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Sample records for focal bacterial nephritis

  1. Radionuclide scintigraphy of bacterial nephritis

    SciTech Connect

    Conway, J.J.; Weiss, S.C.; Shkolnik, A.; Yogev, R.; Firlit, C.; Traisman, E.S.

    1984-01-01

    Pyelonephritis is a leading cause of renal failure and is expected to cost as much as three billion dollars in 1984. The diagnosis of urinary tract infection is usually not difficult. However, localization of the infection within the renal parenchyma as opposed to the collecting system is much more difficult. Flank pain, fever, bacteiuria and evidence of parenchymal involvement by intravenous urography may be absent or unrecognized particularly in the infant. Ultrasound and Nuclear Medicine are advocated as better methods to define parenchymal involvement. Such definition is important in the consideration of treatment since parenchymal involvement of the kidney carries a much more ominous potential outcome than infection restricted to within the collecting system. 38 children with a clinical diagnosis of urinary tract infection were studied. 26 of the patients demonstrated abnormal renal parenchymal findings with Gallium-67 Citrate or Tc-99m Glucoheptonate scintigraphy. Intravenous urography was notably ineffective with only 5 of the 20 interpreted as abnormal due to parenchymal disease or decreased function. 11 were entirely normal while only 5 demonstrated scars or hydronephrosis. Only 10 of 17 patients demonstrated intranvesicoureteral reflux on x-ray or nuclear cystography. Ultrasound depicted 6 of 20 patients as having parenchymal abnormalities. Seven were normal. Nonspecific findings such as dilitation of the renal pelvis or renal enlargement was noted in 11 of the 20 patients. Radionuclide Scintigraphy is the most efficacious modality to detect since acute bacterial nephritis.

  2. Focal Targeting of the Bacterial Envelope by Antimicrobial Peptides

    PubMed Central

    Rashid, Rafi; Veleba, Mark; Kline, Kimberly A.

    2016-01-01

    Antimicrobial peptides (AMPs) are utilized by both eukaryotic and prokaryotic organisms. AMPs such as the human beta defensins, human neutrophil peptides, human cathelicidin, and many bacterial bacteriocins are cationic and capable of binding to anionic regions of the bacterial surface. Cationic AMPs (CAMPs) target anionic lipids [e.g., phosphatidylglycerol (PG) and cardiolipins (CL)] in the cell membrane and anionic components [e.g., lipopolysaccharide (LPS) and lipoteichoic acid (LTA)] of the cell envelope. Bacteria have evolved mechanisms to modify these same targets in order to resist CAMP killing, e.g., lysinylation of PG to yield cationic lysyl-PG and alanylation of LTA. Since CAMPs offer a promising therapeutic alternative to conventional antibiotics, which are becoming less effective due to rapidly emerging antibiotic resistance, there is a strong need to improve our understanding about the AMP mechanism of action. Recent literature suggests that AMPs often interact with the bacterial cell envelope at discrete foci. Here we review recent AMP literature, with an emphasis on focal interactions with bacteria, including (1) CAMP disruption mechanisms, (2) delocalization of membrane proteins and lipids by CAMPs, and (3) CAMP sensing systems and resistance mechanisms. We conclude with new approaches for studying the bacterial membrane, e.g., lipidomics, high resolution imaging, and non-detergent-based membrane domain extraction. PMID:27376064

  3. Lupus Nephritis

    MedlinePlus

    ... can be a sign of lupus nephritis. What tests do health care professionals use to diagnose lupus nephritis? Lupus nephritis ... and blood tests and a kidney biopsy. Urine Test Your health care professional uses a urine sample to look for ...

  4. Interstitial Nephritis

    MedlinePlus

    ... was contributed by: familydoctor.org editorial staff Tags: acute tubulointerstitial nephritis, AIN, interstitial nephritis, kidney disorders, kidney failure, renal failure, renal infection Men, Seniors, Women December 2004 ...

  5. Interstitial nephritis

    MedlinePlus

    ... your risk. Alternative Names Tubulointerstitial nephritis; ... LJ. Tubulointerstitial diseases. In: Lager DJ, Abrahams NA, eds. Practical Renal Pathology . Philadelphia, PA: Elsevier Saunders; 2013:chap 7. ...

  6. Lupus nephritis

    MedlinePlus

    ... American College of Rheumatology Guidelines for Screening, Case Definition, Treatment and Management of Lupus Nephritis. Arthritis Care Res (Hoboken) . ... kidney disease Immune response Incidence ...

  7. Histopathology of lupus nephritis.

    PubMed

    Giannakakis, Konstantinos; Faraggiana, Tullio

    2011-06-01

    The spectrum of morphologic changes in lupus nephritis, either microscopic, ultrastructural, or immunohistological, closely reflects the great variety of immune complexes that are produced in the course of the disease. Every tissue component of the kidney can be affected, but glomeruli are the target structure in most patients. Several attempts have been made to correlate the clinical severity and the outcome of the nephritis with the pathologic features; the current classification and the six classes that resulted from an international study group are entirely based on glomerular changes. Major criteria of classification include the focal or diffuse involvement of the glomerulus, the site of hypercellularity, the site of immune complex deposition and the presence of active and/or sclerotic lesions. Even if less thoroughly investigated than the glomerulus, the interstitial compartment has revealed many interesting features as are vascular lesions, a common and often underestimated feature. Typing of subpopulation of lymphoid infiltrates supports the emerging evidence indicating that B cells are promoting autoimmunity in mechanisms other than autoAb secretion. Many aspects are still debated and/or poorly understood, such as the interpretation of the so-called "full house nephropathy" that closely mimic lupus nephritis in seronegative patients.

  8. Pathology of hereditary nephritis

    PubMed Central

    Joshi, V. V.

    1968-01-01

    This report describes the renal pathology in three siblings with hereditary nephritis. All three cases showed combined features of chronic glomerulonephritis, pyelonephritis, and interstitial nephritis. Foam cells were seen in only one case. These findings support the contention of Krickstein, Gloor, and Balogh (1966) that the renal changes in hereditary nephritis are those of a mixed nephritis. Images PMID:5717545

  9. [Lupus nephritis treatment].

    PubMed

    Santos-Araújo, Carla; Pestana, Manuel

    2008-01-01

    Systemic lupus erithematosus (SLE) is a multiorganic inflammatory disease characterized by a significant morbidity and mortality related not just to disease evolution but also to therapeutic side effects. Sixty percent of SLE patients develop renal disease related to lupus. Moreover, several studies report that lupus nephritis is an important predictor of both renal impairment and global mortality in these patients. In lupus nephritis, the renal biopsy still represents a cornerstone for both histological grading and therapeutical management. Several classification schemes for lupus nephritis based mainly on morphological parameters have been proposed so far. In the WHO grading system the most severe form of lupus nephritis is the diffuse proliferative lupus nephritis or lupus nephritis class IV. In fact, several authors have documented an invariable course to end stage renal failure in these patients, in the absence of specific therapy. Despite the considerable improvement observed since the introduction of corticosteroid and cyclophosphamide treatment, a significant number of patients still present an incomplete response to therapy. Moreover, even in the cases of good response to therapy adverse events related to the treatment such as infertility, hemorrhagic cystitis or increased susceptibility to infection frequently supervenes.

  10. Bacterial genotoxins promote inside-out integrin β1 activation, formation of focal adhesion complexes and cell spreading.

    PubMed

    Levi, Laura; Toyooka, Tatsushi; Patarroyo, Manuel; Frisan, Teresa

    2015-01-01

    Integrins are membrane bound receptors that regulate several cellular processes, such as cell adhesion, migration, survival and proliferation, and may contribute to tumor initiation/progression in cells exposed to genotoxic stress. The extent of integrin activation and its role in cell survival upon intoxication with bacterial genotoxins are still poorly characterized. These toxins induce DNA strand breaks in the target cells and activate the DNA damage response (DDR), coordinated by the Ataxia Telangectasia Mutated (ATM) kinase. In the present study, we demonstrate that induction of DNA damage by two bacterial genotoxins promotes activation of integrin β1, leading to enhanced assembly of focal adhesions and cell spreading on fibronectin, but not on vitronectin. This phenotype is mediated by an ATM-dependent inside-out integrin signaling, and requires the actin cytoskeleton remodeler NET1. The toxin-mediated cell spreading and anchorage-independent survival further relies on ALIX and TSG101, two components of the endosomal sorting complex required for transport (ESCRT), known to regulate integrin intracellular trafficking. These data reveal a novel aspect of the cellular response to bacterial genotoxins, and provide new tools to understand the carcinogenic potential of these effectors in the context of chronic intoxication and infection.

  11. Radiation nephritis causing nephrotic syndrome

    SciTech Connect

    Jennette, J.C.; Ordonez, N.G.

    1983-12-01

    Clinical symptoms of acute radiation nephritis with nephrotic syndrome developed in a fifty-six-year-old woman after abdominal radiation therapy for an astrocytoma of the spinal cord. The diagnosis of radiation nephritis was confirmed by renal biopsy. To our knowledge, this is the first documented case of radiation nephritis associated with nephrotic syndrome.

  12. Streptococcus mutans-induced nephritis in rabbits.

    PubMed Central

    Albini, B.; Nisengard, R. J.; Glurich, I.; Neiders, M. E.; Stinson, M. W.

    1985-01-01

    Intravenous administration of disrupted Streptococcus mutans into rabbits over 23-76 weeks led to severe nephritis involving glomeruli, tubules, and interstitium. Light-microscopic observation of glomeruli documented diffuse endocapillary proliferative glomerulonephritis accompanied often (65%) by epithelial crescents. Electron-microscopic observation revealed humps in glomeruli of 70% of kidney specimens. In the glomeruli of some rabbits, extensive fibrin deposits and sclerosis were evident. Immunofluorescence showed linear, granular, often ribbonlike or patchy immune deposits encompassing, in order of decreasing frequency, C3, IgG, streptococcal antigen, IgA, and IgM. The histopathologic and immunohistologic features of the nephritis seen in rabbits given S mutans thus shows many features of Streptococcus-associated nephritides in man, in particular, the diffuse glomerular nephritis encountered in subacute bacterial endocarditis. Further, analysis of nephritis induced by administration of S mutans may have implications for the evaluation and purification of dental caries vaccines. Images Figure 8 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 9 Figure 10 Figure 11 Figure 12 PMID:3976844

  13. Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs

    SciTech Connect

    Fischman, A.J.; Pike, M.C.; Kroon, D.; Fucello, A.J.; Rexinger, D.; ten Kate, C.; Wilkinson, R.; Rubin, R.H.; Strauss, H.W. )

    1991-03-01

    Four DTPA-derivatized chemotactic peptide analogs: ForNleLFNleYK-DTPA (P1), ForMLFNH(CH2)6NH-DTPA (P2), ForNleLFK(NH2)-DTPA (P3), and ForNleLFK-DTPA (P4), were synthesized and evaluated for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 111In by transchelation and their biodistribution determined in rats at 5, 30, 60 and 120 min after injection. Localization at sites of infection was determined by scintillation camera imaging in animals with deep-thigh infection due to Escherichia coli. Images were recorded from 5 min to 2 hr after injection. All peptides maintained biologic activity (EC50 for O2-production by human PMN's: 3-150 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMN's (EC50 for binding: 7.5-50 nM); biologic activity and receptor binding were highly correlated (r = 0.99). For all the peptides, blood clearance was rapid (half-lives: 21.5, 33.1, 31.6, and 28.7 min for P1, P2, P3, and P4, respectively). Biodistributions of the individual peptides were similar with low levels of accumulation in the heart, lung, liver, spleen, and gastrointestinal tract. In the kidney, P1 had much greater accumulation than other organs. All peptides yielded high quality images of the infection sites within 1 hr of injection. This study demonstrates that 111In-labeled chemotactic peptide analogs were effective agents for the external imaging of focal sites of infection.

  14. Karyomegalic Interstitial Nephritis

    PubMed Central

    Isnard, Pierre; Rabant, Marion; Labaye, Jacques; Antignac, Corinne; Knebelmann, Bertrand; Zaidan, Mohamad

    2016-01-01

    Abstract Karyomegalic interstitial nephritis is a rare cause of hereditary chronic interstitial nephritis, described for the first time over 40 years ago. A 36-year-old woman, of Turkish origin, presented with chronic kidney disease and high blood pressure. She had a history of recurrent upper respiratory tract infections but no familial history of nephropathy. Physical examination was unremarkable. Laboratory tests showed serum creatinine at 2.3 mg/dL with an estimated glomerular filtration rate of 26 mL/min/1.73m2, and gamma-glutamyl transpeptidase and alkaline phosphatase at 3 and 1.5 times the upper normal limit. Urinalysis showed 0.8 g/day of nonselective proteinuria, microscopic hematuria, and aseptic leukocyturia. Immunological tests and tests for human immunodeficiency and hepatitis B and C viruses were negative. Complement level and serum proteins electrophoresis were normal. Analysis of the renal biopsy showed severe interstitial fibrosis and tubular atrophy. Numerous tubular cells had nuclear enlargement with irregular outlines, hyperchromatic aspect, and prominent nucleoli. These findings were highly suggestive of karyomegalic interstitial nephritis, which was further confirmed by exome sequencing of FAN1 gene showing an identified homozygous frameshift mutation due to a one-base-pair deletion in exon 12 (c.2616delA). The present case illustrates a rare but severe cause of hereditary interstitial nephritis, sometimes accompanied by subtle extrarenal manifestations. Identification of mutations in FAN1 gene underscores recent insights linking inadequate DNA repair and susceptibility to chronic kidney disease. PMID:27196444

  15. Pregnancy and Lupus Nephritis.

    PubMed

    Kattah, Andrea G; Garovic, Vesna D

    2015-09-01

    The management of lupus nephritis in pregnancy presents a diagnostic and therapeutic challenge for providers. Pregnancy creates a series of physiologic changes in the immune system and kidney that may result in an increased risk of disease flare and adverse maternal and fetal outcomes, such as preeclampsia, fetal loss, and preterm delivery. Conception should be delayed until disease is in remission to ensure the best pregnancy outcomes. Maternal disease activity and fetal well-being should be monitored closely by an interdisciplinary team, including obstetricians, rheumatologists, and nephrologists throughout pregnancy. Careful attention must be paid to the dosing and potential teratogenicity of medications.

  16. Granulomatous interstitial nephritis

    PubMed Central

    Shah, Shivani; Carter-Monroe, Naima; Atta, Mohamed G.

    2015-01-01

    Granulomatous interstitial nephritis (GIN) is a rare entity detected in ∼0.5–0.9% of all renal biopsies. GIN has been linked to several antibiotics such as cephalosporins, vancomycin, nitrofurantoin and ciprofloxacin. It is also associated with NSAIDs and granulomatous disorders such as sarcoidosis, tuberculosis, fungal infections, and granulomatosis with polyangiitis. Renal biopsy is critical in establishing this diagnosis, and the extent of tubular atrophy and interstitial fibrosis may aid in determining prognosis. Retrospective data and clinical experience suggest that removal of the offending agent in conjunction with corticosteroid therapy often results in improvement in renal function. We describe a patient with a history of multiple spinal surgeries complicated by wound infection who presented with confusion and rash with subsequent development of acute kidney injury. Urinalysis demonstrated pyuria and eosinophiluria, and renal biopsy revealed acute interstitial nephritis with granulomas. These findings were attributed to doxycycline treatment of his wound infection. This review explores the clinical associations, presentation, diagnosis, and treatment of this uncommon cause of acute kidney injury. PMID:26413275

  17. Lupus nephritis. Clinical course as related to morphologic forms and their transitions.

    PubMed

    Baldwin, D S; Gluck, M C; Lowenstein, J; Gallo, G R

    1977-01-01

    An intensive study of the course of lupus nephritis has been undertaken in 88 patients in whom strict morphologic criteria were utilized in classification. All were treated with steroid, and 17 received cytotoxic drugs in addition. Focal proliferative lupus nephritis generally follows a benign course except in the occasional instances when transition to the diffuse proliferative or membranous forms occurs. Membranous lupus nephritis, when characterized by persistent nephrotic syndrome, leads slowly to renal failure, but this progression is aborted in the one-third in whom remission of the nephrotic syndrome can be achieved. A fatal outcome occurs within five years in the majority of those with diffuse proliferative lupus nephritis and the nephrotic syndrome, often in association with necrotizing renal vasculitis, severe hypertension and accelerated renal failure. A small number with the diffuse proliferative form have a remission and then show only mesangial abnormalities, usually, however, with the appearance of glomerular sclerosis. Progressive glomerular sclerosis is observed in some patients and may be a sequel of the remission of the diffuse or focal proliferative lesions, or it may represent still another form of lupus nephritis. Mesangial immune deposits with or without proliferation, at times in the absence of clinical renal disease, are observed early in the course of systemic lupus erythematosus (SLE) and may proceed to the diffuse proliferative or membranous forms. The present observations serve to emphasize the importance of strict morphologic classification in the comparison of different treatment regimens for lupus nephritis. In view of the grave prognosis of established diffuse proliferative lupus nephritis, which probably evolves from a mesangial involvement common to all patients with SLE from its onset, early therapy may be the key to the management of lupus nephritis.

  18. Lupus nephritis management guidelines compared.

    PubMed

    Wilhelmus, Suzanne; Bajema, Ingeborg M; Bertsias, George K; Boumpas, Dimitrios T; Gordon, Caroline; Lightstone, Liz; Tesar, Vladimir; Jayne, David R

    2016-06-01

    In the past years, many (randomized) trials have been performed comparing the treatment strategies for lupus nephritis. In 2012, these data were incorporated in six different guidelines for treating lupus nephritis. These guidelines are European, American and internationally based, with one separate guideline for children. They offer information on different aspects of the management of lupus nephritis including induction and maintenance treatment of the different histological classes, adjunctive treatment, monitoring of the patient, definitions of response and relapse, indications for (repeat) renal biopsy, and additional challenges such as the presence of vascular complications, the pregnant SLE patient, treatment in children and adolescents and considerations about end-stage renal disease and transplantation. In this review, we summarize the guidelines, determine the common ground between them, highlight the differences and discuss recent literature.

  19. Focal bacterial meningitis following ascending bite wound infection leading to paraparesis in a captive California sea lion (Zalophus californianus).

    PubMed

    Braun, Veronika; Eskens, Ulrich; Hartmann, Antje; Lang, Barbara; Kramer, Martin; Schmidt, Martin J

    2015-03-01

    Magnetic resonance imaging was performed on a 15-yr-old captive female California sea lion (Zalophus californianus) with a 2-wk history of progressive paraparesis and a 9-mo history of exudative skin lesion on the left thoracic wall. Magnetic resonance images showed a well-defined muscle infiltrating lesion ventrolateral to the seventh cervical to the third thoracic vertebra on the left side, which extended through the left intervertebral foramina C7 to T3 into the vertebral canal, causing spinal cord compression and displacement as well as inflammation of the spinal cord and nerves. This lesion surprisingly caused no forelimb deficits. Differential diagnoses included abscess formation or neoplasia. Pathologic examination revealed chronic focal purulent meningitis associated with widespread paraspinal fistulous inflammation originating from a chronic dermal ulcer. Mainly Escherichia coli var. haemolytica and Clostridium perfringens were identified as the underlying agents.

  20. The Pathogenesis of Lupus Nephritis

    PubMed Central

    Lech, Maciej

    2013-01-01

    Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

  1. The small G-protein MglA connects to the MreB actin cytoskeleton at bacterial focal adhesions

    PubMed Central

    Treuner-Lange, Anke; Macia, Eric; Guzzo, Mathilde; Hot, Edina; Faure, Laura M.; Jakobczak, Beata; Espinosa, Leon; Alcor, Damien; Ducret, Adrien; Keilberg, Daniela; Castaing, Jean Philippe; Lacas Gervais, Sandra; Franco, Michel

    2015-01-01

    In Myxococcus xanthus the gliding motility machinery is assembled at the leading cell pole to form focal adhesions, translocated rearward to propel the cell, and disassembled at the lagging pole. We show that MglA, a Ras-like small G-protein, is an integral part of this machinery. In this function, MglA stimulates the assembly of the motility complex by directly connecting it to the MreB actin cytoskeleton. Because the nucleotide state of MglA is regulated spatially and MglA only binds MreB in the guanosine triphosphate–bound form, the motility complexes are assembled at the leading pole and dispersed at the lagging pole where the guanosine triphosphatase activating protein MglB disrupts the MglA–MreB interaction. Thus, MglA acts as a nucleotide-dependent molecular switch to regulate the motility machinery spatially. The function of MreB in motility is independent of its function in peptidoglycan synthesis, representing a coopted function. Our findings highlight a new function for the MreB cytoskeleton and suggest that G-protein–cytoskeleton interactions are a universally conserved feature. PMID:26169353

  2. True vasculitis in lupus nephritis.

    PubMed

    Abdellatif, A A; Waris, S; Lakhani, A; Kadikoy, H; Haque, W; Truong, L D

    2010-08-01

    Vascular lesions are encountered frequently in renal biopsy specimens of patients with systemic lupus erythematosus (SLE) and can present in a variety of morphologic forms. True renal lupus vasculitis (TRLV) is one of the rare vascular lesions associated with lupus nephritis that has been infrequently reported in the medical literature. The primary focus on glomerular pathology and collective classification of the vascular lesions under lupus vasculopathy is one of the reasons why this form of inflammatory vasculitis has been under-recognized as a separate disease entity. Here we have comprehensively reviewed the literature on renal vascular involvement in SLE for a better understanding of the epidemiology, morphologic features, pathogenesis, clinical course and treatment of TRLV. It can be morphologically differentiated from other forms of renal vascular lesions in lupus nephritis, i.e. arteriosclerosis, uncomplicated vascular immune deposits, non-inflammatory necrotizing vasculopathy, and thrombotic microangiopathy. Despite close similarities with antineutrophil cytoplasmic autoantibody associated vasculitis (AASV), there are certain morphological differences that warrant a thorough investigation of the possible pauci-immune mechanism of pathogenesis. The vasculitis follows a severe clinical course in general with rapid progression to renal failure, although favorable outcomes have been reported in certain cases. The standard use of steroids and cytotoxic drugs has yielded variable results in the treatment of TRLV. Current treatment modalities being used in lupus nephritis and AASV have been compared in this article with focus on drugs acting on the inflammatory cells implicated in TRLV pathogenesis.

  3. Activation of focal adhesion kinase by Salmonella suppresses autophagy via an Akt/mTOR signaling pathway and promotes bacterial survival in macrophages.

    PubMed

    Owen, Katherine A; Meyer, Corey B; Bouton, Amy H; Casanova, James E

    2014-06-01

    Autophagy has emerged as an important antimicrobial host defense mechanism that not only orchestrates the systemic immune response, but also functions in a cell autonomous manner to directly eliminate invading pathogens. Pathogenic bacteria such as Salmonella have evolved adaptations to protect themselves from autophagic elimination. Here we show that signaling through the non-receptor tyrosine kinase focal adhesion kinase (FAK) is actively manipulated by the Salmonella SPI-2 system in macrophages to promote intracellular survival. In wild-type macrophages, FAK is recruited to the surface of the Salmonella-containing vacuole (SCV), leading to amplified signaling through the Akt-mTOR axis and inhibition of the autophagic response. In FAK-deficient macrophages, Akt/mTOR signaling is attenuated and autophagic capture of intracellular bacteria is enhanced, resulting in reduced bacterial survival. We further demonstrate that enhanced autophagy in FAK(-/-) macrophages requires the activity of Atg5 and ULK1 in a process that is distinct from LC3-assisted phagocytosis (LAP). In vivo, selective knockout of FAK in macrophages resulted in more rapid clearance of bacteria from tissues after oral infection with S. typhimurium. Clearance was correlated with reduced infiltration of inflammatory cell types into infected tissues and reduced tissue damage. Together, these data demonstrate that FAK is specifically targeted by S. typhimurium as a novel means of suppressing autophagy in macrophages, thereby enhancing their intracellular survival.

  4. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

    PubMed Central

    2013-01-01

    Introduction Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures

  5. Polyomavirus-associated nephritis in 2 horses.

    PubMed

    Jennings, S H; Wise, A G; Nickeleit, V; Maes, R K; Cianciolo, R E; Del Piero, F; Law, J M; Kim, Y; McCalla, A C; Breuhaus, B A; Roberts, M C; Linder, K E

    2013-09-01

    Polyomaviruses produce latent and asymptomatic infections in many species, but productive and lytic infections are rare. In immunocompromised humans, polyomaviruses can cause tubulointerstitial nephritis, demyelination, or meningoencephalitis in the central nervous system and interstitial pneumonia. This report describes 2 Standardbred horses with tubular necrosis and tubulointerstitial nephritis associated with productive equine polyomavirus infection that resembles BK polyomavirus nephropathy in immunocompromised humans.

  6. Renoprotective strategies in lupus nephritis: beyond immunosuppression.

    PubMed

    Griffin, B; Lightstone, L

    2013-10-01

    Lupus nephritis needs to be diagnosed promptly and treated specifically with appropriate immunosuppression. However, all patients with lupus nephritis have by definition chronic kidney disease (CKD) as they will have proteinuria with varying degrees of renal impairment. CKD requires careful additional management, not only to reduce the risk of progression to end-stage renal disease but also because it is probably the strongest risk for cardiovascular morbidity and mortality. This review focuses on the evidence underscoring strategies to prevent progression of CKD beyond the "simple" treatment of the lupus nephritis. The strategies include immaculate control of blood pressure, inhibition of the renin-angiotensin system to reduce blood pressure and proteinuria, and the benefits of lifestyle modifications such as tackling smoking, obesity and exercise. We also review the literature on control of dyslipidaemias which, although clearly of cardiovascular benefit, provide less compelling data for offering renoprotection. We touch on the emerging area of the importance of controlling urate levels in protecting against progressive renal impairment. Finally, there is a reminder about the importance of considering the nephrotoxicity of all medications prescribed for patients with lupus nephritis - above all the need to avoid the use of non-steroidal anti-inflammatory drugs. Overall, the theme is that there is much more to the management of patients with lupus nephritis than "just" the nephritis - a multidisciplinary approach involving nephrologists as well as rheumatologists is more likely to provide the appropriate wider care required for all patients with lupus nephritis.

  7. Concurrent Kimura disease and lupus nephritis

    PubMed Central

    Wang, Haitao; Fang, Fang; Sun, Ying; Wang, Songlan; Mao, Yonghui

    2016-01-01

    Abstract Background: Kimura disease is a rare chronic inflammatory disorder with peripheral eosinophilia and elevated serum IgE and is also frequently complicated by nephropathy. Methods: We report a rare case of Kimura disease concomitant with lupus nephritis in a 72-year old male patient with recurrent unexplained lymphadenopathy, renal lesions, and immunologic abnormalities. Results: The patient was successfully managed with gamma immunoglobulin, intravenous pulse methylprednisolone therapy, hydroxychloroquine, and prednisone. Conclusion: This is the first report of a case of Kimura disease concomitant with lupus nephritis and highlights the importance of considering lupus nephritis as a possible concurrent disease in patients with Kimura disease that have immunologic abnormalities. PMID:27741124

  8. Phentermine induced acute interstitial nephritis.

    PubMed

    Shao, Emily Ximin; Wilson, Gregory John; Ranganathan, Dwarakanathan

    2017-03-09

    Acute interstitial nephritis (AIN) has a number of medication-related aetiologies. Antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs are common causes; however, any medication has the potential to cause drug-induced AIN. We report the first case of phentermine-induced AIN. A Caucasian woman aged 43 years presented with a 5-week history of lethargy, left-sided lower abdominal pain, nausea and vomiting. She had been taking phentermine for weight loss for 9 months and had recently ceased the medication. The patient underwent a renal biopsy that showed a predominantly lymphohistiocytic interstitial infiltrate with a moderate number of eosinophils consistent with AIN. Phentermine is increasingly used for weight loss in obese patients. This is the first case implicating phentermine as the causative agent for drug-induced AIN. While rare, phentermine-induced AIN is a possible adverse reaction of phentermine. Physicians and patients need to be aware of this risk.

  9. Insidious loss of renal function in patients with anticardiolipin antibodies and absence of overt nephritis.

    PubMed

    Leaker, B; McGregor, A; Griffiths, M; Snaith, M; Neild, G H; Isenberg, D

    1991-12-01

    Circulating anticardiolipin antibodies are associated with recurrent thrombosis, fetal loss and thrombocytopenia. We have identified four patients with SLE or lupus-like disease who have high circulating levels of ACLA, repeated thrombosis and evidence of renal disease. Their clinical signs and symptoms of lupus activity were minimal, yet all had renal insufficiency with GFR 50 ml/min or less despite no history nor evidence of overt nephritis (proteinuria less than 0.5 g/day and no haematuria). Renal biopsy specimens showed focal ischaemic lesions with no evidence of active lupus nephritis. We describe a new lesion of renal ischaemia secondary to non-inflammatory vascular pathology associated with circulating ACLA.

  10. Treatment of intractable lupus nephritis with total lymphoid irradiation

    SciTech Connect

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-04-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

  11. William Osler and investigation on trench nephritis.

    PubMed

    Smogorzewski, Miroslaw J

    2016-02-01

    The first alarming reports about a new disease called "trench nephritis" affecting soldiers of the British Expeditionary Forces in Flanders appeared in British medical press in 1915th. Soon, the Medical Research Council initiated a special research investigation on trench nephritis at St. Bartholomews Hospital and the results of these studies were discussed during the Royal Society of Medicine meeting in February 1916. William Osler was invited as one of the four main speakers for this presentation. He had lived in England since 1906 and served as the Regius Professor of Medicine at Oxford. At the meeting, Osler summarizes the clinical presentation of trench nephritis as a sudden appearance of swelling with rare cases of anasarca. Fever was not a common early presentation in his experience. He found rapid improvement in most of the cases during hospitalization despite "persistence of a large amount of albumin, of blood, and of cast, with increasing high blood pressure, is an unusual combination in the nephritis of civil life, yet that has been common enough in these cases". He questioned the assumption of a good prognosis in trench nephritis especially in "Cases which are lasting from twelve to fourteen weeks, the chances are that it will become subacute or chronic".

  12. Malignant hypertension in antiphospholipid syndrome without overt lupus nephritis.

    PubMed

    Cacoub, P; Wechsler, B; Piette, J C; Beaufils, H; Herreman, G; Bletry, O; Godeau, P

    1993-01-01

    The antiphospholipid syndrome is usually defined by the association of a clinical manifestation (recurrent venous and/or arterial thrombosis, recurrent spontaneous miscarriages) and a biological abnormality (anticardiolipin antibody, lupus anticoagulant). We retrospectively analyzed the records of 5 patients (4 females, 1 male, aged 30 +/- 12 years) with antiphospholipid syndrome, primary (n = 1) or secondary to systemic lupus erythematosus (n = 4), who developed malignant systemic hypertension with renal insufficiency, in the absence of lupus nephritis. Before the episode of malignant hypertension, all patients had normal systemic blood pressure and renal function. During malignant hypertension the systolic pressure was 206 +/- 39 mmHg and the diastolic pressure 130 +/- 25 mmHg, peak serum creatinine was 204 +/- 95 mumol/l, daily proteinuria was 1.1 +/- 0.8 gr, and complement serum levels were normal in all patients. Renal angiography found normal proximal renal arteries. Renal biopsy showed ischaemic glomeruli without proliferative lesions (n = 5), focal intimal fibrosis either isolated (n = 3) or associated with thrombosis (n = 2) of the intrarenal vessels, and the absence of vasculitis. Immunofluorescence study did not reveal typical lupus deposits. Patients were treated with antihypertensive agents, increasing doses of prednisone (n = 3), and anticoagulant (n = 2) or anti-aggregant therapy (n = 1). After a mean follow-up of 6.8 +/- 5.2 years, 4 patients were still alive with normal blood pressure and renal function, whereas 1 patient died of a probable catastrophic antiphospholipid syndrome. Patients with antiphospholipid syndrome, primary or secondary to systemic lupus erythematosus, may develop malignant hypertension with renal insufficiency and intrarenal vascular lesions, in the absence of lupus nephritis.

  13. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... natural progress. Separate ratings are not to be assigned for disability from disease of the heart and any... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated....

  14. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... natural progress. Separate ratings are not to be assigned for disability from disease of the heart and any... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated....

  15. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... natural progress. Separate ratings are not to be assigned for disability from disease of the heart and any... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated....

  16. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... natural progress. Separate ratings are not to be assigned for disability from disease of the heart and any... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated....

  17. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... natural progress. Separate ratings are not to be assigned for disability from disease of the heart and any... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated....

  18. Radiation nephritis. Clinical manifestations and pathophysiologic mechanisms

    SciTech Connect

    Krochak, R.J.; Baker, D.G.

    1986-05-01

    Radiation nephritis is both volume and dose related. Clinical experience would indicate that a minimum of one third of the renal volume needs to be excluded from nephrotoxic doses which appears to have a threshold of 2,000 cGy. The site of damage leading to renal failure appears to be the microvasculature ultimately expressed as glomerulosclerosis. How much direct damage to the tubular system contributes to this process is unclear, but undoubtedly the resultant systemic physiologic effects potentiate the expression of damage in the irradiated kidney. The acute syndrome, with all the potential manifestations of renal failure, rarely presents sooner than six months and appears to have no clear prodrome, although it would seem reasonable that a subclinical syndrome consisting of abnormalities detectable by urinalysis may occur. Treatment of radiation-induced nephritis or hypertension is no different from treatment for nephritis from any other cause and should be aggressive with lifelong follow-up. Carcinogenesis is a rare late expression of radiation-induced kidney damage. 25 references.

  19. [Acute interstitial nephritis induced by loratadine].

    PubMed

    Alvarez Navascués, R; Bastardo, Z; Fernández Díaz, M; Guerediaga, J; Quiñones, L; Pinto, J

    2003-01-01

    Loratadine is a second generation histamine H1 receptor antagonist, that has high potency antiallergic properties and is associated with low adverse effects compared with other antihistamines. Acute interstitial nephritis is a cause of acute renal failure that is most often induced by drugs or, less frequently, infection or sarcoidosis. Although the number of drugs associated with acute intersticial nephritis is too large, the antihistaminic loratadine have never been reported before. We report a case of an interstitial nephritis with acute renal failure that suggesting hypersensitivity reaction in a 77 old man who had received loratadine (10 mg/day) during ten days before his assessment to our hospital by disseminated pruritic syndrome. The initial suspect was rapidly progressive glomerulonephitis and renal biopsy was practice and treatment with corticosteroids were initiated (prednisone bolus of 500 mg three days and 1 mg/kg/day/later). The loratadine therapy was cessation. He exhibiting a slow and progressive improvement on renal function and one month later, urea and creatinine levels was normal and hematuria and proteinuria had disappeared. The corticosteroids therapy were progressive decreased until withdrawal. We think that this is an interesting case, basing in its clinical presentation and that it had never been reported before.

  20. [Membranous nephritis after renal transplantation].

    PubMed

    Robles, N R; Gómez Campdera, F; Anaya, F; Niembro, E; Junco, E; Valderrábano, F

    1991-02-01

    8 cases of membranous glomerulonephritis (MG) after renal transplants (RT) are presented; one being a recurrence of the original disease and the other 7 due to a different cause of renal insufficiency. The total incidence of MG after transplantation was 1.63%; 1.39% being the incidence of MG of new cases. Only 1 patient showed decrease of renal function and in this case the MG was accompanied by chronic rejection lesions. There was no sign of neoplasias nor drugs producing MG. As far as chronic infections are concerned, only one patient showed B antigen and it was not observed during the immunofluorescent test in the biopsy. 6 patients had urological complications after the renal transplant (3 cases of urinary fistula; 2 cases of obstructive uropathy; 1 case of short ureter). 2 patients experienced the start of hemodialysis due to focal and segmentary glomerulosclerosis. The beginning of proteinuria commences between 2 and 23 months after the RT (median 13,0 +/- 7,5 moths); with a range of between 2.0 and 12.0 gr/day (median: 6.8 +/- 3,2 Z gr/day), this being nephrotic in 4 cases. Proteinuria improved 1 case, and persisted in the other patients at the same level registered previous to the diagnosis. MG is a non-frequent complication or RT and is usually benign. Patients with post-transplant urologic complications could be considered to have a higher risk of developing a MG "de novo".

  1. The medical response to trench nephritis in World War One.

    PubMed

    Atenstaedt, R L

    2006-08-01

    Around the 90-year anniversary of the Battle of the Somme, it is important to remember the international effort that went into responding to the new diseases, which appeared during the First World War, such as trench nephritis. This condition arose among soldiers in spring 1915, characterized by breathlessness, swelling of the face or legs, headache, sore throat, and the presence of albumin and renal casts in urine. It was speedily investigated by the military-medical authorities. There was debate over whether it was new condition or streptococcal nephritis, and the experts agreed that it was a new condition. The major etiologies proposed were infection, exposure, and diet (including poisons). Research pointed to the origin of the disease as being infective rather than toxic, but no definite cause was discovered. A number of labels were given to the disease, including war nephritis. However, trench nephritis was the one used most widely. Trench nephritis was a serious problem for the Allies, leading to 35 000 casualties in the British and 2000 in the American forces. There were also hundreds of deaths. The condition was treated in line with pre-war regimens designed for acute nephritis. No significant preventative methods were implemented for trench nephritis, as there was no consensus regarding causation. The medical response to trench nephritis was largely ineffective, with medical commentators recognizing that there had been a lack of medical progress.

  2. Role of electronmicroscopy in the classification of lupus nephritis.

    PubMed

    Pirani, C L; Olesnicky, L

    1982-07-01

    The role of transmission electronmicroscopy in the clarification of the pleomorphic lesions of lupus nephritis is reviewed. Emphasis is placed on the WHO classification of glomerular lesions and in the importance of electronmicroscopy, particularly the precise identification of the milder forms of glomerular involvement. This is essential for the proper therapeutic management of patients with lupus nephritis and to establish a more accurate prognosis.

  3. Prognosis and predictors of convulsion among pediatric lupus nephritis patients.

    PubMed

    Beiraghdar, Fatemeh; Maddani, Abbas; Taheri, Saeed; Sharifi-Bonab, Mir Mohsen; Esfahani, Taher; Panahi, Yunes; Einollahi, Behzad

    2009-05-01

    In this study, we aimed to analyze features and outcome of convulsion in pediatric lupus nephritis patients. We retrospectively reviewed data of 14 Iranian children with lupus nephritis who developed seizures and compared them with a group of the same number of well matched pediatric lupus nephritis patients. Higher serum creatinine levels and higher frequencies of anemia and lymphopenia were observed in the convulsion group. Multivariable logistic regression analysis revealed that the only risk factor for development of convulsion in pediatric lupus patients with nephritis was lymphopenia. Survival analysis showed that convulsion had no impact on patient and renal function outcomes in our pediatric lupus nephritis subjects. In conclusion, we found that lymphopenia is a predictive factor for convulsion occurrence in our patients and special attention to neurological status assessment may be needed in this situation.

  4. Failure of Gallium-67 scintigraphy to identify reliably noninfectious interstitial nephritis: concise communication

    SciTech Connect

    Graham, G.D.; Lundy, M.M.; Moreno, A.J.

    1983-07-01

    Gallium-67 scintigraphy has been reported to be useful in the diagnosis of noninfectious interstitial nephritis. We studied 12 patients with Ga-67 citrate that were diagnosed as having noninfectious interstitial nephritis on renal biopsy. Only seven of the twelve patients with interstitial nephritis on biopsy were scan-positive. Gallium-67 scintigraphy may not reliably identify noninfectious interstitial nephritis.

  5. Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus

    PubMed Central

    Chung, Sharon A.; Brown, Elizabeth E.; Williams, Adrienne H.; Ramos, Paula S.; Berthier, Celine C.; Bhangale, Tushar; Alarcon-Riquelme, Marta E.; Behrens, Timothy W.; Criswell, Lindsey A.; Graham, Deborah Cunninghame; Demirci, F. Yesim; Edberg, Jeffrey C.; Gaffney, Patrick M.; Harley, John B.; Jacob, Chaim O.; Kamboh, M. Ilyas; Kelly, Jennifer A.; Manzi, Susan; Moser-Sivils, Kathy L.; Russell, Laurie P.; Petri, Michelle; Tsao, Betty P.; Vyse, Tim J.; Zidovetzki, Raphael; Kretzler, Matthias; Kimberly, Robert P.; Freedman, Barry I.; Graham, Robert R.

    2014-01-01

    Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis–predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10−7), 16p12 (SLC5A11; P=5.1×10−7), 6p22 (ID4; P=7.4×10−7), and 8q24.12 (HAS2, SNTB1; P=1.1×10−6). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10−5, respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10−6). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci. PMID:24925725

  6. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

    SYNOPSIS Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that mycophenolate mofetil may be similar to quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil. PMID:25034160

  7. Lansoprazole-induced acute allergic interstitial nephritis in a renal transplant recipient: a case report.

    PubMed

    Yildirim, Tolga; Yilmaz, Rahmi; Baydar, Dilek Ertoy; Kutlugun, Aysun Aybal; Aki, Tuncay; Turgan, Cetin

    2012-12-01

    Drug-induced interstitial nephritis is one of the causes of graft dysfunction in renal transplant recipients. Although commonly implicated as a cause of drug-induced interstitial nephritis in the general population, proton pump inhibitor-induced interstitial nephritis has not yet been reported in renal transplant recipients. Trimethoprim-sulfamethoxazole is responsible for most cases of interstitial nephritis in this population. Here, we describe the first case of proton pump inhibitor-related interstitial nephritis in a renal transplant recipient.

  8. Intramolecular epitope spreading in Heymann nephritis.

    PubMed

    Shah, Pallavi; Tramontano, Alfonso; Makker, Sudesh P

    2007-12-01

    Immunization with megalin induces active Heymann nephritis, which reproduces features of human idiopathic membranous glomerulonephritis. Megalin is a complex immunological target with four discrete ligand-binding domains (LBDs) that may contain epitopes to which pathogenic autoantibodies are directed. Recently, a 236-residue N-terminal fragment, termed "L6," that spans the first LBD was shown to induce autoantibodies and severe disease. We used this model to examine epitope-specific contributions to pathogenesis. Sera obtained from rats 4 weeks after immunization with L6 demonstrated reactivity only with the L6 fragment on Western blot, whereas sera obtained after 8 weeks demonstrated reactivity with all four recombinant fragments of interest (L6 and LBDs II, III, and IV). We demonstrated that the L6 immunogen does not contain the epitopes responsible for the reactivity to the LBD fragments. Therefore, the appearance of antibodies directed at LBD fragments several weeks after the primary immune response suggests intramolecular epitope spreading. In vivo, we observed a temporal association between increased proteinuria and the appearance of antibodies to LBD fragments. These data implicate B cell epitope spreading in antibody-mediated pathogenesis of active Heymann nephritis, a model that should prove valuable for further study of autoimmune dysregulation.

  9. Treatment of young patients with lupus nephritis using calcineurin inhibitors

    PubMed Central

    Tanaka, Hiroshi; Tsuruga, Kazushi; Aizawa-Yashiro, Tomomi; Watanabe, Shojiro; Imaizumi, Tadaatsu

    2012-01-01

    Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contributed to a favorable outcome in children and adolescents with systemic lupus erythematosus (SLE). Nevertheless, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are reviewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide (IVCY) are effective for preserving renal function in adult patients, CPA is a potent immunosuppressive agent that induces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malignancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting the transcription of the early activation genes of interleukin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone (PDN), Tac, and mycophenolate mofetile (MMF) has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and

  10. Renal vascular lesions in lupus nephritis.

    PubMed

    Descombes, E; Droz, D; Drouet, L; Grünfeld, J P; Lesavre, P

    1997-09-01

    We retrospectively studied the prevalence, histologic features, clinical correlations, and long-term outcome of the intrarenal vascular lesions of lupus nephritis (LN) in a series of 169 renal biopsies performed between 1980 and 1994 in 132 patients with systemic lupus erythematosus. The most common vascular lesions were nonspecific sclerotic changes, found in 37% of the biopsies (24% if only the cases with moderate to severe changes are considered). The other common vascular lesions were "immunoglobulin microvascular casts," found in 24% of the biopsies. Vasculitis and thrombotic microangiopathy were rare lesions and were seen in only 4 (2.4%) and 1 (0.6%) cases, respectively. Isolated sclerotic vascular changes were present in biopsies from older patients with a longer duration of LN, compared with the group with no vascular lesions, and were associated with a significantly higher prevalence of hypertension. Overall, however, the long-term renal and patient survival of this group did not differ significantly from that of the patients without vascular changes. Immunoglobulin microvascular casts (IMCs) ("lupus vasculopathy") were characterized by the presence of immunoglobulin deposition within the glomerular capillaries and small arterioles. In the present study we extensively investigated the morphologic and immunologic features of this lesion. The lesions were notable for the absence of endothelial or parietal vascular lesions and of fibrin, platelets, and leukocytes, which indicates that thrombosis is not involved in the vascular obstruction. According to our data immunoglobulin precipitation in the microvasculature seems to play a central role in the pathogenesis of this lesion, which is why we propose the term "immunoglobulin microvascular casts." In general, IMCs were associated with the most severe and active forms of diffuse proliferative lupus nephritis (World Health Organization [WHO] class IV). However our data show that, in contrast to previous studies

  11. Beneficial effect of glucocorticoids on the course of haematogenously acquired Staphylococcus aureus nephritis.

    PubMed

    Verba, V; Sakiniene, E; Tarkowski, A

    1997-03-01

    The effect of combined antibiotic and corticosteroid treatment on the course of haematogenously acquired Staphylococcus aureus nephritis was studied. Mice were given a single injection of S. aureus producing toxic shock syndrome toxin-1 in a dose capable of inducing a high frequency of inflammatory kidney lesions and divided into three groups according to a treatment regimen. In all untreated animals inflammatory infiltrates were seen in kidney cortex and medulla with high frequencies of glomerular (90%) and tubular damage (50%) as well as fibrotic changes (50%). The treatment with antibiotics alone reduced significantly only the occurrence of focal inflammatory infiltrates. In contrast, the mice treated with a combination of antibiotics and corticosteroids displayed in 64% of cases normal histological kidney appearance and a significant decrease in occurrence of glomerular (P<0.01) and tubular (P<0.05) lesions. Immunohistochemically, the combined treatment resulted in a more pronounced decrease in numbers of CD4, IL-2R (four to fivefold) and CD8 positive cells in kidney inflammatory lesions compared to antibiotics only treated group. Thus, glucocorticoids in association with antibiotics are shown to improve the outcome of septic murine nephritis, possibly due to suppression of kidney infiltrating T cells.

  12. Fatal suppurative nephritis caused by Pseudomonas in a chimpanzee

    USGS Publications Warehouse

    Migaki, G.; Asher, D.M.; Casey, H.W.; Locke, L.N.; Gibbs, C.J.; Gajdusek, C.

    1979-01-01

    Reports of nephritis in chimpanzees are relatively rare, compared with those in other nonhuman primates. McClure and Guilloud reported chronic pyelonephritis in a 35-year-old female chimpanzee; Schmidt and Butler reported glomerulonephritis in an 11-year-old female chimpanzee, and Kim reported on a 12-year-old male with subacute interstitial nephritis in a chimpanzee after the animal had recurrent hemolysis due to phenolic intoxication. The present report deals with supprative nephritis caused by Pseudomonas resulting in renal failure in a chimpanzee.

  13. Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be considered the drug of choice?

    PubMed

    Rovin, Brad H; Parikh, Samir V; Hebert, Lee A; Chan, Tak Mao; Mok, Chi Chiu; Ginzler, Ellen M; Hooi, Lai Seong; Brunetta, Paul; Maciuca, Romeo; Solomons, Neil

    2013-01-01

    Severe lupus nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy. Nevertheless, the role of mycophenolate mofetil in treating severe lupus nephritis is unclear, because such patients were excluded from these trials. With this limitation as background, this work addresses the question of mycophenolate mofetil for induction therapy for severe lupus nephritis. We performed a systematic review of the outcomes of treating severe lupus nephritis with mycophenolate mofetil or cyclophosphamide. Because no studies directly addressed this question, these data were extracted from the published literature or obtained by personal communications from investigators. There is no universally accepted definition, and therefore, severe lupus nephritis was arbitrarily defined by renal histology, resistance to therapy, or level of kidney function at presentation. For each trial analyzed, we determined the partial and complete remission rates. Long-term outcomes were compared when available. The pooled results suggest that mycophenolate mofetil and cyclophosphamide are equally effective in inducing remission of severe lupus nephritis. However, relapse rates and risk of developing ESRD were higher for mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short term, mycophenolate mofetil and cyclophosphamide are about equal in inducing remission. However, long-term outcomes suggest better preservation of kidney function and fewer relapses with cyclophosphamide therapy. Therefore, mycophenolate mofetil should not yet be considered the induction drug of choice for severe lupus nephritis.

  14. Focal Choroidal Excavation

    PubMed Central

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-01-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation. PMID:28050329

  15. Focal Choroidal Excavation.

    PubMed

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-12-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation.

  16. Con: Cyclophosphamide for the treatment of lupus nephritis.

    PubMed

    Mok, Chi Chiu

    2016-07-01

    Kidney involvement is a major determinant for morbidity and mortality in patients with systemic lupus erythematosus. The treatment target of lupus renal disease is to induce and maintain remission and to minimize disease or treatment-related comorbidities. Cyclophosphamide (CYC), in conjunction with glucocorticoids, has conventionally been used for the initial treatment of lupus nephritis. However, the major concerns of CYC are its toxicities, such as infertility, urotoxicity and oncogenicity, which are particularly relevant in women of childbearing age. As a result, maintenance therapy of lupus nephritis with an extended course of CYC pulses has largely been replaced by other immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine. Recent randomized controlled trials have demonstrated non-inferiority of MMF to pulse CYC as induction therapy of lupus nephritis. Although MMF as induction-maintenance therapy has been increasingly used in lupus nephritis, its efficacy in the long-term preservation of renal function remains to be elucidated. MMF is not necessarily less toxic than CYC. Meta-analyses of clinical trials show similar incidence of infective complications and gastrointestinal adverse events in both MMF- and CYC-based regimens. However, considering the reduction in gonadal toxicity and the risk of oncogenicity, MMF may be used as first-line therapy of lupus nephritis. Tacrolimus (TAC) has recently been shown to be equivalent to either MMF or CYC for inducing remission of lupus nephritis and may be considered as another non-CYC alternative. Combined low-dose MMF and TAC appears to be more effective than CYC pulses in Chinese patients with lupus nephritis and has the potential to replace the more toxic CYC regimens in high-risk patients. Currently, CYC still plays an important role in the management of lupus nephritis patients with impaired or rapidly deteriorating renal function, crescentic glomerulonephritis or as salvage therapy for

  17. Early Prediction of Lupus Nephritis Using Advanced Proteomics

    DTIC Science & Technology

    2011-06-01

    class V lupus nephritis, including - 1-B glycoprotein by 2D gel electrophoresis, -1-antitrypsin by SELDI-TOF-MS, citrate and taurine by NMR...nephritis, including -1-B glycoprotein by 2D gel electrophoresis, -1-antitrypsin by SELDI-TOF-MS, citrate, taurine and hippurate by NMR spectroscopy...metabolite taurine were significantly elevated (p < 0.01) in membranous LN as compared to proliferative LN patients. There was also a trend towards

  18. Pauci-immune lupus nephritis: possibility or co-incidence?

    PubMed Central

    Cansu, Döndü Üsküdar; Temiz, Gökhan; Açıkalın, Mustafa F.; Korkmaz, Cengiz

    2017-01-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with immune complex formation and renal involvement of lupus and may include several kinds of pathological conditions, but mostly, it is associated with immune complex-induced glomerular disease. Pauci-immune lupus nephritis is a very rare condition. We describe a 45-year-old female patient with pauci-immune crescentic necrotizing lupus nephritis and briefly discuss the possible mechanism and pathogenesis. PMID:28293460

  19. Lupus Nephritis: Animal Modeling of a Complex Disease Syndrome Pathology

    PubMed Central

    McGaha, Tracy L; Madaio, Michael P.

    2014-01-01

    Nephritis as a result of autoimmunity is a common morbidity associated with Systemic Lupus Erythematosus (SLE). There is substantial clinical and industry interest in medicinal intervention in the SLE nephritic process; however, clinical trials to specifically treat lupus nephritis have not resulted in complete and sustained remission in all patients. Multiple mouse models have been used to investigate the pathologic interactions between autoimmune reactivity and SLE pathology. While several models bear a remarkable similarity to SLE-driven nephritis, there are limitations for each that can make the task of choosing the appropriate model for a particular aspect of SLE pathology challenging. This is not surprising given the variable and diverse nature of human disease. In many respects, features among murine strains mimic some (but never all) of the autoimmune and pathologic features of lupus patients. Although the diversity often limits universal conclusions relevant to pathogenesis, they provide insights into the complex process that result in phenotypic manifestations of nephritis. Thus nephritis represents a microcosm of systemic disease, with variable lesions and clinical features. In this review, we discuss some of the most commonly used models of lupus nephritis (LN) and immune-mediated glomerular damage examining their relative strengths and weaknesses, which may provide insight in the human condition. PMID:25722732

  20. 77 FR 38305 - Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus-Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Withdrawal of Guidance AGENCY: Food and... availability of a guidance entitled ``Lupus Nephritis Caused By Systemic Lupus...

  1. Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis.

    PubMed

    Biesecker, G; Katz, S; Koffler, D

    1981-12-01

    The membrane attack complex (MAC) of the complement system was localized in both glomeruli and peritubular regions of 22 kidneys manifesting systemic lupus erythematosus (SLE) nephritis. A similar distribution was observed for immune complex markers (IgG, Clq, and C3) and MAC in glomeruli, although the deposits of MAC were more discrete and showed lesser immunofluorescence staining intensity compared with immunoglobulins and complement components. In contrast, peritubular immune complexes were present in only 7 out of 22 kidneys, involved comparatively small clusters of tubules, exhibited weaker immunofluorescence staining than MAC, and failed to correlate with interstitial foci of inflammation. Granular or irregular, linear aggregates of the MAC were observed at the periphery of larger groups of tubules contiguous to areas of interstitial inflammation. Comparable amounts of IgG, Clq, C3, and MAC were present in blood vessel walls in areas of fibrinoid necrosis. These data suggest that the MAC is a direct mediator of tissue injury occurring in renal glomeruli, tubules, and blood vessels. The discordance between immune complexes and MAC localized in the peritubular region, but not in glomeruli or blood vessels, raises the possibility that both immune complexes and nonimmune agents, such as bacterial antigens, may activate the classical or alternative complement pathways and thereby play a role in the pathogenesis of tubulointerstitial lesions of SLE nephritis.

  2. Overview of lupus nephritis management guidelines and perspective from Asia.

    PubMed

    Mok, Chi Chiu; Yap, Desmond Y H; Navarra, Sandra V; Liu, Zhi-Hong; Zhao, Ming-Hui; Lu, Liangjing; Takeuchi, Tsutomu; Avihingsanon, Yingyos; Yu, Xue-Qing; Lapid, Elizabeth A; Lugue-Lizardo, Lenrore R; Sumethkul, Vasant; Shen, Nan; Chen, Shun-le; Chan, Tak Mao

    2013-12-01

    Lupus nephritis (LN) is a common and important manifestation of systemic lupus erythematosus (SLE). Evidence suggests higher rates of lupus renal involvement in Asian populations, and maybe more severe nephritis, compared with other racial or ethnic groups. The management of LN has evolved considerably over the past three decades, based on observations from clinical studies that investigated different immunosuppressive agents including corticosteroids, cyclophosphamide, azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic therapies. This is accompanied by improvements in both the short-term treatment response rate and long-term renal function preservation. Treatment guidelines for LN have recently been issued by rheumatology and nephrology communities in U.S.A. and Europe. In view of the racial difference in disease manifestation and response to therapy, and the substantial disease burden in Asia, a panel of 15 nephrologists and rheumatologists from different Asian regions with extensive experience in lupus nephritis - the Steering Group for the Asian Lupus Nephritis Network (ALNN) - met and discussed the management of lupus nephritis in Asian patients. The group has also reviewed and deliberated on the recently published recommendations from other parts of the world. This manuscript summarizes the discussions by the group and presents consensus views on the clinical management and treatment of adult Asian patients with LN, taking into account both the available evidence and expert opinion in areas where evidence remains to be sought.

  3. Parasites alter the pathological phenotype of lupus nephritis.

    PubMed

    Miyake, Katsuhisa; Adachi, Keishi; Watanabe, Maho; Sasatomi, Yoshie; Ogahara, Satoru; Abe, Yasuhiro; Ito, Kenji; Dan Justin, Yombo K; Saito, Takao; Nakashima, Hitoshi; Hamano, Shinjiro

    2014-12-01

    Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis.

  4. Parasites alter the pathological phenotype of lupus nephritis

    PubMed Central

    Miyake, Katsuhisa; Adachi, Keishi; Watanabe, Maho; Sasatomi, Yoshie; Ogahara, Satoru; Abe, Yasuhiro; Ito, Kenji; Dan Justin, Yombo K.; Saito, Takao

    2014-01-01

    lpr Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis. PMID:24957876

  5. Environmental factors predicting nephritis in systemic lupus erythematosus.

    PubMed Central

    McAlindon, T; Giannotta, L; Taub, N; D'Cruz, D; Hughes, G

    1993-01-01

    OBJECTIVES--To evaluate social class, ethnic origin, and various endocrine variables as potential risk factors in the development of nephritis in patients with systemic lupus erythematosus (SLE). METHODS--A cross-sectional survey was carried out of all outpatients with SLE attending the lupus Clinic of St Thomas's Hospital from March to October 1992 using retrospective survival data. The main outcome measure was the duration of SLE before the onset of nephritis. RESULTS--Two hundred and ninety six women and 11 men were studied; the male patients were excluded from the analysis. Univariate analysis showed an increased risk of nephritis in patients with SLE of West Indian origin with 54 v 19% with nephritis at five years, in patients of lower social class, in patients who did not drink alcohol, and in those with a history of fetal loss after the onset of lupus. No significant effect of the age of onset of SLE, use of oral contraceptives, normal pregnancy, or smoking was seen. Multivariate analysis showed that ethnic origin did not influence the risk of nephritis independently of social class. CONCLUSIONS--Factors associated with socioeconomic deprivation may increase disease severity in patients with SLE. PMID:8257208

  6. IgG4-Related Tubulointerstitial Nephritis.

    PubMed

    Zhang, Pingchuan; Cornell, Lynn D

    2017-03-01

    Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder that can involve nearly any organ. The disorder has increasingly become known as a distinct clinical entity during the last decade. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-RD in the kidney. Many patients with IgG4-TIN are diagnosed after IgG4-RD has been recognized in other organ systems, but the kidney may also be the first or only site involved. The presenting clinical features of IgG4-TIN are most commonly kidney insufficiency, kidney mass lesion(s), or both. On biopsy, IgG4-TIN shows a dense lymphoplasmacytic infiltrate, increased IgG4+ plasma cells, storiform fibrosis, and often tubular basement membrane immune complex deposits. Elevation of serum IgG4 often accompanies IgG4-RD; however, it is not specific in reaching the diagnosis. Like IgG4-RD in other organs, IgG4-TIN characteristically responds promptly to steroids, although there is a high relapse rate on discontinuation of immunosuppression. The pathogenesis of IgG4-RD is not understood.

  7. [Lupus nephritis: up-to-date].

    PubMed

    Karras, A

    2015-02-01

    Renal involvement is frequent during natural history of systemic lupus erythematosus (SLE) and has a major prognostic value in this systemic disease. Screening for renal symptoms, such as proteinuria, micro-haematuria or renal failure must be performed at initial diagnosis and repeated during subsequent follow-ups. Any significant abnormality of these parameters may reveal active glomerulonephritis (GN) and should lead to a renal biopsy, which will significantly impact the therapeutic choices. Proliferative GN, defined as class III or IV by the actual histo-pathological classification, is the most severe form of SLE-associated nephropathy and can lead to end-stage renal disease (ESRD) in up to 60% of cases, according to ethnicity and follow-up duration. Standard induction treatment of active proliferative GN includes corticosteroids combined with an immunosuppressive drug, which can either be cyclophosphamide or mycophenolate mofetil (MMF). Even though, recent biotherapies have not yet proved their efficacy in the field of lupus nephritis, new protocols are expected, aiming higher remission rates and avoidance of high-dose corticosteroids regimens. When remission is achieved in proliferative GN, a maintenance therapy is required to decrease the risk of relapse, using either azathioprine or MMF. Immunosuppressive drugs are responsible for an increased risk of infectious or neoplastic complications but cardiovascular disease is actually one of the main causes of mortality among lupus patients, especially for patients with SLE-related kidney disease, well before reaching ESRD.

  8. Acute lobar nephritis in children: Not so easy to recognize and manage

    PubMed Central

    Bibalo, Cristina; Apicella, Andrea; Guastalla, Veronica; Marzuillo, Pierluigi; Zennaro, Floriana; Tringali, Carmela; Taddio, Andrea; Germani, Claudio; Barbi, Egidio

    2016-01-01

    Acute lobar nephritis (ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children. PMID:26862513

  9. Do we still need renal biopsy in lupus nephritis?

    PubMed

    Haładyj, Ewa; Cervera, Ricard

    2016-01-01

    The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment.

  10. Acute interstitial nephritis following kudzu root juice ingestion.

    PubMed

    Jung, Jae Myun; Kwon, Soon Hyo; Noh, Hyunjin; Han, Dong Cheol; Jeon, Jin Seok; Jin, So Young

    2013-10-01

    Recently, the use of herbal remedies and complementary and alternative medicine has increased globally. Kudzu root (Pueraria lobata) is a plant commonly used in traditional medicine to promote health. A middle-aged woman consumed kudzu root juice to promote health and well-being for 10 days. Subsequently, she developed anorexia, epigastric discomfort and azotemia. These symptoms improved rapidly within several days after discontinuation of the suspected offending agent and conservative treatment. Acute interstitial nephritis was diagnosed by renal biopsy. To our knowledge, this is the first case report describing acute interstitial nephritis following the ingestion of kudzu root juice.

  11. Tonsillectomy and IgA nephritis.

    PubMed

    Ponticelli, Claudio

    2012-07-01

    IgA nephritis (IgAN) is an autoimmune disease characterized by deposits of IgA in the glomerular mesangium. Clinically, the disease may be punctuated by episodes of macroscopic haematuria often associated with pharingotonsillitis or may be oligosyntomatic with microscopic haematuria and mild proteinuria. The natural course of IgAN may be indolent and benign; however, some 30-50% of patients may progress to end-stage renal disease when follow-up is extended to ≥20 years. In patients with IgAN, circulating IgA1 molecules have an aberrant structure of O-glycans in the hinge region, which is characterized by abbreviated glycans composed of N-acetylgalactosamine, with or without sialic acid. These aberrant IgA1 trigger the production of autoantibodies, with formation of immune complexes that deposit in the mesangium causing inflammation and production of extracellular matrix. A number of experimental and clinical data outlined a possible pathogenetic role of tonsillitis. As a consequence, tonsillectomy has been frequently performed in Japan. Observational studies, made in patients with normal renal function and mild proteinuria, reported that tonsillectomy could reduce the episodes of macrohaematuria as well as the entity of microhaematuria and proteinuria. However, the available studies had short-term follow-up and could not asses the role of tonsillectomy in protecting from renal function deterioration. In a longitudinal retrospective study, Isseki et al. compared the outcome of tonsillectomized patients with IgAN with that of IgAN patients who did not receive tonsillectomy. Tonsillectomized patients had a higher number of remissions and a better slope of glomerular filtration rate in comparison with controls. These data are interesting and suggest that tonsillectomy may prevent renal dysfunction in patients with IgAN and normal renal function. However, the retrospective nature of the study and the presence of some confounding factors require further investigations

  12. Renal failure due to granulomatous interstitial nephritis in native and allograft renal biopsies: experience from a tertiary care hospital.

    PubMed

    Gupta, Pallav; Rana, D S; Bhalla, A K; Gupta, Ashwini; Malik, Manish; Gupta, Anurag; Bhargava, Vinant

    2014-10-01

    Granulomatous interstitial nephritis is a rare cause of renal failure in both native and allograft renal biopsies. Drugs and sarcoidosis are the commonest causes of granulomatous interstitial nephritis as reported in Western countries. Unlike the west, tuberculosis is the commonest cause of granulomatous interstitial nephritis in Indian subcontinent. The etiological factors, clinical course, glomerular and tubulointerstitial changes associated with granulomatous interstitial nephritis have been analyzed in the present study along with the outcome in patients with granulomatous interstitial nephritis.

