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Sample records for rapidly progressive glomerulonephritis

  1. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628

    PubMed Central

    Ma, Frank Y.; Han, Yingjie; Nikolic-Paterson, David J.; Kolkhof, Peter; Tesch, Greg H.

    2015-01-01

    Background/Aim Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Methods Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Results Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). Conclusions The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases. PMID:26700873

  2. Pathological spectrums and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis.

    PubMed

    Chen, Shasha; Chen, Hao; Liu, Zhengzhao; Zhang, Haitao; Hu, Weixin; Tang, Zheng; Liu, Zhihong

    2015-04-01

    The objectives of the study were to investigate the pathological features and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis. One hundred and one cases of biopsy-proven severe LN with rapidly progressive glomerulonephritis (RPGN) were analyzed in this retrospective study. Another 200 severe LN patients without RPGN were randomly enrolled as a control group. Their clinicopathological data and long-term outcome were compared. There were 76 females and 25 males with an average age of 31.9 ± 14.2 years followed for a median period of 4 years. Compared with controls, patients with RPGN had shorter LN duration (p = 0.008), higher level of creatinine (p < 0.001), severe anemia (p = 0.037), heavier hematuria (p < 0.001), severe tubular injury parameters [NAG (p < 0.001), RBP (p < 0.001), C3 (p < 0.001)], higher scores of AI (p = 0.001) and CI (p = 0.004), higher proportions of glomerular sclerosis (0.033) and crescents (p < 0.001), severe tubulointerstitial lesions (p < 0.001) and interstitial inflammation (p < 0.001), lower rate of complete remission (33.9 vs 68.2 %) and higher rate of treatment failure (46.8 vs 7.9 %). The 3-, 5- and 10-year cumulative renal survival rates of RPGN and non-RPGN patients were 65.1 versus 53.9 versus 42.9 and 96.9 versus 94.9 versus 91.7 %, respectively. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for end-stage renal disease (ESRD) in severe LN with RPGN (p < 0.001). In conclusion, RPGN occurred in 3.6 % of LN and is associated with severe renal manifestations, serious sclerotic and crescentic glomeruli lesions, severe tubulointerstitial inflammation, atrophy and fibrosis, prominent leukocyte infiltration and worse treatment response. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for ESRD. 57.1 % of severe LN patients with RPGN might progress to

  3. [Glomerulonephritis].

    PubMed

    Floege, J; Bienert, A

    2013-07-01

    Glomerulonephritides represent a heterogenous group of diseases with different pathophysiology. A definitive diagnosis requires a renal biopsy. The differentiation between a primary or secondary glomerulonephritis is of major clinical relevance, because most secondary forms resolve once the primary cause is treated properly. Assessing the individual prognosis of a patient is of central importance in choosing the best therapeutic regimen. By optimizing the so-called supportive therapy with the control of blood pressure, reduction of proteinuria, cessation of smoking and dietary measures the loss of kidney function can often be slowed down or even stopped. The most common types of glomerulonephritis in Western Europe comprise IgA-nephropathy, membranous glomerulonephritis and rapidly progressive glomerulonephritis (RPGN).

  4. [Simultaneous presence of antibodies against the glomerular basement membrane and anti-myeloperoxidase antibodies in 2 patients with rapidly progressive glomerulonephritis].

    PubMed

    Díaz Rodríguez, C; Costero, O; Torre, A; De Alvaro, F; Gil, F; Picazo, M L; Martínez-Ara, J

    2002-01-01

    We report two patients with rapidly progressive glomerulonephritis without alveolar hemorrhage. Renal biopsy showed extracapillary glomerulonephritis with linear deposits of immunoglobulin G. Serologically anti-glomerular basement membrane antibodies (Ac AMBG) and ANCA anti-myeloperoxidase were present. All patients were treated with steroids, cyclophosphamide and plasma exchange. One patient needed dialysis, and other one died from a renal biopsy complication. We discuss the epidemiologic, pathogenic and prognostic aspects of this association.

  5. [Rapidly progressive ANCA positive glomerulonephritis as the presenting feature of infectious endocarditis].

    PubMed

    Hanf, W; Serre, J-E; Salmon, J-H; Fabien, N; Ginon, I; Dijoud, F; Trolliet, P

    2011-12-01

    The association of positive cytoplasmic antineutrophil antibody (ANCA) necrotizing crescentic glomerulonephritis with endocarditis raises diagnostic issues. Indeed, it is often difficult to determine if the kidney injury is either secondary to an infectious disease or caused by an ANCA-associated small vessel vasculitis. We report a 59-year-old man admitted in nephrology for acute glomerular syndrome in whom the renal biopsy showed a crescentic necrotizing glomerulonephritis. A diagnosis of vasculitis was initially considered in the presence of high titer of ANCA (anti-proteinase 3). Because of associated Staphyloccocus aureus endocarditis the patient received both corticosteroids and antibiotics that allowed remission of both kidney injury and endocarditis. The renal presentation and the disappearance of ANCA support the infectious etiology of this glomerulonephritis rather than an ANCA-associated small vessel vasculitis. It is important to be cautious in the presence of ANCA positive extracapillary glomerulonephritis and endocarditis should be ruled out before initiation of corticosteroids that may be nevertheless necessary in severe acute glomerulonephritis.

  6. The successful treatment of rapidly progressive idiopathic membranoproliferative glomerulo-nephritis Type 1 in a 4-year-old male pediatric patient.

    PubMed

    Fujinaga, S; Ohtomo, Y; Hirano, D; Nishizaki, N; Someya, T; Ohtsuka, Y; Kaneko, K; Shimizu, T

    2010-10-01

    A multivariate analysis [4] revealed that the presence of crescent formation on initial biopsy irrespective of type of membranoproliferative glomerulonephritis (MPGN) was independently associated not only with end-stage renal disease but also with post-transplantation recurrence. In this study, we reported on a 4-year-old male pediatric patient requiring hemodialysis due to rapidly progressive idiopathic MPGN Type 1 with severe nephrotic syndrome and extensive cellular crescent formation on initial biopsy. The patient had been treated intravenously (i.v.) with 9 pulses of methylprednisolone, followed by daily prednisolone, resulting in the withdrawal of dialysis within 1 month. However, since active lesions in the second renal biopsy such as cellular crescents still remained and nephrotic range proteinuria had persisted for more than 2 months, the patient received additional 3 i.v. pulses of methylprednisolone, followed by combinations of alternate-day prednisolone, mizoribine, dipyridamole and warfarin, which lead to complete remission in a short-period of time. The patient has been off the combination therapy for 10 months because the third biopsy prior to the termination of this regimen showed decreased inflammatory activity. There is currently no established protocol for children with crescentic MPGN due to a rarity of its clinicopathological presentation. This case report indicates that early treatment with multiple pulses of methylprednisolone followed by the short-term combination therapy may be of benefit for children with rapidly progressive idiopathic MPGN Type 1, even when both diffuse crescentic changes and nephrotic syndrome are present at onset.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.; Shu, Huidy; Haman, Aissa; Sejvar, James J.; Miller, Bruce L.

    2009-01-01

    In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even days and be quickly fatal. Because many rapidly progressive dementias are treatable, it is paramount to evaluate and diagnose these patients quickly. This review summarizes recent advances in the understanding of the major categories of RPD and outlines efficient approaches to the diagnosis of the various neurodegenerative, toxic-metabolic, infectious, autoimmune, neoplastic, and other conditions that may progress rapidly. PMID:18668637

  11. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.

    2016-01-01

    Purpose of Review This article presents a practical and informative approach to the evaluation of a patient with a rapidly progressive dementia (RPD). Recent Findings Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Aside from prion diseases, the most common causes of RPD are atypical presentations of other neurodegenerative disorders, curable disorders including autoimmune encephalopathies, as well as some infections, and neoplasms. Numerous recent case reports suggest dural arterial venous fistulas sometimes cause RPDs. Summary RPDs, in which patients typically develop dementia over weeks to months, require an alternative differential than the slowly progressive dementias that occur over a few years. Because of their rapid decline, patients with RPDs necessitate urgent evaluation and often require an extensive workup, typically with multiple tests being sent or performed concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often the first diagnosis many neurologists consider when treating a patient with rapid cognitive decline. Many conditions other than prion disease, however, including numerous reversible or curable conditions, can present as an RPD. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis. PMID:27042906

  12. Deficiency of growth factor midkine exacerbates necrotizing glomerular injuries in progressive glomerulonephritis.

    PubMed

    Kojima, Hiroshi; Kosugi, Tomoki; Sato, Waichi; Sato, Yuka; Maeda, Kayaho; Kato, Noritoshi; Kato, Kiyonari; Inaba, Shinichiro; Ishimoto, Takuji; Tsuboi, Naotake; Matsuo, Seiichi; Maruyama, Shoichi; Yuzawa, Yukio; Kadomatsu, Kenji

    2013-02-01

    Inflammatory cell infiltration and fibrin deposition play important roles in the development of crescentic glomerulonephritis (GN). In particular, activation of coagulation is an indispensable factor in crescent formation. However, the mechanisms underlying the pathogenesis of crescent formation have not been completely elucidated. We identified the growth factor midkine (MK) as a novel key molecule in the progression of crescentic GN induced by anti-glomerular basement membrane antibody. Despite the lack of significant differences in autologous and heterologous reactions, MK-deficient (Mdk(-/-)) mice unexpectedly showed a greater number of necrotizing glomerular injuries than wild-type (Mdk(+/+)) mice. Likewise, more tubulointerstitial damage was observed in Mdk(-/-) mice, and this damage positively correlated with glomerular injury. Plasminogen activator inhibitor (PAI)-1 was strongly induced in the injured glomerulus of Mdk(-/-) mice, particularly in crescents and endothelial cells. This enhanced PAI-1 production was associated with an increase in inflammatory cell infiltration and matrix deposition in the glomerulus and the interstitium of Mdk(-/-) mice. In line with these in vivo data, primary cultured endothelial cells derived from Mdk(-/-) mice exhibited higher PAI-1 mRNA expression on fibrin challenge and less fibrinolysis than Mdk(+/+) mice. In contrast, the expression of plasminogen activators was not affected. Our combined data suggest that MK leads to a blockade of PAI-1, which is closely associated with the suppression of crescentic GN.

  13. Rapidly progressive silicon nephropathy.

    PubMed

    Bolton, W K; Suratt, P M; Strugill, B C

    1981-11-01

    Rapidly progressive renal failure developed in four patients with silica exposure. Three presented with manifestations of a connective tissue disorders. All had abnormal proteinuria, hypoalbuminemia and active urinary sediments. Histologically, a distinct constellation of findings was present, consisting of glomerular hypercellularity and sclerosis, crescents, interstitial cellular infiltrates and tubular necrosis with red cell casts as seen on light microscopy. On electron microscopy there was foot process obliteration, characteristic cytoplasmic dense lysosomes, microtubules and dense deposits. Despite vigorous treatment, two patients died of the systemic illness and one is on hemodialysis. The fourth is improved after pulse methylprednisolone therapy. We propose that silica induced this multisystem disease through activation of the immune system and a direct tissue toxic effect.

  14. Mesangial proliferative glomerulonephritis associated with progressive amyloid deposition in hamsters experimentally infected with Leishmania donovani.

    PubMed Central

    Oliveira, A. V.; Roque-Barreira, M. C.; Sartori, A.; Campos-Neto, A.; Rossi, M. A.

    1985-01-01

    In the present work, 42 golden hamsters (Mesocricetus auratus) were infected by intracardiac injection of 5 X 10(6) amastigote forms of Leishmania donovani. Another group of 28 animals served as uninfected controls. Six hamsters of the infected group and four hamsters of the control group were selected randomly and sacrificed at Days 7, 14, 21, 28, 35, 42, and 49 after inoculation. The kidneys were studied by light microscopy, immunofluorescence and electron microscopy. The levels of serum and urinary immunoglobulins were determined. None of the control hamsters had kidney lesions. Light-microscopically the kidneys of infected hamsters showed a marked mesangial proliferation from Day 7 after infection. These changes were more pronounced at Day 21, when a discrete infiltration of mononuclear cells was frequent. These glomerular changes diminished after Day 28 and were replaced by deposits of amyloid. In the beginning these deposits were in the mesangium and progressively became more extensive, involving capillary loops, Bowman's capsule, and interstitium. The immunofluorescence study showed L donovani antigens and hamster immunoglobulins, primarily in the mesangial areas, by Days 7-14 after infection. These deposits extended into contiguous loops from Day 21 to Day 28. In the last 2 weeks the fluorescent staining for L donovani antigens remained intensely positive, whereas the staining for hamster immunoglobulins became moderate to slightly positive. The ultrastructural study revealed mesangial proliferation, mesangial and paramesangial electron-dense deposits, and amyloidosis in the glomeruli of infected animals. The serum immunoglobulins increased from Day 7 after infection, reaching a peak at Day 21 and falling thereafter until Day 49 to near control values. Immunoglobulins were detected in the urine of infected hamsters at day 21, increasing in amount thereafter. Since L donovani antigens and immunoglobulins were identified in the glomerular lesions, it is

  15. Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative glomerulonephritis successfully treated with bortezomib

    PubMed Central

    Grundmann, Franziska; Witthus, Marco; Göbel, Heike; Kisner, Tuelay; Siewert, Rainer; Benzing, Thomas; Kurschat, Christine E.

    2013-01-01

    Extracapillary-proliferative glomerulonephritis is a rare complication of multiple myeloma. Partial remission of kidney involvement with cyclophosphamide therapy has previously been described. We report the case of a 60-year-old male patient diagnosed with rapidly progressive glomerulonephritis associated with IgG kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune extracapillary-proliferative glomerulonephritis without cryoglobulinaemia. Treatment with the proteasome inhibitor bortezomib induced rapid clinical and histological remission of his kidney disease. The patient's renal function remained stable on bortezomib maintenance therapy. Our findings suggest that bortezomib is a promising therapeutic approach to ameliorate severe kidney damage in monoclonal gammopathy- and myeloma-associated pauci-immune extracapillary-proliferative glomerulonephritis. PMID:24282629

  16. Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative glomerulonephritis successfully treated with bortezomib.

    PubMed

    Grundmann, Franziska; Witthus, Marco; Göbel, Heike; Kisner, Tuelay; Siewert, Rainer; Benzing, Thomas; Kurschat, Christine E

    2013-06-01

    Extracapillary-proliferative glomerulonephritis is a rare complication of multiple myeloma. Partial remission of kidney involvement with cyclophosphamide therapy has previously been described. We report the case of a 60-year-old male patient diagnosed with rapidly progressive glomerulonephritis associated with IgG kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune extracapillary-proliferative glomerulonephritis without cryoglobulinaemia. Treatment with the proteasome inhibitor bortezomib induced rapid clinical and histological remission of his kidney disease. The patient's renal function remained stable on bortezomib maintenance therapy. Our findings suggest that bortezomib is a promising therapeutic approach to ameliorate severe kidney damage in monoclonal gammopathy- and myeloma-associated pauci-immune extracapillary-proliferative glomerulonephritis.

  17. Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex-mediated acute lupus glomerulonephritis.

    PubMed

    Ge, Yan; Jiang, Chao; Sung, Sun-Sang J; Bagavant, Harini; Dai, Chao; Wang, Hongyang; Kannapell, Carol C; Cathro, Helen P; Gaskin, Felicia; Fu, Shu Man

    2013-10-21

    Cgnz1 and Agnz1 on the distal region of mouse chromosome 1 are associated with chronic glomerulonephritis (cGN) and acute GN (aGN). NZM2328.Lc1R27 (R27) was generated by introgressing a C57L/J region where Cgnz1 is located to NZM2328. R27 female mice developed aGN mediated by immune complex (IC) deposition and complement activation without progression to cGN with severe proteinuria. End stage renal disease (ESRD) was not seen in R27 mice as old as 15 mo. Thus, aGN and cGN are under separate genetic control, and IC-mediated proliferative GN need not progress to cGN and ESRD. NZM2328 and R27 female mice have comparable immune and inflammatory parameters. In contrast to NZM2328, R27 mice were resistant to sheep anti-mouse GBM serum-induced nephritis, supporting the hypothesis that aGN is mediated by autoimmunity and resistance to the development of cGN is mediated by end organ resistance to damage. Thus, autoimmunity should be considered distinct from end organ damage. The Cgnz1 region has been mapped to a 1.34 MB region with 45 genes. Nine candidate genes were identified. Clinical relevance of these observations is supported by case studies. Clinical implications and the significance to human lupus and other diseases are presented.

  18. Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

    PubMed

    Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

    2015-12-01

    The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. PMID:26634903

  19. Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

    PubMed

    Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

    2015-12-01

    The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules.

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

    PubMed Central

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

    2015-01-01

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

  1. [The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis (GN)].

    PubMed

    Idasiak-Piechocka, I; Krzymański, M

    1996-01-01

    In most cases of glomerulonephritis (GN) long-term course lead to chronic renal failure. The cause of inevitably gradually progress of GN to end-stage renal disease (ESRD) is unclear. The histological abnormalities seen in patients with progressive renal failure consist of focal and segmental glomerulosclerosis and tubulointerstitial nephritis. At present it is considered that tubulointerstitial changes attends almost all forms of progressive glomerular and vascular injury. It was known that chronic tubulointerstitial nephritis is characterized morphologically by tubular atrophy, interstitial fibrosis and interstitial inflammation of variable severity. The pathomechanism of this changes is complicated. Tubular ischaemia results from obliteration of peritubular capillaries, adaptation of tubular function with increased oxygen consumption and increased glomerular capillary permeability to macromolecules are reasons of chronic tubular damage. Injured tubules release growth factors and cytokines, which induce interstitial fibroblast proliferation, chemo-attraction and proliferation of infiltrating cells, and disruption of the balance between synthesis and degradation of cellular constituents. The consequences of these processes are tubular atrophy and interstitial fibrosis. Because of many studies concurred that tubulointerstitial changes determinant the progression of GN, tubular injury markers were searched for. Although over 50 enzymes were detected in human urine, only a few have been used for diagnosis in renal disease. The most widely used are lysosomal enzyme N acetyl-beta-D-glucosaminidase (NAG) and brush border enzymes alanine-aminopeptidase (AAP) and gamma-glutamyltransferase (GGT). tubular damage in hypertension, diabetes and in diagnostics of renal disease. AAP and GGT, brush border enzymes seem to be sensitive markers of renal injury too. Pathological value of GGT was observed even in the early stage of disease. Measurement of urinary excretion of low

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

    PubMed

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

    2016-06-01

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

  3. Progression of glomerulonephritis to end-stage kidney disease in a cat with nephrotic syndrome.

    PubMed

    Kamiie, Junichi; Haishima, Atsuko; Inoue, Kaoru; Ogihara, Kikumi; Ono, Mihoko; Yasuno, Kyohei; Kobayashi, Ryosuke; Aihara, Naoyuki; Ohmuro, Tamio; Shirota, Kinji

    2011-01-01

    A percutaneous renal biopsy was performed on a 3-year-old female Japanese domestic cat with pleural effusion, mild azotemia, hypoalbuminemia, hypercholesterolemia, and proteinuria. Glomerular lesions included mild diffuse hypercellularity and numerous capsular adhesions with segmental sclerosis/hyalinosis of glomerular tufts. Electron microscopy revealed many subendothelial dense deposits with characteristic outer protrusion of glomerular basement membrane. Diffuse and global granular deposits of IgG and C3 were detected along the capillary walls. Tubulo-interstitial changes were mild at the time of biopsy, but progression of the disease was predicted because of the many capsular adhesions of the glomerular tufts. The cat was fed a prescription diet without any other specific or symptomatic therapy after renal biopsy, and died 43 weeks after the biopsy. At necropsy, extensive tubulo-interstitial fibrosis and mononuclear cell infiltration had developed throughout the cortex and outer medulla, and most glomeruli had extensive global sclerosis or obsolescence with less prominent depositions of IgG and C3. PMID:20823662

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

    PubMed Central

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

    2015-01-01

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

  5. Diagnosis and treatment of rapidly progressive dementias

    PubMed Central

    Paterson, Ross W.; Takada, Leonel T.

    2012-01-01

    Summary Rapidly progressive dementias are conditions that typically cause dementia over weeks or months. They are a particular challenge to neurologists as the differential diagnosis often is different from the more typical, slowly progressive dementias. Early and accurate diagnosis is essential, as many of the etiologies are treatable. The information in this review is in part based on experience through our rapidly progressive dementia program at the University of California San Francisco, Memory and Aging Center. As treatment of a rapidly progressive dementia is entirely dependent on the diagnosis, we present a comprehensive, structured, but pragmatic approach to diagnosis, including key clinical, laboratory, and radiologic features. For the 2 most common causes of rapid dementia, treatment algorithms for the autoimmune encephalopathies and symptomatic management for the neurodegenerative causes are discussed. PMID:23634367

  6. Infective endocarditis mimics ANCA associated glomerulonephritis

    PubMed Central

    Reza Ardalan, Mohammad; Trillini, Matias

    2012-01-01

    Background: Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vessel vasculitis. Patients with SBE can also develop multiple serological abnormalities including ANCA. In this report, we present a case of infective endocarditis mimicked ANCA associated glomerulonephritis. Case presentation: A 57-year old male with a clinical picture of rapidly progressive renal failure (RPGN) and positive seology for PR3-ANCA (C-ANCA) was referred to our hospital. The renal histology findings were compatible with focal and segmental glomerular necrosis. After receiving corticosteroid therapy, the patient became febrile and his general condition worsened. Cardiac ultrasound echocardiographic study disclosed multiple large vegetations on the aortic valve. After appropriate antibiotic therapy and valvular surgery, the patient’s condition improved and his serum creatinine reached 1.7 mg/d. Conclusion: Misdiagnosis of SBE as ANCA-associated vasculitis and an inappropriate immunosuppressive therapy can have catastrophic consequences. PMID:24009921

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

    PubMed

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

    2016-01-01

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

  8. Rapidly Progressing Osteomyelitis of the Mandible

    PubMed Central

    Matsumoto, Ken; Okada, Shino; Takeuchi, Noritami; Yura, Yoshiaki

    2013-01-01

    Acute osteomyelitis exists as a refractory disease even now, which usually exhibits systemic symptoms such as fever or malaise and local redness or swelling. The present paper describes a case of acute osteomyelitis of the mandible that was rapidly progressing without typical symptoms. The patient had liver cirrhosis, which should be one of the systemic factors that affect immune surveillance and metabolism. Actinomycotic druses and filaments were detected from the sequestrum. These were considered to play a role in the rapid progression of osteomyelitis without typical symptoms. There has been no evidence of local recurrence 24 months after surgery. PMID:24349802

  9. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    PubMed Central

    Ayoob, Rose M.

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies. PMID:27642522

  10. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis.

    PubMed

    Ayoob, Rose M; Schwaderer, Andrew L

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies. PMID:27642522

  11. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    PubMed Central

    Ayoob, Rose M.

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  12. Rapid Progression of Coronary Atherosclerosis: A Review

    PubMed Central

    Shah, Priyank; Bajaj, Sharad; Virk, Hartaj; Bikkina, Mahesh; Shamoon, Fayez

    2015-01-01

    Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis. PMID:26823982

  13. The role of chemokines in glomerulonephritis.

    PubMed

    Wada, Takashi; Matsushima, Kouji; Kaneko, Shuichi

    2008-05-01

    Leukocyte infiltration to glomeruli plays an essential role in the pathogenesis of glomerulonephritis. Pathophysiological roles of chemokines and their cognate receptors have shed light on the detailed molecular mechanisms of leukocyte trafficking and activation both in clinical and experimental settings of glomerulonephritis. Infiltrating leukocytes and glomerular resident cells interact to promote and exacerbate glomerular injury, eventually leading to glomerulosclerosis. Further, recent studies on chemokines have expanded their universe beyond leukocyte migration to glomeruli, to include homeostasis, development and protection of resident cells in glomeruli. New insights into proteinuria have been uncovered by the regulation of chemokine system. The intervention of chemokines and their cognate receptors may have therapeutic potential to slow the progression of glomerulonephritis.

  14. The Evaluation of Rapidly Progressive Dementia

    PubMed Central

    Rosenbloom, Michael Henry; Atri, Alireza

    2012-01-01

    Background Rapidly progressive dementia (RPD) is a unique set of disorders resulting in cognitive, behavioral, and motor decline within 2 years. A variety of etiologies may contribute to RPD including neurodegenerative, inflammatory, infectious, and toxic-metabolic conditions. Jakob-Creutzfeldt disease (CJD) is frequently the most concerning diagnosis on the differential. The challenge for the neurologist is distinguishing prion disease from reversible processes that result in dementia. Review Summary This review discusses the clinical aspects and the diagnostic work-up of RPD. Particular focus is given to both CJD and the potentially treatable inflammatory conditions that may cause a similar presentation. Furthermore, a standardized step-wise approach is outlined for patients presenting with RPD. Conclusion Neurologists should adopt a standardized approach to the rapidly presenting disease processes that may mimic CJD in their clinical and radiological features. PMID:21364356

  15. Rapidly Progressive Spontaneous Spinal Epidural Abscess

    PubMed Central

    Aktas, Ozgür Yusuf; Guzey, Feyza Karagoz; Tufan, Azmi; Isler, Cihan; Aycan, Nur; Gulsen, İsmail

    2016-01-01

    Spinal epidural abscess (SEA) is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI) remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation. PMID:27688918

  16. Rapidly Progressive Spontaneous Spinal Epidural Abscess.

    PubMed

    Aycan, Abdurrahman; Aktas, Ozgür Yusuf; Guzey, Feyza Karagoz; Tufan, Azmi; Isler, Cihan; Aycan, Nur; Gulsen, İsmail; Arslan, Harun

    2016-01-01

    Spinal epidural abscess (SEA) is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI) remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation. PMID:27688918

  17. Rapidly Progressive Spontaneous Spinal Epidural Abscess

    PubMed Central

    Aktas, Ozgür Yusuf; Guzey, Feyza Karagoz; Tufan, Azmi; Isler, Cihan; Aycan, Nur; Gulsen, İsmail

    2016-01-01

    Spinal epidural abscess (SEA) is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI) remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation.

  18. [Glomerulonephritis in dogs and cats].

    PubMed

    Reinacher, M; Frese, K

    1991-04-01

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

  19. [Primary glomerulonephritis in focus].

    PubMed

    Bourquin, Vincent; Ponte, Belén; Zellweger, Micheal; Levy, Marc; Moll, Solange

    2013-04-10

    The glomerulonephritis (GN) are responsible for a significant amount of end stage renal disease. They may be secondary to another disease or idiopathic. When a secondary etiology has been excluded, it is called primary glomerulonephritis (PGN). Glomerular damage may have different presentations and there are many way to classify them. It is thus difficult for the non-specialist to understand the terminology used. This article is a summary of the most frequently encountered PGN such as: IgA nephropathy, membranous GN, idiopathic nephrotic syndrome, extracapillary and membranoproliferative GN. A brief description is given for each one of the PGN including epidemiology, semiology, histology and a pathophysiology explanation. PMID:23659154

  20. Membranous glomerulonephritis: a morphometric study.

    PubMed

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

    2000-01-01

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

  1. Anti-neutrophil cytoplasmic antibody-associated Pauci-immune crescentic glomerulonephritis complicating Sjögren's syndrome.

    PubMed

    Wang, Wei-Jei; Wu, Hau-Shin; Chu, Tzong-Shinn

    2011-07-01

    Sjögren's syndrome is a chronic autoimmune disease, characterized by specific autoimmune antibodies anti-Ro and anti-La, and it can involve multiple organs, such as the kidneys, lungs, muscles, and nervous system. The most common renal complication of Sjögren's syndrome is tubulointerstitial nephritis, and glomerulonephritis is relatively uncommon. We report the case of an 86-year-old man presenting with recurrent fever, poor appetite, decreased salivary secretion, and body weight loss. Laboratory investigation revealed that serum creatinine was 4.2 mg/dL, proteinuria was 3+, and there was microscopic hematuria. Positive perinuclear anti-neutrophil cytoplasmic antibody, anti-Ro, and anti-La antibodies were detected. Renal biopsy showed crescentic glomerulonephritis with scanty immune complex deposition. The patient was diagnosed with primary Sjögren's syndrome complicated with rapidly progressive glomerulonephritis with positive anti-neutrophil cytoplasmic antibody. Unlike the patients of other case reports, our patient's renal function did not recover after immunosuppressant treatment, and he finally received long-term hemodialysis. Pauci-immune glomerulonephritis is a rare renal complication of Sjögren's syndrome, and progress to renal failure in such patients is possible.

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

    PubMed Central

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

    2013-01-01

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

  3. Familial Glomerulonephritis in Doberman Pinscher Dogs

    PubMed Central

    Wilcock, B. P; Patterson, J. M.

    1979-01-01

    Progressive renal disease in 13 related Doberman pinscher dogs had the histological criteria of membranoproliferative glomerulonephritis. Polyuria, polydipsia and weight loss were the usual initial abnormalities and were observed at one year of age or less in seven of 11 dogs diagnosed antemortem as having renal disease. There was no sex predilection. All dogs were traced to a common male dog no more than four generations previously. ImagesFIGURE 1.FIGURE 2.FIGURE 3.FIGURE 4.FIGURE 5. PMID:498006

  4. Review of autoimmune (lupus-like) glomerulonephritis in murine models.

    PubMed

    Hicks, John; Bullard, Daniel C

    2006-01-01

    While murine models of autoimmune (lupus-like) glomerulonephritis have been available for sometime, it is only recently that immune and inflammatory mechanisms and molecular genetics have been extensively investigated. Genes involved in murine and human lupus nephritis have been discovered and provide insight into this disease process and provide avenues for molecular-targeted therapy. Immune modulation of murine nephritis has provided insight into novel therapy that may attenuate this disease or halt disease progression. With the advances in understanding the pathogenesis of lupus nephritis using translational research modalities, including electron microscopy, and molecular genetics, many "designer" therapies have become available for clinical use and for clinical investigational trials. This paper reviews autoimmune (lupus-like) glomerulonephritis in murine models, candidate genes involved in lupus nephritis, adhesion molecules implicated in murine lupus-like nephritis, immune modulation of murine lupus-like nephritis, and novel and potential therapy for immune complex glomerulonephritis.

  5. Comparative pathology of glomerulonephritis in animals.

    PubMed

    Slauson, D O; Lewis, R M

    1979-03-01

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

  6. Rapidly progressive sacroiliitis in a patient with lymphocytic lymphoma.

    PubMed Central

    Cohen, M R; Carrera, G E; Lundberg, J

    1993-01-01

    Rheumatological manifestations may develop as paraneoplastic syndromes in patients with malignancy. Sacroiliitis and spondyloarthropathy have not, however, been previously associated with cancer. The case is described of a patient with a stage IV diffuse well differentiated lymphocytic lymphoma who developed concomitant sacroiliitis and enthesopathies with rapid progression following the diagnosis of malignancy. Images PMID:8484681

  7. Transient hyporeninemic hypoaldosteronism in acute glomerulonephritis.

    PubMed

    Watanabe, Toru; Nitta, Koju

    2002-11-01

    While hyporeninemic hypoaldosteronism (HH) has been well described in relation to chronic renal diseases, transient HH has rarely been reported. Here we present a 9-year-old boy with acute glomerulonephritis who developed hyperkalemia, which persisted for a period of 3 weeks despite normal values of creatinine clearance and an absence of acidosis. He was diagnosed as having HH because of low basal plasma renin activity and serum aldosterone level. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis. There were no apparent pathological changes in the juxtaglomerular apparatus (JGA). Rapid adrenocorticotropic hormone administration increased adequately both serum aldosterone and cortisol levels. Responses of both plasma renin activity and serum aldosterone level following the furosemide upright provocation were blunted in the hyperkalemic acute phase, but recovered in the normokalemic convalescent phase. Serum levels of human atrial natriuretic peptide were within normal range, both in the hyperkalemic and normokalemic phases. These results suggested that a transient dysfunction of the JGA, without volume expansion or structural damage of the JGA, caused HH in this patient.

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

    PubMed

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

    2015-06-01

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

  9. Dual anti-neutrophil cytoplasmic antibody-related pauci-immune crescentic glomerulonephritis in a patient with Sjögren's syndrome.

    PubMed

    Lee, In Hee; Kim, Seong-Kyu; Kim, Min-Kyung

    2016-09-01

    Sjögren's syndrome is an autoimmune disease that primarily affects exocrine glands. Renal involvement of Sjögren's syndrome may lead to tubulointerstitial disease, whereas secondary glomerulopathies such as anti-neutrophil cytoplasmic antibody (ANCA)-related pauci-immune crescentic glomerulonephritis are rarely observed. In addition, crescent glomerulonephritis that is simultaneously positive for both myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA has never been reported in Sjögren's syndrome. Here, we report a case of pauci-immune crescentic glomerulonephritis exhibiting positivity for both MPO- and PR3-ANCAs in a patient with primary Sjögren's syndrome. A 71-year-old female was hospitalized for cough, blood-tinged sputum, and dyspnea two weeks after diagnosis with Sjögren's syndrome. On admission, serum anti-nuclear antibody, anti-Ro/SS-A antibody, MPO-ANCA, and PR3-ANCA were all positive, and serum blood urea nitrogen and creatinine (Cr) levels were 42.7 and 2.9 mg/dL, respectively. On the seventh day of hospitalization, the patient's serum Cr level was 5.7 mg/dL, indicating rapidly progressive glomerulonephritis. Renal biopsy resulted in the diagnosis of ANCA-related pauci-immune crescentic glomerulonephritis, for which intravenous methylprednisolone (7 mg/kg/day) was administered for three consecutive days, followed by combination therapy with oral prednisolone (1 mg/kg/day) and intravenous cyclophosphamide (500 mg/m(2)). The patient was positive in the Schirmer's I test, and a salivary gland biopsy showed sialadenitis with lympho-plasmacytic infiltrations. On day 28 of hospitalization, the patient was discharged after amelioration of respiratory symptoms and azotemia. At 6 months after discharge, the patient continued to receive appropriate daily medications and was negative for both MPO- and PR3-ANCAs, with a slight elevation in serum Cr levels. PMID:27384449

  10. Rapid progress on the vertebrate tree of life

    PubMed Central

    2010-01-01

    Background Among the greatest challenges for biology in the 21st century is inference of the tree of life. Interest in, and progress toward, this goal has increased dramatically with the growing availability of molecular sequence data. However, we have very little sense, for any major clade, of how much progress has been made in resolving a full tree of life and the scope of work that remains. A series of challenges stand in the way of completing this task but, at the most basic level, progress is limited by data: a limited fraction of the world's biodiversity has been incorporated into a phylogenetic analysis. More troubling is our poor understanding of what fraction of the tree of life is understood and how quickly research is adding to this knowledge. Here we measure the rate of progress on the tree of life for one clade of particular research interest, the vertebrates. Results Using an automated phylogenetic approach, we analyse all available molecular data for a large sample of vertebrate diversity, comprising nearly 12,000 species and 210,000 sequences. Our results indicate that progress has been rapid, increasing polynomially during the age of molecular systematics. It is also skewed, with birds and mammals receiving the most attention and marine organisms accumulating far fewer data and a slower rate of increase in phylogenetic resolution than terrestrial taxa. We analyse the contributors to this phylogenetic progress and make recommendations for future work. Conclusions Our analyses suggest that a large majority of the vertebrate tree of life will: (1) be resolved within the next few decades; (2) identify specific data collection strategies that may help to spur future progress; and (3) identify branches of the vertebrate tree of life in need of increased research effort. PMID:20211001

  11. When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia.

    PubMed

    Day, Gregory S; Tang-Wai, David F

    2014-01-01

    Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.

  12. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    PubMed

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging. PMID:26962957

  13. Glomerulonephritis secondary to Barmah Forest virus infection.

    PubMed

    Katz, I A; Hale, G E; Hudson, B J; Ibels, L S; Eckstein, R P; Dermott, P L

    1997-07-01

    Clinical infection with Barmah Forest virus (BFV) is becoming increasingly recognised with serological testing. We report the first case of glomerulonephritis after BFV infection. The patient required diuretic and antihypertensive therapy, but made an almost complete recovery. BFV infection should be considered in the differential diagnosis of glomerulonephritis. PMID:9236755

  14. Progress in rapid compaction of coal logs for freight pipelines

    SciTech Connect

    Gunnink, B.; Li, Wei

    1998-04-01

    The Capsule Pipeline Research Center (CPRC) at the University of Missouri-Columbia is devoted to performing research in capsule pipelines. Since its inception in 1991, the CPRC has focused on research related to the development and rapid commercialization of coal log pipeline technology. Coal log pipelines are freight pipelines that will transport compacted coal through a water filled pipeline. To fully develop this technology and make it ready for commercial use it is necessary to investigate means for fabricating coal logs. This paper describes research progress on the rapid compaction of coal logs for coal log pipeline transport. Economic studies conducted by the CPRC indicate that the cost of producing coal logs and thus the economic competitiveness of coal log pipelines is directly related to the compaction the necessary to make the coal logs. Previous research has demonstrated the ability to make laboratory scale coal logs with a 5 second compaction times. It was also observed that for rapidly compacted coal logs, coal log circulation performance (resistance to abrasion in a commercial pipeline) is maximized, if the logs are compacted from a coal mixture at an optimal moisture content. For the bituminous Mettiki coal that has been studied, this optimal moisture content is about 9%, if the compaction time is 5 seconds. The practical application of this is that if stockpiled coal is wetter than optimum, it would require drying of the coal to compact it at the optimum moisture content. Obviously, this would effect the cost of coal log fabrication.

  15. [Serodiagnosis of patients with glomerulonephritis].

    PubMed

    Sosunov, A V; Romanova, V I; Shishkin, A N; Lisin, V V

    1990-01-01

    A comprehensive clinical and morphologic examination of 160 nephrologic inpatients included titration of antibodies to respiratory viruses and to HBsAg and of streptolysin O. A correlation was detected between immunity status parameters and the presence and severity of proteinuria in the patients with chronic glomerulonephritis. Besides routine clinical and laboratory examinations, thorough serologic and virologic studies are necessary for this patient population, for such studies will help determine the trigger mechanism of the disease and thus predict the possible development of the condition.

  16. Pauci-immune crescentic glomerulonephritis in the Down's syndrome.

    PubMed

    Cherif, Mejda; Hedri, Hafedh; Ounissi, Mondher; Gergah, Taher; Goucha, Rim; Barbouch, Samia; Abderrahim, Ezzedine; Maiz, Hedi Ben; Kheder, Adel

    2013-11-01

    Kidney disease is a rare complication in patients with the Down's syndrome. However, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most cases have been reported as case reports and include lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, crescentic glomerulonephritis with anti-neutrophil cytoplasmic antibodies (ANCA), amyloidosis and immunotactoid glomerulopathy. We report the observation of a 38-year-old man with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria evolving over two months. There was no history of congenital heart disease or urinary symptoms. Percutaneous renal biopsy revealed fibrous crescents, rupture of Bowman's capsule and peri-glomerular granuloma; there were no deposits on immunofluorescence study. Thoracic computerized tomography scan showed alveolar congestion. The patient tested negative for ANCA. At the time of reporting, the patient is on regular chronic hemodialysis. Our case illustrates a distinct entity that further expands the spectrum of renal disease known to occur in the Down's syndrome. Early detection of the renal disorders may prevent or slow down the progression. PMID:24231490

  17. Pauci-immune crescentic glomerulonephritis in the Down's syndrome.

    PubMed

    Cherif, Mejda; Hedri, Hafedh; Ounissi, Mondher; Gergah, Taher; Goucha, Rim; Barbouch, Samia; Abderrahim, Ezzedine; Maiz, Hedi Ben; Kheder, Adel

    2013-11-01

    Kidney disease is a rare complication in patients with the Down's syndrome. However, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most cases have been reported as case reports and include lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, crescentic glomerulonephritis with anti-neutrophil cytoplasmic antibodies (ANCA), amyloidosis and immunotactoid glomerulopathy. We report the observation of a 38-year-old man with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria evolving over two months. There was no history of congenital heart disease or urinary symptoms. Percutaneous renal biopsy revealed fibrous crescents, rupture of Bowman's capsule and peri-glomerular granuloma; there were no deposits on immunofluorescence study. Thoracic computerized tomography scan showed alveolar congestion. The patient tested negative for ANCA. At the time of reporting, the patient is on regular chronic hemodialysis. Our case illustrates a distinct entity that further expands the spectrum of renal disease known to occur in the Down's syndrome. Early detection of the renal disorders may prevent or slow down the progression.

  18. Pathogenesis diagnosis and management of paraneoplastic glomerulonephritis

    PubMed Central

    Lien, Yeong-Hau H.; Lai, Li-Wen

    2011-01-01

    Paraneoplastic glomerulonephritis is a rare complication of malignancy that is frequently mistaken for idiopathic glomerulonephritis. Failure to recognize paraneoplastic glomerulonephritis can subject patients to ineffective and potentially harmful therapy. Pathology of paraneoplastic glomerulonephritis varies between different types of malignancies. This Review describes the association of glomerulonephritis with both solid tumors and hematological malignancies The pathogenetic mechanisms of many glomerular lesions seem to relate to altered immune responses in the presence of a malignancy Studies in the Buffalo/Mna rat model of spontaneous thymoma and nephrotic syndrome indicate that polarization of the immune response toward a T-helper-2 (TH2) profile has an important role in the development of thymoma-associated glomerular lesions. Furthermore, overexpression of the TH2 cytokine interleukin 13 in transgenic rats induces minimal change disease. Such findings from experimental studies might facilitate the identification of biomarkers that can distinguish paraneoplastic glomerulonephritis from idiopathic and other secondary glomerulonephritides. This Review describes potential pathogenetic mechanisms for paraneoplastic glomerulonephritides associated with different malignancies and highlights the need for a multidisciplinary approach to the management of patients with paraneoplastic glomerulonephritis. PMID:21151207

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

    PubMed Central

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

    2010-01-01

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

  20. Glomerulonephritis

    MedlinePlus

    ... glomerular disease. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner and Rector's The Kidney . 9th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 32. Cattran DC, Reigh ...

  1. Progress in rapid compaction of coal logs for freight pipelines

    SciTech Connect

    Gunnink, B.; Li, W.

    1998-07-01

    The Capsule Pipeline Research Center (CPRC) at the University of Missouri-Columbia is devoted to performing research in capsule pipelines. Since its inception in 1991, the CPRC has focused on research related to the development and rapid commercialization of coal log pipeline technology. Coal log pipelines are freight pipelines that will transport compacted coal through a water filled pipeline. To fully develop this technology and make it ready for commercial use it is necessary to investigate means for fabricating coal logs. This paper describes research progress on the rapid compaction of coal logs for coal log pipeline transport. Economic studies conducted by the CPRC indicate that the cost of producing coal logs and thus the economic competitiveness of coal log pipelines is directly related to the compaction time necessary to make the coal logs. Previous research has demonstrated the ability to make laboratory scale coal logs with a 5 second compaction times. It was also observed that for rapidly compacted coal logs, coal log circulation performance (resistance to abrasion in a commercial pipeline) is maximized, if the logs are compacted from a coal mixture at an optimal moisture content (Gunnink and Yang, 1997). For the bituminous Mettiki coal that has been studied, this optimal moisture content is about 9%, if the compaction time is 5 seconds. The practical application of this is that if stockpiled coal is wetter than optimum, it would require drying of the coal to compact it at the optimum moisture content. Obviously, this would effect the cost of coal log fabrication. The authors hypothesize that an alternative to drying coal exists. If the coal logs are to be made at mix moisture contents that are above the optimum value, then coal log quality can be maintained if the compaction time is increased. In fact, the authors believe that if compaction time is increased such that the bulk density and moisture content of the compacted coal logs are the same, then

  2. Rapidly Progressive Polyneuropathy in a Patient With Monoclonal Gammopathy

    PubMed Central

    Wang, Chen; Guan, Yu-Zhou; Cai, Qian-Qian; Su, Wei; Zhou, Dao-Bin; Li, Jian

    2016-01-01

    Abstract Neuropathy, the dominant clinical feature of POEMS syndrome, is typically distal, symmetric, and slowly progressive with demyelinating changes. After a gradual proximal spread, it usually results in severe muscle weakness and functional disabilities. Cases characterized by acute onset polyneuropathy are rarely described. In the present report, we describe a 32-year-old male diagnosed as POEMS syndrome, but presenting with a rapidly evolving polyneuropathy. Detailed clinical, electrophysiological, and genetic studies revealed a coexisting underdiagnosed inherited axonal neuropathy, namely Charcot-Marie-Tooth disease 2A2. The patient received lenalidomide-based chemotherapy and consolidated by autologous stem cell transplantation for his POEMS syndrome, which improved the neurological disability. In most conditions, only 1 cause is responsible for a patient's polyneuropathy. However, an insidious inherited neuropathy can be overlooked, when an acquired condition is present. The case illustrated here, to the best of our knowledge, is the first one with coexistent axonal type Charcot-Marie-Tooth disease and POEMS syndrome, suggesting that an unrecognized inherited neuropathy may change the disease course of a further acquired neuropathy. PMID:27100445

  3. Report of a case: Retroperitoneal mucinous cystadenocarcinoma with rapid progression

    PubMed Central

    Kamiyama, Hirohiko; Shimazu, Ai; Makino, Yurika; Ichikawa, Ryosuke; Hobo, Takahiro; Arima, Shuei; Nohara, Shigeo; Sugiyama, Yuji; Okumura, Masafumi; Takei, Masahiko; Miura, Hiroyoshi; Namekata, Koji; Tsumura, Hidenori; Okada, Motoi; Takase, Masaru; Matsumoto, Fumio

    2015-01-01

    Introduction Retroperitoneal mucinous cystic neoplasms are uncommon, and little is known about the etiology of the disease. Malignant forms of these are extremely rare. Here, we report a case of primary retroperitoneal mucinous cystadenocarcinoma (PRMC), which demonstrated unexpectedly aggressive progression despite finding only a limited area of adenocarcinoma. Presentation of case A 62-year-old woman with a complaint of abdominal discomfort was admitted to the hospital. Abdominal CT and MRI showed multiple large retroperitoneal cysts dislocating the right kidney nearly to the center of the abdomen. Transabdominal resection of the cysts was performed. Those cysts contained 1100 ml of mucinous fluids in total. Cytological examination of those fluids revealed no malignant cells. The cyst wall was lined with mucinous epithelial cells, and contained some ovarian-type stroma. Also, there was a focal area of adenocarcinoma in the cyst wall, and the lesion was diagnosed as primary retroperitoneal mucinous cystadenocarcinoma. Eight months later, the patient developed lumbar bone metastasis. Chemotherapy with S-1, an oral fluoropyrimidine, and docetaxel had been begun immediately; however, the disease had rapidly spread in the retroperitoneum. Eventually, the patient died of the disease 15 months after surgery. Discussion Retroperitoneal mucinous cystic neoplasms are considered to be metaplasia of embryonal coelomic epithelium. Complete excision without rupture is essential. However, variance of biological aggressiveness might exist in PRMCs. Conclusion Retroperitoneal mucinous cystadenocarcinoma is a rare tumor, and it is urgently necessary to elucidate the etiology of an effective therapy for the disease. PMID:25884614

  4. Rapidly progressive dementias and the treatment of human prion diseases

    PubMed Central

    Lyketsos, Constantine G

    2012-01-01

    Importance of the field Rapidly progressive dementia (RPD) has many possible etiologies and definitive treatment is reliant upon an accurate diagnosis from an appropriate diagnostic work-up. A large portion of the neurodegenerative causes of RPD are due to prion diseases (e.g., Creutzfeldt–Jakob disease). The study of prion diseases, for which there is no currently available treatment, has public health implications and is becoming increasingly more relevant to our understanding of other protein misfolding disorders including Alzheimer’s disease, frontotemporal degeneration, and Parkinson’s disease. Areas covered in this review This article begins with an overview of the etiologies and diagnostic work-up of RPD followed by a detailed review of the literature concerning the treatment of human prion diseases (1971 to present). What the reader will gain The reader will understand the differential diagnosis and work-up of RPD as it pertains to its treatment, as well as an in-depth understanding of treatments of human prion diseases. Take home message An accurate diagnosis of the cause of RPD is of paramount importance when determining appropriate treatment. Most studies of the treatment for human prion diseases are case reports or case series, and results from only one randomized, placebo-controlled study have been reported in the literature (flupirtine). Studies have been hindered by disease heterogeneity and lack of standardized outcome measures. Although no effective prion disease treatment has been revealed through these studies, they provide important considerations for future studies. PMID:21091283

  5. Eculizumab and Recurrent C3 Glomerulonephritis

    PubMed Central

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

    2015-01-01

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

  6. [Yellow nail syndrome in a patient with membranous glomerulonephritis].

    PubMed

    Modrzewska, Katarzyna; Fijołek, Justyna; Ptak, Jakub; Wiatr, Elżbieta

    2012-01-01

    Yellow nail syndrome (YNS) is a condition characterized by yellow-green coloration of nails, respiratory manifestations and lymphoedema. This article presents 52-year-old patient with membranous glomerulonephritis, hospitalized at the National Tuberculosis and Lung Diseases Research Institute in Warsaw, because of suspected allergic aspergillosis. Based on clinical and radiological evaluation the diagnosis of YNS was established. Treatment of renal disease did not affect the course of yellow nail syndrome. During the two-year follow-up, despite stable renal parameters we observed the progression of respiratory manifestations (bronchiectasis, pleural effusions). PMID:22370985

  7. Anti-glomerular basement membrane crescentic glomerulonephritis: A report from India and review of literature

    PubMed Central

    Gupta, A.; Agrawal, V.; Kaul, A.; Verma, R.; Pandey, R.

    2016-01-01

    Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune disease that most commonly presents as rapidly progressive glomerulonephritis with or without pulmonary involvement. It is characterized by the presence of antibodies directed to antigenic targets within glomerular and alveolar basement membranes. This study was performed to evaluate the clinicopathological features and outcome in anti-GBM crescentic glomerulonephritis (CrGN) at a tertiary care center in North India over a period of 9 years (January 2004 to December 2012). A diagnosis of anti-GBM CrGN was made in the presence of >50% crescents, linear deposits of IgG along GBM, and raised serum anti-GBM antibody titer. Of 215 cases of CrGN diagnosed during this period, 11 had anti-GBM CrGN. Anti-GBM CrGN was found at all ages but was most common in the third to fifth decade with no gender predilection (mean age 48 +/- 15 years, 13–67 years). Patients presented with a mean serum creatinine of 10.2 +/- 5.3 mg/dl and sub-nephrotic proteinuria. Pulmonary involvement was present in two patients. Myeloperoxidase-antineutrophil cytoplasmic antibody was positive in two (2/11) elderly patients. Follow-up was available in four patients for a range of 30-270 (mean 99.5 ± 114.5) days, two remained dialysis dependent while two died due to uremia and sepsis. Our findings show that anti-GBM disease is a rare cause of CrGN in India, accounting for only 5% of patients. It usually presents as a renal-limited disease and is associated with a poor renal outcome. PMID:27795626

  8. Progress towards a rapidly rotating ultracold Fermi gas

    NASA Astrophysics Data System (ADS)

    Hu, Ming-Guang; van de Graaff, Michael; Cornell, Eric; Jin, Deborah

    2015-05-01

    We are designing an experiment with the goal of creating a rapidly rotating ultracold Fermi gas, which is promising system in which to study quantum Hall physics. We propose to use selective evaporation of a gas that has been initialized with a modest rotation rate to increase the angular momentum per particle in order to reach rapid rotation. We have performed simulations of this evaporation process for a model optical trap potential. Achieving rapid rotation will require a very smooth, very harmonic, and dynamically variable optical trap. We plan to use a setup consisting of two acousto-optical modulators to ``paint'' an optical dipole trapping potential that can be made smooth, radially symmetric, and harmonic. This project is supported by NSF, NIST, NASA.

  9. Progress towards rapid identification of phytochemicals in plant extracts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New mass spectrometry equipment is bringing closer to reality the rapid accurate assessment of chemical composition of extracts from a variety of plant materials. Using a variety of plant sources, we are using HPLC separation, UV-VIS spectrometry, ion trap mass fragmentation and accurate mass deter...

  10. [A 79-year-old man with rapidly progressive tetraparesis].

