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Sample records for renal glomeruli complement

  1. Stereological Evaluation of Renal Glomeruli in Offspring of Diabetic Female Rats

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    Abdolrahman Dezfoolian

    2009-01-01

    Full Text Available Objective: Although in vitro studies have shown that high concentrations of glucosecan induce dysmorphogenesis of the embryonic kidney, the possible adverse effectsof exposure to intrauterine hyperglycemia on kidney development, especially in regardto nephrogenesis, has not been evaluated.The aim of this study is to investigate the effects of maternal diabetes on glomerulistructures of the offspring, focusing on the following parameters: glomeruli volumeand number, mesangium volume, mesangial cell number and glomerular capillaryvolume.Materials and Methods: Before mating, fifteen female Sprague Dawley rats, dividedinto three groups, were diabetes induced by a single intraperitoneal dose of 65 mg/kg streptozotocyn (STZ. After 30 days of breast feeding, ten offsprings from eachgroup (two per mother were randomly selected for kidney removal. The kidneyswere weighed and their tissues were processed for light microscopy. Glomerular featureswere evaluated quantitatively using dissection as well as the Cavalieri methodand were then compared with sham and control groups.Results: At birth, the mean body weight of diabetic mothers’ offspring (DO was significantlylower than that of the control group’s offspring (CO and sham group’s offspring(SO (p=0.001, however, the mean body weight of the 30 day-old DO was notlower than that of CO and SO (p>0.05. The total renal volumes, cortical volumes,glomerular mean and total volumes, total mesangeal volumes, total capillary volumesand total glomerular numbers were significantly lower in the DO than in CO and SO(p<0.05. The numerical density of glomeruli and mesangial cells per glomeruli weresignificantly greater in DO than in CO and SO (p<0.05.Conclusion: We concluded that intrauterine hyperglycemia is accompanied by anephron deficit which may not be compensated within the first 30 days after birth.

  2. [Renal risks of dietary complements: a forgotten cause].

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    Dori, Olympia; Humbert, Antoine; Burnier, Michel; Teta, Daniel

    2014-02-26

    The use of dietary complements like vitamins, minerals, trace elements, proteins, aminoacids and plant-derived agents is prevalent in the general population, in order to promote health and treat diseases. Dietary complements are considered as safe natural products and are easily available without prescription. However, these can lead to severe renal toxicity, especially in cases of unknown pre-existing chronic kidney disease (CKD). In particular, Chinese herbs including aristolochic acid, high doses of vitamine C, creatine and protein complements may lead to acute and chronic renal failure, sometimes irreversible. Dietary complement toxicity should be suspected in any case of unexplained renal impairement. In the case of pre-existing CKD, the use of potentially nephrotoxic dietary complements should be screened for.

  3. Is the presence of abnormal prion protein in the renal glomeruli of feline species presenting with FSE authentic?

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    Bencsik Anna A

    2010-08-01

    Full Text Available Abstract In a recent paper written by Hilbe et al (BMC vet res, 2009, the nature and specificity of the prion protein deposition in the kidney of feline species affected with feline spongiform encephalopathy (FSE were clearly considered doubtful. This article was brought to our attention because we published several years ago an immunodetection of abnormal prion protein in the kidney of a cheetah affected with FSE. At this time we were convinced of its specificity but without having all the possibilities to demonstrate it. As previously published by another group, the presence of abnormal prion protein in some renal glomeruli in domestic cats affected with FSE is indeed generally considered as doubtful mainly because of low intensity detected in this organ and because control kidneys from safe animals present also a weak prion immunolabelling. Here we come back on these studies and thought it would be helpful to relay our last data to the readers of BMC Vet res for future reference on this subject. Here we come back on our material as it is possible to study and demonstrate the specificity of prion immunodetection using the PET-Blot method (Paraffin Embedded Tissue - Blot. It is admitted that this method allows detecting the Proteinase K (PK resistant form of the abnormal prion protein (PrPres without any confusion with unspecific immunoreaction. We re-analysed the kidney tissue versus adrenal gland and brain samples from the same cheetah affected with TSE using this PET-Blot method. The PET-Blot analysis revealed specific PrPres detection within the brain, adrenal gland and some glomeruli of the kidney, with a complete identicalness compared to our previous detection using immunohistochemistry. In conclusion, these new data enable us to confirm with assurance the presence of specific abnormal prion protein in the adrenal gland and in the kidney of the cheetah affected with FSE. It also emphasizes the usefulness for the re-examination of any

  4. The role of complement in autoimmune renal disease

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    Seelen, M. A.; Daha, M. R.

    2006-01-01

    The predominance of renal involvement in autoimmune diseases can most likely be assigned to the specialised function of the kidneys filtrating over 120 ml plasma per minute. Complement activation by autoantibodies directed against planted antigens or antigens already present in renal tissue in the s

  5. Role of on-site microscopic evaluation of kidney biopsy for adequacy and allocation of glomeruli: comparison of renal biopsies with and without on-site microscopic evaluation.

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    Gilani, S M; Ockner, D; Qu, H

    2013-12-01

    Evaluation of kidney core biopsies ideally begins with on-site microscopic examination for adequacy and allocation of tissue for light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). However, some renal biopsies are not microscopically evaluated by a pathologist at the time of procedure, and are allocated without on-site evaluation. This study compares the actual outcome of these two techniques. We reviewed the reports of patients who underwent kidney biopsy for medical causes in the past two years. Eighty-eight biopsies had on-site microscopic evaluation by pathologists, and 70 biopsies did not undergo on-site evaluation. For biopsies without on-site evaluation, no glomeruli were seen in 5 (7.14%) cases for LM, 11 (15.71%) cases for IF and 6 (8.57%) cases for EM. In cases with on-site evaluation, the absence of glomeruli was identified in 1 (1.13%) case for LM, 3 (3.4%) for IF and 3 (3.4%) for EM. The biopsies with on-site microscopic evaluation had 5.68% of the cases considered as inadequate, while 22% of biopsies without on-site evaluation were considered inadequate. The biopsies with on-site evaluation tended to have more glomeruli obtained during the procedure (p < 0.0005). Without on-site evaluation, the likelihood of getting an inadequate specimen compared to on-site evaluation is nearly four times greater.

  6. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli.

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    Pitera, Jolanta E; Scambler, Peter J; Woolf, Adrian S

    2008-12-15

    FRAS1 is mutated in some individuals with Fraser syndrome (FS) and the encoded protein is expressed in embryonic epidermal cells, localizing in their basement membrane (BM). Syndactyly and cryptophthalmos in FS are sequelae of skin fragility but the bases for associated kidney malformations are unclear. We demonstrate that Fras1 is expressed in the branching ureteric bud (UB), and that renal agenesis occurs in homozygous Fras1 null mutant blebbed (bl) mice on a C57BL6J background. In vivo, the bl/bl bud fails to invade metanephric mesenchyme which undergoes involution, events replicated in organ culture. The expression of glial cell line-derived neurotrophic factor and growth-differentiation factor 11 was defective in bl/bl renal primordia in vivo, whereas, in culture, the addition of either growth factor restored bud invasion into the mesenchyme. Mutant primordia also showed deficient expression of Hoxd11 and Six2 transcription factors, whereas the activity of bone morphogenetic protein 4, an anti-branching molecule, was upregulated. In wild types, Fras1 was also expressed by nascent nephrons. Foetal glomerular podocytes expressed Fras1 transcripts and Fras1 immunolocalized in a glomerular BM-like pattern. On a mixed background, bl mutants, and also compound mutants for bl and my, another bleb strain, sometimes survive into adulthood. These mice have two kidneys, which contain subsets of glomeruli with perturbed nephrin, podocin, integrin alpha3 and fibronectin expression. Thus, Fras1 protein coats branching UB epithelia and is strikingly upregulated in the nephron lineage after mesenchymal/epithelial transition. Fras1 deficiency causes defective interactions between the bud and mesenchyme, correlating with disturbed expression of key nephrogenic molecules. Furthermore, Fras1 may also be required for the formation of normal glomeruli.

  7. Targeting complement activation in brain-dead donors improves renal function after transplantation

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    Damman, Jeffrey; Hoeger, Simone; Boneschansker, Leo; Theruvath, Ashok; Waldherr, Ruediger; Leuvenink, Henri G.; Ploeg, Rutger J.; Yard, Benito A.; Seelen, Marc A.

    2011-01-01

    Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function afte

  8. Isolation and characterization of a novel rat factor H-related protein that is up-regulated in glomeruli under complement attack.

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    Ren, Guohui; Doshi, Mona; Hack, Bradley K; Alexander, Jessy J; Quigg, Richard J

    2002-12-13

    The factor H family in humans is composed of seven distinct proteins, including factor H-related proteins (FHR) 1-5. All members contain tandemly arranged short consensus repeats (SCR) typical of the regulators of complement activation gene family. FHR-5 is unusual for this group of proteins, as it was initially identified as a component of immune deposits in glomerular diseases. During our cloning of the cDNA for rat factor H from glomerular epithelial cells (GEC), we identified an alternative 2729-bp cDNA transcript. The translated sequence encoded a protein containing 11 SCRs, most similar to SCRs 7-15 and 19-20 in native rat factor H, which is the same basic structure of human FHR-5. As such, this rat protein was termed FHR. Recombinant rat FHR produced in a eukaryotic expression system had a molecular mass of 78 kDa. In functional studies, recombinant FHR bound C3b and inhibited the complement alternative pathway in a dose-dependent fashion. Given the prominent expression of FHR-5 in human membranous nephropathy, a disease in which complement activation occurs in the vicinity of GEC, the expression of FHR in a rat model of this disease was evaluated. In both in vitro and in vivo models of complement activation on the GEC, FHR mRNA was up-regulated by a factor of 3-6-fold compared with controls in which complement could not be activated. Thus, we have identified a novel factor H family member in rats. This FHR protein is analogous to human FHR-5, both in structure and in potential involvement in glomerular immune complex diseases.

  9. Down-regulation of integrin β1 and focal adhesion kinase in renal glomeruli under various hemodynamic conditions.

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    Xiaoli Yuan

    Full Text Available Given that integrin β1 is an important component of the connection to maintain glomerular structural integrity, by binding with multiple extracellular matrix proteins and mediating intracellular signaling. Focal adhesion kinase (FAK is the most essential intracellular integrator in the integrin β1-FAK signalling pathway. Here, we investigated the changes of the two molecules and visualized the possible interaction between them under various hemodynamic conditions in podocytes. Mice kidney tissues were prepared using in vivo cryotechnique (IVCT and then were stained and observed using light microscopy, confocal laser scanning microscopy and immunoelectron microscopy. The expression of these molecules were examined by western blot. Under the normal condition, integrin β1 stained continually and evenly at the membrane, and FAK was located in the cytoplasm and nuclei of the podocytes. There were significant colocalized plaques of two molecules. But under acute hypertensive and cardiac arrest conditions, integrin β1 decreased and stained intermittently. Similarly, FAK decreased and appeared uneven. Additionally, FAK translocated to the nuclei of the podocytes. As a result, the colocalization of integrin β1 and FAK reduced obviously under these conditions. Western blot assay showed a consistent result with the immunostaining. Collectively, the abnormal redistribution and decreased expressions of integrin β1 and FAK are important molecular events in regulating the functions of podocytes under abnormal hemodynamic conditions. IVCT could offer considerable advantages for morphological analysis when researching renal diseases.

  10. Presence of. gamma. G and. beta. 1C globulins in renal glomeruli of aging and neonatally x-irradiated mice

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    Guttman, P.H.; Wuepper, K.D.; Fudenberg, H.H.

    1967-01-01

    A renal lesion in rodents, termed progressive intercapillary glomerulosclerosis (IGS), is characterized by gradual increase in the thickness of the mesangium due to cell proliferation, clustering, and pleomorphism of the mesangial cells, accumulation of PAS-positive mesangial matrix and progressive increase in the thickness of capillary basement membranes. Electron microscopy reveals deposits of electron-dense material in kidneys with IGS suggestive of plasma proteins in the mesangial matrix and in the basement membranes. IGS appears early in life and progresses with age. Whole body irradiation or direct irradiation of the kidneys causes acceleration of the glomerular lesion. A latent period precedes the onset of demonstrable histologic changes following x-ray; this latent period is of shorter duration in animals irradiated late in life. In previous studies, the possible role of an immune mechanism in the pathogenesis of IGS was suggested by the following observations: (1) the progressive course of the disease after a latent period following a single exposure to x-ray; (2) the similarity of the lesions to those seen in experimental immune disease of the kidney in rodents; (3) the presence of electron-dense material suggesting plasma protein deposits in the basement membranes and matrix; and (4) the potentiating effect of neonatal thymectomy on the course of radiation-induced IGS.

  11. Corynebacterium renale as a cause of reactions to the complement fixation test for Johne's disease

    NARCIS (Netherlands)

    Gilmour, N.J.L.; Goudswaard, J.

    Complement fixation (C.F.) tests and fluorescent antibody (F.A.) tests were carried out on sera from rabbits inoculated with Corynebacterium renale and Mycobacterium johnei, and on sera from cattle with C. renale pyelonephritis and with Johne's disease. Cross-reactions were a feature of the C.F.

  12. Targeting complement activation in brain-dead donors improves renal function after transplantation.

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    Damman, Jeffrey; Hoeger, Simone; Boneschansker, Leo; Theruvath, Ashok; Waldherr, Ruediger; Leuvenink, Henri G; Ploeg, Rutger J; Yard, Benito A; Seelen, Marc A

    2011-05-01

    Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function after transplantation. Brain death (BD) was induced in Fisher rats by inflation of an epidurally placed balloon catheter and ventilated for 6h. BD animals were treated with soluble complement receptor 1 (sCR1) 1h before or 1h after BD. Kidney transplantation was performed and 7 days after transplantation animals were sacrificed. Plasma creatinine and urea were measured at days 0, 1, 3, 5 and 7 after transplantation. Renal function was significantly better at day 1 after transplantation in recipients receiving a sCR1 pre-treated donor kidney compared to recipients of a non-treated donor graft. Also treatment with sCR1, 1h after the diagnosis of BD, resulted in a better renal function after transplantation. Gene expression of IL-6, IL-1beta and TGF-beta were significantly lower in renal allografts recovered from treated donors. This study shows that targeting complement activation, during BD in the donor, leads to an improved renal function after transplantation in the recipient.

  13. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

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    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  14. Unmasking of complements using proteinase-K in formalin fixed paraffin embedded renal biopsies

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    R Nada

    2016-01-01

    Full Text Available Renal biopsy interpretation requires histopathology, direct immunofluorescence (DIF and electron microscopy. Formalin-fixed, paraffin-embedded tissue (FFPE sent for light microscopy can be used for DIF after antigen retrieval. However, complement staining has not been satisfactory. We standardized DIF using proteinase-K for antigen retrieval in FFPE renal biopsies. A pilot study was conducted on known cases of membranous glomerulonephritis (MGN, membranoproliferative type-1 (MPGN-1, immunoglobulin A nephropathy (IgAN, and anti-glomerular basement disease (anti-GBM. Immunofluorescence panel included fluorescein isothiocyanate (FITC conjugated IgG, IgA, IgM, complements (C3 and C1q, light chains (kappa, lambda and fibrinogen antibodies. After standardization of the technique, 75 renal biopsies and 43 autopsies cases were stained. Out of 43 autopsy cases, immune-complex mediated glomerulonephritis (GN was confirmed in 18 cases (Lupus nephritis-11, IgAN-6, MGN-1, complement-mediated dense deposit disease (DDD-1 and monoclonal diseases in 4 cases (amyloidosis-3, cast nephropathy-1. Immune-mediated injury was excluded in 17 cases (focal segmental glomerulosclerosis -3, crescentic GN-6 [pauci-immune-3, anti-GBM-3], thrombotic microangiopathy-5, atherosclerosis-3. Renal biopsies (n-75 where inadequate or no frozen sample was available; this technique classified 52 mesangiocapillary pattern as MPGN type-1-46, DDD-2 and (C3GN-4. Others were diagnosed as IgAN-3, lupus nephritis-2, MGN-4, diffuse proliferative glomerulonephritis (DPGN-1, Non-IC crescentic GN-1, monoclonal diseases-3. In nine cases, DIF on FFPE tissue could not help in making diagnosis. Proteinase-K enzymatic digestion of FFPE renal biopsies can unmask complements (both C3 and C1q in immune-complexes mediated and complement-mediated diseases. This method showed good results on autopsy tissues archived for as long as 15 years.

  15. Unmasking of complements using proteinase-K in formalin fixed paraffin embedded renal biopsies.

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    Nada, R; Kumar, A; Kumar, V G; Gupta, K L; Joshi, K

    2016-01-01

    Renal biopsy interpretation requires histopathology, direct immunofluorescence (DIF) and electron microscopy. Formalin-fixed, paraffin-embedded tissue (FFPE) sent for light microscopy can be used for DIF after antigen retrieval. However, complement staining has not been satisfactory. We standardized DIF using proteinase-K for antigen retrieval in FFPE renal biopsies. A pilot study was conducted on known cases of membranous glomerulonephritis (MGN), membranoproliferative type-1 (MPGN-1), immunoglobulin A nephropathy (IgAN), and anti-glomerular basement disease (anti-GBM). Immunofluorescence panel included fluorescein isothiocyanate (FITC) conjugated IgG, IgA, IgM, complements (C3 and C1q), light chains (kappa, lambda) and fibrinogen antibodies. After standardization of the technique, 75 renal biopsies and 43 autopsies cases were stained. Out of 43 autopsy cases, immune-complex mediated glomerulonephritis (GN) was confirmed in 18 cases (Lupus nephritis-11, IgAN-6, MGN-1), complement-mediated dense deposit disease (DDD-1) and monoclonal diseases in 4 cases (amyloidosis-3, cast nephropathy-1). Immune-mediated injury was excluded in 17 cases (focal segmental glomerulosclerosis -3, crescentic GN-6 [pauci-immune-3, anti-GBM-3], thrombotic microangiopathy-5, atherosclerosis-3). Renal biopsies (n-75) where inadequate or no frozen sample was available; this technique classified 52 mesangiocapillary pattern as MPGN type-1-46, DDD-2 and (C3GN-4). Others were diagnosed as IgAN-3, lupus nephritis-2, MGN-4, diffuse proliferative glomerulonephritis (DPGN)-1, Non-IC crescentic GN-1, monoclonal diseases-3. In nine cases, DIF on FFPE tissue could not help in making diagnosis. Proteinase-K enzymatic digestion of FFPE renal biopsies can unmask complements (both C3 and C1q) in immune-complexes mediated and complement-mediated diseases. This method showed good results on autopsy tissues archived for as long as 15 years.

  16. Renal infarction due to lupus vasculopathy.

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    Varalaxmi, B; Sandeep, P; Sridhar, A V S S N; Raveendra, P; Kishore, C Krishna; Ram, R; Kumar, V Siva

    2015-08-01

    In the ISN/RPS 2003 classification of lupus nephritis (LN) renal vascular lesions are not mentioned. We present a patient with postpartum lupus vasculopathy. The renal biopsy in our patient showed concentric intimal thickening with narrowed lumen. No inflammatory changes were found. It also revealed immunoglobulin and complement deposition on the wall of the arteriole. These changes indicate lupus vasculopathy. The glomeruli revealed diffuse proliferative glomerulonephritis, with wire loops and cellular crescent in one glomerulus. The patient showed improvement with immunosuppression.

  17. Complement Activation Is Involved in Renal Damage in Human Antineutrophil Cytoplasmic Autoantibody Associated Pauci-Immune Vasculitis

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    Xing, Guang-qun; Chen, Min; Liu, Gang; Heeringa, Peter; Zhang, Jun-jun; Zheng, Xin; Jie, E.; Kallenberg, Cees G. M.; Zhao, Ming-hui

    2009-01-01

    This study was to investigate the evidence for complement activation in renal biopsy specimens of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune vasculitis. Renal biopsy specimens from seven patients with MPO-ANCA positive pauci-immune necr

  18. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli

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    Pitera JE, Scambler PJ, Woolf AS.

    2008-01-01

    FRAS1 is mutated in some individuals with Fraser syndrome (FS) and the encoded protein is expressed in embryonic epidermal cells, localizing in their basement membrane (BM). Syndactyly and cryptophthalmos in FS are sequelae of skin fragility but the bases for associated kidney malformations are unclear. We demonstrate that Fras1 is expressed in the branching ureteric bud (UB), and that renal agenesis occurs in homozygous Fras1 null mutant blebbed (bl) mice on a C57BL6J background. In vivo, th...

  19. Immunofluorescence staining for the detection of immunoglobulins and complement (C3) in dogs with renal disease.

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    Aresu, L; Pregel, P; Bollo, E; Palmerini, D; Sereno, A; Valenza, F

    2008-12-06

    Renal cortical biopsies from 74 dogs with different degrees of renal failure were studied by immunofluorescence to assess the frequency and extent of the deposition of immunoglobulins G, M and A (IgG, IgM, IgA) and complement C3. The dogs were divided into two groups on the basis of their clinical signs, and standard histological and electron microscopical examinations, according to whether their disease was an immune-mediated nephropathy (IMN) or a non-immune-mediated nephropathy (NIMN). In the dogs with an imn there was strong immunofluorescence due to IgG in the mesangium and the glomerular basement membrane and to IgM in the mesangium. The mechanism of immune complex trapping in the glomerulus also resulted in positive reactions to IgM in the dogs with an NIMN.

  20. Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes.

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    Thompson, Cheryl L; Klein, Barbara E K; Klein, Ronald; Xu, Zhiying; Capriotti, Jennifer; Joshi, Tripti; Leontiev, Dmitry; Lee, Kristine E; Elston, Robert C; Iyengar, Sudha K

    2007-09-01

    In this study, we investigated the associations of complement factor H (CFH) and hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal function. Three scales, measuring the course of AMD and drusen development, were examined in two samples: the Family Age-Related Macular degeneration Study (FARMS), consisting of families ascertained through a single individual with severe AMD, and an unascertained population-based family cohort, the Beaver Dam Eye Study (BDES), which was also used to assess longitudinal changes in AMD and associations with renal function. Associations were performed by a regression accounting for known risk factors as well as familial and sibling effects. Strong evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed (P = 9.15 x 10(-5) in BDES, P = 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting that its role is not phenotype-specific. Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate of change of AMD. The rs1061170 polymorphism was also associated with a reduction in estimated glomerular filtration rate (eGFR) (P = 0.046). Another CFH polymorphism, rs800292, was similarly associated with eGFR [beta = -0.90 (P = 0.022)]. Associations between rs743137 (P = 0.05) and rs680638 (P = 0.022) in HMCN1 with calculated creatinine clearance progression were also observed. Both genes appear to play a role in both AMD and renal pathophysiology. These findings support evidence for common pathways influencing ocular and renal function and suggest that further work is required on their common determinants.

  1. Capillary Deposition of Complement C4d and C3d in Chinese Renal Allograft Biopsies

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    Rong Lv

    2015-01-01

    Full Text Available Background. C3d is a product of both the classic and the alternative complement cascades; however, few studies have addressed the role of C3d in renal biopsies and its relationship with long-term graft survival rate is not very clear. Methods. 94 patients with biopsy-proven acute rejection episodes were included in the study. We investigated the associations between histological findings, clinical examinations, and outcome. Results. The overall prevalence for C4dPTC and C3dPTC was 42.6% and 29.8%. There was a significant association between C3dPTC and C4dPTC (P<0.001. C3dPTC and C4dPTC were related with histological types (P=0.024 and P<0.001, resp.. The long-term survival rate for C4dPTC positive transplants was lower than that of C4dPTC negative transplants, but it was not statistic significant in our study (P=0.150. The survival rate of C3dPTC positive group was much lower than the negative group (P=0.014. Patients with double positives for C4dPTC and C3dPTC exhibited the lowest survival rate significantly different from those of the C3dPTC only and C4dPTC only groups (P=0.01 and P=0.0037. Conclusions. This longitudinal cohort study has demonstrated that C3d deposition in the PTC was closely related to renal dysfunction and pathological changes.

  2. Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

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    Paolo Durigutto

    2017-09-01

    Full Text Available Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process. To this end, we generated Ergidina, a neutralizing recombinant anti-C5 human antibody coupled with a cyclic-RGD peptide, with a distinctive homing property for ischemic endothelial cells and effective in controlling tissue damage in a rat model of renal ischemia/reperfusion injury (IRI. As a result of its preferential localization on renal endothelium, the molecule induced complete inhibition of complement activation at tissue level, and local protection from complement-mediated tissue damage without affecting circulating C5. The ex vivo binding of Ergidina to surgically removed kidney exposed to cold ischemia supports its therapeutic use to prevent posttransplant IRI leading to delay of graft function. Moreover, the finding that the ex vivo binding of Ergidina was not restricted to the kidney, but was also seen on ischemic heart, suggests that this RGD-targeted anti-C5 antibody may represent a useful tool to treat organs prior to transplantation. Based on this evidence, we propose preliminary data showing that Ergidina is a novel targeted drug to prevent complement activation on the endothelium of ischemic kidney.

  3. [Terminal complement complex (TCC) levels in urine in patients with renal diseases].

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    Yasuda, K

    2001-03-01

    The terminal complement complex (TCC) has been reported to play an important role in the pathogenesis of proteinuria not only in experimental nephritis but also in human glomerulonephritis. In order to clarify the clinical significance of TCC, the author investigated a total of 129 pediatric patients with the following glomerular diseases: idiopathic nephrotic syndrome (INS; 40 cases), IgA nephropathy (IgAN; 48 cases), mesangio-capillary glomerulonephritis (MPGN; 16 cases), lupus nephritis (LN; 16 cases), purpura nephritis (5 cases) and membranous nephritis (4 cases). Results were analyzed in relation to the responsiveness to steroid treatment in INS and the degree of proteinuria and histopathologic severity in glonerulonephritis groups. In 40 patients who underwent renal biopsy, the localizations of vitronectin and clusterin, both of which are regulatory proteins for TCC, were examined by immunofluorescence microscopy in conjunction with that of TCC for the study of the mechanism of local defense in glomerulonephritis. The urinary TCC levels were elevated in 9 (90%) of 10 patients with steroid-resistant INS, while they were elevated only in 2 of 30 steroid-responsive patients. In glomerulonephritis groups, urinary TCC levels were elevated in 13 of 48 patients with IgAN, 6 of 16 with MPGN, 8 of 16 with LN, 2 of 5 purpural nephritis and 1 of 4 with membranous nephritis. Urinary TCC levels correlated with histological severity in IgAN and showed a reciprocal relation to C3 levels in MPGN and LN. Immunofluorescence findings showed that localization of TCC was quite similar to that of C3 in glomerulonephritis groups. Vitronectin and clusterin were also demonstrated to deposit in similar pattern to TCC. These results suggest that in INS urinary TCC levels could predict the responsiveness to steroid therapy and might be useful as a non-invasive diagnostic method in differential diagnosis of INS. In IgAN, urinary TCC could be a useful marker of histologic severity. The

  4. Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

    NARCIS (Netherlands)

    Damman, Jeffrey; Daha, Mohamed R.; van Son, Willem J.; Leuvenink, Henri G.; Ploeg, Rutger J.; Seelen, Marc A.

    2011-01-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen acti

  5. Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

    NARCIS (Netherlands)

    Damman, Jeffrey; Daha, Mohamed R.; van Son, Willem J.; Leuvenink, Henri G.; Ploeg, Rutger J.; Seelen, Marc A.

    2011-01-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen acti

  6. Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.

    Science.gov (United States)

    Damman, Jeffrey; Daha, Mohamed R; van Son, Willem J; Leuvenink, Henri G; Ploeg, Rutger J; Seelen, Marc A

    2011-04-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together. Complement and TLRs are important mediators of renal ischemia-reperfusion injury (IRI). Besides IRI, complement C3 can also be upregulated and activated in the kidney before transplantation as a direct result of brain death (BD) in the donor. This local upregulation and activation of complement in the donor kidney has been proven to be detrimental for renal allograft outcome. Also TLR4 and several of its major ligands are upregulated by donor BD compared to living donors. Important and in line with the observations above, kidney transplant recipients have a benefit when receiving a kidney from a TLR4 Asp299Gly/Thr399Ile genotypic donor. The role of complement and TLRs and crosstalk between these two innate immune systems in relation to renal injury during donor BD and ischemia-reperfusion are focus of this review. Future strategies to target complement and TLR activation in kidney transplantation are considered.

  7. Role of complement in IgA nephropathy.

    Science.gov (United States)

    Daha, Mohamed R; van Kooten, Cees

    2016-02-01

    Immunoglobulin A nephropathy (IgAN) is characterized by the deposition of IgA in the mesangium of glomeruli. This mesangial IgA has been found to consist mainly of polymeric IgA1 which drives the activation of the mesangial cells and results in excessive production of several inflammatory mediators. The activation of mesangial cells is amplified by the ability of IgA to activate the complement system, originally thought to occur mainly via the alternative pathway of complement. However more recent studies indicate that lectin pathway involvement has a strong association with progression of renal disease. In this review we summarize the contribution of complement to the IgA- mediated inflammatory process.

  8. Complement Inhibition for Prevention and Treatment of Antibody-Mediated Rejection in Renal Allograft Recipients.

    Science.gov (United States)

    Jordan, S C; Choi, J; Kahwaji, J; Vo, A

    2016-04-01

    Therapeutic interventions aimed at the human complement system are recognized as potentially important strategies for the treatment of inflammatory and autoimmune diseases because there is often evidence of complement-mediated injury according to pathologic assessments. In addition, there are a large number of potential targets, both soluble and cell bound, that might offer potential for new drug development, but progress in this area has met with significant challenges. Currently, 2 drugs are approved aimed at inhibition of complement activation. The first option is eculizumab (anti-C5), which is approved for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Eculizumab has also been studied in human transplantation for the treatment and prevention of antibody-mediated rejection (ABMR). Initial data from uncontrolled studies suggested a significant benefit of eculizumab for the prevention of ABMR in highly HLA-sensitized patients, but a subsequent randomized, placebo-controlled trial failed to meet its primary endpoint. Anecdotal data, primarily from case studies, showed benefits in treating complement-mediated ABMR. A second approved complement-inhibiting therapy is C1 esterase inhibitor (C1-INH), which is approved for use in patients with hereditary angioedema, a condition caused by mutations in the gene that codes for C1-INH. A recent placebo-controlled trial of C1-INH for prevention of ABMR in HLA-sensitized patients found that the drug was safe, with evidence for inhibition of systemic complement activation and complement-activating donor-specific antibodies. Other drugs are now under development.

  9. Levels of complement components C3a and C5a in renal injury among trichloroethylene-sensitized BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    查晚生

    2014-01-01

    Objective To determine the levels of complement components C3a and C5a in the kidneys of trichloroethylene(TCE)-sensitized BALB/c mice,and to investigate the role of complement components in TCE-induced renal injury among BALB/c mice.Methods Sixty-two female BALB/c mice were randomly divided into blank control group,vehicle control group,and TCE sensitization

  10. Select Drosophila glomeruli mediate innate olfactory attraction and aversion.

    Science.gov (United States)

    Semmelhack, Julia L; Wang, Jing W

    2009-05-14

    Fruitflies show robust attraction to food odours, which usually excite several glomeruli. To understand how the representation of such odours leads to behaviour, we used genetic tools to dissect the contribution of each activated glomerulus. Apple cider vinegar triggers robust innate attraction at a relatively low concentration, which activates six glomeruli. By silencing individual glomeruli, here we show that the absence of activity in two glomeruli, DM1 and VA2, markedly reduces attraction. Conversely, when each of these two glomeruli was selectively activated, flies showed as robust an attraction to vinegar as wild-type flies. Notably, a higher concentration of vinegar excites an additional glomerulus and is less attractive to flies. We show that activation of the extra glomerulus is necessary and sufficient to mediate the behavioural switch. Together, these results indicate that individual glomeruli, rather than the entire pattern of active glomeruli, mediate innate behavioural output.

  11. Gene expression profiling in glomeruli of diabetic nephropathy rat.

    Science.gov (United States)

    Zhang, Qian; Xiao, Xinhua; Li, Ming; Li, Wenhui; Yu, Miao; Zhang, Huabing; Sun, Xiaofang; Mao, Lili; Xiang, Hongding

    2012-08-01

    Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease (ESRD) as the burden of diabetes increases worldwide. To find improved intervention strategies for this disease, it is necessary to investigate the molecular mechanisms involved. To obtain more insight into processes that lead to DN, mRNA expression profiles of diabetic and normal glomeruli from rat kidneys were compared. Rats were divided into a control group and a DN group randomly. The DN group was injected with streptozotocin. Fasting blood glucose (FBG) and weight were measured monthly. On the 12th week, blood samples were collected and analyzed for plasma creatinine and blood urea nitrogen (BUN). Glomeruli were isolated and Illumina Rat Ref-12 V1.0 Expression Beadchip gene array was performed. Quantitative realtime polymerase chain reaction (Q-RT-PCR) was used to confirm the results of gene array for a selected number of genes. We found FBG, 24-h urinary albumin, serum creatinine and BUN were significantly increased, while urinary creatinine and body weight were significantly decreased in the DN group. Glomeruli from the DN group had 624 genes with differential expression. DAVID (Database for Annotation, Visualization and integrated Discovery) analysis showed that the three most enriched terms were 'cytosol' (GO:0005829), 'translational elongation' (GO:0006414) and 'mitochondion' (GO:0005739). Those genes could be mapped to eight pathways. The most common type of enriched pathway was related to 'extracellular matrix (ECM)-receptor interaction'. Other pathways included those for 'ribosome', 'focal adhesion', 'oxidative phosphorylation', 'transforming growth factor (TGF)-beta signaling pathway', 'Parkinson's disease', 'Alzheimer's disease' and 'renin-angiotensin system'. Q-RT-PCR verified that Atp5b (F1-ATPase beta subunit), Col1a1 (collagen type 1 alpha 1), Cox6c (cytochrome c oxidase subunit VIc), Ndufs3 (NADH dehydrogenase [ubiquinone] Fe-S protein 3) and Tgfb1 (transforming

  12. Heparin/heparan sulphate interactions with complement-a possible target for reduction of renal function loss?

    NARCIS (Netherlands)

    Zaferani, Azadeh; Talsma, Ditmer; Richter, Mareike K. S.; Daha, Mohamed R.; Navis, Gerjan J.; Seelen, Marc A.; van den Born, Jacob

    2014-01-01

    Current management of end-stage renal failure is based on renal replacement therapy by dialysis or transplantation. Increased occurrence of renal failure in both native and transplanted kidneys indicates a need for novel therapies to stop or limit the progression of the disease. Acute kidney injury

  13. Low-dose targeted complement inhibition protects against renal disease and other manifestations of autoimmune disease in MRL/lpr mice.

    Science.gov (United States)

    Atkinson, Carl; Qiao, Fei; Song, Hongbin; Gilkeson, Gary S; Tomlinson, Stephen

    2008-01-15

    Complement appears to play a dual role in the progression of systemic lupus erythematosus, serving a beneficial role in enhancing immune complex clearance, while serving a pathogenic role in inducing local inflammation. To investigate these different roles of complement in a therapeutic setting, MRL/lpr mice were treated with the targeted murine C3 complement inhibitor, CR2-Crry, from 16 to 24 wk of age (after the development of proteinuria). The targeting moiety, CR2, binds to C3 breakdown products deposited at sites of complement activation and has the potential to provide complement inhibition locally without causing systemic inhibition. Administration of CR2-Crry i.v., at a dose of 0.25 mg once a week, was associated with a significant survival benefit, improved kidney function, and a significant reduction in glomerulonephritis and renal vasculitis. The presence of skin lesions and lung bronchiolar and vascular inflammation was also dramatically reduced by CR2-Crry treatment. CR2-Crry treatment also resulted in a significant reduction in autoantibody production, as measured by anti-dsDNA Ab levels, and did not cause an increase in circulating immune complex levels. These effects on autoimmunity and circulating immune complexes represent significant potential advantages over the use of Crry-Ig in MRL/lpr mice, a systemic counterpart of CR2-Crry. CR2-Crry localized preferentially to the kidneys in 16-wk MRL/lpr mice with a kidney-localized half-life of approximately 24 h. Thus, targeted complement inhibition at the C3 level is an effective treatment in murine lupus, even beginning after onset of disease.

  14. Association Between the Proportion of Sclerotic Glomeruli and Serum Creatinine in Primary Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ashraf FAKHRJOU

    2012-05-01

    Full Text Available Objective: To evaluate the possible correlation between the extent of sclerotic glomeruli and the level of serum creatinine and its clearance rate in patients with primary focal segmental glomerolusclerosis.Material and Method: In a cross-sectional study, 50 patients with biopsy-proven primary focal segmental glomerolusclerosis were recruited. The proportion of globally and segmentally sclerosed glomeruli was determined during the first histopathological examination of renal biopsy specimens. Correlations of these variables with on admission serum level of creatinine and its clearance rate were investigated.Results: Twenty-four males and 26 females with a mean age of 39.82±16.45 (range: 16-85 years were enrolled in the study. In a significant fashion, the proportions of segmental and global glomerulosclerosis were directly correlated with the serum level of creatinine and inversely with its clearance rate (r=-0.43 with p=0.002 and r=-0.45 with p=0.001, respectively.Conclusion: Apart from the degree of interstitial fibrosis, the serum level of creatinine and its clearance rate are well correlated with the proportions of both segmentally and globally sclerosed glomeruli in primary focal segmental glomerulosclerosis.

  15. Complement mediated renal inflammation induced by donor brain death : role of renal C5a-C5aR interaction

    NARCIS (Netherlands)

    van Werkhoven, M. B.; Damman, J.; van Dijk, M. C. R. F.; Daha, M. R.; de Jong, I. J.; Leliveld, A.; Krikke, C.; Leuvenink, H. G.; van Goor, H.; van Son, W. J.; Olinga, P.; Hillebrands, J. -L.; Seelen, M. A. J.

    2013-01-01

    Kidneys retrieved from brain-dead donors have impaired allograft function after transplantation compared to kidneys from living donors. Donor brain death (BD) triggers inflammatory responses, including both systemic and local complement activation. The mechanism by which systemic activated complemen

  16. Identification of Tubular Heparan Sulfate as a Docking Platform for the Alternative Complement Component Properdin in Proteinuric Renal Disease

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Hakvoort, Jelleke J.; Navis, Gerjan J.; van Goor, Harry; Daha, Mohamed R.; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2011-01-01

    Properdin binds to proximal tubular epithelial cells (PTEC) and activates the complement system via the alternative pathway in vitro. Cellular ligands for properdin in the kidney have not yet been identified. Because properdin interacts with solid-phase heparin, we investigated whether heparan sulfa

  17. The dual role of complement in the progression of renal disease in NZB/W F(1) mice and alternative pathway inhibition.

    Science.gov (United States)

    Sekine, Hideharu; Ruiz, Phillip; Gilkeson, Gary S; Tomlinson, Stephen

    2011-10-01

    Complement plays a dual role in the progression of systemic lupus erythematosus since it has important protective functions, such as the clearance of immune complexes and apoptotic cells, but is also a mediator of renal inflammation. To investigate this balance in a clinically relevant setting, we investigated how targeted inhibition of all complement pathways vs. targeted inhibition of only the alternative pathway impacts immune and therapeutic outcomes in NZB/W F(1) mice. Following onset of proteinuria, mice were injected twice weekly with CR2-fH (inhibits alternative pathway), CR2-Crry (inhibits all pathways at C3 activation step), sCR2 (C3d targeting vehicle) or saline. Sera were analyzed every 2 weeks for anti-dsDNA antibody levels, and urinary albumin excretion was determined. Kidneys were collected for histological evaluation at 32 weeks. Compared to the control group, all CR2-fH, CR2-Crry and sCR2 treated groups showed significantly reduced serum anti-dsDNA antibody levels and strong trends towards reduced glomerular IgG deposition levels. Glomerular C3 deposition levels were also significantly reduced in all three-treated groups. However, significant reductions of disease activity (albuminuria and glomerulonephritis) were only seen in the CR2-fH treated group. These data highlight the dual role played by complement in the pathogenesis of lupus, and demonstrate a benefit of selectively inhibiting the alternative complement pathway, presumably because of protective contributions from the classical and/or lectin pathways. The sCR2 targeting moiety appears to be contributing to therapeutic outcome via modulation of autoimmunity. Furthermore, these results are largely consistent with our previous data using the MRL/lpr lupus model, thus broadening the significance of these findings.

  18. Sundanese Complementation

    Science.gov (United States)

    Kurniawan, Eri

    2013-01-01

    The focus of this thesis is the description and analysis of clausal complementation in Sundanese, an Austronesian language spoken in Indonesia. The thesis examined a range of clausal complement types in Sundanese, which consists of (i) "yen/(wi)rehna" "that" complements, (ii) "pikeun" "for" complements,…

  19. Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli.

    Science.gov (United States)

    Ilatovskaya, Daria V; Palygin, Oleg; Levchenko, Vladislav; Staruschenko, Alexander

    2015-06-27

    Podocytes (renal glomerular epithelial cells) are known to regulate glomerular permeability and maintain glomerular structure; a key role for these cells in the pathogenesis of various renal diseases has been established since podocyte injury leads to proteinuria and foot process effacement. It was previously reported that various endogenous agents may cause a dramatic overload in intracellular Ca(2+) concentration in podocytes, presumably leading to albuminuria, and this likely occurs via calcium-conducting ion channels. Therefore, it appeared important to study calcium handling in the podocytes both under normal conditions and in various pathological states. However, available experimental approaches have remained somewhat limited to cultured and transfected cells. Although they represent a good basic model for such studies, they are essentially extracted from the native environment of the glomerulus. Here we describe the methodology of studying podocytes as a part of the freshly isolated whole glomerulus. This preparation retains the functional potential of the podocytes, which are still attached to the capillaries; therefore, podocytes remain in the environment that conserves the major parts of the glomeruli filtration apparatus. The present manuscript elaborates on two experimental approaches that allow 1) real-time detection of calcium concentration changes with the help of ratiometric confocal fluorescence microscopy, and 2) the recording of the single ion channels activity in the podocytes of the freshly isolated glomeruli. These methodologies utilize the advantages of the native environment of the glomerulus that enable researchers to resolve acute changes in the intracellular calcium handling in response to applications of various agents, measure basal concentration of calcium within the cells (for instance, to evaluate disease progression), and assess and manipulate calcium conductance at the level of single ion channels.

  20. Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17.

    Science.gov (United States)

    Pagliari, Carla; Simões Quaresma, Juarez Antônio; Kanashiro-Galo, Luciane; de Carvalho, Leda Viegas; Vitoria, Webster Oliveira; da Silva, Wellington Luiz Ferreira; Penny, Ricardo; Vasconcelos, Barbara Cristina Baldez; da Costa Vasconcelos, Pedro Fernando; Duarte, Maria Irma Seixas

    2016-02-01

    Acute kidney injury is an unusual complication during dengue infection. The objective of this study was to better identify the characteristics of glomerular changes focusing on in situ immune cells and cytokines. An immunohistochemical assay was performed on 20 kidney specimens from fatal human cases of dengue hemorrhagic fever (DHF). It was observed a lymphomononuclear infiltrate, neutrophils and nuclear fragmentation in the glomeruli, hydropic degeneration, nuclear retraction, eosinophilic tubules and intense acute congestion. Sickle erythrocytes were frequent in glomeruli and inflammatory infiltrate. The glomeruli presented endothelial swelling and mesangial proliferation. Lymphocytes CD4+ predominated over CD8+ T cells, B cells and natural killer cells. There were also an expressive number of macrophagic CD68+ cells. S100, Foxp3 and CD123 cells were not identified. Cells expressing IL17 and IL18+ cytokines predominated in the renal tissues, while IL4, IL6, IL10, IL13, TNF-alpha and IFN-gamma were rarely visualized. The high number of cells expressing IL17 and IL18+ could reflect the acute inflammatory response and possibly contribute to the local lesion. CD8+ T cells could play a role in the cytotoxic response. DHF is a multifactorial disease of capillary leakage associated with a "Tsunami of cytokines expression". The large numbers of cells expressing IL17 seems to play a role favoring the increased permeability.

  1. Local interneurons define functionally distinct regions within lobster olfactory glomeruli

    Science.gov (United States)

    Wachowiak; Diebel; Ache

    1997-01-01

    Whole-cell recording coupled with biocytin injection revealed four types of interneurons intrinsic to the olfactory lobe (OL) of the spiny lobster Panulirus argus. Each type of neuron had a distinct pattern of arborization within the three anatomically defined regions of OL glomeruli (cap, subcap and base). Type I interneurons innervated all three regions, while types II, III and IV branched only in the cap, subcap and base, respectively. Type I interneurons responded to electrical stimulation of the antennular (olfactory) nerve with a burst of 1­20 action potentials and a 1­10 s depolarization. Type II (cap) interneurons responded to the same input with a burst of 1­3 action potentials followed by a shorter hyperpolarization. Type III (subcap) interneurons responded with a burst of 1­6 action potentials followed by a delayed, 0.5­4 s depolarization. Type IV (base) interneurons responded with a brief depolarization or a burst of 1­3 action potentials followed by a 1 s hyperpolarization. The regionalized arborization and the different response properties of the type II, III and IV interneurons strongly imply that lobster olfactory glomeruli contain functionally distinct regions, a feature that should be useful in understanding the multiple synaptic pathways involved in processing olfactory input.

  2. THE EFFECT OF UNILATERAL NEPHRECTOMY ON THE TOTAL NUMBER OF OPEN GLOMERULI IN THE RABBIT.

    Science.gov (United States)

    Moore, R A; Lukianoff, G F

    1929-07-31

    1. Under the experimental conditions employed, from 44 to 78 per cent of the glomeruli of the normal rabbit kidney contain circulating blood at any one moment. 2. After unilateral nephrectomy the number of glomeruli in the remaining kidney, which contain circulating blood, is increased to 91 to 99 per cent. 3. Compensation for the removal of one kidney is accomplished during the first 10 days at least, by an increase of the number of open glomeruli in the opposite kidney.

  3. Maxillary palp glomeruli and ipsilateral projections in the antennal lobe of Drosophila melanogaster

    Indian Academy of Sciences (India)

    K P Rajashekhar; V R Shamprasad

    2004-12-01

    The antennal lobe was examined by Golgi-silver impregnation to differentiate the glomeruli depending on the source and types of inputs. Thirty-five of the 43 ‘identified’ olfactory glomeruli were Golgi-silver impregnated in the present study. Seven glomeruli compared to three, reported previously, were found to be targets of maxillary palp chemosensory neurons. These include glomeruli VA3, VC2, VM5, VA7m/VA7l of the ventral antennal lobe and DC2, DC3, DM5 of the dorsal antennal lobe. The number of glomeruli receiving the maxillary palp sensory projections tallies with the number of Drosophila olfactory receptors (seven) reported to be expressed exclusively in the maxillary palp. Twenty-eight Golgi-impregnated glomeruli were found to receive input from the antennal nerve. The ratio of glomeruli serving the maxillary palp to those serving the antenna (∼ 1 : 5) matches with the ratio of Drosophila olfactory receptors expressed in these two olfactory organs respectively. In addition to glomerulus V, glomeruli VP1-3, VL1, VL2a/2p and VC3m/3l were found to receive ipsilateral projections. Thus, additional ipsilateral glomeruli have been identified.

  4. Substituting complements

    OpenAIRE

    Dari-Mattiacci, G.; Parisi, F.; Heller, M.

    2009-01-01

    The presence of multiple sellers in the provision of (nonsubstitutable) complementary goods leads to outcomes that are worse than those generated by a monopoly (with a vertically integrated production of complements), a problem known in the economic literature as complementary oligopoly and recently popularized in the legal literature as the tragedy of the anticommons. We ask the following question: how many substitutes for each complement are necessary to render the presence of multiple sell...

  5. Rapidly progressive glomerulonephritis in a patient with renal amyloidosis: Case report and review of the literature

    OpenAIRE

    Anupama, Y. J.; Vankalakunti, M.

    2012-01-01

    Renal amyloidosis is characterized by progressive deposition of extracellular material, most commonly in the glomeruli. Most often, patients present with nephrotic range proteinuria and the disease progresses gradually to renal failure. Rapid worsening of renal functions is rare. We report a case of crescentic glomerulonephritis superimposed on amyloidosis, clinically presenting as rapidly progressive renal failure, and present a review of the literature.

  6. The olfactory bulb and the number of its glomeruli in the common marmoset (Callithrix jacchus).

    Science.gov (United States)

    Moriya-Ito, Keiko; Tanaka, Ikuko; Umitsu, Yoshitomo; Ichikawa, Masumi; Tokuno, Hironobu

    2015-04-01

    The olfactory system has been well studied in mammals such as mice and rats. However, few studies have focused on characterizing this system in diurnal primates that rely on their sense of smell to a lesser extent due to their ecological environment. In the present study, we determined the histological organization of the olfactory bulb in the common marmoset (Callithrix jacchus). We then constructed 3-dimensional models of the glomeruli of the olfactory bulb, and estimated the number of glomeruli. Olfactory glomeruli are the functional units of olfactory processing, and have been investigated in detail using mice. There are approximately 1800 glomeruli in a mouse hemibulb, and olfactory sensory neurons expressing one selected olfactory receptor converge onto one or two glomeruli. Because mice have about 1000 olfactory receptor genes, it is proposed that the number of glomeruli in mammals is nearly double that of olfactory receptor genes. The common marmoset carries only about 400 intact olfactory receptor genes. The present study revealed that the number of glomeruli in a marmoset hemibulb was approximately 1500-1800. This result suggests that the number of glomeruli is not positively correlated with the number of intact olfactory receptor genes in mammals.

  7. Substituting complements

    NARCIS (Netherlands)

    G. Dari-Mattiacci; F. Parisi

    2006-01-01

    The presence of multiple sellers in the provision of (nonsubstitutable) complementary goods leads to outcomes that are worse than those generated by a monopoly (with a vertically integrated production of complements), a problem known in the economic literature as complementary oligopoly and recently

  8. Substituting complements

    NARCIS (Netherlands)

    G. Dari-Mattiacci; F. Parisi

    2009-01-01

    The presence of multiple sellers in the provision of (nonsubstitutable) complementary goods leads to outcomes that are worse than those generated by a monopoly (with a vertically integrated production of complements), a problem known in the economic literature as complementary oligopoly and recently

  9. The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

    Directory of Open Access Journals (Sweden)

    Avi Z Rosenberg

    Full Text Available In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI.The number of glomeruli annotated was consistently higher than those reported (p<0.001; this difference was proportional to the number of glomeruli. In contrast, percent globally sclerotic were similar when calculated on total glomeruli, but greater in FSGS when calculated on average number of glomeruli (p<0.01. The difference in percent globally sclerotic between annotated and those recorded in pathology reports was significant when global sclerosis is greater than 40%.Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli.

  10. Complement receptor 2-mediated targeting of complement inhibitors to sites of complement activation.

    Science.gov (United States)

    Song, Hongbin; He, Chun; Knaak, Christian; Guthridge, Joel M; Holers, V Michael; Tomlinson, Stephen

    2003-06-01

    In a strategy to specifically target complement inhibitors to sites of complement activation and disease, recombinant fusion proteins consisting of a complement inhibitor linked to a C3 binding region of complement receptor (CR) 2 were prepared and characterized. Natural ligands for CR2 are C3 breakdown products deposited at sites of complement activation. Fusion proteins were prepared consisting of a human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the membrane complement inhibitors decay accelerating factor (DAF) or CD59. The targeted complement inhibitors bound to C3-opsonized cells, and all were significantly more effective (up to 20-fold) than corresponding untargeted inhibitors at protecting target cells from complement. CR2 fusion proteins also inhibited CR3-dependent adhesion of U937 cells to C3 opsonized erythrocytes, indicating a second potential anti-inflammatory mechanism of CR2 fusion proteins, since CR3 is involved in endothelial adhesion and diapedesis of leukocytes at inflammatory sites. Finally, the in vivo validity of the targeting strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF, targets to the kidney in mouse models of lupus nephritis that are associated with renal complement deposition.

