ hybridization and immunohistochemistry the temporal expression and cellular sources of EIIIA, EIIIB, and V in a model of proliferation glomerulonephritis that has cell migration, proliferation, and extracellular matrix synthesis as features of tissue remodeling. Macrophages were the first cells to express Fn mRNA showing an EIIIA+, EIIIB-, and V95+ pattern beginning at 8 hours after habu snake venom injection. Migrating mesangial cells at the margins of early lesions (8 and 24 hours) did not overexpress mRNA encoding these Fn variants, but immunofluorescence microscopy revealed V95 and EIIIA protein at the margins of lesions. EIIIB was absent in lesions at this time. At 48 hours and peaking at 72 hours after habu snake venom injection, mesangial cells in central aspects of glomerular lesions expressed abundant mRNA and protein for V95 and EIIIA. EIIIB mRNA and protein was slight in the mesangium at these times. Parietal epithelial cells, particularly adjacent to glomerular lesions, also expressed abundant mRNA and protein for all three variants throughout the course of the disease

  11. Expression of AIM2 is high and correlated with inflammation in hepatitis B virus associated glomerulonephritis

    PubMed Central

    2013-01-01

    Background & aims Innate immunity is the first line of defense against invasive microbial infection, and AIM2 plays an important role in this process by sensing double-stranded DNA viruses. However, the role of AIM2 in regulating the immune response to viruses in vivo, especially in sensing hepatitis B virus (HBV), has not been examined. We hypothesized that the expression of AIM2 increases corresponding to HBV-mediated inflammation in patients with hepatitis B virus associated glomerulonephritis (HBV-GN), a condition which activates inflammatory mechanisms and causes renal damage. To test this hypothesis, we analyzed the expression of AIM2 in HBV-GN patients in relation to the inflammatory response to HBV infection. Methods A total of 79 patients diagnosed with chronic nephritis (CN) were enrolled in this study, including 54 HBV-GN patients as the experimental group and 24 chronic glomerulonephritis (CGN) patients as the negative control group. Six patients diagnosed with chronic hepatitis B (CHB) were also enrolled as positive controls. Each CN patient received renal biopsy, and immunohistochemistry was used to detect the expression of AIM2 and inflammatory factors caspase-1 and IL-1β in the biopsy specimens. CHB patients received liver puncture biopsy, and immunohistochemistry was used to detect the expression of AIM2 in these specimens. Expression of AIM 2 among different groups and in relation to inflammatory factors caspase-1 and IL-1β was analyzed. Results The expression of AIM2 in HBV-GN patients (81.4%) was significantly higher than in CGN patients (4.0%). Among the HBV-GN patients, expression of AIM2 was significantly higher in the high HBV replication group than in the low HBV replication group. AIM2 expression was not correlated with age, gender, HBeAg status in serum, HBV-antigen type deposited in renal tissue or pathological type of HBV-GN. However, AIM2 levels were positively correlated with the expression of caspase-1 and IL-1β in HBV-GN patients

  12. Mechanisms of blast induced brain injuries, experimental studies in rats.

    PubMed

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. PMID:20493951

  13. CXCR3 Is Involved in Tubulointerstitial Injury in Human Glomerulonephritis

    PubMed Central

    Segerer, Stephan; Banas, Bernhard; Wörnle, Markus; Schmid, Holger; Cohen, Clemens D.; Kretzler, Matthias; Mack, Matthias; Kiss, Eva; Nelson, Peter J.; Schlöndorff, Detlef; Gröne, Hermann-Josef

    2004-01-01

    Chemokines play pivotal roles in the recruitment of inflammatory cells into the kidney. The chemokine receptors CXCR3 and CCR5 are expressed on activated T lymphocytes, and expression of CXCR3 by mesangial cells has been suggested. Detailed description of CXCR3 expression might form a rational basis for use as a diagnostic marker and for therapeutic CXCR3 targeting in human glomerulonephritis. We studied the expression of CXCR3 in renal biopsies by immunohistochemistry (n = 45), and real time RT-PCR (n = 78). Biopsies were from patients with IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. Furthermore, cultured human mesangial cells (HMC) were studied for CXCR3 expression, and for functional responses to the ligands CXCL10/IP-10 and CXCL9/Mig. CXCR3-positive cells were rarely found in glomerular tufts, but formed a major part of the tubulointerstitial infiltrates. Consistently, CXCR3 mRNA expression was too low to be quantified in glomerular compartments, and was not detectable in HMC. The published staining for CXCR3 of mesangial cells could be traced to cross-reactivity of an antibody for CXCR3 with a potentially related chemokine receptor as revealed by FACS analysis. Despite an absence of CXCR3 expression, mesangial cells reacted to CXCR3 ligands by proliferation and migration, which was blocked by pertussis toxin but not by an anti-CXCR3 antibody. These results indicate that HMC do not express the classical CXCR3, but may potentially express a related receptor with shared ligand specificity. By immunohistochemistry the number of CXCR3-positive cells, mainly interstitial T cells, correlated with renal function, proteinuria, and percentage of globally sclerosed glomeruli. A significant morphological and numerical correlation between CD3, CXCR3, and CCR5-positive cells indicated a CXCR3/CCR5 double-positive T cell population. No apparent difference in the CXCR3 expression pattern was found between disease entities. CXCR3 expression

  14. Numerical and Experimental Investigations of Tsunami-Induced Sediment Transport

    NASA Astrophysics Data System (ADS)

    Young, Y.; Xiao, H.

    2007-05-01

    As demonstrated by the 2004 Indian Ocean Tsunami, high intensity wave runup and drawdown can mobilize substantial amount of sediment deposits. The resulting erosion and scour damage can undermine building foundations, roadways, sea walls, embankments, and may even lead to eventual collapse of the coastal structure. However, most previous models ignore the effect of tsunami-induced sediment transport and scour due to the complex physics and multiple scaling issues. In this work, a numerical model is presented for the simulation of solitary waves over a uniform sloped movable bed. The depth averaged nonlinear shallow water equations (SWEs) are used to model long waves, the wave profile gradient method is used to detect wave breaking, and the effect of energy-dissipation due to wave breaking is captured as a bore collapse. The effect of sediment transport is modeled via a passive scalar and is fully coupled with the SWEs to form a complete system. New forms of the erosion and deposition fluxes are introduced to account for the effect of the flow velocity, particle fall velocity, wave profile, and pore pressure gradient. The model is validated by comparing the numerical solutions to the measured bed changes obtained from the cross-shore sediment transport experiment under breaking solitary waves conducted by (Kobayashi & Lawrence 2004). To further validate the numerical model, two sets of experimental studies are planned for 2007. The first experimental study focuses on the effect of enhanced transport due to pore pressure gradients, and will be conducted at the 30-ft long flume in the hydraulics lab at the University of Hawaii using multiple grain sizes. The second experimental study focuses on tsunami-induced sediment transport, and will be conducted at the 160-ft long tsunami wave basin at Oregon State University using fine Oregon beach sand with D50=0.20mm. The experimental setups are shown, and scaling issues for the two movable bed physical models are discussed

  15. Sjögren Syndrome and Cryoglobulinemic Glomerulonephritis.

    PubMed

    Anand, Ananya; Krishna, Gopal G; Sibley, Richard K; Kambham, Neeraja

    2015-09-01

    We report the case of a 53-year-old woman with Sjögren syndrome and cryoglobulinemia. The patient presented with nephrotic syndrome, hematuria, and reduced estimated glomerular filtration rate. The kidney biopsy revealed diffuse endocapillary proliferation and leukocyte exudation with focal intraluminal hyaline thrombi, prominent tubulointerstitial inflammation, and vasculitis. Diffuse granular mesangial and segmental to global capillary wall staining was observed on immunofluorescence with antisera to C3 and immunoglobulin M (IgM), with less intense staining indicative of IgG and κ and λ light chains. A biopsy diagnosis of Sjögren syndrome-related cryoglobulinemic membranoproliferative glomerulonephritis and vasculitis was rendered. Subsequent investigations revealed the presence of circulating type II cryoglobulins with cryocrit of 9%. Although rare, Sjögren syndrome is the most common cause of non-hepatitis C virus-related mixed cryoglobulinemia. We discuss the possible pathogenic mechanisms involved in the development of mixed cryoglobulinemia and its evolution to lymphoma, as best described in the setting of hepatitis C virus infection. Although the specific antigen involved is unknown, it is likely that the mixed cryoglobulinemia in Sjögren syndrome is triggered by the long-term B-cell stimulation, resulting in clonal proliferation of B cells. Additional chromosomal aberrations and cytokine milieu alterations, as seen in hepatitis C virus infection, may result in prolonged B-cell survival and progression to non-Hodgkin lymphoma. PMID:25661680

  16. What is new in the management of rapidly progressive glomerulonephritis?

    PubMed

    Greenhall, George H B; Salama, Alan D

    2015-04-01

    Rapidly progressive glomerulonephritis (RPGN) results from severe crescentic damage to glomeruli and leads to irreversible kidney failure if not diagnosed and managed in a timely fashion. Traditional treatment has relied on glucocorticoids and cyclophosphamide, with additional plasmapheresis for certain conditions. Here we describe updates in the management of RPGN, according to the underlying renal pathology. However, there remains a paucity of trials that have enrolled patients with more advanced renal disease, dialysis dependence or with RPGN, and we are therefore still reliant on extrapolation of data from studies of patients with a less severe form of disease. In addition, reporting bias results in publication of cases or cohorts showing benefit for newer agents in advanced disease or RPGN, but it remains unclear how many unsuccessful outcomes in these circumstances take place. Since clinical trials specifically in RPGN are unlikely, use of biologic registries or combination of sufficient sized cohort series may provide indications of benefit outside of a clinical trial setting and should be encouraged, in order to provide some evidence for the efficacy of therapeutic regimens in RPGN and advanced renal disease. PMID:25815169

  17. Glomerulonephritis in a ferret with feline coronavirus infection.

    PubMed

    Fujii, Yuta; Tochitani, Tomoaki; Kouchi, Mami; Matsumoto, Izumi; Yamada, Toru; Funabashi, Hitoshi

    2015-09-01

    A male domestic ferret (Mustela putorius furo), which was purchased from outside of Japan at 13 weeks of age, was euthanized at 18 months of age because of poor health. At autopsy, the liver, spleen, and mesenteric lymph node were enlarged, and white foci were observed on the outer surface of the liver. The outer surface of the mesenteric lymph node was dark red. Histologically, granulomas were observed in the liver, spleen, bone marrow, and lymph nodes, composed mainly of aggregated epithelioid macrophages, some of which were positive to an anti-feline coronavirus (FCoV; Alphacoronavirus 1) antibody in immunohistochemistry. Mesangioproliferative glomerulonephritis was observed, and periodic acid-Schiff-positive deposits were observed along glomerular capillary walls. These deposits stained pale red with periodic acid-methenamine silver stain and red with Masson trichrome stain, and were also observed in the mesangial matrix. In affected glomeruli, glomerular capillary walls and mesangial areas were positive for anti-ferret immunoglobulin G. By electron microscopy, subepithelial and mesangial electron-dense deposits were observed consistent with immune complex deposition. The deposition of immune complexes may have been associated with FCoV infection. PMID:26319601

  18. De novo C3 glomerulonephritis in a renal allograft.

    PubMed

    Nahm, Ji Hae; Song, Seung Hwan; Kim, Yu Seun; Cheong, Hae-Il; Lim, Beom Jin; Kim, Beom Seok; Jeong, Hyeon Joo

    2016-01-01

    C3 glomerulonephritis (C3GN) is a recently described, rare glomerular disease characterized by predominant or sole glomerular C3 deposits. Morphologic features of C3GN are similar to those of dense deposit disease (DDD); however, ribbon-like intramembranous electron-dense deposits are absent in the former. We report a case of de novo C3GN in a renal allograft with morphologic transformation to DDD. A 6-year-old boy presented with congenital left renal agenesis and right ureteropelvic junction obstruction. The patient underwent pyeloplasty but experienced recurrent urinary tract infections. At the age of 22 years, he received a renal allograft from a living related donor. C3GN was diagnosed after 1 year of transplantation; initial histology showed minimal mesangiopathy and this progressed to mesangial proliferation and membranoproliferative features over the next 7 years. Serum creatinine levels were stabilized with anti-rejection treatments for combating repeated episodes of acute rejection; however, glomerular and tubular band-like electron-dense deposits became evident. PMID:26986539

  19. Foraminiferal survival after long term experimentally induced anoxia

    NASA Astrophysics Data System (ADS)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-06-01

    Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

  20. Pentamidine-induced dysglycaemia: experimental models in the rat.

    PubMed

    Assan, R; Assan, D; Delaby, J; Debussche, X; Toublanc, M

    1993-01-01

    In order to analyse further the pathophysiology of pentamidine effects on blood glucose regulation, the following experimental models were established in rats: impairment of the renal function, bile duct ligation, inhibition of the P450 cytochrome enzyme system. In otherwise intact rats, 7.5 mg/day pentamidine was well tolerated whereas doses of 15 mg/day induced severe, relapsing and eventually lethal hypoglycaemia within a few days. Induction of a renal insufficiency of graded severity by treatment with gentamycin, subtotal nephrectomy and total bilateral nephrectomy resulted in repetitive, severe (sometimes lethal) hypoglycaemia, alternating with hyperglycaemia, glucosuria and ketonuria in pentamidine-treated rats (7.5 mg/d). No long-standing insulin-dependent diabetes was observed. In the dysglycemic animals, plasma insulin levels were inappropriate to the concomitant glycaemia; no stimulation was obtained by i.v. glucose. Glucagon levels were higher than normal, suppressible by i.v. glucose, responsive to IV arginine and to hypoglycaemia. Dysglycemic events were more frequent and marked in the rats with the most severe renal functional derangement. They were more frequent in the rats treated with pentamidine mesylate than in those treated with the isethionate salt. Control uremic rats (free of pentamidine) remained euglycaemic. The islets of Langerhans displayed severe vascular congestion and degranulation and necrosis of the B cells, while the non B cells (and particularly the A cells) were intact. Exocrine pancreatitis was occasionally observed in the most severely uremic rats. In contrast with uremic rats, neither surgical ligation of choledocus, nor treatment by P450 cytochrome inhibitors (particularly ketoconazole) precipitated dysglycaemia in the pentamidine-treated rats. These experimental data: 1) strengthen the concept of inappropriate insulin release from pentamidine-lesioned islet B cells due to pentamidine accumulation; 2) indicate a predominant

  1. The Effects of Experimentally Induced Adelphophagy in Gastropod Embryos

    PubMed Central

    Thomsen, Olaf; Collin, Rachel; Carrillo-Baltodano, Allan

    2014-01-01

    Adelphophagy, development where embryos grow large by consuming morphologically distinct nutritive embryos or their own normal siblings is widespread but uncommon among animal phyla. Among invertebrates it is particularly common in some families of marine gastropods and segmented worms, but rare or unknown in other closely related families. In calyptraeid gastropods phylogenetic analysis indicates that adelphophagy has arisen at least 9 times from species with planktotrophic larval development. This pattern of frequent parallel evolution of adelphophagy suggests that the embryos of planktotrophic species might be predisposed to evolve adelphophagy. Here we used embryos of three species of planktotrophic calyptraeids, one from each of three major genera in the family (Bostrycapulus, Crucibulum, and Crepidula), to answer the following 3 questions: (1) Can embryos of species with planktotrophic development benefit, in terms of pre-hatching growth, from the ingestion of yolk and tissue from experimentally damaged siblings? (2) Does ingestion of this material from damaged siblings increase variation in pre-hatching size? and (3) Does this experimentally induced adelphophagy alter the allometry between the velum and the shell, increasing morphological similarity to embryos of normally adelphophagic species? We found an overall increase in shell length and velum diameter when embryos feed on damaged siblings within their capsules. There was no detectable increase in variation in shell length or velum diameter, or changes in allometry. The overall effect of our treatment was small compared to the embryonic growth observed in naturally adelphophagic development. However each embryo in our experiment probably consumed less than one sibling on average, whereas natural adelphophages often each consume 10–30 or more siblings. These results suggest that the ability to consume, assimilate, and benefit from yolk and tissue of their siblings is widespread across calyptraeids

  2. 4-nitroquinoline-1-oxide induced experimental oral carcinogenesis.