  13. Partial (focal) seizure

    MedlinePlus

    ... Jacksonian seizure; Seizure - partial (focal); Temporal lobe seizure; Epilepsy - partial seizures ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

  14. Acute tubulointerstitial nephritis and uveitis syndrome in the elderly.

    PubMed Central

    Salu, P; Stempels, N; Vanden Houte, K; Verbeelen, D

    1990-01-01

    A case of acute tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) in an elderly woman is reported. The present case demonstrates that this entity originally observed in children, and more recently in adults, may also occur in the elderly. The aetiology and treatment are briefly discussed. Images PMID:2407289

  15. Acute tubulointerstitial nephritis and uveitis syndrome in the elderly.

    PubMed

    Salu, P; Stempels, N; Vanden Houte, K; Verbeelen, D

    1990-01-01

    A case of acute tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) in an elderly woman is reported. The present case demonstrates that this entity originally observed in children, and more recently in adults, may also occur in the elderly. The aetiology and treatment are briefly discussed.

  16. Pathogenetic role of glomerular CXCL13 expression in lupus nephritis

    PubMed Central

    Worthmann, K; Gueler, F; von Vietinghoff, S; Davalos-Mißlitz, A; Wiehler, F; Davidson, A; Witte, T; Haller, H; Schiffer, M; Falk, C S; Schiffer, L

    2014-01-01

    Podocytes maintain the structure and function of the glomerular filtration barrier. However, podocytes have recently been implicated in the innate immune response, and their function as non-haematopoietic antigen-presenting cells was highlighted. We have shown previously that excessive expression of the chemokine CXCL13 is a distinctive early event for nephritis in a murine model of systemic lupus erythematosus (SLE). Furthermore, we found that CXCL13 is elevated significantly in the serum of patients with SLE-nephritis. In this study, we were able to show for the first time that (i) CXCL13 is expressed locally in glomeruli in a model for SLE-nephritis in mice and that (ii) incubation of human podocytes with CXCL13 induces receptor stimulation of CXCR5 with activation of signalling pathways, resulting in (iii) secretion of proinflammatory cytokines and chemokines in culture supernatant. This cytokine/chemokine cocktail can lead to (iv) a neutrophil respiratory burst in isolated human granulocytes. Taken together, our results provide further evidence that CXCL13 is involved in the pathogenesis of glomerulonephritis and that podocytes can play an active role in local proinflammatory immune responses. Thus, CXCL13 could be a direct target for the therapy of glomerulonephritis in general and for SLE-nephritis in particular. PMID:24827905

  17. Renal failure due to granulomatous interstitial nephritis after pulmonary sarcoidosis.

    PubMed

    van Dorp, W T; Jie, K; Lobatto, S; Weening, J J; Valentijn, R M

    1987-01-01

    Two patients, who had had pulmonary sarcoidosis, developed renal failure due to sarcoid granulomatous interstitial nephritis after their original pulmonary symptoms had subsided. Treatment with prednisone resulted in almost complete recovery of renal function. Lysozyme and angiotensin-converting enzyme levels and gallium scintigraphy can be of diagnostic value.

  18. Early Prediction of Lupus Nephritis Using Advanced Proteomics

    DTIC Science & Technology

    2010-06-01

    mechanisms of inflammatory lupus nephritis from non inflammatory nephropathies with similar urinary findings. 1.2: Validation of NGAL as a biomarker...Membranous Class V lesions. Kidney biopsies are the choice for diagnosis of LN, but are impractical to accurately assess the course of LN in clinical

  19. The significance of anticardiolipin antibodies in patients with lupus nephritis.

    PubMed

    Abu-Shakra, M; Urowitz, M B; Gladman, D D; Ritchie, S

    1996-02-01

    The objective of this study was to determine whether anticardiolipin antibodies (ACL) in SLE patients are associated with a specific pattern of lupus nephritis and/or with renal microvascular changes. Patients with SLE, followed prospectively between June 1991-May 1994 at The Wellesley Hospital Lupus Clinic, who underwent a renal biopsy were included. The ACL was measured by the ELISA according to international standardized method. Renal biopsy morphology was assessed using the WHO criteria for the classification of lupus nephritis. Renal vascular changes included glomerular hyaline thrombi, intimal fibrosis and intraluminal thrombi of renal arterioles. There were 23 SLE patients. The mean age at diagnosis of SLE was 28.2 years and the mean disease duration was 6.3 years. Of these 10 (43%) had high levels of ACL. No difference in the frequency of severe nephritis (Class III and IV) was identified amongst patients with and without ACL. Mesangial nephritis was more common in patients with ACL 40% vs 0, p = 0.02). Glomerular hyaline thrombi occurred in 3 (13%) patients. None of them had positive ACL. Renal vascular lesions included intimal proliferation in 4 (ACL + , 1) occluded lumens by thrombi in 2 (ACL + 1). Our data indicate that the development of glomerular and/or microvascular changes is not related to the presence of ACL.

  20. Mortality from nephritis and nephrosis in the fibreglass manufacturing industry

    PubMed Central

    Chiazze, L.; Watkins, D. K.; Fryar, C.; Fayerweather, W.; Bender, J. R.; Chiazze, M.

    1999-01-01

    OBJECTIVES: To investigate the question of whether there is an association between exposure to silica or respirable glass fibre and mortality from nephritis or nephrosis among workers in fibrous glass wool manufacturing facilities. METHODS: A case-control study with cases and controls derived from the Owens Corning mortality surveillance system. Two case-control analyses were carried out, one where the cases are defined with nephritis or nephrosis as the underlying cause of death and one where cases are defined as those where nephritis or nephrosis is either the underlying or a contributing cause of death. RESULTS: There is no consistent relation between respirable fibres or respirable silica and nephritis or nephrosis when the analysis is based either on underlying cause only or on underlying plus contributing cause of death. None of the sociodemographic variables considered suggests an increased risk when considering both underlying and contributing cause of death. CONCLUSIONS: These data would seem to support the contention that the most accurate picture of renal disease will be gained from the use of all information on the death certificate and not only the underlying cause. For these data, all odds ratios (ORs) for respirable fibres and silica based on both underlying and contributing cause of death are < 1 with the exception of the highest exposure to silica which is slightly > 1 (OR = 1.04). Although these results do not prove that there is no association between nephritis and nephrosis and exposure to fibreglass or silica in the fibreglass manufacturing environment, they do not support the assertion that such an association exists.   PMID:10448324

  1. Participation of V beta 4(+)-, V beta 7(+)-, and V beta 11(+)-T lymphocytes in haematogenously acquired Staphylococcus aureus nephritis.

    PubMed

    Verba, V; Tarkowski, A

    1996-09-01

    The most frequent pathogen in haematogenously acquired kidney infections in humans in Staphylococcus aureus. In order to characterize in situ the immunological patterns of septic nephritis we developed a murine model of this disease. A single intravenous injection of S. aureus producing toxic shock syndrome toxin-1 resulted in high frequency of inflammatory kidney lesions. Histopathologically, both focal and diffuse inflammatory infiltrates were seen in kidney cortex and medulla. Immunohistochemical evaluation revealed high numbers of Mac-1+ phagocytic cells as well as CD4(+)-and CD8(+)-lymphocytes. The expansion of lymphocytes carrying T-cell receptor V beta chain 4, 7, and 11 families in the kidney was observed. Our results suggest that the haematogenously acquired kidney infection by superantigen-producing staphylococci leads to migration, in situ activation and expansion of responding T-lymphocyte subsets.

  2. [Focal epithelial hyperplasia].

    PubMed

    Vera-Iglesias, E; García-Arpa, M; Sánchez-Caminero, P; Romero-Aguilera, G; Cortina de la Calle, P

    2007-11-01

    Focal epithelial hyperplasia is a rare disease of the oral mucosa caused by the human papilloma virus (HPV). It appears as a benign epithelial growth, usually in the mucosa of the lower lip. It is mainly associated with HPV serotypes 13 and 32 and there is a clear racial predilection for the disease in Native Americans and Eskimos. We describe the case of a 17-year-old girl from Ecuador with multiple papular lesions in both lips that were clinically and histologically consistent with focal epithelial hyperplasia. Analysis by polymerase chain reaction detected HPV serotype 13.

  3. Vitelliform focal choroidal excavation.

    PubMed

    Or, Chris; Forooghian, Farzin

    2014-05-30

    Focal choroidal excavations (FCE) are characterized by foveal or perifoveal choroid excavations seen on optical coherence tomography (OCT). The authors report a case of FCE associated with a vitelliform lesion within the excavation. A case of FCE associated with a small vitelliform lesion has been described previously, but the larger extent of the vitelliform lesion observed in the current case has not been previously reported. This may represent a novel category of FCE, vitelliform focal choroidal excavation, in which deposition of vitelliform material is associated with its development.

  4. SNAP focal plane

    SciTech Connect

    Lampton, Michael L.; Kim, A.; Akerlof, C.W.; Aldering, G.; Amanullah, R.; Astier, P.; Barrelet, E.; Bebek, C.; Bergstrom, L.; Berkovitz, J.; Bernstein, G.; Bester, M.; Bonissent, A.; Bower, C.; Carithers Jr., W.C.; Commins, E.D.; Day, C.; Deustua, S.E.; DiGennaro,R.; Ealet, A.; Ellis, R.S.; Eriksson, M.; Fruchter, A.; Genat, J.-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Harris, S.E.; Harvey, P.R.; Heetderks, H.D.; Holland, S.E.; Huterer, D.; Karcher, A.; Kolbe, W.; Krieger, B.; Lafever, R.; Lamoureux, J.; Levi, M.E.; Levin, D.S.; Linder,E.V.; Loken, S.C.; Malina, R.; Massey, R.; McKay, T.; McKee, S.P.; Miquel, R.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Pratt, R.; Prieto, E.; Refregier, A.; Rhodes, J.; Robinson, K.; Roe, N.; Sholl, M.; Schubnell, M.; Smadja, G.; Smoot, G.; Spadafora, A.; Tarle, G.; Tomasch,A.; von der Lippe, H.; Vincent, R.; Walder, J.-P.; Wang, G.

    2002-07-29

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square-degree field sensitive in the visible and near-infrared wavelength regime. We describe the requirements for the instrument suite and the evolution of the focal plane design to the present concept in which all the instrumentation--visible and near-infrared imagers, spectrograph, and star guiders--share one common focal plane.

  5. Interstitial nephritis induced by protein-overload proteinuria.

    PubMed Central

    Eddy, A. A.

    1989-01-01

    Experimental nephrotic syndrome induced by several immunologic and biochemical methods is associated with the development of tubulointerstitial nephritis (TIN). To investigate the hypothesis that severe sustained proteinuria plays a role in the pathogenesis of TIN, the renal interstitium in a model of protein-overload proteinuria was studied. After uninephrectomy, rats received daily injections of 1.0 g of bovine serum albumin (BSA) or saline (controls) until killing at 1, 2, 4, or 7 weeks. Sections of frozen renal cortex were stained with a panel of monoclonal antibodies reactive with subsets of rat lymphohemopoietic cells, and positive tubulointerstitial cells (TIC) were quantitated by epifluorescence microscopy. BSA rats developed proteinuria, with mean rat urinary albumin excretion rates at 1, 2, 3, and 6 weeks of 35.6 +/- 21.8, 97.2 +/- 46.1, 63.6 +/- 40.8, and 58.6 +/- 24.4 mg/24 hours, respectively (controls, 0.17 +/- 0.16 mg/24 hours). BSA was detectable in the plasma of experimental animals at all periods, with mean values of 26.8 +/- 3.8, 27.8 +/- 2.7, 20.3 +/- 6.2, and 7.0 +/- 1.1 mg/ml (controls, 0.03 +/- 0.04 mg/ml) at 1, 2, 4, and 7 weeks, respectively, whereas plasma anti-BSA antibodies were never detected. A significant mononuclear cell infiltrate was present in the interstitium of experimental animals at all periods. At 1 week, an influx of macrophages was evident that was identified by surface markers OX42 (75+/1000 TIC) (P less than 0.01) and Ia (58+/1000 TIC) (P less than 0.01). Macrophages dominated the infiltrate at all periods. By 2 weeks, a significant population of lymphocytes was also present that was identified by the surface marker OX19 (54+/1000 TIC) (P less than 0.01). This early lymphocytic infiltrate was a mixed lesion of T helper and T cytotoxic cells. However, at 4 and 7 weeks, most lymphocytes expressed the OX8 cytotoxic T cell marker. The proximal tubules of proteinuric rats expressed vimentin intermediate filaments, a marker of

  6. Tubulointerstitial Nephritis and Uveitis Syndrome with non caseating granuloma in bone marrow biopsy.

    PubMed

    Fraga, Maria; Nunes da Silva, Maria João; Lucas, Margarida; Victorino, Rui M

    2014-01-01

    The Tubulointerstitial Nephritis and Uveitis syndrome is a very rare condition, probably under-diagnosed in clinical practice. It is characterized by the combination of an interstitial nephritis and uveitis, and is an exclusion diagnosis. Tissue non caseating granuloma can be rarely present, with only 6 cases reported on bone marrow. We present a case of a 55 year old female with a 3-month history of asthenia and weight loss. Blood tests showed anemia and renal insufficiency. Renal biopsy revealed interstitial nephritis and the bone marrow biopsy showed caseating granuloma. One month later anterior uveitis of the left eye appeared. An extensive exclusion of all possible causes allowed a diagnosis of Tubulointerstitial Nephritis and Uveitis syndrome with caseating granuloma in bone marrow. As ocular and renal manifestations may not occur simultaneously, Tubulointerstitial Nephritis and Uveitis Syndrome should be systematically considered in cases of interstitial nephritis and/or uveitis, and tissue granulomas can be part of this rare syndrome.

  7. Oral focal epithelial hyperplasia.

    PubMed

    Bassioukas, K; Danielides, V; Georgiou, I; Photos, E; Zagorianakou, P; Skevas, A

    2000-01-01

    Focal epithelial hyperplasia (FEH) or Heck disease, is a rare viral infection of the oral mucosa caused by HPV 13 or HPV 32. In Caucasians there have been only a few cases reported. We present the first case in Greece in a young Caucasian girl in which HPV 13 was detected with PCR analysis. The patient was successfully treated with CO2 laser.

  8. An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis.

    PubMed

    Ramírez-Sandoval, Roxana; Luévano-Rodríguez, Nayeli; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Saldívar-Elias, Sergio; Gurrola-Carlos, Reinaldo; Avalos-Díaz, Esperanza; Bollain-y-Goytia, Juan José; Herrera-Esparza, Rafael

    2015-01-01

    Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.

  9. Clinicopathologic associations of anti-endothelial cell antibodies in immunoglobulin A nephropathy and lupus nephritis.

    PubMed

    Wang, M X; Walker, R G; Kincaid-Smith, P

    1993-09-01

    Sera from 45 patients with lupus nephritis (LN), 63 patients with immunoglobulin A nephropathy (IgA N), and 71 glomerulonephritic controls (including 44 mesangial proliferative glomerulonephritis cases, 14 membranous glomerulonephritis cases, and 13 focal segmental glomerular sclerosis cases), and from 33 normal control subjects were tested by a cellular enzyme-linked immunoabsorbent assay for their anti-endothelial cell antibody (AECA) activity. Compared with normal controls, AECAs of the IgG subtype (AECA-IgG) were detected in LN (P < 0.001) and AECAs of the IgA subtype (AECA-IgA) were detected in both IgA N and LN (P = 0.018 and P < 0.001, respectively). Binding activity of AECA to endothelial cells was inhibited by endothelial cell lysate and fibroblast lysate but not by lymphocyte lysate, double stranded-DNA, or bovine serum albumin. Anti-endothelial cell antibody-positive sera also reacted with fibroblasts. In IgA N, associations were found between the presence of AECA and younger age (P = 0.036), proportion of crescents greater than 10% (P = 0.016), fibrin crescents (P = 0.016), and focal and segmental necrotizing lesions (P = 0.047). In LN, inverse associations were found between the presence of AECA and the duration of disease (P = 0.021), elevated serum creatinine levels (P = 0.020), decreased creatinine clearance (P = 0.043), and frequency of chronic renal failure (P = 0.036). Positive associations were observed between the presence of AECA and active lupus (P = 0.017), anti-nuclear antibodies (P = 0.015), and anti-DNA antibodies (P = 0.041). Our results suggest that AECA may be linked with the pathogenesis of LN and IgA N.

  10. Moving East: the Euro-Lupus Nephritis regimen in Asia.

    PubMed

    Houssiau, Frédéric A

    2016-01-01

    Treatment of lupus nephritis is more evidenced-based than ever. Yet many areas of uncertainty persist. The article by Rathi et al. brings a piece to the puzzle by comparing, in a group of Indian patients, the Euro-Lupus low-dose i.v. cyclophosphamide regimen with mycophenolate mofetil. Although some caveats must be raised, the results suggest that, after crossing the Atlantic, the Euro-Lupus regimen may well be moving East.

  11. Early Prediction of Lupus Nephritis Using Advanced Proteomics

    DTIC Science & Technology

    2008-06-01

    nephropathies with similar urinary findings. The respective amendment has been submitted to the CCHMC IRB and the ORP will be notified once approval at...and 133 kDa. These biomarkers were strongly correlated with renal disease activity and with renal damage. For the diagnosis of active nephritis...noninvasive technique for exploring pathological metabolic and toxicological processes in humans42-44 and is being developed as a tool for diagnosis of

  12. Outcomes in African Americans and Hispanics with lupus nephritis.

    PubMed

    Contreras, G; Lenz, O; Pardo, V; Borja, E; Cely, C; Iqbal, K; Nahar, N; de La Cuesta, C; Hurtado, A; Fornoni, A; Beltran-Garcia, L; Asif, A; Young, L; Diego, J; Zachariah, M; Smith-Norwood, B

    2006-05-01

    Poor outcomes have been reported in African Americans and Hispanics compared to Caucasians with lupus nephritis. The purpose of this retrospective analysis was to identify independent predictors of outcomes in African Americans and Hispanics with lupus nephritis. In total, 93 African Americans, 100 Hispanics, and 20 Caucasians with a mean age of 28 +/- 13 years and an annual household income of 32.9 +/- 17.3 (in 1000 US dollars) were studied. World Health Organization (WHO) lupus nephritis classes II, III, IV, and V were seen in 9, 13, 52, and 26%, respectively. Important baseline differences were higher mean arterial pressure (MAP) in African Americans compared to Hispanics and Caucasians (107 +/- 19, 102 +/- 15, and 99 +/- 13 mmHg, P < 0.05), and higher serum creatinine (1.66 +/- 1.3, 1.25 +/- 1.0, and 1.31 +/- 1.0 mg/dl, P < 0.025). African Americans had lower hematocrit compared to Hispanics and Caucasians (29 +/- 5, and 31 +/- 6, and 32 +/- 7%, P < 0.05), and lower annual household income (30.8 +/- 14.9, 33.1 +/- 15.9, and 42.2 +/- 29.3 in 1000 US dollars; P < 0.05). Lower prevalence of WHO class IV was seen in Caucasians (30%) compared to Hispanics (57%, P = 0.03) and African Americans (51%, P = 0.09). Development of doubling creatinine or end-stage renal disease was higher in African Americans and Hispanics than in Caucasians (31, 18, and 10%; P < 0.05), as was the development of renal events or death (34, 20, and 10%; P < 0.025). Our results suggest that both biological factors indicating an aggressive disease and low household income are common in African Americans and Hispanics with lupus nephritis, and outcomes in these groups are worse than in Caucasians.

  13. Early Prediction of Lupus Nephritis Using Advanced Proteomics

    DTIC Science & Technology

    2009-06-01

    nephritis from non inflammatory nephropathies with similar urinary findings. 1.2: Validation of NGAL as a biomarker for predicting SLE disease...R01-DK-069749, R01-DK-53289, P50-DK-52612, and R21-DK-070163 from the National Institute of Diabetes and Digestive and Kidney Diseases) and by the...significant, and P values less than 0.1 were reported to show trends. RESULTS Baseline patient characteristics and treatments . Table 1 summarizes the

  14. Appraisal of lupus nephritis by renal imaging with gallium-67

    SciTech Connect

    Bakir, A.A.; Lopez-Majano, V.; Hryhorczuk, D.O.; Rhee, H.L.; Dunea, G.

    1985-08-01

    To assess the activity of lupus nephritis, 43 patients with systemic lupus erythematosus (SLE) were studied by gallium imaging. Delayed renal visualization 48 hours after the gallium injection, a positive result, was noted in 25 of 48 scans. Active renal disease was defined by the presence of hematuria, pyuria (10 or more red blood cells or white blood cells per high-power field), proteinuria (1 g or more per 24 hours), a rising serum creatinine level, or a recent biopsy specimen showing proliferative and/or necrotizing lesions involving more than 20 percent of glomeruli. Renal disease was active in 18 instances, inactive in 23, and undetermined in seven (a total of 48 scans). Sixteen of the 18 scans (89 percent) in patients with active renal disease showed positive findings, as compared with only four of 23 scans (17 percent) in patients with inactive renal disease (p less than 0.001). Patients with positive scanning results had a higher rate of hypertension (p = 0.02), nephrotic proteinuria (p = 0.01), and progressive renal failure (p = 0.02). Mild mesangial nephritis (World Health Organization classes I and II) was noted only in the patients with negative scanning results (p = 0.02) who, however, showed a higher incidence of severe extrarenal SLE (p = 0.04). It is concluded that gallium imaging is a useful tool in evaluating the activity of lupus nephritis.

  15. Oral focal epithelial hyperplasia.

    PubMed

    López-Jornet, Pía; Camacho-Alonso, Fabio; Berdugo, Lucero

    2010-01-01

    Focal epithelial hyperplasia (FEH) is a benign, asymptomatic disease. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue and, less frequently, on the upper lip, gingiva and palate. FEH is caused by human papillomavirus subtype 13 or 32. The condition occurs in many populations and ethnic groups. We present the clinical case of a 31-year-old male with lesions that clinically and histologically corresponded to FEH.

  16. 75 FR 35492 - Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus-Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Availability AGENCY: Food and Drug... availability of a guidance for industry entitled ``Lupus Nephritis Caused By Systemic Lupus...

  17. [Focal epithelial hyperplasia].

    PubMed

    Delgado, Yolanda; Torrelo, Antonio; Colmenero, Isabel; Zambrano, Antonio

    2005-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferation of the oral mucosa with well defined clinical and histological characteristics. It has been associated with infection of the oral mucosa by types 13 and 32 of the human papillomavirus (HPV), and to a lesser extent, with other types. Its clinical course is variable, although it usually persists for months or years; cases with spontaneous resolution have been described, as have others with prolonged persistence. We present the case of an Ecuadorian boy whose visit was motivated by lesions in the oral mucosa consistent with a diagnosis of FEH, which were confirmed in the histological study, and in which HPV type 13 DNA was identified.

  18. Focal adhesions in osteoneogenesis

    PubMed Central

    Biggs, M.J.P; Dalby, M.J

    2010-01-01

    As materials technology and the field of tissue engineering advances, the role of cellular adhesive mechanisms, in particular the interactions with implantable devices, becomes more relevant in both research and clinical practice. A key tenet of medical device technology is to use the exquisite ability of biological systems to respond to the material surface or chemical stimuli in order to help develop next-generation biomaterials. The focus of this review is on recent studies and developments concerning focal adhesion formation in osteoneogenesis, with an emphasis on the influence of synthetic constructs on integrin mediated cellular adhesion and function. PMID:21287830

  19. A brief contextualization on IgG4 tubulointerstitial nephritis based on a case report in south Brazil.

    PubMed

    Pêgas, Karla Lais; Cambruzzi, Eduardo; Lobato, Gisele

    2016-06-01

    IgG4-related disease (IgG4RD) is a recent inflammatory process of supposed autoimmune etiology, which is characterized by elevated serum IgG4 levels, dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and storiform fibrosis. Tubulointerstitial nephritis is the most common renal manifestation, with different degrees of kidney dysfunction and variable clinical findings. Herein, the authors describe a new case of IgG4 tubulointerstitial nephritis (IgG4TN), and discuss clinic and pathologic criteria. Male patient, 72 years-old, was admitted on hospital service with clinical complaint of asthenia, loss of strength, emaciation, and anosmia. Previous history included type 2 diabetes mellitus. Laboratorial data included normochromic anemia, proteinuria, and creatinine elevation. Bilateral kidney ultrassonography/computed tomography revealed a heterogenous parenchyma, with diffuse irregular dense zones, areas of fibrosis on upper poles, and hydronephrosys. Kidney biopsy showed a dense interstitial lymphoplasmacytic infiltrate, with more than 50 plasma cell per high power field, irregular areas of fibroblastic and collagenous fibrosis, focal tubulitis, and normal glomeruli. Immunofluorescence revealed mild granular deposition of C3c and IgG in the tubular basement membrane. Immunohistochemestry was positive for CD138, lambda and Kappa light chains, and IgG4 (around forty five IgG4 positive plasma cells per high power field). IgG4 serum level was increased. The diagnosis of IgG4TN was then established. The patient received corticotherapy and strict control of glycemia with insulin, with marked improvement of symptoms and creatinine levels.

  20. Tubulointerstitial Nephritis and Uveitis Syndrome in an Elderly Man

    PubMed Central

    Lei, Wen-hui; Xin, Jun; Yu, Xue-ping; Li, Jie; Mao, Ming-feng; Ji, Jian-song; Wu, Chui-fen; Zhu, Chao-yong; Jin, Lie

    2015-01-01

    Abstract Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease of unknown etiology defined by the combination of tubulointerstitial nephritis, uveitis, and biochemical abnormalities. It has been reported that TINU mainly affects adolescents and young women. Here we reported a special case regarding a 60-year-old man with acute renal failure due to TINU syndrome documented by renal biopsy. We present a rare case of an elderly patient, who had been suffering from a fever for 2 weeks, characterized by sudden onset and resolving spontaneously, and accompanied by extreme fatigue, loss of appetite, and shivering. Renal biopsy showed a tubulointerstitial nephritis, with polymorphonuclear infiltration and acute tubulitis. In the outpatient clinic, he was diagnosed with idiopathic bilateral anterior uveitis 1 month ago. Ophthalmological examination revealed anterior asymptomatic bilateral uveitis. Human leukocyte antigen (HLA) typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) was found which supported the suspect of TINU syndrome. The patient was treated with oral prednisone (1 mg/kg) and continued for 8 weeks on tapering doses. Serum creatinine normalized within 3 and 6 months later renal function also recovered completely. This case highlights that TINU syndrome is probably an underdiagnosed disease responsible for some cases of idiopathic anterior uveitis in elderly male patients. It is of critical importance to be aware of this syndrome by nephrologist and ophthalmologists in this special population. Further studies are needed to elucidate clinical characteristic and pathogenesis of TINU syndrome in elderly population. PMID:26632725

  1. Lupus nephritis: the central role of nucleosomes revealed.

    PubMed

    Mortensen, Elin S; Fenton, Kristin A; Rekvig, Ole P

    2008-02-01

    Systemic lupus erythematosus (SLE) is an autoimmune syndrome characterized by autoantibodies to nuclear constituents. Some of these antibodies are diagnostically important, whereas others act as disease-modifying factors. One clinically important factor is autoantibodies against dsDNA and nucleosomes, which have overlapping diagnostic and nephritogenic impact in SLE. Although a scientific focus for 5 decades, the molecular and cellular origin of these antibodies, and why they are associated with lupus nephritis, is still not fully understood. A consensus has, however, evolved that antibodies to dsDNA and nucleosomes are central pathogenic factors in the development of lupus nephritis. In contrast, no agreement has been reached as to which glomerular structures are bound by nephritogenic anti-nucleosome antibodies in vivo. Mutually contradictory paradigms and models have evolved simply because we still lack precise and conclusive data to provide definitive insight into how autoantibodies induce lupus nephritis and which specificity is critical in the nephritic process(es). In this review, data demonstrating the central role of nucleosomes in inducing and binding potentially nephritogenic antibodies to DNA and nucleosomes are presented and discussed. These autoimmune-inducing processes are discussed in the context of Matzinger's danger model (Matzinger P: Friendly and dangerous signals: is the tissue in control? Nat Immunol 2007, 8:11-13; Matzinger P: The danger model: a renewed sense of self. Science 2002, 296:301-305; Matzinger P: Tolerance, danger, and the extended family. Annu Rev Immunol 1994, 12:991-1045) and Medzhitov's and Janeway's (Medzhitov R, Janeway CA Jr: Decoding the patterns of self and nonself by the innate immune system. Science 2002, 296:298-300; Medzhitov R, Janeway CA Jr: How does the immune system distinguish self from nonself? Semin Immunol 2000, 12:185-188; Janeway CA Jr, Medzhitov R: Innate immune recognition. Annu Rev Immunol 2002, 20

  2. Chemokines and Chemokine Receptors in the Development of Lupus Nephritis

    PubMed Central

    2016-01-01

    Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN. PMID:27403037

  3. Granulomatous Interstitial Nephritis Presenting as Hypercalcemia and Nephrolithiasis

    PubMed Central

    Sharmeen, Saika; Kalkan, Esra; Yi, Chunhui; Smith, Steven D.

    2016-01-01

    We report a case of acute kidney injury as the initial manifestation of sarcoidosis. A 55-year-old male was sent from his primary care physician's office with incidental lab findings significant for hypercalcemia and acute kidney injury with past medical history significant for nephrolithiasis. Initial treatment with intravenous hydration did not improve his condition. The renal biopsy subsequently revealed granulomatous interstitial nephritis (GIN). Treatment with the appropriate dose of glucocorticoids improved both the hypercalcemia and renal function. Our case demonstrates that renal limited GIN due to sarcoidosis, although a rare entity, can cause severe acute kidney injury and progressive renal failure unless promptly diagnosed and treated. PMID:26904327

  4. Extensive focal epithelial hyperplasia.

    PubMed

    Hashemipour, Maryam Alsadat; Shoryabi, Ali; Adhami, Shahrzad; Mehrabizadeh Honarmand, Hoda

    2010-01-01

    Heck's disease or focal epithelial hyperplasia is a benign contagious disease caused by human papillomavirus types 13 or 32. It occurs with low frequency in the Iranian population. This condition is characterized by the occurrence of multiple, small papules or nodules in the oral cavity, especially on the labial and buccal mucosa and tongue. In some populations, up to 39% of children are affected. Conservative surgical excision of lesions may be performed for diagnostic or aesthetic purposes. The risk of recurrence after this therapy is minimal, and there seems to be no malignant transformation potential. In the present work, we presented the clinical case of a 12-year-old Iranian girl with oral lesions that clinically and histologically correspond to Heck's disease.

  5. Allergic Interstitial Nephritis Manifesting as a Striated Nephrogram

    PubMed Central

    Moinuddin, Irfan; Bracamonte, Erika; Thajudeen, Bijin; Sussman, Amy; Madhrira, Machaiah; Costello, James

    2015-01-01

    Allergic interstitial nephritis (AIN) is an underdiagnosed cause of acute kidney injury (AKI). Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI) as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI. PMID:26664405

  6. Biopsy proven acute interstitial nephritis after treatment with moxifloxacin

    PubMed Central

    2010-01-01

    Background Acute interstitial nephritis (AIN) is an important cause of reversible acute kidney injury. At least 70% of AIN is caused by various drugs, mainly penicillines and non-steroidal anti-inflammatory drugs. Quinolones are only rarely known to cause AIN and so far cases have been mainly described with older fluoroquinolones. Case Presentation Here we describe a case of biopsy proven interstitial nephritis after moxifloxacin treatment. The patient presented with fever, rigors and dialysis dependent acute kidney injury, just a few days after treatment of a respiratory tract infection with moxifloxacin. The renal biopsy revealed dense infiltrates mainly composed of eosinophils and severe interstitial edema. A course of oral prednisolone (1 mg/kg/day) was commenced and rapidly tapered to zero within three weeks. The renal function improved, and the patient was discharged with a creatinine of 107 μmol/l. Conclusion This case illustrates that pharmacovigilance is important to early detect rare side effects, such as AIN, even in drugs with a favourable risk/benefit ratio such as moxifloxacin. PMID:20731847

  7. Sustained remission in lupus nephritis: still a hard road ahead.

    PubMed

    Quintana, Luis F; Jayne, David

    2016-12-01

    End-stage renal disease caused by lupus nephritis (LN) is an avoidable outcome yet there is considerable uncertainty and variability among nephrologists in their approaches to this disorder. This review discusses recent evidence relevant to the management of LN including recent consensus statements. Long-term results are encouraging compared with 30 years ago, but despite the use of the best available current therapies and achieving high levels of early clinical responses, the kidney often sustains long-term damage and nephritis relapses affect over 50%. Major hurdles to management include the complexity of the clinical presentation, histological features and serological tests, and the absence of reliable outcome predictors or markers of treatment response. The key serological and histopathological characteristics relevant to the practising nephrologist are reviewed, and the limitations of current disease activity markers discussed. There are many potential biomarkers under evaluation, and a framework for their validation is presented. Clinical trials of existing or newer agents for LN have typically been inconclusive and have raised problems of trial design and interpretation that are a barrier to new drug development. The major issues affecting clinical trial design and their potential solutions are summarized.

  8. Therapeutic Effect of Dendrobium candidum on Lupus Nephritis in Mice

    PubMed Central

    Wang, Qiang; Sun, Peng; Wang, Rui; Zhao, Xin

    2017-01-01

    Context: Dendrobium candidum (D. candimum) widely is a functional drug. The curative effect of D. candidum on lupus nephritis has been studied in vivo. Materials and Method: The DBA/2 and B6D2F1 mice were used for this in vivo experiment. The 50% effective dose (ED50) was used to check the effective concentration for this study. Then the SCr, BUN, TC, TG, IL-6, IL-12, TNF-α, and IFN-γ levels were determined by kits. The output of urine protein was determined by means of Coomassie Brilliant Blue, and the auto-antibody dsDNA was determined with titer plate technology and indirect immunofluorescence. The NF-κB, IκB-α, TGF ‘β1, Fas, and FasL expressions were measured by RT-PCR and western blot assay. The component analysis of D. candidum was determined by nuclear magnetic resonance. Results: Based on the ED50 result at 329 mg/kg, 200 and 400 mg/kg doses were chosen for this study. SCr, BUN, TC and TG levels of 400 mg/kg D. candidum mice were lower than control mice, TP and ALB levels were higher than control mice. The control and 400 mg/kg treated mice tested positive for dsDNA at the end of sixth and tenth week after the experiment began. The glomerular number of 400 mg/kg treated mice was more than control group. Treatment with 400 mg/kg D. candidum reduced IL-6, IL-12, TNF-α and IFN-γcytokine levels as compared to control mice. D. candidum decreased NF-κb, TGF ‘β1, Fas, FasL and increased IκB-α expressions in kidney tissue. There were 11 compounds in dry D. candidum, these compounds might make the curative effects of lupus nephritis. Conclusion: D. candidum showed a potential curative effect on lupus nephritis. It could be used as a health medicine on lupus nephritis. SUMMARY D. candidum reduced the SCr, BUN, TC, TG serum levels and raised the TP, ALB levels compared to control group.The glomerular number of D. candidum treated mice was more than control group.D. candidum treated mice showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than

  9. Electromyogram-evoked focal myositis

    PubMed Central

    Snipes, George; Quan, Carolyn

    2017-01-01

    Focal myositis is a rarely reported inflammatory disease of skeletal muscle, particularly of an extremity. It is often misinterpreted as an infectious syndrome, leading to prolonged antibiotic use and a delay in immunosuppressive therapy. Without a confirmed etiology to date, we present a case of recurrent focal myositis following an electromyogram. PMID:28127151

  10. Clearing the complexity: immune complexes and their treatment in lupus nephritis

    PubMed Central

    Toong, Catherine; Adelstein, Stephen; Phan, Tri Giang

    2011-01-01

    Systemic lupus erythematosus (SLE) is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies) and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control. PMID:21694945

  11. Renal allograft granulomatous interstitial nephritis: observations of an uncommon injury pattern in 22 transplant recipients

    PubMed Central

    Ellis, Carla L.; Rogers, Thomas E.; James Chon, W.; Chang, Anthony; Meehan, Shane M.

    2017-01-01

    Abstract Background: Granulomatous interstitial nephritis (GIN) is uncommon in native kidneys, and descriptions in allografts are few. We report clinical and pathologic findings in 22 allograft recipients with GIN identified in renal allograft biopsies and nephrectomies. Methods: Renal allografts with GIN were retrieved from the pathology files of two academic medical centers. Available clinical and pathologic data were compiled retrospectively for a 23-year period. Results: GIN was present in 23 specimens from 22 patients (15 males and 7 females) with allograft dysfunction [serum creatinine averaged 3.3 mg/dL (range 1.4–7.8)], at a mean age of 48 years (range 22–77). GIN was identified in 0.3% of biopsies at a mean of 552 days post transplantation (range 10–5898). GIN was due to viral (5), bacterial (5) and fungal (2) infections in 12 (54.5%), and drug exposure was the likely cause in 5 cases (22.7%). One had recurrent granulomatosis with polyangiitis. In 4 cases, no firm etiology of GIN was established. Of 18 patients with follow up data, 33.3% had a complete response to therapy, 44.5% had a partial response and 22.2% developed graft loss due to fungal and E. coli infections. All responders had graft survival for more than 1 year after diagnosis of GIN. Conclusions: Allograft GIN is associated with a spectrum of etiologic agents and was identified in 0.3% of biopsies. Graft failure occurred in 22% of this series, due to fungal and bacterial GIN; however, most had complete or partial dysfunction reversal and long–term graft survival after appropriate therapy.

  12. Severe nephrotoxic nephritis following conditional and kidney-specific knockdown of stanniocalcin-1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inflammation is the hallmark of nephrotoxic nephritis. Stanniocalcin-1 (STC1), a pro-survival factor, inhibits macrophages, stabilizes endothelial barrier function, and diminishes trans-endothelial migration of leukocytes; consistently, transgenic (Tg) overexpression of STC1 protects from nephrotoxi...

  13. Genetics Home Reference: focal dermal hypoplasia

    MedlinePlus

    ... Home Health Conditions focal dermal hypoplasia focal dermal hypoplasia Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Focal dermal hypoplasia is a genetic disorder that primarily affects the ...

  14. [IgG4 associated nephritis and recurrent hemoptysis: Case report].

    PubMed

    Erlij, Daniel; Rivera, Ángela; Maya, Juan Carlos; Cuellar, Carolina; Correa, Gonzalo; Michalland, Susana; Méndez, Gonzalo P

    2017-01-01

    IgG4 disease is a multi-systemic condition involving pancreas, salivary glands and lymph nodes. Less frequently, it causes interstitial nephritis and involves the lungs. We report a 58 years old male with a four years history of hemoptysis and renal dysfunction characterized by hematuria and proteinuria, responsive to steroidal therapy. The renal biopsy established the diagnosis of IgG4 associated interstitial nephritis. Lung involvement was considered secondary to the same systemic disease.

  15. Tubulointerstitial nephritis in a patient with probable autoimmune lymphoproliferative syndrome.

    PubMed

    Glerup, Mia; Herlin, Troels; Rittig, Søren; Grønbæk, Kirsten; Hokland, Marianne; Hasle, Henrik

    2013-07-01

    Autoimmune lymphoproliferative syndrome (ALPS) is caused by a nonmalignant defective Fas-mediated apoptosis. The main clinical manifestations are chronic lymphadenopathy, splenomegaly, and autoimmune cytopenia. Most patients with ALPS have a FAS germline mutation. ALPS has occasionally been associated with glomerulonephritis and we present the first report of tubulointerstitial nephritis associated with probable ALPS. A 5-year-old girl presented with fever, vomiting, hypertension, and azotemia. No autoantibodies, viral, or streptococcal antibodies were detected. A renal biopsy showed small-vessel vasculitis with normal glomeruli and inflammation in the interstitium. The patient responded to prednisolone treatment and obtained a full renal recovery. Symptoms of connective tissue disorder supervened and after the development of more pronounced splenomegaly, a diagnosis of ALPS was confirmed.

  16. Acute alloxan toxicity causes granulomatous tubulointerstitial nephritis with severe mineralization

    PubMed Central

    Zhang, Lianshan; Terayama, Yui; Nishimoto, Taiki; Kodama, Yasushi; Ozaki, Kiyokazu

    2016-01-01

    Alloxan had been recognized as having a direct nephrotoxic effect different from its diabetogenic action. We encountered previously unreported granulomatous tubulointerstitial nephritis with severe luminal and interstitial mineralization in one diabetic rat after one week of alloxan administration. Histopathologically, many dilated and occluded proximal and distal tubules were segmentally observed in the cortex and outer medulla. The tubular lumen contained minerals and cell debris. Tubular epithelial cells were degenerated and piled up, and they protruded into the lumen, where they enveloped minerals. Mineralization was observed mainly in the tubular lumen, and to some extent in the subepithelium and interstitium. The mineralization beneath the tubular epithelium was often continuous from the subepithelium to the interstitium. In these lesions, the tubular basement membrane was disrupted by mineralization, and a granuloma with multinuclear foreign-body giant cells was formed in the interstitial areas. PMID:27821911

  17. A rare case of lamotrigine-induced acute interstitial nephritis

    PubMed Central

    Matta, Atul; Assalie, Nour Abou; Gupta, Rajib K.; del Pilar Morales, Maria; Conti, Ricardo

    2016-01-01

    Medications, especially non-steroidal anti-inflammatory drugs and antimicrobials, have been most commonly associated with acute interstitial nephritis (AIN); antiepileptic drugs (AEDs) are rarely known to cause AIN. This is a case of a 27-year-old male who was recently started on treatment with lamotrigine for bipolar disorder and was found to have rapidly progressive renal failure. Renal biopsy features were suggestive of AIN. Lamotrigine-induced AIN was suspected to be the most likely cause. Discontinuation of the drug and treatment with steroids resulted in complete renal recovery. Lamotrigine use has been recently gaining popularity, not only as an AED but also as a mood stabilizer. With the use of this drug becoming more popular, it is important to emphasize that – although rare – AIN is one of its potential complications. PMID:27987281

  18. Drug-Induced Acute Interstitial Nephritis with Nifedipine

    PubMed Central

    Golbin, Léonard; Dolley-Hitze, Thibault; Lorcy, Nolwenn; Rioux-Leclercq, Nathalie; Vigneau, Cécile

    2016-01-01

    Background. Acute interstitial nephritis (AIN) is a frequent cause of Acute Kidney Injury (AKI). Drug hypersensitivity is the most common etiology and the list of drugs that can induce AIN is not exhaustive yet. Case Report. Here, we describe the case of a 43-year-old man who was treated with nifedipine (Adalate®) for Raynaud's syndrome. After nifedipine introduction, serum creatininemia progressively increased from 91 to 188 μmol/L in a few months and AKI was diagnosed. Laboratory work-up results indicated the presence of tubular proteinuria and nonspecific inflammatory syndrome. Histological analysis found granulomatous interstitial nephropathy without necrosis in 20% of the kidney biopsy without immunofluorescent deposit. Nifedipine was stopped and corticosteroid treatment was started with a rapid but incomplete reduction of serum creatininemia level to 106 μmol/L. Conclusion. This is the first case of AIN caused by nifedipine. PMID:26955492

  19. Lupus vasculopathy combined with acute renal failure in lupus nephritis.

    PubMed

    Wu, Chien-Te; Fu, Lin-Shien; Wen, Mei-Chin; Hung, Shein-Chung; Chi, Ching-Shiang

    2003-12-01

    Several risk factors have been associated with the prognosis of lupus nephritis. However, few studies have focused on renal vascular lesions (such as thrombi due to immune complexes) as a prognostic factor in this disease. Here we present a case of systemic lupus erythematosus (SLE) in a 12-year-old girl who exhibited acute renal failure and severe hypertension on admission. Renal pathology findings included diffuse proliferative glomerulonephritis (class IVb) and lupus vasculopathy (LV) with immune complex deposition within glomerular capillaries and the preglomerular arteriolar lumen. Her clinical condition deteriorated rapidly, even after cyclophosphamide and methylprednisolone pulse therapy. It improved after 5 days of plasmapheresis and remained stable for up to 6 months under regular treatment. We suggest that renal biopsy performed early in SLE patients with renal involvement should be studied carefully for the presence of vascular lesions. Additionally, plasmapheresis can be considered in patients with LV refractory to other modalities of therapy.

  20. Rapidly progressive lupus nephritis and concomitant thrombotic microangiopathy.

    PubMed

    Gharbi, Chems; Bourry, Edward; Rouvier, Philippe; Hacini, Sabria; Letaief, Ahmed; Baumelou, Alain; Izzedine, Hassane

    2010-10-01

    Although uncommon, thrombotic microangiopathy (TMA) is one of the most serious complications in patients with systemic lupus erythematosus. A 30-year-old black woman admitted to our hospital because of fever, fatigue, 'dark' urine and rapidly progressive renal failure was found to have systemic lupus erythematous and atypical hemolytic uremic syndrome. Kidney biopsy showed WHO class IV lupus nephritis with crescents and TMA. Hemodialysis was initiated for worsening renal failure. The patient was treated with corticosteroids, monthly pulse intravenous Cyclophosphamide, plasmapheresis and Rituximab on a weekly basis for 4 weeks. The patient's blood pressure was aggressively controlled using antihypertensive agents. Despite this extensive therapy, she remained dialysis dependent although hematological parameters returned to normal values.

  1. Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus: role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis.

    PubMed

    Hayakawa, Satoshi; Nakabayashi, Kimimasa; Karube, Miho; Arimura, Yoshihiro; Arimura, Yoshiro; Soejima, Akinori; Yamada, Akira; Fujioka, Yasunori

    2006-06-01

    Class IV-G (A/C) diffuse lupus nephritis and tubulointerstitial (TI) nephritis in a 31-year old woman was studied by light, immunofluorescence (IF), and electron microscopy (EM), to determine the pathogenesis of the TI lesions. The light microscopic findings showed peritubular capillaritis in the interstitium, with ruptures in the capillary structure, lysis of the surrounding tubular basement membrane (TBM), extravasated red blood cells (RBCs), the infiltration of neutrophils and mononuclear cells, and edema. The IF study revealed IgG, IgA, IgM, C1q, C3, and C4 depositions along the TBM, on the capillary walls, and in the interstitium proper. The EM study disclosed the deposition of immune complexes in the TBM, the capillary wall, and the interstitium proper. Based on these findings, the TI nephritis in this patient was considered to be due to peritubular capillaritis secondary to the immune complex depositions in the capillary wall of the interstitium.

  2. Impact of previous lupus nephritis on maternal and fetal outcomes during pregnancy.

    PubMed

    Saavedra, Miguel A; Cruz-Reyes, Claudia; Vera-Lastra, Olga; Romero, Griselda T; Cruz-Cruz, Polita; Arias-Flores, Rafael; Jara, Luis J

    2012-05-01

    Previous reports suggest that renal involvement before pregnancy or active renal disease during pregnancy may be associated with poor fetal and maternal outcomes in systemic lupus erythematosus (SLE) women. We report our experience of fetal and maternal complications in pregnant lupus women with and without previous lupus nephritis. We analyzed the clinical records of pregnant SLE patients attended in a tertiary reference center during a 5-year period. Patients were allocated into two groups according to the presence or absence of previous lupus nephritis. Women were evaluated monthly during pregnancy and at least 1 month postpartum. Maternal and fetal outcomes of pregnancy were abstracted. We included 95 pregnancies in 92 patients. Compared with pregnant women without lupus nephritis (n = 60), pregnancies with previous lupus nephritis (n = 35) were associated with a higher risk of maternal complications (88.5% vs. 43.3%, p = 0.00001), higher rate of lupus flares (54.2% vs. 25%, p = 0.004), and renal flares (45.7% vs. 6.6%, p = 0.00001), but most of which in most instances were reversible. On the other hand, fetal outcome was similar in both groups. Multivariate analysis showed that previous lupus nephritis and active lupus at conception were predictors of adverse maternal outcome. Pregnancies in women with previous lupus nephritis had a higher rate of maternal complications in comparison with those without. However, fetal prognosis was similar in both groups.

  3. Statistical Earthquake Focal Mechanism Forecasts

    NASA Astrophysics Data System (ADS)

    Kagan, Y. Y.; Jackson, D. D.

    2013-12-01

    The new whole Earth focal mechanism forecast, based on the GCMT catalog, has been created. In the present forecast, the sum of normalized seismic moment tensors within 1000 km radius is calculated and the P- and T-axes for the focal mechanism are evaluated on the basis of the sum. Simultaneously we calculate an average rotation angle between the forecasted mechanism and all the surrounding mechanisms. This average angle shows tectonic complexity of a region and indicates the accuracy of the prediction. The method was originally proposed by Kagan and Jackson (1994, JGR). Recent interest by CSEP and GEM has motivated some improvements, particularly to extend the previous forecast to polar and near-polar regions. The major problem in extending the forecast is the focal mechanism calculation on a spherical surface. In the previous forecast as our average focal mechanism was computed, it was assumed that longitude lines are approximately parallel within 1000 km radius. This is largely accurate in the equatorial and near-equatorial areas. However, when one approaches the 75 degree latitude, the longitude lines are no longer parallel: the bearing (azimuthal) difference at points separated by 1000 km reach about 35 degrees. In most situations a forecast point where we calculate an average focal mechanism is surrounded by earthquakes, so a bias should not be strong due to the difference effect cancellation. But if we move into polar regions, the bearing difference could approach 180 degrees. In a modified program focal mechanisms have been projected on a plane tangent to a sphere at a forecast point. New longitude axes which are parallel in the tangent plane are corrected for the bearing difference. A comparison with the old 75S-75N forecast shows that in equatorial regions the forecasted focal mechanisms are almost the same, and the difference in the forecasted focal mechanisms rotation angle is close to zero. However, though the forecasted focal mechanisms are similar

  4. Conformation and glycosylation of a megalin fragment correlate with nephritogenicity in Heymann nephritis.

    PubMed

    Tramontano, Alfonso; Makker, Sudesh P

    2004-02-15

    Active Heymann nephritis (AHN), a rat model of autoimmune glomerulonephritis, is induced by immunization with autologous megalin, a 600-kDa cell surface glycoprotein isolated from crude renal extracts. Recombinant proteins containing a 563-residue N-terminal sequence of megalin were obtained from Escherichia coli and baculovirus-insect cell expression systems. Rats immunized with the soluble, secreted protein encoded by a baculovirus construct elicited high titer anti-megalin autoantibodies and developed glomerular immune deposits and elevated proteinuria consistent with AHN. Rats treated with the bacterial or nonsecreted insect cell proteins produced a milder anti-megalin response and did not develop the disease. Nephritogenicity appeared to correlate with conformational or other structural features of native megalin. All three recombinant proteins were reactive in Western blots with rabbit anti-megalin antiserum, whereas the insect cell-derived proteins reacted preferentially in Western blot and ELISA with anti-megalin autoantibodies from rats with AHN induced by native megalin. Only the secreted insect cell product was stained in a lectin blot, suggesting its specific glycosylation. These observations provide evidence that a megalin N-terminal domain includes B and T cell epitopes sufficient for a pathogenic autoimmune response and that a native-like conformation and glycosylation are essential for the induction of disease. The importance of conformational B cell epitopes for pathogenic autoantibodies recapitulates observations made in other models of organ-specific autoimmune disease. Glycosidic modifications could influence the presentation of either B or T cell epitopes in AHN, consistent with emerging evidence of the role of post-translational modifications in pathogenic autoimmune responses.

  5. Renal Dnase1 Enzyme Activity and Protein Expression Is Selectively Shut Down in Murine and Human Membranoproliferative Lupus Nephritis

    PubMed Central

    Rekvig, Ole Petter

    2010-01-01

    Background Deposition of chromatin-IgG complexes within glomerular membranes is a key event in the pathogenesis of lupus nephritis. We recently reported an acquired loss of renal Dnase1 expression linked to transformation from mild to severe membranoproliferative lupus nephritis in (NZBxNZW)F1 mice. As this may represent a basic mechanism in the progression of lupus nephritis, several aspects of Dnase1 expression in lupus nephritis were analyzed. Methodology/Principal Findings Total nuclease activity and Dnase1 expression and activity was evaluated using in situ and in vitro analyses of kidneys and sera from (NZBxNZW)F1 mice of different ages, and from age-matched healthy controls. Immunofluorescence staining for Dnase1 was performed on kidney biopsies from (NZBxNZW)F1 mice as well as from human SLE patients and controls. Reduced serum Dnase1 activity was observed in both mesangial and end-stage lupus nephritis. A selective reduction in renal Dnase1 activity was seen in mice with massive deposition of chromatin-containing immune complexes in glomerular capillary walls. Mice with mild mesangial nephritis showed normal renal Dnase1 activity. Similar differences were seen when comparing human kidneys with severe and mild lupus nephritis. Dnase1 was diffusely expressed within the kidney in normal and mildly affected kidneys, whereas upon progression towards end-stage renal disease, Dnase1 was down-regulated in all renal compartments. This demonstrates that the changes associated with development of severe nephritis in the murine model are also relevant to human lupus nephritis. Conclusions/Significance Reduction in renal Dnase1 expression and activity is limited to mice and SLE patients with signs of membranoproliferative nephritis, and may be a critical event in the development of severe forms of lupus nephritis. Reduced Dnase1 activity reflects loss in the expression of the protein and not inhibition of enzyme activity. PMID:20856893

  6. Continuously variable focal length lens

    DOEpatents

    Adams, Bernhard W; Chollet, Matthieu C

    2013-12-17

    A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

  7. Genetic models of focal epilepsies.

    PubMed

    Boillot, Morgane; Baulac, Stéphanie

    2016-02-15

    Focal epilepsies were for a long time thought to be acquired disorders secondary to cerebral lesions. However, the important role of genetic factors in focal epilepsies is now well established. Several focal epilepsy syndromes are now proven to be monogenic disorders. While earlier genetic studies suggested a strong contribution of ion channel and neurotransmitter receptor genes, later work has revealed alternative pathways, among which the mammalian target of rapamycin (mTOR) signal transduction pathway with DEPDC5. In this article, we provide an update on the mutational spectrum of neuronal nicotinic acetylcholine receptor genes (CHRNA4, CHRNB2, CHRNA2) and KCNT1 causing autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), and of LGI1 in autosomal dominant epilepsy with auditory features (ADEAF). We also emphasize, through a review of the current literature, the contribution of in vitro and in vivo models developed to unveil the pathogenic mechanisms underlying these two epileptic syndromes.

  8. Focal epithelial hyperplasia: Case report.

    PubMed

    Puriene, Alina; Rimkevicius, Arunas; Gaigalas, Mindaugas

    2011-01-01

    The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources.

  9. BASOPHILS AND THE T HELPER 2 ENVIRONMENT CAN PROMOTE THE DEVELOPMENT OF LUPUS NEPHRITIS

    PubMed Central

    Charles, Nicolas; Hardwick, Donna; Daugas, Eric; Illei, Gabor G.; Rivera, Juan

    2010-01-01

    Summary In systemic lupus erythematosus (SLE) self-reactive antibodies can target the kidney (lupus nephritis) leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE, causes their homing to lymph nodes, promoting TH2 cell differentiation, and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in Lyn−/− mice. SLE patients also have elevated serum IgE, self-reactive IgE's, and activated basophils that express CD62L and the MHC Class II molecule, HLA-DR; parameters that were found to be associated with increased disease activity and active lupus nephritis. Basophils were also present in the lymph nodes and spleen of SLE patients. Thus, in Lyn−/− mice, basophils and IgE autoantibodies amplify autoantibody production that leads to lupus nephritis, and in SLE patients, the presence of IgE autoantibodies and activated basophils are factors associated with disease activity and nephritis. PMID:20512127

  10. Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis.

    PubMed

    D'Cruz, D P; Houssiau, F A; Ramirez, G; Baguley, E; McCutcheon, J; Vianna, J; Haga, H J; Swana, G T; Khamashta, M A; Taylor, J C

    1991-08-01

    Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.

  11. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis

    PubMed Central

    2012-01-01

    Introduction BLyS and APRIL are cytokines from the tumor necrosis factor family which play an important role in systemic lupus erythematosus (SLE). Previous works suggested an association between both molecules and SLE disease activity although their correlation with lupus nephritis is not known. We therefore assessed serum BLyS and APRIL in active lupus nephritis patients. Methods Serum samples from active lupus nephritis and at 6 months post-treatment were obtained. Serum levels of BLyS and APRIL (n = 47) as well as renal mRNA expression were measured. Serum levels of both molecules and clinical data (n = 27) were available at 6 months follow-up. All biopsy-proven lupus nephritis patients were treated with similar immunosuppressive drugs. Results Serum levels of APRIL were associated with proteinuria (Rs = 0.44, P value < 0.01) and degree of histological activity (Rs = 0.34; P value < 0.05) whereas BLyS levels were associated with complement levels (Rs = 0.46; P value < 0.01) and dosage of immunosuppressant. Interestingly, serum APRIL as well as its intrarenal mRNA levels were associated with resistance to treatment. From the receiver operating characteristic (ROC) analysis, high levels (> 4 ng/mL) of serum APRIL predicted treatment failure with a positive predictive value of 93 percent. Conclusion APRIL could be a potential biomarker for predicting difficult-to-treat cases of lupus nephritis. PMID:23171638

  12. The safety and efficacy of MMF in lupus nephritis: a pilot study.

    PubMed

    Kingdon, E J; McLean, A G; Psimenou, E; Davenport, A; Powis, S H; Sweny, P; Burns, A

    2001-01-01

    Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with superimposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3/10 with MMF alone and 1/10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9/13 and steroid dosage was reduced in 8/10 patients. Infections occurred in 3/13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.

  13. Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies

    PubMed Central

    Yung, Susan; Chan, Tak Mao

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortality that affects over half of the SLE population during the course of disease. The etiology of lupus nephritis is multifactorial and remains to be fully elucidated. Accumulating evidence suggests that in addition to forming immune complexes and triggering complement activation, anti-dsDNA antibodies contribute to the pathogenesis of lupus nephritis through binding, either directly or indirectly, to cross-reactive antigens or chromatin materials, respectively, to resident renal cells and/or extracellular matrix components, thereby triggering downstream cellular activation and proliferation as well as inflammatory and fibrotic processes. Several cross-reactive antigens that mediate anti-dsDNA antibody binding have been identified, such as annexin II and alpha-actinin. This review discusses the mechanisms through which anti-dsDNA antibodies contribute to immunopathogenesis in lupus nephritis. Corticosteroids combined with either mycophenolic acid (MPA) or cyclophosphamide is the current standard of care immunosuppressive therapy for severe lupus nephritis. This review also discusses recent data showing distinct effects of MPA and cyclophosphamide on inflammatory and fibrotic processes in resident renal cells. PMID:26441980

  14. Treatment of lupus nephritis: practical issues in Asian countries.

    PubMed

    Yap, Desmond Y H; Chan, Tak Mao

    2015-02-01

    Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus in Asian patients, and is an important cause of renal failure in Asian countries. Immunosuppressive treatments of LN have evolved over the past few decades and resulted in improvements in patient outcomes. Treatment guidelines have been recently published by rheumatology and nephrology communities in the USA and Europe, but the emphasis was more on patients of African or Hispanic descent and Caucasians. There is increasing evidence that racial and ethnic variations are associated with differences in disease manifestations, pharmacogenomics/kinetics, response to therapy and complications of disease or treatment. There is substantial data confirming the efficacy of combined corticosteroids and either cyclophosphamide or mycophenolate mofetil (MMF) as initial treatments for active Class III/IV LN in Asian patients. Azathioprine, MMF or a calcineurin inhibitor, or possibly mizoribine which requires further investigation in non-Japanese patients, in combination with low-dose corticosteroids, can be considered as maintenance immunosuppression to prevent disease flares, and the optimal choice needs to take into account tolerability and prior induction therapy. Treatment costs and accessibility to specialist healthcare facilities, compliance which in turn is related to socio-economic and education status, as well as regional variations in risk of infections, including subacute infection such as tuberculosis or chronic infections such as hepatitis B or C, are issues that are distinctly pertinent in Asia.

  15. Granulomatous interstitial nephritis: Our experience of 14 patients

    PubMed Central

    Naidu, G. D.; Ram, R.; Swarnalatha, G.; Uppin, M.; Prayaga, A. K.; Dakshinamurty, K. V.

    2013-01-01

    Granulomatous interstitial nephritis (GIN) is a rare condition. Drugs, infections, immune processes, and foreign body reaction are the main causes. We identified a total of 14 patients with GIN during a period of 13 years in 2798 renal biopsies. There were 8 males and 6 females in the age range of 20-70 (mean 35 ± 12) years. The serum creatinine at presentation was 6.7 ± 3.8 (range: 2.3-14.7) mg/dl. In nine patients tuberculosis was the causative agent. Drugs (n = 2) and Wegener's granulomatosis (n = 1) were other etiologies. Systemic lupus erythematosis (SLE) and Immunoglobulin A nephropathy (IgAN) were seen in one patient each. Patients with tuberculosis were treated with antituberculous therapy and three of them improved. Four out of six patients who required dialysis at presentation remained dialysis dependent, one of whom underwent renal transplantation. Two patients progressed to end stage renal disease after 7 years and 9 years each. The patients with drug induced GIN had improvement in renal function after prednisolone treatment. Patients with SLE, and Wegener's granulomatosis responded to immunosuppression. Patient with IgAN was on conservative management. Finally, six patients were on conservative management for chronic renal failure. PMID:24339518

  16. Advances in the care of children with lupus nephritis.

    PubMed

    Wenderfer, Scott E; Ruth, Natasha M; Brunner, Hermine I

    2017-01-04

    The care of children with lupus nephritis (LN) has changed dramatically over the past 50 y. The majority of patients with childhood-onset systemic lupus erythematosus (cSLE) develop LN. In the 1960's, prognosis in children was worse than in adults; therapies were limited and toxic. Nearly half of cases resulted in death within 2 y. Since this time, several diagnostic recommendations and disease-specific indices have been developed to assist physicians caring for patients with LN. Pediatric researchers are validating and adapting these indices and guidelines for the treatment of LN in cSLE. Classification systems, activity, and chronicity indices for kidney biopsy have been validated in pediatric cohorts in several countries. Implementation of contemporary immunosuppressive agents has reduced treatment toxicity and improved outcomes. Biomarkers sensitive to LN in children have been identified in the kidney, urine, and blood. Multi-institutional collaborative networks have formed to address the challenges of pediatric LN research. Considerable variation in evaluation and treatment has been addressed for proliferative forms of LN by development of consensus treatment practices. Patient survival at 5 y is now 95-97% and renal survival exceeds 90%. Moreover, international consensus exists for quality indicators for cSLE that consider the unique aspects of chronic disease in childhood.Pediatric Research (2017); doi:10.1038/pr.2016.247.

  17. Acute interstitial nephritis – a reappraisal and update

    PubMed Central

    Raghavan, Rajeev; Eknoyan, Garabed

    2014-01-01

    Acute interstitial nephritis (AIN) is an under recognized and under diagnosed cause of acute kidney injury (AKI). It is estimated to account for 15 – 20% of cases of AKI; it is the reported diagnosis in 2.8% of all kidney biopsies, and 13.5% of biopsies done specifically for acute renal failure. Considerable evidence implicates antigen initiated cell-mediated injury in the pathogenesis of AIN. Drugs account for 70% of all cases, with over 150 different agents incriminated. The remaining cases are due to infections, autoimmune diseases, and rarely idiopathic. The central component of renal injury in AIN is altered tubular function, which usually precedes decrements in filtration rate. The key to early diagnosis is vigilance for the presence of tubular dysfunction in non-oliguric individuals, especially in patients with modest but gradual increments in creatinine level. The utility of urinary biomarkers to diagnose AIN in its early nascent and potentially reversible stage remains to be determined. Prompt recognition, elimination of the offending source of antigen, and use of a limited course of steroid therapy where indicated, will result in complete resolution in ~ 65% of cases, partial resolution in up to 20%, and irreversible damage in the rest. PMID:25079860

  18. Prognostic significance of renal vascular pathology in lupus nephritis.

    PubMed

    Mejía-Vilet, J M; Córdova-Sánchez, B M; Uribe-Uribe, N O; Correa-Rotter, R; Morales-Buenrostro, L E

    2017-01-01

    We performed a retrospective cohort analysis to define the prognostic significance of vascular lesions documented in renal biopsies of lupus nephritis patients. A total of 429 patients were segregated into five groups: (1) no vascular lesions (NVL), (2) arterial sclerosis (AS), (3) non-inflammatory necrotizing vasculitis (NNV), (4) thrombotic microangiopathy (TMA), and (5) true renal vasculitis (TRV). Renal outcomes were analyzed by Cox regression models, and correlations between vascular lesions and activity/chronicity scores were determined by Spearman's coefficients. A total of 200 (46.6%) had NVL, 189 (44.0%) AS, six NNV (1.4%), 23 (5.4%) TMA, and 11 (2.6%) TRV. Patients with NVL were younger, with higher renal function; patients with TMA and TRV had lower renal function and higher arterial pressure at baseline. Antiphospholipid syndrome and positive lupus anticoagulant were more frequently observed in the TMA group. Five-year renal survival was 83% for NVL, 63% for AS, 67% for NNV, 31% for TMA, and 33% for TRV. NNV and TRV were significantly correlated with activity scores, while AS and chronic TMA were correlated with chronicity scores. Renal vascular lesions are associated with renal outcomes but do not behave as independent factors. The addition of vascular lesions to currently used scores should be further explored.