  11. Morphometric Analysis of Nonsclerosed Glomeruli Size and Connective Tissue Content during the Aging Process

    Directory of Open Access Journals (Sweden)

    Vesna R. Stojanović

    2012-01-01

    Full Text Available Number of sclerotic glomeruli increases during the aging process. Consequently, majority of remained nonsclerosed glomeruli become hypertrophic and some of them sclerotic, too. The aim of this study was to quantify the size and connective tissue content of nonsclerosed glomeruli and to evaluate the percentage of hypertrophic ones in examined human cases during the aging. Material was right kidney's tissue of 30 cadavers obtained during routine autopsies. Cadavers were without previously diagnosed kidney disease, diabetes, hypertension, or any other systemic disease. Tissue specimens were routinely prepared for histological and morphometric analysis. Images of the histological slices were analyzed and captured under 400x magnification with digital camera. Further they were morphometrically and statistically analyzed with ImageJ and NCSS-PASS software. Multiple and linear regression of obtained morphometric parameters showed significant increase of glomerular connective tissue area and percentage. Cluster analysis showed the presence of two types of glomeruli. Second type was characterized with significantly larger size, connective tissue content, and significantly lower cellularity, in relation to the first type. Such glomeruli might be considered as hypertrophic. First type of glomeruli was predominant in younger cases, while second type of glomeruli was predominant in cases older than 55 years.

  12. Transvenous Renal Transplant Biopsy via a Transfemoral Approach.

    Science.gov (United States)

    Schmid, A; Jacobi, J; Kuefner, M A; Lell, M; Wuest, W; Mayer-Kadner, I; Benz, K; Schmid, M; Amann, K; Uder, M

    2013-05-01

    Percutaneous renal biopsy (PRB) of kidney transplants might be prevented by an elevated risk of bleeding or limited access to the allograft. In the following, we describe our initial experience with 71 transvenous renal transplant biopsies in 53 consecutive patients with unexplained reduced graft function who were considered unsuitable candidates for PRB (4.2% of all renal transplant biopsies at our institution). Biopsies were performed via the ipsilateral femoral vein with a renal biopsy set designed for transjugular renal biopsy (TJRB) of native kidneys. Positioning of the biopsy system within the transplant vein was achievable in 58 of 71 (81.7%) procedures. The specimen contained a median of 10 glomeruli (range 0-38). Tissue was considered as adequate for diagnosis in 56 of 57 (98.2%) biopsies. With respect to BANFF 50.9% of the specimen were adequate (>10 glomeruli), 47.4% marginally adequate (1-9 glomeruli) and 1.8% inadequate (no glomeruli). After implementation of real-time assessment all specimen contained glomeruli. One of the fifty-eight (1.8%) procedure-related major complications occurred (hydronephrosis requiring nephrostomy due to gross hematuria). Transfemoral renal transplant biopsy (TFRTB) is feasible and appears to be safe compared to PRB. It offers a useful new alternative for histological evaluation of graft dysfunction in selected patients with contraindications to PRB.

  13. Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.

    Science.gov (United States)

    Hoxha, Elion; Kneißler, Ursula; Stege, Gesa; Zahner, Gunther; Thiele, Ina; Panzer, Ulf; Harendza, Sigrid; Helmchen, Udo M; Stahl, Rolf A K

    2012-10-01

    The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA2R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy. Immunohistochemical analysis for PLA2R was faintly positive in kidneys from normal individuals and patients with various other glomerular injuries. In 61 of the 88 patients, PLA2R expression was strongly positive in glomeruli, and in 60 of these patients PLA2R autoantibodies were also detected in the serum. The 27 patients negative for serum PLA2R autoantibodies were faintly positive for PLA2R staining in glomeruli and in 15 of these patients a secondary cause was found. The remaining 12 patients have a yet undetected secondary cause of membranous nephropathy or have different glomerular antigens other than PLA2R. Thus, increased staining for PLA2R in glomeruli of renal biopsies tightly correlates with the presence of PLA2R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy.

  14. Analytical processing of binary mixture information by olfactory bulb glomeruli.

    Directory of Open Access Journals (Sweden)

    Max L Fletcher

    Full Text Available Odors are rarely composed of a single compound, but rather contain a large and complex variety of chemical components. Often, these mixtures are perceived as having unique qualities that can be quite different than the combination of their components. In many cases, a majority of the components of a mixture cannot be individually identified. This synthetic processing of odor information suggests that individual component representations of the mixture must interact somewhere along the olfactory pathway. The anatomical nature of sensory neuron input into segregated glomeruli with the bulb suggests that initial input of odor information into the bulb is analytic. However, a large network of interneurons within the olfactory bulb could allow for mixture interactions via mechanisms such as lateral inhibition. Currently in mammals, it is unclear if postsynaptic mitral/tufted cell glomerular mixture responses reflect the analytical mixture input, or provide the initial basis for synthetic processing with the olfactory system. To address this, olfactory bulb glomerular binary mixture representations were compared to representations of each component using transgenic mice expressing the calcium indicator G-CaMP2 in olfactory bulb mitral/tufted cells. Overall, dorsal surface mixture representations showed little mixture interaction and often appeared as a simple combination of the component representations. Based on this, it is concluded that dorsal surface glomerular mixture representations remain largely analytical with nearly all component information preserved.

  15. Complement inhibition by a novel membrane-targeted complement regulator improve renal function after rat kidney transplantation%新型补体抑制剂对大鼠肾移植缺血再灌注损伤的治疗作用

    Institute of Scientific and Technical Information of China (English)

    董隽; 王晓雄; 肖序仁; 洪宝发

    2001-01-01

    目的:观察新型补体抑制剂APT070对大鼠肾移植缺血再灌注损伤的治疗作用。方法:应用同基因大鼠肾脏移植模型,供肾移植前分别经观察药物APT070、对照药物APT898、相应蛋白多肽链及灌注液灌注,测定术后1~7 d肾脏功能。结果:肾移植术后1~2 d,AFT070灌注组移植肾功能明显好于对照组(P<0.05)。结论:APT 070作为一种可与肾脏组织结合的新型补体抑制剂,可减轻肾脏缺血再灌注损伤。%Objective:to observe the effects of a novel membrane-targeted complememt regulator on renal function after rat kidney transplantation. Methods:Donor kidneys were perfused with APT070, APT898, peptides, and Collins solution before isograft kidney transplantation. Renal functions were measured 1-7 days after transplantation. Results: Renal functions were significantly improved by perfusing donor kidney with APT070, P<0. 05. Conclusion: APT070, a novel membrane-targeted complement regulator can prevent ischemia/reperfusion injury and facilitate short term renal function in rat isograft model.

  16. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    Science.gov (United States)

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range.

  17. Elucidating the Neuronal Architecture of Olfactory Glomeruli in the Drosophila Antennal Lobe

    Directory of Open Access Journals (Sweden)

    Veit Grabe

    2016-09-01

    Full Text Available Olfactory glomeruli are morphologically conserved spherical compartments of the olfactory system, distinguishable solely by their chemosensory repertoire, anatomical position, and volume. Little is known, however, about their numerical neuronal composition. We therefore characterized their neuronal architecture and correlated these anatomical features with their functional properties in Drosophila melanogaster. We quantitatively mapped all olfactory sensory neurons (OSNs innervating each glomerulus, including sexually dimorphic distributions. Our data reveal the impact of OSN number on glomerular dimensions and demonstrate yet unknown sex-specific differences in several glomeruli. Moreover, we quantified uniglomerular projection neurons for each glomerulus, which unraveled a glomerulus-specific numerical innervation. Correlation between morphological features and functional specificity showed that glomeruli innervated by narrowly tuned OSNs seem to possess a larger number of projection neurons and are involved in less lateral processing than glomeruli targeted by broadly tuned OSNs. Our study demonstrates that the neuronal architecture of each glomerulus encoding crucial odors is unique.

  18. Automated renal histopathology: digital extraction and quantification of renal pathology

    Science.gov (United States)

    Sarder, Pinaki; Ginley, Brandon; Tomaszewski, John E.

    2016-03-01

    The branch of pathology concerned with excess blood serum proteins being excreted in the urine pays particular attention to the glomerulus, a small intertwined bunch of capillaries located at the beginning of the nephron. Normal glomeruli allow moderate amount of blood proteins to be filtered; proteinuric glomeruli allow large amount of blood proteins to be filtered. Diagnosis of proteinuric diseases requires time intensive manual examination of the structural compartments of the glomerulus from renal biopsies. Pathological examination includes cellularity of individual compartments, Bowman's and luminal space segmentation, cellular morphology, glomerular volume, capillary morphology, and more. Long examination times may lead to increased diagnosis time and/or lead to reduced precision of the diagnostic process. Automatic quantification holds strong potential to reduce renal diagnostic time. We have developed a computational pipeline capable of automatically segmenting relevant features from renal biopsies. Our method first segments glomerular compartments from renal biopsies by isolating regions with high nuclear density. Gabor texture segmentation is used to accurately define glomerular boundaries. Bowman's and luminal spaces are segmented using morphological operators. Nuclei structures are segmented using color deconvolution, morphological processing, and bottleneck detection. Average computation time of feature extraction for a typical biopsy, comprising of ~12 glomeruli, is ˜69 s using an Intel(R) Core(TM) i7-4790 CPU, and is ~65X faster than manual processing. Using images from rat renal tissue samples, automatic glomerular structural feature estimation was reproducibly demonstrated for 15 biopsy images, which contained 148 individual glomeruli images. The proposed method holds immense potential to enhance information available while making clinical diagnoses.

  19. Fluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions

    Institute of Scientific and Technical Information of China (English)

    Yong-hong SHI; Song ZHAO; Chen WANG; Ying LI; Hui-jun DUAN

    2007-01-01

    Aim: The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy. Methods: Streptozotocin- induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) by gavage. The animals were killed 4 weeks later and urine and blood samples were collected. The kidney tissues were removed and subjected to the following experiments. Rat glomerular mesangial cells (GMC) were cultured under normal glucose (5.5 mmol/L), high glucose (HG, 30 mmol/L), HG+AG490 (10 μmol/L), or HG with fluvastatin (1 pmol/L). Glomeruli or the GMC lysate was immunoprecipi- tated and/or immunoblotted with antibodies against Janus kinase 2 (JAK2), SH2- domain containing tyrosine phosphatase-1 (SHP-1), phosphospecific SHP-2, and signal transducer and activators of transcription (STAT), respectively. Trans- forming growth factor-β (TGF-β) mRNA was measured by RT-PCR. The protein synthesis of TGF-β1 and fibronectin in the culture medium of GMC was detected by ELISA. Results: The phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 increased significantly, and SHP-1 phosphorylation was reduced in glom- eruli of diabetic rats. Treatment with fluvastatin reduced phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 in glomeruli of diabetic rats, but it had no effect on the dephosphorylation of SHP-1. The exposure of GMC to 30 mmol/L glucose caused the activation of JAK2, STAT1, STAT3, and SHP-2. It upregulated TGF-β1 expression and increased protein synthesis of fibronectin. These high glucose-induced changes were suppressed by fluvastatin, as well as AG490, a JAK2 inhibitor. Conclusion: The regulation of the phosphorylation of JAK/STAT by fluvastatin may be responsible for its renal protective effects on diabetic nephropathy.

  20. 慢性失功移植肾组织中C4d的表达与意义%Expression and significance of complement split product C4d in chronic function loss renal allograft

    Institute of Scientific and Technical Information of China (English)

    赵亚昆; 祝清国; 仇宇; 张川; 刘伟; 高治忠

    2012-01-01

    x Objective To observe the expression of C4d in renal allograft with chronic function loss and to investigate the relationship of chronic active antibody-mediated rejection and chronic allograft function loss. Methods Twenty-seven renal allografts of chronic graft injury that had been proved by pathology were analyzed by immunohistochemistry and indirect immunofluores-cence was used to observe the deposition of complement split product C4d in peritubular capillaries. The relationship of C4d and transplant-related factors and prognosis of renal allograft were analyzed. Results All of the 27 patients, 55.6% were C4d deposition positive. The patients with C4d positive sharply demonstrated glomerular basement membrane layered and end-arterium incrassation, while C4d deposition negative group primary demonstrated that tubular atrophy, arteriolar intimal fibrosis and interstitial fibrosis. Incidence of presensitization ( PRA > 10% )and acute rejection were higher in patients with C4d positive, and onset of abnormal allograft function were also earlier in these patients than those of C4d deposition negative group (P <0. 05). Conclusion Chronic active antibody-mediated rejection is involved in chronic' renal function loss after the renal transplantation. Deposition of complement split product C4d in peritubular capillaries is very useful in diagnosis and treatment of antibody mediated rejection.%目的 观察慢性失功移植肾组织中C4d的表达,探讨抗体介导的慢性活动性排斥反应与慢性移植肾失功的关系.方法 对本院27例经病理证实为慢性移植物损伤的移植肾组织行免疫组化或间接免疫荧光法检测肾小管周围毛细血管中C4d的沉积,分析C4d沉积与移植相关因素和移植肾预后的关系.结果 27例患者中,C4d阳性率为55.6%.C4d沉积阳性组病理改变以肾小球基底膜分层和动脉内膜增厚为主,C4d沉积阴性组以肾小管萎缩和间质纤维化为主;C4d沉积阳

  1. Supernumerary Formation of Olfactory Glomeruli Induced by Chronic Odorant Exposure: A Constructivist Expression of Neural Plasticity

    Science.gov (United States)

    Valle-Leija, Pablo; Blanco-Hernández, Eduardo; Drucker-Colín, Rene; Gutiérrez-Ospina, Gabriel; Vidaltamayo, Roman

    2012-01-01

    It is accepted that sensory experience instructs the remodelling of neuronal circuits during postnatal development, after their specification has occurred. The story is less clear with regard to the role of experience during the initial formation of neuronal circuits, whether prenatal or postnatal, since this process is now supposed to be primarily influenced by genetic determinants and spontaneous neuronal firing. Here we evaluated this last issue by examining the effect that postnatal chronic exposure to cognate odorants has on the formation of I7 and M72 glomeruli, iterated olfactory circuits that are formed before and after birth, respectively. We took advantage of double knock-in mice whose I7 and M72 primary afferents express green fluorescent protein and β-galactosidase, correspondingly. Our results revealed that postnatal odorant chronic exposure led to the formation of permanent supernumerary I7 and M72 glomeruli in a dose and time dependent manner. Glomeruli in exposed mice were formed within the same regions of olfactory bulb and occupy small space volumes compared to the corresponding single circuits in non-exposed mice. We suggest that local reorganization of the primary afferents could participate in the process of formation of supernumerary glomeruli. Overall, our results support that sensory experience indeed instructs the permanent formation of specific glomeruli in the mouse olfactory bulb by means of constructivist processes. PMID:22511987

  2. Organization and distribution of glomeruli in the bowhead whale olfactory bulb

    Directory of Open Access Journals (Sweden)

    Takushi Kishida

    2015-04-01

    Full Text Available Although modern baleen whales (Mysticeti retain a functional olfactory system that includes olfactory bulbs, cranial nerve I and olfactory receptor genes, their olfactory capabilities have been reduced to a great degree. This reduction likely occurred as a selective response to their fully aquatic lifestyle. The glomeruli that occur in the olfactory bulb can be divided into two non-overlapping domains, a dorsal domain and a ventral domain. Recent molecular studies revealed that all modern whales have lost olfactory receptor genes and marker genes that are specific to the dorsal domain. Here we show that olfactory bulbs of bowhead whales (Balaena mysticetus lack glomeruli on the dorsal side, consistent with the molecular data. In addition, we estimate that there are more than 4,000 glomeruli elsewhere in the bowhead whale olfactory bulb, which is surprising given that bowhead whales possess only 80 intact olfactory receptor genes. Olfactory sensory neurons that express the same olfactory receptors in rodents generally project to two specific glomeruli in an olfactory bulb, implying an approximate 1:2 ratio of the number of olfactory receptors to the number of glomeruli. Here we show that this ratio does not apply to bowhead whales, reiterating the conceptual limits of using rodents as model organisms for understanding the initial coding of odor information among mammals.

  3. [Oligomeganephronic renal hypoplasia complicated by glomerulonephritis].

    Science.gov (United States)

    Kan'shina, N F; Rykov, V A; Lakhno, P A

    1990-01-01

    Clinico-anatomical data of a rare condition congenital oligomeganephronic renal hypoplasia with a glomerulonephritis as a complication are available for a 13-year-old girl who died of chronic renal failure. Large aglomerular zones consisting of primitive canaliculi in a loose stroma were observed in kidneys that were decreased in size. The glomeruli were few in number, some of them of a large size (2-2.5-fold), firmly attached to the capsule, with pronounced extracapillary proliferation.

  4. High salt intake in pregnancy alters maturation of glomeruli in the rat offspring

    Directory of Open Access Journals (Sweden)

    Nadezda Koleganova

    2012-06-01

    Full Text Available There is currently discussion on the optimal salt intake and uncertainty whether both high and low salt intake is associated with adverse effects. One aspect has so far not be considered, i.e. the potential impact of salt intake during pregnancy on kidney function and blood pressure in the offspring. Faulty fetal programming, amongst others by high or low salt intake, leads to alterations in kidney morphology and albuminuria in the offspring. A low number of glomeruli is known to cause high blood pressure later in life. It was the purpose of the present study to clarify whether very high (or low salt intakes in pregnancy affect kidney development in the offspring. Sprague-Dawley rats were fed normal (0.15%, medium (1.3%, or high (8.0% salt diet during pregnancy and weaning. The number of glomeruli (mature, immature, and S-shape bodies was assessed at 1 week postnatally. The expression of proteins of interest was assessed (by western blotting at 1 week postnatally and at term. There was no difference between the groups with respect to litter size, birth weight, and placenta size. At age 1 week the number of S-shaped bodies was significantly lower (405±308 and the number of mature glomeruli (818±405 and layers of developing glomeruli (7.1±0.6 was significantly higher in the offspring of mothers on high-salt compared to the medium or low salt groups (1044±490, 460±304, and 5.9±0.9 respectively. As a net result the total number of glomeruli was significantly lower in the offspring of mothers on high-salt (9476±1264 compared to the medium or low salt groups (11175±1920. At 1 week of age in the offspring of mothers on high salt the glomeruli were bigger compared to lower salt intake. The expression of Pax-2 (54±23% vs. 100±28% and FGF-2 (72±33% vs. 100±30% was significantly lower in the offspring of mothers on high-salt consistent with their causative role. We conclude that high maternal salt intake during pregnancy accelerates maturation

  5. Renal histology in polycystic kidney disease with incipient and advanced renal failure.

    Science.gov (United States)

    Zeier, M; Fehrenbach, P; Geberth, S; Möhring, K; Waldherr, R; Ritz, E

    1992-11-01

    Renal specimens were obtained at surgery or postmortem from patients with autosomal dominant polycystic kidney disease (ADPKD). Patients had either serum creatinine (SCr) below 350 mumol/liter (N = 12) or terminal renal failure (N = 50). Specimens were examined by two independent observers using a carefully validated score system. Mean glomerular diameters were similar in ADPKD patients with early renal failure (176 +/- 38 microns) and in victims of traffic accidents (177 +/- 23 microns), while they were significantly greater in diabetics with comparable renal function (205 +/- 16 microns). Glomerular diameters in ADPKD patients with terminal renal failure (191 +/- 45 microns) and with early renal failure were not significantly different. On average, 29% of glomeruli (17 to 62) were globally sclerosed in early renal failure, and 49% (19 to 93) in terminal renal failure. The proportion of glomeruli with segmental sclerosis was less than 4% in both groups. Marked vascular sclerosis, interstitial fibrosis, and tubular atrophy were present in early renal failure, and even more so in terminal renal failure. Interstitial infiltrates were scarce and consisted mainly of CD4 positive lymphocytes and CD68 positive macrophages. Immunestaining with monoclonal renin antibodies showed an increased juxtaglomerular index and expression of renin by arterioles adjacent to cysts, as well as by cyst wall epithelia. The data show more severe vascular and interstitial, but not glomerular, changes in ADPKD with advanced as compared to early renal failure.

  6. Complement system in zebrafish.

    Science.gov (United States)

    Zhang, Shicui; Cui, Pengfei

    2014-09-01

    Zebrafish is recently emerging as a model species for the study of immunology and human diseases. Complement system is the humoral backbone of the innate immune defense, and our knowledge as such in zebrafish has dramatically increased in the recent years. This review summarizes the current research progress of zebrafish complement system. The global searching for complement components in genome database, together with published data, has unveiled the existence of all the orthologues of mammalian complement components identified thus far, including the complement regulatory proteins and complement receptors, in zebrafish. Interestingly, zebrafish complement components also display some distinctive features, such as prominent levels of extrahepatic expression and isotypic diversity of the complement components. Future studies should focus on the following issues that would be of special importance for understanding the physiological role of complement components in zebrafish: conclusive identification of complement genes, especially those with isotypic diversity; analysis and elucidation of function and mechanism of complement components; modulation of innate and adaptive immune response by complement system; and unconventional roles of complement-triggered pathways.

  7. Pathological interstitial vascular proliferation adjacent to glomeruli in immunoglobulin a nephropathy

    Directory of Open Access Journals (Sweden)

    Honami Mori

    2016-01-01

    Full Text Available We detected an increase in small arterioles around glomeruli, particularly adjacent to tuft adhesive lesions in immunoglobulin A nephropathy (IgAN, for the 1 st time, as far as we know. We labeled these as periglomerular microarterioles (PGMAs. This study aimed to clarify the pathological significance of PGMAs. Sixty-two patients with IgAN and 19 controls with minor glomerular abnormalities without proteinuria were evaluated in this study. The number of PGMAs located between the Bowman′s capsule and the adjoining tubules was counted for each glomerulus. The mean number of PGMAs per glomerulus in cases of IgAN was significantly higher than those of the controls (0.530 ± 0.477 vs. 0.240 ± 0.182, P <0.05. Serial sections showed that most of the PGMAs were in contact with adjacent glomeruli (71.8%, through tuft adhesive lesions (52.1%, or the vascular pole (19.7%. By single regression analysis, the number of PGMAs was found to be positively correlated with the incidence of glomerular tuft adhesion, glomerular sclerosis, or the area of interstitial fibrosis in IgAN. By multiple regression analysis, the incidence of glomerular tuft adhesion was found to be the only independent pathological feature to correlate with the number of PGMAs (P = 0.0006. We have noticed the existence of PGMAs around glomeruli as a pathological finding of IgAN. Furthermore, the number of PGMAs was associated with the incidence of tuft adhesive lesion in glomeruli of IgAN although there was no relationship between the presence of PGMAs and clinical parameters including urinary protein excretion or creatinine clearance in the present study.

  8. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

    OpenAIRE

    Rosangela Silva Rigo; Cristiano Marcelo Espínola Carvalho; Michael Robin Honer; Gisele Braziliano de Andrade; Iandara Shetter Silva; Leonardo Rigo; Helen Rezende Figueiredo; Wanessa Teixeira Gomes Barreto

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic...

  9. Complement and autoimmunity.

    Science.gov (United States)

    Ballanti, Eleonora; Perricone, Carlo; Greco, Elisabetta; Ballanti, Marta; Di Muzio, Gioia; Chimenti, Maria Sole; Perricone, Roberto

    2013-07-01

    The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.

  10. Defining the complement biomarker profile of c3 glomerulopathy

    DEFF Research Database (Denmark)

    Zhang, Yuzhou; Nester, Carla M; Martin, Bertha;

    2014-01-01

    BACKGROUND AND OBJECTIVES: C3 glomerulopathy (C3G) applies to a group of renal diseases defined by a specific renal biopsy finding: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism involves abnormal control of the alternative complement pathway...

  11. Molecules Great and Small: The Complement System.

    Science.gov (United States)

    Mathern, Douglas R; Heeger, Peter S

    2015-09-04

    The complement cascade, traditionally considered an effector arm of innate immunity required for host defense against pathogens, is now recognized as a crucial pathogenic mediator of various kidney diseases. Complement components produced by the liver and circulating in the plasma undergo activation through the classical and/or mannose-binding lectin pathways to mediate anti-HLA antibody-initiated kidney transplant rejection and autoantibody-initiated GN, the latter including membranous glomerulopathy, antiglomerular basement membrane disease, and lupus nephritis. Inherited and/or acquired abnormalities of complement regulators, which requisitely limit restraint on alternative pathway complement activation, contribute to the pathogenesis of the C3 nephropathies and atypical hemolytic uremic syndrome. Increasing evidence links complement produced by endothelial cells and/or tubular cells to the pathogenesis of kidney ischemia-reperfusion injury and progressive kidney fibrosis. Data emerging since the mid-2000s additionally show that immune cells, including T cells and antigen-presenting cells, produce alternative pathway complement components during cognate interactions. The subsequent local complement activation yields production of the anaphylatoxins C3a and C5a, which bind to their respective receptors (C3aR and C5aR) on both partners to augment effector T-cell proliferation and survival, while simultaneously inhibiting regulatory T-cell induction and function. This immune cell-derived complement enhances pathogenic alloreactive T-cell immunity that results in transplant rejection and likely contributes to the pathogenesis of other T cell-mediated kidney diseases. C5a/C5aR ligations on neutrophils have additionally been shown to contribute to vascular inflammation in models of ANCA-mediated renal vasculitis. New translational immunology efforts along with the development of pharmacologic agents that block human complement components and receptors now permit

  12. HUS and the case for complement.

    Science.gov (United States)

    Conway, Edward M

    2015-10-29

    Hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy that is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Excess complement activation underlies atypical HUS and is evident in Shiga toxin-induced HUS (STEC-HUS). This Spotlight focuses on new knowledge of the role of Escherichia coli-derived toxins and polyphosphate in modulating complement and coagulation, and how they affect disease progression and response to treatment. Such new insights may impact on current and future choices of therapies for STEC-HUS.

  13. Binding of 125I-insulin to the isolated glomeruli of rat kidney.

    Science.gov (United States)

    Kurokawa, K; Silverblatt, F J; Klein, K L; Wang, M S; Lerner, R L

    1979-11-01

    To investigate a possible action of insulin on the glomerulus, the binding 125I-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22 degrees C, 125I-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was less than 25% of total binding. A small fraction of 125I-insulin was degraded during incubation. This binding was specific to insulin in that it was inhibited by unlabeled porcine and beef insulins and to a lesser extent by porcine proinsulin and desalanine-desasparagine insulin, but not by glucagon, parathyroid hormone, vasopressin, calcitonin, and angiotensin II. Increasing concentrations of nonlabeled insulin displaced 125I-insulin binding in a dose-dependent fashion. Scatchard plot of the data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that demonstrate negative cooperativity. The addition of excess nonlabeled insulin to the glomeruli preincubated with 125I-insulin resulted in a rapid dissociation of approximately or equal to 70% of bound 125I-insulin. Insulin decreased the increments in glomerular cyclic AMP levels by epinephrine and by prostaglandin E2, but not those by histamine. These data showed the presence of specific insulin receptors in the glomeruli, and that insulin action may be, at least in part, through modulation of glomerular cyclic AMP concentrations. Such action of insulin may underlie the alteration in glomerular ultrafiltration and the glomerular ultrafiltration and the development of glomerular lesions in diabetes mellitus, a disease in which insulin deficiency or the tissue resistance to insulin exists.

  14. Extraction of glomeruli in whole slide imaging of kidney biopsy specimens

    Science.gov (United States)

    Ishikawa, Masahiro; Watanabe, Sumire; Honda, Natsuki; Kobayashi, Naoki; Abe, Tokiya; Hashiguchi, Akinori; Sakamoto, Michiie

    2017-03-01

    The pathological diagnosis of a transplanted kidney is made on Banff Classification in order to gain an accurate understanding of the condition of the kidney. This type of diagnosis is extremely difficult and, thus, a variety of methods for diagnosis, including diagnosis by electron microscope, are being considered at present. Quantification of the diagnostic information derived by image processing is required for such purposes. This study proposes an automatic extraction method for normal glomeruli for the purpose of quantifying Elastica Van Gieson(EVG)-stained pathology specimens. In addition, we provide a report on the package of methods that we have created for the extraction of the glomerulus in the cortex.

  15. The Expression Profile of Complement Components in Podocytes.

    Science.gov (United States)

    Li, Xuejuan; Ding, Fangrui; Zhang, Xiaoyan; Li, Baihong; Ding, Jie

    2016-03-30

    Podocytes are critical for maintaining the glomerular filtration barrier and are injured in many renal diseases, especially proteinuric kidney diseases. Recently, reports suggested that podocytes are among the renal cells that synthesize complement components that mediate glomerular diseases. Nevertheless, the profile and extent of complement component expression in podocytes remain unclear. This study examined the expression profile of complement in podocytes under physiological conditions and in abnormal podocytes induced by multiple stimuli. In total, 23/32 complement component components were detected in podocyte by conventional RT-PCR. Both primary cultured podocytes and immortalized podocytes expressed the complement factors C1q, C1r, C2, C3, C7, MASP, CFI, DAF, CD59, C4bp, CD46, Protein S, CR2, C1qR, C3aR, C5aR, and Crry (17/32), whereas C4, CFB, CFD, C5, C6, C8, C9, MBL1, and MBL2 (9/32) complement factors were not expressed. C3, Crry, and C1q-binding protein were detected by tandem mass spectrometry. Podocyte complement gene expression was affected by several factors (puromycin aminonucleoside (PAN), angiotensin II (Ang II), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β)). Representative complement components were detected using fluorescence confocal microscopy. In conclusion, primary podocytes express various complement components at the mRNA and protein levels. The complement gene expressions were affected by several podocyte injury factors.

  16. Complement in autoimmune diseases.

    Science.gov (United States)

    Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit

    2017-02-01

    The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli. However, all the 3 pathways converge on Complement C3. Cleavage of C3 and C5 successively leads to the production of the membrane attack complex which is final common effector. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases. But the complement has also been bemusedly described as the proverbial "double edged sword". On one hand, complement is the final effector of tissue injury in autoimmune diseases and on the other, deficiencies of some components of the complement can result in autoimmune diseases. Currently available tools such as enzyme based immunoassays for functional assessment of complement pathways, flow cytometry, next generation sequencing and proteomics-based approaches provide an exciting opportunity to study this ancient yet mysterious element of innate immunity.

  17. Complement in hemolytic anemia.

    Science.gov (United States)

    Brodsky, Robert A

    2015-01-01

    Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

  18. Integration of the antennal lobe glomeruli and three projection neurons in the standard brain atlas of the moth Heliothis virescens

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    Bjarte B Løfaldli

    2010-02-01

    Full Text Available Digital three dimensional standard brain atlases are valuable tools for integrating neuroimaging data of different preparations. In insects, standard brain atlases of five species are available, including the atlas of the female Heliothis virescens moth brain. Like for the other species, the antennal lobes of the moth brain atlas were integrated as one material identity without internal structures. Different from the others, the H. virescens standard brain atlas exclusively included the glomerular layer of the antennal lobe. This was an advantage in the present study for performing a direct registration of the glomerular layer of individual preparations into the standard brain. We here present the H. virescens female standard brain atlas with a new model of the antennal lobe glomeruli integrated into the atlas, i.e. with each of the 66 glomeruli identified and labelled with a specific number. The new model differs from the previous H. virescens antennal lobe model both in respect to the number of glomeruli and the numbering system; the latter according to the system used for the antennal lobe atlases of two other heliothine species. For identifying female specific glomeruli comparison with the male antennal lobe was necessary. This required a new male antennal lobe atlas, included in this paper. As demonstrated by the integration of three antennal lobe projection neurons of different preparations, the new standard brain atlas with the integrated glomruli is a helpful tool for determining the glomeruli innervated as well as the relative position of the axonal projections in the protocerebrum.

  19. Retronasal odor concentration coding in glomeruli of the rat olfactory bulb

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    ShreeHari eGautam

    2014-10-01

    Full Text Available The mammalian olfactory system processes odorants presented orthonasally (inhalation through the nose and also retronasally (exhalation, enabling identification of both external as well as internal objects during food consumption. There are distinct differences between ortho- and retronasal air flow patterns, psychophysics, multimodal integration and glomerular responses. Recent work indicates that rats can also detect odors retronasally, that rats can associate retronasal odors with tastes, and that their olfactory bulbs (OBs can respond to retronasal odorants but differently than to orthonasal odors. To further characterize retronasal OB input activity patterns, experiments here focus on determining the effects of odorant concentration on glomerular activity by monitoring calcium activity in the dorsal OB of rats using a dextran-conjugated calcium-sensitive dye in vivo. Results showed reliable concentration-response curves that differed between odorants, and recruitment of additional glomeruli, as odorant concentration increases. We found evidence of different concentration-response functions between glomeruli, that in turn depended on odor. Further, the relation between dynamics and concentration differed remarkably among retronasal odorants. These dynamics are suggested to reduce the odor map ambiguity based on response amplitude. Elucidating the coding of retronasal odor intensity is fundamental to the understanding of feeding behavior and the neural basis of flavor. These data further establish and refine the rodent model of flavor neuroscience.

  20. Retronasal odor concentration coding in glomeruli of the rat olfactory bulb

    Science.gov (United States)

    Gautam, Shree Hari; Short, Shaina M.; Verhagen, Justus V.

    2014-01-01

    The mammalian olfactory system processes odorants presented orthonasally (inhalation through the nose) and also retronasally (exhalation), enabling identification of both external as well as internal objects during food consumption. There are distinct differences between ortho- and retronasal air flow patterns, psychophysics, multimodal integration, and glomerular responses. Recent work indicates that rats can also detect odors retronasally, that rats can associate retronasal odors with tastes, and that their olfactory bulbs (OBs) can respond to retronasal odorants but differently than to orthonasal odors. To further characterize retronasal OB input activity patterns, experiments here focus on determining the effects of odor concentration on glomerular activity by monitoring calcium activity in the dorsal OB of rats using a dextran-conjugated calcium-sensitive dye in vivo. Results showed reliable concentration-response curves that differed between odorants, and recruitment of additional glomeruli, as odor concentration increased. We found evidence of different concentration-response functions between glomeruli, that in turn depended on odor. Further, the relation between dynamics and concentration differed remarkably among retronasal odorants. These dynamics are suggested to reduce the odor map ambiguity based on response amplitude. Elucidating the coding of retronasal odor intensity is fundamental to the understanding of feeding behavior and the neural basis of flavor. These data further establish and refine the rodent model of flavor neuroscience. PMID:25386123

  1. orco Mutagenesis Causes Loss of Antennal Lobe Glomeruli and Impaired Social Behavior in Ants.

    Science.gov (United States)

    Trible, Waring; Olivos-Cisneros, Leonora; McKenzie, Sean K; Saragosti, Jonathan; Chang, Ni-Chen; Matthews, Benjamin J; Oxley, Peter R; Kronauer, Daniel J C

    2017-08-10

    Life inside ant colonies is orchestrated with diverse pheromones, but it is not clear how ants perceive these social signals. It has been proposed that pheromone perception in ants evolved via expansions in the numbers of odorant receptors (ORs) and antennal lobe glomeruli. Here, we generate the first mutant lines in the clonal raider ant, Ooceraea biroi, by disrupting orco, a gene required for the function of all ORs. We find that orco mutants exhibit severe deficiencies in social behavior and fitness, suggesting they are unable to perceive pheromones. Surprisingly, unlike in Drosophila melanogaster, orco mutant ants also lack most of the ∼500 antennal lobe glomeruli found in wild-type ants. These results illustrate that ORs are essential for ant social organization and raise the possibility that, similar to mammals, receptor function is required for the development and/or maintenance of the highly complex olfactory processing areas in the ant brain. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Renal involvement in antiphospholipid syndrome.

    Science.gov (United States)

    Sciascia, Savino; Cuadrado, Maria José; Khamashta, Munther; Roccatello, Dario

    2014-05-01

    Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.

  3. Wegener's granulomatosis with renal involvement: patient survival and correlations between initial renal function, renal histology, therapy and renal outcome.

    Science.gov (United States)

    Andrassy, K; Erb, A; Koderisch, J; Waldherr, R; Ritz, E

    1991-04-01

    Patient survival and renal outcome were followed in 25 patients with biopsy confirmed Wegener's granulomatosis and renal involvement. Fourteen out of 25 patients required dialysis on admission, 11/25 patients did not. All patients were treated with a novel protocol comprising methylprednisolone and cyclophosphamide. The median follow-up observation was 36 months (12-113 months). With the exception of 1 patient (who died from causes not related to Wegener's granulomatosis) all patients are alive. Among the patients initially requiring dialysis (n = 14) 4 are in terminal renal failure after 0, 7, 21 and 38 months respectively. In the nondialysis group (n = 11) only 1 patient subsequently required chronic dialysis 30 months after clinical admission. Renal failure was due to non-compliance with immunosuppressive therapy in at least 2 patients. Percentage of obsolescent glomeruli and the degree of tubulointerstitial lesions, but not active glomerular lesions (crescents, necroses) predicted renal outcome. The major cause of renal functional impairment was relapse of Wegener's granulomatosis usually within 2 years after clinical remission. Therefore prolonged treatment with cyclophosphamide for at least 2 years after clinical remission is recommended. Two patients with initially negative immunohistology had a second renal biopsy which revealed de novo appearance of mesangial IgA deposits.

  4. The Complement System in Lupus Nephritis.

    Science.gov (United States)

    Birmingham, Daniel J; Hebert, Lee A

    2015-09-01

    The complement system is composed of a family of soluble and membrane-bound proteins that historically has been viewed as a key component of the innate immune system, with a primary role of providing a first-line defense against microorganisms. Although this role indeed is important, complement has many other physiological roles, including the following: (1) influencing appropriate immune responses, (2) disposing of waste in the circulation (immune complexes, cellular debris), and (3) contributing to damage of self-tissue through inflammatory pathways. These three roles are believed to be significant factors in the pathogenesis of systemic lupus erythematosus, particularly its renal manifestation (lupus nephritis), contributing both protective and damaging effects. In this review, we provide an overview of the human complement system and its functions, and discuss its intricate and seemingly contradictory roles in the pathogenesis of lupus nephritis.

  5. TMA: beware of complements.

    Science.gov (United States)

    Ricklin, Daniel; Cines, Douglas B

    2013-09-19

    In this issue of Blood, Jodele and colleagues report that defective complement regulation contributes to the development of thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) with important implications for diagnosis and management of this severe clinical complication.

  6. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    OpenAIRE

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

    The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the a...

  7. Can focused US with a diagnostic US contrast agent favorably affect renal function?

    Science.gov (United States)

    Sica, Domenic A

    2009-12-01

    Focused ultrasonography (US) with simultaneous administration of a US microbubble contrast agent was used to transiently increase the glomerular filtration rate while altering the sieving properties of glomeruli in normal rabbits. In its current form, this process has very limited application potential to states of abnormal renal function.

  8. Finite Complements in English

    Institute of Scientific and Technical Information of China (English)

    Ronald W. Langacker

    2008-01-01

    This paper explores the conceptual basis of finite complimentation in English.It first considem the distinguishing property of a finite clause,namely grounding,effeeted by tense and the modals.Notions crucial for clausal grounding--including a reality conception and the striving for control at the effective and epistemic levelsalso figure in the semantic import of eomplementation.An essential feature of complement constructions is the involvement of multiple conceptualizers,each with their own conception of reality.The different types of complement and their grammatical markings can be characterized on this basis.Finite complements differ from other types by virtue of expressing an autonomous proposition capable of being apprehended by multiple conceptualizers,each from their own vantage point.Acognitive model representing phases in the striving for epistemic control provides a partial basis for the semantic description of predicates taking finite complements.The same model supports the description of both personal and impersonal complement constructions.

  9. Secondary renal amyloidosis in a patient of pulmonary tuberculosis and common variable immunodeficiency

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    Balwani Manish R

    2015-04-01

    Full Text Available Common variable immunodeficiency (CVID usually manifests in the second or third decade of life with recurrent bacterial infections and hypoglobulinemia. Secondary renal amyloidosis with history of pulmonary tuberculosis is rare in CVID, although T cell dysfunction has been reported in few CVID patients. A 40-year-old male was admitted to our hospital with a 3-month history of recurrent respiratory infections and persistent pitting pedal edema. His past history revealed 3 to 5 episodes of recurrent respiratory tract infections and diarrhoea each year since last 20 years. He had been successfully treated for sputum positive pulmonary tuberculosis 8 years back. Laboratory studies disclosed high erythrocyte sedimentation rate (ESR, hypoalbuminemia and nephrotic range proteinuria. Serum immunoglobulin levels were low. CD4/CD8 ratio and CD3 level was normal. C3 and C4 complement levels were normal. Biopsy revealed amyloid A (AA positive secondary renal amyloidosis. Glomeruli showed variable widening of mesangial regions with deposition of periodic schiff stain (PAS pale positive of pink matrix showing apple green birefringence on Congo-red staining. Immunohistochemistry was AA stain positive. Immunofluorescence microscopy revealed no staining with anti-human IgG, IgM, IgA, C3, C1q, kappa and lambda light chains antisera. Patient was treated symptomatically for respiratory tract infection and was discharged with low dose angiotensin receptor blocker. An old treated tuberculosis and chronic inflammation due to recurrent respiratory tract infections were thought to be responsible for AA amyloidosis. Thus pulmonary tuberculosis should be considered in differential diagnosis of secondary causes of AA renal amyloidosis in patients of CVID especially in endemic settings.

  10. Treatment with a Ca(2+) channel blocker, barnidipine, reduces platelet-derived growth factor B-chain mRNA in glomeruli of spontaneously hypertensive rats.

    Science.gov (United States)

    Hashimoto, M; Yamauchi, T; Ogura, T; Oishi, T; Mimura, Y; Otsuka, F; Kashihara, N; Makino, H

    1999-01-01

    We investigated the effect of barnidipine hydrochloride, a Ca(2+) channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-beta(1) in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR. The glomerular level of TGF-beta(1) mRNA expression was not affected by the treatment. Treatment with barnidipine significantly reduced the excretion of urinary protein. Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR.

  11. Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy.

    Science.gov (United States)

    Iwakura, Takamasa; Ohashi, Naro; Kato, Akihiko; Baba, Satoshi; Yasuda, Hideo

    2015-01-01

    Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. Autoantibodies against M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A), which mainly belong to the IgG4 subclass, were reported as associated antibodies for the development of MN. Although PLA2R is a major target antigen for idiopathic MN, the prevalence of MN patients seropositive for PLA2R in Japan is lower than that in other countries. In this study, we conducted immunohistochemical analysis of the presence of THSD7A and PLA2R in renal specimens of MN patients to estimate the prevalence of THSD7A/PLA2R-related idiopathic MN in Japan. Enhanced granular expression of THSD7A and PLA2R was detected in 9.1% and 52.7%, respectively, of the patients with idiopathic MN. Although none of patients with secondary MN displayed enhanced granular expression of THSD7A, 5.4% of them had enhanced granular expression of PLA2R. In conclusion, the prevalence of enhanced granular expression of THSD7A in the glomeruli of Japanese patients with idiopathic MN was higher than the prevalence of MN patients seropositive for THSD7A in USA and Europe.

  12. Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy.

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    Takamasa Iwakura

    Full Text Available Membranous nephropathy (MN is a leading cause of nephrotic syndrome in adults. Autoantibodies against M-type phospholipase A2 receptor (PLA2R and thrombospondin type-1 domain-containing 7A (THSD7A, which mainly belong to the IgG4 subclass, were reported as associated antibodies for the development of MN. Although PLA2R is a major target antigen for idiopathic MN, the prevalence of MN patients seropositive for PLA2R in Japan is lower than that in other countries. In this study, we conducted immunohistochemical analysis of the presence of THSD7A and PLA2R in renal specimens of MN patients to estimate the prevalence of THSD7A/PLA2R-related idiopathic MN in Japan. Enhanced granular expression of THSD7A and PLA2R was detected in 9.1% and 52.7%, respectively, of the patients with idiopathic MN. Although none of patients with secondary MN displayed enhanced granular expression of THSD7A, 5.4% of them had enhanced granular expression of PLA2R. In conclusion, the prevalence of enhanced granular expression of THSD7A in the glomeruli of Japanese patients with idiopathic MN was higher than the prevalence of MN patients seropositive for THSD7A in USA and Europe.

  13. The glomerulo-tubular junction: a target in renal diseases.

    Science.gov (United States)

    Lindop, G B M; Gibson, I W; Downie, T T; Vass, D; Cohen, E P

    2002-05-01

    Both global and segmental glomerulopathies may damage specific areas of the renal glomerulus. Diseases associated with glomerular hyperperfusion cause lesions at the vascular pole, while diseases associated with proteinuria often damage the tubular pole. Atubular glomeruli are now known to be plentiful in a variety of common renal diseases. These glomeruli are disconnected from their tubule at the tubular pole and therefore cannot participate in the production of urine. It is widely believed that the disconnection is a result of external compression by periglomerular fibrosis. However, the variable anatomy and cell populations within both the glomerulus and the beginning of the proximal tubule at the glomerulo-tubular junction may also have important roles to play in the response to damage at this sensitive site of the nephron.

  14. Laboratory tests for disorders of complement and complement regulatory proteins.

    Science.gov (United States)

    Shih, Angela R; Murali, Mandakolathur R

    2015-12-01

    The complement pathway is a cascade of proteases that is involved in immune surveillance and innate immunity, as well as adaptive immunity. Dysfunction of the complement cascade may be mediated by aberrations in the pathways of activation, complement regulatory proteins, or complement deficiencies, and has been linked to a number of hematologic disorders, including paroxysmal noctural hemoglobinuria (PNH), hereditary angioedema (HAE), and atypical hemolytic-uremic syndrome (aHUS). Here, current laboratory tests for disorders of the complement pathway are reviewed, and their utility and limitations in hematologic disorders and systemic diseases are discussed. Current therapeutic advances targeting the complement pathway in treatment of complement-mediated hematologic disorders are also reviewed.

  15. Complement analysis 2016: Clinical indications, laboratory diagnostics and quality control.

    Science.gov (United States)

    Prohászka, Zoltán; Nilsson, Bo; Frazer-Abel, Ashley; Kirschfink, Michael

    2016-11-01

    In recent years, complement analysis of body fluids and biopsies, going far beyond C3 and C4, has significantly enhanced our understanding of the disease process. Such expanded complement analysis allows for a more precise differential diagnosis and for critical monitoring of complement-targeted therapy. These changes are a result of the growing understanding of the involvement of complement in a diverse set of disorders. To appreciate the importance of proper complement analysis, it is important to understand the role it plays in disease. Historically, it was the absence of complement as manifested in severe infection that was noted. Since then complement has been connected to a variety of inflammatory disorders, such as autoimmune diseases and hereditary angioedema. While the role of complement in the rejection of renal grafts has been known longer, the significant impact of complement. In certain nephropathies has now led to the reclassification of some rare kidney diseases and an increased role for complement analysis in diagnosis. Even more unexpected is that complement has also been implicated in neural, ophtalmological and dermatological disorders. With this level of involvement in some varied and impactful health issues proper complement testing is clearly important; however, analysis of the complement system varies widely among laboratories. Except for a few proteins, such as C3 and C4, there are neither well-characterized standard preparations nor calibrated assays available. This is especially true for the inter-laboratory variation of tests which assess classical, alternative, or lectin pathway function. In addition, there is a need for the standardization of the measurement of complement activation products that are so critical in determining whether clinically relevant complement activation has occurred in vivo. Finally, autoantibodies to complement proteins (e.g. anti-C1q), C3 and C4 convertases (C3 and C4 nephritic factor) or to regulatory proteins

  16. Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

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    Jingsong Shi

    2016-01-01

    Full Text Available Objective. To investigate potential drugs for diabetic nephropathy (DN using whole-genome expression profiles and the Connectivity Map (CMAP. Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1 A total of 1065 DEGs (FDR 1.5 were found in late stage DN patients compared with early stage DN patients. (2 Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2, vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs, PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

  17. Retroperitoneoscopic renal biopsy in children

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    Carlos M. Jesus

    2007-08-01

    Full Text Available OBJECTIVE: We present our experience in a series of 17 consecutive pediatric patients submitted to retroperitoneal laparoscopic renal biopsy. MATERIALS AND METHODS: Retroperitoneal laparoscopic renal biopsy (LRB was performed in 5 boys and 12 girls. Mean age was 8.1 years and age range from 2 to 12. Two or three trocars were used to expose the inferior pole of the kidney, remove enough cortical parenchymal specimen and fulgurate the biopsy site. Assessment included surgical time, estimated blood loss, hospitalization period, analgesia requirements, complications and number of glomeruli present in the specimen. RESULTS: LRB was successfully performed in all 15 patients (88%. In two cases, LRB was not possible to be performed. One patient was converted to a transperitoneal laparoscopy due to tear in the peritoneum. The other patient had had previous abdominal surgery and, during retroperitoneal balloon dilation, the peritoneum was opened and the open biopsy was performed. A third patient had postoperatively a perirenal hematoma, which was solved spontaneously. Complication rate was 17.6% (3/17 cases. Mean operative time was 65 minutes, while mean estimated blood loss was 52 mL, mean hospital stay was 2.2 days and mean analgesic requirement was 100 mg of tramadol. The mean number of glomeruli present in the specimen was 60. CONCLUSION: Retroperitoneal laparoscopic renal biopsy in children is a simple, safe. Bleeding is still the most common complication. However, direct vision usually allows a safe control of this drawback. In our institution, laparoscopic approach is the chosen procedure in pediatric patients older than one - year - old.

  18. Complement-coagulation cross-talk: a potential mediator of the physiological activation of complement by low pH

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    Hany Ibrahim Kenawy

    2015-05-01

    Full Text Available The complement system is a major constituent of the innate immune system. It not only bridges innate and adaptive arms of the immune system but also links the immune system with the coagulation system. Current understanding of the role of complement has extended far beyond fighting of infections, and now encompasses maintenance of homeostasis, tissue regeneration and pathophysiology of multiple diseases. It has been known for many years that complement activation is strongly pH sensitive, but only relatively recently has the physiological significance of this been appreciated. Most complement assays are carried out at the physiological pH 7.4. However, pH in some extracellular compartments, for example renal tubular fluid in parts of the tubule, and extracellular fluid at inflammation loci, is sufficiently acidic to activate complement. The exact molecular mechanism of this activation is still unclear, but possible cross talk between the contact system and complement may exist at low pH with subsequent complement activation. The current article reviews the published data on the effect of pH on the contact system and complement activity, the nature of the pH sensor molecules, and the clinical implications of these effects. Of particular interest is chronic kidney disease (CKD accompanied by metabolic acidosis, in which therapeutic alkalinisation of urine has been shown significantly to reduce tubular complement activation products, an effect which may have important implications for slowing progression of CKD.