    PubMed

    Kanojia, Deepak; Vaidya, Milind M

    2006-08-01

    Human oral cancer is the sixth largest group of malignancies worldwide and single largest group of malignancies in the Indian subcontinent. Seventy percent of premalignant cancers appear from premalignant lesions. Only 8-10% of these lesions finally turn into malignancy. The appearance of these premalignant lesions is one distinct feature of human oral cancer. At present there is dearth of biomarkers to identify which of these lesions will turn into malignancy. Regional lymph node metastasis and locoregional recurrence are the major factors responsible for the limited survival of patients with oral cancer. Paucity of early diagnostic and prognostic markers is one of the contributory factors for higher mortality rates. Cancer is a multistep process and because of constrain in availability of human tissues from multiple stages of oral carcinogenesis including normal tissues, animal models are being widely used, aiming for the development of diagnostic and prognostic markers. A number of chemical carcinogens like coal tar, 20 methyl cholanthrene (20MC), 9,10-dimethyl-1,2-benzanthracene (DMBA) and 4-nitroquinoline-1-oxide (4NQO) have been used in experimental oral carcinogenesis. However, 4NQO is the preferred carcinogen apart from DMBA in the development of experimental oral carcinogenesis. 4NQO is a water soluble carcinogen, which induces tumors predominantly in the oral cavity. It produces all the stages of oral carcinogenesis and several lines of evidences suggest that similar histological as well as molecular changes are observed in the human system. In the present review an attempt has been made to collate the information available on mechanisms of action of 4NQO, studies carried out for the development of biomarkers and chemopreventives agents using 4NQO animal models. PMID:16448841

  3. Glomerulonephritis associated with arteritis in marmosets infected with hepatitis A virus.

    PubMed Central

    Morita, M.; Kitajima, K.; Yoshizawa, H.; Itoh, Y.; Iwakiri, S.; Shibata, C.; Mayumi, M.

    1981-01-01

    Seven of 8 marmosets (Saguinus oedipus and Saguinus labiatus) injected i.v. with different inocula of hepatitis A virus isolated from patients in the acute phase of disease developed proliferative glomerulonephritis associated with arteritis. The glomerulonephritis was characterized by immunofluorescent and electron-dense deposits and hypercellularity. Although no antigenic component of the glomerular immune complex was detected, this glomerulonephritis and arteritis may be diagnosed morphologically as an immune complex disease. These findings show the possibility of the appearance of exohepatic disease as an immunologically mediated disease in human hepatitis A virus infection. Images Figs. 2-5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Figs. 10-15 Figs. 16-18 PMID:6452891

  4. Understanding the complement-mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies.

    PubMed

    Lionaki, Sophia; Gakiopoulou, Hara; Boletis, John N

    2016-09-01

    An enhanced understanding of the role of complement in the pathogenesis of membranoproliferative glomerulonephritis has led to reclassification of the latter into immunoglobulin-mediated and non-immunoglobulin-mediated disease. The new classification schema resulted in improved diagnostic clinical algorithms, while it brought into light again the diseases, which are characterized by the presence of glomerular deposits, composed predominantly by C3, in the absence of significant amounts of immunoglobulins in renal biopsy, namely, C3 glomerulopathies (dense deposit disease and C3 glomerulonephritis). Despite the lack of randomized controlled trials following the advances in the understanding of the pathogenetic pathways involved in membranoproliferative glomerulonephritis, it is important that the new mechanistic approach has opened new roads for the exploration and discovery of targeted therapies. PMID:27356907

  5. Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis.

    PubMed

    Luo, Y-H; Kuo, C-F; Huang, K-J; Wu, J-J; Lei, H-Y; Lin, M T; Chuang, W-J; Liu, C-C; Lin, C-F; Lin, Y-S

    2007-09-01

    Streptococcal pyrogenic exotoxin B is an extracellular cysteine protease. Only nephritis-associated strains of group A streptococci secrete this protease and this may be involved in the pathogenesis of post-streptococcal glomerulonephritis. Mice were actively immunized with a recombinant protease inactive exotoxin B mutant or passively immunized with exotoxin B antibody. Characteristics of glomerulonephritis were measured using histology, immunoglobulin deposition, complement activation, cell infiltration, and proteinuria. None of the mice given bovine serum albumin or exotoxin A as controls showed any marked changes. Immunoglobulin deposition, complement activation, and leukocyte infiltration occurred only in the glomeruli of exotoxin B-hyperimmunized mice. One particular anti-exotoxin B monoclonal antibody, 10G, was cross-reactive with kidney endothelial cells and it caused kidney injury and proteinuria when infused into mice. This cross-reactivity may be involved in the pathogenesis of glomerulonephritis following group A streptococcal infection. PMID:17637712

  6. [The function of the hypophyseal-gonadal system in different variants of glomerulonephritis in children].

    PubMed

    Korovina, N A; Gavriushova, L P; Ametov, A S; Tvorogova, T M; Mumladze, E B; Toritsina, L K

    1990-01-01

    A total of 28 children with different varieties of glomerulonephritis were examined for the pituitary-gonadal system (PGS). The examination included measurements of follicle-stimulating and luteinizing hormones, prolactin, estradiol, progesterone and testosterone. To define standards of the content of the hormones under study, 45 children of the control group were examined. The relationship was analyzed between the content of hormones and the disease activity and gravity. The most active phase of glomerulonephritis was characterized by maximal alterations in the content of pituitary and gonadal hormones. The content of the latter ones appeared to be considerably changed in patients with the mixed pattern of glomerulonephritis, attesting to profound functional derangements in the PGS. The intensity of those derangements was determined by the severity of the pathological process. PMID:2259596

  7. Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis.

    PubMed

    Luo, Bangwei; Jiang, Man; Yang, Xiaofeng; Zhang, Zhiyuan; Xiong, Jian; Schluesener, Hermann J; Zhang, Zhiren; Wu, Yuzhang

    2013-08-01

    Experimental autoimmune neuritis (EAN), an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system, is characterized by self-limitation. Here we investigated the regulation and contribution of erythropoietin (EPO) in EAN self-limitation. In EAN sciatic nerves, hypoxia, and protein and mRNA levels of hypoxia-inducible factor 1α (HIF-1α), HIF-2α, EPO and EPO receptor (EPOR) were induced in parallel at disease peak phase but reduced at recovery periods. Further, the deactivation of HIF reduced EAN-induced EPO/EPOR upregulation in EAN, suggesting the central contribution of HIF to EPO/EPOR induction. The deactivation of EPOR signalling exacerbated EAN progression, implying that endogenous EPO contributed to EAN recovery. Exogenous EPO treatment greatly improved EAN recovery. In addition, EPO was shown to promote Schwann cell survival and myelin production. In EAN, EPO treatment inhibited lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3(+)/CD4(+) regulatory T cells and decrease of IFN-γ(+)/CD4(+) Th1 cells. Furthermore, EPO inhibited inflammatory macrophage activation and promoted its phagocytic activity. In summary, our data demonstrated that EPO was induced in EAN by HIF and contributed to EAN recovery, and endogenous and exogenous EPO could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that EPO contributes to the self-recovery of EAN and could be a potent candidate for treatment of autoimmune neuropathies. PMID:23603807

  8. The Cell Nucleus in Physiological and Experimentally Induced Hypometabolism

    NASA Astrophysics Data System (ADS)

    Malatesta, M.

    The main problem for manned space mission is, at present, represented by the mass penalty associated to the human presence. An efficient approach could be the induction of a hypometabolic stasis in the astronauts, thus drastically reducing the physical and psychological requirements of the crew. On the other hand, in the wild, a reduction in resource consumptions physiologi- cally occurs in certain animals which periodically enter hibernation, a hypometabolic state in which both the energy need and energy offer are kept at a minimum. During the last twelve years, we have been studying different tissues of hibernating dormice, with the aim of analyzing their features during the euthermia -hibernation-arousal cycle as well as getting insight into the mechanisms allowing adaptation to hypometabolism. We paid particular attention to the cell nucleus, as it is the site of chief metabolic functions, such as DNA replication and RNA transcription. Our observations revealed no significant modification in the basic features of cell nuclei during hibernation; however, the cell nuclei of hibernating dormice showed unusual nuclear bodies containing molecules involved in RNA pathways. Therefore, we supposed that they could represent storage/assembly sites of several factors for processing some RNA which could be slowly synthesised during hibernation and rapidly and abundantly released in early arousal in order to meet the increased metabolic needs of the cell. The nucleolus also underwent structural and molecular modifications during hibernation, maybe to continue important nucleolar functions, or, alternatively, permit a most efficient reactivation upon arousal. On the basis of the observations made in vivo , we recently tried to experimentally induce a reversible hypometabolic state in in vitro models, using cell lines derived from hibernating and non-hibernating species. By administering the synthetic opioid DADLE, we could significantly reduce both RNA transcrip- tion and

  9. Standardised Models for Inducing Experimental Peritoneal Adhesions in Female Rats

    PubMed Central

    Kraemer, Bernhard; Wallwiener, Christian; Rajab, Taufiek K.; Brochhausen, Christoph; Wallwiener, Markus; Rothmund, Ralf

    2014-01-01

    Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1), brushing of parietal peritoneum only (group 2), sharp excision of parietal peritoneum closed with interrupted sutures (group 3), ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4), bipolar electrocoagulation of the peritoneum (group 5), and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6). Upon second look, there were significant differences in the adhesion incidence between the groups (P < 0.01). Analysis of the fraction of adhesions showed that groups 2 (0%) and 5 (4%) were significantly less than the other groups (P < 0.01). Furthermore, group 6 (69%) was significantly higher than group 1 (48%) (P < 0.05) and group 4 (47%) (P < 0.05). There was no difference between group 3 (60%) and group 6 (P = 0.2). From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models. PMID:24809049

  10. Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis.

    PubMed

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J; Sun, Deming

    2016-03-15

    Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1-20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8-14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was γδ T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor-targeted therapies. PMID:26856700

  11. Confabulation versus experimentally induced false memories in Korsakoff patients.

    PubMed

    Van Damme, Ilse; d'Ydewalle, Géry

    2010-09-01

    The present study focuses on both the clinical symptom of confabulation and experimentally induced false memories in patients suffering from Korsakoff's syndrome. Despite the vast amount of case studies of confabulating patients and studies investigating false memories in the Deese-Roediger-McDermott (DRM) paradigm, the nature of Korsakoff patients' confabulatory behaviour and its association with DRM false memories have been rarely examined. Hence, the first aim of the present study was to evaluate confabulatory responses in a large sample of chronic Korsakoff patients and matched controls by means of the Dalla Barba Confabulation Battery. Second, the association between (provoked) confabulation and the patients' DRM false recognition performance was investigated. Korsakoff patients mainly confabulated in response to questions about episodic memory and questions to which the answer was unknown. A positive association was obtained between confabulation and the tendency to accept unstudied distractor words as being old in the DRM paradigm. On the other hand, there was a negative association between confabulation and false recognition of critical lures. The latter could be attributed to the importance of strategic retrieval at delayed memory testing. PMID:19930792

  12. Albendazole therapy for experimentally induced Paragonimus kellicotti infection in cats.

    PubMed

    Dubey, J P; Hoover, E A; Stromberg, P C; Toussant, M J

    1978-06-01

    The effect of albendazole therapy was studied in 6 cats with pulmonary paragonimiasis induced by experimental inoculation of metacercariae (25/cat) of Paragonimus kellicotti. At 76 to 101 days after they were inoculated, 5 cats were administered an oral aqueous suspension of albendazole in 2 divided doses totaling 20 mg (2 cats), 50 mg (1 cat), or 100 mg (2 cats)/kg of body weight each day for 14 to 21 days. The 6th cat (control) was not administered albendazole. Nine days after cats were given the 50- and 100-mg/kg dosages, Paragonimus ova were not seen in the feces of 3 cats. There was marked reduction in ova production in the feces of the 2 cats administered 20 mg/kg of albendazole. Live flukes were not recovered from the lungs of 3 cats necropsied 4 or 5 weeks after dosing with 50 or 100 mg/kg, but the lungs of the 2 cats administered 20 mg of albendazole/kg yielded 9 and 7 apparently viable flukes. Seventeen live flukes were recovered from the control cat not treated with albendazole. In 4 noninoculated normal cats administered 20 mg (1 cat), 100 mg (1 cat), and 200 mg (2 cats) of albendazole/kg of body weight each day for 14 days, there were no gross or microscopic lesions attributable to the drug. PMID:666077

  13. Preferential effectiveness of cyclosporin in patients receiving kidney transplants after glomerulonephritis.

    PubMed

    Cats, S; Terasaki, P I; Perdue, S; Mickey, M R

    1985-03-01

    Glomerulonephritis patients transplanted with cadaver kidneys had a significantly higher one-year graft survival when immunosuppressed with cyclosporin rather than standard therapy (80% versus 59%, p less than 10(-5]. For nephrosclerosis patients the corresponding rates were 70% and 59% (p greater than 0.05); and in those with antecedent diabetes mellitus, polycystic kidney, and pyelonephritis the differences were negligible. In glomerulonephritis patients, but not in the other groups, cyclosporin was additive to the effect of transfusions and of HLA-A, B and HLA-Dr matching. PMID:2857855

  14. Streptococcal Infection-related Nephritis (SIRN) Manifesting Membranoproliferative Glomerulonephritis Type I.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Yamamoto, Yasutaka; Kobayashi, Naoto; Oda, Takashi; Yamaguchi, Yutaka; Shibata, Takanori

    2016-01-01

    We herein report the case of an 18-year-old boy who developed nephrotic syndrome and hypertension after upper airway inflammation. Post-streptococcal acute glomerulonephritis was diagnosed on the basis of a high antistreptolysin O titer, hypocomplementemia, proteinuria, and microscopic hematuria. A renal biopsy was performed due to persistent proteinuria, and the pathological diagnosis was membranoproliferative glomerulonephritis (MPGN) type I. Glomeruli showed positive staining for nephritis-associated plasmin receptor (NAPlr), a nephritogenic group A streptococcal antigen, and plasmin activity was found in a similar distribution as NAPlr deposition. This rare case of streptococcal infection-related nephritis (SIRN) manifesting MPGN type I supports the histological diversity of SIRN. PMID:26984084

  15. Protracted Clinical Course of Postinfectious Glomerulonephritis in a Previously Healthy Child

    PubMed Central

    Grøndahl, Camilla; Rittig, Søren; Povlsen, Johan Vestergaard; Kamperis, Kostantinos