  19. Nephrotoxic nephritis and glomerulonephritis: animal model versus human disease.

    PubMed

    Muhammad, S

    2014-01-01

    Glomerulonephritis (GN) encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus of the kidney. The pathogenesis of GN is complex. Intricacy arises from factors such as autoimmunity, cancer and structural abnormalities within the kidney. Studies using animal models have highlighted crucial interaction between inflammatory cells and cells intrinsic to the kidney, both of which are fundamental to the pathogenesis of GN. This review aims to provide insight on a 'suitable' model for nephrotoxic nephritis and glomerulonephritis (NTN GN) and relate its experimental validity to humans. The BALB/c NTN murine model and Wistar Kyoto (WKY) rat have held experimental validity in the study of GN in humans. The chemokine receptor CXCR3 also mediates renal T-cell recruitment and subsequent tissue injury in NTN. It is noteworthy to consider CXCR3 blockade in Th1-mediated renal inflammation as future therapeutic options for patients with GN and subsets thereof. Currently used immunosuppressive therapies for GN are not always uniformly effective and are frequently associated with serious side-effects. Corticosteroids are effective in several types of GN owing to their ability to inhibit the pro-inflammatory effects of cytokines known to promote glomerular inflammation. Differences between experimental and human GN complicate translation of experimental therapies into practice. More research is required to translate animal model research into a better comprehension of human GN disease. However, the complexity of GN research makes findings a challenge to replicate.

  20. Obstetric nephrology: lupus and lupus nephritis in pregnancy.

    PubMed

    Stanhope, Todd J; White, Wendy M; Moder, Kevin G; Smyth, Andrew; Garovic, Vesna D

    2012-12-01

    SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancy-related complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy.

  1. Outcome of the acute glomerular injury in proliferative lupus nephritis

    SciTech Connect

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. )

    1989-09-01

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

  2. The prevalence of interstitial nephritis and leptospirosis in 283 raccoons (Procyon lotor) from 5 different sites in the United States.

    PubMed Central

    Hamir, A N; Hanlon, C A; Niezgoda, M; Rupprecht, C E

    2001-01-01

    A retrospective histopathological study was carried out on tissues of 283 raccoons from 5 different geographical locations for presence of interstitial nephritis and renal leptospirosis. Results of this study indicate that although interstitial nephritis was common in raccoons from all locations, the presence of renal leptospiral spirochetes was not. PMID:11708206

  3. Statistical earthquake focal mechanism forecasts

    NASA Astrophysics Data System (ADS)

    Kagan, Yan Y.; Jackson, David D.

    2014-04-01

    Forecasts of the focal mechanisms of future shallow (depth 0-70 km) earthquakes are important for seismic hazard estimates and Coulomb stress, and other models of earthquake occurrence. Here we report on a high-resolution global forecast of earthquake rate density as a function of location, magnitude and focal mechanism. In previous publications we reported forecasts of 0.5° spatial resolution, covering the latitude range from -75° to +75°, based on the Global Central Moment Tensor earthquake catalogue. In the new forecasts we have improved the spatial resolution to 0.1° and the latitude range from pole to pole. Our focal mechanism estimates require distance-weighted combinations of observed focal mechanisms within 1000 km of each gridpoint. Simultaneously, we calculate an average rotation angle between the forecasted mechanism and all the surrounding mechanisms, using the method of Kagan & Jackson proposed in 1994. This average angle reveals the level of tectonic complexity of a region and indicates the accuracy of the prediction. The procedure becomes problematical where longitude lines are not approximately parallel, and where shallow earthquakes are so sparse that an adequate sample spans very large distances. North or south of 75°, the azimuths of points 1000 km away may vary by about 35°. We solved this problem by calculating focal mechanisms on a plane tangent to the Earth's surface at each forecast point, correcting for the rotation of the longitude lines at the locations of earthquakes included in the averaging. The corrections are negligible between -30° and +30° latitude, but outside that band uncorrected rotations can be significantly off. Improved forecasts at 0.5° and 0.1° resolution are posted at http://eq.ess.ucla.edu/kagan/glob_gcmt_index.html.

  4. Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

    PubMed Central

    Liu, Kui; Li, Quan-Zhen; Delgado-Vega, Angelica M.; Abelson, Anna-Karin; Sánchez, Elena; Kelly, Jennifer A.; Li, Li; Liu, Yang; Zhou, Jinchun; Yan, Mei; Ye, Qiu; Liu, Shenxi; Xie, Chun; Zhou, Xin J.; Chung, Sharon A.; Pons-Estel, Bernardo; Witte, Torsten; de Ramón, Enrique; Bae, Sang-Cheol; Barizzone, Nadia; Sebastiani, Gian Domenico; Merrill, Joan T.; Gregersen, Peter K.; Gilkeson, Gary G.; Kimberly, Robert P.; Vyse, Timothy J.; Kim, Il; D’Alfonso, Sandra; Martin, Javier; Harley, John B.; Criswell, Lindsey A.; Wakeland, Edward K.; Alarcón-Riquelme, Marta E.; Mohan, Chandra

    2009-01-01

    Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody–induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody–induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody–induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody–induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody–induced nephritis and lupus. PMID:19307730

  5. Tubulointerstitial Nephritis as the Initial Presentation of Crohn’s Disease and Successful Treatment with Infliximab

    PubMed Central

    Caza, Tiffany; Huang, Dongmei; Beg, Mirza B.

    2017-01-01

    Tubulointerstitial nephritis (TIN) is not commonly associated in aminosalicylate-naïve patients with Crohn’s disease (CD). Our case describes the initial presentation, diagnosis, and management of an adolescent presenting with TIN and underlying CD. Our case emphasizes that CD should be considered in the differential diagnosis of interstitial nephritis as not only a medication-related effect, but also as an extraintestinal manifestation of CD. We also describe successful management of undiagnosed recurring and symptomatic CD-related TIN with infliximab. PMID:28286790

  6. Unusual manifestations of acute Q fever: autoimmune hemolytic anemia and tubulointerstitial nephritis.

    PubMed

    Korkmaz, Serdal; Elaldi, Nazif; Kayatas, Mansur; Sencan, Mehmet; Yildiz, Esin

    2012-05-18

    Q fever is a worldwide zoonotic infection that caused by Coxiella burnetii, a strict intracellular bacterium. It may be manifested by some of the autoimmune events and is classified into acute and chronic forms. The most frequent clinical manifestation of acute form is a self-limited febrile illness which is associated with severe headache, muscle ache, arthralgia and cough. Meningoencephalitis, thyroiditis, pericarditis, myocarditis, mesenteric lymphadenopathy, hemolytic anemia, and nephritis are rare manifestations. Here we present a case of acute Q fever together with Coombs' positive autoimmune hemolytic anemia (AIHA) and tubulointerstitial nephritis treated with chlarithromycin, steroids and hemodialysis. Clinicians should be aware of such rare manifestations of the disease.

  7. Megalocytic interstitial nephritis following acute pyelonephritis with Escherichia coli bacteremia: a case report.

    PubMed

    Kwon, Hee Jin; Yoo, Kwai Han; Kim, In Young; Lee, Seulkee; Jang, Hye Ryoun; Kwon, Ghee Young

    2015-01-01

    Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient's renal function was markedly improved after short-term treatment with high-dose steroid.

  8. Hereditary nephritis (with unusual renal histology): report of a first case from the West Indies.

    PubMed Central

    Hayes, J. S.; Jankey, N.

    1976-01-01

    A 21-year-old Grenadian girl undergoing investigation in Trinidad for anaemia was diagnosed as a case of hereditary nephritis. She had the clinical features of a nephropathy, nerve deafness and an ocular defect. Renal histology was exceptional in that in addition to the typical findings of a hereditary nephritis, cystic areas generally associated with medullary cystic disease were noted. Several members of the patient's maternal family were afflicted with either deafness visual distrubances or renal disease. Images Fig. 1 Fig. 4 PMID:1013001

  9. Lupus nephritis in children – 10 years’ experience

    PubMed Central

    Kuźma-Mroczkowska, Elżbieta; Małdyk, Jadwiga; Pańczyk-Tomaszewska, Małgorzata

    2016-01-01

    Systemic lupus erythematosus (SLE) in children is usually more severe than it is in adults and there is a higher incidence of renal involvement. We described 18 children (16 girls, 2 boys) with lupus nephritis (LN), whose average age was 14.4 ±1.81 years. Disease activity was assessed according to SLEDAI (SLE Disease Activity Index). Renal biopsy was classified according to the INS/RPS (International Society of Nephrology/Renal Pathology Society). The patients were treated with steroids (100%) and pulses of cyclophosphamide (88.9%) or mycophenolate mofetil (11.1%), next azathioprine or mycophenolate mofetil with prednisone in reduced doses. In children with renal/multi-organ insufficiency and/or septicaemia, renal replacement therapy (27.8%), and plasmapheresis (22.2%) were used in the initial treatment. The SLEDAI initial activity was high in 44.4% and moderate in 55.6% of children. LN manifested as: nephrotic syndrome (83.3%), microhaematuria (100%), leukocyturia (60%), hypertension (72.2%), and acute renal injury (83.3%); mean GFR was 54.55 ±33.09 ml/min/1.73 m2. In the renal biopsy, class IV LN according to INS/RPS was mainly diagnosed (82%). At the end of follow-up, mean observation time 32.1±23.36 months: mean GFR was 90.87 ±12.13 ml/min/1.73 m2, proteinuria disappeared in 66.7% and decreased in 33.3% of children to the average of 1.7 g/day (range: 0.5-4.0 g/day), hypertension was observed in 83.4% of children. Intensive immunosuppressive treatment with pulses of cyclophosphamide in early stage of LN in children is very effective. PMID:27833441

  10. Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

    PubMed

    Ebihara, Itaru; Hirayama, Kouichi; Usui, Joichi; Seki, Masanori; Higuchi, Fujiko; Oteki, Takaaki; Kobayashi, Masaki; Yamagata, Kunihiro

    2006-09-01

    We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

  11. Variable focal length deformable mirror

    DOEpatents

    Headley, Daniel; Ramsey, Marc; Schwarz, Jens

    2007-06-12

    A variable focal length deformable mirror has an inner ring and an outer ring that simply support and push axially on opposite sides of a mirror plate. The resulting variable clamping force deforms the mirror plate to provide a parabolic mirror shape. The rings are parallel planar sections of a single paraboloid and can provide an on-axis focus, if the rings are circular, or an off-axis focus, if the rings are elliptical. The focal length of the deformable mirror can be varied by changing the variable clamping force. The deformable mirror can generally be used in any application requiring the focusing or defocusing of light, including with both coherent and incoherent light sources.

  12. Focal hyperhidrosis: diagnosis and management

    PubMed Central

    Haider, Aamir; Solish, Nowell

    2005-01-01

    HYPERHIDROSIS, A CONDITION CHARACTERIZED by excessive sweating, can be generalized or focal. Generalized hyperhidrosis involves the entire body and is usually part of an underlying condition, most often an infectious, endocrine or neurologic disorder. Focal hyperhidrosis is idiopathic, occurring in otherwise healthy people. It affects 1 or more body areas, most often the palms, armpits, soles or face. Almost 3% of the general population, largely people aged between 25 and 64 years, experience hyperhidrosis. The condition carries a substantial psychological and social burden, since it interferes with daily activities. However, patients rarely seek a physician's help because many are unaware that they have a treatable medical disorder. Early detection and management of hyperhidrosis can significantly improve a patient's quality of life. There are various topical, systemic, surgical and nonsurgical treatments available with efficacy rates greater than 90%–95%. PMID:15632408

  13. Stigmatic flat focal field spectrograph

    NASA Astrophysics Data System (ADS)

    Niemczyk, T. M.; Gobeli, G. W.

    Advances in two dimensional detectors have created a need for a spectrograph that can produce high fidelity images. Aberrations that detract from image quality in conventional spectrographs are discussed. Ray trace and experimental results obtained for a unique spectrograph designed for use with array detectors, i.e., designed to produce high fidelity images, are presented. The spectrograph employs toroidal mirrors to achieve stigmatic imaging in a flat focal field.

  14. Almost Unilateral Focal Dermal Hypoplasia

    PubMed Central

    Lee, Solam; Choe, Sung Jay

    2017-01-01

    Focal dermal hypoplasia, caused by mutations in PORCN, is an X-linked ectodermal dysplasia, also known as Goltz syndrome. Only seven cases of unilateral or almost unilateral focal dermal hypoplasia have been reported in the English literature and there have been no previously reported cases in the Republic of Korea. A 19-year-old female presented with scalp defects, skin lesions on the right leg and the right trunk, and syndactyly of the right fourth and fifth toes. Cutaneous examination revealed multiple atrophic plaques and a brown and yellow mass with fat herniation and telangiectasia that was mostly located on the lower right leg. She had syndactyly on the right foot and the scalp lesion appeared to be an atrophic, membranous, fibrotic alopecic scar. A biopsy of the calf revealed upper dermal extension of fat cells, dermal atrophy, and loss of dermal collagen. A diagnosis of almost unilateral focal dermal hypoplasia was made on the basis of physical and histologic findings. Henceforth, the patient was referred to a plastic surgeon and an orthopedics department to repair her syndactyly. PMID:28223754

  15. Persistent Focal Behavior and Physical Activity Performance

    ERIC Educational Resources Information Center

    Erfle, Stephen E.

    2014-01-01

    This article examines the proclivity and performance attributes of focal students across time and activities using data from 9,345 students. Three systematic focal behavior partitions are examined: Across activities, across time, and across activities and time. A student's performance is focal if it ends in 0 or 5 for push-ups and 0 for curl-ups.…

  16. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

    PubMed Central

    Tamirou, Farah; D'Cruz, David; Sangle, Shirish; Remy, Philippe; Vasconcelos, Carlos; Fiehn, Christoph; Ayala Guttierez, Maria del Mar; Gilboe, Inge-Magrethe; Tektonidou, Maria; Blockmans, Daniel; Ravelingien, Isabelle; le Guern, Véronique; Depresseux, Geneviève; Guillevin, Loïc; Cervera, Ricard; Houssiau, Frédéric A

    2016-01-01

    Objective To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. Methods In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. Results Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. Conclusions The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome. Trial registration number NCT00204022. PMID:25757867

  17. Heparin-Related Thrombocytopenia Triggered by Severe Status of Systemic Lupus Erythematosus and Bacterial Infection

    PubMed Central

    Nakajima, Shihoko; Ando, Taiki; Oda, Keisuke; Sugita, Manabu; Maeda, Kunimi; Nakiri, Yutaka

    2016-01-01

    A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT. PMID:27699076

  18. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease.

    PubMed

    Cornell, Lynn D; Chicano, Sonia L; Deshpande, Vikram; Collins, A Bernard; Selig, Martin K; Lauwers, Gregory Y; Barisoni, Laura; Colvin, Robert B

    2007-10-01

    Autoimmune pancreatitis (AIP) is a mass-forming chronic fibroinflammatory condition centered on the pancreatobiliary system and characterized by predominant immunoglobulin G4 (IgG4)-positive plasma cells. Recent reports have brought to light the multiorgan involvement of this disease. We describe a series of 5 cases of tubulointerstitial nephritis (TIN) associated with AIP and characterize the clinical, pathologic, ultrastructural, and immunopathologic features of TIN. The specimens consisted of 4 biopsies and 1 nephrectomy. The average patient age was 64 years (range 45 to 78) and the male to female ratio was 4:1. All had histologic and/or clinical and radiographic evidence of AIP, mass-forming sclerosing cholangitis, or both. The clinical impression in 4 patients was a renal mass or vasculitis. Two patients had renal insufficiency. Histologic preparations revealed a dense tubulointerstitial lymphoplasmacytic infiltrate. Eosinophils were often numerous. Tubulitis and tubular injury were present, along with tubular atrophy with focally thickened tubular basement membranes (TBMs). The histologic appearance ranged from a cellular, inflammatory pattern without tubular atrophy to a striking expansive interstitial fibrosis with tubular destruction. The nephrectomy specimen demonstrated a masslike nodular pattern of inflammation with normal renal tissue elsewhere. Glomeruli were uninvolved. By immunohistochemistry or immunofluorescence, numerous plasma cells in the infiltrate were positive for IgG4. TBM granular IgG deposits, predominantly of the IgG4 subclass, were detected in 4 of 5 cases by either immunofluorescence or immunohistochemistry. By electron microscopy, corresponding amorphous electron-dense deposits were present in the TBM in these cases. This type of TIN, typically characterized by a masslike lesion consisting of a lymphoplasmacytic infiltrate with eosinophils and prominent IgG4-positive plasma cells and immune-complex deposits in the TBM, may be part of

  19. [Case of suspicious lansoprazole-associated collagenous colitis in ANCA-associated nephritis].

    PubMed

    Sasatomi, Yoshie; Takahata, Masafumi; Abe, Yasuhiro; Ishimura, Atsunori; Miyake, Katsuhisa; Ogahara, Satoru; Murata, Toshiaki; Nakashima, Hitoshi; Maeda, Kazuhiro; Saito, Takao

    2010-01-01

    In January 2003, a 70-year-old female consulted a doctor for a fever of unknown origin. She had microscopic hematuria, proteinuria, BUN 41 mg/dL, Cr 2.1 mg/dL and MPO-ANCA 44 U/mL, and was suspected of having ANCA-associated nephritis. A renal biopsy was not conducted because the patient had just one kidney. She was treated with prednisolone (PSL ; 40 mg/day). Subsequently, because of Cr level improvement, the amount of PSL was decreased. In October 2006, the patient again had microscopic hematuria, proteinuria and a slightly elevated Cr level. Lowering of BP and dehydration caused by a common cold were considered to be the cause of her renal dysfunction. She was admitted to Fukuoka University Hospital for 2 weeks, where she received diet therapy and a changed medication schedule in which furosemide was stopped and the dose of enalapril was decreased from 5 mg/day to 2.5 mg/day. Because the MPO-ANCA level was < 10 EU, the amount of PSL was not changed. After 11 months, treatment with lansoprazole at 30 mg/day was started. At the end of the same month, however, she exhibited gait disturbance due to swelling, redness and tenderness in the bilateral pedal joints. After one month of receiving lansoprazole, she experienced a high fever and an elevated Cr level. Accordingly she was again admitted to the hospital, where she was diagnosed with venous thrombosis in the lower limbs, and warfarization was begun. Her condition improved, gradually, and she was discharged from the hospital. After the discharge, she began to exhibit watery diarrhea three to four times per day. Therefore, treatment with warfarin potassium was stopped 50 days after it was begun. In spite of the cessation of warfarization, the diarrhea continued. She underwent bacterial culturing and lower endoscopic examinations (no biopsy was done), which showed erosion of the colon, but the cause of the diarrhea was not found. After 181 days of treatment with lansoprazole, administration of this drug was stopped

  20. Karyomegalic Interstitial Nephritis: A Case Report and Review of the Literature.

    PubMed

    Isnard, Pierre; Rabant, Marion; Labaye, Jacques; Antignac, Corinne; Knebelmann, Bertrand; Zaidan, Mohamad

    2016-05-01

    Karyomegalic interstitial nephritis is a rare cause of hereditary chronic interstitial nephritis, described for the first time over 40 years ago.A 36-year-old woman, of Turkish origin, presented with chronic kidney disease and high blood pressure. She had a history of recurrent upper respiratory tract infections but no familial history of nephropathy. Physical examination was unremarkable. Laboratory tests showed serum creatinine at 2.3 mg/dL with an estimated glomerular filtration rate of 26 mL/min/1.73m, and gamma-glutamyl transpeptidase and alkaline phosphatase at 3 and 1.5 times the upper normal limit. Urinalysis showed 0.8 g/day of nonselective proteinuria, microscopic hematuria, and aseptic leukocyturia. Immunological tests and tests for human immunodeficiency and hepatitis B and C viruses were negative. Complement level and serum proteins electrophoresis were normal. Analysis of the renal biopsy showed severe interstitial fibrosis and tubular atrophy. Numerous tubular cells had nuclear enlargement with irregular outlines, hyperchromatic aspect, and prominent nucleoli. These findings were highly suggestive of karyomegalic interstitial nephritis, which was further confirmed by exome sequencing of FAN1 gene showing an identified homozygous frameshift mutation due to a one-base-pair deletion in exon 12 (c.2616delA).The present case illustrates a rare but severe cause of hereditary interstitial nephritis, sometimes accompanied by subtle extrarenal manifestations. Identification of mutations in FAN1 gene underscores recent insights linking inadequate DNA repair and susceptibility to chronic kidney disease.

  1. Relationship between urinary protein changes in lupus nephritis and renal pathology.

    PubMed

    Li, M; Gao, W J; Ma, J J; Zhu, Y; Li, X F

    2015-07-28

    This study investigated the relationship between urinary protein excretion in lupus nephritis New Zealand black mice and renal pathology. A total of 328 lupus nephritis New Zealand black mice were established by a backcross hybridization method, and renal pathology was determined. The urinary protein excretion of the backcross mice over 24 h was compared and analyzed. Urinary protein excretion over 24 h differed significantly across different pathological types (1.9, 2.4, 2.9 and 4.9 g in types II, III, IV, and V, respectively) in the backcross mice (P < 0.05). Moreover, it correlated with pathology grade (r = 0.391, P = 0.0001) as well as activity index, chronic index, renal tubular interstitial activity index, and renal tubular interstitial lesions (P < 0.05) but not with vascular lesions (P = 0.683). Urinary protein excretion from lupus nephritis is closely associated with renal pathology. Urinary protein changes can be used to determine lupus nephritis pathology and have some clinical significance for treatment and prognosis.

  2. The significance of arterial hypertension at the onset of clinical lupus nephritis.

    PubMed

    Naiker, I P; Chrystal, V; Randeree, I G; Seedat, Y K

    1997-04-01

    The prognostic importance of hypertension at the onset of clinical lupus nephritis is not well established. We studied retrospectively 44 patients with lupus nephritis in order to ascertain the prevalence of hypertension at presentation and to investigate a possible association between hypertension and renal functional impairment. A correlation was also sought between hypertension and histological class of lupus nephritis. Hypertension was graded as mild (diastolic 95-99 mmHg), moderate (100-114) or severe (> 115). Impaired renal function (creatinine > 120 mumol/l) was graded as mild (120-200 mumol/l), moderate (200-350 mumol/l), or severe (> 350 mumol/l). Histological class and the presence of hypertensive renal vascular lesions was recorded. The prevalence of hypertension was 38%. There were 17 hypertensives and 27 normotensives. The incidence of renal impairment was greater in the hypertensives, 47% vs 18.5% (p = 0.04). Mean serum creatinine was also higher higher in this group (p = 0.02). The presence of hypertensive renal vascular lesions identified a high-risk subgroup who had a higher incidence of renal functional impairment and worse renal function than the hypertensive group as a whole. Even at an early stage, hypertension and hypertensive renal vascular lesions correlated well with renal functional impairment. Aggressive treatment of hypertension is therefore essential in early lupus nephritis in order to prevent further deterioration of renal function as the disease evolves.

  3. Ibuprofen-induced Henoch–Schönlein purpura nephritis: First reported case

    PubMed Central

    Seong, Christopher Lim Thiam; Shanmuganathan, Malini

    2016-01-01

    Ibuprofen is a nonsteroidal anti-inflammatory drug that is used widely in treating pain, fever, and inflammation. Its side effects are mainly due to acute renal impairment and gastric discomfort. We hereby report a rare case of Henoch–Schönlein purpura nephritis secondary to ibuprofen consumption which has not been reported in literature before. PMID:28066119

  4. Herpes virus infection associated with interstitial nephritis in a beaked whale (Mesoplodon densirostris)

    PubMed Central

    2012-01-01

    Background The capacity for herpesvirus to cause disease in cetaceans is unclear and may be varied depending on the different conditions of individuals and between different species. Kidney pathology and intralesional virus-associated infection have been rarely reported in cetaceans. Result On April 2004, an old adult male Blainville’s beaked whale (Mesoplodon densirostris) 420 cm long with a poor body condition was stranded on Tenerife Island. During necropsy, no gross lesions were observed in the kidneys. However, membranous glomerulonephritis, multifocal interstitial lymphoplasmacytic nephritis and acute multifocal necrotizing tubulointerstitial nephritis with intranuclear inclusion bodies was diagnosed by histological analysis. Tissue samples were submitted for bacteriological analysis and molecular viral screening. Conclusion A novel alpha herpesvirus associated with interstitial nephritis was identified in an old adult male Blainville's beaked whale (M. densirostris) with a poor body condition stranded in the Canary Islands. This report suggests that identification of herpesvirus infection could be used as a differential diagnosis for interstitial nephritis in cetaceans. PMID:23237059

  5. Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis

    PubMed Central

    Pang, Yun; Tan, Ying; Li, Yongzhe; Zhang, Jianchun; Guo, Yongbing; Guo, Zhiling; Zhang, Chengying; Yu, Feng; Zhao, Ming-hui

    2016-01-01

    Abstract Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort. The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence. The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P

  6. Bone Disease in Newly Diagnosed Lupus Nephritis Patients

    PubMed Central

    Resende, Aline Lázara; dos Reis, Luciene Machado; Dias, Cristiane Bitencourt; Custódio, Melani Ribeiro; Jorgetti, Vanda; Woronik, Viktoria

    2014-01-01

    Introduction Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology. Methods We studied 15 pre-menopausal patients with ≤2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D3 [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis. Results LN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31–87) ml/min/1,73 m2. They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4–20). Urinary MCP1 correlated negatively with 25(OH)D (r = −0.53, p = 0.003) and positively with serum deoxypyridinoline (r = 0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0.±9.1 vs. 22.9±5.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient’s bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61±0.82 vs. 1.08±0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-κB ligand (RANKL) (1.76±0.92 vs. 0.41±0.28%, p<0.001) when compared to controls. Discussion Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters

  7. Mycophenolate mofetil versus azathioprine for maintenance treatment of lupus nephritis.

    PubMed

    Kaballo, Babikir G; Ahmed, Ahmed Elias; Nur, Musa Mohammed; Khalid, Ismail Osman; Abu-Aisha, Hasan

    2016-01-01

    To compare the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) drugs in the maintenance therapy of lupus nephritis (LN) patients, we studied 81 Sudanese patients with LN (32 in Class III, 34 in Class IV, and 15 in combined Class V + IV of the ISN/RPS 2003 Classification). All patients received induction therapy consisting of monthly intravenous pulse doses of cyclophosphamide (CYC) (500 mg/m 2 of body-surface area) for six months, plus three consecutive pulses of intravenous methylprednisolone 15 mg/kg/day of body weight (maximum 500 mg). Subsequently, 41 (50.6%) patients were randomized into a group that received oral MMF (22 mg/kg/day), and 40 (49.4%) patients randomized to a group that received oral AZA (2 mg/kg/day). All patients initially received oral prednisone (1 mg/kg of body weight daily) for four weeks. The baseline characteristics of the two groups were similar. Total remission rate was 75.3% (80.5% in MMF and 70% in AZA), complete remission rate of 54.3% (56.1% with MMF and 52.5% with AZA), and a partial remission rate of 21% (24.4% with MMF and 17.5% with AZA) over 29 months. During maintenance therapy, six patients died (four in the AZA group and two in the MMF group), and end-stage renal disease (ESRD) developed in five patients (three in the AZA group and two in the MMF group). During the 36-months of the study, both groups had comparable event-free survival rate for the composite end point of death or ESRD and rate of relapse-free survival. Furthermore, both groups had no significant differences in terms of frequency of hospitalization, amenorrhea, infection, nausea, and vomiting. We conclude that our study showed that short-term therapy with intravenous CYC followed by maintenance therapy with oral MMF or AZA had similar efficacy and safety for the treatment of patients with moderate to severe LN.

  8. Treatable intracranial hypertension in patients with lupus nephritis.

    PubMed

    Nampoory, M R; Johny, K V; Gupta, R K; Constandi, J N; Nair, M P; al-Muzeiri, I

    1997-01-01

    Idiopathic intracranial hypertension is a disorder of intracerebral pressure regulation and patients run the risk of permanent visual loss. Intracranial hypertension (IH) has been reported rarely in systemic lupus erythematosus (SLE). We reviewed the medical records of 127 patients with lupus nephritis (LN) who were followed up from 1987 to 1996 in our unit. There were six patients with IH which gave a disease prevalence of 4.7% in those with LN. All were females giving a disease prevalence of 5.2% for that sex, a high rate of occurrence of IH in patients with LN. Their age ranged from 22 to 34 y (27.8 +/- 3.6 y). Headache, vomiting and diplopia were the common presenting symptoms and had started 7.3 +/- 4.4 weeks prior to the diagnosis of IH. The cerebrospinal (CSF) opening pressure (413.3 +/- 77.0 mmH2O) was raised in all cases. Biochemical and cytological analyses of CSF were normal. The only abnormal radiological finding was partially empty sella in one patient on magnetic resonance imaging (MRI) (performed in three patients) or computed tomography (CT) (performed in all patients). All patients had serological evidences of active lupus disease at the time of diagnosis of IH. The renal histology was WHO type IV in four cases and III and V in one each indicating severe renal involvement. Laboratory evidences of procoagulant activity were found in the form of positive anticardiolipin antibody (aCL) in two patients, lupus anticoagulant (LA) in two and an otherwise unexplained isolated prolongation of activated partial thromboplastin time (APTT) in the other two. Clinically, one or more episodes of symptomatic venous or arterial thrombosis had occurred in all subjects. In addition to symptomatic measures, all subjects were treated with prednisolone, azathioprine, cyclophosphamide and plasmapheresis according to the protocol of our unit. One patient who did not receive plasmapheresis and cyclophosphamide had a relapse while all others recovered completely. None

  9. Pro: The use of calcineurin inhibitors in the treatment of lupus nephritis.

    PubMed

    Mok, Chi Chiu

    2016-10-01

    Renal disease in systemic lupus erythematosus (SLE) carries significant morbidity and mortality. Cyclophosphamide (CYC)- and mycophenolate mofetil (MMF)-based induction regimens are not ideal in terms of efficacy and toxicity. The adverse effects of CYC, such as infection risk, infertility, urotoxicity and oncogenicity, limit its use in lupus nephritis. Although MMF is non-inferior to CYC as induction therapy and has reduced gonadal toxicity and oncogenic potential, meta-analyses of clinical trials do not show a lower rate of infective and gastrointestinal complications. Tacrolimus (TAC) has recently been shown to have equal efficacy to either MMF or CYC for inducing remission of lupus nephritis. A low-dose combination of MMF and TAC appears to be more effective than intravenous CYC pulses in Chinese patients, and has potential to replace the more toxic CYC regimens in high-risk subgroups. TAC may be considered as another non-CYC alternative for induction therapy of lupus nephritis and in those with refractory disease or intolerance to CYC or MMF. TAC has no negative effect on fertility in younger women, and unlike MMF and CYC, it is safe in pregnancy. However, TAC has a narrow therapeutic window and drug level monitoring is required to ensure drug exposure and minimize acute toxicities. Current evidence for the efficacy of TAC in lupus nephritis is limited to 6 months and the incidence of renal flare after discontinuation of therapy or switching to azathioprine appears to be higher than other induction agents. Long-term data and the incidence of chronic nephrotoxicity of TAC as maintenance therapy in lupus nephritis are currently lacking and further prospective trials are needed to address these issues.

  10. Focal epithelial hyperplasia: Heck disease.

    PubMed

    Cohen, P R; Hebert, A A; Adler-Storthz, K

    1993-09-01

    Two sisters of Mexican ancestry had focal epithelial hyperplasia (FEH). The lesions on the oral mucosa of the older child were initially misinterpreted as representing sexual abuse. Microscopic evaluation of a hematoxylin and eosin-stained section from a lower lip papule demonstrated the histologic features of FEH. Although human papillomavirus (HPV) type 13 and HPV32 have been most consistently present in FEH lesions, types 6, 11, 13, and 32 were not detected in the paraffin-embedded tissue specimen of our patient using an in situ hybridization technique. The lesions persisted or recurred during management using destructive modalities; subsequently, they completely resolved spontaneously.

  11. Interferon Induced Focal Segmental Glomerulosclerosis

    PubMed Central

    Bayram Kayar, Nuket; Alpay, Nadir; Hamdard, Jamshid; Emegil, Sebnem; Bag Soydas, Rabia; Baysal, Birol

    2016-01-01

    Behçet's disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS) is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet's disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon. PMID:27847659

  12. SNAP Satellite Focal Plane Development

    SciTech Connect

    Bebek, C.; Akerlof, C.; Aldering, G.; Amanullah, R.; Astier, P.; Baltay, C.; Barrelet, E.; Basa, S.; Bercovitz, J.; Bergstrom, L.; Berstein, G.P.; Bester, M.; Bohlin, R.; Bonissent, A.; Bower, C.; Campbell, M.; Carithers, W.; Commins, E.; Day, C.; Deustua, S.; DiGennaro, R.; Ealet, A.; Ellis, R.; Emmett, W.; Eriksson, M.; Fouchez,D.; Fruchter, A.; Genat, J-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Heetderks, H.; Holland, S.; Huterer, D.; Johnson, W.; Kadel, R.; Karcher,A.; Kim, A.; Kolbe, W.; Lafever, R.; Lamoureaux, J.; Lampton, M.; Lefevre, O.; Levi, M.; Levin, D.; Linder, E.; Loken, S.; Malina, R.; Mazure, A.; McKay, T.; McKee, S.; Miquel, R.; Morgan, N.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Roe, N.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Prieto, E.; Rabinowitz,D.; Refregier, A.; Rhodes, J.; Schubnell, M.; Sholl, M.; Smadja, G.; Smith, R.; Smoot, G.; Snyder, J.; Spadafora, A.; Szymkowiak, A.; Tarle,G.; Taylor, K.; Tilquin, A.; Tomasch, A.; Vincent, D.; von der Lippe, H.; Walder, J-P.; Wang, G.

    2003-07-07

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square degree field in the visible and near-infrared wavelength regime. The requirements for the instrument suite and the present configuration of the focal plane concept are presented. A two year R&D phase, largely supported by the Department of Energy, is just beginning. We describe the development activities that are taking place to advance our preparedness for mission proposal in the areas of detectors and electronics.

  13. Pathogenesis of Focal Segmental Glomerulosclerosis

    PubMed Central

    Lim, Beom Jin; Yang, Jae Won; Do, Woo Sung; Fogo, Agnes B.

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice. PMID:27744657

  14. Acute tubulo-interstitial nephritis in a dog after halothane anaesthesia and administration of flunixin meglumine and trimethoprim-sulphadiazine.

    PubMed

    McNeil, P E

    1992-08-15

    Acute tubulo-interstitial nephritis was diagnosed post mortem when a dog died four days after surgery for a femoral head resection. Possible causative factors associated with halothane anaesthesia, flunixin meglumine analgesia and prophylactic antibiotic therapy with trimethoprim-sulphadiazine are discussed. It is concluded that death was due to renal failure associated with tubulo-interstitial nephritis as a result of a combination of ischaemic and toxic events.

  15. Predictors of Relapse and End Stage Kidney Disease in Proliferative Lupus Nephritis: Focus on Children, Adolescents, and Young Adults

    PubMed Central

    Gipson, Debbie S.; Massengill, Susan A.; Dooley, Mary Anne; Primack, William A.; Ferris, Maria A.; Hogan, Susan L.

    2009-01-01

    Background and objectives: The prevalence and significance of remission and relapse in children, adolescents, and young adults with lupus nephritis in the United States are poorly understood. Patterns and predictors of disease progression in a southeastern U.S. pediatric cohort with severe lupus nephritis are presented. Design, settings, participants, & measurements: Individuals age 21 or less with kidney biopsy-proven lupus nephritis followed in the Glomerular Disease Collaborative Network were included. Cox regression models were used to evaluate predictors of relapse and end stage kidney disease (ESKD). Results: Seventy-three subjects with a mean age of 15.6 ± 3.4 yr were included. Five-year kidney survival was 77%. Complete and partial remission rates within 1 yr of induction therapy were 25 and 64%, respectively. Relapse and ESKD rates were similar between complete and partial responders. Relapse occurred in 35% of responders (complete or partial) in 45 ± 32 mo. Disease relapse was a predictor of ESKD (HR = 10.12, P < 0.0001). Treatment resistance was documented in African Americans more often than non-African Americans (eight versus 0; P = 0.03). ESKD HR associated with treatment resistance was 6.25, P < 0.002. Conclusions: Remission whether complete or partial is associated with improved kidney survival in children with lupus nephritis. Nephritis relapse is a strong predictor of progression to ESKD. Treatment resistance portends a high risk of ESKD and disproportionately affects African American children with lupus nephritis. PMID:19820130

  16. Inclusion of renal vascular lesions in the 2003 ISN/RPS system for classifying lupus nephritis improves renal outcome predictions.

    PubMed

    Wu, Li-Hua; Yu, Feng; Tan, Ying; Qu, Zhen; Chen, Meng-Hua; Wang, Su-Xia; Liu, Gang; Zhao, Ming-Hui

    2013-04-01

    The 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) pathological classification system of lupus nephritis specified the importance of vascular damage and indicated this should be included in the diagnostic summary. Few pathological studies of lupus nephritis, however, focus on the patterns of renal vascular involvement. Here we assessed renal vascular lesions in lupus nephritis based on the 2003 ISN/RPS classification system and evaluated their association with clinical and pathological data in a large cohort from a single center in China. Among 341 patients with lupus nephritis, 279 were diagnosed with single or multiple renal vascular lesions that included 253 with vascular immune complex deposits, 82 with atherosclerosis, 60 with thrombotic microangiopathy, 13 with noninflammatory necrotizing vasculopathy, and 2 with true renal vasculitis. Patients with thrombotic microangiopathy had the poorest renal outcome. In multivariate Cox hazard analysis after inclusion of renal vascular lesions, the new chronicity index score became a significantly better independent risk factor for renal outcome (hazard ratio 2.32). Thus, renal vascular lesions are common in lupus nephritis and closely correlate with clinical disease activity and renal outcome. Inclusion of a detailed description of renal vascular lesions in the ISN/RPS classification of lupus nephritis may strengthen its predictive value for renal outcome.

  17. Reducing progression of experimental lupus nephritis via inhibition of the B7/CD28 signaling pathway

    PubMed Central

    HUANG, LI; KONG, YONG; WANG, JING; SUN, JIE; SHI, QIN; QIU, YU-HUA

    2015-01-01

    The aim of the present study was to evaluate the effects of the B7/cluster of differentiation (CD)28 signaling pathway on experimental lupus nephritis and examine the molecular mechanism involved by inhibiting the B7/CD28 signaling pathway. A lupus nephritis model in C57BL/6 J mice was induced via intraperitoneal injection of pristane. A recombinant B7-1 short hairpin RNA (shRNA) lentivirus vector was constructed by synthesis and splicing. A neutralizing mouse anti-human B7-1 antibody termed 4E5 was also prepared. The mouse model of lupus nephritis was treated with B7-1 shRNA and 4E5 via injection through the tail vein. The silencing effects of B7-1 shRNA lentiviral infection on target molecules were evaluated using immunofluorescence and flow cytometry. The levels of protein in the urine were detected using Albustix test paper each month over 10 months. The concentration of interleukin (IL)-4 and interferon-γ in the serum was determined using an ELISA. The immune complex (IC) deposits in the kidney were analyzed using direct immunofluorescence. The results demonstrated that the C57BL/6 J mouse lupus nephritis model was successfully constructed with immune cells activated in the spleen of the mice, increases in the concentration of anti-nuclear antibody (ANA) and anti-double stranded DNA antibodies as well as positive IC formation. Following B7-1 shRNA lentivirus or 4E5 treatment, CD11b+B7-1+, CD11c+B7-1+ and CD21+B7-1+ cells in the spleen of the mice were significantly reduced. The concentration of ANA and IL-4 in the serum was also decreased. The concentration of urine protein was reduced and it was at its lowest level in the 4E5 early intervention group. It was also revealed that the immunofluorescence intensity of the IC deposits was weak in the 4E5 early intervention group. In conclusion, inhibiting the B7-1/CD28 signaling pathway is able to alleviate experimental lupus nephritis and provides an experimental basis for the therapeutic use of blocking the B7

  18. RF/Optical Demonstration: Focal Plane Assembly

    NASA Astrophysics Data System (ADS)

    Hoppe, D. J.; Chung, S.; Kovalik, J.; Gama, E.; Fernandez, M. M.

    2016-11-01

    In this article, we describe the second-generation focal plane optical assembly employed in the RF/optical demonstration at DSS-13. This assembly receives reflected light from the two mirror segments mounted on the RF primary. The focal plane assembly contains a fast steering mirror (FSM) to stabilize the focal plane spot, a pupil camera to aid in aligning the two segments, and several additional cameras for receiving the optical signal prior to as well as after the FSM loop.

  19. Digital scanner infrared focal plane technology

    NASA Astrophysics Data System (ADS)

    Ortiz, M. A.; Malone, N. R.; Harris, M.; Shin, J.; Byers, S.; Price, D.; Vampola, J.

    2011-09-01

    Advancements in finer geometry and technology advancements in circuit design now allow placement of digital architecture on cryogenic focal planes while using less power than heritage analog designs. These advances in technology reduce the size, weight, and power of modern focal planes. In addition, the interface to the focal plane is significantly simplified and is more immune to Electromagnetic Interference (EMI). The cost of the customer's instrument after integration with the digital scanning Focal Plane Array (FPA) has been significantly reduced by placing digital architecture such as Analog to digital convertors and Low Voltage Differential Signaling (LVDS) Inputs and Outputs (I/O) on the Read Out Integrated Circuit (ROIC).

  20. Focal epithelial hyperplasia - an update.

    PubMed

    Said, Ahmed K; Leao, Jair C; Fedele, Stefano; Porter, Stephen R

    2013-07-01

    Focal epithelial hyperplasia (FEH) is an asymptomatic benign mucosal disease, which is mostly observed in specific groups in certain geographical regions. FEH is usually a disease of childhood and adolescence and is generally associated with people who live in poverty and of low socioeconomic status. Clinically, FEH is typically characterized by multiple, painless, soft, sessile papules, plaques or nodules, which may coalesce to give rise to larger lesions. Human papillomavirus (HPV), especially genotypes 13 and 32, have been associated and detected in the majority of FEH lesions. The clinical examination and social history often allow diagnosis, but histopathological examination of lesional tissue is usually required to confirm the exact diagnosis. FEH sometimes resolves spontaneously however, treatment is often indicated as a consequence of aesthetic effects or any interference with occlusion. There remains no specific therapy for FEH, although surgical removal, laser excision or possibly topical antiviral agents may be of benefit. There remains no evidence that FEH is potentially malignant.

  1. Smov Baseline Focal Plane Check

    NASA Astrophysics Data System (ADS)

    Gilmozzi, Roberto

    1994-01-01

    This test will be executed during the period after the servicing mission and before the extension of the COSTAR assembly. Its purpose is to verify that the FOS, HRS, and FOC focal planes have not been altered by the activities performed by Story and the Astronauts during the servicing mission. A large unknown deviation in aperture position would severly impact subsequent COSTAR alignment activities. If this test reveals a deviation, we may be able to compensate for any offsets prior to the complex and delicate COSTAR alignment calibrations. This enhanced version of the Heptathlon is designed to verify course alignments and measure relative aperture positions to within a few arcsecs. SPECIAL REQUIREMENTS: ***This test uses pre-servicing parameters for HRS, FOS, and FOC and the Cycle 4 parameters for WFPC2.*** ***This test requires special alignment and special guide stars.** ***This test requires special commanding for telemetry setups.**

  2. Bacterial Sialidase

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Data shows that elevated sialidase in bacterial vaginosis patients correlates to premature births in women. Bacterial sialidase also plays a significant role in the unusual colonization of Pseudomonas aeruginosa in cystic fibrosis patients. Crystals of Salmonella sialidase have been reproduced and are used for studying the inhibitor-enzyme complexes. These inhibitors may also be used to inhibit a trans-sialidase of Trypanosome cruzi, a very similar enzyme to bacterial sialidase, therefore preventing T. cruzi infection, the causitive agent of Chagas' disease. The Center for Macromolecular Crystallography suggests that inhibitors of bacterial sialidases can be used as prophylactic drugs to prevent bacterial infections in these critical cases.

  3. Visceral leishmaniasis in a kidney transplant recipient: parasitic interstitial nephritis, a cause of renal dysfunction.

    PubMed

    Dettwiler, S; McKee, T; Hadaya, K; Chappuis, F; van Delden, C; Moll, S

    2010-06-01

    Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.

  4. Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

    PubMed

    Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

    2012-05-01

    Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

  5. Granulomatous interstitial nephritis: a clinicopathologic study of 46 cases from a single institution.

    PubMed

    Bijol, Vanesa; Mendez, Gonzalo P; Nosé, Vânia; Rennke, Helmut G

    2006-01-01

    Acute interstitial nephritis is commonly seen in kidney biopsies of patients with acute renal failure; however, granulomatous interstitial nephritis (GIN) is rare. We identified 46 cases of GIN in a 17-year period in this institution and we investigated their most probable etiologies. Complete clinical information was available in 38 patients. Seventeen of 38 patients (44.7%) were classified as drug-induced. Renal sarcoidosis was responsible for 28.9% of cases, and the remaining 15.9% of cases included Wegeners granulomatosis, foreign body giant cell reaction, GIN secondary to intravesical bacillus Calmette-Guérin therapy for bladder cancer, and xanthogranulomatous pyelonephritis. Clinical investigation failed to reveal possible etiology in 4 patients (10.5%), classified as idiopathic. We concluded that three quarters of our cases were either drug-induced or due to sarcoidosis; only a small proportion of our cases occurred secondary to any other cause or to unknown factors.

  6. Granulomatous interstitial nephritis associated with Primary Sjögren's syndrome.

    PubMed

    Bitik, B; Gonul, I I; Haznedaroglu, S; Goker, B; Tufan, A

    2017-02-14

    Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic and plasmacytic infiltration of the exocrine glands. Tubulointerstitial nephritis (TIN) is the most common type of renal involvement in pSS. However, clinically significant renal involvement is uncommon. Granulomatous interstitial nephritis (GIN) is a rare histopathological entity characterized by the presence of granulomas against a background of interstitial inflammation. GIN is not a typical and commonly seen form of TIN in pSS. Herein, we report on a patient who was concurrently diagnosed with pSS and GIN and was treated successfully with rituximab (RTX). pSS should be considered in the differential diagnosis of GIN, and RTX may be a good option in the treatment of this patient group.

  7. Mesangial cell-specific antibodies are central to the pathogenesis of lupus nephritis.

    PubMed

    Seret, Guillaume; Le Meur, Yannick; Renaudineau, Yves; Youinou, Pierre

    2012-01-01

    Not only is nephritis a common complaint in systemic lupus erythematosus, but it is also the most life-threatening complication of the disease. Anti-double-stranded DNA antibodies (Abs), which are found in up to 80% of these patients, might be nephritogenic per se. That is, they may cross-react with mesangial cell (MC) surface proteins, such as alpha-actinin and annexin A2, they may cross-react with mesangial matrix protein such as laminine and fibronectin, or they may recognize chromatin material previously deposited in the glomeruli. The consequence of the binding of anti-MC Abs may be their internalization, which results in activation and proliferation of these MCs. In turn, these activated MCs are suspected of promoting immune complex formation by sequestering and thereby protecting chromatin from degradation. The present paper will explain the mechanisms through which such autoAbs may initiate nephritis.

  8. The history of pulse therapy in lupus nephritis (1976-2016).

    PubMed

    Scheinberg, Morton

    2016-01-01

    Pulse therapy with methylprednisolone became standard of care for the treatment of worsening lupus nephritis since its introduction in 1976. Even today, 40 years since its introduction, it is still a gold standard for this clinical condition. In this communication, we have reviewed the events that surrounded the use of this therapy by one of the authors of the original paper published in Lancet 40 years ago.

  9. Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis

    PubMed Central

    Xia, Yumin; Campbell, Sean R.; Broder, Anna; Herlitz, Leal; Abadi, Maria; Wu, Ping; Michaelson, Jennifer S.; Burkly, Linda C.; Putterman, Chaim

    2012-01-01

    Previously it was shown that the TNF superfamily member TWEAK (TNFSF12) acts through its receptor, Fn14, to promote proinflammatory responses in kidney cells, including the production of MCP-1, RANTES, IP-10 and KC. In addition, the TWEAK/Fn14 pathway promotes mesangial cell proliferation, vascular cell activation, and renal cell death. To study the relevance of the TWEAK/Fn14 pathway in the pathogenesis of antibody-induced nephritis using the mouse model of nephrotoxic serum nephritis (NTN), we induced NTN by passive transfer of rabbit anti-glomerular antibodies into Fn14 knockout (KO) and wild type (WT) mice. Severe proteinuria as well as renal histopathology were induced in WT but not in Fn14 KO mice. Similarly, a pharmacologic approach of anti-TWEAK mAb administration into WT mice in the NTN model significantly ameliorated proteinuria and improved kidney histology. Anti-TWEAK treatment did not affect the generation of mouse anti-rabbit antibodies; however, within the kidney there was a significant decrease in glomerular immunoglobulin deposition, as well as macrophage infiltrates and tubulointerstitial fibrosis. The mechanism of action is most likely due to reductions in downstream targets of TWEAK/Fn14 signaling, including reduced renal expression of MCP-1, VCAM-1, IP-10, RANTES as well as Fn14 itself, and other molecular pathways associated with fibrosis in anti-TWEAK treated mice. Thus, TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the NTN model, apparently mediating a cascade of pathologic events locally in the kidney rather than by impacting the systemic immune response. Disrupting TWEAK/Fn14 interactions may be an innovative kidney-protective approach for the treatment of lupus nephritis and other antibody-induced renal diseases. PMID:22982296

  10. Treatment of lupus nephritis with total lymphoid irradiation. Observations during a 12-79-month followup

    SciTech Connect

    Strober, S.; Farinas, M.C.; Field, E.H.; Solovera, J.J.; Kiberd, B.A.; Myers, B.D.; Hoppe, R.T.

    1988-07-01

    Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.

  11. Serum thiols as a biomarker of disease activity in lupus nephritis.

    PubMed

    Lalwani, Pritesh; de Souza, Giselle Katiane Bonfim Bacelar; de Lima, Domingos Savio Nunes; Passos, Luiz Fernando Souza; Boechat, Antonio Luiz; Lima, Emerson Silva

    2015-01-01

    Lupus Nephritis (LN) develops in more than half of the Systemic Lupus Erythematous (SLE) patients. However, lack of reliable, specific biomarkers for LN hampers clinical management of patients and impedes development of new therapeutics. The goal of this study was to investigate whether oxidative stress biomarkers in patients with SLE is predictive of renal pathology. Serum biochemical and oxidative stress markers were measured in patients with inactive lupus, active lupus with and without nephritis and compared to healthy control group. To assess the predictive performance of biomarkers, Receiver Operating Characteristic (ROC) curves were constructed and cut-offs were used to identify SLE patients with nephritis. We observed an increased oxidative stress response in all SLE patients compared to healthy controls. Among the several biomarkers tested, serum thiols had a significant inverse association with SLE Disease Activity Index (SLEDAI). Interestingly, thiols were able too aptly differentiate between SLE patients with and without renal pathology, and serum thiol levels were not affected by immunosuppressive drug therapy. The decreased thiols in SLE correlated significantly with serum creatinine and serum C3 levels. Further retrospective evaluation using serum creatinine or C3 levels in combination with thiol's cutoff values from ROC analysis, we could positively predict chronicity of renal pathology in SLE patients. In summary, serum thiols emerge as an inexpensive and reliable indicator of LN, which may not only help in early identification of renal pathology but also aid in the therapeutic management of the disease, in developing countries with resource poor settings.

  12. Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A-I amyloidosis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Ravani, Pietro; Obici, Laura; Dallera, Nadia; Del Barba, Andrea; Negrinelli, Alessandro; Tardanico, Regina; Nardi, Matilde; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2015-06-01

    Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.

  13. Tubulointerstitial Nephritis and Uveitis Syndrome in an Elderly Man: Case Report and Literature Review.

    PubMed

    Lei, Wen-Hui; Xin, Jun; Yu, Xue-Ping; Li, Jie; Mao, Ming-Feng; Ji, Jian-Song; Wu, Chui-Fen; Zhu, Chao-Yong; Jin, Lie

    2015-11-01

    Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease of unknown etiology defined by the combination of tubulointerstitial nephritis, uveitis, and biochemical abnormalities. It has been reported that TINU mainly affects adolescents and young women. Here we reported a special case regarding a 60-year-old man with acute renal failure due to TINU syndrome documented by renal biopsy.We present a rare case of an elderly patient, who had been suffering from a fever for 2 weeks, characterized by sudden onset and resolving spontaneously, and accompanied by extreme fatigue, loss of appetite, and shivering. Renal biopsy showed a tubulointerstitial nephritis, with polymorphonuclear infiltration and acute tubulitis. In the outpatient clinic, he was diagnosed with idiopathic bilateral anterior uveitis 1 month ago. Ophthalmological examination revealed anterior asymptomatic bilateral uveitis. Human leukocyte antigen (HLA) typing (HLA-DQA1*0101/0201 and HLA-DQB1*0303/0503) was found which supported the suspect of TINU syndrome. The patient was treated with oral prednisone (1 mg/kg) and continued for 8 weeks on tapering doses. Serum creatinine normalized within 3 and 6 months later renal function also recovered completely.This case highlights that TINU syndrome is probably an underdiagnosed disease responsible for some cases of idiopathic anterior uveitis in elderly male patients. It is of critical importance to be aware of this syndrome by nephrologist and ophthalmologists in this special population. Further studies are needed to elucidate clinical characteristic and pathogenesis of TINU syndrome in elderly population.

  14. A Rare Case of Tubulointerstitial Nephritis and Uveitis Syndrome Treated with a Multi-Specialty Approach.

    PubMed

    Purt, Boonkit; Hiremath, Siri; Smith, Sarah; Erzurum, Sergul; Sarac, Erdal

    2016-11-21

    BACKGROUND It is important for an ophthalmologist and nephrologist to look for hidden causes of uveitis and nephritis, respectively. Delay in diagnosis leads to increased morbidity and failure to systemically manage the patient results in future recurrence of disease. It is likely that TINU remains underdiagnosed and could potentially account for some of the cases of idiopathic uveitis, especially when greater than 50% of uveitis cases have no identifiable cause. Fewer than 300 cases of tubulointerstitial nephritis and uveitis (TINU) syndrome have been reported. In TINU syndrome, inflammation affects the renal tubules, interstitial tissue, and uveal tract. Its pathogenesis remains poorly understood. CASE REPORT We report a rare case of TINU syndrome in a 23-year-old female who was treated using a multispecialty approach. Her primary care physician diagnosed her with proteinuria and acute kidney injury and referred her to the nephrologist, who later referred her to the ophthalmologist. A left kidney biopsy confirmed acute interstitial nephritis. Following the discovery of a "pink eye", the patient was referred to ophthalmology and diagnosed with anterior uveitis, confirming TINU syndrome. Without the additional findings of uveitis, the diagnosis would have been missed. Resolution was obtained through steroid therapy. CONCLUSIONS Correctly diagnosing TINU syndrome requires a multispecialty approach and may not be obvious upon initial presentation. Therefore, the ophthalmologist needs to consider TINU in the differential diagnosis for a patient with bilateral uveitis and evaluate a urinalysis for proteinuria as part of the work up.

  15. Impact of the ALMS and MAINTAIN trials on the management of lupus nephritis.

    PubMed

    Morris, Heather K; Canetta, Pietro A; Appel, Gerald B

    2013-06-01

    Current treatment of lupus nephritis consists of both induction and maintenance therapy, with the latter being designed to consolidate remissions and prevent relapses. Long-term maintenance treatment with intravenous cyclophosphamide was effective but associated with considerable toxicity. A small but well-designed controlled trial found that for post-induction maintenance therapy, both oral mycophenolate mofetil (MMF) and oral azathioprine were superior in efficacy and had reduced toxicity than a regimen of continued every third month intravenous cyclophosphamide. Although these oral agents were rapidly accepted and utilized as maintenance medications, their usage was based on scant evidence and there were no comparisons between the two. Recently, two relatively large, randomized, well-controlled, multicenter trials dealing with maintenance therapy for severe lupus nephritis have been completed. The Aspreva Lupus Management Study (ALMS) maintenance and MAINTAIN nephritis trials provide important information regarding the comparative efficacy and safety of MMF and azathioprine as maintenance therapies, as well as information on the effect of dosage and duration of treatment with these agents.

  16. Plasma levels of M-CSF are increased in ANCA-associated vasculitides with active nephritis.

    PubMed

    Ramirez, Giuseppe A; Blasi, Miriam; Sciorati, Clara; Rovere-Querini, Patrizia; Manfredi, Angelo A

    2015-01-01

    Anti-Neutrophil Cytoplasmic Antibodies (ANCA)-associated vasculitides (AAV) are characterized by small vessel injury and in some cases granulomatous lesions and glomerular inflammation. The pathogenic bases of these clinical phenotypes are incompletely understood, but evidence from patients with AAV and other inflammatory diseases suggest a role for monocyte/macrophages in the perpetuation of tissue injury. Macrophage colony stimulating factor (M-CSF) is a promoter of monocyte recruitment and macrophage proliferation, involved in mesangial cell proliferation and experimental nephritis development. Serum concentrations of M-CSF mark and herald the onset of lupus nephritis. Plasma samples from 29 patients with AAV (18 granulomatosis with polyangiitis, GPA, 6 eosinophilic granulomatosis with polyangiitis, EGPA, and 5 microscopic polyangiitis, MPA) and from 10 healthy controls were collected together with clinical data. Patients with AAV had higher levels of M-CSF when compared to controls. M-CSF levels correlated positively with the BVAS, serum C-reactive protein and erythrocyte sedimentation rate, while haemoglobin correlated inversely with M-CSF. Patients with active renal disease had significantly higher levels of M-CSF when compared to the other subgroups. M-CSF levels did not differ between ANCA subserotypes and were not associated with the involvement of other organs. In conclusion, M-CSF is higher in patients with AAV and active nephritis and could contribute to the pathogenesis of these diseases. In addition, M-CSF could behave as a useful marker of renal involvement in AAV.

  17. Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice.

    PubMed

    Kulkarni, Onkar; Pawar, Rahul D; Purschke, Werner; Eulberg, Dirk; Selve, Norma; Buchner, Klaus; Ninichuk, Volha; Segerer, Stephan; Vielhauer, Volker; Klussmann, Sven; Anders, Hans-Joachim

    2007-08-01

    The monocyte chemoattractant protein CCL2 is crucial for monocyte and T cell recruitment from the vascular to the extravascular compartment at sites of inflammation. CCL2 is expressed in human lupus nephritis and was shown to mediate experimental lupus; therefore, CCL2 antagonists may be beneficial for therapy. This study describes the l-enantiomeric RNA oligonucleotide mNOX-E36, a so-called Spiegelmer that binds murine CCL2 with high affinity and neutralizes its action in vitro and in vivo. The mirror image configuration of the Spiegelmer confers nuclease resistance and thus excellent biostability. mNOX-E36 does not induce type I IFN via Toll-like receptor-7 or cytosolic RNA receptors, as recently shown for certain synthetic D-RNA. Autoimmune-prone MRL(lpr/lpr) mice that were treated with a polyethylene glycol form of mNOX-E36 from weeks 14 to 24 of age showed prolonged survival associated with a robust improvement of lupus nephritis, peribronchial inflammation, and lupus-like inflammatory skin lesions. Thus, mNOX-E36-based inhibition of CCL2 represents a novel strategy for the treatment of autoimmune tissue injury, such as lupus nephritis.

  18. Noninflammatory necrotizing vasculopathy in lupus nephritis: a single-center experience.

    PubMed

    Chu, H; Wu, L H; Song, D; Yu, F; Zhao, M H

    2014-01-01

    In this study, we assessed the clinicopathological features of lupus nephritis patients with renal noninflammatory necrotizing vasculopathy (NNV). A total of 142 renal biopsies with lupus nephritis were reviewed, including nine cases presented with NNV and 36 without renal vascular lesions. The comparisons of clinical, laboratory and pathological features, treatments, as well as renal outcome between the two groups were further performed. In comparison with the no renal vascular lesions group, patients with NNV changes had significantly higher proportions of noninfection leukocyturia (p = 0.013) and leukocytopenia (p = 0.042), significantly higher serum creatinine (p = 0.012), lower hemoglobin (p = 0.002) and serum C3 (p < 0.001) levels. Renal pathological activity indices and chronicity indices were significantly higher in the NNV group (p = 0.002 and p = 0.006, respectively) than those in the no vascular lesions group. Regarding renal prognosis, the presence of NNV was not a risk factor for renal outcome (p = 0.327). In conclusion, NNV was not infrequent in renal biopsies of lupus nephritis. It was commonly associated with active clinical status and proliferative glomerular lesions of lupus.

  19. Bullous Systemic Lupus Erythematosus and Lupus Nephritis in a Young Girl

    PubMed Central

    Momen, Tooba; Madihi, Yahya

    2016-01-01

    Bullous systemic lupus erythematosus (BSLE) is an autoimmune blistering disease occurring in patients with systemic lupus erythematosus (SLE). It is a rare disease, especially in children. A 14-year-old girl initially presented with fatigue, generalized vesiculobullous skin lesions, and ulcers over the hard palate and oral mucosa. Clinical investigations revealed hematuria and proteinuria, a high erythrocyte sedimentation rate and titer of antinuclear antibody, and anti-double-stranded DNA. Skin biopsy findings were suggestive of BSLE. A renal biopsy confirmed the features of class V lupus nephritis. Based on the clinical features and investigations, a diagnosis of BSLE with nephritis was made. She received methylprednisolone pulse therapy and hydroxychloroquine; however, it did not alleviate the vesiculobullous eruption, so treatment with dapsone started and resulted in the dramatic disappearance of the lesions. Interruption of dapsone due to hemolysis did not aggravate the bullous disease. During follow-up, she had multiple flare-ups of disease and nephritis without rebound of bullous lesions. BSLE is a rare presentation of SLE in children. Differentiating it from other skin bullous diseases and SLE with blister is important for the correct management. The unusual presentation of this disease may delay the diagnosis and therefore requires a high index of clinical suspicion. PMID:27974963

  20. To TDM or not to TDM in lupus nephritis patients treated with MMF?

    PubMed

    van Gelder, Teun; Berden, Jo H M; Berger, Stefan P

    2015-04-01

    Mycophenolic acid (MPA) has become the cornerstone in the treatment of lupus nephritis. However, response rates are still far from ideal in clinical trials. Uncertainty exists regarding the correct dosing of MPA, and the recommended doses vary between recently published guidelines. Side effects are an additional problem resulting in frequent dose reduction and possible suboptimal exposure.In this review, we discuss the large variability between patients in drug exposure to MPA and the evidence for a relationship between drug exposure and efficacy in lupus nephritis. Methods for drug monitoring of MPA are discussed, and based on the current literature, we suggest as potential target levels a pre-dose level of 3.0 mg/L and an area under the concentration-versus-time curve between 35 and 45 mg h/L.Therapeutic drug monitoring may improve response rates in lupus nephritis by preventing low exposure and at the same time may reduce unnecessary side effects in patients who have high drug exposure with standard dose MPA. We specifically advise assessment of MPA drug exposure early after start of treatment and before concluding that treatment with MPA has failed.