  19. Complement-Coagulation Cross-Talk: A Potential Mediator of the Physiological Activation of Complement by Low pH.

    Science.gov (United States)

    Kenawy, Hany Ibrahim; Boral, Ismet; Bevington, Alan

    2015-01-01

    The complement system is a major constituent of the innate immune system. It not only bridges innate and adaptive arms of the immune system but also links the immune system with the coagulation system. Current understanding of the role of complement has extended far beyond fighting of infections, and now encompasses maintenance of homeostasis, tissue regeneration, and pathophysiology of multiple diseases. It has been known for many years that complement activation is strongly pH sensitive, but only relatively recently has the physiological significance of this been appreciated. Most complement assays are carried out at the physiological pH 7.4. However, pH in some extracellular compartments, for example, renal tubular fluid in parts of the tubule, and extracellular fluid at inflammation loci, is sufficiently acidic to activate complement. The exact molecular mechanism of this activation is still unclear, but possible cross-talk between the contact system (intrinsic pathway) and complement may exist at low pH with subsequent complement activation. The current article reviews the published data on the effect of pH on the contact system and complement activity, the nature of the pH sensor molecules, and the clinical implications of these effects. Of particular interest is chronic kidney disease (CKD) accompanied by metabolic acidosis, in which therapeutic alkalinization of urine has been shown significantly to reduce tubular complement activation products, an effect, which may have important implications for slowing progression of CKD.

  20. Anatomical organization of antennal-lobe glomeruli in males and females of the scarab beetle Holotrichia diomphalia (Coleoptera: Melolonthidae).

    Science.gov (United States)

    Hu, Ji-Hua; Wang, Zhi-Ying; Sun, Fan

    2011-09-01

    The glomerular organization of the primary olfactory brain center, the antennal lobe, was studied in males and females of Holotrichia diomphalia adults using serial histological sections labeled by the reduced silver-stain technique. The results revealed an apparent sexual dimorphism. Whereas an enlarged cap-shaped glomerulus was found at the antennal nerve entrance into the antennal lobe in males, no such unit was present in females. Also the size of the antennal lobe differed between the sexes, the antennal lobe of males being larger than that of females. We estimated the total number of glomeruli at approximately 60 units in the female antennal lobe. In males, we could discriminate only those glomeruli that were located in the anterior area of the antennal lobe.

  1. Pharmacological characterization of the P2 receptors profile in the podocytes of the freshly isolated rat glomeruli.

    Science.gov (United States)

    Ilatovskaya, Daria V; Palygin, Oleg; Levchenko, Vladislav; Staruschenko, Alexander

    2013-11-15

    Calcium flux in the podocytes is critical for normal and pathophysiological regulation of these types of cells, and excessive calcium signaling results in podocytes damage and improper glomeruli function. Purinergic activation of P2 receptors is a powerful and rapid signaling process; however, the exact physiological identity of P2 receptors subtypes in podocytes remains essentially unknown. The goal of this study was to determine the P2 receptor profile in podocytes of the intact Sprague-Dawley rat glomeruli using available pharmacological tools. Glomeruli were isolated by differential sieving and loaded with Fluo-4/Fura Red cell permeable calcium indicators, and the purinergic response in the podocytes was analyzed with ratiometric confocal fluorescence measurements. Various P2 receptors activators were tested and compared with the effect of ATP, specifically, UDP, MRS 2365, bzATP, αβ-methylene, 2-meSADP, MRS 4062, and MRS 2768, were analyzed. Antagonists (MRS 2500, 5-BDBD, A438079, and NF 449) were tested when 10 μM ATP was applied as the EC50 for ATP activation of the calcium influx in the podocytes was determined to be 10.7 ± 1.5 μM. Several agonists including MRS 2365 and 2-meSADP caused calcium flux. Importantly, only the P2Y1-specific antagonist MRS 2500 (1 nM) precluded the effects of ATP concentrations of the physiological range. Immunohistochemical analysis confirmed that P2Y1 receptors are highly expressed in the podocytes. We conclude that P2Y1 receptor signaling is the predominant P2Y purinergic pathway in the glomeruli podocytes and P2Y1 might be involved in the pathogenesis of glomerular injury and could be a target for treatment of kidney diseases.

  2. Ultrasound-guided renal biopsy with automated biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Pil Yeob; Kwon, Jae Soo [Masan Samsung Hospital, Masan (Korea, Republic of)

    1998-01-01

    To elevate the diagnostic yield and complications of percutaneous ultrasound-guided renal biopsy using a biopsy gun in patients with diffuse renal disease. Using an automated biopsy gun mounted with a 16 G needle, biopsies were performed on 90 patients with diffuse renal disease. In a total of 95 biopsies, diagnostic yield, the mean number of glomeruli and frequency of complication were retrospectively analysed. Tissue adequate for histological diagnosis was obtained in 92 % of procedures. Mean glomerular yield was 8.3, and complications were seen in 26% of the procedures, 25 % of these were minor, and 1% were major. For the diagnosis of diffuse renal disease, ultrasound-guided percutaneous renal biopsy using an automated biopsy gun is accurate and safe. (author). 25 refs., 1 tab.

  3. Effects of Heparin on Transforming Growth Factor-β1 and Extracellular Matrix Components in the Glomeruli of Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    李元红; 彭荔薰; 张木勋; 欧阳金芝; 张建华

    2003-01-01

    The effects of heparin on the expression of transforming growth factor-β1 (TGF-β1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twenty-six rats were randomly divided into control group (C, n= 8), diabetic group (D, n=9), and diabetes+heparin group (DH, n=9). After 8-week therapy of heparin (200 U once daily by abdominal injection), TGF-β1, LN and FN expression in glomeruli was detected by immunohistochemical method. The results showed that the expression levels of TGF-β1, LN and FN were higher in group D than in group C. It was found that heparin could reduce 24-h urinary albumin excretion and inhibit overexpression of TGF-β1, LN and FN in glomeruli of diabetic rats. It suggested that the inhibitory effect of heparin on diabetic glomerular sclerosis was at least partly related with the inhibition of TGF-β1 expression.

  4. Material properties in complement activation

    DEFF Research Database (Denmark)

    Moghimi, S. Moein; Andersen, Alina Joukainen; Ahmadvand, Davoud

    2011-01-01

    -immune performance’ relationship studies in nanomedicine research at many fronts. The interaction between nanomaterials and the complement system is complex and regulated by inter-related factors that include nanoscale size, morphology and surface characteristics. Each of these parameters may affect complement...... activation differently and through different sensing molecules and initiation pathways. The importance of material properties in triggering complement is considered and mechanistic aspects discussed. Mechanistic understanding of complement events could provide rational approaches for improved material design...

  5. Resveratrol ameliorates renal damage, increases expression of heme oxygenase-1, and has anti-complement, anti-oxidative, and anti-apoptotic effects in a murine model of membranous nephropathy.

    Directory of Open Access Journals (Sweden)

    Chia-Chao Wu

    Full Text Available Idiopathic membranous nephropathy (MN is an autoimmune-mediated glomerulonephritis and a common cause of nephrotic syndrome in adults. There are limited available treatments for MN. We assessed the efficacy of resveratrol (RSV therapy for treatment of MN in a murine model of this disease.Murine MN was experimentally induced by daily subcutaneous administration of cationic bovine serum albumin, with phosphate-buffered saline used in control mice. MN mice were untreated or given RSV. Disease severity and pathogenesis was assessed by determination of metabolic and histopathology profiles, lymphocyte subsets, immunoglobulin production, oxidative stress, apoptosis, and production of heme oxygenase-1 (HO1.MN mice given RSV had significantly reduced proteinuria and a marked amelioration of glomerular lesions. RSV also significantly attenuated immunofluorescent staining of C3, although there were no changes of serum immunoglobulin levels or immunocomplex deposition in the kidneys. RSV treatment of MN mice also reduced the production of reactive oxygen species (ROS, reduced cell apoptosis, and upregulated heme oxygenase 1 (HO1. Inhibition of HO1 with tin protoporphyrin IX partially reversed the renoprotective effects of RSV. The HO1 induced by RSV maybe via Nrf2 signaling.Our results show that RSV increased the expression of HO1 and ameliorated the effects of membranous nephropathy in a mouse model due to its anti-complement, anti-oxidative, and anti-apoptotic effects. RSV appears to have potential as a treatment for MN.

  6. Microglia, Alzheimer's Disease, and Complement

    Directory of Open Access Journals (Sweden)

    Helen Crehan

    2012-01-01

    Full Text Available Microglia, the immune cell of the brain, are implicated in cascades leading to neuronal loss and cognitive decline in Alzheimer’s disease (AD. Recent genome-wide association studies have indicated a number of risk factors for the development of late-onset AD. Two of these risk factors are an altered immune response and polymorphisms in complement receptor 1. In view of these findings, we discuss how complement signalling in the AD brain and microglial responses in AD intersect. Dysregulation of the complement cascade, either by changes in receptor expression, enhanced activation of different complement pathways or imbalances between complement factor production and complement cascade inhibitors may all contribute to the involvement of complement in AD. Altered complement signalling may reduce the ability of microglia to phagocytose apoptotic cells and clear amyloid beta peptides, modulate the expression by microglia of complement components and receptors, promote complement factor production by plaque-associated cytokines derived from activated microglia and astrocytes, and disrupt complement inhibitor production. The evidence presented here indicates that microglia in AD are influenced by complement factors to adopt protective or harmful phenotypes and the challenge ahead lies in understanding how this can be manipulated to therapeutic advantage to treat late onset AD.

  7. The fate of nephrons in congenital and heritable renal disorders

    Directory of Open Access Journals (Sweden)

    Robert L. Chevalier

    2013-06-01

    Full Text Available Most chronic kidney disease in infants and children results from congenital anomalies of the kidneys and urinary tract, including obstructive nephropathy. Although less common, inherited disorders such as polycystic kidney disease (PKD and cystinosis also lead to progressive tubular injury and nephron loss. At the present time, therapies to slow progression of kidney disease are mainly directed renal interstitial fibrosis, a final common pathway. To target earlier events in congenital renal disorders, we have investigated in animal models the response of the renal proximal tubule, which appears to be particularly susceptible to injury. Unilateral ureteral obstruction (UUO causes marked oxidative stress and rapid death of proximal tubular cells in the adult mouse, leading to the formation of atubular glomeruli. This occurs also following UUO in the neonate (during completion of nephrogenesis, but tubular cell death is delayed until proximal tubular mitochondrial maturation is complete. In the pcy mutant mouse, a model of autosomal dominant PKD, tubular cysts develop in the neonatal period, and progressively enlarge, eventually causing obstruction of neighboring nephrons and formation of atubular glomeruli. In the ctns mutant mouse with nephropathic cystinosis, injury results from accumulation of cystine crystals. This results in oxidative stress and stimulates flattening (rather than death of proximal tubular cells (“swan neck deformity”, and onset of the Fanconi syndrome. Progression to severe proximal tubular atrophy and formation of atubular glomeruli develops in later adult life. These studies suggest that early treatment of congenital renal disorders should target protection of proximal tubules from oxidative injury. We are currently investigating the use of antioxidants that are selectively concentrated in mitochondria. Since children with congenital renal disorders are born with a reduced nephron number (which cannot be regenerated

  8. Increased expression of lysosome membrane protein 2 in glomeruli of patients with idiopathic membranous nephropathy

    NARCIS (Netherlands)

    Rood, I.M.; Merchant, M.L.; Wilkey, D.W.; Zhang, T.; Zabrouskov, V.; Vlag, J. van der; Dijkman, H.B.P.M.; Willemsen, B.K.; Wetzels, J.F.M.; Klein, J.B.; Deegens, J.K.J.

    2015-01-01

    Urinary microvesicles constitute a rich source of membrane-bound and intracellular proteins that may provide important clues of pathophysiological mechanisms in renal disease. In the current study, we analyzed and compared the proteome of urinary microvesicles from patients with idiopathic

  9. Comparison of various needles in renal biopsy : clinical and animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Hee; Kim, Seung Hyup; Choi, Kuk Myeong; Kim, Hyun Beom; Yeon, Kyung Mo [Seoul National Univ. (Korea, Republic of). Coll. of Medicine

    1998-03-01

    The purpose of this paper is to compare the efficacy of 14 gauge (G) Vim-Silverman needle biopsy with that of 16G automatic gun biopsy for kidneys and to determine the optimal needle size for renal biopsy. We retrospectively reviewed the pathologic and medical records of 119 (110 native, 9 allograft) patients who had undergone 14G Vim-Silverman needle biopsy and 71 (34 native, 37 allograft) who had undergone 16G automatic gun biopsy. The number of retrieved glomeruli and post-biopsy complications were compared between the two groups. Ex vivo renal biopsies of a dog were performed using an automatic gun mounted with 14G-20G needles and the numbers of retrieved glomeruli were compared. Although significantly more glomeruli were retrieved in the 14G Vim-Silverman needle biopsy group, the number retrieved in the 16G automatic gun biopsy group was sufficient for adequate pathologic interpretation. Experimental study suggests that when an 18G automatic gun in used, sufficient glomeruli are retrieved. (author). 16 refs., 4 tabs., 3 figs.

  10. Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

    Science.gov (United States)

    Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.

  11. The effects of simultaneous hyperlipemia-hyperglycemia on the resistance arteries, myocardium and kidney glomeruli.

    Science.gov (United States)

    Costache, G; Popov, D; Georgescu, A; Cenuse, M; Jinga, V V; Simionescu, M

    2000-01-01

    The experimental model of Golden Syrian hamster subjected to concomitant hyperlipemia (diet-induced) and diabetes (by streptozotocin injection) for 24 weeks is characterised by the prevalence of micro- and macroangiopathies. We have used the hyperlipemic-diabetic (HD) hamsters to investigate: a) whether there is an alteration in the reactivity of the resistance arteries (mean internal diameter: 210-250 microm), b) if present, which are the structural and biochemical changes that accompany the functional modifications, and c) to examine the pathomorphological changes induced by the association of hyperlipemia and diabetes on vital organs such as myocardium and kidney glomeruli. To these aims, biochemical assays of plasma components, light- and electronmicroscopy, myographic, morphometric and spectrofluorimetric techniques were used. The mesenteric resistance arteries of HD hamsters exhibited (as compared to similar arteries in normals) a decreased contractile response to noradrenaline (1.86+/-0.35 vs. 2.43+/-0.21), and an impeded endothelium dependent relaxation to acetylcholine (approximately 61.40% vs. approximately 79.80%). The association of hyperlipemia with diabetes induced changes in morphology of the resistance arteries consisting in approximately 10% increase of the intima plus media cross-sectional area, approximately 20% decrease of the vascular lumen area, and approximately 2.85 fold augmentation of the wall to lumen ratio. The resistance arteries exhibited structural modifications of the endothelium (up to 8 copies of Weibel-Palade bodies/endothelial cell), and smooth muscle cells (secretory phenotype), and in the vessels media small calcification cores appeared embedded in a hyperplasic extracellular matrix. The vascular mesenteric bed of the HD hamsters contained approximately 2.30 and approximately 1.30 fold increased concentrations of AGE-collagen and pentosidine, respectively, above the normal values. The HD hamsters displayed also modifications

  12. ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse

    Science.gov (United States)

    Göçeroğlu, Arda; Berden, Annelies E.; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W.; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D.; Hagen, E. Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A.; Jayne, David R. W.; Bajema, Ingeborg M.

    2016-01-01

    Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different. PMID:27973575

  13. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  14. Complement system in lung disease.

    Science.gov (United States)

    Pandya, Pankita H; Wilkes, David S

    2014-10-01

    In addition to its established contribution to innate immunity, recent studies have suggested novel roles for the complement system in the development of various lung diseases. Several studies have demonstrated that complement may serve as a key link between innate and adaptive immunity in a variety of pulmonary conditions. However, the specific contributions of complement to lung diseases based on innate and adaptive immunity are just beginning to emerge. Elucidating the role of complement-mediated immune regulation in these diseases will help to identify new targets for therapeutic interventions.

  15. Renal histology and immunopathology in distal renal tubular acidosis.

    Science.gov (United States)

    Feest, T G; Lockwood, C M; Morley, A R; Uff, J S

    1978-11-01

    Renal biospy studies are reported from 10 patients with distal renal tubular acidosis (DRTA). On the biopsies from 6 patients who had associated immunological abnormalities immunofluorescent studies for immunoglobulins, complement, and fibrin were performed. Interstitial cellular infiltration and fibrosis were common findings in patients with and without immunological abnormalities, and were usually associated with nephrocalcinosis and/or recurrent urinary infection. No immune deposits were demonstrated in association with the renal tubules. This study shows that DRTA in immunologically abnormal patients is not caused by tubular deposition of antibody or immune complexes. The possibility of cell mediated immune damage is discussed.

  16. Renal arteriography

    Science.gov (United States)

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Review Date 1/5/2016 Updated by: Jason Levy, ...

  17. Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

    Science.gov (United States)

    Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

    2016-08-03

    Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation.

  18. Comparison of needles size in pediatric renal biopsy with sono-guided percutaneous-automated gun technique

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Chul; Park, Jin Yong [Chungnam National Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-11-01

    To compare the efficacy of a 20-gauge and an 18-gauge needle in sono-guided percutaneous automated gun biopsy for establishing the specific diagnosis of renal parenchymal disease in pediatric kidneys. In 60 pediatric patients with renal parenchymal diseases, percutaneous sono-guided gun biopsy was performed by an experienced radiologist. In two groups of 30 patients, regardless of their age, two needle passes were performed, using alternately an 18-gauge or a 20-gauge biopsy needle. The core of renal tissue thus obtained was examined with light, immunofluorescent or electron microscopy by the renal pathologist. The mean number of intact glomeruli of whole tissue core per biopsy, as seen on the light microscopy, and post-bioptic complications were compared between the two different needle size groups. The number (mean{+-}1 standard deviation) of glomeruli obtained per biopsy was 17{+-}8 in the 18-gauge needle group, and 14{+-}5 in the 20-gauge group. Between two groups, there was no major post-bioptic complication requiring specific treatment, nor a statistically significant difference in the frequency of minor complications. Even though more glomeruli were obtained with an 18-gauge needle, the number obtained with a 20-gauge needle also permitted adequate pathologic examination. Both an 18-gauge and a 20-gauge needle may thus be suitable for renal biopsy in pediatric patients.

  19. Complement system regulation and C3 glomerulopathy%补体系统调控异常与C3肾小球病

    Institute of Scientific and Technical Information of China (English)

    肖慧捷; 何瑞娟

    2013-01-01

    Complement system is a key system for immune surveillance and homeostasis. Excessive activation of complement system, especially the activation of alternative pathway may play a very important role in the pathogenesis of primary and secondary glomerulonephritis. C3 glomerulopathy is a newly named disease characterized by evident C3 deposition in the glomeruli with little or no immunoglobulin under immunofluorescence (IF). Its clinical and pathological manifestations vary a lot. The decreased plasma C3 and Factor H( FH) suggest that abnormal regulation of complement system plays an importment role in its pathogenesis. C3 glomerulopathy varies a lot as to its clinical manifestation, treatment and prognosis. The inhibition of excessive complement activation might be the key to treating C3 glomerulopathy.

  20. Tight temporal coupling between synaptic rewiring of olfactory glomeruli and the emergence of odor-guided behavior in Xenopus tadpoles.

    Science.gov (United States)

    Terni, Beatrice; Pacciolla, Paolo; Masanas, Helena; Gorostiza, Pau; Llobet, Artur

    2017-12-01

    Olfactory sensory neurons (OSNs) are chemoreceptors that establish excitatory synapses within glomeruli of the olfactory bulb. OSNs undergo continuous turnover throughout life, causing the constant replacement of their synaptic contacts. Using Xenopus tadpoles as an experimental system to investigate rewiring of glomerular connectivity, we show that novel OSN synapses can transfer information immediately after formation, mediating olfactory-guided behavior. Tadpoles recover the ability to detect amino acids 4 days after bilateral olfactory nerve transection. Restoration of olfactory-guided behavior depends on the efficient reinsertion of OSNs to the olfactory bulb. Presynaptic terminals of incipient synaptic contacts generate calcium transients in response to odors, triggering long lasting depolarization of olfactory glomeruli. The functionality of reconnected terminals relies on well-defined readily releasable and cytoplasmic vesicle pools. The continuous growth of non-compartmentalized axonal processes provides a vesicle reservoir to nascent release sites, which contrasts to the gradual development of cytoplasmic vesicle pools in conventional excitatory synapses. The immediate availability of fully functional synapses upon formation supports an age-independent contribution of OSNs to the generation of odor maps. © 2017 Wiley Periodicals, Inc.

  1. Complement evasion by Staphylococcus aureus

    NARCIS (Netherlands)

    Jongerius, I.

    2010-01-01

    The complement system is the first line of defense against invading microorganisms. Activation of the complement system results in the coverage of bacteria with C3b, resulting in phagocytosis, and formation of C5a which is important for chemotaxis of neutrophils towards the site of infection. Staphy

  2. Evolution of the complement system.

    Science.gov (United States)

    Nonaka, Masaru

    2014-01-01

    The mammalian complement system constitutes a highly sophisticated body defense machinery comprising more than 30 components. Research into the evolutionary origin of the complement system has identified a primitive version composed of the central component C3 and two activation proteases Bf and MASP in cnidaria. This suggests that the complement system was established in the common ancestor of eumetazoa more than 500 million years ago. The original activation mechanism of the original complement system is believed to be close to the mammalian lectin and alternative activation pathways, and its main role seems to be opsonization and induction of inflammation. This primitive complement system has been retained by most deuterostomes without major change until the appearance of jawed vertebrates. At this stage, duplication of the C3, Bf and MASP genes as well as recruitment of membrane attack components added the classical and lytic pathways to the primitive complement system, converting it to the modern complement system. In contrast, the complement system was lost multiple times independently in the protostome lineage.

  3. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  4. In Situ Localization of C3 Synthesis in Experimental Acute Renal Allograft Rejection

    OpenAIRE

    2000-01-01

    Recent evidence has implicated complement in renal transplant injury and identified the kidney as a source of complement components. We therefore investigated the local gene expression of complement component C3, pivotal to complement activation pathways and a mediator of inflammatory injury, in a rat renal transplant model. By reverse transcriptase-polymerase chain reaction, the expression of C3 mRNA increased in two phases. The first phase coincided with post-ischemic injury over 2 days pos...

  5. An Artificial Olfaction System Formed by a Massive Sensors Array Dispersed in a Diffusion Media and an Automatically Formed Glomeruli Layer

    Science.gov (United States)

    Di Natale, Corrado; Martinelli, Eugenio; Paolesse, Roberto; D'Amico, Arnaldo; Filippini, Daniel; Lundström, Ingemar

    2009-05-01

    Optical imaging is a read-out technique for sensors that can easily provide advances in artificial olfaction implementing features such as the large number of receptors and the glomeruli layer. In this paper an artificial olfaction system based on the imaging of a continuous layer of chemical indicators is illustrated. The system results in an array of thousands of sensors, corresponding to the pixels of the image. The choice of Computer Screen Photoassisted Technology as a platform for optical interrogation of the sensing layer allows for the definition of a strategy for an automatic definition of the glomeruli layer based on the classification of the optical fingerprints of the image pixels. Chemical indicators are dissolved into a polymeric matrix mimicking the functions of the olfactory mucosa. The system is here illustrated with a simple experiment. Data are treated applying a lateral inhibition to the glomeruli layer resulting in a dynamic pattern resembling that observed in natural olfaction.

  6. Complement in health and disease.

    Science.gov (United States)

    Carroll, Maria V; Sim, Robert B

    2011-09-16

    The complement system consists of about 35-40 proteins and glycoproteins present in blood plasma or on cell surfaces. Its main biological function is to recognise "foreign" particles and macromolecules, and to promote their elimination either by opsonisation or lysis. Although historically complement has been studied as a system for immune defence against bacteria, it has an important homeostatic role in which it recognises damaged or altered "self" components. Thus complement has major roles in both immune defence against microorganisms, and in clearance of damaged or "used" host components. Since complement proteins opsonise or lyse cells, complement can damage healthy host cells and tissues. The system is regulated by many endogenous regulatory proteins. Regulation is sometimes imperfect and both too much and too little complement activation is associated with many diseases. Excessive or inappropriate activation can cause tissue damage in diseases such as rheumatoid arthritis, age-related macular degeneration (AMD), multiple sclerosis, ischemia-reperfusion injury (e.g. ischemic stroke). Insufficient complement activity is associated with susceptibility to infection (mainly bacterial) and development of autoimmune disease, like SLE (systemic lupus erythematosus).

  7. Renal Primordia Activate Kidney Regenerative Events in a Rat Model of Progressive Renal Disease

    Science.gov (United States)

    Imberti, Barbara; Corna, Daniela; Rizzo, Paola; Xinaris, Christodoulos; Abbate, Mauro; Longaretti, Lorena; Cassis, Paola; Benedetti, Valentina; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    New intervention tools for severely damaged kidneys are in great demand to provide patients with a valid alternative to whole organ replacement. For repairing or replacing injured tissues, emerging approaches focus on using stem and progenitor cells. Embryonic kidneys represent an interesting option because, when transplanted to sites such as the renal capsule of healthy animals, they originate new renal structures. Here, we studied whether metanephroi possess developmental capacity when transplanted under the kidney capsule of MWF male rats, a model of spontaneous nephropathy. We found that six weeks post-transplantation, renal primordia developed glomeruli and tubuli able to filter blood and to produce urine in cyst-like structures. Newly developed metanephroi were able to initiate a regenerative-like process in host renal tissues adjacent to the graft in MWF male rats as indicated by an increase in cell proliferation and vascular density, accompanied by mRNA and protein upregulation of VEGF, FGF2, HGF, IGF-1 and Pax-2. The expression of SMP30 and NCAM was induced in tubular cells. Oxidative stress and apoptosis markedly decreased. Our study shows that embryonic kidneys generate functional nephrons when transplanted into animals with severe renal disease and at the same time activate events at least partly mimicking those observed in kidney tissues during renal regeneration. PMID:25811887

  8. Complement Evasion by Pathogenic Leptospira.

    Science.gov (United States)

    Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

    2016-01-01

    Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira. Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira, have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host.

  9. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.

    Directory of Open Access Journals (Sweden)

    Cynthia A Batchelder

    Full Text Available Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease.

  10. Heat differentiated complement factor profiling.

    Science.gov (United States)

    Hamsten, Carl; Skattum, Lillemor; Truedsson, Lennart; von Döbeln, Ulrika; Uhlén, Mathias; Schwenk, Jochen M; Hammarström, Lennart; Nilsson, Peter; Neiman, Maja

    2015-08-03

    Complement components and their cascade of reactions are important defense mechanisms within both innate and adaptive immunity. Many complement deficient patients still remain undiagnosed because of a lack of high throughput screening tools. Aiming towards neonatal proteome screening for immunodeficiencies, we used a multiplex profiling approach with antibody bead arrays to measure 9 complement proteins in serum and dried blood spots. Several complement components have been described as heat sensitive, thus their heat-dependent detectability was investigated. Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. Measurements of C7, C8 and factor I were negatively affected by heating and non-heated samples should be used in analysis of these components. In addition, a proof of concept study demonstrated the feasibility of labeling eluates from dried blood spots to perform a subsequent correct classification of C2-deficiencies. Our study demonstrates the potential of using multiplexed single binder assays for screening of complement components that open possibilities to expand such analysis to other forms of deficiencies.

  11. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

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    Rosangela Silva Rigo

    2013-04-01

    Full Text Available Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL. Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05 between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  12. Renal histopathological findings in dogs with visceral leishmaniasis.

    Science.gov (United States)

    Rigo, Rosangela Silva; Carvalho, Cristiano Marcelo Espínola; Honer, Michael Robin; Andrade, Gisele Braziliano de; Silva, Iandara Shetter; Rigo, Leonardo; Figueiredo, Helen Rezende; Barreto, Wanessa Teixeira Gomes

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  13. Role of megalin and cubilin in renal physiology and pathophysiology.

    Science.gov (United States)

    Christensen, E I; Nielsen, R

    2007-01-01

    Megalin and cubilin are endocytic receptors highly expressed in the endocytic apparatus of the renal proximal tubule. These receptors appear to be responsible for the tubular clearance of most proteins filtered in the glomeruli. Cubilin is a peripheral membrane protein, and therefore it does not have an endocytosis signaling sequence. It appears that megalin is responsible for internalization of cubilin and its ligands in addition to internalizing its own ligands. The proteinuria observed in megalin-deficient mice, in dogs lacking functional cubilin, and in patients with distinct mutations of the cubilin gene illustrates the importance of the receptors.

  14. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

    Directory of Open Access Journals (Sweden)

    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  15. Renal involvement in non-Hodgkin lymphoma: proven by renal biopsy.

    Science.gov (United States)

    Li, Shi-Jun; Chen, Hui-Ping; Chen, Ying-Hua; Zhang, Li-hua; Tu, Yuan-Mao; Liu, Zhi-hong

    2014-01-01

    To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin's lymphoma (NHL) by renal biopsy. The clinical features and histological findings at the time of the renal biopsy were assessed for each patient. We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients. A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.

  16. Reno-invasive fungal infection presenting as acute renal failure: importance of renal biopsy for early diagnosis.

    Science.gov (United States)

    Ranjan, Priyadarshi; Chipde, Saurabh Sudhir; Vashistha, Saurabh; Kumari, Neeraj; Kapoor, Rakesh

    2014-11-01

    Renal zygomycosis, caused by invasive fungi, is a rare and potentially fatal infection. The patient usually presents with non-specific symptoms and renal failure. A 34-year-old male non-diabetic and without any predisposing factors for systemic fungal infection presented to the emergency department with diffuse abdominal pain, high-grade fever and acute renal failure with a serum creatinine of 6.5. A computed tomography showed bilateral diffuse globular nephromegaly. A urine smear for fungal examination showed right angle branching hyphae and kidney biopsy showed fungal hyphae within the glomeruli, tubules and interstitium. Although radiological investigations can give us a clue, the definitive diagnosis can only be made by kidney biopsy. A high index of suspicion and timely diagnosis is important for a proper management.

  17. Efficacy and Complications of Ultrasound-Guided Percutaneous Renal Biopsy Using Automatic Biopsy Gun in Pediatric Diffuse Renal Disease: Analysis of 97 Cases

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seung Min; Chung, Tae Woong; Yoon, Woong [Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2007-09-15

    To evaluate the diagnostic efficacy and complications of ultrasound-guided percutaneous renal biopsy using automatic biopsy gun in patients with pediatric diffuse renal disease. Using an 18G automatic biopsy gun, biopsies were performed on 97 pediatric patients with clinically suspicious diffuse renal disease. The acquired tissue specimens were analyzed by photomicroscopy, immunofluorescence, and electron microscopy to support the diagnosis. In the 97 biopsies, the success of the histologic diagnosis, number of glomeruli, and complication rates were retrospectively evaluated by analyzing the variable exams and clinical records. Adequate tissue for histologic diagnosis was obtained in 91 of 97 biopsies (94%) and the mean number of glomeruli was 9.6. Complications such as minute pain, gross hematuria, and small perirenal hematoma presented in 22 of the 97 biopsies (23%), all of which either improved within 5-72 hours or did not need specific treatment. Ultrasound-guided percutaneous renal biopsy using 18G automatic biopsy gun is an effective and safe method for the histologic diagnosis of pediatric diffuse renal disease without any major complication

  18. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  19. Urinary Soluble CD163 in Active Renal Vasculitis.

    Science.gov (United States)

    O'Reilly, Vincent P; Wong, Limy; Kennedy, Claire; Elliot, Louise A; O'Meachair, Shane; Coughlan, Alice Marie; O'Brien, Eoin C; Ryan, Michelle M; Sandoval, Diego; Connolly, Emma; Dekkema, Gerjan J; Lau, Jiaying; Abdulahad, Wayel H; Sanders, Jan-Stephan F; Heeringa, Peter; Buckley, Colm; O'Brien, Cathal; Finn, Stephen; Cohen, Clemens D; Lindemeyer, Maja T; Hickey, Fionnuala B; O'Hara, Paul V; Feighery, Conleth; Moran, Sarah M; Mellotte, George; Clarkson, Michael R; Dorman, Anthony J; Murray, Patrick T; Little, Mark A

    2016-09-01

    A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV. Copyright © 2016 by the American Society of Nephrology.

  20. Complement sentences - complementizers of causative-manipulative verbs

    Directory of Open Access Journals (Sweden)

    Alanović Milivoj B.

    2015-01-01

    Full Text Available This paper presents the key structural and semantic features of the complement sentences that have the primary function of direct or indirect objects of one type of causative verbs - causative-manipulative verbs. Since the syntactic literature frequently discusses the structural characteristics of the complement sentences, the main objective of this article is focused on the semantic diversity of this type of sentences. The goal of the article is to determine the dependence of the realized meaning of a sentence on the semantic type of the main verb. Although the conjunction da is a typical subordinator of these sentences, a series of communicative verbs allows the use of complement sentences with interrogative adverbs and pronouns in the function of conjunctions. [Projekat Ministarstva nauke Republike Srbije, br.178004: Standardni srpski jezik - sintaksička, semantička i pragmatička istraživanja

  1. Release of glomerular heparan-/sup 35/SO/sub 4/ proteoglycan by heparin from glomeruli of streptozocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Klein, D.J.; Oegema, T.R. Jr.; Brown, D.M.

    1989-01-01

    Abnormalities in the incorporation of heparan sulfate proteoglycan into the glomerular basement membrane have been implicated in the pathogenesis of various proteinuric states, including diabetes mellitus. To understand further the interactions between proteoglycans and glomerular extracellular matrices, glomeruli were isolated from normal and streptozocin-induced diabetic rats after in vivo exposure to 35S-labeled sulfate and were treated with heparin in vitro. Heparin treatment released a unique heparan sulfate proteoglycan from glomerular cell surface or extracellular matrix proteoglycan receptors. Another, smaller heparan sulfate proteoglycan was the most abundant proteoglycan released into medium and was released constitutively in medium with or without added heparin. While the two heparin-extracted proteoglycans copurified on anion-exchange and gel-filtration chromatographic columns, they were resolved by composite 0.6% agarose--1.8% polyacrylamide gel electrophoresis. Glomeruli from diabetic rats contained decreased proportions of the heparin-releasable heparan sulfate proteoglycan and more constitutively released heparan sulfate proteoglycan. The apparent molecular weight and intrinsic charge of the heparin-released proteoglycan mixture and the apparent molecular weight and sulfation pattern of their 35S-labeled glycosaminoglycan chains after nitrous acid deaminative cleavage were similar in the two groups. A brief trypsin digestion of heparin-treated glomeruli released proportionately less integral membrane and extracellular matrix 35S-labeled proteoglycans and 35S-labeled glycopeptides from diabetic glomeruli than form control glomeruli. Elution of these 35S-labeled macromolecules from anion-exchange columns and migration in agarose-polyacrylamide gels were similar in the two groups.

  2. Force Dynamics of Verb Complementation

    Directory of Open Access Journals (Sweden)

    Jacek Woźny

    2015-12-01

    Full Text Available Force Dynamics of Verb Complementation The concepts of motion and force are both extensively discussed in cognitive linguistics literature. But they are discussed separately. The first usually in the context of ‘motion situations’ (Talmy, Slobin, Zlatev, the other as part of the Force Dynamics framework, which was developed by Talmy. The aim of this paper is twofold: first, to argue that the concepts of force and motion should not be isolated but considered as two inseparable parts of force-motion events. The second goal is to prove that the modified Force Dynamics (force-motion framework can be used for precise characterization of the verb complementation patterns. To this end, a random sample of 50 sentences containing the verb ‘went’ is analyzed, demonstrating the differences between the categories of intensive and intransitive complementation with respect to the linguistically coded parameters of force and motion.

  3. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...... in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  4. Renal perfusion scintiscan

    Science.gov (United States)

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  5. Complement: Alive and Kicking Nanomedicines

    DEFF Research Database (Denmark)

    Andersen, Alina Joukainen; Hashemi, S.H.; Andresen, Thomas Lars;

    2009-01-01

    Administration of liposome- and polymer-based clinical nanomedicines, as well as many other proposed multifunctional nanoparticles, often triggers hypersensitivity reactions without the involvement of IgE. These anaphylactic reactions are believed to be secondary to activation of the complement s...

  6. Milk immunoglobulins and complement factors.

    Science.gov (United States)

    Korhonen, H; Marnila, P; Gill, H S

    2000-11-01

    The importance of colostrum for the growth and health of newborn offspring is well known. In bovine colostrum, the antibody (immunoglobulin) complement system provides a major antimicrobial effect against a wide range of microbes and confers passive immunity until the calf's own immune system has matured. Bovine serum and lacteal secretions contain three major classes of immunoglobulins: IgG, IgM and IgA. The immunoglobulins are selectively transported from the serum into the mammary gland, as a result of which the first colostrum contains very high concentrations of immunoglobulins (40-200 mg/ml). IgG1 accounts for over 75 % of the immunoglobulins in colostral whey, followed by IgM, IgA and IgG2. All these immunoglobulins decrease within a few days to a total immunoglobulin concentration of 0.7-1.0 mg/ml, with IgG1 representing the major Ig class in milk throughout the lactation period. Together with the antibodies absorbed from colostrum after birth, the complement system plays a crucial role in the passive immunisation of the newborn calf. The occurrence of haemolytic or bactericidal complement activity in bovine colostrum and milk has been demonstrated in several studies. This review deals with the characteristics of bovine Igs and the complement system to be exploited as potential ingredients for health-promoting functional foods.

  7. Role of complement in xenotransplantation.

    Science.gov (United States)

    Mollnes, Tom Eirik; Fiane, A E

    2002-01-01

    The xenotransplantation research is driven by the increasing gap between the number of patients with end-stage organ failure on waiting lists for transplantation and the supply of allografts. The lack of success in developing suitable artificial organs for permanent treatment of organ failure has further strengthened the need for xenotransplantation research. Pigs are now generally accepted to be the source animal of choice. Transplantation of pig organs to humans faces several barriers which have to be overcome before it comes to clinical application: (1) anatomical and physiological conditions; (2) immunological rejection mechanisms; (3) molecular compatibility between signal molecules of the two species; (4) risk of transmission of microorganisms, particularly pig endogenous retroviruses; and (5) legal and ethical aspects both with respect to the animal and the recipient. Here we will focus on the role of the complement system in the rejection of immediately vascularized pig-to-primate xenografts. The hyperacute rejection occurring within minutes after transplantation is mediated by binding of natural antibodies to the Galalpha(l-3)Gal epitope on the endothelial cells with subsequent complement activation. Whereas inhibition of complement activation protects against hyperacute rejection, the role of complement in the later rejection phases is less clarified.

  8. The lectin pathway of complement

    DEFF Research Database (Denmark)

    Ballegaard, Vibe Cecilie Diederich; Haugaard, Anna Karen; Garred, P

    2014-01-01

    The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2...

  9. 21 CFR 866.4100 - Complement reagent.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement reagent. 866.4100 Section 866.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... Complement reagent. (a) Identification. A complement reagent is a device that consists of complement,...

  10. Intravenous renal cell transplantation with SAA1-positive cells prevents the progression of chronic renal failure in rats with ischemic-diabetic nephropathy.

    Science.gov (United States)

    Kelly, Katherine J; Zhang, Jizhong; Han, Ling; Wang, Mingsheng; Zhang, Shaobo; Dominguez, Jesus H

    2013-12-15

    Diabetic nephropathy, the most common cause of progressive chronic renal failure and end-stage renal disease, has now reached global proportions. The only means to rescue diabetic patients on dialysis is renal transplantation, a very effective therapy but severely limited by the availability of donor kidneys. Hence, we tested the role of intravenous renal cell transplantation (IRCT) on obese/diabetic Zucker/SHHF F1 hybrid (ZS) female rats with severe ischemic and diabetic nephropathy. Renal ischemia was produced by bilateral renal clamping of the renal arteries at 10 wk of age, and IRCT with genetically modified normal ZS male tubular cells was given intravenously at 15 and 20 wk of age. Rats were euthanized at 34 wk of age. IRCT with cells expressing serum amyloid A had strong and long-lasting beneficial effects on renal function and structure, including tubules and glomeruli. However, donor cells were found engrafted only in renal tubules 14 wk after the second infusion. The results indicate that IRCT with serum amyloid A-positive cells is effective in preventing the progression of chronic kidney disease in rats with diabetic and ischemic nephropathy.

  11. Efficacy of Targeted Complement Inhibition in Experimental C3 Glomerulopathy

    Science.gov (United States)

    Ruseva, Marieta M.; Peng, Tao; Lasaro, Melissa A.; Bouchard, Keith; Liu-Chen, Susan; Sun, Fang; Yu, Zhao-Xue; Marozsan, Andre; Wang, Yi

    2016-01-01

    C3 glomerulopathy refers to renal disorders characterized by abnormal accumulation of C3 within the kidney, commonly along the glomerular basement membrane (GBM). C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). There is no effective treatment for C3 glomerulopathy. We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. CR2-FH partially restored plasma C3 levels in FH-deficient mice 2 hours after intravenous injection. CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration of CR2-FH for 1 week. In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy. PMID:26047789

  12. Cinnabar Induces Renal Inflammation and Fibrogenesis in Rats

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    Ying Wang

    2015-01-01

    Full Text Available The purpose of this study was to investigate whether cinnabar causes renal inflammation and fibrosis in rats. Rats were dosed orally with cinnabar (1 g/kg/day for 8 weeks or 12 weeks. The control rats were treated with solvent (5% carboxymethylcellulose solution over the same time periods, respectively. Renal mercury (RHg, urinary mercury (UHg, serum creatinine (SCr, urine kidney injury molecule 1 (KIM-1, renal pathology, and renal mediators were examined. At both 8 weeks and 12 weeks, RHg, UHg, and urine KIM-1 were significantly higher in the cinnabar group than in the control group, although SCr was unchanged. Kidney lesions in the cinnabar-treated rats occurred mainly in the tubules and interstitium, including vacuolization, protein casts, infiltration of inflammatory cells, and slight increase in interstitial collagen. In addition, mild mesangial proliferation was observed in glomeruli. Moreover, the expression of inflammatory and fibrogenic mediators was upregulated in the cinnabar group. In conclusion, cinnabar may cause kidney damage due to the accumulation of mercury, and renal inflammation and slight fibrogenesis may occur in rats. In the clinic, the potential risk of renal injury due to the prolonged consumption of cinnabar should be considered even though the agent is relatively nontoxic.

  13. Complement evasion by Plasmodium falciparum

    OpenAIRE

    Holopainen, Saila

    2008-01-01

    Patologian oppiaine Malaria remains one of the major health problems in many tropical countries, especially in sub-Saharan Africa. Among the most characteristic features of the malaria pathogens, protozoan parasites of the genus Plasmodium, is their ability to evade the immune defences of the host for extended periods of time. The complement system (C) is an essential part of the innate system in the first line of defense. It consists of over 30 soluble or membrane-bound components. C...

  14. Complement Activation Alters Platelet Function

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  15. Atypical hemolytic uremic syndrome: update on the complement system and what is new.

    Science.gov (United States)

    Hirt-Minkowski, Patricia; Dickenmann, Michael; Schifferli, Jürg A

    2010-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and predominant renal impairment. It is characterized by the absence of Shiga toxin-producing bacteria as a triggering factor. During the last decade, aHUS has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Recent advances in understanding the pathogenesis of aHUS have led to a revised classification of the syndrome. Normal plasma levels of CFH and CFI do not preclude the presence of a mutation in these genes. Further, genotype-phenotype correlations of aHUS have clinical significance in predicting renal recovery and transplant outcome. Therefore, it is important to make a comprehensive analysis and perform genetic screening of the complement system in patients with aHUS to allow a more precise approach, especially before transplantation. This may also provide opportunities for more specific treatments in the near future, as complement inhibition could represent a therapeutic target in these patients who have a considerably poor prognosis in terms of both mortality and progression to end-stage renal disease and a great risk of disease recurrence after transplantation.

  16. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  17. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    lesion. Three cases of renal angiomyolipoma, 2 of which underwent perfusion-fixation, were studied by electron microscopy to clarify the cellular composition of this lesion. In the smooth muscle cells abundant accumulation of glycogen was found, whereas the lipocytes disclosed normal ultrastructural......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

  18. Role of complement in glomerular diseases.

    Science.gov (United States)

    Mao, Song; Zhang, Jianhua

    2016-01-01

    The complement system, composed of nearly 30 proteins, is a key regulator of immunity. The complement system is critical for protecting hosts from invading pathogens. Dysregulation of this system is associated with susceptibility to infection and various autoimmune diseases. Furthermore, complement activation due to the defective regulation of the alternative pathway will induce glomerular diseases. Anti-complement therapy has been applied in various glomerular diseases. Signaling pathways might be very important in the pathogenesis of glomerular diseases. This review will give a relatively complete signaling pathway flowchart for complement and a comprehensive understanding of the underlying role of complement in glomerular diseases.

  19. Superoxide anion production and expression of gp91(phox) and p47(phox) are increased in glomeruli and proximal tubules of cisplatin-treated rats.

    Science.gov (United States)

    Trujillo, Joyce; Molina-Jijón, Eduardo; Medina-Campos, Omar Noel; Rodríguez-Muñoz, Rafael; Reyes, José Luis; Barrera, Diana; Pedraza-Chaverri, José

    2015-04-01

    The chemotherapeutic drug cisplatin has some side effects including nephrotoxicity that has been associated with reactive oxygen species production, particularly superoxide anion. The major source of superoxide anion is nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase. However, the specific segment of the nephron in which superoxide anion is produced has not been identified. Rats were sacrificed 72 h after cisplatin injection (7.5 mg/kg), and kidneys were obtained to isolate glomeruli and proximal and distal tubules. Cisplatin induced superoxide anion production in glomeruli and proximal tubules but not in distal tubules. This enhanced superoxide anion production was prevented by diphenylene iodonium, an inhibitor of NADPH oxidase. Consistently, this effect was associated with the increased expression of gp91(phox) and p47(phox), subunits of NADPH oxidase. The enhanced superoxide anion production in glomeruli and proximal tubules, associated with the increased expression of gp91(phox) and p47(phox), is involved in the oxidative stress in cisplatin-induced nephrotoxicity.

  20. Curcumin Rescues Diabetic Renal Fibrosis by Targeting Superoxide-Mediated Wnt Signaling Pathways.

    Science.gov (United States)

    Ho, Cheng; Hsu, Yung-Chien; Lei, Chen-Chou; Mau, Shu-Ching; Shih, Ya-Hsueh; Lin, Chun-Liang

    2016-03-01

    The purposes of this study were to investigate whether curcumin can weaken diabetic nephropathy by modulating both oxidative stress and renal injury from Wnt signaling mediation. Wnt5a/β-catenin depression and induction of superoxide synthesis are associated with high glucose (HG) induced transforming growth factor (TGF)-β1 and fibronectin expression in mesangial cells. Curcumin resumes HG depression of Wnt/β-catenin signaling and alleviates HG induction of superoxide, TGF-β1 and fibronectin expression in renal mesangial cell. Exogenous curcumin alleviated urinary total proteinuria and serum superoxide level in diabetic rats. Based on laser-captured microdissection for quantitative real-time polymerase chain reaction, it was found that diabetes significantly increased TGF-β1 and fibronectin expression in line with depressed Wnt5a expression. Curcumin treatment reduced the TGF-β1 and fibronectin activation and the inhibiting effect of diabetes on Wnt5a/β-catenin expression in renal glomeruli. Immunohistochemistry showed that curcumin treatment significantly reduced 8-hydroxy-2'-deoxyguanosine, TGF-β1 and fibronectin, and was in line with the restoration of the suppressed Wnt5a expression immunoreactivities in glomeruli of diabetic rats. Curcumin alleviated extracellular matrix accumulation in diabetic nephropathy by not only preventing the diabetes-mediated superoxide synthesis but also resuming downregulation of Wnt/β-catenin signaling. These findings suggest that regulation of Wnt activity by curcumin is a feasible alternative strategy to rescue diabetic renal injury.

  1. Determination of optimal blood pressure for patients with IgA nephropathy based on renal histology.

    Science.gov (United States)

    Osawa, Y; Narita, I; Imai, N; Iino, N; Iguchi, S; Ueno, M; Shimada, H; Nishi, S; Arakawa, M; Gejyo, F

    2001-03-01

    To evaluate the optimal BP control for patients with IgA nephropathy (IgAN) based on the histologic severity of the nephropathy and the degree of renal dysfunction. We analyzed 332 consecutive renal biopsy specimens and clinical data from patients with IgAN. Patients were divided into three groups based on their BP at the time of biopsy: an optimal BP (SBP or = 140 mmHg and/or DBP > or = 90 mmHg), and an intermediate BP group. Each biopsy specimen was evaluated for mesangial proliferation, degree of sclerosis and/or hyalinosis of the arterioles and the interlobular artery using a semiquantitative method. Creatinine clearance and the percentage of sclerosed glomeruli were also determined. Both the degree of renal dysfunction and the histologic changes correlated significantly with BP, even in patients with a BP <140/90 mmHg. The patients with an optimal BP at the time of biopsy had significantly less histologic damage with respect to mesangial proliferation and vessel changes than those with an intermediate or hypertensive BP. In the patients with a hypertensive BP, the percentage of sclerotic glomeruli was significantly higher and the creatinine clearance was significantly lower. The optimal BP proposed by the WHO in 1999 prevents histologic evidence of renal damage for patients with IgAN.

  2. The complement system and adverse pregnancy outcomes.

    Science.gov (United States)

    Regal, Jean F; Gilbert, Jeffrey S; Burwick, Richard M

    2015-09-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child.

  3. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all acknowle

  4. Renal fallure

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920705 Endothelin and acute renal failure:study on their relationship and possiblemechanisms. LIN Shanyan(林善锬), et al.Renal Res Lab, Huashan Hosp, Shanghai MedUniv, Shanghai, 200040. Natl Med J China 1992;72(4): 201-205. In order to investigate the role of endothelin

  5. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  6. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  7. Knowledge of renal histology alters patient management in over 40% of cases.

    Science.gov (United States)

    Richards, N T; Darby, S; Howie, A J; Adu, D; Michael, J

    1994-01-01

    There is great debate as to whether the benefit gained from the knowledge of renal histology outweighs the risk to the patient from the biopsy procedure. We conducted a prospective study of 276 native renal biopsies performed on 266 patients from a single centre in 1991 to assess the effect of the knowledge of renal histology on patient management. Biopsies were performed under ultrasound guidance using the Trucut biopsy needle. The indications for biopsy were: non-nephrotic proteinuria alone (25), haematuria and proteinuria (28), nephrotic range proteinuria (28), acute renal failure (31), haematuria alone (36), and chronic renal failure (128). Two hundred and sixty-three biopsies were successful. The mean number of glomeruli obtained was 23, range 0-115. Eight patients developed macroscopic haematuria of which two required blood transfusion. The result of the biopsy altered management in 24/28 (86%) of cases of nephrotic range proteinuria, 22/31 (71%) of cases of acute renal failure, 58/128 (45%) of cases of chronic renal failure, 9/28 (32%) of cases with haematuria and proteinuria, 3/25 (12%) of cases with non-nephrotic proteinuria alone, and 1/36 (3%) of cases with haematuria alone. management was altered in 42% of cases overall. These data suggest that knowledge of renal histology is essential in the management of patients with renal disease.

  8. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    Science.gov (United States)

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

    2011-07-01

    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.