    PubMed

    Ishigaki, Y; Hironishi, M; Toganou, T; Matsumoto, T; Ohta, S; Suda, K; Nishi, K; Yamaguchi, H; Mizuno, Y

    1993-11-01

    We report a 79-year-old man who developed progressive gait disturbance and sensory loss. He had been doing well except for hepatitis B virus hepatitis until 72 years of age when he developed angina pectoris for which aorto-coronary bypass operation was performed when he was 73-year-old (1986). In 1990, he developed pulmonary fibrosis for which prednisolone was prescribed. His liver function deteriorated, and the liver function tests suggested liver cirrhosis. He noted an onset of gait disturbance in the middle of June in 1992 when he was 79-year-old. His gait disturbance deteriorated progressively, and he developed edema and loss of sensation in his both legs. He became unable to walk unassisted in the beginning of July. He fractured his right external malleolus after falling down from a chair. He became unable to stand by himself, and he was admitted to the cardiology service of our hospital on July 18, 1992, and the neurology service was asked to see the patient on July 30 of the same month. The patient was well developed and well nourished man in no acute distress. General physical examination revealed slight jaundice, left carotid bruit, and slight pitting pretibial edema. His temperature was 37.3 degrees C. On neurologic examination, he was alert and mentally sound without dementia. He showed a slight weakness in the facial muscles bilaterally and mild dysarthria and dysphagia, however, the other cranial nerves appeared intact. He was unable to stand unassisted. The muscle tone was hypotonic, however, no focal muscle atrophy was noted, nor was observed fasciculatory twitches.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. B-Cell Depletion Salvage Therapy in Rapidly Progressive Dermatomyositis Related Interstitial Lung Disease.

    PubMed

    Eissa, Khaled; Palomino, Jaime

    2016-01-01

    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). Glucocorticoids are the initial standard treatment. However, many patients fail to respond and continue to progress despite treatment with high dose glucocorticoids. The efficacy of rituximab has been suggested in case reports and case series of refractory antisynthetase (AS) syndrome, but data on patients without auto-antibodies or with rapidly progressive ILD are scarce. We report a case of rapidly progressive dermatomyositis (DM) associated ILD treated successfully with B-cell depletion therapy. PMID:27389378

  12. Reanalysis of membranoproliferative glomerulonephritis patients according to the new classification: a multicenter study☆

    PubMed Central

    Woo, Sung Ae; Young Ju, Hye; Hyo Kwon, Soon; Lee, Ji-Hye; Jeong Choi, Soo; Cheol Han, Dong; Duk Hwang, Seung; Hong, Sae-Yong; Jin, So-Young; Gil, Hyo-Wook

    2014-01-01

    Background All types of membranoproliferative glomerulonephritis (MPGN) are progressive diseases with poor prognoses. Recently, a newly proposed classification of these diseases separated them into immune complex- and complement-mediated diseases. We investigated the frequency of C3 glomerulonephritis among previously diagnosed MPGN patients. Methods We conducted a retrospective study of patients diagnosed with MPGN at three tertiary care institutions between 2001 and 2010. We investigated the incidence of complement-mediated disease among patients diagnosed with MPGN. Progressive renal dysfunction was defined as a 50% reduction in the glomerular filtration rate or the need for renal replacement therapy. Results Among the 3,294 renal biopsy patients, 77 (2.3%) were diagnosed with MPGN; 31 cases were excluded, of which seven were diagnosed with systemic lupus nephritis, and the others were not followed for a minimum of 12 months after biopsy. Based on the new classification, complement-mediated MPGN was diagnosed in two patients (4.3%); only one patient developed progressive renal dysfunction. Among the immune complex-mediated MPGN patients, 17 patients developed progressive renal dysfunction. Serum albumin and creatinine levels at the time of MPGN diagnosis were risk factors of renal deterioration, after adjusting for low C3 levels and nephrotic syndrome. Conclusion Complement-mediated glomerulonephritis was present in 4.3% of patients previously diagnosed with MPGN. PMID:26885475

  13. Noncongophilic fibrillary glomerulonephritis in a cat.

    PubMed

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

    2008-05-01

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

  14. Atypical membranoproliferative glomerulonephritis in a cat.

    PubMed

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

    2001-07-01

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

  15. Immune profile of IgA-dominant diffuse proliferative glomerulonephritis.

    PubMed

    Wallace, Eric; Maillard, Nicolas; Ueda, Hiroyuki; Hall, Stacy; Fatima, Huma; Novak, Jan; Julian, Bruce A

    2014-10-01

    The diagnosis of IgA-dominant post-infectious glomerulonephritis (PIGN) may be challenging, as it must be differentiated from that of active IgA nephropathy. Predominant clinicopathologic features of IgA-dominant PIGN substantially overlap with those of active IgA nephropathy. Here, we present a case of a 67-year-old woman with rapidly rising serum creatinine, proteinuria and severe hypertension. The kidney biopsy findings included some features of IgA-dominant PIGN while others were more consistent with classical IgA nephropathy. We describe this patient's immune profile at the time of acute kidney injury and review the literature regarding differentiation of the two entities.

  16. Immune profile of IgA-dominant diffuse proliferative glomerulonephritis

    PubMed Central

    Wallace, Eric; Maillard, Nicolas; Ueda, Hiroyuki; Hall, Stacy; Fatima, Huma; Novak, Jan; Julian, Bruce A.

    2014-01-01

    The diagnosis of IgA-dominant post-infectious glomerulonephritis (PIGN) may be challenging, as it must be differentiated from that of active IgA nephropathy. Predominant clinicopathologic features of IgA-dominant PIGN substantially overlap with those of active IgA nephropathy. Here, we present a case of a 67-year-old woman with rapidly rising serum creatinine, proteinuria and severe hypertension. The kidney biopsy findings included some features of IgA-dominant PIGN while others were more consistent with classical IgA nephropathy. We describe this patient's immune profile at the time of acute kidney injury and review the literature regarding differentiation of the two entities. PMID:25878780

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

    PubMed Central

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

    2016-01-01

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

  18. [Oligomeganephronic renal hypoplasia complicated by glomerulonephritis].

    PubMed

    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.

  19. Monoclonal gammopathy-associated proliferative glomerulonephritis.

    PubMed

    Sethi, Sanjeev; Rajkumar, S Vincent

    2013-11-01

    Monoclonal gammopathy is characterized by circulating monoclonal immunoglobulin owing to clonal proliferation of immunoglobulin-producing B lymphocytes or plasma cells. Clonal proliferation of B lymphocytes is seen in B-cell lymphoma/leukemia, and clonal plasma cell proliferation is seen in multiple myeloma and monoclonal gammopathy of undetermined significance. The monoclonal immunoglobulin in the setting of a B-cell or plasma cell disorder can cause a proliferative glomerulonephritis via 2 mechanisms: (1) glomerular deposition of the monoclonal immunoglobulin with activation of the classical pathway of complement (direct mechanism), resulting in an immunoglobulin-positive C3-positive glomerulonephritis, and (2) glomerular deposition of complement factors of the alternative and terminal pathway via inhibition of alternative pathway-regulating proteins by the monoclonal immunoglobulin (indirect mechanism), resulting in immunoglobulin-negative C3-positive glomerulonephritis (C3 glomerulopathy). Evaluation should include serum and urine electrophoresis and immunofixation as well as serum-free light-chain assay. If a monoclonal immunoglobulin is detected on these tests, bone marrow biopsy or imaging is needed to exclude more advanced plasma cell dyscrasia. Evaluation of alternative pathway of complement should be done in patients with Ig-negative C3-positive glomerulonephritis. If monoclonal gammopathy is due to an underlying malignant disease such as myeloma, lymphoma, or chronic lymphocytic leukemia, then specific treatment should be aimed at treating the malignant disease, with the goal of eradicating the clonal cells producing the immunoglobulin. In contrast, if monoclonal gammopathy is due to a monoclonal gammopathy of undetermined significance, treatment options include bortezomib, cyclophosphamide, and dexamethasone for a non-IgM monoclonal immunoglobulin and rituximab alone or in combination with cyclophosphamide and dexamethasone for an IgM monoclonal

  20. Hydralazine associated pauci-immune glomerulonephritis.

    PubMed

    Suneja, Manish; Baiswar, Shalanki; Vogelgesang, Scott A

    2014-03-01

    Hydralazine is a medication that has been used to manage hypertension and heart failure. In this case series, we report 4 patients who presented to a large, Midwestern academic medical center on chronic hydralazine therapy with acute kidney injury, nephritic urine sediment on urine microscopy, and the simultaneous presence of autoantibodies suggesting both drug-induced lupus and drug-induced vasculitis. All of them had evidence of pauci-immune glomerulonephritis on kidney biopsy. All the patients reported in our series are white women older than 60 years who were receiving hydralazine for more than 12 months at a dose of 150 mg or more. On initial presentation, all had evidence of acute kidney injury with nephritic sediment. These patients also had high titers of serum anti-neutrophil cytoplasmic antibodies of the antimyeloperoxidase subtype and simultaneous presence of multiple autoantibodies. All of them subsequently underwent a kidney biopsy, which revealed pauci-immune glomerulonephritis. This case series draws rheumatologists' attention to the possibility of pauci-immune glomerulonephritis in patients taking hydralazine, highlights the presence of multiple antibodies in these cases, and questions the long-term use of hydralazine especially in an elderly female population.

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

    PubMed

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

    2008-01-01

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

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

    PubMed

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

    2008-01-01

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

  3. Plasma exchange and ribavirin for rapidly progressive severe fever with thrombocytopenia syndrome.

    PubMed

    Oh, Won Sup; Heo, Sang Taek; Kim, Sun Hyung; Choi, Won Jun; Han, Myung Guk; Kim, Ji Young

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. Although the increasing numbers of cases and deaths is of great concern, an effective treatment strategy for SFTS has not been established. We present the cases of two patients with rapidly progressing SFTS who were successfully treated with plasma exchange and ribavirin.

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

    PubMed

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

    2016-01-01

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

  5. Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection.

    PubMed

    Zhang, Zhi-Qiang; Casimiro, Danilo R; Schleif, William A; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A; Shiver, John W

    2007-05-10

    Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4(+) T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection.

  6. Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

    SciTech Connect

    Zhang Zhiqiang . E-mail: zhiqiang_zhang@merck.com; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

    2007-05-10

    Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4{sup +} T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection.

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

    PubMed

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

    1994-01-01

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

  8. Axial mitochondrial myopathy in a patient with rapidly progressive adult-onset scoliosis.

    PubMed

    Hiniker, Annie; Wong, Lee-Jun; Berven, Sigurd; Truong, Cavatina K; Adesina, Adekunle M; Margeta, Marta

    2014-01-01

    Axial myopathy can be the underlying cause of rapidly progressive adult-onset scoliosis; however, the pathogenesis of this disorder remains poorly understood. Here we present a case of a 69-year old woman with a family history of scoliosis affecting both her mother and her son, who over 4 years developed rapidly progressive scoliosis. The patient had a history of stable scoliosis since adolescence that worsened significantly at age 65, leading to low back pain and radiculopathy. Paraspinal muscle biopsy showed morphologic evidence of a mitochondrial myopathy. Diagnostic deficiencies of electron transport chain enzymes were not detected using standard bioassays, but mitochondrial immunofluorescence demonstrated many muscle fibers totally or partially deficient for complexes I, III, IV-I, and IV-IV. Massively parallel sequencing of paraspinal muscle mtDNA detected multiple deletions as well as a 40.9% heteroplasmic novel m.12293G > A (MT-TL2) variant, which changes a G:C pairing to an A:C mispairing in the anticodon stem of tRNA Leu(CUN). Interestingly, these mitochondrial abnormalities were not detected in the blood of either the patient or her son, suggesting that the patient's rapidly progressive late onset scoliosis was due to the acquired paraspinal mitochondrial myopathy; the cause of non-progressive scoliosis in the other two family members currently remains unexplained. Notably, this case illustrates that isolated mitochondrial myopathy can underlie rapidly-progressive adult-onset scoliosis and should be considered in the differential diagnosis of the primary axial myopathy.

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

    PubMed

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

    2009-11-01

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

  10. Rapidly solidified ceramics: Processing, structure, and magnetic properties. Progress report, September 1984--January 1985

    SciTech Connect

    Kalonji, G.M.; O`Handley, R.C.

    1985-12-31

    Since its initiation in September 1984, work under this contract has progressed in two areas: construction of a gas atomizer for rapid solidification of ceramics; and characterization of rapidly solidified materials in the SrO-Fe{sub 2}O{sub 3}, BaO-Fe{sub 2}O{sub 3}, MnFe{sub 2}O{sub 4}-SiO{sub 2}, and CoFe{sub 2}O{sub 4}-SiO{sub 2} systems. This report summarize this work.

  11. Atypical presentation of Creutzfeldt-Jakob disease: a rare but important cause of rapidly progressive dementia.

    PubMed

    Taillefer, Marguerite S; Tangarorang, Glendo L; Kuchel, George A; Menkes, Daniel L

    2011-09-01

    We report an atypical presentation of sporadic Creutzfeldt-Jakob disease (CJD) in a 74-year-old woman that illustrates the difficulty in diagnosing this rare, but important, cause of rapidly progressive dementia. Despite well-established criteria, this diagnosis is often missed or substantially delayed (Table 1). In this case, a precipitous cognitive decline associated with a urinary tract infection initiallysuggested delirium. Although atypical CJD was considered as a cause when symptoms persisted, a definitive diagnosis was established postmortem when the cerebrospinal fluid (CSF) prion protein 14-3-3 tested positive. Creutzfeldt-Jakob disease must be considered in the differential diagnosis of rapidly progressive dementia as Connecticut accounts for approximately three of the more than 200 cases diagnosed nationally.

  12. Vascular Ehlers-Danlos syndrome presenting as rapidly progressive multiple arterial aneurysms and dissections.

    PubMed

    Mortani Barbosa, Eduardo J; Pyeritz, Reed E; Litt, Harold; Desjardins, Benoit

    2011-12-01

    Life expectancy in vascular Ehlers-Danlos syndrome (EDS) is shortened due to spontaneous rupture of arteries, the colon and the gravid uterus. Two adolescent males with vascular EDS illustrate rapid progression of arterial aneurysms, dissections, and rupture. Radiologic imaging played an important role in initially diagnosing and monitoring the evolution of arterial involvement. Both prophylactic and emergency management remain largely ineffective in this connective tissue disorder; however, noninvasive imaging may provide important prognostic information. PMID:22065459

  13. Membranoproliferative glomerulonephritis in a young cat.

    PubMed

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

    2008-12-01

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

  14. Experimental proliferative glomerulonephritis in the cat.

    PubMed

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

    1992-01-01

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

  15. Monosomy 3 status of uveal melanoma metastases is associated with rapidly progressive tumors and short survival.

    PubMed

    Abdel-Rahman, Mohamed H; Cebulla, Colleen M; Verma, Vishal; Christopher, Benjamin N; Carson, William E; Olencki, Thomas; Davidorf, Frederick H

    2012-07-01

    The aim of the study was to investigate the molecular genetics of uveal melanoma (UM) metastases and correlate it with disease progression. Twelve pathologically confirmed UM metastases from 11 patients were included. Molecular genetic alterations in chromosomes 3 (including the BAP1 region), 8q, 6p, and 1p were investigated by microsatellite genotyping. Mutations in codon 209 of GNAQ and GNA11 genes were studied by restriction-fragment length polymorphism (RFLP). We identified monosomy of chromosome 3 in tumors from four patients with an average survival of 5 months (range 1-8 months) from time of diagnosis of metastatic disease. In contrast, tumors with either disomy or partial chromosome 3 alterations showed significantly slower metastatic disease progression with an average survival of 69 months (range 40-123 months, p = 0.003). Alterations in chromosomal arms 1p, 6p, and 8q and mutations in either GNAQ or GNA11 showed no association with disease progression. Prominent mononuclear inflammatory infiltrate was observed in tumors from patients with slowly progressive disease. In conclusion, in UM metastases, monosomy 3 is associated with highly aggressive, rapidly progressive disease while disomy or partial change of 3 and prominent mononuclear inflammatory infiltrate in the tumor is associated with better prognosis. These findings should be considered when designing clinical trials testing effectiveness of various therapies of metastatic UM.

  16. Sjögren Syndrome and Cryoglobulinemic Glomerulonephritis.

    PubMed

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

    2015-09-01

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

  17. De novo C3 glomerulonephritis in a renal allograft.

    PubMed

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

    2016-01-01

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

  18. De novo C3 glomerulonephritis in a renal allograft.

    PubMed

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

    2016-01-01

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

  19. [A case of membranous nephropathy with ANCA-associated necrotizing glomerulonephritis during oral administration of PTU for Graves' disease].

    PubMed

    Fujii, Takayuki; Kawamata, Toyotaka; Ueda, Shiro; Akikusa, Bunshiro; Hasegawa, Shigeru; Tsukahara, Tsunemichi; Iesato, Kenji; Ogawa, Makoto; Saisho, Hiromitsu

    2003-01-01

    We experienced a coincidental case of two types of glomerulopathy associated with Graves' disease. A 64-year-old man, who had been treated with propylthiouracil(PTU) for Graves' disease for 15 years, was admitted to our hospital for macroscopic hematuria and rapidly progressive deterioration of renal function. Although his thyroid function had been within the normal range during treatment, the level of thyrotropin receptor antibody(TRAb) gradually increased from a year before admission. Serological tests revealed that he was positive for myeloperoxidase-antineutrophil cytoplasmic antibody(MPO-ANCA). The renal biopsy specimen showed necrotizing and crescentic glomerulonephritis(GN) superimposed on membranous nephropathy(MN). This is a rare case of MN complicated with ANCA associated crescentic GN in a Graves' disease patient. Association of these two renal alterations was not clearly defined. MN involved with Graves' disease also has been rarely reported. Some reports demonstrated deposition of thyroglobulin and other thyroid related antigens in the glomeruli. In the present case, long-term impairment of Graves' disease and elevation of TRAb might have been responsible for the formation and deposition of thyroid-associated immune complex in the glomeruli. As for crescentic GN, PTU might have induced ANCA-associated GN independently of MN. This case is instructive for considering the relation between Graves' disease and renal injury.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  2. Rapidly progressive kidney failure induced by fungal mycelia obstructing indwelling ureteral stents.

    PubMed

    Dubert, Marie; Loi, Valeria; Tligui, Mohamed; Hertig, Alexandre

    2012-12-14

    Antibiotics reduce the commensal flora in the gut, thereby facilitating the overgrowth of undesirable microorganisms such as Candida albicans. Here, we report the case of a 48-year-old woman with a history of obstructive uropathy consecutive to a radiation therapy, in whom both indwelling ureteral stents were rapidly occluded by fungal mycelia, resulting in a rapidly progressive kidney failure. Ascendant infection by C albicans had occurred after a 2- week course of antibiotics, prescribed for a perforative peritonitis also due to radiation-induced colitis. As shown by iterative CT scans made before (at the time of the diagnosis of peritonitis) and after the antibiotic course, kidney failure was explained by a sudden and bilateral pyelocaliceal dilation, due to the obstruction of the ureteral stents. Fungal mycelia were objectivised during the replacement procedure. Intravenous fluconazole was started, and renal function recovered ad integrum with the relief of the obstruction.

  3. Rapidly progressive kidney failure induced by fungal mycelia obstructing indwelling ureteral stents

    PubMed Central

    Dubert, Marie; Loi, Valeria; Tligui, Mohamed; Hertig, Alexandre

    2012-01-01

    Antibiotics reduce the commensal flora in the gut, thereby facilitating the overgrowth of undesirable microorganisms such as Candida albicans. Here, we report the case of a 48-year-old woman with a history of obstructive uropathy consecutive to a radiation therapy, in whom both indwelling ureteral stents were rapidly occluded by fungal mycelia, resulting in a rapidly progressive kidney failure. Ascendant infection by C albicans had occurred after a 2- week course of antibiotics, prescribed for a perforative peritonitis also due to radiation-induced colitis. As shown by iterative CT scans made before (at the time of the diagnosis of peritonitis) and after the antibiotic course, kidney failure was explained by a sudden and bilateral pyelocaliceal dilation, due to the obstruction of the ureteral stents. Fungal mycelia were objectivised during the replacement procedure. Intravenous fluconazole was started, and renal function recovered ad integrum with the relief of the obstruction. PMID:23242091

  4. CLINICAL AND GENETIC PREDICTORS AND PROGNOSTIC MODEL OF RAPIDLY PROGRESSIVE HEPATIC FIBROSIS IN CHRONIC HEPATITIS C.

    PubMed

    Dubinskaya, G; Sizova, L; Koval, T; Kovalyova, Е; Kaydashev, I

    2016-07-01

    The search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender - ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) - ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity - ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) - ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) - ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin - ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase - ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity - 85.5%, specificity - 68.3%, total number of the appropriate assignments - 76.8%, positive and negative predictive value - 72,6% and 82.7%,, respectively, the AUC ROC-curve - 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual

  5. CLINICAL AND GENETIC PREDICTORS AND PROGNOSTIC MODEL OF RAPIDLY PROGRESSIVE HEPATIC FIBROSIS IN CHRONIC HEPATITIS C.

    PubMed

    Dubinskaya, G; Sizova, L; Koval, T; Kovalyova, Е; Kaydashev, I

    2016-07-01

    The search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender - ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) - ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity - ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) - ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) - ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin - ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase - ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity - 85.5%, specificity - 68.3%, total number of the appropriate assignments - 76.8%, positive and negative predictive value - 72,6% and 82.7%,, respectively, the AUC ROC-curve - 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual

  6. [Two Cases of Rapidly Progressive Community-acquired Pneumonia Due to Pseudomonas aeruginosa].

    PubMed

    Takakura, Akira; Katono, Ken; Harada, Shinya; Igawa, Satoshi; Katagiri, Masato; Yanase, Nobuo; Masuda, Noriyuki

    2015-01-01

    Pseudomonas aeruginosa is a significant causative bacterium in hospital-acquired pneumonia and nursing and healthcare-associated pneumonia, but it seems to be rare in community-acquired pneumonia (CAP). We report two cases of severe CAP due to P. aeruginosa. Case 1: A 52-year-old man was referred to our hospital for chest and back pain. He was being treated for diabetes mellitus and had a long history of smoking. Chest images showed consolidation in the right upper lobe. Soon after hospitalization, he developed sepsis shock and died seven hours later. Case 2: A 73-year-old man with a history of heavy smoking was referred to our hospital for right chest pain. Chest images showed right upper lobe pneumonia. Although wide-spectrum antimicrobial agents were administrated, he died ten hours after admission. In both cases, there was a rapid progression to death, despite administration of a broad spectrum of antibiotics and treatment for sepsis. In cases of CAP involving the right upper lobe, the possibility of bacteremia and rapid progress should be considered. PMID:26548298

  7. Haematuria on the Spanish Registry of Glomerulonephritis.

    PubMed

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

    2016-01-01

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

  8. siRNA-Based Therapy Ameliorates Glomerulonephritis

    PubMed Central

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

    2010-01-01

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

  9. Haematuria on the Spanish Registry of Glomerulonephritis

    PubMed Central

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

    2016-01-01

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

  10. ANCA positivity in a patient with infective endocarditis-associated glomerulonephritis: a diagnostic dilemma.

    PubMed

    Ghosh, Gopal Chandra; Sharma, Brijesh; Katageri, Bhimarey; Bhardwaj, Minakshi

    2014-09-01

    Glomerulonephritis (GN) is an immunological phenomenon in bacterial endocarditis. These may be pauci-immune/vasculitic GN, post-infective GN, and sub-endothelial membranoproliferative glomerulonephritis. Each type of glomerulonephritis usually occurs in isolation. We report a case of infective endocarditis with dual existence of pauci-immune/vasculitic GN and post infective type of GN at the same time.

  11. Silica and glomerulonephritis: case report and review of the literature

    SciTech Connect

    Osorio, A.M.; Thun, M.J.; Novak, R.F.; Van Cura, E.J.; Avner, E.D.

    1987-03-01

    A 54-year-old foundry worker with extensive silica exposure, but no pulmonary disease, developed the nephrotic syndrome and renal failure over a 3-month period. Renal biopsy demonstrated a proliferative glomerulonephritis; energy dispersive x-ray analysis detected silicon within the renal tubules. Measurements of respirable silica at the foundry revealed levels up to 2.5 times the current occupational standard. Similar glomerular disease has been reported in silica-exposed animals and workers with silicosis. This case suggests that clinicians should include silica exposure in the differential diagnosis of unexplained diffuse proliferative glomerulonephritis, renal disease may occur without clinically evident pulmonary disease in silica exposure, and silica-induced glomerulonephritis warrants further clinical and epidemiologic research.

  12. [Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis with acute pancreatitis: a case report].

    PubMed

    Iida, Takeshi; Amari, Yoshifumi; Yurugi, Takatomi; Nakajima, Fumitaka

    2015-01-01

    We report here a case of a 64-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis who developed acute pancreatitis. The patient was admitted to our hospital because of abnormal urinalysis findings, edema, and progressive renal failure. Laboratory studies showed a high white blood cell count (11,570/μL), anemia (hemoglobin 7.8 g/dL), and elevated serum creatinine (2.36 mg/dL) and C-reactive protein (12.20 mg/dL) levels. Furthermore, the MPO-ANCA titer was very high (1,625 U/mL, normal range < 10 U/mL). Histopathological findings of the renal biopsy were consistent with microscopic polyangiitis. Accordingly, we diagnosed MPO-ANCA-associated glomerulonephritis. On the day after the renal biopsy, the patient complained of low back pain. Computed tomography (CT) revealed postbiopsy hemorrhage. Thereafter, the patient's symptoms and laboratory studies gradually worsened. A repeat CT performed a few days later revealed no changes in the perirenal hematoma; however, an enlarged pancreas head was incidentally observed. There was no obvious cause of acute pancreatitis, and MPO-ANCA-associated vasculitis, although rare, was suspected as the cause. We initiated prednisolone pulse therapy for vasculitis along with the administration of nafamostat mesilate and ulinastatin for acute pancreatitis. Subsequently, the levels of pancreatic enzymes gradually increased, but several days later, abdominal magnetic resonance imaging showed improvement in the pancreas head. The pancreatitis gradually resolved over time. Acute pancreatitis occurring concurrently with MPO-ANCA-associated glomerulonephritis is extremely rare. To our knowledge, only a few such cases have been reported and have suggested that steroid therapy may play a role in triggering pancreatic involvement. In our case, however, an enlarged pancreas head was observed before steroid therapy was initiated. Therefore, we consider our case to be very rare. PMID

  13. Exome sequencing results in successful riboflavin treatment of a rapidly progressive neurological condition

    PubMed Central

    Petrovski, Slavé; Shashi, Vandana; Petrou, Steven; Schoch, Kelly; McSweeney, Keisha Melodi; Dhindsa, Ryan S.; Krueger, Brian; Crimian, Rebecca; Case, Laura E.; Khalid, Roha; El-Dairi, Maysantoine A.; Jiang, Yong-Hui; Mikati, Mohamad A.; Goldstein, David B.

    2015-01-01

    Genetically targeted therapies for rare Mendelian conditions are improving patient outcomes. Here, we present the case of a 20-mo-old female suffering from a rapidly progressing neurological disorder. Although diagnosed initially with a possible autoimmune condition, analysis of the child's exome resulted in a diagnosis of Brown–Vialetto–Van Laere syndrome 2 (BVVLS2). This new diagnosis led to a change in the therapy plan from steroids and precautionary chemotherapy to high-dose riboflavin. Improvements were reported quickly, including in motor strength after 1 mo. In this case, the correct diagnosis and appropriate treatment would have been unlikely in the absence of exome sequencing and careful interpretation. This experience adds to a growing list of examples that emphasize the importance of early genome-wide diagnostics. PMID:27148561

  14. Human leukocyte antigen (HLA) DR4. Positive association with rapidly progressing periodontitis.

    PubMed

    Katz, J; Goultschin, J; Benoliel, R; Brautbar, C

    1987-09-01

    The relationship between human leukocyte antigens (HLA) determinants and periodontitis has been examined by several authors without showing any particular pattern. However, no study has investigated the HLA-D determinants, which are generally associated with immune disorders, and rapidly progressive periodontitis (RPP). The HLA profile of 10 RPP patients was compared with that of a healthy control population (n = 120). Although no significant difference was found for HLA-A, HLA-B, and HLA-C, HLA-DR4 of the HLA-D group was found in 80% of patients but only in 38.3% of controls. A high frequency of HLA-DR4 has been reported in rheumatoid arthritis (RA) patients. This finding may be significant in light of previous reports highlighting similarities between RA and periodontal disease. PMID:3498813

  15. Enterovirus causes rapidly progressive dementia in a 28-year-old immunosuppressed woman.

    PubMed

    Mantri, Sneha; Shah, Binit B

    2016-08-01

    Enterovirus in the nervous system can present with protean manifestations, including polio-like paralysis, movement disorders, and seizures. This is a report of a single case of a rapidly progressive dementing illness in a young woman with common variable immunodeficiency (CVID). Over the course of several months, she developed profound aphasia, apraxia, and cerebellar signs. She underwent brain biopsy which was suggestive of toxoplasmosis; despite an adequate course of treatment, she continued to decline and ultimately died. Autopsy and PCR testing revealed diffuse coxsackie B3 infiltration in the meninges and brain parenchyma. To our knowledge, this is the first description of enterovirus causing a dementing illness in a young immunosuppressed adult. We highlight the need for a broad differential diagnosis, especially for immunocompromised individuals, who may present in an atypical fashion. PMID:26727905

  16. [Retroperitoneal angiomyolipoma with rapidly progressing intracystic hemorrhage and lymph node involvement: a case report].

    PubMed

    Shiba, Masahiro; Takatera, Hiroshi

    2003-10-01

    We report a very rare case of retroperitoneal angiomyolipoma with rapidly progressing intracytic hemorrhage and lymph node involvement in a 34-year-old female. She was admitted to our hospital complaining of a severe pain in the lower abdominal region, followed by oligemic shock. Abdominal enhanced computed tomography (CT) demonstrated a retroperitoneal giant cyst with intracystic hematoma, which displaced the left kidney anteriorly. Because transarterial embolization was unsuccessful transabdominal left nephrectomy combined with excision of the giant cyst was performed to keep the continuing hemorrhage under control. Simultaneously, a swollen paraaortic lymph node was also resected. The histologic findings of resected tissue and lymph node were retroperitoneal angiomyolipoma with lymph node involvement. The patient is being followed up at our hospital without recurrence.

  17. A Challenging Case of Rapid Progressive Kaposi Sarcoma After Renal Transplantation

    PubMed Central

    Reuter, Stefan; Vrachimis, Alexis; Huss, Sebastian; Wardelmann, Eva; Weckesser, Mathias; Pavenstädt, Hermann

    2014-01-01

    Abstract De-novo malignancy is a serious posttransplant complication. While the incidence of Kaposi sarcoma (KS) is low, the time for its diagnosis is early after renal transplantation. Typically, it can be identified because of the classical skin lesion. We herein report an unusual case of rapid progressive KS without skin lesions in a 52-year-old patient leading to death within 8 months after kidney transplantation. This striking case illustrates the usefulness of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for demonstrating the cause of unexplained deterioration of patient’s condition. Early identification of KS is critical because early (modification of) therapy can substantially improve patient’s prognosis. PMID:25192485

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

    PubMed Central

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

    2016-01-01

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

  19. Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β

    PubMed Central

    Cohen, Mark L.; Kim, Chae; Haldiman, Tracy; ElHag, Mohamed; Mehndiratta, Prachi; Pichet, Termsarasab; Lissemore, Frances; Shea, Michelle; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Appleby, Brian S.; Surewicz, Krystyna; Surewicz, Witold K.; Sajatovic, Martha; Tatsuoka, Curtis; Zhang, Shulin; Mayo, Ping; Butkiewicz, Mariusz; Haines, Jonathan L.; Lerner, Alan J.

    2015-01-01

    Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but the cause of variable progression rates and phenotypes of sporadic Alzheimer’s disease is largely unknown. We aimed to investigate the relationship between diverse structural assemblies of amyloid-β and rates of clinical decline in Alzheimer’s disease. Using novel biophysical methods, we analysed levels, particle size, and conformational characteristics of amyloid-β in the posterior cingulate cortex, hippocampus and cerebellum of 48 cases of Alzheimer’s disease with distinctly different disease durations, and correlated the data with APOE gene polymorphism. In both hippocampus and posterior cingulate cortex we identified an extensive array of distinct amyloid-β42 particles that differ in size, display of N-terminal and C-terminal domains, and conformational stability. In contrast, amyloid-β40 present at low levels did not form a major particle with discernible size, and both N-terminal and C- terminal domains were largely exposed. Rapidly progressive Alzheimer’s disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-β42, with higher levels of distinctly structured amyloid-β42 particles composed of 30–100 monomers, and fewer particles composed of < 30 monomers. The link between rapid clinical decline and levels of amyloid-β42 with distinct structural characteristics suggests that different conformers may play an important role in the pathogenesis of distinct Alzheimer’s disease phenotypes. These findings indicate that Alzheimer’s disease exhibits a wide spectrum of amyloid-β42 structural states and imply the existence of prion-like conformational strains.

  20. Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β

    PubMed Central

    Cohen, Mark L.; Kim, Chae; Haldiman, Tracy; ElHag, Mohamed; Mehndiratta, Prachi; Pichet, Termsarasab; Lissemore, Frances; Shea, Michelle; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Appleby, Brian S.; Surewicz, Krystyna; Surewicz, Witold K.; Sajatovic, Martha; Tatsuoka, Curtis; Zhang, Shulin; Mayo, Ping; Butkiewicz, Mariusz; Haines, Jonathan L.; Lerner, Alan J.

    2015-01-01

    Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but the cause of variable progression rates and phenotypes of sporadic Alzheimer’s disease is largely unknown. We aimed to investigate the relationship between diverse structural assemblies of amyloid-β and rates of clinical decline in Alzheimer’s disease. Using novel biophysical methods, we analysed levels, particle size, and conformational characteristics of amyloid-β in the posterior cingulate cortex, hippocampus and cerebellum of 48 cases of Alzheimer’s disease with distinctly different disease durations, and correlated the data with APOE gene polymorphism. In both hippocampus and posterior cingulate cortex we identified an extensive array of distinct amyloid-β42 particles that differ in size, display of N-terminal and C-terminal domains, and conformational stability. In contrast, amyloid-β40 present at low levels did not form a major particle with discernible size, and both N-terminal and C- terminal domains were largely exposed. Rapidly progressive Alzheimer’s disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-β42, with higher levels of distinctly structured amyloid-β42 particles composed of 30–100 monomers, and fewer particles composed of < 30 monomers. The link between rapid clinical decline and levels of amyloid-β42 with distinct structural characteristics suggests that different conformers may play an important role in the pathogenesis of distinct Alzheimer’s disease phenotypes. These findings indicate that Alzheimer’s disease exhibits a wide spectrum of amyloid-β42 structural states and imply the existence of prion-like conformational strains. PMID:25688081

  1. Progress on the development of rapid methods for antimicrobial susceptibility testing.

    PubMed

    Pulido, Marina R; García-Quintanilla, Meritxell; Martín-Peña, Reyes; Cisneros, José Miguel; McConnell, Michael J

    2013-12-01

    Antimicrobial susceptibility testing is essential for guiding the treatment of many types of bacterial infections, especially in the current context of rising rates of antibiotic resistance. The most commonly employed methods rely on the detection of phenotypic resistance by measuring bacterial growth in the presence of the antibiotic being tested. Although these methods are highly sensitive for the detection of resistance, they require that the bacterial pathogen is isolated from the clinical sample before testing and must employ incubation times that are sufficient for differentiating resistant from susceptible isolates. Knowledge regarding the molecular determinants of antibiotic resistance has facilitated the development of novel approaches for the rapid detection of resistance in bacterial pathogens. PCR-based techniques, mass spectrometry, microarrays, microfluidics, cell lysis-based approaches and whole-genome sequencing have all demonstrated the ability to detect resistance in various bacterial species. However, it remains to be determined whether these methods can achieve sufficient sensitivity and specificity compared with standard phenotypic resistance testing to justify their use in routine clinical practice. In the present review, we discuss recent progress in the development of methods for rapid antimicrobial susceptibility testing and highlight the limitations of each approach that still remain be addressed.

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

    PubMed

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

    2016-08-01

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

  3. Membranous glomerulonephritis after haematopoietic cell transplantation for multiple myeloma.

    PubMed

    Rossi, L; Cardarelli, F; Vampa, M L; Buzio, C; Olivetti, G

    2001-07-01

    Renal involvement during graft-versus-host disease following haematopoietic cell transplantation for multiple myeloma has never been described. We report a case of a recipient who developed nephrotic syndrome and membranous glomerulonephritis 22 months after the graft and 6 months after cyclosporine withdrawal. Symptoms resolved when immunosuppressive therapy was reinstituted.

  4. Mechanics of progressive failures leading to rapid shallow landslides using the fiber bundle model

    NASA Astrophysics Data System (ADS)

    Cohen, Denis; Schwarz, Massimiliano; Or, Dani

    2010-05-01

    Shallow landslides are often sudden events caused by the rapid failure of a slip surface. Yet, such global failure is the culmination of a series of steps that begin with the initiation and growth of local cracks and failure planes that, with increased load eventually coalesce to form a continuous surface. The dynamics of such failure events is controlled, in part, by the rate of soil weakening during water infiltration and by distribution of tree roots that span across these failure zones. Conventional approaches rely on static limit-equilibrium analysis to compute the ratio of soil resistive strength to gravitational driving forces (factor of safety) to determine slope stability, often ignoring dynamics leading to failure as well as heterogeneities associated with land cover, subsurface material properties, hydrologic pathways, and presence of biological elements such as roots. Casting the problem in terms of stable or unstable slope does not describe the progressive formation of cracks in heterogeneous soils or the failure of roots that stretch across tension cracks or basal shear planes. Here we use the fiber bundle model (FBM) to describe soil and root failure focusing on landslide initiation. The FBM consists of a bundle of parallel, elastic-brittle fibers of identical length and stiffness stretched quasi-statically between two plates. Heterogeneity is introduced by fibers having finite threshold strength drawn randomly from a probability density function. Step-loading of the bundle causes weak fibers to break and load redistribution (either global or local) among surviving fibers can trigger secondary, tertiary, and so on, failures, a process known as an avalanche. We illustrate the potential utility of the FBM for two cases: (1) modeling of lateral root reinforcement where fibers represent roots of different sizes and strengths, and (2) modeling of progressive weakening of soils by water infiltration where fibers are analogs of bonds between soil aggregates

  5. Rapidly Progressing Refractory Hodgkin Lymphoma: A Case Report and a Possible Explanation.

    PubMed

    Jóna, Ádám; Irsai, Gábor; Barna, Sándor; Méhes, Gábor; Illés, Árpád; Váróczy, László

    2016-01-01

    Introduction. Hodgkin lymphoma is a highly curable lymphoid malignancy; however treatment of a significant number of patients remains challenging. Case Report. The authors present an unusually rapidly progressing case of refractory advanced stage classical nodular sclerosis subtype Hodgkin lymphoma with unfavorable prognosis. A 66-year-old male patient was refractory for first-line doxorubicin, bleomycin, vinblastin, dacarbazine (ABVD) treatment with persistent disease; therefore physicians changed treatment for dexamethasone, cytarabine, and cisplatin (DHAP) and later ifosfamide, gemcitabine, and vinorelbine (IGEV) regimen. Unfortunately the patient developed acute kidney and respiratory failure and died after 6 months of treatment. Current and retrospective histological examination of the patient's lymph node biopsy, skin lesion, and autopsy revealed the same aberrantly expressing CD4 positive nodular sclerosis subtype Hodgkin lymphoma. Conclusion. Aberrant expression of T-cell antigens on the Hodgkin and Reed/Sternberg cells could be associated with inferior outcome. T-cell associated antigens should be investigated more often in patients not responding sufficiently to treatment and hence treatment should be intensified or targeted therapy (brentuximab vedotin) should be considered. PMID:27429620

  6. Rapidly Progressing Refractory Hodgkin Lymphoma: A Case Report and a Possible Explanation

    PubMed Central

    Irsai, Gábor; Barna, Sándor; Méhes, Gábor; Illés, Árpád; Váróczy, László

    2016-01-01

    Introduction. Hodgkin lymphoma is a highly curable lymphoid malignancy; however treatment of a significant number of patients remains challenging. Case Report. The authors present an unusually rapidly progressing case of refractory advanced stage classical nodular sclerosis subtype Hodgkin lymphoma with unfavorable prognosis. A 66-year-old male patient was refractory for first-line doxorubicin, bleomycin, vinblastin, dacarbazine (ABVD) treatment with persistent disease; therefore physicians changed treatment for dexamethasone, cytarabine, and cisplatin (DHAP) and later ifosfamide, gemcitabine, and vinorelbine (IGEV) regimen. Unfortunately the patient developed acute kidney and respiratory failure and died after 6 months of treatment. Current and retrospective histological examination of the patient's lymph node biopsy, skin lesion, and autopsy revealed the same aberrantly expressing CD4 positive nodular sclerosis subtype Hodgkin lymphoma. Conclusion. Aberrant expression of T-cell antigens on the Hodgkin and Reed/Sternberg cells could be associated with inferior outcome. T-cell associated antigens should be investigated more often in patients not responding sufficiently to treatment and hence treatment should be intensified or targeted therapy (brentuximab vedotin) should be considered. PMID:27429620

  7. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis

    NASA Astrophysics Data System (ADS)

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-09-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862) while for subacute ILD patients (disease duration 3–6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM.

  8. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis

    PubMed Central

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-01-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3–6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM. PMID:27615411

  9. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis.

    PubMed

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-01-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3-6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM. PMID:27615411

  10. Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis

    PubMed Central

    Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie

    2016-01-01

    Abstract The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome. A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome. The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%). In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options. PMID:27258503

  11. Rapidly progressed aortic stenosis in a patient with previous diagnosis of polycythemia vera and post-polycythemia vera myelofibrosis.

    PubMed

    Kiso, Shohei; Naito, Ryo; Fukao, Kosuke; Hiki, Makoto; Miyazaki, Tetsuro; Takagi, Atsutoshi; Miyauchi, Katsumi; Daida, Hiroyuki

    2016-06-01

    Polycythemia vera (PV) is a chronic myeloproliferative disease that is often complicated with thromboembolism. However, aortic stenosis (AS) could be a manifestation of the cardiovascular complications of PV possibly through shear stress and atherosclerosis. We report a rare case of rapidly progressed AS in a patient with PV.

  12. An immunohistological study of feline glomerulonephritis using the peroxidase-antiperoxidase method.

    PubMed

    Arthur, J E; Lucke, V M; Newby, T J; Bourne, F J

    1984-07-01

    Twenty-two cases of feline glomerulonephritis were investigated for the presence of immune complexes within the glomerulus using the peroxidase-antiperoxidase (PAP) method. This method was used with formalin-fixed paraffin-wax embedded tissues which were pretreated with trypsin and with frozen sections of kidney tissue. Of a total of 25 kidney specimens examined (two cats had repeated biopsies) the composition of the deposits was 23/25 IgG, 17/25 C3, 11/25 IgM and 2/25 IgA. Serial studies of two cats showed a progression of the disease from initial nephrotic syndrome to chronic renal failure. With the more severe form of the disease there was a tendency for the deposition of complement and more than one class of immunoglobulin within the glomeruli. PMID:6382492

  13. Spontaneous mesangiocapillary glomerulonephritis in Finn cross lambs from Alberta.

    PubMed Central

    Frelier, P F; Pritchard, J; Armstrong, D L; Nagge, W T; Lewis, R M

    1984-01-01

    A spontaneous mesangiocapillary glomerulonephritis occurred in three, one to three month old Finnish Landrace cross lambs from a flock in northern Alberta. The ram was a purebred Finn sheep, and the ewes were Finn-Rambouillet and Finn-Suffolk-Rambouillet crosses. The lambs were found dead without previous clinical signs. Histologically there was marked thickening of glomerular capillary basement membranes, proliferation of mesangial cells, and peri-glomerular fibrosis. An interstitial infiltration of plasma cells and lymphocytes was present with occasional tubular degeneration and proteinaceous cast formation. Focal leukoencephalomalacia was present in one lamb. Electron microscopy demonstrated deposition of electron-dense deposits in a subendothelial location with occasional fusion of overlying foot processes in glomerular capillaries. Indirect immunofluorescence studies demonstrated positive staining material in glomerular capillary walls. These findings in Finnish Landrace cross lambs are characteristic of mesangiocapillary glomerulonephritis, a condition heretofore not reported in North America. Images Fig. 1. Fig. 2. PMID:6372972

  14. Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma

    PubMed Central

    Aderhold, Kimberly; Carpenter, Lisa; Brown, Krysta; Donato, Anthony

    2015-01-01

    Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy. PMID:26380134

  15. Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma.

    PubMed

    Aderhold, Kimberly; Carpenter, Lisa; Brown, Krysta; Donato, Anthony

    2015-01-01

    Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy. PMID:26380134

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

    PubMed Central

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

    2016-01-01

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

  17. Membranous glomerulopathy with superimposed pauci-immune necrotizing crescentic glomerulonephritis

    PubMed Central

    Fatima, Huma; Siew, Edward D.; Dwyer, Jamie P.; Paueksakon, Paisit

    2012-01-01

    We describe a 61-year-old woman with acute kidney injury, nephrotic range proteinuria and hematuria. Kidney biopsy showed membranous glomerulopathy (MG) with superimposed pauci-immune necrotizing crescentic glomerulonephritis (PNCGN). Coexistent MG and PNCGN is a rare occurrence. The diagnosis of such an exceptionally rare combination relies on the combination of renal biopsy findings and serologic testing. We also review previous reported cases and discuss possible pathogenesis of this rare dual glomerulopathy. PMID:26069808

  18. Dense deposit disease is not a membranoproliferative glomerulonephritis.

    PubMed

    Walker, Patrick D; Ferrario, Franco; Joh, Kensuke; Bonsib, Stephen M

    2007-06-01

    Dense deposit disease (first reported in 1962) was classified as subtype II of membranoproliferative glomerulonephritis in the early 1970s. Over the last 30 years, marked differences in etiology and pathogenesis between type I membranoproliferative glomerulonephritis and dense deposit disease have become apparent. The sporadic observation that dense deposit disease can be seen with markedly different light microscopy appearances prompted this study. The goal was to examine a large number of renal biopsies from around the world to characterize the histopathologic features of dense deposit disease. Eighty-one cases of dense deposit disease were received from centers across North America, Europe and Japan. Biopsy reports, light microscopy materials and electron photomicrographs were reviewed and histopathologic features scored. Sixty-nine cases were acceptable for review. Five patterns were seen: (1) membranoproliferative n=17; (2) mesangial proliferative n=30; (3) crescentic n=12; (4) acute proliferative and exudative n=8 and (5) unclassified n=2. The age range was 3-67 years, with 74% in the range of 3-20 years; 15% 21-30 years and 11% over 30 years. Males accounted for 54% and females 46%. All patients with either crescentic dense deposit disease or acute proliferative dense deposit disease were between the ages of 3 and 18 years. The essential diagnostic feature of dense deposit disease is not the membranoproliferative pattern but the presence of electron dense transformation of the glomerular basement membranes. Based upon this study and the extensive data developed over the past 30 years, dense deposit disease is clinically distinct from membranoproliferative glomerulonephritis and is morphologically heterogeneous with only a minority of cases having a membranoproliferative pattern. Therefore, dense deposit disease should no longer be regarded as a subtype of membranoproliferative glomerulonephritis. PMID:17396142

  19. Transient hyperkalemia and hypoaldosteronism in a patient with acute glomerulonephritis.

    PubMed

    Opastirakul, Sauwalak; Chartapisak, Wattana

    2002-04-01

    The authors describe a 7-year-old boy with acute glomerulonephritis, who developed acute renal failure in the early course of his disease. While the renal function and other clinical manifestations gradually improved, hyperkalemia occurred unexpectedly, and returned to normal level spontaneously after a short period of symptomatic treatment. With the result of a low transtubular potassium gradient (TTKG) level, it was concluded that hypoaldosteronism was the major cause of hyperkalemia in this patient.

  20. [Autoimmune hepatitis and membranous glomerulonephritis under immune therapy in chronic hepatitis C].

    PubMed

    Paparoupa, Maria; Huy Ho, Ngoc Ahn; Schuppert, Frank

    2016-05-01

    A 63-year-old patient is evaluated for an unclear weight loss with general malaise and fatigue for several months. Serological examination reveales the first diagnosis of a hepatitis-C-virus-genotype-1b-infection with an initial viral load of 980 000 IU / ml. The duration of the infection is suggested to be more than 6 months. Because of the initially elevated anti-nuclear-antibodies (ANA) the diagnosis of an autoimmune hepatitis needs to be excluded. All other liver related autoantibodies and the immunoglobulins (Ig) IgG, IgA and IgM are normal. A liver biopsy is conducted. After a short test with non-pegylated interferon (IFN) liver enzymes remain stable and treatment with pegylated IFN-alfa-2a and ribavirin (RBV) is initiated. The patient is a "rapid viral responder" and his viral load is found under the detection limit within 4 weeks under therapy. On the 16th week, liver enzymes increase rapidly. ANA's and IgG-immunoglobulins are positive. A second lever biopsy does not confirm the diagnosis of autoimmune hepatitis and the treatment is continued under careful observation of all relevant liver parameters. 21 weeks after the initiation of the treatment, massive peripheral edema, hypoproteinemia and proteinuria are observed. The renal biopsy reveales membranous glomerulonephritis. Because of the preserved renal function, no acute immunosuppression is initiated and the treatment gets completed after overall 24 weeks. Liver and renal parameters return quickly back to normal after treatment discharge. This is the first report of a combined autoimmune reaction with development of autoimmune hepatitis and glomerulonephritis under INF and RBV antiviral therapy for a chronic hepatitis-C-infection. The occurrence of autoimmune manifestations should especially be considered in genetically susceptible individuals or those with positive autoimmunity markers. The initiation of INF for the treatment of chronic hepatitis-C-infection has to be critically evaluated since

  1. ANCA negative pauci-immune glomerulonephritis with systemic involvement.

    PubMed

    Sampathkumar, K; Ramakrishnan, M; Sah, A K; Gowtham, S; Ajeshkumar, R N

    2010-01-01

    Systemic vasculitides (SV) are a group of diseases with multi system involvement and varied clinical presentation. Anti-neutrophil cytoplasmic antibody (ANCA) testing has high sensitivity and specificity for SV. We describe the clinical course of four patients who had pauci-immune glomerulonephritis with systemic involvement without serological ANCA positivity; they were followed up for a cumulative 55 patient months. The mean Birmingham vasculitis score score was 23. All four had systemic symptoms with arthralgias and fever (100%). Neurological manifestations were seen in two patients (66%). Accelerated hypertension was seen in one. One patient had pulmonary renal syndrome. Renal manifestation was characterized by nephrotic range of proteinuria with glomerular hematuria in all (100%) and severe renal failure requiring dialysis in three (66%). At admission the mean blood urea was 146 +/- 19 mg% and mean serum creatinine was 5.6 +/- 1.9 mg%. Renal biopsy revealed focal proliferative glomerulonephritis with crescents only in 20-30% of glomeruli. There was significant chronic interstitial involvement in two patients (66%). Therapy with pulse steroids, cyclophosphamide, and mycophenolate mofetil (MMF) was effective in three patients while one died with lung hemorrhage. In conclusion, majority of patients with ANCA negative pauci-immune glomerulonephritis have multi-system involvement at admission. Renal biopsy is characterized by focal proliferative lesions with crescents and significant chronic interstitial fibrosis. Immunosuppressive drugs in the form of corticosteroids, MMF and cyclophosphamide bring about marked renal recovery in most patients. PMID:20535271

  2. Aprotinin induced lipohypertrophy and glomerulonephritis in an insulin dependent diabetic.

    PubMed

    Dandona, P; Mier, A; Boag, F; Chappell, M; Beckett, A G

    1985-07-01

    In an insulin dependent diabetic who was hyperglycaemic and ketotic despite 3,000 u of insulin injected subcutaneously in 2 divided doses daily, 50 u of intravenous insulin infused over 24 hr restored normal glucose homeostasis. A combination of insulin (800 u) and aprotinin (10,000 u) given twice daily also produced adequate glucose homeostasis for a period of 12 months. The patient then developed local hypertrophy of subcutaneous tissue at the injection site and her diabetic control deteriorated. Non-selective proteinuria followed and she developed nephrotic syndrome. Renal biopsy revealed a membraneous glomerulonephritis with subepithelial immune complexes, appearances consistent with a drug-induced glomerulonephritis. Withdrawal of aprotinin led to a gradual remission of nephrotic syndrome and proteinuria over several months. During this period, her diabetes was well controlled with continuous subcutaneous infusion of insulin at a dose of 500 u/24 hr. This case report demonstrates: the effective use of aprotinin for prolonged periods in insulin dependent diabetics with abnormal absorption of subcutaneously injected insulin; aprotinin induced lipohypertrophy which was not observed when insulin was injected alone; aprotinin-associated glomerulonephritis and nephrotic syndrome; the effective use of CSII--at higher insulin doses--in such patients with subcutaneous malabsorption of insulin.