  1. Characteristics and influence factors of pathologic transformation in the subclasses of class IV lupus nephritis.

    PubMed

    Gao, Jian-jun; Cai, Guang-yan; Liu, Shu-wen; Tang, Li; Zhang, Xue-guang; Yang, Yang; Chen, Pu; Liu, Shu-xin; Ji, Jia-yao; Shi, Suo-zhu; Yin, Zhong; Chen, Xiang-mei

    2012-06-01

    The study explored the characteristics and correlation factors of transformation in subclasses of class IV lupus nephritis. Patients with class IV lupus nephritis were subjected to repeat biopsies after 6 months of induction treatment. Transformation rate between two subclasses, class IV-S and class IV-G, was compared. Influence Factors of transformation were evaluated. Class IV-G had more severe hypertension and higher score of immunofluorescence index, glomerular active lesions, tubular and vascular lesions. Class IV-S had a higher percentage of glomerular fibrinoid necrosis. Class IV-S appeared a higher rate of transformation to class II than class IV-G (57% vs. 27%). In each subclass, active lesion also showed a higher rate of transformation to class II than active/chronic lesion (IV-G: 41.2% vs. 12.5%; IV-S: 71.4% vs. 42.8%). Patients who maintained class IV had higher blood pressure, obvious proteinuria, declined kidney function, and lower C3 level. Immunosuppressive therapy, urine protein, and vascular lesions were independent risk factors for the pathologic transformation. The rate of transformation in class IV-S was higher than that in class IV-G. The transformation is most likely to benefit from immunosuppressive therapy. Urine protein and vascular lesions are correlated with the transformation in class IV lupus nephritis.

  2. An Overlapping Case of Lupus Nephritis and IgG4-Related Kidney Disease.

    PubMed

    Zaarour, Mazen; Weerasinghe, Chanudi; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie

    2015-07-01

    We report a case of a 71-year-old Filipino female who was admitted to the hospital for abdominal pain, vomiting and diarrhea of 8 days duration. The patient was found to have marked acute kidney injury (AKI), which required hemodialysis in the next 3 days. Extensive workup revealed hematuria, subnephrotic range proteinuria, elevated anti-nuclear antibody (ANA) and elevated total immunoglobulin G (IgG) levels, with normal IgG4 and anti-dsDNA levels. On kidney biopsy, mild membranous glomerulonephritis was found, along with autoimmune tubulointerstitial nephritis (TIN) with a "full-house" pattern of immune deposits. These findings were suggestive of lupus interstitial nephritis. However, IgG4+ plasma cells were detected in the interstitium by immunostaining, favoring a diagnosis of IgG4-related kidney disease (IgG4-RKD). Our case highlights the difficulty in differentiating lupus nephritis (LN) from IgG4-RKD in some patients, raising the suspicion that these two entities can co-exist.

  3. An Overlapping Case of Lupus Nephritis and IgG4-Related Kidney Disease

    PubMed Central

    Zaarour, Mazen; Weerasinghe, Chanudi; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie

    2015-01-01

    We report a case of a 71-year-old Filipino female who was admitted to the hospital for abdominal pain, vomiting and diarrhea of 8 days duration. The patient was found to have marked acute kidney injury (AKI), which required hemodialysis in the next 3 days. Extensive workup revealed hematuria, subnephrotic range proteinuria, elevated anti-nuclear antibody (ANA) and elevated total immunoglobulin G (IgG) levels, with normal IgG4 and anti-dsDNA levels. On kidney biopsy, mild membranous glomerulonephritis was found, along with autoimmune tubulointerstitial nephritis (TIN) with a “full-house” pattern of immune deposits. These findings were suggestive of lupus interstitial nephritis. However, IgG4+ plasma cells were detected in the interstitium by immunostaining, favoring a diagnosis of IgG4-related kidney disease (IgG4-RKD). Our case highlights the difficulty in differentiating lupus nephritis (LN) from IgG4-RKD in some patients, raising the suspicion that these two entities can co-exist. PMID:26015827

  4. Lupus Nephritis in Asia: Clinical Features and Management

    PubMed Central

    Yap, Desmond Y.H.; Chan, Tak Mao

    2015-01-01

    Background Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. Summary Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed. Corticosteroids combined with either cyclophosphamide (CYC) or mycophenolic acid (MPA) is the current standard-of-care induction regimen for severe LN irrespective of race or ethnicity. However, the preference for MPA or CYC, and possibly the optimum dose for MPA, is influenced by the patient's origin. Also, there is an insufficient evidence base for reduced-dose intravenous CYC in Asian patients. Health economics and access to prompt diagnosis and treatment are still challenging issues in some Asian regions. The former represents a significant obstacle limiting the access of patients to MPA despite the proven efficacy of the drug as an induction agent and its superiority over azathioprine (AZA) in preventing disease flares when used for long-term maintenance immunosuppression. Calcineurin inhibitors such as tacrolimus deserve further investigation in view of their additional effect on podocytes by reducing proteinuria and the promising data from Asian patients. Despite considerable advances in the clinical management of LN over the past few decades with resultant improvements in patients' outcomes, there are still knowledge gaps and unmet clinical needs. Asia has made substantial contributions to the evidence base that guides clinical management and continues to offer invaluable opportunities for research pursuits. Key Messages

  5. Focal liver lesions found incidentally

    PubMed Central

    Algarni, Abdullah A; Alshuhri, Abdullah H; Alonazi, Majed M; Mourad, Moustafa Mabrouk; Bramhall, Simon R

    2016-01-01

    Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision. PMID:27028805

  6. Focal brain inflammation and autism.

    PubMed

    Theoharides, Theoharis C; Asadi, Shahrzad; Patel, Arti B

    2013-04-09

    Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Autism spectrum disorders (ASD) are characterized by social and learning disabilities that affect as many as 1/80 children in the USA. There is still no definitive pathogenesis or reliable biomarkers for ASD, thus significantly curtailing the development of effective therapies. Many children with ASD regress at about age 3 years, often after a specific event such as reaction to vaccination, infection, stress or trauma implying some epigenetic triggers, and may constitute a distinct phenotype. ASD children respond disproportionally to stress and are also affected by food and skin allergies. Corticotropin-releasing hormone (CRH) is secreted under stress and together with neurotensin (NT) stimulates mast cells and microglia resulting in focal brain inflammation and neurotoxicity. NT is significantly increased in serum of ASD children along with mitochondrial DNA (mtDNA). NT stimulates mast cell secretion of mtDNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. The phosphatase and tensin homolog (PTEN) gene mutation, associated with the higher risk of ASD, which leads to hyper-active mammalian target of rapamycin (mTOR) signalling that is crucial for cellular homeostasis. CRH, NT and environmental triggers could hyperstimulate the already activated mTOR, as well as stimulate mast cell and microglia activation and proliferation. The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD.

  7. Early vision and focal attention

    NASA Astrophysics Data System (ADS)

    Julesz, Bela

    1991-07-01

    At the thirty-year anniversary of the introduction of the technique of computer-generated random-dot stereograms and random-dot cinematograms into psychology, the impact of the technique on brain research and on the study of artificial intelligence is reviewed. The main finding-that stereoscopic depth perception (stereopsis), motion perception, and preattentive texture discrimination are basically bottom-up processes, which occur without the help of the top-down processes of cognition and semantic memory-greatly simplifies the study of these processes of early vision and permits the linking of human perception with monkey neurophysiology. Particularly interesting are the unexpected findings that stereopsis (assumed to be local) is a global process, while texture discrimination (assumed to be a global process, governed by statistics) is local, based on some conspicuous local features (textons). It is shown that the top-down process of "shape (depth) from shading" does not affect stereopsis, and some of the models of machine vision are evaluated. The asymmetry effect of human texture discrimination is discussed, together with recent nonlinear spatial filter models and a novel extension of the texton theory that can cope with the asymmetry problem. This didactic review attempts to introduce the physicist to the field of psychobiology and its problems-including metascientific problems of brain research, problems of scientific creativity, the state of artificial intelligence research (including connectionist neural networks) aimed at modeling brain activity, and the fundamental role of focal attention in mental events.

  8. The frequency and outcome of lupus nephritis: results from an international inception cohort study

    PubMed Central

    O’Keeffe, Aidan G.; Su, Li; Urowitz, Murray B.; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Clarke, Ann E.; Wallace, Daniel J.; Merrill, Joan T.; Isenberg, David A.; Rahman, Anisur; Ginzler, Ellen M.; Fortin, Paul; Gladman, Dafna D.; Sanchez-Guerrero, Jorge; Petri, Michelle; Bruce, Ian N.; Dooley, Mary Anne; Ramsey-Goldman, Rosalind; Aranow, Cynthia; Alarcón, Graciela S.; Fessler, Barri J.; Steinsson, Kristjan; Nived, Ola; Sturfelt, Gunnar K.; Manzi, Susan; Khamashta, Munther A.; van Vollenhoven, Ronald F.; Zoma, Asad A.; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Lim, S. Sam; Stoll, Thomas; Inanc, Murat; Kalunian, Kenneth C.; Kamen, Diane L.; Maddison, Peter; Peschken, Christine A.; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Thompson, Kara; Farewell, Vernon

    2016-01-01

    Objective. To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. Methods. Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. Results. There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. Conclusion. LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN. PMID:26342222

  9. Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study.

    PubMed

    Moroni, Gabriella; Doria, Andrea; Giglio, Elisa; Imbasciati, Enrico; Tani, Chiara; Zen, Margherita; Strigini, Francesca; Zaina, Barbara; Tincani, Angela; Gatto, Mariele; de Liso, Federica; Grossi, Claudia; Meroni, Pier Luigi; Cabiddu, Gianfranca; Messa, Piergiorgio; Ravani, Pietro; Mosca, Marta

    2016-11-01

    Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal

  10. Effect of methylprednisolone and "pulse" therapy with methylprednisolone sodium succinate on autologous immune complex nephritis in rats.

    PubMed

    Nakagawa, H; Sagae, Y; Tomabechi, N; Oikawa, S; Tsurufuji, S

    1980-02-01

    Autologous immune complex (AIC) nephritis was induced in rats with a single foot-pad injection of renal tubular epithelial antigen suspended in complete Freund's adjuvant. It was suggested by gel filtration of serum on Sephadex G-200 column that increase in the concentration of macroglobulins was the first alteration reflected on the serum proteins after immunization; the concentration of macroglobulins increased while the concentrations of albumin and gamma-globulin still remained in the normal range. The effect of 6 alpha-methylprednisolone sodium succinate (MP-S), 6 alpha-methylprednisolone (MP) and cyclophosphamide on the AIC nephritis in rats was studied. "Pulse" therapy, that is, an intraperitoneal administration of a large dose (26.5 mg/kg) of MP-S for 3 successive days a week and followed by an intermission for 4 days a week was started from the week of immunization with renal tubular epithelial antigen and continued for 8 weeks, resulting in the retardation of the AIC nephritis induction associated with a partial suppression of the development of proteinuria. Treatment with MP (4 mg/kg) or cyclophosphamide (10 mg/kg) every other day from the week of immunization for 8 weeks partially retarded or completely suppressed the AIC nephritis induction, respectively. On the other hand, the MP-S "pulse" therapy and the MP treatment of rats suffering from the already established AIC nephritis resulted in no apparent improvement of the disease.

  11. A Review of Focal Reducer Interferometer Systems

    DTIC Science & Technology

    1986-06-01

    searches. G.Courtes has also proposed a design for a focal reducer for the E.S.O. 3.6m. Ritchey -Chretien telescope (Fig. 4b). He uses a Schmidt camera...spaced components, with a modified Wynne camera design (Fig. 7). The instrument proposed used folded optics and would operate at the F/8 Ritchey Cretien ...G.Courtes for the 3.6m Ritchey Chretien telescope . a, telescope focal plane and field lens; b, collimator; c, camera. Figure 5 The focal reducer of A.B

  12. Do focal colors look particularly "colorful"?

    PubMed

    Witzel, Christoph; Franklin, Anna

    2014-04-01

    If the most typical red, yellow, green, and blue were particularly colorful (i.e., saturated), they would "jump out to the eye." This would explain why even fundamentally different languages have distinct color terms for these focal colors, and why unique hues play a prominent role in subjective color appearance. In this study, the subjective saturation of 10 colors around each of these focal colors was measured through a pairwise matching task. Results show that subjective saturation changes systematically across hues in a way that is strongly correlated to the visual gamut, and exponentially related to sensitivity but not to focal colors.

  13. Unilateral Isolated Proximal Femoral Focal Deficiency

    PubMed Central

    Doğer, Emek; Köpük, Şule Y.; Çakıroğlu, Yiğit; Çakır, Özgür; Yücesoy, Gülseren

    2013-01-01

    Objective. To discuss a patient with a prenatal diagnosis of unilateral isolated femoral focal deficiency. Case. Antenatal diagnosis of unilateral isolated femoral focal deficiency was made at 20 weeks of gestation. The length of left femur was shorter than the right, and fetal femur length was below the fifth percentile. Proximal femoral focal deficiency was diagnosed. After delivery, the diagnosis was confirmed with skeletal radiographs and magnetic resonance imaging. In prenatal ultrasonographic examination, the early recognition and exclusion of skeletal dysplasias is important; moreover, treatment plans should be initiated, and valuable information should be provided to the family. PMID:23984135

  14. Mosaic focal plane for star sensors

    NASA Astrophysics Data System (ADS)

    Chang, N. C.

    1981-02-01

    The basic principles of star sensors are reviewed with reference to the advantages of replacing photodiodes, image dissectors, and vidicons with mosaic charge transfer device (CTD) focal planes. The desirable characteristics of CTD focal planes include: high uniformity, high transfer effect, low dark current, low hot and cold spots, low dead space, low angular misalignment, high coplanarity, and high thermal stability. An implementation of a mosaic CTD array star sensor which achieves high angular position accuracy and frequency attitude update is presented. Two focal plane packaging concepts, the planar and vertical board packagings, are examined.

  15. Finding the Focal Axes of Offset Antennas

    NASA Technical Reports Server (NTRS)

    Schmidt, R. F.

    1982-01-01

    Focal axis of offset paraboloidal reflector antennas determined by direct measurement instead of trial and error. Two feed horns transmit sum or difference pattern to antenna under test, which reflects energy to far-field detector. When axis of feed horns coincides with focal axis of antenna reflector, far-field detector records minimum in amplitude difference and maximum in absolute-magnitude phase difference between sum and difference signals.

  16. An uncommon focal epithelial hyperplasia manifestation.

    PubMed

    dos Santos-Pinto, Lourdes; Giro, Elisa Maria Aparecida; Pansani, Cyneu Aguiar; Ferrari, Junia; Massucato, Elaine Maria Sgavioli; Spolidório, Luis Carlos

    2009-01-01

    Focal epithelial hyperplasia is a rare, contagious disease associated with infection of the oral mucosa by human papillomavirus types 13 or 32, characterized by multiple soft papules of the same color as the adjacent normal mucosa. It mainly affects the lower lip, buccal mucosa, and tongue. The purpose of this case report was to describe a rare verrucal lesion located in the upper gingiva that was clinically and histologically consistent with focal epithelial hyperplasia.

  17. Sighting optics including an optical element having a first focal length and a second focal length

    DOEpatents

    Crandall, David Lynn

    2011-08-01

    One embodiment of sighting optics according to the teachings provided herein may include a front sight and a rear sight positioned in spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus, for a user, images of the front sight and the target.

  18. Bacterial Tracheitis

    MedlinePlus

    ... as a complication of croup (see Croup ) or endotracheal intubation (insertion of a plastic breathing tube through the ... irregularities that distinguish bacterial tracheitis from croup. Treatment Endotracheal intubation Antibiotics With treatment, most children recover completely. Very ...

  19. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis.

    PubMed

    Dieker, Jürgen; Schlumberger, Wolfgang; McHugh, Neil; Hamann, Philip; van der Vlag, Johan; Berden, Jo H

    2015-11-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system.

  20. Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity.

    PubMed

    Gupta, Ranjan; Yadav, Akhilesh; Aggarwal, Amita

    2016-11-01

    Urinary MCP-1 (uMCP-1) levels reflect lupus nephritis (LN) disease activity. However, long-term prospective studies evaluating it as a biomarker are lacking. SLE patients with active nephritis (AN), active disease without nephritis (ANR), and inactive disease (ID) were enrolled. AN patients were followed up every 3 months for 1 year. Urine and serum samples were collected at baseline from all and at follow-up visits in AN group. Urine samples from healthy subjects (HC), rheumatoid arthritis (RA), and diabetic nephropathy (DM) patients (20 each) served as controls. Serum (sMCP-1) and uMCP-1 was measured using ELISA. Urinary values were normalized for creatinine excretion. Nonparametric tests were used. A total of 121 SLE patients were enrolled. Baseline uMCP-1 was significantly higher in AN as compared to ANR, ID, HC, and RA (p < 0.001), but it was not different from DM and showed good correlation with rSLEDAI and SLEDAI (r = 0.52 and 0.47, p < 0.001) but not with sMCP-1. On ROC analysis to differentiate between AN and ANR, uMCP-1 performed better than sMCP-1, anti-dsDNA antibodies, C3 and C4. uMCP-1 and not sMCP-1 decreased significantly at all follow-up visits (p < 0.001). uMCP-1 remained persistently elevated in a patient who developed CKD and rose before conventional markers in two patients with relapse of LN. uMCP-1 correlates well with LN disease activity and helps differentiate between AN and ANR patients. Its levels fall with treatment and may have a potential to predict poor response and relapse of LN. uMCP-1 is most likely generated locally in the kidney.

  1. Renal apolipoprotein A-I amyloidosis: a rare and usually ignored cause of hereditary tubulointerstitial nephritis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Obici, Laura; Tardanico, Regina; Röcken, Christoph; Viola, Battista Fabio; Capistrano, Mariano; Donadei, Simona; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2005-12-01

    Apolipoprotein A-I amyloidosis is a rare, late-onset, autosomal dominant condition characterized by systemic deposition of amyloid in tissues, the major clinical problems being related to renal, hepatic, and cardiac involvement. Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-I amyloidosis in five families of Italian ancestry. In all of the affected family members, the disease was caused by the Leu75Pro heterozygous mutation in exon 4 of apolipoprotein A-I gene, as demonstrated by direct sequencing and RFLP analysis. Immunohistochemistry confirmed that amyloid deposits were specifically stained with an anti-apolipoprotein A-I antibody. The clinical phenotype was mainly characterized by a variable combination of kidney and liver disturbance. The occurrence of renal involvement seemed to be almost universal, although its severity varied greatly ranging from subclinical organ damage to overt, slowly progressive renal dysfunction. The renal presentation was consistent with a tubulointerstitial disease, as suggested by the findings of defective urine-concentrating capacity, moderate polyuria, negative urinalysis, and mild tubular proteinuria. Histology confirmed tubulointerstitial nephritis. Surprising, amyloid was restricted to nonglomerular regions and limited to the renal medulla. This location of apolipoprotein A-I amyloid differs sharply from other systemic amyloidoses that are mainly characterized by glomerular and vascular deposits. The tubulointerstitial nephritis as a result of hereditary apolipoprotein A-I amyloidosis is a rare disease and a challenging diagnosis to recognize. Patients who present with familial tubulointerstitial nephritis associated with liver disease require a high index of suspicion for apolipoprotein A-I amyloidosis.

  2. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

    PubMed

    Zavada, J; Pesickova, Ss; Rysava, R; Olejarova, M; Horák, P; Hrncír, Z; Rychlík, I; Havrda, M; Vítova, J; Lukác, J; Rovensky, J; Tegzova, D; Böhmova, J; Zadrazil, J; Hána, J; Dostál, C; Tesar, V

    2010-10-01

    Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

  3. Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy

    PubMed Central

    Li, Qiu-Yu; Yu, Feng; Zhou, Fu-De; Zhao, Ming-Hui

    2016-01-01

    Abstract The aim of this study was to evaluate the efficacy of plasmapheresis in patients with lupus nephritis-combined thrombotic microangiopathy (TMA) in a Chinese cohort. Clinical and therapeutic data of patients with lupus nephritis–combined TMA were collected retrospectively. A comparison between those with and without plasmapheresis was performed. Seventy patients with renal biopsy-proven TMA in lupus nephritis were treated with conventional combined corticosteroid and immunosuppressive agents as induction therapy, 9 of the 70 patients received additional plasmapheresis. The plasmapheresis group presented with more severe SLE and renal activity indices, including a significant higher ratio of neurologic disorder (P = 0.025), lower level of platelet count (P = 0.009), higher value of serum creatinine (P = 0.038), higher percentage of anti-cardiolipin antibodies positive (P = 0.001), and higher Systemic Lupus Erythematosus Disease Activity Index scores (P = 0.012), than that of the nonplasmapheresis group. However, the plasmapheresis group had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.03). As the baseline data were significantly different between the 2 groups, the propensity score match was further designed to avoid retrospective bias. After re-analysis, the plasmapheresis group still had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.018). More importantly, the plasmapheresis group had significant less composite endpoints than that of the nonplasmapheresis group (P = 0.005). Our study suggested that additional plasmapheresis on conventional induction therapy may benefit patients with lupus nephritis-combined TMA, which warrants further explorations. PMID:27149490

  4. Unmet medical needs in lupus nephritis: solutions through evidence-based, personalized medicine

    PubMed Central

    Anders, Hans-Joachim; Weidenbusch, Marc; Rovin, Brad

    2015-01-01

    Lupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy. This review discusses the underlying reasons for these unmet medical needs and options of how to overcome them in the future. PMID:26413272

  5. Transverse myelitis in a patient with severe lupus nephritis: a case report.

    PubMed

    Mitwalli, Ahmed H; Memon, Nawaz Ali; Abu-Aisha, Hassan; Al-Wakeel, Jamal S; Tarif, Nauman; Askar, Akram; Hammad, Durdana

    2002-01-01

    We report here a case of severe lupus nephritis, Raynaud's phenomenon, digital gangrene and optic neuritis who, developed acute transverse myelitis (ATM). SLE can present virtually with any complication in the central nervous system (CNS) and ATM is a rare but serious manifestation. It is noteworthy that ATM developed in this patient while she was on intravenous cyclophosphamide (IVC) therapy having already finished six doses of monthly infusions of 10 mg/kg body weight. The patient responded well to methyl-prednisolone pulse therapy, IVC and plasmapheresis. She recovered fully and is doing well after nine months of follow-up.

  6. IgG4-Related Tubulointerstitial Nephritis Pattern in 18F-FDG PET/CT.

    PubMed

    Bélissant, Ophélie; Guernou, Mohamed; Rouvier, Philippe; Compain, Caroline; Bonardel, Gérald

    2015-10-01

    A 17-year-old adolescent girl was admitted with chronic arthralgia, Raynaud phenomenon, pericarditis, and evidences of chronic diffuse inflammation. F-FDG PET/CT scan was performed to search systemic vasculitis and showed diffuse moderate uptake in the kidneys. We suggested the existence of a nephritis, but the ultrasonography result was normal, and no treatment was introduced. Another F-FDG PET/CT scan was performed 7 months later to explore abdominal pain. It showed again diffuse intense uptake in both kidneys. A proteinuria was highlighted, and renal biopsy allowed to diagnose IgG4-related disease.

  7. Focal Mechanism determination of local M

    NASA Astrophysics Data System (ADS)

    Vales, Dina; Custório, Susana; Carrilho, Fernando

    2015-04-01

    We determine the focal mechanisms of local small (ML<3.9) earthquakes that occurred between 2013 and 2014 in mainland Portugal. These low magnitude events were recorded by several stations that provide first-motion polarity solutions. However, only few stations are located near the epicenter and record a waveform with a signal-to-noise ratio (SNR) high enough to allow full waveform modelling. To overcome this limitation, we used a new approach called cyclic scanning of the polarity solutions (CSPS) (Fojtíková and Zahradnik, 2014), which performs a joint inversion of full waveform and first motion polarities to retrieve the focal mechanism. This methodology has the advantage of yielding reliable focal mechanism solutions, even when high SNR waveforms are available from only a few near field stations (or in the limiting case, only with one single station). To apply the CSPS method one needs to: i) run the the FOCal MEChanism (FOCMEC) code (Snoke, 2003) to obtain a suite of the DC solutions corresponding to the first motion polarities, and then ii) perform the waveform modelling in order to decrease the uncertainty. The ISOLated Asperities (ISOLA) software (Sokos and Zahradník, 2008, 2013) is used in this second step. We applied this method to weak events recorded by a network of 30 broadband seismic stations that transmit data in real-time to Instituto Português do Mar e da Atmosfera (IPMA), the institution responsible for seismic monitoring in Portugal. We interpret the obtained fault plane solutions in light of active faults and regional tectonics, and in comparison with focal mechanisms previously inferred for events in the region. The focal mechanisms obtained for small earthquakes allow us to significantly expand the database of available focal mechanisms in mainland Portugal, contributing to the understanding of active deformation in the region.

  8. Transparent Meta-Analysis: Does Aging Spare Prospective Memory with Focal vs. Non-Focal Cues?

    PubMed Central

    Uttl, Bob

    2011-01-01

    Background Prospective memory (ProM) is the ability to become aware of a previously-formed plan at the right time and place. For over twenty years, researchers have been debating whether prospective memory declines with aging or whether it is spared by aging and, most recently, whether aging spares prospective memory with focal vs. non-focal cues. Two recent meta-analyses examining these claims did not include all relevant studies and ignored prevalent ceiling effects, age confounds, and did not distinguish between prospective memory subdomains (e.g., ProM proper, vigilance, habitual ProM) (see Uttl, 2008, PLoS ONE). The present meta-analysis focuses on the following questions: Does prospective memory decline with aging? Does prospective memory with focal vs. non-focal cues decline with aging? Does the size of age-related declines with focal vs. non-focal cues vary across ProM subdomains? And are age-related declines in ProM smaller than age-related declines in retrospective memory? Methods and Findings A meta-analysis of event-cued ProM using data visualization and modeling, robust count methods, and conventional meta-analysis techniques revealed that first, the size of age-related declines in ProM with both focal and non-focal cues are large. Second, age-related declines in ProM with focal cues are larger in ProM proper and smaller in vigilance. Third, age-related declines in ProM proper with focal cues are as large as age-related declines in recall measures of retrospective memory. Conclusions The results are consistent with Craik's (1983) proposal that age-related declines on ProM tasks are generally large, support the distinction between ProM proper vs. vigilance, and directly contradict widespread claims that ProM, with or without focal cues, is spared by aging. PMID:21304905

  9. Focal Plane Metrology for the LSST Camera

    SciTech Connect

    A Rasmussen, Andrew P.; Hale, Layton; Kim, Peter; Lee, Eric; Perl, Martin; Schindler, Rafe; Takacs, Peter; Thurston, Timothy; /SLAC

    2007-01-10

    Meeting the science goals for the Large Synoptic Survey Telescope (LSST) translates into a demanding set of imaging performance requirements for the optical system over a wide (3.5{sup o}) field of view. In turn, meeting those imaging requirements necessitates maintaining precise control of the focal plane surface (10 {micro}m P-V) over the entire field of view (640 mm diameter) at the operating temperature (T {approx} -100 C) and over the operational elevation angle range. We briefly describe the hierarchical design approach for the LSST Camera focal plane and the baseline design for assembling the flat focal plane at room temperature. Preliminary results of gravity load and thermal distortion calculations are provided, and early metrological verification of candidate materials under cold thermal conditions are presented. A detailed, generalized method for stitching together sparse metrology data originating from differential, non-contact metrological data acquisition spanning multiple (non-continuous) sensor surfaces making up the focal plane, is described and demonstrated. Finally, we describe some in situ alignment verification alternatives, some of which may be integrated into the camera's focal plane.

  10. Bacterial rheotaxis.

    PubMed

    Marcos; Fu, Henry C; Powers, Thomas R; Stocker, Roman

    2012-03-27

    The motility of organisms is often directed in response to environmental stimuli. Rheotaxis is the directed movement resulting from fluid velocity gradients, long studied in fish, aquatic invertebrates, and spermatozoa. Using carefully controlled microfluidic flows, we show that rheotaxis also occurs in bacteria. Excellent quantitative agreement between experiments with Bacillus subtilis and a mathematical model reveals that bacterial rheotaxis is a purely physical phenomenon, in contrast to fish rheotaxis but in the same way as sperm rheotaxis. This previously unrecognized bacterial taxis results from a subtle interplay between velocity gradients and the helical shape of flagella, which together generate a torque that alters a bacterium's swimming direction. Because this torque is independent of the presence of a nearby surface, bacterial rheotaxis is not limited to the immediate neighborhood of liquid-solid interfaces, but also takes place in the bulk fluid. We predict that rheotaxis occurs in a wide range of bacterial habitats, from the natural environment to the human body, and can interfere with chemotaxis, suggesting that the fitness benefit conferred by bacterial motility may be sharply reduced in some hydrodynamic conditions.

  11. Atypical Hemolytic Uremic Syndrome Secondary to Lupus Nephritis, Responsive to Eculizumab

    PubMed Central

    Raufi, Alexander G.; Scott, Shruti; Darwish, Omar; Harley, Kevin; Kahlon, Kanwarpal; Desai, Sheetal; Lu, Yuxin; Tran, Minh-Ha

    2016-01-01

    Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia. PMID:27781079

  12. Anticardiolipin antibody isotype profile in lupus nephritis--a cross sectional survey.

    PubMed

    Azizah, M R; Loo, C S; Zulkifli, M N; Shahnaz, M; Zaki, M; Nasuruddin, B A

    1998-09-01

    Thirty-six patients with lupus nephritis (LN) attending the Nephrology Clinic, Hospital Kuala Lumpur were studied for the prevalence of anticardiolipin antibody (ACA) isotypes (IgG and IgM) and other associated antibodies, antinuclear antibody (ANA) and anti-ds DNA antibody and to determine the possible association between serological and clinical parameters. The study population consisted of 20 (55.6%) Malays, 15 (41.7%) Chinese and 1 (2.8%) Indian with a mean age of 31.4 +/- 11.3 years, range 14 to 60 years. The female to male ratio was 11:1. The average time between diagnosis and blood sampling was 4.4 years (range 0.25 to 15 years). Increased ACA levels were found in 20 (55.6%) patients where raised IgG ACA and IgM ACA were observed in 20 (55.6%) and 2 (5.6%) cases respectively. ANA and anti-ds DNA antibodies were detected in 22 (61.1%) and 4 (11.1%) individuals respectively, with the majority (82%) showing a speckled pattern of nuclear staining. However, neither the IgM ACA nor IgG ACA showed any significant association with thrombosis or any other clinical parametres. Our preliminary study indicates that ACA is a frequent finding in lupus nephritis and that the IgG isotype is more prevalent.

  13. A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial Nephritis.

    PubMed

    Airik, Rannar; Schueler, Markus; Airik, Merlin; Cho, Jang; Porath, Jonathan D; Mukherjee, Elina; Sims-Lucas, Sunder; Hildebrandt, Friedhelm

    2016-12-01

    Karyomegalic interstitial nephritis (KIN) is a chronic interstitial nephropathy characterized by tubulointerstitial nephritis and formation of enlarged nuclei in the kidneys and other tissues. We recently reported that recessive mutations in the gene encoding FANCD2/FANCI-associated nuclease 1 (FAN1) cause KIN in humans. FAN1 is a major component of the Fanconi anemia-related pathway of DNA damage response (DDR) signaling. To study the pathogenesis of KIN, we generated a Fan1 knockout mouse model, with abrogation of Fan1 expression confirmed by quantitative RT-PCR. Challenging Fan1(-/-) and wild-type mice with 20 mg/kg cisplatin caused AKI in both genotypes. In contrast, chronic injection of cisplatin at 2 mg/kg induced KIN that led to renal failure within 5 weeks in Fan1(-/-) mice but not in wild-type mice. Cell culture studies showed decreased survival and reduced colony formation of Fan1(-/-) mouse embryonic fibroblasts and bone marrow mesenchymal stem cells compared with wild-type counterparts in response to treatment with genotoxic agents, suggesting that FAN1 mutations cause chemosensitivity and bone marrow failure. Our data show that Fan1 is involved in the physiologic response of kidney tubular cells to DNA damage, which contributes to the pathogenesis of CKD. Moreover, Fan1(-/-) mice provide a new model with which to study the pathomechanisms of CKD.

  14. Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients

    PubMed Central

    Makarova, Tatiana A.; Zvonova, Elena V.; Anilina, Alina M.; Stolyarevich, Ekaterina S.

    2016-01-01

    Lupus nephritis is one of the most severe Systemic Lupus Erythematosus features, defining treatment modality and prognosis. Our retrospective study, including 178 patients treated for lupus nephritis during 23 years with mostly cyclophosphamide-based initial regimens followed by azathioprine or mycophenolic acid, demonstrates 84.8% of renal response with 19.2% of flares, 15-year patient survival 78.7% and kidney survival 76.3%, and low damage accrual. Both patient and kidney survival significantly differ for subgroups that achieved complete or partial renal response and nonresponders: patient 15-year survival 95% versus 65% versus 35%; kidney 15-year survival 100% versus 58% versus 0%, respectively. 51% (24 out of 47) of patients evaluated at the end of the study period sustained complete renal response; however, only 9 of them had 0 disease activity according to SELENA SLEDAI scale, while 13 patients had scores 2–4 due to the serological abnormalities only. We conclude that (1) initial treatment with cyclophosphamide followed by azathioprine is effective and can be used in agreement with International Guidelines until the evidence for biological treatments benefits becomes available; (2) complete and even partial renal response have positive prognostic value, and failure to achieve renal response negatively influences kidney and patient survival; (3) the validity of complete renal response in SLE is questioned by the absence of conventional definition of SLE remission. PMID:28050564

  15. Role of TWEAK/Fn14 signalling pathway in lupus nephritis and other clinical settings.

    PubMed

    González-Sánchez, Diego A; Álvarez, Cristian M; Vásquez, Gloria; Gómez-Puerta, José A

    2016-08-29

    Knowledge of the signalling pathways involved in various diseases has enabled advances in the understanding of pathophysiological, diagnostic and therapeutic models of several inflammatory and autoimmune diseases. Systemic lupus erythematosus is a widely studied autoimmune disease that can affect multiple organs, with a major impact on morbidity and mortality when it involves the kidneys. Over the past 10 years, interest in the role of the TWEAK/Fn14 signalling pathway in lupus nephritis, as well as other clinical settings, has increased. By reviewing the literature, this article assesses the role of this pathway in lupus nephritis, underlines the importance of TWEAK in urine (uTWEAK) as a biomarker of the disease and stresses the favourable results published in the literature from the inhibition of the TWEAK/Fn14 pathway as a therapeutic target in experimental animal models, demonstrating its potential application in other settings. Results of ongoing clinical trials and future research will give us a better understanding of the real benefit of blocking this pathway in the clinical course of several conditions.

  16. Attenuation of immune complex nephritis in NZB/WF1 mice by a prostacyclin analogue.

    PubMed Central

    Utsunomiya, Y; Ogura, M; Kawamura, T; Mitarai, T; Maruyama, N; Sakai, O

    1995-01-01

    Although prostaglandins have been shown to inhibit the evolution of the nephritis in NZB/W mice, the mechanisms of this effect are unknown. To characterize such inhibition, we injected the prostacyclin (PGI2) analogue, beraprost, into NZB/W mice, using 0.5 mg, 1.0 mg or 5.0 mg beraprost/kg body weight of test animals three times in 1 week when the mice were 2 months old. Evaluation included measurement of urine albumin excretion, serological parameters and splenic T cell subset, as well as examination of renal histology by light and fluorescence microscopy. Mice given beraprost showed a marked decrease in urine albumin excretion and in glomerular hypercellularity compared with untreated controls. Maximal beneficial effects occurred when the dose was 5.0 mg/kg of beraprost. These effects correlated with a reduction of immune complex deposition in glomeruli. In addition, beraprost reduced serum levels of immunoglobulins and anti-double-stranded DNA antibodies, and decreased the number of helper (L3T4+) T cells in splenocytes. These results indicate that beraprost attenuates the nephritis of NZB/W mice, and that the source of this effect is the reduced production of autoantibodies and deposition of immune complexes in glomeruli. Images Fig. 2 Fig. 3 Fig. 4 PMID:7882569

  17. Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

    PubMed Central

    2012-01-01

    Introduction Microthrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN. Methods Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data. Results Microthrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome. Conclusions Microthrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series. PMID:22640796

  18. [Tubulointerstitial nephritis associated with treatment with selective Cox-2 inhibitors, celecoxib and rofecoxib].

    PubMed

    Ortiz, M; Mon, C; Fernández, M J; Sánchez, R; Mampaso, F; Alvarez Ude, F

    2005-01-01

    The nephrotoxic effect of nonselective nonsteroidal anti-inflamatory drugs (NSAIDS) has been widely described. The main benefit of the Cox-2 inhibitors in relation to the NSAIDS is the production of a very similar analgesic effect, but with fewer gastrointestinal side effects. However, their effects on renal function are little known as yet and their long-term safety is still pending definition. The use of selective Cox-2 inhibitors as anti-inflamatory analgesic is becoming more and more common in our environment. We report two cases of tubulointersticial nephritis confirmed by renal biopsy, associated with administration of the two Cox-2 inhibitors currently available on the market, celecoxib and rofecoxib. In both cases, we were talking about elderly women, with deterioration of the general condition and acute renal failure. In the former case, renal biopsy showed an acute tubulo-intersticial nephritis (TIN) so highly "variegated" in its histologic expression. In the second case, was associated with strong indications of chronicity. Treatment with steroid was initiated in both patients and improvement of renal function was observed.

  19. [Case of lupus vasculopathy associated with lupus nephritis class IV-G (A)].

    PubMed

    Eguchi, Eriko; Shimazu, Keiji; Takaori, Kouji; Nishiguchi, Kensuke; Mori, Keita; Yorifuji, Soushi; Murakami, Toru; Koshikawa, Masao; Tanaka, Atsuo; Kuwahara, Takashi

    2010-01-01

    Various renal vascular lesions are complicated with systemic lupus erythematosus (SLE), and are often overlooked in the actual renal biopsy specimen. We report a case of biopsy-proven lupus vasculopathy, with lupus nephritis class IV-G (A). She developed SLE at 15 years of age, and was treated with prednisolone(PSL) and cyclophosphamide (CTX). Sometimes she experienced a flare-up clinically or serologically, requiring a dose increase of oral PSL. At 40 years of age, she visited our hospital after discontinuation of hospital visits for about 4 months. Oral PSL at 30 mg per day was not effective for urinary abnormalities, increase of anti double-stranded DNA (ds-DNA) antibody titer and decrease in complement components. On admission she had hypertension (180/92 mmHg) and signs of microangiopathic hemolytic anemia. Renal biopsy findings showed the glomerular changes of lupus nephritis, WHO class IV-G (A), and lupus vasculopathy, which is marked luminal narrowing or total occlusion by abundant subendothelial accumulation of immunoglobulins and complement components. In addition to PSL, intravenous pulse CTX promptly achieved clinical remission. When lupus vasculopathy is complicated, CTX may be useful.

  20. NMR based serum metabolomics reveals a distinctive signature in patients with Lupus Nephritis

    PubMed Central

    Guleria, Anupam; Pratap, Avadhesh; Dubey, Durgesh; Rawat, Atul; Chaurasia, Smriti; Sukesh, Edavalath; Phatak, Sanat; Ajmani, Sajal; Kumar, Umesh; Khetrapal, Chunni Lal; Bacon, Paul; Misra, Ramnath; Kumar, Dinesh

    2016-01-01

    Management of patient with Lupus Nephritis (LN) continues to remain a challenge for the treating physicians because of considerable morbidity and even mortality. The search of biomarkers in serum and urine is a focus of researchers to unravel new targets for therapy. In the present study, the utility of NMR-based serum metabolomics has been evaluated for the first time in discriminating LN patients from non-nephritis lupus patients (SLE) and further to get new insights into the underlying disease processes for better clinical management. Metabolic profiling of sera obtained from 22 SLE patients, 40 LN patients and 30 healthy controls (HC) were performed using high resolution 1D 1H-CPMG and diffusion edited NMR spectra to identify the potential molecular biomarkers. Using multivariate analysis, we could distinguish SLE and LN patients from HC and LN from SLE patients. Compared to SLE patients, the LN patients had increased serum levels of lipid metabolites (including LDL/VLDL lipoproteins), creatinine and decreased levels of acetate. Our results revealed that metabolic markers especially lipids and acetate derived from NMR spectroscopy has high sensitivity and specificity to distinguish LN among SLE patients and has the potential to be a useful adjunctive tool in diagnosis and clinical management of LN. PMID:27739464

  1. Interstitial nephritis, acute renal failure in a patient with non-fulminant hepatitis A infection.

    PubMed

    Vaboe, A L; Leh, S; Forslund, T

    2002-02-01

    This is the first report from Norway of a patient with interstitial nephritis and renal failure due to non-fulminant hepatitis A virus (HAV) infection. HAV infection was confirmed by positive anti-HAV IgM serology. All tests for other virus infections were negative. At admittance serum creatinine (s-Creat) and blood urea nitrogen (BUN) concentration were 539 microlmol/l and 32.6 mmol/l increasing the following days to 890 micromol/l and 39.9 mmol/l, respectively. Nine courses of hemodialysis had to be given. Kidney biopsy specimen showed interstitial edema, lymphocytic cell infiltration and acute tubular injury with normal glomeruli. Examination with immunohistochemistry was negative. In contrast to the findings associated with HBV and HCV infection in which glomerular disease is predominantly found, the HAV infection in our patient was associated with interstitial nephritis and acute tubular necrosis. The prognosis of the renal failure due to HAV infection was good although the recovery was substantially delayed.

  2. Genome-wide profiling identifies associations between lupus nephritis and differential methylation of genes regulating tissue hypoxia and type 1 interferon responses

    PubMed Central

    Mok, Amanda; Solomon, Olivia; Nayak, Renuka R; Coit, Patrick; Quach, Hong L; Nititham, Joanne; Sawalha, Amr H; Barcellos, Lisa F; Criswell, Lindsey A; Chung, Sharon A

    2016-01-01

    Objective Previous studies have shown that differential DNA methylation is associated with SLE susceptibility. How DNA methylation affects the clinical heterogeneity of SLE has not been fully defined. We conducted this study to identify differentially methylated CpG sites associated with nephritis among women with SLE. Methods The methylation status of 428 229 CpG sites across the genome was characterised for peripheral blood cells from 322 women of European descent with SLE, 80 of whom had lupus nephritis, using the Illumina HumanMethylation450 BeadChip. Multivariable linear regression adjusting for population substructure and leucocyte cell proportions was used to identify differentially methylated sites associated with lupus nephritis. The influence of genetic variation on methylation status was investigated using data from a genome-wide association study of SLE. Pathway analyses were used to identify biological processes associated with lupus nephritis. Results We identified differential methylation of 19 sites in 18 genomic regions that was associated with nephritis among patients with SLE (false discovery rate q<0.05). Associations for four sites in HIF3A, IFI44 and PRR4 were replicated when examining methylation data derived from CD4+ T cells collected from an independent set of patients with SLE. These associations were not driven by genetic variation within or around the genomic regions. In addition, genes associated with lupus nephritis in a prior genome-wide association study were not differentially methylated in this epigenome-wide study. Pathway analysis indicated that biological processes involving type 1 interferon responses and the development of the immune system were associated with nephritis in patients with SLE. Conclusions Differential methylation of genes regulating the response to tissue hypoxia and interferon-mediated signalling is associated with lupus nephritis among women with SLE. These findings have not been identified in genetic

  3. Focal Adhesion-Independent Cell Migration.

    PubMed

    Paluch, Ewa K; Aspalter, Irene M; Sixt, Michael

    2016-10-06

    Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion-independent migration, and highlight the remaining open questions for the future.

  4. Measuring microfocus focal spots using digital radiography

    SciTech Connect

    Fry, David A

    2009-01-01

    Measurement of microfocus spot size can be important for several reasons: (1) Quality assurance during manufacture of microfocus tubes; (2) Tracking performance and stability of microfocus tubes; (3) Determining magnification (especially important for digital radiography where the native spatial resolution of the digital system is not adequate for the application); (4) Knowledge of unsharpness from the focal spot alone. The European Standard EN 12543-5 is based on a simple geometrical method of calculating focal spot size from unsharpness of high magnification film radiographs. When determining microfocus focal spot dimensions using unsharpness measurements both signal-to-noise (SNR) and magnification can be important. There is a maximum accuracy that is a function of SNR and therefore an optimal magnification. Greater than optimal magnification can be used but it will not increase accuracy.

  5. Solid-state curved focal plane arrays

    NASA Technical Reports Server (NTRS)

    Nikzad, Shouleh (Inventor); Hoenk, Michael (Inventor); Jones, Todd (Inventor)

    2010-01-01

    The present invention relates to curved focal plane arrays. More specifically, the present invention relates to a system and method for making solid-state curved focal plane arrays from standard and high-purity devices that may be matched to a given optical system. There are two ways to make a curved focal plane arrays starting with the fully fabricated device. One way, is to thin the device and conform it to a curvature. A second way, is to back-illuminate a thick device without making a thinned membrane. The thick device is a special class of devices; for example devices fabricated with high purity silicon. One surface of the device (the non VLSI fabricated surface, also referred to as the back surface) can be polished to form a curved surface.

  6. Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice.

    PubMed Central

    Vyse, T J; Drake, C G; Rozzo, S J; Roper, E; Izui, S; Kotzin, B L

    1996-01-01

    F1 hybrids of New Zealand black (NZB) and New Zealand white (NZW) mice are a model of human systemic lupus erythematosus. These mice develop a severe immune com-plex-mediated nephritis, in which antinuclear autoantibodies are believed to play the major role. We used a genetic analysis of (NZB x NZW)F1 x NZW backcross mice to provide insight into whether different autoantibodies are subject to separate genetic influences and to determine which autoantibodies are most important in the development of lupus-like nephritis. The results showed one set of loci that coordinately regulated serum levels of IgG antibodies to double-stranded DNA, single-stranded DNA, total histones, and chromatin, which overlapped with loci that were linked to the production of autoantibodies to the viral glycoprotein, gp70. Loci linked with anti-gp70 compared with antinuclear antibodies demonstrated the strongest linkage with renal disease, suggesting that autoantibodies to gp70 are the major pathogenic antibodies in this model of lupus nephritis. Interestingly, a distal chromosome 4 locus, Nba1, was linked with nephritis but not with any of the autoantibodies measured, suggesting that it contributes to renal disease at a checkpoint distal to autoantibody production. PMID:8878426

  7. Achromatic phase shifting focal plane masks

    NASA Astrophysics Data System (ADS)

    Newman, Kevin

    The search for life on other worlds is an exciting scientific endeavor that could change the way we perceive our place in the universe. Thousands of extrasolar planets have been discovered using indirect detection techniques. One of the most promising methods for discovering new exoplanets and searching for life is direct imaging with a coronagraph. Exoplanet coronagraphy of Earth-like planets is a challenging task, but we have developed many of the tools necessary to make it feasible. The Phase-Induced Amplitude Apodization (PIAA) Coronagraph is one of the highest-performing architectures for direct exoplanet imaging. With a complex phase-shifting focal plane mask, the PIAA Complex Mask Coronagraph (PIAACMC) can approach the theoretical performance limit for any direct detection technique. The architecture design is flexible enough to be applied to any arbitrary aperture shape, including segmented and obscured apertures. This is an important feature for compatibility with next-generation ground and space-based telescopes. PIAA and PIAACMC focal plane masks have been demonstrated in monochromatic light. An important next step for high-performance coronagraphy is the development of broadband phase-shifting focal plane masks. In this dissertation, we present an algorithm for designing the PIAA and PIAACMC focal plane masks to operate in broadband. We also demonstrate manufacturing of the focal plane masks, and show laboratory results. We use simulations to show the potential performance of the coronagraph system, and the use of wavefront control to correct for mask manufacturing errors. Given the laboratory results and simulations, we show new areas of exoplanet science that can potentially be explored using coronagraph technology. The main conclusion of this dissertation is that we now have the tools required to design and manufacture PIAA and PIAACMC achromatic focal plane masks. These tools can be applied to current and future telescope systems to enable new

  8. Extensive Focal Epithelial Hyperplasia: A Case Report.

    PubMed

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  9. A simple method for focal length measurement

    NASA Astrophysics Data System (ADS)

    Ma, Hua; Ren, Huan; Zhang, Lin; Shi, Zhengdong; Yuan, Quan; Yang, Yi

    2016-09-01

    A simple method for focal length measurement based on image processing is demonstrated and discussed. The collimated beam, detector, motorized translation stage and computer make up of this test system. The two spots pass through the tested lens is accepted by detector, which is transferred twice by motorized translation stage. By acquired the difference of two spots by image processing, the focal length of the tested lens can be gained. The error sources in the measurement are analyzed. Then the results of experiment show that the relative error was 0.1%. This method can be used in workshop and labs for its convenience and low cost.

  10. Natural course of symptomatic focal choroidal excavation.

    PubMed

    Pierro, Luisa; Casalino, Giuseppe; Introini, Ugo; Gagliardi, Marco; Sergenti, Jessica; Cascavilla, Maria Lucia; Bandello, Francesco

    2015-01-01

    A 32-year-old man was referred to the authors' department for nonspecified macular dystrophy with persistent metamorphopsia in the right eye diagnosed 10 years before and followed using optical coherence tomography. The patient underwent a comprehensive ocular examination, including multimodal imaging evaluation and electrofunctional testing. The diagnosis was consistent with nonconforming focal choroid excavation. Over 10 years, no complications occurred, visual acuity was stable, and optical coherence tomography showed no progression of the lesion during follow-up. In this case, nonconforming symptomatic focal choroid excavation was a nonprogressive condition with good long-term visual outcome.

  11. [Liver ultrasound: focal lesions and diffuse diseases].

    PubMed

    Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

    2016-01-01

    Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed.

  12. Crystal diffraction lens with variable focal length

    DOEpatents

    Smither, R.K.

    1991-04-02

    A method and apparatus for altering the focal length of a focusing element of one of a plurality of pre-determined focal lengths by changing heat transfer within selected portions of the element by controlled quantities is disclosed. Control over heat transfer is accomplished by manipulating one or more of a number of variables, including: the amount of heat or cold applied to surfaces; type of fluids pumped through channels for heating and cooling; temperatures, directions of flow and rates of flow of fluids; and placement of channels. 19 figures.

  13. Crystal diffraction lens with variable focal length

    DOEpatents

    Smither, Robert K.

    1991-01-01

    A method and apparatus for altering the focal length of a focusing element o one of a plurality of pre-determined focal lengths by changing heat transfer within selected portions of the element by controlled quantities. Control over heat transfer is accomplished by manipulating one or more of a number of variables, including: the amount of heat or cold applied to surfaces; type of fluids pumped through channels for heating and cooling; temperatures, directions of flow and rates of flow of fluids; and placement of channels.

  14. Actinic Granuloma with Focal Segmental Glomerulosclerosis

    PubMed Central

    Phasukthaworn, Ruedee; Chanprapaph, Kumutnart; Vachiramon, Vasanop

    2016-01-01

    Actinic granuloma is an uncommon granulomatous disease, characterized by annular erythematous plaque with central clearing predominately located on sun-damaged skin. The pathogenesis is not well understood, ultraviolet radiation is recognized as precipitating factor. We report a case of a 52-year-old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years. The clinical presentation and histopathologic findings support the diagnosis of actinic granuloma. During that period of time, she also developed focal segmental glomerulosclerosis. The association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies. PMID:27293392

  15. [Antiperspirants for the therapy of focal hyperhidrosis].

    PubMed

    Streker, M; Kerscher, M

    2012-06-01

    In Europe often no clear distinction is made between deodorant and antiperspirant. Particularly in Germany, the labeling "deo" is used for both. Only antiperspirants are capable of influencing the activity of eccrine sweat glands. In the treatment of focal hyperhidrosis, the use of aluminum chloride solutions represents the first choice. The efficacy is well documented in a variety of studies. Subjective side effects include pruritus and - less often - irritant dermatitis, which can be treated symptomatically and usually does not require discontinuation of the treatment. Rare variants of focal hyperhidrosis like auriculotemporal syndrome, Ross syndrome and nevus sudoriferus also are suitable for treatment with topical aluminum chloride hexahydrate solutions.

  16. Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.

    PubMed

    Moroni, Gabriella; Doria, Andrea; Giglio, Elisa; Tani, Chiara; Zen, Margherita; Strigini, Francesca; Zaina, Barbara; Tincani, Angela; de Liso, Federica; Matinato, Caterina; Grossi, Claudia; Gatto, Mariele; Castellana, Paola; Limardo, Monica; Meroni, Pier Luigi; Messa, Piergiorgio; Ravani, Pietro; Mosca, Marta

    2016-11-01

    The aim of this multicenter study was to assess the present risk of fetal complications and the inherent risk factors in pregnant women with lupus nephritis. Seventy-one pregnancies in 61women (59 Caucasians and 2 Asians) with lupus nephritis were prospectively followed between October 2006 and December 2013. All patients received a counselling visit within 3 months before the beginning of pregnancy and were followed by a multidisciplinary team. At baseline mild active nephritis was present in 15 cases (21.1%). Six pregnancies (8.4%) resulted in fetal loss. Arterial hypertension at baseline (P = 0.003), positivity for lupus anticoagulant (P = 0.001), anticardiolipin IgG antibodies (P = 0.007), antibeta2 IgG (P = 0.018) and the triple positivity for antiphospholipid antibodies (P = 0.004) predicted fetal loss. Twenty pregnancies (28.2%) ended pre-term and 12 newborns (16.4%) were small for gestational age. Among the characteristics at baseline, high SLE disease activity index (SLEDAI) score (P = 0.027), proteinuria (P = 0.045), history of renal flares (P = 0.004), arterial hypertension (P = 0.009) and active lupus nephritis (P = 0.000) increased the probability of preterm delivery. Odds for preterm delivery increased by 60% for each quarterly unit increase in SLEDAI and by 15% for each quarterly increase in proteinuria by 1 g per day. The probability of having a small for gestational age baby was reduced by 85% in women who received hydroxychloroquine therapy (P = 0.023). In this study, the rate of fetal loss was low and mainly associated with the presence of antiphospholipid antibodies. Preterm delivery remains a frequent complication of pregnancies in lupus. SLE and lupus nephritis activity are the main risk factors for premature birth. Arterial hypertension predicted both fetal loss and preterm delivery. Based on our results the key for a successful pregnancy in lupus nephritis is a multidisciplinary approach with close medical, obstetric

  17. Sensory-motor integration in focal dystonia.

    PubMed

    Avanzino, Laura; Tinazzi, Michele; Ionta, Silvio; Fiorio, Mirta

    2015-12-01

    Traditional definitions of focal dystonia point to its motor component, mainly affecting planning and execution of voluntary movements. However, focal dystonia is tightly linked also to sensory dysfunction. Accurate motor control requires an optimal processing of afferent inputs from different sensory systems, in particular visual and somatosensory (e.g., touch and proprioception). Several experimental studies indicate that sensory-motor integration - the process through which sensory information is used to plan, execute, and monitor movements - is impaired in focal dystonia. The neural degenerations associated with these alterations affect not only the basal ganglia-thalamic-frontal cortex loop, but also the parietal cortex and cerebellum. The present review outlines the experimental studies describing impaired sensory-motor integration in focal dystonia, establishes their relationship with changes in specific neural mechanisms, and provides new insight towards the implementation of novel intervention protocols. Based on the reviewed state-of-the-art evidence, the theoretical framework summarized in the present article will not only result in a better understanding of the pathophysiology of dystonia, but it will also lead to the development of new rehabilitation strategies.

  18. [Focal epithelial hyperplasia. An unusual clinical aspect].

    PubMed

    Bodokh, I; Lacour, J P; Rainero, C; Orth, G; Perrin, C; Hoffman, P; Santini, J; Ortonne, J P

    1993-01-01

    We report a case of focal epithelial hyperplasia in a child born in France of Algerian parents. The clinical appearance was unusual in that certain lesions were verrucous and pediculate. A virological study revealed the presence of papillomavirus 32, one of the two types of HPV specifically associated with this entity.

  19. MTI Focal Plane Assembly Design and Performance

    SciTech Connect

    Ballard, M.; Rienstra, J.L.

    1999-06-17

    The focal plane assembly for the Multispectral Thermal Imager (MTI) consists of sensor chip assemblies, optical filters, and a vacuum enclosure. Sensor chip assemblies, composed of linear detector arrays and readout integrated circuits, provide spatial resolution in the cross-track direction for the pushbroom imager. Optical filters define 15 spectral bands in a range from 0.45 {micro}m to 10.7 {micro}m. All the detector arrays are mounted on a single focal plane and are designed to operate at 75 K. Three pairs of sensor chip assemblies (SCAs) are required to provide cross-track coverage in all 15 spectral bands. Each pair of SCAs includes detector arrays made from silicon, iridium antimonide, and mercury cadmium telluride. Read out integrated circuits multiplex the signals from the detectors to 18 separate video channels. Optical filter assemblies defining the spectral bands are mounted over the linear detector arrays. Each filter assembly consists of several filter strips bonded together side-by-side. The MTI focal plane assembly has been integrated with the rest of the payload and has undergone detailed testing and calibration. This paper includes representative test data for the various spectral bands and the overall performance of the focal plane assembly.

  20. Pure Gerstmann's syndrome from a focal lesion.

    PubMed

    Roeltgen, D P; Sevush, S; Heilman, K M

    1983-01-01

    It is controversial whether a focal lesion can specifically induce Gerstmann's syndrome (dyscalculia, left-right disorientation, finger agnosia, and agraphia). Also, Gerstmann's tetrad has been attributed to other cerebral symptoms, particularly aphasia. We examined a patient who had all four symptoms of Gerstmann's syndrome, without other symptoms or signs, and who had a discrete left parietal lesion.

  1. Complex source description of focal regions.

    PubMed

    Monzon, Cesar; Forester, Donald W; Moore, Peter

    2006-04-01

    Closed-form solutions of the two-dimensional homogeneous wave equation are presented that provide focal-region descriptions corresponding to a converging bundle of rays. The solutions do have evanescent wave content and can be described as a source-sink pair or particle-antiparticle pair, collocated in complex space, with the complex location being critical in the determination of beam shape and focal region size. The wave solutions are not plagued by singularities, have a finite energy, and have a limitation on how small the focal size can get, with a penalty for limiting small spot sizes in the form of impractically high associated reactive energy. The electric-field-defined spot-size limiting value is 0.35lambda x 0.35lambda, which is about 38% of the Poynting-vector-defined minimum spot size (0.8lambda x 0.4lambda) and corresponds to a condition related to the maximum possible beam angle. A multiple set of solutions is introduced, and the elementary solutions are used to produce new solutions via superposition, resulting in fields with chiral character or with increased depth of focus. We do not claim generality, as the size of focal regions exhibited by the closed-form solutions has a lower bound and hence is not able to account for Pendry's "ideal lens" scenario.

  2. Optical interconnections to focal plane arrays

    SciTech Connect

    Rienstra, J.L.; Hinckley, M.K.

    2000-11-01

    The authors have successfully demonstrated an optical data interconnection from the output of a focal plane array to the downstream data acquisition electronics. The demonstrated approach included a continuous wave laser beam directed at a multiple quantum well reflectance modulator connected to the focal plane array analog output. The output waveform from the optical interconnect was observed on an oscilloscope to be a replica of the input signal. They fed the output of the optical data link to the same data acquisition system used to characterize focal plane array performance. Measurements of the signal to noise ratio at the input and output of the optical interconnection showed that the signal to noise ratio was reduced by a factor of 10 or more. Analysis of the noise and link gain showed that the primary contributors to the additional noise were laser intensity noise and photodetector receiver noise. Subsequent efforts should be able to reduce these noise sources considerably and should result in substantially improved signal to noise performance. They also observed significant photocurrent generation in the reflectance modulator that imposes a current load on the focal plane array output amplifier. This current loading is an issue with the demonstrated approach because it tends to negate the power saving feature of the reflectance modulator interconnection concept.

  3. Dual band QWIP focal plane array

    NASA Technical Reports Server (NTRS)

    Gunapala, Sarath D. (Inventor); Choi, Kwong Kit (Inventor); Bandara, Sumith V. (Inventor)

    2005-01-01

    A quantum well infrared photodetector (QWIP) that provides two-color image sensing. Two different quantum wells are configured to absorb two different wavelengths. The QWIPs are arrayed in a focal plane array (FPA). The two-color QWIPs are selected for readout by selective electrical contact with the two different QWIPs or by the use of two different wavelength sensitive gratings.

  4. Estimation of focal and extra-focal radiation profiles based on Gaussian modeling in medical linear accelerators.

    PubMed

    Anai, Shigeo; Arimura, Hidetaka; Nakamura, Katsumasa; Araki, Fujio; Matsuki, Takaomi; Yoshikawa, Hideki; Yoshidome, Satoshi; Shioyama, Yoshiyuki; Honda, Hiroshi; Ikeda, Nobuo

    2011-07-01

    The X-ray source or focal radiation is one of the factors that can degrade the conformal field edge in stereotactic body radiotherapy. For that reason, it is very important to estimate the total focal radiation profiles of linear accelerators, which consists of X-ray focal-spot radiation and extra-focal radiation profiles. Our purpose in this study was to propose an experimental method for estimating the focal-spot and extra-focal radiation profiles of linear accelerators based on triple Gaussian functions. We measured the total X-ray focal radiation profiles of the accelerators by moving a slit in conjunction with a photon field p-type silicon diode. The slit width was changed so that the extra-focal radiation could be optimally included in the total focal radiation. The total focal radiation profiles of an accelerator at 4-MV and 10-MV energies were approximated with a combination of triple Gaussian functions, which correspond to the focal-spot radiation, extra-focal radiation, and radiation transmitted through the slit assembly. As a result, the ratios of the Gaussian peak value of the extra-focal radiation to that of the focal spot for 4 and 10 MV were 0.077 and 0.159, respectively. The peak widths of the focal-spot and extra-focal radiation profiles were 0.57 and 25.0 mm for 4 MV, respectively, and 0.60 and 22.0 mm for 10 MV, respectively. We concluded that the proposed focal radiation profile model based on the triple Gaussian functions may be feasible for estimating the X-ray focal-spot and extra-focal radiation profiles.

  5. Comparison of Renal Response Parameters for Juvenile Membranous Plus Proliferative Lupus Nephritis Versus Isolated Proliferative Lupus Nephritis: A Cross-Sectional Analysis of the CARRA Registry

    PubMed Central

    Boneparth, Alexis; Ilowite, Norman T.