    2016-01-01

    Acute postinfectious glomerulonephritis (PIGN) affects children typically after upper respiratory tract or skin infections with streptococci but can complicate the course of other infections. In children, it is generally a self-limiting disease with excellent prognosis. This paper reports a previously healthy 4-year-old boy who experienced a protracted course of PIGN with persisting episodes of gross haematuria, proteinuria, decreased complement C3c levels but normal P-creatinine levels. Due to the protracted course and the nephrotic-range proteinuria, a renal biopsy was performed 6 months after the initial presentation and the overall pathology was consistent with acute endocapillary glomerulonephritis. PMID:27226969

  16. Anticoccidial effect of mananoligosacharide against experimentally induced coccidiosis in broiler.

    PubMed

    Chand, Naila; Faheem, Hassan; Khan, Rifat Ullah; Qureshi, Muhammad Subhan; Alhidary, Ibrahim A; Abudabos, Alaeldein M

    2016-07-01

    The aim of this study was to find the effect of mananoligosacharide (MOS) in comparison with amprolium hydrochloride on performance and integrity of gut in experimentally induced coccidiosis in broiler. A total of 300, day-old male broiler chickens (Ross 308) was randomly allocated to four treatments. Each group was further divided into five replicates of 15 birds each. Group A was kept as control; group B was contaminated with Eimeria tenella, while groups C and D were infected with E. tenella and treated with MOS (0.8 g/kg feed) and anticoccidial drug, amprolium hydrochloride (12 g/100 l water), respectively. The results showed that weight gain, feed intake, and feed conversion ratio (FCR) were significantly higher (P < 0.05) in infected + MOS-treated group compared to the other groups. The result of oocyte per gram (OPG) was significantly higher (P < 0.05) in the group infected with coccidiosis during 5th, 7th, 10th, and 12th day post infection (dpi). Furthermore, the OPG was significantly lower (P < 0.05) in infected groups treated with MOS and amprolium at the studied periods (5, 7, and 10 dpi). At 12 dpi, the infected group treated with MOS showed significantly lower OPG compared to the other groups suggesting the effectiveness of MOS in comparison to amprolium. The result of pinpoint hemorrhages, thickness of cecal wall, bloody fecal contents, and mucoid contents in the cecum were significant highly (P < 0.05) in birds fed with infected oocytes. It was also noted that the differences were not significant in these parameters between amprolium and MOS-treated birds showing the effectiveness of the prebiotic agent. It was concluded from the results of the present study that MOS improved growth performance and reversed the lesions of E. tenella. PMID:27068898

  17. Experimental validation of a numerical model for subway induced vibrations

    NASA Astrophysics Data System (ADS)

    Gupta, S.; Degrande, G.; Lombaert, G.

    2009-04-01

    This paper presents the experimental validation of a coupled periodic finite element-boundary element model for the prediction of subway induced vibrations. The model fully accounts for the dynamic interaction between the train, the track, the tunnel and the soil. The periodicity or invariance of the tunnel and the soil in the longitudinal direction is exploited using the Floquet transformation, which allows for an efficient formulation in the frequency-wavenumber domain. A general analytical formulation is used to compute the response of three-dimensional invariant or periodic media that are excited by moving loads. The numerical model is validated by means of several experiments that have been performed at a site in Regent's Park on the Bakerloo line of London Underground. Vibration measurements have been performed on the axle boxes of the train, on the rail, the tunnel invert and the tunnel wall, and in the free field, both at the surface and at a depth of 15 m. Prior to these vibration measurements, the dynamic soil characteristics and the track characteristics have been determined. The Bakerloo line tunnel of London Underground has been modelled using the coupled periodic finite element-boundary element approach and free field vibrations due to the passage of a train at different speeds have been predicted and compared to the measurements. The correspondence between the predicted and measured response in the tunnel is reasonably good, although some differences are observed in the free field. The discrepancies are explained on the basis of various uncertainties involved in the problem. The variation in the response with train speed is similar for the measurements as well as the predictions. This study demonstrates the applicability of the coupled periodic finite element-boundary element model to make realistic predictions of the vibrations from underground railways.

  18. Renal tubular angiogenic dysregulation in anti-Thy1.1 glomerulonephritis.

    PubMed

    Cina, Davide P; Xu, Hui; Liu, Limin; Farkas, Laszlo; Farkas, Daniela; Kolb, Martin; Margetts, Peter J

    2011-02-01

    Peritubular vascular changes and hypoxia after glomerular injury may explain subsequent tubulointerstitial injury and fibrosis. Several studies suggested that the expected tubulointerstitial angiogenic response is actively suppressed in this setting. The mechanism of this aberrant response has not been clearly identified. We used a common model of glomerular injury in rats to assess vascular changes and to identify potential factors associated with this aberrant response. Anti-Thy1.1 antibody administration (1 or 4 weekly doses) led to a dose-dependent renal damage characterized by elevated urea and tubulointerstitial fibrosis as assessed by Picro-Sirius Red staining. We quantified peritubular capillaries using CD31 and CD34 immunohistochemistry and showed that tubular angiogenic dysregulation was associated with peritubular capillary rarefaction. Using laser capture microdissection, we demonstrated an early induction of fibrogenic and angiogenic factors in the glomeruli and a subsequent dysregulated angiogenic response in the tubulointerstitial compartment. Proximal tubules of anti-Thy1.1-treated animals had increased pigment epithelial-derived factor (PEDF) expression by immunohistochemistry. Protein taken by laser capture microdissection also showed that PEDF was upregulated. Temporally associated with PEDF expression was a transient downregulation of tubular hypoxia-inducible factor (HIF)1α. In a human proximal tubular cell culture, we show that PEDF downregulates HIF1α protein and gene expression in cells exposed to 1% oxygen. In anti-Thy1.1 glomerulonephritis, there is aberrent tubular angiogenesis associated with glomerular injury and tubulointersititial fibrosis. We showed that PEDF may be involved by downregulating HIF1α. Further work is needed to elucidate the mechanism of PEDF upregulation and action in the tubules. PMID:21048020

  19. Incidence of post-transplant glomerulonephritis and its impact on graft outcome

    PubMed Central

    An, Jung Nam; Lee, Jung Pyo; Oh, Yun Jung; Oh, Yun Kyu; Ha, Jong-won; Chae, Dong-Wan; Kim, Yon Su; Lim, Chun Soo

    2012-01-01

    Background Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN. Methods Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study. Results The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors. Conclusion We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care. PMID:26889425

  20. Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

    PubMed Central

    Peters, D. N.; Steinberg, H.; Anderson, W. I.; Hornbuckle, W. E.; Cote, P. J.; Gerin, J. L.; Lewis, R. M.; Tennant, B. C.

    1992-01-01

    Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1632459

  1. HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases

    PubMed Central

    Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng

    2016-01-01

    Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7–20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular “hump-shape” immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis. PMID:27512989

  2. Membranous glomerulonephritis in rheumatoid arthritis unrelated to gold, D-penicillamine or other connective tissue disease.

    PubMed

    Zarza, L P; Sanchez, E N; Acin, P A; Ara, J M; Baños, J G

    1996-07-01

    We report a 58-year-old woman with classical rheumatoid arthritis (RA) who developed a membranous glomerulonephritis (MGN). She had never been treated with gold or D-penicillamine; other connective tissue diseases as well as hepatitis B were excluded. We suggest that the responsible cause of MGN is RA. PMID:8853174

  3. Clinical, Pathological, and Prognostic Characteristics of Glomerulonephritis Related to Staphylococcal Infection

    PubMed Central

    Wang, Si-Yang; Bu, Ru; Zhang, Qi; Liang, Shuang; Wu, Jie; Liu, Xue-Guang Zhang Shu-Wen; Cai, Guang-Yan; Chen, Xiang-Mei

    2016-01-01

    Abstract Staphylococcal infection has become a common cause of postinfectious glomerulonephritis in the past 3 decades. Because few investigations focus on this disease, the demographics and clinicopathological features of glomerulonephritis related to staphylococcal infection are not well characterized. We conducted a pooled analysis of published literature in electronic databases and analyzed the clinical features, laboratory findings, and histopathological changes. The patients were divided into 4 groups based on their prognosis: remission, persistent renal dysfunction, end-stage renal disease (ESRD), or death. A logistic regression model was used to identify the determinants of disease outcome. A total of 83 (64 men) patients with glomerulonephritis related to staphylococcal infection from 31 reports were analyzed. The mean age was 58 years (58 ± 17). Majority of the reports originated from Taiwan, Japan, and the United States. Clinical characteristics of the cases were hematuria (82/83), proteinuria (78/83), and acute kidney injury (75/83). Visceral abscesses (26/83) and skin infections (24/83) were the common sites of infection. Methicillin-resistant Staphylococcus aureus was the most common pathogen. The dominant or codominant deposition of IgA or C3 along the glomeruli was an important feature identified by immunofluorescence. There were 19 patients (22.9%) that progressed to dialysis-dependent ESRD. Twelve patients (14.5%) died. A univariate regression analysis indicated that diabetes mellitus (DM) (odds ratio [OR] 2.96; 95% confidence interval [CI] 1.03–8.48; P = 0.04) and age (OR 4.80; 95% CI 1.84–12.53; P = 0.001) were risk factors for ESRD or death. A multivariate regression analysis also revealed that age (OR 4.90; 95% CI 1.82–13.18; P = 0.002) and DM (OR 3.07; 95% CI 0.98–9.59; P = 0.05) were independent risk factors for unfavorable prognosis. Glomerulonephritis related to staphylococcal infection has different features

  4. Clinical, Pathological, and Prognostic Characteristics of Glomerulonephritis Related to Staphylococcal Infection.

    PubMed

    Wang, Si-Yang; Bu, Ru; Zhang, Qi; Liang, Shuang; Wu, Jie; Liu, Xue-Guang Zhang Shu-Wen; Cai, Guang-Yan; Chen, Xiang-Mei

    2016-04-01

    Staphylococcal infection has become a common cause of postinfectious glomerulonephritis in the past 3 decades. Because few investigations focus on this disease, the demographics and clinicopathological features of glomerulonephritis related to staphylococcal infection are not well characterized.We conducted a pooled analysis of published literature in electronic databases and analyzed the clinical features, laboratory findings, and histopathological changes. The patients were divided into 4 groups based on their prognosis: remission, persistent renal dysfunction, end-stage renal disease (ESRD), or death. A logistic regression model was used to identify the determinants of disease outcome.A total of 83 (64 men) patients with glomerulonephritis related to staphylococcal infection from 31 reports were analyzed. The mean age was 58 years (58 ± 17). Majority of the reports originated from Taiwan, Japan, and the United States. Clinical characteristics of the cases were hematuria (82/83), proteinuria (78/83), and acute kidney injury (75/83). Visceral abscesses (26/83) and skin infections (24/83) were the common sites of infection. Methicillin-resistant Staphylococcus aureus was the most common pathogen. The dominant or codominant deposition of IgA or C3 along the glomeruli was an important feature identified by immunofluorescence. There were 19 patients (22.9%) that progressed to dialysis-dependent ESRD. Twelve patients (14.5%) died. A univariate regression analysis indicated that diabetes mellitus (DM) (odds ratio [OR] 2.96; 95% confidence interval [CI] 1.03-8.48; P = 0.04) and age (OR 4.80; 95% CI 1.84-12.53; P = 0.001) were risk factors for ESRD or death. A multivariate regression analysis also revealed that age (OR 4.90; 95% CI 1.82-13.18; P = 0.002) and DM (OR 3.07; 95% CI 0.98-9.59; P = 0.05) were independent risk factors for unfavorable prognosis.Glomerulonephritis related to staphylococcal infection has different features than typical

  5. The Occurrence or Fibrillary Glomerulonephritis in Patients with Diabetes Mellitus May Not Be Coincidental: A Report of Four Cases

    PubMed Central

    González-Cabrera, Fayna; Henríquez-Palop, Fernando; Ramírez-Puga, Ana; Santana-Estupiñán, Raquel; Plaza-Toledano, Celia; Antón-Pérez, Gloria; Marrero-Robayna, Silvia; Ramírez-Medina, Davinia; Gallego-Samper, Roberto; Vega-Díaz, Nicanor; Camacho-Galan, Rafael; Rodríguez-Pérez, José C.

    2013-01-01

    Although clinical presentation of fibrillary glomerulonephritis is similar to most forms of glomerulonephritis, it is usually difficult to make the diagnosis. Clinical manifestations include proteinuria, microscopic haematuria, nephrotic syndrome, and impairment of renal function. A diagnosis of fibrillary glomerulonephritis is only confirmed by renal biopsy and it must comprise electronmicroscopy-verified ultrastructural findings. We report four cases between 45–50 years old with documented type 2 diabetes mellitus (T2DM) and arterial hypertension. All patients were found to have fibrils on kidney biopsy. The differential diagnosis of fibrils in the setting of diabetes mellitus is also discussed. PMID:23762079

  6. Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis.

    PubMed

    Gan, Poh-Yi; O'Sullivan, Kim M; Ooi, Joshua D; Alikhan, Maliha A; Odobasic, Dragana; Summers, Shaun A; Kitching, A Richard; Holdsworth, Stephen R

    2016-05-01

    Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4(+) effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. PMID:26374606

  7. Therapeutic effects and mechanism of conditioned media from human mesenchymal stem cells on anti-GBM glomerulonephritis in WKY rats.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Ohtaki, Hirokazu; Matsumoto, Kei; Wada, Yukihiro; Suzuki, Taihei; Yamamoto, Yasutaka; Saito, Tomohiro; Hihara, Kei; Tachibana, Shohei; Honda, Kazuho; Shibata, Takanori

    2016-06-01

    Recent studies have demonstrated that conditioned media derived from mesenchymal stem cells (MSC-CM) have therapeutic effects in various experimental diseases. However, the therapeutic mechanism is not fully understood. In the present study, we investigated the therapeutic effects and mechanism of MSC-CM in experimental antiglomerular basement membrane glomerulonephritis. We administered either MSC-CM or vehicle from day 0 to day 10 after the induction of nephrotoxic serum nephritis in Wistar-Kyoto rats. In vitro, we analyzed the effects of MSC-CM on TNF-α-mediated cytokine production in cultured normal human mesangial cells, proximal tubular (HK-2) cells, human umbilical vein endothelial cells, and monocytes (THP-1 and peripheral blood mononuclear cells). Compared with vehicle treatment, MSC-CM treatment improved proteinuria and renal dysfunction. Histologically, MSC-CM-treated rats had reduced crescent formation and glomerular ED1(+) macrophage infiltration and increased glomerular ED2(+) macrophage infiltration. Increased serum monocyte chemoattractant protein (MCP)-1 levels were observed in MSC-CM-treated rats. Renal cortical mRNA expression levels of proinflammatory cytokines, such as TNF-α and IL-6, and of the T helper cell 1 cytokine interferon-γ were greatly decreased by MSC-CM treatment. In vitro, pretreatment with MSC-CM blocked TNF-α-mediated IL-8 release in normal human mesangial cells and HK-2 cells. TNF-α-mediated MCP-1 release was enhanced by pretreatment with MSC-CM in human umbilical vein endothelial cells and HK-2 cells and was strikingly enhanced in THP-1 cells. Stimulation of peripheral blood mononuclear cells with a combination of MCP-1 and IL-4 enhanced the expression of M2-associated genes compared with IL-4 alone. We demonstrated that MSC-CM had therapeutic effects in experimental antiglomerular basement membrane glomerulonephritis that were mediated through anti-inflammatory effects that were partly due to acceleration of M2 macrophage

  8. Induced thermoluminescence study of experimentally shock-loaded oligoclase

    NASA Technical Reports Server (NTRS)

    Ivliev, A. I.; Kashkarov, L. L.; Badjukov, D. D.