  3. Posterior segment findings in a patient with immunotactoid glomerulonephritis

    PubMed Central

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

    2015-01-01

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

  4. Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

    PubMed

    Rabasco, Cristina; Cavero, Teresa; Román, Elena; Rojas-Rivera, Jorge; Olea, Teresa; Espinosa, Mario; Cabello, Virginia; Fernández-Juarez, Gema; González, Fayna; Ávila, Ana; Baltar, José María; Díaz, Montserrat; Alegre, Raquel; Elías, Sandra; Antón, Monserrat; Frutos, Miguel Angel; Pobes, Alfonso; Blasco, Miguel; Martín, Francisco; Bernis, Carmen; Macías, Manuel; Barroso, Sergio; de Lorenzo, Alberto; Ariceta, Gema; López-Mendoza, Manuel; Rivas, Begoña; López-Revuelta, Katia; Campistol, José María; Mendizábal, Santiago; de Córdoba, Santiago Rodríguez; Praga, Manuel

    2015-11-01

    C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis. PMID:26221755

  5. Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

    PubMed

    Rabasco, Cristina; Cavero, Teresa; Román, Elena; Rojas-Rivera, Jorge; Olea, Teresa; Espinosa, Mario; Cabello, Virginia; Fernández-Juarez, Gema; González, Fayna; Ávila, Ana; Baltar, José María; Díaz, Montserrat; Alegre, Raquel; Elías, Sandra; Antón, Monserrat; Frutos, Miguel Angel; Pobes, Alfonso; Blasco, Miguel; Martín, Francisco; Bernis, Carmen; Macías, Manuel; Barroso, Sergio; de Lorenzo, Alberto; Ariceta, Gema; López-Mendoza, Manuel; Rivas, Begoña; López-Revuelta, Katia; Campistol, José María; Mendizábal, Santiago; de Córdoba, Santiago Rodríguez; Praga, Manuel

    2015-11-01

    C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

  6. Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge.

    PubMed

    N Cagney, Daniel; Alexander, Brian M; Hodi, F Stephen; Buchbinder, Elizabeth I; Ott, Patrick A; Aizer, Ayal A

    2016-09-01

    Novel systemic therapies with anti-tumor activity in the brain including small molecules targeting BRAF and MEK, and immune checkpoint inhibition, offer the possibility of improved control of intracranial disease. A number of prospective trials support the judicious use of modern systemic therapies in patients with melanoma and limited brain metastases .The intracranial clinical course of patients who progress extracranially on BRAF/MEK inhibition remains poorly described in the literature. In this report, we highlight a series of clinical cases, with rapid progression of intracranial disease following discontinuation of dabrafenib/trametinib for extracranial disease progression or toxicity, a previously unreported finding in the medical literature with significant implications for patient care.

  7. Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cottenie, Ellen; Menezes, Manoj P; Rossor, Alexander M; Morrow, Jasper M; Yousry, Tarek A; Dick, David J; Anderson, Janice R; Jaunmuktane, Zane; Brandner, Sebastian; Blake, Julian C; Houlden, Henry; Reilly, Mary M

    2013-05-01

    Charcot-Marie-Tooth disease type 4J (CMT4J), a rare form of demyelinating CMT, caused by recessive mutations in the phosphoinositide phosphatase FIG4 gene, is characterised by progressive proximal and distal weakness and evidence of chronic denervation in both proximal and distal muscles. We describe a patient with a previous diagnosis of CMT1 who presented with a two year history of rapidly progressive weakness in a single limb, resembling an acquired inflammatory neuropathy. Nerve conduction studies showed an asymmetrical demyelinating neuropathy with conduction block and temporal dispersion. FIG4 sequencing identified a compound heterozygous I41T/K278YfsX5 genotype. CMT4J secondary to FIG4 mutations should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy, especially if there is a background history of a more slowly progressive neuropathy.

  8. Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis

    PubMed Central

    Pinto, Sergio Wyton L.; Mastroianni-Kirsztajn, Gianna; Sesso, Ricardo

    2015-01-01

    Background Scarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998, that were also previously evaluated 2 and 5 years after the acute episode. Methods In this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria. Results Comparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m2 and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p = 0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed additional reduction of renal function using serum creatinine, eGFR and cystatin C. Conclusions During the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur. PMID:25962068

  9. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    SciTech Connect

    Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

    2011-02-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  10. Syndrome of rapid-onset end-stage renal disease: a new unrecognized pattern of CKD progression to ESRD.

    PubMed

    Onuigbo, Macaulay A C

    2010-01-01

    By most estimates, we have an increasing worldwide end-stage renal disease (ESRD) epidemic. This is despite at least two decades of intensified reno-protection strategies, including attempts at optimal hypertension management, optimization of diabetic control, smoking cessation efforts, and the extensive application of renin-angiotensin-aldosterone system (RAAS) blockade in both diabetic and nondiabetic chronic nephropathies. The current consensus is that chronic kidney disease (CKD) progression to ESRD is a continuous, progressive, and predictable loss of estimated glomerular filtration rate (eGFR) in CKD patients, inexorably leading to ESRD. Our recent experience in a Mayo Health System Hypertension Clinic, as well as new reports associating ESRD development in CKD patients with episodes of acute kidney injury (AKI), led us to hypothesize that CKD to ESRD progression may not be that predictable, after all. Among a 100 high-risk CKD patient cohort that we have followed up prospectively since 2002, we demonstrated that in 15 of 17 (88%) patients who progressed to ESRD, progression from CKD to ESRD was unpredictable, nonlinear, abrupt, and rapid, and this followed AKI secondary to medical and surgical events. We have coined a new term, the syndrome of rapid-onset end-stage renal disease (SORO-ESRD), to represent this unrecognized syndrome. Larger studies are warranted to confirm our single-center findings. If confirmed to represent a significant proportion of the ESRD population, at least here in the United States, this finding will demand major paradigm shifts in the current concepts of reno-protection and "A-V Fistula first" programs.

  11. Proliferative glomerulonephritis with monoclonal IgG deposits in a patient with autoimmune hemolytic anemia.

    PubMed

    Fujiwara, Takashi; Komatsuda, Atsushi; Ohtani, Hiroshi; Togashi, Masaru; Sawada, Ken-Ichi; Wakui, Hideki

    2013-06-01

    A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.

  12. Toward quantitating the burden of glomerulonephritis in the United States.

    PubMed

    Cattran, Daniel C

    2016-10-01

    Previous data attempting to quantitate the national burden of glomerulonephritis (GN) have been derived from regional biopsy series or end-stage renal disease registries. Wetmore et al. is the first to address this question based on claims data extracted from 2 large U.S. health care systems. Although there are limitations, it provides broad-based epidemiological data that demonstrate a significant underestimate of the extent of GN disease and provide an important first step in its quantitation. PMID:27633866

  13. Monoclonal gammopathy associated membranous glomerulonephritis: A rare entity

    PubMed Central

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

    2015-01-01

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

  14. Developing Learning Progressions in Support of the New Science Standards: A RAPID Workshop Series

    ERIC Educational Resources Information Center

    Rogat, Aaron

    2011-01-01

    The hypothetical learning progressions presented here are the products of the deliberations of two working groups of science education researchers, each group also including a state science curriculum supervisor, organized by the Consortium for Policy Research in Education (CPRE), with support from the National Science Foundation. Their charge was…

  15. Statins and progressive renal disease.

    PubMed

    Buemi, Michele; Senatore, Massimino; Corica, Francesco; Aloisi, Carmela; Romeo, Adolfo; Cavallaro, Emanuela; Floccari, Fulvio; Tramontana, Domenico; Frisina, Nicola

    2002-01-01

    Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans.

  16. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome

    PubMed Central

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

    2016-01-01

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

  17. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease

    PubMed Central

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

    2016-01-01

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

  18. [The role of oxygen radicals in the pathogenesis of glomerulonephritis].

    PubMed

    Zima, T; Tesar, V; Stípek, S; Nĕmecek, K; Pláteník, J

    1995-11-15

    In the pathogenesis of glomerulonephritis, acute renal failure, pyelonephritis and other diseases of the kidneys oxygen radicals are involved. Some types of glomerulonephritis are characterized by infiltration of the glomeruli by neutrophils and monocytes which can form oxygen radicals (superoxide, hydrogen peroxide). The increased amount of cAMP in glomeruli can be due to oxygen radicals. Cyclic nucleotides modulate the inflammatory or immune response in glomerular disease and play a part in the action of local mediators of the inflammation. Oxygen radicals act as second messenger for the activation of cytokines via NF-kappaB transcription factor, they stimulate the formation of TNF-alpha, IL-1, IL-6 and influence the expression of monocyte-specific cytokines (CSF-1 and MCP-1). Radicals formed by the system myeloperoxidase--hydrogen peroxide--halogen derivatives activate proteolytic enzymes (proteinases) which break down collagen and other components of the extracellular matrix present in the basal membrane of glomeruli and in the mesangium. Oxygen radicals and proteinases can cause and amplify glomerular damage. Glucocorticoid administration leads to an increased activity of endogenous antioxidant enzymes in the glomerulus and reduced the of lipid peroxidation.

  19. A strategy to find gene combinations that identify children who progress rapidly to type 1 diabetes after islet autoantibody seroconversion.

    PubMed

    Bonifacio, Ezio; Krumsiek, Jan; Winkler, Christiane; Theis, Fabian J; Ziegler, Anette-Gabriele

    2014-01-01

    We recently developed a novel approach capable of identifying gene combinations to obtain maximal disease risk stratification. Type 1 diabetes has a preclinical phase including seroconversion to autoimmunity and subsequent progression to diabetes. Here, we applied our gene combination approach to identify combinations that contribute either to islet autoimmunity or to the progression from islet autoantibodies to diabetes onset. We examined 12 type 1 diabetes susceptibility genes (INS, ERBB3, PTPN2, IFIH1, PTPN22, KIAA0350, CD25, CTLA4, SH2B3, IL2, IL18RAP, IL10) in a cohort of children of parents with type 1 diabetes and prospectively followed from birth. The most predictive combination was subsequently applied to a smaller validation cohort. The combinations of genes only marginally contributed to the risk of developing islet autoimmunity, but could substantially modify risk of progression to diabetes in islet autoantibody-positive children. The greatest discrimination was provided by risk allele scores of five genes, INS, IFIH1, IL18RAP, CD25, and IL2 genes, which could identify 80 % of islet autoantibody-positive children who progressed to diabetes within 6 years of seroconversion and discriminate high risk (63 % within 6 years; 95 % CI 45-81 %) and low risk (11 % within 6 years; 95 % CI 0.1-22 %; p = 4 × 10(-5)) antibody-positive children. Risk stratification by these five genes was confirmed in a second cohort of islet autoantibody children. These findings highlight genes that may affect the rate of the beta-cell destruction process once autoimmunity has initiated and may help to identify islet autoantibody-positive subjects with rapid progression to diabetes.

  20. Rapid Progression to Decompensated Cirrhosis, Liver Transplant, and Death in HIV-Infected Men After Primary Hepatitis C Virus Infection

    PubMed Central

    Fierer, Daniel S.; Dieterich, Douglas T.; Fiel, M. Isabel; Branch, Andrea D.; Marks, Kristen M.; Fusco, Dahlene N.; Hsu, Ricky; Smith, Davey M.; Fierer, Joshua

    2013-01-01

    Background. We and others have shown that primary hepatitis C (HCV) infection in men infected with human immunodeficiency virus (HIV) causes early-onset liver fibrosis; however, little is known about the long-term natural history of the liver disease in these HIV-infected men. Methods. We followed a cohort of HIV-infected men with primary HCV infection in New York City. Results. Four men who were not cured after their primary HCV infection developed decompensated cirrhosis within 17 months to 6 years after primary HCV infection. Three died within 8 years of primary HCV infection, and 1 survived after liver transplant done 2 years after primary HCV infection. Three of the 4 men had AIDS at the time of primary HCV infection, and the most rapid progression occurred in the 2 men with the lowest CD4 counts at the time of HCV infection. Liver histopathology was most consistent with HCV-induced damage even though some had exposures to other potential hepatotoxins. Conclusions. Primary HCV infection resulted in decompensated cirrhosis and death within 2–8 years in 4 HIV-infected men. The rapid onset of fibrosis due to primary HCV infection in HIV-infected men cannot therefore be considered benign. The rate of continued progression to liver failure may be proportional to the degree of underlying immunocompromise caused by HIV infection. More research is needed to better define the mechanisms behind accelerated liver damage. PMID:23264364

  1. Pauci-Immune Necrotizing and Crescentic Glomerulonephritis with Membranous Lupus Nephritis, Fifteen Years after Initial Diagnosis of Secondary Membranous Nephropathy

    PubMed Central

    Burkhart, Ryan; Shah, Nina; Abel, Michael; Oliver, James D.; Lewin, Matthew

    2015-01-01

    Renal involvement in systemic lupus erythematosus (SLE) is usually immune complex mediated and may have multiple different presentations. Pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) refers to extensive glomerular inflammation with few or no immune deposits that may result in rapid decline in renal function. We report a case of a 79-year-old Hispanic male with a history of secondary membranous nephropathy (diagnosed by renal biopsy 15 years previously) who was admitted with acute kidney injury and active urinary sediment. P-ANCA titers and anti-myeloperoxidase antibodies were positive. The renal biopsy was diagnostic for NCGN superimposed on a secondary membranous nephropathy. A previous diagnosis of SLE based on American College of Rheumatology criteria was discovered via Veteran's Administration records review after the completion of treatment for pauci-immune NCGN. ANCAs are detected in 20–31% of patients with SLE. There may be an association between SLE and ANCA seropositivity. In patients with lupus nephritis and biopsy findings of necrotizing and crescentic glomerulonephritis, without significant immune complex deposition, ANCA testing should be performed. In patients with secondary membranous nephropathy SLE should be excluded. PMID:26558120

  2. High Soluble CD14 Levels at Primary HIV-1 Infection Predict More Rapid Disease Progression.

    PubMed

    Krastinova, Evguenia; Lecuroux, Camille; Leroy, Carole; Seng, Remonie; Cabie, Andre; Rami, Agathe; Venet, Alain; Meyer, Laurence; Goujard, Cecile

    2015-09-15

    The soluble CD14 (sCD14) level was found associated with mortality during the chronic phase of human immunodeficiency virus (HIV) infection. Here we assessed its prognostic value in 138 patients with primary HIV infection. Higher sCD14 levels were associated with death, from myocardial infarction, but this was based on 3 deaths only. Among 68 untreated patients, those with higher sCD14 levels had more rapid spontaneous CD4 cell decline during the first 18 months following primary infection. This association persisted after adjustment for age, the CD4 cell count, and HIV viral load at diagnosis.

  3. Combination of cyclophosphamide and interferon-β halts progression in patients with rapidly transitional multiple sclerosis

    PubMed Central

    Patti, F; Cataldi, M; Nicoletti, F; Reggio, E; Nicoletti, A; Reggio, A

    2001-01-01

    The effects of combined treatment with cyclophosphamide (CTX) and interferon-β (IFN-β) are described in selected patients with "rapidly transitional" multiple sclerosis. This form of multiple sclerosis is extremely active with very frequent and severe attacks which produce a dramatic increase on the expanded disability status scale (EDSS). Ten patients with rapidly transitional multiple sclerosis were previously treated with interferon-β, but none benefited by this treatment. Monthly treatment with intravenous CTX, from 500 mg/m2 to 1500 mg/m2 to obtain a chronic lymphocytopenia (600/mm3 to 900/mm3) produced a marked and significant reduction in the number of relapses (p<0.0001), disability previously accumulated (p<0.0001), and a reduction of T2 MRI burden of lesion. This particular group of patients benefited by combining cyclophosphamide and IFN-β. The possibility is considered of carrying out further studies to test the efficacy of the association between the two drugs for patients who are not responsive to IFN-β or other active disease modifying therapies.

 PMID:11511721

  4. MM1+2C sporadic Creutzfeldt-Jakob disease presenting as rapidly progressive nonfluent aphasia.

    PubMed

    Allegri, Ricardo F; Bartoloni, Leonardo; Iturry, Mónica; Romero, Carlos; Begué, Christián; Sevlever, Gustavo; Taratuto, Ana Lía

    2014-01-01

    We report a 77-year-old man, presenting with progressive aphasia as an initial symptom, who developed severe dementia over the course of 20 months. Frontal cortex PrPSc western blot was type 2 and codon 129 was MM; brain neuropathology showed cortical vacuoles with perivacuolar PrP immunostaining characteristic of MM2C. Cerebellum showed focal coarse, patchy staining in different sections of the molecular layer, diffuse fine punctuate and coarse PrP immunopositive deposits in the granule cell layer, and focal synaptic immunostaining in the molecular layer, suggestive of MM1+2C by histotyping. This clinical presentation has not yet been described in an MM1+2C subtype by histotyping.

  5. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    PubMed Central

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  6. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, July--September 1992

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1992-11-01

    Knowledge of the thermodynamic and morphological properties of coal associated with rapid heating decomposition pathways is essential to progress in coal utilization technology. Specifically, knowledge of the heat of devolatilization, surface area and density of coal as a function of rank characteristics, temperature and extent of devolatilization in the context of rapid heating conditions is required both, for the fundamental determination of kinetic parameters of coal devolatilization, and to refine existing devolatilization sub-models used in comprehensive coal combustion codes. The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: The specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars.

  7. Leptospirosis Presenting with Rapidly Progressing Acute Renal Failure and Conjugated Hyperbilirubinemia: A Case Report.

    PubMed

    Pothuri, Pallavi; Ahuja, Keerat; Kumar, Viki; Lal, Sham; Tumarinson, Taisiya; Mahmood, Khalid

    2016-01-01

    BACKGROUND Unexplained renal insufficiency combined with hepatic failure is a common problem encountered by clinicians. As with many disease processes involving multi-organ systems, reversible causes are usually not readily identifiable, and for many patients their health deteriorates rapidly. We present a rare cause of acute renal failure and hyperbilirubinemia occurring simultaneously, with leptospirosis presenting as Weil's disease. CASE REPORT A 53-year-old male presented to our clinic with complaints of anuria over the past two days. His symptoms started with dark urine, severe cramps in the thighs, and chills. The patient was a visitor to the United States from Guyana. Positive physical examination findings included mild tachycardia and hypotension, scleral icterus, and tenderness over abdomen, costovertebral angles, and thighs. The patient had a high white blood cell count, thrombocytopenia, renal/hepatic insufficiency, and an urinary tract infection (UTI). The patient was initially treated under the suspicion of acute kidney injury secondary to rhabdomyolysis and pyelonephritis. The patient continued to deteriorate with decreasing platelet counts, worsening renal function, hyperbilirubinemia, and respiratory distress, with no improvement with hemodialysis. Broad-spectrum antibiotics were administered, including doxycycline, due to a high suspicion of leptospirosis. The patient's condition drastically improved after initiation of doxycycline. On subsequent days, the patient's Leptospira antibody results were available, showing titers of more than 1:3200. Hemodialysis was discontinued as the patient started producing urine with improved kidney function. CONCLUSIONS As world travel becomes more economically feasible, we will continue to encounter foreign endemic diseases. Leptospirosis presenting as Weil's disease is a common cause of renal and hyperbilirubinemia in endemic areas. Often, as was the case for our patient where the time from presentation to acute

  8. An Autopsy Case of Anti-melanoma Differentiation-associated Gene-5 Antibody-positive Clinical Amyopathic Dermatomyositis Complicated by Rapidly Progressive Interstitial Lung Disease.

    PubMed

    Yoshida, Naomi; Kaieda, Shinjiro; Tomozoe, Kumi; Tajiri, Morihiro; Wakasugi, Daisuke; Okamoto, Masaki; Tominaga, Masaki; Ida, Hiroaki; Hoshino, Tomoaki

    2016-01-01

    A 62-year-old man presented with heliotrope rash, Gottron's sign, and mild muscle weakness. Both of his lung fields showed interstitial changes that worsened rapidly. He was diagnosed with clinical amyopathic dermatomyositis with rapidly progressive interstitial lung disease. The patient died of respiratory failure, despite the administration of immunosuppressive therapy. Autopsy revealed diffuse alveolar damage. An antibody analysis, which was performed postmortem, detected the presence of anti-melanoma differentiation-associated gene (MDA)-5 antibodies. Clinicians should note the clinical, radiologic, and serologic findings to predict anti-MDA-5 antibody-associated rapidly progressive interstitial lung disease. PMID:27301523

  9. Leptospirosis Presenting with Rapidly Progressing Acute Renal Failure and Conjugated Hyperbilirubinemia: A Case Report

    PubMed Central

    Pothuri, Pallavi; Ahuja, Keerat; Kumar, Viki; Lal, Sham; Tumarinson, Taisiya; Mahmood, Khalid

    2016-01-01

    Patient: Male, 53 Final Diagnosis: Leptospirosis Symptoms: — Medication: — Clinical Procedure: None Specialty: Infectious Diseases Objective: Rare disease Background: Unexplained renal insufficiency combined with hepatic failure is a common problem encountered by clinicians. As with many disease processes involving multi-organ systems, reversible causes are usually not readily identifiable, and for many patients their health deteriorates rapidly. We present a rare cause of acute renal failure and hyperbilirubinemia occurring simultaneously, with leptospirosis presenting as Weil’s disease. Case Report: A 53-year-old male presented to our clinic with complaints of anuria over the past two days. His symptoms started with dark urine, severe cramps in the thighs, and chills. The patient was a visitor to the United States from Guyana. Positive physical examination findings included mild tachycardia and hypotension, scleral icterus, and tenderness over abdomen, costovertebral angles, and thighs. The patient had a high white blood cell count, thrombocytopenia, renal/hepatic insufficiency, and an urinary tract infection (UTI). The patient was initially treated under the suspicion of acute kidney injury secondary to rhabdomyolysis and pyelonephritis. The patient continued to deteriorate with decreasing platelet counts, worsening renal function, hyperbilirubinemia, and respiratory distress, with no improvement with hemodialysis. Broad-spectrum antibiotics were administered, including doxycycline, due to a high suspicion of leptospirosis. The patient’s condition drastically improved after initiation of doxycycline. On subsequent days, the patient’s Leptospira antibody results were available, showing titers of more than 1:3200. Hemodialysis was discontinued as the patient started producing urine with improved kidney function. Conclusions: As world travel becomes more economically feasible, we will continue to encounter foreign endemic diseases. Leptospirosis

  10. Large cross-sectional study of presbycusis reveals rapid progressive decline in auditory temporal acuity.

    PubMed

    Ozmeral, Erol J; Eddins, Ann C; Frisina, D Robert; Eddins, David A

    2016-07-01

    The auditory system relies on extraordinarily precise timing cues for the accurate perception of speech, music, and object identification. Epidemiological research has documented the age-related progressive decline in hearing sensitivity that is known to be a major health concern for the elderly. Although smaller investigations indicate that auditory temporal processing also declines with age, such measures have not been included in larger studies. Temporal gap detection thresholds (TGDTs; an index of auditory temporal resolution) measured in 1071 listeners (aged 18-98 years) were shown to decline at a minimum rate of 1.05 ms (15%) per decade. Age was a significant predictor of TGDT when controlling for audibility (partial correlation) and when restricting analyses to persons with normal-hearing sensitivity (n = 434). The TGDTs were significantly better for males (3.5 ms; 51%) than females when averaged across the life span. These results highlight the need for indices of temporal processing in diagnostics, as treatment targets, and as factors in models of aging. PMID:27255816

  11. Large cross-sectional study of presbycusis reveals rapid progressive decline in auditory temporal acuity.

    PubMed

    Ozmeral, Erol J; Eddins, Ann C; Frisina, D Robert; Eddins, David A

    2016-07-01

    The auditory system relies on extraordinarily precise timing cues for the accurate perception of speech, music, and object identification. Epidemiological research has documented the age-related progressive decline in hearing sensitivity that is known to be a major health concern for the elderly. Although smaller investigations indicate that auditory temporal processing also declines with age, such measures have not been included in larger studies. Temporal gap detection thresholds (TGDTs; an index of auditory temporal resolution) measured in 1071 listeners (aged 18-98 years) were shown to decline at a minimum rate of 1.05 ms (15%) per decade. Age was a significant predictor of TGDT when controlling for audibility (partial correlation) and when restricting analyses to persons with normal-hearing sensitivity (n = 434). The TGDTs were significantly better for males (3.5 ms; 51%) than females when averaged across the life span. These results highlight the need for indices of temporal processing in diagnostics, as treatment targets, and as factors in models of aging.

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

    PubMed Central

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

    1974-01-01

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

  13. [A case of crescentic glomerulonephritis developed under oral anastrozole treatment].

    PubMed

    Yoshimoto, Shuhei; Nakatani, Kimihiko; Maruyama, Naoki; Fujiki, Kengo; Nakano, Tomoya; Ueshima, Kazuhiro; Fujimoto, Takatomi; Oka, Hiroyasu; Ishikawa, Hirofumi; Inoue, Fumitaka

    2013-02-01

    A 69-year-old postmenopausal woman who was prescribed anastrozole for 10 months after surgical removal of her breast cancer, was referred to our hospital for acute renal failure. Because it was possible that her renal failure was related to her treatment with anastrozole, the treatment was immediately discontinued. After renal biopsy was performed to examine her renal failure, she was diagnosed as crescentic glomerulonephritis, probably related with the treatment of anastrozole. Twenty mg of oral prednisolone was administered daily after methylprednisolone pulse therapy(500 mg/day intravenous administration for three days). Her renal dysfunction was gradually improved. Renal dysfunction was considered to be a rare complication of anastrozole. Patients who are prescribed anastrozole should be watched carefully for the development of renal dysfunction.

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

    PubMed

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

    2013-11-01

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

  15. Glomerulonephritis and managing the risks of chronic renal disease.

    PubMed

    Singh, Gurmeet R

    2009-12-01

    The rising global burden of chronic renal disease, the high cost of providing renal replacement therapies, and renal disease also being a risk factor for cardiovascular disease is increasing focus on renal disease prevention. This article focuses on the aspects of renal disease (specifically poststreptococcal glomerulonephritis [PSGN] and chronic kidney disease [CKD]) in Indigenous populations in Australia, New Zealand, Canada, and the United States that diverge from those typically seen in the general population of those countries. The spectrum of renal and many other diseases seen in Indigenous people in developed countries is similar to that seen in developing countries. Diseases like PSGN that have largely disappeared in developed countries still occur frequently in Indigenous people. CKD during the childhood years is due to congenital anomalies of the kidney and urinary tract in up to 70% of cases and occurs later in polycystic kidney disease and childhood-onset diabetes. Several risk factors for CKD in adulthood are already present in childhood.

  16. Final Progress Report: Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes Feasibility Study

    SciTech Connect

    Rawool-Sullivan, Mohini; Bounds, John Alan; Brumby, Steven P.; Prasad, Lakshman; Sullivan, John P.

    2012-04-30

    This is the final report of the project titled, 'Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes,' PMIS project number LA10-HUMANID-PD03. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). It summarizes work performed over the FY10 time period. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). Human analysts begin analyzing a spectrum based on features in the spectrum - lines and shapes that are present in a given spectrum. The proposed work was to carry out a feasibility study that will pick out all gamma ray peaks and other features such as Compton edges, bremsstrahlung, presence/absence of shielding and presence of neutrons and escape peaks. Ultimately success of this feasibility study will allow us to collectively explain identified features and form a realistic scenario that produced a given spectrum in the future. We wanted to develop and demonstrate machine learning algorithms that will qualitatively enhance the automated identification capabilities of portable radiological sensors that are currently being used in the field.

  17. Rapidly progressing fatal reperfusion syndrome caused by acute critical ischemia of the lower limb.

    PubMed

    Szijártó, Attila; Turóczi, Zsolt; Szabó, József; Kaliszky, Péter; Gyurkovics, Endre; Arányi, Péter; Regáli, László; Harsányi, László; Lotz, Gábor

    2013-01-01

    The most severe complication of ischemia-reperfusion injury following lower limb arterial surgery is reperfusion syndrome. Therefore, our aim was to describe the extent of muscle damage and the reperfusion syndrome-related remote organ lesions in detail, through a well-documented case of long-lasting infrarenal aorta thrombosis. After urgent revascularization, several clinical signs of multiple organ dysfunction were detectable, including the circulatory, urinary, respiratory, gastrointestinal, and hemostatic systems. Upon histological examination, intraoperative muscle biopsy showed severe muscle damage. Muscle fiber viability was assessed with a special nitroblue tetrazolium staining-based viability test developed by our team; the obtained results indicated significant degree of muscle damage before this was confirmed by conventional histological methods. Thorough postmortem examination confirmed the presence of remote organ damage. The pathological findings included acute tubular necrosis, myocardial and jejunal infarctions, ischemic pancreatitis, and diffuse alveolar damage with hyaline membrane formation in the lungs and focal centrilobular liver necrosis. By using special staining techniques, the presence of myoglobin and lipofuscin deposits was confirmed in the kidney samples. In this paper, we present a patient who developed all major complications following long-lasting arterial occlusion. We also introduce a novel method to assess the degree of ischemic injury, which may be suitable in the near future for the rapid detection of irreversible muscle injury. Therefore, the mortality of the disease might be reduced.

  18. Glomerulonephritis in water buffaloes (Bubalus bubalis) naturally infected by Fasciola hepatica.

    PubMed

    Marques, Sandra Márcia Tietz; Scroferneker, Maria Lúcia; Edelweiss, Maria Isabel Albano

    2004-08-13

    Glomerulonephritis caused by Fasciola hepatica was observed in buffaloes. Renal biopsies of 20 buffaloes, 11 with F. hepatica and 9 uninfected buffaloes (controls), were examined by light microscopy, direct and indirect immunofluorescence, and immunohistochemical analysis. The biopsies of seven (63.6%) infected buffaloes revealed membranoproliferative glomerulonephritis, three biopsies (27.3%) showed mesangioproliferative glomerulonephritis, and one kidney presented normal biopsy specimens. In the control group, seven buffaloes (77.8%) presented normal biopsy specimens, while two (22.2%) revealed glomerulonephritis-one with a membranoproliferative pattern, and the other with a mesangioproliferative pattern-with extensive inflammatory cell infiltrate. Our conclusion is that glomerulopathy is associated with fascioliasis and that buffaloes are suitable as a naturally existing experimental model of renal injury by circulating immune complexes.

  19. Rapid mass spectrometric DNA diagnostics for assessing microbial community activity during bioremediation. 1997 annual progress report

    SciTech Connect

    Benner, W.H.; Hunter-Cevera, J.

    1997-01-01

    'The effort of the past year''s activities, which covers the first year of the project, was directed at developing DNA-based diagnostic procedures for implementation in high through-put analytical instrumentation. The diagnostic procedures under evaluation are designed to identify specific genes in soil microorganisms that code for pollutant-degrading enzymes. Current DNA-based diagnostic procedures, such as the ligase chain reaction (LCR) and the polymerase chain reaction (PCR), rely on gel electrophoresis as a way to score a diagnostic test. The authors are attempting to implement time-of-flight (TOF) mass spectrometry as a replacement for gel separations because of its speed advantage and potential for sample automation. The authors anticipate that if TOF techniques can be implemented in the procedures, then a very large number of microorganisms and soil samples can be screened for the presence of specific pollutant-degrading genes. The use of DNA-based procedures for the detection of biodegrading organisms or genes that code for pollutant-degrading enzymes constitutes a critical technology for following biochemical transformation and substantiating the impact of bioremediation. DNA-based technology has been demonstrated to be a sensitive technique for tracking micro-organism activity at the molecular level. These procedures can be tuned to identify groups of organisms, specific organisms, and activity at the molecular level. They are developing a P-monitoring strategy that relies on the combined use of DNA diagnostics with mass spectrometry as the detection scheme. The intent of this work is a two-fold evaluation of (1) the feasibility of replacing the use of gel separations for identifying polymerase chain reaction (PCR) products with a rapid and automatable form of electrospray mass spectrometry and (2) the use of matrix-assisted-laser-desorption-ionization mass spectrometry (MALDI-MS) as a tool to score oligonucleotide ligation assays (OLA).'

  20. Unilaterally and rapidly progressing white matter lesion and elevated cytokines in a patient with Tay-Sachs disease.

    PubMed

    Hayase, Tomomi; Shimizu, Jun; Goto, Tamako; Nozaki, Yasuyuki; Mori, Masato; Takahashi, Naoto; Namba, Eiji; Yamagata, Takanori; Momoi, Mariko Y

    2010-03-01

    We report the case of a girl with Tay-Sachs disease who had convulsions and deteriorated rapidly after an upper respiratory infection at the age of 11 months. At the age of 16 months, her seizures became intractable and magnetic resonance imaging of the brain showed high signal intensity on T2-weighted images and marked swelling in the white matter and basal nucelei of the right hemisphere. Her seizures and right hemisphere lesion improved with glycerol and dexamethasone treatment. When dexamethasone was discontinued, her symptoms worsened and lesions later appeared in the left hemisphere. Her cerebrospinal fluid showed elevated levels of the cytokines TNF-alpha and IL-5. It is considered that inflammation contributes to disease progression in Tay-Sachs disease.

  1. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease

    PubMed Central

    Hill, Rebecca M.; Kuijper, Sanne; Lindsey, Janet C.; Petrie, Kevin; Schwalbe, Ed C.; Barker, Karen; Boult, Jessica K.R.; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L.; Poon, Evon; Robinson, Simon P.; Ruddle, Ruth; Raynaud, Florence I.; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W.; Wharton, Stephen B.; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S.; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J.; Weiss, William A.; Chesler, Louis; Clifford, Steven C.

    2015-01-01

    Summary We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. PMID:25533335

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

    PubMed Central

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

    2015-01-01

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

  3. Whole Exome Sequencing of Rapid Autopsy Tumors and Xenograft Models Reveals Possible Driver Mutations Underlying Tumor Progression.

    PubMed

    Xie, Tao; Musteanu, Monica; Lopez-Casas, Pedro P; Shields, David J; Olson, Peter; Rejto, Paul A; Hidalgo, Manuel

    2015-01-01

    Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy due to its propensity to invade and rapidly metastasize and remains very difficult to manage clinically. One major hindrance towards a better understanding of PDAC is the lack of molecular data sets and models representative of end stage disease. Moreover, it remains unclear how molecularly similar patient-derived xenograft (PDX) models are to the primary tumor from which they were derived. To identify potential molecular drivers in metastatic pancreatic cancer progression, we obtained matched primary tumor, metastases and normal (peripheral blood) samples under a rapid autopsy program and performed whole exome sequencing (WES) on tumor as well as normal samples. PDX models were also generated, sequenced and compared to tumors. Across the matched data sets generated for three patients, there were on average approximately 160 single-nucleotide mutations in each sample. The majority of mutations in each patient were shared among the primary and metastatic samples and, importantly, were largely retained in the xenograft models. Based on the mutation prevalence in the primary and metastatic sites, we proposed possible clonal evolution patterns marked by functional mutations affecting cancer genes such as KRAS, TP53 and SMAD4 that may play an important role in tumor initiation, progression and metastasis. These results add to our understanding of pancreatic tumor biology, and demonstrate that PDX models derived from advanced or end-stage likely closely approximate the genetics of the disease in the clinic and thus represent a biologically and clinically relevant pre-clinical platform that may enable the development of effective targeted therapies for PDAC.

  4. Functional and structural changes in end-stage kidney disease due to glomerulonephritis induced by the recombinant alpha3(IV)NC1 domain.

    PubMed

    Nishibayashi, Seiji; Hattori, Katsuji; Hirano, Takahiro; Uehara, Kenji; Nakano, Yoshimasa; Aihara, Miki; Yamada, Yoshihisa; Muraguchi, Masahiro; Iwata, Fusako; Takiguchi, Yoshiharu

    2010-01-01

    The aim of this study was to develop and characterize a rat glomerulonephritis model, which progresses to renal fibrosis and renal failure. A single immunization of female WKY rats with more than 10 microg of recombinant alpha3(IV)NC1 protein caused severe proteinuria followed by progressive increases in plasma creatinine and blood urea nitrogen (BUN) level within 42 days. Sequential histopathological evaluation revealed crescent formation in glomeruli followed by tubular dilation and interstitial fibrosis. Hydroxyproline content and expression of type I collagen and smooth muscle actin genes in the renal cortex increased as renal dysfunction progressed. Furthermore, the TGF-beta1 level in the renal cortex also increased. In the evaluation of antinephritic agents in this model, prednisolone and mycophenolate mofetil (MMF) treatment significantly decreased plasma creatinine and BUN, and suppressed renal fibrosis and histological changes involving crescent formation, compared with the vehicle-treated nephritic rats, whereas lisinopril treatment failed to improve renal function and histology. We demonstrated that immunization of female WKY rats with a sufficient dose of recombinant alpha3(IV)NC1 induces end-stage kidney disease accompanied by renal fibrosis. The relatively short period needed to induce the disease and the high incidence of functional and structural changes were considered a great advantage of this model for clarifying the mechanisms of progressive glomerulonephritis and for evaluating agents used to treat renal failure. PMID:20484849

  5. Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis

    PubMed Central

    Stangou, M.; Bantis, C.; Skoularopoulou, M.; Korelidou, L.; Kouloukouriotou, D.; Scina, M.; Labropoulou, I. T.; Kouri, N. M.; Papagianni, A.; Efstratiadis, G.

    2016-01-01

    IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829

  6. Radiation cataracts: mechanisms involved in their long delayed occurrence but then rapid progression

    PubMed Central

    Pendergrass, William; Singh, Narendra; Schwartz, Jeffrey

    2008-01-01

    Purpose This study was directed to assess the DNA damage and DNA repair response to X-ray inflicted lens oxidative damage and to investigate the subsequent changes in lens epithelial cell (LEC) behavior in vivo that led to long delayed but then rapidly developing cataracts. Methods Two-month-old C57Bl/6 female mice received 11 Grays (Gy) of soft x-irradiation to the head only. The animals’ eyes were examined for cataract status in 30 day intervals by slit lamp over an 11 month period post-irradiation. LEC migration, DNA fragment, free DNA retention, and reactive oxygen species (ROS) presence were established in the living lenses with fluorescent dyes using laser scanning confocal microscopy (LSCM). The extent and removal of initial LEC DNA damage were determined by comet assay. Immunohistochemistry was used to determine the presence of oxidized DNA and the response of a DNA repair protein in the lenses. Results This treatment resulted in advanced cortical cataracts that developed 5–11 months post-irradiation but then appeared suddenly within a 30 day period. The initially incurred DNA strand breaks were repaired within 30 min, but DNA damage remained as shown 72 h post-irradiation by the presence of the DNA adduct, 8-hydroxyguanosine (8-OHG), and a DNA repair protein, XRCC1. This was followed months later by abnormal behavior by LEC descendant cells with abnormal differentiation and migration patterns as seen with LSCM and fluorescent dyes. Conclusions The sudden development of cortical cataracts several months post-irradiation coupled with the above findings suggests an accumulation of damaged descendants from the initially x-irradiated LECs. As these cells migrate abnormally and leave acellular lens surface sites, eventually a crisis point may arrive for lens entry of environmental O2 with resultant ROS formation that overwhelms protection by resident antioxidant enzymes and results in the coagulation of lens proteins. The events seen in this study indicate

  7. Novel therapeutic approaches to lupus glomerulonephritis: translating animal models to clinical practice.

    PubMed

    Bagavant, Harini; Kalantarinia, Kambiz; Scindia, Yogesh; Deshmukh, Umesh

    2011-03-01

    Systemic lupus erythematosus is a chronic autoimmune disease frequently affecting the kidney. Renal involvement is characterized by glomerular immune complex deposits and proliferative glomerulonephritis progressing to glomerulosclerosis and kidney failure. The development of systemic lupus erythematosus is regulated genetically, and lupus susceptibility genes have been linked to immune hyper-responsiveness and loss of immune regulation. In addition to the systemic immune defects, recent studies in animal models show that susceptibility to lupus nephritis is influenced by intrinsic renal factors. Thus, renal cell responses to immune-mediated glomerular injury determine disease outcome. This supports the idea that future treatments for lupus nephritis need to focus on regulating end-organ responses. The feasibility of this approach has been shown in animal models of kidney disease. For more than 50 years, the emphasis in management of lupus nephritis has been suppression of autoimmune responses and systemic control of inflammation. This review describes recently developed targeted drug delivery technologies and potential targets that can regulate glomerular cell responses, offering a novel therapeutic approach for lupus nephritis.

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

    PubMed

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

    1991-01-01

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

  9. HLA Bw35 antigen and mesangial IgA glomerulo-nephritis: a poor prognosis marker?

    PubMed

    Berthoux, F C; Genin, C; Gagne, A; Le Petit, J C; Sabatier, J C

    1979-01-01

    Familial cases of mesangial IgA glomerulonephritis (MGN) have raised the possibility of a genetic control in this disease. In 50 patients with MGN, diagnosed on renal biopsy, and in 105 controls, we have compared the distribution of HLA antigens (A and B loci). We found a significant increase in the frequency of HLA Bw35 antigen in the patient group compared with controls (36% versus 13%: p less than 0.02). There was no significant difference between the Bw35 positive and negative MGN subgroups, in clinical, serological, and pathological data. Both subgroups had elevated mean serum IgA levels (154% of normal), and also mean serum IgM levels (146%). However, the follow-up data exhibited a significantly worse prognosis (p less than 0.01) in the Bw35 positive subgroup: 9 out of 18 patients versus 4 out of 32 progressed to chronic renal failure (serum creatinine greater than 1.5 mg/dl). We have established a genetic linkage between the HLA complex and the occurrence of MGN. The Bw35 antigen may serve as a marker (risk of disease = 4), in particular for poor prognosis cases.

  10. Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy

    SciTech Connect

    Donadio, J.V. Jr.; Anderson, C.F.; Mitchell, J.C.; Holley, K.E.; Ilstrup, D.M.; Fuster, V.; Chesebro, J.H.

    1984-05-31

    Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of /sup 51/Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m/sup 2/ of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.

  11. Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.

    PubMed

    Wang, Nan; Rajasekaran, Narendiran; Hou, Tieying; Macaubas, Claudia; Mellins, Elizabeth D

    2015-01-01

    Type I diabetes (T1D), mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC) transplantation. Older non-obese diabetic (NOD) mice recipients (3m, at disease-onset stage) receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage). FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg) and lower proportion of proliferating T conventional cells (Tcon) in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN), blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.

  12. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, January--March 1993

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1993-07-01

    Knowledge of the thermodynamic and morphological properties of coal associated with rapid heating decomposition pathways is essential to progress in coal utilization technology. Specifically, knowledge of the heat of devolatilization, surface area and density of coal as a function of rank characteristics, temperature and extent of devolatilization in the context of rapid heating conditions is required both, for the fundamental determination of kinetic parameters of coal devolatilization, and to refine existing devolatilization sub-models used in comprehensive coal combustion codes. The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: the specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars. Morphological characterization of the parent coal samples has been completed by the University of Pittsburgh. Results are presented for true density, CO{sub 2} surface area, mercury porosimetry, and particle size and shape measurements using image analysis. The heat of thermal decomposition of PSOC 1451D (Task 5) will be calculated from the data reported here. The Task 10 effort, Morphological Characterization of Coal/Char Samples as a Function of Extent of Devolatilization, will continue at the University of Pittsburgh. Work will focus on measurement of the morphological characteristics of the char samples as a function of extent of reaction.

  13. Immune responses in rapidly progressive dementia: a comparative study of neuroinflammatory markers in Creutzfeldt-Jakob disease, Alzheimer's disease and multiple sclerosis.

    PubMed

    Stoeck, Katharina; Schmitz, Matthias; Ebert, Elisabeth; Schmidt, Christian; Zerr, Inga

    2014-10-15

    Immunological responses may contribute to disease progression and clinical heterogeneity in neurodegenerative dementia, for example, Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD). Recently, a rapidly progressive form of AD (rpAD) has been described. On neuropathological grounds classical AD and rpAD are not distinguishable at present. All those protein aggregopathies show a state of chronic inflammation with microglia activation and production of proinflammatory cytokines. In this context, it is hypothesized that the severity of the surrounding inflammation substantially contributes to disease progression and accelerated disease courses as seen in rpAD.

  14. Timing of eculizumab therapy for C3 glomerulonephritis

    PubMed Central

    Rodriguez-Osorio, Laura; Ortiz, Alberto

    2015-01-01

    Eculizumab is an anti-C5 antibody that inhibits C5 cleavage and prevents the generation of the terminal complement complex C5b-9. Eculizumab is licensed to treat paroxysmal nocturnal haemoglobinuria or atypical haemolytic uraemic syndrome (aHUS). Clinical trials are ongoing for C3 glomerulopathy. Given the unfamiliarity of physicians with these rare diseases and the variability of clinical presentation, a delayed initiation of eculizumab therapy is common. Thus, the question arises as to what extent improvement of kidney function may be expected when patients have been dialysis dependent for weeks or months already when eculizumab is initiated. Furthermore, given the high cost and potential adverse effects of eculizumab, the question arises of when to stop therapy because of futility when patients with kidney-only manifestations remain dialysis dependent. In literature reports, eculizumab was stopped as early as after 3 weeks because the patient remained dialysis dependent. In this issue of CKJ, Inman et al. report on eculizumab-induced reversal of dialysis-dependent kidney failure from C3 glomerulonephritis, illustrating both the potential benefit of eculizumab for this complement-mediated disease and the need for lengthy therapy—dialysis independency was reached after 5 months of eculizumab. Indeed, there are reports of renal function recovery when eculizumab was initiated after 4 months on dialysis and of recovery of renal function 2.0–3.5 months after initiation of eculizumab in dialysis-dependent patients with C3 glomerulopathy or aHUS. PMID:26251715

  15. Nephritogenic-antinephritogenic antibody network in lupus glomerulonephritis.

    PubMed

    Doria, A; Gatto, M

    2012-12-01

    Lupus glomerulonephritis (LGN) is one of the most threatening manifestations of systemic lupus erythematosus (SLE) and a major predictor of poor prognosis. The mechanisms leading to kidney inflammation are not completely clear; however, autoantibodies seem to play a pivotal role. Apoptosis dysregulation in SLE is likely to trigger generation of autoantibodies, the released nucleosomes being the driving autoantigen for further epitope amplification and selection of DNA or nucleosome-specific B cells. Growing evidence supports a multistep path to LGN involving initial autoantibody binding to chromatin fragments in the mesangial matrix, where they can induce mesangial inflammation leading to a shut-down of the renal DNase gene, generation and deposition of secondary necrotic chromatin on the glomerular basement membrane favouring antibody binding, complement activation and development of membrano-proliferative glomerular lesions. Anti-DNA IgG antibodies display the major pathogenetic potential in LGN initiation; however, other isotypes (IgA or IgE) as well as autoantibodies targeting other molecules (e.g. anti-C1q, anti-C reactive protein) can perpetuate renal injury. Conversely, protective autoantibodies are also likely in SLE which can contain renal damage targeting either DNA (i.e. IgM anti-DNA) or other molecules (e.g. pentraxin 3). Thus, lupus nephritogenic-antinephritogenic antibodies orchestrate the balance between harm and defence of renal tissue.

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

    PubMed Central

    Zhong, Yifei; Wu, Yingwei; Liu, Ruijie; Deng, Yueyi; Mallipattu, Sandeep; Klotman, Paul; Chuang, Peter; He, John Cijiang

    2011-01-01

    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 phoshodiesterase 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. PMID:22258322

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

    PubMed

    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.

  18. An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

    PubMed

    Cilekar, Murat; Erkasap, Serdar; Oner, Ulku; Akici, Murat; Ciftci, Evrim; Dizen, Hayrettin; Turel, Serkan; Kavak, Ozgu I; Yilmaz, Sezgin

    2015-01-01

    Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

  19. The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

    PubMed

    Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

    2013-01-01

    A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between

  20. Green tea polyphenol (-)-epigallocatechin-3-gallate restores Nrf2 activity and ameliorates crescentic glomerulonephritis.

    PubMed

    Ye, Ting; Zhen, Junhui; Du, Yong; Zhou, Jason K; Peng, Ai; Vaziri, Nosratola D; Mohan, Chandra; Xu, Yan; Zhou, Xin J

    2015-01-01

    Crescentic glomerulonephritis (GN) is the most severe form of GN and is associated with significant morbidity and mortality despite aggressive immunotherapy with steroids, cytotoxic drugs, and plasmapheresis. We examined the therapeutic efficacy of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG, 50 mg/kg BW/day x3 weeks), a potent anti-inflammatory and anti-oxidant agent, on experimental crescentic GN induced in 129/svJ mice by administration of rabbit anti-mouse glomerular basement membrane sera. Routine histology and key molecules involved in inflammatory and redox signaling were studied. EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. The improvements in renal function and histology were accompanied by the restoration of Nrf2 signaling (which was impaired in vehicle-treated mice) as shown by increased nuclear translocation of Nrf2 and cytoplasmic glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione peroxidase. EGCG-treated mice also showed reduction in p-Akt, p-JNK, p-ERK1/2 and p-P38 as well as restoration of PPARγ and SIRT1 levels. Lower dose of EGCG (25 mg/kg BW/day x2 weeks) treatment also significantly decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. Thus, our data illustrate the efficacy of EGCG in reversing the progression of crescentic GN in mice by targeting multiple signaling and inflammatory pathways as well as countering oxidative stress.

  1. N-3 Polyunsaturated Fatty Acids and Autoimmune-Mediated Glomerulonephritis

    PubMed Central

    Pestka, James J.

    2010-01-01

    Consumption of n-3 polyunsaturated fatty acids (PUFAs) found in fish oil suppresses inflammatory processes making these fatty acids attractive candidates for both the prevention and amelioration of several organ-specific and systemic autoimmune diseases. Both pre-clinical and clinical studies have been conducted to determine whether fish oils containing the n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can be used in the prevention and treatment of immunoglobulin A nephropathy (IgAN) and lupus nephritis. In a toxin-induced mouse model that mimics the early stages of IgAN, n-3 PUFA consumption suppresses aberrant interleukin (IL)-6-driven IgA production and mesangial IgA immune complex deposition by impairing phosphorylation of upstream kinases and activation of transcription factors essential for IL-6 gene transcription. n-3 PUFAs can also suppress production of anti-double-stranded DNA IgG antibodies and the resultant development of lupus nephritis in the NZBW F1 mouse and related models. These effects have been linked in part to impaired expression of proinflammatory cytokines and adhesion molecules as well as increases in antioxidant enzymes in kidney and immune organs. Several recent clinical trials have provided compelling evidence that n-3 PUFA supplementation could be useful in treatment of human IgAN and lupus nephritis, although some other studies suggest such supplementation might be without benefit. Future investigations employing genomics/proteomics and novel genetically altered mice should provide further insight into how n-3 PUFAs modulate these diseases as well help to identify clinically relevant biomarkers. The latter could be employed in future well-designed, long-term clinical studies that will resolve current controversies on n-3 PUFA efficacy in autoimmune-mediated glomerulonephritis. PMID:20189790

  2. Follow-up of patients with epidemic poststreptococcal glomerulonephritis.

    PubMed

    Pinto, S W; Sesso, R; Vasconcelos, E; Watanabe, Y J; Pansute, A M

    2001-08-01

    In 1998 there was a large outbreak of acute glomerulonephritis (GN) in Nova Serrana, Brazil, caused by group C Streptococcus zooepidemicus and linked to the consumption of contaminated cheese produced with unpasteurized milk. This study describes the follow-up of these patients after a mean of 2 years following the acute episode. Of 134 patients identified in 1998, 69 patients were reexamined and underwent measurements of blood pressure, 24-hour creatinine clearance, microalbuminuria (radioimmunoassay), and urine sediment analysis. Of the original group of 134 patients, 3 patients died in the acute phase and 5 patients (3.7%) required chronic dialysis. Of 69 patients reevaluated, 65 patients (94%) were adults (mean age, 39 +/- 2 [SE] years) and 47 patients (68%) were women. At the follow-up examination, we found arterial hypertension in 42% of subjects (27 of 64 subjects), serum creatinine levels greater than 1.2 mg/dL in 12% (10 of 68 subjects), reduced creatinine clearance (<80 mL/min/1.73 m(2)) in 30% (20 of 67 subjects, 2 of them on chronic dialysis therapy), and increased microalbuminuria (>20 microg/min) in 34% (22 of 65 subjects). Increased microalbuminuria and/or reduced creatinine clearance were detected in 48% of the subjects (31 of 65 subjects). Patients with microalbuminuria had greater diastolic blood pressure than those without microalbuminuria (mean, 98 +/- 4 versus 88 +/- 2 mm Hg; P = 0.02). In conclusion, after a mean of 2 years, patients with epidemic poststreptococcal GN caused by S zooepidemicus present a high rate of hypertension and frequent abnormalities of renal function, with some having reached end-stage renal disease. Longer follow-up will be important to define the prognosis of these patients.