    2014-01-01

    Lupus nephritis (LN) affects many patients with juvenile systemic lupus erythematosus (SLE) and is a significant cause of disease morbidity. Membraneous plus proliferative LN (M+PLN) may represent a more difficult to treat subtype of juvenile LN, compared to isolated proliferative LN (PLN.) In this retrospective observational study, we utilized data from the Childhood Arthritis and Rheumatism Research Alliance (CARRA) registry to compare response rates for pediatric M+PLN versus PLN. Response was assessed at the most recent CARRA registry visit gathered ≥ 6 months after diagnostic kidney biopsy. Estimated glomerular filtration rate (GFR) less than 90 ml/min/1.73m2, indicating renal insufficiency, was found in 16.1% of patients with M+PLN and 6.1% of patients with PLN (P=0.071). We found no significant difference in achievement of response in either hematuria or proteinuria between PLN and M+PLN groups or between subgroups determined by presence of class III vs. class IV proliferative disease. Exposure rates to mycophenolate, cyclophosphamide, and rituximab were similar between groups. Future studies will be necessary to correlate pediatric LN renal histology data with treatment response as well as other disease outcome measures. PMID:24729278

  6. X-ray sources of medical linear accelerators: focal and extra-focal radiation.

    PubMed

    Jaffray, D A; Battista, J J; Fenster, A; Munro, P

    1993-01-01

    A computerized tomography (CT) reconstruction technique has been used to make quantitative measurements of the size and shape of the focal spot in medical linear accelerators. Using this technique, we have measured the focal spots in a total of nine accelerators, including (i) two Varian Clinac 2100c's, (ii) two Atomic Energy of Canada Ltd. (AECL) Therac-25's, (iii) two AECL Therac 6's, (iv) a Siemens KD-2, (v) a Varian Clinac 600c (4 MV), and (vi) an AECL Therac-20. Some of these focal spots were monitored for changes over a 2-yr period. It has been found that (i) the size and shape of the source spot varies greatly between accelerators of different design ranging from 0.5 to 3.4 mm in full width at half maximum (FWHM); and (ii) for accelerators of the same design, the focal spots are very similar. In addition to the measurements of the focal spot, a new technique for measuring the magnitude and distribution of extra-focal radiation originating from the linear accelerator head (flattening filter, primary collimator) has also been developed. The extra-focal radiation produced by a Varian Clinac 2100c accelerator was measured using this technique and it was found that the extra-focal radiation accounts for as much as 8% of the total photon fluence reaching the isocenter. The majority (75%) of this extra-focal radiation originates from within a circle 6 cm in diameter at the target plane. The source MTFs for each of the measured focal spots have been calculated in order to assess their influence on the spatial resolution of verification images. The limiting spatial resolution (i.e., 10% modulation) for all the source MTFs is 1.8 mm-1 or greater when used for transmission radiography at a magnification of 1.2. The extra-focal radiation, which produces a low-frequency drop in the source MTFs of up to 8%, changes with field size. As a result, the source MTFs of linear accelerators depend not only on the design of individual accelerators and image magnification, but also

  7. Clinical outcomes of kidney transplants on patients with end-stage renal disease secondary to lupus nephritis, polycystic kidney disease and diabetic nephropathy

    PubMed Central

    Nieto-Ríos, John Fredy; Builes-Rodriguez, Sheila Alexandra; Restrepo-Correa, Ricardo Cesar; Aristizabal-Alzate, Arbey; Ocampo-Kohn, Catalina; Serna-Campuzano, Angélica; Cardona-Díaz, Natalia; Giraldo-Ramirez, Nelson Darío; Zuluaga-Valencia, Gustavo Adolfo

    2016-01-01

    Background: Patients with lupus nephritis could progress to end-stage renal disease (10-22%); hence, kidney transplants should be considered as the treatment of choice for these patients. Objective: To evaluate the clinical outcomes after kidney transplants in patients with chronic kidney diseases secondary to lupus nephritis, polycystic kidney disease and diabetes nephropathy at Pablo Tobon Uribe Hospital. Methods: A descriptive and retrospective study performed at one kidney transplant center between 2005 and 2013. Results: A total of 136 patients, 27 with lupus nephritis (19.9%), 31 with polycystic kidney disease (22.8%) and 78 with diabetes nephropathy (57.4%), were included in the study. The graft survivals after one, three and five years were 96.3%, 82.5% and 82.5% for lupus nephritis; 90%, 86% and 76.5% for polycystic kidney disease and 91.7%, 80.3% and 67.9% for diabetes nephropathy, respectively, with no significant differences (p= 0.488); the rate of lupus nephritis recurrence was 0.94%/person-year. The etiology of lupus vs diabetes vs polycystic disease was not a risk factor for a decreased time of graft survival (Hazard ratio: 1.43; 95% CI: 0.52-3.93). Conclusion: Kidney transplant patients with end stage renal disease secondary to lupus nephritis has similar graft and patient survival success rates to patients with other kidney diseases. The complication rate and risk of recurrence for lupus nephritis are low. Kidney transplants should be considered as the treatment of choice for patients with end stage renal disease secondary to lupus nephritis. PMID:27226665

  8. Vasculitis and vasculopathy in Lupus Nephritis: Clinical variability, outcome, and new insight into treatment.

    PubMed

    Kaul, A; Agrawal, V; Bhaduaria, D; Agrawal, Vikas; Prasad, Narayan; Gupta, Amit; Sharma, R K

    2017-01-01

    More than 50% of patients with systemic lupus erythematosus (SLE) have renal involvement at presentation or during their illness. Lupus nephritis (LN) encompasses several patterns of renal disease, including glomerular, tubulointerstitial, and vascular pathologies. The presence and significance of renal vascular lesions (VLs) are often overlooked. VLs in LN are not rare with an incidence of 10%-40% on renal biopsies from various studies and their presence is often labeled as poor prognostic markers. The current treatment protocol for LN is mainly based on the glomerular pathology, and no guidelines/consensus exists for treatment of LN with VLs. We describe the clinical presentation, course, response to therapy, and outcomes in five patients with SLE with histological evidence of renal VLs.

  9. Lupus vasculopathy combined with renal infarction: unusual manifestation of lupus nephritis.

    PubMed

    Sugimoto, Toshiro; Kanasaki, Keizo; Morita, Yoshikata; Yokomaku, Yukiyo; Narita, Mitsuhiro; Koyama, Tetsuro; Tanaka, Yuki; Kashiwagi, Atsunori; Koya, Daisuke

    2005-11-01

    A 30-year-old woman with a 10-year history of systemic lupus erythematosus was admitted to our hospital because of the onset of hypertension and renal dysfunction. Renal arteriogram revealed multiple renal infarctions, and cut-off or tapering-stenosis in the interlobular arteries. Renal biopsy showed concentric intimal thickening with narrowed lumen in some arterioles and deposition of IgG/IgM/complement 3 in the wall of arteriole without any active lesions or immune complex deposition in glomeruli. The present case indicates that this type of renal vascular lesion in lupus nephritis, lupus vasculopathy, may cause renal infarction and the loss of renal function without active glomerular lesions.

  10. Therapy of lupus nephritis: lessons learned from clinical research and daily care of patients

    PubMed Central

    2012-01-01

    Despite numerous randomized clinical trials over the last three decades for identifying the optimal treatment option for lupus nephritis, renal involvement still significantly impacts the survival and quality of life of patients with lupus and the search for the ideal immunosuppressive regimen is far from complete. The purpose of this review is to summarize the major recent achievements in the field. More specifically, the following topics will be discussed: intravenous cyclophosphamide versus mycophenolate mofetil (MMF) for induction; azathioprine versus MMF for maintenance; targeted therapies. The review will address clues for optimal global care, such as the need for complete initial evaluation, the importance of patient education, the unmasking of non-compliance to therapy, the reason for an early treatment switch in non-responding patients, the need for prolonged immunosuppression, optimal renal protection, and prevention of cardiovascular disease and other comorbidities. PMID:22293173

  11. Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in autoimmune murine lupus nephritis.

    PubMed Central

    Wuthrich, R. P.; Jevnikar, A. M.; Takei, F.; Glimcher, L. H.; Kelley, V. E.

    1990-01-01

    Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein regulating interactions among immune cells. To determine whether altered expression of ICAM-1 occurs in autoimmune lupus nephritis, we studied ICAM-1 expression in kidneys of normal and autoimmune MRL-lpr and (NZBX NZW)F1 (NZB/W) mice. By immunoperoxidase staining, ICAM-1 is constitutively expressed at low levels in proximal tubules (PT), endothelium and interstitial cells in normal C3H/FeJ mice. In nephritic MRL-lpr and NZB/W kidneys, staining for ICAM-1 is increased in the PT, particularly in the brush border, and is prominent in the glomerular mesangium and the endothelium of large vessels. By Western blot analysis, ICAM-1 is not detected in the urine of normal BALB/c and C3H/FeJ or autoimmune MRL-lpr. By Northern blot analysis, nephritic MRL-lpr and NZB/W have a two- to fivefold increase in steady state levels of ICAM-1 transcripts in the kidney as compared with normal or prenephritic mice. This is paralleled by an increase in MHC class II transcripts. In cultured PT cells, ICAM-1 is expressed at basal levels in PT and is increased by the cytokines interferon-gamma, IL-1 alpha, and TNF-alpha. Thus cytokine-mediated upregulation of ICAM-1 in lupus nephritis may promote interaction of immune cells with renal tissue. The predominant apical expression of ICAM-1 opposite to the basolateral Ia expression suggests a novel role for this adhesion molecule in PT. Images Figure 1 Figure 2 Figure 3 Figure 6 Figure 7 PMID:1968316

  12. Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

    PubMed Central

    Dieker, Jürgen; Berden, Jo H.; Bakker, Marinka; Briand, Jean-Paul; Muller, Sylviane; Voll, Reinhard; Sjöwall, Christopher; Herrmann, Martin; Hilbrands, Luuk B.; van der Vlag, Johan

    2016-01-01

    Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis. PMID:27780265

  13. Antibodies to glycolipids activate complement and promote proteinuria in passive Heymann nephritis.

    PubMed

    Susani, M; Schulze, M; Exner, M; Kerjaschki, D

    1994-04-01

    Passive Heymann nephritis is an experimental rat model of human membranous nephropathy induced by injection of antisera against crude renal cortical fractions such as Fx1A or rat tubular microvilli. This results in the formation of subepithelial immune deposits, the activation of the C5b-9 membrane attack complex of complement, and severe proteinuria. While the formation of immune deposits is attributed to in situ immune complex formation with antibodies specific for the gp330-Heymann nephritis antigenic complex (HNAC), activation of complement and proteinuria appear to be caused by at least one additional antibody species present in anti-Fx1A sera. We have separated by affinity absorption polyspecific antisera against Fx1A and rat microvilli into one IgG fraction directed specifically against microvillar proteins (anti-Fx1A-prot) and another IgG fraction specific for glycolipids (ant-Fx1A-lip) of tubular microvilli. When injected into rats, the anti-Fx1A-prot fraction induced immune deposits but failed to activate complement or produce proteinuria, similar to results obtained with affinity-purified anti-gp330 IgG. When the antibodies of the anti-Fx1A-lip fraction were injected alone they did not bind to glomeruli. By contrast, when the IgGs specific for the Fx1A-prot fraction (or for gp330-HNAC) were combined with those directed against the Fx1A-lip glycolipid preparation, immune deposits were formed, in situ complement activation was observed, and also proteinuria was induced. It is concluded that within anti-Fx1A and anti-microvillar sera there are at least two IgG fractions of relevance for the development of PHN: one directed against the gp330-HNAC complex which is responsible for the development of immune deposits, and a second specific for glycolipid antigen(s) which activate(s) the complement cascade.

  14. Satisfaction with control of systemic lupus erythematosus and lupus nephritis: physician and patient perspectives

    PubMed Central

    Mozaffarian, Neelufar; Lobosco, Steve; Lu, Peng; Roughley, Adam; Alperovich, Gabriela

    2016-01-01

    Purpose Patient satisfaction with disease control of systemic lupus erythematosus (SLE) is an important component of medical management. This analysis evaluated patient and physician satisfaction with disease control of SLE, factors associated with satisfaction/dissatisfaction, and the degree of physician–patient concordance of these parameters. Patients and methods Data were extracted from the US Adelphi Real World Lupus Disease Specific Programme®, a cross-sectional survey of 50 rheumatologists, 25 nephrologists, and their patients with non-nephritis SLE (NNSLE) or lupus nephritis (LN). Results Physicians reported moderate or severe disease activity in 25.0% of patients with NNSLE and in 50.5% of patients with LN, and were satisfied with disease control in 78.6% (132/168) and 73.8% (152/206) of patients, respectively. For patients, 75.8% (75/99) with NNSLE were satisfied with their current treatment, compared with 65.5% (74/113) with LN. Physician–patient agreement (70.7%) on the level of satisfaction was “slight” (kappa =0.1445) for NNSLE; patients were more frequently dissatisfied than physicians with regard to joint tenderness, fatigue, anxiety, pain on movement, malar rash, and photosensitivity. Physician–patient agreement (71.4%) on the level of satisfaction was “fair” (kappa =0.3695) for LN; patients expressed greater dissatisfaction than physicians for headache, photosensitivity, and anxiety, whereas physicians were more dissatisfied with regard to joint swelling, kidney function, and blood pressure control. In general, patients with NNSLE or LN who were dissatisfied (or whose physicians were dissatisfied) were more likely to have joint swelling, joint stiffness, malar rash, hair loss, depression, and fatigue, have moderate or severe disease, or to be currently experiencing disease flare. Conclusion These data highlight the patient and physician dissatisfaction with real-world disease control of SLE. PMID:27784995

  15. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens

    PubMed Central

    Bruschi, Maurizio; Galetti, Maricla; Sinico, Renato Alberto; Moroni, Gabriella; Bonanni, Alice; Radice, Antonella; Tincani, Angela; Pratesi, Federico; Migliorini, Paola; Murtas, Corrado; Franceschini, Franco; Trezzi, Barbara; Brunini, Francesca; Gatti, Rita; Tardanico, Regina; Barbano, Giancarlo; Piaggio, Giorgio; Messa, Piergiorgio; Ravani, Pietro; Scolari, Francesco; Candiano, Giovanni; Martini, Alberto; Allegri, Landino

    2015-01-01

    Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti–α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti–α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti–α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis. PMID:25398787

  16. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens.

    PubMed

    Bruschi, Maurizio; Galetti, Maricla; Sinico, Renato Alberto; Moroni, Gabriella; Bonanni, Alice; Radice, Antonella; Tincani, Angela; Pratesi, Federico; Migliorini, Paola; Murtas, Corrado; Franceschini, Franco; Trezzi, Barbara; Brunini, Francesca; Gatti, Rita; Tardanico, Regina; Barbano, Giancarlo; Piaggio, Giorgio; Messa, Piergiorgio; Ravani, Pietro; Scolari, Francesco; Candiano, Giovanni; Martini, Alberto; Allegri, Landino; Ghiggeri, Gian Marco

    2015-08-01

    Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti-α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti-α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti-α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

  17. Impact of Fli-1 transcription factor on autoantibody and lupus nephritis in NZM2410 mice

    PubMed Central

    Mathenia, J; Reyes-Cortes, E; Williams, S; Molano, I; Ruiz, P; Watson, D K; Gilkeson, G S; Zhang, X K

    2010-01-01

    The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Increased levels of Fli-1 mRNA were present in the peripheral blood lymphocytes from lupus patients; furthermore, transgenic overexpression of Fli-1 in normal mice resulted in the development of a lupus-like disease. Lupus nephritis is a major cause of death in both lupus patients as well as in animal models. In this study, we generated Fli-1 heterozygous knockout (Fli-1+/-) NZM2410 mice (of which the wild-type is a widely used lupus murine model) that expressed decreased levels of Fli-1 and investigated the impact of Fli-1 expression on lupus nephritis development and survival. Ninety-three per cent of the Fli-1+/− NZM2410 mice survived to the age of 52 weeks compared to only 35% of wild-type NZM2410 mice. Autoantibodies, including anti-dsDNA and anti-glomerular basement antigen, in Fli-1+/− NZM2410 mice were statistically significantly lower when compared to wild-type NZM2410 mice at the ages of 30 and 34 weeks. Total B cell and activated B cell populations in the spleens from Fli-1+/− NZM2410 mice were decreased significantly compared to wild-type NZM2410 mice. Fli-1+/− NZM2410 mice also had remarkably diminished proteinuria and decreased renal pathological scores when compared with wild-type NZM2410 mice. Expression of early growth response 1 (Egr-1) was decreased significantly in the kidneys from Fli-1+/− NZM2410 mice when compared to wild-type littermates. Our data indicate that expression of Fli-1 plays an important role in lupus disease development in NZM2410 mice. PMID:20731671

  18. Anti-Proliferative Actions of T-Type Calcium Channel Inhibition in Thy1 Nephritis

    PubMed Central

    Cove-Smith, Andrea; Mulgrew, Christopher J.; Rudyk, Olena; Dutt, Neelanjana; McLatchie, Linda M.; Shattock, Michael J.; Hendry, Bruce M.

    2014-01-01

    Aberrant proliferation of mesangial cells (MCs) is a key finding in progressive glomerular disease. TH1177 is a small molecule that has been shown to inhibit low-voltage activated T-type Ca2+ channels (TCCs). The current study investigates the effect of TH1177 on MC proliferation in vitro and in vivo. The effect of Ca2+ channel inhibition on primary rat MC proliferation in vitro was studied using the microculture tetrazolium assay and by measuring bromodeoxyuridine incorporation. In vivo, rats with Thy1 nephritis were treated with TH1177 or vehicle. Glomerular injury and average glomerular cell number were determined in a blinded fashion. Immunostaining for Ki-67 and phosphorylated ERK were also performed. The expression of TCC isoforms in healthy and diseased tissue was investigated using quantitative real-time PCR. TCC blockade caused a significant reduction in rat MC proliferation in vitro, whereas L-type inhibition had no effect. Treatment of Thy1 nephritis with TH1177 significantly reduced glomerular injury (P < 0.005) and caused a 49% reduction in glomerular cell number (P < 0.005) compared to the placebo. TH1177 also reduced Ki-67-positive and pERK-positive cells per glomerulus by 52% (P < 0.01 and P < 0.005, respectively). These results demonstrate that TH1177 inhibits MC proliferation in vitro and in vivo, supporting the hypothesis that TCC inhibition may be a useful strategy for studying and modifying MC proliferative responses to injury. PMID:23746655

  19. Serum Beta 2-Microglobulin/Cystatin C Index: A Useful Biomarker in Lupus Nephritis?

    PubMed Central

    Madureira Silva, Marcus Vinicius; Moscoso-Solorzano, Grace T.; Nishida, Sonia K.; Mastroianni-Kirsztajn, Gianna

    2012-01-01

    Background Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease with frequent flares. Our aim was to evaluate the beta 2-microglobulin/cystatin C (β2M/CysC) index versus other markers as a predictor factor for assessment of SLE reactivation. Methods We prospectively analyzed 42 patients with lupus nephritis. Disease activity was classified using SLEDAI-2K and BILAG. Routine renal function and laboratory markers of SLE activity were performed, as well as serum β2M (Sβ2M)/serum CysC (SCysC) and Sβ2M/serum creatinine (SCreat) indexes determinations. Results The 42 enrolled patients had a mean age of 37.7 ± 13.1 years, 88% were female and 67% Caucasians; mean estimated glomerular filtration rate was 61.9 ± 20.0 ml/min/1.73 m2. There was a strong correlation between SCreat versus SCysC (r = 0.887), SCreat versus Sβ2M (r = 0.865), and SCysC versus Sβ2M (r = 0.880). Multivariate analysis showed that the Sβ2M/SCreat index is a prognostic factor predicting active lupus nephritis. Conclusion As SCysC is a good marker of renal function, it would be expected that the Sβ2M/SCysC index could be a better indicator of renal activity than Sβ2M/SCreat, but in the present study it did not add relevant clinical information in the assessment of renal activity in SLE. PMID:22811690

  20. Impact of Fli-1 transcription factor on autoantibody and lupus nephritis in NZM2410 mice.

    PubMed

    Mathenia, J; Reyes-Cortes, E; Williams, S; Molano, I; Ruiz, P; Watson, D K; Gilkeson, G S; Zhang, X K

    2010-11-01

    The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Increased levels of Fli-1 mRNA were present in the peripheral blood lymphocytes from lupus patients; furthermore, transgenic overexpression of Fli-1 in normal mice resulted in the development of a lupus-like disease. Lupus nephritis is a major cause of death in both lupus patients as well as in animal models. In this study, we generated Fli-1 heterozygous knockout (Fli-1(+/)⁻ ) NZM2410 mice (of which the wild-type is a widely used lupus murine model) that expressed decreased levels of Fli-1 and investigated the impact of Fli-1 expression on lupus nephritis development and survival. Ninety-three per cent of the Fli-1(+/)⁻ NZM2410 mice survived to the age of 52 weeks compared to only 35% of wild-type NZM2410 mice. Autoantibodies, including anti-dsDNA and anti-glomerular basement antigen, in Fli-1(+/)⁻ NZM2410 mice were statistically significantly lower when compared to wild-type NZM2410 mice at the ages of 30 and 34 weeks. Total B cell and activated B cell populations in the spleens from Fli-1(+/)⁻ NZM2410 mice were decreased significantly compared to wild-type NZM2410 mice. Fli-1(+/)⁻ NZM2410 mice also had remarkably diminished proteinuria and decreased renal pathological scores when compared with wild-type NZM2410 mice. Expression of early growth response 1 (Egr-1) was decreased significantly in the kidneys from Fli-1(+/)⁻ NZM2410 mice when compared to wild-type littermates. Our data indicate that expression of Fli-1 plays an important role in lupus disease development in NZM2410 mice.

  1. DESI focal plate mechanical integration and cooling

    NASA Astrophysics Data System (ADS)

    Lambert, A. R.; Besuner, R. W.; Claybaugh, T. M.; Silber, J. H.

    2016-08-01

    The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the Universe using the Baryon Acoustic Oscillation technique[1]. The spectra of 40 million galaxies over 14000 sq. deg will be measured during the life of the experiment. A new prime focus corrector for the KPNO Mayall telescope will deliver light to 5000 fiber optic positioners. The fibers in turn feed ten broad-band spectrographs. This paper describes the mechanical integration of the DESI focal plate and the thermal system design. The DESI focal plate is comprised of ten identical petal assemblies. Each petal contains 500 robotic fiber positioners. Each petal is a complete, self-contained unit, independent from the others, with integrated power supply, controllers, fiber routing, and cooling services. The major advantages of this scheme are: (1) supports installation and removal of complete petal assemblies in-situ, without disturbing the others, (2) component production, assembly stations, and test procedures are repeated and parallelizable, (3) a complete, full-scale prototype can be built and tested at an early date, (4) each production petal can be surveyed and tested as a complete unit, prior to integration, from the fiber tip at the focal surface to the fiber slit at the spectrograph. The ten petal assemblies will be installed in a single integration ring, which is mounted to the DESI corrector. The aluminum integration ring attaches to the steel corrector barrel via a flexured steel adapter, isolating the focal plate from differential thermal expansions. The plate scale will be kept stable by conductive cooling of the petal assembly. The guider and wavefront sensors (one per petal) will be convectively cooled by forced flow of air. Heat will be removed from the system at ten liquid-cooled cold plates, one per petal, operating at ambient temperature. The entire focal plate structure is enclosed in an insulating shroud, which serves as a thermal barrier

  2. A variable-focal-length telescope

    NASA Astrophysics Data System (ADS)

    Irkaev, Bahor; Popov, Gennadiy; Nekhaeva, Svetlana

    2005-04-01

    A special additional optical system (AOS) to develop any telescope into a zoom or a variable-focal-length telescope (variotelescope) is proposed. This system permits the telescope optics and detector (charge-couped device) to be matched in order to obtain the best resolution. An analysis of the resolution of the system consisting of the ‘V-telescope and detector’ is performed, and it is shown that the best way to match the optics and detector is to change the focal length, that is to change the image scale. The proposed AOS consists of two spherical mirrors: a large concave mirror and a small convex mirror. The AOS is illustrated by means of figures and tables.

  3. Extensive Focal Epithelial Hyperplasia: A Case Report

    PubMed Central

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis. PMID:26351501

  4. Focal region fields of distorted reflectors

    NASA Technical Reports Server (NTRS)

    Buris, N. E.; Kauffman, J. F.

    1988-01-01

    The problem of the focal region fields scattered by an arbitrary surface reflector under uniform plane wave illumination is solved. The physical optics (PO) approximation is used to calculate the current induced on the reflector. The surface of the reflector is described by a number of triangular domain-wise 5th degree bivariate polynomials. A 2-dimensional Gaussian quadrature is employed to numerically evaluate the integral expressions of the scattered fields. No Freshnel or Fraunhofer zone approximations are made. The relation of the focal fields problem to surface compensation techniques and other applications are mentioned. Several examples of distorted parabolic reflectors are presented. The computer code developed is included, together with instructions on its usage.

  5. Gastric hyperplastic polyp with focal cancer.

    PubMed

    Markowski, Adam Roman; Guzinska-Ustymowicz, Katarzyna

    2016-05-01

    This paper reports a rare case of early adenocarcinoma within the gastric hyperplastic polyp, that was completely resected during an endoscopic procedure, and discusses current recommendations in such cases. Endoscopic resection of polyps with focal dysplasia or cancer is commonly indicated, as long as the procedure can be performed safely. After complete excision of a polyp with atypical focal lesion, endoscopic surveillance is suggested. The frequency of surveillance endoscopy should depend on the precise histopathological diagnosis and possibility of confirming the completeness of the endoscopic resection. If the completeness of the procedure is confirmed both macro- and microscopically, gastric resection does not have to be performed. A follow-up esophago-gastroduodenoscopy should be performed at 1 year and then at 3 years.

  6. Gastric hyperplastic polyp with focal cancer

    PubMed Central

    Markowski, Adam Roman; Guzinska-Ustymowicz, Katarzyna

    2016-01-01

    This paper reports a rare case of early adenocarcinoma within the gastric hyperplastic polyp, that was completely resected during an endoscopic procedure, and discusses current recommendations in such cases. Endoscopic resection of polyps with focal dysplasia or cancer is commonly indicated, as long as the procedure can be performed safely. After complete excision of a polyp with atypical focal lesion, endoscopic surveillance is suggested. The frequency of surveillance endoscopy should depend on the precise histopathological diagnosis and possibility of confirming the completeness of the endoscopic resection. If the completeness of the procedure is confirmed both macro- and microscopically, gastric resection does not have to be performed. A follow-up esophago-gastroduodenoscopy should be performed at 1 year and then at 3 years. PMID:25361760

  7. Focal colors are universal after all

    PubMed Central

    Regier, Terry; Kay, Paul; Cook, Richard S.

    2005-01-01

    It is widely held that named color categories in the world's languages are organized around universal focal colors and that these focal colors tend to be chosen as the best examples of color terms across languages. However, this notion has been supported primarily by data from languages of industrialized societies. In contrast, recent research on a language from a nonindustrialized society has called this idea into question. We examine color-naming data from languages of 110 nonindustrialized societies and show that (i) best-example choices for color terms in these languages cluster near the prototypes for English white, black, red, green, yellow, and blue, and (ii) best-example choices cluster more tightly across languages than do the centers of category extensions, suggesting that universal best examples (foci) may be the source of universal tendencies in color naming. PMID:15923257

  8. Error compensation research on the focal plane attitude measurement instrument

    NASA Astrophysics Data System (ADS)

    Zhou, Hongfei; Zhang, Feifan; Zhai, Chao; Zhou, Zengxiang; Liu, Zhigang; Wang, Jianping

    2016-07-01

    The surface accuracy of astronomical telescope focal plate is a key indicator to precision stellar observation. Combined with the six DOF parallel focal plane attitude measurement instrument that had been already designed, space attitude error compensation of the attitude measurement instrument for the focal plane was studied in order to measure the deformation and surface shape of the focal plane in different space attitude accurately.

  9. Focal epithelial hyperplasia in a Turkish family.

    PubMed

    Gökahmetoğlu, Selma; Ferahbaş, Ayten; Canöz, Özlem

    2014-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferative condition that is more frequently found in children of certain ethnic groups. Human papillomavirus (HPV) 13 and 32 genotypes has been consistently detected in these lesions. In this study a daughter, mother and father had FEH, and HPV 13 was shown by sequence analysis in the lesions of these patients. Cryotherapy was applied to the lesions and the lesions improved, but did not recover properly. In conclusion, HPV genotyping should be performed in FEH cases.

  10. Extensive focal epithelial hyperplasia: case report.

    PubMed

    Durso, Braz Campos; Pinto, José Marcelo Vargas; Jorge, Jacks; de Almeida, Oslei Paes

    2005-11-01

    Focal epithelial hyperplasia (FEH) is a rare benign lesion caused by human papillomavirus subtype 13 or 32. The condition occurs in numerous populations and ethnic groups. A higher incidence in close communities and among family members indicates infectious pathogenesis. A 21-year-old woman with FEH is described, in whom the lesions had persisted for 10 years. A literature review is also presented, with emphasis on manifestations in the oral mucosa and histopathological features.

  11. Likelihood analysis of earthquake focal mechanism distributions

    NASA Astrophysics Data System (ADS)

    Kagan, Yan Y.; Jackson, David D.

    2015-06-01

    In our paper published earlier we discussed forecasts of earthquake focal mechanism and ways to test the forecast efficiency. Several verification methods were proposed, but they were based on ad hoc, empirical assumptions, thus their performance is questionable. We apply a conventional likelihood method to measure the skill of earthquake focal mechanism orientation forecasts. The advantage of such an approach is that earthquake rate prediction can be adequately combined with focal mechanism forecast, if both are based on the likelihood scores, resulting in a general forecast optimization. We measure the difference between two double-couple sources as the minimum rotation angle that transforms one into the other. We measure the uncertainty of a focal mechanism forecast (the variability), and the difference between observed and forecasted orientations (the prediction error), in terms of these minimum rotation angles. To calculate the likelihood score we need to compare actual forecasts or occurrences of predicted events with the null hypothesis that the mechanism's 3-D orientation is random (or equally probable). For 3-D rotation the random rotation angle distribution is not uniform. To better understand the resulting complexities, we calculate the information (likelihood) score for two theoretical rotational distributions (Cauchy and von Mises-Fisher), which are used to approximate earthquake source orientation pattern. We then calculate the likelihood score for earthquake source forecasts and for their validation by future seismicity data. Several issues need to be explored when analyzing observational results: their dependence on forecast and data resolution, internal dependence of scores on forecasted angle and random variability of likelihood scores. Here, we propose a simple tentative solution but extensive theoretical and statistical analysis is needed.

  12. High speed multi focal plane optical system

    NASA Technical Reports Server (NTRS)

    Minott, P. O. (Inventor)

    1983-01-01

    An apparatus for eliminating beamsplitter generated optical aberrations in a pupil concentric optical system providing a plurality of spatially separated images on different focal planes or surfaces is presented. The system employs a buried surface beamsplitter having spherically curved entrance and exit faces which are concentric to a system aperture stop with the entrance face being located in the path of a converging light beam directed there from an image forming objective element which is also concentric to the aperture stop.

  13. Focal epileptic seizures mimicking sleep paralysis.

    PubMed

    Galimberti, Carlo Andrea; Ossola, Maria; Colnaghi, Silvia; Arbasino, Carla

    2009-03-01

    Sleep paralysis (SP) is a common parasomnia. The diagnostic criteria for SP, as reported in the International Classification of Sleep Disorders, are essentially clinical, as electroencephalography (EEG)-polysomnography (PSG) is not mandatory. We describe a subject whose sleep-related events fulfilled the diagnostic criteria for SP, even though her visual hallucinations were elementary, repetitive and stereotyped, thus differing from those usually reported by patients with SP. Video/EEG-PSG documented the focal epileptic nature of the SP-like episodes.

  14. Focal plane scanner with reciprocating spatial window

    NASA Technical Reports Server (NTRS)

    Mao, Chengye (Inventor)

    2000-01-01

    A focal plane scanner having a front objective lens, a spatial window for selectively passing a portion of the image therethrough, and a CCD array for receiving the passed portion of the image. All embodiments have a common feature whereby the spatial window and CCD array are mounted for simultaneous relative reciprocating movement with respect to the front objective lens, and the spatial window is mounted within the focal plane of the front objective. In a first embodiment, the spatial window is a slit and the CCD array is one-dimensional, and successive rows of the image in the focal plane of the front objective lens are passed to the CCD array by an image relay lens interposed between the slit and the CCD array. In a second embodiment, the spatial window is a slit, the CCD array is two-dimensional, and a prism-grating-prism optical spectrometer is interposed between the slit and the CCD array so as to cause the scanned row to be split into a plurality of spectral separations onto the CCD array. In a third embodiment, the CCD array is two-dimensional and the spatial window is a rectangular linear variable filter (LVF) window, so as to cause the scanned rows impinging on the LVF to be bandpass filtered into spectral components onto the CCD array through an image relay lens interposed between the LVF and the CCD array.

  15. Focus in Grade 1: Teaching with Curriculum Focal Points

    ERIC Educational Resources Information Center

    Fuson, Karen; Clements, Douglas; Beckmann, Sybilla

    2010-01-01

    "Focus in Grade 1: Teaching with Curriculum Focal Points" describes and illustrates learning paths for the mathematical concepts and skills of each grade 1 Focal Point as presented in Curriculum Focal Points for Prekindergarten through Grade 8 Mathematics. It includes representational supports for teaching and learning that can facilitate…

  16. Dynamics of Focal Fibrillation Waves during Persistent Atrial Fibrillation.

    PubMed

    Lanters, Eva A H; Allessie, Maurits A; DE Groot, Natasja M S

    2016-04-01

    The incidence and appearance of focal fibrillation waves on the right and left atrial epicardial surface were visualized during 10 seconds of persistent atrial fibrillation in a 71-year-old woman with valvular heart disease. The frequent, nonrepetitive, widespread, and capricious distribution of focal waves suggests that transmural conduction of fibrillation waves is most likely the mechanism underlying focal fibrillation waves.

  17. Co-existing autosomal dominant polycystic kidney disease and nephrotic syndrome in a Nigerian patient with lupus nephritis.

    PubMed

    Akinbodewa, A A; Adejumo, O A; Ogunsemoyin, A O; Osasan, S A; Adefolalu, O A

    2016-01-01

    A little over 30 cases on co-existing nephrotic syndrome and autosomal dominant polycystic kidney disease (ADPKD) have been reported from different regions of the world since 1957. We present a case report on co-existence of nephrotic syndrome (secondary to lupus nephritis) with ADPKD in a 24-year-old woman from Nigeria. She was positive for anti-double stranded DNA. Renal histology showed International Society of Nephrology/Renal Pathology Society Class II lupus nephritis. The co-existence of nephrotic syndrome and ADPKD may have been overlooked in Africa in the past. There is a need to screen for nephrotic syndrome in patients with ADPKD among clinicians in the African setting.

  18. Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis

    PubMed Central

    Malone, Andrew F; Phelan, Paul J; Hall, Gentzon; Cetincelik, Umran; Homstad, Alison; Alonso, Andrea; Jiang, Ruiji; Lindsey, Thomas; Wu, Guanghong; Sparks, Matthew A; Smith, Stephen R; Webb, Nicholas J A; Kalra, Philip; Adeyemo, Adebowale; Shaw, Andrey S; Conlon, Peter J; Jennette, J Charles; Howell, David N; Winn, Michelle P; Gbadegesin, Rasheed A

    2014-01-01

    Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes including inherited genetic defects with significant proteinuria being the predominant clinical finding at presentation. Mutations in COL4A3 and COL4A4 are known to cause Alport syndrome, thin basement membrane nephropathy, and to result in pathognomonic glomerular basement membrane findings. Secondary FSGS is known to develop in classic Alport Syndrome at later stages of the disease. Here, we present seven families with rare or novel variants in COL4A3 or COL4A4 (six with single and one with two heterozygous variants) from a cohort of 70 families with a diagnosis of hereditary FSGS. The predominant clinical findings at diagnosis were proteinuria associated with hematuria. In all seven families, there were individuals with nephrotic range proteinuria with histologic features of FSGS by light microscopy. In one family, electron microscopy showed thin glomerular basement membrane, but four other families had variable findings inconsistent with classical Alport nephritis. There was no recurrence of disease after kidney transplantation. Families with COL4A3 and COL4A4 variants that segregated with disease represent 10% of our cohort. Thus, COL4A3 and COL4A4 variants should be considered in the interpretation of next-generation sequencing data from such patients. Furthermore, this study illustrates the power of molecular genetic diagnostics in the clarification of renal phenotypes. PMID:25229338

  19. Acute tubulointerstitial nephritis/drug induced acute kidney injury; an experience from a single center in Pakistan

    PubMed Central

    Naqvi, Rubina; Mubarak, Muhammad; Ahmed, Ejaz; Akhtar, Fazal; Naqvi, Anwar; Rizvi, Adib

    2016-01-01

    Introduction: There is no information in literature specifically on the prevalence and clinicopathological characteristics of acute tubulointerstitial nephritis/drug induced acute kidney injury (AKI) from Pakistan. Objectives: We aim to report a series of cases from patients developing AKI after exposure to some medications or finding of interstitial nephritis on histopathology. Patients and Methods: This is an observational study of patients identified as having AKI after exposure to medications. AKI was defined according to RIFLE criteria and all patients fell from risk to loss category on arrival. On ultrasonography, all patients had normal size non-obstructed kidneys. Renal biopsy findings were consistent with tubule interstitial nephritis. Results: Mean age of patients was 36.41 ± 17.40 years. Among total of 155, 80 were male and 75 female. Regarding drugs, most common was exposure to aminoglycoside in 34 (22%) followed by use of non-steroidal anti-inflammatory analgesics in 28, contrast induced agents in 11. Renal biopsy was performed in 58 patients. In half of these, insulting agent was not known and in rest either multiple medications were ingested or there was denial to substance use or recovery was delayed despite discontinuation of responsible medication. Renal replacement therapy was required on arrival in 119/155 (hemodialysis = 115, peritoneal dialysis = 4) cases. Complete renal recovery was observed in 71%, while 7.7% expired during acute phase, partial renal recovery was seen in 15% and 5% disappeared after first discharge from the hospital. Conclusion: Tubulointerstitial nephritis may occur with many drugs of common use. Early and intensive efforts must be made to consider and then timely correct the injury to the kidney. PMID:27069962

  20. Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy: A Case Series Study.

    PubMed

    Li, Qiu-Yu; Yu, Feng; Zhou, Fu-De; Zhao, Ming-Hui

    2016-05-01

    The aim of this study was to evaluate the efficacy of plasmapheresis in patients with lupus nephritis-combined thrombotic microangiopathy (TMA) in a Chinese cohort.Clinical and therapeutic data of patients with lupus nephritis-combined TMA were collected retrospectively. A comparison between those with and without plasmapheresis was performed.Seventy patients with renal biopsy-proven TMA in lupus nephritis were treated with conventional combined corticosteroid and immunosuppressive agents as induction therapy, 9 of the 70 patients received additional plasmapheresis. The plasmapheresis group presented with more severe SLE and renal activity indices, including a significant higher ratio of neurologic disorder (P = 0.025), lower level of platelet count (P = 0.009), higher value of serum creatinine (P = 0.038), higher percentage of anti-cardiolipin antibodies positive (P = 0.001), and higher Systemic Lupus Erythematosus Disease Activity Index scores (P = 0.012), than that of the nonplasmapheresis group. However, the plasmapheresis group had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.03). As the baseline data were significantly different between the 2 groups, the propensity score match was further designed to avoid retrospective bias. After re-analysis, the plasmapheresis group still had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.018). More importantly, the plasmapheresis group had significant less composite endpoints than that of the nonplasmapheresis group (P = 0.005).Our study suggested that additional plasmapheresis on conventional induction therapy may benefit patients with lupus nephritis-combined TMA, which warrants further explorations.

  1. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies.

    PubMed

    Hill, Gary S; Karoui, Khalil El; Karras, Alexandre; Mandet, Chantal; Duong Van Huyen, Jean-Paul; Nochy, Dominique; Bruneval, Patrick

    2011-03-01

    IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with lupus nephritis, and 26 with primary FSGS. Capsular adhesions with no lesions in the underlying tuft, consistent with podocyte abnormality or loss, were found regularly in FSGS and IgAN, but infrequently in lupus. Fifteen biopsies of patients with IgAN were studied immunohistochemically using markers for podocytes, Bowman's parietal epithelial cells, proliferating cells, and macrophages. Cytokeratins CK-8 and C2562 differentiated normal podocytes (negative) from parietal epithelial cells (variably positive). There was focal loss of the podocyte markers synaptopodin, glomerular epithelial protein 1 (GLEPP-1), nephrin, and vascular endothelial growth factor (VEGF), particularly at sites of capsular adhesions in otherwise histologically normal glomeruli. Cells displaying the parietal epithelial cell markers PAX2 (paired box gene 2) and the cytokeratins were also positive for the proliferating cell marker, proliferating cell nuclear antigen. These cells gathered at sites of adhesion, and in response to active lesions in the tuft, grew inward along the adhesion onto the tuft, forming a monolayer positive for parietal markers and the podocyte marker Wilms tumor protein-1 (WT-1). These cells deposited a layer of collagen over the sclerosing tuft. Thus, all biopsies of patients with IgAN had changes basically identical to those classically described in FSGS. Hence, our study strongly suggests that podocytopathy of a type similar to that in primary FSGS occurs frequently in IgAN.

  2. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis

    PubMed Central

    Kain, Renate; Exner, Markus; Brandes, Ricarda; Ziebermayr, Reinhard; Cunningham, Dawn; Alderson, Carol A; Davidovits, Agnes; Raab, Ingrid; Jahn, Renate; Ashour, Oliver; Spitzauer, Susanne; Sunder-Plassmann, Gere; Fukuda, Minoru; Klemm, Per; Rees, Andrew J; Kerjaschki, Dontscho

    2009-01-01

    Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present in almost all individuals with FNGN. Consequently, its prevalence is nearly twice that of the classical ANCAs that recognize myeloperoxidase or proteinase-3. Furthermore, antibodies to LAMP-2 cause pauci-immune FNGN when injected into rats, and a monoclonal antibody to human LAMP-2 (H4B4) induces apoptosis of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P41–49) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with FimH develop pauci-immune FNGN and also develop antibodies to rat and human LAMP-2. Finally, we show that infections with fimbriated pathogens are common before the onset of FNGN. Thus, FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN. PMID:18836458

  3. Focal transmural necrotic tracheitis in commercial meat turkeys.

    PubMed

    Sentíes-Cué, Gabriel; Crespo, Rocio; Chin, R P

    2003-01-01

    This report describes an unusual presentation of severe focal necrotic tracheitis in a flock of 8-wk-old commercial turkeys. The flock was kept on a range that is located near a cotton field. The cotton field had been chemically defoliated 2 wk before the birds were submitted for necropsy. At necropsy, most of the birds had a 1-cm, yellow-white constricture in the upper third of the trachea at which the lumen was partially occluded by necrotic tissue. Microscopically, there was severe, transmural necrosis with an accumulation of inflammatory exudate in the tracheal lumen and numerous bacteria within the necrotic debris, mucosa, and lamina propria. Mixed bacteria were isolated from the trachea. No viruses were detected. Neither abnormal heavy metal concentrations in the liver nor paraquat in the respiratory tract were detected. The exact cause of this severe, necrotic tracheitis was not determined. Based on the clinical history and laboratory findings, it was concluded that a combination of a toxic irritant, possibly an aerosolized cotton defoliant, and bacterial infections were likely the cause of this lesion.

  4. The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis.

    PubMed

    Baskin, Esra; Ozen, Seza; Cakar, Nilgun; Bayrakci, Umut S; Demirkaya, Erkan; Bakkaloglu, Aysin

    2010-01-01

    Cyclophosphamide (CYC) has been the landmark in the treatment of lupus nephritis. However, long-term treatment with CYC is associated with significant side effects. We aimed to evaluate the efficacy of short-term intravenous (IV) CYC treatment as a remission induction treatment followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as a maintenance treatment. Twenty patients (18 girls) with biopsy-proven class III (5) and IV (15) lupus nephritis were included in to the study. Detailed clinical and laboratory data and patient outcomes were evaluated. All patients received three methylprednisolone (MP) IV pulses, followed by oral prednisone 0.5-1 mg/kg per day and one IV pulse of CYC per month for 6 months. Azathioprine was started as a remission-maintaining treatment. In ten of 20 patients, treatment was switched to MMF. The mean age at the time of diagnosis was 16.11 +/- 3.49 years, and the mean duration of follow-up was 49.6 +/- 27 months. Fourteen patients (70%) had complete remission, three (15%) had partial remission, one (5%) continued to have active disease, and two (10%) progressed to end-stage renal disease. Nine of the patients (45%) with complete remission had received AZA, and switching to MMF increased complete remission rate (additional five patients; 25%). In conclusion, short-term (6-month) IV bolus CYC treatment followed by AZA is a safe and effective treatment in children with severe lupus nephritis, and using MMF increases remission rate in resistant cases.

  5. Optical Chromatography of Bacterial Spores

    NASA Astrophysics Data System (ADS)

    Sundbeck, Steven; Terray, Alex; Arnold, Jonathan; Leski, Tomasz; Hart, Sean

    2007-03-01

    The technique of optical chromatography uses a laser mildly focused against fluid flow in a microfluidic channel to trap microscopic particles. Particles in the channel near the focal point of the laser are drawn toward the beam axis and then accelerated via optical pressure against the fluid flow, reaching an equilibrium point when the optical and fluidic forces on the particle are balanced. This equilibrium point may occur at differing distances from the focal point for microscopic particles with differing properties, such as size, shape, morphology, and refractive index. Thus, identification and separation of particles may be achieved in the system. Optical chromatography may be used as a detection technique for biological particles of interest, either directly or as a means of concentrating and filtering a sample. Of particular interest would be reliable methods for detection of Bacillus anthracis, a common weaponized biological agent. In this work we present optical chromatography experiments on bacterial spores which may be environmentally present with B. anthracis spores and interfere with detection.

  6. Bacterial Hydrodynamics

    NASA Astrophysics Data System (ADS)

    Lauga, Eric

    2016-01-01

    Bacteria predate plants and animals by billions of years. Today, they are the world's smallest cells, yet they represent the bulk of the world's biomass and the main reservoir of nutrients for higher organisms. Most bacteria can move on their own, and the majority of motile bacteria are able to swim in viscous fluids using slender helical appendages called flagella. Low-Reynolds number hydrodynamics is at the heart of the ability of flagella to generate propulsion at the micrometer scale. In fact, fluid dynamic forces impact many aspects of bacteriology, ranging from the ability of cells to reorient and search their surroundings to their interactions within mechanically and chemically complex environments. Using hydrodynamics as an organizing framework, I review the biomechanics of bacterial motility and look ahead to future challenges.

  7. A kinetic model for RNA-interference of focal adhesions

    PubMed Central

    2013-01-01

    Background Focal adhesions are integrin-based cell-matrix contacts that transduce and integrate mechanical and biochemical cues from the environment. They develop from smaller and more numerous focal complexes under the influence of mechanical force and are key elements for many physiological and disease-related processes, including wound healing and metastasis. More than 150 different proteins localize to focal adhesions and have been systematically classified in the adhesome project (http://www.adhesome.org). First RNAi-screens have been performed for focal adhesions and the effect of knockdown of many of these components on the number, size, shape and location of focal adhesions has been reported. Results We have developed a kinetic model for RNA interference of focal adhesions which represents some of its main elements: a spatially layered structure, signaling through the small GTPases Rac and Rho, and maturation from focal complexes to focal adhesions under force. The response to force is described by two complementary scenarios corresponding to slip and catch bond behavior, respectively. Using estimated and literature values for the model parameters, three time scales of the dynamics of RNAi-influenced focal adhesions are identified: a sub-minute time scale for the assembly of focal complexes, a sub-hour time scale for the maturation to focal adhesions, and a time scale of days that controls the siRNA-mediated knockdown. Our model shows bistability between states dominated by focal complexes and focal adhesions, respectively. Catch bonding strongly extends the range of stability of the state dominated by focal adhesions. A sensitivity analysis predicts that knockdown of focal adhesion components is more efficient for focal adhesions with slip bonds or if the system is in a state dominated by focal complexes. Knockdown of Rho leads to an increase of focal complexes. Conclusions The suggested model provides a kinetic description of the effect of RNA

  8. Integrated focal-plane array /IFPA/ approach to large-area infrared focal plane architecture

    NASA Astrophysics Data System (ADS)

    Warren, R. E.

    1980-01-01

    A modular approach to IFPA design is presented which makes it possible to obtain a high-density infrared focal plane amendable to parallel manufacturing techniques as well as to serial plane integration and test. The percent fill factor of the design is dependent on the dimension of the individual detectors; each submodule is manufactured from identical components. The technologies including cables, interconnects, multilayer interconnect structures, and subassembly test requirements, which have direct application to scanning as well as staring integrated focal plane arrays, are discussed.

  9. Efficacy of lacosamide by focal seizure subtype.

    PubMed

    Sperling, Michael R; Rosenow, Felix; Faught, Edward; Hebert, David; Doty, Pamela; Isojärvi, Jouko

    2014-10-01

    The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (≥50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment.

  10. Characterization of DECam focal plane detectors

    SciTech Connect

    Diehl, H.Thomas; Angstadt, Robert; Campa, Julia; Cease, Herman; Derylo, Greg; Emes, John H.; Estrada, Juan; Kibik, Donna; Flaugher, Brenna L.; Holland, Steve E.; Jonas, Michelle; /Fermilab /Madrid, CIEMAT /LBL, Berkeley /Argonne /Pennsylvania U.

    2008-06-01

    DECam is a 520 Mpix, 3 square-deg FOV imager being built for the Blanco 4m Telescope at CTIO. This facility instrument will be used for the 'Dark Energy Survey' of the southern galactic cap. DECam has chosen 250 ?m thick CCDs, developed at LBNL, with good QE in the near IR for the focal plane. In this work we present the characterization of these detectors done by the DES team, and compare it to the DECam technical requirements. The results demonstrate that the detectors satisfy the needs for instrument.

  11. The Simbol-X Focal Plane

    NASA Astrophysics Data System (ADS)

    Laurent, P.

    2009-05-01

    The Simbol-X focal plane is designed to detect photons focused by the mirror in the 0.5 to 100 keV energy band. Composed of two detectors, it will measure the position, energy, and arrival time of each incoming X-ray. On top of it will be a collimator to shield all photons not coming from the mirror field of view. The whole system is surrounded by an active and passive shielding in order to ensure the required very low background.

  12. Laser skin perforator with focal point detection

    NASA Astrophysics Data System (ADS)

    Ponce, L.; Arronte, M.; Cabrera, J. L.; Flores, T.

    2006-02-01

    The development of laser skin perforator device for obtaining blood samples is presented. The use of photoelectric proximity photoelectric sensor permits to determine the focal point eliminating any contact and them avoiding the risk of contamination. Perforation of about 0.2 mm - 0.5 mm in diameter can be obtained in order to take the sample of blood. The method permits to make the blood analysis not only avoiding the contamination risk but also diminishing the pain sensation in comparison with metal lancet.

  13. Kartagener syndrome with focal segmental glomerulosclerosis.

    PubMed

    Momeni, Ali; Doroushi, Behzad; Taheri, Nadia

    2013-11-01

    Primary ciliary dyskinesia is characterized by congenital impairment of mucociliary clearance. Kartagener syndrome (KS) is a clinical variant of primary ciliary dyskinesia which is involved in situs inversus associated with chronic respiratory infections. In addition, glomerular disease in KS syndrome is rare and reported cases are limited. We had a 27-year-old female patient with KS who presented with proteinuria, hematuria, normal kidney function, and a family history of systemic lupus erythematosus. Kidney biopsy showed segmental scar with adhesion to Bowman capsule, which was indicative of focal segmental glomerulosclerosis.

  14. Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis.

    PubMed

    Negi, Vir S; Devaraju, Panneer; Gulati, Reena

    2015-09-01

    SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40-75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian

  15. Antibodies to glycolipids activate complement and promote proteinuria in passive Heymann nephritis.

    PubMed Central

    Susani, M.; Schulze, M.; Exner, M.; Kerjaschki, D.

    1994-01-01

    Passive Heymann nephritis is an experimental rat model of human membranous nephropathy induced by injection of antisera against crude renal cortical fractions such as Fx1A or rat tubular microvilli. This results in the formation of subepithelial immune deposits, the activation of the C5b-9 membrane attack complex of complement, and severe proteinuria. While the formation of immune deposits is attributed to in situ immune complex formation with antibodies specific for the gp330-Heymann nephritis antigenic complex (HNAC), activation of complement and proteinuria appear to be caused by at least one additional antibody species present in anti-Fx1A sera. We have separated by affinity absorption polyspecific antisera against Fx1A and rat microvilli into one IgG fraction directed specifically against microvillar proteins (anti-Fx1A-prot) and another IgG fraction specific for glycolipids (ant-Fx1A-lip) of tubular microvilli. When injected into rats, the anti-Fx1A-prot fraction induced immune deposits but failed to activate complement or produce proteinuria, similar to results obtained with affinity-purified anti-gp330 IgG. When the antibodies of the anti-Fx1A-lip fraction were injected alone they did not bind to glomeruli. By contrast, when the IgGs specific for the Fx1A-prot fraction (or for gp330-HNAC) were combined with those directed against the Fx1A-lip glycolipid preparation, immune deposits were formed, in situ complement activation was observed, and also proteinuria was induced. It is concluded that within anti-Fx1A and anti-microvillar sera there are at least two IgG fractions of relevance for the development of PHN: one directed against the gp330-HNAC complex which is responsible for the development of immune deposits, and a second specific for glycolipid antigen(s) which activate(s) the complement cascade. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8160779

  16. The piriform cortex and human focal epilepsy.

    PubMed

    Vaughan, David N; Jackson, Graeme D

    2014-01-01

    It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic - being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability.

  17. Phase retrieval in the focal plane

    NASA Astrophysics Data System (ADS)

    Gaessler, W.; Peter, D.; Storz, C.

    Phase retrieval in the focal plane is a very appealing technique, which would simplify the optomechanics of an Adaptive Optics (AO) system a lot and could gain sensitivity under certain conditions. For conventional AO systems the limiting magnitude of the system does not depend on the diameter of the telescope, since any wave front sensor splits the light into sub-apertures, which are in number related to the telescope diameter. Having this in mind the phase retrieval technique looks promising as it breaks this paradigm in the diffraction limited case and thus yields some gain in limiting magnitude with larger telescope diameter. Until now this path was not followed deeply in astronomical AO systems, as the solution of the inversion is non unique and demands much higher calculation power as in conventional AO. This might change with state of the art computers. We give a short overview of some existing techniques and algorithms of focal plane AO and report results of other groups, which tested them in laboratory and on sky. To solve the drawback of the large computational demands and to increase the sensitivity we propose a bootstrapping process with dynamical binning.

  18. Ultrasound elastographic techniques in focal liver lesions

    PubMed Central

    Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

    2016-01-01

    Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses. PMID:26973405

  19. The Piriform Cortex and Human Focal Epilepsy

    PubMed Central

    Vaughan, David N.; Jackson, Graeme D.

    2014-01-01

    It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic – being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability. PMID:25538678

  20. Idiopathic focal epilepsies: the "lost tribe".

    PubMed

    Pal, Deb K; Ferrie, Colin; Addis, Laura; Akiyama, Tomoyuki; Capovilla, Giuseppe; Caraballo, Roberto; de Saint-Martin, Anne; Fejerman, Natalio; Guerrini, Renzo; Hamandi, Khalid; Helbig, Ingo; Ioannides, Andreas A; Kobayashi, Katsuhiro; Lal, Dennis; Lesca, Gaetan; Muhle, Hiltrud; Neubauer, Bernd A; Pisano, Tiziana; Rudolf, Gabrielle; Seegmuller, Caroline; Shibata, Takashi; Smith, Anna; Striano, Pasquale; Strug, Lisa J; Szepetowski, Pierre; Valeta, Thalia; Yoshinaga, Harumi; Koutroumanidis, Michalis

    2016-09-01

    The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The

  1. Musical anhedonia after focal brain damage.

    PubMed

    Belfi, Amy M; Evans, Erin; Heskje, Jonah; Bruss, Joel; Tranel, Daniel

    2017-03-01

    People listen to music because it is pleasurable. However, there are individual differences in the reward value of music. At the extreme low end of this continuum, individuals who derive no pleasure from music are said to have 'musical anhedonia.' Cases of acquired musical anhedonia following focal brain damage are rare, with only a handful having been reported in the scientific literature. Here, we surveyed a large sample of patients with focal brain damage to identify the frequency, specificity, and neural correlates of acquired musical anhedonia. Participants completed the Musical anhedonia Questionnaire and the Barcelona Music Reward Questionnaire (Mas-Herrero et al., 2013) to assess changes in musical enjoyment and reward following brain injury. Neuroanatomical data were analyzed with a proportional MAP-3 method to create voxelwise lesion proportion difference maps. No clear or consistent neuroanatomical correlates of musical anhedonia were identified. One patient with damage to the right-hemisphere putamen and internal capsule displayed specific and severe acquired musical anhedonia. These findings indicate that acquired musical anhedonia is very uncommon, a result which is consistent with the fact that only a small number of such cases have been reported in the literature. This rarity could have positive implications for the therapeutic potentialities of music in patients with severe neurological disorders.

  2. ORFEUS focal plane instrumentation: The Berkeley spectrometer

    NASA Technical Reports Server (NTRS)

    Hurwitz, Mark; Bowyer, Stuart

    1988-01-01

    A spectrograph for the ORFEUS mission that incorporates four varied line-space, spherically figured diffraction gratings was designed. The ORFEUS, a 1-m normal incidence telescope is equipped with 2 focal plane spectrographs. The Berkeley spectrograph was developed with an optimizing raytracing computer code. Each grating accepts the light from 20 percent of the aperture of the telescope primary mirror and has a unique set of characteristics to cover a sub-bandpass within the 390 to 1200 A spectral range. Two photon-counting detectors incorporating a time delay readout system are used to record the spectra from all four gratings simultaneously. The nominal design achieves a spectral resolution (FWHM) in excess of 5500 at all wavelengths within the bandpass. The resolution is limited primarily by the detector spatial resolution. The 1 sigma astigmatism of this design varies between 13 and 150 micrometer on the same focal surface. An independent, direct imaging system tracks the drift of the target within the spectrometer aperture and allows measurement of the misalignment between the telescope optical axis and that of the external star tracker. The resolution and astigmatism achievable with this design are superior to those of a standard Rowland spectrograph designed with the same constraints.

  3. Visual function and perinatal focal cerebral infarction.

    PubMed Central

    Mercuri, E; Atkinson, J; Braddick, O; Anker, S; Nokes, L; Cowan, F; Rutherford, M; Pennock, J; Dubowitz, L

    1996-01-01

    AIMS: To evaluate the visual function of infants with perinatal cerebral infarction in whom the site and size of the lesion has been determined using magnetic resonance imaging (MRI). METHODS: Twelve infants with cerebral infarction on MRI were studied with a battery of tests specifically designed to evaluate visual function in infancy. This included tests: for visual attention (fixation shifts); of cerebral asymmetry (optokinetic nystagmus, visual fields); for assessment of acuity (forced choice preferential looking); and neurophysiological measures of vision (phase reversal and orientation reversal visual evoked potential). RESULTS: A considerable incidence of abnormalities on at least one of the tests for visual function used was observed. The presence or severity of visual abnormalities could not always be predicted by the site and extent of the lesion seen on imaging. CONCLUSIONS: Early focal lesions affecting the visual pathway can, to some extent, be compensated for by the immature developing brain. These data suggest that all the infants presenting with focal lesions need to be investigated with a detailed assessment of various aspects of vision. Images PMID:8949687

  4. Ultrasound elastographic techniques in focal liver lesions.

    PubMed

    Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

    2016-03-07

    Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.

  5. Focal embolic cerebral ischemia in the rat

    PubMed Central

    Zhang, Li; Zhang, Rui Lan; Jiang, Quan; Ding, Guangliang; Chopp, Michael; Zhang, Zheng Gang

    2015-01-01

    Animal models of focal cerebral ischemia are well accepted for investigating the pathogenesis and potential treatment strategies for human stroke. Occlusion of the middle cerebral artery (MCA) with an endovascular filament is a widely used model to induce focal cerebral ischemia. However, this model is not amenable to thrombolytic therapies. As thrombolysis with recombinant tissue plasminogen activator (rtPA) is a standard of care within 4.5 hours of human stroke onset, suitable animal models that mimic cellular and molecular mechanisms of thrombosis and thrombolysis of stroke are required. By occluding the MCA with a fibrin-rich allogeneic clot, we have developed an embolic model of MCA occlusion in the rat, which recapitulates the key components of thrombotic development and of thrombolytic therapy of rtPA observed from human ischemic stroke. The surgical procedures of our model can be typically completed within approximately 30 min and are highly adaptable to other strains of rats as well as mice for both genders. Thus, this model provides a powerful tool for translational stroke research. PMID:25741989

  6. Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics.

    PubMed

    Schober, Markus; Raghavan, Srikala; Nikolova, Maria; Polak, Lisa; Pasolli, H Amalia; Beggs, Hilary E; Reichardt, Louis F; Fuchs, Elaine

    2007-02-26

    In response to alphabeta1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable for epidermal adhesion and basement membrane assembly, both of which require alphabeta1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of alphabeta1 integrin in regulating cytoskeletal dynamics and orchestrating polarized keratinocyte migration out of epidermal explants. Fak-null keratinocytes display an aberrant actin cytoskeleton, which is tightly associated with robust, peripheral focal adhesions and microtubules. We find that without FAK, Src, p190RhoGAP, and PKL-PIX-PAK, localization and/or activation at focal adhesions are impaired, leading to elevated Rho activity, phosphorylation of myosin light chain kinase, and enhanced tensile stress fibers. We show that, together, these FAK-dependent activities are critical to control the turnover of focal adhesions, which is perturbed in the absence of FAK.

  7. Bacterial vaginosis.

    PubMed Central

    Spiegel, C A

    1991-01-01

    Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which Lactobacillus spp., the predominant organisms in the healthy vagina, are replaced by a mixed flora including Prevotella bivia, Prevotella disiens, Porphyromonas spp., Mobiluncus spp., and Peptostreptococcus spp. All of these organisms except Mobiluncus spp. are also members of the endogenous vaginal flora. While evidence from treatment trials does not support the notion that BV is sexually transmitted, recent studies have shown an increased risk associated with multiple sexual partners. It has also been suggested that the pathogenesis of BV may be similar to that of urinary tract infections, with the rectum serving as a reservoir for some BV-associated flora. The organisms associated with BV have also been recognized as agents of female upper genital tract infection, including pelvic inflammatory disease, and the syndrome BV has been associated with adverse outcome of pregnancy, including premature rupture of membranes, chorioamnionitis, and fetal loss; postpartum endometritis; cuff cellulitis; and urinary tract infections. The mechanisms by which the BV-associated flora causes the signs of BV are not well understood, but a role for H2O2-producing Lactobacillus spp. in protecting against colonization by catalase-negative anaerobic bacteria has been recognized. These and other aspects of BV are reviewed. PMID:1747864

  8. Clozapine-induced interstitial nephritis - a rare but important complication: a case report

    PubMed Central

    2009-01-01

    Introduction Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case. Case presentation A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day). After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction. Conclusion Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated. PMID:20126316

  9. Exacerbation of lupus nephritis by high sodium chloride related to activation of SGK1 pathway.

    PubMed

    Yang, Xi; Yao, Genhong; Chen, Weiwei; Tang, Xiaojun; Feng, Xuebing; Sun, Lingyun

    2015-12-01

    The objective of this study is to explore the effects of high salt diet (HSD) on the severity of lupus nephritis (LN) and its mechanism. MRL/lpr mice were randomly divided into two groups, which were fed with normal diet or sodium-rich chow and tap. C57BL/6 mice were selected as control. Spleen Th1, Th2, Th17 and Treg cells were detected by flow cytometry. Serum TGF-β and IL-17 were measured by enzyme-linked immunosorbent assay. CD4(+) T cells from Systemic Lupus Erythematosus (SLE) patients and healthy donors were treated by NaCl with or without SGK1 inhibitor. Then, Th17 and Treg cells were detected. The HSD MRL/lpr mice had decreased survival rate and increased disease severity. The frequencies of Th1 and Th17 cells increased in HSD treatment group. The ratios of Th1/Th2 and Th17/Treg in HSD treated MRL/lpr mice significantly increased. Serum TGF-β increased after HSD treatment. In vitro, high salt could up-regulate Th17 cells of CD4(+) T cells. The effects of high salt treatment on CD4(+) T cells were reversed by SGK1 inhibitor. Our findings demonstrated that excessive intake of salt in diet is an aggravating factor for LN. High salt diet may deteriorate LN through SGK1 pathway.

  10. A Unique Cause of Proteinuria in Pregnancy: Class II Lupus Nephritis with Concomitant Minimal Change Disease

    PubMed Central

    Kunjal, Ryan; Adam-Eldien, Rabie; Makary, Raafat; Jo-Hoy, Francois; Heilig, Charles W.

    2016-01-01

    We report the case of a 22-year-old African American female who presented to another facility for routine follow-up in the 34th week of pregnancy with lower extremity swelling and nephrotic-range proteinuria. Although she was normotensive, it was initially thought that she had preeclampsia. She was monitored carefully and delivery was induced at 37 weeks of gestation. She was transferred to our hospital, where she was diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria. Renal biopsy revealed a surprising finding of minimal change disease (MCD) concomitant with class II lupus nephritis (LN). She was managed with pulses and then tapering doses of steroid therapy with dramatic resolution of the nephrotic syndrome. This case demonstrates not only the rare de novo occurrence of SLE in pregnancy, but the unique finding of MCD coexisting with class II LN. We propose that altered T cell activity may be the link between these seemingly distinct entities. PMID:27781205

  11. Avian nephritis virus (ANV) on Brazilian chickens farms: circulating genotypes and intra-genotypic diversity.

    PubMed

    Espinoza, Luis Luna; Beserra, Laila A R; Soares, Rodrigo M; Gregori, Fabio

    2016-12-01

    Avian nephritis virus (ANV), which belongs to the family Astroviridae, is associated with different clinical manifestations (including enteric disorders). Despite being frequently found in the avian industry worldwide, information regarding genetic features of these viruses in Brazil is scarce. Therefore, sixty fecal sample pools (5-6 birds of the same flock), representing 60 poultry farms from six Brazilian States, were screened using an astrovirus-specific hemi-nested-PCR assay targeting the conserved ORF1b gene, followed by nucleotide sequencing of amplified products. PCR and phylogenetic analysis confirmed the detection of 21 positive samples to ANV (35 %). In order to investigate the genetic diversity represented by these viruses, amplification, cloning and phylogenetic analysis of the deduced amino acid sequence of ORF2 gene were attempted. Eight samples were successfully cloned (generating 32 clones in total) and sequenced. Based on phylogenetic analysis of ORF2, sequences defined in this study were classified into three genotypes: genotype 5, which has already been described in birds, and two other novel genotypes, tentatively named genotype 8 and 9, all of which occurred in single or mixed infections. Moreover, high intra-genotypic diversity and co-circulation of distinct strains in a same host population were observed. This study revealed the presence of new strains of ANV in Brazilian poultry and their circulation in commercial chicken flocks.