    1993-01-01

    Artificially induced thermoluminescence (TL) in oligoclase samples which were shock-loaded up to 27 GPa was measured. The essential increase of the TL sensitivity in relation to the total gamma-ray irradiation dose was observed only in samples at the 27 GPa pressure. This result can be explained by the initiation of additional radiation damages in the shocked oligoclace crystal lattice.

  9. COMPARISON OF METHODS FOR EVALUATION OF EXPERIMENTALLY INDUCED EMPHYSEMA

    EPA Science Inventory

    Four methods to quantify induced emphysema, in a manner economically applicable to large numbers of animals, are compared by correlation analyses. Lung tissue used was from rats pretreated intratracheally with elastase or saline prior to exposure to air or (NH4)2SO4 or NH4NO3 aer...

  10. The Effects of a Selective CK2 Inhibitor on Anti-glomerular Basement Membrane Glomerulonephritis in Rats.

    PubMed

    Shi, Junfeng; Liu, Ning; Xiao, Ying; Takei, Yoshinori; Yasue, Misato; Suzuki, Yamato; Hou, Zengye; Ohno, Hiroaki; Yamada, Masateru; Fuchi, Nobuhiro; Oshida, Keiyu; Miyamoto, Yohei; Tsujimoto, Gozoh; Hirasawa, Akira

    2015-01-01

    Protein kinase CK2 ("casein kinase II") is a protein serine/threonine kinase that plays critical roles in biological processes such as cell growth, cell cycle progression, and apoptosis. So far, we have identified that one catalytic isozyme of CK2, CK2α, is over-expressed in the kidney during the progression of glomerulonephritis (GN). Moreover, we have shown that in vivo inhibition of CK2 by administration of CK2 inhibitors was effective in the treatment of experimental GN. Hence the development of potent CK2 inhibitors should be considered in therapeutic strategies for GN. In the present study we identified compound 13, a pyrazine derivative, as a potent CK2 inhibitor. By performing enzyme kinetics analysis in vitro, we characterized the inhibition of compound 13 toward each CK2 catalytic isozyme. Furthermore, in vivo, we demonstrated that compound 13 is effective in attenuating proteinuria, decreasing the enhanced level of blood urea nitrogen and serum creatinine, and ameliorating glomerular crescent formation in an experimental GN rat model. On the other hand, cellular apoptosis was detected in the rat testis following administration of compound 13. This study provides clues for new strategies for developing applicable compounds into CK2-targeted GN treatments. PMID:26328489

  11. Experimentally induced muscle pain induces hypoalgesia in heterotopic deep tissues, but not in homotopic deep tissues.

    PubMed

    Graven-Nielsen, T; Babenko, V; Svensson, P; Arendt-Nielsen, L

    1998-03-23

    The ability of muscle pain to generate somatosensory sensibility changes is controversial. Thus, in the present study, tonic infusion of hypertonic saline (5%, 7.1 ml administered over 15 min) into the tibialis anterior (TA) muscle was used as an experimental model to induce local and referred pain. The sensibility to high-intensity pressure stimuli applied to the local pain area, referred pain area and an arm was assessed in 14 healthy volunteers. Infusion of isotonic (0.9%) saline into the other leg served as control. The subject continuously scored the pain intensity on an electronic visual analogue scale (VAS). Pressure pain threshold (PPT) was determined on the TA muscle (2 cm and 10 cm from the infusion site), at the frontal aspect of the ankle (area of referred pain) and on the arm. To minimise the skin component of the PPT, the skin covering the assessment sites was anaesthetised with an anaesthetic creme. The PPTs were obtained before and after cutaneous analgesia, 1 min and 10 min after infusion start and 10 min after the pain had disappeared. Infusion of hypertonic saline caused significantly (P<0. 05) higher VAS scores than infusion of isotonic saline. A significant (P<0.04) increase of the PPT (i.e., decreased sensibility) was found at the ankle and on the arm during muscle pain compared to the control condition. No significant differences in PPTs on the TA muscle were found during saline-induced muscle pain compared to the infusion of isotonic saline. The decrease in deep sensibility at the heterotopic sites (referred pain area and arm), but not at homotopic sites (TA muscle), probably reflected the phenomenon of diffuse noxious inhibitory control (DNIC). The inhibitory mechanism during muscle pain was shown to be effective for the deep tissue sensibility in healthy subjects. Thus, a pathologically disturbed inhibitory mechanism may result in widespread deep hyperalgesia in muscle pain patients. PMID:9518613

  12. Clinical and experimental experiences of graft-induced dyskinesia.

    PubMed

    Lane, Emma L

    2011-01-01

    Clinical trials evaluating transplantation of fetal tissue for the treatment of Parkinson's disease identified the unexpected side effect of abnormal movements in the 'off'l-DOPA state. Termed graft-induced dyskinesia (GID), various hypotheses have been put forward as to their cause but unfortunately the significant differences in clinical trial protocols and lack of a truly representative animal model has hindered the search for a conclusive basis for their appearance. Likely causative factors have been identified through careful examination of patient data and the use of amphetamine-induced dyskinesia in a rodent model of Parkinson's disease. New trials being planned in Europe hope to avoid GID, whilst maximizing on the functional benefit that can be afforded by this treatment approach but questions still remain as to the underlying mechanism. PMID:21907087

  13. Experimental Feedback Control of Flow Induced Cavity Tones

    NASA Technical Reports Server (NTRS)

    Cabell, Randolph H.; Kegerise, Michael A.; Cox, David E.; Gibbs, Gary P.

    2002-01-01

    An experimental study of the application of discrete-time, linear quadratic control design methods to the cavity tone problem is described. State space models of the dynamics from a synthetic jet actuator at the leading edge of the cavity to two pressure sensors in the cavity were computed from experimental data. Variations in model order, control order, control bandwidth, and properties of a Kalman state estimator were studied. Feedback control reduced the levels of multiple cavity tones at Mach 0.275, 0.35, and 0.45. Closed loop performance was often limited by excitation of sidebands of cavity tones, and creation of new tones in the spectrum. State space models were useful for explaining some of these limitations, but were not able to account for non-linear dynamics, such as interactions between tones at different frequencies.

  14. Experimental study of microwave-induced thermoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Jacobs, Ryan T.

    Microwave-Induced Thermoacoustic Imaging (TAI) is a noninvasive hybrid modality which improves contrast by using thermoelastic wave generation induced by microwave absorption. Ultrasonography is widely used in medical practice as a low-cost alternative and supplement to magnetic resonance imaging (MRI). Although ultrasonography has relatively high image resolution (depending on the ultrasonic wavelength at diagnostic frequencies), it suffers from low image contrast of soft tissues. In this work samples are irradiated with sub-microsecond electromagnetic pulses inducing acoustic waves in the sample that are then detected with an unfocused transducer. The advantage of this hybrid modality is the ability to take advantage of the microwave absorption coefficients which provide high contrast in tissue samples. This in combination with the superior spatial resolution of ultrasound waves is important to providing a low-cost alternative to MRI and early breast cancer detection methods. This work describes the implementation of a thermoacoustic experiment using a 5 kW peak power microwave source.

  15. Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury

    PubMed Central

    Wang, Zheng; Guo, Qiong-Ya; Zhang, Xiao-Ju; Li, Xiao; Li, Wen-Ting; Ma, Xi-Tao; Ma, Li-Jun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson’s trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKKα, phosphorylated IKKα (p-IKKα), NF-κB P65, TNF-α and IL-1β, and reduced I-κB expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits TGF-β1 production and α-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-κB and TGF-β1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis. PMID:24886817

  16. Comparison of methods for evaluation of experimentally induced emphysema

    SciTech Connect

    Busch, R.H.; Buschbom, R.L.; Smith, L.G.

    1984-04-01

    Four methods to quantify induced emphysema, in a manner economically applicable to large numbers of animals, are compared by correlation analyses. Lung tissue used was from rats pretreated intratracheally with elastase or saline prior to exposure to air or (NH/sub 4/)/sub 2/SO/sub 4/ or NH/sub 4/NO/sub 3/ aerosols. The most sensitive quantitative evaluation was from mean chord length (MCL) measurements on scanning electron micrographs (SEM). Four-corner and parallel-line grids provided similar results, and reducing sample size to one selected field per lobe yielded a high degree of reliability for MCL measurements. Alveolar-pore perimeter and area (also measured on SEM photographs) were increased by induced emphysema, but were not reliable indicators for degree of pulmonary involvement. Both subjective score (grading the degree of emphysema) and percentage-area-affected determinations indicated the presence of emphysema, but with less sensitivity than MCL measurements. However, these two subgross methods (performed with a dissecting microscope) provided valuable information on the distribution of pulmonary lesions; emphysema was induced in a nonuniform but consistent and progressive pattern in the two lobes of the lung studied. 23 studied.

  17. Heartworm (Dirofilaria immitis) disease and glomerulonephritis in a black-footed cat (Felis nigripes).

    PubMed

    Deem, S L; Heard, D J; LaRock, R

    1998-06-01

    A 6-yr-old, 1.36-kg, intact female black-footed cat (Felis nigripes) was presented to the Veterinary Medical Teaching Hospital, University of Florida, with a history of depression, lethargy, and anorexia. Cardiac dysfunction and renal failure were diagnosed on the basis of antemortem and postmortem findings. At necropsy, heartworms (Dirofilaria immitis), glomerulonephritis, and endometritis were present. The glomerulonephritis could have been immune mediated and may have been associated with the heartworm infection or the chronic endometritis or both. Heartworm disease should be included in the list of differential diagnoses for any exotic cat housed outdoors in an endemic heartworm region that dies peracutely or has suggestive gastrointestinal or respiratory signs. Heartworm prophylaxis and annual serologic testing in exotic cats housed outdoors in heartworm endemic regions are recommended. PMID:9732037

  18. Nephrotic range proteinuria in c-ANCA-positive crescentic glomerulonephritis with linear immune deposits

    PubMed Central

    Singh, N. P.; Gulati, S.; Garg, V.; Beniwal, P.; Garg, S.

    2008-01-01

    The three broad groups of rapidly progressing glomerulonephritis are anti glomerular basement membrane (anti-GBM) disease, renal vasculitis characterized by antineutrophil cytoplasmic antibody positivity, and a heterogeneous group with granular immune deposits. Anti-GBM disease with cytoplasmic antineutrophilic antibodies (c-ANCA) positivity (type III disease) is not known to present with nephrotic syndrome. We report here a rare presentation of nephrotic syndrome in Type III disease. Larger studies are warranted to determine whether the amount and/or type of immune deposits decide the range of proteinuria. These studies are also required to elucidate the impact of immune complex deposition on renal disease in c-ANCA-positive glomerulonephritis and to outline its pathogenetic mechanism. PMID:20142931

  19. Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease

    PubMed Central

    Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng

    2016-01-01

    Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450

  20. Familial C3 glomerulonephritis associated with mutations in the gene for complement factor B.

    PubMed

    Imamura, Hideaki; Konomoto, Takao; Tanaka, Etsuko; Hisano, Satoshi; Yoshida, Yoko; Fujimura, Yoshihiro; Miyata, Toshiyuki; Nunoi, Hiroyuki

    2015-05-01

    We report the first case of familial C3 glomerulonephritis (C3GN) associated with mutations in the gene for complement factor B (CFB). A 12-year-old girl was diagnosed with biopsy-proven C3GN. Her mother had a history of treatment for membranoproliferative glomerulonephritis, and her brother had hypocomplementemia without urinary abnormalities. DNA analysis revealed heterozygosity for CFB p.S367R in the patient, mother and brother. Evaluation of the structure-function relationship supports that this mutation has gain-of-function effects in CFB. The present case suggests that CFB has an important role in the etiology of C3GN and provides a new insight into anticomplement therapy approaches. PMID:25758434

  1. Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report.

    PubMed

    Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja

    2008-01-01

    We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID:24179353

  2. Experimental Feedback Control of Flow Induced Cavity Tones

    NASA Technical Reports Server (NTRS)

    Cabell, Randolph H.; Kegerise, Michael A.; Cox, David E.; Gibbs, Gary P.

    2005-01-01

    Discrete-time, linear quadratic methods were used to design feedback controllers for reducing tones generated by flow over a cavity. The dynamics of a synthetic jet actuator mounted at the leading edge of the cavity as observed by two microphones in the cavity were modeled over a broad frequency range using state space models computed from experimental data. Variations in closed loop performance as a function of model order, control order, control bandwidth, and state estimator design were studied using a cavity in the Probe Calibration Tunnel at NASA Langley. The controller successfully reduced the levels of multiple cavity tones at the tested flow speeds of Mach 0.275, 0.35, and 0.45. In some cases, the closed loop results were limited by excitation of sidebands of the cavity tones, or the creation of new tones at frequencies away from the cavity tones. Nonetheless, the results validate the combination of optimal control and experimentally-generated state space models, and suggest this approach may be useful for other flow control problems. The models were not able to account for non-linear dynamics, such as interactions between tones at different frequencies.

  3. Experimental distinction of Autler-Townes splitting from electromagnetically induced transparency using coupled mechanical oscillators system

    PubMed Central

    Liu, Jingliang; Yang, Hujiang; Wang, Chuan; Xu, Kun; Xiao, Jinghua

    2016-01-01

    Here we experimentally demonstrated the electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) effects in mechanical coupled pendulums. The analogue of EIT and ATS has been studied in mechanical systems and the intrinsic physics between these two phenomena are also been discussed. Exploiting the Akaike Information Criterion, we discern the ATS effect from EIT effect in our experimental results. PMID:26751738

  4. An Attempt to Reverse Performance Deficits Associated With Depression and Experimentally Induced Helplessness

    ERIC Educational Resources Information Center

    Kilpatrick-Tabak, Blair; Roth, Susan

    1978-01-01

    The learned helplessness model of depression predicts that any effective treatment for reactive depression should also reverse performance deficits associated with experimentally induced helplessness, and vice versa. This study tests that prediction with college students who were exposed to experimental manipulations designed to induce…

  5. Experimental distinction of Autler-Townes splitting from electromagnetically induced transparency using coupled mechanical oscillators system

    NASA Astrophysics Data System (ADS)

    Liu, Jingliang; Yang, Hujiang; Wang, Chuan; Xu, Kun; Xiao, Jinghua

    2016-01-01

    Here we experimentally demonstrated the electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) effects in mechanical coupled pendulums. The analogue of EIT and ATS has been studied in mechanical systems and the intrinsic physics between these two phenomena are also been discussed. Exploiting the Akaike Information Criterion, we discern the ATS effect from EIT effect in our experimental results.