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

    PubMed

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

    1985-03-01

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

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

    PubMed

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

    2016-01-01

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

  5. CD4+-T-Cell and CD20+-B-Cell Changes Predict Rapid Disease Progression after Simian-Human Immunodeficiency Virus Infection in Macaques†

    PubMed Central

    Steger, Krista K.; Dykhuizen, Marta; Mitchen, Jacque L.; Hinds, Paul W.; Preuninger, Brenda L.; Wallace, Marianne; Thomson, James; Montefiori, David C.; Lu, Yichen; Pauza, C. David

    1998-01-01

    Simian-human immunodeficiency virus 89.6PD (SHIV89.6PD) was pathogenic after intrarectal inoculation of rhesus macaques. Infection was achieved with a minimum of 2,500 tissue culture infectious doses of cell-free virus stock, and there was no evidence for transient viremia in animals receiving subinfectious doses by the intrarectal route. Some animals experienced rapid progression of disease characterized by loss of greater than 90% of circulating CD4+ T cells, sustained decreases in CD20+ B cells, failure to elicit virus-binding antibodies in plasma, and high levels of antigenemia. Slower-progressing animals had moderate but varying losses of CD4+ T cells; showed increases in circulating CD20+ B cells; mounted vigorous responses to antibodies in plasma, including neutralizing antibodies; and had low or undetectable levels of antigenemia. Rapid progression led to death within 30 weeks after intrarectal inoculation. Plasma antigenemia at 2 weeks after inoculation (P ≤ 0.002), B- and T-cell losses (P ≤ 0.013), and failure to seroconvert (P ≤ 0.005) were correlated statistically with rapid progression. Correlations were evident by 2 to 4 weeks after intrarectal SHIV inoculation, indicating that early events in the host-pathogen interaction determined the clinical outcome. PMID:9445063

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

    PubMed

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

    1992-07-01

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

  7. Progressive subretinal fibrosis in patients with rheumatoid arthritis and renal dysfunction.

    PubMed

    Matsuo, T; Matsuo, N

    1998-01-01

    We present two patients (56-year-old and 71-year-old women) who developed subretinal fibrosis in parallel with exacerbation of rheumatoid arthritis and deteriorated renal function. The first patient developed subretinal fibrosis in the right eye, coupled with multifocal choroiditis and serous retinal detachment in both eyes, in the course of rapidly progressive glomerulonephritis complicated with rheumatoid arthritis. Antineutrophil cytoplasmic antibody was positive in a perinuclear pattern (pANCA) and the increased dose of prednisolone to 40 mg/day resulted in subsidence of the subretinal inflammation. The second patient developed subretinal fibrosis in the left eye with mottled retinal pigment epithelium of both eyes, in the course of rheumatoid arthritis and stable chronic renal failure. Although the manifestations of subretinal fibrosis and concurrent renal dysfunction were different between these two patients, subretinal fibrosis might be noted as a complication of rheumatoid arthritis and renal dysfunction.

  8. Pathology Image Of the Month: Rapidly Progressive Hemorrhagic Cellulitis of Bilateral Lower Extremities with Subsequent Septic Shock and Death.

    PubMed

    Connor, Ellen E; Jackson, Nicole R; McGoey, Robin R

    2016-01-01

    A 51-year-old man presented to a community based emergency department with bilateral lower extremity swelling that began four days prior and that had evolved into recent blister formation on the left lower extremity. Medical history was significant only for hypertension and a recent self-described episode of "food poisoning" five days earlier characterized by diarrhea, nausea, and vomiting that quickly resolved. Physical exam revealed marked bilateral lower extremity edema and an ecchymotic rash below the knee. In addition to the rash, there were large flaccid bullae on the left leg, mostly intact but some notable for draining of scanty serosanguinous fluid. The patient was tachycardic with a rate of 114 bpm and initial labs showed thrombocytopenia (platelets 56 x 103/uL [140-440 x 103/uL]), hypoglycemia (15mg/dl [70-105mg/dl]), an elevated creatinine (2.7mg/dL [0.7- 1.25mg/dL]), and aspartate aminotransferase (AST 156U/L [5- 34U/L]). Two sets of blood cultures were drawn, broad spectrum antibiotics including doxycycline were empirically initiated and then he was subsequently transported to a tertiary care hospital for escalation of care. Within hours of presentation to the tertiary care facility, the rash appeared progressively hemorrhagic and bullous, lactic acidosis and coagulopathy developed and hemodynamic instability and septic shock necessitated endotracheal intubation and vasopressors. He was taken to the operating room for skin debridement but was emergently converted to bilateral above the knee lower extremity amputations due to the extent of the soft tissue necrosis. The patient remained intubated and in critical condition following surgery and the ecchymotic rash reappeared at the amputation sites. A newly developed ecchymotic rash with bullae formation was noted on the right upper extremity forearm. At that time, the clinicians were notified that four out of four blood culture bottles from admission were rapidly growing a microorganism. The family

  9. A rare case of rapidly progressive dementia with elevated RT-QuIC and negative 14-3-3 and tau proteins.

    PubMed

    Trikamji, Bhavesh; Hamlin, Clive; Baldwin, Kelly J

    2016-05-01

    Creutzfeldt-Jakob disease (CJD) is characterized by rapidly progressing dementia with death usually occurring within 6 months. There is no verified disease-specific pre-mortem diagnostic test besides brain biopsy. We describe a 66 y old previously high functioning male who presented with a 5 month history of rapidly progressive dementia. Neurological examination revealed a score of 19/30 on MOCA testing. An extensive workup into various causes of dementia including electroencephalography and imaging studies was unremarkable. The cerebrospinal fluid was sent to National Prion Disease Center and it revealed elevated RT-QuIC levels with negative 14-3-3 and T tau proteins. Based on literature review, our case is one of few living subjects with elevated RT-QuIC levels and negative 14-3-3 and tau proteins. PMID:27249661

  10. Determinants of glomerular filtration in experimental glomerulonephritis in the rat.

    PubMed Central

    Maddox, D A; Bennett, C M; Deen, W M; Glassock, R J; Knutson, D; Daugharty, T M; Brenner, B M

    1975-01-01

    Pressures and flows were measured in surface glomerular capillaries, efferent arterioles, and proximal tubules of 22 Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Linear deposits of rabbit and rat IgG and C3 component of complement were demonstrated in glomerular capillary walls by immunofluorescence microscopy. Light microscopy revealed diffuse proliferative glomerulonephritis, and proteinuria was present. Although whole kidney and single nephron glomerular filtration rate (GFR) in NSN (0.8 plus or minus 0.04 SE2 ml/min and 2 plus or minus 2 nl/min, respectively) remained unchanged from values in 16 weight-matched NORMAL HYDROPENIC control rats (0.8 plus or minus 0.08 and 28 plus or minus 2), important alterations in glomerular dynamics were noted. Mean transcapillary hydraulic pressure difference (deltaP) averaged 41 plus or minus 1 mm Hg in NSN versus 32 plus or minus 1 in controls (P LESS THAN 0.005). Oncotic pressures at the afferent (piA) end of the glomerular capillary were similar in both groups ( 16 mm /g) but increased much less by the efferent end (piE) in NSN (to 29 plus or minus 1 mm Hg) than in controls (33 plus or minus 1, P less than 0.025). Hence, equality between deltaP and piE, denoting filtration pressure equilibrium, obtained in control but not in NSN rats. While glomerular plasma flow rate was slightly higher in NSN (88 plus or minus 8 nl/min) than in controls (76 plus or minus 6, P greater than 0.2), the failure to achieve filtration equilibrium in NSN rats was primarily the consequence of a marked fall in the glomerular capillary ultrafiltration coefficient, Kf, to a mean value of 0.03 nl/(s times mm Hg), considerably lower than that found recently for the normal rat, 0.08 nl/(s times mm Hg). Thus, despite extensive glomerular injury, evidenced morphologically and by the low Kf, GFR remained normal. This maintenance of GFR resulted primarily from increases in deltaP, which tended to increase the net driving

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

    PubMed Central

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

    1992-01-01

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

  12. Extensive complement activation in hereditary porcine membranoproliferative glomerulonephritis type II (porcine dense deposit disease).

    PubMed Central

    Jansen, J. H.; Høgåsen, K.; Mollnes, T. E.

    1993-01-01

    Massive glomerular deposits of C3 and the terminal C5b-9 complement complex (TCC), but no immune complex deposits were detected by immunofluorescence in porcine membranoproliferative glomerulonephritis type II. TCC deposits were always observed with concomitant deposits of vitronectin (S-protein) in membranoproliferative glomerulonephritis, in contrast to a piglet with mesangial glomerulopathy where TCC was present without vitronectin co-deposition. Enzyme immunoassays revealed extensive systemic complement activation in 1-week-old affected piglets, observed by low plasma C3 (about 5% of normal) and high plasma TCC (about 10 x normal). Affected piglets revealed some plasma complement activation already at birth, 3 to 4 weeks before recognizable clinical disease. It is concluded that porcine membranoproliferative glomerulonephritis represents a nonimmune complex-mediated glomerulonephritis caused by unrestricted systemic complement activation with C3 consumption, TCC formation, and glomerular trapping of complement activation products. A pathogenetic mechanism of a defective or missing complement regulation protein is suggested. Images Figure 1 Figure 2 Figure 3 PMID:8238252

  13. General acteoside of Rehmanniae leaves in the treatment of primary chronic glomerulonephritis: a randomized controlled trial.

    PubMed

    Qiu, HongYu; Fan, WenXing; Fu, Ping; Zuo, Chuan; Feng, Ping; Liu, Fang; Zhou, Li; Chen, Feng; Zhong, Hui; Liang, YaPing; Shi, Mei

    2013-01-01

    The objective of the study was to investigate the effectiveness and efficacy of the randomized, parallel, and controlled trial of Traditional Chinese Medicine, general acteoside of Rehmanniae leaves, compared with piperazine ferulate in the treatment of primary chronic glomerulonephritis. Rehmanniae leaves and piperazine ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis. A total of 400 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (general acteoside of Rehmanniae leaves, two 200mg tablets, bid) or the control group (piperazine ferulate, four 50-mg tablets, bid ). The primary outcome was 24-h urinary protein. Secondary outcome measures included estimated glomerular filtration rate (eGFR), erythrocyturia, and electrolytes. After 8 weeks of treatment, the treatment group and the control group showed a mean reduction in 24-h proteinuria of 34.81% and 37.66%. The 95% CI of difference of the mean reduction in 24-h proteinuria between the two groups was [-11.50%, 5.80%]. No significant differences were found between the two groups in the erythrocyturia reduction. Neither group showed obvious changes between baseline and 8 weeks in eGFR or electrolytes. Adverse events occurred at a similarly low rate in the treatment group (1.5%) and control group (2.5%, P = 0.7238). Both general acteoside of Rehmanniae leaves and piperazine ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis.

  14. Chronic glomerulonephritis and exposure to solvents: a case-referent study.

    PubMed Central

    Porro, A; Lomonte, C; Coratelli, P; Passavanti, G; Ferri, G M; Assennato, G

    1992-01-01

    To evaluate the risk of chronic glomerulonephritis in subjects exposed to solvent vapours, a case-referent study was carried out. The case group, including 60 patients (44 men and 16 women) with non-systemic chronic glomerulonephritis, established by biopsy, was compared with 120 control subjects (60 patients with traumatic fractures and 60 patients affected by nephrolithiasis) matched by sex and age. Information on occupational and non-occupational exposure to solvent was obtained by questionnaire. The exposure scores drawn from questionnaires were significantly higher in the case group than in the referent groups for both total and occupational solvent exposure. No significant differences in non-occupational exposure were found. The odds ratio of chronic glomerulonephritis for occupationally exposed (score > 0) was 3.9 (95% confidence interval (95% CI) 1.64-8.33). When IgA nephropathy patients (n = 27) were separately evaluated, an increased risk was found for both total and occupational exposure. Using a logistic regression model, a dose-response effect for occupational exposure was seen. The results support the hypothesis that chronic glomerulonephritis may be related to environmental factors such as exposure to hydrocarbons. PMID:1419865

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  18. [AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: HOW AND WHY SHOULD WE IDENTIFY THE PATIENTS "RAPIDLY PROGRESSING" TO END-STAGE RENAL DISEASE?].

    PubMed

    Bodson, A; Meunier, P; Krzesinski, J-M; Jouret, F

    2016-04-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterised by the progressive development of multiple and bilateral cysts in kidneys and other organs. Most patients with ADPKD will develop, sooner or later, end-stage renal disease (ESRD). The morbidity and mortality associated with ESRD prompt physicians to identify early ADPKD patients considered as "rapid progressors", who have the greatest risk to rapidly develop ESRD. The rate of progression can be assessed by clinical--especially with the "predicting renal outcome in polycystic kidney disease score" (PROPKD-Score)-, biological (a decline of the glomerular filtration rate (GFR) of 4.4-5.9 ml/min/year and/or the doubling of serum creatinine within a 36-month period), or radiological criteria (total kidney volume (TKV) adjusted for the size > 600 cc/m and/or TKV annual growth rate > 5 %). Nowadays, there is no curative treatment for ADPKD. However, vasopressin-2 receptor antagonists, such as tolvaptan, appear to slow down the growth of renal cysts and the slope of GFR decline. The current management of ADPKD patients is mostly based on correcting the risk factors for progression, i.e. encouraging (over)-hydration, normalizing blood pressure, stimulating smoking cessation. PMID:27295898

  19. Podocyte Detachment Is Associated with Renal Prognosis in ANCA-Associated Glomerulonephritis

    PubMed Central

    Zou, Rong; Wang, Su-xia; Liu, Gang; Yu, Feng; Chen, Min; Zhao, Ming-Hui

    2016-01-01

    Abstract The prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) is unfavorable despite immunosuppressive therapy. It has been suggested that the loss of podocytes is a hallmark of progressive kidney disease. However, it is unclear about podocyte injuries and their predictive values on the prognosis in ANCA-GN. Therefore, the current study aimed to investigate the podocyte injury in renal histopathology and its association with renal prognosis of patients with ANCA-GN. A total of 170 patients with ANCA-GN were recruited in this study. Morphometric investigation of podocytes by electron microscopy including foot process width (FPW), podocyte density per glomerulus (Nv), and glomerular basement membrane (GBM) width were measured and calculated in ANCA-GN patients. Cox regression analysis was used to analyze the association between podocyte injuries and prognosis of patients with ANCA-GN. Foot processes broadening, podocyte detachment, and GBM thickening could be observed in electron micrographs in the specimens of 158/170 (92.9%), 142/170 (83.5%), and 150/170 (88.2%) patients, respectively. Compared with normal controls, FPW and GBM width in ANCA-GN patients was significantly higher (1269.39 ± 680.19 vs 585.81 ± 77.16, P = 0.004; 668.23 ± 208.73 vs 354.23 ± 52.70, P = 0.000, respectively), while the podocyte density was significantly lower (55.90 ± 36.32 vs 255.23 ± 47.29, P = 0.000). The podocyte density was independently associated with the recovery of renal function in logistic regression analysis (OR, 1.083; 95% CI, 1.025–1.440; P = 0.005). Furthermore, multivariate analysis revealed that podocyte density was an independent predictor of end-stage renal disease (ESRD) (model A: HR, 0.950; 95% CI, 0.919–1.982; P = 0.002; model B: HR, 0.953; 95% CI, 0.922–0.985; P = 0.004). Podocyte structural damage and detachment occurred frequently in patients with ANCA

  20. Mercury-induced autoimmune glomerulonephritis in inbred rats. I. Kinetics and species specificity of autoimmune responses.

    PubMed

    Michaelson, J H; McCoy, J P; Hirszel, P; Bigazzi, P E

    1985-01-01

    The nephropathy observed in rats after administration of mercuric chloride can be used to clarify the mechanisms underlying renal autoimmunity induced by chemicals. As a necessary preliminary step in the study of this animal model, we have investigated the kinetics and species-specificity of autoimmune responses to renal antigens. By a recently developed enzyme-linked immunosorbent assay (ELISA), circulating autoantibodies to the glomerular basement membrane of the kidney (anti-GBM) have been detected within 8 days after the initiation of mercuric chloride treatment. Anti-GBM antibodies reach a peak by 15 days and then decrease rapidly in the following 2 weeks. Extensive cross-reactions between rat and human GBM antigens have been detected by ELISA, indicating a high degree of conservation of some renal autoantigens and suggesting certain similarities between the autoimmune response induced in rats by mercuric chloride and that observed in human glomerulonephritis caused by anti-GBM. Dose-response studies have been performed to ascertain whether anti-GBM responses are correlated with massive kidney damage and release of renal antigens. We have noted that a wide range of levels of mercuric chloride are capable of stimulating the production of anti-GBM and that animals receiving this chemical in as low a concentration as 0.02 mg/100 g body weight (i.e. a dose ten times lower than those causing massive nephrotoxic effects) still have anti-GBM specifically bound to their kidneys. Thus, it is possible that the administration of mercury compounds to BN rats results in kidney autoimmunity not only because of the release of renal autoantigens, but also through the activation of specific lymphocytes and/or disruption of regulatory networks. Finally, we have observed that both BN and MAXX rats produce anti-GBM after mercuric chloride treatment, while M520 rats do not. Since the MAXX strain was initially obtained from a cross of BN and Lewis rats and shares antigens of the

  1. Predictors of Rapid Progression of Glomerular and Non-Glomerular Kidney Disease in Children: The CKiD Cohort

    PubMed Central

    Warady, Bradley A.; Abraham, Alison G.; Schwartz, George J.; Wong, Craig S.; Muñoz, Alvaro; Betoko, Aisha; Mitsnefes, Mark; Kaskel, Frederick; Greenbaum, Larry A.; Mak, Robert H.; Flynn, Joseph; Moxey-Mims, Marva M.; Furth, Susan

    2015-01-01

    Background Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and factors associated with progression. Study Design Prospective assessment of risk factors for the composite event of renal replacement therapy (RRT) or 50% glomerular filtration rate (GFR) decline. Setting and Participants 496 children with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. Outcomes Parametric failure time models were used to characterize adjusted associations between baseline levels and changes of predictors and the time to composite event. Results The cohort consisted of 398 children with non-glomerular and 98 children with glomerular disease, of whom 29% and 41%, respectively progressed to the composite event after a median follow-up of 5.2 and 3.7 years. Demographic, clinical characteristics and outcomes differed substantially according to underlying diagnosis, hence risk factors for progression were assessed in stratified analyses and formal interactions by diagnosis were performed. Among non-glomerular patients and after adjusting for baseline GFR, times to the composite event were significantly reduced with Up/c > 2 mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male gender and anemia by 79%, 69%, 38%, 40%, 38% and 45%, respectively. Among patients with glomerular disease, Up/c > 0.5 mg/mg, hypoalbuminemia and elevated blood pressure significantly reduced times to the composite event by 94%, 71% and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model which was cross validated internally. Limitations small number of events in glomerular patients and use of internal cross validation. Conclusions Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to RRT/50% decline of GFR in

  2. Rapid progression of late onset axonal Charcot–Marie–Tooth disease associated with a novel MPZ mutation in the extracellular domain

    PubMed Central

    Laurà, Matilde; Milani, Micaela; Morbin, Michela; Moggio, Maurizio; Ripolone, Michela; Jann, Stefano; Scaioli, Vidmer; Taroni, Franco; Pareyson, Davide

    2007-01-01

    Myelin protein zero (MPZ) is a major component of compact myelin in peripheral nerves where it plays an essential role in myelin formation and adhesion. MPZ gene mutations are usually responsible for demyelinating neuropathies, namely Charcot–Marie–Tooth (CMT) type 1B, Déjèrine–Sottas neuropathy and congenital hypomyelinating neuropathy. Less frequently, axonal CMT (CMT2) associated with MPZ mutations has been described. We report six patients (one sporadic case and five subjects from two apparently unrelated families) with a late onset, but rapidly progressive, axonal peripheral neuropathy. In all patients, molecular analysis demonstrated a novel heterozygous missense mutation (208C>T) in MPZ exon 2, causing the Pro70Ser substitution in the extracellular domain. The diagnosis of CMT2 associated with MPZ mutations should be considered in both sporadic and familial cases of late onset, progressive polyneuropathy. The mechanism whereby compact myelin protein mutations cause axonal neuropathy remains to be elucidated. PMID:17940173

  3. Rapid progression of late onset axonal Charcot-Marie-Tooth disease associated with a novel MPZ mutation in the extracellular domain.

    PubMed

    Laurà, Matilde; Milani, Micaela; Morbin, Michela; Moggio, Maurizio; Ripolone, Michela; Jann, Stefano; Scaioli, Vidmer; Taroni, Franco; Pareyson, Davide

    2007-11-01

    Myelin protein zero (MPZ) is a major component of compact myelin in peripheral nerves where it plays an essential role in myelin formation and adhesion. MPZ gene mutations are usually responsible for demyelinating neuropathies, namely Charcot-Marie-Tooth (CMT) type 1B, Déjèrine-Sottas neuropathy and congenital hypomyelinating neuropathy. Less frequently, axonal CMT (CMT2) associated with MPZ mutations has been described. We report six patients (one sporadic case and five subjects from two apparently unrelated families) with a late onset, but rapidly progressive, axonal peripheral neuropathy. In all patients, molecular analysis demonstrated a novel heterozygous missense mutation (208C>T) in MPZ exon 2, causing the Pro70Ser substitution in the extracellular domain. The diagnosis of CMT2 associated with MPZ mutations should be considered in both sporadic and familial cases of late onset, progressive polyneuropathy. The mechanism whereby compact myelin protein mutations cause axonal neuropathy remains to be elucidated. PMID:17940173

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

    PubMed Central

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

    2016-01-01

    Background: Tacrolimus inhibits hepatitis B virus entry into hepatocytes through targeting the HBV receptor, sodium taurocholate cotransporting polypeptide. This study was performed to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis patients with biopsy-proven membranous nephropathy. Method: A cohort of 42 patients was enrolled in this retrospective study. Twenty-three patients received Tacrolimus (0.05 mg/kg/day) in combination entecavir over 24 weeks, whereas the other 19 patients only received entecavir monotherapy. Results: The probability of proteinuria remission in the Tacrolimus+entecavir group was 69 and 87% after 12 and 24 weeks, whereas was only 26 and 42%, respectively, in the entecavir group. The mean time to partial or complete remission was 18.6 weeks in the Tacrolimus+entecavir group and 34.3 weeks in the entecavir group (P<0.001). A decrease in the HBV DNA titer was observed in all patients with active HBV replication. None of the HBV carriers in the Tacrolimus+entecavir group showed evidence of HBV reactivation. The serum creatinine and alanine aminotransferase levels remained stable in both groups. The Tacrolimus target trough concentration was 5-10 ng/mL. Conclusion: Tacrolimus combined with entecavir rapidly and effectively induced remission of HBV-GN in Chinese adults. Furthermore, Tacrolimus may have a synergistic antiviral effect with entecavir. PMID:27186284

  5. Acute poststreptococcal glomerulo-nephritis in general practice: the contribution of infection to its onset and course.

    PubMed

    Higgins, P M

    1996-04-01

    Twenty-one patients considered to have acute poststreptococcal glumerulo-nephritis were encountered during 35 years of general practice. In ten of them good evidence of active streptococcal infection at the time of discovery of nephritis was recorded. The more complete the data the more convincing was the evidence of active infection. In over half of those whose urine were routinely cultured pathogens were isolated and over a third were treated for infection of the urinary tract. Such infections were associated with adverse effects and prolonged illness. As compared with children, adults in general had a longer history of ill-health, were less likely to present with acute infections and more likely to have urinary tract infections and prolonged illness. Vigorous antistreptococcal treatment was followed by rapid recovery in those patients so treated whose illnesses were not complicated by urinary tract infections. Concurrent streptococcal infection and secondary infection of the urinary tract may contribute more to the onset of acute poststreptococcal glomerulo-nephritis and to its course than is currently believed.

  6. Rapidly progressive renal failure—a rare presentation of granulomatous interstitial nephritis due to tuberculosis—case report and review of literature

    PubMed Central

    K. Sharma, Raj; Krishnasamy, Jaisuresh; Ruhela, Vivek; Kumari, Niraj

    2011-01-01

    Granulomatous interstitial nephritis (GIN) is a rare manifestation of renal tuberculosis (TB). We report a case of rapidly progressive renal failure (RPRF), granulomatous inflammation of cervical lymph node and GIN as presenting manifestations of TB. Aspiration cytology of cervical lymph node showed granulomatous necrotizing inflammation with acid-fast bacilli (AFB). The renal biopsy and urine specimen did not show AFB. Urine polymerase chain reaction (PCR) for Mycobacterium tuberculosis was positive. We observe that GIN due to TB can present as RPRF and emphasize the value of PCR-based techniques in making a correct diagnosis. PMID:25984199

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

    PubMed Central

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

    2016-01-01

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

  8. Nephrotic syndrome due to immunoglobulin M mesangial glomerulonephritis preceding juvenile idiopathic arthritis.

    PubMed

    Voyer, Luis E; Alvarado, Caupolican; Cuttica, Rubén J; Balestracci, Alejandro; Zardini, Marta; Lago, Néstor

    2013-05-21

    The association between nephrotic syndrome and juvenile idiopathic arthritis have rarely been described in pediatric patients. We report a child with steroid-responsive nephrotic syndrome, with frequent relapses, who presented with a new relapse of nephrotic syndrome associated with arthritis and uveitis at 21 months in remission after treatment with chlorambucil. Juvenile idiopathic arthritis was diagnosed and kidney biopsy examination showed mesangial glomerulonephritis with immunoglobulin M deposits. To our knowledge, only 2 cases of nephrotic syndrome preceding juvenile idiopathic arthritis have been reported, one without histopathology assessment and the other with minimal change disease. Although mesangial glomerulonephritis with nephrotic syndrome and juvenile idiopathic arthritis could have been coincidental, the immune pathogenic mechanism accepted for both diseases suggests they could be related.

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

    PubMed

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

    1998-06-01

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

  10. A five-year analysis of the incidence of glomerulonephritis at Cairo University Hospital-Egypt.

    PubMed

    Ibrahim, Salwa; Fayed, Ahmed; Fadda, Sawsan; Belal, Dawlet

    2012-07-01

    Our study aimed to obtain a comprehensive review of the incidence of biopsy-proven glomerulonephritis (GN) at the Cairo University Hospitals, Egypt, over the last five years. We analyzed the clinical and pathological data of all renal biopsy samples that were performed during the period from July 2003 to July 2008. Renal biopsy samples of 924 patients were referred for pathological assessment during the period of the study [437 male and 487 female patients; their mean age was 26.5 ± 14.6 years (range: 2.5-71 years)]. Focal segmental glomerulo-nephritis was the most frequent cause of primary GN (21.21%), followed by mesangial proliferative GN (18.93%), diffuse proliferative GN (13.96%), focal proliferative GN (12.77%) and membranous GN (10.93%). The results could be explained by the high incidence of lupus nephritis among the study subjects as well as the relatively young age of the study group.

  11. Proliferative glomerulonephritis associated with monoclonal immune deposits: A case report and review of literature

    PubMed Central

    Fatima, R.; Jha, R.; Gowrishankar, S.; Narayen, G.; Rao, B. S.

    2014-01-01

    Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a newly recognized entity caused by monoclonal deposition of IgG. PGNMID resembles immune complex glomerulonephritis (GN) on light and electron microscopy. The monotypic immunoglobulin deposits seen on immunofluorescence (IF) clinches the diagnosis. We report a case of proliferative GN associated MGRS and review the relevant literature. The patient had significant proteinuria and elevated serum creatinine. The renal biopsy showed proliferative GN with focal crescents and monoclonal immune deposits confirming a diagnosis of PGNMID. Serum work up showed no monoclonal proteins. Proliferative GN as a manifestation of a monoclonal gammopathy needs to be borne in mind especially in renal biopsies of older patients. PMID:25484532

  12. A Patient with Refractory Psoriasis Who Developed Sebaceous Carcinoma on the Neck during Cyclosporine Therapy and Showed Rapid Progression.

    PubMed

    Shima, Tomoko; Yamamoto, Yuki; Okuhira, Hisako; Mikita, Naoya; Furukawa, Fukumi

    2016-01-01

    We report a patient who developed sebaceous carcinoma on the neck during therapy with immunosuppressive agents (cyclosporine, corticosteroid, methotrexate) for refractory psoriasis vulgaris, which showed rapid enlargement, leading to a fatal outcome. Multiple-organ metastases were detected. Weekly carboplatin + paclitaxel therapy resulted in the disappearance of tumor cells, but the patient died of febrile neutropenia. The development of sebaceous carcinoma is rare among psoriasis patients receiving immunosuppressive agents including cyclosporine. PMID:27462222

  13. Systemic lupus erythematosus with membranous glomerulonephritis and transverse myelitis associated with anabolic steroid use.

    PubMed

    Radis, C D; Callis, K P

    1997-10-01

    This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed. PMID:9336429

  14. [Presence of hepatitis C virus in renal tissue in membranoproliferative glomerulonephritis and cryoglobulinemia].

    PubMed

    Tormo, A; Rivera, F; Muñoz, C; Trigueros, M

    2003-01-01

    Although hepatitis C virus infection has been documented in several extrahepatic diseases, the deposition of HCV RNA in glomerular structures has proved to be difficult to demonstrate. We report a patient with membranoproliferative glomerulonephritis, type III circulating cryoglobulins and hepatitis C virus infection with detection of HCV RNA in serum, cryoprecipitate and renal tissue using specific RT-PCR technique. These data confirm that HCV could have a direct role in renal damage.

  15. Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.

    PubMed Central

    Høgåsen, K; Jansen, J H; Mollnes, T E; Hovdenes, J; Harboe, M

    1995-01-01

    We have recently described hereditary membranoproliferative glomerulonephritis type II in the pig. All affected animals had excessive complement activation, revealed as low plasma C3, elevated plasma terminal complement complex, and massive deposits of complement in the renal glomeruli, and eventually died of renal failure within 11 wk of birth. The aim of the present study was to investigate the cause of complement activation in this disease. Transfusion of normal porcine plasma to affected piglets inhibited complement activation and increased survival. Plasma was successively fractionated and the complement inhibitory effect of each fraction tested in vivo. A single chain 150-kD protein which showed the same complement inhibitory effect as whole plasma was finally isolated. Immunologic cross-reactivity, functional properties, and NH2-terminal sequence identified the protein as factor H. By Western blotting and enzyme immunoassay, membranoproliferative glomerulonephritis-affected piglets were demonstrated to be subtotally deficient in factor H. At 1 wk of age, median (range) factor H concentration was 1.6 mg/liter (1.1-2.3) in deficient animals (n = 13) and 51 mg/liter (26-98) in healthy littermates (n = 52). Our data show that hereditary porcine membrano-proliferative glomerulonephritis type II is caused by factor H deficiency. Images PMID:7883953

  16. [Fibrillary glomerulo-nephritis: a rare form of glomerular disease with organized deposits].

    PubMed

    Cabrera, Marta B; Szlabi, Susana; Flores, Jorge; Mukdsi, Jorge H

    2011-01-01

    We describe the case of a 67 year-old female who presented weakness and fatigue. Laboratory data showed nephrotic level of proteinuria and dyslipidemia. A renal biopsy was performed, and studied by light microscopy, immuno-fluorescence and electron microscopy. Ultra-structural analysis revealed the existence of organized fibrillary deposits, straight and without ramifications, the thickness of which ranged from 15 to 20 nm. These fibres were identified, by light microscopy, as slightly nodular mesangial expansions PAS positive, Congo red negative and weakly positive for IgG. Given the above findings, the diagnosis was fibrillary glomerulonephritis. Glomerular lesions with organized deposits may exhibit syndromic and pathological overlap. For this reason it is important to initially discriminate between positive and negative Congo red deposits, using, in the latter case, transmission electron microscopy to distinguish between immuno-tactoid and fibrillary glomerulonephritis. This differentiation relies not only on ultrastructural features, but on different clinical characteristics. Unlike what happens with fibrillary glomerulonephritis, the immuno-tactoid shows a strong association with lymphoproliferative processes.

  17. Epithelial-mesenchymal transition (EMT) of renal tubular cells in canine glomerulonephritis.

    PubMed

    Aresu, Luca; Rastaldi, Maria Pia; Scanziani, Eugenio; Baily, James; Radaelli, Enrico; Pregel, Paola; Valenza, Federico

    2007-11-01

    Tubulo-interstitial fibrosis in dogs may result from primary injury to the interstitium or develop secondary to other renal diseases. As in human renal pathology, tubular epithelial cells (TEC) are believed to actively participate in the mechanisms of renal fibrosis. In this study, we examined the changes in the tubular epithelial component in two specific canine diseases. Immunohistochemistry showed the expression of the epithelial marker cytokeratin, the smooth muscle marker alpha-SMA, the mesenchymal marker vimentin and PCNA in 20 dogs with membranous glomerulonephritis and membrano-proliferative glomerulonephritis. Results showed that the loss of the epithelial marker in TEC was directly correlated to the grade of tubulo-interstitial disease present and independent of the type of glomerulonephritis. Varying degrees of vimentin positivity were detected in tubular epithelium in areas of inflammation, and low numbers of scattered alpha-SMA-positive cells were also observed. Immunohistochemistry showed that epithelial tubular cells lose their cytokeratin staining characteristics and transdifferentiate into cells exhibiting key mesenchymal immunophenotypic feature of vimentin-positive staining in both diseases investigated. The integrity of the tubular basement membrane is likely to be fundamental in maintaining the epithelial phenotype of TEC. Animal models provide opportunities for investigating the pathogenesis of renal fibrosis in humans.

  18. WILD-TYPE GROSS LEUKEMIA VIRUS AND THE PATHOGENESIS OF THE GLOMERULONEPHRITIS OF NEW ZEALAND MICE

    PubMed Central

    Mellors, Robert C.; Shirai, Toshikazu; Aoki, Tadao; Huebner, Robert J.; Krawczynski, Krzysztof

    1971-01-01

    The pathogenesis of the spontaneous glomerulonephritis of NZB and (NZB x NZW) F1 hybrid mice is related at least in part to the formation of natural antibody against antigens of the G (Gross) system, and apparently to the deposition in the glomeruli of immune complexes of G natural antibody with G soluble antigen (GSA), type-specific antigen specified by wild-type Gross leukemia virus. G natural antibody and GSA are detectable in the acid-buffer eluate of the kidneys of NZB mice during the course of the glomerulonephritis. (NZB x NZW) F1 hybrid mice develop glomerulonephritis and produce GSA and free G natural antibody earlier in life than do NZB mice. The proteinuria manifestation of the gomerulonephritis of (NZB x NZW) F1 hybrid mice becomes increasingly prevalent as GSA undergoes immune elimination from the circulation. Gross leukemia virus-specified antigens together with bound immunoglobulins are located in the glomerular lesions of (NZB x NZW) F1 hybrid mice, both in the mesangium as observed in NZB mice and also in the wall of the peripheral capillary loops of the glomeruli. PMID:4924198

  19. A rapidly progressing, deadly disease of Actias selene (Indianmoonmoth) larvae associated with a mixed bacterial and baculoviral infection.

    PubMed

    Skowron, Marta A; Guzow-Krzemińska, Beata; Barańska, Sylwia; Jędrak, Paulina; Węgrzyn, Grzegorz

    2015-09-01

    The outbreak of an infectious disease in captive-bred Lepidoptera can cause death of all the caterpillars within days. A mixed baculoviral-bacterial infection observed among Actias selene (Hubner 1807), the Indian moon moth (Insecta: Lepidoptera: Saturniidae), larvae was characterized and followed by a photographic documentation of the disease progression. The etiological agents were determined using mass spectrometry and polymerase chain reaction (PCR). It appeared that the disease was caused by a mixed infection of larvae with a baculovirus and Morganella morganii. A molecular phylogenetic analysis of the virus and microbiological description of the pathogenic bacterium are presented. PMID:26333395

  20. Metastasizing mixed tumor of the parotid gland: a rare tumor with unusually rapid progression in a cardiac transplant recipient.

    PubMed

    Sampson, B A; Jarcho, J A; Winters, G L

    1998-11-01

    We report the case of a 69-year-old man who had a mixed tumor (pleomorphic adenoma) removed from his parotid gland 3 years after orthotopic heart transplantation. Two years later, he presented with widely metastatic mixed tumor, which resulted in his death within 6 months. Metastatic mixed tumor is histologically identical to a benign mixed tumor, but it inexplicably metastasizes. Such tumors are rare and have not been reported to date in a transplant recipient. This case illustrates the rapid and aggressive course that malignancies can follow in an immunosuppressed population. Mixed tumors are common salivary neoplasms, so transplant recipients should be carefully followed after resection for evidence of metastatic spread.

  1. Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging.

    PubMed

    Sawiak, Stephen J; Perumal, Sunthara Rajan; Rudiger, Skye R; Matthews, Loren; Mitchell, Nadia L; McLaughlan, Clive J; Bawden, C Simon; Palmer, David N; Kuchel, Timothy; Morton, A Jennifer

    2015-01-01

    Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy.

  2. Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging

    PubMed Central

    Sawiak, Stephen J.; Perumal, Sunthara Rajan; Rudiger, Skye R.; Matthews, Loren; Mitchell, Nadia L.; McLaughlan, Clive J.; Bawden, C. Simon; Palmer, David N.; Kuchel, Timothy; Morton, A. Jennifer

    2015-01-01

    Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy. PMID:26161747

  3. Outcome analysis of aromatase inhibitor therapy to increase adult height in males with predicted short adult stature and/or rapid pubertal progress: a retrospective chart review

    PubMed Central

    Shams, Kim; Cameo, Tamara; Fennoy, Ilene; Hassoun, Abeer A.; Lerner, Shulamit E.; Aranoff, Gaya S.; Sopher, Aviva B.; Yang, Christine; McMahon, Donald J.; Oberfield, Sharon E.

    2015-01-01

    Background Aromatase inhibitors (AIs) have been used off-label to increase adult height in short adolescent males. Studies have shown that AIs increase the predicted adult height (PAH) while delaying bone age (BA) maturation. We sought to determine whether AI therapy increases PAH in boys with short stature or rapid pubertal progression, and to evaluate any untoward effects. Methods The charts of 27 boys with BA ≥ 13 and short stature [height ≥ 2 standard deviation (SD) below the mean or ≥ 2 SD below mid-parental target height (MPTH)] or rapid pubertal progress, treated with anastrozole were reviewed. Outcome measures included anthropomorphic, hormonal, and metabolic data. Results The AI therapy averaged 21 months (range 14–30 months) for all, with Rx group 1 receiving < 18 months therapy (n = 7) and Rx group 2 receiving 18–30 months therapy (n = 20). Post-therapy, in Rx group 1 and all subjects, there was no significant change in the PAH, height SDS, or BA/chronological age (CA). In Rx group 2, there was a small, nonsignificant increase in PAH, no change in height SDS, and a small decrease in BA/CA. Post-therapy PAH was different from MPTH in all and in both Rx groups 1 and 2, p < 0.02. Eight of them achieved near-final height, averaging 6.73 ± 1.40 cm less than MPTH and 1.91 ± 0.86 cm less than the pre-therapy PAH. Post-therapy, the initially decreased estradiol did not persist but mildly increased testosterone and decreased high-density lipoprotein were noted, as was an increase in hematocrit, and decrease in growth velocity. Conclusions We suggest that although bone age progression may be slightly delayed with longer duration of therapy, an overall short-term AI therapy does not lead to a final height that is greater than the predicted pre-therapy height. PMID:24756052

  4. Rapidly Progressive Hypertrophic Cardiomyopathy in an Infant with Noonan syndrome with multiple Lentigines. Palliative Treatment with a Rapamycin Analog

    PubMed Central

    Hahn, Andreas; Lauriol, Jessica; Thul, Josef; Behnke-Hall, Kachina; Logeswaran, Tushiha; Schänzer, Anne; Böğürcü, Nuray; Garvalov, Boyan K.; Zenker, Martin; Gelb, Bruce D.; von Gerlach, Susanne; Kandolf, Reinhard; Kontaridis, Maria I.; Schranz, Dietmar

    2015-01-01

    Noonan syndrome with multiple lentigines (NSML) frequently manifests with hypertrophic cardiomyopathy (HCM). Recently, it was demonstrated that mTOR inhibition reverses HCM in NSML mice. We report for the first time on the effects of treatment with a rapamycin analog in an infant with LS and a malignant form of HCM. In the boy, progressive HCM was diagnosed during the first week of life and diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in the PTPN11 gene. Immunoblotting with antibodies against pERK, pAkt, and pS6RP in fibroblasts demonstrated reduced RAS/MAPK and enhanced Akt/mTOR pathway activities. Because of the patient’s critical condition, everolimus therapy was started at age 24 weeks and continued until heart transplantation at age 36 weeks. Prior to surgery, heart failure improved from NYHA stage IV to II and brain natriuretic peptide values decreased from 9600 to <1000 pg/ml, but no reversal of cardiac hypertrophy was observed. Examination of the explanted heart revealed severe hypertrophy and myofiber disarray with extensive perivascular fibrosis. These findings provide evidence that Akt/mTOR activity is enhanced in NSML with HCM and suggest that rapamycin treatment could be principally feasible for infantile NSML. But the preliminary experiences made in this single patient indicate that therapy should start early to prevent irreversible cardiac remodelling. PMID:25708222

  5. Management of Membranous Glomerulonephritis in Pregnancy: A Multidisciplinary Challenge

    PubMed Central

    Ope-Adenuga, Sherifat; Moretti, Michael; Lakhi, Nisha

    2015-01-01

    We present a case of 28-year-old female, who had a past obstetrical history complicated by uncontrolled blood pressure, early onset preeclampsia, and a fetal demise at 29 weeks. Her blood pressure normalized after each pregnancy, and no diagnosis of renal disease was ever established. In her most recent pregnancy, she remained normotensive and initially presented with normal blood urea nitrogen and creatinine levels. However, after the early first trimester, she developed nephrotic range proteinuria, hypoalbuminemia, and peripheral edema. After delivery of the baby, all clinical symptoms rapidly resolved and laboratory values normalized. We review the clinical course, diagnosis, and management of new onset nephrotic syndrome in pregnancy. PMID:26793398

  6. Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

    PubMed

    Birnbaum, Yochai; Mahaffey, Kenneth W; Criger, Douglas A; Gates, Kathy B; Barbash, Gabriel I; Barbagelata, Alejandro; Clemmensen, Peter; Sgarbossa, Elena B; Gibbons, Raymond J; Rahman, M Atiar; Califf, Robert M; Granger, Chistopher B; Wagner, Galen S

    2002-01-01

    We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion. PMID:12077570

  7. Case of streptococcal toxic shock syndrome caused by rapidly progressive group A hemolytic streptococcal infection during postoperative chemotherapy for cervical cancer.

    PubMed

    Nogami, Yuya; Tsuji, Kousuke; Banno, Kouji; Umene, Kiyoko; Katakura, Satomi; Kisu, Iori; Tominaga, Eiichiro; Aoki, Daisuke

    2014-01-01

    Streptococcal toxic shock syndrome (STSS) is a severe infectious disease caused by group A hemolytic streptococcus (Streptococcus pyogenes). This condition is a serious disease that involves rapidly progressive septic shock. We experienced a case of STSS caused by primary peritonitis during treatment with paclitaxel and cisplatin (TP therapy) as postoperative chemotherapy for cervical cancer. STSS mostly develops after extremity pain, but initial influenza-like symptoms of fever, chill, myalgia and gastrointestinal symptoms may also occur. TP therapy is used to treat many cancers, including gynecological cancer, but may cause adverse reactions of neuropathy and nephrotoxicity and sometimes fever, arthralgia, myalgia, abdominal pain and general malaise. The case reported here indicates that development of STSS can be delayed after chemotherapy and that primary STSS symptoms may be overlooked because they may be viewed as adverse reactions to chemotherapy. To our knowledge, this is the first report of a case of STSS during chemotherapy. PMID:23937219

  8. Lung histopathological pattern in a survivor with rapidly progressive interstitial lung disease and anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

    PubMed

    Suzuki, Atsushi; Kondoh, Yasuhiro; Taniguchi, Hiroyuki; Tabata, Kazuhiko; Kimura, Tomoki; Kataoka, Kensuke; Ono, Kenzo; Hashisako, Mikiko; Fukuoka, Junya

    2016-01-01

    Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are specific indicators of patients with dermatomyositis, particularly clinically amyopathic dermatomyositis (CADM). CADM is occasionally accompanied by fatal, treatment-resistant, rapidly-progressive interstitial lung disease (RP-ILD). All previous reports showed that histopathological findings in RP-ILD with anti-MDA5 antibody-positive CADM indicated diffuse alveolar damage (DAD). This is the first report describing a non-DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM, which was improved by immunosuppressive therapy. This case may be a milder clinical phenotype than a typical DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM. PMID:27354955

  9. High-dose intravenous immunoglobulin therapy for rapidly progressive interstitial pneumonitis accompanied by anti-melanoma differentiation-associated gene 5 antibody-positive amyopathic dermatomyositis

    PubMed Central

    Hamada-Ode, Kazu; Taniguchi, Yoshinori; Kimata, Takahito; Kawaguchi, Yasushi; Shimamura, Yoshiko; Kuwana, Masataka; Fujimoto, Shimpei; Terada, Yoshio

    2015-01-01

    Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive amyopathic dermatomyositis (ADM) associated with rapidly progressive interstitial pneumonitis (RPIP) frequently has a poor prognosis and optimal treatment is not well defined. Here, we report a 62-year-old Japanese man with anti-MDA5 antibody-positive ADM associated with RPIP presented with progressive shortness of breath, Heliotrope rash, Gottron’s papules, arthralgia, and fatigue but no sign of muscle weakness. Laboratory investigation revealed serum levels of the following biomarkers: ferritin, 1393 ng/mL; Krebs von der Lungen-6, 1880 U/mL; and creatine kinase, 85 U/L. Computed tomography (CT) images showed diffuse ground-glass opacity in both lung fields. Because anti-MDA5 was positive, we made a diagnosis of ADM associated with RPIP and initiated treatment. Following five courses of combination therapy with prednisolone, cyclosporine A, and intravenous cyclophosphamide (IVCY), IVCY treatment was switched to high-dose intravenous immunoglobulin therapy (IVIg) because of the reactivation of interstitial pneumonia with an increased serum ferritin level. Additional treatment with IVIg improved RPIP, with normalization of anti-ADM antibody levels. Therefore, IVIg mayt be a new candidate treatment for anti-MDA5 antibody-positive ADM associated with RPIP. PMID:27708934

  10. Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice

    PubMed Central

    Jacob, Alexander; Chaves, Lee; Eadon, Michael T; Chang, Anthony; Quigg, Richard J; Alexander, Jessy J

    2013-01-01

    Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh−/−) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19+ B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness. PMID:23347386

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

    PubMed

    McGil Ugwu, G I

    2015-09-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1978-08-01

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

  15. Polyarthritis and membranoproliferative glomerulonephritis as paraneoplastic manifestation of Hodgkin's lymphoma: A case report and literature review.

    PubMed

    Erlij, Daniel; Calderón, Beatriz; Rivera, Angela; Mella, Cristián; Valladares, Ximena; Roessler, Emilio; Rivera, María Teresa; Méndez, Gonzalo

    2016-01-01

    Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment.

  16. [Effects of an antiinflammatory drug (diclofenac) in primary chronic glomerulo-nephritis (author's transl)].

    PubMed

    Lagrue, G; Hirbec, G

    Chronic Glomerulo-Nephritis (GN) are among nephrologic diseases, frequent and severe. In most of them immunological process are involved. Non steroïdal antiinflammatory drugs are able to reduce proteinuria, mainly in Membrano-Proliferative GN and IgA Mesengial GN. A protracted administration is necessary for proteinuria reappeared when treatment is interrupted. With long term administration renal prognosis is improved and severe renal insufficiency delayed. Among active antiinflammatory drugs (indometacine, ketoprofen, diclofenac, flurbiprofen, etc.) diclofenac is one of the best tolerated.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

    PubMed Central

    2014-01-01

    Background No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Methods Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years’ follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. Results 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years’ follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years’ follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Conclusions Our results suggest using three years’ follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable

  1. Humoral immune response in patients with IgA and IgM glomerulonephritis.

    PubMed Central

    Pasternack, A; Mustonen, J; Leinikki, P

    1986-01-01

    A single dose of inactivated mumps virus vaccine was administered to male patients with IgA glomerulonephritis (IgA-GN), IgM glomerulonephritis (IgM-GN) and to healthy males. Antibodies to mumps virus were determined using an enzyme-linked immunosorbent assay. Patients with IgA-GN showed a higher and more sustained IgG and IgA antibody response compared to patients with IgM-GN or healthy controls. Before vaccination, patients with IgM-GN had higher levels of IgG antibodies than the controls or those with IgA-GN. However, the IgA antibody and IgG responses after vaccination were low. IgM antibody responses did not vary among the groups studied. It is concluded that patients with IgA-GN are high responders for IgA and IgG antibody production. Patients with IgM-GN are low responders, especially for IgA antibody. PMID:3955883

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

    PubMed

    Ravnskov, U

    2000-08-01

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

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

    PubMed

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

    2012-12-01

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

  4. Experimental glomerulonephritis in the mouse associated with mesangial deposition ofautologous ferritin immune complexes.

    PubMed

    Stilmant, M M; Couser, W G; Cotran, R S

    1975-06-01

    Mice undergoing prolonged (5 to 8 weeks) immunization with cadium-free feeritin were studied 1 to 32 days following the last ferritin injection. Urine protein was measured and renal tissue examined by light, immunofluorescence, and electron microscopy. Immunized animals developed significant proteinuria and circulating antibody to ferritin.by light microscopy, proetinuric animals had a proliferative glomerular lesion with mesangial hypercellularity and martrix increase, focal and segmental necrosis, fibrin deposits, and occasional crescents. Iron stains revealed prominent mesangial iron deposition. In immunized animals, IgG and C3 deposits were localized mainly in the mesanglium. Electron microscopic studies revealed marked deposition of ferratin complexesexpanded mesangial matrix and mesangial interposition. Ferratin immune complexes were also visualized in epithelial spaces. In the latter location ferritin immune complexes occasionally formed characteristic electron-dense subepithelial deposits. In this model, mesangial and subepithelial localization of autologous ferritin immune complexes is associated with development of glomerulonephritis and characteristic mesangial lesions resembling those seen in some types of human glomerulonephritis.

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

    PubMed

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

    2010-11-01

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

  6. The role of Th1 and Th17 cells in glomerulonephritis

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. Hydralazine-induced ANCA-positive pauci-immune glomerulonephritis: a case report and literature review.

    PubMed

    Dobre, Mirela; Wish, Jay; Negrea, Lavinia

    2009-01-01

    We report a case of hydralazine-induced alveolar hemorrhage and anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immune glomerulonephritis, with serum anti-histone antibodies present, features not previously described in the literature with this drug. A 50-year-old Caucasian female had hypertension treated with hydralazine 75mg TID for three years, and a lung nodule followed up periodically with chest-computed tomographies. She was admitted to the hospital for hemoptysis and newly discovered diffuse pulmonary ground-glass opacities. Transbronchial lung biopsy showed alveolar hemorrhage. Serum creatinine was 3.5 mg/dL and urinalysis showed 2+blood, 30-50RBC/hpf and red blood cell casts. ANCA against myeloperoxidase were present. Anti-double-stranded DNA, ANA, and anti-histone antibodies were positive. Serum complements were normal. Renal biopsy revealed focal crescentic necrotizing glomerulonephritis with negative immunofluorescence, consistent with pauci-immune ANCA-positive vasculitis. Serum creatinine returned to baseline three days after hydralazine was discontinued, and the hemoptysis resolved after treatment with cyclophosphamide and prednisone was started. We concluded that this case represents a hydralazine-induced small vessel vasculitis rather than an idiopathic one. The possibility of hydralazine-induced vasculitis should be considered when patients treated with hydralazine develop a pulmonary-renal syndrome. Anti-histone antibodies may be present in the absence of full classification criteria of drug-induced lupus.

  9. Rapidly Progressive Seeding of a Community Acquired Pathogen in an Immune-competent Host--End Organ Damage from Head to Bone.