  9. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der

    2007-01-01

    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  10. Acute Systolic Heart Failure Associated with Complement-Mediated Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    John L. Vaughn

    2015-01-01

    Full Text Available Complement-mediated hemolytic uremic syndrome (otherwise known as atypical HUS is a rare disorder of uncontrolled complement activation that may be associated with heart failure. We report the case of a 49-year-old female with no history of heart disease who presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given her normal ADAMSTS13 activity, evidence of increased complement activation, and renal biopsy showing evidence of thrombotic microangiopathy, she was diagnosed with complement-mediated HUS. She subsequently developed acute hypoxemic respiratory failure secondary to pulmonary edema requiring intubation and mechanical ventilation. A transthoracic echocardiogram showed evidence of a Takotsubo cardiomyopathy with an estimated left ventricular ejection fraction of 20%, though ischemic cardiomyopathy could not be ruled out. Treatment was initiated with eculizumab. After several failed attempts at extubation, she eventually underwent tracheotomy. She also required hemodialysis to improve her uremia and hypervolemia. After seven weeks of hospitalization and five doses of eculizumab, her renal function and respiratory status improved, and she was discharged in stable condition on room air and independent of hemodialysis. Our case illustrates a rare association between acute systolic heart failure and complement-mediated HUS and highlights the potential of eculizumab in stabilizing even the most critically-ill patients with complement-mediated disease.

  11. Current Understanding of the Role of Complement in IgA Nephropathy

    Science.gov (United States)

    Maillard, Nicolas; Wyatt, Robert J.; Julian, Bruce A.; Kiryluk, Krzysztof; Gharavi, Ali; Fremeaux-Bacchi, Veronique

    2015-01-01

    Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan–binding lectin–associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome–wide association studies identified deletion of complement factor H–related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1–containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease. PMID:25694468

  12. ON COMPLEMENTED SUBGROUPS OF FINITE GROUPS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H ∩ K = 1. In this case, K is called a complement of H in G.In this note some results on complemented subgroups of finite groups are obtained.

  13. Complement in the Homeostatic and Ischemic Brain

    Science.gov (United States)

    Alawieh, Ali; Elvington, Andrew; Tomlinson, Stephen

    2015-01-01

    The complement system is a component of the immune system involved in both recognition and response to pathogens, and it is implicated in an increasing number of homeostatic and disease processes. It is well documented that reperfusion of ischemic tissue results in complement activation and an inflammatory response that causes post-reperfusion injury. This occurs following cerebral ischemia and reperfusion and triggers secondary damage that extends beyond the initial infarcted area, an outcome that has rationalized the use of complement inhibitors as candidate therapeutics after stroke. In the central nervous system, however, recent studies have revealed that complement also has essential roles in synaptic pruning, neurogenesis, and neuronal migration. In the context of recovery after stroke, these apparent divergent functions of complement may account for findings that the protective effect of complement inhibition in the acute phase after stroke is not always maintained in the subacute and chronic phases. The development of effective stroke therapies based on modulation of the complement system will require a detailed understanding of complement-dependent processes in both early neurodegenerative events and delayed neuro-reparatory processes. Here, we review the role of complement in normal brain physiology, the events initiating complement activation after cerebral ischemia-reperfusion injury, and the contribution of complement to both injury and recovery. We also discuss how the design of future experiments may better characterize the dual role of complement in recovery after ischemic stroke. PMID:26322048

  14. Complement in Lupus Nephritis: New Perspectives

    Science.gov (United States)

    Bao, Lihua; Cunningham, Patrick N.; Quigg, Richard J.

    2015-01-01

    Background Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Summary Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. Key Messages SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical

  15. Renal teratogens.

    Science.gov (United States)

    Morgan, Thomas M; Jones, Deborah P; Cooper, William O

    2014-09-01

    In utero exposure to certain drugs early in pregnancy may adversely affect nephrogenesis. Exposure to drugs later in pregnancy may affect the renin-angiotensin system, which could have an impact on fetal or neonatal renal function. Reduction in nephron number and renal function could have adverse consequences for the child several years later. Data are limited on the information needed to guide decisions for patients and providers regarding the use of certain drugs in pregnancy. The study of drug nephroteratogenicity has not been systematized, a large, standardized, global approach is needed to evaluate the renal risks of in utero drug exposures.

  16. Complement the hemostatic system: an intimate relationship.

    Science.gov (United States)

    Weitz, Ilene Ceil

    2014-05-01

    The complement system is important part of our innate immune system and interacts directly with the hemostatic system. Disorders of complement activation or dysregulation resulting in excess complement generation, such as Paroxysmal Nocturnal Hemoglobinuria (PNH), atypical Hemolytic uremic Syndrome (aHUS) and antiphospholipid syndrome (APLS) have been associated with significant thrombophilia. Terminal Complement (C5b-9) deposition on endothelial and tumor cell membranes has also been reported in a variety of cancer. Recent developments in complement inhibition have given us new insights into the mechanism of thrombosis in these disorders.

  17. The Complement System in Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Xuebin Qin; Bin Gao

    2006-01-01

    The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors.Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases.

  18. The role of heparan sulfate as determining pathogenic factor in complement factor H-associated diseases.

    Science.gov (United States)

    Loeven, Markus A; Rops, Angelique L W M M; Berden, Jo H M; Daha, Mohamed R; Rabelink, Ton J; van der Vlag, Johan

    2015-02-01

    Complement factor H (FH) systemically inhibits excessive complement activation in the microenvironment of host cells, but for instance not on microbes. This self-recognition is mediated by two binding sites that recognize distinctly sulfated heparan sulfate (HS) domains. The interaction with HS not only concentrates FH on host cells, but directly affects its activity, evoking novel models of conformational activation. Genetic aberrations in the HS-binding domains systemically disturb the protective function of FH, yet the resulting loss of complement control affects mainly ocular and renal tissues. Recent results suggest that the specific expression of HS domains in these tissues restricts the interaction of HS to a single binding site within FH. This lack of redundancy could predispose eyes and kidneys to complement-mediated damage, making HS a central determinant for FH-associated diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The Semantics of Complementation in English: A Cognitive Semantic Account of Two English Complement Constructions

    Science.gov (United States)

    Smith, Michael B.

    2009-01-01

    Studies on complementation in English and other languages have traditionally focused on syntactic issues, most notably on the constituent structures of different complement types. As a result, they have neglected the role of meaning in the choice of different complements. This paper investigates the semantics of complementation within the…

  20. Sarcoidose renal

    Directory of Open Access Journals (Sweden)

    AQUINO MARIA ENEDINA CLAUDINO DE

    2001-01-01

    Full Text Available Em uma mulher de 62 anos, branca, em avaliação pré-operatória de facectomia, foram detectadas alterações urinárias, tendo sido firmados os diagnósticos de calculose renal esquerda e exclusão renal homolateral. No pré-operatório da nefrectomia foram evidenciados processo pulmonar intersticial bilateral e adenopatia torácica, cuja investigação foi adiada para após a cirurgia. No rim retirado foram detectados granulomas epitelióides não necrotizantes, o mesmo ocorrendo posteriormente em biópsia transbrônquica. A paciente foi tratada com metilprednisolona, com discreta melhora pulmonar, o que não ocorreu com a função renal. O diagnóstico final foi de sarcoidose com envolvimento pulmonar, ganglionar torácico e renal.

  1. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  2. Renal heparan sulfate proteoglycans modulate fibroblast growth factor 2 signaling in experimental chronic transplant dysfunction.

    Science.gov (United States)

    Katta, Kirankumar; Boersema, Miriam; Adepu, Saritha; Rienstra, Heleen; Celie, Johanna W A M; Mencke, Rik; Molema, Grietje; van Goor, Harry; Berden, Jo H M; Navis, Gerjan; Hillebrands, Jan-Luuk; van den Born, Jacob

    2013-11-01

    Depending on the glycan structure, proteoglycans can act as coreceptors for growth factors. We hypothesized that proteoglycans and their growth factor ligands orchestrate tissue remodeling in chronic transplant dysfunction. We have previously shown perlecan to be selectively up-regulated in the glomeruli and arteries in a rat renal transplantation model. Using the same model, here we present quantitative RT-PCR profiling data on proteoglycans and growth factors from laser-microdissected glomeruli, arterial tunicae mediae, and neointimae at 12 weeks after transplantation. In glomeruli and neointimae of allografts, selective induction of the matrix heparan sulfate proteoglycan perlecan was observed, along with massive accumulation of fibroblast growth factor 2 (FGF2). Profiling the heparan sulfate polysaccharide side chains revealed conversion from a non-FGF2-binding heparan sulfate phenotype in control and isografted kidneys toward a FGF2-binding phenotype in allografts. In vitro experiments with perlecan-positive rat mesangial cells showed that FGF2-induced proliferation is dependent on sulfation and can be inhibited by exogenously added heparan sulfate. These findings indicate that matrix proteoglycans such as perlecan serve as functional docking platforms for FGF2 in chronic transplant dysfunction. We speculate that heparin-like glycomimetics could be a promising intervention to retard development of glomerulosclerosis and neointima formation in chronic transplant dysfunction.

  3. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  4. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  5. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  6. Renal Hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  7. Effects of Sodium Selenite on Formaldehyde Induced Renal Toxicity in Mice

    Directory of Open Access Journals (Sweden)

    Shabnam Mohammadi 1,2 * , Maryam Moghimian 3, Hanieh Torabzadeh 4, Mahla Langari 4, Roghayeh Nazeri 4, Zahra Karimi 4, Elham Sangari 4, Najmeh Jagarmi 5, Alireza Mohammad Zadeh 3, Mehdi Karimi 7, Kamyar Tavakkoli 8, Ali Delshad 9, Fatemeh Mohammadzadeh 3, Majid Ghayour-Mobarhan 10

    2016-12-01

    Full Text Available Background: Formaldehyde is widely used for industrial applications. Renal injury is an adverse effect associated with formaldehyde. Few studies have explored the potential benefits of protective factors on formaldehyde induced renal toxicity. This study evaluated the dose dependent effects of sodium selenite on the biochemical and histopathological effects of formaldehyde on murine kidney. Methods: Forty eight adult Balb/c male mice were randomized into six groups: a control group, a formaldehyde group and experimental III-VI groups. Formaldehyde group was injected with 10 mg/kg formaldehyde and groups III-VI received intraperitoneally doses of 0.1, 0.2, 0.4, 0.8 mg/kg selenium. After two weeks, a stereological study was done in accordance with the principle of Cavalieri and serum concentrations of urea and creatinine were measured. Data were analyzed using ANOVA and SPSS software. Results: Glomerosclerosis, necrosis and vacuolization were observed in the convoluted tubules of animals treated with formaldehyde. The biochemical markers, volume and count of glomeruli in the group treated with formaldehyde was significantly difference compared to the control group (P<0.05. The volume of the glomeruli in the group treated with 0.2 and 0.4 mg selenium and urea level in the group treated with 0.4 and 0.1 mg/kg selenium was significantly difference compared to the control group (P <0.05. The count of glomeruli and creatinine level in the selenium group was significantly difference compared to the control group (P ≤ 0.0001. Conclusions: A dose of 0.2 mg/kg of sodium selenite caused partial protective effect on the renal tissue and function in exposed to formaldehyde.

  8. Efficacy and complications of ultrasound-guided percutaneous renal biopsy using 18 G automatic biopsy gun in diffuse renal disease: Analysis of 203 cases

    Energy Technology Data Exchange (ETDEWEB)

    Gwon, Dong Il; Lee, Kang Hoon; Song, Kyung Sup; An, Suk Joo; Son, Sang Bum; Kim, Hyeon Suk [The Catholic University of Korea, St. Paul' s Hospital, Seoul (Korea, Republic of); Kim, Jee Young; Kim, Won Young; Park, Young Ha [The Catholic University of Korea, St. Vincent' s Hospital, Suwon (Korea, Republic of)

    2000-12-15

    To evaluate the efficacy and complications of ultrasound-guided percutaneous renal biopsy using 18G automatic biopsy gun in patients with diffuse renal disease. 203 ultrasound-guided renal biopsies using 18G automatic biopsy gun were performed in 197 patients for the diagnosis of diffuse renal disease. The success and complication rates were retrospectively evaluated by analysis of pathologic and clinical records and post-procedure ultrasonograms of the patients. Out of 203 renal biopsies, adequate tissues for pathologic diagnosis were obtained in 184 (90.6%) biopsies. The mean number of needle passes was 2.08, and the mean number of retrieved glomeruli was 7.71 {+-} 4.23. Minor complications occurred in seven biopsies (3.45%) including asymptomatic macroscopic hematuria in five (2.45%) and small subcapsular hematomas in two (1%). No patients required transfusion or surgery because of biopsy-related complication. Ultrasound-guided percutaneous renal biopsy using 18G automatic biopsy gun was an effective method for the pathologic diagnosis of diffuse renal disease and safe with low complication rate related to the procedure.

  9. Proteomic analysis of formalin-fixed paraffin-embedded glomeruli suggests depletion of glomerular filtration barrier proteins in two-kidney, one-clip hypertensive rats.

    Science.gov (United States)

    Finne, Kenneth; Vethe, Heidrun; Skogstrand, Trude; Leh, Sabine; Dahl, Tone D; Tenstad, Olav; Berven, Frode S; Reed, Rolf K; Vikse, Bjørn Egil

    2014-12-01

    It is well known that hypertension may cause glomerular damage, but the molecular mechanisms involved are still incompletely understood. In the present study, we used formalin-fixed paraffin-embedded (FFPE) tissue to investigate changes in the glomerular proteome in the non-clipped kidney of two-kidney one-clip (2K1C) hypertensive rats, with special emphasis on the glomerular filtration barrier. 2K1C hypertension was induced in 6-week-old Wistar Hannover rats (n = 6) that were sacrificed 23 weeks later and compared with age-matched sham-operated controls (n = 6). Tissue was stored in FFPE tissue blocks and later prepared on tissue slides for laser microdissection. Glomeruli without severe morphological damage were isolated, and the proteomes were analysed using liquid chromatography-tandem mass spectrometry. 2K1C glomeruli showed reduced abundance of proteins important for slit diaphragm complex, such as nephrin, podocin and neph1. The podocyte foot process had a pattern of reduced abundance of transmembrane proteins but unchanged abundances of the podocyte cytoskeletal proteins synaptopodin and α-actinin-4. Lower abundance of important glomerular basement membrane proteins was seen. Possible glomerular markers of damage with increased abundance in 2K1C were transgelin, desmin and acyl-coenzyme A thioesterase 1. Microdissection and tandem mass spectrometry could be used to investigate the proteome of isolated glomeruli from FFPE tissue. Glomerular filtration barrier proteins had reduced abundance in the non-clipped kidney of 2K1C hypertensive rats. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

  10. The complement system in human cardiometabolic disease.

    Science.gov (United States)

    Hertle, E; Stehouwer, C D A; van Greevenbroek, M M J

    2014-10-01

    The complement system has been implicated in obesity, fatty liver, diabetes and cardiovascular disease (CVD). Complement factors are produced in adipose tissue and appear to be involved in adipose tissue metabolism and local inflammation. Thereby complement links adipose tissue inflammation to systemic metabolic derangements, such as low-grade inflammation, insulin resistance and dyslipidaemia. Furthermore, complement has been implicated in pathophysiological mechanisms of diet- and alcohol induced liver damage, hyperglycaemia, endothelial dysfunction, atherosclerosis and fibrinolysis. In this review, we summarize current evidence on the role of the complement system in several processes of human cardiometabolic disease. C3 is the central component in complement activation, and has most widely been studied in humans. C3 concentrations are associated with insulin resistance, liver dysfunction, risk of the metabolic syndrome, type 2 diabetes and CVD. C3 can be activated by the classical, the lectin and the alternative pathway of complement activation; and downstream activation of C3 activates the terminal pathway. Complement may also be activated via extrinsic proteases of the coagulation, fibrinolysis and the kinin systems. Studies on the different complement activation pathways in human cardiometabolic disease are limited, but available evidence suggests that they may have distinct roles in processes underlying cardiometabolic disease. The lectin pathway appeared beneficial in some studies on type 2 diabetes and CVD, while factors of the classical and the alternative pathway were related to unfavourable cardiometabolic traits. The terminal complement pathway was also implicated in insulin resistance and liver disease, and appears to have a prominent role in acute and advanced CVD. The available human data suggest a complex and potentially causal role for the complement system in human cardiometabolic disease. Further, preferably longitudinal studies are needed to

  11. Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Yay, A; Akkuş, D; Yapıslar, H; Balcıoglu, E; Sonmez, M F; Ozdamar, S

    2014-11-01

    Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus.

  12. JAK2-STAT3 pathway regulates the expression of complement factor B in autosomal dominant polycystic kidney disease

    Institute of Scientific and Technical Information of China (English)

    周晨晨

    2014-01-01

    Objective To investigate the role of JAK2-STAT3pathway in the expression of complement factor B(CFB)in autosomal dominant polycystic kidney disease(ADP KD).Methods Renal tissue samples of patients with ADPKD after nephrectomy were collected.Normal rena tissue samples as control were taken from patients afte radical nephrectomy.Renal tissue samples of Han:SPRD Cy/+rats(ADPKD model)and wild-type Han:

  13. Postoperative Atypical Hemolytic Uremic Syndrome Associated with Complement C3 Mutation

    Directory of Open Access Journals (Sweden)

    Eiji Matsukuma

    2014-01-01

    Full Text Available Atypical hemolytic uremic syndrome (aHUS can be distinguished from typical or Shiga-like toxin-induced HUS. The clinical outcome is unfavorable; up to 50% of affected patients progress to end-stage renal failure and 25% die during the acute phase. Multiple conditions have been associated with aHUS, including infections, drugs, autoimmune conditions, transplantation, pregnancy, and metabolic conditions. aHUS in the nontransplant postsurgical period, however, is rare. An 8-month-old boy underwent surgical repair of tetralogy of Fallot. Neurological disturbances, acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia developed 25 days later, and aHUS was diagnosed. Further evaluation revealed that his complement factor H (CFH level was normal and that anti-FH antibodies were not detected in his plasma. Sequencing of his CFH, complement factor I, membrane cofactor protein, complement factor B, and thrombomodulin genes was normal. His ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin-1 repeats 13 activity was also normal. However, he had a potentially causative mutation (R425C in complement component C3. Restriction fragment length polymorphism analysis revealed that his father and aunt also had this mutation; however, they had no symptoms of aHUS. We herein report a case of aHUS that developed after cardiovascular surgery and was caused by a complement C3 mutation.

  14. Complement defects in patients with chronic rhinosinusitis

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Lange, Bibi; Kjeldsen, Anette D;

    2012-01-01

    The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS), and more specifically studied...... whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper...... on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. We found that the frequency of complement defects...

  15. Complement diagnostics: concepts, indications, and practical guidelines.

    Science.gov (United States)

    Nilsson, Bo; Ekdahl, Kristina Nilsson

    2012-01-01

    Aberrations in the complement system have been shown to be direct or indirect pathophysiological mechanisms in a number of diseases and pathological conditions such as autoimmune disease, infections, cancer, allogeneic and xenogeneic transplantation, and inflammation. Complement analyses have been performed on these conditions in both prospective and retrospective studies and significant differences have been found between groups of patients, but in many diseases, it has not been possible to make predictions for individual patients because of the lack of sensitivity and specificity of many of the assays used. The basic indications for serological diagnostic complement analysis today may be divided into three major categories: (a) acquired and inherited complement deficiencies; (b) disorders with complement activation; (c) inherited and acquired C1INH deficiencies. Here, we summarize indications, techniques, and interpretations for basic complement analyses and present an algorithm, which we follow in our routine laboratory.

  16. Complement Diagnostics: Concepts, Indications, and Practical Guidelines

    Directory of Open Access Journals (Sweden)

    Bo Nilsson

    2012-01-01

    Full Text Available Aberrations in the complement system have been shown to be direct or indirect pathophysiological mechanisms in a number of diseases and pathological conditions such as autoimmune disease, infections, cancer, allogeneic and xenogeneic transplantation, and inflammation. Complement analyses have been performed on these conditions in both prospective and retrospective studies and significant differences have been found between groups of patients, but in many diseases, it has not been possible to make predictions for individual patients because of the lack of sensitivity and specificity of many of the assays used. The basic indications for serological diagnostic complement analysis today may be divided into three major categories: (a acquired and inherited complement deficiencies; (b disorders with complement activation; (c inherited and acquired C1INH deficiencies. Here, we summarize indications, techniques, and interpretations for basic complement analyses and present an algorithm, which we follow in our routine laboratory.

  17. Role of Complement in Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Berentsen, Sigbjørn

    2015-09-01

    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  18. Role of Complement in Autoimmune Hemolytic Anemia

    OpenAIRE

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorder...

  19. Differences in complement activation between complement-resistant and complement-sensitive Moraxella (Branhamella) catarrhalis strains occur at the level of membrane attack complex formation.

    OpenAIRE

    Verduin, C.M.; Jansze, M.; Hol, C; Mollnes, T E; Verhoef, J; Van Dijk, H.

    1994-01-01

    The mechanism of resistance to human complement-mediated killing in Moraxella catarrhalis was studied by comparing different complement-sensitive and complement-resistant M. catarrhalis strains in a functional bystander hemolysis assay and an enzyme-linked immunosorbent assay (ELISA) for soluble terminal complement complexes. Complement-resistant stains appeared to activate complement to the same extent as, or even slightly better than, complement-sensitive strains. This indicates that comple...

  20. Complement defects in patients with chronic rhinosinusitis.

    Directory of Open Access Journals (Sweden)

    Maria Q Gaunsbaek

    Full Text Available The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS, and more specifically studied whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. We found that the frequency of complement defects was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Our studies show that defects in the complement system collectively may play an immunological role related to the development of CRS. However, an association between severity of symptoms and presence of complement defects could not be demonstrated.

  1. Complement: an overview for the clinician.

    Science.gov (United States)

    Varela, Juan Carlos; Tomlinson, Stephen

    2015-06-01

    The complement system is an essential component of the immune system. It is a highly integrative system and has a number of functions, including host defense, removal of injured cells and debris, modulation of metabolic and regenerative processes, and regulation of adaptive immunity. Complement is activated via different pathways and it is regulated tightly by several mechanisms to prevent host injury. Imbalance between complement activation and regulation can manifest in disease and injury to self. This article provides an outline of complement activation pathways, regulatory mechanisms, and normal physiologic functions of the system.

  2. On distribution of complementizers in contemporary Serbian

    Directory of Open Access Journals (Sweden)

    Moskovljević Jasmina

    2004-01-01

    Full Text Available The paper investigates the principles governing the distribution of complementizers in contemporary Serbian. Evidence is presented that the distribution of da, što, kako, gde, da li, and numerous interrogative pronouns and adverbials which may function as complementizers is determined not only by matrix-verb subcategorization properties and semantic co-occurrence restrictions which hold between the predicate and its complement, but by the lexical an syntactic properties of the particular verb class (or subclass to which matrix predicate belongs as well. According to their ability to govern a particular complementizer, ten major verb subclasses are identified in contemporary Serbian, and their specific properties are signaled.

  3. Role of Complement in Multiorgan Failure

    Directory of Open Access Journals (Sweden)

    Daniel Rittirsch

    2012-01-01

    Full Text Available Multiorgan failure (MOF represents the leading cause of death in patients with sepsis and systemic inflammatory response syndrome (SIRS following severe trauma. The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed.

  4. Roflumilast enhances the renal protective effects of retinoids in an HIV-1 transgenic mouse model of rapidly progressive renal failure.

    Science.gov (United States)

    Zhong, Yifei; Wu, Yingwei; Liu, Ruijie; Deng, Yueyi; Mallipattu, Sandeep K; Klotman, Paul E; Chuang, Peter Y; He, John C

    2012-05-01

    Retinoic acid decreases proteinuria and glomerulosclerosis in several animal models of kidney disease by protecting podocytes from injury. Our recent in vitro studies suggest that all-trans retinoic acid induces podocyte differentiation by activating the retinoic acid receptor-α (RARα)/cAMP/PKA/CREB pathway. When used in combination with all-trans retinoic acid, an inhibitor of phosphodiesterase 4 further enhanced podocyte differentiation by increasing intracellular cAMP. Additionally, we found that Am580, a specific RARα agonist, has similar renal protective effects as all-trans retinoic acid in a rederived colony of HIV-1 transgenic mice with rapidly progressive renal failure (HIV-Tg) that mimics human HIV-associated nephropathy. Treatment with either the inhibitor of phosphodiesterase 4, roflumilast, or Am580 significantly reduced proteinuria, attenuated kidney injury, and improved podocyte differentiation in these HIV-Tg mice. Additional renal protective effects were found when roflumilast was combined with Am580. Consistent with the in vitro data, glomeruli from HIV-Tg mice treated with both Am580 and roflumilast had more active phosphorylated CREB than with either agent alone. Thus, phosphodiesterase 4 inhibitors could be used in combination with RARα agonists to provide additional renal protection.

  5. Progressive glomerulosclerosis and renal failure following perinatal gamma radiation in the beagle

    Energy Technology Data Exchange (ETDEWEB)

    Jaenke, R.S.; Phemister, R.D.; Norrdin, R.W.

    1980-06-01

    The renal effects of whole body irradiation in the perinatal period were studied in the dog. Ninety-three dogs received a single sublethal exposure in the range of 270 to 435 R in either late gestation (55 days postcoitus) or early postnatal life (2 days postpartum) and were sacrificed at 70 days, 2, or 4 years of age. Early renal lesions in 70-day-old irradiated dogs were characterized by arrested glomerular maturation and degeneration resulting in reduced functional renal mass. Mature glomeruli exhibited mesangial proliferation. At 2 and 4 years of age, surviving irradiated dogs exhibited sever renal disease associated with progressive glomerular damage which was characterized by mesangial proliferation and compression of capillary lumina, epithelial degeneration and focal capsular adhesions, and ultimately obliterative glomerulosclerosis. Twenty-one of the 93 irradiated dogs died in renal failure before 4 years of age with advanced glomerulosclerosis. The phatogenesis of this progressive renal lesion may be related to the interaction of three specific factors. These include (1) the effect of direct radiation damage to mature kidney components; (2) the loss of outer cortical nephrons resulting in increased work load of the surviving nephrons; and (3) the effect of compensatory hypertrophy related to the loss of renal parenchyma as the rapid growth rates associated with kidney maturation.

  6. Renal amyloidosis in a patient with X-linked agammaglobulinemia (Bruton's disease) and bronchiectasis.

    Science.gov (United States)

    Gonzalo-Garijo, M A; Sánchez-Vega, S; Pérez-Calderón, R; Pérez-Rangel, I; Corrales-Vargas, S; Fernández de Mera, J J; Robles, R

    2014-01-01

    We present a patient with Bruton's disease and bronchiectasis who developed renal AA amyloidosis. A 38 year-old man was diagnosed with X-linked agammaglobulinemia (Bruton's disease) when he was 3 years old, and he has been treated with parenteral immunoglobulin since then. Eighteen years later, he was diagnosed with central pulmonary bronchiectasis by computerized tomography (CT). In 2008, he gradually developed anemia, edema of lower limbs, and loss of weight. Laboratory studies revealed deterioration of renal function, normocytic normochromic anemia and nephrotic range proteinuria. Hepatitis B and C and HIV serology were negative. Ultrasound and CT of abdomen were normal. A renal biopsy revealed deposits with positive PAS and Congo red staining in glomeruli, interstitium, and vessel's walls. Immunohistochemistry showed positive staining of the A amyloid. Direct immunofluorescence was positive with thioflavin and showed focal and glomerular mesangial IgG deposits, suggesting renal AA amyloidosis. For 2 years the patient conducted pharmacological treatment and follow-up for the Nephrology department with poor prognosis and progression of renal function impairment. In January 2011 he began dialysis treatment with improvement, and he is currently on the waiting list for renal transplantation. We present a patient with Bruton's disease and bronchiectasis who developed renal AA amyloidosis a finding rarely reported.

  7. Review on complement analysis method and the roles of glycosaminoglycans in the complement system.

    Science.gov (United States)

    Li, Lian; Li, Yan; Ijaz, Muhammad; Shahbaz, Muhammad; Lian, Qianqian; Wang, Fengshan

    2015-12-10

    Complement system is composed of over 30 proteins and it plays important roles in self-defence and inflammation. There are three activation pathways, including classical pathway, alternative pathway and lectin pathway, in complement system, and they are associated with many diseases such as osteoarthritis and age-related macular degeneration. Modulation of the complement system may be a promising strategy in the treatment of related diseases. Glycosaminoglycans are anionic linear polysaccharides without branches. They are one kind of multi-functional macromolecules which have great potential in regulating complement system. This review is organized around two aspects between the introduction of complement system and the interaction of glycosaminoglycans with complement system. Three complement activation pathways and the biological significance were introduced first. Then functional analysis methods were compared to provide a strategy for potential glycosaminoglycans screen. Finally, the roles of glycosaminoglycans played in the complement system were summed up.

  8. Noun complement clauses as referential modifiers

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    Carlos de Cuba

    2017-01-01

    Full Text Available A number of recent analyses propose that so-called noun complement clauses should be analyzed as a type of relative clause. In this paper, I present a number of complications for any analysis that equates noun complement clauses to relative clauses, and conclude that this type of analysis is on the wrong track. I present cross-linguistic evidence showing that the syntactic behavior of noun complement clauses does not pattern with relative clauses. Patterns of complementizer choice and complementizer drop as well as patterns involving main clause phenomena and extraction differ in the two constructions, which I argue is unexpected under a relative clause analysis that involves operator movement. Instead I present an alternative analysis in which I propose that the referentiality of a noun complement clause is linked to its syntactic behavior. Following recent work, I claim that referential clauses have a syntactically truncated left-periphery, and this truncation can account for the lack of main clause phenomena in noun complement clauses. I argue that the truncation analysis is also able to accommodate complementizer data patterns more easily than relative clause analyses that appeal to operator movement.

  9. Complement pathways and meningococcal disease : diagnostic aspects

    DEFF Research Database (Denmark)

    Sjöholm, A G; Truedsson, L; Jensenius, Jens Christian

    2001-01-01

    Complement is an immunological effector system that bridges innate and acquired immunity in several ways. There is a striking association between susceptibility to meningococcal disease and various forms of complement deficiency (1,2). In defense against bacterial infection, the most important...

  10. Hyperbolic structures on a toric arrangement complement

    NARCIS (Netherlands)

    Shen, Dali

    2015-01-01

    This thesis studies the geometric structures on toric arrangement complements. Inspired by the special hypergeometric functions associated with a root system, we consider a family of connections on a total space which is the product of the complement of a toric arrangement (=finite union of hypertor

  11. The complement system in systemic autoimmune disease

    NARCIS (Netherlands)

    Chen, Min; Daha, Mohamed R.; Kallenberg, Cees G. M.

    2010-01-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via

  12. Complement associated pathogenic mechanisms in myasthenia gravis.

    Science.gov (United States)

    Tüzün, Erdem; Christadoss, Premkumar

    2013-07-01

    The complement system is profoundly involved in the pathogenesis of acetylcholine receptor (AChR) antibody (Ab) related myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). The most characteristic finding of muscle pathology in both MG and EAMG is the abundance of IgG and complement deposits at the nerve-muscle junction (NMJ), suggesting that AChR-Ab induces muscle weakness by complement pathway activation and consequent membrane attack complex (MAC) formation. This assumption has been supported with EAMG resistance of complement factor C3 knockout (KO), C4 KO and C5 deficient mice and amelioration of EAMG symptoms following treatment with complement inhibitors such as cobra venom factor, soluble complement receptor 1, anti-C1q, anti-C5 and anti-C6 Abs. Moreover, the complement inhibitor decay accelerating factor (DAF) KO mice exhibit increased susceptibility to EAMG. These findings have brought forward improvisation of novel therapy methods based on inhibition of classical and common complement pathways in MG treatment.

  13. The role of complement in AMD.

    Science.gov (United States)

    Zipfel, Peter F; Lauer, Nadine; Skerka, Christine

    2010-01-01

    Age related macular degeneration (AMD) is a common form of blindness in the western world and genetic variations of several complement genes, including the complement regulator Factor H, the central complement component C3, Factor B, C2, and also Factor I confer a risk for the disease. However deletion of a chromosomal segment in the Factor H gene cluster on human chromosome 1, which results in the deficiency of the terminal pathway regulator CFHR1, and of the putative complement regulator CFHR3 has a protective effect for development of AMD. The Factor H gene encodes two proteins Factor H and FHL1 which are derived from alternatively processed transcripts. In particular a sequence variation at position 402 of both Factor H and FHL1 is associated with a risk for AMD. A tyrosine residue at position 402 represents the protective and a histidine residue the risk variant. AMD is considered a chronic inflammatory disease, which can be caused by defective and inappropriate regulation of the continuously activated alternative complement pathway. This activation generates complement effector products and inflammatory mediators that stimulate further inflammatory reactions. Defective regulation can lead to formation of immune deposits, drusen and ultimately translate into damage of retinal pigment epithelial cells, rupture of the interface between these epithelial cells and the Bruch's membrane and vision loss. Here we describe the role of complement in the retina and summarize the current concept how defective or inappropriate local complement control contributes to inflammation and the pathophysiology of AMD.

  14. Functional networks of aging markers in the glomeruli of IgA nephropathy: a new therapeutic opportunity

    Science.gov (United States)

    Jiang, Hong; Liang, Ludan; Qin, Jing; Lu, Yingying; Li, Bingjue; Wang, Yucheng; Lin, Chuan; Zhou, Qin; Feng, Shi; Yip, Shun H.; Xu, Feng; Lai, EnYin; Wang, Junwen; Chen, Jianghua

    2016-01-01

    IgA nephropathy(IgAN) is the most common primary glomerular disease in China. Primary infections always occur before IgAN. However, the pathology of IgAN is still unclear. Previously we found that LL37, a protein secreted by senescent cells, was specific for the progression of IgAN, and also played a role in the neutrophil function. So we hypothesized that the infiltration of neutrophils, inflammation factors, and aging markers, which were modulated by functional networks, induced the immune response and renal injury. RNA-Sequencing (RNA-seq) can be used to study the whole transcriptome and detect splicing variants that are expressed in a specific cell type or tissue. We separate glomerulus from the renal biopsy tissues. After RNA extraction, the sequences were analyzed with Illumina HiSeq 2000/2500. 381 genes with differential expression between the IgAN patients and the healthy controls were identified. Only PLAU, JUN, and FOS were related to DNA damage, telomere dysfunction-induced aging markers, neutrophil function and IgA nephropathy. The networks showed the possibility of these genes being connected. We conclude that DNA damage and telomere dysfunction could play important roles in IgA nephropathy. In addition, neutrophils are also important factors in this disease. The networks of these markers showed the mechanism pathways that are involved in the duration of the occurrence and progression of IgA nephropathy and might be a new therapeutic opportunity for disease treatment. PMID:27127888

  15. Complement activation by Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, E T; Kharazmi, A; Garred, P

    1993-01-01

    In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm...... mode of growth. In this study we investigated the role of biofilms in activation of complement, a major contributor to the inflammatory process. Complement activation by P. aeruginosa was examined in a complement consumption assay, production of C3 and factor B conversion products assessed by crossed...... immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact...

  16. Renal Cysts

    Science.gov (United States)

    ... as “simple” cysts, meaning they have a thin wall and contain water-like fluid. Renal cysts are fairly common in ... simple kidney cysts, meaning they have a thin wall and only water-like fluid inside. They are fairly common in ...

  17. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  18. Drug-induced renal injury

    African Journals Online (AJOL)

    Drugs can cause acute renal failure by causing pre-renal, intrinsic or post-renal toxicity. Pre-renal ... incidence of drug dose adjustment in renal impairment in the SAMJ. ... Fever, haemolytic anaemia, thrombocytopenia, renal impairment and.

  19. Complement system part II: role in immunity

    Directory of Open Access Journals (Sweden)

    Nicolas S. Merle

    2015-05-01

    Full Text Available The complement system has been considered for a long time as a simple lytic system, aimed to kill bacteria infecting the host organism. Nowadays this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing a direct killing by C5b-9 membrane attack complex by triggering inflammatory responses with the anaphylatoxins C3a and C5a and helps the mounting of an adaptive immune response, involving antigen presenting cells, T- and B- lymphocytes. But it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Also examples will be discussed, where inadequate complement activation becomes a disease cause, including atypical hemolytic uremic syndrome (aHUS, C3 glomerulopathies (C3G and systemic lupus erythematosus (SLE. Age related macular degeneration (AMD and cancer will be described as examples showing that complement contributes to a large variety of diseases, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target.

  20. Complement System Part II: Role in Immunity

    Science.gov (United States)

    Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

    2015-01-01

    The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922

  1. Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.

    Directory of Open Access Journals (Sweden)

    Lionel Lattenist

    Full Text Available The Endothelial Protein C Receptor (EPCR is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR and antibody-mediated (ABMR rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR, we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation.

  2. Renal phenotypic investigations of megalin-deficient patients: novel insights into tubular proteinuria and albumin filtration.

    Science.gov (United States)

    Storm, Tina; Tranebjærg, Lisbeth; Frykholm, Carina; Birn, Henrik; Verroust, Pierre J; Nevéus, Tryggve; Sundelin, Birgitta; Hertz, Jens Michael; Holmström, Gerd; Ericson, Katharina; Christensen, Erik I; Nielsen, Rikke

    2013-03-01

    The reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients. Direct sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples. In the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli. This study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.

  3. Indications and results of renal biopsy in children: A single-center experience from Morocco

    Directory of Open Access Journals (Sweden)

    Fatima Zohra Souilmi

    2015-01-01

    Full Text Available The contribution of renal biopsy (RB is of major importance in the management of many renal diseases in children. Specific indications for performing biopsy in children include steroid-resistant nephrotic syndrome (NS and secondary nephropathies. The aim of our study was to report the common histological varieties of kidney diseases in children in Morocco. In this retrospective and descriptive study, we included all renal biopsies performed in patients under 16 years in the Department of Pediatrics of Hassan II University Hospital, Fez, Morocco from July 2009 to December 2013. Biopsy samples without glomeruli and those with less than five glomeruli or repeat biopsies on the same patient were excluded from our study. We performed 112 RBs during this period; the average age at the time of RB was 10.05 ± 4 years and the sex-ratio was 1.07. The indications for RB were NS with hematuria and/or renal failure (RF in 32.1%, active urinary sediment in 21.4%, isolated NS in 15.2%, RF in 13.4% and steroid-resistant NS in 10.7% of cases. Primary nephropathies represented 59.8% of cases, with a predominance of minimal change disease (MCD seen in 40.2% of the cases. Secondary nephropathies accounted for 27.7% of the cases, with a predominance of lupus nephritis (11.6%, followed by Henoch-Schonlein purpura nephritis (6.2% of cases and post-streptococcal glomerulonephritis (3.6%. There was one case of hepatitis B virus-associated membranous glomerulonephritis. Chronic glomerulonephritis accounted for 12.5% of the cases. Vascular and tubulo-interstitial nephritis were rare. Our study confirmed that primary glomerular nephropathy was the most common renal disease in children. The most common lesion was MCD. Secondary nephropathies were less frequent, with a predominance of lupus nephritis.

  4. Renal failure (chronic)

    OpenAIRE

    Clase, Catherine

    2011-01-01

    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  5. Viral mimicry of the complement system

    Indian Academy of Sciences (India)

    John Bernet; Jayati Mullick; Akhilesh K Singh; Arvind Sahu

    2003-04-01

    The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign pathogens. Although viruses are smaller in size and have relatively simple structure, they are not immune to complement attack. Thus, activation of the complement system can lead to neutralization of cell-free viruses, phagocytosis of C3b-coated viral particles, lysis of virus-infected cells, and generation of inflammatory and specific immune responses. However, to combat host responses and succeed as pathogens, viruses not only have developed/adopted mechanisms to control complement, but also have turned these interactions to their own advantage. Important examples include poxviruses, herpesviruses, retroviruses, paramyxoviruses and picornaviruses. In this review, we provide information on the various complement evasion strategies that viruses have developed to thwart the complement attack of the host. A special emphasis is given on the interactions between the viral proteins that are involved in molecular mimicry and the complement system.

  6. Properdin in complement activation and tissue injury.

    Science.gov (United States)

    Lesher, Allison M; Nilsson, Bo; Song, Wen-Chao

    2013-12-15

    The plasma protein properdin is the only known positive regulator of complement activation. Although regarded as an initiator of the alternative pathway of complement activation at the time of its discovery more than a half century ago, the role and mechanism of action of properdin in the complement cascade has undergone significant conceptual evolution since then. Despite the long history of research on properdin, however, new insight and unexpected findings on the role of properdin in complement activation, pathogen infection and host tissue injury are still being revealed by ongoing investigations. In this article, we provide a brief review on recent studies that shed new light on properdin biology, focusing on the following three topics: (1) its role as a pattern recognition molecule to direct and trigger complement activation, (2) its context-dependent requirement in complement activation on foreign and host cell surfaces, and (3) its involvement in alternative pathway complement-mediated immune disorders and considerations of properdin as a potential therapeutic target in human diseases.

  7. Infections Revealing Complement Deficiency in Adults

    Science.gov (United States)

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.

    2016-01-01

    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  8. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Yingchun Wang

    2015-01-01

    Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

  9. Renale Osteopathie

    OpenAIRE

    Horn S

    2001-01-01

    Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Thera...

  10. Renale Knochenerkrankungen

    Directory of Open Access Journals (Sweden)

    Mayer G

    2008-01-01

    Full Text Available Störungen des Mineral- und Knochenstoffwechsels sind bei fast allen Patienten mit chronischen Nierenerkrankungen anzutreffen. Pathogenetisch spielt eine Neigung zur Phosphatretention bei einer Reduktion der glomerulären Filtrationsrate die zentrale Rolle. Neben typischen, aber sehr variablen Veränderungen der Knochenstruktur (renale Osteopathie besteht auch eine sehr enge Assoziation zwischen diesen Störungen und dem massiv erhöhten kardiovaskulären Risiko der Patienten.

  11. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  12. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  13. Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

    Science.gov (United States)

    Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

    2014-01-01

    A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

  14. Autocrine Effects of Tumor-Derived Complement

    Directory of Open Access Journals (Sweden)

    Min Soon Cho

    2014-03-01

    Full Text Available We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

  15. Heredity in fundamental left complemented algebras

    Directory of Open Access Journals (Sweden)

    Marina Haralampidou

    2016-06-01

    Full Text Available In the present paper, we introduce the notion of a fundamental complemented linear space, through continuous projections. This notion is hereditary. Relative to this, we prove that if a certain topological algebra is fundamental, then a concrete subspace is fundamental too. For a fundamental complemented linear space, we define the notion of continuity of the complementor. In some cases, we employ a generalized notion of complementation, that of (left precomplementation. In our main result, the continuity of the complementor for a certain fundamental complemented (topological algebra is inherited to the induced vector complementor of the underlying linear space of a certain right ideal. Weakly fundamental algebras are also considered in the context of locally convex ones.

  16. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    Energy Technology Data Exchange (ETDEWEB)

    Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.; Baumunk, D. [University of Magdeburg, Department of Urology (Germany); Buhtz, P. [Institute of Pathology, University of Magdeburg (Germany); Fischbach, F.; Pech, M. [University of Magdeburg, Department of Radiology (Germany); Mahnkopf, D. [Institute of Medical Technology and Research (Germany); Kropf, S. [Institute of Biometry, University of Magdeburg (Germany); Roessner, A. [Institute of Pathology, University of Magdeburg (Germany); Ricke, J. [University of Magdeburg, Department of Radiology (Germany); Schostak, M.; Liehr, U.-B. [University of Magdeburg, Department of Urology (Germany)

    2013-04-15

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  17. Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb

    Science.gov (United States)

    Bressel, Olaf Christian; Khan, Mona

    2015-01-01

    ABSTRACT Chemosensory specificity in the main olfactory system of the mouse relies on the expression of ∼1,100 odorant receptor (OR) genes across millions of olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE), and on the coalescence of OSN axons into ∼3,600 glomeruli in the olfactory bulb. A traditional approach for visualizing OSNs and their axons consists of tagging an OR gene genetically with an axonal marker that is cotranslated with the OR by virtue of an internal ribosome entry site (IRES). Here we report full cell counts for 15 gene‐targeted strains of the OR‐IRES‐marker design coexpressing a fluorescent protein. These strains represent 11 targeted OR genes, a 1% sample of the OR gene repertoire. We took an empirical, “count every cell” strategy: we counted all fluorescent cell profiles with a nuclear profile within the cytoplasm, on all serial coronal sections under a confocal microscope, a total of 685,673 cells in 56 mice at postnatal day 21. We then applied a strain‐specific Abercrombie correction to these OSN counts in order to obtain a closer approximation of the true OSN numbers. We found a 17‐fold range in the average (corrected) OSN number across these 11 OR genes. In the same series of coronal sections, we then determined the total volume of the glomeruli (TGV) formed by coalescence of the fluorescent axons. We found a strong linear correlation between OSN number and TGV, suggesting that TGV can be used as a surrogate measurement for estimating OSN numbers in these gene‐targeted strains. J. Comp. Neurol. 524:199–209, 2016. © 2015 Wiley Periodicals, Inc. PMID:26100963

  18. Complement activation and inhibition: a delicate balance

    DEFF Research Database (Denmark)

    Sjöberg, A P; Trouw, L A; Blom, A M

    2009-01-01

    Complement is part of the innate immune defence and not only recognizes microbes but also unwanted host molecules to enhance phagocytosis and clearance. This process of opsonisation must be tightly regulated to prevent immunopathology. Endogenous ligands such as dying cells, extracellular matrix...... activation. Disturbances to the complement regulation on endogenous ligands can lead to diseases such as age-related macular degeneration, neurological and rheumatic disorders. A thorough understanding of these processes might be crucial to developing new therapeutic strategies....

  19. The complement system in systemic autoimmune disease.

    Science.gov (United States)

    Chen, Min; Daha, Mohamed R; Kallenberg, Cees G M

    2010-05-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via the classical pathway has long been recognized in immune complex-mediated diseases such as cryoglobulinemic vasculitis and systemic lupus erythematosus (SLE). In SLE, the role of complement is somewhat paradoxical. It is involved in autoantibody-initiated tissue damage on the one hand, but, on the other hand, it appears to have protective features as hereditary deficiencies of classical pathway components are associated with an increased risk for SLE. There is increasing evidence that the alternative pathway of complement, even more than the classical pathway, is involved in many systemic autoimmune diseases. This is true for IgA-dominant Henoch Schönlein Purpura, in which additional activation of the lectin pathway contributes to more severe disease. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis the complement system was considered not to be involved since immunoglobulin deposition is generally absent in the lesions. However, recent studies, both in human and animal models, demonstrated complement activation via the alternative pathway as a major pathogenic mechanism. Insight into the role of the various pathways of complement in the systemic autoimmune diseases including the vasculitides opens up new ways of treatment by blocking effector pathways of complement. This has been demonstrated for monoclonal antibodies to C5 or C5a in experimental anti-phospholipid antibody syndrome and ANCA-associated vasculitis.

  20. Sorbents in acute renal failure and end-stage renal disease: middle molecule and cytokine removal.

    Science.gov (United States)

    Winchester, James F; Silberzweig, Jeffrey; Ronco, Claudio; Kuntsevich, Viktoria; Levine, Daniel; Parker, Tom; Kellum, John A; Salsberg, Jamie A; Quartararo, Peter; Levin, Nathan W

    2004-01-01

    Renal replacement therapy in acute renal failure (ARF) and chronic renal failure (end-stage renal disease; ESRD) has been based on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle-molecular-weight toxins, consisting of low-molecular-weight proteins and peptides (LMWP) and cytokines involved in inflammation. High-flux dialyzers are not efficient at removing LMWP, and for this reason, sorbents have been studied to augment or replace dialysis. Removal of LMWP such as beta2-microglobulin, leptin, complement factor D, angiogenin and cytokines such as interleukin (IL)-1, IL-6, IL-10, IL-18 and tumor necrosis factor-alpha has been established in animal models of sepsis and in ESRD patients using sorbents. Sorbent devices added to hemodialysis, or the use of such devices alone in inflammatory states, including sepsis, ARF, cardiopulmonary bypass, pre-explantation of donor organs and ESRD, are being studied.

  1. Differential renal glomerular changes induced by 5/6 nephrectomization between common marmoset monkeys (Callithrix jacchus) and rats.

    Science.gov (United States)

    Suzuki, Yui; Yamaguchi, Itaru; Onoda, Noriko; Saito, Takashi; Myojo, Kensuke; Imaizumi, Minami; Takada, Chie; Kimoto, Naoya; Takaba, Katsumi; Yamate, Jyoji

    2013-07-01

    We have been investigating the relevance and availability of 5/6 nephrectomized (Nx) common marmoset monkeys (Callithrix jacchus) as a chronic renal failure model. As a part of this investigation, renal glomerular changes in the Nx marmosets were histopathologically and immunohistochemically evaluated, and then compared with those in 5/6 Nx SD rats. In the Nx marmosets, the blood and urine parameters were elevated, excluding urine protein; histopathologically, enlargement of Bowman's capsule and atrophy of the glomeruli were observed in all animals, and other slight changes were also observed in 1 or 2 marmosets. There were no significant changes in the mesangial matrix injury score, vimentin and desmin positivity or the number of WT1 positive cells between the control and Nx marmoset groups. On the other hand, in the Nx rats, the blood and urine parameters were elevated; histopathologically, various changes were observed in the glomeruli, and the mesangial matrix injury score, vimentin and desmin positivity were increased, while the number of WT1 positive cells was decreased; these histopathological impacts on the renal glomerulus at 13 weeks after Nx in rats were more severe than that in the Nx marmosets. Because the glomerular basement membrane (GBM) was much thicker in the marmosets than in the rats in electron microscopy, the weaker pathological changes in the Nx marmosets might be due to the GBM thickness. This study showed for the first time glomerular lesions developed in the Nx marmosets, and the possible pathogenesis of the glomerular lesions was discussed.

  2. Myocardial infarction causes inflammation and leukocyte recruitment at remote sites in the myocardium and in the renal glomerulus.

    Science.gov (United States)

    Ruparelia, Neil; Digby, Janet E; Jefferson, Andrew; Medway, Debra J; Neubauer, Stefan; Lygate, Craig A; Choudhury, Robin P

    2013-05-01

    Acute myocardial infarction (AMI) results in the recruitment of leukocytes to injured myocardium. Additionally, myocardium remote to the infarct zone also becomes inflamed and is associated with adverse left ventricular remodelling. Renal ischaemic syndromes have been associated with remote organ inflammation and impaired function. Here, we tested the hypothesis that AMI results in remote organ (renal) inflammation. Mice were subjected to either AMI, sham procedure or no procedure and the inflammatory response in peripheral blood, injured and remote myocardium, and kidneys was studied at 24 h. AMI resulted in increased circulating neutrophils (P infarcted myocardium and in remote myocardium. VCAM-1 mRNA was increased in both infarcted and remote myocardium. VCAM-1 protein was also increased in the kidneys of AMI mice (P < 0.05) and immunofluorescence revealed localisation of VCAM-1 to glomeruli, associated with leukocyte infiltration and increased local inflammatory mRNA expression. We conclude that in addition to local inflammation, AMI results in remote organ inflammation evidenced by (1) increased expression of mRNA for inflammatory cytokines, (2) marked upregulation of VCAM-1 in renal glomeruli, and (3) the recruitment and infiltration of leukocytes in the kidney.