  6. Effects of flunarizine on experimentally-induced convulsions in animals.

    PubMed

    Drago, F; Valerio, C; Clementi, G; Scapagnini, U

    1986-01-01

    D,L-allylglycine-induced seizures in rats were antagonized by flunarizine and other antiepileptic drugs. In this respect, the spectrum of flunarizine appears to be similar to that of diphenylhydantoin. A behavioral analysis of the effects of various drugs on amygdaloid kindled rats showed that flunarizine exerts anticonvulsive effects in this model with an ED50 of 42.8 mg/kg. Furthermore, flunarizine (1, 5, 25 and 50 mg/kg i.p.) reduced seizure parameters in rats injected with strychnine or pentetrazol. In this case, flunarizine reduced seizure intensity and increased the percentage of survival. In another study on genetically epileptic beagles, flunarizine significantly affected the REM and deep slow-wave sleep latencies. PMID:3609879

  7. Experimental Studies of Laser-Induced Breakdown in Transparent Dielectrics

    SciTech Connect

    Carr, C W

    2003-09-23

    The mechanisms by which transparent dielectrics damage when exposed to high power laser radiation has been of scientific and technological interest since the invention of the laser. In this work, a set of three experiments are presented which provide insight into the damage initiation mechanisms and the processes involved in laser-induced damage. Using an OPO (optical parametric oscillator) laser, we have measured the damage thresholds of deuterated potassium dihydrogen phosphate (DKDP) from the near ultraviolet into the visible. Distinct steps, whose width is of order K{sub b}T, are observed in the damage threshold at photon energies associated with the number of photons (3{yields}2 or 4{yields}3) needed to promote a ground state electron across the energy gap. The wavelength dependence of the damage threshold suggests that a primary mechanism for damage initiation in DKDP is a multi-photon process in which the order is reduced through excited defect state absorption. In-situ fluorescence microscopy, in conjunction with theoretical calculations by Liu et al., has been used to establish that hydrogen displacement defects are potentially responsible for the reduction in the multi-photon cross-section. During the damage process, the material absorbs energy from the laser pulse and produces an ionized region that gives rise to broadband emission. By performing a time-resolved investigation of this emission, we demonstrate both that it is blackbody in nature, and we provide the first direct measurement of the localized temperature during and following laser damage initiation for various optical materials. For excitation using nanosecond laser pulses, the plasma, when confined in the bulk, is in thermal equilibrium with the lattice. These results allow for a detailed characterization of temperature, pressure, and electron densities occurring during laser-induced damage.

  8. Hypolipidemic effect of gypenosides in experimentally induced hypercholesterolemic rats

    PubMed Central

    2013-01-01

    Background To investigate the anti-hyperlipidemic effect of gynosaponins (GPs) in hyperlipidemic rats induced by high lipid diet. Methods Animal model of hyperlipidemia was established by high-fat and high-cholesterol diet. Rats were randomly divided into 6 groups, except the normal and model groups, rats in GPs groups were daily administered intragastrically with GPs (50, 100, and 200 mg/kg), and rats in simvastatin group were daily administered intragastrically with simvastatin (10 mg/kg). It was measured that the contents of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in the serum, TG and TC in the liver during this experiment, respectively. The left lobe of liver was observed by histopathological staining, and the immunohistochemical staining was used to observe the effects on the effect of GPs on liver functions. Results Compared with the model group, GPs groups could remarkably decrease the content of lipids, GSH-Px, SOD, CAT and MDA in the serum and TC and TG in the liver of the hyperlipidemic rats. The pathomorphological results of hepatic tissue showed that fatty degeneration and inflammatory reaction of GPs groups were lightened compared with the model group. Conclusions The results show that GPs has good effects on the treatment of hyperlipidemia induced by high lipid diet in rats. The possible anti-hyperlipidemia mechanism maybe those GPs can regulate the disorder of lipid metabolism as well as ameliorate hepatic function. PMID:24160562

  9. Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).

    PubMed

    Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

    2013-11-01

    Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans. PMID:23696447

  10. Histochemical changes in the testes of lead induced experimental rats.

    PubMed

    Chowdhury, A R; Rao, R V; Gautam, A K

    1986-01-01

    The experiments were performed on mature male rats divided in five groups, one control and four experimental in which the animals received 1 mg, 2 mg, 4 mg and 6 mg/kg body weight lead acetate intraperitoneally respectively, over a period of 30 days. ALA-D and lead was estimated in the blood by the use of atomic absorption spectrophotometer and ATP-ase, AMP-ase, Alk-ase were histochemically localized. Significant increase in blood and testis of lead levels along with decrease of ALA-D levels were observed. Changes in the testicular tissue were encountered. Other details concerned with the damage of the testicular tissue are discussed. PMID:3030829

  11. Dietary oregano essential oil alleviates experimentally induced coccidiosis in broilers.

    PubMed

    Mohiti-Asli, M; Ghanaatparast-Rashti, M

    2015-06-15

    An experiment was conducted to determine the effects of oregano essential oil on growth performance and coccidiosis prevention in mild challenged broilers. A total of 250 1-d-old chicks were used in a completely randomized design with 5 treatments and 5 replicates with 10 birds in each replication. Experimental treatments included: (1) negative control (NC; unchallenged), (2) positive control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500 ppm oregano oil in diet. At 22 d of age, all the experimental groups except for NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either supplementation rate increased body weight gain (P=0.039) and improved feed conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using 500 ppm oregano oil in challenged broilers diet increased European efficiency factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the effect being similar to unchallenged birds. In general, challenged birds fed 500 ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It could be concluded that supplementation of oregano oil at the dose of 500 ppm in diet may have beneficial effect on prevention of coccidiosis in broilers. PMID:25864115

  12. The combination of tacrolimus and entecavir improves the remission of HBV-associated glomerulonephritis without enhancing viral replication

    PubMed Central

    Wang, Lifen; Ye, Zhiming; Liang, Huaban; Zhang, Bin; Xu, Lixia; Feng, Zhonglin; Liu, Shuangxin; Shi, Wei

    2016-01-01

    Background: Tacrolimus inhibits hepatitis B virus entry into hepatocytes through targeting the HBV receptor, sodium taurocholate cotransporting polypeptide. This study was performed to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis patients with biopsy-proven membranous nephropathy. Method: A cohort of 42 patients was enrolled in this retrospective study. Twenty-three patients received Tacrolimus (0.05 mg/kg/day) in combination entecavir over 24 weeks, whereas the other 19 patients only received entecavir monotherapy. Results: The probability of proteinuria remission in the Tacrolimus+entecavir group was 69 and 87% after 12 and 24 weeks, whereas was only 26 and 42%, respectively, in the entecavir group. The mean time to partial or complete remission was 18.6 weeks in the Tacrolimus+entecavir group and 34.3 weeks in the entecavir group (P<0.001). A decrease in the HBV DNA titer was observed in all patients with active HBV replication. None of the HBV carriers in the Tacrolimus+entecavir group showed evidence of HBV reactivation. The serum creatinine and alanine aminotransferase levels remained stable in both groups. The Tacrolimus target trough concentration was 5-10 ng/mL. Conclusion: Tacrolimus combined with entecavir rapidly and effectively induced remission of HBV-GN in Chinese adults. Furthermore, Tacrolimus may have a synergistic antiviral effect with entecavir.

  13. Epithelial impedance analysis in experimentally induced colon cancer.

    PubMed Central

    Davies, R J; Joseph, R; Kaplan, D; Juncosa, R D; Pempinello, C; Asbun, H; Sedwitz, M M

    1987-01-01

    Epithelial impedance analysis was used to measure the alterations in resistance of the large bowel in a murine model of large bowel cancer. The technique was able to resolve the epithelial resistance from the total resistance of the bowel wall. A progressive decrease in resistance of the bowel epithelium occurs during carcinogenesis induced with dimethyhydrazine. About a 21% decrease in epithelial resistance from 22.0 +/- 1.3 omega.cm-2 to 17.5 +/- 1.1 omega cm-2 (p less than 0.025) was observed after 20 wk of carcinogen administration. The sensitivity of the technique in detecting altered epithelial resistance in premalignant bowel mucosa was improved by examining the impedance profile in a sodium-free Ringer's solution where the epithelium of control colons had a resistance of 24.4 +/- 1.8 omega.cm-2 compared with 19.0 +/- 1.1 omega.cm-2 (p less than 0.02) in colons from animals treated for only 4 wk with the carcinogen. Epithelial impedance analysis would seem to be a sensitive technique capable of identifying changes in the electrical properties or the large bowel early in disease states. PMID:3427187

  14. Chemically induced skin carcinogenesis: Updates in experimental models (Review).

    PubMed

    Neagu, Monica; Caruntu, Constantin; Constantin, Carolina; Boda, Daniel; Zurac, Sabina; Spandidos, Demetrios A; Tsatsakis, Aristidis M

    2016-05-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands‑on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro‑inflammatory cytokines, and simultaneous inflammation sustained by pro‑inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  15. Experimental treatment of antipsychotic-induced movement disorders.

    PubMed

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  16. Experimentally induced photosensitization in cattle with Cooperia pedunculata.

    PubMed

    Casteel, S W; Rowe, L D; Bailey, E M; Fiske, R A; Bridges, C W

    1988-04-01

    Photosensitization was induced in 2 Charolais heifers following administration of a mixture of air-dried, ground, green (75%) and dead (25%) leaves of the south Texas forb, Cooperia pedunculata, and subsequent exposure to sunlight. Plant material used in this study was collected from a pasture where natural cases of primary bovine photosensitization were occurring. Signs of photosensitization were observed in one heifer after 2 doses of plant material--10 g/kg on day 1 and 5 g/kg on day 2. Continued administration of plant material at 5 g/kg/d on days 3, 4, 7, 8, and 9 resulted in severe signs and lesions of photosensitization and death on day 23. A second heifer developed signs of mild photosensitization following administration of plant material at 1.7 g/kg/d for 4 days. This heifer recovered by day 18. Clinical and pathologic findings of this trial were consistent with the primary form of photosensitization observed in natural cases seen in cattle of south Texas exposed to this plant. PMID:3381477

  17. Experimental treatment of antipsychotic-induced movement disorders

    PubMed Central

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  18. Chemically induced skin carcinogenesis: Updates in experimental models (Review)

    PubMed Central

    NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  19. Experimentally induced metamorphosis in axolotls reduces regenerative rate and fidelity

    PubMed Central

    Stier, Adrian C.; Michonneau, François; Smith, Matthew D.; Pasch, Bret; Maden, Malcolm

    2014-01-01

    Abstract While most tetrapods are unable to regenerate severed body parts, amphibians display a remarkable ability to regenerate an array of structures. Frogs can regenerate appendages as larva, but they lose this ability around metamorphosis. In contrast, salamanders regenerate appendages as larva, juveniles, and adults. However, the extent to which fundamental traits (e.g., metamorphosis, body size, aging, etc.) restrict regenerative ability remains contentious. Here we utilize the ability of normally paedomorphic adult axolotls (Ambystoma mexicanum) to undergo induced metamorphosis by thyroxine exposure to test how metamorphosis and body size affects regeneration in age‐matched paedomorphic and metamorphic individuals. We show that body size does not affect regeneration in adult axolotls, but metamorphosis causes a twofold reduction in regeneration rate, and lead to carpal and digit malformations. Furthermore, we find evidence that metamorphic blastemal cells may take longer to traverse the cell cycle and display a lower proliferative rate. This study identifies the axolotl as a powerful system to study how metamorphosis restricts regeneration independently of developmental stage, body size, and age; and more broadly how metamorphosis affects tissue‐specific changes.

  20. Flagella-induced immunity against experimental cholera in adult rabbits.

    PubMed Central

    Yancey, R J; Willis, D L; Berry, L J

    1979-01-01

    The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone. PMID:478635

  1. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    PubMed

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-01-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders. PMID:27598124

  2. Experimental Investigation of Cavitation Induced Feedline Instability from an Orifice

    NASA Technical Reports Server (NTRS)

    Hitt, Matthew A.; Lineberry, David M.; Ahuja, Vineet; Frederick, Robert A,

    2012-01-01

    This paper details the results of an experimental investigation into the cavitation instabilities created by a circular orifice conducted at the University of Alabama in Huntsville Propulsion Research Center. This experiment was conducted in concert with a computational simulation to serve as a reference point for the simulation. Testing was conducted using liquid nitrogen as a cryogenic propellant simulant. A 1.06 cm diameter thin orifice with a rounded inlet was tested in an approximately 1.25 kg/s flow with inlet pressures ranging from 504.1 kPa to 829.3 kPa. Pressure fluctuations generated by the orifice were measured using a high frequency pressure sensor located 0.64 tube diameters downstream of the orifice. Fast Fourier Transforms were performed on the high frequency data to determine the instability frequency. Shedding resulted in a primary frequency with a cavitation related subharmonic frequency. For this experiment, the cavitation instability ranged from 153 Hz to 275 Hz. Additionally, the strength of the cavitation occur red as a function of cavitation number. At lower cavitation numbers, the strength of the cavitation instability ranged from 2.4 % to 7 % of the inlet pressure. However, at higher cavitation numbers, the strength of the cavitation instability ranged from 0.6 % to 1 % of the inlet pressure.

  3. Experimental particle acceleration by water evaporation induced by shock waves

    NASA Astrophysics Data System (ADS)

    Scolamacchia, T.; Alatorre Ibarguengoitia, M.; Scheu, B.; Dingwell, D. B.; Cimarelli, C.

    2010-12-01

    Shock waves are commonly generated during volcanic eruptions. They induce sudden changes in pressure and temperature causing phase changes. Nevertheless, their effects on flowfield properties are not well understood. Here we investigate the role of gas expansion generated by shock wave propagation in the acceleration of ash particles. We used a shock tube facility consisting of a high-pressure (HP) steel autoclave (450 mm long, 28 mm in internal diameter), pressurized with Ar gas, and a low-pressure tank at atmospheric conditions (LP). A copper diaphragm separated the HP autoclave from a 180 mm tube (PVC or acrylic glass) at ambient P, with the same internal diameter of the HP reservoir. Around the tube, a 30 cm-high acrylic glass cylinder, with the same section of the LP tank (40 cm), allowed the observation of the processes occurring downstream from the nozzle throat, and was large enough to act as an unconfined volume in which the initial diffracting shock and gas jet expand. All experiments were performed at Pres/Pamb ratios of 150:1. Two ambient conditions were used: dry air and air saturated with steam. Carbon fibers and glass spheres in a size range between 150 and 210 μm, were placed on a metal wire at the exit of the PVC tube. The sudden decompression of the Ar gas, due to the failure of the diaphragm, generated an initial air shock wave. A high-speed camera recorded the processes between the first 100 μsec and several ms after the diaphragm failure at frame rates ranging between 30,000 and 50,000 fps. In the experiments with ambient air saturated with steam, the high-speed camera allowed to visualize the condensation front associated with the initial air shock; a maximum velocity of 788 m/s was recorded, which decreases to 524 m/s at distance of 0.5 ±0.2 cm, 1.1 ms after the diaphragm rupture. The condensation front preceded the Ar jet front exhausting from the reservoir, by 0.2-0.5 ms. In all experiments particles velocities following the initial

  4. Experimental investigation of the flow induced by artificial cilia.

    PubMed

    Hussong, J; Schorr, N; Belardi, J; Prucker, O; Rühe, J; Westerweel, J

    2011-06-21

    The fluid transport produced by rectangular shaped, magnetically actuated artificial cilia of 70 μm length and 20 μm width was determined by means of phase-locked Micro Particle Image Velocimetry (μPIV) measurements in a closed microfluidic chamber. The phase-averaged flow produced by the artificial cilia reached up to 130 μm s(-1) with an actuation cycle frequency of 10 Hz. Analysis of the measured flow data indicate that the present system is capable of achieving volume flow rates of V[combining dot above](cilia) = 14 ± 4 μl min(-1) in a micro channel of 0.5 × 5 mm(2) cross-sectional area when no back pressure is built up. This corresponds to an effective pressure gradient of 6 ± 1 Pa m(-1), which equals a pressure difference of 0.6 ± 0.1 mPa over a distance of 100 μm between two rows of cilia. These results were derived analytically from the measured velocity profile by treating the cilia as a thin boundary layer. While the cilia produce phase-averaged velocities of the order of O(10(2)μm s(-1)), time-resolved measurements showed that the flow field reverses two times during one actuation cycle inducing instantaneous velocities of up to approximately 2 mm s(-1). This shows that the flow field is dominated by fluid oscillations and flow rates are expected to increase if the beating motion of the cilia is further improved. PMID:21614349