    PubMed

    Torres-Miranda, Daisy; Al-Saffar, Farah; Ibrahim, Saif; Font-Diaz, Stephanie

    2015-01-01

    This report describes a 64-years-old male patient that presented to our hospital with a chief complaint of acute worsening of his usual chronic lower back pain, progressive weakness in lower extremities and subjective fevers at home. Spine CT failed to demonstrate any infectious foci but showed partially visualized lung cavitary lesion and renal pole abnormalities. Blood cultures grew methicillin-sensitive Staphylococcus Aureus (MSSA). Transthoracic echocardiogram (TTE) showed no signs of infective endocarditis (IE). Later, the patient experienced an acute deterioration on clinical status and examination showed development of a new murmur. He also developed new hemiparesis with up-going babinski reflex. A head MRI showed multiple infarcts. MRI spine displayed osteomyelitis at T12-L1. Cerebro-spinal fluid was positive for meningitis. A transesophageal echocardiogram (TEE) was performed demonstrating new severe mitral and mild tricuspid regurgitations with a definitive 1.5 cm mobile vegetation on posterior mitral leaflet. We present is a very interesting case of a rapidly progressive MSSA infection. MSSA meningitis is a rare disease; there are only few reported cases in the literature to date. We describe a case of MSSA bacteremia, of questionable source, that resulted in MSSA endocarditis affecting right and left heart in a patient who did not have a history of intravenous drug use (IVDU) or immunosuppression. The case was complicated by septic emboli to systemic circulation involving the kidneys, vertebral spine (osteomyelitis), lungs and brain with consequent meningitis and stroke. Even when MSSA infections are well known, to our knowledge there are no previous case reports describing such an acute-simultaneous-manifestation of multi-end-organ failure, including meningitis and stroke. These latter are rarely reported, even individually. PMID:26434076

  10. Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data

    PubMed Central

    Granger, Benjamin; Combe, Bernard; Le Loet, Xavier; Saraux, Alain; Guillemin, Francis; Fautrel, Bruno

    2016-01-01

    Introduction Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX). Methods We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for ≥3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS≥5 points during the first year. Results At 1 year, the mean vSHS score was 1.7±5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC) <0.7. The AUC for the BEST and SONORA matrices were 0.73 and 0.76. Presence of rheumatoid factor (RF)—or anti-citrullinated protein antibodies (ACPAs) and initial structural damage were always predictive of RRP at 1 year. Disease Activity Score in 28 joints (DAS28) and C reactive protein (ASPIRE threshold) were not associated with RRP. Conclusions Matrices to identify patients at risk of RRP tested in the ESPOIR cohort seem to perform moderately. There is no matrix that shows clearly superior performance. PMID:27252898

  11. Using SAR and GPS for Hazard Management and Response: Progress and Examples from the Advanced Rapid Imaging and Analysis (ARIA) Project

    NASA Astrophysics Data System (ADS)

    Owen, S. E.; Simons, M.; Hua, H.; Yun, S. H.; Agram, P. S.; Milillo, P.; Sacco, G. F.; Webb, F.; Rosen, P. A.; Lundgren, P.; Milillo, G.; Manipon, G. J. M.; Moore, A. W.; Liu, Z.; Polet, J.; Cruz, J.

    2014-12-01

    ARIA is a joint JPL/Caltech project to automate synthetic aperture radar (SAR) and GPS imaging capabilities for scientific understanding, hazard response, and societal benefit. We have built a prototype SAR and GPS data system that forms the foundation for hazard monitoring and response capability, as well as providing imaging capabilities important for science studies. Together, InSAR and GPS have the ability to capture surface deformation in high spatial and temporal resolution. For earthquakes, this deformation provides information that is complementary to seismic data on location, geometry and magnitude of earthquakes. Accurate location information is critical for understanding the regions affected by damaging shaking. Regular surface deformation measurements from SAR and GPS are useful for monitoring changes related to many processes that are important for hazard and resource management such as volcanic deformation, groundwater withdrawal, and landsliding. Observations of SAR coherence change have a demonstrated use for damage assessment for hazards such as earthquakes, tsunamis, hurricanes, and volcanic eruptions. These damage assessment maps can be made from imagery taken day or night and are not affected by clouds, making them valuable complements to optical imagery. The coherence change caused by the damage from hazards (building collapse, flooding, ash fall) is also detectable with intelligent algorithms, allowing for rapid generation of damage assessment maps over large areas at fine resolution, down to the spatial scale of single family homes. We will present the progress and results we have made on automating the analysis of SAR data for hazard monitoring and response using data from the Italian Space Agency's (ASI) COSMO-SkyMed constellation of X-band SAR satellites. Since the beginning of our project with ASI, our team has imaged deformation and coherence change caused by many natural hazard events around the world. We will present progress on our

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

    PubMed

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

    2016-01-01

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

  13. [A case of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive crescentic glomerulonephritis induced by propylthiouracil (PTU)].

    PubMed

    Kato, H; Osajima, A; Tanaka, H; Serino, R; Kabashima, N; Tamura, M; Segawa, K; Anai, H; Takasugi, M; Nakajima, Y

    1997-07-01

    We have experienced a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis induced by propylthiouracil (PTU). A 45-year-old female had been treated with PTU for 4 years after the diagnosis of hyperthyroidism. She was referred to out hospital because of abrupt macroscopic hematuria and moderate proteinuria after several days of upper respiratory tract infection. On admission, her laboratory findings showed deterioration of renal function. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes. Her serology was found to be MPO-ANCA-positive and cytoplasmic-ANCA-negative. Based of these findings, we diagnosed idiopathic crescentic glomerulonephritis. Following the initiation of steroid pulse therapy, her urinary protein excretion and renal function gradually improved in parallel with a decrease in the MPO-ANCA titer. Although steroid therapy effectively responded to their renal function without the withdrawal of PTU, it seems that PTU may be closely associated with the development of (MPO-ANCA)-related glomerulonephritis in this case. Therefore, hyperthyroidism patients treated with PTU should be paced under vigilant observation by monitoring their urinalysis and serum creatinine level.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. Membranoproliferative glomerulonephritis

    MedlinePlus

    ... glomeruli. The glomeruli of the kidney help filter wastes and fluids from the blood to form urine. ... the glomerular basement membrane. This membrane helps filter wastes and extra fluids from the blood. Damage to ...

  17. Transplantation-based gene therapy for inflammatory diseases: focus on glomerulonephritis.

    PubMed

    Yokoo, T; Ohashi, T

    2001-07-01

    Over the past decade, bone marrow transplantation has come to be considered an ideal therapeutic strategy for the treatment of certain diseases affecting the hematopoietic system such as hemophilia, and several clinical trials have been performed. Although traditionally used for the treatment of lethal diseases, it is speculated that this approach could also be used in the treatment of non-lethal but much more common diseases, which are resistant to conventional therapies, and affect a large number of patients physically and even financially. Inflammation may be one target for transplantation-based gene therapy, since macrophages and neutrophils, which are basically derived from hematopoietic stem cells, have been identified as key determinants in the development of diseases. This article focuses on the glomerulonephritis as a model of local inflammation and reviews recent investigations on transplantation-based gene therapy for inflammatory diseases.

  18. Nephrotic-range proteinuria on interferon-β treatment: immune-induced glomerulonephritis or other pathway?

    PubMed

    Yuste, C; Rapalai, M; Pritchard, B A; Jones, T J; Tucker, B; Ramakrishna, S B

    2014-04-01

    We present a case report of a 37-year-old woman with multiple sclerosis (MS) who developed nephrotic-range proteinuria secondary to membrano proliferative glomerulonephritis (MPGN)-like disease with mesangial C3 deposition without evidence of immune-complex deposition in the context of long-term interferon-β (IFN-β) therapy. The complete remission of proteinuria following cessation of IFN-β, strongly suggests causality. To our knowledge, this is the second case report of MPGN associated with IFN-β use. This being the case, the negative immune screen, normal inflammatory markers and the absence of immune complex deposits would imply a different pathway to that previously suggested. PMID:25852870

  19. Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis.

    PubMed

    Mustonen, J; Pasternack, A; Helin, H; Nikkilä, M

    1985-01-01

    In an unselected series of patients with IgA glomerulonephritis, old age, high blood pressure, and high urinary protein excretion at the time of renal biopsy were found to correlate with impaired renal function, whereas sex, estimated duration of the disease, or high serum IgA levels did not. The following clinical features were favorable prognostic signs: asymptomatic proteinuria, macroscopic hematuria, and isolated microscopic hematuria. The degree of diffuse mesangial alteration and the presence of segmental glomerular lesions correlated clearly with the subsequent clinical outcome. Vascular lesions, i.e. arteriosclerosis and renal vascular deposition of C3, were most often present in patients with severe glomerulopathy. The presence of electron-dense deposits in glomerular capillary walls was also an unfavorable prognostic finding. Renal biopsy findings of interstitial infiltrates of inflammatory cells and IgA distributed along glomerular capillary walls were usually associated with extrarenal manifestations of the disease. PMID:4014321

  20. Eculizumab-induced reversal of dialysis-dependent kidney failure from C3 glomerulonephritis

    PubMed Central

    Inman, Melissa; Prater, Ginnie; Fatima, Huma; Wallace, Eric

    2015-01-01

    C3 glomerulopathy (C3G) is characterized by C3 deposits with minimal immunoglobulin deposition caused by alternative complement pathway dysregulation. Unfortunately, no therapeutic intervention has consistently improved outcomes for patients with C3G. Eculizumab, a monoclonal antibody to C5, is currently the only approved complement-specific agent with some efficacy in the treatment of C3 glomerulonephritis (C3GN). Here, we describe a patient with acute crescentic C3GN with no identified complement mutation or family history of renal disease who required dialysis for 6 months. Five months after initiation of eculizumab, she became dialysis independent, showing improvement is possible after adequate time on eculizumab. PMID:26251714

  1. Successful steroid treatment in a patient with membranoproliferative glomerulonephritis associated with hepatitis C virus.

    PubMed

    Sanai, Toru; Watanabe, Izumi; Hirano, Tadashi; Nakayama, Masaru; Sakai, Hironori; Uesugi, Noriko; Masutani, Kohsuke; Katafuchi, Ritsuko; Hirakata, Hideki; Iida, Mitsuo

    2009-01-01

    Thirteen years ago, a 65-year-old woman was diagnosed to have chronic active hepatitis with hepatitis C virus. After starting interferon alpha administration, she noticed edema and hypoalbuminemia. Renal biopsy revealed mesangial proliferation with focal endocapillary proliferation, and double contour of the glomerular basement membrane due to mesangial interposition. Interferon alpha was discontinued, and proteinuria and edema gradually decreased. She was re-admitted due to a relapse of proteinuria 8 years later. Biopsy revealed moderate mesangial and endcapillary proliferation presenting a lobular pattern, in addition to the presence of hyaline thrombi. Granular staining of immunoglobulin M and of C3 in capillary walls were detected. Since cryoglobulinemia was positive, a final diagnosis of cryoglobulinemic membranoproliferative glomerulonephritis was made. Prednisolone was started with an initial dose of 20 mg/day. Proteinuria and hypoalbuminemia improved, and prednisolone was tapered to 5 mg/day 9 months after the 2nd renal biopsy. The hepatitis C virus-RNA titer fluctuated.

  2. Phospholipase A2 Receptor-Positive Idiopathic Membranous Glomerulonephritis with Onset at 95 Years: Case Report

    PubMed Central

    Kubota, Keiichi; Hoshino, Junichi; Ueno, Toshiharu; Mise, Koki; Hazue, Ryo; Sekine, Akinari; Yabuuchi, Junko; Yamanouchi, Masayuki; Suwabe, Tatsuya; Kikuchi, Koichi; Sumida, Keiichi; Hayami, Noriko; Sawa, Naoki; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Akiyama, Shinichi; Maruyama, Shoichi; Ubara, Yoshifumi

    2016-01-01

    A 95-year-old woman was admitted to our hospital for evaluation of bilateral lower-limb edema persisting for 3 months. Serum creatinine was 1.55 mg/dl, and urinary protein excretion was 9.1 g/day. Renal biopsy revealed stage 1 membranous glomerulonephritis (MGN) with immunoglobulin G4-dominant staining. This patient did not have any underlying disease such as infection with hepatitis B or C virus or malignancy, and anti-phospholipase A2 receptor (PLA2R) antibody was detected in the serum. Accordingly, idiopathic MGN was diagnosed. Corticosteroid therapy was avoided, but hemodialysis was required to treat generalized edema. The patient is currently doing well. This is the oldest reported case of idiopathic MGN with positivity for anti-PLA2R antibody. PMID:27390744

  3. Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN

    PubMed Central

    Salvadori, Maurizio; Rosso, Giuseppina

    2016-01-01

    This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies. PMID:27458560

  4. Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN.

    PubMed

    Salvadori, Maurizio; Rosso, Giuseppina

    2016-07-01

    This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies. PMID:27458560

  5. Hydrogen peroxide-inducible clone-5 regulates mesangial cell proliferation in proliferative glomerulonephritis in mice.

    PubMed

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

    2015-01-01

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

  6. Platelets are not critical effector cells for the time course of murine passive crescentic glomerulonephritis.

    PubMed

    Hohenstein, Bernd; Daniel, Christoph; Johnson, Richard J; Amann, Kerstin U; Hugo, Christian P M

    2013-01-01

    Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days. Platelets were depleted using anti-glycoprotein Ibα antibodies (p0p3/p0p4) every 4th day. Mice treated with equal amounts of sterile Phosphate buffered solution or rat-IgG served as controls. Blood, urine, and tissues were harvested on days 3 and 28. Renal tissue sections were evaluated after immunostaining using (semi)quantitative and computer-assisted image analysis. Compared to controls, efficient depletion was achieved as indicated by a markedly prolonged bleeding time and a more than 90% reduction in platelet counts (800/nl vs. 42/nl; P < 0.001). Functional (creatinine-clearance and proteinuria) parameters demonstrated no significant differences between the groups. Neither parameters of renal injury (glomerulosclerosis and fibrosis) nor glomerular/tubulointerstitial matrix expansion (by collagen IV staining), glomerular capillary rarefaction (lectin staining), and the glomerular/tubulointerstitial proliferative response (proliferating cell nuclear antigen) demonstrated any differences between platelet-depleted mice and PBS- or rat-IgG-treated nephritic mice at any time point. Despite effective platelet inhibition/depletion, neither the short- nor long-term course of passive crescentic nephrotoxic nephritis was affected. These data indicate that platelets play a minor role during the time course of this disease model in the mouse.

  7. Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis.

    PubMed

    Hiramatsu, Rikako; Ubara, Yoshifumi; Sawa, Naoki; Hasegawa, Eiko; Kawada, Masahiro; Imafuku, Aya; Sumida, Keiichi; Mise, Koki; Yamanouchi, Masayuki; Ueno, Toshiharu; Sekine, Akinari; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Wake, Atsushi; Taniguchi, Shuichi

    2016-04-01

    Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.

  8. Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN.

    PubMed

    Salvadori, Maurizio; Rosso, Giuseppina

    2016-07-01

    This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.

  9. Anaerococcus urinomassiliensis sp. nov., isolated from a urine sample of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis.

    PubMed

    Morand, A; Cornu, F; Tsimaratos, M; Lagier, J-C; Cadoret, F; Fournier, P-E; Raoult, D

    2016-09-01

    We report the main characteristics of 'Anaerococcus urinomassiliensis' strain FC4(T) (CSURP2143) that was isolated from a urine sample of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis.

  10. Experience in the diagnosis of glomerulonephritis using combined light microscopical, ultrastructural and immunofluorescence techniques--an analysis of 134 cases.

    PubMed

    Dische, F E; Parsons, V

    1977-09-01

    The contribution of electron and immunofluorescence microscopy to renal biopsy diagnosis is illustrated by the results obtained in a personal series of patients with various types of glomerulonephritis. Introductory notes on the ultrastructure of the glomerular capillary and on immunological processes are also included. Immunofluorescent staining has particular value in demonstrating IgG-containing deposits in early membranous glomerulonephritis at a stage when ordinary microscopy is inconclusive. It is capable of throwing light on the mechanism of glomerular damage in severe extracapillary proliferation and in some cases of recurrent haematuria, but is less successful in separating minimal change disease from proliferative processes. Electron microscopy reveals the precise site of immune deposits and fibrin together with basement membrane changes, the microtubular structures common in SLE, and other details. It is concluded that for the accurate diagnosis of kidney disease it is essential to supplement light microscopy by one, or preferably both these methods.

  11. Complement activation in progressive renal disease

    PubMed Central

    Fearn, Amy; Sheerin, Neil Stephen

    2015-01-01

    Chronic kidney disease (CKD) is common and the cause of significant morbidity and mortality. The replacement of functioning nephrons by fibrosis is characteristic of progressive disease. The pathways that lead to fibrosis are not fully understood, although chronic non-resolving inflammation in the kidney is likely to drive the fibrotic response that occurs. In patients with progressive CKD there is histological evidence of inflammation in the interstitium and strategies that reduce inflammation reduce renal injury in pre-clinical models of CKD. The complement system is an integral part of the innate immune system but also augments adaptive immune responses. Complement activation is known to occur in many diverse renal diseases, including glomerulonephritis, thrombotic microangiopathies and transplant rejection. In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease. PMID:25664245

  12. Statin Attenuates Experimental Anti-Glomerular Basement Membrane Glomerulonephritis Together with the Augmentation of Alternatively Activated Macrophages

    PubMed Central

    Fujita, Emiko; Shimizu, Akira; Masuda, Yukinari; Kuwahara, Naomi; Arai, Takashi; Nagasaka, Shinya; Aki, Kaoru; Mii, Akiko; Natori, Yasuhiro; Iino, Yasuhiko; Katayama, Yasuo; Fukuda, Yuh

    2010-01-01

    Macrophages are heterogeneous and include classically activated M1 and alternatively activated M2 macrophages, characterized by pro- and anti-inflammatory functions, respectively. Macrophages that express heme oxygenase-1 also exhibit anti-inflammatory effects. We assessed the anti-inflammatory effects of statin in experimental anti-glomerular basement membrane glomerulonephritis and in vitro, focusing on the macrophage heterogeneity. Rats were induced anti-glomerular basement membrane glomerulonephritis and treated with atorvastatin (20 mg/kg/day) or vehicle (control). Control rats showed infiltration of macrophages in the glomeruli at day 3 and developed crescentic glomerulonephritis by day 7, together with increased mRNA levels of the M1 macrophage-associated cytokines, interferon-γ, tumor necrosis factor-α, and interleukin-12. In contrast, statin reduced the level of proteinuria, reduced infiltration of macrophages in glomeruli with suppression of monocyte chemotactic protein-1 expression, and inhibited the formation of necrotizing and crescentic lesions. The number of glomerular ED3-positive macrophages decreased with down-regulation of M1 macrophage-associated cytokines. Furthermore, statin augmented ED2-positive M2 macrophages with up-regulation of the M2 macrophage-associated chemokines and cytokines, chemokine (C-C motif) Iigand-17 and interleukin-10. Statin also increased the glomerular interleukin-10-expressing heme oxygenase-1-positive macrophages. Statin inhibited macrophage development, and suppressed ED3-positive macrophages, but augmented ED2-positive macrophages in M2-associated cytokine environment in vitro. We conclude that the anti-inflammatory effects of statin in glomerulonephritis are mediated through inhibition of macrophage infiltration as well as augmentation of anti-inflammatory macrophages. PMID:20696778

  13. ELECTRON MICROSCOPIC STUDIES OF HUMAN GLOMERULONEPHRITIS WITH FERRITIN-CONJUGATED ANTIBODY

    PubMed Central

    Andres, Giuseppe A.; Accinni, Lidia; Hsu, Konrad C.; Zabriskie, John B.; Seegal, Beatrice C.

    1966-01-01

    1. Kidney biopsies from 4 cases of severe acute glomerulonephritis were obtained 11 to 25 days after the onset of clinical manifestations of the disease. These tissues were treated with ferritin-conjugated antibodies to 7S γ-globulin, β1C, and Type 12 streptococcal products. Adjacent pieces of the biopsied material were treated with control ferritin-labeled antisera or with ferritin alone. As further controls, normal renal tissue and renal tissue from patients with other kidney diseases were treated with the same antisera. The 3 antisera to 7S γ-globulin, β1C and Type 12 streptococcus were specifically bound in electron-opaque foreign material in the following renal areas: (a) the lumen of glomerular capillaries; (b) medullary arteriolar walls (2 cases); (c) pinocytic vacuoles and absorption droplets of endothelial or mesangial cells; (d) canals between proliferating mesangial or endothelial cells which connect the capillary lumen with the deep mesangial region or with the endothelial side of the basement membrane; (e) basement membrane proper; (f) subendothelial and certain subepithelial deposits; and (g) Bowman's space. 2. None of the 3 ferritin-conjugated antisera listed above were bound to the nuclei of glomerular cells or to portions of the cytoplasm other than those specified. 3. Ferritin-conjugated antisera to pneumococcus Type II and vaccinia virus and ferritin alone were not bound to any structures in the glomerular tissue. 4. None of the ferritin-conjugated antisera bound to normal renal tissue or to kidney tissue from other renal disease. 5. The data obtained are compatible with the following working hypothesis: Antigen-antibody aggregates of Type 12 streptococcal products, γ-globulin, and complement are present in the circulating blood of patients with severe acute glomerulonephritis. Large amounts of the complexes are caught in the filtering system of the glomeruli. The inflammatory reactions seen in the glomerular structures result from the

  14. Modeling rapidly rotating stars

    NASA Astrophysics Data System (ADS)

    Rieutord, M.

    2006-06-01

    We review the quest of modeling rapidly rotating stars during the past 40 years and detail the challenges to be taken up by models facing new data from interferometry, seismology, spectroscopy... We then present the progress of the ESTER project aimed at giving a physically self-consistent model for the structure and evolution of rapidly rotating stars.

  15. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report

    PubMed Central

    Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  16. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report.

    PubMed

    Vitaliti, Giovanna; Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  17. Optimizing the translational value of animal models of glomerulonephritis: insights from recent murine prototypes.

    PubMed

    Foster, Mary H

    2016-09-01

    Animal models are indispensable for the study of glomerulonephritis, a group of diseases that destroy kidneys but for which specific therapies do not yet exist. Novel interventions are urgently needed, but their rational design requires suitable in vivo platforms to identify and test new candidates. Animal models can recreate the complex immunologic microenvironments that foster human autoimmunity and nephritis and provide access to tissue compartments not readily examined in patients. Study of rat Heymann nephritis identified fundamental disease mechanisms that ultimately revolutionized our understanding of human membranous nephropathy. Significant species differences in expression of a major target antigen, however, and lack of spontaneous autoimmunity in animals remain roadblocks to full exploitation of preclinical models in this disease. For several glomerulonephritides, humanized models have been developed to circumvent cross-species barriers and to study the effects of human genetic risk variants. Herein we review humanized mouse prototypes that provide fresh insight into mediators of IgA nephropathy and origins of antiglomerular basement membrane nephritis and Goodpasture's disease, as well as a means to test novel therapies for ANCA vasculitis. Additional and refined model systems are needed to mirror the full spectrum of human disease in a genetically diverse population, to facilitate development of patient-specific interventions, to determine the origin of nephritogenic autoimmunity, and to define the role of environmental exposures in disease initiation and relapse. PMID:27335377

  18. Taking the pulse of a sick kidney: arterial stiffness in glomerulonephritis.

    PubMed

    Doyon, Anke; Schaefer, Franz

    2011-02-01

    Arterial stiffness is an increasingly recognized independent predictor of cardiovascular morbidity. Vessel volume and wall texture are the main determinants of pulse wave velocity (PWV), the most commonly used indicator of arterial elasticity. Hence, measurements of PWV will be affected by the site of measurement and the overall dimensions of the vascular tree as well as by alterations of vascular morphology. In children, methodological heterogeneity and the lack of pediatric reference values complicate the interpretation of PWV. Arterial elasticity is altered in numerous clinical conditions such as vasculitis, end-stage renal disease, and diabetes. Novel evidence suggests that acute postinfectious glomerulonephritis, but not pyelonephritis, is also associated with increased arterial stiffness, the persistence of which may predict the emergence of chronic kidney disease. We review the potential mechanisms underlying the link between acute and chronic kidney disease and impaired arterial elasticity. These might include activation of the renin-angiotensin system, sympathetic hyperactivation, and a subclinical state of inflammation. In view of the excessive cardiovascular comorbidity associated with kidney disease, the increasing evidence of the prognostic relevance of arterial stiffness should encourage further research investigating the usefulness of PWV as a biomarker in acute and chronic kidney disorders.

  19. Combined optical coherence tomography and optical coherence elastography for glomerulonephritis classification

    NASA Astrophysics Data System (ADS)

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Mohammadzai, Qais; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Chang, Anthony; Mohan, Chandra; Larin, Kirill V.

    2016-03-01

    Acute Glomerulonephritis caused by anti-glomerular basement membrane disease has a high mortality due to delayed diagnosis. Thus, an accurate and early diagnosis is critical for preserving renal function. Currently, blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution. Optical coherence tomography (OCT) is a noninvasive imaging technique that provides superior spatial resolution (micron scale) as compared to ultrasound and CT. Pathological changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signal, such as optical attenuation and speckle variance. Moreover, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, we utilized OCT to detect the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, classification accuracy using only optical metrics was clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improved from 76% to 95%. These results show that OCT combined with OCE can be potentially useful for nephritis detection.

  20. A chromosomal translocation causing multiple abnormalities including open eyelids at birth and glomerulonephritis.

    PubMed

    Guarnieri, Mary H; Cacheiro, Nestor L; Rudofsky, Ulrich H; Montgomery, Jeffry C; Collins, Doris N; Flaherty, Lorraine A

    2002-08-01

    We have characterized the phenotype of a mouse with a t(2;13) reciprocal translocation induced by chlorambucil. It results in abnormal eyelid formation as well as a series of neurological, physiological, and immunological abnormalities. This mutant has been termed T(2;13)1Fla/+. T(2;13)1Fla/+ mice exhibit open eyelids at birth, a dilute coat color, hyperactivity, and occasional circling and stargazing activity. At 1-6 months, T(2;13)1Fla/+ mice show signs of immune complex-mediated glomerulonephritis and die prematurely. Additionally, double-stranded DNA autoantibodies have been found in sera of T(2;13)1Fla/+ mice. Cytogenetic analysis situated the translocation breakpoint at the proximal end of Chromosome (chr) 2 at band A2, and on Chr 13 at band A4. The mutant phenotype completely correlated with the presence of the translocation. Additional genetic studies have mapped the mutation and translocation breakpoint to Chr 13 between D13Mit16 and D13Mit64, and to Chr 2 proximal to D2Mit5. By fluorescent in situ hybridization (FISH), the position of this mutation/translocation on Chr 13 has been mapped to a region less than 1cM from D13Mit61. PMID:12226706

  1. An essential role of interleukin-17 receptor signaling in the development of autoimmune glomerulonephritis.

    PubMed

    Ramani, Kritika; Pawaria, Sudesh; Maers, Kelly; Huppler, Anna R; Gaffen, Sarah L; Biswas, Partha S

    2014-09-01

    In recent years, proinflammatory cytokines in the nephritic kidney appear to contribute to the pathogenesis of AGN. The complex inflammatory cytokine network that drives renal pathology is poorly understood. IL-17, the signature cytokine of Th17 cells, which promotes autoimmune pathology in a variety of settings, is beginning to be identified in acute and chronic kidney diseases as well. However, the role of IL-17-mediated renal damage in the nephritic kidney has not been elucidated. Here, with the use of a murine model of experimental AGN, we showed that IL-17RA signaling is critical for the development of renal pathology. Despite normal systemic autoantibody response and glomerular immune-complex deposition, IL-17RA(-/-) mice exhibit a diminished influx of inflammatory cells and kidney-specific expression of IL-17 target genes correlating with disease resistance in AGN. IL-17 enhanced the production of proinflammatory cytokines and chemokines from tECs. Finally, we were able to show that neutralization of IL-17A ameliorated renal pathology in WT mice following AGN. These results clearly demonstrated that IL-17RA signaling significantly contributes to renal tissue injury in experimental AGN and suggest that blocking IL-17RA may be a promising therapeutic strategy for the treatment of proliferative and crescentic glomerulonephritis.

  2. A case of acute post-streptococcal glomerulonephritis that developed posterior reversible encephalopathy syndrome.

    PubMed

    Kasap, Belde; Çarman, Kürşat Bora; Yiş, Uluç

    2014-12-01

    A 10-year male patient presented with swelling in the face, legs and scrotal area which developed 8 days after tonsillitis treatment. Acute post-sterotococcal glomerulonephritis (APSGN) was considered in the patient whose urinalysis revealed hematuria and proteinuria at nephrotic level, whose urea, creatinine, lipid profile and anti-streptolysine O antibody levels were increased, albumin and C3 value were decreased and whose 24-hour urine test revealed proteinuria. Renal biopsy was found to be compatible with APSGN. In the follow-up, severe headache, vomiting and convulsion were observed under antihypertensive and diuretic treatment and when the blood pressure was 130/80 mmHg (the 99(th) percentile for the patient: 129/88 mmHg). During the follow-up, the blood pressure values increased to 160/90 mmHg. The electroencephalogram (EEG) performed was found to be normal and magnetic resonance imaging (MRI) findings were compatible with posterior reversible encephalopathy syndrome (PRES). MRI was found to be normal at the first month following antihypertensive and anticonvulsive treatment. In the first year of the follow-up, the blood pressure, neurological examination and urinalysis findings were found to be normal. This patient was presented to draw attention to the fact that PRES can also present with a blood pressure tending to increase and with blood pressure values which are not so high. PMID:26078688

  3. Clinical and Immunologic Characteristics of Patients With ANCA-Associated Glomerulonephritis Combined With Membranous Nephropathy

    PubMed Central

    Zou, Rong; Liu, Gang; Cui, Zhao; Chen, Min; Zhao, Ming-Hui

    2015-01-01

    Abstract The concurrent antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) and membranous nephropathy (MN) have been increasingly documented, mainly in case studies and case series; however, the differences of clinical and pathologic characteristics as well as outcomes between ANCA-GN patients with and without MN remain unclear. The current study investigated the clinical and immunologic features of patients with combined ANCA-GN and MN in a large cohort. Twenty-seven of 223 patients had combined ANCA-GN and MN; they had significantly higher levels of initial serum creatinine, higher Birmingham Vasculitis Activity Score and poorer renal outcome than ANCA-GN patients without MN (P < 0.05). ANCA-GN patients with MN could recognize the light chain of myeloperoxidase more frequently than those without MN (P < 0.05). The prevalence of circulating anti-PLA2R antibodies and glomerular PLA2R deposits was significantly lower in patients with combined ANCA-GN and MN than that in patients with idiopathic MN (P < 0.05). Compared with the idiopathic MN patients, the patients with combined ANCA-GN and MN had significantly higher recognition frequency of immunoglobulin (Ig) G2 and IgG3, and significantly lower recognition frequency of IgG4 (P < 0.05). Patients with combined ANCA-GN and MN had distinct clinical features and a different pathogenesis of MN. PMID:26376387

  4. Enigma (partially) resolved: phospholipase A2 receptor is the cause of "idiopathic" membranous glomerulonephritis.

    PubMed

    Truong, Luan D; Seshan, Surya V

    2015-12-15

    Membranous glomerulonephritis (MGN) is a very significant kidney disease. It is one of the frequent causes of heavy protein excretion in urine. MGN is thought to be an immune-mediated disease caused by glomerular deposition of antigen-antibody complexes. The pathogenic antigen, however, has been an enigma until recently. It was discovered in 2009 that phospholipase A2 receptor (PLA2R), a normal transmembrane protein in podocyte plasma membrane, is the antigen causing MGN. Within 5 yr of its discovery, this seminal finding has leaded to novel insights into the treatment of this disease including diagnosis, therapy, and prediction of outcome. This finding also paves the way for fundamental studies on how and why autoimmunity against PLA2R develops. The discovery of PLA2A as the cause of "idiopathic" MGN after a half century of speculation, followed by further fundamental insights with such an expedient and successful application in patient care, embodies the elegance of science at its junction with society. This perspective traces the story of this remarkable discovery.

  5. Membranoproliferative glomerulonephritis with isolated C3 deposits: case report and literature review.

    PubMed

    Darouich, Sihem; Goucha, Rym; Jaafoura, Mohamed Habib; Zekri, Semy; Kheder, Adel; Ben Maiz, Hédi

    2011-02-01

    Membranoproliferative glomerulonephritis with isolated C3 deposits (MPGNC3) is an uncommon condition characterized by overt glomerular C3 deposits in the absence of immunoglobulins and intramembranous dense deposits. Here the authors describe the clinical and morphological features of primary MPGNC3 in a 13-year-old boy and critically review the previously published cases. The patient presented with nephrotic syndrome and microscopic hematuria. Blood tests revealed very low circulating C3 levels. The renal biopsy exhibited subendothelial, subepithelial, and mesangial deposits, with C3 but not immunoglobulins seen on immunofluorescence. This case and the review of the literature indicate that the serum complement profile with decreased levels of C3 and normal levels of classical pathway components together with glomerular deposits containing exclusively complement C3 is highly suggestive of alternative pathway activation. The diagnosis of acquired and/or genetic complement abnormalities in some cases supports that complement dysregulation is implicated in the pathogenesis of MPGNC3. Such data show great promise to provide new therapy strategies based on modulation of the complement system activity.

  6. Interagency partnering for weed prevention--progress on development of a National Early Detection and Rapid Response System for Invasive Plants in the United States

    USGS Publications Warehouse

    Westbrooks, R.; Westbrooks, R.

    2011-01-01

    Over the past 50 years, experience has shown that interagency groups provide an effective forum for addressing various invasive species issues and challenges on multiple land units. However, more importantly, they can also provide a coordinated framework for early detection, reporting, identification and vouchering, rapid assessment, and rapid response to new and emerging invasive plants in the United States. Interagency collaboration maximizes the use of available expertise, resources, and authority for promoting early detection and rapid response (EDRR) as the preferred management option for addressing new and emerging invasive plants. Currently, an interagency effort is underway to develop a National EDRR System for Invasive Plants in the United States. The proposed system will include structural and informational elements. Structural elements of the system include a network of interagency partner groups to facilitate early detection and rapid response to new invasive plants, including the Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW), State Invasive Species Councils, State Early Detection and Rapid Response Coordinating Committees, State Volunteer Detection and Reporting Networks, Invasive Plant Task Forces, and Cooperative Weed Management Areas. Informational elements and products being developed include Regional Invasive Plant Atlases, and EDRR Guidelines for EDRR Volunteer Network Training, Rapid Assessment and Rapid Response, and Criteria for Selection of EDRR Species. System science and technical support elements which are provided by cooperating state and federal scientists, include EDRR guidelines, training curriculum for EDRR volunteers and agency field personnel, plant identification and vouchering, rapid assessments, as well as predictive modeling and ecological range studies for invasive plant species.

  7. Recurrent Proliferative Glomerulonephritis With Monoclonal IgG Deposits After a Renal Transplant Which Was Insensitive to Pulse Therapy Remitted by Double Filtration Plasmapheresis.

    PubMed

    Wu, Di; Chen, Jin-Song; Cheng, Dong-Rui; Chen, Hao; Li, Xue; Ji, Shu-Ming; Xie, Ke-Nan; Ni, Xue-Feng; Liu, Zhi-Hong; Wen, Ji-Qiu

    2015-10-01

    Proliferative glomerulonephritis with monoclonal IgG deposits manifesting as a nephrotic syndrome recently has been described as a renal disease with the pathological features of mesangial and subendothelial deposits of monoclonal IgG. Eight cases of recurrent proliferative glomerulonephritis with monoclonal IgG deposits after a renal transplant have been reported. Almost all of these patients had a certain remission of proteinuria by steroids alone or with cyclophosphamide, and had further remission through other special treatments (ie, rituximab and plasmapheresis). We present a case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits of the IgG3? subtype after a renal transplant, which was insensitive to pulse intravenous methyl-prednisolone and cyclophosphamide remitted by double filtration plasmapheresis. This case report reveals that recurrent proliferative glomerulo-nephritis with monoclonal IgG deposits may be insensitive to intravenous pulse therapy of methylprednisolone and cyclophosphamide. We advocate double filtration plasmapheresis as an effective treatment of proliferative glomerulo-nephritis with monoclonal IgG deposits on remission of proteinuria.

  8. Natural history of chronic myelomonocytic leukemia: gene sequencing identifies multiple clonal molecular abnormalities associated with rapid progression to acute myeloid leukemia

    PubMed Central

    Xiang, Zhifu; Kaur, Varinder; Aburiziq, Ibrahim K; Mehta, Paulette; Emanuel, Peter; Schichman, Steven A

    2014-01-01

    Key Clinical Message Gene panel sequencing in a CMML patient without any detectable genetic abnormality by conventional genetic studies identified four concurrent somatic mutations in three genes. Gene panel mutation analysis is a rapidly emerging clinical tool to demonstrate the clonality in hematologic malignancies, and to identify the potential targets for therapy. PMID:25548628

  9. Association of Retinoid X Receptor Alpha Gene Polymorphism with Clinical Course of Chronic Glomerulonephritis

    PubMed Central

    Grzegorzewska, Alicja E.; Ostromecki, Grzegorz; Zielińska, Paulina; Mostowska, Adrianna; Niemir, Zofia; Polcyn-Adamczak, Magdalena; Pawlik, Magdalena; Sowińska, Anna; Jagodziński, Paweł P.

    2015-01-01

    Background Vitamin D (VD), VD binding protein, VD receptor (VDR), and retinoids are involved in pathogenesis of chronic glomerulonephritis (ChGN). We aimed to compare distribution of VD pathway gene polymorphisms in ChGN patients showing glomerular filtration rate (GFR) category 1–3, GFR category 5D, and healthy controls in order to elucidate the role of VD-related polymorphisms in the course of ChGN. Material/Methods GFR category 1–3 ChGN patients (n=195), GFR category 5D ChGN patients (n=178), and controls (n=751) underwent testing for polymorphisms of genes encoding VD binding protein (GC, rs2298849, rs7041, rs1155563), VDR (VDR, rs2228570, rs1544410), and retinoid X receptor alpha (RXRA, rs10776909, rs10881578, rs749759). Results Among GFR 1–3 subjects possessing TT genotype of RXRA rs10776909, 75% of patients had nephrotic syndrome, and 37.5% had glomerular hyperfiltration defined as GFR >140 ml/min/1.73 m2, and, consequently, serum creatinine was lower in these patients compared to the remaining subjects (0.67±0.26 vs. 0.94±0.34, P=0.014). In GFR category 5D ChGN patients, frequencies of RXRA rs10776909 allele T (25% vs. 19%) and CT+TT (46% vs. 34%) were higher compared to frequencies of respective variants in controls (Ptrend=0.004, Pgenotype=0.008). Conclusions RXRA rs10776909 allele T is specifically involved in the pathogenesis of ChGN. This risk allele may be also associated with worse clinical course of ChGN. PMID:26610845

  10. Hematuria duration does not predict kidney function at 1 year in ANCA-associated glomerulonephritis

    PubMed Central

    Chen, Teresa K.; Murakami, Christine; Manno, Rebecca L.; Geetha, Duvuru

    2015-01-01

    Objectives Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year. Methods We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (>5 rbc/hpf) duration, defined as <90 days vs. ≥90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria. Results Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3] mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p < 0.001, respectively). Hematuria resolution (<90 days vs. ≥90 days) was not predictive of eGFR at 1 year (p = 0.93). Conclusions In ANCA-GN, hematuria duration does not predict eGFR at 1 year. Our findings provide support that among individuals who are otherwise considered to be in clinical remission, the persistence of hematuria should not delay transition from induction to maintenance immunosuppression. PMID:24775913

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

    PubMed Central

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

    2016-01-01

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

  12. Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice

    PubMed Central

    Bauer, Eva; Schlederer, Michaela; Scheicher, Ruth; Horvath, Jaqueline; Aigner, Petra; Schiefer, Ana-Iris; Kain, Renate; Regele, Heinz; Hoermann, Gregor; Steiner, Günter; Kenner, Lukas; Sexl, Veronika; Villunger, Andreas; Moriggl, Richard; Stoiber, Dagmar

    2016-01-01

    The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity. PMID:26919255

  13. Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice.

    PubMed

    Bauer, Eva; Schlederer, Michaela; Scheicher, Ruth; Horvath, Jaqueline; Aigner, Petra; Schiefer, Ana-Iris; Kain, Renate; Regele, Heinz; Hoermann, Gregor; Steiner, Günter; Kenner, Lukas; Sexl, Veronika; Villunger, Andreas; Moriggl, Richard; Stoiber, Dagmar

    2016-03-15

    The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity. PMID:26919255

  14. Acute diffuse proliferative post-infectious glomerulonephritis in renal allograft--a case report and literature review.

    PubMed

    Alsaad, Khaled O; Aloudah, Nourah; Alhamdan, Hanouf M; Alamir, Abdulrahman; Fakeeh, Khalid

    2014-05-01

    PVN is a well-known cause of renal allograft dysfunction and failure. The diagnosis is established by examination of tissue from the renal graft, and confirmed by immunohistochemical or in situ hybridization techniques. Electron microscopy can be utilized as an ancillary modality to identify the viral particles ultrastructurally. The tubular epithelial cells are the primary target of PV cytopathic effect; however, PV-associated glomerular changes have also been described. Immune-type electron-dense deposits in the TBMs have been described in the setting of PVN, and rarely, likewise have glomerular subepithelial hump-like deposits. Diffuse immune-mediated proliferative glomerulonephritis in the setting of PVN has not been reported before. In this report, we describe an 11-yr-old kidney transplant recipient boy who developed immune-mediated glomerulonephritis with light microscopic, immunofluorescence, and ultrastructural features compatible with acute PIGN superimposing chronic PVN, discuss this unusual association and the possible mechanisms of antigen clearance in PVN and present a literature review. PMID:24506276

  15. Rapid pressure swing absorption cleanup of post-shift reactor synthesis gas. Technical progress report No. 4, June 1, 1991--September 31, 1991

    SciTech Connect

    Sirkar, K.K.; Majumdar, S.; Bhaumik, S.

    1991-10-31

    This investigation is concerned with the separation of gas mixtures using a novel concept of rapid pressure swing absorption (RAPSAB) of gas in a stationary absorbent liquid through gas-liquid interfaces immobilized in the pore mouths of hydrophobic microporous membranes. The process is implemented in a module well-packed with hydrophobic microporous hollow fiber membranes. The specific objectives are (1) to fiber membranes. The specific objectives are (1) to develop a theoretical model which will provide guidelines for selecting an efficient RAPSAB process cycle which includes desorption; (2) to demonstrate the concept experimentally with a simple gas mixture (e.g., Co{sub 2}-N{sub 2}) and a simple absorbent liquid such as water, and (3) to extend the concept to reactive absorbent liquids for the separation of CO, Co{sub 2} from the post-shift reactor synthesis gas. A simplified theoretical description of the novel rapid pressure swing absorption process has been developed. The absorption part of the pressure swing absorption cycle has been predicted for CO{sub 2}-N{sub 2}-water system. Numerical simulation of the model is being carried out for different operating conditions for selecting an optimum pressure swing cycle.

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

    PubMed Central

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

    1994-01-01

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

  17. Serum levels of 12 renal function and injury markers in patients with glomerulonephritis.

    PubMed

    Serwin, Natalia M; Wiśniewska, Magda; Jesionowska, Anna; Skwirczyńska, Edyta; Marcinowska, Zuzanna; Dołęgowska, Barbara

    2016-08-01

    INTRODUCTION    Glomerulonephritis (GN) is a complex disease that affects the function of the whole nephron. There are few data on the serum levels of the most common biomarkers of kidney function and injury in GN, or the studies provide ambiguous results. OBJECTIVES    The aim of the study was to evaluate the levels of known kidney-specific and nonspecific markers of renal function or injury in the serum of patients with diagnosed primary or secondary GN, with or without the presence of nephrotic syndrome (NS) and arterial hypertension (AH). PATIENTS AND METHODS    The study included 58 patients with diagnosed GN and 6 patients with congenital defects (CD) of the kidney and AH (CD+AH). The serum levels of β2-microglobulin (β2M), neutrophil‑gelatinase associated lipocalin (NGAL), osteopontin, trefoil factor 3 (TFF-3), calbindin, glutathione-S‑transferase- π (GST-π), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and monocyte chemoattractant protein 1 (MCP-1) were measured with Kidney Toxicity Panels 1 and 2 using the Bio-Plex method. Renalase levels were measured using an enzyme-linked immunosorbent assay. RESULTS    In the whole group and in the subgroups (GN, GN+AH, GN+NS, CD+AH), NGAL, KIM-1, TFF-3, IL-18, β2M, and calbindin levels correlated with estimated glomerular filtration rate (eGFR). In patients with NS, this correlation for calbindin was reversed. Renalase, MCP-1, GST-π, and osteopontin levels were independent of eGFR. Increase in IL-18 levels in the group with GN was assiociated with lower odds of the kidney disease. When this group was divided according to eGFR into subgroups G1-G5, TFF-3, NGAL, and β2M levels increased with the stage of the disease. CONCLUSIONS In patients with NS, renalase and MCP-1 might regulate each other's levels. Further studies are needed to investigate associations between renalase, MCP-1, and osteopontin as factors unrelated to eGFR in GN. NS may contribute to the loss of calbindin from

  18. The incidence of possible causes of membranoproliferative glomerulonephritis: a single-center experience

    PubMed Central

    Pavinic, J; Miglinas, M

    2015-01-01

    Background: Diagnosis of membranoproliferative glomerulonephritis (MPGN) is based on kidney biopsy findings: unique glomerular injury pattern and characteristic changes on light, electron microscopy and immunohistochemical analysis. The purpose of this study was to identify possible etiology and incidence of glomerular injury among patients with a diagnosed MPGN. Materials and Methods: A retrospective analysis (years 2000-2014) of 81 clinical cases with a diagnosis of MPGN based on biopsy results was performed. Records were examined, and data about viral, bacterial infections, autoimmune and hematological diseases was collected. Test results of blood C3 and C4 factors of the complement system, and results of kidney biopsy immunohistochemical analysis were investigated. Statistical analysis was performed using Statistical Package for the Social Sciences and p-value less than 0.05 was considered statistically significant. Results: Study population consisted of 55 males (67.9%) and 26 females (32.1%). The average patients’ age was 48.53 (standard deviation ± 16.67) years. The identified etiology of MPGN was: idiopathic in 26 cases (32.10%), bacterial infections in 20 cases (24.69%), viral hepatitis in 16 cases (19.75%), autoimmune diseases in 11 cases (13.58%), and hematological diseases in eight cases (9.88%). Changes of the concentration of complement component C3 as well as component C4 were found; their concentration was decreased in 26 (32.1%) and 17 (20.99%) patients’ respectively while concentration was within the normal range in 11 (13.58%) and 19 (23.46%) patients respectively. Immunohistochemistry results revealed immunoglobulin (Ig) deposits: C3+/Ig+ was found in 47 (58.02%) cases, C3-/Ig+ was found in 16 (19.75%) cases and in six (7.41%) cases test was not performed. The total number of immunoglobulin positive biopsies (C3+/Ig+ and C3-/Ig+, also called immune-complex mediated MPGN) was 63 (77.78%). Complement-mediated MPGN (C3+/Ig-) was less common

  19. Epidemiology of Histologically Proven Glomerulonephritis in Africa: A Systematic Review and Meta-Analysis

    PubMed Central

    Okpechi, Ikechi G.; Ameh, Oluwatoyin I.; Bello, Aminu K.; Ronco, Pierre; Swanepoel, Charles R.; Kengne, Andre P.

    2016-01-01

    Background and aim Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. Materials and methods We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. Results Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50–4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2–22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3–21.1), mesangiocapillary GN (MCGN); 11.8% (9.2–14.6), crescentic GN; 2.0% (0.9–3.5) and IgA nephropathy 2.8% (1.3–4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0–18.4) and 7.7% (4.5–11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. Conclusions Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases

  20. Sulodexide and glycosaminoglycans in the progression of renal disease.

    PubMed

    Masola, Valentina; Zaza, Gianluigi; Gambaro, Giovanni

    2014-02-01

    Experimental data in cell cultures and animal models suggest that sulodexide and glycosaminoglycans are potentially effective drugs to treat chronic kidney diseases and prevent progression to renal failure. However, no conclusive evidence support the use of them in human renal disease. In acute and chronic glomerulonephritis, only few studies have been performed. Sulodexide has been more intensely investigated in diabetic nephropathy (DN) where the body of data supports its effectiveness as an antialbuminuric agent in early stages. Unfortunately, there is no study in DN patients on the effect of sulodexide on clinical end points.

  1. Translational Mini-Review Series on Complement Factor H: Therapies of renal diseases associated with complement factor H abnormalities: atypical haemolytic uraemic syndrome and membranoproliferative glomerulonephritis

    PubMed Central

    Noris, M; Remuzzi, G

    2008-01-01

    Genetic and acquired abnormalities in complement factor H (CFH) have been associated with two different human renal diseases: haemolytic uraemic syndrome and membrano proliferative glomerulonephritis. The new genetic and pathogenetic findings in these diseases and their clinical implications for the management and cure of patients are reviewed in this paper. PMID:18070148

  2. Post-infection immunocomplex glomerulonephritis and Legionnaires' disease in a patient with adult Still's disease during treatment with interleukin 1 receptor antagonist anakinra: a case report

    PubMed Central

    2011-01-01

    Introduction Legionellosis is a systemic disease that primarily affects the lungs. However, dysfunction in many organ systems, including the kidneys, has also been described. There are only a few reported cases of renal dysfunction in patients with legionellosis. Case presentation A 27-year-old Caucasian woman with known adult Still's disease was admitted to our hospital for community-acquired pneumonia, due to Legionella infection, with acute renal failure. Although her respiratory symptoms responded well to antibiotic treatment, her renal function worsened, with severe proteinuria and edema. A renal biopsy showed extracapillary and endocapillary proliferative glomerulonephritis with accompanying chronic and acute interstitial nephritis. This was consistent with a post-infection immunocomplex glomerulonephritis. After initiation of steroid therapy, her renal function improved. Additionally, therapy with diuretics and an angiotensin-converting enzyme inhibitor was initiated because of persistent proteinuria. Under this treatment regimen, her severe edema and proteinuria disappeared. Conclusion To the best of our knowledge, there is only a handful of reported cases of post-infection glomerulonephritis with a nephrotic syndrome in a patient with legionellosis. Our findings suggest that, in patients with Legionnaires' disease with renal failure, post-infection immunocomplex glomerulonephritis should be considered and steroid therapy may be an effective modality to treat the renal complication. PMID:21740588

  3. [A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course].

    PubMed

    Kato, Kuniyuki; Michishita, Yoshihiro; Oyama, Kenichi; Hatano, Yoshiaki; Nozawa, Tatsuru; Ishibashi, Masahisa; Konda, Ryuichiro; Sasaki, Akira

    2016-01-01

    A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis. PMID:26809542

  4. Management of Ruptured and Rapidly Progressive Mycotic Cerebral Aneurysms in the Setting of Unilateral Carotid Occlusion and Endocarditis with Valve Failure

    PubMed Central

    Rennert, Robert C.; Santiago-Dieppa, David R.; Pannell, J. Scott; Khalessi, Alexander A.

    2015-01-01

    Mycotic cerebral aneurysms can present unique neurosurgical challenges. We report a patient with left carotid occlusions, a ruptured left middle cerebral artery mycotic aneurysm, and a rapidly appearing unruptured left anterior cerebral artery/anterior communicating artery (ACA/ACom) mycotic aneurysm in the setting of mitral valve endocarditis with a perivalvular leak and evolving congestive heart failure. Following medical stabilization and antibiotic administration, a combined endovascular (with contralateral access via the ACom) and open surgical approach was used to selectively secure both aneurysms with preservation of distal flow, allowing lifesaving cardiac valve replacement. This case illustrates the therapeutic complexity of mycotic cerebral aneurysms, which we discuss in the context of an increasing reliance on endovascular approaches. PMID:26623231

  5. Stop chronic kidney disease progression: Time is approaching

    PubMed Central

    Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

    2016-01-01

    Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression. PMID:27152262

  6. Stop chronic kidney disease progression: Time is approaching.

    PubMed

    Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

    2016-05-01

    Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression. PMID:27152262

  7. Magnetization-prepared rapid acquisition with gradient echo magnetic resonance imaging signal and texture features for the prediction of mild cognitive impairment to Alzheimer's disease progression.

    PubMed

    Martinez-Torteya, Antonio; Rodriguez-Rojas, Juan; Celaya-Padilla, José M; Galván-Tejada, Jorge I; Treviño, Victor; Tamez-Peña, Jose

    2014-10-01

    Early diagnoses of Alzheimer's disease (AD) would confer many benefits. Several biomarkers have been proposed to achieve such a task, where features extracted from magnetic resonance imaging (MRI) have played an important role. However, studies have focused exclusively on morphological characteristics. This study aims to determine whether features relating to the signal and texture of the image could predict mild cognitive impairment (MCI) to AD progression. Clinical, biological, and positron emission tomography information and MRI images of 62 subjects from the AD neuroimaging initiative were used in this study, extracting 4150 features from each MRI. Within this multimodal database, a feature selection algorithm was used to obtain an accurate and small logistic regression model, generated by a methodology that yielded a mean blind test accuracy of 0.79. This model included six features, five of them obtained from the MRI images, and one obtained from genotyping. A risk analysis divided the subjects into low-risk and high-risk groups according to a prognostic index. The groups were statistically different ([Formula: see text]). These results demonstrated that MRI features related to both signal and texture add MCI to AD predictive power, and supported the ongoing notion that multimodal biomarkers outperform single-modality ones.