  3. Role of complement in neurodegeneration and neuroinflammation.

    Science.gov (United States)

    Bonifati, Domenico Marco; Kishore, Uday

    2007-02-01

    The complement system provides an innate defence mechanism against pathogenic microorganisms. Although viewed for many years as an immune-privileged organ, the central nervous system contains many components of the immune system, including components of the complement system that are synthesized by astrocytes, microglia, and neurons. During the past two decades, a wide range of inflammatory markers, typically absent in the normal elderly population, have been reported in Alzheimer's disease brains. It is becoming evident that sustained brain inflammation might be an essential cofactor in Alzheimer disease and other neurodegenerative disorders such as Parkinson disease, dementia with Lewy bodies, Huntington's and prion diseases. The complement system may be useful in eliminating aggregated and toxic proteins associated with these neurological disorders and thus have a protective effect. However, an exaggerated or insufficient activation of the complement system can have deleterious effect through the activation of microglia, secretion of many proinflammatory cytokines, and generation of oxidative products. The role of complement-mediated inflammation in Alzheimer disease has drawn greater attention recently in view of new therapeutic advances made in the management of the disease. This review is meant to update the role of complement in Alzheimer's disease and other neurodegenerative disorders in view of recent vaccination and immunotherapeutic approaches.

  4. Surviving mousepox infection requires the complement system.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Moulton

    2008-12-01

    Full Text Available Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice that lack C3, the central component of the complement cascade. In C3(-/- mice, ectromelia virus disseminated earlier to target organs and generated higher peak titers compared to the congenic controls. Also, increased hepatic inflammation and necrosis correlated with these higher tissue titers and likely contributed to the morbidity in the C3(-/- mice. In vitro, the complement system in naïve C57BL/6 mouse sera neutralized ectromelia virus, primarily through the recognition of the virion by natural antibody and activation of the classical and alternative pathways. Sera deficient in classical or alternative pathway components or antibody had reduced ability to neutralize viral particles, which likely contributed to increased viral dissemination and disease severity in vivo. The increased mortality of C4(-/- or Factor B(-/- mice also indicates that these two pathways of complement activation are required for survival. In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection.

  5. Complement and thrombosis in the antiphospholipid syndrome.

    Science.gov (United States)

    Oku, Kenji; Nakamura, Hiroyuki; Kono, Michihiro; Ohmura, Kazumasa; Kato, Masaru; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Amengual, Olga; Atsumi, Tatsuya

    2016-10-01

    The involvement of complement activation in the pathophysiology of antiphospholipid syndrome (APS) was first reported in murine models of antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously reported that complement activation is prevalent and may function as a source of procoagulant cell activation in the sera of APS patients. Recently, autoantibodies against C1q, a component of complement 1, were reported to be correlated with complement activation in systemic lupus erythematosus. These antibodies target neoepitopes of deformed C1q bound to various molecules (i.e., anionic phospholipids) and induce accelerated complement activation. We found that anti-C1q antibodies are more frequently detected in primary APS patients than in control patients and in refractory APS patients with repeated thrombotic events. The titer of anti-C1q antibodies was significantly higher in refractory APS patients than in APS patients without flare. The binding of C1q to anionic phospholipids may be associated with the surge in complement activation in patients with anti-C1q antibodies when triggered by 'second-hit' biological stressors such as infection. Such stressors will induce overexpression of anionic phospholipids, with subsequent increases in deformed C1q that is targeted by anti-C1q antibodies.

  6. Humoral pattern recognition and the complement system.

    Science.gov (United States)

    Degn, S E; Thiel, S

    2013-08-01

    In the context of immunity, pattern recognition is the art of discriminating friend from foe and innocuous from noxious. The basis of discrimination is the existence of evolutionarily conserved patterns on microorganisms, which are intrinsic to these microorganisms and necessary for their function and existence. Such immutable or slowly evolving patterns are ideal handles for recognition and have been targeted by early cellular immune defence mechanisms such as Toll-like receptors, NOD-like receptors, RIG-I-like receptors, C-type lectin receptors and by humoral defence mechanisms such as the complement system. Complement is a proteolytic cascade system comprising around 35 different soluble and membrane-bound proteins. It constitutes a central part of the innate immune system, mediating several major innate effector functions and modulating adaptive immune responses. The complement cascade proceeds via controlled, limited proteolysis and conformational changes of constituent proteins through three activation pathways: the classical pathway, the alternative pathway and the lectin pathway, which converge in common effector functions. Here, we review the nature of the pattern recognition molecules involved in complement activation, as well as their close relatives with no or unknown capacity for activating complement. We proceed to examine the composition of the pattern recognition complexes involved in complement activation, focusing on those of the lectin pathway, and arrive at a new model for their mechanism of operation, supported by recently emerging evidence.

  7. Bilateral Renal Mass-Renal Disorder: Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ozlem Tiryaki

    2013-01-01

    Full Text Available A 30-year-old woman has presented complaining of weakness and fatigue to her primary care physician. The renal sonography is a routine step in the evaluation of new onset renal failure. When the renal masses have been discovered by sonography in this setting, the functional imaging may be critical. We reported a case about bilateral renal masses in a young female patient with tuberculosis and renal insufficiency. Magnetic resonance (MR has revealed the bilateral renal masses in patient, and this patient has been referred to our hospital for further management. The patient’s past medical and surgical history was unremarkable.

  8. Distal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by a defect ...

  9. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  10. Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney.

    Science.gov (United States)

    Java, Anuja; Liszewski, M Kathryn; Hourcade, Dennis E; Zhang, Fan; Atkinson, John P

    2015-10-01

    The regulators of complement activation gene cluster encodes a group of proteins that have evolved to control the amplification of complement at the critical step of C3 activation. Complement receptor 1 (CR1) is the most versatile of these inhibitors with both receptor and regulatory functions. While expressed on most peripheral blood cells, the only epithelial site of expression in the kidney is by the podocyte. Its expression by this cell population has aroused considerable speculation as to its biologic function in view of many complement-mediated renal diseases. The goal of this investigation was to assess the role of CR1 on epithelial cells. To this end, we utilized a Chinese hamster ovary cell model system. Among our findings, CR1 reduced C3b deposition by ∼ 80% during classical pathway activation; however, it was an even more potent regulator (>95% reduction in C3b deposition) of the alternative pathway. This inhibition was primarily mediated by decay accelerating activity. The deposited C4b and C3b were progressively cleaved with a t½ of ∼ 30 min to C4d and C3d, respectively, by CR1-dependent cofactor activity. CR1 functioned intrinsically (i.e, worked only on the cell on which it was expressed). Moreover, CR1 efficiently and stably bound but didn't internalize C4b/C3b opsonized immune complexes. Our studies underscore the potential importance of CR1 on an epithelial cell population as both an intrinsic complement regulator and an immune adherence receptor. These results provide a framework for understanding how loss of CR1 expression on podocytes may contribute to complement-mediated damage in the kidney.

  11. Dimerization of complement factor H-related proteins modulates complement activation in vivo.

    Science.gov (United States)

    Goicoechea de Jorge, Elena; Caesar, Joseph J E; Malik, Talat H; Patel, Mitali; Colledge, Matthew; Johnson, Steven; Hakobyan, Svetlana; Morgan, B Paul; Harris, Claire L; Pickering, Matthew C; Lea, Susan M

    2013-03-19

    The complement system is a key component regulation influences susceptibility to age-related macular degeneration, meningitis, and kidney disease. Variation includes genomic rearrangements within the complement factor H-related (CFHR) locus. Elucidating the mechanism underlying these associations has been hindered by the lack of understanding of the biological role of CFHR proteins. Here we present unique structural data demonstrating that three of the CFHR proteins contain a shared dimerization motif and that this hitherto unrecognized structural property enables formation of both homodimers and heterodimers. Dimerization confers avidity for tissue-bound complement fragments and enables these proteins to efficiently compete with the physiological complement inhibitor, complement factor H (CFH), for ligand binding. Our data demonstrate that these CFHR proteins function as competitive antagonists of CFH to modulate complement activation in vivo and explain why variation in the CFHRs predisposes to disease.

  12. The epidermal growth factor receptor is a regulator of epidermal complement component expression and complement activation

    DEFF Research Database (Denmark)

    Abu-Humaidan, Anas H A; Ananthoju, Nageshwar; Mohanty, Tirthankar;

    2014-01-01

    The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin...... wounds in vivo and in cultured keratinocytes after exposure to supernatant from stimulated mononuclear cells. In contrast, the epidermal expression of complement components was downregulated in ex vivo injured skin lacking the stimulation from infiltrating inflammatory cells but with intact injury......-induced epidermal growth factor receptor (EGFR)-mediated growth factor response. In cultured primary keratinocytes, stimulation with the potent EGFR ligand, TGF-α, yielded a significant downregulation of complement component expression. Indeed, EGFR inhibition significantly enhanced the induction of complement...

  13. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  14. Neuroprotection from complement-mediated inflammatory damage.

    Science.gov (United States)

    Kulkarni, Amod P; Kellaway, Laurie A; Lahiri, Debomoy K; Kotwal, Girish J

    2004-12-01

    Several neurodegenerative disorders, such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are associated with inflammatory damage. The complex process of neuroinflammation involves various components of the immune system and the central nervous system. Particularly, brain astrocytes and microglial cells generate several inflammatory mediators like cytokines, leukotrienes, superoxide radicals, eicasonoids, and the components of the complement cascade. Complement plays an important role in the etiology of most of the neuroinflammatory disorders. To prevent long-term dysfunction inflammation in the central nervous system must be modulated with neuroprotective agents such as nonsteroidal anti-inflammatory drugs, steroids, phenolic thiazoles, nitrones, catechins, nitric oxide synthetase inhibitors, flavonoids, and phosphodiesterase inhibitors. Few drugs are found to be effective and their therapeutic benefit is hampered by side effects. Most of the neuroprotective agents are free radical scavengers and many inhibit only one or two aspects of inflammation. The complement inhibitory activity of most of these agents is either unknown or not established. Thus, there is doubt regarding their therapeutic value in most of the inflammatory disorders in which complement plays a major role. In this context the role of a multifunctional protein, vaccinia virus complement control protein (VCP), is quite significant as it may play a pivotal role in the treatment of several neuroinflammatory disorders. VCP is known to inhibit both complement pathways involved in inflammation. It is also known to inhibit cytokines and chemokines in inflammation. Our recent studies on rats demonstrate that VCP administration inhibits macrophage infiltration, reduces spinal cord destruction, and improves motor skills associated with spinal cord injury, establishing VCP as a strong candidate for neuroprotection. Thus, complement inhibitors such as VCP can serve as neuroprotective

  15. Complement genetics, deficiencies, and disease associations.

    Science.gov (United States)

    Mayilyan, Karine R

    2012-07-01

    The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

  16. Renale Osteopathie

    Directory of Open Access Journals (Sweden)

    Horn S

    2001-01-01

    Full Text Available Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Therapiemöglichkeiten. Wir beeinflussen dadurch nicht nur die Morbidität und Lebensqualität, sondern auch die Mortalität unserer Patienten.

  17. Renal disease in pregnancy.

    Science.gov (United States)

    Thorsen, Martha S; Poole, Judith H

    2002-03-01

    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.

  18. Protein engineering to target complement evasion in cancer.

    Science.gov (United States)

    Carter, Darrick; Lieber, André

    2014-01-21

    The complement system is composed of soluble factors in plasma that enhance or "complement" immune-mediated killing through innate and adaptive mechanisms. Activation of complement causes recruitment of immune cells; opsonization of coated cells; and direct killing of affected cells through a membrane attack complex (MAC). Tumor cells up-regulate complement inhibitory factors - one of several strategies to evade the immune system. In many cases as the tumor progresses, dramatic increases in complement inhibitory factors are found on these cells. This review focuses on the classic complement pathway and the role of major complement inhibitory factors in cancer immune evasion as well as on how current protein engineering efforts are being employed to increase complement fixing or to reverse complement resistance leading to better therapeutic outcomes in oncology. Strategies discussed include engineering of antibodies to enhance complement fixation, antibodies that neutralize complement inhibitory proteins as well as engineered constructs that specifically target inhibition of the complement system.

  19. Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.

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    Maja T Lindenmeyer

    Full Text Available Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1. The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1 and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease.

  20. Complement in therapy and disease: Regulating the complement system with antibody-based therapeutics.

    Science.gov (United States)

    Melis, Joost P M; Strumane, Kristin; Ruuls, Sigrid R; Beurskens, Frank J; Schuurman, Janine; Parren, Paul W H I

    2015-10-01

    Complement is recognized as a key player in a wide range of normal as well as disease-related immune, developmental and homeostatic processes. Knowledge of complement components, structures, interactions, and cross-talk with other biological systems continues to grow and this leads to novel treatments for cancer, infectious, autoimmune- or age-related diseases as well as for preventing transplantation rejection. Antibodies are superbly suited to be developed into therapeutics with appropriate complement stimulatory or inhibitory activity. Here we review the design, development and future of antibody-based drugs that enhance or dampen the complement system.

  1. Inhibition of Complement Retards Ankylosing Spondylitis Progression

    Science.gov (United States)

    Yang, Chaoqun; Ding, Peipei; Wang, Qingkai; Zhang, Long; Zhang, Xin; Zhao, Jianquan; Xu, Enjie; Wang, Na; Chen, Jianfeng; Yang, Guang; Hu, Weiguo; Zhou, Xuhui

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-β1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-β1 and RANKL, were elevated upon in vitro complement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy. PMID:27698377

  2. Complement factor H related proteins (CFHRs).

    Science.gov (United States)

    Skerka, Christine; Chen, Qian; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T

    2013-12-15

    Factor H related proteins comprise a group of five plasma proteins: CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5, and each member of this group binds to the central complement component C3b. Mutations, genetic deletions, duplications or rearrangements in the individual CFHR genes are associated with a number of diseases including atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathies (C3 glomerulonephritis (C3GN), dense deposit disease (DDD) and CFHR5 nephropathy), IgA nephropathy, age related macular degeneration (AMD) and systemic lupus erythematosus (SLE). Although complement regulatory functions were attributed to most of the members of the CFHR protein family, the precise role of each CFHR protein in complement activation and the exact contribution to disease pathology is still unclear. Recent publications show that CFHR proteins form homo- as well as heterodimers. Genetic abnormalities within the CFHR gene locus can result in hybrid proteins with affected dimerization or recognition domains which cause defective functions. Here we summarize the recent data about CFHR genes and proteins in order to better understand the role of CFHR proteins in complement activation and in complement associated diseases.

  3. Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

    Directory of Open Access Journals (Sweden)

    Yijuan Sun

    2012-01-01

    Full Text Available AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis.

  4. Renal calculus

    CERN Document Server

    Pyrah, Leslie N

    1979-01-01

    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  5. Dissecting the relationships of IgG subclasses and complements in membranous lupus nephritis and idiopathic membranous nephropathy

    Science.gov (United States)

    Na, Woong; Yi, Kijong; Park, Moon Hyang

    2017-01-01

    Membranous lupus nephritis (MLN) and idiopathic membranous nephropathy (IMN) are kidney diseases with similar morphology, but distinct etiologies, both producing glomeruli with immune deposits. Immunoglobulins and complements, the main components of the deposits, can be detected by immunofluorescence (IF) microscopy. Previous researches characterized the immune deposits only individually, but not the interactions between them. To study these relationships we analyzed an IF profile of IgG subclasses and complements (IgG1, IgG2, IgG3, IgG4, C3, C1q, and C4) in 53 and 95 cases of biopsy-confirmed MLNs and IMNs, respectively, mainly using information theory and Bayesian networks. We identified significant entropy differences between MLN and IMN for all markers except C3 and IgG1, but mutual information (a measure of mutual dependence) were not significantly different for all the pairs of markers. The entropy differences between MLN and IMN, therefore, were not attributable to the mutual information. These findings suggest that disease type directly and/or indirectly influences the glomerular deposits of most of IgG subclasses and complements, and that the interactions between any pair of the markers were similar between the two diseases. A Markov chain of IgG subclasses was derived from the mutual information about each pair of IgG subclass. Finally we developed an integrated disease model, consistent with the previous findings, describing the glomerular immune deposits of the IgG subclasses and complements based on a Bayesian network using the Markov chain of IgG subclasses as seed. The relationships between the markers were effectively explored by information theory and Bayesian network. Although deposits of IgG subclasses and complements depended on both disease type and the other markers, the interaction between the markers appears conserved, independent from the disease type. The disease model provided an integrated and intuitive representation of the

  6. The Lectin Pathway of Complement and Biocompatibility

    DEFF Research Database (Denmark)

    Hein, Estrid; Garred, Peter

    2015-01-01

    In modern health technologies the use of biomaterials in the form of stents, haemodialysis tubes, artificial implants, bypass circuits etc. is rapidly expanding. The exposure of synthetic, foreign surfaces to the blood and tissue of the host, calls for strict biocompatibility in respect to contac...... been broadly documented. However, the specific role of lectin pathway and the pattern recognition molecules initiating the pathway has only been transiently investigated. Here we review the current data on the field....... activation, the coagulation system and the complement system. The complement system is an important part of the initial immune response and consists of fluid phase molecules in the blood stream. Three different activation pathways can initiate the complement system, the lectin, the classical...

  7. Extremal Matching Energy of Complements of Trees

    Directory of Open Access Journals (Sweden)

    Wu Tingzeng

    2016-08-01

    Full Text Available Gutman and Wagner proposed the concept of the matching energy which is defined as the sum of the absolute values of the zeros of the matching polynomial of a graph. And they pointed out that the chemical applications of matching energy go back to the 1970s. Let T be a tree with n vertices. In this paper, we characterize the trees whose complements have the maximal, second-maximal and minimal matching energy. Furthermore, we determine the trees with edge-independence number p whose complements have the minimum matching energy for p = 1, 2, . . . , [n/2]. When we restrict our consideration to all trees with a perfect matching, we determine the trees whose complements have the second-maximal matching energy.

  8. Supramolecular Control over Split-Luciferase Complementation.

    Science.gov (United States)

    Bosmans, Ralph P G; Briels, Jeroen M; Milroy, Lech-Gustav; de Greef, Tom F A; Merkx, Maarten; Brunsveld, Luc

    2016-07-25

    Supramolecular split-enzyme complementation restores enzymatic activity and allows for on-off switching. Split-luciferase fragment pairs were provided with an N-terminal FGG sequence and screened for complementation through host-guest binding to cucurbit[8]uril (Q8). Split-luciferase heterocomplex formation was induced in a Q8 concentration dependent manner, resulting in a 20-fold upregulation of luciferase activity. Supramolecular split-luciferase complementation was fully reversible, as revealed by using two types of Q8 inhibitors. Competition studies with the weak-binding FGG peptide revealed a 300-fold enhanced stability for the formation of the ternary heterocomplex compared to binding of two of the same fragments to Q8. Stochiometric binding by the potent inhibitor memantine could be used for repeated cycling of luciferase activation and deactivation in conjunction with Q8, providing a versatile module for in vitro supramolecular signaling networks.

  9. Applying complement therapeutics to rare diseases.

    Science.gov (United States)

    Reis, Edimara S; Mastellos, Dimitrios C; Yancopoulou, Despina; Risitano, Antonio M; Ricklin, Daniel; Lambris, John D

    2015-12-01

    Around 350 million people worldwide suffer from rare diseases. These may have a genetic, infectious, or autoimmune basis, and several include an inflammatory component. Launching of effective treatments can be very challenging when there is a low disease prevalence and limited scientific insights into the disease mechanisms. As a key trigger of inflammatory processes, complement has been associated with a variety of diseases and has become an attractive therapeutic target for conditions involving inflammation. In view of the clinical experience acquired with drugs licensed for the treatment of rare diseases such as hereditary angioedema and paroxysmal nocturnal hemoglobinuria, growing evidence supports the safety and efficacy of complement therapeutics in restoring immune balance and preventing aggravation of clinical outcomes. This review provides an overview of the candidates currently in the pharmaceutical pipeline with potential to treat orphan diseases and discusses the molecular mechanisms triggered by complement involved with the disease pathogenesis.

  10. The extracellular RNA complement of Escherichia coli.

    Science.gov (United States)

    Ghosal, Anubrata; Upadhyaya, Bimal Babu; Fritz, Joëlle V; Heintz-Buschart, Anna; Desai, Mahesh S; Yusuf, Dilmurat; Huang, David; Baumuratov, Aidos; Wang, Kai; Galas, David; Wilmes, Paul

    2015-01-21

    The secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but they also play roles in inter-kingdom exchanges and pathogenicity. To date, released products, such as small molecules, DNA, peptides, and proteins, have been well studied in bacteria. However, the bacterial extracellular RNA complement has so far not been comprehensively characterized. Here, we have analyzed, using a combination of physical characterization and high-throughput sequencing, the extracellular RNA complement of both outer membrane vesicle (OMV)-associated and OMV-free RNA of the enteric Gram-negative model bacterium Escherichia coli K-12 substrain MG1655 and have compared it to its intracellular RNA complement. Our results demonstrate that a large part of the extracellular RNA complement is in the size range between 15 and 40 nucleotides and is derived from specific intracellular RNAs. Furthermore, RNA is associated with OMVs and the relative abundances of RNA biotypes in the intracellular, OMV and OMV-free fractions are distinct. Apart from rRNA fragments, a significant portion of the extracellular RNA complement is composed of specific cleavage products of functionally important structural noncoding RNAs, including tRNAs, 4.5S RNA, 6S RNA, and tmRNA. In addition, the extracellular RNA pool includes RNA biotypes from cryptic prophages, intergenic, and coding regions, of which some are so far uncharacterised, for example, transcripts mapping to the fimA-fimL and ves-spy intergenic regions. Our study provides the first detailed characterization of the extracellular RNA complement of the enteric model bacterium E. coli. Analogous to findings in eukaryotes, our results suggest the selective export of specific RNA biotypes by E. coli, which in turn indicates a potential role for extracellular bacterial RNAs in intercellular communication. © 2015 The

  11. Activation of Complement Following Total Hip Replacement.

    Science.gov (United States)

    Thordardottir, S; Vikingsdottir, T; Bjarnadottir, H; Jonsson, H; Gudbjornsson, B

    2016-03-01

    The aim of this study was to investigate whether complement activation, via the classical and alternative pathways, occurs following a cemented total hip replacement (THR) surgery due to osteoarthritis. Blood samples were collected systematically from 12 patients - six male and six women, with a median age of 75 (range: 59-90 years) - preoperatively, 6 h post-operatively and on the first, second and third post-operative day. Total function of classical (CH50) and alternative pathways (AH50) was evaluated, along with the determination of serum concentrations of the complement proteins C3, C4, C3d, the soluble terminal complement complex (sTCC) sC5b-9, as well as C-reactive protein (CRP) and albumin. Measurements of CRP and albumin levels elucidated a marked inflammatory response following the operation. The CH50, AH50 and C3 and C4 levels were significantly lower 6 h after the surgery compared with the preoperative levels, but elevated above the preoperative levels during the following 3 days. The complement activation product C3d levels increased continually during the whole observation period, from 13.5 AU/ml (range: 8-19 AU/ml) preoperative to 20 AU/ml (range: 12-34 AU/ml) on the third post-operative day. Furthermore, we observed an increase in the sC5b-9 levels between the preoperative and the third post-operative day. These results demonstrate a significant activation of the complement system following cemented THR. Further studies are needed to elucidate the time frame and the pathogenic role of this observed complement activation.

  12. [Extracorporeal renal replacement therapies in acute renal failure].

    Science.gov (United States)

    Schaefer, R M; Barenbrock, M; Teschner, M; Bahner, U

    2000-05-15

    The most serious forms of acute renal failure (ARF) are nowadays encountered in the intensive care unit (ICU), where up to 25% of new patients are reported to develop ARF. Lethality rates may reach 50 to 90% when the ARF is part of a multiple organ dysfunction syndrome. A multitude of extracorporeal procedures have been introduced into intensive care medicine. Applied with adequate skills and experience, most of these techniques will suffice to replace excretory renal function. However, because of low efficacy arterio-venous procedures (CAVH and CAVHD) have been abandoned for the veno-venous, pump-driven techniques (CVVH and CVVHD). Up to now, there is no consensus whether continuous or intermittent renal replacement therapy is more advantageous. In many cases, oliguric patients with circulatory instability will be treated by CVVH, even though there is no prospective study to show that in terms of outcome continuous treatment is superior to intermittent hemodialysis. It is equally conceivable to treat such patients with daily, prolonged (intermittent) hemodialysis. Apparently, the dose of replacement therapy, be it continuous filtration (36 to 48 l/24 h) or intermittent hemodialysis (daily 3 to 4 h) with a target BUN of less than 50 mg/dl, is more important than the modality of treatment. Moreover, there is good evidence that the use of biocompatible membranes (no complement- or leukocyte activation) is preferable and that with high-volume hemofiltration bicarbonate-containing replacement fluids should be used. However, despite all the technical advances, we firmly believe that the skills and the experience of those physicians and nurses who actually perform renal replacement therapy in the ICU are more important than the modality of treatment applied.

  13. Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E;

    1984-01-01

    Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease g...

  14. Analysis of clinical and renal pathological characteristics in patients with ANCA-associated vasculitis%抗中性粒细胞胞质抗体相关性血管炎的临床及肾脏病理分析

    Institute of Scientific and Technical Information of China (English)

    牟翠萍; 赵秀芬; 钱军; 毛慧娟; 邢昌赢; 刘佳; 孙彬; 张莉; 张波; 张承宁; 任海滨; 俞香宝

    2012-01-01

    renal pathological characteristics of patients with ANCA associated vasculitis ( AAV) , and to explore the clinical feature of patients with complement deposition in renal pathology. Methodology:From Jan,2006 to Jan,2012,ninety six patients diagnosed as AAV were collected and their clinical and pathological data were retrospectively analyzed. Results: They were 53 males and 43 females ( ratio 1.2: 1) with an age 58. 4 ± 16. 6 (ranged from 15 ~83) years old,and older than 65 years old in 42. 3% . The median duration of disease was 57 days from 30 to 115 days. Their clinical manifestations were diverse and complicated. The most commonly involved organs were kidney in 84 cases (87. 5% ) ,and lung in 61 (63. 5% ). In renal pathology;51 of 96 patients were performed renal biopsy. The histological examinations showed crescent formation in 86. 3% ,fibrinoid necrosis of glomeruli in 54. 9% ,global sclerosis in 64. 7% and tubular interstitial fibrosis in 62. 7%. According to the degree of glomerular pathological change assessed by light microscopy ,44 cases with pathological diagnosis of AAV were classified as four general categories: Focal (15) , Crescentic (7) , Mixed (12) and Sclerotic (10 cases). The patients of focal subtype presented with significantly lower serum creatinine than that the other three subtypes ( Pd2 < 0. 01、Pb1 < 0. 05、and Pc1 < 0. 05 ). After the immunosuppressive therapy, the patients of crescentic subtype had a bigger decrease of serum creatine, compared with those who presented with other subtypes ( Pa2 < 0. 01、Pb2 < 0. 01、Pc1< 0. 05 ) . ESRD developed in one of 15 patients with focal, 2 of 7 patients with crescentic,2 of 12 patients with mixed,and 3 of 10 patients with sclerotic subtype vasculitis during the follow-up period. The patients with complement deposition ( n = 22 ) had a higher level of erythrocyte sedimentation rate ( ESR) ( P = 0. 023 ) , higher initial serum creatinine ( P = 0. 021 ) and serum ureanitrogen ( P = 0. 012 ) , lower

  15. L^2-Betti numbers of hypersurface complements

    CERN Document Server

    Maxim, Laurentiu

    2012-01-01

    In \\cite{DJL07} it was shown that if $\\scra$ is an affine hyperplane arrangement in $\\C^n$, then at most one of the $L^2$--Betti numbers $b_i^{(2)}(\\C^n\\sm \\scra,\\id)$ is non--zero. In this note we prove an analogous statement for complements of complex affine hyperurfaces in general position at infinity. Furthermore, we recast and extend to this higher-dimensional setting results of \\cite{FLM,LM06} about $L^2$--Betti numbers of plane curve complements.

  16. Behcet's syndrome and renal involvement: a histological and immunofluorescent study of eleven renal biopsies.

    Science.gov (United States)

    Herreman, G; Beaufils, H; Godeau, P; Cassou, B; Wechsler, B; Boujeau, J; Chomette, G

    1982-01-01

    The finding of focal glomerulonephritis in a patient with Behcet's syndrome led us to perform systematic renal biopsies in ten other patients with the disease. None of the patients had symptoms of renal disease. Proteinuria was found in five, two of whom had associated leukocyturia. By light microscopy mesangial and extramembranous glomerular deposits were observed in eight patients. Arterioles in ten patients showed subendothelial and medial hyaline deposits. A granular pattern of fluorescent staining identified the presence of the third component of complement in these deposits. Circulating immune deposits were sought and found in six out of seven patients. The finding of circulating immune complexes and deposition of complement in glomerular and arteriolar tissues supports an immune complex mediated nephropathy and is consistent with the hypothesis of an immunological pathogenesis in Behcet's syndrome.

  17. Renal actinomycosis with concomitant renal vein thrombosis.

    Science.gov (United States)

    Chang, Dong-Suk; Jang, Won Ik; Jung, Ji Yoon; Chung, Sarah; Choi, Dae Eun; Na, Ki-Ryang; Lee, Kang Wook; Shin, Yong-Tai

    2012-02-01

    Renal actinomycosis is a rare infection caused by fungi of the genus Actinomyces. A 74-year-old male was admitted to our hospital because of gross hematuria with urinary symptoms and intermittent chills. Computed tomography of the abdomen showed thrombosis in the left renal vein and diffuse, heterogeneous enlargement of the left kidney. After nephrectomy, sulfur granules with chronic suppurative inflammation were seen microscopically, and the histopathological diagnosis was renal actinomycosis. Our case is the first report of renal actinomycosis with renal vein thrombosis.

  18. Effects of salt restriction on renal growth and glomerular injury in rats with remnant kidneys.

    Science.gov (United States)

    Lax, D S; Benstein, J A; Tolbert, E; Dworkin, L D

    1992-06-01

    Male Munich-Wistar rats underwent right nephrectomy and infarction of two thirds of the left kidney. Rats were randomly assigned to ingest standard chow (REM) or a moderately salt restricted chow (LS). A third group of rats were fed the low salt diet and were injected with an androgen (LSA). Eight weeks after ablation, glomerular volume and glomerular capillary radius were markedly increased in REM. This increase was prevented by the low salt diet, however, the antihypertrophic effect of the diet was overcome by androgen. Values for glomerular volume and capillary radius were similar in LSA and REM. Morphologic studies revealed that approximately 25% of glomeruli were abnormal in REM. Much less injury was observed in salt restricted rats, however, the protective effect of the low salt diet was significantly abrogated when renal growth was stimulated in salt restricted rats by androgen. Micropuncture studies revealed that glomerular pressure was elevated in all three groups and not affected by diet or androgen. Serum cholesterol was also similar in the three groups. These findings indicate that renal and glomerular hypertrophy are correlated with the development of glomerular injury after reduction in renal mass and suggest that dietary salt restriction lessens renal damage, at least in part, by inhibiting compensatory renal growth.

  19. Applications of urinary proteomics in renal disease research using animal models.

    Science.gov (United States)

    Lv, Yang; Cai, Guangyan; Chen, Xiangmei

    2015-01-01

    Animal models of renal disease are essential tools in research on kidney disease and have provided valuable insights into pathogenesis. Use of animal models minimises inter-individual differences, allows specific pathological changes to be examined, and facilitates collection of tissue samples. Thus, mechanistic research and identification of biomarkers are possible. Various animal models manifesting specific pathological lesions can be used to investigate acute or chronic kidney disease (CKD). Urine, a terminal metabolic product, is produced via glomerular filtration, reabsorption, and excretion in the tubular and collecting ducts, reflecting the functions of glomeruli or tubular tissue stimulated in various ways or subject to disease. Almost 70 % of urinary proteins originate from the kidney (the other 30 % come from plasma), and urinary sampling is important to noninvasively detect renal disease. Proteomics is powerful when used to screen urine components. Increasingly, urine proteomics is used to explore the pathogenesis of kidney disease in animals and to identify novel biomarkers of renal disease. In this section, we will introduce the field of urinary proteomics as applied in different models of animal renal disease and the valuable role played by proteomics in noninvasive diagnosis and rational treatment of human renal disease.

  20. Antihypertensive effect of thymectomy in Lyon hypertensive rats. Vascular reactivity, renal histology, and sodium excretion.

    Science.gov (United States)

    Bataillard, A; Blanc-Brunat, N; Vivier, G; Medeiros, I; Zhang, B L; Touraine, J L; Sassard, J

    1996-02-01

    The aim of this study was to search for the possible mechanisms involved in the antihypertensive effect of neonatal thymectomy that we previously observed in Lyon hypertensive (LH) rats. To that end, we studied in LH and normotensive control (LN) rats the consequences of neonatal thymectomy on vascular reactivity, renal structure, and pressure-natriuresis. The increase in pressor responses to angiotensin I and phenylephrine noted in LH rats as compared to LN animals was abolished by neonatal thymectomy. Histological study showed that kidneys from LH rats exhibited arterial wall hypertrophy, segmental hyalinization of the glomeruli, and were infiltrated by mononuclear cells. All these features of kidney injury were reduced in neonatally thymectomized LH rats. Lastly, the responses of isolated perfused kidneys from LH rats to stepwise reductions in renal perfusion pressure differed from those of LN rats by decreased renal perfusion flow and natriuresis. Neonatal thymectomy tended to improve sodium excretion in parallel with a slight decrease in renal vascular resistances. It is concluded that the normalization of vascular responsiveness to vasoconstrictor factors, the alleviation of renal lesions and, to a lesser extent, the moderate improvement of pressure natriuresis may account, at least in part, for the antihypertensive effect of neonatal thymectomy in LH rats.

  1. Calcineurin inhibitor toxicity in renal allografts: Morphologic clues from protocol biopsies

    Directory of Open Access Journals (Sweden)

    Sharma Alok

    2010-10-01

    Full Text Available Background: Calcineurin inhibitors (cyclosporine and tacrolimus are important constituents of post renal transplant immunosuppression. However, renal toxicity limits their utility. Histological features of calcineurin inhibitor toxicity (CNIT have been the subject of few studies using protocol biopsy samples, and consensus on diagnostic criteria is still evolving. Aims: To analyze the spectrum of histological changes in protocol renal allograft biopsies with evidence of CNIT and identify additional features that are likely to help the pathologist in arriving at a diagnosis. Materials and Methods: One hundred and forty protocol allograft biopsies performed at 1, 6 and 12 months post renal transplant were studied. The defining features of CNIT included: isometric vacuolization of proximal tubular cells, arteriolar hyalinosis with medial/peripheral nodules and striped pattern of tubular atrophy/interstitial fibrosis. Other features such as global glomerulosclerosis, vacuolization of smooth muscle cells of arterioles, tubular microcalcinosis, ischemic shrinkage of glomeruli and hyperplasia of juxtaglomerular apparatus (JGA were also analyzed and graded semiquantitatively. Results: CNIT was seen in 17/140 protocol biopsies (12.1%. In addition to the diagnostic criteria, arteriolar hyalinosis, smooth muscle cell vacuolization of arterioles and hyperplasia of JGA were found to be useful indicators of CNIT. Conclusions: There is a relatively high incidence of CNIT in protocol allograft biopsies. A critical analysis of renal biopsy in adequate number of serial step sections to identify these features is mandatory, as many of these features are subtle and are likely to be missed if not specifically sought.

  2. TRANSPLANTE RENAL

    Directory of Open Access Journals (Sweden)

    Soraia Geraldo Rozza Lopes

    2014-01-01

    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  3. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930564 Dwell times affect the local host de-fence mechanism of peritoneal dialysis patients.WANG Tao(汪涛),et al.Renal Instit,SunYatsen Med Univ,Guangzhou,510080.Chin JNephrol 1993;9(2):75—77.The effect of different intraperitoneal awelltimes on the local host defence in 6 peritonealdialysis patients was studied.A significant de-crease in the number of peritoneal cells,IgG con-centration and the phagoeytosis and bactericidalactivity of macrophages was determined when thedwell time decreased from 12 to 4 hs or form 4 to0.5hs,but the peroxidase activity in macrophagesincreased significantly.All variables,except theperoxidase activity in macrophages,showed nosignificant difference between patients of high or

  4. Traumatismo renal

    OpenAIRE

    Rocha, Sofia Rosa Moura Gomes da

    2009-01-01

    Introdução: A realização deste trabalho visa a elaboração de uma revisão sistematizada subordinada à temática da traumatologia renal. Objectivos: Os principais objectivos deste trabalho são: apurar a etiologia, definir a classificação, analisar o diagnóstico e expôr o tratamento e as complicações. Desenvolvimento: Os traumatismos são a principal causa de morte antes dos 40 anos. O rim é o órgão do aparelho génito-urinário mais frequentemente atingido. Os traumatismos renais são mais fre...

  5. Therapeutic complement inhibition in complement-mediated hemolytic anemias: Past, present and future.

    Science.gov (United States)

    Risitano, Antonio M; Marotta, Serena

    2016-06-01

    The introduction in the clinic of anti-complement agents represented a major achievement which gave to physicians a novel etiologic treatment for different human diseases. Indeed, the first anti-complement agent eculizumab has changed the treatment paradigm of paroxysmal nocturnal hemoglobinuria (PNH), dramatically impacting its severe clinical course. In addition, eculizumab is the first agent approved for atypical Hemolytic Uremic Syndrome (aHUS), a life-threatening inherited thrombotic microangiopathy. Nevertheless, such remarkable milestone in medicine has brought to the fore additional challenges for the scientific community. Indeed, the list of complement-mediated anemias is not limited to PNH and aHUS, and other human diseases can be considered for anti-complement treatment. They include other thrombotic microangiopathies, as well as some antibody-mediated hemolytic anemias. Furthermore, more than ten years of experience with eculizumab led to a better understanding of the individual steps of the complement cascade involved in the pathophysiology of different human diseases. Based on this, new unmet clinical needs are emerging; a number of different strategies are currently under development to improve current anti-complement treatment, trying to address these specific clinical needs. They include: (i) alternative anti-C5 agents, which may improve the heaviness of eculizumab treatment; (ii) broad-spectrum anti-C3 agents, which may improve the efficacy of anti-C5 treatment by intercepting the complement cascade upstream (i.e., preventing C3-mediated extravascular hemolysis in PNH); (iii) targeted inhibitors of selective complement activating pathways, which may prevent early pathogenic events of specific human diseases (e.g., anti-classical pathway for antibody-mediated anemias, or anti-alternative pathway for PNH and aHUS). Here we briefly summarize the status of art of current and future complement inhibition for different complement-mediated anemias

  6. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses.

    Directory of Open Access Journals (Sweden)

    Guido Moll

    Full Text Available Infusion of human third-party mesenchymal stromal cells (MSCs appears to be a promising therapy for acute graft-versus-host disease (aGvHD. To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46 and DAF (CD55, but were protected from complement lysis via expression of protectin (CD59. Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.

  7. Sodium depletion enhances renal expression of (pro)renin receptor via cyclic GMP-protein kinase G signaling pathway.

    Science.gov (United States)

    Huang, Jiqian; Siragy, Helmy M

    2012-02-01

    (Pro)renin receptor (PRR) is expressed in renal vasculature, glomeruli, and tubules. The physiological regulation of this receptor is not well established. We hypothesized that sodium depletion increases PRR expression through cGMP- protein kinase G (PKG) signaling pathway. Renal PRR expressions were evaluated in Sprague-Dawley rats on normal sodium or low-sodium diet (LS) and in cultured rat proximal tubular cells and mouse renal inner medullary collecting duct cells exposed to LS concentration. LS augmented PRR expression in renal glomeruli, proximal tubules, distal tubules, and collecting ducts. LS also increased cGMP production and PKG activity. In cells exposed to normal sodium, cGMP analog increased PKG activity and upregulated PRR expression. In cells exposed to LS, blockade of guanylyl cyclase with 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one decreased PKG activity and downregulated PRR expression. PKG inhibition decreased phosphatase protein phosphatase 2A activity; suppressed LS-mediated phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, c-Jun, and nuclear factor-κB p65; and attenuated LS-mediated PRR upregulation. LS also enhanced DNA binding of cAMP response element binding protein 1 to cAMP response elements, nuclear factor-κB p65 to nuclear factor-κB elements, and c-Jun to activator protein 1 elements in PRR promoter in proximal tubular cells. We conclude that sodium depletion upregulates renal PRR expression via the cGMP-PKG signaling pathway by enhancing binding of cAMP response element binding protein 1, nuclear factor-κB p65, and c-Jun to PRR promotor.

  8. Graphs whose complement and square are isomorphic

    DEFF Research Database (Denmark)

    Milanic, M.; Pedersen, Anders Sune; Pellicer, D.;

    2014-01-01

    We study square-complementary graphs, that is, graphs whose complement and square are isomorphic. We prove several necessary conditions for a graph to be square-complementary, describe ways of building new square-complementary graphs from existing ones, construct infinite families of square...

  9. Cross-Cultural Analysis on Complements

    Institute of Scientific and Technical Information of China (English)

    刘恒

    2014-01-01

    Nativized varieties of English must reflect native pragmatic norms and cultural conventions. Complements, as a polite social behavior, is analyzed from the perspective of Chinese English speaker and American English speaker to emphasize the im-portance of the cross-cultural differences in pragmatic uses.

  10. Spacelab carrier complement thermal design and performance

    Science.gov (United States)

    Bancroft, S.; Key, R.; Kittredge, S.

    1992-01-01

    The present discussion of the Spacelab carrier complement, which encompasses a Module Carrier, a Module-Pallet Carrier, and a Multiplexer/Demultiplexer Pallet, gives attention to both active and passive thermal performance capabilities, and presents ground testing and analytical results obtained to date. An account is given of the prospective use of a Spacelab Multipurpose Experiment Support Structure.

  11. 21 CFR 866.5240 - Complement components immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement components immunological test system....5240 Complement components immunological test system. (a) Identification. A complement components... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids,...

  12. Complement Constructions in English: Fairly Difficult for EFL Language Learners

    Science.gov (United States)

    Fazeli, Fatemeh; Shokrpour, Nasrin

    2012-01-01

    Complement constructions vary significantly in English and Persian. There are more complementation structures in English than in Persian and a complement structure in Persian might have more than one equivalent in English. Producing complement structures (CSs) in English is very difficult for native speakers of Persian, especially in an EFL…

  13. Characterization of the complement inhibitory function of rhesus rhadinovirus complement control protein (RCP).

    Science.gov (United States)

    Okroj, Marcin; Mark, Linda; Stokowska, Anna; Wong, Scott W; Rose, Nicola; Blackbourn, David J; Villoutreix, Bruno O; Spiller, O Brad; Blom, Anna M

    2009-01-02

    Rhesus rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi sarcoma-associated herpesvirus. Both these viruses encode complement inhibitors as follows: Kaposi sarcoma-associated herpesvirus-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as a complement inhibitor. Here, we performed comparative analyses for two variants of RCP protein, encoded by RRV strains H26-95 and 17577. Both RCP variants and KCP inhibited human and rhesus complement when tested in hemolytic assays measuring all steps of activation via the classical and the alternative pathway. RCP variants from both RRV strains supported C3b and C4b degradation by factor I and decay acceleration of the classical C3 convertase, similar to KCP. Additionally, the 17577 RCP variant accelerated decay of the alternative C3 convertase, which was not seen for KCP. In contrast to KCP, RCP showed no affinity to heparin and is the first described complement inhibitor in which the binding site for C3b/C4b does not interact with heparin. Molecular modeling shows a structural disruption in the region of RCP that corresponds to the KCP-heparin-binding site. This makes RRV a superior model for future in vivo investigations of complement evasion, as RCP does not play a supportive role in viral attachment as KCP does.

  14. Non-specific adsorption of complement proteins affects complement activation pathways of gold nanomaterials.

    Science.gov (United States)

    Quach, Quang Huy; Kah, James Chen Yong

    2017-04-01

    The complement system is a key humoral component of innate immunity, serving as the first line of defense against intruders, including foreign synthetic nanomaterials. Although gold nanomaterials (AuNMs) are widely used in nanomedicine, their immunological response is not well understood. Using AuNMs of three shapes commonly used in biomedical applications: spherical gold nanoparticles, gold nanostars and gold nanorods, we demonstrated that AuNMs activated whole complement system, leading to the formation of SC5b-9 complex. All three complement pathways were simultaneously activated by all the AuNMs. Recognition molecules of the complement system interacted with all AuNMs in vitro, except for l-ficolin, but the correlation between these interactions and corresponding complement pathway activation was only observed in the classical and alternative pathways. We also observed the mediating role of complement activation in cellular uptake of all AuNMs by human U937 promonocytic cells, which expresses complement receptors. Taken together, our results highlighted the potential immunological challenges for clinical applications of AuNMs that were often overlooked.

  15. Role of complement and complement regulatory proteins in the complications of diabetes.

    Science.gov (United States)

    Ghosh, Pamela; Sahoo, Rupam; Vaidya, Anand; Chorev, Michael; Halperin, Jose A

    2015-06-01

    It is well established that the organ damage that complicates human diabetes is caused by prolonged hyperglycemia, but the cellular and molecular mechanisms by which high levels of glucose cause tissue damage in humans are still not fully understood. The prevalent hypothesis explaining the mechanisms that may underlie the pathogenesis of diabetes complications includes overproduction of reactive oxygen species, increased flux through the polyol pathway, overactivity of the hexosamine pathway causing intracellular formation of advanced glycation end products, and activation of protein kinase C isoforms. In addition, experimental and clinical evidence reported in past decades supports a strong link between the complement system, complement regulatory proteins, and the pathogenesis of diabetes complications. In this article, we summarize the body of evidence that supports a role for the complement system and complement regulatory proteins in the pathogenesis of diabetic vascular complications, with specific emphasis on the role of the membrane attack complex (MAC) and of CD59, an extracellular cell membrane-anchored inhibitor of MAC formation that is inactivated by nonenzymatic glycation. We discuss a pathogenic model of human diabetic complications in which a combination of CD59 inactivation by glycation and hyperglycemia-induced complement activation increases MAC deposition, activates pathways of intracellular signaling, and induces the release of proinflammatory, prothrombotic cytokines and growth factors. Combined, complement-dependent and complement-independent mechanisms induced by high glucose promote inflammation, proliferation, and thrombosis as characteristically seen in the target organs of diabetes complications.

  16. Mixed organic solvents induce renal injury in rats.

    Directory of Open Access Journals (Sweden)

    Weisong Qin

    Full Text Available To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16 and 25% (4/16, respectively. Urinary N-Acetyl-β-(D-Glucosaminidase (NAG activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM. Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

  17. A mouse model of early-onset renal failure due to a xanthine dehydrogenase nonsense mutation.

    Directory of Open Access Journals (Sweden)

    Sian E Piret

    Full Text Available Chronic kidney disease (CKD is characterized by renal fibrosis that can lead to end-stage renal failure, and studies have supported a strong genetic influence on the risk of developing CKD. However, investigations of the underlying molecular mechanisms are hampered by the lack of suitable hereditary models in animals. We therefore sought to establish hereditary mouse models for CKD and renal fibrosis by investigating mice treated with the chemical mutagen N-ethyl-N-nitrosourea, and identified a mouse with autosomal recessive renal failure, designated RENF. Three-week old RENF mice were smaller than their littermates, whereas at birth they had been of similar size. RENF mice, at 4-weeks of age, had elevated concentrations of plasma urea and creatinine, indicating renal failure, which was associated with small and irregularly shaped kidneys. Genetic studies using DNA from 10 affected mice and 91 single nucleotide polymorphisms mapped the Renf locus to a 5.8 Mbp region on chromosome 17E1.3. DNA sequencing of the xanthine dehydrogenase (Xdh gene revealed a nonsense mutation at codon 26 that co-segregated with affected RENF mice. The Xdh mutation resulted in loss of hepatic XDH and renal Cyclooxygenase-2 (COX-2 expression. XDH mutations in man cause xanthinuria with undetectable plasma uric acid levels and three RENF mice had plasma uric acid levels below the limit of detection. Histological analysis of RENF kidney sections revealed abnormal arrangement of glomeruli, intratubular casts, cellular infiltration in the interstitial space, and interstitial fibrosis. TUNEL analysis of RENF kidney sections showed extensive apoptosis predominantly affecting the tubules. Thus, we have established a mouse model for autosomal recessive early-onset renal failure due to a nonsense mutation in Xdh that is a model for xanthinuria in man. This mouse model could help to increase our understanding of the molecular mechanisms associated with renal fibrosis and the

  18. Discrimination between Host and Pathogens by the Complement System

    OpenAIRE

    Pangburn, Michael K.; Ferreira, Viviana P.; Cortes, Claudio

    2008-01-01

    Pathogen-specific complement activation requires direct recognition of pathogens and/or the absence of complement control mechanisms on their surfaces. Antibodies direct complement activation to potential pathogens recognized by the cellular innate and adaptive immune systems. Similarly, the plasma proteins MBL and ficolins direct activation to microorganisms expressing common carbohydrate structures. The absence of complement control proteins permits amplification of complement by the altern...

  19. Complement Component C3 Binds to Activated Normal Platelets without Preceding Proteolytic Activation and Promotes Binding to Complement Receptor 1

    NARCIS (Netherlands)

    O.A. Hamad; P.H. Nilsson; D. Wouters; J.D. Lambris; K.N. Ekdahl; B. Nilsson

    2010-01-01

    It has been reported that complement is activated on the surface of activated platelets, despite the presence of multiple regulators of complement activation. To reinvestigate the mechanisms by which activated platelets bind to complement components, the presence of complement proteins on the surfac

  20. Blood pressure, renal biochemical parameters and histopathology in an original rat model of essential hypertension (SHRSP/Kpo strain).

    Science.gov (United States)

    Kato, Takashi; Mizuguchi, Nobuyuki; Ito, Akihiko

    2015-01-01

    Hypertensive nephropathy, a consequence of chronic high blood pressure, is increasingly a cause of end-stage renal diseases and its correct management is very important for clinical outcome. Spontaneously hypertensive rat (SHR/Kpo) and stroke-prone SHR (SHRSP/Kpo) strains represent models of human essential hypertension. However, the kidney injuries in SHR/Kpo and SHRSP/Kpo are not well defined. We therefore characterized the renal pathophysiology of SHR/Kpo and SHRSP/Kpo compared with normotensive control (WKY/Kpo) rats. The SHRSP/Kpo exhibited increased systolic blood pressure at 10 weeks of age, and proteinuria and increased blood urea nitrogen (BUN) and serum creatinine levels at 20 weeks. We simultaneously detected mononuclear cell infiltration, tubular injuries, accumulation of extracellular matrix and marked expression of α-SMA in the tubulointerstitium. Additionally, TGF-β1 and CTGF were up-regulated in the kidney of SHRSP/Kpo. We lastly focused on changes in glomerular cells of SHRSP/Kpo. Nestin, a podocyte marker, was detected but decreased slightly in 20-week-old SHRSP/Kpo. PECAM-1 expression was increased in SHRSP/Kpo glomeruli, indicating the thickening of glomerular endothelial cells. Moreover, we found that α-SMA, a myofibroblast marker, was also upregulated in the glomeruli of SHRSP/Kpo at 20 weeks. These findings suggest that SHRSP/Kpo could be a valuable animal model for human hypertensive nephropathy.

  1. A zebrafish model for uremic toxicity: role of the complement pathway.

    Science.gov (United States)

    Berman, Nathaniel; Lectura, Melisa; Thurman, Joshua M; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p 50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement.

  2. Effects of PEG-PLA-nano artificial cells containing hemoglobin on kidney function and renal histology in rats.

    Science.gov (United States)

    Liu, Zun Chang; Chang, Thomas M S

    2008-01-01

    This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology.