  5. Predictions of Experimentally Observed Stochastic Ground Vibrations Induced by Blasting

    PubMed Central

    Kostić, Srđan; Perc, Matjaž; Vasović, Nebojša; Trajković, Slobodan

    2013-01-01

    In the present paper, we investigate the blast induced ground motion recorded at the limestone quarry “Suva Vrela” near Kosjerić, which is located in the western part of Serbia. We examine the recorded signals by means of surrogate data methods and a determinism test, in order to determine whether the recorded ground velocity is stochastic or deterministic in nature. Longitudinal, transversal and the vertical ground motion component are analyzed at three monitoring points that are located at different distances from the blasting source. The analysis reveals that the recordings belong to a class of stationary linear stochastic processes with Gaussian inputs, which could be distorted by a monotonic, instantaneous, time-independent nonlinear function. Low determinism factors obtained with the determinism test further confirm the stochastic nature of the recordings. Guided by the outcome of time series analysis, we propose an improved prediction model for the peak particle velocity based on a neural network. We show that, while conventional predictors fail to provide acceptable prediction accuracy, the neural network model with four main blast parameters as input, namely total charge, maximum charge per delay, distance from the blasting source to the measuring point, and hole depth, delivers significantly more accurate predictions that may be applicable on site. We also perform a sensitivity analysis, which reveals that the distance from the blasting source has the strongest influence on the final value of the peak particle velocity. This is in full agreement with previous observations and theory, thus additionally validating our methodology and main conclusions. PMID:24358140

  6. Generation of hydroxyl radicals during ascites experimentally induced in broilers.

    PubMed

    Arab, H A; Jamshidi, R; Rassouli, A; Shams, G; Hassanzadeh, M H

    2006-04-01

    Increased metabolic rates, pulmonary hypertension and cardiac dysfunction are the most important features of the ascites syndrome in broiler chickens. However, the mechanism of cell injury causing the pathogenesis of the syndrome is not clearly understood. Our study aimed to examine the generation of hydroxyl radicals (OH*) in broiler chickens experiencing ascites. The hundred and fifty 1-d-old chickens were purchased from a local hatchery and reared in an open poultry house for 46 d. They were divided at random into three groups and ascites was induced in two groups by exposing them to low temperature or administration of triiodothyronine (T(3)). The third group served as control and was reared normally. Haematological, biochemical and pathological tests were used to determine the incidence of ascites: including total red blood cell (RBC), packed cell volume (PCV), release of alanine transaminase (ALT) and aspartate transaminase (AST) and ratio of right ventricular weight to total ventricular weight (RV/TV). A salicylate hydroxylation method was used to examine the generation of hydroxyl radicals (OH*) in treated groups. TWo hydroxylated salicylic acid metabolites, 2,3- and 2,5-dihydroxy benzoic acid (2,3- and 2,5-DHBA), were measured by HPLC to detect the generation of OH*. An ascites syndrome was observed in T(3) and low-temperature treated groups, as shown by necropsy changes and increases in f RBC, PCV, ALT, AST and the ratio of RV/TV. Concentrations of 2,3- and 2,5-DHBA were increased in groups experiencing ascites compared to control group. It is suggested that reactive oxygen species that is OH* ions, may be involved in the pathogenesis of the ascites syndrome in broiler chickens. PMID:16641033

  7. Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.

    PubMed

    Renard, E; Gaudin, A; Bienvenu, G; Amiaud, J; Farges, J C; Cuturi, M C; Moreau, A; Alliot-Licht, B

    2016-02-01

    Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria. PMID:26472753

  8. Experimental demonstration of population inversion driven by retroreflection-induced bichromatic adiabatic passage

    SciTech Connect

    Conde, Alvaro Peralta; Yatsenko, Leonid P.; Klein, Jens; Oberst, Martin; Halfmann, Thomas

    2005-11-15

    We present experimental data to demonstrate coherently driven population inversion by retroreflection-induced bichromatic adiabatic passage in metastable helium atoms. Complete and robust population transfer from an initial to a target state is induced by coherent interaction of the atoms in a supersonic beam with two counterpropagating and temporally delayed laser pulses of different intensities. The radiation fields intersect the atomic beam slightly tilted away from normal incidence, thereby inducing Doppler shifts of the atomic resonance between the initial and the target state. Thus the laser pulses produce a bichromatic field in the rest frame of each atom, which induces complete coherent population transfer by an adiabatic passage process.

  9. Experimental gastric ulcers induced by immobilization and electric shock of rats and their pharmacotherapy

    NASA Technical Reports Server (NTRS)

    Zabrodin, O. N.

    1980-01-01

    The mechanism of development of experimental gastric ulcers, induced in rats by combined immobilization and electric shock, was analyzed pharmacologically with peripheral neurotropic agents. It is concluded that: (1) The most marked preventive effect in the development of the experimentally induced gastric ulcers was displayed by agents capable of blocking the ascending activation system of the reticular formation. (2) Sympathetic fibers, which disrupt the trophism of the gastric wall, form the efferent portion of the reflex arc. (3) Gastric secretion does not appear to be the primary cause of ulceration.

  10. T cells, adhesion molecules and modulation of apoptosis in visceral leishmaniasis glomerulonephritis

    PubMed Central

    2010-01-01

    Background Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-α, IL-1α were searched and quantified. Results We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the

  11. Antineutrophil Cytoplasmic Antibody-associated Vasculitis Superimposed on Infection-related Glomerulonephritis Secondary to Pulmonary Mycobacterium avium Complex Infection.

    PubMed

    Asano, Shuichi; Mizuno, Shige; Okachi, Shotaro; Aso, Hiromichi; Wakahara, Keiko; Hashimoto, Naozumi; Ito, Satoru; Kozaki, Yohei; Katsuno, Takayuki; Maruyama, Shoichi; Hasegawa, Yoshinori

    2016-01-01

    A 73-year-old woman was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection and received no treatment. Disease progression was evident one year later with the development of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) titers and systemic symptoms of a fever, polyarthritis, purpura, and rapidly progressive glomerulonephritis. Her symptoms did not improve with antibiotic treatment. A renal biopsy revealed crescentic glomerulonephritis with immunodeposition. According to these findings, she was diagnosed with ANCA-associated vasculitis (AAV) superimposed on infection-related glomerulonephritis (IRGN). Although there was a risk of aggravating an underlying infection, the combination therapy of corticosteroid and antibiotics improved AAV, IRGN, and even the lung radiological findings. To the best of our knowledge, this is the first case of AAV and IRGN secondary to pulmonary MAC infection. PMID:27580547

  12. IgA-dominant post-infectious glomerulonephritis presenting as a fatal pulmonary-renal syndrome.

    PubMed

    Saad, Marc; Daoud, Magda; Nasr, Patricia; Syed, Rafeel; El-Sayegh, Suzanne

    2015-01-01

    Over the last decades, post-infectious glomerulonephritis underwent major changes in its epidemiology, pathophysiology, and outcomes. We are reporting a case of IgA-dominant post-infectious glomerulonephritis (IgA-PIGN) presenting as a fatal pulmonary-renal syndrome. An 86-year-old Filipino man presented with worsening dyspnea, hemoptysis, and decreased urine output over 2 weeks. Past medical history is significant for hypertension, chronic kidney disease stage III, and pneumonia 3 weeks prior treated with intravenous cefazolin for methicillin-sensitive Staphylococcus aureus bacteremia. Physical examination was remarkable for heart rate of 109/min and respiratory rate of 25/min saturating 99% on 3 liters via nasal cannula. There were bibasilar rales in the lungs and bilateral ankle edema. A chest radiograph showed bibasilar opacifications. Blood work was significant for hemoglobin of 8.3 g/dL and creatinine of 9.2 mg/dL (baseline of 1.67). TTE showed EF 55%. Urinalysis revealed large blood and red blood cell casts. Kidney ultrasound showed bilateral echogenicity compatible with renal disease. Pulse methylprednisolone therapy and hemodialysis were initiated with patient's condition precluding kidney biopsy. Serology workup for rapidly progressive glomerulonephritis was negative. On day 7, the patient required mechanical ventilation; bronchoscopy showed alveolar hemorrhage and plasmapheresis was initiated. Renal biopsy revealed IgA-PIGN with endocapillary and focal extracapillary proliferative and exudative features. IgA-PIGN occurs in diabetic elderly (mean age of 60 years), 0-16 weeks after an infection mainly by Staphylococcus. However, this nondiabetic patient had normal complement IgA-PIGN with fatal pulmonary-renal syndrome. Understanding the pathogenesis and identifying the nephrotoxic bacteria species and the aberrant IgA molecule will open new insights toward prevention and treatment. PMID:26347210

  13. IgA-dominant post-infectious glomerulonephritis presenting as a fatal pulmonary-renal syndrome

    PubMed Central

    Saad, Marc; Daoud, Magda; Nasr, Patricia; Syed, Rafeel; El-Sayegh, Suzanne

    2015-01-01

    Over the last decades, post-infectious glomerulonephritis underwent major changes in its epidemiology, pathophysiology, and outcomes. We are reporting a case of IgA-dominant post-infectious glomerulonephritis (IgA-PIGN) presenting as a fatal pulmonary-renal syndrome. An 86-year-old Filipino man presented with worsening dyspnea, hemoptysis, and decreased urine output over 2 weeks. Past medical history is significant for hypertension, chronic kidney disease stage III, and pneumonia 3 weeks prior treated with intravenous cefazolin for methicillin-sensitive Staphylococcus aureus bacteremia. Physical examination was remarkable for heart rate of 109/min and respiratory rate of 25/min saturating 99% on 3 liters via nasal cannula. There were bibasilar rales in the lungs and bilateral ankle edema. A chest radiograph showed bibasilar opacifications. Blood work was significant for hemoglobin of 8.3 g/dL and creatinine of 9.2 mg/dL (baseline of 1.67). TTE showed EF 55%. Urinalysis revealed large blood and red blood cell casts. Kidney ultrasound showed bilateral echogenicity compatible with renal disease. Pulse methylprednisolone therapy and hemodialysis were initiated with patient’s condition precluding kidney biopsy. Serology workup for rapidly progressive glomerulonephritis was negative. On day 7, the patient required mechanical ventilation; bronchoscopy showed alveolar hemorrhage and plasmapheresis was initiated. Renal biopsy revealed IgA-PIGN with endocapillary and focal extracapillary proliferative and exudative features. IgA-PIGN occurs in diabetic elderly (mean age of 60 years), 0–16 weeks after an infection mainly by Staphylococcus. However, this nondiabetic patient had normal complement IgA-PIGN with fatal pulmonary-renal syndrome. Understanding the pathogenesis and identifying the nephrotoxic bacteria species and the aberrant IgA molecule will open new insights toward prevention and treatment. PMID:26347210

  14. Novel Role of Toll-Like Receptor 3 in Hepatitis C-Associated Glomerulonephritis

    PubMed Central

    Wörnle, Markus; Schmid, Holger; Banas, Bernhard; Merkle, Monika; Henger, Anna; Roeder, Maximilian; Blattner, Simone; Bock, Elisabeth; Kretzler, Matthias; Gröne, Hermann-Josef; Schlöndorff, Detlef

    2006-01-01

    Hepatitis C virus (HCV) infection is frequently complicated by glomerulonephritis with immune complexes containing viral RNA. We examined the potential influence of Toll-like receptors (TLRs), specifically TLR3 recognition of viral dsRNA exemplified by polyriboinosinic:polyribocytidylic acid [poly(I:C) RNA]. Normal human kidney stained positive for TLR3 on mesangial cells (MCs), vascular smooth muscle cells, and collecting duct epithelium. Cultured MCs have low TLR3 mRNA levels with predominant intracellular protein localization, which was increased by tumor necrosis factor-α, interleukin (IL)-1β, interferon (IFN)-γ, and the TLR3 ligand poly(I:C) RNA. Poly(I:C) RNA stimulation of MCs increased mRNA and protein synthesis of IL-6, IL-1β, M-CSF, IL-8/CXCL8, RANTES/CCL5, MCP-1/CCL2, and ICAM-I; it also increased anti-proliferative and proapoptotic effects, the latter of which was decreased by inhibiting caspase-8. In microdissected glomeruli of normal and non-HCV membranoproliferative glomerulonephritis biopsies, TLR3 mRNA expression was low. In contrast TLR3 mRNA expression was significantly increased in hepatitis C-positive glomerulonephritis and was associated with enhanced mRNA for RANTES/CCL5 and MCP-1/CCL2. We hypothesize that immune complexes containing viral RNA activate mesangial TLR3 during HCV infection, thereby contributing to chemokine/cytokine release and effecting proliferation and apoptosis. Thus, TLR3 expression on renal cells, and especially MCs, may establish a link between viral infections and glomerular diseases. PMID:16436653

  15. Temporal Changes in Post-Infectious Glomerulonephritis in Japan (1976-2009)

    PubMed Central

    Usui, Joichi; Tawara-Iida, Takashi; Takada, Kenji; Ebihara, Itaru; Ueda, Atsushi; Iwabuchi, Satoshi; Ishizu, Takashi; Iitsuka, Tadashi; Takemura, Katsumi; Kawamura, Tetsuya; Kaneko, Shuzo; Sakai, Kentaro; Kai, Hirayasu; Gomibuchi, Tomoka; Nagata, Michio; Kobayashi, Masaki; Koyama, Akio; Suka, Machi; Radhakrishnan, Jai; Yamagata, Kunihiro

    2016-01-01

    Background The incidence of post-infectious glomerulonephritis (PIGN) in developed countries has decreased over the last 50 years. Here we identified the trends of the incidence of PIGN in Japan during the past four decades. Methods We explored the frequency, clinicopathological findings, and prognosis of PIGN based on 6,369 cases from the Renal Biopsy Database of our institute in the Kanto region of Japan, diagnosed histologically from 1976 to 2009. Results The numbers of PIGN cases were 131 (2.1%) in total, and 2.4%, 1.1%, 2.6% and 2.1% identified in the 1970s, 1980s, 1990s, and 2000s, respectively. Acute glomerulonephritis (AGN), including post-streptococcal glomerulonephritis (PSGN), accounted for almost all of the PIGN cases in the 1970s, but decreased to approx. 40%–50% since the 1990s. In the 1990s, Staphylococcus aureus infection-related nephritis (SARN) showed a rapid increase in rate, reaching 30%. The incidence of hepatitis C virus infection-associated GN (HCVGN) has increased since the 1990s. The average age at onset rose from 33 to 51 years over the study period. These transitions can be summarized as increases in SARN and HCVGN and decreases in PSGN and other types of AGN, since SARN and HCVGN have older onsets compared to PSGN and other AGN types. The clinicopathological features were marked for each PIGN. Regarding the prognosis, the renal death rates of both the SARN and HCVGN groups were significantly higher than those of other PIGN. Conclusion Based on our analysis of the Renal Biopsy Database, the incidence of PIGN in Japan reached its peak in the 1990s. The temporal changes in the incidence of PIGN reflected the trends in infectious diseases of each decade and the continual aging of the population, with a related higher susceptibility to infections. PMID:27286043

  16. Acute glomerulonephritis in children of the Niger Delta region of Nigeria.

    PubMed

    McGil Ugwu, G I

    2015-09-01

    A three-year retrospective study was conducted to determine the incidence, pattern of presentation and other clinical and biochemical features as well as outcome of treatment of patients admitted with acute glomerulonephritis at the Delta State University Teaching Hospital, Oghara and GN Children's Clinic, Warri. The case notes of all the children who presented with renal diseases from January 2010 to December 2012 were retrieved and those with acute glomerulonephritis were analyzed. A total of 20 patients (13 male and seven female) with acute glomerulonephritis were seen during the three-year period under review. Twelve patients (60%) were from the low socioeconomic class, six (30%) from the middle class and only two (10%) were from the high-income group. The presentation of the illness was most common between October and January. The age range of the patients was three to 13 years, with an average age of eight years. Seventeen (85%) of the patients were in the school-going age group (>5 years to 10 years). The most common symptom/sign noted was anemia in 90% of the patients, followed by oliguria/anuria and edema seen in 80% of the patients. Seventy percent of the patients had cola-colored urine, while 55% had hypertension. Some patients gave a history suggestive of previous streptococcal infection. More patients had sore throat (25%) than skin infection (10%). All the patients had proteinuria, while 90% had hematuria. The most common complication was acute kidney injury, seen in eight (40%) of the patients, followed by hypertensive encephalopathy, which occurred in three (15%) patients. Most patients (60%) were hospitalized for one to two weeks. The outcome of the management of these patients showed 14 (70%) of the patients recovered fully while three (15%) had persistent hematuria and two (10%) had persistent proteinuria. Ninety-five percent of the patients recovered from the acute illness and one patient (5%), a boy aged nine years old, died. PMID:26354592

  17. Nutrient induced type 2 and chemical induced type 1 experimental diabetes differently modulate gastric GLP-1 receptor expression.