  8. Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatin

    PubMed Central

    Diaz Perez, Silvia V.; Kim, Rachel; Li, Ziwei; Marquez, Victor E.; Patel, Sanjeet; Plath, Kathrin; Clark, Amander T.

    2012-01-01

    Human embryonic stem cells (hESCs) are pluripotent cell types derived from the inner cell mass of human blastocysts. Recent data indicate that the majority of established female XX hESC lines have undergone X chromosome inactivation (XCI) prior to differentiation, and XCI of hESCs can be either XIST-dependent (class II) or XIST-independent (class III). XCI of female hESCs precludes the use of XX hESCs as a cell-based model for examining mechanisms of XCI, and will be a challenge for studying X-linked diseases unless strategies are developed to reactivate the inactive X. In order to recover nuclei with two active X chromosomes (class I), we developed a reprogramming strategy by supplementing hESC media with the small molecules sodium butyrate and 3-deazaneplanocin A (DZNep). Our data demonstrate that successful reprogramming can occur from the XIST-dependent class II nuclear state but not class III nuclear state. To determine whether these small molecules prevent XCI, we derived six new hESC lines under normoxic conditions (UCLA1–UCLA6). We show that class I nuclei are present within the first 20 passages of hESC derivation prior to cryopreservation, and that supplementation with either sodium butyrate or DZNep preserve class I nuclei in the self-renewing state. Together, our data demonstrate that self-renewal and survival of class I nuclei are compatible with normoxic hESC derivation, and that chemical supplementation after derivation provides a strategy to prevent epigenetic progression and retain nuclei with two active X chromosomes in the self-renewing state. PMID:22058289

  9. Rapid depletion of mutant eukaryotic initiation factor 5A at restrictive temperature reveals connections to actin cytoskeleton and cell cycle progression.

    PubMed

    Chatterjee, Ishita; Gross, Stephane R; Kinzy, Terri Goss; Chen, Kuang Yu

    2006-03-01

    Eukaryotic initiation factor 5A (eIF5A) is the only protein in nature that contains hypusine, an unusual amino acid derived from the modification of lysine by spermidine. Two genes, TIF51A and TIF51B, encode eIF5A in the yeast Saccharomyces cerevisiae. In an effort to understand the structure-function relationship of eIF5A, we have generated yeast mutants by introducing plasmid-borne tif51A into a double null strain where both TIF51A and TIF51B have been disrupted. One of the mutants, tsL102A strain (tif51A L102A tif51aDelta tif51bDelta) exhibits a strong temperature-sensitive growth phenotype. At the restrictive temperature, tsL102A strain also exhibits a cell shape change, a lack of volume change in response to temperature increase and becomes more sensitive to ethanol, a hallmark of defects in the PKC/WSC cell wall integrity pathway. In addition, a striking change in actin dynamics and a complete cell cycle arrest at G1 phase occur in tsL102A cells at restrictive temperature. The temperature-sensitivity of tsL102A strain is due to a rapid loss of mutant eIF5A with the half-life reduced from 6 h at permissive temperature to 20 min at restrictive temperature. Phenylmethyl sulfonylfluoride (PMSF), an irreversible inhibitor of serine protease, inhibited the degradation of mutant eIF5A and suppressed the temperature-sensitive growth arrest. Sorbitol, an osmotic stabilizer that complement defects in PKC/WSC pathways, stabilizes the mutant eIF5A and suppresses all the observed temperature-sensitive phenotypes. PMID:16408210

  10. A historical study of American patients with anti-neutrophil cytoplasmic antibody negative pauci-immune glomerulonephritis.

    PubMed

    Shah, Shivani; Havill, John; Rahman, M Hafizur; Geetha, Duvuru

    2016-04-01

    Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of ANCA-associated vasculitis. The lack of ANCA antibodies may indicate a variation in clinical presentation and outcomes of this disease. We identified 74 adult patients between 1995 and 2009 with the diagnosis of pauci-immune glomerulonephritis. Demographics, histological features, and treatment outcomes were compared between ANCA-positive and ANCA-negative patients. These factors were correlated with renal function at presentation and follow-up. Of the 74 patients, 57 were ANCA-positive, and 17 were ANCA-negative. Demographics and mean Birmingham Vasculitis Activity Score were similar between ANCA-negative and ANCA-positive patients at presentation. Renal function was significantly worse at presentation in the ANCA-negative patients (eGFR 16.59 vs. 31.89 ml/min/1.73 m(2), p = 0.03). Patients in the ANCA-negative group had a significantly higher interstitial fibrosis score compared to the ANCA-positive group (2.1 vs.1.6, p = 0.04). The median time to remission was shorter in the ANCA-negative patients (51 vs. 78 days, p = 0.01). Long-term renal function and 1-year patient and renal survival were similar between ANCA-negative and ANCA-positive patients. Baseline eGFR, percentage of normal glomeruli, glomerular sclerosis, and tubulointerstitial scarring predicted eGFR at 1 year in both groups similarly. This is the first historical review of American patients with pauci-immune glomerulonephritis, comparing patients with ANCA-negative and ANCA-positive serology. Although ANCA-negative patients present with lower eGFR and more interstitial fibrosis, 1-year and long-term outcomes in both groups are similar.

  11. Glomerular expression of interleukin-1 receptor antagonist and interleukin-1 beta genes in antibody-mediated glomerulonephritis.

    PubMed Central

    Tam, F. W.; Smith, J.; Cashman, S. J.; Wang, Y.; Thompson, E. M.; Rees, A. J.

    1994-01-01

    Interleukin-1 (IL-1) is a powerful proinflammatory cytokine whose function is modulated by a natural IL-1 receptor antagonist (IL-1ra). There are few data about kinetics of in vivo synthesis of IL-1ra at tissue level, except in response to bacterial endotoxin. The purpose of this study was to examine the kinetics of local expression of IL-1ra gene in relation to IL-1 beta gene in a model of anti-glomerular basement membrane antibody-mediated glomerulonephritis. Rats were killed in groups of 5 or 6 at 0, 4, 6, 24, 48, and 96 hours after induction of glomerulonephritis. Messenger RNA for IL-1ra and IL-1 beta was undetectable by Northern blot in normal glomeruli but increased markedly 4 to 6 hours after induction of nephritis. The increase in IL-1ra mRNA was more sustained than that of IL-1 beta mRNA. In situ hybridization showed that IL-1 beta mRNA increased diffusely within glomeruli, while IL-1ra mRNA was expressed more discretely. Expression of these mRNA in noninflamed tissues, spleens and lungs, was different, particularly increase in IL-1ra mRNA was more substantial than that of IL-1 beta. These observations suggest that differential expression of IL-1ra and IL-1 beta might focus inflammation in glomeruli while protecting more distant sites. They also raise the possibility of reducing glomerular injury by therapeutic measures that upregulate glomerular synthesis of IL-1ra while reducing that of IL-1 beta. Images Figure 1 Figure 2 Figure 4 Figure 5 PMID:8030744

  12. Myositis autoantibodies in Korean patients with inflammatory myositis: Anti-140-kDa polypeptide antibody is primarily associated with rapidly progressive interstitial lung disease independent of clinically amyopathic dermatomyositis

    PubMed Central

    2010-01-01

    Background To investigate the association between myositis autoantibodies and clinical subsets of inflammatory myositis in Korean patients. Methods Immunoprecipitation was performed using the sera of classic polymyositis (PM) (n = 11) and dermatomyositis (DM) (n = 38) patients who met the Bohan and Peter criteria for definite inflammatory myositis. A panel of defined myositis autoantibodies was surveyed to investigate the association between each autoantibody and clinical subsets of inflammatory myositis. Results Either MSAs, anti-p140, or anti-p155/140 antibodies were found in 63.3% (31/49) of the study subjects. Anti-140-kDa-polypeptide (anti-p140) (18.4%, 9/49) and anti-155/140-kDa polypeptide (anti-p155/140) (16.3%, 8/49) antibodies were the most common, followed by anti-Mi2 (14.3%, 7/49), anti-ARS (12.2%, 6/49) and anti-SRP (2.0%, 1/49) antibodies. All MSAs and anti-p140 and anti-p155/140 antibodies were mutually exclusive. Anti-p140 (23.7%, 9/38), anti-p155/140 (21.1%, 8/38), and anti-Mi2 (18.4%, 3/38) antibodies were found exclusively in DM patients. Anti-p140 antibody was associated with rapidly progressive interstitial lung disease (ILD) (p = 0.001), with a sensitivity of 100.0% (4/4) and a specificity of 85.3% (29/34) in DM patients. Anti-p155/140 antibody was associated with cancer-associated DM (p = 0.009), with a sensitivity of 55.6% (5/9) and a specificity of 89.7% (26/29). Cancer-associated survival was significantly worse when anti-p155/140 antibody was present (19.2 ± 7.6 vs. 65.0 ± 3.5 months, p = 0.032). Finally, anti-ARS antibodies were associated with stable or slowly progressive ILD in PM and DM patients (p = 0.005). Conclusions Anti-p140 and anti-p155/140 antibodies were commonly found autoantibodies in Korean patients with inflammatory myositis. Despite the lack of clinically amyopathic DM patients in the study subjects, a strong association was observed between anti-p140 antibody and rapidly progressive ILD. Anti-p155/140 antibody was

  13. Beneficial effect of the inosine monophosphate dehydrogenase inhibitor mycophenolate mofetil on survival and severity of glomerulonephritis in systemic lupus erythematosus (SLE)-prone MRLlpr/lpr mice.

    PubMed

    Jonsson, C A; Svensson, L; Carlsten, H

    1999-06-01

    The aim of the present study was to evaluate the therapeutic effect of mycophenolate mofetil (MMF) on the course of disease in SLE-prone MRLlpr/lpr mice. Three-months-old mice displaying clinical symptoms of glomerulonephritis were given MMF (100 mg/kg per day) orally via the drinking water. Control mice received i.p. injections of cyclophosphamide (CYC) (1.8 mg/mouse per week) or saline. Survival, albuminuria and haematuria, immunoglobulin levels and anti-dsDNA antibodies in serum, frequencies of immunoglobulin-producing B lymphocytes and glomerular deposits of immunoglobulin and C3 were analysed. The results showed that MMF treatment significantly prolonged survival and reduced the occurrence of albuminuria and haematuria in MRLlpr/lpr mice. In addition, the number of immunoglobulin-producing B cells and serum levels of IgG and IgG anti-dsDNA antibodies were reduced after MMF and CYC treatment. MMF treatment significantly reduced the extent of deposition of C3 in glomeruli. We conclude that the reduced severity of glomerulonephritis following treatment of lupus-prone mice with MMF was as efficacious as that of CYC. These results warrant clinical trials of MMF in SLE patients with glomerulonephritis.

  14. The rapidly moving telescope - A progress report

    NASA Technical Reports Server (NTRS)

    Barthelmy, S. D.; Cline, T. L.; Teegarden, B. J.; Von Rosenvinge, T. T.

    1992-01-01

    A ground-based optical telescope system has been constructed with the capability to locate fast optical transients that may be associated with gamma-ray bursts (GRBs). The instrument has been integrated and operated during a shakedown period at GSFC, Maryland. Results of 35 hours of 'state mode' data are presented. The telescope has the proven capability to slew to any point on the night sky within 1.0 sec, track that position with better than one arcsecond stability, and image a 9 x 12 arcmin field of view with 1 arcsec angular resolution with 1.5 sec time resolution. The telescope-CCD camera system has a sensitivity of 13th magnitude for transients and 14th mag for field stars. In the 35 hr of operation many single frame transients of instrumental and optical origin have been observed; no two-sequential frame astrophysical transients have been identified. The combined rate of instrumental transients (predominantly sea-level muons) is 7.2/hr and of optical transients (satellite glints, airplane strobe lights, and meteors) is 5.1/hr. The RMT will operate in conjunction with the MIT Explosive Transient Camera survey instrument at Kitt Peak National Observatory, Tucson. The RMT is now being installed at Kitt Peak. Full operation will begin this summer.

  15. The rapidly moving telescope - A progress report

    NASA Astrophysics Data System (ADS)

    Barthelmy, S. D.; Cline, T. L.; Teegarden, B. J.; von Rosenvinge, T. T.

    A ground-based optical telescope system has been constructed with the capability to locate fast optical transients that may be associated with gamma-ray bursts (GRBs). The instrument has been integrated and operated during a shakedown period at GSFC, Maryland. Results of 35 hours of 'state mode' data are presented. The telescope has the proven capability to slew to any point on the night sky within 1.0 sec, track that position with better than one arcsecond stability, and image a 9 x 12 arcmin field of view with 1 arcsec angular resolution with 1.5 sec time resolution. The telescope-CCD camera system has a sensitivity of 13th magnitude for transients and 14th mag for field stars. In the 35 hr of operation many single frame transients of instrumental and optical origin have been observed; no two-sequential frame astrophysical transients have been identified. The combined rate of instrumental transients (predominantly sea-level muons) is 7.2/hr and of optical transients (satellite glints, airplane strobe lights, and meteors) is 5.1/hr. The RMT will operate in conjunction with the MIT Explosive Transient Camera survey instrument at Kitt Peak National Observatory, Tucson. The RMT is now being installed at Kitt Peak. Full operation will begin this summer.

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

    PubMed

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

    2016-06-01

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

  17. Increased risk for lymphoma and glomerulonephritis in a closed population of cats exposed to feline leukemia virus.

    PubMed

    Francis, D P; Essex, M; Jakowski, R M; Cotter, S M; Lerer, T J; Hardy, W D

    1980-03-01

    Feline leukemia virus (FeLV)-associated diseases were observed in a household in eastern Connecticut having 134 cats over a period of five and a half years. FeLV-positive cats had a much higher mortality rate (34.6 deaths per 1000 cat-months of follow-up) than did FeLV-negative cats (8.9 deaths per 1000 cat-months of follow-up). The leading cause of death was glomerulonephritis followed by lymphoma. The relative risk for virus-positive cats as compared to virus-negative cats for the two diseases was 9.9 and 9.6, respectively. The major risk factors for the development of lymphoma were virus positivity and low antibody titer to the feline oncornavirus-associated cell membrane antigen (FOCMA). No significant differences in cancer incidence were seen between the two major breeds (Abyssinian and Burmese) in the household. An older age at arrival in the house decreased death rates for all causes in the household, but it did not significantly affect death rates from lymphoma, although there was a positive trend. PMID:6244730

  18. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  19. Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor

    PubMed Central

    Alexander, Jessy J.; Chaves, Lee D.; Chang, Anthony; Dighe, Shruti; Jacob, Alexander; Quigg, Richard J.

    2016-01-01

    Activation of complement generates C5a which leads to signaling through C5aR1. This is tightly controlled, including by the plasma proteins factor H (FH) and carboxypeptidase N. Here we studied a chronic serum sickness (CSS) model of glomerulonephritis (GN) in which there is an active humoral immune response, formation of glomerular immune complexes (ICs), and resulting glomerular inflammation. The antibody response, glomerular IC deposition, the degree of GN, and consequent renal functional insufficiency in CSS were all worse in FH−/− mice compared to wild-type FH+/+ animals. This was ameliorated in the former by giving a C5aR1 antagonist for the final 3 weeks of the 5-week protocol. In contrast, blocking CP-mediated inactivation of C5a increased these disease measures. Thus, complement regulation by both plasma FH and CP to limit the quantity of active C5a is important in conditions where the humoral immune response is directed to a continuously present foreign antigen. Signaling through C5aR1 enhances the humoral immune response as well as the inflammatory response to ICs that have formed in glomeruli. Both effects are relevant even after disease has begun. Thus, pharmacological targeting of C5a in IC-mediated GN has potential clinical relevance. PMID:26166765

  20. Heparin-binding EGF-like growth factor contributes to reduced glomerular filtration rate during glomerulonephritis in rats

    PubMed Central

    Feng, Lili; Garcia, Gabriela E.; Yang, Young; Xia, Yiyang; Gabbai, Francis B.; Peterson, Orjan W.; Abraham, Judith A.; Blantz, Roland C.; Wilson, Curtis B.

    2000-01-01

    Heparin-binding epidermal growth factor–like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, is expressed during inflammatory and pathological conditions. We have cloned the rat HB-EGF and followed the expression of HB-EGF in rat kidneys treated with anti– glomerular basement membrane (anti–GBM) antibody (Ab) to induce glomerulonephritis (GN). We observed glomerular HB-EGF mRNA and protein within 30 minutes of Ab administration and showed by in situ hybridization that glomerular HB-EGF mRNA expression was predominantly in mesangial and epithelial cells. Expression of HB-EGF correlated with the onset of decreased renal function in this model. To test the direct effect of HB-EGF on renal function, we infused the renal cortex with active rHB-EGF, prepared from transfected Drosophila melanogaster cells. This treatment induced a significant decrease in single nephron GFR (SNGFR), single nephron plasma flow, and glomerular ultrafiltration coefficient and an increase in the glomerular capillary hydrostatic pressure gradient. In addition, anti–HB-EGF Ab administered just before anti-GBM Ab blocked the fall in SNGFR and GFR at 90 minutes without any change in the glomerular histologic response. These studies suggest that HB-EGF expressed early in the anti-GBM Ab GN model contributes to the observed acute glomerular hemodynamic alterations. PMID:10675360

  1. Using Methane 14C to Determine the Origin of the Rapid Methane Rise at the End of the Younger Dryas 11,600 Years Ago: Increased Wetland Production or Methane Hydrates? A Progress Report.

    NASA Astrophysics Data System (ADS)

    Petrenko, V. V.; Severinghaus, J.; Brook, E.; Reeh, N.

    2002-12-01

    The atmospheric methane concentration rose from about 500 parts per billion (ppb) to about 750 ppb over a period of just 150 years at the termination of the Younger Dryas cold period 11,600 years ago, as indicated by Greenland ice core records. The start of this rapid methane increase was synchronous with an even more rapid climate warming -- Greenland ice core nitrogen and argon isotope records indicate that temperatures rose 5 - 10 ?C over just a few decades. There has been considerable debate about the source of this methane rise. Currently, the two main hypotheses attribute the methane rise either to increased bacterial methane production in wetlands, or to the dissociation of large quantities of methane hydrates on the ocean floor. Here we describe the progress of a project whose aim is to determine the origin of this methane rise. Our approach involves using 14C of ancient methane (derived from air bubbles in glacial ice) to determine its source. Methane hydrates are hundreds of thousands to millions of years old, and should contain virtually no 14C, whereas wetland-derived methane will have 14C content identical to that of atmospheric CO2 at the time of production. Obtaining enough ancient methane for a 14C measurement requires very large samples -- about 2 cubic meters. We have been able to locate a site on the western margin of the Greenland ice sheet where large amounts of uncontaminated ancient ice are available at the surface. Furthermore, our measurements of oxygen isotopes in the ice, as well as measurements of methane and oxygen and nitrogen isotopes in the air trapped in this ice have allowed us to date the ice and precisely locate the ice that contains the end-of-Younger-Dryas methane increase signal. Our data also demonstrate that the methane record in this ice is uncontaminated and suitable for methane 14C analysis. During the past year, we also constructed and are testing a device for melting and extracting air from large volumes of glacial ice.

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

    PubMed

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

    2016-04-01

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

  3. Cholesterol-Independent Suppression of Lymphocyte Activation, Autoimmunity, and Glomerulonephritis by Apolipoprotein A-I in Normocholesterolemic Lupus-Prone Mice.

    PubMed

    Black, Leland L; Srivastava, Roshni; Schoeb, Trenton R; Moore, Ray D; Barnes, Stephen; Kabarowski, Janusz H

    2015-11-15

    Apolipoprotein (Apo)A-I, the major lipid-binding protein of high-density lipoprotein, can prevent autoimmunity and suppress inflammation in hypercholesterolemic mice by attenuating lymphocyte cholesterol accumulation and removing tissue-oxidized lipids. However, whether ApoA-I mediates immune-suppressive or anti-inflammatory effects under normocholesterolemic conditions and the mechanisms involved remain unresolved. We transferred bone marrow from systemic lupus erythematosus (SLE)-prone Sle123 mice into normal, ApoA-I-knockout (ApoA-I(-/-)) and ApoA-I-transgenic (ApoA-I(tg)) mice. Increased ApoA-I in ApoA-I(tg) mice suppressed CD4(+) T and B cell activation without changing lymphocyte cholesterol levels or reducing major ApoA-I-binding oxidized fatty acids. Unexpectedly, oxidized fatty acid peroxisome proliferator-activated receptor γ ligands 13- and 9-hydroxyoctadecadienoic acid were increased in lymphocytes of autoimmune ApoA-I(tg) mice. ApoA-I reduced Th1 cells independently of changes in CD4(+)Foxp3(+) regulatory T cells or CD11c(+) dendritic cell activation and migration. Follicular helper T cells, germinal center B cells, and autoantibodies were also lower in ApoA-I(tg) mice. Transgenic ApoA-I also improved SLE-mediated glomerulonephritis. However, ApoA-I deficiency did not have the opposite effects on autoimmunity or glomerulonephritis, possibly as the result of compensatory increases in ApoE on high-density lipoprotein. We conclude that, although compensatory mechanisms prevent the proinflammatory effects of ApoA-I deficiency in normocholesterolemic mice, increasing ApoA-I can attenuate lymphocyte activation and autoimmunity in SLE independently of cholesterol transport, possibly through oxidized fatty acid peroxisome proliferator-activated receptor γ ligands, and it can reduce renal inflammation in glomerulonephritis.

  4. Glomerular clusterin is associated with PKC-alpha/beta regulation and good outcome of membranous glomerulonephritis in humans.

    PubMed

    Rastaldi, M P; Candiano, G; Musante, L; Bruschi, M; Armelloni, S; Rimoldi, L; Tardanico, R; Sanna-Cherchi, S; Cherchi, S Sanna; Ferrario, F; Montinaro, V; Haupt, R; Parodi, S; Carnevali, M L; Allegri, L; Camussi, G; Gesualdo, L; Scolari, F; Ghiggeri, G M

    2006-08-01

    Mechanisms for human membranous glomerulonephritis (MGN) remain elusive. Most up-to-date concepts still rely on the rat model of Passive Heymann Nephritis that derives from an autoimmune response to glomerular megalin, with complement activation and membrane attack complex assembly. Clusterin has been reported as a megalin ligand in immunodeposits, although its role has not been clarified. We studied renal biopsies of 60 MGN patients by immunohistochemistry utilizing antibodies against clusterin, C5b-9, and phosphorylated-protien kinase C (PKC) isoforms (pPKC). In vitro experiments were performed to investigate the role of clusterin during podocyte damage by MGN serum and define clusterin binding to human podocytes, where megalin is known to be absent. Clusterin, C5b-9, and pPKC-alpha/beta showed highly variable glomerular staining, where high clusterin profiles were inversely correlated to C5b-9 and PKC-alpha/beta expression (P=0.029), and co-localized with the low-density lipoprotein receptor (LDL-R). Glomerular clusterin emerged as the single factor influencing proteinuria at multivariate analysis and was associated with a reduction of proteinuria after a follow-up of 1.5 years (-88.1%, P=0.027). Incubation of podocytes with MGN sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, serum de-complementation, or protein-A treatment. Preliminary in vitro experiments showed podocyte binding of biotinilated clusterin, co-localization with LDL-R and specific binding inhibition with anti-LDL-R antibodies and with specific ligands. These data suggest a central role for glomerular clusterin in MGN as a modulator of inflammation that potentially influences the clinical outcome. Binding of clusterin to the LDL-R might offer an interpretative key for the pathogenesis of MGN in humans.

  5. The concept of 'glomerulonephritis'. the fascinating history of evolution and emergence of a specialist's nosology focus on Italy and Torino.

    PubMed

    Stratta, P; Canavese, C; Sandri, L; Ciccone, G; Santi, S; Barolo, S; Messuerotti, A; Quaglia, M; Mazzucco, G; Fop, F; Segoloni, G P; Piccoli, G

    1999-01-01

    Though the term 'nephritis' first appeared in the 19th century, this word did not bear the same meaning as it does today; indeed, for many years it was used to indicate 'renal diseases' (in the sense of Bright's disease) in a larger sense. This review summarizes the long gestation of the concept of 'glomerulonephritis' from the prehistory of medicine up to the beginning of the second half of the 20th century with emphasis on Italy and, in particular, on Torino, which was the capital of the Kingdom of Italy from 1861 to 1865. To the best of our kowledge, this is the first study reporting an epidemiology survey of Bright's disease in Italy from 1880 up to 1960. Towards the end of the 19th century, Bright's disease accounted for 26 deaths/year/10(5) population (in comparison with more than 200 from tuberculosis) in Italy, roughly paralleling that reported in the USA. At the beginning of the 20th century, Bright's disease was the seventh cause of death (almost 1% of total deaths) in Italy. Furthermore, in Italy, as elsewhere, autopsy studies showed a higher percentage of deaths attributed to Bright's disease (5-7%) in comparison with those obtained from vital statistics. In 1960, just before the beginning of renal replacement therapy, Bright's disease accounted for 15.7 deaths/year/10(5) population (= 1.46% of all deaths), roughly paralleling that reported in the United Kingdom (13.8/10(5) population = 1.25% of deaths). Probably, it was difficult to recognize the real incidence of chronic renal diseases leading to death in the 1960s, and vital statistics were able to furnish only approximate estimates. However, noteworthy is the fact that these values were very close to those estimated as being the annual need for renal replacement therapy (10-20 cases/year/10(5) population).

  6. Glomerulonephritis with mesangial deposits of IgA unassociated with systemic disease.

    PubMed Central

    Katz, A.; Underdown, B. J.; Minta, J. O.; Lepow, I. H.

    1976-01-01

    Typical features of IgA-associated nephritis were found in renal biopsies from 16 of 355 consecutive patients. Generalized segmental mesangial proliferation was noted in biopsies from most patients, and dense deposits were detected by electron microscopy in mesangial regions of approximately 50% of biopsies. Immunofluorescent studies showed IgA to be the predominant immunoglobulin in glomueruli; IgG was present in less than 50% of biopsies and IgM in only 12%. The serum IgA value was significantly increased (P les than 0.001) in 50% of patients and the mean IgA/IgG ratio was significantly increase (P less than 0.001) for the patient group as a whole, which suggests a selective increase in IgA. Mesangial deposits of C3 were present in 15 of 16 biopsies and properdin was noted in all biopsies tested; C4 was not demonstrated in any biopsy. This suggests activation of the alternative complement pathway. The results of this study support the concept that IgA-associated nephritis is a unique condition that in some patients gives rise to idiopathic recurrent hematuria. Although the prognosis is good in the majority of patients, the renal disease may progress. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:801796

  7. Abnormal immune complex processing and spontaneous glomerulonephritis in complement factor H-deficient mice with human complement receptor 1 on erythrocytes.

    PubMed

    Alexander, Jessy J; Hack, Bradley K; Jacob, Alexander; Chang, Anthony; Haas, Mark; Finberg, Robert W; Quigg, Richard J

    2010-09-15

    Complement receptor 1 (CR1) on human erythrocytes (Es) and complement factor H (CFH) on rodent platelets perform immune adherence, which is a function that allows the processing of immune complexes (ICs) bearing C3 by the mononuclear phagocyte system. Similar immune adherence occurs in the glomerular podocyte by CR1 in humans and CFH in rodents. As a model for human IC processing, we studied transgenic mice lacking CFH systemically but with human CR1 on Es. These CR1(hu)Tg/CFH(-/-) mice spontaneously developed proliferative glomerulonephritis, which was accelerated in a chronic serum sickness model by active immunization with heterologous apoferritin. ICs containing Ag, IgG and C3 bound to Es in CR1(hu)Tg/CFH(-/-) mice. In this setting, there was increased IC deposition in glomeruli, attributable to the presence of CR1 on Es, together with the absence of CFH on platelets and podocytes. In the absence of plasma CFH, the accumulated ICs activated complement, which led to spontaneous and chronic serum sickness-induced proliferative glomerulonephritis. These findings illustrate the complexities of complement-dependent IC processing by blood cells and in the glomerulus, and the importance of CFH as a plasma complement regulator.

  8. Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis.

    PubMed Central

    Lovett, D. H.; Johnson, R. J.; Marti, H. P.; Martin, J.; Davies, M.; Couser, W. G.

    1992-01-01

    Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury. Images Figure 2 Figure 3 Figure 5 Figure 4 Figure 6 Figure 7 Figure 8 and Figure 9 Figure 10 Figure 11 Figure 12 PMID:1321565

  9. Application of urinary indicator proteins in the non-invasive assessment of glomerulo-tubular lesions in patients with chronic glomerulonephritis and rheumatoid arthritis.

    PubMed

    Weber, M H; Verwiebe, R; Janning, G; Scheler, F

    1989-01-01

    As the semiautomated electrophoretic analysis of proteinuria still needs technical experience, interest was focused on easy-to-perform methods of urinary protein measurement. SRID-tests for albumin, transferrin, IgG, alpha-1-microglobulin and a spectrophotometrical test for beta-NAG were carried out in 50 normal controls and compared to PCI/ECI-values of patients suffering from rheumatoid arthritis (n = 52) and various types of chronic glomerulonephritis (n = 41). Elevated levels of alpha-1-M and beta-NAG in chronic glomerulonephritis were interpreted as indicative for tubulointerstitial involvement in the chronic inflammatory process. PCI/ECI elevation in individual RA-samples may be caused by functional impairment of tubular protein handling due to chronic ingestion of non-steroid analgesics. The serum assays for transferrin (TF) and IgG based on SRID technique turned out to be too insensitive for the application on unconcentrated urine of normal control persons. In renal patients, however, TF-PCI values above 30 mg/g crea and IgG-PCI values above 50 mg/g crea have to be interpreted as pathologic indicating damage of the glomerular basement membrane. To elucidate TF- and IgG-values in urines with low protein content, highly sensitive nephelometric methods should be used. Concentration of urinary proteins using membrane filters may lead to protein losses, resulting in miscalculation of PC-indices.

  10. Transgene therapy for rat anti-Thy1.1 glomerulonephritis via mesangial cell vector with a polyethylenimine/decorin nanocomplex

    NASA Astrophysics Data System (ADS)

    Sun, Jian-Yong; Sun, Yu; Wu, Hui-Juan; Zhang, Hong-Xia; Zhao, Zhong-Hua; Chen, Qi; Zhang, Zhi-Gang

    2012-08-01

    Polyethylenimine (PEI), a cationic polymer, is one of the most efficient non-viral vectors for transgene therapy. Decorin (DCN), a leucine-rich proteoglycan secreted by glomerular mesangial cells (MC), is a promising anti-fibrotic agent for the treatment of glomerulonephritis. In this study, we used PEI-DCN nanocomplexes with different N/P ratios to transfect MC in vitro and deliver the MC vector with PEI-DCN expressing into rat anti-Thy1.1 nephritis kidney tissue via injection into the left renal artery in vivo. The PEI-plasmid DNA complex at N/P 20 had the highest level of transfection efficiency and the lowest level of cytotoxicity in cultured MC. Following injection, the ex vivo gene was transferred successfully into the glomeruli of the rat anti-Thy1.1 nephritis model by the MC vector with the PEI-DCN complex. The exogenous MC with DCN expression was located mainly in the mesangium and the glomerular capillary. Over-expression of DCN in diseased glomeruli could result in the inhibition of collagen IV deposition and MC proliferation. The pathological changes of rat nephritis were alleviated following injection of the vector. These findings demonstrate that the DCN gene delivered by the PEI-DNA nanocomplex with the MC vector is a promising therapeutic method for the treatment of glomerulonephritis.

  11. Acute post-streptococcal glomerulonephritis in the Northern Territory of Australia: a review of 16 years data and comparison with the literature.

    PubMed

    Marshall, Catherine S; Cheng, Allen C; Markey, Peter G; Towers, Rebecca J; Richardson, Leisha J; Fagan, Peter K; Scott, Lesley; Krause, Vicki L; Currie, Bart J

    2011-10-01

    Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0-54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6-94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed.

  12. Suppression of mesangial proliferative glomerulonephritis development in rats by inhibitors of cAMP phosphodiesterase isozymes types III and IV.

    PubMed Central

    Tsuboi, Y; Shankland, S J; Grande, J P; Walker, H J; Johnson, R J; Dousa, T P

    1996-01-01

    Excessive mesangial cell (MC) proliferation is a hallmark of many glomerulopathies. In our recent study on cultured rat MC (Matousovic, K., J.P. Grande, C.C.S. Chini, E.N. Chini, and T.P. Dousa. 1995. J. Clin. Invest. 96:401-410) we found that inhibition of isozyme cyclic-3',5'-nucleotide phosphodiesterase (PDE) type III (PDE-III) suppressed MC mitogenesis by activating cAMP-dependent protein kinase (PKA) and by decreasing activity of mitogen-activated protein kinase (MAPK). We also found that inhibition of another PDE isozyme, PDE-IV, suppresses superoxide generation in glomeruli (Chini, C.C.S., E.N. Chini, J.M. Williams, K. Matousovic, and T.P. Dousa. 1994. Kidney Int. 46:28-36). We thus explored whether administration in vivo of the selective PDE-III antagonist, lixazinone (LX), together with the specific PDE-IV antagonist, rolipram (RP), can attenuate development of mesangioproliferative glomerulonephritis (MSGN) induced in rats by anti-rat thymocyte serum (ATS). Unlike the vehicle-treated MSGN rats, rats with MSGN treated with LX and RP did not develop proteinuria and maintained normal renal function when examined 5 d after injection of ATS. In PAS-stained kidneys from PDE-antagonists-treated MSGN-rats the morphology of glomeruli showed a reduction in cellularity compared with control rats with ATS. Compared with MSGN rats receiving vehicle, the MSGN rats receiving PDE-antagonists had less glomerular cell proliferation (PCNA delta -65%), a significantly lesser macrophage infiltration (delta -36% ED-1) and a significant reduction of alpha-smooth muscle actin expression by activated MC; in contrast, immunostaining for platelet antigens and laminin were not different. The beneficial effect of PDE inhibitors was not due to a moderate decrease (approximately -20%) in systolic blood pressure (SBP); as a similar decrease in SBP due to administration of hydralazine, a drug devoid of PDE inhibitory effect, did not reduce severity of MSGN in ATS-injected rats. We

  13. Rapid diagnostic tests for malaria.

    PubMed

    Visser, Theodoor; Daily, Jennifer; Hotte, Nora; Dolkart, Caitlin; Cunningham, Jane; Yadav, Prashant

    2015-12-01

    Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them.

  14. Rapid diagnostic tests for malaria

    PubMed Central

    Daily, Jennifer; Hotte, Nora; Dolkart, Caitlin; Cunningham, Jane; Yadav, Prashant

    2015-01-01

    Abstract Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them. PMID:26668438

  15. Glomerulonephritis (For Parents)

    MedlinePlus

    ... organs in the back that are shaped like kidney beans. They filter blood and help remove waste products from the body. Tiny filtering units within the kidneys do this with the help of blood vessels ...

  16. Elevated Expression of Pentraxin 3 in Anti-neutrophil Cytoplasmic Antibody-associated Glomerulonephritis with Normal Serum C-reactive Protein.

    PubMed

    Ishida, Risa; Nakai, Kentaro; Fujii, Hideki; Goto, Shunsuke; Hara, Shigeo; Imai, Naofumi; Nishi, Shinichi

    2015-01-01

    A 20-year-old woman was admitted to our hospital with an elevated serum creatinine level of 1.61 mg/dL and a normal C-reactive protein level of less than 0.1 mg/dL. Her myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA) titer was slightly increased at 9.2 U/mL; a kidney biopsy revealed that 23 of 32 glomeruli had crescents. The expression of pentraxin 3 was detected in her kidney and her plasma pentraxin 3 level was elevated at 63.53 ng/mL. Plasma pentraxin 3 levels may be an activity marker for ANCA-associated glomerulonephritis, particularly when serum C-reactive protein levels are within the normal limits.

  17. Tenascin-C promotes healing of Habu-snake venom-induced glomerulonephritis: studies in knockout congenic mice and in culture.

    PubMed Central

    Nakao, N.; Hiraiwa, N.; Yoshiki, A.; Ike, F.; Kusakabe, M.

    1998-01-01

    Mice without the gene for tenascin-C, a multifunctional extracellular matrix protein expressed in many important biological events, including wound healing, did not show any phenotype. However, it is now obvious that the phenotype of deletion of one gene frequently depends on the genetic background. Therefore, we have newly generated tenascin-C knockout mice (KO) by backcrossing original KO into three congenic lines: C57BL/6N, BALB/cA, and GRS/A (GR). And we investigated the disease course of reversible kidney injury, Habu-snake venom-induced proliferative glomerulonephritis. In all strains, the disease was more severe in KO, but the severity varied with the strain. The KO-GR showed irreversibility; all treated KO-GR died by the 4th month due to renal failure. The diseased KO-GR showed abnormal regenerative reactions, including reduced proliferation of mesangial cells, key players in glomerulonephritis, and reduced production of some kinds of cytokines and matrices, leading to poor formation of granulation tissue. In culture, the mesangial cells from the KO-GR had the same potential for proliferation and response to cytokines as controls, but interestingly, to achieve this potential, they required contact with tenascin-C. These reactions were blocked by an anti-tenascin monoclonal antibody. The results of the present study, the first report showing the most dramatic phenotype so far discovered, have strongly suggested the importance of tenascin-C in the resolution of the renal inflammation and that of the genetic background on which the KO was developed. Images Figure 2 Figure 5 PMID:9588892

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

    PubMed Central

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

    2015-01-01

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

  19. Activation of Autophagy and Nucleotide-Binding Domain Leucine-Rich Repeat–Containing-Like Receptor Family, Pyrin Domain–Containing 3 Inflammasome during Leishmania infantum–Associated Glomerulonephritis

    PubMed Central

    Esch, Kevin J.; Schaut, Robert G.; Lamb, Ian M.; Clay, Gwendolyn; Morais Lima, Ádila L.; do Nascimento, Paulo R.P.; Whitley, Elizabeth M.; Jeronimo, Selma M.B.; Sutterwala, Fayyaz S.; Haynes, Joseph S.; Petersen, Christine A.

    2016-01-01

    Chronic kidney disease is a major contributor to human and companion animal morbidity and mortality. Renal complications are sequelae of canine and human visceral leishmaniasis (VL). Despite the high incidence of infection-mediated glomerulonephritis, little is known about pathogenesis of VL-associated renal disease. Leishmania infantum–infected dogs are a naturally occurring model of VL-associated glomerulonephritis. Membranoproliferative glomerulonephritis type I [24 of 25 (96%)], with interstitial lymphoplasmacytic nephritis [23 of 25 (92%)], and glomerular and interstitial fibrosis [12 of 25 (48%)] were predominant lesions. An ultrastructural evaluation of glomeruli from animals with VL identified mesangial cell proliferation and interposition. Immunohistochemistry demonstrated significant Leishmania antigen, IgG, and C3b deposition in VL dog glomeruli. Asymptomatic and symptomatic dogs had increased glomerular nucleotide-binding domain leucine-rich repeat–containing-like receptor family, pyrin domain containing 3 and autophagosome-associated microtubule-associated protein 1 light chain 3 associated with glomerular lesion severity. Transcriptional analyses from symptomatic dogs confirmed induction of autophagy and inflammasome genes within glomeruli and tubules. On the basis of temporal VL staging, glomerulonephritis was initiated by IgG and complement deposition. This deposition preceded presence of nucleotide-binding domain leucine-rich repeat–containing-like receptor family, pyrin domain containing 3–associated inflammasomes and increased light chain 3 puncta indicative of autophagosomes in glomeruli from dogs with clinical VL and renal failure. These findings indicate potential roles for inflammasome complexes in glomerular damage during VL and autophagy in ensuing cellular responses. PMID:26079813

  20. Skin infections and immunoglobulin A in serum, sweat, and saliva of patients recovered from poststreptococcal acute glomerulonephritis or acute rheumatic fever and their siblings.

    PubMed

    Potter, E V; Vincente, J B; Mayon-WHite, R T; Shaughnessy, M A; Poon-King, T; Earle, D P

    1982-06-01

    Differences in hygienic habits and base-line secretory immunoglobulin (Ig) A which might have contributed to the prevalence of skin infections and/or absence of increased serum IgA values were sought in patients with poststreptococcal acute glomerulonephritis (nephritis) in contrast to patients with acute rheumatic fever in Trinidad by studying patients and their siblings after the patients had recovered from these diseases. The overall history of skin infections was similar at this time in all groups, although they had been much more common in patients with nephritis and their families at the time of acute illness. The recovered nephritis patients bathed slightly less often than the other individuals, used a cream or lotion after bathing rather than coconut oil, and tended to sweat less than the others, but none of these differences was statistically significant. Neither were significant differences demonstrated in amounts of IgA and IgG in serum and saliva of recovered nephritis patients and their siblings compared to recovered rheumatic fever patients and their siblings, while only small amounts of IgA and IgG were present in any sweat, and probably had been transuded rather than secreted. These studies suggest that the lower serum IgA titers in patients with nephritis compared to patients with rheumatic fever in Trinidad do not reflect basic differences in serum IgA or secretory IgA as measured in saliva, and that IgA is not secreted by the eccrine glands.

  1. Immune complex glomerulonephritis in experimental kala-azar. II: Detection and characterization of parasite antigens and antibodies eluted from kidneys of Leishmania donovani-infected hamsters.

    PubMed Central

    Sartori, A; Roque-Barreira, M C; Coe, J; Campos-Neto, A

    1992-01-01

    In a previous report analysing kidney sections by immunofluorescence we showed that hamsters infected with L. donovani develop a glomerulonephritis (GN) associated with deposition of hamster immunoglobulins and parasite antigens in the glomeruli. In this study we characterize these immune components eluted from the kidneys. The eluted immunoglobulins showed specificity for L. donovani antigens and hamster immunoglobulins (rheumatoid factor-like activity). The four isotypes IgG1, IgG2, IgA and IgM were detected. Several L. donovani antigens were detected in the renal eluates by Western blot and immunoprecipitation using 125I-labelled eluates. Proteins with mol. wt of 134, 82, 52, 31, and 26 kD were detected by Western blot and proteins with 134, 110, 93, 89 and 48 kD were detected by immunoprecipitation. With the exception of the 134 kD protein which was recognized by both rabbit anti-promastigote and rabbit anti-amastigote sera all the others were recognized only by the anti-amastigote serum. The 134 kD protein was the only one isolated from the kidneys of infected hamster immunocomplexed with IgG and was the only one detected in a promastigote lysate using IgG from L. donovani-infected hamsters. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:1544224

  2. Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome.

    PubMed

    Fang, Celia J; Fremeaux-Bacchi, Veronique; Liszewski, M Kathryn; Pianetti, Gaia; Noris, Marina; Goodship, Timothy H J; Atkinson, John P

    2008-01-15

    The hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Genetic studies demonstrate that heterozygous mutations of membrane cofactor protein (MCP;CD46) predispose to atypical HUS (aHUS), which is not associated with exposure to Shiga toxin (Stx). Among the initial 25 MCP mutations in patients with aHUS were 2, R69W and A304V, that were expressed normally and for which no dysfunction was found. The R69W mutation is in complement control protein module 2, while A304V is in the hydrophobic transmembrane domain. In addition to 3 patients with aHUS, the A304V mutation was identified in 1 patient each with fatal Stx-HUS, the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and glomerulonephritis with C3 deposits. A major goal was to assess if these putative mutations lead to defective complement regulation. Permanent cell lines expressing the mutated proteins were complement "challenged," and membrane control of C3 fragment deposition was monitored. Both the R69W and A304V MCP mutations were deficient in their ability to control the alternative pathway of complement activation on a cell surface, illustrating the importance of modeling transmembrane proteins in situ.

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

    PubMed

    Wei, S S; Sinniah, R

    2013-01-01

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

  4. [Membranous glomerulonephritis. Experience at the Instituto Nacional de la Nutrición Salvador Zubirán].

    PubMed

    Correa-Rotter, R; Gamba, G; Ochoa, C; Onuma, L; Reyes, E; Tamayo, J A; Peña, J C

    1990-01-01

    The purpose of this retrospective study was to study the incidence of idiopathic and secondary forms of membranous nephropathy in our institution, its clinical course and progression to chronic renal failure, and the risk factors associated with it. Two hundred fourteen (16%) of the 1,287 renal biopsies obtained between 1962 and 1988 were primary glomerular diseases and 28 of this 214 (13%) were idiopathic membranous nephropathy. On the other hand 59 of 1,287 biopsies were membranous nephropathy of whom 28 were idiopathic, 27 secondary to systemic lupus erythematosus, 2 due to drugs, one associated with rheumatoid arthritis, and one more with breast cancer. The clinical picture was: nephrotic syndrome in 84%, hypertension in 15%, non-nephrotic proteinuria in 14%, chronic renal failure in 8.4%, and renal vein thrombosis in 6.3%. In the idiopathic group 75% of the patients were male while in the lupus group 85% were female. For the analysis of progression to chronic renal failure we excluded 5 patients with renal failure when the biopsy was taken, 2 because the nephropathy was due to drugs, one associated with breast cancer, and nine were within the first year of follow-up. Thus, for this analysis the group consisted of 22 patients with idiopathic form and 20 with systemic lupus erythematosus. The idiopathic and lupus groups were similar except for a lower serum albumin in the former. The progression to renal failure was seen in 9 patients: six in the idiopathic group and the other 3 in the lupus group; this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Rapid Reading, Yes

    ERIC Educational Resources Information Center

    Frommer, Harvey

    1971-01-01

    Recommends instruction in rapid reading fo high school and college students and asserts that flexibility of speed and reasoning provide the foundation for effective rapid reading. Describes the components of rapid reading as orientation, selection, clarification, arrangement, review, and study. (RW)

  6. Immunoglobulin D Multiple Myeloma With Rapidly Progressing Renal Failure.

    PubMed

    Modi, Jwalant; Kamal, Jeanne; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie

    2015-08-01

    Immunoglobulin D (IgD) multiple myeloma (MM) is a very rare form of myeloma affecting less than 2% of all myeloma patients. It has a multiorgan involvement with renal failure being the key feature. We present here a case of IgD MM in a 62-year-old white male, smoker with past medical history of hypertension, who presented to emergency department with complaints of lower abdominal pain, constipation and decreased urination. Physical exam was unremarkable. Laboratory investigation showed S.Cr 5.99 mg/dL, hemoglobin 8.7 g/dL and corrected S.Ca 10.6 mg/dL. Urine dipstick showed 100 protein and TP/Cr ratio was 23. Serology was positive for serum free lambda chain level of 8,947.6 mg/L as well with free κ/λ ratio < 0.01. The results of serum and urine electrophoresis and immunofixation were also supportive of diagnosis of IgD MM. IgD level was remarkably elevated (27,300 mg/L) too. CT scan of abdomen/pelvis was negative for obstructive uropathy. Skeletal survey showed a solitary lytic lesion in the iliac crest. His kidney function deteriorated next day requiring hemodialysis. The bone marrow biopsy was positive for plasma cell hypercellularity (70-80%) and flow cytometry showed 8% monoclonal IgD lambda plasma cells. The patient was started on bortezomib and dexamethasone and he underwent bone marrow transplant 6 months later. He is doing well hematologically now but he remains dialysis-dependent. IgD MM is a very rare disease affecting younger population with poor prognosis; patients often end up on hemodialysis despite better control of the hematological component. PMID:26124916

  7. Evidence-based Management of Rapidly Progressing Systemic Sclerosis

    PubMed Central

    Khanna, Dinesh; Denton, Christopher P.

    2009-01-01

    Systemic sclerosis has the highest case-specific mortality of any of the autoimmune rheumatic diseases as well as causing major morbidity. It is a major clinical challenge and one that has previously provoked substantial nihilism due to the limited therapeutic options available and perceived lack of evidence for clinical effectiveness of those treatments that are currently in use. However this situation is changing and there are emerging data supporting efficacy for some treatment approaches for this patient group together with a growing number of exciting potential novel approaches to treatment that are moving into the clinical arena. Some of the recent clinical trials are reviewed and discussed in detail. PMID:20534372

  8. Rapidly Progressive Acute Pustular Secondary Cutaneous Anaplastic Large Cell Lymphoma.

    PubMed

    Mordorski, Breanne; Friedman, Adam; Han, George

    2016-09-01

    Cutaneous anaplastic large cell lymphoma (ALCL) is an uncommon diagnosis that may either present as a primary cutaneous process or develop secondary to systemic disease. It is imperative to distinguish between these two entities due to differences in treatment recommendations and prognosis. Here, their salient features will be reviewed. It is also important that clinicians recognize atypical clinical morphologies of cutaneous ALCL, including pustular lesions, which may masquerade as infectious or other inflammatory conditions, thereby delaying the onset of treatment. In this report, we present a case of secondary cutaneous ALCL associated with an atypical pustular morphology and an aggressive, fatal course.

    J Drugs Dermatol. 2016;15(9):1132-1135. PMID:27602978

  9. Immunoglobulin A nephropathy: current progress and future directions.

    PubMed

    Zhang, Chunlei; Zeng, Xuehui; Li, Zhongxin; Wang, Zhe; Li, Shunmin

    2015-08-01

    Immunoglobulin A (IgA) nephropathy is the most prevalent form of primary glomerulonephritis that often leads to end-stage kidney failure, thereby representing a major health challenge worldwide. Tremendous effort has been dedicated to the diagnosis, monitoring, and treatment of the disease, and the past several years have witnessed exciting advances that have enriched our understanding of the biology, etiology, and pathology of IgA nephropathy. The disease is characterized by predominant deposition of IgA immune complexes that progressively causes activation of mesangial cells, glomerular inflammation, and ultimately renal injury. Multiple recent independent high-throughput studies in cohorts have identified key susceptibility alleles, such as the major histocompatibility complex loci that are significantly associated with the risk of disease occurrence. Notably, a fraction of these risk loci encode proteins that participate in immune defense against mucosal pathogens, particularly intestinal nematodes, indicating a linkage between IgA-mediated antihelminth immunity and the pathogenesis of IgA nephropathy. The emerging "omics" technology also allows for systemic analysis of urinary and serum samples as a noninvasive procedure for diagnosis and prognosis, as demonstrated by several studies implicating the proteomic signature and microRNA profile as promising diagnostic and prognostic parameters. In the clinic, the current treatment protocol relies on suppression of the renin-angiotensin system to control blood pressure and proteinuria. This review scrutinizes and summarizes recent relevant findings that aim to translate researchers' benchside knowledge of disease initiation and development into patients' bedside diagnosis and therapy. PMID:25797891

  10. Upregulation of group IB secreted phospholipase A(2) and its M-type receptor in rat ANTI-THY-1 glomerulonephritis.

    PubMed

    Beck, S; Beck, G; Ostendorf, T; Floege, J; Lambeau, G; Nevalainen, T; Radeke, H H; Gurrieri, S; Haas, U; Thorwart, B; Pfeilschifter, J; Kaszkin, M

    2006-10-01

    Treatment of rat glomerular mesangial cell (GMC) cultures with pancreatic secreted phospholipase A(2) (sPLA(2)-IB) results in an enhanced expression of sPLA(2)-IIA and COX-2, possibly via binding to its specific M-type sPLA(2) receptor. In the current study, we have investigated the expression and regulation of sPLA(2)-IB and its receptor during glomerulonephritis (GN). In vivo we used the well-established rat model of anti-Thy 1.1 GN (anti-Thy 1.1-GN) to study the expression of sPLA(2)-IB and the M-type sPLA(2) receptor by immunohistochemistry. In addition, in vitro we determined the interkeukin (IL)-1beta-regulated mRNA and protein expression in primary rat glomerular mesangial and endothelial cells as well as in rat peripheral blood leukocytes (PBLs). Shortly after induction of anti-Thy 1.1-GN, sPLA(2)-IB expression was markedly upregulated in the kidney at 6-24 h. Within glomeruli, the strongest sPLA(2)-IB protein expression was detected on infiltrated granulocytes and monocytes. However, at the same time, the M-type receptor was also markedly upregulated on resident glomerular cells. In vitro, the most prominent cytokine-stimulated secretion of sPLA(2)-IB was observed in monocytes isolated from rat PBLs. Treating glomerular endothelial cells (GECs) with cytokines elicited only weak sPLA(2)-IB expression, but treatment of these cells with exogenous sPLA(2)-IB resulted in a marked expression of the endogenous sPLA(2)-IB. Mesangial cells did not express sPLA(2)-IB at all. The M-type sPLA(2) receptor protein was markedly upregulated on cytokine-stimulated mesangial and endothelial cells as well as on lymphocytes and granulocytes. During anti-Thy 1.1 rat GN, sPLA(2)-IB and the M-type sPLA(2) receptor are induced as primary downstream genes stimulated by inflammatory cytokines. Subsequently, both sPLA(2)-IB and the M-type sPLA(2) receptor are involved in the autocrine and paracrine amplification of the inflammatory process in different resident and infiltrating

  11. Medical Progress

    PubMed Central

    Starzl, Thomas E.; Demetris, Anthony J.; Van Thiel, David

    2010-01-01

    Advances in the management of both chronic and acute hepatic disease have been made possible and even mandated by the development of liver transplantation. The clinical use of transplantation has proceeded at a rapid pace since a Consensus Development Conference of the National Institutes of Health concluded in June 1983 that liver transplantation had become a service and not simply an experimental procedure.1 The liver can be transplanted as an extra (auxiliary) organ at an ectopic site, or in the orthotopic location after the removal of the host liver (Fig. 1). This article will focus primarily on the orthotopic procedure. However, there has been renewed interest in the auxiliary operation, which will be discussed separately. PMID:2674716

  12. Indochinese power progress

    SciTech Connect

    Hennagir, T.