  12. Cleaved Form of Osteopontin in Urine as a Clinical Marker of Lupus Nephritis

    PubMed Central

    Kitagori, Koji; Yoshifuji, Hajime; Oku, Takuma; Sasaki, Chiyomi; Miyata, Hitomi; Mori, Keita P.; Nakajima, Toshiki; Ohmura, Koichiro; Kawabata, Daisuke; Yukawa, Naoichiro; Imura, Yoshitaka; Murakami, Kosaku; Nakashima, Ran; Usui, Takashi; Fujii, Takao; Sakai, Kaoru; Yanagita, Motoko; Hirayama, Yoshitaka; Mimori, Tsuneyo

    2016-01-01

    We assessed the utility of two forms of osteopontin (OPN), OPN full and its cleaved form (OPN N-half), in plasma and urine as markers of disease activity in lupus nephritis (LN). Samples were collected from patients with systemic lupus erythematosus (SLE) (LN: N = 29, non-LN: N = 27), IgA nephropathy (IgAN) (N = 14), minimal change nephrotic syndrome (MCNS) (N = 5), diabetic nephropathy (DN) (N = 14) and healthy volunteers (HC) (N = 17). While there was no significant difference in urine OPN full concentration between groups, urine OPN N-half concentration was significantly higher in patients with LN than HC (p < 0.05). Moreover, urine OPN N-half was higher in LN patients with overt proteinuria (urine protein/creatinine ratio: P/C > 0.5) than LN patients with minimal proteinuria (P/C < 0.5, p < 0.0001), and also higher than in DN patients with overt proteinuria (P/C > 0.5, p < 0.01). Urine thrombin activity correlated with urine OPN N-half concentration (p < 0.0001), but not with urine OPN full concentration. These results suggest that urine OPN N-half concentration reflects renal inflammation. Thus, urine OPN N-half may be a novel disease activity marker for LN. PMID:27992535

  13. Mechanisms and kinetics for platelet and neutrophil localization in immune complex nephritis

    SciTech Connect

    Johnson, R.J.; Alpers, C.E.; Pruchno, C.; Schulze, M.; Baker, P.J.; Pritzl, P.; Couser, W.G. )

    1989-11-01

    We have previously reported that both neutrophils (PMNs) and platelets mediate proteinuria in a model of subendothelial immune complex (IC) nephritis (GN) in the rat. In order to understand the interaction of PMNs and platelets in this model, we quantitated the uptake of {sup 111}In-labelled platelets in glomeruli and correlated this with the number of PMNs observed histologically at 10 and 30 minutes, 1, 4 and 24 hours following induction of GN. Platelet accumulation was biphasic with a major peak at 10 minutes and a minor peak at four hours. Early platelet accumulation was complement dependent, and PMN-independent. PMN accumulation occurred after the initial platelet influx, peaking at one and four hours, was complement dependent, but was not affected by platelet depletion. Complement depletion significantly reduced proteinuria. This is the first documentation that platelet accumulation in glomeruli in IC GN is complement dependent. In addition, the enhancement of PMN-mediated injury by the platelet in this model does not involve effects of platelets on PMN localization, thus implying a functional interaction between these cells within the glomerulus.

  14. Leukotriene D4 is a mediator of proteinuria and glomerular hemodynamic abnormalities in passive Heymann nephritis.

    PubMed Central

    Katoh, T; Lianos, E A; Fukunaga, M; Takahashi, K; Badr, K F

    1993-01-01

    We assessed the role of leukotrienes (LTs) in Munich-Wistar rats with passive Heymann nephritis (PHN), an animal model of human membranous nephropathy. 10 d after injection of anti-Fx1A antibody, urinary protein excretion rate (Upr) in PHN was significantly higher than that of control. Micropuncture studies demonstrated reduced single nephron plasma flow and glomerular filtration rates, increased transcapillary hydraulic pressure difference, pre- and postglomerular resistances, and decreased ultrafiltration coefficient in PHN rats. Glomerular LTB4 generation from PHN rats was increased. Administration of the 5-LO activating protein inhibitor MK886 for 10 d markedly blunted proteinuria and normalized glomerular hemodynamic abnormalities in PHN rats. An LTD4 receptor antagonist SK&F 104353 led to an immediate reduction in Upr and to reversal of glomerular hemodynamic impairment. Ia(+) cells/glomerulus were increased in PHN rats. In x-irradiated PHN rats, which developed glomerular macrophage depletion, augmented glomerular LT synthesis was abolished. Thus, in the autologous phase of PHN, LTD4 mediates glomerular hemodynamic abnormalities and a hemodynamic component of the accompanying proteinuria. The synthesis of LTD4 likely occurs directly from macrophages or from macrophage-derived LTA4, through LTC4 synthase in glomerular cells. Images PMID:8386188

  15. Features and outcomes of lupus nephritis in Morocco: analysis of 114 patients

    PubMed Central

    Haddiya, Intissar; Hamzaoui, Hakim; Tachfouti, Nabil; Hamany, Zitouna Al; Radoui, Aicha; Zbiti, Najoua; Amar, Yamama; Rhou, Hakima; Benamar, Loubna; Ouzeddoun, Naima; Bayahia, Rabea

    2013-01-01

    Background There is wide variation in clinical presentation and outcome of lupus nephritis (LN) among different ethnic groups. Few data for LN exist on North Africans, especially those from Morocco. The aim of our study was to review retrospectively the features and outcome of LN in Moroccan patients. Patients and methods We performed a single-center retrospective study. A total of 114 patients with LN were included. All patients met American Rheumatism Association criteria. LN was classified according to the International Society of Nephrology/Renal Pathology Society classification. We adopted previously defined outcome criteria for LN. Results There were 101 females and 13 males, with a mean age of 29.9 years. At first presentation, we noted hypertension in 33%, hematuria in 76%, nephrotic syndrome in 53%, and renal failure in 60% of cases. Renal biopsy revealed predominant proliferative classes in more than 80% of patients. Patients received different regimens mainly based on intravenous cyclophosphamide. After a mean follow-up of 22 months, remission occurred in 45.5%, relapses in 82%, end-stage renal failure in 21%, and death in 16% of cases. Infection and neurological and cardiovascular diseases were the most frequent causes of death. Conclusion LN seems to be severe in our study, with a predominance of proliferative forms, severe renal manifestations, and poor renal and overall survival. PMID:24294005

  16. Early-stage lupus nephritis treated with N-acetylcysteine: A report of two cases.

    PubMed

    Li, Ming; Gao, Wenjuan; Ma, Jingjing; Zhu, Yun; Li, Xingfu

    2015-08-01

    The oxidative-antioxidative status is closely associated with the progression of systemic lupus erythematosus (SLE), and oxidative stress is customarily found in patients with SLE. N-acetylcysteine (NAC), a typical antioxidant, is reliable and often applied for clinical treatment. Lupus nephritis (LN) is a kidney disorder associated with SLE, but the treatment of LN with antioxidants is rarely documented. The present report describes two cases of early-stage LN that were orally treated with 1,200 mg NAC in addition to the standard therapy with hydroxychloroquine and calcitriol. Following the NAC administration, the glutathione level largely increased while the level of the lipid peroxidation biomarker 8-iso-prostaglandin F2α declined in both cases. In addition, the routine blood counts, 24-h urine protein, erythrocyte sedimentation rate and the SLE disease activity index were markedly improved. In conclusion, the present report of two cases has shown that NAC, as an antioxidant, may exert a beneficial effect to modulate the oxidative status in LN; however, the underlying mechanisms require further investigation.

  17. Early-stage lupus nephritis treated with N-acetylcysteine: A report of two cases

    PubMed Central

    LI, MING; GAO, WENJUAN; MA, JINGJING; ZHU, YUN; LI, XINGFU

    2015-01-01

    The oxidative-antioxidative status is closely associated with the progression of systemic lupus erythematosus (SLE), and oxidative stress is customarily found in patients with SLE. N-acetylcysteine (NAC), a typical antioxidant, is reliable and often applied for clinical treatment. Lupus nephritis (LN) is a kidney disorder associated with SLE, but the treatment of LN with antioxidants is rarely documented. The present report describes two cases of early-stage LN that were orally treated with 1,200 mg NAC in addition to the standard therapy with hydroxychloroquine and calcitriol. Following the NAC administration, the glutathione level largely increased while the level of the lipid peroxidation biomarker 8-iso-prostaglandin F2α declined in both cases. In addition, the routine blood counts, 24-h urine protein, erythrocyte sedimentation rate and the SLE disease activity index were markedly improved. In conclusion, the present report of two cases has shown that NAC, as an antioxidant, may exert a beneficial effect to modulate the oxidative status in LN; however, the underlying mechanisms require further investigation. PMID:26622376

  18. Soluble Fas and the −670 Polymorphism of Fas in Lupus Nephritis

    PubMed Central

    Bollain-y-Goytia, Juan José; Arellano-Rodríguez, Mariela; Torres-Del-Muro, Felipe de Jesús; Daza-Benítez, Leonel; Francisco Muñoz-Valle, José; Avalos-Díaz, Esperanza; Herrera-Esparza, Rafael

    2014-01-01

    This study was performed to clarify the role of soluble Fas (sFas) in lupus nephritis (LN) and establish a potential relationship between LN and the −670 polymorphism of Fas in 67 patients with systemic lupus erythematosus (SLE), including a subset of 24 LN patients with proteinuria. Additionally, a group of 54 healthy subjects (HS) was included. The allelic frequency of the −670 polymorphism of Fas was determined using PCR-RFLP analysis, and sFas levels were assessed by ELISA. Additionally, the WT-1 protein level in urine was measured. The Fas receptor was determined in biopsies by immunohistochemistry (IHC) and in situ hybridization (FISH) and apoptotic features by TUNEL. Results. The −670 Fas polymorphism showed that the G allele was associated with increased SLE susceptibility, with an odds ratio (OR) of 1.86. The sFas was significantly higher in LN patients with the G/G genotype, and this subgroup exhibited correlations between the sFas level and proteinuria and increased urinary WT-1 levels. LN group shows increased expression of Fas and apoptotic features. In conclusion, our results indicate that the G allele of the −670 polymorphism of Fas is associated with genetic susceptibility in SLE patients with elevated levels of sFas in LN with proteinuria. PMID:25505993

  19. Relevance of anti-C1q autoantibodies to lupus nephritis.

    PubMed

    Tsirogianni, Alexandra; Pipi, Elena; Soufleros, Kostantinos

    2009-09-01

    The first component of the classical pathway of the complement system (C1q) is considered to have a crucial role in the clearance of immune complexes (ICs) as well as in the removal of waste material originating from apoptotic cells. A prolonged exposure of C1q epitopes to the immune system could eventually lead to an autoimmune response against itself. Although autoantibodies against C1q are found in several diseases, their clinical interest originates from their strong association to active lupus nephritis (LN). Several studies indicate that anti-C1q autoantibodies could serve as a reliable serologic marker in the assessment of LN activity compared to other immunological tests. Additionally, it was suggested that anti-C1q autoantibodies could play a role in LN pathogenesis. Their potential pathogenic actions likely depend on genetic background, titers, Ig classes and subclasses, and specific epitopes of anti-C1q autoantibodies as well as C1q availability and allocation. It is still unclear which different types of anti-C1q autoantibodies dominate in each case and if their upregulation is pathogenic, an epiphenomenon of aberrant tissue damage, or compensatory to an uncontrolled immune response.

  20. Akt-dependent enhanced migratory capacity of Th17 cells from children with lupus nephritis.

    PubMed

    Kshirsagar, Sudhir; Riedl, Magdalena; Billing, Heiko; Tönshoff, Burkhard; Thangavadivel, Shanmugapriya; Steuber, Christian; Staude, Hagen; Wechselberger, Gottfried; Edelbauer, Monika

    2014-11-15

    Th17 cells infiltrate the kidneys of patients with lupus nephritis (LN) and are critical for the pathogenesis of this disease. In this study, we show that enhanced activity of Stat3 in CD4(+)CD45RA(-)Foxp3(-) and Foxp3(low) effector T cells from children with LN correlates with increased frequencies of IL-17-producing cells within these T cell populations. The levels of retinoic acid-related orphan receptor c and IL-17 mRNA are significantly higher in PBMCs from children with LN than in those from controls. Mammalian target of rapamycin inhibition by rapamycin reduces both Stat3 activation in effector T cells and the frequency of IL-17-producing T cells in lupus patients. Complement factor C5a slightly increases the expression of IL-17 and induces activation of Akt in anti-CD3-activated lupus effector T cells. Th17 cells from children with LN exhibit high Akt activity and enhanced migratory capacity. Inhibition of the Akt signaling pathway significantly decreases Th17 cell migration. These findings indicate that the Akt signaling pathway plays a significant role in the migratory activity of Th17 cells from children with LN and suggest that therapeutic modulation of the Akt activity may inhibit Th17 cell trafficking to sites of inflammation and thus suppress chronic inflammatory processes in children with LN.

  1. Acute tubulo-interstitial nephritis requiring dialysis associated with intermittent rifampicin use: case report.

    PubMed

    Gallieni, M; Braidotti, P; Cozzolino, M; Romagnoli, S; Carpani, P

    1999-07-01

    Rifampicin is one of the most effective antibiotics used for the treatment of tuberculosis and severe staphylococcal infections. Intermittent administration of high doses of rifampicin has been associated with frequent adverse reactions, including hepatotoxicity and nephrotoxicity, sometimes resulting in acute renal failure. We describe a case of rifampicin-associated acute renal failure, with biopsy findings of tubulointerstitial nephritis; inflammatory cells were characterized by immunohistochemistry, which showed immunoreactivity for CD3 and CD5 (T lymphocytes) and for CD68 (macrophages). The patient presented with a very rapid systemic reaction to the offending drug and rapid deterioration of renal function, which required dialysis treatment. The response to rifampicin discontinuation was excellent: no further therapy was required, as renal function began to improve within several days and returned to normal values (serum creatinine 1.17 mg/dl) seven months after the onset of symptoms. When prescribing rifampicin the physician should investigate previous use of the drug, because re-exposure is a critical factor in predicting the possibility of drug-induced acute renal failure.

  2. Initial Validation of a Novel Protein Biomarker Panel for Active Pediatric Lupus Nephritis

    PubMed Central

    Suzuki, Michiko; Wiers, Kristina; Brooks, Elizabeth B.; Greis, Kenneth D.; Haines, Kathleen; Klein-Gitelman, Marisa S.; Olson, Judyann; Onel, Karen; O’Neil, Kathleen M.; Silverman, Earl D.; Tucker, Lori; Ying, Jun; Devarajan, Prasad; Brunner, Hermine I.

    2009-01-01

    Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS-proteins for detecting activity of LN over time. Using surface-enhanced or matrix assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), α1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African-American) and 30 controls with juvenile idiopathic arthritis. All urinary PS-proteins were significantly higher with active versus inactive LN or in patients without LN (all p<0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 months before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001) and L-PGDS (p < 0.01) occurred, indicating that these PS-proteins are biomarkers of LN activity and may help anticipate the future course of LN. PMID:19218887

  3. Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

    PubMed Central

    Xue, Jing; Yang, Jiali; Yang, Lijuan; Zhou, Shaolan; Ji, Chen; Wang, Xuemei; Yu, Nan

    2017-01-01

    An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0.0001); in particular the serum DKK-1 concentration was even higher in LN-SLE patients relative to non-LN SLE subjects (p < 0.0001). Intriguingly, concentrations of above examined proteins in SLE patients showed no correlation between serum and urine. Moreover, a combination of DKK-1 with anti-dsDNA and/or levels of complement C3 and C4 could not increase the specificity and/or sensitivity for identification of patients with LN diseases, but both ROC curve and multiple-factor nonconditional logistic regression analysis showed that serum DKK-1 was considered better positive biomarker for identification of LN in SLE patients. These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN. PMID:28373995

  4. Kidney Expression of Toll Like Receptors in Lupus Nephritis: Quantification and Clinicopathological Correlations

    PubMed Central

    Miranda, Francesca; Bombardieri, Michele; Valesini, Guido

    2016-01-01

    Objective. The study aimed at locating and quantifying Toll Like Receptor (TLR) 3, 7, 8, and 9 expression in kidney of patients with lupus nephritis (LN) and correlating them with clinicopathological features. Methods. Kidney sections from 26 LN patients and 4 controls were analyzed by immunohistochemistry using anti-human TLR3, TLR7, TLR8, and TLR9 polyclonal antibodies; the number of TLR-positive nuclei/mm2 was evaluated on digitalized images. Results. Compared to controls, LN showed a significantly higher amount of glomerular and tubulointerstitial TLR9 (p = 0.003 and p = 0.007), whole and tubulointerstitial TLR3 (p = 0.026 and p = 0.031), and a higher tubulointerstitial TLR7 (p = 0.022). TLR9 positively correlated with activity index (p = 0.0063) and tubular TLR7 with chronicity index (p = 0.026). TLR9 positively correlated with Renal-SLEDAI (p = 0.01). Conclusions. This is the first study quantifying kidney expressions of TLRs in LN patients; the results show an overexpression of TLR3, TLR7, and TLR9 and demonstrate a correlation with clinicopathological indices supporting a role of these mediators in the pathogenesis of LN. PMID:27635115

  5. Association of interstitial nephritis with tubule cell injury and proliferation in NZB/NZW mice.

    PubMed Central

    Hurd, E R; Ziff, M

    1978-01-01

    The relationship between renal interstitial mononuclear cell infiltration and renal tubule cell (TC) proliferation has been examined in (NZB X NZW) F1 hybrid (B/W) and control mice. TC proliferation was measured by tritiated thymidine ([3H]TdR) injection, autoradiographic examination of kidney sections and enumeration of labelled tubule cells. In B/W mice interstitial infiltration began at 5 months and reached a peak at 9 months. Proliferation of TC began at 7 months and also reached a peak at 9 months. Control mice consisting of NZB, CBA/J and C57Bl/6J mice showed no increase with age. When the percentages of labelled TC in areas adjacent to interstitial infiltrates and distant from them were compared, the TC adjacent to infiltrates showed an approximately four-fold greater amount of labelling. Ultrathin light and electron microscopic sections demonstrated TC injury in areas in close proximity to infiltrates. These studies suggest that mononuclear cells in the interstitial infiltrate may be injurious to TC, leading to a sequence of injury and subsequent regeneration of these cells. In diseases in which interstitial nephritis is present, such as Sjögren's syndrome, the interstitial infiltrate may contribute to the observed TC dysfunction. Images FIG. 1 FIG. 2 FIG. 5 FIG. 6 FIG. 7 FIG. 8 FIG. 9 PMID:668188

  6. Granulomatous interstitial nephritis secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma.

    PubMed

    Nasr, Samih H; Shanafelt, Tait D; Hanson, Curtis A; Fidler, Mary E; Cornell, Lynn D; Sethi, Sanjeev; Chaffee, Kari G; Morris, Joseph; Leung, Nelson

    2015-06-01

    Granulomatous interstitial nephritis (GIN) is an uncommon pathologic lesion encountered in 0.5% to 5.9% of renal biopsies. Drugs, sarcoidosis, and infections are responsible for most cases of GIN. Malignancy is not an established cause of GIN. Here, we report a series of 5 patients with GIN secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients were mostly elderly white males with an established history of CLL/SLL who presented with severe renal impairment (median peak serum creatinine, 7.3 mg/dL), leukocyturia, and mild proteinuria. One had nephromegaly. In 2 patients, the development and relapse of renal insufficiency closely paralleled the level of lymphocytosis. Kidney biopsy in all patients showed GIN concomitant with CLL/SLL leukemic interstitial infiltration. Granulomas were nonnecrotizing and epithelioid and were associated with giant cells. One biopsy showed granulomatous arteritis. One patient had a granulomatous reaction in lymph nodes and skin. Steroids with/without CLL/SLL-directed chemotherapy led to partial improvement of kidney function in all patients except 1 who had advanced cortical scarring on biopsy. In conclusion, we report an association between CLL/SLL and GIN. Patients typically present with severe renal failure due to both GIN and leukemic interstitial infiltration, which tends to respond to steroids with/without CLL/SLL-directed chemotherapy. The pathogenesis of GIN in this clinical setting is unknown but may represent a local hypersensitivity reaction to the CLL/SLL tumor cells.

  7. Association of Serum CXCL13 with Intrarenal Ectopic Lymphoid Tissue Formation in Lupus Nephritis

    PubMed Central

    Chen, Wen Li; Long, Kang Xia; Zhang, Xiao

    2016-01-01

    Aims. To assess the concentrations of serum CXCL13 and intrarenal ectopic lymphoid tissue (ELT) profiles and their correlation in the patients with lupus nephritis (LN). Methods. Serum CXCL13 levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of CD3, CD20, and CD21 in renal biopsy specimens was tested using immunohistochemical methods. Results. Serum CXCL13 levels were significantly higher in the LN group than those in the SLE group without LN and also in the type III and IV LN patients than in type V LN patients. LN patients with positive CD20 expression (CD20+ LN) had a longer disease course and poorer response to combination therapy and higher serum CXCL13 levels than CD20− LN patients. Moreover, the serum CXCL13 level was positively correlated with the number of B cells/HP in the renal tissue of LN patients. The coexpression patterns of CD3, CD20, and CD21 in the renal tissue of LN patients with different WHO pathological types were significantly different. Serum CXCL13 levels were significantly higher in ELT-2 type LN patients than in 0 or 1 type LN patients. Conclusions. This study suggested that increased serum levels of CXCL13 might be involved in renal ELT formation and renal impairment process in LN. PMID:27990444

  8. IgG4- related disease as a rare cause of tubulointerstitial nephritis.

    PubMed

    Lee, Lennard Y W; Yap, Hsiu; Sampson, Steve; Ford, Brian; Hayman, Grant; Marsh, James; Bansal, Amolak S

    2014-07-01

    Isolated IgG4 tubulointerstitial nephritis (TIN) is a rare disorder characterized by raised serum IgG4 levels and histological findings of dense lymphoplasmacytic infiltrates rich in IgG4 positive plasma cells. We report a case of isolated IgG4 TIN that presented with acute kidney injury in an 84 year old man with a polyclonal increase in his total IgG and a raised IgE of 381 kUA/L but without evidence of systemic autoimmunity. We draw a parallel with IgG4-related autoimmune pancreatitis and show raised levels of circulating regulatory T cells. Importantly the plasma levels of the T regulatory cell cytokine, IL10, the TH1 cytokines IL12 and IFNγ, the proinflammatory TNF α and immune regulatory IL27 were all highly raised. Furthermore, the level of IL21 that promotes IgG4 production was also very significantly elevated. These results suggest efforts of the immune system to reduce inflammation and suppress an exaggerated Th2 response. A raised serum IgG in the setting of acute kidney injury and in the absence of autoimmunity and chronic infection should encourage an assessment of the IgG subclasses. Prompt steroid treatment of those with a raised IgG4 may reduce ongoing renal damage.

  9. Longitudinal study of circulating immune complexes in a patient with Staphylococcus albus-induced shunt nephritis.

    PubMed Central

    Harkiss, G D; Brown, D L; Evans, D B

    1979-01-01

    The direct measurement and partial characterization of circulating immune complexes has been performed in a longitudinal study of a patient with Staphylococcus albus-induced shunt nephritis. The high levels of immune complexes were associated with cryoglobulinaemia and hypocomplementaemia. The activation of complement was found to be via the classical pathway, but the functioning of the alternative pathway may have been impaired in vivo due to very low levels of C3. The host response to the infection was also characterized by the production of a marked macroglobulinaemia, high titres of rheumatoid factor and a typical acute phase increase in the C-reactive protein level. Immune complex levels were persistently elevated many months after the removal of the focus of the infection. A possible explanation for this surprising finding may lie in the nature of the antigens in the immune complexes. It was found that the immune complexes contained both antibodies to and antigens from Staphlococcus albus. In particular, glycerol teichoic acid and staphylococcal nuclease were identified as components of the immune complexes present during the acute phase. Glycerol teichoic acid was also identified in the immune complexes found later although other Staphylococcus albus antigens as yet unidentified were also present and persisted in the circulation for several months. Images FIG. 3 FIG. 4 PMID:115626

  10. Effects of shikonin isolated from zicao on lupus nephritis in NZB/W F1 mice.

    PubMed

    Wang, Xin Chang; Feng, Jian; Huang, Feng; Fan, Yong Sheng; Wang, Yan Yan; Cao, Ling Yong; Wen, Cheng Pin

    2009-09-01

    The present study was performed to evaluate the potential protective effects of Shikonin extracted from Zicao on lupus nephritis (LN) using NZB/W F1 mice. Oral administration of Shikonin (24, 40 mg/kg body weight/d) or vehicle was applied to sixty female NZB/W F1 mice of 28-week-old with LN. Treatment with Shikonin for 14 weeks suppressed proteinuria dose-dependently with the mean proteinuria of 274.0 mg/dl and 160.3 mg/dl for low-dose and high-dose Shikonin groups, respectively, compared to 499.2 mg/dl for the vehicle. Also, Shikonin was observed to reduce circulating adhesion molecules significantly and down-regulate intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA expression in kidney. However, anti-double stranded (ds)DNA antibody in mice with low or high Shikonin dose administration both exhibited no significant elevation, differing from vehicle group. Kidney histological examination showed that renal glomerular lesions were alleviated after Shikonin application. These results suggest that Shikonin has therapeutic effects on LN in NZB/W F1 mice, to which inhibition of anti-dsDNA may be potential contribution, and its part mechanism is related to suppression of mRNA expression of cell adhesion molecules (CAMs) in the kidney.

  11. Urinary CD8+ T-cell counts discriminate between active and inactive lupus nephritis

    PubMed Central

    2013-01-01

    Introduction Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Early detection of initial renal manifestations and relapses during follow-up is pivotal to prevent loss of renal function. Apart from renal biopsies, current urinary and serological diagnostic tests fail to accurately demonstrate the presence of active LN. Previously, we demonstrated that effector memory T-cells (CD45RO+CCR7-;TEM) migrate into the urine during active LN. The objective of this study was to assess the diagnostic value of urinary T-cells in comparison with traditional markers of active LN. Methods T-cells in the urine during active LN and remission were investigated. Twenty-two, in most cases biopsy-proven, active LN patients and 24 SLE patients without active LN were enrolled and serial measurements were performed in 16 patients. Results Analysis of the urinary sediment in active renal disease showed an increased number of CD8+ T-cells and absence of these cells during remission. Enumerating T-cell counts in LN patients with a history of renal involvement was a superior marker of active LN in comparison to traditional markers, such as proteinuria and s-creatinine. Conclusions In conclusion, urinary T-cells, in particular CD8+ T cells, are a promising marker to assess renal activity in LN patients, in particular in those with prior renal involvement. PMID:23445537

  12. Increased urinary excretion of platelet activating factor in mice with lupus nephritis

    SciTech Connect

    Macconi, D.; Noris, M.; Benfenati, E.; Quaglia, R.; Pagliarino, G. ); Remuzzi, G. Ospedali Riuniti di Bergamo )

    1991-01-01

    Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-(1{prime},2{prime}-{sup 3}H)alkyl) is filtered through the glomerulus and excreted in the urine. The results show that: (1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, (2) PAF levels increased when animals started to develop high grade proteinuria, (3) after intravenous injection of ({sup 3}H) PAF In nephritic mice, a negligible amount of ({sup 3}H) ether lipid, corresponding to ({sup 3}H)1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.

  13. Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis.

    PubMed

    Berthier, Celine C; Bethunaickan, Ramalingam; Gonzalez-Rivera, Tania; Nair, Viji; Ramanujam, Meera; Zhang, Weijia; Bottinger, Erwin P; Segerer, Stephan; Lindenmeyer, Maja; Cohen, Clemens D; Davidson, Anne; Kretzler, Matthias

    2012-07-15

    Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these preclinical models. In this study, we used an unbiased transcriptional network approach to define, in molecular terms, similarities and differences among three lupus models and human LN. Genome-wide gene-expression networks were generated using natural language processing and automated promoter analysis and compared across species via suboptimal graph matching. The three murine models and human LN share both common and unique features. The 20 commonly shared network nodes reflect the key pathologic processes of immune cell infiltration/activation, endothelial cell activation/injury, and tissue remodeling/fibrosis, with macrophage/dendritic cell activation as a dominant cross-species shared transcriptional pathway. The unique nodes reflect differences in numbers and types of infiltrating cells and degree of remodeling among the three mouse strains. To define mononuclear phagocyte-derived pathways in human LN, gene sets activated in isolated NZB/W renal mononuclear cells were compared with human LN kidney profiles. A tissue compartment-specific macrophage-activation pattern was seen, with NF-κB1 and PPARγ as major regulatory nodes in the tubulointerstitial and glomerular networks, respectively. Our study defines which pathologic processes in murine models of LN recapitulate the key transcriptional processes active in human LN and suggests that there are functional differences between mononuclear phagocytes infiltrating different renal microenvironments.

  14. Small bowel bacterial overgrowth

    MedlinePlus

    Overgrowth - intestinal bacteria; Bacterial overgrowth - intestine; Small intestinal bacterial overgrowth; SIBO ... intestine does not have a high number of bacteria. Excess bacteria in the small intestine may use ...

  15. The relative contribution of co-infection to focal infection risk in children.

    PubMed

    Lello, Joanne; Knopp, Stefanie; Mohammed, Khalfan A; Khamis, I Simba; Utzinger, Jürg; Viney, Mark E

    2013-03-07

    Co-infection is ubiquitous in people in the developing world but little is known regarding the potential for one parasite to act as a risk factor for another. Using generalized linear mixed modelling approaches applied to data from school-aged children from Zanzibar, Tanzania, we determined the strength of association between four focal infections (i.e. Ascaris lumbricoides, Trichuris trichiura, hookworm and self-reported fever, the latter used as a proxy for viral, bacterial or protozoal infections) and the prevalence or intensity of each of the helminth infections. We compared these potential co-infections with additional risk factors, specifically, host sex and age, socioeconomic status and physical environment, and determined what the relative contribution of each risk factor was. We found that the risk of infection with all four focal infections was strongly associated with at least one other infection, and that this was frequently dependent on the intensity of that other infection. In comparison, no other incorporated risk factor was associated with all focal infections. Successful control of infectious diseases requires identification of infection risk factors. This study demonstrates that co-infection is likely to be one of these principal risk factors and should therefore be given greater consideration when designing disease-control strategies. Future work should also incorporate other potential risk factors, including host genetics which were not available in this study and, ideally, assess the risks via experimental manipulation.

  16. CT appearance of focal fatty infiltration of the liver

    SciTech Connect

    Halvorsen, R.A.; Korobkin, M.; Ram, P.C.; Thompson, W.M.

    1982-08-01

    Focal fatty infiltration of the liver is an entity that may be confused with liver metastasis on computed tomography (CT). The imaging results and medical records of 16 patients with CT appearance suggestive of focal fatty liver were reviewed, three of whom had the simultaneous presence of metastitic liver disease. Focal fatty liver often has a distinctive appearance with CT, usually with a nonspherical shape, absence of mass effect, and density close to water. Liver metastases are usually round or oval, and unless cystic or necrotic, they have CT attenuation values closer to normal liver parenchyma than water. A radionuclide liver scan almost always resolves any confusion about the differential diagnosis of focal fatty liver: a well defined focus of photon deficiency is due to neoplasm rather than focal fatty infiltration. Sonography sometimes helps to confirm the CT impression, but may be misleading if the diagnosis of focal or diffuse fatty infiltration is not suspected before the examination.

  17. Deep Moonquake Focal Mechanisms: Recovery and Implications

    NASA Technical Reports Server (NTRS)

    Knapmeyer, Martin; Weber, Renee C.

    2011-01-01

    A defining characteristic of deep moonquakes is their tendency to occur with tidal periodicity, prompting previous studies to infer that they are related to the buildup and release of tidal stress within the Moon. In studies of tidal forcing, a key constraint is the focal mechanism: the fault parameters describing the type of failure moonquakes represent. The quality of the lunar seismic data and the limited source/receiver geometries of the Apollo seismic network prohibit the determination of deep moonquake fault parameters using first-motion polarities, as is typically done in terrestrial seismology. Without being able to resolve tidal stress onto a known failure plane, we can examine only gross qualities of the tidal stress tensor with respect to moonquake occurrence, so we cannot fully address the role of tidal stress in moonquake generation. We will examine the extent to which shear (S) and compression (P) wave amplitude ratios can constrain moonquake fault geometry by determining whether, for a given cluster, there exists a focal mechanism that can produce a radiation pattern consistent with the amplitudes measured by the Apollo instruments. Amplitudes are read in the ray coordinate frame, directly from seismograms for which the P and S arrivals are clearly identifiable on all long-period channels of the four Apollo stations. We apply an empirical station correction to account for site effects and the differences between P- and S-wave attenuation. Instead of focusing on the best fitting solution only, we formulate the inverse problem using a falsification criterion: all source orientations that do not reproduce the observed SV/P ratios within an error margin derived from the uncertainty of amplitude readings are rejected. All others are accepted as possible solutions. The inversion is carried out using an exhaustive grid search on a regular grid with predefined step size, encompassing all possible combinations of strike, dip and slip. To assess the

  18. Physical Activity Performance of Focal Middle School Students

    ERIC Educational Resources Information Center

    Erfle, Stephen E.; Gelbaugh, Corey M.

    2013-01-01

    Histograms of push-ups and curl-ups from a sample of more than 9,000 students show periodic spikes at five and 10 unit intervals. This article argues that these spikes are related to focal points, a game theoretic concept popularized by Nobel Laureate Thomas Schelling. Being focal on one test makes one more likely to be focal on the other. Focal…

  19. Botulinum toxin physiology in focal hand and cranial dystonia.

    PubMed

    Karp, Barbara Illowsky

    2012-11-20

    The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features, such as task specificity in focal hand dystonia which is not a common feature of cranial dystonia. The physiologic effects of botulinum toxin in these 2 disorders also show both similarities and differences. This paper compares and contrasts the physiology of focal hand and cranial dystonias and of botulinum toxin in the management of these disorders.

  20. Focal Length Affects Depicted Shape and Perception of Facial Images.

    PubMed

    Třebický, Vít; Fialová, Jitka; Kleisner, Karel; Havlíček, Jan

    2016-01-01

    Static photographs are currently the most often employed stimuli in research on social perception. The method of photograph acquisition might affect the depicted subject's facial appearance and thus also the impression of such stimuli. An important factor influencing the resulting photograph is focal length, as different focal lengths produce various levels of image distortion. Here we tested whether different focal lengths (50, 85, 105 mm) affect depicted shape and perception of female and male faces. We collected three portrait photographs of 45 (22 females, 23 males) participants under standardized conditions and camera setting varying only in the focal length. Subsequently, the three photographs from each individual were shown on screen in a randomized order using a 3-alternative forced-choice paradigm. The images were judged for attractiveness, dominance, and femininity/masculinity by 369 raters (193 females, 176 males). Facial width-to-height ratio (fWHR) was measured from each photograph and overall facial shape was analysed employing geometric morphometric methods (GMM). Our results showed that photographs taken with 50 mm focal length were rated as significantly less feminine/masculine, attractive, and dominant compared to the images taken with longer focal lengths. Further, shorter focal lengths produced faces with smaller fWHR. Subsequent GMM revealed focal length significantly affected overall facial shape of the photographed subjects. Thus methodology of photograph acquisition, focal length in this case, can significantly affect results of studies using photographic stimuli perhaps due to different levels of perspective distortion that influence shapes and proportions of morphological traits.

  1. A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial

    PubMed Central

    Tamirou, Farah; Lauwerys, Bernard R; Dall'Era, Maria; Mackay, Meggan; Rovin, Brad; Cervera, Ricard; Houssiau, Frédéric A

    2015-01-01

    Background Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts. Trial registration number: NCT00204022. PMID:26629352

  2. Smart trigger logic for focal plane arrays

    DOEpatents

    Levy, James E; Campbell, David V; Holmes, Michael L; Lovejoy, Robert; Wojciechowski, Kenneth; Kay, Randolph R; Cavanaugh, William S; Gurrieri, Thomas M

    2014-03-25

    An electronic device includes a memory configured to receive data representing light intensity values from pixels in a focal plane array and a processor that analyzes the received data to determine which light values correspond to triggered pixels, where the triggered pixels are those pixels that meet a predefined set of criteria, and determines, for each triggered pixel, a set of neighbor pixels for which light intensity values are to be stored. The electronic device also includes a buffer that temporarily stores light intensity values for at least one previously processed row of pixels, so that when a triggered pixel is identified in a current row, light intensity values for the neighbor pixels in the previously processed row and for the triggered pixel are persistently stored, as well as a data transmitter that transmits the persistently stored light intensity values for the triggered and neighbor pixels to a data receiver.

  3. Design of large aperture focal plane shutter

    NASA Astrophysics Data System (ADS)

    Hu, Jia-wen; Ma, Wen-li; Huang, Jin-long

    2012-09-01

    To satisfy the requirement of large telescope, a large aperture focal plane shutter with aperture size of φ200mm was researched and designed to realize, which could be started and stopped in a relative short time with precise position, and also the blades could open and close at the same time at any orientation. Timing-belts and stepper motors were adopted as the drive mechanism. Velocity and position of the stepper motors were controlled by the PWM pulse generated by DSP. Exponential curve is applied to control the velocity of the stepper motors to make the shutter start and stop in a short time. The closing/open time of shutter is 0.2s, which meets the performance requirements of large telescope properly.

  4. Stabilized dispersive focal plane systems for space

    NASA Astrophysics Data System (ADS)

    Roming, Peter W. A.; Bayless, Amanda J.; Beebe, Chip R.; Brooks, Mark J.; Davis, Michael W.; Klar, Robert A.; Roberts, John M.; Rose, Randall J.; Winters, Gregory S.

    2012-09-01

    As the costs of space missions continue to rise, the demand for compact, low mass, low-cost technologies that maintain high reliability and facilitate high performance is increasing. One such technology is the stabilized dispersive focal plane system (SDFPS). This technology provides image stabilization while simultaneously delivering spectroscopic or direct imaging functionality using only a single optical path and detector. Typical systems require multiple expensive optical trains and/or detectors, sometimes at the expense of photon throughput. The SDFPS is ideal for performing wide-field low-resolution space-based spectroscopic and direct-imaging surveys. In preparation for a suborbital flight, we have built and ground tested a prototype SDFPS that will concurrently eliminate unwanted image blurring due to the lack of adequate platform stability, while producing images in both spectroscopic and direct-imaging modes. We present the overall design, testing results, and potential scientific applications.

  5. Deep Moonquake Focal Mechanisms: Recovery and Implications

    NASA Technical Reports Server (NTRS)

    Weber, Renee C.; Knapmeyer, Martin

    2012-01-01

    A defining characteristic of deep moonquakes is their tendency to occur with tidal periodicity, prompting previous studies to infer that they are related to the buildup and release of tidal stress within the Moon [refs]. In studies of tidal forcing, a key constraint is the focal mechanism: the fault parameters describing the type of failure moonquakes represent. The quality of the lunar seismic data and the limited source/receiver geometries of the Apollo seismic network prohibit the determination of deep moonquake fault parameters using first-motion polarities, as is typically done in terrestrial seismology [ref]. Without being able to resolve tidal stress onto a known failure plane, we can examine only gross qualities of the tidal stress tensor with respect to moonquake occurrence, so we cannot fully address the role of tidal stress in moonquake generation.

  6. Mycelia as a focal point for horizontal gene transfer among soil bacteria

    PubMed Central

    Berthold, Tom; Centler, Florian; Hübschmann, Thomas; Remer, Rita; Thullner, Martin; Harms, Hauke; Wick, Lukas Y.

    2016-01-01

    Horizontal gene transfer (HGT) is a main mechanism of bacterial evolution endowing bacteria with new genetic traits. The transfer of mobile genetic elements such as plasmids (conjugation) requires the close proximity of cells. HGT between genetically distinct bacteria largely depends on cell movement in water films, which are typically discontinuous in natural systems like soil. Using laboratory microcosms, a bacterial reporter system and flow cytometry, we here investigated if and to which degree mycelial networks facilitate contact of and HGT between spatially separated bacteria. Our study shows that the network structures of mycelia promote bacterial HGT by providing continuous liquid films in which bacterial migration and contacts are favoured. This finding was confirmed by individual-based simulations, revealing that the tendency of migrating bacteria to concentrate in the liquid film around hyphae is a key factor for improved HGT along mycelial networks. Given their ubiquity, we propose that hyphae can act as focal point for HGT and genetic adaptation in soil. PMID:27811990

  7. Pneumatic release of focal vitreomacular traction.

    PubMed

    Claus, M G; Feron, E; Veckeneer, M

    2017-03-01

    PurposeTo study the efficacy of a single intravitreal injection of expansile gas as a valuable alternative to current treatment options (conservative, pharmacological, and surgical) in patients with symptomatic, focal vitreomacular traction (VMT).Patients and methodsThis study comprises a retrospective, interventional case series of patients. Twenty eyes in seventeen patients with symptomatic and persisting focal VMT were treated in an outpatient setting with an intravitreal gas injection of 0.2 ml. In 19 eyes, 100% hexafluoroethane (C2F6) was used. One eye received sulfur hexafluoride (SF6). To all but three patients posturing advice was given. Patients were reviewed with a full-eye examination and ocular coherence tomography (OCT) after 14 days and later. The primary outcome measure was the release of VMT on OCT.ResultsIn 17 of the 20 (85.0%) treated eyes, a release of VMT was achieved as documented on OCT. The release of VMT was diagnosed during the first month after injection in 11 eyes of 11 patients and within 3 months in 16 eyes of 15 patients. In all but five of our patients, best corrected visual acuity (BCVA) remained stable or improved. In four patients, the progression or development of cataract was the probable cause of the decrease in BCVA. One patient developed a stage II macular hole after injection and needed vitrectomy. None of the treated patients developed retinal breaks.ConclusionIntravitreal expansile gas injection could offer a minimally invasive, low-cost alternative treatment in patients with symptomatic, persisting VMT. Additional studies on a larger number of patients are required.

  8. Focal symmetrical encephalomalacia in a goat.

    PubMed

    Oliveira, Diego M; Pimentel, Luciano A; Pessoa, André F; Dantas, Antônio F M; Uzal, Francisco; Riet-Correa, Franklin

    2010-09-01

    Focal symmetrical encephalomalacia (FSE) is the most prominent lesion seen in the chronic form of enterotoxemia caused by Clostridium perfringens type D in sheep. However, this lesion has not been reported in goats. The current paper reports a case of FSE in a goat from the state of Paraíba in the Brazilian semiarid region. As reported by the farmer, 30, 4-48-month-old animals from a flock of 150 goats died after showing nervous signs, including blindness and recumbence, for periods varying between 1 and 14 days. The flock was grazing native pasture supplemented with wheat and corn bran. Additionally, lactating goats were supplemented with soybeans. A 4-month-old goat with nervous signs was examined clinically and then necropsied 3 days after the onset of clinical signs. Bilateral, focal, and symmetrical areas of brown discoloration were observed in the internal capsule and thalamus. Histologic lesions in these areas consisted of multifocal, bilateral malacia with a few neutrophils; endothelial cell swelling; perivascular edema; and hemorrhages. The etiology of these lesions was not determined. However, FSE is considered pathognomonic for C. perfringens type D enterotoxemia in sheep, and it is speculated that this microorganism was the etiologic agent in the present case. The flock had been vaccinated against type D enterotoxemia only once, approximately 3 months before the beginning of the outbreak. Insufficient immunity due to the incorrect vaccination protocol, low efficacy of the vaccine used, and a diet including large amounts of highly fermentable carbohydrates were suspected to be predisposing factors for this outbreak.

  9. Sighting optics including an optical element having a first focal length and a second focal length and methods for sighting

    DOEpatents

    Crandall, David Lynn

    2011-08-16

    Sighting optics include a front sight and a rear sight positioned in a spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus for a user images of the front sight and the target.

  10. A conserved anti-DNA antibody idiotype associated with nephritis in murine and human systemic lupus erythematosus.

    PubMed

    Weisbart, R H; Noritake, D T; Wong, A L; Chan, G; Kacena, A; Colburn, K K

    1990-04-01

    In order to identify unique structural features of pathogenic autoantibodies to DNA in SLE, a murine anti-anti-DNA (anti-Id) mAb (mAb 1C7) was produced in response to immunization of lupus mice with a syngeneic anti-DNA mAb (mAb 3E10). Immunization of lupus mice with mAb 3E10 inhibited production of native anti-DNA antibodies, suppressed development of lupus kidney disease (nephritis), and induced production of anti-anti-DNA (anti-Id) antibodies. mAb 1C7 bound F(ab')2 fragments of mAb 3E10, and it bound other murine anti-DNA mAb, but not murine mAb or polyclonal serum antibodies unreactive with DNA. Moreover, binding of mAb 1C7 anti-Id to mAb 3E10 was inhibited by DNA, suggesting anti-Id binding within or near the binding site for DNA. Furthermore, mAb 1C7 bound serum IgG immunoglobulins from 9/12 patients with lupus nephritis and serum anti-DNA antibodies compared to only 3/12 SLE patients with comparable serum levels of anti-DNA antibodies, but without nephritis (p = 0.04), and only 1/53 SLE patients without serum anti-DNA antibodies, 0/49 patients with rheumatoid arthritis, and 1/47 healthy subjects (p less than 0.001). These results provide evidence that mAb 1C7 identifies a conserved Id associated with anti-DNA antibodies in murine and human SLE and may be useful as a structural probe to characterize pathogenic anti-DNA antibodies in SLE.

  11. Effects of Integrated Traditional Chinese and Western Medicine for the Treatment of Lupus Nephritis: A Meta-Analysis of Randomized Trials

    PubMed Central

    Heng, Mingli; Tu, Jinli; Hao, Yu; Zhao, Ye; Tian, Jinhui

    2016-01-01

    After a thorough search through the database as CNKI database, VIP database, Wanfang database, PubMed, and Cochrane Library, the clinical experimental articles have been selected out on the effects of Integrated Traditional Chinese and Western Medicine on the treatment of lupus nephritis. A meta-analysis was carried out in terms of clinical efficacy criteria and safety criteria by RevMan 5.3 software. Based on the results, we cautiously conclude that Integrated Traditional Chinese and Western Medicine used for lupus nephritis could improve the clinical efficacy while at same time lower the 24-hour urine protein, serum creatinine, and adverse drug reactions. PMID:28105057

  12. Non-uniform Progression of Chronic Tubulointerstitial Nephritis and Widespread Nephrocalcification in a Patient with Anorexia Nervosa.

    PubMed

    Hasegawa, Sho; Shibata, Maki; Mochizuki, Makoto; Katsuki, Takashi; Tada, Manami; Hinoshita, Fumihiko

    2017-01-01

    Although patients with anorexia nervosa (anorexia) are known to show tubulointerstitial nephritis (TIN), the pathophysiology of its progression is not fully understood. We herein report a 31-year-old woman with anorexia who showed acute exacerbation of chronic kidney disease. Renal biopsy showed non-uniform chronic TIN; some areas were obsolete lesions and other areas were active lesions. In addition, many calcium-containing crystals were widely deposited in the distal tubules. The results suggest that chronic TIN in the setting of anorexia does not uniformly progress and that not only TIN but also widespread calcification of distal tubules might aggravate the renal function of anorexia patients.

  13. Primary Sjögren's syndrome with chronic tubulointerstitial nephritis and lymphadenopathy mimicking IgG4-related disease.

    PubMed

    Kawano, Mitsuhiro; Suzuki, Yasunori; Yamada, Kazunori; Mizushima, Ichiro; Matsumura, Masami; Nakajima, Kenichi; Yamagishi, Masakazu; Yamaguchi, Yutaka

    2015-07-01

    We describe a 62-year-old woman with Sjögren's syndrome (SS) presenting with tubulointerstitial nephritis (TIN) and lymphadenopathy mimicking IgG4-related disease (IgG4-RD). Computed tomography revealed multiple swollen lymph nodes. Biopsy of the largest lymph node showed reactive lymphadenopathy with dense IgG4 positive plasma cell (IgG4 + PC) infiltration. Renal biopsy showed chronic plasma cell-rich TIN with IgG4 + PC infiltration. This case suggests that Immunoglobulin G4 immunostaining does not always support the diagnosis of IgG4-RD in the differential diagnosis between SS and IgG4-RD.

  14. Hemorrhagic nephritis and enteritis in a goose flock in Poland--disease course analysis and characterization of etiologic agent.

    PubMed

    Gaweł, Andrzej; Woźniakowski, Grzegorz; Samorek-Salamonowicz, Elzbieta; Kozdruń, Wojciech; Bobrek, Kamila; Bobusia, Katarzyna; Nowak, Marcin

    2014-12-01

    Hemorrhagic nephritis enteritis of geese (HNEG) is an epizootic viral disease caused by infection with goose hemorrhagic polyomavirus (GHPV) that affects domestic geese. This study describes the epizootic analysis, laboratory diagnosis, and molecular characterization of GHPV isolates associated with HNEG cases in Poland. HNEG symptoms persisted in infected flocks for 2 wk with a 32% mortality rate. Primary gross lesions included hemorrhaging of the kidneys, intestines, and lungs. Histopathologic examination confirmed HNEG and identified that the causative agent was similar to other GHPV isolates and identical to the Toulouse 2008 isolate.

  15. Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults

    PubMed Central

    Legendre, Mathieu; Devilliers, Hervé; Perard, Laurent; Groh, Matthieu; Nefti, Habdelamid; Dussol, Bertrand; Trad, Salim; Touré, Fatouma; Abad, Sébastien; Boffa, Jean-Jacques; Frimat, Luc; Torner, Stéphane; Seidowsky, Alexandre; Massy, Ziad André; Saadoun, David; Rieu, Virginie; Schoindre, Yoland; Heron, Emmanuel; Frouget, Thierry; Lionet, Arnaud; Glowacki, François; Arnaud, Laurent; Mousson, Christiane; Besancenot, Jean-François; Rebibou, Jean-Michel; Bielefeld, Philip

    2016-01-01

    Abstract Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis. We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015. Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8–77.4) with a median serum creatinine level at 207 μmol/L (range 100–1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m2 (range 2–73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10–2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m2 (range 17–119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = −0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = −0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated

  16. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

    PubMed

    Bastian, H M; Roseman, J M; McGwin, G; Alarcón, G S; Friedman, A W; Fessler, B J; Baethge, B A; Reveille, J D

    2002-01-01

    The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95

  17. Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus

    PubMed Central

    Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa; Eberhard, Anne; Ardoin, Stacy; Singer, Nora; Onel, Karen; Tucker, Lori; O’Neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I.

    2015-01-01

    Objective To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. Methods In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score: ≤ 10 vs. > 10; Tubulointerstitial Activity Index (TIAI) score: ≤ 5 vs. > 5) or the absence vs. presence of LN chronicity [NIH Chronicity Index (NIH-CI) score: 0 vs. ≥ 1]. Results There were 10, 50 and 23 patients with class I/II, III/IV and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with LN-activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between LN-activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture LN chronicity was 23.5% and 91.7%, respectively. Despite designed to measure LN-activity, SLICC-RAS and SLEDAI-R scores significantly differed with LN chronicity status. Conclusion Current clinical indices of LN fail to discriminate ISN/RPS Class in children. Despite its shortcomings, the SLEDAI-R appears to best for measuring LN activity in a clinical setting. The SDI-R is a poor correlate of LN chronicity. PMID:26213987

  18. Fiberglass or silica exposure and increased nephritis or ESRD (end-stage renal disease).

    PubMed

    Goldsmith, J R; Goldsmith, D F

    1993-06-01

    The U.S. multiplant cohort mortality study of workers producing manufactured mineral fibers is finding increasing mortality from nephritis and/or nephrosis. We examine other data sets to see if similar effects can be identified. In a case-referent study among Michigan patients with end-stage renal disease (ESRD), men with exposures to silica have elevated odds ratio for ESRD. In a California occupational mortality study based on 1979-81 data, a number of the construction trades, farmers, and farm laborers show excess mortality for renal disease. The highest mortality ratio is found in the category including insulation workers. This ratio remains significantly elevated when adjusted for estimated exposures to smoking, alcohol, and for socio-economic status. California mortality data from 20 years earlier (1959-61) fail to show much excess renal disease in construction workers, but do for farmers. In Singapore, granite workers with a long-term exposure to silica have excess excretion of albumin and similar compounds compared to less exposed controls, leading to the presumption that silica exposure can lead to silica nephrotoxicity. Balkan nephropathy has been associated with consumption of well water high in silica. In the Negev of Israel, dust storms are a vehicle for increasing respiratory uptake of silica. The Beduin, thought to be a population with maximal exposures, have higher rates of ESRD than do Jews in the age groups over 60 years. Although high blood concentrations of silica are found in persons with renal failure, the close association with elevated creatinine has been interpreted as evidence that the buildup of silica is due to renal failure, rather than vice-versa.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Feline morbillivirus, a previously undescribed paramyxovirus associated with tubulointerstitial nephritis in domestic cats

    PubMed Central

    Woo, Patrick C. Y.; Lau, Susanna K. P.; Wong, Beatrice H. L.; Fan, Rachel Y. Y.; Wong, Annette Y. P.; Zhang, Anna J. X.; Wu, Ying; Choi, Garnet K. Y.; Li, Kenneth S. M.; Hui, Janet; Wang, Ming; Zheng, Bo-Jian; Chan, K. H.; Yuen, Kwok-Yung

    2012-01-01

    We describe the discovery and isolation of a paramyxovirus, feline morbillivirus (FmoPV), from domestic cat (Felis catus). FmoPV RNA was detected in 56 (12.3%) of 457 stray cats (53 urine, four rectal swabs, and one blood sample) by RT-PCR. Complete genome sequencing of three FmoPV strains showed genome sizes of 16,050 bases, the largest among morbilliviruses, because of unusually long 5′ trailer sequences of 400 nt. FmoPV possesses identical gene contents (3′-N-P/V/C-M-F-H-L-5′) and is phylogenetically clustered with other morbilliviruses. IgG against FmoPV N protein was positive in 49 sera (76.7%) of 56 RT-PCR–positive cats, but 78 (19.4%) of 401 RT-PCR–negative cats (P < 0.0001) by Western blot. FmoPV was isolated from CRFK feline kidney cells, causing cytopathic effects with cell rounding, detachment, lysis, and syncytia formation. FmoPV could also replicate in subsequent passages in primate Vero E6 cells. Infected cell lines exhibited finely granular and diffuse cytoplasmic fluorescence on immunostaining for FmoPV N protein. Electron microscopy showed enveloped virus with typical “herringbone” appearance of helical N in paramyxoviruses. Histological examination of necropsy tissues in two FmoPV-positive cats revealed interstitial inflammatory infiltrate and tubular degeneration/necrosis in kidneys, with decreased cauxin expression in degenerated tubular epithelial cells, compatible with tubulointerstitial nephritis (TIN). Immunohistochemical staining revealed FmoPV N protein-positive renal tubular cells and mononuclear cells in lymph nodes. A case-control study showed the presence of TIN in seven of 12 cats with FmoPV infection, but only two of 15 cats without FmoPV infection (P < 0.05), suggesting an association between FmoPV and TIN. PMID:22431644

  20. Interferon (IFN)-λ is a potential mediator in lupus nephritis

    PubMed Central

    Zickert, Agneta; Oke, Vilija; Svenungsson, Elisabet; Sundström, Yvonne; Gunnarsson, Iva

    2016-01-01

    Objectives Interferon (IFN)-α is thought to be central in the pathogenesis for lupus nephritis (LN) and recent studies also indicate a role for IFNλ. Little is known about these cytokines in the context of treatment response. We studied levels of IFNα and IFNλ in patients with LN in association with clinical and histological response (HR) to treatment. Methods Fifty-six patients with active LN were included. Renal biopsies were performed at baseline and after immunosuppressive therapy. Serum levels of IFNα and IFNλ were analysed at both biopsy occasions and in 163 controls. The biopsies were evaluated according to the International Society of Nephrology/Renal Pathology Society classification. Clinical response was defined according to recent definitions. HR was defined as class I, II or III/IV-C on repeat biopsies. The expression of IFNλ in renal tissue was assessed by immunohistochemistry. Results At baseline, serum levels of both IFNα and IFNλ were higher in patients versus controls (p=0.01 and p=0.03, respectively). There was no correlation between IFNα and IFNλ. Overall, IFNα decreased after treatment (p=0.003) but IFNλ remained unchanged. However in patients with HR, IFNλ decreased (p=0.01). The highest levels of IFNλ were seen in patients with poor HR. Immunostaining of renal tissue revealed expression of IFNλ, particularly in crescent formations, inflammatory infiltrates and tubular cells. Conclusions The study supports a role for IFNλ in LN, both in circulation and at a tissue level. Levels of IFNα and IFNλ did not correlate and were affected differently by immunosuppression, indicating that they are differently involved in subgroups of LN. Persistent increased levels of IFNλ were associated to an unfavourable HR to treatment. PMID:27933198

  1. Complement in lupus nephritis: the good, the bad, and the unknown.

    PubMed

    Bao, Lihua; Quigg, Richard J

    2007-01-01

    The complement system consists of 3 pathways and more than 30 proteins, including those with biological activity that directly or indirectly mediate the effects of this system, plus a set of regulatory proteins necessary to prevent injudicious complement activation on host tissue. The role for complement in the pathogenesis of systemic lupus erythematosus (SLE) is paradoxic. On one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classic pathway components are associated with an increased risk for SLE. On the other hand, immune complex-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathologic features that are logical consequences of complement activation. By using accurate mouse models of SLE, we have gained remarkable insights into pathogenic features likely relevant to the human disease, and the ability to test potential therapies, some of which have made it to standard clinical use. Studies in genetically altered mice and using recombinant protein inhibitors of complement have confirmed what was believed but unproven-early complement proteins C1q and C4 are protective whereas complement activation later in the pathways is proinflammatory and deleterious. Two complement inhibitors, soluble complement receptor 1 (TP10, Avant Immunotherapeutics, Needham, MA) and a monoclonal anti-C5 antibody (Eculizumab, Alexion Pharmaceuticals, Inc., Cheshire, CT) have been shown to inhibit complement safely and now are being investigated in a variety of clinical conditions. Although these and others earlier in their clinical development hold promise to be used therapeutically in lupus nephritis, this optimism must be tempered by the fact that the clinical trials to prove this remain fraught with obstacles.

  2. Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems

    PubMed Central

    Hsieh, Song-Chou; Tsai, Chang-Youh; Yu, Chia-Li

    2016-01-01

    Lupus nephritis (LN) is one of the most frequent and serious complications in the patients with systemic lupus erythematosus. Autoimmune-mediated inflammation in both renal glomerular and tubulointerstitial tissues is the major pathological finding of LN. In clinical practice, the elevated anti-dsDNA antibody titer concomitant with reduced complement C3 and C4 levels has become the predictive and disease-activity surrogate biomarkers in LN. However, more and more evidences suggest that autoantibodies other than anti-dsDNA antibodies, such as anti-nucleosome, anti-C1q, anti-C3b, anti-cardiolipin, anti-endothelial cell, anti-ribonuclear proteins, and anti-glomerular matrix (anti-actinin) antibodies, may also involve in LN. Researchers have demonstrated that the circulating preformed and in situ-formed immune complexes as well as the direct cytotoxic effects by those cross-reactive autoantibodies mediated kidney damage. On the other hand, many efforts had been made to find useful urine biomarkers for LN activity via measurement of immune-related mediators, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic signature, and assessment of mRNA and exosomal-derived microRNA from urine sediment cell. Our group had also devoted to this field with some novel findings. In this review, we briefly discuss the possible mechanisms of LN and try to figure out the potential serum and urine biomarkers in LN. Finally, some of the unsolved problems in this field are discussed. PMID:27843374

  3. Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis*

    PubMed Central

    Vasilev, Vasil V.; Noe, Remi; Dragon-Durey, Marie-Agnes; Chauvet, Sophie; Lazarov, Valentin J.; Deliyska, Boriana P.; Fremeaux-Bacchi, Veronique; Dimitrov, Jordan D.; Roumenina, Lubka T.

    2015-01-01

    Lupus nephritis (LN) is a complication of the autoimmune disease systemic lupus erythematosus. Because the complement system plays a critical role in orchestrating inflammatory and immune responses as well as in the clearance of immune complexes, autoreactivity to complement components may have considerable pathological consequences. Autoantibodies against the central complement component C3 have been reported in systemic lupus erythematosus, but their molecular mechanism and functional relevance are not well understood. The objective of this study was to evaluate the frequency and the functional properties of the anti-C3 autoantibodies. Anti-C3 autoantibodies were measured in plasma of 39 LN patients, and identification of their epitopes on the C3 molecule was performed. By using surface plasmon resonance, we analyzed the influence of patient-derived IgG antibodies on the interaction of C3b with Factor B, Factor H, and complement receptor 1. The capacity of these antibodies to dysregulate the C3 convertase on the surface of endothelial cell was measured by flow cytometry. Here we report that the frequency of anti-C3 autoantibodies in LN is ∼30%. They inhibited interactions of the negative complement regulators Factor H and complement receptor 1 with C3b. An enhanced C3 deposition was also observed on human endothelial cells in the presence of C3 autoantibodies. In addition, anti-C3 autoantibody levels correlated with disease activity. In conclusion, the anti-C3 autoantibodies in LN may contribute to the autoimmune pathology by their capacity to overactivate the complement system. PMID:26245903

  4. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo: α-Enolase and Annexin AI

    PubMed Central

    Bruschi, Maurizio; Sinico, Renato Alberto; Moroni, Gabriella; Pratesi, Federico; Migliorini, Paola; Galetti, Maricla; Murtas, Corrado; Tincani, Angela; Madaio, Michael; Radice, Antonella; Franceschini, Franco; Trezzi, Barbara; Bianchi, Laura; Giallongo, Agata; Gatti, Rita; Tardanico, Regina; Scaloni, Andrea; D’Ambrosio, Chiara; Carnevali, Maria Luisa; Messa, Piergiorgio; Ravani, Pietro; Barbano, Giancarlo; Bianco, Beatrice; Bonanni, Alice; Scolari, Francesco; Martini, Alberto; Candiano, Giovanni; Allegri, Landino

    2014-01-01

    Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti–α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti–α-enolase/low anti-annexin AI IgG2 and patients with low anti–α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti–α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum. PMID:24790181

  5. Glomerular autoimmune multicomponents of human lupus nephritis in vivo: α-enolase and annexin AI.

    PubMed

    Bruschi, Maurizio; Sinico, Renato Alberto; Moroni, Gabriella; Pratesi, Federico; Migliorini, Paola; Galetti, Maricla; Murtas, Corrado; Tincani, Angela; Madaio, Michael; Radice, Antonella; Franceschini, Franco; Trezzi, Barbara; Bianchi, Laura; Giallongo, Agata; Gatti, Rita; Tardanico, Regina; Scaloni, Andrea; D'Ambrosio, Chiara; Carnevali, Maria Luisa; Messa, Piergiorgio; Ravani, Pietro; Barbano, Giancarlo; Bianco, Beatrice; Bonanni, Alice; Scolari, Francesco; Martini, Alberto; Candiano, Giovanni; Allegri, Landino; Ghiggeri, Gian Marco

    2014-11-01

    Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-α-enolase/low anti-annexin AI IgG2 and patients with low anti-α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum.

  6. TAC-TIC use of tacrolimus-based regimens in lupus nephritis.

    PubMed

    Kraaij, Tineke; Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN.

  7. [Renal thrombotic microangiopathy and antiphospholipid syndrome nephropathy in a patient with lupus nephritis].