    PubMed

    Bloch, Olga; Broide, Efrat; Ben-Yehudah, Gilad; Cantrell, Dror; Shirin, Haim; Rapoport, Micha J

    2015-01-01

    T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R) expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO) by high-energy (HE) diet and by streptozotocin (STZ) in Sprague Dawly (SD) rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis. PMID:25893200

  18. Renal granuloma and immunoglobulin M-complex glomerulonephritis: a case of common variable immunodeficiency?

    PubMed

    Benoit, Geneviève; Lapeyraque, Anne-Laure; Sartelet, Hervé; Saint-Cyr, Claire; Le Deist, Françoise; Haddad, Elie

    2009-03-01

    Common variable immunodeficiency (CVID) is characterized by reduced serum immunoglobulin levels and recurrent bacterial infections. Granulomatous infiltrations are occasionally found in the lymphoid or solid organs of affected patients, but renal involvement is rare. We present a case of possible CVID with interstitial noncaseating granuloma and immunoglobulin (IgM)-complex glomerulonephritis with a membranoproliferative pattern and with a favorable response to corticosteroids, intravenously administered immunoglobulins (IVIGs) and rituximab. CVID must be included in the differential diagnosis of renal granuloma and should be differentiated from sarcoidosis to ensure appropriate therapy. PMID:18696117

  19. Intestinal Intravascular Large B-cell Lymphoma Mimicking Ulcerative Colitis with Secondary Membranoproliferative Glomerulonephritis.

    PubMed

    Kaneyuki, Daisuke; Komeno, Yukiko; Yoshimoto, Hiroshi; Yoshimura, Naoki; Iihara, Kuniko; Ryu, Tomiko

    2016-01-01

    A 47-year-old woman with ulcerative colitis (UC) was admitted to our hospital for renal dysfunction and progressive anemia. Colonoscopy revealed intestinal lesions and pathological findings showed intravascular large B-cell lymphoma (IVLBCL). According to the polymerase chain reaction analysis of sequential rectal specimens, we concluded that she suffered from intestinal BCL, not UC. After chemotherapy, her renal function progressed to nephrotic syndrome. The pathological findings of renal biopsy specimens indicated membranoproliferative glomerulonephritis (MPGN). Chemotherapy was continued and led to the remission of BCL and MPGN. We herein describe the first case of intestinal IVLBCL mimicking UC with secondary MPGN. PMID:27580553

  20. Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

    PubMed

    Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi

    2015-01-01

    We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure. PMID:25876581

  1. Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center experience

    PubMed Central

    Rampelli, S. K.; Rajesh, N. G.; Srinivas, B. H.; Harichandra Kumar, K. T.; Swaminathan, R. P.; Priyamvada, P. S.

    2016-01-01

    There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36–0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04–0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022). PMID:27512296

  2. Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center experience.

    PubMed

    Rampelli, S K; Rajesh, N G; Srinivas, B H; Harichandra Kumar, K T; Swaminathan, R P; Priyamvada, P S

    2016-01-01

    There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36-0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04-0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022). PMID:27512296

  3. Necrotizing and crescentic glomerulonephritis with membranous nephropathy in a patient exposed to levamisole-adulterated cocaine

    PubMed Central

    Carrara, Camillo; Emili, Stefano; Lin, Mercury; Alpers, Charles E.

    2016-01-01

    Levamisole is an antihelminthic agent widely used as an adulterant of illicit cocaine recently implicated as a cause of antineutrophil cytoplasmic antibody (ANCA)–associated microscopic polyangiitis in cocaine abusers. An isolated case of membranous nephropathy (MN) associated with levamisole exposure has also been reported. We report the first case, to our knowledge, of a patient with both microscopic polyangiitis manifest as a pauci-immune necrotizing and crescentic glomerulonephritis and concurrent MN in the setting of chronic cocaine abuse and presumed levamisole exposure, raising the hypothesis that levamisole was the causative agent in the development of this rare dual glomerulopathy. PMID:26985374

  4. Nephrotic Syndrome Secondary to Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits of Lambda Light Chain

    PubMed Central

    Yun, Seongseok; Braunhut, Beth L.; Walker, Courtney N.; Bhati, Waheed; Sussman, Amy N.; Anwer, Faiz

    2014-01-01

    We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent. PMID:25136462

  5. Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse

    PubMed Central

    Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg; Kumagai, Kazuyoshi; Harkema, Jack R.; Holian, Andrij; Pestka, James J.

    2015-01-01

    Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory responses in the lungs as evidenced by extensive perivascular and peribronchial lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid tissue (ELT). In addition, there were elevated concentrations of immunoglobulins and the cytokines MCP-1, TNF-α and IL-6 in bronchoalveolar lavage fluid. cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2-induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1 mouse corresponded closely to systemic inflammatory and autoimmune responses as well as the early initiation of pathological outcomes in the kidney. These findings suggest that following airway exposure to crystalline silica, in mice genetically prone to SLE, the lung serves as a platform for triggering systemic autoimmunity and glomerulonephritis. PMID:25978333

  6. Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

    NASA Technical Reports Server (NTRS)

    Tyavokin, V. V.; Tjawokin, W. W.

    1980-01-01

    A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

  7. Towards new avenues in the management of lupus glomerulonephritis.

    PubMed

    Mok, C C

    2016-04-01

    Renal involvement in systemic lupus erythematosus (SLE) carries substantial morbidity and mortality. Conventional immunosuppressive agents (cyclophosphamide and azathioprine) have suboptimal efficacy and substantial toxicity. Mycophenolate mofetil has emerged as an alternative agent for both induction and maintenance therapy in lupus nephritis because of its reduced gonadal toxicity, despite its failure to demonstrate superiority over cyclophosphamide in pivotal studies. The calcineurin inhibitor tacrolimus has equivalent efficacy to cyclophosphamide and mycophenolate mofetil for inducing remission of lupus nephritis. Although rituximab has shown promise in refractory lupus nephritis, combining rituximab with mycophenolate mofetil as initial therapy offers no additional benefit. Considerable interethnic variation is evident in the efficacy and tolerability of the various immunosuppressive regimens, which necessitates individualized treatment and comparison of the efficacy of new regimens across different ethnic groups. For example, low-dose combinations of tacrolimus and mycophenolate mofetil seem to be more effective than pulse cyclophosphamide as induction therapy in Chinese patients. The same regimen has also been used successfully to treat refractory proliferative and membranous lupus nephritis in patients of various ethnic groups. Finally, novel serum and urinary biomarkers are being validated for diagnosis, prognostic stratification and early recognition of flares in lupus nephritis. PMID:26729459

  8. Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil.

    PubMed

    Sharma, Bhupesh; Singh, Nirmal; Singh, Manjeet

    2008-03-01

    Present study was designed to investigate modulation of experimental dementia by Pitavastatin and donepezil. Learning and memory of the swiss albino mice were studied on Morris water-maze. Celecoxib orally (p.o.)/Streptozotocin (STZ) intracerebroventricular administrations were used to induce experimental dementia. Brain acetyl cholinesterase activity was measured by EllMann's method to assess cholinergic activity of the brain. Brain thio barbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively, to assess total oxidative stress in brain. Total serum cholesterol level was measured by Allain's method. Celecoxib/STZ treatments produced a significant loss of learning and memory. Pitavastatin/Donepezil successfully attenuated this Celecoxib/STZ induced dementia. Higher levels of brain acetyl-cholinesterase (AChE) activity, TBARS and lower level of GSH were observed in Celecoxib/STZ treated animals, which were significantly attenuated by Donepezil. Pitavastatin also attenuated the Celecoxib/STZ induced high levels of TBARS & low levels of GSH without effecting AChE activity and total serum cholesterol levels. Celecoxib induced dementia noted in the present study may be attributed to its stimulatory effect on amyloid beta-42, brain AChE activity, and oxidative stress. Sub-diabetogenic STZ induced memory deficits closely related to Alzheimer's disease. Reversal of Celecoxib/STZ induced memory deficits by Pitavastatin may be due to its antioxidative, anti beta amyloid aggregatory property, and by Donepezil, due to its anticholinesterase and neuroprotective actions. PMID:18208924

  9. Antineutrophil Cytoplasmic Antibodies-Negative Pauci-Immune Crescentic Glomerulonephritis Associated with Multiple Myeloma.

    PubMed

    Anaele, Cyriacus Uzoma; Srisung, Weeraporn; Tomacruz, Yvette; Laski, Melvin

    2015-01-01

    Pauci-immune crescentic glomerulonephritis (PICGN) is most commonly associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of chronic, sclerosing ANCA-negative PICGN discovered when a patient presented with multiple myeloma. A 57-year-old woman presented with complaints of nausea, emesis and weakness. She was found to be in renal failure with a serum creatinine of 9.4 mg/dl, mild hyperkalemia and acidosis. She was noted to have normochromic, normocytic anemia with normal platelet and white cell counts, normal plasma proteins and serum protein electrophoresis. Further studies revealed increased concentrations of κ and λ light chains in a ratio of 34.89; a bone marrow biopsy found 12% plasma cells. Serum protein electrophoresis revealed no spike. ANCA, anti-glomerular basement membrane, antineutrophil antibody, hepatitis panel and serum complements were normal. A kidney biopsy result showed chronic sclerosing PICGN plus tubular necrosis, severe tubular atrophy, interstitial fibrosis and severe arteriosclerosis. Congo red stains were negative and electron microscopy showed no intraglomerular deposits. The patient was subsequently treated for myeloma with bortezomib and dexamethasone with good hematologic response but never recovered renal function. She remains on outpatient hemodialysis. Renal manifestations of myeloma often involve glomerular deposition disease, tubulointerstitial disease, with characteristic proteinaceous casts, or both. In contrast, our patient demonstrated neither of these findings but had chronic sclerosing PICGN. Crescentic glomerulonephritis occurring in patients with plasma cell dyscrasias has been previously reported, but the association remains extremely rare. PMID:26120578

  10. Granulomatosis with Polyangiitis Presenting as Pauci-Immune Crescentic Glomerulonephritis in Pregnancy

    PubMed Central

    Kunjal, Ryan; Makary, Raafat; Poenariu, Andreea

    2016-01-01

    Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN). The diagnosis was consistent with granulomatosis with polyangiitis (GPA). Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management. PMID:27293925

  11. Antineutrophil Cytoplasmic Antibodies-Negative Pauci-Immune Crescentic Glomerulonephritis Associated with Multiple Myeloma

    PubMed Central

    Anaele, Cyriacus Uzoma; Srisung, Weeraporn; Tomacruz, Yvette; Laski, Melvin

    2015-01-01

    Pauci-immune crescentic glomerulonephritis (PICGN) is most commonly associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of chronic, sclerosing ANCA-negative PICGN discovered when a patient presented with multiple myeloma. A 57-year-old woman presented with complaints of nausea, emesis and weakness. She was found to be in renal failure with a serum creatinine of 9.4 mg/dl, mild hyperkalemia and acidosis. She was noted to have normochromic, normocytic anemia with normal platelet and white cell counts, normal plasma proteins and serum protein electrophoresis. Further studies revealed increased concentrations of κ and λ light chains in a ratio of 34.89; a bone marrow biopsy found 12% plasma cells. Serum protein electrophoresis revealed no spike. ANCA, anti-glomerular basement membrane, antineutrophil antibody, hepatitis panel and serum complements were normal. A kidney biopsy result showed chronic sclerosing PICGN plus tubular necrosis, severe tubular atrophy, interstitial fibrosis and severe arteriosclerosis. Congo red stains were negative and electron microscopy showed no intraglomerular deposits. The patient was subsequently treated for myeloma with bortezomib and dexamethasone with good hematologic response but never recovered renal function. She remains on outpatient hemodialysis. Renal manifestations of myeloma often involve glomerular deposition disease, tubulointerstitial disease, with characteristic proteinaceous casts, or both. In contrast, our patient demonstrated neither of these findings but had chronic sclerosing PICGN. Crescentic glomerulonephritis occurring in patients with plasma cell dyscrasias has been previously reported, but the association remains extremely rare. PMID:26120578

  12. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome: A case report and literature review.

    PubMed

    Huang, Yan-Mei; Zhou, Hui-Rong; Zhang, Ling; Yang, Ke-Ke; Luo, Jiang-Xi; Zhao, Hai-Lu

    2016-06-01

    Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function.Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5-12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old.We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7-33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy.Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID:27368022

  13. The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades.

    PubMed

    Woo, K-T; Chan, C-M; Mooi, C Y; -L-Choong, H; Tan, H-K; Foo, M; Lee, G S L; Anantharaman, V; Lim, C-H; Tan, C-C; Lee, E J C; Chiang, G S C; Tan, P H; Boon, T H; Fook-Chong, S; Wong, K-S

    2010-11-01

    This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries. PMID:20979946

  14. The Role of Nephritis-Associated Plasmin Receptor (NAPlr) in Glomerulonephritis Associated with Streptococcal Infection

    PubMed Central

    Oda, Takashi; Yoshizawa, Nobuyuki; Yamakami, Kazuo; Sakurai, Yutaka; Takechi, Hanako; Yamamoto, Kojiro; Oshima, Naoki; Kumagai, Hiroo

    2012-01-01

    It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexes in situ and/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate. We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected by in situ zymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity. PMID:23118507

  15. CD34+ fibroblast-like cells in the interstitial infiltrates in glomerulonephritis - an immunohistochemical observation.