    1995-07-01

    Fifty years ago, U.S. engineers, fresh with the new-found success of building North America`s landmark dam projects, first considered building a series of multipurpose hydro-electric dams along the ancient Southeast Asian Mekong River descending from Tibet`s snowy plateau to the warm waters of the South China Sea. Recent transmission interconnection agreements such as those between Laos and Thailand and the incorporation of international partnering agreements for power project development are helping to reshape electric industry relationships throughout the region of the Mekong. Former economic pragmatism is being rapidly replaced by a general movement toward positive market forces. Progress continues as international players bring a varied assortment of financial packages and models to the project development table.

  13. Rapid Airplane Parametric Input Design (RAPID)

    NASA Technical Reports Server (NTRS)

    Smith, Robert E.

    1995-01-01

    RAPID is a methodology and software system to define a class of airplane configurations and directly evaluate surface grids, volume grids, and grid sensitivity on and about the configurations. A distinguishing characteristic which separates RAPID from other airplane surface modellers is that the output grids and grid sensitivity are directly applicable in CFD analysis. A small set of design parameters and grid control parameters govern the process which is incorporated into interactive software for 'real time' visual analysis and into batch software for the application of optimization technology. The computed surface grids and volume grids are suitable for a wide range of Computational Fluid Dynamics (CFD) simulation. The general airplane configuration has wing, fuselage, horizontal tail, and vertical tail components. The double-delta wing and tail components are manifested by solving a fourth order partial differential equation (PDE) subject to Dirichlet and Neumann boundary conditions. The design parameters are incorporated into the boundary conditions and therefore govern the shapes of the surfaces. The PDE solution yields a smooth transition between boundaries. Surface grids suitable for CFD calculation are created by establishing an H-type topology about the configuration and incorporating grid spacing functions in the PDE equation for the lifting components and the fuselage definition equations. User specified grid parameters govern the location and degree of grid concentration. A two-block volume grid about a configuration is calculated using the Control Point Form (CPF) technique. The interactive software, which runs on Silicon Graphics IRIS workstations, allows design parameters to be continuously varied and the resulting surface grid to be observed in real time. The batch software computes both the surface and volume grids and also computes the sensitivity of the output grid with respect to the input design parameters by applying the precompiler tool

  14. Histopathologic patterns of adult renal disease in Kermanshah, Iran: A 6-year review of two referral centers

    PubMed Central

    Mardanpour, Keykhosro; Rahbar, Mahtab

    2013-01-01

    Background: The pattern of glomerular diseases in northwest Iran is unknown. This study was conducted to evaluate the histological pattern of renal diseases in this region. Methods: We retrospectively studied the reports of 266 native adult renal biopsies at the Imam Reza and Taleghani Hospitals from June 2007 to June 2012. Pathological findings include minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), mesangioproliferative glomerulonephritis (MPGN), mesangiocapillary glomerulonephritis (MCGN), post streptococcal proliferative glomerulonephritis (PSPGN), membranous glomerulonephritis (MGN), hypertensive nephropathy (HN), crescentic glomerulonephritis or rapid progressive glomerulonephritis (CGN or RPGN), chronic tubular interstitial necrosis (CTIN), chronic sclerosing glomerulonephritis (CGN), Alport syndrome, acute tubular necrosis (ATN), lupus nephritis, renal amyloidosis. The data were collected and analyzed. Results: The mean age of the patients was 37.41±15.78 years. Nephrotic syndrome was observed in 155 (58.3%) cases which was higher in frequency in females (61.9%) (p<0.005), followed by renal insufficiency in 87 (32.7%) cases. Totally, 187 (70.3%) had primary glomerulonephritis (GN) whereas, 79 (29.7%) had secondary GN. MCD was found to be the most common histological pattern (44%) and CGN (1.12%) was the least common. The frequencies of secondary glomerulonephritis (GN) include lupus nephritis to be the most frequent (41.8%) followed by chronic tubulo interstitial nephritis (38%) and type II diabetic nephropathy (19%). Conclusion: The results showed that minimal change disease ranked first followed by focal segmental glomerulosclerosis. We hope that this will form the basis for developing a renal biopsy registry across the continent in Iran. PMID:24009967

  15. Macrophage A2A Adenosine Receptors Are Essential to Protect from Progressive Kidney Injury.

    PubMed

    Truong, Luan D; Trostel, Jessica; McMahan, Rachel; Chen, Jiang-Fan; Garcia, Gabriela E

    2016-10-01

    A2A adenosine receptors (A2ARs) are endogenous inhibitor of inflammation. Macrophages that are key effectors of kidney disease progression express A2ARs. We investigated the role of A2ARs in kidney inflammation in a macrophage-mediated anti-glomerular basement membrane reactive serum-induced immune nephritis in A2AR-deficient mice. Sub-threshold doses of glomerular basement membrane-reactive serum induced more severe and prolonged kidney damage with higher levels of proinflammatory cytokines and greater accumulation of inflammatory cells in A2AR(-/-) mice than wild-type (WT) mice. To investigate the role of macrophage A2AR in progressive kidney injury, glomerulonephritis was induced in CD11b-DTR transgenic mice. Macrophages were selectively depleted in the established phase of the disease and reconstituted with macrophages from WT or A2AR-deficient mice and then treated with an A2AR agonist. In mice receiving WT macrophages and treated with an A2AR agonist, the glomerular cellularity, crescent formation, sclerotic glomeruli, and tubulointerstitial injury were significantly reduced compared with the control group. In contrast, in mice reconstituted with A2AR-deficient macrophages and treated with an A2AR agonist, the kidney injury was more severe with increased deposition of collagen I, III, and IV. These findings suggest that disruption of the protective A2AR amplifies inflammation to accelerate glomerular damage and endogenous macrophage A2ARs are essential to protect from progressive kidney fibrosis.

  16. RAPID and DDS

    NASA Technical Reports Server (NTRS)

    Utz, Hans Heinrich

    2011-01-01

    This talk gives an overview of the the Robot Applications Programmers Interface Delegate (RAPID) as well as the distributed systems middleware Data Distribution Service (DDS). DDS is an open software standard, RAPID is cleared for open-source release under NOSA. RAPID specifies data-structures and semantics for high-level telemetry published by NASA robotic software. These data-structures are supported by multiple robotic platforms at Johnson Space Center (JSC), Jet Propulsion Laboratory (JPL) and Ames Research Center (ARC), providing high-level interoperability between those platforms. DDS is used as the middleware for data transfer. The feature set of the middleware heavily influences the design decision made in the RAPID specification. So it is appropriate to discuss both in this introductory talk.

  17. Post-streptococcal glomerulonephritis (GN)

    MedlinePlus

    ... following: Decreased urine output Rust-colored urine Swelling (edema), general swelling, swelling of the abdomen, swelling of ... Exams and Tests A physical examination shows swelling (edema), especially in the face. Abnormal sounds may be ...

  18. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  19. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  20. Rapid microbiology - raising awareness.

    PubMed

    Bailie, Jonathan

    2016-01-01

    A 'high-level overview' of some of the emerging rapid microbiology technologies designed to help healthcare engineering and infection control teams working in hospitals and other healthcare facilities more rapidly identify potentially hazardous levels of waterborne microorganisms in their water systems, enabling them to take prompt remedial action, and a look at the some of the 'pros and cons' of such testing techniques, was given by Nalco technical director, Howard Barnes, the vice-chair of the Legionella Control Association (LCA), at a recent LCA open day. HEJ editor, Jonathan Bailie, reports.

  1. Rapid road repair vehicle

    SciTech Connect

    Mara, L.M.

    1999-09-07

    Disclosed are improvements to a rapid road repair vehicle comprising an improved cleaning device arrangement, two dispensing arrays for filling defects more rapidly and efficiently, an array of pre-heaters to heat the road way surface in order to help the repair material better bond to the repaired surface, a means for detecting, measuring, and computing the number, location and volume of each of the detected surface imperfection, and a computer means schema for controlling the operation of the plurality of vehicle subsystems. The improved vehicle is, therefore, better able to perform its intended function of filling surface imperfections while moving over those surfaces at near normal traffic speeds.

  2. Rapid road repair vehicle

    DOEpatents

    Mara, Leo M.

    1999-01-01

    Disclosed are improvments to a rapid road repair vehicle comprising an improved cleaning device arrangement, two dispensing arrays for filling defects more rapidly and efficiently, an array of pre-heaters to heat the road way surface in order to help the repair material better bond to the repaired surface, a means for detecting, measuring, and computing the number, location and volume of each of the detected surface imperfection, and a computer means schema for controlling the operation of the plurality of vehicle subsystems. The improved vehicle is, therefore, better able to perform its intended function of filling surface imperfections while moving over those surfaces at near normal traffic speeds.

  3. Rapid small lot manufacturing

    SciTech Connect

    Harrigan, R.W.

    1998-05-09

    The direct connection of information, captured in forms such as CAD databases, to the factory floor is enabling a revolution in manufacturing. Rapid response to very dynamic market conditions is becoming the norm rather than the exception. In order to provide economical rapid fabrication of small numbers of variable products, one must design with manufacturing constraints in mind. In addition, flexible manufacturing systems must be programmed automatically to reduce the time for product change over in the factory and eliminate human errors. Sensor based machine control is needed to adapt idealized, model based machine programs to uncontrolled variables such as the condition of raw materials and fabrication tolerances.

  4. Rapid Prototyping of Composite Structures

    NASA Technical Reports Server (NTRS)

    Colton, Jonathan S.

    1998-01-01

    This progress report for the project Rapid Production of Composite Structures covers the period from July 14, 1997 to June 30, 1998. It will present a short overview of the project, followed by the results to date and plans for the future. The goal of this research is to provide a minimum 100x reduction in the time required to produce arbitrary, laminated products without the need for a separate mold or an autoclave. It will accomplish this by developing the science underlying the rapid production of composite structures, specifically those of carbon fiber-epoxy materials. This scientific understanding will be reduced to practice in a demonstration device that will produce a part on the order of 12" by 12" by 6". Work in the past year has focussed on developing an understanding of the materials issues and of the machine design issues. Our initial goal was to use UV cureable resins to accomplish full cure on the machine. Therefore, we have centered our materials work around whether or not UV cureable resins will work. Currently, the answer seems to be that they will not work, because UV light cannot penetrate the carbon fibers, and because no "shadow" curing seems to occur. As a result, non-UV cureable resins are being investigated. This has resulted in a change in the machine design focus. We are now looking into a "dip and place" machine design, whereby a prepreg layer would have one side coated with a curing agent, and then would be placed onto the previous layer. This would lead to cure at the interface, but not to the top of the layer. The formulation of the resins to accomplish this task at room or slightly elevated temperatures is being investigated, as is the machine design needed to apply the curing agent and then cure or partially cure the part. A final, out-of-autoclave, post-cure may be needed with this strategy, as final cure on the machine may not be possible, as it was for the initial UV cure strategy. The remainder of this report details the progress

  5. Information Loss from Technological Progress

    NASA Astrophysics Data System (ADS)

    Townsend, P. D.

    2014-12-01

    Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies.

  6. Rapid Cycling and Its Treatment

    MedlinePlus

    ... may be rapid, ultra-rapid or ultradian cycling. Biological rhythm disturbances: This theory proposes that people with rapid cycling have daily biological rhythms that are out of sync with typical “ ...

  7. Rapid steroid hormone actions via membrane receptors.

    PubMed

    Schwartz, Nofrat; Verma, Anjali; Bivens, Caroline B; Schwartz, Zvi; Boyan, Barbara D

    2016-09-01

    Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17β-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects. PMID:27288742

  8. Rapid Prototyping Reconsidered

    ERIC Educational Resources Information Center

    Desrosier, James

    2011-01-01

    Continuing educators need additional strategies for developing new programming that can both reduce the time to market and lower the cost of development. Rapid prototyping, a time-compression technique adapted from the high technology industry, represents one such strategy that merits renewed evaluation. Although in higher education rapid…

  9. Rapid Prototyping in PVS

    NASA Technical Reports Server (NTRS)

    Munoz, Cesar A.; Butler, Ricky (Technical Monitor)

    2003-01-01

    PVSio is a conservative extension to the PVS prelude library that provides basic input/output capabilities to the PVS ground evaluator. It supports rapid prototyping in PVS by enhancing the specification language with built-in constructs for string manipulation, floating point arithmetic, and input/output operations.

  10. AFRPL Rapid Indexing System.

    ERIC Educational Resources Information Center

    Beltran, Alfred A.

    A modified Keyword Out of Context (KWOC) system was developed to gain rapid control over more than 8,000 scattered, unindexed documents. This was the first step in providing the technical information support required by Air Force Rocket Propulsion Laboratory scientists and engineers. Implementation of the KWOC system, computer routines, and…

  11. Learning numerical progressions.

    PubMed

    Vitz, P C; Hazan, D N

    1974-01-01

    Learning of simple numerical progressions and compound progressions formed by combining two or three simple progressions is investigated. In two experiments, time to solution was greater for compound vs simple progressions; greater the higher the progression's solution level; and greater if the progression consisted of large vs small numbers. A set of strategies is proposed to account for progression learning based on the assumption S computes differences between integers, differences between differences, etc., in a hierarchical fashion. Two measures of progression difficulty, each a summary of the strategies, are proposed; C1 is a count of the number of differences needed to solve a progression; C2 is the same count with higher level differences given more weight. The measures accurately predict in both experiments the mean time to solve 16 different progressions with C2 being somewhat superior. The measures also predict the learning difficulty of 10 other progressions reported by Bjork (1968).

  12. Rapid display of radiographic images

    NASA Astrophysics Data System (ADS)

    Cox, Jerome R., Jr.; Moore, Stephen M.; Whitman, Robert A.; Blaine, G. James; Jost, R. Gilbert; Karlsson, L. M.; Monsees, Thomas L.; Hassen, Gregory L.; David, Timothy C.

    1991-07-01

    The requirements for the rapid display of radiographic images exceed the capabilities of widely available display, computer, and communications technologies. Computed radiography captures data with a resolution of about four megapixels. Large-format displays are available that can present over four megapixels. One megapixel displays are practical for use in combination with large-format displays and in areas where the viewing task does not require primary diagnosis. This paper describes an electronic radiology system that approximates the highest quality systems, but through the use of several interesting techniques allows the possibility of its widespread installation throughout hospitals. The techniques used can be grouped under three major system concepts: a local, high-speed image server, one or more physician's workstations each with one or more high-performance auxiliary displays specialized to the radiology viewing task, and dedicated, high-speed communication links between the server and the displays. This approach is enhanced by the use of a progressive transmission scheme to decrease the latency for viewing four megapixel images. The system includes an image server with storage for over 600 4-megapixel images and a high-speed link. A subsampled megapixel image is fetched from disk and transmitted to the display in about one second followed by the full resolution 4-megapixel image in about 2.5 seconds. Other system components include a megapixel display with a 6-megapixel display memory space and frame-rate update of image roam, zoom, and contrast. Plans for clinical use are presented.

  13. Progress in front propagation research

    NASA Astrophysics Data System (ADS)

    Fort, Joaquim; Pujol, Toni

    2008-08-01

    We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined.

  14. Rapid road repair vehicle

    DOEpatents

    Mara, L.M.

    1998-05-05

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find at the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was not heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past. 2 figs.

  15. Rapid road repair vehicle

    DOEpatents

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  16. Rapid climate change

    SciTech Connect

    Morantine, M.C.

    1995-12-31

    Interactions between insolation changes due to orbital parameter variations, carbon dioxide concentration variations, the rate of deep water formation in the North Atlantic and the evolution of the northern hemisphere ice sheets during the most recent glacial cycle will be investigated. In order to investigate this period, a climate model is being developed to evaluate the physical mechanisms thought to be most significant during this period. The description of the model sub-components will be presented. The more one knows about the interactions between the sub-components of the climate system during periods of documented rapid climate change, the better equipped one will be to make rational decisions on issues related to impacts on the environment. This will be an effort to gauge the feedback processes thought to be instrumental in rapid climate shifts documented in the past, and their potential to influence the current climate. 53 refs.

  17. Rapid Detection of Pathogens

    SciTech Connect

    David Perlin

    2005-08-14

    Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents. Many select agents are highly transmissible in the early stages of disease, and it is critical to identify infected patients and limit the risk to the remainder of the population and to stem potential panic in the general population. Nucleic acid-based molecular approaches for identification overcome many of the deficiencies associated with conventional culture methods by exploiting both large- and small-scale genomic differences between organisms. PCR-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for bacterial, fungal and many viral pathogenic agents. When combined with fluorescence-based oligonucleotide detection systems, this approach provides real-time, quantitative, high fidelity analysis capable of single nucleotide allelic discrimination (4). These probe systems offer rapid turn around time (<2 h) and are suitable for high throughput, automated multiplex operations that are critical for clinical diagnostic laboratories. In this pilot program, we have used molecular beacon technology invented at the Public health Research Institute to develop a new generation of molecular probes to rapidly detect important agents of infectious diseases. We have also developed protocols to rapidly extract nucleic acids from a variety of clinical specimen including and blood and tissue to for detection in the molecular assays. This work represented a cooperative research development program between the Kramer-Tyagi/Perlin labs on probe development

  18. Rapidly refuelable fuel cell

    DOEpatents

    Joy, Richard W.

    1985-01-01

    A rapidly refuelable dual cell of an electrochemical type wherein a single anode cooperates with two cathodes and wherein the anode has a fixed position and the cathodes are urged toward opposite faces of the anodes at constant and uniform force. The associated cathodes are automatically retractable to permit the consumed anode remains to be removed from the housing and a new anode inserted between the two cathodes.

  19. New Rapid Spore Assay

    NASA Astrophysics Data System (ADS)

    Kminek, Gerhard; Conley, Catharine

    2012-07-01

    The presentation will detail approved Planetary Protection specifications for the Rapid Spore Assay for spacecraft components and subsystems. Outlined will be the research and studies on which the specifications were based. The research, funded by ESA and NASA/JPL, was conducted over a period of two years and was followed by limited cleanroom studies to assess the feasibility of this assay during spacecraft assembly.

  20. Rapidly refuelable fuel cell

    DOEpatents

    Joy, R.W.

    1982-09-20

    A rapidly refuelable dual cell of an electrochemical type is described wherein a single anode cooperates with two cathodes and wherein the anode has a fixed position and the cathodes are urged toward opposite faces of the anodes at constant and uniform force. The associated cathodes are automatically retractable to permit the consumed anode remains to be removed from the housing and a new anode inserted between the two cathodes.

  1. Rapid adhesive bonding concepts

    NASA Technical Reports Server (NTRS)

    Stein, B. A.; Tyeryar, J. R.; Hodges, W. T.

    1984-01-01

    Adhesive bonding in the aerospace industry typically utilizes autoclaves or presses which have considerable thermal mass. As a consequence, the rates of heatup and cooldown of the bonded parts are limited and the total time and cost of the bonding process is often relatively high. Many of the adhesives themselves do not inherently require long processing times. Bonding could be performed rapidly if the heat was concentrated in the bond lines or at least in the adherends. Rapid adhesive bonding concepts were developed to utilize induction heating techniques to provide heat directly to the bond line and/or adherends without heating the entire structure, supports, and fixtures of a bonding assembly. Bonding times for specimens are cut by a factor of 10 to 100 compared to standard press bonding. The development of rapid adhesive bonding for lap shear specimens (per ASTM D1003 and D3163), for aerospace panel bonding, and for field repair needs of metallic and advanced fiber reinforced polymeric matrix composite structures are reviewed.

  2. Right-Rapid-Rough

    NASA Technical Reports Server (NTRS)

    Lawrence, Craig

    2003-01-01

    IDEO (pronounced 'eye-dee-oh') is an international design, engineering, and innovation firm that has developed thousands of products and services for clients across a wide range of industries. Its process and culture attracted the attention of academics, businesses, and journalists around the world, and are the subject of a bestselling book, The Art of Innovation by Tom Kelley. One of the keys to IDEO's success is its use of prototyping as a tool for rapid innovation. This story covers some of IDEO's projects, and gives reasons for why they were successful.

  3. Rapid and Quiet Drill

    NASA Technical Reports Server (NTRS)

    Sherrit, Stewart; Badescu, Mircea; Bar-Cohen, Yoseph; Chang, Zensheu; Bao, Xiaoqi

    2007-01-01

    This describes aspects of the rapid and quiet drill (RAQD), which is a prototype apparatus for drilling concrete or bricks. The design and basic principle of operation of the RAQD overlap, in several respects, with those of ultrasonic/ sonic drilling and coring apparatuses described in a number of previous NASA Tech Briefs articles. The main difference is that whereas the actuation scheme of the prior apparatuses is partly ultrasonic and partly sonic, the actuation scheme of the RAQD is purely ultrasonic. Hence, even though the RAQD generates considerable sound, it is characterized as quiet because most or all of the sound is above the frequency range of human hearing.

  4. Rapid prototype and test

    SciTech Connect

    Gregory, D.L.; Hansche, B.D.

    1996-06-01

    In order to support advanced manufacturing, Sandia has acquired the capability to produce plastic prototypes using stereolithography. Currently, these prototypes are used mainly to verify part geometry and ``fit and form`` checks. This project investigates methods for rapidly testing these plastic prototypes, and inferring from prototype test data actual metal part performance and behavior. Performances examined include static load/stress response, and structural dynamic (modal) and vibration behavior. The integration of advanced non-contacting measurement techniques including scanning laser velocimetry, laser holography, and thermoelasticity into testing of these prototypes is described. Photoelastic properties of the epoxy prototypes to reveal full field stress/strain fields are also explored.

  5. Rapid Prototyping of Composite Structures

    NASA Technical Reports Server (NTRS)

    Colton, Jonathan S.

    1998-01-01

    This final report for the project Rapid Production of Composite Structures covers the period from July 14, 1997 to September 30, 1998. It will present a short overview of the project, followed by the results to date and plans for the future. The goal of this research is to provide a minimum 100x reduction in the time required to produce arbitrary, laminated products without the need for a separate mold or an autoclave. It will accomplish this by developing the science underlying the rapid production of composite structures, specifically those of carbon fiber-epoxy materials. This scientific understanding will be reduced to practice in a demonstration device that will produce a part on the order of 12in. by 12in. by 6in. Work in the past year has focussed on developing an understanding of the materials issues and of the machine design issues. Our initial goal was to use UV cureable resins to accomplish full cure on the machine. Therefore, we have centered our materials work around whether or not UV cureable resins will work. Currently, the answer seems to be that they will not work, because UV light cannot penetrate the carbon fibers, and because no "shadow" curing seems to occur. As a result, non-UV cureable resins are being investigated. This has resulted in a change in the machine design focus. We are now looking into a "dip and place" machine design, whereby a prepreg layer would have one side coated with a curing agent, and then would be placed onto the previous layer. This would lead to cure at the interface, but not to the top of the layer. The formulation of the resins to accomplish this task at room or slightly elevated temperatures is being investigated, as is the machine design needed to apply the curing agent and then cure or partially cure the part. A final, out-of-autoclave, post-cure may be needed with this strategy, as final cure on the machine may not be possible, as it was for the initial UV cure strategy. The remainder of this report details the

  6. Rapid Decisions From Experience

    PubMed Central

    Zeigenfuse, Matthew D.; Pleskac, Timothy J.; Liu, Taosheng

    2014-01-01

    In many everyday decisions, people quickly integrate noisy samples of information to form a preference among alternatives that offer uncertain rewards. Here, we investigated this decision process using the Flash Gambling Task (FGT), in which participants made a series of choices between a certain payoff and an uncertain alternative that produced a normal distribution of payoffs. For each choice, participants experienced the distribution of payoffs via rapid samples updated every 50 ms. We show that people can make these rapid decisions from experience and that the decision process is consistent with a sequential sampling process. Results also reveal a dissociation between these preferential decisions and equivalent perceptual decisions where participants had to determine which alternatives contained more dots on average. To account for this dissociation, we developed a sequential sampling rank-dependent utility model, which showed that participants in the FGT attended more to larger potential payoffs than participants in the perceptual task despite being given equivalent information. We discuss the implications of these findings in terms of computational models of preferential choice and a more complete understanding of experience-based decision making. PMID:24549141

  7. Rapid cognitive and functional decline: Creutzfeldt-Jakob disease.

    PubMed

    Dameron, Matthew

    2013-09-01

    The emergence of "mad cow disease" has sparked interest in prion diseases, including Creutzfeldt-Jakob disease, a spongiform encephalopathy that can mimic other rapidly progressive dementias. A systematic approach to evaluation and diagnostic testing can help rule out other causes. PMID:24317229

  8. Progressive Pigmentary Purpura

    MedlinePlus

    ... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

  9. RAVE: Rapid Visualization Environment

    NASA Technical Reports Server (NTRS)

    Klumpar, D. M.; Anderson, Kevin; Simoudis, Avangelos

    1994-01-01

    Visualization is used in the process of analyzing large, multidimensional data sets. However, the selection and creation of visualizations that are appropriate for the characteristics of a particular data set and the satisfaction of the analyst's goals is difficult. The process consists of three tasks that are performed iteratively: generate, test, and refine. The performance of these tasks requires the utilization of several types of domain knowledge that data analysts do not often have. Existing visualization systems and frameworks do not adequately support the performance of these tasks. In this paper we present the RApid Visualization Environment (RAVE), a knowledge-based system that interfaces with commercial visualization frameworks and assists a data analyst in quickly and easily generating, testing, and refining visualizations. RAVE was used for the visualization of in situ measurement data captured by spacecraft.

  10. Rapid shallow breathing index

    PubMed Central

    Karthika, Manjush; Al Enezi, Farhan A.; Pillai, Lalitha V.; Arabi, Yaseen M.

    2016-01-01

    Predicting successful liberation of patients from mechanical ventilation has been a focus of interest to clinicians practicing in intensive care. Various weaning indices have been investigated to identify an optimal weaning window. Among them, the rapid shallow breathing index (RSBI) has gained wide use due to its simple technique and avoidance of calculation of complex pulmonary mechanics. Since its first description, several modifications have been suggested, such as the serial measurements and the rate of change of RSBI, to further improve its predictive value. The objective of this paper is to review the utility of RSBI in predicting weaning success. In addition, the use of RSBI in specific patient populations and the reported modifications of RSBI technique that attempt to improve the utility of RSBI are also reviewed. PMID:27512505

  11. Rapid Polymer Sequencer

    NASA Technical Reports Server (NTRS)

    Stolc, Viktor (Inventor); Brock, Mathew W. (Inventor)

    2011-01-01

    Method and system for rapid and accurate determination of each of a sequence of unknown polymer components, such as nucleic acid components. A self-assembling monolayer of a selected substance is optionally provided on an interior surface of a pipette tip, and the interior surface is immersed in a selected liquid. A selected electrical field is impressed in a longitudinal or transverse direction at the tip, a polymer sequence is passed through the tip, and a change in an electrical current signal is measured as each polymer component passes through the tip. Each measured change in electrical current signals is compared with a database of reference signals, with each reference signal identified with a polymer component, to identify the unknown polymer component. The tip preferably has a pore inner diameter of no more than about 40 nm and is prepared by heating and pulling a very small section of a glass tubing.

  12. rapidMCR

    2011-11-04

    rapidMCR is a user friendly software package that includes automatic preprocessing, analysis, and viewing of hyperspectral image data sets. Currently, this software package specifically preprocesses and analyzes hyperspectral fluorescence image data sets that have been created on Sandia hyperspectral imaging microscopes; however, this software can be modified to include spectroscopic image data sets from other (non-Sandia developed) instruments as well. This software relies on using prior information about the spectroscopic image data sets by conductingmore » a rigorous characterization of the instrument. By characterizing the instrument for noise and artifacts, we can implement our algorithms to account for the effects specific to a particular instrument. This allows us to automate the data preprocessing while improving the analysis results.« less

  13. rapidMCR

    SciTech Connect

    2011-11-04

    rapidMCR is a user friendly software package that includes automatic preprocessing, analysis, and viewing of hyperspectral image data sets. Currently, this software package specifically preprocesses and analyzes hyperspectral fluorescence image data sets that have been created on Sandia hyperspectral imaging microscopes; however, this software can be modified to include spectroscopic image data sets from other (non-Sandia developed) instruments as well. This software relies on using prior information about the spectroscopic image data sets by conducting a rigorous characterization of the instrument. By characterizing the instrument for noise and artifacts, we can implement our algorithms to account for the effects specific to a particular instrument. This allows us to automate the data preprocessing while improving the analysis results.

  14. Rapid shallow breathing index.

    PubMed

    Karthika, Manjush; Al Enezi, Farhan A; Pillai, Lalitha V; Arabi, Yaseen M

    2016-01-01

    Predicting successful liberation of patients from mechanical ventilation has been a focus of interest to clinicians practicing in intensive care. Various weaning indices have been investigated to identify an optimal weaning window. Among them, the rapid shallow breathing index (RSBI) has gained wide use due to its simple technique and avoidance of calculation of complex pulmonary mechanics. Since its first description, several modifications have been suggested, such as the serial measurements and the rate of change of RSBI, to further improve its predictive value. The objective of this paper is to review the utility of RSBI in predicting weaning success. In addition, the use of RSBI in specific patient populations and the reported modifications of RSBI technique that attempt to improve the utility of RSBI are also reviewed. PMID:27512505

  15. Solid state rapid thermocycling

    SciTech Connect

    Beer, Neil Reginald; Spadaccini, Christopher

    2014-05-13

    The rapid thermal cycling of a material is targeted. A solid state heat exchanger with a first well and second well is coupled to a power module. A thermoelectric element is coupled to the first well, the second well, and the power module, is configured to transfer thermal energy from the first well to the second well when current from the power module flows through the thermoelectric element in a first direction, and is configured to transfer thermal energy from the second well to the first well when current from the power module flows through the thermoelectric element in a second direction. A controller may be coupled to the thermoelectric elements, and may switch the direction of current flowing through the thermoelectric element in response to a determination by sensors coupled to the wells that the amount of thermal energy in the wells falls below or exceeds a pre-determined threshold.

  16. Diet for rapid weight loss

    MedlinePlus

    ... diet; VLCD; Low-calorie diet; LCD; Very low energy diet; Weight loss - rapid weight loss; Overweight - rapid ... AM, Aveyard P. Clinical effectiveness of very-low-energy diets in the management of weight loss: a ...

  17. Rapid geophysical surveyor

    SciTech Connect

    Roybal, L.G.; Carpenter, G.S.; Josten, N.E.

    1993-01-01

    The Rapid Geophysical Surveyor (RGS) is a system designed to rapidly and economically collect closely-spaced geophysical data used for characterization of Department of Energy (DOE) waste sites. Geophysical surveys of waste sites are an important first step in the remediation and closure of these sites; especially older sties where historical records are inaccurate and survey benchmarks have changed due to refinements in coordinate controls and datum changes. Closely-spaced data are required to adequately differentiate pits, trenches, and soil vault rows whose edges may be only a few feet from each other. A prototype vehicle designed to collect magnetic field data was built at the Idaho national Engineering Laboratory (INEL) during the summer of 1992. The RGS was one of several projects funded by the Buried Waste Integrated Demonstration (BWID) program. This vehicle was demonstrated at the Subsurface Disposal Area (SDA) within the Radioactive Waste Management Complex (RWMC) on the INEL in September of 1992. Magnetic data were collected over two areas in the SDA, with a total survey area of about 1.7 acres. Data were collected at a nominal density of 2 1/2 inches along survey lines spaced 1 foot apart. Over 350,000 data points were collected over a 6 day period corresponding to about 185 man-days using conventional ground survey techniques. This report documents the design and demonstration of the RGS concept including the presentation of magnetic data collected at the SDA. The surveys were able to show pit and trench boundaries and determine details of their spatial orientation never before achieved.

  18. Rapid geophysical surveyor

    SciTech Connect

    Roybal, L.G.; Carpenter, G.S.; Josten, N.E.

    1993-07-01

    The Rapid Geophysical Surveyor (RGS) is a system designed to rapidly and economically collect closely-spaced geophysical data used for characterization of Department of Energy (DOE) waste sites. Geophysical surveys of waste sites are an important first step in the remediation and closure of these sites; especially older sties where historical records are inaccurate and survey benchmarks have changed due to refinements in coordinate controls and datum changes. Closely-spaced data are required to adequately differentiate pits, trenches, and soil vault rows whose edges may be only a few feet from each other. A prototype vehicle designed to collect magnetic field data was built at the Idaho national Engineering Laboratory (INEL) during the summer of 1992. The RGS was one of several projects funded by the Buried Waste Integrated Demonstration (BWID) program. This vehicle was demonstrated at the Subsurface Disposal Area (SDA) within the Radioactive Waste Management Complex (RWMC) on the INEL in September of 1992. Magnetic data were collected over two areas in the SDA, with a total survey area of about 1.7 acres. Data were collected at a nominal density of 2 1/2 inches along survey lines spaced 1 foot apart. Over 350,000 data points were collected over a 6 day period corresponding to about 185 man-days using conventional ground survey techniques. This report documents the design and demonstration of the RGS concept including the presentation of magnetic data collected at the SDA. The surveys were able to show pit and trench boundaries and determine details of their spatial orientation never before achieved.

  19. Rapid population growth.

    PubMed

    1972-01-01

    At the current rate of population growth, world population by 2000 is expected to reach 7 billion or more, with developing countries accounting for some 5.4 billion, and economically advanced nations accounting for 1.6 billion. 'Population explosion' is the result of falling mortality rates and continuing high birth rates. Many European countries, and Japan, have already completed what is termed as demographic transition, that is, birth rates have fallen to below 20 births per 1000 population, death rates to 10/1000 population, and annual growth rates are 1% or less; annual growth rates for less developed countries ranged from 2 to 3.5%. Less developed countries can be divided into 3 groups: 1) countries with both high birth and death rates; 2) countries with high birth rates and low death rates; and 3) countries with intermediate and declining birth rates and low death rates. Rapid population growth has serious economic consequences. It encourages inequities in income distribution; it limits rate of growth of gross national product by holding down level of savings and capital investments; it exerts pressure on agricultural production and land; and it creates unemployment problems. In addition, the quality of education for increasing number of chidren is adversely affected, as high proportions of children reduce the amount that can be spent for the education of each child out of the educational budget; the cost and adequacy of health and welfare services are affected in a similar way. Other serious consequences of rapid population growth are maternal death and illness, and physical and mental retardation of children of very poor families. It is very urgent that over a billion births be prevented in the next 30 years to reduce annual population growth rate from the current 2% to 1% per year. PMID:12261450

  20. Advances in rapid prototyping

    SciTech Connect

    Atwood, C.L.; McCarty, G.D.; Pardo, B.T.; Bryce, E.A.

    1993-12-31

    Recent advances in stereolithography and selective laser sintering have had a significant impact on the overall quality of parts produced using these rapid prototyping processes. The development and implementation of 3D System`s QuickCast{trademark} resin and software for building investment casting patterns have proven to be major steps toward fabricating highly accurate patterns with very good surface finishes. Sandia uses patterns generated from rapid prototyping processes to reduce the cycle time and cost of fabricating prototype parts in support of a Sandia National Laboratories managed program called FASTCAST. As participants in the Beta test program for QuickCast{trademark} resin and software, they experienced a steep learning curve and were able to build accurate parts in a short period of time. It is now possible, using this technology, to produce highly accurate prototype parts as well as acceptable firs article and small lots size production parts. They use the Selective Laser Sintering (SLS) process to fabricate prototype wax patterns for investment casting. DTM Corporation recently introduced the use of their polycarbonate material for fabricating investment casting patterns. The polycarbonate material is processed significantly faster, with improved strength, dimensional stability, and without a support structure during the build process. Sandia is currently changing from investment casting wax to polycarbonate for the fabrication of investment casting patterns using the SLS process. This presentation will focus on the successes with these new materials from the standpoints of application, accuracy, surface finish, and post processing. Also presented will be examples of parts manufactured by these processes.

  1. Progress with parasite plastids.

    PubMed

    Wilson, R J M Iain

    2002-05-31

    This review offers a snapshot of our current understanding of the origin, biology, and metabolic significance of the non-photosynthetic plastid organelle found in apicomplexan parasites. These protists are of considerable medical and veterinary importance world-wide, Plasmodium spp., the causative agent of malaria being foremost in terms of human disease. It has been estimated that approximately 8% of the genes currently recognized by the malarial genome sequencing project (now nearing completion) are of bacterial/plastid origin. The bipartite presequences directing the products of these genes back to the plastid have provided fresh evidence that secondary endosymbiosis accounts for this organelle's presence in these parasites. Mounting phylogenetic evidence has strengthened the likelihood that the plastid originated from a red algal cell. Most importantly, we now have a broad understanding of several bacterial metabolic systems confined within the boundaries of the parasite plastid. The primary ones are type II fatty acid biosynthesis and isoprenoid biosynthesis. Some aspects of heme biosynthesis also might take place there. Retention of the plastid's relict genome and its still ill-defined capacity to participate in protein synthesis might be linked to an important house-keeping process, i.e. guarding the type II fatty acid biosynthetic pathway from oxidative damage. Fascinating observations have shown the parasite plastid does not divide by constriction as in typical plants, and that plastid-less parasites fail to thrive after invading a new cell. The modes of plastid DNA replication within the phylum also have provided surprises. Besides indicating the potential of the parasite plastid for therapeutic intervention, this review exposes many gaps remaining in our knowledge of this intriguing organelle. The rapid progress being made shows no sign of slackening.

  2. The Rapid Transient Surveyor

    NASA Astrophysics Data System (ADS)

    Baranec, Christoph; Tonry, John; Wright, Shelley; Tully, R. Brent; Lu, Jessica R.; Takamiya, Marianne Y.; Hunter, Lisa

    2016-01-01

    The next decade of astronomy will be dominated by large area surveys (see the detailed discussion in the Astro-2010 Decadal survey and NRC's recent OIR System Report). Ground-based optical transient surveys, e.g., LSST, ZTF and ATLAS and space-based exoplanet, supernova, and lensing surveys such as TESS and WFIRST will join the Gaia all-sky astrometric survey in producing a flood of data that will enable leaps in our understanding of the universe. There is a critical need for further characterization of these discoveries through high angular resolution images, deeper images, spectra, or observations at different cadences or periods than the main surveys. Such follow-up characterization must be well matched to the particular surveys, and requires sufficient additional observing resources and time to cover the extensive number of targets.We describe plans for the Rapid Transient Surveyor (RTS), a permanently mounted, rapid-response, high-cadence facility for follow-up characterization of transient objects on the U. of Hawai'i 2.2-m telescope on Maunakea. RTS will comprise an improved robotic laser adaptive optics system, based on the prototype Robo-AO system (formerly at the Palomar 1.5-m and now at the Kitt Peak 2.2-m telescope), with simultaneous visible and near-infrared imagers as well as a near-infrared integral field spectrograph (R~100, λ = 850 - 1830 nm, 0.15″ spaxels, 8.7″×6.0″ FoV). RTS will achieve an acuity of ~0.07″ in visible wavelengths and < 0.16″ in the near infrared leading to an increase of the infrared point-source sensitivity against the sky background by a factor of ~9, crucial for efficient near-infrared spectroscopy.RTS will allow us to map the dark matter distribution in the z < 0.1 local universe with ten times better accuracy and precision than previous experiments. ATLAS will discover several thousand SNIae per year, measuring SNIa peak brightness, and decline rates, while RTS will measure reddening by dust, confirm SN type and

  3. Measuring disease progression in corticobasal syndrome.

    PubMed

    Huang, Nancy; Hornberger, Michael; Hodges, John R; Burrell, James R

    2014-08-01

    Corticobasal syndrome (CBS) is a complex neurodegenerative disorder with marked clinical, neuropsychological, and pathological heterogeneity. Measurement of disease progression in CBS is complex and little understood. This study aimed to establish clinical and neuropsychological indicators of prognosis in CBS. Patients with CBS were retrospectively recruited from a frontotemporal dementia specific research clinic. All patients underwent detailed clinical and neuropsychological testing including the frontotemporal dementia rating scale (FRS). Using the differences in FRS logit scores over a period of 12 months, CBS patients were divided into rapid and slow progressor groups. Demographic, clinical and neuropsychological features were compared between the two groups. Sixteen participants who met defined criteria were included (9 males, 7 females; mean age 65.8 ± 22 years; median symptom duration 51.8 ± 22 years; mean duration of follow-up 11.4 ± 2.8 months). There were no significant differences between the rapid and slow progressors in age, gender, symptom duration, motor/cognitive presentation, and ACE-R scores at baseline. Clinically, slow progressors were significantly more likely to have a motor speech disorder, with a trend for more frequent dysgraphia, whereas rapid progressors were more likely to exhibit surface dyslexia. Rapid and slow progressor groups did not differ on neuropsychological performance. The presence of motor speech disorder, dysgraphia, and surface dyslexia may be useful in differentiating patients with rapid progression of CBS from those with a more indolent disease course. PMID:24893591

  4. Immune mediated crescentic MPGN secondary to HBV infection: A rare presentation for a common infection.

    PubMed

    Mareddy, Aswani Srinivas; Rangaswamy, Dharshan; Vankalakunti, Mahesha; Attur, Ravindra Prabhu; Nagaraju, Shankar Prasad; Koti, Neeraja

    2016-01-01

    Hepatitis B virus (HBV) infection presenting as crescentic glomerulonephritis in the absence of cryoglobulinemia is an extremely rare phenomenon. We report a case of a 44-year-old male with HBV infection, who underwent kidney biopsy for rapidly progressive renal failure and nephrotic range proteinuria. Histopathological evaluation of the kidney biopsy was consistent with immune complex mediated crescentic membranoproliferative glomerulonephritis (MPGN). The patient achieved complete renal and virological remission with steroids, plasmapheresis and antiviral therapy. This case report summarises the importance of early initiation of immunosuppression and plasmapheresis under antiviral coverage for improved clinical outcomes.

  5. Prognosis in glomerulonephritis. A follow-up study of 395 consecutive, biopsy-verified cases. I. Classification, renal histology and outcome. Report from a Copenhagen study group of renal diseases.

    PubMed

    Brahm, M; Balsløv, J T; Brun, C; Gerstoft, J; Jørgensen, F; Jørgensen, H E; Larsen, M; Larsen, S; Lorenzen, I; Løber, M

    1985-01-01

    Between 1967 and 1977, 395 consecutive cases of glomerulonephritis (GN) were collected by a Copenhagen study group. The diagnosis was established by histological and biochemical criteria. Light microscopy investigations of thin silver-stained sections were applied. In a follow-up in 1980 all cases were categorized by one of the following end points: death without uremia, uremia, recovery, or censored cases. The course is presented in figures showing the cumulated distribution of outcomes in relation to observation time. Each histological subgroup of GN had its own characteristic course with respect to initial rates of changes in the renal state, as well as to frequency of recovery, uremia and death. The prognosis was good in minimal changes GN and proliferative GN, bad in unclassified GN and worst in extracapillary GN. When part of a connective tissue disease, GN carried a poor prognosis. We conclude that histological classification of GN based on light microscopy offers a reliable means of predicting the long-term prognosis.

  6. Rapid Evaporation of microbubbles

    NASA Astrophysics Data System (ADS)

    Gautam, Jitendra; Esmaeeli, Asghar

    2008-11-01

    When a liquid is heated to a temperature far above its boiling point, it evaporates abruptly. Boiling of liquid at high temperatures can be explosive and destructive, and poses a potential hazard for a host of industrial processes. Explosive boiling may occur if a cold and volatile liquid is brought into contact with a hot and non-volatile liquid, or if a liquid is superheated or depressurized rapidly. Such possibilities are realized, for example, in the depressurization of low boiling point liquefied natural gas (LNG) in the pipelines or storage tanks as a result of a leak. While boiling of highly heated liquids can be destructive at macroscale, the (nearly) instantaneous pace of the process and the release of large amount of kinetic energy make the phenomena extremely attractive at microscale where it is possible to utilize the released energy to derive micromechanical systems. For instance, there is currently a growing interest in micro-explosion of liquid for generation of micro bubbles for actuation purposes. The aim of the current study is to gain a fundamental understanding of the subject using direct numerical simulations. In particular, we seek to investigate the boundary between stable and unstable nucleus growth in terms of the degree of liquid superheat and to compare the dynamics of unstable and stable growth.

  7. Rapid Polymer Sequencer

    NASA Technical Reports Server (NTRS)

    Stolc, Viktor (Inventor); Brock, Matthew W (Inventor)

    2013-01-01

    Method and system for rapid and accurate determination of each of a sequence of unknown polymer components, such as nucleic acid components. A self-assembling monolayer of a selected substance is optionally provided on an interior surface of a pipette tip, and the interior surface is immersed in a selected liquid. A selected electrical field is impressed in a longitudinal direction, or in a transverse direction, in the tip region, a polymer sequence is passed through the tip region, and a change in an electrical current signal is measured as each polymer component passes through the tip region. Each of the measured changes in electrical current signals is compared with a database of reference electrical change signals, with each reference signal corresponding to an identified polymer component, to identify the unknown polymer component with a reference polymer component. The nanopore preferably has a pore inner diameter of no more than about 40 nm and is prepared by heating and pulling a very small section of a glass tubing.

  8. Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males

    PubMed Central

    Shoji, Tatsuya; Shinzawa, Maki; Hasuike, Yukiko; Nagatoya, Katsuyuki; Yamauchi, Atsushi; Hayashi, Terumasa; Kuragano, Takayuki; Moriyama, Toshiki; Isaka, Yoshitaka; Nakanishi, Takeshi

    2016-01-01

    Background Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. Study Design Multicenter retrospective cohort study. Setting & Participants 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. Predictor Uric acid levels at renal biopsy. Outcomes The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". Measurements The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. Results An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. Limitations A cohort analyzed retorospectively. Conclusions This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID:27560997

  9. [Marine microbial metagenomics: progress and prospect].

    PubMed

    Li, Xiang; Qin, Ling; Dai, Shi-kun; Jiang, Shu-mei; Liu, Zhi-heng

    2007-06-01

    Preliminary statistics showed that there are more than one million species of microbes in marine environments that formed a dynamic genetic reservoir, among which the majority are not revealed and categorized due to barrier in cultivation techniques. However, the situation has changed in recent years because of the rapid development of phylogenetic studies based on small ribosomal RNA and rDNA sequencing independent to standard laboratory cultivation. These changes have significantly altered our understanding about microbial diversity and microbial ecology. In this review, we highlight some of recent progress and innovation in research on microbial diversity, and propose a metagenomic scheme as an alternative to overcome some of the barriers that still remain for exploitation of marine microbial diversity for its enormous potential in pharmaceutical applications. We believe that rapid progress in marine metagenomics allows direct access to the genomes of numerous non-cultivable microorganisms for their associated chemical prosperity.

  10. Rapid Active Sampling Package

    NASA Technical Reports Server (NTRS)

    Peters, Gregory

    2010-01-01

    A field-deployable, battery-powered Rapid Active Sampling Package (RASP), originally designed for sampling strong materials during lunar and planetary missions, shows strong utility for terrestrial geological use. The technology is proving to be simple and effective for sampling and processing materials of strength. Although this originally was intended for planetary and lunar applications, the RASP is very useful as a powered hand tool for geologists and the mining industry to quickly sample and process rocks in the field on Earth. The RASP allows geologists to surgically acquire samples of rock for later laboratory analysis. This tool, roughly the size of a wrench, allows the user to cut away swaths of weathering rinds, revealing pristine rock surfaces for observation and subsequent sampling with the same tool. RASPing deeper (.3.5 cm) exposes single rock strata in-situ. Where a geologist fs hammer can only expose unweathered layers of rock, the RASP can do the same, and then has the added ability to capture and process samples into powder with particle sizes less than 150 microns, making it easier for XRD/XRF (x-ray diffraction/x-ray fluorescence). The tool uses a rotating rasp bit (or two counter-rotating bits) that resides inside or above the catch container. The container has an open slot to allow the bit to extend outside the container and to allow cuttings to enter and be caught. When the slot and rasp bit are in contact with a substrate, the bit is plunged into it in a matter of seconds to reach pristine rock. A user in the field may sample a rock multiple times at multiple depths in minutes, instead of having to cut out huge, heavy rock samples for transport back to a lab for analysis. Because of the speed and accuracy of the RASP, hundreds of samples can be taken in one day. RASP-acquired samples are small and easily carried. A user can characterize more area in less time than by using conventional methods. The field-deployable RASP used a Ni

  11. Progress towards a dengue vaccine.

    PubMed

    Webster, Daniel P; Farrar, Jeremy; Rowland-Jones, Sarah

    2009-11-01

    The spread of dengue virus throughout the tropics represents a major, rapidly growing public health problem with an estimated 2.5 billion people at risk of dengue fever and the life-threatening disease, severe dengue. A safe and effective vaccine for dengue is urgently needed. The pathogenesis of severe dengue results from a complex interaction between the virus, the host, and, at least in part, immune-mediated mechanisms. Vaccine development has been slowed by fears that immunisation might predispose individuals to the severe form of dengue infection. A pipeline of candidate vaccines now exists, including live attenuated, inactivated, chimeric, DNA, and viral-vector vaccines, some of which are at the stage of clinical testing. In this Review, we present what is understood about dengue pathogenesis and its implications for vaccine design, the progress that is being made in the development of a vaccine, and the future challenges.

  12. The progressive outer retinal necrosis syndrome.

    PubMed

    Holland, G N

    1994-01-01

    The progressive outer retinal necrosis (PORN) syndrome is a recently described clinical variant of necrotizing herpetic retinopathy in patients with the acquired immunodeficiency syndrome (AIDS). It is caused by varicellazoster virus infection of the retina. Its course and clinical features distinguish it from the acute retinal necrosis syndrome and CMV retinopathy. Early disease is characterized by multifocal deep retinal opacification. Lesions rapidly coalesce and progress to total retinal necrosis over a short period of time. Despite aggressive therapy with intravenous antivirial drugs, prognosis is poor; disease progression and/or recurrence is common, and the majority of patients develop no light perception vision. Total retinal detachments are common. Prophylaxis against retinal detachment using laser retinopexy has not been useful in most cases. PORN syndrome is an uncommon, but devastating complication of AIDS.

  13. The progressive outer retinal necrosis syndrome.

    PubMed

    Holland, G N

    1994-01-01

    The progressive outer retinal necrosis (PORN) syndrome is a recently described clinical variant of necrotizing herpetic retinopathy in patients with the acquired immunodeficiency syndrome (AIDS). It is caused by varicellazoster virus infection of the retina. Its course and clinical features distinguish it from the acute retinal necrosis syndrome and CMV retinopathy. Early disease is characterized by multifocal deep retinal opacification. Lesions rapidly coalesce and progress to total retinal necrosis over a short period of time. Despite aggressive therapy with intravenous antivirial drugs, prognosis is poor; disease progression and/or recurrence is common, and the majority of patients develop no light perception vision. Total retinal detachments are common. Prophylaxis against retinal detachment using laser retinopexy has not been useful in most cases. PORN syndrome is an uncommon, but devastating complication of AIDS. PMID:7852023

  14. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    PubMed Central

    Kwiatkowska, Ewa; Gołembiewska, Edyta; Ciechanowski, Kazimierz; Kędzierska, Karolina

    2012-01-01

    Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. (1997)). In available literature, there were reports of human's glomerulonephritis associated with Borrelia burgdorferi infection. These cases refer to membranous and mesangial proliferative glomerulonephritis (Kirmizis and Chatzidimitriou (2010), Zachäus (2008), and Kirmizis et al. (2004)). In this paper, we present the case of minimal-change disease (MCD) as a result of Borrelia burgdorferi infection. PMID:24527240

  15. Progress towards understanding baryon resonances

    SciTech Connect

    Crede, Volker; Roberts, Winston

    2013-07-01

    The composite nature of baryons manifests itself in the existence of a rich spectrum of excited states, in particular in the important mass region 1?2 GeV for the light-flavoured baryons. The properties of these resonances can be identified by systematic investigations using electromagnetic and strong probes, primarily with beams of electrons, photons, and pions. After decades of research, the fundamental degrees of freedom underlying the baryon excitation spectrum are still poorly understood. The search for hitherto undiscovered but predicted resonances continues at many laboratories around the world. Recent results from photo- and electroproduction experiments provide intriguing indications for new states and shed light on the structure of some of the known nucleon excitations. The continuing study of available data sets with consideration of new observables and improved analysis tools have also called into question some of the earlier findings in baryon spectroscopy. Other breakthrough measurements have been performed in the heavy-baryon sector, which has seen a fruitful period in recent years, in particular at the B factories and the Tevatron. First results from the large hadron collider indicate rapid progress in the field of bottom baryons. In this review, we discuss the recent experimental progress and give an overview of theoretical approaches.