    PubMed

    Sakamaki, Yusuke; Konishi, Konosuke; Hashiguchi, Akinori; Tomita, Shigeki; Kubota, Eiji; Itoh, Hiroshi; Hayashi, Koichi

    2016-01-01

    The patient was a 48-year-old Japanese woman diagnosed as having systemic lupus erythematosus at the age of 21 years when she presented with fever and an erythematous skin rash on her face and extremities. Prednisolone was initiated at that time. Thirteen days before admission to our hospital, she was referred to us by her family physician. Upon admission, blood tests showed pancytopenia, hypocomplementemia, and renal dysfunction, as well as the presence of lupus anticoagulant. Urinalysis showed abundant proteinuria and heavy microscopic hematuria. After performing a renal biopsy, we initiated immunosuppressive therapy and an anticoagulant. On the 22nd hospital day, microangiopathic hemolytic anemia appeared with the progression of thrombocytopenia and renal failure, and the patient subsequently underwent ten sessions of plasma exchange. After the commencement of the plasma exchange, her general condition improved. Her renal dysfunction, however, continued to progress, and hemodialysis was started on the 36th hospital day. The light microscopy showed severe endo- and extra-capillary proliferative glomerulonephritis with abundant crescents, and massive thrombi in the capillary lumen of the glomeruli. The arterioles contained occlusive hyaline materials. An immunofluorescence study showed granular staining of immunoglobulins and complements along the glomerular capillary wall. An electron microscopy examination revealed the presence of electron-dense deposits in the subepithelial and intramembranous areas of the glomeruli, but subendothelial deposits were absent. For cases with lupus nephritis (LN), immunosuppressive therapy based on corticosteroid remains the mainstay of treatment. However, immunosuppression alone may be insufficient when antiphospholipid antibody syndrome and thrombotic microangiopathy (TMA) are also present, and other treatment modalities including antiplatelet therapy, anticoagulation, and plasma exchange are likely to be necessary, as

  8. CD3+CD8+CD28− T Lymphocytes in Patients with Lupus Nephritis

    PubMed Central

    Krajewska, Magdalena

    2016-01-01

    The results of studies on the CD3+CD8+CD28− cells in SLE are inconsistent since several analyses describe CD3+CD8+CD28− as either immunosuppressive or cytotoxic. The aim of this study is to inquire whether the quantitative changes of CD3+CD8+CD28− T lymphocytes subpopulation are related to the clinical status of patients with lupus nephritis. Evaluation of Foxp3 expression on CD3+CD8+CD28− cells may shed some light on functional properties of these cells. 54 adult SLE patients and 19 sex and age matched healthy volunteers were enrolled in the study. There were 15 patients in inactive (SLEDAI ≤ 5) and 39 in active (SLEDAI > 5) phase of disease. We determined absolute count of CD3+CD8+CD28− and CD3+CD8+CD28−Foxp3+ subpopulations by flow cytometry. We observed a statistically significant increase in absolute count and percentage of CD3+CD8+CD28− in SLE patients compared to HC (p < 0.001). Moreover there was significant positive correlation between increasing absolute count of CD3+CD8+CD28− cells and disease activity measured by SLEDAI (rs = 0.281, p = 0.038). Active LN patients had increased absolute count of CD3+CD8+CD28− cells compared to HC. Positive correlation of CD3+CD8+CD28− number with disease activity, and lack of Foxp3 expression on these cells, suggests that CD3+CD8+CD28− lymphocytes might be responsible for an increased proinflammatory response in the exacerbation of SLE. PMID:27446964

  9. The expression of EBV-encoded LMP1 in young patients with lupus nephritis.

    PubMed

    Ding, Yan; He, Xiaojie; Liao, Wang; Yi, Zhuwen; Yang, Huilan; Xiang, Wei

    2015-01-01

    One of the major disease manifestations of systemic lupus erythematosus (SLE) is lupus nephritis (LN), and the underlying mechanisms are not yet understood. Epstein-Barr virus (EBV) reactivation was associated with the induction of SLE, with EBV-encoded latent membrane protein1 (LMP1) plays a vital role in this process. Although it was reported that LN was associated with LMP1, most of these results are from patients with ages differed greatly (range, 10-56 years). Given the increased prevalence of EBV infection in young patients, we focused on the association of LN and LMP1 expression in the renal tissues of young patients (range, 6-16 years) in this study. We found that the positive rate of LMP1 in the renal tissues was significantly higher in patients with LN compared with control (P<0.001), which is consistent with the previous reports. The positive rates of LMP1 were similar between the patients of initial onset and relapse, and there was no detectable difference between the patients with and without concurrent infection (P>0.05). However, we reported for the first time about the positive correlation of LMP1 with classification of LN. The proportion of young patients positive for anti‑Sm antibody was significantly higher in the LMP1 positive group compared with the LMP1 negative control (P>0.05). These results indicate that EBV infection in the renal of young patients may lead to the increased severity of LN, and the expression of anti-Sm is likely contributed to this process.

  10. Nested N-terminal megalin fragments induce high-titer autoantibody and attenuated Heymann nephritis.

    PubMed

    Tramontano, Alfonso; Knight, Thomas; Vizzuso, Domenica; Makker, Sudesh P

    2006-07-01

    It was shown previously that an N-terminal fragment (nM60) that encompasses amino acid residues 1 to 563 of megalin could induce active Heymann nephritis (AHN) as efficiently as the native protein. For delineation of a minimal structure within this fragment that is sufficient to induce AHN, smaller protein fragments that encompass residues 1 to 236 (L6), 1 to 195 (L5), 1 to 156 (L4), and 1 to 120 (L3), representing successive C-terminal truncations within ligand-binding repeats of nM60, were cloned and produced in a baculovirus insect cell expression system. Protein fragments L4, L5, and L6 clearly were glycosylated. All four fragments stimulated proliferation of megalin-sensitized lymph node cells and induced high-titer anti-megalin autoantibodies in Lewis rats. A full-blown disease, as assessed by severity of proteinuria, was observed in rats that were immunized with L6 and L5, whereas animals that were immunized with L4 and L3 developed only mild disease. The proteinuria levels correlated with staining for complement (C3, C5b-9) and IgG1 isotype in glomerular immune deposits. The results suggest that one or more molecular determinants on the region that comprises amino acid residues 157 to 236 contribute to the induction of a full-blown form of AHN. Study of the structure, conformation, and posttranslational modifications of these determinants could provide greater insight into the molecular correlates of immunopathogenesis in this disease model.

  11. Long-term outcome in biopsy-proven acute interstitial nephritis treated with steroids

    PubMed Central

    Tanna, Anisha; Salama, Alan D.; Tam, Frederick W. K.; Cairns, Tom; Taube, David; Cook, H. Terence; Ashby, Damien; Duncan, Neil D.; Pusey, Charles D.

    2017-01-01

    Abstract Background: There are no prospective randomized controlled trials describing the outcome of acute interstitial nephritis (AIN) treated with steroids, and retrospective studies are limited. Methods: We identified adult patients with a diagnosis of AIN without glomerular pathology over a 14-year period. Treated patients all received oral prednisolone and three also recieved IV methylprednisolone. Data were collected retrospectively on estimated glomerular filtration rate (eGFR), change in eGFR from time of biopsy, dependence on renal replacement therapy (RRT) and mortality, and outcomes were analysed according to the treatment prescribed. Results: A total of 187 eligible patients with AIN were identified and 158 were treated with steroids. There was no difference in median eGFR or dependence on RRT at the time of biopsy. Steroid-treated patients had significantly higher eGFR at all time points post-biopsy up to 24 months, when median eGFR was 43 mL/min in the steroid-treated group and 24 mL/min in the untreated group (P  =  0.01). Fewer patients in the steroid-treated group were dialysis dependent by 6 months (3.2% versus 20.6%, P  =  0.0022) and 24 months (5.1% versus 24.1%, P  =  0.0019). Conclusions: This large retrospective study suggests a benefit of steroids in treatment of AIN with greater improvement in eGFR and fewer patients progressing to end-stage renal disease.

  12. Single-centre experience of granulomatous interstitial nephritis-time for a new approach?

    PubMed

    Oliveira, Ben; Jayawardene, Satish; Shah, Sapna

    2017-04-01

    Background: Differentiating between renal-limited sarcoidosis and tuberculosis (TB) infection as a cause of granulomatous interstitial nephritis (GIN) can be difficult. This series compares clinical features and response to treatment between the different underlying aetiologies in order to propose a management algorithm for GIN to assist with diagnosis and treatment. Methods: This retrospective study reports on all patients presenting with a histological diagnosis of GIN between 2000 and 2012 at our unit. Results: Twenty-one patients were identified, 57% were male and the mean age was 53 years. Eight cases were associated with sarcoidosis with evidence of extra-renal disease and five with renal-limited sarcoidosis. Five patients had GIN that may have been related to TB infection or to renal-limited sarcoidosis, and three were idiopathic or drug related. All those with sarcoidosis were treated with steroids and renal function, as measured by estimated glomerular filtration rate (eGFR), improved from a mean of 24 mL/min at baseline to 37 mL/min at 1 year. Baseline eGFR was 19 mL/min in those with possible TB infection. Four received steroids as well as anti-TB drugs. Anti-TB therapy was delayed in four patients by a mean of 22 months due to difficulties in diagnosis. Two patients with TB developed end-stage kidney disease and the remaining three patients had a mean eGFR of 28 mL/min at 1 year. Conclusions: This series represents the largest cohort of patients with GIN in the UK and supports previous findings that patients with sarcoid have a favourable outcome with steroid treatment. Those with TB have an inferior prognosis, perhaps due to delayed diagnosis. We suggest an algorithm when investigating a diagnosis of GIN with the aim of expediting diagnosis and considering a trial of anti-TB therapy in order to prevent deterioration of renal function.

  13. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide

    PubMed Central

    Verstuyft, Céline; Costedoat-Chalumeau, Nathalie; Hummel, Aurélie; Le Guern, Véronique; Sacré, Karim; Meyer, Olivier; Daugas, Eric; Goujard, Cécile; Sultan, Audrey; Lobbedez, Thierry; Galicier, Lionel; Pourrat, Jacques; Le Hello, Claire; Godin, Michel; Morello, Rémy; Lambert, Marc; Hachulla, Eric; Vanhille, Philippe; Queffeulou, Guillaume; Potier, Jacky; Dion, Jean-Jacques; Bataille, Pierre; Chauveau, Dominique; Moulis, Guillaume; Farge-Bancel, Dominique; Duhaut, Pierre; Saint-Marcoux, Bernadette; Deroux, Alban; Manuzak, Jennifer; Francès, Camille; Aumaitre, Olivier; Bezanahary, Holy; Becquemont, Laurent; Bienvenu, Boris

    2016-01-01

    Objective To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. Results Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02–24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064–10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. Conclusion This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients. PMID:27002825

  14. Plasma ficolin levels and risk of nephritis in Danish patients with systemic lupus erythematosus.

    PubMed

    Tanha, Nima; Pilely, Katrine; Faurschou, Mikkel; Garred, Peter; Jacobsen, Søren

    2017-02-01

    Given the scavenging properties of ficolins, we hypothesized that variation in the plasma concentrations of the three ficolins may be associated with development of lupus nephritis (LN), type of LN, end-stage renal disease (ESRD), and/or mortality among patients with systemic lupus erythematosus (SLE). SLE patients attending a Danish tertiary rheumatology referral center were included. Plasma concentrations of ficolin-1, ficolin-2, and ficolin-3 were determined and dichotomized by the median into high and low. LN was defined by clinical criteria; type of LN by renal biopsy; ESRD follow-up time was defined as time from onset of LN to the development of ESRD or censoring at the end of follow-up. The study included 112 SLE patients with median disease duration of 8 years of which 53 (47%) had LN at the time of inclusion. During a median follow-up of 10 years, five patients developed ESRD. Sixteen patients died. Odds ratios (ORs) of LN were 1.2 (95% CI: 0.6-2.7), 4.1 (95% CI: 1.7-9.7), and 0.9 (95% CI: 0.4-2.0) for patients with low ficolin-1, ficolin-2, and ficolin-3 plasma levels, respectively. The distribution of histological classes differed between patients with high and low plasma levels of ficolin-1 (p = 0.009). Patients with high ficolin-1 plasma levels had an increased risk of ESRD. There was no association between the levels of the analyzed plasma ficolins and mortality. Low plasma ficolin-2 levels were associated with an increased risk of having LN. High plasma levels of ficolin-1 were associated with the histological subtype of LN and development of ESRD.

  15. Feline morbillivirus, a previously undescribed paramyxovirus associated with tubulointerstitial nephritis in domestic cats.

    PubMed

    Woo, Patrick C Y; Lau, Susanna K P; Wong, Beatrice H L; Fan, Rachel Y Y; Wong, Annette Y P; Zhang, Anna J X; Wu, Ying; Choi, Garnet K Y; Li, Kenneth S M; Hui, Janet; Wang, Ming; Zheng, Bo-Jian; Chan, K H; Yuen, Kwok-Yung

    2012-04-03

    We describe the discovery and isolation of a paramyxovirus, feline morbillivirus (FmoPV), from domestic cat (Felis catus). FmoPV RNA was detected in 56 (12.3%) of 457 stray cats (53 urine, four rectal swabs, and one blood sample) by RT-PCR. Complete genome sequencing of three FmoPV strains showed genome sizes of 16,050 bases, the largest among morbilliviruses, because of unusually long 5' trailer sequences of 400 nt. FmoPV possesses identical gene contents (3'-N-P/V/C-M-F-H-L-5') and is phylogenetically clustered with other morbilliviruses. IgG against FmoPV N protein was positive in 49 sera (76.7%) of 56 RT-PCR-positive cats, but 78 (19.4%) of 401 RT-PCR-negative cats (P < 0.0001) by Western blot. FmoPV was isolated from CRFK feline kidney cells, causing cytopathic effects with cell rounding, detachment, lysis, and syncytia formation. FmoPV could also replicate in subsequent passages in primate Vero E6 cells. Infected cell lines exhibited finely granular and diffuse cytoplasmic fluorescence on immunostaining for FmoPV N protein. Electron microscopy showed enveloped virus with typical "herringbone" appearance of helical N in paramyxoviruses. Histological examination of necropsy tissues in two FmoPV-positive cats revealed interstitial inflammatory infiltrate and tubular degeneration/necrosis in kidneys, with decreased cauxin expression in degenerated tubular epithelial cells, compatible with tubulointerstitial nephritis (TIN). Immunohistochemical staining revealed FmoPV N protein-positive renal tubular cells and mononuclear cells in lymph nodes. A case-control study showed the presence of TIN in seven of 12 cats with FmoPV infection, but only two of 15 cats without FmoPV infection (P < 0.05), suggesting an association between FmoPV and TIN.

  16. Granulomatous nephritis in psittacines associated with parasitism by the trematode Paratanaisia spp.

    PubMed

    Luppi, Marcela M; de Melo, Alan L; Motta, Rafael O C; Malta, Marcelo C C; Gardiner, C H; Santos, Renato L

    2007-05-31

    Trematodes belonging to the family Eucotylidae are parasites of the kidney and ureter, and affect several bird species. However, psittacines have not been identified as hosts of these parasites. Three birds, an adult female blue and gold macaw (Ara ararauna), an adult female blue-winged macaw (Propyrrhura maracana) and an adult male white-eared parakeet (Pyrrhura leucotis) were admitted at the Veterinary Hospital of the Fundação Zoo-Botânica de Belo Horizonte, Brazil (FZB/BH). All three birds had severe dehydration and cachexia. The blue and gold macaw presented with dyspnea, apathy, and incoordination. Blood cell counts indicated discrete anemia and leucopenia. Blood biochemistry revealed significant increase in levels of uric acid (61 mg/dl) and blood urea nitrogen (22 mg/dl). The bird died within 24 h after admission. The other two birds were admitted with similar clinical signs, but died prior to a complete clinical examination. At the necropsy, in all the three birds, the kidneys were enlarged with brown-yellowish discoloration and irregular cortical surface. On the cut surface, there was a brown-yellowish material with few visible parasites flowing out of the parenchyma. When fragments of the kidneys were placed in 10% formalin, a large number of trematodes came out of the renal parenchyma. The parasites were identified as Paratanaisia robusta infecting all three birds, and P. bragai infecting the blue-winged macaw and the white-eared parakeet. Histologically, there was an interstitial, multifocal to coalescent, lymphoplasmacytic infiltrate with some epithelioid macrophages, and a few heterophils, characterizing a granulomatous nephritis. Adult worms and eggs were observed within dilated tubules and in the renal pelvis. In the blue and gold macaw, some parasite eggs were located interstitially associated with an intense adjacent granulomatous reaction.

  17. Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus

    PubMed Central

    1996-01-01

    Nucleosome-specific T helper (Th) cells provide major histocompatibility complex class II-restricted, cognate help to nephritogenic antinuclear autoantibody-producing B cells in lupus. However, the lupus Th cells do not respond when components of the nucleosome, such as free DNA or histones, are individually presented by antigen-presenting cells. Thus critical peptide epitopes for the pathogenic Th cells are probably protected during uptake and processing of the native nucleosome particle as a whole. Therefore, herein we tested 145 overlapping peptides spanning all four core histones in the nucleosome. We localized three regions in core histones, one in H2B at amino acid position 10-33 (H2B(10-33)), and two in H4, at position 16- 39 (H4(16-39)) and position 71-94 (H4(71-94)), that contained the peptide epitopes recognized by the pathogenic autoantibody-inducing Th cells of lupus. The peptide autoepitopes also triggered the pathogenic Th cells of (SWR x NZB)F1 lupus mice in vivo to induce the development of severe lupus nephritis. The nucleosomal autoepitopes stimulated the production of Th1-type cytokines, consistent with immunoglobulin IgG2a, IgG2b, and IgG3 being the isotypes of nephritogenic autoantibodies induced in the lupus mice. Interestingly, the Th cell epitopes overlapped with regions in histones that contain B cell epitopes targeted by autoantibodies, as well as the sites where histones contact with DNA in the nucleosome. Identification of the disease-relevant autoepitopes in nucleosomes will help in understanding how the pathogenic Th cells of spontaneous systemic lupus erythematosus emerge, and potentially lead to the development of peptide-based tolerogenic therapy for this major autoimmune disease. PMID:8676066

  18. TAC-TIC use of tacrolimus-based regimens in lupus nephritis

    PubMed Central

    Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

  19. Two Types of Renovascular Lesions in Lupus Nephritis with Clinical Thrombotic Thrombocytopenic Purpura.

    PubMed

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

    2015-01-01

    Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid-hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients.

  20. Multicentric Castleman Disease With Tubulointerstitial Nephritis Mimicking IgG4-related Disease: Two Case Reports.

    PubMed

    Zoshima, Takeshi; Yamada, Kazunori; Hara, Satoshi; Mizushima, Ichiro; Yamagishi, Masakazu; Harada, Kenichi; Sato, Yasuharu; Kawano, Mitsuhiro

    2016-04-01

    Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs.

  1. DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis.

    PubMed

    Cai, Minchao; Zhou, Tong; Wang, Xuan; Shang, Minghua; Zhang, Yueyue; Luo, Maocai; Xu, Chundi; Yuan, Weijie

    2016-03-01

    Podocytes, the main target of immune complex, participate actively in the development of glomerular injury as immune cells. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune molecular that has an immune recognition function, and is involved in mediation of cell adhesion and immunoregulation. Here we explored the expression of DC-SIGN on podocytes and its role in immune and inflammatory responses in lupus nephritis (LN). Expression of DC-SIGN and immunoglobulin (Ig)G1 was observed in glomeruli of LN patients. DC-SIGN was co-expressed with nephrin on podocytes. Accompanied by increased proteinuria of LN mice, DC-SIGN and IgG1 expressions were observed in the glomeruli from 20 weeks, and the renal function deteriorated up to 24 weeks. Mice with anti-DC-SIGN antibody showed reduced proteinuria and remission of renal function. After the podocytes were stimulated by serum of LN mice in vitro, the expression of DC-SIGN, major histocompatibility complex (MHC) class II and CD80 was up-regulated, stimulation of T cell proliferation was enhanced and the interferon (IFN)-γ/interleukin (IL)-4 ratio increased. However, anti-DC-SIGN antibody treatment reversed these events. These results suggested that podocytes in LN can exert DC-like function through their expression of DC-SIGN, which may be involved in immune and inflammatory responses of renal tissues. However, blockage of DC-SIGN can inhibit immune functions of podocytes, which may have preventive and therapeutic effects.

  2. Peritoneal dialysis treatment for severe lupus nephritis patients complicated with essential organ dysfunction.

    PubMed

    Zhou, Yan; Yu, Yusheng; Tang, Zheng; Li, Shijun; Hu, Weixin; Luo, Chunlei; Liu, Zhihong

    2015-12-01

    The aim of the present study was to evaluate the clinical efficacy of peritoneal dialysis (PD) in patients with severe lupus nephritis (LN) complicated with organ dysfunction. In total, 13 severe LN patients complicated with multiple-organ dysfunction, who underwent PD treatment between November 2003 and September 2010, were enrolled in the study. Six patients received methylprednisolone pulse therapy due to lupus activity and progressive renal failure. These patients were complicated with severe edema, cardiac insufficiency and severe hypoalbuminemia. PD was applied to the patients, followed by the administration of immunosuppressants. Patients were followed-up to review the parameters of renal function, the immunological indexes and the systemic lupus erythematosus disease activity index. The results indicated that the general state of health was markedly improved following PD treatment, with edema abatement and improvement of heart function and physical strength. Serum creatinine levels significantly decreased from 6.3±1.6 to 2.6±1.0 mg/dl. A total of 10 cases ceased PD treatment during the follow-up, while three cases continued PD to the end of the follow-up period. The levels of albumin and hemoglobin exhibited a marked increase from 29.7±5.7 to 35.2±5.5 g/l and 8.7±1.8 to 9.8±1.8 g/l, respectively. There was one case of peritonitis, one case of peritoneal leakage and two cases of pneumonia. Therefore, PD may be a successful treatment method for severe LN patients complicated with essential organ dysfunction. PD not only improved the symptoms of edema and heart failure, but also played an important role in preserving residual renal function and improving the nutritional state of the patients. Thus, PD can be considered as a treatment option for patients with severe LN associated with acute kidney injury, however, selecting a suitable immunosuppressant during PD treatment is essential.

  3. Erythropoiesis-stimulating Agent Use among Patients with Lupus Nephritis Approaching End-stage Renal Disease

    PubMed Central

    Gómez-Puerta, José A; Waikar, Sushrut S; Solomon, Daniel H; Liu, Jun; Alarcón, Graciela S; Winkelmayer, Wolfgang C; Costenbader, Karen H

    2014-01-01

    Objectives Little is known about erythropoiesis-stimulating agents (ESAs) utilization among lupus nephritis (LN) patients with incipient ESRD. We aimed to identify sociodemographic and clinical factors associated with ESA use among incident LN ESRD patients. Methods Among all individuals age ≥18 with incident ESRD from 1995-2008 in the U.S. Renal Data System (USRDS), we identified those with systemic lupus erythematosus (ICD-9 code 710.0) as the cause of ESRD. ESA use at ESRD onset was ascertained from the Medical Evidence Report. Year of onset, age, sex, race/ethnicity, medical insurance, employment status, residential region, clinical factors and comorbidities were considered potentially associated with ESA use in multivariable-adjusted logistic regression analyses. Results We identified 12,533 individuals with incident LN ESRD (1% of entire population). Of those, 4,288 (34%) received an ESA preceding ESRD. In multivariable-adjusted models, ESA users had higher serum albumin and hemoglobin concentrations, were more likely to be women, and to live in the Northeast. Conversely, Medicaid beneficiaries, the uninsured, unemployed, African Americans, Hispanics, and those with IV drug use, congestive heart failure and obesity had lower ESA use. Conclusion Among all U.S. patients and those with LN who developed ESRD, approximately one third received ESAs. Patient sex, race, age, medical insurance, residential region and clinical factors were significantly associated with ESA therapy. While there are no guidelines for ESA use in LN patients approaching ESRD, there has been wide sociodemographic variation, raising questions about ESA prescription practices. PMID:24672742

  4. Focus in Grade 8: Teaching with Curriculum Focal Points

    ERIC Educational Resources Information Center

    Schielack, Jane

    2010-01-01

    This book describes and illustrates learning paths for the mathematical concepts and skills of each grade 8 Focal Point as presented in Curriculum Focal Points for Prekindergarten through Grade 8 Mathematics. It includes representational supports for teaching and learning that can facilitate understanding, stimulate productive discussions about…

  5. Focal epithelial hyperplasia caused by human papillomavirus 13.

    PubMed

    Saunders, Natasha R; Scolnik, Dennis; Rebbapragada, Anuradha; Koelink, Eric; Craw, Lindsey; Roth, Sherryn; Aronson, Leya; Perusini, Stephen; Silverman, Michael S

    2010-06-01

    Focal epithelial hyperplasia is a benign, papulo-nodular disease of the oral cavity. It is rare, affecting primarily Native American populations during childhood. It is closely associated with human papillomavirus 13 and 32. This report describes the diagnosis of 2 cases of focal epithelial hyperplasia in children from southern Guyana. The diagnosis was made using clinical criteria, polymerase chain reaction, and DNA sequencing.

  6. Focal Manual for CAI Coding on the TSS/8 System.

    ERIC Educational Resources Information Center

    Kirbs, H. Dewey; And Others

    Basic information is provided in this manual for coding drill-and-practice CAI (computer-assisted instruction) applications in the language FOCAL (Formulating On-line Calculations in Algebraic Language). This language is available on the Digital Equipment Corporation Time-Sharing 8 system (TSS/8). While FOCAL is oriented toward solution of…

  7. Focally spared area of fatty liver caused by arterioportal shunt

    SciTech Connect

    Arita, Takeshi; Matsunaga, Naofumi; Honma, Yutaka

    1996-05-01

    We describe a case with a focally spared area in fatty liver caused by arterioportal shunt. Furthermore, we discuss the cause of the focally spared area related to a localized dilution or reduction in portal blood flow. 13 refs., 1 fig.

  8. An update on focal therapy for prostate cancer.

    PubMed

    Perera, Marlon; Krishnananthan, Nishanth; Lindner, Uri; Lawrentschuk, Nathan

    2016-11-01

    Globally, the increased uptake of serum PSA level screening led to an increase in the number of diagnoses of low-risk and intermediate-risk prostate cancer. Traditionally, these patients have been considered for either active surveillance programmes or radical whole-gland therapies, such as prostatectomy or radiotherapy. Focal therapy is an emerging treatment option that involves the focal ablation of prostate cancer with preservation of surrounding healthy tissue. This approach might result in reduced morbidity when compared with whole-gland therapies. In current practice, much controversy surrounds optimal patient selection and preoperative tumour localization strategies. Focal therapy modalities include cryotherapy, high-intensity focused ultrasound, laser ablation, photodynamic therapy, irreversible electroporation, radiofrequency ablation and focal brachytherapy. However, as long-term oncological data for focal therapies are lacking, formal recommendations for its use cannot be made.

  9. Combined Scanning Transmission Electron Microscopy Tilt- and Focal Series

    SciTech Connect

    Dahmen, Tim; Baudoin, Jean-Pierre G; Lupini, Andrew R; Kubel, Christian; Slusallek, Phillip; De Jonge, Niels

    2014-01-01

    In this study, a combined tilt- and focal series is proposed as a new recording scheme for high-angle annular dark-field scanning transmission electron microscopy (STEM) tomography. Three-dimensional (3D) data were acquired by mechanically tilting the specimen, and recording a through-focal series at each tilt direction. The sample was a whole-mount macrophage cell with embedded gold nanoparticles. The tilt focal algebraic reconstruction technique (TF-ART) is introduced as a new algorithm to reconstruct tomograms from such combined tilt- and focal series. The feasibility of TF-ART was demonstrated by 3D reconstruction of the experimental 3D data. The results were compared with a conventional STEM tilt series of a similar sample. The combined tilt- and focal series led to smaller missing wedge artifacts, and a higher axial resolution than obtained for the STEM tilt series, thus improving on one of the main issues of tilt series-based electron tomography.

  10. An empirical assessment of the focal species hypothesis.

    PubMed

    Lindenmayer, D B; Lane, P W; Westgate, M J; Crane, M; Michael, D; Okada, S; Barton, P S

    2014-12-01

    Biodiversity surrogates and indicators are commonly used in conservation management. The focal species approach (FSA) is one method for identifying biodiversity surrogates, and it is underpinned by the hypothesis that management aimed at a particular focal species will confer protection on co-occurring species. This concept has been the subject of much debate, in part because the validity of the FSA has not been subject to detailed empirical assessment of the extent to which a given focal species actually co-occurs with other species in an assemblage. To address this knowledge gap, we used large-scale, long-term data sets of temperate woodland birds to select focal species associated with threatening processes such as habitat isolation and loss of key vegetation attributes. We quantified co-occurrence patterns among focal species, species in the wider bird assemblage, and species of conservation concern. Some, but not all, focal species were associated with high levels of species richness. One of our selected focal species was negatively associated with the occurrence of other species (i.e., it was an antisurrogate)-a previously undescribed property of nominated focal species. Furthermore, combinations of focal species were not associated with substantially elevated levels of bird species richness, relative to levels associated with individual species. Our results suggest that although there is some merit to the underpinning concept of the FSA, there is also a need to ensure that actions are sufficiently flexible because management tightly focused on a given focal species may not benefit some other species, including species of conservation concern, such of which might not occur in species-rich assemblages.

  11. Multiwavelength infrared focal plane array detector

    NASA Technical Reports Server (NTRS)

    Forrest, Stephen R. (Inventor); Olsen, Gregory H. (Inventor); Kim, Dong-Su (Inventor); Lange, Michael J. (Inventor)

    1995-01-01

    A multiwavelength focal plane array infrared detector is included on a common substrate having formed on its top face a plurality of In.sub.x Ga.sub.1-x As (x.ltoreq.0.53) absorption layers, between each pair of which a plurality of InAs.sub.y P.sub.1-y (y<1) buffer layers are formed having substantially increasing lattice parameters, respectively, relative to said substrate, for preventing lattice mismatch dislocations from propagating through successive ones of the absorption layers of decreasing bandgap relative to said substrate, whereby a plurality of detectors for detecting different wavelengths of light for a given pixel are provided by removing material above given areas of successive ones of the absorption layers, which areas are doped to form a pn junction with the surrounding unexposed portions of associated absorption layers, respectively, with metal contacts being formed on a portion of each of the exposed areas, and on the bottom of the substrate for facilitating electrical connections thereto.

  12. HgCdTe hybrid focal plane

    NASA Astrophysics Data System (ADS)

    Rode, J. P.

    1984-09-01

    Second-generation IR systems, consisting of 2-D mosaics of IR detectors, have been under intense development for the last few years. One of the most successful architectures has been a HgCdTe hybrid focal plane array (FPA), using a Si charge-coupled device (CCD) readout chip interfaced to epitaxial HgCdTe. Detection is made by backside-illuminated photovoltaic detectors with high fill factors and quantum efficiency. The detectors are coupled into the CCD by In bumps which mass bond each detector in the mosaic to a CCD input. Advances have been made in uniform, large area HgCdTe detector material that can be grown with a bandgap from less than 0.1 eV to greater than 1 eV. CCD architectures have been developed with simple, linear inputs and dynamic ranges up to 80 dB. Hybrid FPAs are currently being tested in prototype imaging systems, for detecting thermal differences as well as reflected sunlight in the IR. In the 3-5μm region, these arrays have proven capable of noise-equivalent temperature differences as low as 0.01 K, acquired at a 400 Hz frame rate. In addition to improving current imaging systems, these area arrays allow new system concepts to be brought to fruition.

  13. Nonhuman primate models of focal cerebral ischemia

    PubMed Central

    Fan, Jingjing; Li, Yi; Fu, Xinyu; Li, Lijuan; Hao, Xiaoting; Li, Shasha

    2017-01-01

    Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  14. Advanced dynamic pyroelectric focal plane array

    NASA Astrophysics Data System (ADS)

    Unglaub, Ricardo A. G.; Celinska, Jolanta B.; McWilliams, Christopher R.; Paz de Araujo, Carlos A.; Forbes, Timothy; Pankin, Jayson D.

    2010-04-01

    The pyroelectric effect has been characterized for single-pixel elements consisting of strontium bismuth tantalate (SBT) ferroelectric material as the sensing elements. These pixels have been integrated into second-generation focal plane arrays. The constituent second-generation pixels include thermal insulating layers and an infrared absorber layer. The MEMS-less arrays are operated in active mode, a technique that eliminates radiation choppers found in other passive pyroelectric IR imagers. This paper addresses the results of precursor 2x2 to 14x14 second-generation arrays of SBT elements, the active detection mechanism, and the unique read-out, interrogation signal, and the synchronization electronics. The second-generation 14x14 pixels array was implemented to demonstrate the performance of an active pyroelectric array as a precursor to larger size arrays using different pixel dimensions. The active mode detection eliminates the use of a chopper, enables the dynamic partition of the array into pixel domains in which pixel sensitivity in the domains can be adjusted independently. This unique feature in IR detection can be applied to the simultaneous tracking of diverse contrast objects. In addition, by controlling the thickness of the absorber material the arrays can be optimized for maximum response at specified wavelengths by means of quarter-wavelength interferometry.

  15. Focal cerebral mantle disruption in fetal hydrocephalus.

    PubMed

    Humphreys, Peter; Muzumdar, Dattatraya P; Sly, Lloyd E; Michaud, Jean

    2007-04-01

    A variety of developmental brain anomalies have been described in individuals with fetal hydrocephalus, regardless of etiology. Examples include callosal dysgenesis, periventricular gray matter heterotopia, hippocampal and white matter hypoplasia, and cortical polygyration. The present report draws attention to another anomaly not reported in previous case series of fetal hydrocephalus: focal cerebral mantle disruption. Neonatal imaging findings (where available) and post-shunt, stable-state magnetic resonance imaging, or pathological findings were reviewed in 77 subjects with fetal hydrocephalus (55 myelomeningocele, 16 sporadic aqueductal stenosis, 6 miscellaneous). Of these, 12 subjects (15.6%) demonstrated a combination of absence of the septum pellucidum and severe thinning or absence of the posteromesial cerebral mantle. On axial sequences, this combination created the illusion of a common ventricle, as in lobar holoprosencephaly. All 12 subjects had massive hydrocephalus at birth, accompanied in 7 by posteromesial ventricular diverticula. Two subjects, and one other subject with distinct lateral ventricles, demonstrated unilateral or bilateral mantle clefts suggestive of schizencephaly. Close radiological (n = 2) or pathological (n = 1) inspection showed that the clefts were only partially lined with gray matter and contained a transverse gliotic membrane. These findings are consistent with the hypothesis that massive early fetal hydrocephalus may completely disrupt cerebral mantle formation, particularly in the posteromesial hemispheres.

  16. Causes and pathogenesis of focal segmental glomerulosclerosis

    PubMed Central

    Fogo, Agnes B.

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. The initial injuries vary widely. Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS. Varying phenotypes of the sclerosis are also manifest, with varying prognosis. The so-called tip lesion has the best prognosis, whereas the collapsing type of FSGS has the worst prognosis. New insights into glomerular cell injury response and repair may pave the way for possible therapeutic strategies. PMID:25447132

  17. Successful treatment of tubulointerstitial nephritis and uveitis with steroid and azathioprine in a 12-year-old boy

    PubMed Central

    Kim, Ji Eun; Park, Se Jin; Oh, Ji Young; Jeong, Hyeon Joo; Kim, Ji Hong

    2016-01-01

    Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, often underdiagnosed or misdiagnosed in children. We describe the case of a 12-year-old boy who presented to Severance Hospital with a 1-month history of bilateral conjunctival injection. He was first evaluated by an Ophthalmologist in another hospital and diagnosed with panuveitis. Laboratory tests indicated renal failure, and a renal biopsy confirmed the diagnosis of acute tubulointerstitial nephritis. An extensive exclusion of all possible causes allowed a diagnosis of TINU syndrome. The patient was treated with a systemic corticosteroid (initially prednisolone, 2 mg/kg and later deflazacort 1 mg/kg) and topical steroid drops for 1 month. Azathioprine was later added to the treatment regimen and the systemic steroid was slowly tapered. The final outcome of renal-ocular disease was favorable in the patient. However, long-term follow-up is necessary to properly manage frequent relapses and incomplete renal recovery. TINU should be considered as a differential diagnosis in children with uveitis or acute renal failure. PMID:28018458

  18. An unusual form of crystal-forming chronic interstitial nephritis following long-term exposure to tosufloxacin tosilate.

    PubMed

    Okada, Hirokazu; Watanabe, Yusuke; Kotaki, Shuhei; Ikeda, Naofumi; Takane, Hiroshi; Kanno, Yoshihiko; Sugahara, Souichi; Ban, Shinichi; Nagata, Makoto; Suzuki, Hiromichi

    2004-11-01

    Fluoroquinolones are known to cause acute renal failure because of interstitial nephritis with or without epithelioid granulomas. We report the first case of slowly progressive renal failure caused by crystal-forming chronic interstitial nephritis with non-Langerhans' cell histiocytosis after long-term exposure to a fluoroquinolone, tosufloxacin tosilate. Lesions consisted of spindle- to cuboidal-shaped histiocytes with minimal collagenous matrix and low-level lymphocyte infiltration replacing normal tubulointerstitial structure of the kidney. Histiocytes were positive for CD68, but negative for S-100, suggesting they were derived from macrophages. There were numerous rhomboid- to needle-shaped crystal deposits in the cytoplasm of histiocytes, which showed bright birefringence under polarized light. No immunoglobulin deposits were seen in the kidney, and no evidence of paraproteinemia/lymphoproliferative diseases was identified in this patient. Despite a negative drug lymphocyte-stimulating test result using tosufloxacin tosilate, withdrawal of the drug and treatment with steroids gradually improved renal function. In this report, we describe the clinical course and histopathologic findings of this patient and discuss the possible pathogenesis.

  19. Post-transplant immune complex nephritis in a patient with systemic lupus erythematosus associated with ANCA vasculitis.

    PubMed

    Sanchez, Carlos; Rebolledo, Alejandra; Gahona, Junior; Rojas, Mauricio; Jiménez, Raquel; Bojórquez, Aurora

    2017-01-29

    Nearly 20% of SLE corresponds to the pediatric population, and 75% of them have kidney involvement representing an important etiology of chronic kidney disease. A correlation between SLE and ANCA-associated vasculitis has been identified as an overlapping syndrome. Kidney allograft recurrence is rare in SLE when disease control is achieved and with nowadays immunosuppression treatment. Histologic transformation is unusual, especially when there are negative serologic markers and no immune complex deposition reported in native kidneys. A 17-year-old female with crescentic glomerulonephritis, p-ANCA-positive antibodies with pauci-immune pattern in kidney biopsy develops end-stage renal disease requiring hemodialysis. Deceased donor kidney transplant was performed receiving triple immunosuppression thereafter. Thirteen months later serum creatinine rises without evidence of infection, urinary obstruction, or clinical and serologic disease relapse. Allograft biopsy reports mesangial proliferation and "full-house" immunofluorescence. The role of ANCA in SLE physiopathology is controversial, and its relation with lupus nephritis is also discordant. ANCA could represent an important factor in the heterogeneity of systemic lupus erythematosus and lupus nephritis.

  20. Acute Kidney Injury, Recurrent Seizures, and Thrombocytopenia in a Young Patient with Lupus Nephritis: A Diagnostic Dilemma

    PubMed Central

    2016-01-01

    Introduction. Posterior reversible encephalopathy syndrome (PRES) is a constellation of clinical and radiologic findings. Fluctuations in blood pressure, seizures, and reversible brain MRI findings mainly in posterior cerebral white matter are the main manifestations. PRES has been associated with multiple conditions such as autoimmune disorders, pregnancy, organ transplant, and thrombotic microangiopathy (TMA). Case Presentation. A 22-year-old woman with history of Systemic Lupus Erythematous complicated with chronic kidney disease secondary to lupus nephritis class IV presented with recurrent seizures and uncontrolled hypertension. She was found to have acute kidney injury and thrombocytopenia. Repeat kidney biopsy showed diffuse endocapillary and extracapillary proliferative and membranous lupus nephritis (ISN-RPS class IV-G+V) and endothelial swelling secondary to severe hypertension but no evidence of TMA. Brain MRI showed reversible left frontal and parietal lesions that resolved after controlling the blood pressure, making PRES the diagnosis. Conclusion. PRES is an important entity that must be recognized and treated early due to the potential reversibility in the early stages. Physicians must have high suspicion for these unusual presentations. We present a case where performing kidney biopsy clinched the diagnosis in our patient with multiple confounding factors. PMID:28044115

  1. Passive immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta protects from LPS enhancing glomerular injury in nephrotoxic nephritis in rats.

    PubMed Central

    Karkar, A M; Koshino, Y; Cashman, S J; Dash, A C; Bonnefoy, J; Meager, A; Rees, A J

    1992-01-01

    Glomerular injury caused by injection of heterologous anti-glomerular basement membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small doses of bacterial lipopolysaccharide (LPS). We have investigated the involvement of tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha and IL-1 beta in this phenomenon by passive immunization against these cytokines. Anti-TNF-alpha or anti-IL-1 beta antibodies given 1.5 h before the induction of nephritis significantly decreased injury in this model, whether assessed by the magnitude of albuminuria, the prevalence of glomerular capillary thrombi or the intensity of glomerular neutrophil infiltrate. Albuminuria in anti-GBM Ab alone was 11 +/- 3, LPS/anti-GBM Ab 87 +/- 22, and anti-TNF-alpha antibodies/LPS/anti-GBM Ab 21 +/- 6 mg/24 h (mean +/- s.e.) P < 0.05. Passive immunization with antibodies to IL-1 beta had a similar effect (anti-GBM Ab, 0.6 +/- 0.1, LPS/anti-GBM Ab, 92 +/- 19, anti-IL-1 beta antibodies/LPS/anti-GBM Ab 39 +/- 8 mg/24 h, P < 0.05). The prevalence of glomerular capillary thrombi was also reduced significantly by these treatments; from 22 +/- 5% to 4 +/- 1% in the case of anti-TNF-alpha antibodies and 28 +/- 5% to 13 +/- 4% with anti-IL-1 beta antibodies. Similarly, the glomerular neutrophil infiltrate was also reduced by these treatments; from 42 +/- 3 to 25 +/- 1 in the case of anti-TNF-alpha and 47 +/- 2 to 30 +/- 1 with anti-IL-1 beta antibodies. In contrast, passive immunization against IL-1 alpha had no effect on either albumin excretion (4 +/- 3, 83 +/- 22 and 77 +/- 24 mg/24 h), glomerular capillary thrombi (2 +/- 1; 19 +/- 5 and 16 +/- 3) or glomerular neutrophil infiltrate (22 +/- 3; 47 +/- 5 and 48 +/- 5 from the three groups respectively). These results demonstrate that enhanced antibody mediated injury in the kidney is modulated by TNF-alpha and IL-1 beta but not by IL-1 alpha. PMID:1385027

  2. Serum Cytokines Th1, Th2, and Th17 Expression Profiling in Active Lupus Nephritis-IV: From a Southern Chinese Han Population

    PubMed Central

    Wang, Yin; Hu, Weiping; Wang, Ning; Sun, Qingyi; Liu, Qingyan; Liu, Xiaocong; Hou, Xianghua; Cheng, Ao

    2016-01-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV. PMID:27738386

  3. Mammographic resolution: influence of focal spot intensity distribution and geometry.

    PubMed

    Nickoloff, E L; Donnelly, E; Eve, L; Atherton, J V; Asch, T

    1990-01-01

    The influence of focal spot intensity distribution and geometry upon mammographic image quality were evaluated. The modulation transfer functions (MTF's) for eight different intensity distributions were determined and plotted in a manner to eliminate the effects of magnification and focal spot dimension. The results indicated that the total cross-sectional area is important for focal spots with uniform intensity distributions and equivalent diameters. For equivalent focal spot dimensions, intensity distributions with edge bands were shown to have less spatial resolution than uniform intensity distributions. Focal spots with greater intensities towards their centers provided better resolution than either uniform intensity distributions or distributions with edge bands for equivalent sizes. The type of intensity distribution was also shown to affect the accuracy of star pattern measurements of focal spot size; this method of measurement is only precise for a uniform square intensity distribution. Errors obtained with several other intensity distributions were tabulated. The variations of the effective focal spot size with position along the anode-cathode axis were shown to be of a factor of approximately two to three. The combined effects of geometric blur and film/screen blur were present for various heights above the cassette tray on several different mammographic systems.

  4. Focal spot measurements using a digital flat panel detector

    PubMed Central

    Jain, Amit; Panse, A.; Bednarek, Daniel R.; Rudin, Stephen

    2014-01-01

    Focal spot size is one of the crucial factors that affect the image quality of any x-ray imaging system. It is, therefore, important to measure the focal spot size accurately. In the past, pinhole and slit measurements of x-ray focal spots were obtained using direct exposure film. At present, digital detectors are replacing film in medical imaging so that, although focal spot measurements can be made quickly with such detectors, one must be careful to account for the generally poorer spatial resolution of the detector and the limited usable magnification. For this study, the focal spots of a diagnostic x-ray tube were measured with a 10-μm pinhole using a 194-μm pixel flat panel detector (FPD). The two-dimensional MTF, measured with the Noise Response (NR) Method was used for the correction for the detector blurring. The resulting focal spot sizes based on the FWTM (Full Width at Tenth Maxima) were compared with those obtained with a very high resolution detector with 8-μm pixels. This study demonstrates the possible effect of detector blurring on the focal spot size measurements with digital detectors with poor resolution and the improvement obtained by deconvolution. Additionally, using the NR method for measuring the two-dimensional MTF, any non-isotropies in detector resolution can be accurately corrected for, enabling routine measurement of non-isotropic x-ray focal spots. This work presents a simple, accurate and quick quality assurance procedure for measurements of both digital detector properties and x-ray focal spot size and distribution in modern x-ray imaging systems. PMID:25302004

  5. Focal spot measurements using a digital flat panel detector

    NASA Astrophysics Data System (ADS)

    Jain, Amit; Panse, A.; Bednarek, Daniel R.; Rudin, Stephen

    2014-03-01

    Focal spot size is one of the crucial factors that affect the image quality of any x-ray imaging system. It is, therefore, important to measure the focal spot size accurately. In the past, pinhole and slit measurements of x-ray focal spots were obtained using direct exposure film. At present, digital detectors are replacing film in medical imaging so that, although focal spot measurements can be made quickly with such detectors, one must be careful to account for the generally poorer spatial resolution of the detector and the limited usable magnification. For this study, the focal spots of a diagnostic x-ray tube were measured with a 10-μm pinhole using a 194-μm pixel flat panel detector (FPD). The twodimensional MTF, measured with the Noise Response (NR) Method was used for the correction for the detector blurring. The resulting focal spot sizes based on the FWTM (Full Width at Tenth Maxima) were compared with those obtained with a very high resolution detector with 8-μm pixels. This study demonstrates the possible effect of detector blurring on the focal spot size measurements with digital detectors with poor resolution and the improvement obtained by deconvolution. Additionally, using the NR method for measuring the two-dimensional MTF, any non-isotropies in detector resolution can be accurately corrected for, enabling routine measurement of non-isotropic x-ray focal spots. This work presents a simple, accurate and quick quality assurance procedure for measurements of both digital detector properties and x-ray focal spot size and distribution in modern x-ray imaging systems.

  6. Focal spot measurements using a digital flat panel detector.

    PubMed

    Jain, Amit; Panse, A; Bednarek, Daniel R; Rudin, Stephen

    2014-03-19

    Focal spot size is one of the crucial factors that affect the image quality of any x-ray imaging system. It is, therefore, important to measure the focal spot size accurately. In the past, pinhole and slit measurements of x-ray focal spots were obtained using direct exposure film. At present, digital detectors are replacing film in medical imaging so that, although focal spot measurements can be made quickly with such detectors, one must be careful to account for the generally poorer spatial resolution of the detector and the limited usable magnification. For this study, the focal spots of a diagnostic x-ray tube were measured with a 10-μm pinhole using a 194-μm pixel flat panel detector (FPD). The two-dimensional MTF, measured with the Noise Response (NR) Method was used for the correction for the detector blurring. The resulting focal spot sizes based on the FWTM (Full Width at Tenth Maxima) were compared with those obtained with a very high resolution detector with 8-μm pixels. This study demonstrates the possible effect of detector blurring on the focal spot size measurements with digital detectors with poor resolution and the improvement obtained by deconvolution. Additionally, using the NR method for measuring the two-dimensional MTF, any non-isotropies in detector resolution can be accurately corrected for, enabling routine measurement of non-isotropic x-ray focal spots. This work presents a simple, accurate and quick quality assurance procedure for measurements of both digital detector properties and x-ray focal spot size and distribution in modern x-ray imaging systems.

  7. Focal Length Affects Depicted Shape and Perception of Facial Images

    PubMed Central

    Třebický, Vít; Fialová, Jitka; Kleisner, Karel; Havlíček, Jan

    2016-01-01

    Static photographs are currently the most often employed stimuli in research on social perception. The method of photograph acquisition might affect the depicted subject’s facial appearance and thus also the impression of such stimuli. An important factor influencing the resulting photograph is focal length, as different focal lengths produce various levels of image distortion. Here we tested whether different focal lengths (50, 85, 105 mm) affect depicted shape and perception of female and male faces. We collected three portrait photographs of 45 (22 females, 23 males) participants under standardized conditions and camera setting varying only in the focal length. Subsequently, the three photographs from each individual were shown on screen in a randomized order using a 3-alternative forced-choice paradigm. The images were judged for attractiveness, dominance, and femininity/masculinity by 369 raters (193 females, 176 males). Facial width-to-height ratio (fWHR) was measured from each photograph and overall facial shape was analysed employing geometric morphometric methods (GMM). Our results showed that photographs taken with 50 mm focal length were rated as significantly less feminine/masculine, attractive, and dominant compared to the images taken with longer focal lengths. Further, shorter focal lengths produced faces with smaller fWHR. Subsequent GMM revealed focal length significantly affected overall facial shape of the photographed subjects. Thus methodology of photograph acquisition, focal length in this case, can significantly affect results of studies using photographic stimuli perhaps due to different levels of perspective distortion that influence shapes and proportions of morphological traits. PMID:26894832

  8. Magnetoencephalography (MEG) predicts focal epileptogenicity in cavernomas

    PubMed Central

    Stefan, H; Scheler, G; Hummel, C; Walter, J; Romstock, J; Buchfelder, M; Blumcke, I

    2004-01-01

    Objective: The aim of this study was to identify the irritative epileptic zone in patients with cavernomas by means of magnetoencephalography (MEG). Method: Among 82 patients operated for epilepsy, whose presurgical evaluation had included MEG, histological assessment of the tissue removed had confirmed cavernomas in eight. These eight patients had epilepsy since 18.6 (SD 12.7) years on average. The monitoring lasted about 2.1 (SD 1.3) hours and a median 20.9 (SD 14.3) spikes per hour were recorded. Spontaneous brain activity was recorded by means of a 74 channel dual unit MEG system (Magnes II, 4-D Neuroimaging) with simultaneous EEG recording (31 scalp electrodes). Spike analysis was performed using different source (moving dipole, current density reconstruction) and head models (spherical shells, BEM). Co-registration of neurophysiological and imaging data (MRI) was based upon anatomical landmarks. Results: In 6/8 patients co-localisation from the cavernoma and epileptic zone was found. In two patients the focus was localised in the parieto-occipital lobe, in three patients in the frontal lobe and in three patients in the temporal lobe. In one case of temporal and one case of frontal lobe focus localisation there was no spatial relationship to the cavernoma. Conclusion: In cases of focal seizures due to a single cavernoma, MEG may precisely delineate the epileptogenic tissue bordering the lesion. In patients with multiple cavernomas or dual pathology, MSI may reveal the complexity of the case, and contribute to the decision about further invasive diagnostics and more sophisticated therapeutic measures. MEG is a promising method for prediction of the epileptic zone in cavernoma related epilepsies, and thus it can contribute to decision making about and planning of epilepsy surgery. PMID:15314122

  9. Recovery of Deep Moonquake Focal Mechanisms

    NASA Technical Reports Server (NTRS)

    Weber, Renee C.; Knapmeyer, Martin

    2012-01-01

    Deep moonquakes are clustered not only in space but also in time: their recurrence times correspond to the durations of the anomalistic and draconic months, with some clusters preferring one of the two periods, while others are active with both periods. A key constraint for the understanding of the connection between the orbital motion of the Moon and its seismic activity is the focal mechanism: the orientation of the fault surface on which failure occurs during the quake. Due to the small aperture of the Apollo seismic network and the strong scattering of seismic waves within the lunar crust, the evaluation of P wave first motions to constrain the strike and dip of the fault planes is not feasible. Instead we evaluate the amplitude ratios of P and S waves. Seismograms are rotated into the P-SV-SH coordinate frame and amplitudes are determined as averages over short time windows after the arrival to reduce the impact of the scattering coda, which is independent of the source orientation. We allow for reversals of the fault motion, as observed for some clusters in previous studies, by taking into account the absolute amplitude only, without sign. An empirical site correction factor is applied to correct for amplitude distortions in the crust. We construct ensembles of fault plane solutions using an exhaustive grid search by accepting all orientations that reproduce the measured amplitude ratios within the observed standard deviations. Since all events of a given cluster are supposed to share the same fault plane, the combination of the individual inversion results further constrains the orientation. We evaluate 106 events from 25 different moonquake clusters. The most active cluster A001 contributes 37 events, while others contribute 1 to 9 events per cluster. Comparison of fault orientations with the variation of the tidal stress results in preferred orientations.

  10. Deep ultraviolet (254 nm) focal plane array

    NASA Astrophysics Data System (ADS)

    Cicek, Erdem; Vashaei, Zahra; McClintock, Ryan; Razeghi, Manijeh

    2011-10-01

    We report the synthesis, fabrication and testing of a 320 × 256 focal plane array (FPA) of back-illuminated, solarblind, p-i-n, AlxGa1-xN-based detectors, fully realized within our research laboratory. We implemented a novel pulsed atomic layer deposition technique for the metalorganic chemical vapor deposition (MOCVD) growth of crackfree, thick, and high Al composition AlxGa1-xN layers. Following the growth, the wafer was processed into a 320 × 256 array of 25 μm × 25 μm pixels on a 30 μm pixel-pitch and surrounding mini-arrays. A diagnostic mini-array was hybridized to a silicon fan-out chip to allow the study of electrical and optical characteristics of discrete pixels of the FPA. At a reverse bias of 1 V, an average photodetector exhibited a low dark current density of 1.12×10-8 A/cm2. Solar-blind operation is observed throughout the array with peak detection occurring at wavelengths of 256 nm and lower and falling off three orders of magnitude by 285 nm. After indium bump deposition and dicing, the FPA is hybridized to a matching ISC 9809 readout integrated circuit (ROIC). By developing a novel masking technology, we significantly reduced the visible response of the ROIC and thus the need for external filtering to achieve solar- and visible-blind operation is eliminated. This allowed the FPA to achieve high external quantum efficiency (EQE): at 254 nm, average pixels showed unbiased peak responsivity of 75 mA/W, which corresponds to an EQE of ~37%. Finally, the uniformity of the FPA and imaging properties are investigated.

  11. Focal conduction block in a case of tarsal tunnel syndrome.

    PubMed

    Almeida, Diogo F; Scremin, Luciano; Zúniga, Sérgio F; Oh, Shin J

    2010-09-01

    We report a case of tarsal tunnel syndrome (TTS) with focal conduction block across the tarsal tunnel (TT). A 46-year-old woman had pain in the left foot, sensory loss on the plantar surface, and positive Tinel sign over the TT. TTS was confirmed by magnetic resonance imaging (MRI) scan and surgery. Motor nerve conduction studies showed focal conduction block across the TT. Conduction block has rarely been reported in TTS. In this case, conduction block provides evidence for focal demyelination as the primary pathological process in TTS.

  12. The Characteristics of Broad and Narrow Focal Zone Lithotripters

    NASA Astrophysics Data System (ADS)

    Pishchalnikov, Yuri A.; McAteer, James A.; VonDerHaar, R. Jason; Pishchalnikova, Irina V.; Williams, James C.

    2008-09-01

    The focal width of a lithotripter is a measure of the diameter of its focal zone, the region where acoustic pressures are at least half the maximum positive pressure generated at a given power level. Different lithotripters have different focal widths. The Dornier HM3, for example, has a focal width of ˜10-12 mm and for many years this was the widest focal zone among clinical machines. Electromagnetic lithotripters tend to have narrower focal zones, in the range of ˜4-6 mm. Recent studies suggesting that focal width plays an important role in stone breakage prompted this assessment of two electromagnetic lithotripters. Acoustical mapping using a fiber optic probe hydrophone (FOPH-500) and breakage of U-30 gypsum model stones were used to compare a conventional lithotripter (Dornier DoLi-50) and a broad focal zone device (XiXin XX-ES). FOPH mapping characterized the focal width of the DoLi to be about 5mm and that of the XX-ES to be much wider (˜18 mm). For stone breakage experiments the DoLi was fired at power level 3 (mid-range) and the XX-ES was operated at the recommended clinical setting of 9.3 kV. Both lithotripters were fired at 60 SW/min. U-30 model stones held in a 2mm mesh basket were positioned at the clinical target point on the acoustic axis and at 5mm steps laterally, and the number of SW's to complete fragmentation was counted. Breakage on-axis was similar for the two machines (DoLi 676±105 SW's versus XX-ES 644±123 SW's, p>0.6), but at 15mm the DoLi required nearly twice the number of SW's as the XX-ES (DoLi 3006±780 SW's versus 1726±972 SW's, p<0.006). This demonstrates that a broad focal zone lithotripter is more effective in breaking stones off axis and supports the idea that focal width is an important feature, likely to be relevant in the clinical setting where respiratory motion may limit the effectiveness of narrow focal zone machines.

  13. Test chamber for low-background IR focal plane testing

    NASA Technical Reports Server (NTRS)

    Staller, Craig; Capps, Richard W.; Butler, Douglas; Moss, Nancy; Norwood, Wynn

    1989-01-01

    A unique and versatile vacuum chamber has been designed for JPL's IR Focal Plane Technology Group. This chamber is equipped with multiple ports for cryogen and electrical vacuum feedthroughs, pumping units, vacuum gages, sources, and detector camera heads. The design incorporates a liquid-nitrogen-cooled optical table and radiation shield for low-background IR detector testing. Focal planes can be tested at temperatures ranging from 300 K to that of liquid helium. This paper describes the design and construction of this low-background IR focal plane test chamber and discusses some of its distinctive features. An analysis of the test chamber's performance is also presented.

  14. Controlling the thermally induced focal shift in laser processing heads

    NASA Astrophysics Data System (ADS)

    Negel, Jan-Philipp; Abt, Felix; Blázquez-Sánchez, David; Austerschulte, Armin; Hafner, Margit; Liebig, Thomas; von Strobl-Albeg, Philipp; Weber, Rudolf; Abdou Ahmed, Marwan; Voss, Andreas; Graf, Thomas

    2012-03-01

    A system being able to in situ measure and control not simply the distance between the workpiece and the focusing optics, but the true focal position on the workpiece including the thermally induced focal shift in a laser processing head is presented. In order to achieve this, a bundle of astigmatic measurement beams is used following the same optical path as the welding beam. A camera and a software algorithm allow to keep the focal position constant within a range of 4 mm and with a resolution between 150 μm and 500 μm.

  15. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

    PubMed

    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

    2016-01-01

    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  16. Long-term Outcome of Lupus Nephritis Class II in Argentine Patients

    PubMed Central

    Collado, Maria Victoria; Dorado, Enrique; Rausch, Silvia; Gomez, Graciela; Khoury, Marina; Zazzetti, Federico; Gargiulo, María; Suarez, Lorena; Chaparro, Rafael; Paira, Sergio; Galvan, Laura; Juarez, Vicente; Pisoni, Cecilia; Garcia, Mercedes; Martinez, Liliana; Alvarez, Analia; Alvarez, Clarisa; Barreira, Juan; Sarano, Judith

    2016-01-01

    Background There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. Methods A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. Results Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133). In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). Conclusions This

  17. A Lower Proportion of Regulatory B Cells in Patients with Henoch–Schoenlein Purpura Nephritis

    PubMed Central

    Qu, Zhihui; Zhao, Songchen; Zhang, Li; Li, Man; Sun, Xiguang; Jiang, Yanfang

    2016-01-01

    Background Henoch—Schoenlein purpura is the one of most common types of systemic vasculitis that involves impaired renal function and Henoch-Schoenlein purpura nephritis (HSPN). The diagnosis of this condition is largely based on immunohistologic detection of immunoglobulin A1-containing immune complex in the glomerular deposits of mesangium. Despite clinical advances, the etiopathogenesis of HSPN is still largely unknown. Methods In this study, we enrolled 25 newly diagnosed HSPN patients and 14 healthy controls. Then, fractions of B cell subtypes were determined in venous blood using flow cytometry. The serum interleukin (IL)-10 concentration was determined by enzyme-linked immunosorbent assay. Results Compared to those in healthy controls, the numbers of CD38+CD19+, CD86+CD19+, CD38+CD86+CD19+, and CD95+CD19+ B cells per microliter of blood were significantly higher in HSPN patients. In contrast, the numbers of CD5+CD19+, IL-10+CD19+, CD5+CD1d+CD19+, and IL-10+CD5+CD1d+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly lower in HSPN patients. Following treatment, the numbers of CD38+CD19+ and CD86+CD19+ B cells per microliter of blood were significantly reduced in HSPN patients. However, the numbers of CD5+CD1d+CD19+, CD5+CD1d+IL-10+CD19+, and IL-10+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly increased in HSPN patients following treatment. The estimated glomerular filtration rate (eGFR) was negatively correlated with the number of CD38+CD19+ B cells but positively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration. The 24-h urinary protein concentration was positively correlated with the number of CD38+CD19+B cells but negatively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration

  18. Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

    PubMed

    Yen, T-H; Yang, H-Y; Yeh, Y-H; Chu, P-H; Wen, C-J; Fu, J-F; Wang, I-K; Liang, C-C; Chang, C-T; Chen, K-H; Tian, Y-C; Hung, C-C; Lin, J-L; Yang, C-W

    2013-02-01

    This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).

  19. Real-time focal stack compositing for handheld mobile cameras

    NASA Astrophysics Data System (ADS)

    Solh, Mashhour

    2013-03-01

    Extending the depth of field using a single lens camera on a mobile device can be achieved by capturing a set of images each focused at a different depth or focal stack then combine these samples of the focal stack to form a single all-in-focus image or an image refocused at a desired depth of field. Focal stack compositing in real time for a handheld mobile camera has many challenges including capturing, processing power, handshaking, rolling shutter artifacts, occlusion, and lens zoom effect. In this paper, we describe a system for a real time focal stack compositing system for handheld mobile device with an alignment and compositing algorithms. We will also show all-in-focus images captured and processed by a cell phone camera running on Android OS.

  20. [Familial Focal Segmental Glomerulosclerosis, a vademecum for clinical nephrologist].

    PubMed

    Caridi, Gianluca; Lugani, Francesca; Bonanni, Elisa; Rossi, Roberta; Carrea, Alba; Ghiggeri, Gian Marco

    2015-01-01

    The new genomic technologies (Next Generation Sequencing, NGS) are opening a new era in Genomic Medicine. This simple guide gives a state-of-the-art description of the genes that cause Focal Segmental Glomerulosclerosis and nephrotic syndrome.

  1. Creation of identical multiple focal spots with prescribed axial distribution.

    PubMed

    Yu, Yanzhong; Zhan, Qiwen

    2015-10-01

    We present a scheme for the construction of coaxially equidistant multiple focal spots with identical intensity profiles for each individual focus and a predetermined number and spacing. To achieve this, the radiation field from an antenna is reversed and then gathered by high numerical aperture objective lenses. Radiation patterns from three types of line sources, i.e., the electric current, magnetic current and electromagnetic current distributions, with cosine-squared taper are respectively employed to generate predominately longitudinally polarized bright spots, azimuthally polarized doughnuts, and focal spots with a perfect spherically symmetric intensity distribution. The required illuminations at the pupil plane of a 4Pi focusing configuration for the creation of these identical multiple focal spots can be easily derived by solving the inverse problem of the antenna radiation field. These unique focal field distributions may find potential applications in laser direct writing and optical microscopy, as well as multiple-particle trapping, alignment, and acceleration along the optical axis.

  2. Oral focal mucinosis: a rare case with literature review

    PubMed Central

    Sowmya, G V; Manjunatha, Bhari Sharanesha; Nahar, Prashant; Aggarwal, Hersheal

    2015-01-01

    Oral focal mucinosis (OFM) is an unusual disease that affects diverse localised areas of the mouth, where the connective tissue undergoes focal degeneration. It was described for the first time by Tomich in 1974. It presents as an asymptomatic pedunculated or sessile growth, commonly on the gingiva, with most cases being in women. Its pathogenesis is linked to overproduction of hyaluronic acid by fibroblasts during collagen production, ensuing in focal myxoid degeneration. It has no characteristic features and diagnosis depends on histological scrutiny. We report a rare case of oral focal mucinosis affecting a 54-year-old man who presented with a sessile gingival growth mimicking a common tumour-like lesion. PMID:25759271

  3. Focal MRI and Learning Disability with Reduced Automaticity.

    PubMed

    Millichap, J Gordon

    2015-09-01

    Investigators from the Boston Children's Hospital, Harvard Medical School, MA, performed a retrospective analysis of 1,587 children referred for a learning disability, and 127 had a focal deficit demonstrated on either a neurologic or neuropsychological evaluation.