  3. Early complement components in Alzheimer's disease brains.

    Science.gov (United States)

    Veerhuis, R; Janssen, I; Hack, C E; Eikelenboom, P

    1996-01-01

    Activation products of the early complement components C1, C4 and C3 can be found colocalized with diffuse and fibrillar beta-amyloid (beta/A4) deposits in Alzheimer's disease (AD) brains. Immunohistochemically, C1-esterase inhibitor (C1-Inh) and the C1 subcomponents C1s and C1r can not, or only occasionally, be detected in plaques or in astrocytes. The present finding that C1q, C1s and C1-Inh mRNA are present in both AD and control brains suggests that the variable immunohistochemical staining results for C1r, C1s and C1-Inh are due to a rapid consumption, and that the inability to detect C1s, C1r or C1-Inh is probably due to the dissociation of C1s-C1-Inh and C1r-C1-Inh complexes from the activator-bound C1q into the fluid phase. Employing monoclonal antibodies specific for different forms of C1-Inh, no complexed C1-Inh could be found, whereas inactivated C1-Inh seems to be present in astrocytes surrounding beta/A4 plaques in AD brains. These findings, together with our finding (using reverse transcriptase-polymerase chain reaction) that C1-Inh is locally produced in the brain, suggest that in the brain complement activation at the C1 level is regulated by C1-Inh. Immunohistochemically, no evidence for the presence of the late complement components C5, C7 and C9, or of the membrane attack complex (MAC), was found in beta/A4 plaques. In contrast to the mRNA encoding the early components, that of the late complement components appears to be hardly detectable (C7) or absent (C9). Thus, without blood-brain-barrier impairment, the late complement components are probably present at too low a concentration to allow the formation of the MAC, which is generally believed to be responsible for at least some of the neurodegenerative effects observed in AD. Therefore, the present findings support the idea that in AD, complement does not function as an inflammatory mediator through MAC formation, but through the action of early component activation products.

  4. Adenovirus Activates Complement by Distinctly Different Mechanisms In Vitro and In Vivo: Indirect Complement Activation by Virions In Vivo▿

    OpenAIRE

    Tian, Jie; Xu, Zhili; Jeffrey S Smith; Hofherr, Sean E.; Barry, Michael A.; Byrnes, Andrew P.

    2009-01-01

    Understanding innate immunity is key to improving the safety of adenovirus (Ad) vectors for systemic gene therapy. Ad has been shown to activate complement in vitro, but activation of complement after Ad injection in vivo has not been directly measured. Using complement protein C3a as a marker of complement activation, we show that types 2 and 5 human Ads cause rapid complement activation after intravenous injection in mice. Unexpectedly, the mechanisms in vivo were different than those in vi...

  5. Two Myxobolus spp. infecting the kidney of Nile tilapia (Oreochromis niloticus) in the River Nile at Beni-Suef governorate, Egypt, and the associated renal changes.

    Science.gov (United States)

    Abdel-Baki, Abdel-Azeem S; Abdel-Haleem, Heba M; Sakran, Thabet; Zayed, Eman; Ibrahim, Khalid E; Al-Quraishy, Saleh

    2015-03-01

    Two Myxobolus spp. are described from the kidney of the Nile tilapia (Oreochromis niloticus) collected from the River Nile, Egypt. The prevalence of infection was 61 % (47/77), with the infected fish in each case parasitized by the two Myxobolus species simultaneously. The infection was exhibited as free spores in Bowman capsules and renal glomeruli, which makes their original structures difficult to discern. In some cases, the infection appeared as a fibrous plasmodia-like structure containing degenerated developmental stages and spores in the interstitium. The paper identifies each species based on the morphological characteristics of its spores and identifies the histological impacts of Myxobolus infection in this species of fish.

  6. Complementation analysis of ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Jaspers, N.G.; Painter, R.B.; Paterson, M.C.; Kidson, C.; Inoue, T.

    1985-01-01

    In a number of laboratories genetic analysis of ataxia-telangiectasia (AT) has been performed by studying the expression of the AT phenotype in fused somatic cells or mixtures of cell-free extracts from different patients. Complementation of the defective response to ionizing radiation was observed frequently, considering four different parameters for radiosensitivity in AT. The combined results from studies on cultured fibroblasts or lymphoblastoid cells from 17 unrelated families revealed the presence of at least four and possibly nine complementation groups. These findings suggest that there is an extensive genetic heterogeneity in AT. More extensive studies are needed for an integration of these data and to provide a set of genetically characterized cell strains for future research of the AT genetic defect.

  7. Tanker avionics and aircrew complement evaluation.

    Science.gov (United States)

    Moss, R W; Barbato, G J

    1982-11-01

    This paper describes an effort to determine control and display criteria for operating SAC's KC-135 tanker with a reduced crew complement. The Tanker Avionics and Aircrew Complement Evaluation (TAACE) Program was a four-phase effort addressing the control and display design issues associated with operating the tanker without the navigator position. Discussed are: the mission analysis phase, during which the tanker's operational responsibilities were defined and documented; the design phase, during which alternative crew station design concepts were developed; the mockup evaluation phase, which accomplished initial SAC crew member assessment of cockpit designs; and the simulation phase, which validated the useability of the crew system redesign. The paper also describes a recommended crew station configuration and discusses some of the philosophy underlying the selection of cockpit hardware and systems.

  8. Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation.

    Directory of Open Access Journals (Sweden)

    Ran Sun

    2015-12-01

    Full Text Available Trichinella spiralis expresses paramyosin (Ts-Pmy as a defense mechanism. Ts-Pmy is a functional protein with binding activity to human complement C8 and C9 and thus plays a role in evading the attack of the host's immune system. In the present study, the binding activity of Ts-Pmy to human complement C1q and its ability to inhibit classical complement activation were investigated.The binding of recombinant and natural Ts-Pmy to human C1q were determined by ELISA, Far Western blotting and immunoprecipitation, respectively. Binding of recombinant Ts-Pmy (rTs-Pmy to C1q inhibited C1q binding to IgM and consequently inhibited C3 deposition. The lysis of antibody-sensitized erythrocytes (EAs elicited by the classical complement pathway was also inhibited in the presence of rTs-Pmy. In addition to inhibiting classical complement activation, rTs-Pmy also suppressed C1q binding to THP-1-derived macrophages, thereby reducing C1q-induced macrophages migration.Our results suggest that T. spiralis paramyosin plays an important role in immune evasion by interfering with complement activation through binding to C1q in addition to C8 and C9.

  9. Complementing the sugar code: role of GAGs and sialic acid in complement regulation

    Directory of Open Access Journals (Sweden)

    Alex eLangford-Smith

    2015-02-01

    Full Text Available Sugar molecules play a vital role on both microbial and mammalian cells, where they are involved in cellular communication, govern microbial virulence and modulate host immunity and inflammatory responses. The complement cascade, as part of a host’s innate immune system, is a potent weapon against invading bacteria but has to be tightly regulated to prevent inappropriate attack and damage to host tissues. A number of complement regulators, such as factor H and properdin, interact with sugar molecules, such as glycosaminoglycans and sialic acid, on host and pathogen membranes and direct the appropriate complement response by either promoting the binding of complement activators or inhibitors. The binding of these complement regulators to sugar molecules can vary from location to location, due to their different specificities and because distinct structural and functional subpopulations of sugars are found in different human organs, such as the brain, kidney and eye. This review will cover recent studies that have provided important new insights into the role of glycosaminoglycans and sialic acid in complement regulation and how sugar recognition may be compromised in disease

  10. Text and Voice: Complements, Substitutes or Both?

    OpenAIRE

    Andersson, Kjetil; Foros, Øystein; Steen, Frode

    2006-01-01

    Text messaging has become an important revenue component for European and Asian mobile operators. We develop a simple model of demand for mobile services incorporating the existence of call externalities and network effects. We show that when incoming messages and calls stimulate outgoing communications, services that are perceived as substitutes, such as mobile text and voice, may evolve into complements in terms of the price effect when the network size becomes large. We esti...

  11. Complement and phagocytes - A complicated interaction.

    Science.gov (United States)

    Roos, Dirk

    2015-11-01

    Mohamed Daha and I share a common interest in innate immunity. Working in institutes only 25 miles away from each other, that meant ample opportunity and relevance for collaboration. And so we did. Moreover, we have both been members of boards and councils of Dutch national organizations, and we have also become good friends. In this short recollection, I look back on 40 years of common activities in complement research and friendship.

  12. Complement and Immunoregulation in Tissue Injury

    Science.gov (United States)

    2015-12-01

    transplantation, sepsis , and cardiovascular interventions. Ischemia induces local cellular changes such as membrane perturbation, cytoskeletal...intestinal epithelial cells Several reports have provided evidence that acute inflammatory conditions including sepsis and endotoxemia can stimulate...that detects complement precursor C3 and fragments of C3 including c3a, c3b and c3c. Intestinal tissue sections from sham-operated mice displayed

  13. Creatinine clearance, urinary excretion of glomerular basement membrane antigens and renal histology in congenital nephrotic syndrome of Finnish type.

    Science.gov (United States)

    Huttunen, N P

    1977-04-01

    The endogenous creatinine clearance and urinary excretion rate of glomerular basement membrane (GBM) antigens were followed from 2 to 19 months in fifteen patients with congenital nephrotic syndrome (CNF). The quantitative examination of renal morphology was made on fourteen of these patients. Creatinine clearance increased during the first few months of life and thereafter gradually decreased. The urinary excretion rate of GBM antigens rose during the course of the disease. The creatinine clearance did not correlate significantly with glomerular fibrosis but it did correlate with tubular atrophy and interstitial fibrosis. The urinary excretion of GBM antigens correlated significantly with glomerular and interstitial fibrosis and with tubular atrophy. It is concluded that there is a clear progress in the disease and the renal histological changes probably are caused by accumulation of GBM material in glomeruli.

  14. Effect of Hypotensive Drugs on Dynamics of Nitroxide-Producing Renal Function in Rats with Nephrogenic Hypertension.

    Science.gov (United States)

    Eliseeva, E V; Romanchenko, E F; Dyuizen, I V; Tyrtyshnikova, A V; Pigolkin, Yu I

    2017-01-01

    An original model of nephrogenic hypertension in rats was used for histochemical mapping of NADPH diaphorase (NO synthase) in various renal segments to examine the effect of hypotensive drugs furosemide, bendazol, and clonidine on the time course of nitroxide production in the kidneys. In various nephron segments, these drugs modulated NO synthesis in different ways. Clonidine induced a stable up-regulation of NO synthesis, which can maintain active vasodilation and gradually diminish the rennin production. Bendazol also enhanced NO synthase activity in renal glomeruli and collecting tubules, but this effect was less pronounced and short lasting. During the first week after injection of bendazol, insignificant elevation of NO synthase activity was observed in the proximal nephron segments. Furosemide exerted the least effect on NO production in kidneys.

  15. Circulating C3 levels predict renal and global outcome in patients with renal vasculitis.

    Science.gov (United States)

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Cavero, Teresa; Guerrero, Carmen; Praga, Manuel; Fernandez-Juarez, Gema

    2016-11-01

    Several studies have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis. We aimed to assess the association between baseline serum C3 (sC3) levels and long-term outcomes in patients with renal vasculitis. This retrospective study included 111 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Serum levels of C3 were measured at the onset and the study population was divided into three tertiles according to sC3 concentrations (tertile 1 128 mg/dl). Patients with lower sC3 (tertile 1) were compared with those having higher levels of sC3 (tertile 2 and tertile 3). Histological, clinical, and laboratory data were recorded for analysis. The primary end point was the composite of end-stage renal disease (ESRD) and death from any cause. Lower sC3 levels were associated with a higher need for dialysis and lower response rate to treatment (p = 0.04 and p = 0.007, respectively). Renal and global survival at 1 and 5 years was 53 and 46 % in patients with lower sC3 (tertile 1) compared with 72 and 65 % in patients with higher sC3 (upper two tertiles) (p = 0.04). In a multivariate Cox-regression model, when adjusted by renal function and histopatholologic categories, lower sC3 remained as an independent predictor of ESRD and death (HR, 1.9; 95 % CI, 1.1 to 3.4; p = 0.02). Baseline serum C3 levels have an independent prognostic value in predicting long-term renal and global survival in patients with renal vasculitis.

  16. Age-related macular degeneration: Complement in action.

    Science.gov (United States)

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  17. Regenerative medicine for the kidney: renotropic factors, renal stem/progenitor cells, and stem cell therapy.

    Science.gov (United States)

    Maeshima, Akito; Nakasatomi, Masao; Nojima, Yoshihisa

    2014-01-01

    The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.

  18. Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats.

    Science.gov (United States)

    Zhu, Xia; Cheng, Ya-Qin; Du, Lei; Li, Yu; Zhang, Fan; Guo, Hao; Liu, Yao-Wu; Yin, Xiao-Xing

    2015-02-01

    This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB.

  19. C4d immunoreactivity of intraoperative zero-hour biopsy in renal allograft.

    Science.gov (United States)

    Lee, C; Park, J H; Suh, J H; Kim, H W; Moon, K C

    2014-12-01

    C4d deposition in the peritubular capillaries is known to be correlated with antibody-mediated rejection (AMR) in renal allografts. An intraoperative zero-hour biopsy during transplantation is considered an indicator to indirectly determine the status of the donor kidney. In this study, we investigated the relationship between C4d immunoreactivity of intraoperative zero-hour biopsy in renal allograft, thought to be due to donor condition, and acute rejection episodes during follow-up. We collected 147 renal transplantation cases examining intraoperative zero-hour biopsy with C4d immunohistochemical staining. All cases were from the Seoul National University Hospital between 2010 and 2011. Of the 147 cases, 24 (16.3%) showed strong C4d staining in the glomeruli, 38 (25.9%) showed weak staining, and the remainder (57.8%) showed negative staining. Nine cases (6.1%) showed positive C4d staining in the arterioles, and the remainder (93.9%) were negative. There were no significant differences between acute T-cell-mediated rejection and acute AMR episodes in the renal allograft specimens during follow-up according to the glomerular or arteriolar C4d immunoreactivity of the intraoperative zero-hour biopsy specimens.

  20. Unexpected recovery from longterm renal failure in severe diffuse proliferative lupus nephritis

    Directory of Open Access Journals (Sweden)

    Ross Sophia

    2012-08-01

    Full Text Available Abstract Background Severe renal manifestation of systemic lupus erythematosus (SLE is not uncommon and is associated with an indeterminate prognosis. Complete remission can be obtained, however, at least in the young when chronic lesions are absent and adequate anti-inflammatory therapy is immediately initiated. Case presentation We report the unusual case of a 12-year-old girl who presented with severe oliguric renal failure, macrohematuria and skin rash. Renal biopsy revealed the diagnosis of severe diffuse proliferative glomerulonephritis (GN with cellular crescents in 15 out of 18 glomeruli and full-house pattern in immunofluorescence indicating lupus nephritis IVB according to WHO, IV-G(A according to ISN/RPS classification. The serological parameters confirmed the diagnosis of SLE and the patient was immediately treated with methylprednisolone, cyclophosphamide and immunoadsorption. Initially, despite rapid amelioration of her general condition, no substantial improvement of renal function could be achieved and the patient needed hemodialysis treatment for 12 weeks. Unexpectedly, in the further follow-up at first diuresis increased and thereafter also creatinine levels substantially declined so that hemodialysis could be discontinued. Today, 6 years after the initial presentation, the patient has normal renal function and a SLEDAI score of 0 under a continuous immunosuppressive therapy with Mycophenolate mofetil (MMF and low dose steroid. Conclusion Despite the severity of the initial renal injury and the unfavourable renal prognosis the kidney apparently has a tremendous capacity to recover in young patients when the damage is acute and adequate anti-inflammatory therapy is initiated without delay.

  1. Kidney (Renal) Failure

    Science.gov (United States)

    ... How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain proper fluid ... marrow and strengthen the bones. The term kidney (renal) failure describes a situation in which the kidneys have ...

  2. Renal arteries (image)

    Science.gov (United States)

    A renal angiogram is a test used to examine the blood vessels of the kidneys. The test is performed ... main vessel of the pelvis, up to the renal artery that leads into the kidney. Contrast medium ...

  3. The constant region contributes to the antigenic specificity and renal pathogenicity of murine anti-DNA antibodies.

    Science.gov (United States)

    Xia, Yumin; Pawar, Rahul D; Nakouzi, Antonio S; Herlitz, Leal; Broder, Anna; Liu, Kui; Goilav, Beatrice; Fan, Manxia; Wang, Ling; Li, Quan-Zhen; Casadevall, Arturo; Putterman, Chaim

    2012-12-01

    Affinity for DNA and cross-reactivity with renal antigens are associated with enhanced renal pathogenicity of lupus autoantibodies. In addition, certain IgG subclasses are enriched in nephritic kidneys, suggesting that isotype may determine the outcome of antibody binding to renal antigens. To investigate if the isotype of DNA antibodies affects renal pathogenicity by influencing antigen binding, we derived IgM, IgG1, IgG2b and IgG2a forms of the PL9-11 antibody (IgG3 anti-DNA) by in vitro class switching or PCR cloning. The affinity and specificity of PL9-11 antibodies for nuclear and renal antigens were analyzed using ELISA, Western blotting, surface plasmon resonance (SPR), binding to mesangial cells, and glomerular proteome arrays. Renal deposition and pathogenicity were assayed in mice injected with PL9-11 hybridomas. We found that PL9-11 and its isotype-switched variants had differential binding to DNA and chromatin (IgG3>IgG2a>IgG1>IgG2b>IgM) by direct and competition ELISA, and SPR. In contrast, in binding to laminin and collagen IV the IgG2a isotype actually had the highest affinity. Differences in affinity of PL9-11 antibodies for renal antigens were mirrored in analysis of specificity for glomeruli, and were associated with significant differences in renal pathogenicity in vivo and survival. Our novel findings indicate that the constant region plays an important role in the nephritogenicity of antibodies to DNA by affecting immunoglobulin affinity and specificity. Increased binding to multiple glomerular and/or nuclear antigens may contribute to the renal pathogenicity of anti-DNA antibodies of the IgG2a and IgG3 isotype. Finally, class switch recombination may be another mechanism by which B cell autoreactivity is generated.

  4. [Renal leiomyoma. Case report].

    Science.gov (United States)

    Joual, A; Guessous, H; Rabii, R; Benjelloun, M; Benlemlih, A; Skali, K; el Mrini, M; Benjelloun, S

    1999-01-01

    The authors report a case of renal leiomyoma observed in a 56-year-old man. This cyst presented in the from of loin pain. Computed tomography revealed a homogeneous renal tumor. Treatment consisted of radical nephrectomy. Histological examination of the specimen showed benign renal leiomyoma.

  5. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  6. Successful isolated liver transplantation in a child with atypical hemolytic uremic syndrome and a mutation in complement factor H.

    Science.gov (United States)

    Haller, W; Milford, D V; Goodship, T H J; Sharif, K; Mirza, D F; McKiernan, P J

    2010-09-01

    A male infant was diagnosed with atypical hemolytic uremic syndrome (aHUS) at the age of 5.5 months. Sequencing of the gene (CFH) encoding complement factor H revealed a heterozygous mutation (c.3644G>A, p.Arg1215Gln). Despite maintenance plasmapheresis he developed recurrent episodes of aHUS and vascular access complications while maintaining stable renal function. At the age of 5 years he received an isolated split liver graft following a previously established protocol using pretransplant plasma exchange (PE) and intratransplant plasma infusion. Graft function, renal function and disease remission are preserved 2 years after transplantation. Preemptive liver transplantation prior to the development of end stage renal disease is a valuable option in the management of aHUS associated with CFH mutations.

  7. Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach.

    Science.gov (United States)

    Grumach, Anete Sevciovic; Kirschfink, Michael

    2014-10-01

    Complement deficiencies comprise between 1 and 10% of all primary immunodeficiencies (PIDs) according to national and supranational registries. They are still considered rare and even of less clinical importance. This not only reflects (as in all PIDs) a great lack of awareness among clinicians and general practitioners but is also due to the fact that only few centers worldwide provide a comprehensive laboratory complement analysis. To enable early identification, our aim is to present warning signs for complement deficiencies and recommendations for diagnostic approach. The genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4) is often associated with autoimmune diseases whereas individuals, deficient of properdin or of the terminal pathway components (C5 to C9), are highly susceptible to meningococcal disease. Deficiency of C1 Inhibitor (hereditary angioedema, HAE) results in episodic angioedema, which in a considerable number of patients with identical symptoms also occurs in factor XII mutations. New clinical entities are now reported indicating disease association with partial complement defects or even certain polymorphisms (factor H, MBL, MASPs). Mutations affecting the regulators factor H, factor I, or CD46 and of C3 and factor B leading to severe dysregulation of the alternative pathway have been associated with renal disorders, such as atypical hemolytic uremic syndrome (aHUS) and - less frequent - with membranoproliferative glomerulonephritis (MPGN). We suggest a multi-stage diagnostic protocol starting based on the recognition of so called warning signs which should aid pediatricians and adult physicians in a timely identification followed by a step-wise complement analysis to characterize the defect at functional, protein and molecular level.

  8. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.;

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three...

  9. Factor H-related proteins determine complement-activating surfaces.

    Science.gov (United States)

    Józsi, Mihály; Tortajada, Agustin; Uzonyi, Barbara; Goicoechea de Jorge, Elena; Rodríguez de Córdoba, Santiago

    2015-06-01

    Complement factor H-related proteins (FHRs) are strongly associated with different diseases involving complement dysregulation, which suggests a major role for these proteins regulating complement activation. Because FHRs are evolutionarily and structurally related to complement inhibitor factor H (FH), the initial assumption was that the FHRs are also negative complement regulators. Whereas weak complement inhibiting activities were originally reported for these molecules, recent developments indicate that FHRs may enhance complement activation, with important implications for the role of these proteins in health and disease. We review these findings here, and propose that FHRs represent a complex set of surface recognition molecules that, by competing with FH, provide improved discrimination of self and non-self surfaces and play a central role in determining appropriate activation of the complement pathway.

  10. Begin and start: aspect and complement choice

    Directory of Open Access Journals (Sweden)

    Tünde Nagy

    2008-01-01

    Full Text Available The paper offers a semantic analysis of begin and start and their non-finite complementation: the to-infinitive and –ing constructions. The core idea of the paper is that the aspectual constructions ‘begin+ to infinitive’, ‘begin + ing’, ‘start+ to infinitive’, and ‘start+ ing’ have both a schematic and a prototypical meaning, and that the subtle differences between them are motivated by several factors, like viewing (perfectivity vs. imperfectivity, temporality (future orientation vs. ongoing reading dynamicity (graduality vs. abruptness, agentivity, etc.

  11. On Wiener index of graph complements

    Directory of Open Access Journals (Sweden)

    Jaisankar Senbagamalar

    2014-06-01

    Full Text Available Let $G$ be an $(n,m$-graph. We say that $G$ has property $(ast$ if for every pair of its adjacent vertices $x$ and $y$, there exists a vertex $z$, such that $z$ is not adjacent to either $x$ or $y$. If the graph $G$ has property $(ast$, then its complement $overline G$ is connected, has diameter 2, and its Wiener index is equal to $binom{n}{2}+m$, i.e., the Wiener index is insensitive of any other structural details of the graph $G$. We characterize numerous classes of graphs possessing property $(ast$, among which are trees, regular, and unicyclic graphs.

  12. [Treatment of acute renal failure--concepts and controversies. 2. Extracorporeal renal replacement and peritoneal dialysis].

    Science.gov (United States)

    Gabriel, A; Müller, E; Tarnow, J

    2001-04-01

    Therapy of prolonged acute renal failure regularly requires a renal replacement therapy. This can be achieved by different extracorporal renal replacement therapies (ERRT) or by peritoneal dialysis. ERRT are classified according to the physical principle underlying toxin elimination as hemodialysis (diffusion) and hemofiltration (convection). Another classification refers to intermittent or continuous application modes. Biocompatibility of membranes is judged according to their activation of the complement system. Prospective randomized studies did not consolidate the assumptions about the benefit of particular modalities proposed on theoretical foundations. Mortality, duration and complication rates of acute renal failure are not significantly decreased by use of biocompatible membranes. Continuous modalities are not generally preferable but optimize treatment in hemodynamically unstable patients, in whom they endorse fluid balancing and maintenance of sufficient arterial blood pressure. The use of demanding hemofiltration techniques for cytokine removal should be limited to clinical studies. The effects of ERRT-"intensity" and the best timing for initiation of ERRT have not been evaluated sufficiently. The choice of the ERRT modality is subject to clinical judgement (criterion: hemodynamic situation), practical aspects (criteria: availability of equipment and handling experience), and costs. Prior to their general use new and expensive technical modalities and membrane types should be thoroughly evaluated in studies with regard to outcome-related aspects such as patient survival and preservation of renal function.

  13. Postpartum renal vein thrombosis.

    Science.gov (United States)

    Rubens, D; Sterns, R H; Segal, A J

    1985-01-01

    Renal vein thrombosis in adults is usually a complication of the nephrotic syndrome. Rarely, it has been reported in nonnephrotic women postpartum. The thrombosis may be a complication of the hypercoagulable state associated with both the nephrotic syndrome and pregnancy. Two postpartum patients with renal vein thrombosis and no prior history of renal disease are reported here. Neither patient had heavy proteinuria. In both cases, pyelonephritis was suspected clinically and the diagnosis of renal vein thrombosis was first suggested and confirmed by radiologic examination. Renal vein thrombosis should be considered in women presenting postpartum with flank pain.

  14. Renal infarction resulting from traumatic renal artery dissection.

    Science.gov (United States)

    Kang, Kyung Pyo; Lee, Sik; Kim, Won; Jin, Gong Yong; Na, Ki Ryang; Yun, Il Yong; Park, Sung Kwang

    2008-06-01

    Renal artery dissection may be caused by iatrogenic injury, trauma, underlying arterial diseases such as fibromuscular disease, atherosclerotic disease, or connective tissue disease. Radiological imaging may be helpful in detecting renal artery pathology, such as renal artery dissection. For patients with acute, isolated renal artery dissection, surgical treatment, endovascular management, or medical treatment have been considered effective measures to preserve renal function. We report a case of renal infarction that came about as a consequence of renal artery dissection.

  15. Hyperbolicity of the complement of plane algebraic curves

    CERN Document Server

    Dethloff, G E; Dethloff, Gerd; Schumacher, Georeg

    1993-01-01

    The paper is a contribution of the conjecture of Kobayashi that the complement o f a generic plain curve of degree at least five is hyperbolic. The main result is that the complement of a generic configuration of three quadr ics is hyperbolic and hyperbolically embedded as well as the complement of two q uadrics and a line.

  16. The Production of Complement Clauses in Children with Language Impairment

    Science.gov (United States)

    Steel, Gillian; Rose, Miranda; Eadie, Patricia

    2016-01-01

    Purpose: The purpose of this research was to provide a comprehensive description of complement-clause production in children with language impairment. Complement clauses were examined with respect to types of complement structure produced, verb use, and both semantic and syntactic accuracy. Method: A group of 17 children with language impairment…

  17. Complement activation by tubular cells is mediated by properdin binding

    NARCIS (Netherlands)

    Gaarkeuken, E.M.; Siezenga, M.A.; Zuidwijk, K.; Kooten, C. van; Rabelink, T.J.; Daha, M.R.; Berger, S.P.

    2008-01-01

    Activation of filtered complement products on the brush border of the tubular epithelium is thought to be a key factor underlying proteinuria-induced tubulointerstitial injury. However, the mechanism of tubular complement activation is still unclear. Recent studies on mechanisms of complement activa

  18. The Production of Complement Clauses in Children with Language Impairment

    Science.gov (United States)

    Steel, Gillian; Rose, Miranda; Eadie, Patricia

    2016-01-01

    Purpose: The purpose of this research was to provide a comprehensive description of complement-clause production in children with language impairment. Complement clauses were examined with respect to types of complement structure produced, verb use, and both semantic and syntactic accuracy. Method: A group of 17 children with language impairment…

  19. Alterations in the renal elastin-elastase system in type 1 diabetic nephropathy identified by proteomic analysis.

    Science.gov (United States)

    Thongboonkerd, Visith; Barati, Michelle T; McLeish, Kenneth R; Benarafa, Charaf; Remold-O'Donnell, Eileen; Zheng, Shirong; Rovin, Brad H; Pierce, William M; Epstein, Paul N; Klein, Jon B

    2004-03-01

    Diabetes now accounts for >40% of patients with ESRD. Despite significant progress in understanding diabetic nephropathy, the cellular mechanisms that lead to diabetes-induced renal damage are incompletely defined. For defining changes in protein expression that accompany diabetic nephropathy, the renal proteome of 120-d-old OVE26 transgenic mice with hypoinsulinemia, hyperglycemia, hyperlipidemia, and proteinuria were compared with those of background FVB nondiabetic mice (n = 5). Proteins derived from whole-kidney lysate were separated by two-dimensional PAGE and identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Forty-one proteins from 300 visualized protein spots were differentially expressed in diabetic kidneys. Among these altered proteins, expression of monocyte/neutrophil elastase inhibitor was increased, whereas elastase IIIB was decreased, leading to the hypothesis that elastin expression would be increased in diabetic kidneys. Renal immunohistochemistry for elastin of 325-d-old FVB and OVE26 mice demonstrated marked accumulation of elastin in the macula densa, collecting ducts, and pelvicalyceal epithelia of diabetic kidneys. Elastin immunohistochemistry of human renal biopsies from patients with type 1 diabetes (n = 3) showed increased elastin expression in renal tubular cells and the interstitium but not glomeruli. These results suggest that coordinated changes in elastase inhibitor and elastase expression result in increased tubulointerstitial deposition of elastin in diabetic nephropathy. The identification of these coordinated changes in protein expression in diabetic nephropathy indicates the potential value of proteomic analysis in defining pathophysiology.

  20. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H;

    1985-01-01

    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...

  1. The Complement System in Flavivirus Infections

    Science.gov (United States)

    Conde, Jonas N.; Silva, Emiliana M.; Barbosa, Angela S.; Mohana-Borges, Ronaldo

    2017-01-01

    The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processed by viral and host proteases into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) that are involved in viral replication and pathogenicity. The complement system has been described to play an important role in flavivirus infection either by protecting the host and/or by influencing disease pathogenesis. In this mini-review, we will explore the role of complement system inhibition and/or activation against infection by the Flavivirus genus, with an emphasis on dengue and West Nile viruses. PMID:28261172

  2. Complementing asteroseismology with 4MOST spectroscopy

    Science.gov (United States)

    de Jong, R. S.; 4MOST Consortium; 4MOST Spectroscopy Consortium

    2016-09-01

    4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the areas of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO. 4MOST will have an unique operations concept in which 5-years public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. As a dedicated spectroscopic survey facility with a large field-of-view, a high multiplex that can be reconfigured quickly, and with a broad wavelength coverage, 4MOST is particularly well suited to complement the upcoming asteroseismology space missions like TESS and PLATO. Here we show that, by dedicating the observing time during twilight and poor observing conditions to bright stars, 4MOST will obtain resolution {R>18 000} spectra of nearly all stars brighter than ˜ 12th magnitude at Dec TESS and PLATO missions and place any planets found in a full chemo-dynamical context of the star formation history of the Galaxy, yield very accurate ages and masses for all stars that can be characterized with asteroseismology, and allow removal of contaminants from target samples (e.g., spectroscopic binaries).

  3. Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation

    NARCIS (Netherlands)

    Damman, Jeffrey; Nijboer, Willemijn N.; Schuurs, Theo A.; Leuvenink, Henri G.; Morariu, Aurora M.; Tullius, Stefan G.; van Goor, Harry; Ploeg, Rutger J.; Seelen, Marc A.

    2011-01-01

    Background. Kidneys derived from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Strikingly, early and profound serum levels of IL-6 in brain-dead donors are observed. IL-6 is the main regulator of the acute phase response (APR). The aim of this

  4. Atypical haemolytic uraemic syndrome associated with a hybrid complement gene.

    Directory of Open Access Journals (Sweden)

    Julian P Venables

    2006-10-01

    Full Text Available BACKGROUND: Sequence analysis of the regulators of complement activation (RCA cluster of genes at chromosome position 1q32 shows evidence of several large genomic duplications. These duplications have resulted in a high degree of sequence identity between the gene for factor H (CFH and the genes for the five factor H-related proteins (CFHL1-5; aliases CFHR1-5. CFH mutations have been described in association with atypical haemolytic uraemic syndrome (aHUS. The majority of the mutations are missense changes that cluster in the C-terminal region and impair the ability of factor H to regulate surface-bound C3b. Some have arisen as a result of gene conversion between CFH and CFHL1. In this study we tested the hypothesis that nonallelic homologous recombination between low-copy repeats in the RCA cluster could result in the formation of a hybrid CFH/CFHL1 gene that predisposes to the development of aHUS. METHODS AND FINDINGS: In a family with many cases of aHUS that segregate with the RCA cluster we used cDNA analysis, gene sequencing, and Southern blotting to show that affected individuals carry a heterozygous CFH/CFHL1 hybrid gene in which exons 1-21 are derived from CFH and exons 22/23 from CFHL1. This hybrid encodes a protein product identical to a functionally significant CFH mutant (c.3572C>T, S1191L and c.3590T>C, V1197A that has been previously described in association with aHUS. CONCLUSIONS: CFH mutation screening is recommended in all aHUS patients prior to renal transplantation because of the high risk of disease recurrence post-transplant in those known to have a CFH mutation. Because of our finding it will be necessary to implement additional screening strategies that will detect a hybrid CFH/CFHL1 gene.

  5. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury.

    Science.gov (United States)

    Farrar, Conrad A; Tran, David; Li, Ke; Wu, Weiju; Peng, Qi; Schwaeble, Wilhelm; Zhou, Wuding; Sacks, Steven H

    2016-05-01

    Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

  6. Refractory anemia leading to renal hemosiderosis and renal failure

    OpenAIRE

    Sujatha Siddappa; K M Mythri; Kowsalya, R.; Ashish Parekh

    2011-01-01

    Renal hemosiderosis is a rare cause of renal failure and, as a result, may not be diagnosed unless a detailed history, careful interpretation of blood parameters and renal biopsy with special staining is done. Here, we present a rare case of renal hemosiderosis presenting with renal failure.

  7. Refractory anemia leading to renal hemosiderosis and renal failure

    Directory of Open Access Journals (Sweden)

    Sujatha Siddappa

    2011-01-01

    Full Text Available Renal hemosiderosis is a rare cause of renal failure and, as a result, may not be diagnosed unless a detailed history, careful interpretation of blood parameters and renal biopsy with special staining is done. Here, we present a rare case of renal hemosiderosis presenting with renal failure.

  8. Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights.

    Science.gov (United States)

    Perkins, Stephen J; Okemefuna, Azubuike I; Nan, Ruodan; Li, Keying; Bonner, Alexandra

    2009-10-06

    X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. They are useful when either a large protein cannot be crystallized, in which case scattering yields a solution structure, or a crystal structure has been determined and requires validation in solution. These solution structures are determined by the application of constrained modelling methods based on known subunit structures. First, an appropriate starting model is generated. Next, its conformation is randomized to generate thousands of models for trial-and-error fits. Comparison with the experimental data identifies a small family of best-fit models. Finally, their significance for biological function is assessed. We illustrate this in application to structure determinations for secretory immunoglobulin A, the most prevalent antibody in the human body and a first line of defence in mucosal immunity. We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. We discuss the importance of complementary data from analytical ultracentrifugation, and structural studies of protein-protein complexes. We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function.

  9. complement C3, Complement C4 and C-reactive protein

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... Serum levels of complement C3, C4 and C-reactive protein were determined in 24 male smokers ... ability to alter the function of immune cells (Sopori, 2002). ... history of ≥1 cigarette per day and smoking period of at least 6.

  10. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Directory of Open Access Journals (Sweden)

    María F Albertoni Borghese

    Full Text Available Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day, a dual endothelin receptor antagonist (ERA. The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  11. Renal replacement therapy for acute renal failure.

    Science.gov (United States)

    Macedo, E; Bouchard, J; Mehta, R L

    2009-09-01

    Renal replacement therapy became a common clinical tool to treat patients with severe acute kidney injury (AKI) since the 1960s. During this time dialytic options have expanded considerably; biocompatible membranes, bicarbonate dialysate and dialysis machines with volumetric ultrafiltration control have improved the treatment for acute kidney injury. Along with advances in methods of intermittent hemodialysis, continuous renal replacement therapies have gained widespread acceptance in the treatment of dialysis-requiring AKI. However, many of the fundamental aspects of the renal replacement treatment such as indication, timing of dialytic intervention, and choice of dialysis modality are still controversial and may influence AKI patient's outcomes. This review outlines current concepts in the use of dialysis techniques for AKI and suggests an approach for selecting the optimal method of renal replacement therapy.

  12. [Biological roles of complement and recent topics in clinical medicine].

    Science.gov (United States)

    Wakamiya, Nobutaka

    2012-08-01

    The complement has been identified as a complementation factor to compensate for the function of an antibody. The complement consists of C1-C9, a complement-related molecule, and its regulating molecules. Three major biological roles of the complement have been classified: First: opsonization following phagocytosis and the elimination of microbes; second: direct destruction of bacteria due to membrane attack complex (MAC); third: complement activation following the induction of anaphylactoid factors and local recruitment and activation of neutrophilic leukocytes. In this review, the basic findings and recent treatments of paroxysmal nocturnal hemoglobinuria (PNH) and hereditary angioedema (HAE) are summarized. Finally, there is a short review of a rare autosomal recessive disorder of 3MC syndrome and new biological functions of complement factors except for that of innate immunity are proposed.

  13. The Complement System and Antibody-Mediated Transplant Rejection.

    Science.gov (United States)

    Stites, Erik; Le Quintrec, Moglie; Thurman, Joshua M

    2015-12-15

    Complement activation is an important cause of tissue injury in patients with Ab-mediated rejection (AMR) of transplanted organs. Complement activation triggers a strong inflammatory response, and it also generates tissue-bound and soluble fragments that are clinically useful markers of inflammation. The detection of complement proteins deposited within transplanted tissues has become an indispensible biomarker of AMR, and several assays have recently been developed to measure complement activation by Abs reactive to specific donor HLA expressed within the transplant. Complement inhibitors have entered clinical use and have shown efficacy for the treatment of AMR. New methods of detecting complement activation within transplanted organs will improve our ability to diagnose and monitor AMR, and they will also help guide the use of complement inhibitory drugs.

  14. Targeted complement inhibition and microvasculature in transplants: a therapeutic perspective.

    Science.gov (United States)

    Khan, M A; Hsu, J L; Assiri, A M; Broering, D C

    2016-02-01

    Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during allograft acceptance. The complement cascade releases the powerful proinflammatory mediators C3a and C5a anaphylatoxins, C3b, C5b opsonins and terminal membrane attack complex into tissues, which are deleterious if unchecked. Blocking complement mediators has been considered to be a promising approach in the modern drug discovery plan, and a significant number of therapeutic alternatives have been developed to dampen complement activation and protect host cells. Numerous immune cells, especially macrophages, develop both anaphylatoxin and opsonin receptors on their cell surface and their binding affects the macrophage phenotype and their angiogenic properties. This review discusses the mechanism that complement contributes to angiogenic injury, and the development of future therapeutic targets by antagonizing activated complement mediators to preserve microvasculature in rejecting the transplanted organ.

  15. Theoretical implications of complement structure acquisition in Korean.

    Science.gov (United States)

    Kim, Y J

    1989-10-01

    The acquisition of complement phrasal constructions in Korean is examined in spontaneous speech data from two children, who were observed from one and a half to three years of age. In spite of typological differences between English and Korean, both syntactic and semantic characteristics are found to be shared by children acquiring complement constructions in the two languages. However, certain language-specific features of Korean complement structures make it possible to address theoretical points concerning the structure of infinitival complements which cannot be resolved with the acquisition data on English. The error pattern in the acquisition of certain 'subject-equi' verbs in Korean poses problems both for LFG and GB accounts of the constituent structure of infinitival complements and the acquisition of those constructions. On the basis of the Korean data, I propose that base-generated VP complements are acquired first, with semantically motivated reanalysis of previously acquired infinitival complement structures occurring at a later stage.

  16. The role of complement in experimental autoimmune myasthenia gravis

    Science.gov (United States)

    Kusner, Linda L.; Kaminski, Henry J.

    2012-01-01

    Complement plays an important role in the pathophysiology of experimental autoimmune myasthenia gravis (EAMG). The deposition of IgG at the neuromuscular junction, followed by the activation and observance of C3 at the site, and finally the insertion of the membrane attack complex, which results in the destruction of the plasma membrane at the neuromuscular junction. Animal models’ of complement-deficient components show the importance of the mediated lysisin EAMG. These events have regulators that allow for the limitation in the cascade and the ability of the cell to inhibit complement at many places along the pathway. The complement regulatory proteins have many roles in reducing the activation of the complement cascade and the inflammatory pathways. Mice deficient in complement regulatory proteins, decay accelerating factor and CD59, demonstrate a significant increase in the destruction at the neuromuscular junction. Inhibition of complement-mediated lysis is an attractive therapeutic in MG. PMID:23252907

  17. Renal function after renal artery stenting

    Institute of Scientific and Technical Information of China (English)

    George S. Hanzel; Mark Downes; Peter A. McCullough

    2005-01-01

    @@ Atherosclerotic renal artery stenosis (ARAS), a common clinical finding, is increasing in prevalence as the population ages. ARAS is seen in ~ 7% of persons over 65 years of age1 and in ~ 20% of patients at the time of coronary angiography.2 It is an important cause of chronic kidney disease and may result in 11-14% of cases of end stage renal disease.3

  18. Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3.

    Directory of Open Access Journals (Sweden)

    Michal Potempa

    2009-02-01

    Full Text Available Periodontitis is an inflammatory disease of the supporting structures of the teeth caused by, among other pathogens, Prevotella intermedia. Many strains of P. intermedia are resistant to killing by the human complement system, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with recombinant cysteine protease of P. intermedia (interpain A resulted in a drastic decrease in bactericidal activity of the serum. Furthermore, a clinical strain 59 expressing interpain A was more serum-resistant than another clinical strain 57, which did not express interpain A, as determined by Western blotting. Moreover, in the presence of the cysteine protease inhibitor E64, the killing of strain 59 by human serum was enhanced. Importantly, we found that the majority of P. intermedia strains isolated from chronic and aggressive periodontitis carry and express the interpain A gene. The protective effect of interpain A against serum bactericidal activity was found to be attributable to its ability to inhibit all three complement pathways through the efficient degradation of the alpha-chain of C3 -- the major complement factor common to all three pathways. P. intermedia has been known to co-aggregate with P. gingivalis, which produce gingipains to efficiently degrade complement factors. Here, interpain A was found to have a synergistic effect with gingipains on complement degradation. In addition, interpain A was able to activate the C1 complex in serum, causing deposition of C1q on inert and bacterial surfaces, which may be important at initial stages of infection when local inflammatory reaction may be beneficial for a pathogen. Taken together, the newly characterized interpain A proteinase appears to be an important virulence factor of P. intermedia.

  19. Acidosis activates complement system in vitro

    Directory of Open Access Journals (Sweden)

    Michael Emeis

    1998-01-01

    Full Text Available We investigated the in vitro effect of different form s of acidosis (pH 7.0 on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 μ mol/ml blood or lactic acid (5.5 μ mol/ml to heparin blood (N=12 caused significant activation of C3a and C5a compared to control (both p=0.002. Respiratory acidosis activated C3a (p=0.007 and C5a (p=0.003 compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5.

  20. Acidosis activates complement system in vitro.

    Science.gov (United States)

    Emeis, M; Sonntag, J; Willam, C; Strauss, E; Walka, M M; Obladen, M

    1998-01-01

    We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5. PMID:9927235

  1. Lectin Complement Pathway Proteins in Healthy Individuals

    DEFF Research Database (Denmark)

    Troldborg, Anne; Hansen, Annette; Hansen, Søren W K

    2017-01-01

    Since the discovery of the lectin pathway of complement activation, numerous clinical cohorts have been examined for one or more of the proteins, with the intention of uncovering the functions of the proteins or with the aim of discovering new biomarkers or diagnostic tools. To unveil the abnormal......, it is pivotal to know the normal. Our aim was to describe the concentrations of the eleven known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigations in different cohorts. We examined...... the concentrations of all lectin pathway proteins (mannan-binding lectin (MBL), H-ficolin, L-ficolin, M-ficolin, collectin-K1, collectin-L1, MBL-associated serine protease 2 (MASP-2), MASP-3, MBL associated protein of 44 kDa (MAp44) and MAp19 in 300 Danish blood donors in serum and EDTA plasma in established assays...

  2. Comparison of diagnostic quality of kidney biopsy obtained using 16g and 18g needles in patients with diffuse renal disease

    Directory of Open Access Journals (Sweden)

    Komal Arora

    2012-01-01

    Full Text Available To determine the diagnostic quality and complication rates of 16G and 18G needles in biopsy of the kidney, we performed renal biopsy using a biopsy gun under ultrasound guidance in 50 patients who were prospectively and evenly assigned to one of the two needle biopsy methods from April 2007 until May 2008. Two cores of renal biopsy specimen were obtained in each case and subjected to histopathological and immunoflourescence (IF examination. Pain associated with the procedure was assessed using a visual analog scale. The number of glomeruli retrieved using the 16G needle ranged from 0 to 30 (mean 9.42 ± 5.5 and those retrieved using 18G needle ranged from 0 to 19 (mean 7.72 ± 4.4, P <0.05. The quality of biopsy was poorer with 18G needle as compared with 16G needles because of a higher amount of fragmentation and crushing artifact. There was no difference in the compli-cation rates between the two needles (2% each. The 16G needle was associated with significantly more pain than the 18G needle. We conclude that our study demonstrates the benefit of the larger 16G needle in providing more tissue and glomeruli, which is more diagnostically useful. However, the use of 16G needle was associated with significantly more pain than the 18G needle, and may be a better compromise for diagnostic usefulness and patient acceptability.

  3. A new mouse model for renal lesions produced by intravenous injection of diphtheria toxin A-chain expression plasmid

    Directory of Open Access Journals (Sweden)

    Nakamura Shingo

    2004-04-01

    Full Text Available Abstract Background Various animal models of renal failure have been produced and used to investigate mechanisms underlying renal disease and develop therapeutic drugs. Most methods available to produce such models appear to involve subtotal nephrectomy or intravenous administration of antibodies raised against basement membrane of glomeruli. In this study, we developed a novel method to produce mouse models of renal failure by intravenous injection of a plasmid carrying a toxic gene such as diphtheria toxin A-chain (DT-A gene. DT-A is known to kill cells by inhibiting protein synthesis. Methods An expression plasmid carrying the cytomegalovirus enhancer/chicken β-actin promoter linked to a DT-A gene was mixed with lipid (FuGENE™6 and the resulting complexes were intravenously injected into adult male B6C3F1 mice every day for up to 6 days. After final injection, the kidneys of these mice were sampled on day 4 and weeks 3 and 5. Results H-E staining of the kidney specimens sampled on day 4 revealed remarkable alterations in glomerular compartments, as exemplified by mesangial cell proliferation and formation of extensive deposits in glomerular basement membrane. At weeks 3 and 5, gradual recovery of these tissues was observed. These mice exhibited proteinuria and disease resembling sub-acute glomerulonephritis. Conclusions Repeated intravenous injections of DT-A expression plasmid DNA/lipid complex caused temporary abnormalities mainly in glomeruli of mouse kidney. The disease in these mice resembles sub-acute glomerulonephritis. These DT-A gene-incorporated mice will be useful as animal models in the fields of nephrology and regenerative medicine.

  4. Imaging of renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jevtic, V. E-mail: vladimir.jevtic@mf.uni-lj.si

    2003-05-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.

  5. The complement system in systemic lupus erythematosus: an update.

    Science.gov (United States)

    Leffler, Jonatan; Bengtsson, Anders A; Blom, Anna M

    2014-09-01

    The complement system plays a major role in the autoimmune disease, systemic lupus erythematosus (SLE). However, the role of complement in SLE is complex since it may both prevent and exacerbate the disease. In this review, we explore the latest findings in complement-focused research in SLE. C1q deficiency is the strongest genetic risk factor for SLE, although such deficiency is very rare. Various recently discovered genetic associations include mutations in the complement receptors 2 and 3 as well as complement inhibitors, the latter related to earlier onset of nephritis. Further, autoantibodies are a distinct feature of SLE that are produced as the result of an adaptive immune response and how complement can affect that response is also being reviewed. SLE generates numerous disease manifestations involving contributions from complement such as glomerulonephritis and the increased risk of thrombosis. Furthermore, since most of the complement system is present in plasma, complement is very accessible and may be suitable as biomarker for diagnosis or monitoring of disease activity. This review highlights the many roles of complement for SLE pathogenesis and how research has progressed during recent years.

  6. A vital role for complement in heart disease.

    Science.gov (United States)

    Lappegård, Knut T; Garred, Peter; Jonasson, Lena; Espevik, Terje; Aukrust, Pål; Yndestad, Arne; Mollnes, Tom E; Hovland, Anders

    2014-10-01

    Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.

  7. Does injection of metanephric mesenchymal cells improve renal function in rats?

    Directory of Open Access Journals (Sweden)

    Yu-qing Jiao

    2011-01-01

    Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

  8. Identification of Type VI Collagen Synthesizing Cells in Human Diabetic Glomerulosclerosis Using Renal Biopsy Sections

    Directory of Open Access Journals (Sweden)

    Mohammed Shawkat Razzaque

    1997-01-01

    Full Text Available Although the role of extracellular matrices in the development of glomerulosclerosis has been discussed widely, the cellular origin of type VI collagen in diabetic nephropathy (DN has remained relatively unexplored. This study reports the distribution and cellular origin of type VI collagen in DN. Type VI collagen‐specific oligonucleotide probes and monoclonal antibody were used to assess the relative expression of mRNA for \\alpha1 (VI chain and its translated protein in paraffin‐embedded renal biopsy sections of DN. By immunohistochemistry, compared to the control, increased deposition of type VI collagen was noted in the diffuse and nodular lesions of diabetic glomeruli. For cellular localization of type VI collagen mRNA, paraffin‐embedded renal sections of the control and DN were hybridized in situ with digoxigenin (Dig‐labeled antisense oligo‐DNA probe complementary to a part of \\alpha1 (VI mRNA. In comparison to the control kidney sections, increased numbers of intraglomerular cells (both mesangial and epithelial cells were positive for α1 (VI mRNA in renal biopsy sections of DN. From the results, we conclude that overexpression of type VI collagen by intraglomerular cells with its increased deposition might significantly contribute to the glomerulosclerosis found in DN.

  9. Utility of urinary markers in the assessment of renal dysfunction in canine babesiosis.

    Science.gov (United States)

    Winiarczyk, Dagmara; Adaszek, Łukasz; Bartnicki, Michał; Abramowicz, Beata; Łyp, Paweł; Madany, Jacek; Winiarczyk, Stanisław

    2017-04-19

    Canine babesiosis is a common and clinically significant tick-borne disease caused by haemoprotozoan parasites of the genus Babesia. Acute renal failure is considered to be one of the most prevalent complications of canine babesiosis. This complication leads to a decrease in the glomerular filtration rate and in consequence causes azotemia and uremia. The objective of this study was to assess the localization and extent of renal damage in dogs infected with Babesia canis using an urinary marker for glomerular (urinary immunoglobulin G, uIgG), proximal tubular dysfunction (urinary retinol binding protein, uRBP) and distal tubular dysfunction (urinary Tamm-Horsfal protein, uTHP). Material und methods: In 10 dogs naturally infected with B. canis and 10 healthy control dogs the levels of urinary biomarkers were measured using commercially available ELISA tests. Higher concentrations of uIgG, uRBP and uTHP were found in the urine of all dogs with babesiosis than in those from the control group. This indicates that in the course of the disease, the glomeruli as well as the renal tubules become damaged. The study results allow a better understanding of the pathogenesis of canine babesiosis. However, in order to fully determine the extent and the nature of the damage to the kidneys of the infected dogs, it is advisable to conduct additional histopathological examinations of these organs.