  16. Rapidly solidified ceramics: Processing, structure, and magnetic properties

    SciTech Connect

    Kalonji, G.M.; O'Handley, R.C.

    1985-01-01

    Since its initiation in September 1984, work under this contract has progressed in two areas: construction of a gas atomizer for rapid solidification of ceramics; and characterization of rapidly solidified materials in the SrO-Fe{sub 2}O{sub 3}, BaO-Fe{sub 2}O{sub 3}, MnFe{sub 2}O{sub 4}-SiO{sub 2}, and CoFe{sub 2}O{sub 4}-SiO{sub 2} systems. This report summarize this work.

  17. RapidMic: Rapid Computation of the Maximal Information Coefficient

    PubMed Central

    Tang, Dongming; Wang, Mingwen; Zheng, Weifan; Wang, Hongjun

    2014-01-01

    To discover relationships and associations rapidly in large-scale datasets, we propose a cross-platform tool for the rapid computation of the maximal information coefficient based on parallel computing methods. Through parallel processing, the provided tool can effectively analyze large-scale biological datasets with a markedly reduced computing time. The experimental results show that the proposed tool is notably fast, and is able to perform an all-pairs analysis of a large biological dataset using a normal computer. The source code and guidelines can be downloaded from https://github.com/HelloWorldCN/RapidMic. PMID:24526831

  18. Glaucoma progression associated with Leber's hereditary optic neuropathy.

    PubMed

    Nucci, Carlo; Martucci, Alessio; Mancino, Raffaele; Cerulli, Luciano

    2013-02-01

    The purpose of this article is to describe a case of open-angle glaucoma progression associated with Leber's hereditary optic neuropathy. Single case analysis method is used. A 53-year-old woman with a previous diagnosis of glaucoma presented with progressive visual field loss. Complete ophthalmological examination and blood tests were negative for other concomitant diseases. Genetic counseling revealed mitochondrial DNA mutation compatible with the diagnosis of Leber's hereditary optic neuropathy. In conclusion, the case describes the concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We hypothesize that the two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the consequent rapid progression of visual impairment. Screening for mitochondrial DNA mutations may be requested in patients with glaucoma who, despite pharmacologically controlled intraocular pressure, show rapid progression of the disease.

  19. Progress With Nonhuman Animal Models of Addiction.

    PubMed

    Crabbe, John C

    2016-09-01

    Nonhuman animals have been major contributors to the science of the genetics of addiction. Given the explosion of interest in genetics, it is fair to ask, are we making reasonable progress toward our goals with animal models? I will argue that our goals are changing and that overall progress has been steady and seems likely to continue apace. Genetics tools have developed almost incredibly rapidly, enabling both more reductionist and more synthetic or integrative approaches. I believe that these approaches to making progress have been unbalanced in biomedical science, favoring reductionism, particularly in animal genetics. I argue that substantial, novel progress is also likely to come in the other direction, toward synthesis and abstraction. Another area in which future progress with genetic animal models seems poised to contribute more is the reconciliation of human and animal phenotypes, or consilience. The inherent power of the genetic animal models could be more profitably exploited. In the end, animal research has continued to provide novel insights about how genes influence individual differences in addiction risk and consequences. The rules of the genetics game are changing so fast that it is hard to remember how comparatively little we knew even a generation ago. Rather than worry about whether we have been wasting time and resources asking the questions we have been, we should look to the future and see if we can come up with some new ones. The valuable findings from the past will endure, and the sidetracks will be forgotten. PMID:27588527

  20. Can China afford rapid aging?

    PubMed

    Jiang, Quanbao; Yang, Shucai; Sánchez-Barricarte, Jesús J

    2016-01-01

    China's rapid aging has caused widespread concern, but it seems that the situations and consequences of rapid aging are not adequately acknowledged. This study analyzed the problem of ageing in China from the aspects of elderly people's health status, income source, daily care, suicide, the weak social security system in terms of pension, health expenses, and long-term care costs as well as incoming accelerating ageing process in China. All these factors indicate that it is difficult for China to afford the issue of a rapidly aging population. PMID:27478724

  1. [Rapid diagnosis of respiratory infection].

    PubMed

    Hashimoto, Toru

    2012-08-01

    The identification of pathogens is very important for the diagnosis and treatment of respiratory infectious disease. Bacterial culture is a basic method to identify various pathogens, but it takes several days to get the final results. Many new methods for the rapid diagnosis of respiratory infection have been developed in recent years. This has changed the treatment of respiratory infection. Broad-spectrum antibiotics were often used to treat respiratory infection previously, but rapid diagnosis has changed the choice of antibiotics from broad-spectrum to specific ones. New methods of rapid diagnosis are very useful and powerful tools in the treatment of respiratory infection.

  2. Progress in renewables

    NASA Astrophysics Data System (ADS)

    San Martin, R. L.

    This is a status report on progress made in the conduct of eleven Federally-supported renewable energy programs. Considerable progress has been made in the establishment and development of an infrastructure to support sustained growth. Unique technical problems led to the research and development of materials and designs which have achieved energy conversion efficiencies of up to 25% for electricity and 92% for heat in solar thermal systems. Overall, enough real progress has been made to provide a sound technology base upon which renewable energy systems industries can reasonably continue development.

  3. Rapid Prototyping of Patterned Multifunctional Nanostructures

    SciTech Connect

    FAN,HONGYOU; LU,YUNFENG; LOPEZ,GABRIEL P.; BRINKER,C. JEFFREY

    2000-07-18

    The ability to engineer ordered arrays of objects on multiple length scales has potential for applications such as microelectronics, sensors, wave guides, and photonic lattices with tunable band gaps. Since the invention of surfactant templated mesoporous sieves in 1992, great progress has been made in controlling different mesophases in the form of powders, particles, fibers, and films. To date, although there have been several reports of patterned mesostructures, materials prepared have been limited to metal oxides with no specific functionality. For many of the envisioned applications of hierarchical materials in micro-systems, sensors, waveguides, photonics, and electronics, it is necessary to define both form and function on several length scales. In addition, the patterning strategies utilized so far require hours or even days for completion. Such slow processes are inherently difficult to implement in commercial environments. The authors present a series of new methods of producing patterns within seconds. Combining sol-gel chemistry, Evaporation-Induced Self-Assembly (EISA), and rapid prototyping techniques like pen lithography, ink-jet printing, and dip-coating on micro-contact printed substrates, they form hierarchically organized silica structures that exhibit order and function on multiple scales: on the molecular scale, functional organic moieties are positioned on pore surfaces, on the mesoscale, mono-sized pores are organized into 1-, 2-, or 3-dimensional networks, providing size-selective accessibility from the gas or liquid phase, and on the macroscale, 2-dimensional arrays and fluidic or photonic systems may be defined. These rapid patterning techniques establish for the first time a link between computer-aided design and rapid processing of self-assembled nanostructures.

  4. Rapid deployment intrusion detection system

    SciTech Connect

    Graham, R.H.

    1997-08-01

    A rapidly deployable security system is one that provides intrusion detection, assessment, communications, and annunciation capabilities; is easy to install and configure; can be rapidly deployed, and is reusable. A rapidly deployable intrusion detection system (RADIDS) has many potential applications within the DOE Complex: back-up protection for failed zones in a perimeter intrusion detection and assessment system, intrusion detection and assessment capabilities in temporary locations, protection of assets during Complex reconfiguration, and protection in hazardous locations, protection of assets during Complex reconfiguration, and protection in hazardous locations. Many DOE user-need documents have indicated an interest in a rapidly deployable intrusion detection system. The purpose of the RADIDS project is to design, develop, and implement such a system. 2 figs.

  5. Progress and promise.

    PubMed

    Kamphaus, Randy W

    2012-12-01

    This editorial introduces the current issue of the journal School Psychology Quarterly (SPQ).There has been an impressive and promising progress of school psychology science has been reflected in every issue of SPQ, including the current one.

  6. Progressive hemifacial atrophy

    PubMed Central

    Sande, Abhijeet; Risbud, Mukund; Kshar, Avinash; Paranjpe, Arati Oka

    2013-01-01

    Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive but self-limited atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications that appear in association to this disorder are: trigeminal neuralgia, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and, it becomes stable. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology and treatment of progressive hemifacial atrophy. PMID:23878573

  7. Orion Progress - Spring 2010

    NASA Video Gallery

    NASA and contractor teams are designing, building and testing the next generation human spacecraft Orion. Progress on Orion is highlighted by employees working on the project, along with video of t...

  8. Comparison of spectacle classical progressive and office progressive lenses.

    PubMed

    Kozlík, Marek; Knollová, Libuse Nováková

    2013-04-01

    This paper elaborates on analysis of progressive spectacle lenses, to correct presbyopia, which are nowadays offered at the market. The paper describes different types of progressive lenses, their parameters, length and width of their progressive segments. It also describes degressive spectacles lenses--progressive lenses on middle and near distance. The main part of the paper is a comparison of functional differences among different types of progressive spectacles lenses. The paper also addresses correctness of choice of progressive lenses for different works and professions. Lastly, it elaborates on differences of centration of different types of progressive lenses and parameters for correct choice of glasses frame for progressive spectacles lenses. PMID:23837232

  9. [Progressive visual agnosia].

    PubMed

    Sugimoto, Azusa; Futamura, Akinori; Kawamura, Mitsuru

    2011-10-01

    Progressive visual agnosia was discovered in the 20th century following the discovery of classical non-progressive visual agnosia. In contrast to the classical type, which is caused by cerebral vascular disease or traumatic injury, progressive visual agnosia is a symptom of neurological degeneration. The condition of progressive visual loss, including visual agnosia, and posterior cerebral atrophy was named posterior cortical atrophy (PCA) by Benson et al. (1988). Progressive visual agnosia is also observed in semantic dementia (SD) and other degenerative diseases, but there is a difference in the subtype of visual agnosia associated with these diseases. Lissauer (1890) classified visual agnosia into apperceptive and associative types, and it in most cases, PCA is associated with the apperceptive type. However, SD patients exhibit symptoms of associative visual agnosia before changing to those of semantic memory disorder. Insights into progressive visual agnosia have helped us understand the visual system and discover how we "perceive" the outer world neuronally, with regard to consciousness. Although PCA is a type of atypical dementia, its diagnosis is important to enable patients to live better lives with appropriate functional support.

  10. The fabrication of rapidly solidified high temperature aluminum alloys

    NASA Astrophysics Data System (ADS)

    Gilman, P. S.; Rateick, R. G.; Testa, A.

    The application of rapid solidification/powder metallurgy processing to metallic materials has led to a series of rapidly solidified aluminum-iron-vanadium-silicon alloys which combine a balanced set of elevated temperature strengths and ambient temperature properties critical for aerospace use. The rapidly solidified Al-Fe-V-Si alloys are finding widespread interest throughout the aerospace community. However, to be fully utilized the high temperature Al-Fe-V-Si alloys must be amendable to traditional metalworking, machining and finishing operations. Powder metallurgy derived high performance alloys at times have proven difficult to fabricate. Recent progress in the fabrication of the high temperature Al-Fe-V-Si alloys into desirable product forms will be discussed, for example the production of thin foils and spun metal components. The effects of various fabrication sequences on material properties will be described.

  11. Nanomaterial-enabled Rapid Detection of Water Contaminants.

    PubMed

    Mao, Shun; Chang, Jingbo; Zhou, Guihua; Chen, Junhong

    2015-10-28

    Water contaminants, e.g., inorganic chemicals and microorganisms, are critical metrics for water quality monitoring and have significant impacts on human health and plants/organisms living in water. The scope and focus of this review is nanomaterial-based optical, electronic, and electrochemical sensors for rapid detection of water contaminants, e.g., heavy metals, anions, and bacteria. These contaminants are commonly found in different water systems. The importance of water quality monitoring and control demands significant advancement in the detection of contaminants in water because current sensing technologies for water contaminants have limitations. The advantages of nanomaterial-based sensing technologies are highlighted and recent progress on nanomaterial-based sensors for rapid water contaminant detection is discussed. An outlook for future research into this rapidly growing field is also provided.

  12. Air quality progress in North American megacities: A review

    NASA Astrophysics Data System (ADS)

    Parrish, David D.; Singh, Hanwant B.; Molina, Luisa; Madronich, Sasha

    2011-12-01

    Air quality progress in the North American megacities of Los Angeles, New York, and Mexico City is reviewed, compared, and contrasted. Enormous progress made in North America over the last 5 decades provides a template for other megacities of the world, especially in developing countries, attempting to achieve rapid economic growth without compromising air quality. While the progress to date has been impressive, many challenges remain including the need to improve air quality while simultaneously mitigating climate change. The impact of pollutant emissions from megacities is felt long distances away from the local sources but no policy mechanisms currently exist to mitigate air quality impacts resulting from such pollution transport.

  13. Rapid extracellular acidification induced by glucose metabolism in non-proliferating cells of Serratia marcescens.

    PubMed

    Solé, M; Rius, N; Lorén, J G

    2000-03-01

    The addition of glucose or other sugars to resting cells of Serratia maurcescens induced rapid acidification of the extracellular medium. This acidification was due to the catabolism of sugars. The rate of acidification depended on the carbon source and its concentration. HPLC analysis of the supernatants demonstrated that the progressive fall in pH resulted from the rapid production of lactic, acetic, pyruvic and citric acids. Other microorganisms were tested for their ability to produce this rapid acidification of the medium. This study may provide a rapid and simple method for metabolism studies.

  14. Progressive multiple sclerosis

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.

    2015-01-01

    Purpose to Review To highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS). To highlight results of clinical trial experience to date and review ongoing clinical trials and perspective new treatment options. Explain the challenges of clinical trial design in PMS. Recent Findings MS has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms. The classification of the course of PMS has been re-organized into categories of active vs. inactive inflammatory disease and the presence vs. absence of gradual disease progression. This differentiation allows clearer conceptualization of PMS and possibly even more efficient recruitment of PMS subjects into clinical trials. Clinical trial experience to date in PMS has been negative with anti-inflammatory medications used in relapsing MS. Simvastatin was recently tested in a phase II trial and showed a 43% reduction on annualized atrophy progression in secondary progressive MS. Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod, and anti-B-cell therapy ocrelizumab. Several efforts for development of outcome measures in PMS are ongoing. Summary PMS represents a significant challenge, as the pathogenesis of the disease is not well understood, no validated outcome metrics have been established, and clinical trial experience to date has been disappointing. Advances in the understanding of the disease and lessons learned in previous clinical trials are paving the way for successful development of disease modifying agents for this disease. PMID:25887766

  15. A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells

    PubMed Central

    1995-01-01

    Necrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. Gp130 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti- gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in approximately 90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PR3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a

  16. Water Resources of Rapides Parish

    USGS Publications Warehouse

    Griffith, J.M.

    2009-01-01

    Rapides Parish, located in central Louisiana, contains fresh groundwater and surface-water resources. In 2005, about 443 million gallons per day (Mgal/d) were withdrawn from water sources in Rapides Parish. About 92 percent (409 Mgal/d) was withdrawn from surface water, and 8 percent (34 Mgal/d) was withdrawn from groundwater. Withdrawals for power generation accounted for 91 percent (403 Mgal/d) of the total water withdrawn. Withdrawals for other uses included public supply (27 Mgal/d), irrigation (9 Mgal/d), and aquaculture (3 Mgal/d). Water withdrawals in the parish generally increased from 1960 to 1995 and decreased from 1995 to 2005. This fact sheet summarizes basic information on the water resources of Rapides Parish, La. Information on groundwater and surface-water availability, quality, development, use, and trends is based on previously published reports listed in the references section.

  17. Juvenile myopia progression, risk factors and interventions

    PubMed Central

    Myrowitz, Elliott H.

    2011-01-01

    The development and progression of early onset myopia is actively being investigated. While myopia is often considered a benign condition it should be considered a public health problem for its visual, quality of life, and economic consequences. Nearly half of the visually impaired population in the world has uncorrected refractive errors, with myopia a high percent of that group. Uncorrected visual acuity should be screened for and treated in order to improve academic performance, career opportunities and socio-economic status. Genetic and environmental factors contribute to the onset and progression of myopia. Twin studies have supported genetic factors and research continues to identify myopia genetic loci. While multiple myopia genetic loci have been identified establishing myopia as a common complex disorder, there is not yet a genetic model explaining myopia progression in populations. Environmental factors include near work, education levels, urban compared to rural location, and time spent outdoors. In this field of study where there continues to be etiology controversies, there is recent agreement that children who spend more time outdoors are less likely to become myopic. Worldwide population studies, some completed and some in progress, with a common protocol are gathering both genetic and environmental cohort data of great value. There have been rapid population changes in prevalence rates supporting an environmental influence. Interventions to prevent juvenile myopia progression include pharmacologic agents, glasses and contact lenses. Pharmacological interventions over 1–2 year trials have shown benefits. Peripheral vision defocus has been found to affect the emmetropization process and may be affected by wearing glasses or contacts. Accommodation accuracy also has been implicated in myopia progression. Further research will aim to assess both the role and interaction of environmental influences and genetic factors. PMID:23961008

  18. Saccharomycotina and Taphrinomycotina – progress in circumscription of genera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Much progress has been made in understanding relationships among the yeasts. DNA barcoding (D1/D2, ITS) has provided a rapid means for species identification and phylogenetic analysis of gene sequences has shown that the Ascomycota is comprised of three major lineages, i.e, Saccharomycotina (buddin...

  19. Immune Inflammation and Disease Progression in Idiopathic Pulmonary Fibrosis.

    PubMed

    Balestro, Elisabetta; Calabrese, Fiorella; Turato, Graziella; Lunardi, Francesca; Bazzan, Erica; Marulli, Giuseppe; Biondini, Davide; Rossi, Emanuela; Sanduzzi, Alessandro; Rea, Federico; Rigobello, Chiara; Gregori, Dario; Baraldo, Simonetta; Spagnolo, Paolo; Cosio, Manuel G; Saetta, Marina

    2016-01-01

    The clinical course in idiopathic pulmonary fibrosis (IPF) is highly heterogeneous, with some patients having a slow progression and others an accelerated clinical and functional decline. This study aims to clinically characterize the type of progression in IPF and to investigate the pathological basis that might account for the observed differences in disease behavior. Clinical and functional data were analyzed in 73 IPF patients, followed long-time as candidates for lung transplantation. The forced vital capacity (FVC) change/year (< or ≥10% predicted) was used to define "slow" or "rapid" disease progression. Pathological abnormalities were quantified in the explanted lung of 41 out of 73 patients undergoing lung transplantation. At diagnosis, slow progressors (n = 48) showed longer duration of symptoms and lower FVC than rapid progressors (n = 25). Eleven slow and 3 rapid progressors developed an acute exacerbation (AE) during follow-up. Quantitative lung pathology showed a severe innate and adaptive inflammatory infiltrate in rapid progressors, markedly increased compared to slow progressors and similar to that observed in patients experiencing AE. The extent of inflammation was correlated with the yearly FVC decline (r = 0.52, p = 0.005). In conclusion an innate and adaptive inflammation appears to be a prominent feature in the lung of patients with IPF and could contribute to determining of the rate of disease progression. PMID:27159038

  20. Progress in molecular precursors for electronic materials

    SciTech Connect

    Buhro, W.E.

    1996-09-01

    Molecular-precursor chemistry provides an essential underpinning to all electronic-materials technologies, including photovoltaics and related areas of direct interest to the DOE. Materials synthesis and processing is a rapidly developing field in which advances in molecular precursors are playing a major role. This article surveys selected recent research examples that define the exciting current directions in molecular-precursor science. These directions include growth of increasingly complex structures and stoichiometries, surface-selective growth, kinetic growth of metastable materials, growth of size-controlled quantum dots and quantum-dot arrays, and growth at progressively lower temperatures. Continued progress in molecular-precursor chemistry will afford precise control over the crystal structures, nanostructures, and microstructures of electronic materials.

  1. Pesticide reregistration progress report

    SciTech Connect

    Not Available

    1993-01-01

    The report is produced by the Special Review and Reregistration Division (SRRD), Office of Pesticide Programs, U.S. Environmental Protection Agency (EPA), on progress towards pesticide reregistration as mandated under 1988 amendments to the Federal Insecticide, Fungicide, and Rodenticide Act. The report shows the status of reregistration through the first quarter of the 1993 fiscal year. SRRD is in the process of re-evaluating the format and information in the Progress Report, as a result of the October 1992 Customer Survey sent to the recipients of the report. Results of the survey will be incorporated in the April 1993 issue of the report.

  2. Summary of progress in inertial confinement fusion

    SciTech Connect

    Younger, S.M.

    1992-01-01

    Progress in inertial confinement fusion (ICF) has been very rapid over the past two years. Significant advances have been made in the production of smooth laser beams, the focusing of light ions beams, and the development of heavy ion accelerators. The availability of advanced target diagnostics on several major drivers has resulted in an extensive database of target performance over a wide range of conditions. Theoretical models of ICF targets are approaching the predictive level with two and even three dimensional calculations becoming routine. Within the next several years information should be available to allow confident extrapolation to ignition on the next generation driver.

  3. Summary of progress in inertial confinement fusion

    SciTech Connect

    Younger, S.M.

    1992-12-31

    Progress in inertial confinement fusion (ICF) has been very rapid over the past two years. Significant advances have been made in the production of smooth laser beams, the focusing of light ions beams, and the development of heavy ion accelerators. The availability of advanced target diagnostics on several major drivers has resulted in an extensive database of target performance over a wide range of conditions. Theoretical models of ICF targets are approaching the predictive level with two and even three dimensional calculations becoming routine. Within the next several years information should be available to allow confident extrapolation to ignition on the next generation driver.

  4. Progress in ISOL target ion source systems

    NASA Astrophysics Data System (ADS)

    Köster, U.; Arndt, O.; Bouquerel, E.; Fedoseyev, V. N.; Frånberg, H.; Joinet, A.; Jost, C.; Kerkines, I. S. K.; Kirchner, R.; Targisol Collaboration

    2008-10-01

    The heart of every ISOL (isotope separation on-line) facility is its target and ion source system. Its efficiency, selectivity and rapidity is decisive for the production of intense and pure ion beams of short-lived isotopes. Recent progress in ISOL target and ion source technology is discussed at the examples of radioactive ion beams of exotic zinc and tin isotopes that were purified by isothermal chromatography and molecular sideband separation respectively. An outlook is given to which other elements these purification methods are applicable.

  5. Geothermal Progress Monitor: Report No. 14

    SciTech Connect

    Not Available

    1992-12-01

    This issue of the Geothermal Progress Monitor, the 14th since its inception in 1980, highlights the anticipated rapid growth in the use of geothermal heat pumps and documents the continued growth in the use of geothermal energy for power generation, both in this country and abroad. In countries with a relatively large demand for new generation capacity, geothermal, if available, is being called on as a preferable alternative to the use of domestic or imported oil. On the other hand, in this country where current demand for new capacity is less, geothermal energy is commonly being put to use in small power generation units operating on the hot water resource.

  6. Knowledge Exchange Within the Rapid Climate Change Program (RAPID)

    NASA Astrophysics Data System (ADS)

    Wallace, C.; Srokosz, M.

    2008-12-01

    The Rapid Climate Change Program (RAPID) is a major UK-led science program investigating the susceptibility to and risk of abrupt change in the climate system, with a particular focus on the role of the Atlantic Meridional Overturning Circulation (AMOC). RAPID commenced in 2001, with initial funding to 2008 and has just entered its second phase - RAPID-WATCH - extending some aspects of the program until 2014. Scientifically, a key focus of the program has concerned the development and deployment of a continuous AMOC observing system, although the program has also supported research into a number of other aspects of rapid climate change, including paleo studies of past rapid changes, modeling of the past and future climate, and the development of methods with which to aid the quantification of future risks. Given the societal implications that abrupt climate change associated with the AMOC may have for the North Atlantic region, a major focus within the program has been the implementation of a Knowledge Exchange strategy with which to engage key decision and policy makers within the UK political and industrial sectors. This interaction is especially pertinent for those decision makers involved in the development of adaptive capacities that must incorporate resilience to so-called high-impact, low-probability class threats. We will summarize here the main aspects of our approach, outlining activities/methods used both to satisfy the obvious need to transfer key scientific findings from the program to users, but also in facilitating a return flow of knowledge which can be used by scientists to refine the impact and utility of scientific output. We will draw on particular experience gained from the program's involvement in i: personnel exchanges with central government departments; ii: interaction and co-operation with third party stakeholder organizations (e.g. the UK Climate Impacts Program); and iii: provision of written and oral briefings. Throughout, techniques

  7. Evolution of rapid nerve conduction.

    PubMed

    Castelfranco, Ann M; Hartline, Daniel K

    2016-06-15

    Rapid conduction of nerve impulses is a priority for organisms needing to react quickly to events in their environment. While myelin may be viewed as the crowning innovation bringing about rapid conduction, the evolution of rapid communication mechanisms, including those refined and enhanced in the evolution of myelin, has much deeper roots. In this review, a sequence is traced starting with diffusional communication, followed by transport-facilitated communication, the rise of electrical signaling modalities, the invention of voltage-gated channels and "all-or-none" impulses, the emergence of elongate nerve axons specialized for communication and their fine-tuning to enhance impulse conduction speeds. Finally within the evolution of myelin itself, several innovations have arisen and have been interactively refined for speed enhancement, including the addition and sealing of layers, their limitation by space availability, and the optimization of key parameters: channel density, lengths of exposed nodes and lengths of internodes. We finish by suggesting several design principles that appear to govern the evolution of rapid conduction. This article is part of a Special Issue entitled SI: Myelin Evolution.

  8. Rapid-Equilibrium Enzyme Kinetics

    ERIC Educational Resources Information Center

    Alberty, Robert A.

    2008-01-01

    Rapid-equilibrium rate equations for enzyme-catalyzed reactions are especially useful because if experimental data can be fit by these simpler rate equations, the Michaelis constants can be interpreted as equilibrium constants. However, for some reactions it is necessary to use the more complicated steady-state rate equations. Thermodynamics is…

  9. Rapid Prototyping Enters Mainstream Manufacturing.

    ERIC Educational Resources Information Center

    Winek, Gary

    1996-01-01

    Explains rapid prototyping, a process that uses computer-assisted design files to create a three-dimensional object automatically, speeding the industrial design process. Five commercially available systems and two emerging types--the 3-D printing process and repetitive masking and depositing--are described. (SK)

  10. Rapidly Deployed Modular Telemetry System

    NASA Technical Reports Server (NTRS)

    Varnavas, Kosta A. (Inventor); Sims, William Herbert, III (Inventor)

    2013-01-01

    The present invention is a telemetry system, and more specifically is a rapidly deployed modular telemetry apparatus which utilizes of SDR technology and the FPGA programming capability to reduce the number of hardware components and programming required to deploy a telemetry system.

  11. [Progress in proteogenomics of prokaryotes].

    PubMed

    Zhang, Chengpu; Xu, Ping; Zhu, Yunping

    2014-07-01

    With the rapid development of genome sequencing technologies, a large amount of prokaryote genomes have been sequenced in recent years. To further investigate the models and functions of genomes, the algorithms for genome annotations based on the sequence and homology features have been widely implemented to newly sequenced genomes. However, gene annotations only using the genomic information are prone to errors, such as the incorrect N-terminals and pseudogenes. It is even harder to provide reasonable annotating results in the case of the poor genome sequencing results. The transcriptomics based on the technologies such as microarray and RNA-seq and the proteomics based on the MS/MS have been used widely to identify the gene products with high throughput and high sensitivity, providing the powerful tools for the verification and correction of annotated genome. Compared with transcriptomics, proteomics can generate the protein list for the expressed genes in the samples or cells without any confusion of the non-coding RNA, leading the proteogenomics an important basis for the genome annotations in prokaryotes. In this paper, we first described the traditional genome annotation algorithms and pointed out the shortcomings. Then we summarized the advantages of proteomics in the genome annotations and reviewed the progress of proteogenomics in prokaryotes. Finally we discussed the challenges and strategies in the data analyses and potential solutions for the developments of proteogenomics.

  12. Stillbirths: progress and unfinished business.

    PubMed

    Frøen, J Frederik; Friberg, Ingrid K; Lawn, Joy E; Bhutta, Zulfiqar A; Pattinson, Robert C; Allanson, Emma R; Flenady, Vicki; McClure, Elizabeth M; Franco, Lynne; Goldenberg, Robert L; Kinney, Mary V; Leisher, Susannah Hopkins; Pitt, Catherine; Islam, Monir; Khera, Ajay; Dhaliwal, Lakhbir; Aggarwal, Neelam; Raina, Neena; Temmerman, Marleen

    2016-02-01

    This first paper of the Lancet Series on ending preventable stillbirths reviews progress in essential areas, identified in the 2011 call to action for stillbirth prevention, to inform the integrated post-2015 agenda for maternal and newborn health. Worldwide attention to babies who die in stillbirth is rapidly increasing, from integration within the new Global Strategy for Women's, Children's and Adolescents' Health, to country policies inspired by the Every Newborn Action Plan. Supportive new guidance and metrics including stillbirth as a core health indicator and measure of quality of care are emerging. Prenatal health is a crucial biological foundation to life-long health. A key priority is to integrate action for prenatal health within the continuum of care for maternal and newborn health. Still, specific actions for stillbirths are needed for advocacy, policy formulation, monitoring, and research, including improvement in the dearth of data for effective coverage of proven interventions for prenatal survival. Strong leadership is needed worldwide and in countries. Institutions with a mandate to lead global efforts for mothers and their babies must assert their leadership to reduce stillbirths by promoting healthy and safe pregnancies.

  13. Progress on plague vaccine development.

    PubMed

    Rosenzweig, Jason A; Jejelowo, Olufisayo; Sha, Jian; Erova, Tatiana E; Brackman, Sheri M; Kirtley, Michelle L; van Lier, Cristina J; Chopra, Ashok K

    2011-07-01

    Yersinia pestis (YP), the gram-negative plague bacterium, has shaped human history unlike any other pathogen known to mankind. YP (transmitted by the bite of an infected flea) diverged only recently from the related enteric pathogen Yersinia pseudotuberculosis but causes radically different diseases. Three forms of plague exist in humans: bubonic (swollen lymph nodes or bubos), septicemic (spread of YP through the lymphatics or bloodstream from the bubos to other organs), and contagious, pneumonic plague which can be communicated via YP-charged respiratory droplets resulting in person-person transmission and rapid death if left untreated (50-90% mortality). Despite the potential threat of weaponized YP being employed in bioterrorism and YP infections remaining prevalent in endemic regions of the world where rodent populations are high (including the four corner regions of the USA), an efficacious vaccine that confers immunoprotection has yet to be developed. This review article will describe the current vaccine candidates being evaluated in various model systems and provide an overall summary on the progress of this important endeavor.

  14. Stillbirths: progress and unfinished business.

    PubMed

    Frøen, J Frederik; Friberg, Ingrid K; Lawn, Joy E; Bhutta, Zulfiqar A; Pattinson, Robert C; Allanson, Emma R; Flenady, Vicki; McClure, Elizabeth M; Franco, Lynne; Goldenberg, Robert L; Kinney, Mary V; Leisher, Susannah Hopkins; Pitt, Catherine; Islam, Monir; Khera, Ajay; Dhaliwal, Lakhbir; Aggarwal, Neelam; Raina, Neena; Temmerman, Marleen

    2016-02-01

    This first paper of the Lancet Series on ending preventable stillbirths reviews progress in essential areas, identified in the 2011 call to action for stillbirth prevention, to inform the integrated post-2015 agenda for maternal and newborn health. Worldwide attention to babies who die in stillbirth is rapidly increasing, from integration within the new Global Strategy for Women's, Children's and Adolescents' Health, to country policies inspired by the Every Newborn Action Plan. Supportive new guidance and metrics including stillbirth as a core health indicator and measure of quality of care are emerging. Prenatal health is a crucial biological foundation to life-long health. A key priority is to integrate action for prenatal health within the continuum of care for maternal and newborn health. Still, specific actions for stillbirths are needed for advocacy, policy formulation, monitoring, and research, including improvement in the dearth of data for effective coverage of proven interventions for prenatal survival. Strong leadership is needed worldwide and in countries. Institutions with a mandate to lead global efforts for mothers and their babies must assert their leadership to reduce stillbirths by promoting healthy and safe pregnancies. PMID:26794077

  15. 1992 PVUSA progress report

    SciTech Connect

    Ellyn, W.

    1992-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generating systems. This report updates the progress of the PVUSA project, reviews the status and performance of the various PV installations during 1992, and summarizes key accomplishments and conclusions from work to date.

  16. Opportunities and progress.

    PubMed

    Litchfield, John H

    2014-01-01

    In this review, I cover my professional experiences in food science and technology and related areas of applied and industrial microbiology over the span of my career. It emphasizes opportunities and technological problems that I encountered together with my progress in follow-up development of products and processes. PMID:24580071

  17. Basic Measures of Progress.

    ERIC Educational Resources Information Center

    Calkins, Julia; Ling, Thomson; Moore, Eric; Halle, Tamara; Hair, Beth; Moore, Kris; Zaslow, Marty

    This document provides a compilation of measures of progress toward school readiness and three contributing conditions as used in several local, state, and national surveys. The report begins with a legend listing the surveys examined, their acronyms, and contact information. The remainder of the report, in tabular format, lists measures of…

  18. Mystery in Progress.

    ERIC Educational Resources Information Center

    Hall, Kristen

    1989-01-01

    Describes "Mystery in Progress," a traveling exhibit which traces the development of Predynastic Egypt. The exhibit provides a time line for Predynastic Egypt, depicts the history of the Hierakonpolis expedition, documents the formation of Egypt's first centralized nation state, and summarizes the emergence of a unified Egypt. (LS)

  19. Learning Progressions & Climate Change

    ERIC Educational Resources Information Center

    Parker, Joyce M.; de los Santos, Elizabeth X.; Anderson, Charles W.

    2015-01-01

    Our society is currently having serious debates about sources of energy and global climate change. But do students (and the public) have the requisite knowledge to engage these issues as informed citizenry? The learning-progression research summarized here indicates that only 10% of high school students typically have a level of understanding…

  20. MCNP Progress & Performance Improvements

    SciTech Connect

    Brown, Forrest B.; Bull, Jeffrey S.; Rising, Michael Evan

    2015-04-14

    Twenty-eight slides give information about the work of the US DOE/NNSA Nuclear Criticality Safety Program on MCNP6 under the following headings: MCNP6.1.1 Release, with ENDF/B-VII.1; Verification/Validation; User Support & Training; Performance Improvements; and Work in Progress. Whisper methodology will be incorporated into the code, and run speed should be increased.

  1. Progressive Response Surfaces

    NASA Technical Reports Server (NTRS)

    Romero, V. J.; Swiler, L. P.

    2004-01-01

    Response surface functions are often used as simple and inexpensive replacements for computationally expensive computer models that simulate the behavior of a complex system over some parameter space. Progressive response surfaces are ones that are built up progressively as global information is added from new sample points in the parameter space. As the response surfaces are globally upgraded based on new information, heuristic indications of the convergence of the response surface approximation to the exact (fitted) function can be inferred. Sampling points can be incrementally added in a structured fashion, or in an unstructured fashion. Whatever the approach, at least in early stages of sampling it is usually desirable to sample the entire parameter space uniformly. At later stages of sampling, depending on the nature of the quantity being resolved, it may be desirable to continue sampling uniformly over the entire parameter space (Progressive response surfaces), or to switch to a focusing/economizing strategy of preferentially sampling certain regions of the parameter space based on information gained in early stages of sampling (Adaptive response surfaces). Here we consider Progressive response surfaces where a balanced indication of global response over the parameter space is desired.We use a variant of Moving Least Squares to fit and interpolate structured and unstructured point sets over the parameter space. On a 2-D test problem we compare response surface accuracy for three incremental sampling methods: Progressive Lattice Sampling; Simple-Random Monte Carlo; and Halton Quasi-Monte-Carlo sequences. We are ultimately after a system for constructing efficiently upgradable response surface approximations with reliable error estimates.

  2. When Less Is More in Cognitive Diagnosis: A Rapid Online Method for Diagnosing Learner Task-Specific Expertise

    ERIC Educational Resources Information Center

    Kalyuga, Slava

    2008-01-01

    Rapid cognitive diagnosis allows measuring current levels of learner domain-specific knowledge in online learning environments. Such measures are required for individualizing instructional support in real time, as students progress through a learning session. This article describes 2 experiments designed to validate a rapid online diagnostic…

  3. Urine synaptopodin excretion is an important marker of glomerular disease progression

    PubMed Central

    Kwon, Soon Kil; Kim, Seung Jung; Kim, Hye-Young

    2016-01-01

    Background/Aims: Podocytes play an important role in maintaining the glomerular filtration barrier and in formation of the slit diaphragm. Podocyte loss is associated with chronic kidney disease progression, but it is not clear whether urinary podocyte proteins in urine reflect the clinical extent of glomerular damage. We investigated the correlation between the amounts of urinary podocyte proteins and renal function and albuminuria. Methods: The study enrolled 33 patients with diabetic kidney disease or glomerular disease and measured urinary podocytes proteins using Western blotting. Urinary podocyte proteins were measured according to the density of the bands on Western blotting. We measured serum creatinine and the spot urine albumin/creatinine ratio as markers of renal damage, and compared the correlation of urinary podocyte protein in the glomerular disease patients. Results: The mean patient age was 49.3 ± 16.5 years, the mean serum creatinine level was 2.30 ± 1.76 mg/dL, and the mean albumin/creatinine ratio was 4.85 ± 3.52. Among the podocyte proteins, urine synaptopodin showed strong correlation with serum creatinine by multivariate regression analysis (p < 0.001) and showed linear correlation (r = 0.429, p < 0.01). Urine podocyte proteins were increased in patients with diabetes, and synaptopodin showed the greatest significant difference (7.68 ± 5.61 vs. 2.56 ± 3.11, p < 0.001), but this might be associated with renal impairment. The urine albumin excretion did not differ between the diabetics and non-diabetics (p = 0.73). Conclusions: Urine synaptopodin is associated with serum creatinine elevation in the patients with glomerulonephritis including diabetic kidney disease regardless of urine albumin excretion. We suggest that the urine synaptopodin level can predict glomerular damage independently of the urine albumin excretion. PMID:27604800

  4. A Rapid Turnaround Cryogenic Detector Characterization System

    NASA Technical Reports Server (NTRS)

    Benford, Dominic j.; Dipirro, Michael J.; Forgione, Joshua B.; Jackson, Clifton E.; Jackson, Michael L.; Kogut, Al; Moseley, S. Harvey; Shirron, Peter J.

    2004-01-01

    Upcoming major NASA missions such as the Einstein Inflation Probe and the Single Aperture Far-Infrared Observatory require arrays of detectors with thousands of elements, operating at temperatures near l00 mK and sensitive to wavelengths from approx. 100 microns to approx. 3 mm. Such detectors represent a substantial enabling technology for these missions, and must be demonstrated soon in order for them to proceed. In order to make rapid progress on detector development, the cryogenic testing cycle must be made convenient and quick. We have developed a cryogenic detector characterization system capable of testing superconducting detector arrays in formats up to 8 x 32, read out by SQUID multiplexers. The system relies on the cooling of a two-stage adiabatic demagnetization refrigerator immersed in a liquid helium bath. This approach permits a detector to be cooled from 300K to 50 mK in about 4 hours, so that a test cycle begun in the morning will be over by the end of the day. Tine system is modular, with two identical immersible units, so that while one unit is cooling, the second can be reconfigured for the next battery of tests. We describe the design, construction, and performance of this cryogenic detector testing facility.

  5. Adaptive spectroscopy for rapid chemical identification

    NASA Astrophysics Data System (ADS)

    Dinakarababu, Dineshbabu V.; Gehm, Michael E.

    2009-05-01

    Spectroscopic chemical identification is fundamentally a classification task where sensor measurements are compared to a library of known compounds with the hope of determining an unambiguous match. When the measurement signal-to-noise ratio (SNR) is very low (e.g. from short exposure times, weak analyte signatures, etc.), classification can become very challenging, requiring a multiple-measurement framework such as sequential hypothesis testing, and dramatically extending the time required to classify the sample. There are a wide variety of defense, security, and medical applications where rapid identification is essential, and hence such delays are disastrous. In this paper, we discuss an approach for adaptive spectroscopic detection where the introduction of a tunable spectral filter enables the system to measure the projection of the sample spectrum along arbitrary bases in the spectral domain. The net effect is a significant reduction in time-to-decision in low SNR cases. We describe the general operation of such an instrument, present results from initial simulations, and report on our experimental progress.

  6. Using the Synergy Model to guide the practice of rapid response teams.

    PubMed

    Arashin, Kelly A

    2010-01-01

    The goals of Rapid Response Teams are to provide interventional care upon recognizing a clinical change in a patient's condition and to prevent further progression of declining health. There are many clinical situations in which the critical care nurse or advanced practice nurse can apply the Synergy Model to patient care. Understanding how the Synergy Model can guide the Rapid Response Team interventions and practice by identifying and matching patient and nurse characteristics can possibly achieve improved patient outcomes.

  7. Rapid hydropyrolysis of resid oil

    SciTech Connect

    Mathur, V.K.; Salahuddin, M.A.; Mohamed, A.R.

    1994-12-31

    The objective of this investigation was to study the rapid hydropyrolysis of Arabian Light atmospheric resid oil and vacuum resid oil for the production of light distillates. The results of this study have been divided into the effect of exposure time, temperature, and gaseous atmosphere. The heat flux used was in the range of 70 to about 97 watt/cm{sup 2}. The results from ASTM simulated distillation of the hydrogenated oil obtained at various experimental conditions are also presented.

  8. Rapid synthesis of beta zeolites

    SciTech Connect

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  9. Rapid demineralization in acidic buffers.

    PubMed

    Eggert, F M; Germain, J P

    1979-01-22

    The demineralization of routine histological specimens in buffers of weakly ionized organic acids, unbuffered formic acid, and EDTA was investigated. The rate of demineralization was measured by a chemical method and from radiographs. Lactate-containing buffers and buffers of formic acid with its potassium salt were more rapid in effect than any other agent. Acidic buffers and unbuffered formic acid produced rapid diffuse demineralization with secondary precipitation of calcium salts. Preservation of dental enamel in such buffers resulted from the significantly slower rate of enamel demineralization than that for bone and dentine. In rapid demineralizing agents the secondary salts were quickly redissolved while in slow buffers these salts persisted. Multivalent ions such as citrate and maleate slowed the rate of demineralization, and a citrate-containing buffer was the slowest of all the agents tested. Demineralization in EDTA exhibited a different pattern with the establishment of a well-defined front of demineralization without apparent reprecipitation. EDTA attacked enamel, bone and dentine at the same rate. An attempt was made to relate the observed rates of demineralization to current theories of the demineralization process.

  10. Progressive cone dystrophy.

    PubMed Central

    Ripps, H; Noble, K G; Greenstein, V C; Siegel, I M; Carr, R E

    1987-01-01

    Psychophysical, reflectometric, and electrophysiological studies were performed on four members of a dominant pedigree with progressive cone dystrophy. The two youngest individuals were asymptomatic at the initial examination, and none of the subjects complained of problems associated with night vision. Absent or grossly reduced cone-mediated ERG responses revealed the widespread loss of cone function. Moderate elevations (1 log unit) in absolute threshold together with reductions in rhodopsin levels in the midperipheral retina provided evidence of a mild impairment of the rod system also, although not to the degree seen in a cone-rod dystrophy. The progressive nature of the disease was apparent from the case histories and the changes in visual performance that occurred on re-test after a 5-year interval. Likewise, the results of incremental threshold measurements at several retinal loci suggested that peripheral cones may be affected earlier and more severely than those in the central retina. PMID:3502298

  11. Progressive compressive imager

    NASA Astrophysics Data System (ADS)

    Evladov, Sergei; Levi, Ofer; Stern, Adrian

    2012-06-01

    We have designed and built a working automatic progressive sampling imaging system based on the vector sensor concept, which utilizes a unique sampling scheme of Radon projections. This sampling scheme makes it possible to progressively add information resulting in tradeoff between compression and the quality of reconstruction. The uniqueness of our sampling is that in any moment of the acquisition process the reconstruction can produce a reasonable version of the image. The advantage of the gradual addition of the samples is seen when the sparsity rate of the object is unknown, and thus the number of needed measurements. We have developed the iterative algorithm OSO (Ordered Sets Optimization) which employs our sampling scheme for creation of nearly uniform distributed sets of samples, which allows the reconstruction of Mega-Pixel images. We present the good quality reconstruction from compressed data ratios of 1:20.

  12. Progress in Scientific Visualization

    SciTech Connect

    Max, N

    2004-11-15

    Visualization of observed data or simulation output is important to science and engineering. I have been particularly interested in visualizing 3-D structures, and report here my personal impressions on progress in the last 20 years in visualizing molecules, scalar fields, and vector fields and their associated flows. I have tried to keep the survey and list of references manageable, so apologize to those authors whose techniques I have not mentioned, or have described without a reference citation.

  13. COSMIC monthly progress report

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Activities of the Computer Software Management and Information Center (COSMIC) are summarized for the month of January 1994. Tables showing the current inventory of programs available from COSMIC are presented and program processing and evaluation activities are discussed. Marketing and customer service activities in this period are presented as is the progress report of NASTRAN maintenance and support. Tables of disseminations and budget summary conclude the report.

  14. ISABELLE: a progress report

    SciTech Connect

    Hahn, H

    1980-01-01

    This paper discusses the ISABELLE project, which has the objective of constructing a high-energy proton colliding beam facility at Brookhaven National Laboratory. The major technical features of the intersecting storage accelerators with their projected performance are described. Application of over 1000 superconducting magnets in the two rings represents the salient characteristic of the machine. The status of the entire project, the technical progress made so far, and difficulties encountered are reviewed.

  15. Progression of myopia.

    PubMed Central

    Kennedy, R H

    1995-01-01

    BACKGROUND: Myopia is an important public health problem because it is common and is associated with increased risk for chorioretinal degeneration, retinal detachment, and other vision-threatening abnormalities. In animals, ocular elongation and myopia progression can be lessened with atropine treatment. This study provides information about progression of myopia and atropine therapy for myopia in humans. METHODS: A total of 214 residents of Olmsted County, Minnesota (118 girls and 96 boys; median age, 11 years; range, 6 to 15 years) received atropine for myopia from 1967 through 1974. Control subjects were matched by age, sex, refractive error, and date of baseline examination to 194 of those receiving atropine. Duration of treatment with atropine ranged from 18 weeks to 11.5 years (median 3.5 years). RESULTS: Median follow-up from initial to last refraction in the atropine group (11.7 years) was similar to that in the control group (12.4 years). Photophobia and blurred vision were frequently reported, but no serious adverse effects were associated with atropine therapy. Mean myopia progression during atropine treatment adjusted for age and refractive error (0.05 diopters per year) was significantly less than that among control subjects (0.36 diopters per year) (P < .001). Final refractions standardized to the age of 20 years showed a greater mean level of myopia in the control group (3.78 diopters) than in the atropine group (2.79 diopters) (P < .001). CONCLUSIONS: The data support the view that atropine therapy is associated with decreased progression of myopia and that beneficial effects remain after treatment has been discontinued. PMID:8719698

  16. In Transition: Primate Genomics at a Time of Rapid Change

    PubMed Central

    Rogers, Jeffrey

    2013-01-01

    The field of nonhuman primate genomics is undergoing rapid change and making impressive progress. Exploiting new technologies for DNA sequencing, researchers have generated new whole-genome sequence assemblies for multiple primate species over the past 6 years. In addition, investigations of within-species genetic variation, gene expression and RNA sequences, conservation of non-protein-coding regions of the genome, and other aspects of comparative genomics are moving at an accelerating speed. This progress is opening a wide array of new research opportunities in the analysis of comparative primate genome content and evolution. It also creates new possibilities for the use of nonhuman primates as model organisms in biomedical research. This transition, based on both new technology and the new information being generated in regard to human genetics, provides an important justification for reevaluating the research goals, strategies, and study designs used in primate genetics and genomics. PMID:24174444

  17. Primary-Progressive MS (PPMS)

    MedlinePlus

    ... MS? Types of MS Primary progressive MS (PPMS) Primary progressive MS (PPMS) Share Smaller Text Larger Text Print In this article Overview PPMS is characterized by worsening neurologic function ( ...

  18. Rapid cognitive decline: not always Creutzfeldt-Jakob disease.

    PubMed

    Randall, A; Ellis, R; Hywel, B; Davies, R R; Alusi, S H; Larner, A J

    2015-01-01

    A patient with rapidly progressive cognitive decline over an approximately four month period was suspected to have sporadic Creutzfeldt-Jakob disease. Features thought to support this diagnosis included psychiatric symptoms (anxiety and depression), visual hallucinations and a visual field defect. However, the finding of papilloedema broadened the differential diagnosis. Although standard brain imaging and electroencephalography had shown only non-specific abnormalities, subsequent cerebral angiography disclosed an intracranial dural arteriovenous fistula. Following embolisation, the patient made a good functional recovery. Intracranial dural arteriovenous fistula merits consideration in any patient with subacute cognitive decline, and should be included in the differential diagnosis of sporadic Creutzfeldt-Jakob disease. PMID:26517100

  19. Rapid Thermal Processing (RTP) of semiconductors in space

    NASA Technical Reports Server (NTRS)

    Anderson, T. J.; Jones, K. S.

    1993-01-01

    The progress achieved on the project entitled 'Rapid Thermal Processing of Semiconductors in Space' for a 12 month period of activity ending March 31, 1993 is summarized. The activity of this group is being performed under the direct auspices of the ROMPS program. The main objective of this program is to develop and demonstrate the use of advanced robotics in space with rapid thermal process (RTP) of semiconductors providing the test technology. Rapid thermal processing is an ideal processing step for demonstration purposes since it encompasses many of the characteristics of other processes used in solid state device manufacturing. Furthermore, a low thermal budget is becoming more important in existing manufacturing practice, while a low thermal budget is critical to successful processing in space. A secondary objective of this project is to determine the influence of microgravity on the rapid thermal process for a variety of operating modes. In many instances, this involves one or more fluid phases. The advancement of microgravity processing science is an important ancillary objective.

  20. Rapid diagnosis of pulmonary tuberculosis

    PubMed Central

    Sarmiento, José Mauricio Hernández; Restrepo, Natalia Builes; Mejía, Gloria Isabel; Zapata, Elsa; Restrepo, Mary Alejandra; Robledo, Jaime

    2014-01-01

    Introduction World Health Organization had estimated 9.4 million tuberculosis cases on 2009, with 1.7 million of deaths as consequence of treatment and diagnosis failures. Improving diagnostic methods for the rapid and timely detection of tuberculosis patients is critical to control the disease. The aim of this study was evaluating the accuracy of the cord factor detection on the solid medium Middlebrook 7H11 thin layer agar compared to the Lowenstein Jensen medium for the rapid tuberculosis diagnosis. Methods Patients with suspected tuberculosis were enrolled and their sputum samples were processed for direct smear and culture on Lowenstein Jensen and BACTEC MGIT 960, from which positive tubes were subcultured on Middlebrook 7H11 thin layer agar. Statistical analysis was performed comparing culture results from Lowenstein Jensen and the thin layer agar, and their corresponding average times for detecting Mycobacterium tuberculosis. The performance of cord factor detection was evaluated determining its sensitivity, specificity, positive and negative predictive value. Results 111 out of 260 patients were positive for M. tuberculosis by Lowenstein Jensen medium with an average time ± standard deviation for its detection of 22.3 ± 8.5 days. 115 patients were positive by the MGIT system identifying the cord factor by the Middlebrook 7H11 thin layer agar which average time ± standard deviation was 5.5 ± 2.6 days. Conclusion The cord factor detection by Middlebrook 7H11 thin layer agar allows early and accurate tuberculosis diagnosis during an average time of 5 days, making this rapid diagnosis particularly important in patients with negative sputum smear. PMID:25419279