  4. Compact Focal Plane Assembly for Planetary Science

    NASA Technical Reports Server (NTRS)

    Brown, Ari; Aslam, Shahid; Huang, Wei-Chung; Steptoe-Jackson, Rosalind

    2013-01-01

    A compact radiometric focal plane assembly (FPA) has been designed in which the filters are individually co-registered over compact thermopile pixels. This allows for construction of an ultralightweight and compact radiometric instrument. The FPA also incorporates micromachined baffles in order to mitigate crosstalk and low-pass filter windows in order to eliminate high-frequency radiation. Compact metal mesh bandpass filters were fabricated for the far infrared (FIR) spectral range (17 to 100 microns), a game-changing technology for future planetary FIR instruments. This fabrication approach allows the dimensions of individual metal mesh filters to be tailored with better than 10- micron precision. In contrast, conventional compact filters employed in recent missions and in near-term instruments consist of large filter sheets manually cut into much smaller pieces, which is a much less precise and much more labor-intensive, expensive, and difficult process. Filter performance was validated by integrating them with thermopile arrays. Demonstration of the FPA will require the integration of two technologies. The first technology is compact, lightweight, robust against cryogenic thermal cycling, and radiation-hard micromachined bandpass filters. They consist of a copper mesh supported on a deep reactive ion-etched silicon frame. This design architecture is advantageous when constructing a lightweight and compact instrument because (1) the frame acts like a jig and facilitates filter integration with the FPA, (2) the frame can be designed so as to maximize the FPA field of view, (3) the frame can be simultaneously used as a baffle for mitigating crosstalk, and (4) micron-scale alignment features can be patterned so as to permit high-precision filter stacking and, consequently, increase the filter bandwidth and sharpen the out-of-band rolloff. The second technology consists of leveraging, from another project, compact and lightweight Bi0.87Sb0.13/Sb arrayed thermopiles

  5. Focal epithelial hyperplasia. A rare disease in our area.

    PubMed

    Segura-Saint-Gerons, Rafael; Toro-Rojas, Mariano; Ceballos-Salobreña, Alejandro; Aparicio-Soria, Jose Luis; Fuentes-Vaamonde, Helena

    2005-01-01

    Focal epithelial hyperplasia is a benign, asymptomatic disease, occurring with very low frequency within our population. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue, and less frequently on the upper lip, gingiva and palate. We present the clinical case of a 9-year-old Saharan girl with lesions that clinically and histologically corresponded to a focal epithelial hyperplasia.

  6. Inflammatory pancreatic masses: problems in differentiating focal pancreatitis from carcinoma

    SciTech Connect

    Neff, C.C.; Simeone, J.F.; Wittenberg, J.; Mueller, P.R.; Ferrucci, J.T. Jr.

    1984-01-01

    The authors studied 19 patients with focal inflammatory masses of the pancreas over an 18-month period. In 13 cases, transhepatic cholangiography and/or endoscopic retrograde cholangiopancreatography were unsuccessful in differentiating pancreatitis from carcinoma. Eighteen patients had a history of alcohol abuse, and 12 had had pancreatitis previously. Pre-existing glandular injury appears to be a prerequisite to formation of focal inflammatory pancreatic masses.

  7. Traceability of high focal length cameras with diffractive optical elements

    NASA Astrophysics Data System (ADS)

    Lages Martins, L.; Silva Ribeiro, A.; Sousa, J. Alves e.

    2016-11-01

    This paper describes the use of diffractive optical elements (DOEs) for metrological traceable geometrical testing of high focal length cameras applied in the observation of large- scale structures. DOEs and related mathematical models are briefly explained. Laboratorial activities and results are described for the case of a high focal length camera used for longdistance displacement measurement of a long-span (2278 m) suspension bridge.

  8. Orion: The Largest Infrared Hybrid Focal Plane in Production

    NASA Astrophysics Data System (ADS)

    Fowler, Albert M.; Merrill, Michael; Ball, William J.; Henden, Arne A.; Vrba, Frederick J.; McCreight, Craig R.

    2003-03-01

    Orion is a program to develop a 2048x2048 infrared focal plane using InSb PV detectors. It is the natural follow-on to the successful Aladdin 1024x1024 program, which was the largest IR focal plane of the 90's. Although the pixels are somewhat smaller than Aladdin, the overall focal plane is over 50mm in size and for the present is the largest IR focal plane of the 21st century. The work is being done by Raytheon Infrared Operations (RIO but better known as SBRC) by many of the same people who created the Aladdin focal plane. The design is very similar to the successful Aladdin design with the addition of reference pixels to lower noise and drift effects in long integrations. So far we have made five focal plane modules with hybridized InSb detectors. In this paper we will discuss the unique design features of this device as well as present test data taken from these devices.

  9. Focal-contact clusterization of osteoblasts under mechanical stresses

    NASA Astrophysics Data System (ADS)

    Guignandon, A.; Akhouayri, O.; Laroche, N.; Alexandre, C.; Vico, L.

    We compared quantitatively vinculin-related adhesion parameters in osteoblastic cells submitted to opposite mechanical stress (i.e. low deformation and frequency strain regimens (strained condition) and microgravity exposure (relaxed condition). In both ROS 17/2.8 and rat primary osteoblastic cells, 1% cyclic deformations at 0.05 Hz during a daily 10 min episode over 7 days stimulated cell growth whereas relaxed ROS proliferated similarly to static culture (BC). We studied short term (up to 24 hrs) adaptation of focal contact re-organization in these two conditions. Strain induced a biphasic response comprising new focal contacts formation followed by their clusterization in both ROS and primary osteoblasts. Microgravity exposure induced a reduction in focal contact number and clusterization in ROS cells. To relate the proliferation (strain) or the survival (relaxed) status of ROS cells with focal contact organization, we inhibited ERKs proliferative-dependent pathway. Inhibition of proliferation by PD98059 was overcome although not fully restored by strain and strain-induced clusterization of vinculin positive contact still occurs in presence of PD98059 whereas the increase in focal contact number is abolished. In conclusion, we showed that focal contacts are mechanoeffectors and we suggested that their morphological organization might serve as a discriminant functional parameter between survival and proliferation status in ROS 17/2.8 osteoblastic cells.

  10. Cryogenic focal plane flatness measurement with optical zone slope tracking

    NASA Astrophysics Data System (ADS)

    Edelstein, Jerry; Sirk, Martin; Jelinsky, Patrick N.; Besuner, Robert W.; Hoff, Matthew; Perry, Paul; Heetderks, Henry D.; Bebek, Christopher J.; Levi, Michael E.

    2011-10-01

    We describe a non-contact optical measurement method used to determine the surface flatness of a cryogenic sensor array developed for the JDEM mission. Large focal planes envisioned for future visible to near infra-red astronomical large area point-source surveys such as JDEM, WFIRST, or EUCLID must operate at cryogenic temperatures while maintaining focal plane flatness within a few 10's of μm over half-meter scales. These constraints are imposed by sensitivity conditions that demand low noise observations from the sensors and the large-field, fast optical telescopes necessary to obtain the science yield. Verifying cryogenic focal plane flatness is challenging because μm level excursions need to be measured within and across many multi-cm sized sensors using no physical contact and while situated within a high-vacuum chamber. We have used an optical metrology Shack-Hartmann scheme to measure the 36x18 cm focal plane developed for the JDEM mission at the Lawrence Berkeley National Laboratory. The focal plane holds a 4x8 array of CCDs and HgCdTe detectors. The flatness measurement scheme uses a telescope-fed micro-lens array that samples the focal plane to determine slope changes of individual sensor zones.

  11. Recurrent Focal Segmental Glomerulosclerosis and Abatacept: Case Report.

    PubMed

    Alkandari, Omar; Nampoory, Narayanan; Nair, Prasad; Atta, Ahmed; Zakaria, Zakaria; Mossad, Ahmed; Yagan, Jude; Al-Otaibi, Torki

    2016-08-01

    Focal segmental glomerulosclerosis is a common cause of end-stage renal disease in children. Focal segmental glomerulosclerosis recurrence in renal transplants is a challenging disease, and can cause graft dysfunction and loss. Different therapies exist with varying responses, from complete remission to resistance to all modes of treatment. Abatacept was recently introduced as a treatment for primary focal segmental glomerulosclerosis in native kidneys and in recurrent disease after transplant. We present a pediatric case with immunosuppression-resistant primary NPHS2-negative focal segmental glomerulosclerosis recur-rence after renal transplant. The standard therapy for recurrent focal segmental glomerulosclerosis (rituximab, plasmapheresis, high-dose cyclosporine, and corticosteroids) was tried but failed to induce remission. Abatacept (10 mg/kg) was given at 0, 2, and 4 weeks (total, 3 doses) with no good response. We conclude that abatacept may work in patients with B7-1-positive focal segmental glomerulosclerosis recurrence and its efficacy is uncertain in disease with B7-1-negative or unknown staining status.

  12. A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation.

    PubMed

    Tegtmeyer, Nicole; Hartig, Roland; Delahay, Robin M; Rohde, Manfred; Brandt, Sabine; Conradi, Jens; Takahashi, Seiichiro; Smolka, Adam J; Sewald, Norbert; Backert, Steffen

    2010-07-23

    Fibronectin, a 250-kDa eukaryotic extracellular matrix protein containing an RGD motif plays crucial roles in cell-cell communication, development, tissue homeostasis, and disease development. The highly complex fibrillar fibronectin meshwork orchestrates the functions of other extracellular matrix proteins, promoting cell adhesion, migration, and intracellular signaling. Here, we demonstrate that CagL, a 26-kDa protein of the gastric pathogen and type I carcinogen Helicobacter pylori, mimics fibronectin in various cellular functions. Like fibronectin, CagL contains a RGD motif and is located on the surface of the bacterial type IV secretion pili as previously shown. CagL binds to the integrin receptor alpha(5)beta(1) and mediates the injection of virulence factors into host target cells. We show that purified CagL alone can directly trigger intracellular signaling pathways upon contact with mammalian cells and can complement the spreading defect of fibronectin(-/-) knock-out cells in vitro. During interaction with various human and mouse cell lines, CagL mimics fibronectin in triggering cell spreading, focal adhesion formation, and activation of several tyrosine kinases in an RGD-dependent manner. Among the activated factors are the nonreceptor tyrosine kinases focal adhesion kinase and Src but also the epidermal growth factor receptor and epidermal growth factor receptor family member Her3/ErbB3. Interestingly, fibronectin activates a similar range of tyrosine kinases but not Her3/ErbB3. These findings suggest that the bacterial protein CagL not only exhibits functional mimicry with fibronectin but is also capable of activating fibronectin-independent signaling events. We thus postulate that CagL may contribute directly to H. pylori pathogenesis by promoting aberrant signaling cross-talk within host cells.

  13. Clinical features and outcomes of diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis in children

    PubMed Central

    Fu, Haidong; Mao, Jianhua; Xu, Yanping; Gu, Weizhong; Zhu, Xiujuan; Liu, Aimin

    2016-01-01

    OBJECTIVE: To investigate the outcomes of childhood diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis (DEP-HSPN) in response to early diagnosis and prompt treatment. METHODS: Eleven cases of DEP-HSPN in children were investigated in comparison to HSPN without diffuse endocapillary proliferation (non-DEP-HSPN). RESULTS: DEP-HSPN had a higher prevalence of nephrotic syndrome but a lower prevalence of hematuria compared to non-DEP-HSPN. IgA, IgG and IgM antibody deposition was found in DEP-HSPN by histopathological examination. Proteinuria cleared in all 11 cases through treatment with steroids and/or immunosuppressive drugs. However, half of the DEP-HSPN patients continuously had hematuria after treatment. CONCLUSION: The early diagnosis and prompt initiation of immunosuppressive treatment based on renal biopsy are important for achieving favorable outcomes. PMID:27652838

  14. Two Cases of Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody (PR3-ANCA)-related Nephritis in Infectious Endocarditis

    PubMed Central

    Hirai, Kazuya; Miura, Naoto; Yoshino, Masabumi; Miyamoto, Kanyu; Nobata, Hironobu; Nagai, Takuhito; Suzuki, Keisuke; Banno, Shogo; Imai, Hirokazu

    2016-01-01

    We herein report two cases of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA)-related nephritis in infectious endocarditis. In both cases, the patients were middle-aged men with proteinuria and hematuria, hypoalbuminemia, decreased kidney function, anemia, elevated C-reactive protein (CRP) levels, and PR3-ANCA positivity. Each had bacteremia, due to Enterococcus faecium in one and Streptococcus bovis in the other. One patient received aortic valve replacement therapy for aortic regurgitation with vegetation, and the other underwent tricuspid valve replacement therapy and closure of a ventricular septic defect to treat tricuspid regurgitation with vegetation. These patients' urinary abnormalities and PR3-ANCA titers improved at 6 months after surgery following antibiotic treatment without steroid therapy. PMID:27904114

  15. Delay in growth and the development of nephritis in rats treated with interferon preparations in the neonatal period.

    PubMed Central

    Gresser, I.; Morel-Maroger, L.; Châtelet, F.; Maury, C.; Tovey, M.; Bandu, M. T.; Buywid, J.; Delauche, M.

    1979-01-01

    Suckling rats were injected for 14 to 17 days with potent rat-cell-culture interferon preparations or various heterologous interferon or control preparations. Only treatment with rat interferon resulted in a delay in growth and maturation of different organs and the subsequent development of an "immune complex" type nephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis, whereas only 3 of 99 rats in the various control groups had minimal renal lesions. Deposits of IgG and C3 along the glomerular basement membrane were only seen in interferon-treated rats. Images Figure 6 Figure 3 Figure 2 Figure 5 Figure 4 Figure 1 PMID:156503

  16. Pregnancy and patients with preexisting lupus nephritis: 15 years of experience at a single center in Korea.

    PubMed

    Koh, J H; Ko, H S; Lee, J; Jung, S M; Kwok, S-K; Ju, J H; Park, S-H

    2015-06-01

    We investigated obstetric outcomes and comorbidities during pregnancy in females with preexisting lupus nephritis (LN) and identified predictors for renal flare. In cases of renal flare during pregnancy, we assessed the long-term post-delivery renal outcome. We performed a retrospective analysis of 183 systemic lupus erythematosus (SLE) pregnancies including blood chemistry, urinalysis, urinary protein, and disease activity recorded at prepregnancy, during pregnancy, and at one month, six months, and one year post-delivery. Pregnancies with preexisting LN had a greater frequency of adverse obstetric outcomes and maternal comorbidity. Renal flares occurred in 50.7% of pregnancies with preexisting LN, 89.2% of which were reactivations. Renal flare among pregnancies with SLE was predicted based on preexisting lupus nephritis (OR 17.73; 95% CI, 5.770-54.484), an active disease prior to pregnancy (OR 2.743; 95% CI, 1.074-7.004), and prepregnancy eGFR < 90 ml/min/1.73 m(2) (OR 11.151; 95% CI, 3.292-37.768). Persistent LN one year after delivery was observed in 33.3% of pregnancies. The median follow-up time after delivery was 5.9 (3.1-9.7) years and chronic kidney disease (CKD) occurred in 21.4% of pregnancies with renal flare. In patients with renal flare, failing to achieve a ≥ 50% reduction in urine protein levels within six months, longer total duration of renal flare, and acute kidney injury at renal flare was associated with CKD development. Females with preexisting LN should achieve remission before pregnancy. When patients experience renal flares during pregnancy, it is important to reduce the proteinuria level by >50% within six months and to achieve early remission for excellent long-term renal outcomes.

  17. Interleukin-10 receptor expression and signalling were down-regulated in CD4+ T cells of lupus nephritis patients

    PubMed Central

    Cui, H D; Qi, Z M; Yang, L L; Qi, L; Zhang, N; Zhang, X L; Du, S Y; Jiang, Y

    2011-01-01

    Studies have indicated that interleukin (IL)-10 has a pathogenic role in systemic lupus erythematosus (SLE); however, a protective effect of IL-10 in SLE was also observed. Because the exact mechanism of IL-10 signalling in the pathogenesis of SLE is unclear, this study sought to assess the expression and signalling of interleukin-10 receptor (IL-10R) in peripheral leucocytes from patients with SLE. We used flow cytometry to examine the expression of IL-10R1 on different peripheral leucocytes from 28 SLE patients, of whom 14 had lupus nephritis (LN) and 14 were healthy controls. We also examined the effects of IL-10 on phosphorylation of signal transducer and activator of transcription (STAT)-3 and STAT-1 in peripheral blood mononuclear cells (PBMCs) obtained from 13 SLE patients and seven healthy controls. Plasma cytokines were detected by flow cytometric bead array (CBA) techniques. Although IL-10R1 expression levels on each peripheral leucocyte subset from 28 SLE patients and 14 healthy controls were similar, the expression levels on CD4+ T cells from LN patients were significantly lower than on CD4+ T cells from controls and SLE patients without nephritis (P < 0·01). IL-10R1 expression levels on CD4+ and CD8+ T cells were correlated negatively with the SLE disease activity index (P < 0·01). Additionally, the phosphorylation of STAT-3 was delayed and reduced in PBMCs from LN patients and active SLE patients. Plasma IL-10 levels were significantly higher in LN patients than controls. IL-10R1 expression on CD4+ T cells and signalling in PBMCs were down-regulated in LN patients, indicating that IL-10 and its receptor may have a special role in LN pathogenesis. PMID:21635228

  18. CD40 Gene Silencing Reduces the Progression of Experimental Lupus Nephritis Modulating Local Milieu and Systemic Mechanisms

    PubMed Central

    Ripoll, Èlia; Merino, Ana; Goma, Montse; Aran, Josep M.; Bolaños, Nuria; de Ramon, Laura; Herrero-Fresneda, Immaculada; Bestard, Oriol; Cruzado, Josep M.; Grinyó, Josep M.; Torras, Juan

    2013-01-01

    Lupus nephritis (LN) is an autoimmune disorder in which co-stimulatory signals have been involved. Here we tested a cholesterol-conjugated-anti-CD40-siRNA in dendritic cells (DC) in vitro and in a model of LPS to check its potency and tissue distribution. Then, we report the effects of Chol-siRNA in an experimental model of mice with established lupus nephritis. Our in vitro studies in DC show a 100%intracellular delivery of Chol-siRNA, with a significant reduction in CD40 after LPS stimuli. In vivo in ICR mice, the CD40-mRNA suppressive effects of our Chol-siRNA on renal tissue were remarkably sustained over a 5 days after a single preliminary dose of Chol-siRNA. The intra-peritoneal administration of Chol-siRNA to NZB/WF1 mice resulted in a reduction of anti-DNA antibody titers, and histopathological renal scores as compared to untreated animals. The higher dose of Chol-siRNA prevented the progression of proteinuria as effectively as cyclophosphamide, whereas the lower dose was as effective as CTLA4. Chol-siRNA markedly reduced insterstitialCD3+ and plasma cell infiltrates as well as glomerular deposits of IgG and C3. Circulating soluble CD40 and activated splenic lymphocyte subsets were also strikingly reduced by Chol-siRNA. Our data show the potency of our compound for the therapeutic use of anti-CD40-siRNA in human LN and other autoimmune disorders. PMID:23799000

  19. Intraglomerular basement membrane translocation of immune complex (IC) in the development of passive in situ IC nephritis of rats.

    PubMed Central

    Fujigaki, Y.; Nagase, M.; Honda, N.

    1993-01-01

    A study was performed to elucidate the mechanisms of charge-based immune complex nephritis. A chronological observation after induction of nephritis was made by immunoelectron microscopy to clarify whether antigen (Ag) remains in association with antibody (Ab) and C3 during the translocation through the glomerular basement membrane (GBM). Fifteen minutes after intrarenal perfusion with cationized ferritin (pI > 10.0) as Ag, followed by injection of rabbit anti-ferritin Ab, deposition of subendothelial Ag-Ab-C3 complexes was observed. Between 2 hours and 1 day, a large number of Ag in close association with Ab was noted in the lamina densa, but only a small amount of C3 was detectable. During this time Ag and Ab in the subendothelial region gradually decreased. However, C3 reappeared in the subepithelial region together with the Ag-Ab complex after 1 day, and the subendothelial C3 significantly decreased. At 2 hours and day 1, the distributions of Ag and Ab in the GBM were similar in immersion-fixed kidneys regardless of the preperfusion with phosphate-buffered saline. On the other hand, the passage of Ag across the lamina densa was delayed in the experimental rats as compared with the controls. Significant albuminuria also appeared on day 1. Despite the general concept that Ab binding to cationized Ag results in low avidity immune complex, cationized Ag translocated across the GBM in close association with Ab. The complement was activated biphasically in the subendothelial and in the subepithelial space. The subendothelial complement activation may have contributed to the translocation of immune complex. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8456943

  20. Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Clavarino, Giovanna; Jourde-Chiche, Noémie; Ouili, Saber; Paul, Stéphane; Gout, Evelyne; Sarrot-Reynauld, Françoise; Bardin, Nathalie; Boëlle, Pierre -Yves; Chiche, Laurent; Bouillet, Laurence; Thielens, Nicole M.; Cesbron, Jean-Yves; Dumestre-Pérard, Chantal

    2016-01-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p≤0.001). This association with renal involvement was higher with anti-ficolin-3 or anti-C1q antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other serological biomarker. These results suggest that anti-ficolin-3 antibodies could be useful for the diagnosis of active nephritis in SLE patients. PMID:27631981

  1. The safety of isotretinoin in patients with lupus nephritis: a comprehensive review.

    PubMed

    Miziołek, Bartosz; Bergler-Czop, Beata; Stańkowska, Anna; Brzezińska-Wcisło, Ligia

    2017-03-01

    Oral isotretinoin (13-cis-retinoinc acid) is a derivative of vitamin A and belongs to the first generation of retinoids, which act as synthetic isomers of retinoic acid (RA). It is a very effective agent in a treatment of acne vulgaris; however, multiple side effects related to therapy with retinoids preclude the use of isotretinoin in less severe acne vulgaris. A significant limitation for the administration of isotretinoin appears in case of concomitant kidney disease with a special attention regarding the safety of the agent in patients with lupus nephritis (LN). The aim of this review is an assessment of the safety of isotretinoin for the treatment of acne vulgaris in patients with LN. We searched both MEDLINE and SCOPUS databases, as well as several dermatological textbooks, to present all limitations and benefits of therapy with isotretinoin or its isomer (ATRA) for patients with kidney diseases. Several mouse models of SLE revealed a significant modulatory influence of retinoids on autoimmune injury of the glomerular unit. Retinoids were demonstrated to affect mononuclear cell infiltrations of renal tissue allowing for a reduction in the overall glomerular damage. Presumptively, they can affect a synthesis of autoantibodies significantly limiting their deposition in the glomerular unit. Moreover, retinoids were also shown to affect the synthesis of different cytokines specific both for lymphocytes Th1 (IL-2, IL-12, INFγ) ant Th2 (IL-4, IL-10). The influence of retinoids on the course of LN seems to be more multidimensional than only restricted to immune aspects and these synthetic RA isomers manifest also antiproteinuric activity in comparable extent to steroidal agents. The agents were demonstrated to counteract a loss of podocytes after the injury of the glomerular unit. They can promote a differentiation of renal progenitor cells (RPCs) within the Bowman capsule into mature podocytes leading to regeneration of podocyte number. Additionally, retinoids can

  2. 3D printing of microscopic bacterial communities

    PubMed Central

    Connell, Jodi L.; Ritschdorff, Eric T.; Whiteley, Marvin; Shear, Jason B.

    2013-01-01

    Bacteria communicate via short-range physical and chemical signals, interactions known to mediate quorum sensing, sporulation, and other adaptive phenotypes. Although most in vitro studies examine bacterial properties averaged over large populations, the levels of key molecular determinants of bacterial fitness and pathogenicity (e.g., oxygen, quorum-sensing signals) may vary over micrometer scales within small, dense cellular aggregates believed to play key roles in disease transmission. A detailed understanding of how cell–cell interactions contribute to pathogenicity in natural, complex environments will require a new level of control in constructing more relevant cellular models for assessing bacterial phenotypes. Here, we describe a microscopic three-dimensional (3D) printing strategy that enables multiple populations of bacteria to be organized within essentially any 3D geometry, including adjacent, nested, and free-floating colonies. In this laser-based lithographic technique, microscopic containers are formed around selected bacteria suspended in gelatin via focal cross-linking of polypeptide molecules. After excess reagent is removed, trapped bacteria are localized within sealed cavities formed by the cross-linked gelatin, a highly porous material that supports rapid growth of fully enclosed cellular populations and readily transmits numerous biologically active species, including polypeptides, antibiotics, and quorum-sensing signals. Using this approach, we show that a picoliter-volume aggregate of Staphylococcus aureus can display substantial resistance to β-lactam antibiotics by enclosure within a shell composed of Pseudomonas aeruginosa. PMID:24101503

  3. Monolithically integrated HgCdTe focal plane arrays

    NASA Astrophysics Data System (ADS)

    Velicu, Silviu; Lee, Tae-Seok; Ashokan, Renganathan; Grein, Christoph H.; Boieriu, Paul; Chen, Y. P.; Dinan, John H.; Lianos, Dimitrios

    2003-12-01

    The cost and performance of hybrid HgCdTe infrared focal plane arrays are constrained by the necessity of fabricating the detector arrays on a CdZnTe substrate. These substrates are expensive, fragile, are available only in small rectangular formats, and are not a good thermal expansion match to the silicon readout integrated circuit. We discuss in this paper an infrared sensor technology based on monolithically integrated infrared focal plane arrays that could replace the conventional hybrid focal plane array technology. We have investigated the critical issues related to the growth of HgCdTe on Si read-out integrated circuits and the fabrication of monolithic focal plane arrays: (1) the design of Si read-out integrated circuits and focal plane array layouts, (2) the low temperature cleaning of Si(001) wafers, (3) growth of CdTe and HgCdTe layers on read-out integrated circuits, (4) array fabrication, interconnection between focal plane array and read-out integrated circuit input nodes and demonstration of the photovoltaic operation, and (5) maintenance of the read-out integrated circuit characteristics after substrate cleaning, molecular beam epitaxy growth and device fabrication. Crystallographic, optical and electrical properties of the grown layers are presented. Electrical properties for diodes fabricated on misoriented Si and read-out integrated circuit substrates are discussed. The fabrication of arrays with demonstrated I-V properties show that monolithic integration of HgCdTe-based infrared focal plane arrays on Si read-out integrated circuits is feasible and could be implemented in the 3rd generation of infrared systems.

  4. Demonstrating Bacterial Flagella.

    ERIC Educational Resources Information Center

    Porter, John R.; And Others

    1992-01-01

    Describes an effective laboratory method for demonstrating bacterial flagella that utilizes the Proteus mirabilis organism and a special harvesting technique. Includes safety considerations for the laboratory exercise. (MDH)

  5. The relationship between force and focal complex development

    PubMed Central

    Galbraith, Catherine G.; Yamada, Kenneth M.; Sheetz, Michael P.

    2002-01-01

    To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin–ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin–ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella. PMID:12446745

  6. Laser multi-reflection confocal long focal-length measurement

    NASA Astrophysics Data System (ADS)

    Li, Zhigang; Qiu, Lirong; Zhao, Weiqian; Xiao, Yang

    2016-06-01

    We propose a new laser multi-reflection confocal focal-length measurement (MCFM) method to meet the requirements of a high-precision measurement for a long focal-length more than 2 m. It places an optical flat and a reflector behind the test lens for reflecting the measuring beam repeatedly, and then, uses the property that the peak points of confocal response curves precisely corresponds to the convergence points of a multi-reflected measuring beam to exactly identify the positions of the convergence points. Subsequently, it obtains the position variation of the reflector with a different number of reflections by a distance measuring instrument, and thereby achieving the high precise long focal-length measurement. The theoretical analyses and preliminary experimental results indicate that MCFM has a relative standard uncertainty of 0.066% for a test lens with the focal-length of 9.76 m. MCFM can provide a novel approach for the high-precision focal-length measurement.

  7. MR imaging features of focal liver lesions in Wilson disease.

    PubMed

    Dohan, Anthony; Vargas, Ottavia; Dautry, Raphael; Guerrache, Youcef; Woimant, France; Hamzi, Lounis; Boudiaf, Mourad; Poujois, Aurelia; Faraoun, Sid Ahmed; Soyer, Philippe

    2016-09-01

    Hepatic involvement in Wilson disease (WD) manifests as a diffuse chronic disease in the majority of patients. However, in a subset of patients focal liver lesions may develop, presenting with a wide range of imaging features. The majority of focal liver lesions in patients with WD are benign nodules, but there are reports that have described malignant liver tumors or dysplastic nodules in these patients. Because of the possibility of malignant transformation of liver nodules, major concerns have been raised with respect to the management and follow-up of patients with WD in whom focal liver lesions have been identified. The assessment of liver involvement in patients with WD is generally performed with ultrasonography. However, ultrasonography conveys limited specificity so that magnetic resonance (MR) imaging is often performed to improve lesion characterization. This review was performed to illustrate the spectrum of MR imaging features of focal liver lesions that develop in patients with WD. It is assumed that familiarity with the MR imaging presentation of focal liver lesions in WD may help clarify the actual nature of hepatic nodules in patients with this condition.

  8. Combined scanning transmission electron microscopy tilt- and focal series.

    PubMed

    Dahmen, Tim; Baudoin, Jean-Pierre; Lupini, Andrew R; Kübel, Christian; Slusallek, Philipp; de Jonge, Niels

    2014-04-01

    In this study, a combined tilt- and focal series is proposed as a new recording scheme for high-angle annular dark-field scanning transmission electron microscopy (STEM) tomography. Three-dimensional (3D) data were acquired by mechanically tilting the specimen, and recording a through-focal series at each tilt direction. The sample was a whole-mount macrophage cell with embedded gold nanoparticles. The tilt-focal algebraic reconstruction technique (TF-ART) is introduced as a new algorithm to reconstruct tomograms from such combined tilt- and focal series. The feasibility of TF-ART was demonstrated by 3D reconstruction of the experimental 3D data. The results were compared with a conventional STEM tilt series of a similar sample. The combined tilt- and focal series led to smaller "missing wedge" artifacts, and a higher axial resolution than obtained for the STEM tilt series, thus improving on one of the main issues of tilt series-based electron tomography.

  9. Hot spot liver scan in focal nodular hyperplasia

    SciTech Connect

    Piers, D.A.; Houthoff, H.J.; Krom, R.A.F.; Schuur, K.H.; Sikkens, H.; Weits, J.

    1980-12-01

    In scintigraphy of the liver with radiocolloid, space-occupying lesions generally are visualized as regions of decreased accumulation of radioactivity. Rarely focal areas of increased activity are depicted; most are related to altered vascular dynamics in the liver secondary to obstruction of the superior or inferior vena cava or the hepatic veins. There are reports of single cases of focally increased activity due to a hepatic hemangioma, hepatic venoocclusive disease, herniation of a part of the liver, and a liver hot spot found after radiocolloid injection via a malpositioned central venous catheter in one of the hepatic vein branches. In patients with focal nodular hyperplasia, liver scans with solitary defects as well as normal patterns are found. In some cases, increased uptake of colloid in the lesion has been documented. Pasquier and Dorta reported a patient with a palpable mass in the left liver lobe with increased accumulation of radioactivity on the radiocolloid liver scan. The histologic diagnosis was hamartoma, but reviewing the description and considering the confusion in the past concerning the nomenclature, this case is suggestive of focal nodular hyperplasia. We report a patient with focal nodular hyperplasia who had increased radiocolloid uptake in the lesion. The radionuclide studies are compared with angiography, sonography, and computed tomography. An explanation for the localized increased colloid accumulation based on histologic findings is suggested.

  10. The use of angiogenic and antiangiogenic factors in the differential diagnosis of pre-eclampsia, antiphospholipid syndrome nephropathy and lupus nephritis.

    PubMed

    de Jesus, G R; de Jesus, N R; Levy, R A; Klumb, E M

    2014-10-01

    Pre-eclampsia (PE) is a major cause of maternal mortality and morbidity, perinatal deaths, preterm birth and intrauterine growth restriction. Differential diagnosis with antiphospholipid syndrome (APS) nephropathy and systemic lupus erythematosus (SLE) nephritis during pregnancy is difficult, if not sometimes impossible, as all three diseases may present hypertension and proteinuria. Improvement in diagnosis of PE has also offered new paths for differential diagnosis with other conditions and the analysis of angiogenic (vascular endothelial growth factor, placental growth factor) and antiangiogenic factors (serum soluble fms-like tyrosine kinase 1, soluble endoglin) is promising for differentiation between PE, APS nephropathy and SLE nephritis. This article reviews published studies about those factors in non-pregnant and pregnant patients with APS and SLE, comparing with patterns described in PE.

  11. Association of Acute Interstitial Nephritis with Carnivora, a Venus Flytrap Extract, in a 30-Year-Old Man with Hodgkin's Lymphoma

    PubMed Central

    Ziolkowski, Susan; Moore, Catherine

    2014-01-01

    Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and has been associated with a variety of medications. This is the case of 30-year-old man with Hodgkin's lymphoma who on routine labs before chemotherapy was found to have acute nonoliguric renal failure. A kidney biopsy was performed and confirmed the diagnosis of acute interstitial nephritis. The patient had taken several medications including a higher dose of Carnivora, a Venus flytrap extract, composed of numerous amino acids. The medication was discontinued and kidney function improved towards the patient's baseline indicating that this may be the possible cause of his AIN. Proximal tubular cell uptake of amino acids increasing transcription of nuclear factor-kappaB is a proposed mechanism of AIN from this compound. PMID:24839571

  12. Clinical Presentation of Tubulointerstitial Nephritis Caused by Amyloid Light-chain Amyloidosis in a Patient with Sjögren's Syndrome

    PubMed Central

    Inoue, Reiko; Fujigaki, Yoshihide; Kobayashi, Kana; Tamura, Yoshifuru; Ota, Tatsuru; Shibata, Shigeru; Ishida, Tsuyoshi; Kondo, Fukuo; Yamaguchi, Yutaka; Uchida, Shunya

    2017-01-01

    We report a 70-year-old woman with Sjögren's syndrome who had severe renal dysfunction with mild proteinuria and elevated urinary low-molecular-weight proteins. Based on these clinical presentations, interstitial nephritis due to Sjögren's syndrome was strongly suspected. Unexpectedly, renal pathology revealed amyloid light-chain (AL) lambda-type depositions predominantly in the vasculatures with severe tubulointerstitial damage. Concentrated urine immunofixation was positive for Bence Jones lambda-type monoclonal proteins. Given the involvement in other organs, systemic AL amyloidosis was diagnosed. The patient underwent chemotherapy, but hemodialysis was ultimately instituted. It should be remembered that renal amyloidosis occurs as a clinical presentation of interstitial nephritis. PMID:28202864

  13. Serial kinetics of the antibody response against the complete Brucella melitensis ORFeome in focal vertebral brucellosis.

    PubMed

    Cannella, Anthony P; Lin, Jennifer C; Liang, Li; Atluri, Vidya; Gotuzzo, Eduardo; Felgner, Philip L; Tsolis, Renee M; Vinetz, Joseph M

    2012-03-01

    Human brucellosis is a common zoonosis worldwide. Here we present a case of focal vertebral brucellosis in a 71-year-old Mexican-American woman who contracted infection from unpasteurized goat milk. Standard agglutination serology was negative; the diagnosis was established by the isolation of Brucella melitensis from abscess fluid. A B. melitensis protein microarray comprised of nearly all proteins encoded by the bacterial genome was used to determine the kinetics of this patient's antibody responses to the complete collection of open reading frames existing in the genome (ORFeome). Three patterns of antibody responses against B. melitensis antigens were seen for serum samples obtained on days 0 (pretreatment), 14, 49, 100, and 180: (i) stable titers over time, (ii) a steady fall in titers, and (iii) an initial rise in titers followed by declining titers. Sera from this patient with chronic brucellosis recognized some of the same B. melitensis proteins as those recognized by sera from acute/subacute, blood culture-positive brucellosis patients but also recognized a distinct set of proteins. This study is the first to determine the kinetics of the human antibody responses to the complete repertoire of proteins encoded by a bacterial genome and demonstrates fundamentally different immunopathogenetic mechanisms between acute human brucellosis and chronic human brucellosis. While an extension of these findings to a larger patient population is necessary, these findings have important clinical and diagnostic implications and lead toward new insights into the fundamental immunopathogenesis of brucellosis.

  14. Focal depth measurement of scanning helium ion microscope

    SciTech Connect

    Guo, Hongxuan; Itoh, Hiroshi; Wang, Chunmei; Zhang, Han; Fujita, Daisuke

    2014-07-14

    When facing the challenges of critical dimension measurement of complicated nanostructures, such as of the three dimension integrated circuit, characterization of the focal depth of microscopes is important. In this Letter, we developed a method for characterizing the focal depth of a scanning helium ion microscope (HIM) by using an atomic force microscope tip characterizer (ATC). The ATC was tilted in a sample chamber at an angle to the scanning plan. Secondary electron images (SEIs) were obtained at different positions of the ATC. The edge resolution of the SEIs shows the nominal diameters of the helium ion beam at different focal levels. With this method, the nominal shapes of the helium ion beams were obtained with different apertures. Our results show that a small aperture is necessary to get a high spatial resolution and high depth of field images with HIM. This work provides a method for characterizing and improving the performance of HIM.

  15. Bilaterally symmetric focal cortical dysplasia in a golden retriever dog.

    PubMed

    Casey, K M; Bollen, A W; Winger, K M; Vernau, K M; Dickinson, P J; Higgins, R J; Sisó, S

    2014-11-01

    A 10-year-old golden retriever dog was referred with a 24-h history of generalized seizures. Magnetic resonance imaging of the brain found no abnormalities on 3 mm transverse sections and the dog was subsequently humanely destroyed. Microscopically there was bilaterally symmetrical focal disorganization of cortical grey matter within the tips of the right and left suprasylvian gyri of the temporal cortex. The focal abnormal cortical lamination was characterized by loss of pyramidal neurons with abnormal, irregular, angular, remaining neurons occasionally forming clusters, surrounded by fibrillary astrogliosis and microgliosis and vascular proliferation. These histological findings are consistent with focal cortical dysplasia, a cerebral cortical malformation that causes seizures in people, but not reported previously in the dog.

  16. Experimental characterization of extra-focal radiation in CT scanners

    NASA Astrophysics Data System (ADS)

    Whiting, Bruce R.; Porras-Chaverri, Mariela A.; Evans, Joshua D.; Williamson, Jeffrey F.

    2016-03-01

    Quantitative computed tomography (CT) applications based on statistical iterative reconstruction algorithms require accurate models of the CT acquisition process, with a key component being the x-ray fan beam intensity. We present a method to experimentally determine the extra-focal radiation profile incident on individual CT detectors. Using a tungsten cylinder as a knife edge, a super-sampled signal was created from sinogram data, which traced the "occlusion" of the x-ray source as seen by a detector. By differentiating this signal and correcting for finite detector size and motion blur, the effective source profile can be recovered. Extra-focal scatter was found to be on the order of 1-3 percent of the focal beam intensity, with lower relative magnitude at the isocenter and increasing towards the edge of the fan beam, with its profile becoming asymmetric at large angles. The implications for reconstruction algorithms and QCT applications will be discussed.

  17. LiteBIRD: Mission Overview and Focal Plane Layout

    NASA Astrophysics Data System (ADS)

    Matsumura, T.; Akiba, Y.; Arnold, K.; Borrill, J.; Chendra, R.; Chinone, Y.; Cukierman, A.; de Haan, T.; Dobbs, M.; Dominjon, A.; Elleflot, T.; Errard, J.; Fujino, T.; Fuke, H.; Goeckner-wald, N.; Halverson, N.; Harvey, P.; Hasegawa, M.; Hattori, K.; Hattori, M.; Hazumi, M.; Hill, C.; Hilton, G.; Holzapfel, W.; Hori, Y.; Hubmayr, J.; Ichiki, K.; Inatani, J.; Inoue, M.; Inoue, Y.; Irie, F.; Irwin, K.; Ishino, H.; Ishitsuka, H.; Jeong, O.; Karatsu, K.; Kashima, S.; Katayama, N.; Kawano, I.; Keating, B.; Kibayashi, A.; Kibe, Y.; Kida, Y.; Kimura, K.; Kimura, N.; Kohri, K.; Komatsu, E.; Kuo, C. L.; Kuromiya, S.; Kusaka, A.; Lee, A.; Linder, E.; Matsuhara, H.; Matsuoka, S.; Matsuura, S.; Mima, S.; Mitsuda, K.; Mizukami, K.; Morii, H.; Morishima, T.; Nagai, M.; Nagasaki, T.; Nagata, R.; Nakajima, M.; Nakamura, S.; Namikawa, T.; Naruse, M.; Natsume, K.; Nishibori, T.; Nishijo, K.; Nishino, H.; Nitta, T.; Noda, A.; Noguchi, T.; Ogawa, H.; Oguri, S.; Ohta, I. S.; Otani, C.; Okada, N.; Okamoto, A.; Okamoto, A.; Okamura, T.; Rebeiz, G.; Richards, P.; Sakai, S.; Sato, N.; Sato, Y.; Segawa, Y.; Sekiguchi, S.; Sekimoto, Y.; Sekine, M.; Seljak, U.; Sherwin, B.; Shinozaki, K.; Shu, S.; Stompor, R.; Sugai, H.; Sugita, H.; Suzuki, T.; Suzuki, A.; Tajima, O.; Takada, S.; Takakura, S.; Takano, K.; Takei, Y.; Tomaru, T.; Tomita, N.; Turin, P.; Utsunomiya, S.; Uzawa, Y.; Wada, T.; Watanabe, H.; Westbrook, B.; Whitehorn, N.; Yamada, Y.; Yamasaki, N.; Yamashita, T.; Yoshida, M.; Yoshida, T.; Yotsumoto, Y.

    2016-08-01

    LiteBIRD is a proposed CMB polarization satellite project to probe the inflationary B-mode signal. The satellite is designed to measure the tensor-to-scalar ratio with a 68 % confidence level uncertainty of σ _r<10^{-3}, including statistical, instrumental systematic, and foreground uncertainties. LiteBIRD will observe the full sky from the second Lagrange point for 3 years. We have a focal plane layout for observing frequency coverage that spans 40-402 GHz to characterize the galactic foregrounds. We have two detector candidates, transition-edge sensor bolometers and microwave kinetic inductance detectors. In both cases, a telecentric focal plane consists of approximately 2× 10^3 superconducting detectors. We will present the mission overview of LiteBIRD, the project status, and the TES focal plane layout.

  18. Emerging concepts regarding B cells and autoantibodies in murine lupus nephritis. B cells have multiple roles; all autoantibodies are not equal.

    PubMed

    Madaio, M P; Shlomchik, M J

    1996-03-01

    Despite observations linking the severity of lupus nephritis to the quantity and location of glomerular immune deposits, it had been difficult to decipher the primary role of B cells and autoantibodies in this process. Newer technologies have provided the means to evaluate the roles of whole B cell populations and individual immunoglobulins in lupus lesions. In this review, recent advances in this area are summarized, with particular emphasis on work from the authors' laboratories. The results implicate a primary role for B cells and immunoglobulins in lupus nephritis, including glomerular, interstitial, and vascular lesions. Multiple antibody-ligand interactions participate in glomerular immune deposit formation in individuals with lupus nephritis. Recent evidence suggests that in situ formation of immune deposits by either cross-reactivity of autoantibodies with intrinsic glomerular antigens (i.e., anti-DNA antibodies with laminin) or direct interaction of autoantibodies with circulating autoantigens lodged within glomeruli (i.e., anti-DNA antibodies with histone/DNA). The predominant autoantibody-glomerular antigen interaction(s) in a given individual influences the principal location of immune deposition, which in turn influences the pathologic and clinical expression of disease. It is believed that these phenomena contribute to the phenotypic diversity commonly observed among individuals with lupus nephritis. Furthermore, these consequences are dependent on properties unique to both subsets of lupus autoantibodies and to their target antigen ligands within the glomerulus. Thus, the autoantibody variable or antigen binding region, along with the nature and location of the target glomerular antigen (or site of circulating antigen deposition), are influential in initiating these perturbations.

  19. Contractility Modulates Cell Adhesion Strengthening Through Focal Adhesion Kinase and Assembly of Vinculin-Containing Focal Adhesions

    PubMed Central

    Dumbauld, David W.; Shin, Heungsoo; Gallant, Nathan D.; Michael, Kristin E.; Radhakrishna, Harish; García, Andrés J.

    2010-01-01

    Actin-myosin contractility modulates focal adhesion assembly, stress fiber formation, and cell migration. We analyzed the contributions of contractility to fibroblast adhesion strengthening using a hydrodynamic adhesion assay and micropatterned substrates to control cell shape and adhesive area. Serum addition resulted in adhesion strengthening to levels 30–40% higher than serum-free cultures. Inhibition of myosin light chain kinase or Rho-kinase blocked phosphorylation of myosin light chain to similar extents and eliminated the serum-induced enhancements in strengthening. Blebbistatin-induced inhibition of myosin II reduced serum-induced adhesion strength to similar levels as those obtained by blocking myosin light chain phosphorylation. Reductions in adhesion strengthening by inhibitors of contractility correlated with loss of vinculin and talin from focal adhesions without changes in integrin binding. In vinculin-null cells, inhibition of contractility did not alter adhesive force, whereas controls displayed a 20% reduction in adhesion strength, indicating that the effects of contractility on adhesive force are vinculin-dependent. Furthermore, in cells expressing FAK, inhibitors of contractility reduced serum-induced adhesion strengthening as well as eliminated focal adhesion assembly. In contrast, in the absence of FAK, these inhibitors did not alter adhesion strength or focal adhesion assembly. These results indicate that contractility modulates adhesion strengthening via FAK-dependent, vinculin-containing focal adhesion assembly. PMID:20205236

  20. Focal therapy in prostate cancer: the current situation

    PubMed Central

    Jácome-Pita, FX; Sánchez-Salas, R; Barret, E; Amaruch, N; Gonzalez-Enguita, C; Cathelineau, X

    2014-01-01

    Prostate cancer is one of the most significant pathologies in the field of urology. The adoption of screening strategies and improvements in biopsies have resulted in an increase in early-stage tumour detection. Radical global therapies provide very good oncological results in localised prostate cancer. However, excess treatment in low- and, in some cases, intermediate-risk groups affects the quality of life of these patients. In the case of localised prostate cancer, focal therapies offer a minimally invasive option with good results with respect to established treatments. Although this is currently not a standard treatment, it represents the therapeutic approach with the greatest potential. This literature review has the following objectives: to define selection criteria for patients who are candidates for focal therapy, to assess the current situation and results of the different therapeutic options, and to define procedures in cases of recurrence and for follow-ups. We concluded that focal therapy is a viable therapeutic alternative for localised prostate cancer, specifically cryosurgery and high-intensity targeted ultrasound, which have acceptable oncologic results and a lower comorbidity compared with global treatments. Studies with a high level of scientific evidence are still needed to validate these results. Acquisition of evidence A search was carried out on the Medline (PubMed), EMBASE, Web of Science and Cochrane databases of all papers published before 31 July 2013. We included clinical studies and literature reviews that evaluated primary focal therapy for prostate cancer confirmed by biopsy and excluded focal rescue therapy studies. The keywords used were focal therapy and prostate cancer. Initially, we found 42 articles; 15 studies were excluded because they did not meet the minimum criteria for inclusion. A total of 1350 cases were treated throughout 27 studies. PMID:24944577

  1. Preliminary Oklahoma Optimal Fault Orientations Determined by Focal Mechanism Solutions

    NASA Astrophysics Data System (ADS)

    Darold, A. P.; Holland, A. A.

    2015-12-01

    Six hundred and eighty-eight focal mechanisms were calculated between 2010 and 2015 and used to determine optimally oriented fault orientations within the contemporary stress field in Oklahoma. The contemporary stress, maximum horizontal stress (shmax) orientation of N85°E, is determined from the orientation of the P- and T-axes of the 688 focal mechanisms used. The majority of the focal mechanism solutions were computed using earthquakes occurring in central and north-central Oklahoma, a region where the greatest numbers of recent earthquakes have occurred. The focal mechanisms used in this compilation include Regional Moment Tensor solutions and first-motion focal mechanisms. We determined a mean shmax of 83.2° with a standard deviation of 21.3° azimuth. The median shmax is 84.8° with 633 observations. From the probability density functions, it is possible to define orientations of optimal, moderately optimal and sub-optimal fault strikes. The focal mechanism distribution is dominated by strike-slip motion on steeply dipping faults and thus fault strike is restricted to the range of 0° to 180°. Optimal fault strike orientation ranges between 45°-60°, 105°-120° and 135°-150° and represent fault orientations most likely for failure. Moderately optimal fault strike orientation ranges between 15°-45°, 60°-75°, 90°-105° and 120°-135° and represent fault orientations moderately likely for failure. All other orientations of fault strike are sub-optimal orientations and have a low likelihood of failure. These results do not indicate that failure cannot occur on sub-optimal fault strikes, but suggest that they are less likely. We apply these results to the most comprehensive Oklahoma fault map to date. Identifying optimal fault orientations is important for determining the potential earthquake hazard of both naturally occurring and triggered seismicity.

  2. Vimentin in Bacterial Infections

    PubMed Central

    Mak, Tim N.; Brüggemann, Holger

    2016-01-01

    Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection. PMID:27096872

  3. Determination of long focal length of lenses with Talbot interferometer

    NASA Astrophysics Data System (ADS)

    Jin, Xiaorong; Yu, Honglei; Bai, Jian; Hou, Xiyun

    2012-10-01

    In this paper, a method for high-accuracy determination of long focal length based on Talbot interferometer is presented. Through changing the angle between two gratings, systematic errors are reduced effectively by calibration. The collimation of the light is determined by a standard concave mirror. The experimental results reveal that the relative error is 0.1%, and the repeatability is better than 0.1%. As the method is simple and somewhat insensitive to environmental effects, it is especially useful for measuring long focal-length lenses.

  4. Magnetic-resonance-guided biopsy of focal liver lesions.

    PubMed

    Smith, Ethan A; Grove, Jason J; Van Der Spek, Abraham F L; Jarboe, Marcus D

    2017-03-03

    Image-guided biopsy techniques are widely used in clinical practice. Commonly used methods employ either ultrasound (US) or computed tomography (CT) for image guidance. In certain patients, US or CT guidance may be suboptimal, or even impossible, because of artifacts, suboptimal lesion visualization, or both. We recently began performing magnetic resonance (MR)-guided biopsy of focal liver lesions in select pediatric patients with lesions that are not well visualized by US or CT. This report describes our experience performing MR-guided biopsy of focal liver lesions, with case examples to illustrate innovative techniques and novel aspects of these procedures.

  5. Oral focal epithelial hyperplasia: report of five cases.

    PubMed

    Borborema-Santos, Cristina Maria; Castro, Maria Marta de; Santos, Paulo José Benevides dos; Talhari, Sinésio; Astolfi-Filho, Spartaco

    2006-01-01

    Focal epithelial hyperplasia or Heck's disease is a rare contagious disease caused by human papillomavirus types 13 or 32, initially described among Native American populations. This condition is characterized by the occurrence of multiple small papules or nodules in oral cavity, especially on labial and buccal mucosa and tongue. This report describes the diagnosis of focal epithelial hyperplasia in five Central Amazonian Indians who sought treatment at the Amazonas State Foundation of Tropical Medicine (FMT-AM), using clinical criteria, polymerase chain reaction (PCR) and DNA sequencing.

  6. Wavelet Transform of Fixed Pattern Noise in Focal Plane Arrays

    DTIC Science & Technology

    1994-02-01

    AD-A276 963 1111111111 I NAWCWPNS TP 8185 Wavelet Transform of Fixed Pattern Noise in Focal Plane Arrays OTIC by ELECTE Dr. Gary Hewer MAR 151994 and...REPORT TYPE AND DATES COVERED IFebruary 1994 Final; 199 ,L TTLE ND SBTILE LFUNDNG UBER Wavelet Transform of Fixed Pattern Noise in Focal Plane Arrays...nonlinearity 71,(w) = sgn(w)(IwI-t). with threshold t to each empirical sample value w in the wavelet transform d scales. After thresholding the wavelet

  7. Differences in the occurrence of hypertension among (NZB X NZW)F1, MRL-lpr, and BXSB mice with lupus nephritis.

    PubMed

    Rudofsky, U H; Dilwith, R L; Roths, J B; Lawrence, D A; Kelley, V E; Magro, A M

    1984-07-01

    Lupus-prone (NZB X NZW)F1 (B X W) mice and MRL-lpr and BXSB mice were examined for the prevalence of hypertension and levels of plasma renin activity (PRA). Hypertension (greater than 145 mmHg) was observed only in female and male B X W mice with severe nephritis; in female MRL-lpr and male BXSB mice severe nephritis developed without blood pressure elevation (80-135 mmHg). The B X W parental strains, NZB and NZW, and the MRL-lpr congenic partners, MRL- +, did not become hypertensive as they aged. Other strains of mice, aged 3-32 months (A/HeN, BALB/cJ, BALB/cByJ, B10.S/Sg, B10.D2/ oSn , CBA/J, C3H/HeJ, SJL/J and [SJL X NZW]F1), also had normal blood pressure (98-122 mmHg). All mice with lupus nephritis had low PRA, even those with hypertension; furthermore, the MRL-lpr strain had low or undetectable PRA (2 +/- 1 ng/ml/hr), even when kidneys were normal. NZB, NZW, and MRL- + mice had normal PRA (10-16 ng/ml/hr). Thus, B X W mice frequently developed low renin hypertension during the last phase of their renal disease; whereas MRL-lpr and BXSB mice died from renal disease without observable increases in blood pressure.

  8. Septins and Bacterial Infection

    PubMed Central

    Torraca, Vincenzo; Mostowy, Serge

    2016-01-01

    Septins, a unique cytoskeletal component associated with cellular membranes, are increasingly recognized as having important roles in host defense against bacterial infection. A role for septins during invasion of Listeria monocytogenes into host cells was first proposed in 2002. Since then, work has shown that septins assemble in response to a wide variety of invasive bacterial pathogens, and septin assemblies can have different roles during the bacterial infection process. Here we review the interplay between septins and bacterial pathogens, highlighting septins as a structural determinant of host defense. We also discuss how investigation of septin assembly in response to bacterial infection can yield insight into basic cellular processes including phagocytosis, autophagy, and mitochondrial dynamics. PMID:27891501

  9. Treatment of patients with systemic lupus erythematosus including nephritis with chlorambucil.

    PubMed

    Snaith, M L; Holt, J M; Oliver, D O; Dunnill, M S; Halley, W; Stephenson, A C

    1973-04-28

    Six female patients with systemic lupus erythematosus (S.L.E.) have been treated with chlorambucil. In five the decision was taken after failure by corticosteroids to control progressive renal disease in the face of unacceptable corticosteroid toxicity. After the introduction of chlorambucil renal function improved and all patients remain well six, six, five, three, and two-and-a-half years later, respectively. On renal biopsy five had focal proliferative glomerulonephritis. Repeat biopsy in two cases showed quantitative improvement. The sixth patient was treated with chlorambucil because of failure by corticosteroids to control peripheral vascular lesions and haemolysis and she remains well four years later. In four patients is it probable that amenorrhoea was related to chlorambucil treatment, but there were no other important side effects although one patient developed a degree of marrow depression during treatment. Chlorambucil may hold advantages over the immunosuppressive drugs normally recommended in this condition, azathioprine and cyclophosphamide, as it appears less liable to cause important marrow suppression and, unlike cyclophosphamide is not associated with alopecia and haemorrhagic cystitis.

  10. ABC transporters: bacterial exporters.

    PubMed Central

    Fath, M J; Kolter, R

    1993-01-01

    The ABC transporters (also called traffic ATPases) make up a large superfamily of proteins which share a common function and a common ATP-binding domain. ABC transporters are classified into three major groups: bacterial importers (the periplasmic permeases), eukaryotic transporters, and bacterial exporters. We present a comprehensive review of the bacterial ABC exporter group, which currently includes over 40 systems. The bacterial ABC exporter systems are functionally subdivided on the basis of the type of substrate that each translocates. We describe three main groups: protein exporters, peptide exporters, and systems that transport nonprotein substrates. Prototype exporters from each group are described in detail to illustrate our current understanding of this protein family. The prototype systems include the alpha-hemolysin, colicin V, and capsular polysaccharide exporters from Escherichia coli, the protease exporter from Erwinia chrysanthemi, and the glucan exporters from Agrobacterium tumefaciens and Rhizobium meliloti. Phylogenetic analysis of the ATP-binding domains from 29 bacterial ABC exporters indicates that the bacterial ABC exporters can be divided into two primary branches. One branch contains the transport systems where the ATP-binding domain and the membrane-spanning domain are present on the same polypeptide, and the other branch contains the systems where these domains are found on separate polypeptides. Differences in substrate specificity do not correlate with evolutionary relatedness. A complete survey of the known and putative bacterial ABC exporters is included at the end of the review. PMID:8302219

  11. Focal length evaluation by inverse ray-tracing Ronchi test

    NASA Astrophysics Data System (ADS)

    Juarez-Salazar, Rigoberto; Diaz-Gonzalez, Gerardo; Robledo-Sánchez, Carlos

    2016-09-01

    A simple method to evaluate the focal length of concave mirrors is proposed. The inverse ray-tracing approach of the Ronchi test is used in the measurement stage. The theoretical principles are given and a numerical method for ronchigram processing is proposed. The results verify the feasibility of the proposal.

  12. [Focal epithelial hyperplasia (Heck's disease) in a Turkish family].

    PubMed

    Weidner, F

    1996-12-01

    A 31-year-old Turkish patient and some family members suffered from multiple hyperplastic oral mucosal papules. Intralesional papilloma virus was not found but the patient had elevated levels of CD8 lymphocytes in his peripheral blood. We diagnosed focal epithelial hyperplasia of Heck.

  13. Focal epithelial hyperplasia (Heck disease) associated with AIDS.

    PubMed

    Viraben, R; Aquilina, C; Brousset, P; Bazex, J

    1996-01-01

    Focal epithelial hyperplasia (FEH) of the oral mucosa occurring in a HIV-infected man is described. Molecular biology disclosed an HPV-32 type in oral lesions. The association of FEH and AIDS is uncommon although many HPV subtypes may manifest during HIV infection.

  14. Extra focal convective suppressing solar collector. Final technical progress report

    SciTech Connect

    1996-05-01

    This progress report describes work done on the Extra Focal Convective Suppressing Solar Collector. The topics of the report include sensor refinement for the tracking electronics, tracking controller refinement, system optics evaluation, absorber system material evaluation and performance, tracking hardware evaluation and refinement, and full scale prototype construction and testing.

  15. The Focal Surface of the JEM-EUSO Telescope

    NASA Technical Reports Server (NTRS)

    Kawasaki, Yoshiya

    2007-01-01

    Extreme Universe Space Observatory onboard JEM/EP (JEM-EUSO) is a space mission to study extremely high-energy cosmic rays. The JEM-EUSO instrument is a wide-angle refractive telescope in near-ultraviolet wavelength region to observe time-resolved atmospheric fluorescence images of the extensive air showers from the International Space Station. The focal surface is a spherical curved surface, and its area amounts to about 4.5 square m. The focal surface detector is covered with about 6,000 multi-anode photomultipliers (MAPMTs). The focal surface detector consists of Photo-Detector-Modules, each of which consists of 9 Elementary Cells (ECs). The EC contains 4 units of the MAPMTs. Therefore, about 1,500 ECs or about 160 PDMS are arranged on the whole of the focal surface of JEM- EUSO. The EC is a basic unit of the front-end electronics. The PDM is a, basic unit of the data acquisition system

  16. Prototype focal plane assembly for multispectral remote sensing

    SciTech Connect

    Rienstra, J.L.; Vampola, J.A.

    1995-09-01

    Sandia National Laboratories and several subsystem contractors are developing technologies applicable to multispectral remote sensing. A prototype multispectral sensor system is under development. The three major subsystems making up the prototype sensor are the focal plane assembly (FPA), the cryocooler, and the telescope. This paper covers the focal plane assembly, which is the basis of the sensor system. The focal plane assembly includes sensor chip assemblies, optical filters, and a vacuum enclosure with cold shielding The optical filters define 15 spectral bands in a range from 0.45 {mu}m to 10.7 {mu}m. All the linear arrays are mounted on a single motherboard and are designed to operate at 75 K. The four spectral bands covering the visible to near infrared have roughly 2400 pixels each, and the remaining 11 spectral bands have roughly 600 pixels each. The average total rate of multispectral data from the FPA is approximately 16.4 megapixels per second. The diverse requirements for the focal plane assembly make this a challenging, sensor to design and build.

  17. Chemical-genetic attenuation of focal neocortical seizures.

    PubMed

    Kätzel, Dennis; Nicholson, Elizabeth; Schorge, Stephanie; Walker, Matthew C; Kullmann, Dimitri M

    2014-05-27

    Focal epilepsy is commonly pharmacoresistant, and resective surgery is often contraindicated by proximity to eloquent cortex. Many patients have no effective treatment options. Gene therapy allows cell-type specific inhibition of neuronal excitability, but on-demand seizure suppression has only been achieved with optogenetics, which requires invasive light delivery. Here we test a combined chemical-genetic approach to achieve localized suppression of neuronal excitability in a seizure focus, using viral expression of the modified muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO). Systemic administration of CNO suppresses focal seizures evoked by two different chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure effect in a chronic model of focal neocortical epilepsy. Chemical-genetic seizure attenuation holds promise as a novel approach to treat intractable focal epilepsy while minimizing disruption of normal circuit function in untransduced brain regions or in the absence of the specific ligand.

  18. Therapeutic epilepsy research: from pharmacological rationale to focal adenosine augmentation

    PubMed Central

    Boison, Detlev; Stewart, Kerry-Ann

    2009-01-01

    Epilepsy is a common seizure disorder affecting approximately 70 million people worldwide. Current pharmacotherapy is neuron-centered, frequently accompanied by intolerable side-effects, and fails to be effective in about one third of patients. Therefore, new therapeutic concepts are needed. Recent research suggests an astrocytic basis of epilepsy, presenting the possibility of novel therapeutic targets. In particular, dysfunction of the astrocyte-controlled, endogenous, adenosine-based seizure control system of the brain is implicated in seizure generation. Thus, astrogliosis – a pathological hallmark of the epileptic brain – is associated with upregulation of the adenosine-removing enzyme adenosine kinase (ADK), resulting in focal adenosine deficiency. Both astrogliotic upregulation of ADK in epilepsy and transgenic overexpression of ADK are associated with seizures, and inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. These findings link adenosine deficiency with seizures and predict that adenosine augmentation therapies (AATs) will likely be effective in preventing seizures. Given the widespread systemic and central side effects of systemically administered AATs, focal AATs (i.e., limited to the astrogliotic lesion) are a necessity. This Commentary will discuss the pharmacological rationale for the development of focal AATs. Additionally, several AAT strategies will be discussed: (1) adenosine released from silk-based brain implants; (2) adenosine released from locally implanted encapsulated cells; (3) adenosine released from stem cell-derived brain implants; and (4) adenosine augmenting gene therapies. Finally, new developments and therapeutic challenges in using focal AATs for epilepsy therapy will critically be evaluated. PMID:19682439

  19. Quantum-Well Infrared Photodetector (QWIP) Focal Plane Assembly

    NASA Technical Reports Server (NTRS)

    Jhabvala, Murzy; Jhabvala, Christine A.; Ewin, Audrey J.; Hess, Larry A.; Hartmann, Thomas M.; La, Anh T.

    2012-01-01

    A paper describes the Thermal Infrared Sensor (TIRS), a QWIP-based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a far-infrared imager operating in the pushbroom mode with two IR channels: 10.8 and 12 microns. The focal plane will contain three 640x512 QWIP arrays mounted on a silicon substrate. The silicon substrate is a custom-fabricated carrier board with a single layer of aluminum interconnects. The general fabrication process starts with a 4-in. (approx.10-cm) diameter silicon wafer. The wafer is oxidized, a single substrate contact is etched, and aluminum is deposited, patterned, and alloyed. This technology development is aimed at incorporating three large-format infrared detecting arrays based on GaAs QWIP technology onto a common focal plane with precision alignment of all three arrays. This focal plane must survive the rigors of flight qualification and operate at a temperature of 43 K (-230 C) for five years while orbiting the Earth. The challenges presented include ensuring thermal compatibility among all the components, designing and building a compact, somewhat modular system and ensuring alignment to very tight levels. The multi-array focal plane integrated onto a single silicon substrate is a new application of both QWIP array development and silicon wafer scale integration. The Invar-based assembly has been tested to ensure thermal reliability.

  20. Spectrum of PORCN mutations in Focal Dermal Hypoplasia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...