    PubMed

    Gluhovschi, Cristina; Potencz, Elena; Lazar, Elena; Petrica, Ligia; Bozdog, Gheorghe; Gadalean, Florica; Bob, Flaviu; Gluhovschi, Adrian; Cioca, Daniel; Velciov, Silvia

    2012-12-01

    CD34 cells in the interstitial infiltrates in glomerulonephritis (GN) could be the turning point between regenerative processes and interstitial fibrosis. The aim of our study was to assess the presence of CD34+ cells in the interstitial infiltrates in GN. A cross-sectional study of 33 patients with glomerulonephritis, mean age: 43.3 ±11.31 years, 20 male and 13 female, was conducted. Conventional stains, as well as immunohistochemistry for the CD34 antigen were employed on kidney biopsies. Strength of immunohistochemical reaction was assessed semi-quantitatively. Regarding the percentage of cases with CD34+ cells in the interstitial infiltrates out of 33 patients: cells of interstitial infiltrates were 27.3% positive. The percentage of cases showing CD34+ cells at the level of interstitial infiltrates was: 44.4% in FSGS, 14.3% in membranoproliferative GN, 28.6% in membranous nephropathy, 20% in mesangial proliferative GN, 0% in minimal change disease, and 50% in crescentic GN. With the exception of minimal change disease, CD34+ cells were found in the interstitial infiltrates in all histopathological forms of GN. Some of these cells were spindle-shaped fibroblast-like cells. As inflammation in the tubulointerstitial compartment either resolves or proceeds to fibrosis, aims at reversing this process will benefit from analyses of the interstitial infiltrates harboring CD34+ cells. PMID:23359197

  16. A case of infectious endocarditis-associated crescentic glomerulonephritis with intracranial hemorrhage.

    PubMed

    Miyata, Eri; Nakayama, Masaru; Amano, Kazushi; Hirano, Tadashi; Uesugi, Noriko

    2010-01-01

    A 55-year-old woman was admitted to our hospital because of fever and renal impairment. The patient had undergone a tooth extraction 11 months prior to admission. Echocardiography demonstrated vegetation on the mitral valve, and Streptococcus mitis was detected on blood culture. Accordingly, infectious endocarditis (IE) was diagnosed. Renal biopsy showed crescentic glomerulonephritis. Based on the negative staining for immunoglobulins and complement components in immunofluorescence study and lack of dense deposits on electron microscopy, the renal involvement was considered to be of the pauci-immune type. Subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) developed simultaneously following commencement of antibiotic therapy. The intracranial involvement improved by conservative therapy. Antibiotic treatment resulted in gradual control of IE infection and improvement of renal function. A repeated renal biopsy, performed about 5 months after the first biopsy, showed amelioration of glomerular injury and interstitial damage. To our knowledge, our case was the second to report simultaneous developments of both SAH and SDH secondary to IE. We postulate that the glomerular injury was associated with IE. We report here a rare case of IE-associated crescentic glomerulonephritis with complications of SAH and SDH. PMID:20155718

  17. Classifying murine glomerulonephritis using optical coherence tomography and optical coherence elastography.

    PubMed

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Chang, Anthony; Mohan, Chandra; Larin, Kirill V

    2016-08-01

    Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys. PMID:26791097

  18. Revisiting post-infectious glomerulonephritis in the emerging era of C3 glomerulopathy

    PubMed Central

    Khalighi, Mazdak A.; Wang, Shihtien; Henriksen, Kammi J.; Bock, Margret; Keswani, Mahima; Meehan, Shane M.; Chang, Anthony

    2016-01-01

    Background Post-infectious glomerulonephritis (PIGN) is an immune complex-mediated glomerular injury that typically resolves. Dominant C3 deposition is characteristic of PIGN, but with the emergence of C3 glomerulonephritis (C3GN) as a distinct entity, it is unclear how the pathologic similarities between PIGN and C3GN should be reconciled. Therefore, nephrologists and nephropathologists need additional guidance at the time of biopsy. Methods We studied 23 pediatric and young adult patients diagnosed with PIGN. Patients were divided into two groups, one with co-dominance between C3 and immunoglobulins and the other meeting proposed diagnostic criteria for C3GN. Clinical and pathological features were compared. Results No clinical and/or pathological features could distinguish between those with C3-co-dominant deposits and those with C3 dominance. Nearly all patients in both groups regained their baseline renal function without clinical intervention. Conclusions Although the identification of abnormalities of the alternative pathway of complement is characteristic of C3GN, testing is not widely available and the turnaround time often exceeds 1 month. Our study found that PIGN with either co-dominant or dominant C3 deposition in a cohort of young patients has excellent short-term outcomes. Close clinical observation for persistent abnormalities, such as hypocomplementemia, prolonged hematuria or proteinuria, is recommended to single out patients that may harbor intrinsic complement abnormalities. PMID:27274823

  19. Renal infarction and immune-mediated glomerulonephritis in sheep (Ovis aries) chronically implanted with indwelling catheters.

    PubMed

    Rao, Varada P; Poutahidis, Theofilos; Marini, Robert P; Holcombe, Hilda; Rogers, Arlin B; Fox, James G

    2006-07-01

    Microbial infections are common sequelae in humans and animals implanted with long-term intravascular catheters. Understanding the pathophysiology of infectious morbidity is critical to improving quality of care in catheterized subjects. Here, we describe findings in 6 clinically healthy, male sheep implanted with indwelling aortic or cardiac catheters for 6 to 10 mo. We isolated multiple bacterial species including Serratia spp., Enterobacter agglomerans, Eschericia coli, Klebsiella oxytoca, and K. pneumoniae in aerobic cultures from catheter tips. Although sheep were clinically asymptomatic, 1 or both kidneys from all animals contained wedge-shaped infarcts of varying size and number. Microscopic examination revealed (a) marked fibrosis with mild inflammatory cell infiltrate consistent with chronic foreign body reaction around catheters; (b) moderate to severe, diffuse, subacute to chronic membranoproliferative glomerulonephritis and mild, multifocal chronic interstitial nephritis; and (c) mesangial immune-complex deposition as demonstrated by direct immunofluorescence technique. The finding of bacterial colonization of catheters together with chronic glomerulonephritis and immune-complex deposits in kidneys in clinically asymptomatic sheep underscores the need for close microbiologic monitoring of catheter implants and assessment of kidney function in animals instrumented for long-term vascular access. PMID:16884173

  20. Lutheran/basal cell adhesion molecule accelerates progression of crescentic glomerulonephritis in mice

    PubMed Central

    Huang, Jin; Filipe, Anne; Rahuel, Cécile; Bonnin, Philippe; Mesnard, Laurent; Guérin, Coralie; Wang, Yu; Le Van Kim, Caroline; Colin, Yves; Tharaux, Pierre-Louis

    2014-01-01

    Migration of circulating leukocytes from the vasculature into the surrounding tissue is an important component of the inflammatory response. Among the cell surface molecules identified as contributing to leukocyte extravasation is VCAM-1, expressed on activated vascular endothelium, which participates in all stages of leukocyte–endothelial interaction by binding to leukocyte surface expressed integrin VLA-4. However, not all VLA-4-mediated events can be linked to VCAM-1. A novel interaction between VLA-4 and endothelial Lutheran (Lu) blood group antigens and basal cell adhesion molecule (BCAM) proteins has been recently shown, suggesting that Lu/BCAM may have a role in leukocyte recruitments in inflamed tissues. Here, we assessed the participation of Lu/BCAM in the immunopathogenesis of crescentic glomerulonephritis. High expression of Lu/BCAM in glomeruli of mice with rapidly progressive glomerulonephritis suggests a potential role for the local expression of Lu/BCAM in nephritogenic recruitment of leukocytes. Genetic deficiency of Lu/BCAM attenuated glomerular accumulation of T cells and macrophages, crescent formation, and proteinuria, correlating with reduced fibrin and platelet deposition in glomeruli. Furthermore, we found a pro-adhesive interaction between human monocyte α4β1 integrin and Lu/BCAM proteins. Thus, Lu/BCAM may have a critical role in facilitating the accumulation of monocytes and macrophages, thereby exacerbating renal injury. PMID:24429403

  1. Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis

    PubMed Central

    Jirholt, Pernilla; Turesson, Olof; Wing, Kajsa; Holmdahl, Rikard; Kihlberg, Jan; Stern, Anna; Mårtensson, Inga-Lill; Henningsson, Louise; Gustafsson, Kenth; Gjertsson, Inger

    2016-01-01

    Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naïve mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases. PMID:27159398

  2. Tissue factor initiates glomerular fibrin deposition and promotes major histocompatibility complex class II expression in crescentic glomerulonephritis.

    PubMed Central

    Erlich, J. H.; Holdsworth, S. R.; Tipping, P. G.

    1997-01-01

    Increased glomerular tissue factor (TF) expression is associated with glomerular fibrin deposition and renal failure in human and experimental crescentic glomerulonephritis (GN). However, the in vivo functional contribution of TF to the development of glomerular fibrin deposition, crescent formation, and renal failure in GN has not been established. The contribution of TF to fibrin deposition and renal injury was studied in a rabbit model of crescentic GN in which glomerular macrophage infiltration, augmented TF expression, and fibrin deposition are prominent. Administration of anti-TF antibody inhibited glomerular TF activity in nephritic glomeruli by 96%, without affecting macrophage accumulation or systemic indices of coagulation. Anti-TF antibody significantly reduced glomerular fibrin deposition (fibrin scores, 0.43 +/- 0.10 (treated) and 1.40 +/- 0.19 (control); P < 0.0005), crescent formation (0.33 +/- 0.05 (treated) and 1.0 +/- 0.06 (control); P < 0.0005), and development of renal failure (serum creatinine, 168 +/- 22 mumol/l (treated) and 267 +/- 35 mumol/l (control); P < 0.04). This was associated with significant reduction in proteinuria (1189 +/- 277 mg/24 hours (treated) and 2060 +/- 336 mg/24 hours (control); P < 0.03) and expression of MHC class II antigen in glomeruli (1.25 +/- 0.41 (treated) and 2.83 +/- 0.53 (control); P < 0.03) and in tubules and interstitial areas. These data demonstrate that TF is the major in vivo initiator of fibrin deposition in crescentic GN. The reduction in proteinuria and glomerular major histocompatibility class II antigen expression by TF inhibition suggests that TF may also activate other mediators that contribute to glomerular injury. Images Figure 1 PMID:9060825

  3. Four different synthetic peptides of proteolipid protein induce a distinct antibody response in MP4-induced experimental autoimmune encephalomyelitis.

    PubMed

    Recks, Mascha S; Grether, Nicolai B; van der Broeck, Franziska; Ganscher, Alla; Wagner, Nicole; Henke, Erik; Ergün, Süleyman; Schroeter, Michael; Kuerten, Stefanie

    2015-07-01

    Here we studied the autoantibody specificity elicited by proteolipid protein (PLP) in MP4-induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis (MS). In C57BL/6 (B6) mice, antibodies were induced by immunization with one of the two extracellular and by the intracellular PLP domain. Antibodies against extracellular PLP were myelin-reactive in oligodendrocyte cultures and induced mild spinal cord demyelination upon transfer into B cell-deficient J(H)T mice. Remarkably, also antibodies against intracellular PLP showed binding to intact oligodendrocytes and were capable of inducing myelin pathology upon transfer into J(H)T mice. In MP4-immunized mice peptide-specific T(H)1/T(H)17 responses were mainly directed against the extracellular PLP domains, but also involved the intracellular epitopes. These data suggest that both extracellular and intracellular epitopes of PLP contribute to the pathogenesis of MP4-induced EAE already in the setting of intact myelin. It remains to be elucidated if this concept also applies to MS itself. PMID:25959684

  4. Modeling Chemotherapy-Induced Hair Loss: From Experimental Propositions toward Clinical Reality.

    PubMed

    Botchkarev, Vladimir A; Sharov, Andrey A

    2016-03-01

    Chemotherapy-induced hair loss is one of the most devastating side effects of cancer treatment. To study the effects of chemotherapeutic agents on the hair follicle, a number of experimental models have been proposed. Yoon et al. report that transplantation of human scalp hair follicles onto chemotherapy-treated immunodeficient mice serves as an excellent in vivo model for chemotherapy-induced hair loss. Yoon et al. demonstrate that (i) the response of human hair follicles grafted onto immunodeficient mice to cyclophosphamide resembles the key features of the chemotherapy-induced hair loss seen in patients with cancer and (ii) this human in vivo model for chemotherapy-induced hair loss is closer to clinical reality than to any earlier models. Undoubtedly, this model will serve as a valuable tool for analyses of the mechanisms that underlie this devastating side effect of anti-cancer therapy. PMID:26902124

  5. DETECTORS AND EXPERIMENTAL METHODS: Equivalent properties of single event burnout induced by different sources

    NASA Astrophysics Data System (ADS)

    Yang, Shi-Yu; Cao, Zhou; Da, Dao-An; Xue, Yu-Xiong

    2009-05-01

    The experimental results of single event burnout induced by heavy ions and 252Cf fission fragments in power MOSFET devices have been investigated. It is concluded that the characteristics of single event burnout induced by 252Cf fission fragments is consistent to that in heavy ions. The power MOSFET in the “turn-off" state is more susceptible to single event burnout than it is in the “turn-on" state. The thresholds of the drain-source voltage for single event burnout induced by 173 MeV bromine ions and 252Cf fission fragments are close to each other, and the burnout cross section is sensitive to variation of the drain-source voltage above the threshold of single event burnout. In addition, the current waveforms of single event burnouts induced by different sources are similar. Different power MOSFET devices may have different probabilities for the occurrence of single event burnout.

  6. Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

    PubMed

    Lavezzo, A; Melillo, G; Clavenna, G; Omini, C

    1992-06-01

    The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough. PMID:1611233

  7. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  8. α-1-Antitrypsin detected by MALDI imaging in the study of glomerulonephritis: Its relevance in chronic kidney disease progression.

    PubMed

    Smith, Andrew; L'Imperio, Vincenzo; De Sio, Gabriele; Ferrario, Franco; Scalia, Carla; Dell'Antonio, Giacomo; Pieruzzi, Federico; Pontillo, Claudia; Filip, Szymon; Markoska, Katerina; Granata, Antonio; Spasovski, Goce; Jankowski, Joachim; Capasso, Giovambattista; Pagni, Fabio; Magni, Fulvio

    2016-06-01

    Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes. PMID:26749278

  9. Protective effect of ketoconazole against experimentally induced gastric ulcers in rats.

    PubMed

    Al Moutaery, Ahmed R

    2003-01-01

    Recent studies suggest the critical role of inflammatory mediators in the genesis and healing of gastric ulcers. Ketoconazole a commonly used anti-fungal agent has a potent immunomodulatory action. The present investigation was undertaken to study the effect of ketoconazole on chemically and stress induced gastric ulcers in rats. Experimental gastric lesions in rats were induced by water immersion restraint stress, indomethacin and ethanol. Acid secretion studies were undertaken in pylorus ligated rats with and without ketoconazole. The level of myeloperoxidase (marker of neutrophil activity) non-protein sulfhydryl compounds and gastric wall mucus were measured after ethanol induced gastric lesions. Ketoconazole treatment resulted in significant protection against stress; indomethacin and ethanol induced gastric lesions in rats. Ketoconazole also dose dependently attenuated ethanol induced increase in myeloperoxidase activity and protected gastric mucosa against ethanol-induced depletion of non-protein sulfhydryl. These findings point towards the mediation of neutrophils and sulfhydryl compounds in ketoconazole induced cytoprotection. In conclusion, this study clearly shows anti-acid secretory, anti-ulcer and cytoprotective activity of ketoconazole. PMID:15686104

  10. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization

    PubMed Central

    Dominguez, Elisa; Raoul, William; Calippe, Bertrand; Sahel, José-Alain; Guillonneau, Xavier; Paques, Michel; Sennlaub, Florian

    2015-01-01

    Aims Branch retinal vein occlusion (BRVO) leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined. Methods and Results We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC) apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC) dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO. Conclusion Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease. PMID:26208283