  10. Incidental renal neoplasms

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen;

    2014-01-01

    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  11. Insuficiencia renal aguda.

    OpenAIRE

    Carlos Hernán Mejía

    2009-01-01

    Acute renal failure (ARF) is a clinic syndrome characterized by decline in renal function occurring over a short time period. Is a relatively common complication in hospitalized critically ill patients and is associated with high morbidity and mortality. ARF has often a multi-factorial etiology syndrome usually approached diagnostically as pre-renal, post-renal, or intrinsic ARF. Most intrinsic ARF is caused by ischemia or nephrotoxins and is classically associated with acute tubular necrosis...

  12. Hemodinâmica glomerular renal no roedor Calomys callosus

    Directory of Open Access Journals (Sweden)

    Mirian A. Boim

    1989-03-01

    . This rodent presented a significant number of superficial glomeruli, allowing to evaluate glomerular hemodynamics and renal microcirculation parameters. Despite mean arterial pressure similar to the Munich- Wistar (MW rats, mean glomerular capillary hydraulic pressure was lower in Calomys callosum due to a lower post glomerular resistance in this rodent when compared to MW rats. The mean glomerular plasma flow rate was relatively elevated when compared with single nephron glomerular filtration rate, which in turn blunted the lower intraglomerular hydraulic pressure, and thus increased the single nephron glomerular filtration rate per g/kidney. The present work suggests that despite of the technical difficulties imposed by the reduced size of the Calomys callosus, the study of the renal function and glomerular hemodynamics is possible, establishing therefore, a model for the study such renal function.

  13. Isolated Renal Hydatidosis Presenting as Renal Mass: A Diagnostic Dilemma

    Directory of Open Access Journals (Sweden)

    Datteswar Hota

    2015-07-01

    Full Text Available Hydatid disease is a parasitic infestation by larval form of Echinococcus granulosus. Isolated renal involvement is extremely rare. There are no specific signs and symptoms of renal hydatidosis. However it may present as palpable mass, flank pain, hematuria, malaise, fever, and hydatiduria or as a complication of it such as infection, abscess, hemorrhage, necrosis and pelviureteric junction obstruction, renal failure etc. Except hydatiduria, none are pathognomonic for renal hydatidosis. There is no literature on renal hydatidosis presenting as renal mass we report 2 cases of isolated renal hydatidosis, which mimicked a renal mass on imaging study.

  14. Distal renal tubular acidosis in recurrent renal stone formers

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    (1.1%) had complete distal renal tubular acidosis and 14 (15.5%) incomplete distal renal tubular acidosis. Our results confirm that distal renal tubular acidification defects are associated with a more severe form of stone disease and make distal renal tubular acidosis one of the most frequent...... metabolic disturbances in renal stone formers. Distal renal tubular acidosis (dRTA) was relatively more common in female stone formers and most often found in patients with bilateral stone disease (36%). Since prophylactic treatment in renal stone formers with renal acidification defects is available...

  15. Renal pelvis or ureter cancer

    Science.gov (United States)

    Transitional cell cancer of the renal pelvis or ureter; Kidney cancer - renal pelvis; Ureter cancer ... Cancer can grow in the urine collection system, but it is uncommon. Renal pelvis and ureter cancers ...

  16. Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule.

    Science.gov (United States)

    Christensen, E I; Birn, H

    2001-04-01

    The multiligand, endocytic receptors megalin and cubilin are colocalized in the renal proximal tubule. They are heavily expressed in the apical endocytic apparatus. Megalin is a 600-kDa transmembrane protein belonging to the low-density lipoprotein-receptor family. The cytoplasmic tail contains three NPXY motifs that mediate the clustering in coated pits and are possibly involved in signaling functions. Cubilin, also known as the intestinal intrinsic factor-cobalamin receptor, is a 460-kDa receptor with no transmembrane domain and no known signal for endocytosis. Because the two receptors bind each other with high affinity and colocalize in several tissues, it is highly conceivable that megalin mediates internalization of cubilin and its ligands. Both receptors are important for normal tubular reabsorption of proteins, including albumin. Among the proteins normally filtered in the glomeruli, cubilin has been shown to bind albumin, immunoglobulin light chains, and apolipoprotein A-I. The variety of filtered ligands identified for megalin include vitamin-binding proteins, hormones, enzymes, apolipoprotein H, albumin, and beta(2)- and alpha(1)-microglobulin. Loss of these proteins and vitamins in the urine of megalin-deficient mice illustrates the physiological importance of this receptor.

  17. Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

    Science.gov (United States)

    Hess, Christoph; Kemper, Claudia

    2016-08-16

    Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings.

  18. Complement, a target for therapy in inflammatory and degenerative diseases.

    Science.gov (United States)

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

  19. Protein ultrastructure and the nanoscience of complement activation.

    Science.gov (United States)

    Vorup-Jensen, Thomas; Boesen, Thomas

    2011-09-16

    The complement system constitutes an important barrier to infection of the human body. Over more than four decades structural properties of the proteins of the complement system have been investigated with X-ray crystallography, electron microscopy, small-angle scattering, and atomic force microscopy. Here, we review the accumulated evidence that the nm-scaled dimensions and conformational changes of these proteins support functions of the complement system with regard to tissue distribution, molecular crowding effects, avidity binding, and conformational regulation of complement activation. In the targeting of complement activation to the surfaces of nanoparticulate material, such as engineered nanoparticles or fragments of the microbial cell wall, these processes play intimately together. This way the complement system is an excellent example where nanoscience may serve to unravel the molecular biology of the immune response.

  20. PROTEIN ENGINEERING TO TARGET COMPLEMENT EVASION IN CANCER

    OpenAIRE

    Carter, Darrick; Lieber, André

    2013-01-01

    The complement system is composed of soluble factors in plasma that enhance or “complement” immune-mediated killing through innate and adaptive mechanisms. Activation of complement causes recruitment of immune cells; opsonization of coated cells; and direct killing of affected cells through a membrane attack complex (MAC). Tumor cells up-regulate complement inhibitory factors -one of several strategies to evade the immune system. In many cases as the tumor progresses, dramatic increases in co...

  1. The Complement of Normal Fuzzy Numbers: An Exposition

    Directory of Open Access Journals (Sweden)

    Mamoni Dhar

    2013-07-01

    Full Text Available In this article, our main intention is to revisit the existing definition of complementation of fuzzy sets and thereafter various theories associated with it are also commented on. The main contribution of this paper is to suggest a new definition of complementation of fuzzy sets on the basis of reference function. Some other results have also been introduced whenever possible by using this new definition of complementation.

  2. The Complement of Normal Fuzzy Numbers: An Exposition

    OpenAIRE

    Mamoni Dhar; Baruah, Hemanta K

    2013-01-01

    In this article, our main intention is to revisit the existing definition of complementation of fuzzy sets and thereafter various theories associated with it are also commented on. The main contribution of this paper is to suggest a new definition of complementation of fuzzy sets on the basis of reference function. Some other results have also been introduced whenever possible by using this new definition of complementation.

  3. Initiation and Regulation of Complement during Hemolytic Transfusion Reactions

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    Sean R. Stowell

    2012-01-01

    Full Text Available Hemolytic transfusion reactions represent one of the most common causes of transfusion-related mortality. Although many factors influence hemolytic transfusion reactions, complement activation represents one of the most common features associated with fatality. In this paper we will focus on the role of complement in initiating and regulating hemolytic transfusion reactions and will discuss potential strategies aimed at mitigating or favorably modulating complement during incompatible red blood cell transfusions.

  4. Complement component 5 promotes lethal thrombosis

    Science.gov (United States)

    Mizuno, Tomohiro; Yoshioka, Kengo; Mizuno, Masashi; Shimizu, Mie; Nagano, Fumihiko; Okuda, Tomoyuki; Tsuboi, Naotake; Maruyama, Shoichi; Nagamatsu, Tadashi; Imai, Masaki

    2017-01-01

    Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. PMID:28205538

  5. Altmetrics - a complement to conventional metrics.

    Science.gov (United States)

    Melero, Remedios

    2015-01-01

    Emerging metrics based on article-level does not exclude traditional metrics based on citations to the journal, but complements them. Both can be employed in conjunction to offer a richer picture of an article use from immediate to long terms. Article-level metrics (ALM) is the result of the aggregation of different data sources and the collection of content from multiple social network services. Sources used for the aggregation can be broken down into five categories: usage, captures, mentions, social media and citations. Data sources depend on the tool, but they include classic metrics indicators based on citations, academic social networks (Mendeley, CiteULike, Delicious) and social media (Facebook, Twitter, blogs, or Youtube, among others). Altmetrics is not synonymous with alternative metrics. Altmetrics are normally early available and allow to assess the social impact of scholarly outputs, almost at the real time. This paper overviews briefly the meaning of altmetrics and describes some of the existing tools used to apply this new metrics: Public Library of Science--Article-Level Metrics, Altmetric, Impactstory and Plum.

  6. Altmetrics – a complement to conventional metrics

    Science.gov (United States)

    Melero, Remedios

    2015-01-01

    Emerging metrics based on article-level does not exclude traditional metrics based on citations to the journal, but complements them. Both can be employed in conjunction to offer a richer picture of an article use from immediate to long terms. Article-level metrics (ALM) is the result of the aggregation of different data sources and the collection of content from multiple social network services. Sources used for the aggregation can be broken down into five categories: usage, captures, mentions, social media and citations. Data sources depend on the tool, but they include classic metrics indicators based on citations, academic social networks (Mendeley, CiteULike, Delicious) and social media (Facebook, Twitter, blogs, or Youtube, among others). Altmetrics is not synonymous with alternative metrics. Altmetrics are normally early available and allow to assess the social impact of scholarly outputs, almost at the real time. This paper overviews briefly the meaning of altmetrics and describes some of the existing tools used to apply this new metrics: Public Library of Science - Article-Level Metrics, Altmetric, Impactstory and Plum. PMID:26110028

  7. The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

    Directory of Open Access Journals (Sweden)

    Sean Shaw

    2009-12-01

    Full Text Available Soluble epoxide hydrolase inhibitors (sEHIs are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.

  8. Complement system in dermatological diseases – fire under the skin

    Directory of Open Access Journals (Sweden)

    Jaana Helena Panelius

    2015-01-01

    Full Text Available The complement system plays a key role in several dermatological diseases. Overactivation, deficiency or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex (MAC on epidermal or vascular cells can cause direct tissue damage and inflammation e.g. in SLE, phospholipid antibody syndrome and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g. hydralazine, procainamide could interact with C4A, C4B or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1 inhibitor and anti-C5 antibody, eculizumab that could alleviate symptoms in diseases associated with excessive complement activation.The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders.

  9. [Hemorrhagic bilateral renal angiomyolipoma].

    Science.gov (United States)

    Benjelloun, Mohamed; Rabii, Redouane; Mezzour, Mohamed Hicham; Joual, Abdenbi; Bennani, Saâd; el Mrini, Mohamed

    2003-09-01

    Renal angiomyolipoma is a rare benign tumour, often associated with congenital diseases especially de Bourneville's tuberous sclerosis. Bilateral angiomyolipoma is exceptional. The authors report a case of bilateral renal angiomyolipoma in a 33-year-old patient presenting with haemorrhagic shock. In the light of this case and a review of the literature, the authors discuss the diagnostic and therapeutic aspects of this disease.

  10. FARMACOFISIOLOGÍA RENAL

    Directory of Open Access Journals (Sweden)

    Musso CG

    2014-03-01

    Full Text Available Renal physiology plays a key role in the pharmacokinetics of many drugs. Knowledge of the particularities of each nephron function (filtration, secretion, reabsorption and excretion and each of renal tubular transport mechanisms (simple diffusion, facilitated diffusion, facilitated transport, active transport, endocytosis and pinocytosis is fundamental to achieve better management of drug prescriptions.

  11. Shock Wave Lithotripsy Does Not Impair Renal Function in a Swine Model of Metabolic Syndrome

    Science.gov (United States)

    Johnson, Cynthia D.; Connors, Bret A.; Evan, Andrew P.; Phillips, Carrie L.; Liu, Ziyue

    2015-01-01

    Abstract Purpose: To determine whether shock wave lithotripsy (SWL) may be a risk factor for renal functional impairment in a swine model of metabolic syndrome (MetS). Materials and Methods: Nine-month-old female Ossabaw pigs were fed an excess calorie atherogenic diet to induce MetS. At 15 months of age, the MetS pigs were treated with 2000 SWs or an overtreatment dose of 4000 SWs targeted at the upper pole calyx of the left kidney (24 kV at 120 SWs/min using the unmodified Dornier HM3 lithotripter; n=5–6 per treatment group). Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured in conscious pigs before and ∼60 days after SWL to provide a qualitative assessment of how well both kidneys were filtering (glomerular filtration rate [GFR]). Bilateral renal function was assessed at ∼65 days post-SWL in anesthetized pigs with GFR and effective renal plasma flow (ERPF) quantified by the renal clearance of inulin and para-amino hippurate, respectively. Results: Cr and BUN values were within normal limits before SWL and remained unchanged after lithotripsy in both the 2000 SW- and 4000 SW-treated pigs. GFR and ERPF of kidneys treated with SWL at either SW dose were similar to the contralateral nontreated kidney. Chronic histological changes in the SW-treated pole of the kidney included interstitial fibrosis, sclerotic glomeruli, and dilated and atrophic tubules. Conclusions: Our results are consistent with the view that a single SWL session does not result in renal impairment, even in the presence of MetS. PMID:25285417

  12. Diagnosis of Henoch-Schönlein purpura: renal or skin biopsy?

    Science.gov (United States)

    Davin, Jean-Claude; Weening, Jan J

    2003-12-01

    Henoch-Schönlein purpura (HSP) is a form of systemic vasculitis characterized by vascular wall deposits of predominantly IgA, typically involving small vessels in skin, gut, and glomeruli and associated with purpura, intestinal colic, hematuria, and arthralgia or arthritis. HSP nephritis leads to chronic renal failure in up to 20% of pediatric patients after 20 years of follow-up in selected series. The risk is related to the initial clinical presentation and is maximal (more than 50%) when initial signs are a combination of nephrotic and nephritic syndromes. Although less important, the risk persists for mild renal symptoms or when the patient has apparently completely recovered from the renal disease. Other types of non-IgA-related leukocytoclastic vasculitis may be difficult to discriminate from HSP, thus confounding the diagnosis. The clinical picture of HSP is often incomplete and renal signs can become manifest years after initial signs. When based on clinical signs only, the diagnosis of HSP can therefore be missed, and some patients risk developing silent chronic renal failure after decades without appropriate treatment. Patients can also be overdiagnosed as HSP and thus submitted to unnecessary follow-up. It is therefore important that HSP should be correctly diagnosed from the initial signs. As the finding of IgA deposits in vessel walls associated with the characteristic signs of small-vessel vasculitis is a sine qua non in the diagnosis, a skin biopsy should be performed for histological and immunofluorescence studies in cases of clinical suspicion of HSP. The systematic diagnostic use of a cutaneous biopsy should not only improve the follow-up of patients with HSP but will also allow a reliable epidemiological study of vasculitis in children and a better knowledge of the disease.

  13. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

    Directory of Open Access Journals (Sweden)

    Heleen Rienstra

    Full Text Available BACKGROUND: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. METHODS: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin and chondroitin sulfate proteoglycan (versican expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively expression were (semi- quantitatively analyzed using immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

  14. A Challenging Twist in Pulmonary Renal Syndrome

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    Rajaie Namas

    2014-01-01

    Full Text Available Case. We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. A 75-year-old African American woman with history of high blood pressure on hydralazine for 3 years presented with acute onset of shortness of breath and hemoptysis. Lab workup revealed a severe normocytic anemia and a serum creatinine of 5.09 mg/dL (baseline 0.9. Bronchoscopy demonstrated active pulmonary hemorrhage. A urine sample revealed red cell casts and a renal biopsy demonstrated pauci-immune, focally necrotizing glomerulonephritis with small crescents consistent with possible anti-neutrophil cytoplasmic antibody-positive renal vasculitis. Serologies showed high-titer MPO-ANCA and high-titer anti-histone antibodies. She was treated with intravenous steroids and subsequently with immunosuppression after cessation of hydralazine. The patient was subsequently discharged from hospital after a rapid clinical improvement. Conclusion. Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis is a rare adverse effect and can present as a severe vasculitic syndrome with multiple organ involvement. Features of this association include the presence of high titer of anti-myeloperoxidase anti-neutrophil cytoplasmic antibody with multiantigenicity, positive anti-histone antibodies, and the lack of immunoglobulin and complement deposition. Prompt cessation of hydralazine may be sufficient to reverse disease activity but immunosuppression may be needed.

  15. CD55 is a key complement regulatory protein that counteracts complement-mediated inactivation of Newcastle Disease Virus.

    Science.gov (United States)

    Rangaswamy, Udaya S; Cotter, Christopher R; Cheng, Xing; Jin, Hong; Chen, Zhongying

    2016-08-01

    Newcastle disease virus (NDV) is being developed as an oncolytic virus for virotherapy. In this study we analysed the regulation of complement-mediated inactivation of a recombinant NDV in different host cells. NDV grown in human cells was less sensitive to complement-mediated virus inactivation than NDV grown in embryonated chicken eggs. Additionally, NDV produced from HeLa-S3 cells is more resistant to complement than NDV from 293F cells, which correlated with higher expression and incorporation of complement regulatory proteins (CD46, CD55 and CD59) into virions from HeLa-S3 cells. Further analysis of the recombinant NDVs individually expressing the three CD molecules showed that CD55 is the most potent in counteracting complement-mediated virus inactivation. The results provide important information on selecting NDV manufacture substrate to mitigate complement-mediated virus inactivation.

  16. Primary renal hydatidosis

    Directory of Open Access Journals (Sweden)

    Johnsy Merla Joel

    2016-01-01

    Full Text Available Echinococcosis or hydatidosis caused by the tapeworm, Echinococcus granulosus, has the highest prevalence in endemic regions and sheep farming areas. The most common organ involved is the liver (50–75% followed by the lungs (15–20% and other organs (10–20%. Primary involvement of the kidney without the involvement of the liver and lungs, i.e., isolated renal hydatid disease is extremely rare even in endemic areas. The incidence of renal echinococcosis is 2–4%. Renal hydatid cysts usually remain asymptomatic for many years and are multiloculated. A 63-year-old male presented with left loin pain. Computed tomography scan abdomen revealed a presumptive diagnosis of renal hydatid disease. The nephrectomy specimen received in histopathology confirmed the diagnosis. We describe a rare case of primary renal hydatidosis.

  17. Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement.

    Science.gov (United States)

    Córdova-Sánchez, Bertha M; Mejía-Vilet, Juan M; Morales-Buenrostro, Luis E; Loyola-Rodríguez, Georgina; Uribe-Uribe, Norma O; Correa-Rotter, Ricardo

    2016-07-01

    Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20-7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75-37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03-2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01-1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01-22.1, p = 0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological

  18. High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

    Science.gov (United States)

    Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

    2015-11-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis.

  19. Keeping It All Going-Complement Meets Metabolism.

    Science.gov (United States)

    Kolev, Martin; Kemper, Claudia

    2017-01-01

    The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity-indicating that complement's function is likely broader than initially anticipated-the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond "classic" immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature-mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement's emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions. We will also

  20. Complement C3 in Bernese Mountain dogs.

    Science.gov (United States)

    Gerber, Bernhard; Eichenberger, Simone; Joller-Jemelka, Helen I; Wittenbrink, Max M; Reusch, Claudia E

    2010-06-01

    Previous research suggests that low serum concentrations of the third component of complement (C3) are associated with both the susceptibility to infectious agents such as Borrelia burgdorferi and the development of glomerular disease. We hypothesized that low levels of C3 are associated with the coincident occurrence of B. burgdorferi infection and glomerulonephritis in Bernese Mountain dogs. The aims of this study were to evaluate the serum concentration of C3 in Bernese Mountain dogs with and without antibodies against B. burgdorferi and to compare this concentration with that of healthy control dogs. Eighty-three clinically healthy Bernese Mountain dogs and 46 control dogs were included. Antibodies against B. burgdorferi were determined using an ELISA with a whole cell sonicate as antigen. Results were confirmed using Western blot. C3 was measured using a single radial immunodiffusion test. Results were reported as the percentage concentration of C3 compared with that in pooled preserved canine serum (100% C3 concentration). Median C3 concentration was 128.5% in Bernese Mountain dogs with antibodies against B. burgdorferi, 133.5% in B. burgdorferi-negative Bernese Mountain dogs, 87.8% in positive control dogs, and 102.2% in negative control dogs. Within Bernese Mountain and control groups, C3 was lower in dogs with antibodies against B. burgdorferi compared with those without. Percentage concentration of C3 was higher in healthy Bernese Mountain dogs compared with control dogs. Low C3 concentration is not an explanation for the high prevalence of B. burgdorferi infections and glomerular disease in Bernese Mountain dogs.

  1. APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo

    Science.gov (United States)

    Snyder, Elizabeth M.; McCarty, Christopher; Mehalow, Adrienne; Svenson, Karen L.; Murray, Stephen A.; Korstanje, Ron; Braun, Robert E.

    2017-01-01

    Editing of the human and murine ApoB mRNA by APOBEC1, the catalytic enzyme of the protein complex that catalyzes C-to-U RNA editing, creates an internal stop codon within the APOB coding sequence, generating two protein isoforms. It has been long held that APOBEC1-mediated editing activity is dependent on the RNA binding protein A1CF. The function of A1CF in adult tissues has not been reported because a previously reported null allele displays embryonic lethality. This work aimed to address the function of A1CF in adult mouse tissues using a conditional A1cf allele. Unexpectedly, A1cf-null mice were viable and fertile with modest defects in hematopoietic, immune, and metabolic parameters. C-to-U RNA editing was quantified for multiple targets, including ApoB, in the small intestine and liver. In all cases, no changes in RNA editing efficiency were observed. Blood plasma analysis demonstrated a male-specific increase in solute concentration and increased cellularity in the glomeruli of male A1cf-null mice. Urine analysis showed a reduction in solute concentration, suggesting abnormal water homeostasis and possible kidney abnormalities exclusive to the male. Computational identification of kidney C-to-U editing sites from polyadenylated RNA-sequencing identified a number of editing sites exclusive to the kidney. However, molecular analysis of kidney C-to-U editing showed no changes in editing efficiency with A1CF loss. Taken together, these observations demonstrate that A1CF does not act as the APOBEC1 complementation factor in vivo under normal physiological conditions and suggests new roles for A1CF, specifically within the male adult kidney. PMID:28069890

  2. APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo.

    Science.gov (United States)

    Snyder, Elizabeth M; McCarty, Christopher; Mehalow, Adrienne; Svenson, Karen L; Murray, Stephen A; Korstanje, Ron; Braun, Robert E

    2017-04-01

    Editing of the human and murine ApoB mRNA by APOBEC1, the catalytic enzyme of the protein complex that catalyzes C-to-U RNA editing, creates an internal stop codon within the APOB coding sequence, generating two protein isoforms. It has been long held that APOBEC1-mediated editing activity is dependent on the RNA binding protein A1CF. The function of A1CF in adult tissues has not been reported because a previously reported null allele displays embryonic lethality. This work aimed to address the function of A1CF in adult mouse tissues using a conditional A1cf allele. Unexpectedly, A1cf-null mice were viable and fertile with modest defects in hematopoietic, immune, and metabolic parameters. C-to-U RNA editing was quantified for multiple targets, including ApoB, in the small intestine and liver. In all cases, no changes in RNA editing efficiency were observed. Blood plasma analysis demonstrated a male-specific increase in solute concentration and increased cellularity in the glomeruli of male A1cf-null mice. Urine analysis showed a reduction in solute concentration, suggesting abnormal water homeostasis and possible kidney abnormalities exclusive to the male. Computational identification of kidney C-to-U editing sites from polyadenylated RNA-sequencing identified a number of editing sites exclusive to the kidney. However, molecular analysis of kidney C-to-U editing showed no changes in editing efficiency with A1CF loss. Taken together, these observations demonstrate that A1CF does not act as the APOBEC1 complementation factor in vivo under normal physiological conditions and suggests new roles for A1CF, specifically within the male adult kidney.

  3. Complement and membrane-bound complement regulatory proteins as biomarkers and therapeutic targets for autoimmune inflammatory disorders, RA and SLE.

    Science.gov (United States)

    Das, Nibhriti

    2015-11-01

    Complement system is a major effecter system of the innate immunity that bridges with adaptive immunity. The system consists of about 40 humoral and cell surface proteins that include zymogens, receptors and regulators. The zymogens get activated in a cascade fashion by antigen-antibody complex, antigen alone or by polymannans, respectively, by the classical, alternative and mannose binding lectin (MBL) pathways. The ongoing research on complement regulators and complement receptors suggest key role of these proteins in the initiation, regulation and effecter mechanisms of the innate and adaptive immunity. Although, the complement system provides the first line of defence against the invading pathogens, its aberrant uncontrolled activation causes extensive self tissue injury. A large number of humoral and cell surface complement regulatory protein keep the system well-regulated in healthy individuals. Complement profiling had brought important information on the pathophysiology of several infectious and chronic inflammatory disorders. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases that affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This brief review discusses on the complement system, its functions and its importance as biomarkers and therapeutic targets for autoimmune diseases with focus on SLE and RA.

  4. Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement

    DEFF Research Database (Denmark)

    Mortensen, Sofia; Kidmose, Rune Thomas; Petersen, Steen Vang;

    2015-01-01

    Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface...... for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details...

  5. [Renal histology in 44 patients with specific antibodies of soluble nuclear antigens].

    Science.gov (United States)

    Meyer, O; Gaudreau, A; Peltier, A P

    1980-10-01

    The authors studied the correlations between renal histology and specific antinuclear antibodies of soluble nuclear antigens (anti-Sm, anti-RNP, anti-protein) in 44 patients with such auto-antibodies. They were mostly patients with lupus erythematosus (35/44), more rarely mixed collagen disease or Sjögren's disease. The presence of any one of the specific antibodies of nuclear antigens is not associated with any special renal prognosis; thus the presence of anti-RNP does not mean that there are no histological renal lesions. The renal prognosis depends in fact on the presence of anti-ADN native antibodies. Among the other laboratory parameters (rheumatoid factors, complement levels, cryoglobulinemia) only hypocomplementemia seems to be associated with a poor renal prognosis, the presence of rheumatoid factor has perhaps a protective role.

  6. Renal replacement therapy after cardiac surgery; renal function recovers

    DEFF Research Database (Denmark)

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis

    2013-01-01

    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  7. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  8. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  9. Complement activation in leprosy: a retrospective study shows elevated circulating terminal complement complex in reactional leprosy.

    Science.gov (United States)

    Bahia El Idrissi, N; Hakobyan, S; Ramaglia, V; Geluk, A; Morgan, B Paul; Das, P Kumar; Baas, F

    2016-06-01

    Mycobacterium leprae infection gives rise to the immunologically and histopathologically classified spectrum of leprosy. At present, several tools for the stratification of patients are based on acquired immunity markers. However, the role of innate immunity, particularly the complement system, is largely unexplored. The present retrospective study was undertaken to explore whether the systemic levels of complement activation components and regulators can stratify leprosy patients, particularly in reference to the reactional state of the disease. Serum samples from two cohorts were analysed. The cohort from Bangladesh included multi-bacillary (MB) patients with (n = 12) or without (n = 46) reaction (R) at intake and endemic controls (n = 20). The cohort from Ethiopia included pauci-bacillary (PB) (n = 7) and MB (n = 23) patients without reaction and MB (n = 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P ≤ 0·01), C4d (P ≤ 0·05) and iC3b (P ≤ 0·05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P ≤ 0·001 without R; P < 0·05 with R) were also elevated in MB patients, irrespective of a reaction. Similar analysis of the Ethiopian cohort confirmed that, irrespective of a reaction, serum TCC levels were increased significantly in patients with reactions compared to patients without reactions (P ≤ 0·05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions. © 2016 British Society for Immunology.

  10. Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy.

    Science.gov (United States)

    Wijkström, Julia; González-Quiroz, Marvin; Hernandez, Mario; Trujillo, Zulma; Hultenby, Kjell; Ring, Anneli; Söderberg, Magnus; Aragón, Aurora; Elinder, Carl-Gustaf; Wernerson, Annika

    2017-05-01

    fewer glomeruli. This study confirms the renal morphology of MeN: chronic glomerular and tubulointerstitial damage with glomerulosclerosis and chronic glomerular ischemia. Follow-up data show that eGFRs, on average, deteriorated. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Assessing reprogramming by chimera formation and tetraploid complementation.

    Science.gov (United States)

    Li, Xin; Xia, Bao-long; Li, Wei; Zhou, Qi

    2015-01-01

    Pluripotent stem cells can be evaluated by pluripotent markers expression, embryoid body aggregation, teratoma formation, chimera contribution and even more, tetraploid complementation. Whether iPS cells in general are functionally equivalent to normal ESCs is difficult to establish. Here, we present the detailed procedure for chimera formation and tetraploid complementation, the most stringent criterion, to assessing pluripotency.

  12. Complement in neuroinflammation : Studies in leprosy and Amyotrophic Lateral Sclerosis

    NARCIS (Netherlands)

    Bahia El Idrissi, N.

    2017-01-01

    The complement system is a part of the innate immunity, and plays an important role in host immunity and inflammation. We previously identified the terminal membrane attack complex (MAC) of the complement system as a key determinant of neurodegeneration and demonstrated that its inhibition is neurop

  13. How antibodies use complement to regulate antibody responses.

    Science.gov (United States)

    Sörman, Anna; Zhang, Lu; Ding, Zhoujie; Heyman, Birgitta

    2014-10-01

    Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.

  14. Complementation of mutant phenotypes and genotypes of cultured mammalian cells

    NARCIS (Netherlands)

    A.J.R. de Jonge

    1985-01-01

    textabstractThis dissertation describes experiments aimed at the complementation of a genetic mutation in cultured mammalian cells in order to investigate several aspects of the structure and functioning of the human genome. Complementation is indicated by the correction of a biochemical function in

  15. Demand Heterogeneity and the Adoption of Platform Complements

    NARCIS (Netherlands)

    J. Rietveld (Joost); J.P. Eggers

    2016-01-01

    textabstractThis paper offers a demand-based theory of how platform maturity affects the adoption of platform complements. We argue that differences between early and late adopters of the platform include willingness to pay for the platform-and-complement bundle, risk preferences, preference for

  16. Demand Heterogeneity and the Adoption of Platform Complements

    NARCIS (Netherlands)

    J. Rietveld (Joost); J.P. Eggers

    2016-01-01

    textabstractThis paper offers a demand-based theory of how platform maturity affects the adoption of platform complements. We argue that differences between early and late adopters of the platform include willingness to pay for the platform-and-complement bundle, risk preferences, preference for nov

  17. Molecular interplay between bacteria and the terminal complement pathway

    NARCIS (Netherlands)

    Berends, E.T.M.

    2015-01-01

    The plasma proteins of the complement system fulfill important immune defense functions, including opsonization of bacteria for phagocytosis, generation of chemo-attractants and direct bacterial killing via assembly of the Membrane Attack Complex (MAC or C5b-9 complex). The terminal complement pathw

  18. Complement inhibitors to treat IgM-mediated autoimmune hemolysis.

    Science.gov (United States)

    Wouters, Diana; Zeerleder, Sacha

    2015-11-01

    Complement activation in autoimmune hemolytic anemia may exacerbate extravascular hemolysis and may occasionally result in intravascular hemolysis. IgM autoantibodies as characteristically found in cold autoantibody autoimmune hemolytic anemia, in cold agglutinin disease but also in a considerable percentage of patients with warm autoantibodies are very likely to activate complement in vivo. Therapy of IgM-mediated autoimmune hemolytic anemia mainly aims to decrease autoantibody production. However, most of these treatments require time to become effective and will not stop immediate ongoing complement-mediated hemolysis nor prevent hemolysis of transfused red blood cells. Therefore pharmacological inhibition of the complement system might be a suitable approach to halt or at least attenuate ongoing hemolysis and improve the recovery of red blood cell transfusion in autoimmune hemolytic anemia. In recent years, several complement inhibitors have become available in the clinic, some of them with proven efficacy in autoimmune hemolytic anemia. In the present review, we give a short introduction on the pathogenesis of autoimmune hemolytic anemia, followed by an overview on the complement system with a special focus on its regulation. Finally, we will discuss complement inhibitors with regard to their potential efficacy to halt or attenuate hemolysis in complement-mediated autoimmune hemolytic anemia.

  19. Production of Infinitival Complements by Children with Specific Language Impairment

    Science.gov (United States)

    Arndt, Karen Barako; Schuele, C. Melanie

    2012-01-01

    The purpose of this study was to explore the production of infinitival complements by children with specific language impairment (SLI) as compared with mean length of utterance (MLU)-matched children in an effort to clarify inconsistencies in the literature. Spontaneous language samples were analysed for infinitival complements (reduced…

  20. The emerging role of complement inhibitors in transplantation.

    Science.gov (United States)

    Frémeaux-Bacchi, Véronique; Legendre, Christophe M

    2015-11-01

    The role of complement in the biology of kidney transplantation is becoming more and more significant, especially but not only because we now have access to drugs inhibiting complement. After describing the main characteristics of complement biology, both activation of the complement cascade and the many regulatory factors, we will review the precise role of complement in kidney transplant biology. Complement activation has been involved in ischemia-reperfusion injury, in the recurrence of several diseases such as atypical hemolytic uremic syndrome, C3 glomerulopathies, and antiphospholipid syndrome, as well as the process of antibody-mediated rejection, either acute or chronic. There are many potentially interesting drugs interfering with complement inhibition that have been or may be studied in kidney transplantation. Currently, the bulk of data concerns eculizumab, a monoclonal antibody blocking the complement cascade at the C5. Its efficacy has been demonstrated in the treatment and prevention of recurrence of atypical hemolytic uremic syndrome with an overall good safety profile. Although it has been reported to be efficacious to prevent antibody-mediated rejection, properly designed trials are currently being performed to state this efficacy. In addition, randomized trials are, in the process, regarding the prevention of ischemia-reperfusion injury after kidney transplantation.

  1. Molecular interplay between bacteria and the terminal complement pathway

    NARCIS (Netherlands)

    Berends, E.T.M.

    2015-01-01

    The plasma proteins of the complement system fulfill important immune defense functions, including opsonization of bacteria for phagocytosis, generation of chemo-attractants and direct bacterial killing via assembly of the Membrane Attack Complex (MAC or C5b-9 complex). The terminal complement

  2. Schur complements of matrices with acyclic bipartite graphs

    DEFF Research Database (Denmark)

    Britz, Thomas Johann; Olesky, D.D.; van den Driessche, P.

    2005-01-01

    Bipartite graphs are used to describe the generalized Schur complements of real matrices having nos quare submatrix with two or more nonzero diagonals. For any matrix A with this property, including any nearly reducible matrix, the sign pattern of each generalized Schur complement is shown to be ...

  3. Identification of a central role for complement in osteoarthritis.

    Science.gov (United States)

    Wang, Qian; Rozelle, Andrew L; Lepus, Christin M; Scanzello, Carla R; Song, Jason J; Larsen, D Meegan; Crish, James F; Bebek, Gurkan; Ritter, Susan Y; Lindstrom, Tamsin M; Hwang, Inyong; Wong, Heidi H; Punzi, Leonardo; Encarnacion, Angelo; Shamloo, Mehrdad; Goodman, Stuart B; Wyss-Coray, Tony; Goldring, Steven R; Banda, Nirmal K; Thurman, Joshua M; Gobezie, Reuben; Crow, Mary K; Holers, V Michael; Lee, David M; Robinson, William H

    2011-11-06

    Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'. Although low-grade inflammation is detected in osteoarthritis, its role is unclear. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis.

  4. Complement Attack against Aspergillus and Corresponding Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Cornelia Speth

    2012-01-01

    Full Text Available Invasive aspergillosis shows a high mortality rate particularly in immunocompromised patients. Perpetually increasing numbers of affected patients highlight the importance of a clearer understanding of interactions between innate immunity and fungi. Innate immunity is considered to be the most significant host defence against invasive fungal infections. Complement represents a crucial part of this first line defence and comprises direct effects against invading pathogens as well as bridging functions to other parts of the immune network. However, despite the potency of complement to attack foreign pathogens, the prevalence of invasive fungal infections is increasing. Two possible reasons may explain that phenomenon: First, complement activation might be insufficient for an effective antifungal defence in risk patients (due to, e.g., low complement levels, poor recognition of fungal surface, or missing interplay with other immune elements in immunocompromised patients. On the other hand, fungi may have developed evasion strategies to avoid recognition and/or eradication by complement. In this review, we summarize the most important interactions between Aspergillus and the complement system. We describe the various ways of complement activation by Aspergillus and the antifungal effects of the system, and also show proven and probable mechanisms of Aspergillus for complement evasion.

  5. Polysomnographic correlates of inflammatory complement components in young healthy males.

    Science.gov (United States)

    Hussain, M Ejaz; Golam Sarwar, Abu Hasnath M; Alam, Mohd Shoeb; Noohu, Majumi M; Zannat, Wassilatul; Pandi-Perumal, Seithikurippu R; Bahammam, Ahmed S; Manzar, Md Dilshad

    2016-01-01

    A growing body of evidence has delineated the predominant role of humoral mediators of inflammation in linking sleep with immunity. Nonetheless, characterization of the relationship between complement components with inflammatory functions and objective sleep measures has not been performed. In this study we investigated the relationships between objective measures of sleep and complement components with inflammatory functions. Thirty-six healthy male university students (age, 23.94±4.23 years; BMI, 23.44±2.67 kg/m(2)) completed the study. An RMS Quest 32 polysomnograph (PSG) was used for sleep recording. Non-fasting blood was collected before subjects went to bed on the second night in the sleep laboratory to estimate complement component 3 (C-3), complement component 4 (C-4), complement factor-H (Factor-H), C1-inhibitor (C1INH), complement factor I (CFI) and other inflammatory mediators, such as IL-6 and sICAM-1. Multiple linear regression analysis was used to assess the association between PSG sleep measures and inflammatory mediators. Higher values of C-3 and lower values of sICAM-1, C1INH, and CFI (adjusted model, R2=0.211, ppro-inflammatory complement components and decreased anti-inflammatory complement components.

  6. A vital role for complement in heart disease

    DEFF Research Database (Denmark)

    Lappegård, Knut T; Garred, Peter; Jonasson, Lena;

    2014-01-01

    Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors...

  7. Renal neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Brian R Lane

    2009-01-01

    Full Text Available Objectives: Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Materials and Methods: The clinicopathologic features of renal NETs diagnosed at a single institution were reviewed along with all reported cases in the worldwide literature. Results: Eighty renal NETs have been described, including nine from our institution. Differentiation between renal NETs and the more common renal neoplasms (renal cell carcinoma, transitional cell carcinoma can be difficult since clinical, radiographic, and histopathologic features overlap. Immunohistochemical staining for neuroendocrine markers, such as synaptophysin and chromogranin, can be particularly helpful in this regard. Renal carcinoids are typically slow-growing, may secrete hormones, and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. Nephrectomy can be curative for clinically localized NETs, but multimodality treatment is indicated for advanced disease. Conclusions: A spectrum of NETs can rarely occur in the kidney. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. Diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical neuroendocrine markers.

  8. Pregnancy and renal transplantation.

    Science.gov (United States)

    Başaran, O; Emiroğlu, R; Seçme, S; Moray, G; Haberal, M

    2004-01-01

    Ovarian dysfunction, anovulatory vaginal bleeding, amenorrhea, high prolactin levels, and loss of libido are the causes of infertility in women with chronic renal failure. After renal transplantation, endocrine function generally improves after recovery of renal function. In this study we retrospectively evaluated the prepregnancy and postdelivery renal function, outcome of gestation, as well as maternal and fetal complications for eight pregnancies in eight renal transplant recipients between November 1975 and March 2003 of 1095 among 1425. Eight planned pregnancies occurred at a mean of 3.6 years posttransplant. Spontaneous abortion occured in the first trimester in one case. One intrauterine growth retardation was observed with a full-term pregnancy; one intrauterine growth retardation and preterm delivery; one preeclampsia with preterm delivery and urinary tract infection; and one preeclampsia with preterm delivery and oligohydramnios. The mean gestation period was 35.5 +/- 3.0 weeks (31.2 to 38.0). Pregnancy had no negative impact on renal function during a 2-year follow-up. No significant proteinuria or acute rejection episodes were observed. Among the seven deliveries, no congenital anomaly was documented and no postpartum problems for the child and the mother were observed. Our study suggests that successful pregnancy is possible in renal transplant recipients. In cases with good graft function and absence of severe proteinuria or hypertension, pregnancy does not affect graft function or patient survival; however, fetal problems are encountered such as intrauterine growth retardation, low birth weight, and preeclampsia.

  9. Renal autotransplantation: current perspectives.

    Science.gov (United States)

    Stewart, B H; Banowsky, L H; Hewitt, C B; Straffon, R A

    1976-01-01

    Autotransplantation, with or without an extracorporeal renal operation, has been done 39 times in 37 patients. Indications for the procedure included severe ureteral injury in 4 patients, failed supravesical diversion in 2, renal carcinoma in a solitary kidney in 1, renovascular hypertension in 1 and donor arterial reconstruction before renal transplantation in 29. Success was obtained in all but 2 procedures, both of which involved previously operated kidneys with severe inflammation and adhesions involving the renal pelvis and pedicle. Based on our experience and a review of currently available literature we believe that renal autotransplantation and extracorporeal reconstruction can provide the best solution for patients with severe renovascular and ureteral disease not correctable by conventional operative techniques. The technique can be of particular value in removing centrally located tumors in solitary kidneys and in preparing donor kidneys with abnormal arteries for renal transplantation. The role of autotransplantation in the management of advanced renal trauma and calculus disease is less clear. A long-term comparison of patients treated by extracorporeal nephrolithotomy versus conventional lithotomy techniques will be necessary before a conclusion is reached in these disease categories.

  10. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  11. Eculizumab prevents recurrent antiphospholipid antibody syndrome and enables successful renal transplantation.

    Science.gov (United States)

    Lonze, B E; Zachary, A A; Magro, C M; Desai, N M; Orandi, B J; Dagher, N N; Singer, A L; Carter-Monroe, N; Nazarian, S M; Segev, D L; Streiff, M B; Montgomery, R A

    2014-02-01

    Renal transplantation in patients with antiphospholipid antibodies has historically proven challenging due to increased risk for thrombosis and allograft failure. This is especially true for patients with antiphospholipid antibody syndrome (APS) and its rare subtype, the catastrophic antiphospholipid antibody syndrome (CAPS). Since a critical mechanism of thrombosis in APS/CAPS is one mediated by complement activation, we hypothesized that preemptive treatment with the terminal complement inhibitor, eculizumab, would reduce the extent of vascular injury and thrombosis, enabling renal transplantation for patients in whom it would otherwise be contraindicated. Three patients with APS, two with a history of CAPS, were treated with continuous systemic anticoagulation together with eculizumab prior to and following live donor renal transplantation. Two patients were also sensitized to human leukocyte antigens (HLA) and required plasmapheresis for reduction of donor-specific antibodies. After follow-up ranging from 4 months to 4 years, all patients have functioning renal allografts. No systemic thrombotic events or early graft losses were observed. While the appropriate duration of treatment remains to be determined, this case series suggests that complement inhibitors such as eculizumab may prove to be effective in preventing the recurrence of APS after renal transplantation.

  12. Midterm renal functions following acute renal infarction

    Directory of Open Access Journals (Sweden)

    Sakir Ongun

    2015-10-01

    Full Text Available The aim of this study was to explore clinical features of renal infarction (RI that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA only, whereas patients with atrial fibrillation (AF or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8% with RI had atrial fibrillation (AF as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9% had elevated serum lactate dehydrogenase (LDH, 18 patients (78.2% had leukocytosis, and 16 patients (69.5% had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m2 at admission and increased to 82.3 ± 23.4 mL/min/1.73 m2 at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  13. Midterm renal functions following acute renal infarction.

    Science.gov (United States)

    Ongun, Sakir; Bozkurt, Ozan; Demir, Omer; Cimen, Sertac; Aslan, Guven

    2015-10-01

    The aim of this study was to explore clinical features of renal infarction (RI) that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT) and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA) only, whereas patients with atrial fibrillation (AF) or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR) referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD) formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8%) with RI had atrial fibrillation (AF) as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9%) had elevated serum lactate dehydrogenase (LDH), 18 patients (78.2%) had leukocytosis, and 16 patients (69.5%) had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m(2) at admission and increased to 82.3 ± 23.4 mL/min/1.73 m(2) at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  14. Physicochemical signatures of nanoparticle-dependent complement activation

    Science.gov (United States)

    Thomas, Dennis G.; Chikkagoudar, Satish; Heredia-Langner, Alejandro; Tardiff, Mark F.; Xu, Zhixiang; Hourcade, Dennis E.; Pham, Christine T. N.; Lanza, Gregory M.; Weinberger, Kilian Q.; Baker, Nathan A.

    2014-01-01

    Nanoparticles are potentially powerful therapeutic tools that have the capacity to target drug payloads and imaging agents. However, some nanoparticles can activate complement, a branch of the innate immune system, and cause adverse side-effects. Recently, we employed an in vitro hemolysis assay to measure the serum complement activity of perfluorocarbon nanoparticles that differed by size, surface charge, and surface chemistry, quantifying the nanoparticle-dependent complement activity using a metric called Residual Hemolytic Activity (RHA). In the present work, we have used a decision tree learning algorithm to derive the rules for estimating nanoparticle-dependent complement response based on the data generated from the hemolytic assay studies. Our results indicate that physicochemical properties of nanoparticles, namely, size, polydispersity index, zeta potential, and mole percentage of the active surface ligand of a nanoparticle, can serve as good descriptors for prediction of nanoparticle-dependent complement activation in the decision tree modeling framework.

  15. Complement C3 and High Risk of Venous Thromboembolism

    DEFF Research Database (Denmark)

    Nørgaard, Ina; Nielsen, Sune Fallgaard; Nordestgaard, Børge Grønne

    2016-01-01

    BACKGROUND: Complement activation may contribute to venous thromboembolism, including deep venous thrombosis and pulmonary embolism. We tested the hypothesis that high complement C3 concentrations are associated with high risk of venous thromboembolism in the general population. METHODS: We...... similar for deep venous thrombosis and pulmonary embolism separately. The multivariable-adjusted hazard ratio for venous thromboembolism for a 1-g/L increase in complement C3 was 2.43 (1.74-3.40). CONCLUSIONS: High concentrations of complement C3 were associated with high risk of venous thromboembolism...... included 80 517 individuals without venous thromboembolism from the Copenhagen General Population Study recruited in 2003-2012. Plasma complement C3 concentrations were measured at baseline, and venous thromboembolism (n = 1176) was ascertained through April 2013 in nationwide registries. No individuals...

  16. Complement system part I - molecular mechanisms of activation and regulation

    Directory of Open Access Journals (Sweden)

    Nicolas eMerle

    2015-06-01

    Full Text Available Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins and the membrane attack complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly we will discuss the development and benefits of therapies using complement inhibitors.

  17. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...... on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...... participate in intercellular bridging. Finally, current studies suggest that CR2 may also play a role in the determination of B-cell tolerance towards self-antigens and thereby hold the key to the previously observed correlation between deficiencies of the early complement components and autoimmune disease....

  18. Complement regulators in human disease: lessons from modern genetics.

    Science.gov (United States)

    K Liszewski, M; Atkinson, J P

    2015-03-01

    First identified in human serum in the late 19th century as a 'complement' to antibodies in mediating bacterial lysis, the complement system emerged more than a billion years ago probably as the first humoral immune system. The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function-altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating 'hyperinflammatory complement phenotypes'. To treat these 'complementopathies', a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. Additional therapeutic reagents are on the horizon.

  19. Protease-dependent mechanisms of complement evasion by bacterial pathogens.

    Science.gov (United States)

    Potempa, Michal; Potempa, Jan

    2012-09-01

    The human immune system has evolved a variety of mechanisms for the primary task of neutralizing and eliminating microbial intruders. As the first line of defense, the complement system is responsible for rapid recognition and opsonization of bacteria, presentation to phagocytes and bacterial cell killing by direct lysis. All successful human pathogens have mechanisms of circumventing the antibacterial activity of the complement system and escaping this stage of the immune response. One of the ways in which pathogens achieve this is the deployment of proteases. Based on the increasing number of recent publications in this area, it appears that proteolytic inactivation of the antibacterial activities of the complement system is a common strategy of avoiding targeting by this arm of host innate immune defense. In this review, we focus on those bacteria that deploy proteases capable of degrading complement system components into non-functional fragments, thus impairing complement-dependent antibacterial activity and facilitating pathogen survival inside the host.

  20. The Role of Complement in Antibody Therapy for Infectious Diseases.

    Science.gov (United States)

    Wibroe, Peter P; Helvig, Shen Y; Moein Moghimi, S

    2014-04-01

    The complement system is part of the innate immune system, eliciting central immunoregulatory functions. Detection of foreign surfaces is either achieved through complement-specific patternrecognition molecules or mediated by antigen recognition of antibodies. Immunoglobulin A (IgA), IgG, and IgM all have the potential to initiate a complement response, with the efficiency and response development closely related to the antibody isotype, multimeric state, and degree of glycosylation. A group of serum proteins constitutes the central effector functions of complement, thus allowing direct cell lysis, opsonization, and inflammation. These effector functions can be used in antibody therapies, especially against infectious diseases, as the target membranes lack complement regulatory proteins. The relative contribution of each function and the interplay with direct antibody-mediated clearance is not fully exploited, thus suggesting an option for further rational optimization of antibody therapies.

  1. Novel Evasion Mechanisms of the Classical Complement Pathway.

    Science.gov (United States)

    Garcia, Brandon L; Zwarthoff, Seline A; Rooijakkers, Suzan H M; Geisbrecht, Brian V

    2016-09-15

    Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules.

  2. The complement system in ischemia-reperfusion injuries.

    Science.gov (United States)

    Gorsuch, William B; Chrysanthou, Elvina; Schwaeble, Wilhelm J; Stahl, Gregory L

    2012-11-01

    Tissue injury and inflammation following ischemia and reperfusion of various organs have been recognized for many years. Many reviews have been written over the last several decades outlining the role of complement in ischemia/reperfusion injury. This short review provides a current state of the art knowledge on the complement pathways activated, complement components involved and a review of the clinical biologics/inhibitors used in the clinical setting of ischemia/reperfusion. This is not a complete review of the complement system in ischemia and reperfusion injury but will give the reader an updated view point of the field, potential clinical use of complement inhibitors, and the future studies needed to advance the field.

  3. Lactulose and renal failure.

    Science.gov (United States)

    Vogt, B; Frey, F J

    1997-01-01

    The introduction of lactulose as a new therapeutic agent for treatment of hepatic encephalopathy was a major breakthrough in this field. It was hypothesized that lactulose might prevent postoperative renal impairment after biliary surgery in patients with obstructive jaundice. The presumable mechanism purported was the diminished endotoxinemia by lactulose. Unfortunately, such a reno-protective effect has not been shown conclusively until now in clinical studies. In chronic renal failure lactulose is known to promote fecal excretion of water, sodium, potassium, amonium, urea, creatinine and protons. Thus, lactulose could be useful for the treatment of chronic renal failure. However, compliance to the therapy represents a major problem.

  4. Renal tubule cell repair following acute renal injury.

    Science.gov (United States)

    Humes, H D; Lake, E W; Liu, S

    1995-01-01

    Experimental data suggests the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent upon predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair and ischemic and nephrotoxic acute renal failure, and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes. In this regard, there is a prominent vasoconstrictor response of the renal vasculature during the postischemic period of developing acute renal failure. The intravenous administration of pharmacologic doses of atrial natriuretic factor (ANF) in the postischemic period have proven efficacious by altering renal vascular resistance, so that renal blood flow and glomerular filtration rate improve. ANF also appears to protect renal tubular epithelial integrity and holds significant promise as a therapeutic agent in acute renal failure. Of equal or greater promise are the therapeutic interventions targeting the proliferative reparative zone during the postischemic period. The exogenous administration of epidermal growth factor or insulin-like growth factor-1 in the postischemic period have effectively decreased the degree of renal insufficiency as measured by the peak serum creatinine and has hastened renal recovery as measured by the duration of time required to return the baseline serum creatinine values. A similarly efficacious role for hepatocyte growth factor has also been recently demonstrated.

  5. Systemic complement activation in age-related macular degeneration.

    Science.gov (United States)

    Scholl, Hendrik P N; Charbel Issa, Peter; Walier, Maja; Janzer, Stefanie; Pollok-Kopp, Beatrix; Börncke, Florian; Fritsche, Lars G; Chong, Ngaihang V; Fimmers, Rolf; Wienker, Thomas; Holz, Frank G; Weber, Bernhard H F; Oppermann, Martin

    2008-07-02

    Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (pAMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  6. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  7. Hemolytic plate assay for quantification of active human complement component C3 using methylamine-treated plasma as complement source

    DEFF Research Database (Denmark)

    Ploug, M; Jessen, T E; Welinder, K. G.

    1985-01-01

    A hemolytic plate assay specific for active human complement component C3 is described. The method is well suited for tracing active C3 during preparative purification or for screening of plasma samples. The assay is based on activation of the alternative pathway of complement by unmodified rabbi...

  8. Renal scintigraphy in veterinary medicine.

    Science.gov (United States)

    Tyson, Reid; Daniel, Gregory B

    2014-01-01

    Renal scintigraphy is performed commonly in dogs and cats and has been used in a variety of other species. In a 2012 survey of the members of the Society of Veterinary Nuclear Medicine, 95% of the respondents indicated they perform renal scintigraphy in their practice. Renal scintigraphy is primarily used to assess renal function and to evaluate postrenal obstruction. This article reviews how renal scintigraphy is used in veterinary medicine and describes the methods of analysis. Species variation is also discussed.

  9. Keeping It All Going—Complement Meets Metabolism

    Science.gov (United States)

    Kolev, Martin; Kemper, Claudia

    2017-01-01

    The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity—indicating that complement’s function is likely broader than initially anticipated—the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond “classic” immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature—mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement’s emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions

  10. USG assisted and USG guided percutaneous renal biopsy at Nepal Medical College Teaching Hospital: a three and half years study.

    Science.gov (United States)

    Tuladhar, A S; Shrestha, A; Pradhan, S; Manandhar, D N; Chhetri Poudyal, P K; Rijal, A; Poudel, P; Maskey, A; Bhoomi, K K

    2014-09-01

    A prospective study was carried out from 2009 to 2013 in the Department of Radiology and Imaging of Nepal Medical College and Teaching Hospital, Attarkhel, Jorpati, Kathmandu, Nepal, in which a total of 75 patients underwent percutaneous renal biopsy with a 16 or 18 gauge needles. This was done blindly by marking a site on the skin, or, whenever there was difficulty with the blind procedure, by direct real time USG guidance. In all cases, the marking in the skin was done by the radiologist and the biopsy was performed by the Nephrologist, with the aid of the radiologist in cases of real-time USG guided renal biopsy. This study was carried out to assess the safety and efficacy of the USG aided, and USG guided renal biopsy, to see for the types and severity of complications arising from renal biopsies to determine the optimal period of observation required after the procedure. All renal biopsies were performed after the patients were admitted to the hospital at least 1 day prior to the procedure. Coagulation profile was done in all patients prior to the procedure. All patients were kept under strict complete bed rest for 24 hours post procedure. The ages of the patients ranged between 14 years to 71 years, with 42 female and 33 male patients. A mean of 21.8 glomeruli was obtained in each specimen, with absent glomerular yield seen in only 3 patients. Minimal change disease was seen in 19 patients, being the most common histopathological diagnosis followed by a spectrum of others. The overall complication rate was 4% and all of these were self-limiting needing no other intervention, or management except for observation and bed rest. Late complications were not seen. Percutaneous renal biopsy with the help of USG is a safe and efficacious procedure with less chance of minor complications.

  11. Parenchymal injury in remnant-kidney model may be linked to apoptosis of renal cells mediated by nitric oxide.

    Science.gov (United States)

    Hruby, Zbigniew; Rosinski, Maciej; Tyran, Bronislaw

    2008-01-01

    The importance of apoptotic cell death in the pathogenesis of progressive renal sclerosis has been well established. While activity of vasorelaxant nitric oxide is conceivable in the remnant hyperfiltrating kidney and nitric oxide has been reported to cause apoptosis, we postulated that this mechanism of cell death may be operating in progressive renal fibrosis. The intensity of apoptosis in glomerular and tubular cells was assessed (light microscopy, TUNEL method) in the remnant-kidney model of progressive renal fibrosis in rats undergoing 5/6 nephrectomy. Numbers of apoptotic cells were correlated with expression of mRNA for inducible nitric oxide synthase (iNOS; RT-PCR in situ), generation of nitrite in renal tissue, an index of glomerulosclerosis, proteinuria and creatinine clearance. A control group of 5/6 nephrectomized rats received an iNOS inhibitor, L-NAME, in drinking water during the 4 weeks after nephrectomy. Number of apoptotic cells gradually increased in experimental rats both in glomeruli and tubules, until termination of the study 3 months after 5/6 nephrectomy. At 3 months postinduction, the intensity of tubular cell apoptosis was significantly correlated with creatinine clearance (p<0.05), while glomerular cell apoptosis was correlated with the index of glomerulosclerosis, also at 3 months (p<0.0025). Along with the apoptosis, the levels of iNOS mRNA for, and generation of, nitrite in renal tissue had risen until termination of the study. The generation of nitrites correlated with the number of apoptotic glomerular cells (p<0.025). Treatment with the iNOS inhibitor resulted in a significant reduction in number of apoptotic cells (p<0.01). Apoptotic depletion of renal tubular and glomerular cells linked to activity of iNOS may contribute to progression of chronic kidney tissue injury in the 5/6 nephrectomy model.

  12. Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway.

    Science.gov (United States)

    Huang, Junying; Chen, Zhiquan; Li, Jie; Chen, Qiuhong; Li, Jingyan; Gong, Wenyan; Huang, Jiani; Liu, Peiqing; Huang, Heqing

    2017-02-23

    Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The following findings were observed: (1) Expression of CK2α was upregulated in kidneys of db/db and KKAy diabetic mice; (2) Inhibition of CK2α kinase activity or knockdown of CK2α protein expression suppressed high glucose-induced expressions of FN and ICAM-1 in glomerular mesangial cells (GMCs); (3) Inhibition of CK2α kinase activity or knockdown of CK2α protein expression not only restrained IκB degradation, but also suppressed HG-induced nuclear accumulation, transcriptional activity and DNA binding activity of NF-κB in GMCs; (4) Treatment of TBB or CK2α RNAi adenovirus infection ameliorated renal fibrosis in diabetic animals; (5) Treatment of TBB or CK2α RNAi adenovirus infection suppressed IκB degradation and NF-κB nuclear accumulation in glomeruli of diabetic animals. This study indicates the essential role of CK2α in regulating the diabetic renal pathological process of inflammatory fibrosis via NF-κB pathway, and inhibition of CK2α may serve as a promising therapeutic strategy for diabetic nephropathy.

  13. Eruca sativa seeds possess antioxidant activity and exert a protective effect on mercuric chloride induced renal toxicity.

    Science.gov (United States)

    Sarwar Alam, M; Kaur, Gurpreet; Jabbar, Zoobi; Javed, Kaleem; Athar, Mohammad

    2007-06-01

    Mercuric chloride (HgCl(2)) is a well-known nephrotoxic agent. Increasing number of evidences suggest the role of oxidative stress in HgCl(2) induced nephrotoxicity. Eruca sativa is widely used in folklore medicines and has a good reputation as a remedy of renal ailments. In the present study, the antioxidant potential of ethanolic extract of E. sativa seeds was determined and its protective effect on HgCl(2) induced renal toxicity was investigated. The extract was found to possess a potent antioxidant effect, with a large amount of polyphenols and a high reducing ability. HPLC analysis of the extract revealed glucoerucin and flavonoids to be the major antioxidants present in it. E. sativa extract significantly scavenged several reactive oxygen species (ROS) and reactive nitrogen species (RNS). Feeding of the extract to rats afforded a significant protection against HgCl(2) induced renal toxicity. Subcutaneous administration of 4 mg/kg body weight HgCl(2) induced renal injury evident as a marked elevation in serum creatinine and blood urea nitrogen levels, and histopathological changes such as necrosis, oedema and congestion of stroma and glomeruli. Oxidative modulation of renal tissues following HgCl(2) exposure was evident from a significant elevation in lipid peroxidation and attenuation in glutathione (GSH) contents and activities of antioxidant enzymes viz., catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione reductase (GR). Oral administration of E. sativa extract to rats at a dose regimen: 50-200 mg/kg body weight for 7 days prior to HgCl(2) treatment significantly and dose dependently protected against alterations in all these diagnostic parameters. The data obtained in the present study suggests E. sativa seeds to possess a potent antioxidant and renal protective activity and preclude oxidative damage inflicted to the kidney.

  14. Primary renal synovial sarcoma

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    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  15. Renal protection in diabetes

    DEFF Research Database (Denmark)

    Parving, H H; Tarnow, L; Rossing, P

    1996-01-01

    BACKGROUND: The combination of diabetes and hypertension increases the chances of progressive renal disorder and, ultimately, renal failure. Roughly 40% of all diabetics, whether insulin-dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end......-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. Diabetic nephropathy is a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic...... nephropathy. The relationship between arterial blood pressure and diabetic nephropathy is a complex one, with diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. OVERVIEW: Calcium antagonists antagonize preglomerular vasoconstriction. Additional putative...

  16. Renal primitive neuroectodermal tumors.

    Science.gov (United States)

    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  17. Renal vein thrombosis

    Science.gov (United States)

    ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood clots Dehydration Nephrotic syndrome Pulmonary embolus Renal Tumor Review Date 5/19/2015 Updated by: Charles Silberberg, ...

  18. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie;

    2014-01-01

    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according......Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...

  19. Complete renal recovery from severe acute renal failure after thrombolysis of bilateral renal vein thrombosis.

    Science.gov (United States)

    Ramadoss, Suresh; Jones, Robert G; Foggensteiner, Lukas; Willis, Andrew P; Duddy, Martin J

    2012-10-01

    A previously healthy young man presented with acute renal failure due to extensive spontaneous deep vein thrombosis, including the inferior vena cava (IVC) and both renal veins. The patient was treated with selectively delivered thrombolytic therapy over a 7-day-period, which resulted in renal vein patency and complete recovery of renal function. A stent was placed over a segment stenosis of the IVC. No thrombophilic factors were identified. Bilateral renal vein thrombosis in young fit individuals is an unusual cause of acute renal failure. Thrombolytic therapy, even with delay, can completely restore renal function.

  20. Mechanism of alcohol-induced impairment in renal development: Could it be reduced by retinoic acid?

    Science.gov (United States)

    Gray, Stephen P; Cullen-McEwen, Luise A; Bertram, John F; Moritz, Karen M

    2012-09-01

    1. Prenatal alcohol exposure impairs kidney development, resulting in a reduced nephron number. However, the mechanism through which alcohol acts to disrupt renal development is largely unknown. Retinoic acid (RA) is critically involved in kidney development and it has been proposed that a diminished concentration of RA is a contributing factor to fetal alcohol syndrome. 2. In the present study we proposed that the ethanol-induced inhibition of ureteric branching morphogenesis and glomerular development in the cultured rat kidney would be ameliorated by coculture with exogenous RA and that examining the expression profile of key genes involved in the development of the kidney would provide insights into the potential molecular pathways involved. 3. Whole rat metanephroi cultured in the presence of exogenous RA (10-20 nmol/L) without ethanol appeared larger and had significantly more ureteric branch points, tips and glomeruli than metanephroi cultured in control media. Those cultured in the presence of ethanol alone (0.2%) had 20% fewer ureteric branch points, tips and glomeruli, which was ameliorated by coculture with retinoic acid. 4. Gene expression analysis identified changes in the expression of enzymes involved in the metabolism of alcohol in conjunction with changes in key regulators of kidney development, including cRET. 5. These results demonstrate that the teratogenic effects of alcohol in vitro on kidney development resulting in reduced ureteric branching morphogenesis and glomerular development can be ameliorated through coculture with RA. These results provide the foundation for future research into the mechanism through which alcohol acts to disrupt kidney development.

  1. OBSTETRIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    Rajeshwari

    2015-11-01

    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  2. Renal papillary necrosis

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    Stephen A. Geller

    2013-12-01

    Full Text Available In 1877, Dr. Nikolaus Friedreich (1825-1882; student of Virchow who became Professor of Pathology at Heidelberg and who also described Friedreich’s ataxia first described renal papillary necrosis (RPN in patients with prostatic hypertrophy and secondary hydronephrosis. Thereafter in 1937, Froboese and Günther emphasized the association of this entity with diabetes mellitus. These authors also observed renal papillary necrosis in cases of urinary tract obstruction even in the absence of diabetes mellitus.

  3. [Hyperuricemia and renal risk].

    Science.gov (United States)

    Viazzi, Francesca; Bonino, Barbara; Ratto, Elena; Desideri, Giovambattista; Pontremoli, Roberto

    2015-01-01

    Recent studies have revealed an association between elevated levels of uric acid and conditions correlated to chronic kidney diseases such as hypertension, cardiovascular and cerebral disease, insulin resistance. Several pathogenetic mechanisms at cellular and tissue levels could justify a direct correlation between serum uric acid levels and renal damage. Growing evidence indicating a correlation between urate lowering therapy and renal morbidity could encourage the use of urate lowering therapy in primary or secondary prevention in chronic kidney disease.

  4. Complement in Pancreatic Disease—Perpetrator or Savior?

    Science.gov (United States)

    Bettac, Lucas; Denk, Stephanie; Seufferlein, Thomas; Huber-Lang, Markus

    2017-01-01

    The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation. Beyond that, the extent of pancreas–complement interaction covers complex pro- and anti-inflammatory mechanisms, which to this day remain to be fully elucidated. This review provides a comprehensive overview of the pathophysiological role of complement in diseases of the exocrine pancreas, based on existing experimental and clinical data. Participation of complement in acute and chronic pancreatitis is addressed, as well as its role in tumor immunology. Therapeutic strategies targeting complement in these diseases have long been proposed but have not yet arrived in the clinical setting. PMID:28144242

  5. Complement factor B expression profile in a spontaneous uveitis model.

    Science.gov (United States)

    Zipplies, Johanna K; Kirschfink, Michael; Amann, Barbara; Hauck, Stefanie M; Stangassinger, Manfred; Deeg, Cornelia A

    2010-12-01

    Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation.

  6. Complement activation promotes muscle inflammation during modified muscle use

    Science.gov (United States)

    Frenette, J.; Cai, B.; Tidball, J. G.

    2000-01-01

    Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

  7. Complement in different stages of HIV infection and pathogenesis.

    Science.gov (United States)

    Speth, Cornelia; Stoiber, Heribert; Dierich, Manfred P

    2003-04-01

    The complement system is one of the most important weapons of innate immunity and is involved in all infectious processes. It is not only a mechanism for direct protection against an invading pathogen but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defence cascade in the body. One of the greatest challenges for the complement system is infection by HIV with its chronic course and sequential destruction of immune cells and immune organs. Due to its dual role as direct effector and as fine tuner of adaptive immunity, we focussed on complement in this review and analysed in detail the contribution of complement to the antiviral defence and to HIV pathogenesis on the one hand and the complement evasion strategies of the virus on the other hand. In the present review, this interplay between complement and the virus is illuminated for the three different stages of HIV pathogenesis and for events during therapy: (1) the acute infection process with the early events in mucosa and serum; (2) the asymptomatic stage with the complex interplay between complement-induced lysis and viral evasion strategies; (3) the symptomatic infection and AIDS stage with progressive destruction of the lymph nodes, opportunistic infections and development of neuropathogenesis, and (4) finally, during highly active antiretroviral therapy and in vaccination approaches. Copyright 2003 S. Karger AG, Basel

  8. Review of Thrombotic Microangiopathy (TMA, and Post- Renal Transplant TMA

    Directory of Open Access Journals (Sweden)

    Ardalan Mohammad

    2006-01-01

    Full Text Available Thrombotic microangiopathy (TMA is a rare but devastating disorder; it involves small vessels and is characterized by intravascular thrombi of aggregated platelets leading to thrombocytopenia and variable degrees of organ ischemia and anemia, which is due to erythrocyte fragmentation in microcirculation. Childhood cases with predominant renal involvement are referred as the hemolytic uremic syndrome (HUS, and adults with major central neurological involvement are labeled as thrombotic thrombocytopenia purpura (TTP. Endothelial damage due to toxins and/or lack of defense against complement activation have a central role. Recent discovery of the von Willebrand Factor cleaving protease (ADAMTS 13 has offered new insight into the pathogenesis of TMA. TMA is also a well-recognized serious complication of renal transplantation. Clinical features of intravascular hemolysis are not always found. It may occur as de novo or recurrent and the majority of de novo cases are related to cyclosporin therapy. Viral infections, severe renal ischemia and acute vascular rejection are less frequent causes. Recurrence is negligible in diarrhea-associated HUS in childhood, but non-diarrheal HUS recurs in majority of adults following renal transplantation. Renal transplantation is contraindicated in familial/relapsing recurrent forms of HUS.

  9. Laparoscopic Renal Cryoablation

    Science.gov (United States)

    Schiffman, Marc; Moshfegh, Amiel; Talenfeld, Adam; Del Pizzo, Joseph J.

    2014-01-01

    In light of evidence linking radical nephrectomy and consequent suboptimal renal function to adverse cardiovascular events and increased mortality, research into nephron-sparing techniques for renal masses widely expanded in the past two decades. The American Urological Association (AUA) guidelines now explicitly list partial nephrectomy as the standard of care for the management of T1a renal tumors. Because of the increasing utilization of cross-sectional imaging, up to 70% of newly detected renal masses are stage T1a, making them more amenable to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. Cryosurgery has emerged as a leading option for renal ablation, and compared with surgical techniques it offers benefits in preserving renal function with fewer complications, shorter hospitalization times, and allows for quicker convalescence. A mature dataset exists at this time, with intermediate and long-term follow-up data available. Cryosurgical recommendations as a first-line therapy are made at this time in limited populations, including elderly patients, patients with multiple comorbidities, and those with a solitary kidney. As more data emerge on oncologic efficacy, and technical experience and the technology continue to improve, the application of this modality will likely be extended in future treatment guidelines. PMID:24596441

  10. Neonatal renal vein thrombosis.

    Science.gov (United States)

    Brandão, Leonardo R; Simpson, Ewurabena A; Lau, Keith K

    2011-12-01

    Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for pediatric hematologists and nephrologists. The precise mechanism for the onset and propagation of renal thrombosis within the neonatal population is unclear, but there is suggestion that acquired and/or inherited thrombophilia traits may increase the risk for renal thromboembolic disease during the newborn period. This review summarizes the most recent studies of neonatal RVT, examining its most common features, the prevalence of acquired and inherited prothrombotic risk factors among these patients, and evaluates their short and long term renal and thrombotic outcomes as they may relate to these risk factors. Although there is some consensus regarding the management of neonatal RVT, the most recent antithrombotic therapy guidelines for the management of childhood thrombosis do not provide a risk-based algorithm for the acute management of RVT among newborns with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition associated with a high mortality rate, it is associated with significant morbidity due to renal impairment. Recent evidence to evaluate the effects of heparin-based anticoagulation and thrombolytic therapy on the long term renal function of these patients has yielded conflicting results. Long term cohort studies and randomized trials may be helpful to clarify the impact of acute versus prolonged antithrombotic therapy for reducing the morbidity that is associated with neonatal RVT.

  11. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

    OpenAIRE

    Zhi-xiang Yuan; Jingxin Mo; Guixian Zhao; Gang Shu; Hua-lin Fu; Wei Zhao

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...

  12. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  13. Complement-Mediated Glomerular Diseases: A Tale of 3 Pathways

    Directory of Open Access Journals (Sweden)

    Andrew S. Bomback

    2016-09-01

    Full Text Available A renewed interest in the role of complement in the pathogenesis of glomerular diseases has improved our understanding of their basic, underlying physiology. All 3 complement pathways—classical, lectin, and alternative—have been implicated in glomerular lesions both rare (e.g., dense deposit disease and common (e.g., IgA nephropathy. Here we review the basic function of these pathways and highlight, with a disease-specific focus, how activation can lead to glomerular injury. We end by exploring the promise of complement-targeted therapies as disease-specific interventions for glomerular diseases.

  14. Early intra-articular complement activation in ankle fractures

    DEFF Research Database (Denmark)

    Schmal, Hagen; Salzmann, Gian M; Niemeyer, Philipp;

    2014-01-01

    osteochondritis dissecans (OCD) of the ankle. All fractures needed external fixation during which joint effusions were collected. Fluid analysis was done by ELISA measuring aggrecan, bFGF, IL-1 β, IGF-1, and the complement components C3a, C5a, and C5b-9. The time periods between occurrence of fracture...... and OCD patients, bFGF, IGF-1, and all complement components were significantly higher concentrated in ankle joints with fractures (P Complement activation and inflammatory cell infiltration characterize the joint biology following acute ankle fractures....

  15. Staphylococcal Proteases Aid in Evasion of the Human Complement System

    DEFF Research Database (Denmark)

    Jusko, Monika; Potempa, Jan; Kantyka, Tomasz

    2014-01-01

    Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first...... lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component...

  16. Dysregulation of apoptosis: a possible mechanism leading to chronic progressive renal histological changes in lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To evakuate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes. Methods Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsies from 25 patients with type Ⅳ lupus nephritis (LN),12 patientswith lgA nephropathy lgAN, 4 patients with idiopathic easangnioproliferative lomerulonephritis(MsPGN) and 3 patients with acute poststreptococcal gornerulonephritis (APGN).Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults wes used as control. Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patiants. Results Compared to other proliferative glomerulonephritis and controls, the patients with lupus nephritis had lase apoptotic cells, a higher ratio of PCNA+cells/TdT+cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r=0.4983 (P=0.0132), r -0.8399 (P<0.001), r=0.6614 (,P=0.0033),respactively. P/T retios in the glomerulus and tubule had a positive correlation with 24-hour urinary protein,r=0.8554(P<0.001) and r=0.7134 (P=0.001); and a negative correlation with crsetinine clearance (Ccr), r=-0.4880(P=0.0133) and r=-0.7229(P=0.001),which in tubules positively correlated with serum creatinine (Scr), r=0.4107 (P=0.0414). Conclusions Apoptosis is reduced in proliferative lupus nephritis. Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renalhistopathological changes.

  17. Manifestation of renal disease in obesity: pathophysiology of obesity-related dysfunction of the kidney

    Directory of Open Access Journals (Sweden)

    John A D’Elia

    2009-11-01

    Full Text Available John A D’Elia, Bijan Roshan, Manish Maski, Larry A WeinrauchJoslin Diabetes Center, Renal Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston and Cambridge, MassachusettsAbstract: Albuminuria in individuals whose body mass index exceeds 40 kg/m2 is associated with the presence of large glomeruli, thickened basement membrane and epithelial cellular (podocyte distortion. Obstructive sleep apnea magnifies glomerular injury as well, probably through a vasoconstrictive mechanism. Insulin resistance from excess fatty acids is exacerbated by decreased secretion of high molecular weight adiponectin from adipose cells in the obese state. Adiponectin potentiates insulin in its post-receptor signaling resulting in glucose oxidation in mitochondria. Recent studies of podocyte physiology have concentrated on the structural and functional requirements that prevent glomerular albumin leakage. The architecture of the podocyte involves nephrin and podocin, proteins that cooperate to keep slit pores between foot processes competent to retain albumin. Insulin and adiponectin are necessary for high-energy phosphate generation. When fatty acids bind to albumin, the toxicity to proximal renal tubules is magnified. Albumin and fatty acids are elevated in urine of individuals with obesity related nephrotic syndrome. Fatty acid accumulation and resistin inhibit insulin and adiponectin. Study of cytokines produced by adipose tissue (adiponectin and leptin and macrophages (resistin has led to a better understanding of the relationship between weight and hypertension. Leptin, is presumably secreted after food intake to inhibit the midbrain/ hypothalamic appetite centers. Resistance to leptin results in excess signaling to hypothalamic sympathetics leading to hypertension. Demonstration of the existence of a cerebral receptor mutation provide evidence for a role in hypertension of a central nervous

  18. Accelerated renal disease is associated with the development of metabolic syndrome in a glucolipotoxic mouse model.

    Science.gov (United States)

    Martínez-García, Cristina; Izquierdo, Adriana; Velagapudi, Vidya; Vivas, Yurena; Velasco, Ismael; Campbell, Mark; Burling, Keith; Cava, Fernando; Ros, Manuel; Oresic, Matej; Vidal-Puig, Antonio; Medina-Gomez, Gema

    2012-09-01

    Individuals with metabolic syndrome are at high risk of developing chronic kidney disease (CKD) through unclear pathogenic mechanisms. Obesity and diabetes are known to induce glucolipotoxic effects in metabolically relevant organs. However, the pathogenic role of glucolipotoxicity in the aetiology of diabetic nephropathy is debated. We generated a murine model, the POKO mouse, obtained by crossing the peroxisome proliferator-activated receptor gamma 2 (PPARγ2) knockout (KO) mouse into a genetically obese ob/ob background. We have previously shown that the POKO mice showed: hyperphagia, insulin resistance, hyperglycaemia and dyslipidaemia as early as 4 weeks of age, and developed a complete loss of normal β-cell function by 16 weeks of age. Metabolic phenotyping of the POKO model has led to investigation of the structural and functional changes in the kidney and changes in blood pressure in these mice. Here we demonstrate that the POKO mouse is a model of renal disease that is accelerated by high levels of glucose and lipid accumulation. Similar to ob/ob mice, at 4 weeks of age these animals exhibited an increased urinary albumin:creatinine ratio and significantly increased blood pressure, but in contrast showed a significant increase in the renal hypertrophy index and an associated increase in p27(Kip1) expression compared with their obese littermates. Moreover, at 4 weeks of age POKO mice showed insulin resistance, an alteration of lipid metabolism and glomeruli damage associated with increased transforming growth factor beta (TGFβ) and parathyroid hormone-related protein (PTHrP) expression. At this age, levels of proinflammatory molecules, such as monocyte chemoattractant protein-1 (MCP-1), and fibrotic factors were also increased at the glomerular level compared with levels in ob/ob mice. At 12 weeks of age, renal damage was fully established. These data suggest an accelerated lesion through glucolipotoxic effects in the renal pathogenesis in POKO mice.

  19. Accelerated renal disease is associated with the development of metabolic syndrome in a glucolipotoxic mouse model

    Directory of Open Access Journals (Sweden)

    Cristina Martínez-García

    2012-09-01

    Individuals with metabolic syndrome are at high risk of developing chronic kidney disease (CKD through unclear pathogenic mechanisms. Obesity and diabetes are known to induce glucolipotoxic effects in metabolically relevant organs. However, the pathogenic role of glucolipotoxicity in the aetiology of diabetic nephropathy is debated. We generated a murine model, the POKO mouse, obtained by crossing the peroxisome proliferator-activated receptor gamma 2 (PPARγ2 knockout (KO mouse into a genetically obese ob/ob background. We have previously shown that the POKO mice showed: hyperphagia, insulin resistance, hyperglycaemia and dyslipidaemia as early as 4 weeks of age, and developed a complete loss of normal β-cell function by 16 weeks of age. Metabolic phenotyping of the POKO model has led to investigation of the structural and functional changes in the kidney and changes in blood pressure in these mice. Here we demonstrate that the POKO mouse is a model of renal disease that is accelerated by high levels of glucose and lipid accumulation. Similar to ob/ob mice, at 4 weeks of age these animals exhibited an increased urinary albumin:creatinine ratio and significantly increased blood pressure, but in contrast showed a significant increase in the renal hypertrophy index and an associated increase in p27Kip1 expression compared with their obese littermates. Moreover, at 4 weeks of age POKO mice showed insulin resistance, an alteration of lipid metabolism and glomeruli damage associated with increased transforming growth factor beta (TGFβ and parathyroid hormone-related protein (PTHrP expression. At this age, levels of proinflammatory molecules, such as monocyte chemoattractant protein-1 (MCP-1, and fibrotic factors were also increased at the glomerular level compared with levels in ob/ob mice. At 12 weeks of age, renal damage was fully established. These data suggest an accelerated lesion through glucolipotoxic effects in the renal pathogenesis in POKO mice.

  20. Relationship Between Type of Hypertension and Renal Arteriolosclerosis in Chronic Glomerular Disease

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    Keiji Kono

    2016-06-01

    Full Text Available Background/Aims: Hypertension (HT is a common complication in patients with chronic kidney disease (CKD. However, the relationship between circadian rhythm disorder of blood pressure (BP and intra-renal damage remains unclear. Methods: Ninety patients with chronic glomerular disease (CGD were included in the present study. On the basis of the clinic BP (CBP and 24 h-ambulatory BP (ABP measurements, the patients were divided into the following groups; normotension (NT, white coat HT (WHT, masked HT (MHT, and sustained HT (SHT. For renal histopathological assessment, we evaluated each biopsy specimen for sclerotic glomeruli (SG, interstitial fibrosis (IF, intimal thickening of intra-lobular arteries (ILA, and arteriolar hyalinosis (AH. Results: The prevalence of NT, WHT, MHT and SHT was 60.0%, 3.3%, 23.3%, and 13.4%, respectively. Compared with circadian BP pattern, all-day HT was most prevalent in the SHT group, whereas nighttime HT was most prevalent in the MHT group. The results of histological analysis showed that the SHT group had more severe SG and IF and the MHT group had more severe IF compared to the NT group. As for renal arteriolosclerosis, the MHT and SHT groups had more severe AH compared with the NT group, whereas ILA was comparable among all four groups. Furthermore, multivariate analysis revealed that ILA was significantly correlated only with age, whereas AH was significantly correlated with age and HT based on ABP, but not HT based on CBP. Conclusions: Our findings suggest that renal AH was severe not only in the SHT group, but also in the MHT group. Careful ABP monitoring should be recommended in patients with CGD.

  1. Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus.

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    Bancha Satirapoj

    Full Text Available Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated.Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114, microalbuminuria (n=100 and macroalbuminuria (n=114. The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy.Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77 ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29 ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19 ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63 ng/mgCr] (P<0.01.Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86, 0.99 (95%CI, 0.98 to 1.00 and 0.95 (95%CI, 0.91 to 0.98, respectively.The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.

  2. Renal mass dosing and graft function in children transplanted from pediatric donors.

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    de Petris, L; Faraggiana, Tullio; Rizzoni, Gianfranco

    2002-06-01

    It has been suggested that "renal mass dosing" may affect graft evolution. Between 1993 and 1999, 43 children, aged 4-17 years, received 43 pediatric cadaveric grafts. The ratio between graft volume (calculated by ultrasound within the first 24 h from transplantation, by ellipsoid formula) and the recipient's body surface area (BSA) ranged between 14.1 and 110 ml/m(2). Three groups were identified: group 1, 14-29 ml/m(2) (13 patients); group 2, 30-39 ml/m(2) (16 patients); group 3, 40-110 ml/m(2) (14 patients). As a consequence of the different renal volume increments in the three groups during the first year after transplant, no differences in the absolute renal volume were observed at the end of follow-up. The average follow-up was 38 months (range 12-80). In the 37 routine graft biopsies, performed on average 13 months after transplantation and with more than five glomeruli, maximum mean glomerular diameters were mostly above normal values. There were no significant differences among the three groups. At the end of follow-up, the three groups did not differ in microalbuminuria, proteinuria, glomerular function or in incidence of hypertension. From this retrospective study, we conclude that the very wide range of renal mass dosing did not cause differences in medium-term graft evolution. A longer follow-up will be necessary to ascertain the possible influence of disproportion between pediatric donors and recipients, on a long-term graft outcome.

  3. Renal allograft rejection: sonography and scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; Cohen, W.N.

    1980-07-01

    A total of 30 renal allograft patients who had sonographic B scanning and radionuclide studies of the transplant was studied as to whether: (1) the allograft rejection was associated with any consistent and reliable sonographic features and (2) the sonograms complemented the radionuclide studies. Focal areas of decreased parenchymal echogenicity were the most striking and consistent sonographic finding in chymal echogenicity were the most striking and consistens sonographic finding in allograft rejection. This was observed in most of the patients exhibiting moderate or severe rejection, but was frequently absent with mild rejection. Areas of decreased parenchymal echogenicity were not seen during episodes of acute tubular necrosis. Therefore, sonography showing zones of decreased parenchymal echogenicity was complementary to radionuclide studies in the diagnosis of allograft rejection versus acute tubular necrosis. Corticomedullary demarcation was difficult to interpret because of technical variables, and was inconsistently related to rejection in this series.

  4. Visualization of molecular interactions using bimolecular fluorescence complementation analysis: characteristics of protein fragment complementation.

    Science.gov (United States)

    Kerppola, Tom K

    2009-10-01

    Investigations of the molecular processes that sustain life must include studies of these processes in their normal cellular environment. The bimolecular fluorescence complementation (BiFC) assay provides an approach for the visualization of protein interactions and modifications in living cells. This assay is based on the facilitated association of complementary fragments of a fluorescent protein that are fused to interaction partners. Complex formation by the interaction partners tethers the fluorescent protein fragments in proximity to each other, which can facilitate their association. The BiFC assay enables sensitive visualization of protein complexes with high spatial resolution. The temporal resolution of BiFC analysis is limited by the time required for fluorophore formation, as well as the stabilization of complexes by association of the fluorescent protein fragments. Many modifications and enhancements to the BiFC assay have been developed. The multicolor BiFC assay enables simultaneous visualization of multiple protein complexes in the same cell, and can be used to investigate competition among mutually exclusive interaction partners for complex formation in cells. The ubiquitin-mediated fluorescence complementation (UbFC) assay enables visualization of covalent ubiquitin family peptide conjugation to substrate proteins in cells. The BiFC assay can also be used to visualize protein binding to specific chromatin domains, as well as other molecular scaffolds in cells. BiFC analysis therefore provides a powerful approach for the visualization of a variety of processes that affect molecular proximity in living cells. The visualization of macromolecular interactions and modifications is of great importance owing to the central roles of proteins, nucleic acids and other macromolecular complexes in the regulation of cellular functions. This tutorial review describes the BiFC assay, and discusses the advantages and disadvantages of this experimental approach

  5. Pathological spectrum of cytomegalovirus infection of renal allograft recipients-an autopsy study from north India.

    Science.gov (United States)

    Joshi, Kusum; Nada, Ritambhra; Radotra, Bishan Das; Jha, Vivekanand; Sakhuja, Vinay

    2004-07-01

    This is a retrospective study of autopsy material to highlight the histo-morphological changes in cytomegalovirus (CMV) infection amongst renal allograft recipients. Nineteen out of 80 patients (23.75%) autopsied during a seventeen-year period (1985-2001) had CMV infection. Pulmonary infection was present in 14 out of 19 cases of which four had isolated lung involvement. Likewise, there were two cases each of isolated oesophageal and renal involvement; one case with isolated colonic involvement. The other 10 cases had multi-organ involvement and the organs involved were kidneys (4), esophagus (6), stomach (1), colon (5), adrenals (3), pancreas (3), liver (1) and spleen (1). Pulmonary infection with CMV was associated with acute pneumonitis in 3 cases and lymphocytic interstitial pneumonitis in 9 instances. Four out of 6 cases had acute tubulo-interstitial nephritis induced by CMV and only two cases had no significant inflammatory response. Glomerular involvement in the form of CMV inclusions in the glomeruli was present in only one case. Gastrointestinal CMV infection (15) presented as acute necrotizing ulceration because of predominant endothelial involvement. Post transplant survival period varied from one month to three years, with majority (14) of the patients having survived for less than one year.

  6. Interstitial nephritis, acute renal failure in a patient with non-fulminant hepatitis A infection.

    Science.gov (United States)

    Vaboe, A L; Leh, S; Forslund, T

    2002-02-01

    This is the first report from Norway of a patient with interstitial nephritis and renal failure due to non-fulminant hepatitis A virus (HAV) infection. HAV infection was confirmed by positive anti-HAV IgM serology. All tests for other virus infections were negative. At admittance serum creatinine (s-Creat) and blood urea nitrogen (BUN) concentration were 539 microlmol/l and 32.6 mmol/l increasing the following days to 890 micromol/l and 39.9 mmol/l, respectively. Nine courses of hemodialysis had to be given. Kidney biopsy specimen showed interstitial edema, lymphocytic cell infiltration and acute tubular injury with normal glomeruli. Examination with immunohistochemistry was negative. In contrast to the findings associated with HBV and HCV infection in which glomerular disease is predominantly found, the HAV infection in our patient was associated with interstitial nephritis and acute tubular necrosis. The prognosis of the renal failure due to HAV infection was good although the recovery was substantially delayed.

  7. Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria

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    E.V. Seliverstova

    2015-04-01

    Full Text Available The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes, and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals.

  8. Development of a porcine renal extracellular matrix scaffold as a platform for kidney regeneration.

    Science.gov (United States)

    Choi, Seock Hwan; Chun, So Young; Chae, Seon Yeong; Kim, Jin Rae; Oh, Se Heang; Chung, Sung Kwang; Lee, Jin Ho; Song, Phil Hyun; Choi, Gyu-Seog; Kim, Tae-Hwan; Kwon, Tae Gyun

    2015-04-01

    Acellular scaffolds, possessing an intact three-dimensional extracellular matrix (ECM) architecture and biochemical components, are promising for regeneration of complex organs, such as the kidney. We have successfully developed a porcine renal acellular scaffold and analyzed its physical/biochemical characteristics, biocompatibility, and kidney reconstructive potential. Segmented porcine kidney cortexes were treated with either 1% (v/v) Triton X-100 (Triton) or sodium dodecyl sulfate (SDS). Scanning electron microscopy showed both treatments preserved native tissue architecture, including porosity and composition. Swelling behavior was higher in the Triton-treated compared with the SDS-treated scaffold. Maximum compressive strength was lower in the Triton-treated compared with the SDS-treated scaffold. Attenuated total reflective-infrared spectroscopy showed the presence of amide II (-NH) in both scaffolds. Furthermore, richer ECM protein and growth factor contents were observed in the Triton-treated compared with SDS-treated scaffold. Primary human kidney cell adherence, viability, and proliferation were enhanced on the Triton-treated scaffold compared with SDS-treated scaffold. Following murine in vivo implantation, tumorigenecity was absent for both scaffolds after 8 weeks and in the Triton-treated scaffold only, glomeruli-like structure formation and neovascularity were observed. We identified 1% Triton X-100 as a more suitable decellularizing agent for porcine renal ECM scaffolds prior to kidney regeneration.

  9. Cardiovascular and Renal Effects of High Salt Diet in GDNF+/- Mice with Low Nephron Number

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    Julia Schlote

    2013-09-01

    Full Text Available Aims: To test the suggested association of low nephron number and later development of renal and cardiovascular disease we investigated the effects of high sodium diet in heterozygous GDNF+/- mice. Methods: Aged wild type and GDNF+/- mice were grouped together according to high sodium (HS, 4% or low sodium (LS, 0.03% diet for 4 weeks. The heart, the aorta and the kidneys were processed for morphometric and stereological evaluations and TaqMan PCR. Results: On HS GDNF+/- mice showed significantly higher drinking volume and urine production than wt and mean arterial blood pressure tended to be higher. Heart weight was higher in GDNF+/- than in wt, but the difference was only significant for LS. HS significantly increased cardiac interstitial tissue in GDNF+/-, but not in wt. On LS GDNF+/- mice had significantly larger glomeruli than wt and HS led to an additional two fold increase of glomerular area compared to LS. On electron microscopy glomerular damage after HS was seen in GDNF+/-, but not in wt. Dietary salt intake modulated renal IL-10 gene expression in GDNF+/-. Conclusion: In the setting of 30% lower nephron number HS diet favoured maladaptive changes of the kidney as well as of the cardiovascular system.

  10. 肾组织石蜡切片直接免疫荧光染色方法的再改良%Further Improvement in Method of Direct Immunofluorescence Staining of Paraffin-embedded Renal Sections

    Institute of Scientific and Technical Information of China (English)

    郑爱萍; 熊祖应

    2012-01-01

    目的 探讨肾组织石蜡切片直接免疫荧光染色再改良的方法,以提高石蜡切片的诊断准确率.方法 选择2010年6-12月在北京大学深圳医院行肾组织活检确诊为肾小球疾病的患者44例,其中IgA肾病20例,狼疮性肾炎12例,膜性肾病12例.对其肾组织除常规冰冻切片直接免疫荧光染色外,对石蜡切片进行高温、高压修复和胃蛋白酶消化处理,再分别行免疫球蛋白( IgA、IgG、lgM)、补体(C3、C1q)、纤维蛋白(Fib)、HBsAg及HBcAg直接免疫荧光染色,比较石蜡与冰冻切片的直接免疫荧光染色结果.结果 冰冻切片:肾小球数1~12个,平均5个;石蜡切片:肾小球数7~30个,平均15个.20例IgA肾病、12例狼疮性肾炎、12例膜性肾病患者的肾组织行冰冻(IgA、IgG、IgM、C3、C1q、Fib、HbcAg和HbsAg)直接免疫荧光染色时在不同荧光强度中所占比例与行石蜡直接免疫荧光染色比较差异均无统计学意义(均P>0.05).结论 再改良的肾组织石蜡切片直接免疫荧光染色是冰冻切片失败时较好的补救手段.其石蜡切片组织结构更清晰,免疫复合物沉积部位较冰冻切片更易判断.%Objective To improve the method of direct immunofluorescence staining of paraffin-embedded renal sections,and to increase the diagnostic accuracy of paraffin sections. Methods Conventional frozen sections were processed for direct immunofluorescence staining in 44 patients (20 cases of IgA nephropathy,12 cases of lupus nephritis and 12 cases of membranous nephropa-thy) who underwent renal biopsy for diagnosis of glomerular disease in Shenzhen hospital of Peking university between June 2010 and December 2010. In addition,paraffin-embedded renal sections were exposed to high temperature,high pressure and pepsin,and were examined by direct immunofluorescence staining for immunoglobulins (IgA,IgG and IgM) .complement components (C3,Clq) ,fibrin (Fib), HBsAg and HBcAg. Results of immunofluorescence

  11. Glomerular C3d as a novel prognostic marker for renal vasculitis.

    Science.gov (United States)

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Guerrero, Carmen; Campos-Martin, Yolanda; García-Díaz, Eugenio; Mollejo, Manuela; Fernandez-Juarez, Gema

    2016-10-01

    Pauci-immune necrotizing crescentic glomerulonephritis is the histologic substrate of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Several studies in animal models have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis, but only small series have analyzed the prognostic implications of complement glomerular deposits. This study aimed to assess the clinical and prognostic implications of C3d- and C4d-positive glomerular staining in renal vasculitis. Eighty-five patients with a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis were included in the study. C3d and C4d were analyzed by immunohistochemical staining using a polyclonal antibody. The primary predictors were glomerular C3d- and C4d-positive staining. The primary end point was the cumulative percentage of patients who developed end-stage renal disease. Glomerular staining for C3d and C4d was observed in 42 (49.4%) of 85 biopsies and 38 (44.7%) of 85 biopsies, respectively. C3d-positive staining was associated with the severity of renal impairment and with a lower response rate to treatment (P=.003 and P=.04, respectively). Renal survival at 2 and 5 years was 60.9% and 51.8% in C3d-positive patients compared with 87.7% and 78.9% in C3d-negative patients (P=.04). C4d-positive staining did not show any impact in renal outcome. When adjusted by renal function and other histologic parameters, C3d staining remained as an independent predictor for renal survival (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7; P=.03). Therefore, this study demonstrates that C3d-positive glomerular staining is an independent risk factor for the development of end-stage renal disease in ANCA-associated renal vasculitis.

  12. Peptide Inhibitor of Complement C1 (PIC1 Rapidly Inhibits Complement Activation after Intravascular Injection in Rats.

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    Julia A Sharp

    Full Text Available The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1. In this study, we determined that the lead PIC1 variant demonstrates a salt-dependent binding to C1q, the initiator molecule of the classical pathway. Additionally, this peptide bound to the lectin pathway initiator molecule MBL as well as the ficolins H, M and L, suggesting a common mechanism of PIC1 inhibitory activity occurs via binding to the collagen-like tails of these collectin molecules. We further analyzed the effect of arginine and glutamic acid residue substitution on the complement inhibitory activity of our lead derivative in a hemolytic assay and found that the original sequence demonstrated superior inhibitory activity. To improve upon the solubility of the lead derivative, a pegylated, water soluble variant was developed, structurally characterized and demonstrated to inhibit complement activation in mouse plasma, as well as rat, non-human primate and human serum in vitro. After intravenous injection in rats, the pegylated derivative inhibited complement activation in the blood by 90% after 30 seconds, demonstrating extremely rapid function. Additionally, no adverse toxicological effects were observed in limited testing. Together these results show that PIC1 rapidly inhibits classical complement activation in vitro and in vivo and is functional for a variety of animal species, suggesting its utility in animal models of classical complement-mediated diseases.

  13. Atypical Hemolytic Uremic Syndrome Recurrence after Renal Transplantation

    Science.gov (United States)

    Bouatou, Yassine; Bacchi, Véronique Frémeaux; Villard, Jean; Moll, Solange; Martin, Pierre-Yves; Hadaya, Karine

    2015-01-01

    Abstract Risk for atypical hemolytic uremic syndrome (aHUS) recurrence after renal transplantation is low with an isolated membrane cofactor protein mutation (MCP). We report the case of a 32-year-old woman with a MCP who underwent kidney transplantation with a good evolution at 12 months. At 15 and 35 months, 2 episodes of thrombotic microangiopathy (TMA), after a miscarriage and a preeclampsia, were misinterpreted as triggered by tacrolimus. After each episode however serum creatinine returned to baseline. Five years after transplantation, she had a self-limited rhinosinusitis followed 3 weeks later by an oliguric renal failure. Her complement profile was normal. Graft biopsy showed C3 glomerulonephritis with no “humps” on electron microscopy. No significant renal function improvement followed methylprednisolone pulsing. A second biopsy showed severe acute TMA lesions with C3 glomerular deposits. Despite weekly eculizumab for 1 month, dialysis was resumed. A new workup identified the “at-risk” complement factor H haplotype. Thus, aHUS recurrence should be ruled out in aHUS patients considered at low recurrence risk when a TMA is found in graft biopsy. Prompt eculizumab therapy should be considered to avoid graft loss as aHUS recurrence can first present as a C3 glomerulonephritis. PMID:27500215

  14. Initial evidence demonstrating the association between the vascular status in surgically resected renal parenchymal pathology and sexual function.

    Science.gov (United States)

    Sejima, T; Iwamoto, H; Masago, T; Morizane, S; Yao, A; Umekita, Y; Honda, M; Takenaka, A

    2015-01-01

    Our goal is to evaluate the association between histopathology of glomerulosclerosis (GS) and atherosclerosis (AS) in the nephrectomized normal parenchyma together with patients' background, and erectile dysfunction (ED) of patients treated with radical nephrectomy (RN) for renal cell carcinoma (RCC). ED was assessed with the International Index of Erectile Function in 65 patients who were less than age 70 years at the time of questionnaire. Glomeruli status was assessed by the extent of global GS. AS was graded based on lumen occlusion and frequency of involvement. Patients' backgrounds included any comorbidities, post-RN renal insufficiency, tumor pathology, demographics and social status. The presence of diabetes mellitus and lack of a spouse were independent predictors for severe ED, whereas G0/1 AS was an independent predictor for mild/no ED. The extent of global GS was significantly lower in patients with mild/no ED than in other patients. Our study represents the first report identifying healthy arterial status in the renal parenchyma as a significant indicator of favorable erectile function and that the evaluation of AS severity is not a superior indicator of severe ED in the presence of comorbidities or social status among patients treated with RN.

  15. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D.

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis. PMID:26306443

  16. Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest

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    Brad E. Zacharia

    2009-01-01

    Full Text Available Out-of-hospital cardiac arrest (OHCA is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.

  17. The Complement-Fixation Test in Hepatic Coccidiosis of Rabbits

    Science.gov (United States)

    Rose, M. Elaine

    1961-01-01

    Antibodies to Eimeria stiedae were measured in rabbit serum by complement fixation. The titre rose to a maximum at about the 22nd day after infection, remained at this level for about 20 days and then declined. Antibodies were still detectable up to 160 days after infection. Evidence of past or present slight E. stiedae infection was found in clinically normal rabbits whose sera fixed complement with E. stiedae antigens. Challenge of rabbits which had recovered from a near-fatal infection had no effect upon the complement fixation titres of their sera. The serum of a rabbit which had been injected with alum-precipitated antigen fixed complement with E. stiedae antigens. However, the animal was still susceptible to a superimposed oral infection which had the effect of further increasing the serum titre. PMID:14493840

  18. Lessons learned from mice deficient in lectin complement pathway molecules

    DEFF Research Database (Denmark)

    Genster, Ninette; Takahashi, Minoru; Sekine, Hideharu

    2014-01-01

    in complement activation, pathogen infection, coagulation, host tissue injury and developmental biology have been revealed by in vivo investigations. This review provides an overview of the mice deficient in lectin pathway molecules and highlights some of the most important findings that have resulted from......The lectin pathway of the complement system is initiated when the pattern-recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11, bind to invading pathogens or damaged host cells. This leads to activation of MBL/ficolin/collectin-11 associated serine proteases (MASPs), which...... in turn activate downstream complement components, ultimately leading to elimination of the pathogen. Mice deficient in the key molecules of lectin pathway of complement have been generated in order to build knowledge of the molecular mechanisms of the lectin pathway in health and disease. Despite...

  19. The 'Complementality' Realities Between History and the Social ...

    African Journals Online (AJOL)

    The 'Complementality' Realities Between History and the Social Science. ... of society and process of change, which are the subject matter of history. ... nature of the relationship between History as a distinct discipline and the Social Sciences, ...

  20. Malignant renal tumors in children

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    Justin Scott Lee

    2015-05-01

    Full Text Available Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma.