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

PubMed

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

2014-09-01

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

Role of immunoflourescence in the diagnosis of glomerulonephritis.

PubMed

Nasir, Humaira; Chaudhry, Sarah; Raza, Wajiha; Moatasim, Ambreen; Mamoon, Nadira; Akhtar, Noreen

2012-03-01

To correlate the findings of immunoflorescence (IF) with morphology in renal biopsies of patients with glomerulonephritis (GN) of both primary and secondary nature. The cross-sectional analytical study was conducted at the Shifa International Hospital's Department of Pathology form March 2007 to August 2008, during which a total of 207 renal biopsies were done. Of them, the study included 92 cases which were diagnosed as primary or secondary glomerulonephritis under light microscope. Those cases were selected in which both light microscopy (LM) and immunoflorescence were done. Of the 92 patients, 79 (85.8%) were adults (> or = 19 years) and 13 (14%) were children (< 19 years). The mean age of adults was 36.44 +/- 11.55 (range 19-69 years) and that of the children was 10.54 +/- 3.85 years (range 4-18 years). immunoflorescence changed the morphologic diagnosis in 20 (21.73%) cases. The pattern of disease was: membranous glomerulonephritis in 24%, focal segmental glomerulosclerosis (FSGS) in 18.4%, mesangiocapillary glomerulonephritis in 2%, and minimal change disease (MCD) in 16% of the cases. Light microscopy alone can misdiagnose renal disease. This is especially important in cases of early stage membranous, IgA nephropathy (IgAN), Lupus nephritis and IgM nephropathy (IgMN), as these entities can only be diagnosed by correlating the microscopic, immunoflorescence findings and clinical details.

Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

PubMed

Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

2017-06-15

Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-level laser therapy improves crescentic glomerulonephritis in rats.

PubMed

Yamato, Masanori; Kaneda, Akira; Kataoka, Yosky

2013-07-01

Low-level laser therapy (LLLT) can reduce inflammation in a variety of clinical conditions, including trauma, postherpetic neuralgia, and rheumatoid arthritis. However, the effect of LLLT on internal organs has not been elucidated. The goal of the present study was to investigate the anti-inflammatory effect of daily external LLLT in an animal model of crescentic glomerulonephritis. Crescentic glomerulonephritis was induced in male Wister Kyoto rats by intravenous injection of antibody for glomerular basement membrane (GBM). The rats were irradiated with a low-reactive level diode laser with an infrared wavelength of 830 nm from the shaved skin surface once a day for 14 days (irradiation spot size on the skin surface, 2.27 cm(2); power intensity, 880 mW/cm(2); irradiation mode, continuous mode; irradiation time, 250 s; energy, 500 J; energy density, 220 J/cm(2)). After laser irradiation for 14 days, animals were killed, and the extent of inflammation was evaluated. Expression of gene for inflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α) was assessed by reverse transcription polymerase chain reaction. Crescent formation in glomeruli and infiltration of macrophages and lymphocytes were assessed by histochemical observation. Injection of anti-GBM antibody induced severe glomerulonephritis with crescent formation. Histological observations indicated that LLLT suppressed crescent formation and infiltration of ED1+ macrophages and CD8+ lymphocytes into the glomeruli. LLLT attenuated the levels of IL-1β and TNF-α messenger RNA in the renal cortex. Externally directed LLLT suppresses the activity of rat anti-GBM crescentic glomerulonephritis in rats. LLLT has the potential to be used for direct treatment of glomerulonephritis.

Proliferative glomerulonephritis with acute renal failure-a rare manifestation in seronegative rheumatoid arthritis.

PubMed

Dutta, P K; Khan, I H

2009-01-01

A 55 years old lady with advanced rheumatoid arthritis (RA) presented with severe acute renal failure with significant proteinuria preceded by fever for 14 days. She had no history of taking drugs usually responsible for glomerulonephritis, neither had she any clinico-biochemical evidence of peri-infectious glomerulonephritis. Acute interstitial nephritis (AIN) was excluded by absence of eosinophilia and eosinophils in urine. Renal biopsy reveled absence of amyloidosis and showed Focal segmental proliferative glomerulonephritis (FSGN). Patient was successfully managed with methyl-prednisolone followed by steroid and immunosuppressive and patient came over renal failure. So FSGN should be considered as one of the causes of acute renal failure in a patient with seronegative RA which may respond to immune-therapy like rapidly progressive glomerulonephritis.

Recorded ICR Overview Presentations

EPA Pesticide Factsheets

This presentation provides a brief overview of the applicability of the EPA’s Plywood and Composite Wood Products Information Collection Request, or “ICR,” for facilities that produce kiln‐dried lumber.

Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis.

PubMed

Guo, Ling; Luo, Shi; Du, Zhengwu; Zhou, Meiling; Li, Peiwen; Fu, Yao; Sun, Xun; Huang, Yuan; Zhang, Zhirong

2017-10-12

Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.Mesangial cell-mediated glomerulonephritis is a frequent cause of kidney disease. Here the authors show that celastrol loaded in albumin nanoparticles efficiently targets mesangial cells, and is effective in rat models.

[Outcome of rapidly progressive glomerulonephritis post-streptococcal disease in children].

PubMed

Jellouli, Manel; Maghraoui, Sondos; Abidi, Kamel; Hammi, Yosra; Goucha, Rim; Naija, Ouns; Zarrouk, Chokri; Gargah, Tahar

2015-11-01

Rapidly progressive glomerulonephritis is a rare form of postinfectious glomerulonephritis. The aim of this study was to describe the outcome of our patients with severe post-streptococcal glomerulonephritis. This retrospective study was conducted in the department of pediatrics in Charles-Nicolle Hospital during a period of 13 years (1997-2009). Twenty-seven children were identified. The mean age was 8.7 years. All patients presented renal failure at presentation. The mean serum creatinine at presentation was 376.9 μmol/L. Six patients presented nephrotic syndrome. Twenty-six children had renal biopsies. Renal biopsies showed crescents in 24 cases. Eighteen children received pulse dose of corticosteroids (66.6%) and 6 children (22%) received pulse dose of corticosteroids and cyclophosphamide. Eleven patients required dialysis. At last follow-up, 22 patients (81.5%) had normal kidney function, 2 had renal dysfunction and 3 reached end stage renal disease. The only significant determinant for renal survival was the supportive dialysis (P=0.015). Rapidly progressive glomerulonephritis is uncommon. There have been significant advancements in supportive, as well as specific therapy, but the outcome continues to be poor. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats.

PubMed

Togashi, Yuko; Imura, Naoko; Miyamoto, Yohei

2013-11-01

The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis. Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage. In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent. Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.

[Glomerulonephritis and vasculitis as causes of arterial hypertension].

PubMed

Eicken, Sibylle; Gugger, Mathias; Marti, Hans-Peter

2012-05-01

The various types of glomerulonephritis, including many forms of vasculitis, are responsible for about 15% of cases of end-stage renal disease (ESRD). Arterial hypertension represents a frequent finding in patients suffering from glomerulonephritis or vasculitis and hypertension also serves as an indicator for these severe types of diseases. In addition, there are symptoms and signs like hematuria, proteinuria and renal failure. Especially, rapidly progressive glomerulonephritis (RPGN) constitutes a medical emergency and must not be missed by treating physicians. This disease can either occur limited to the kidneys or in the context of a systemic inflammatory disorder, like a vasculitis. If left untreated, RPGN can lead to a necrotizing destruction of glomeruli causing irreversible kidney damage within several months or even weeks. With respect to the immunologically caused vasculitis, there are - depending upon the severity and type of organ involved - many clinical warning signs to be recognized, such as arterial hypertension, hemoptysis, arthalgias, muscle pain, palpable purpura, hematuria, proteinuria and renal failure. In addition, constitutional signs, such as fever and loss of body weight may occur concurrently. Investigations of glomerulonephritis or vasculitis must contain a careful and complete examination of family history and medications used by the respective patient. Thereafter, a thorough clinical examination must follow, including skin, joints and measurement of arterial blood pressure. In addition, a spectrum of laboratory analyses is required in blood, such as full blood screen, erythrocyte sedimentation rate, CRP, creatinine, urea and glucose, and in urine, including urinalysis looking for hematuria, red cell casts and proteinuria. Importantly, proteinuria needs to be quantified by the utilization of a random urine sample. Proteinuria > 3g/d is diagnostic for a glomerular damage. These basic tests are usually followed by more specialized analyses

Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis.

PubMed

Moeller, Marcus J; Soofi, Abdulsalaam; Hartmann, Inge; Le Hir, Michel; Wiggins, Roger; Kriz, Wilhelm; Holzman, Lawrence B

2004-01-01

Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin of glomerular crescents remains unresolved. A genetic cell lineage-mapping study with a novel transgenic mouse model was performed to investigate whether visceral glomerular epithelial cells, termed podocytes, are precursors of cells that populate cellular crescents. The podocyte-specific 2.5P-Cre mouse line was crossed with the ROSA26 reporter line, resulting in irreversible constitutive expression of beta-galactosidase in doubly transgenic 2.5P-Cre/ROSA26 mice. In these mice, crescentic glomerulonephritis was induced with a previously described rabbit anti-glomerular basement membrane antiserum nephritis approach. Interestingly, beta-galactosidase-positive cells derived from podocytes adhered to the parietal basement membrane and populated glomerular crescents during the early phases of cellular crescent formation, accounting for at least one-fourth of the total cell mass. In cellular crescents, the proliferation marker Ki-67 was expressed in beta-galactosidase-positive and beta-galactosidase-negative cells, indicating that both cell types contributed to the formation of cellular crescents through proliferation in situ. Podocyte-specific antigens, including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular crescents, suggesting that podocytes underwent profound phenotypic changes in this nephritis model.

Defining ICR-Mo, an intrinsic colistin resistance determinant from Moraxella osloensis.

PubMed

Wei, Wenhui; Srinivas, Swaminath; Lin, Jingxia; Tang, Zichen; Wang, Shihua; Ullah, Saif; Kota, Vishnu Goutham; Feng, Youjun

2018-05-14

Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella species are a putative reservoir for MCR-1/2 genetic determinants. Here, we report the functional definition of ICR-Mo from M. osloensis, a chromosomally encoded determinant of colistin resistance, in close relation to current MCR-1/2 family. ICR-Mo transmembrane protein was prepared and purified to homogeneity. Taken along with an in vitro enzymatic detection, MALDI-TOF mass spectrometry of bacterial lipid A pools determined that the ICR-Mo enzyme might exploit a possible "ping-pong" mechanism to accept the phosphoethanolamine (PEA) moiety from its donor phosphatidylethanolamine (PE) and then transfer it to the 1(or 4')-phosphate position of lipid A via an ICR-Mo-bound PEA adduct. Structural decoration of LPS-lipid A by ICR-Mo renders the recipient strain of E. coli resistant to polymyxin. Domain swapping assays indicate that the two domains of ICR-Mo cannot be functionally-exchanged with its counterparts in MCR-1/2 and EptA, validating its phylogenetic position in a distinct set of MCR-like genes. Structure-guided functional mapping of ICR-Mo reveals a PE lipid substrate recognizing cavity having a role in enzymatic catalysis and the resultant conference of antibiotic resistance. Expression of icr-Mo in E. coli significantly prevents the formation of reactive oxygen species (ROS) induced by colistin. Taken together, our results define a member of a group of intrinsic colistin resistance genes phylogenetically close to the MCR-1/2 family, highlighting the evolution of transferable colistin resistance.

Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice

PubMed Central

Kitching, A R; Huang, X R; Ruth, A-J; Tipping, P G; Holdsworth, S R

2002-01-01

The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in BALB/c mice. This strain of mice develops antibody and complement dependent glomerulonephritis under this protocol. Sensitized BALB/c mice developed high levels of circulating autologous antibody titres, intense glomerular deposition of mouse immunoglobulin and complement, significant proteinuria, renal impairment, significant glomerular necrosis and a minor component of crescent formation 10 days after challenge with a nephritogenic antigen (sheep anti-GBM globulin). Early treatment during the primary immune response, or continuous treatment throughout the disease with CTLA4-Fc, significantly suppressed mouse anti-sheep globulin antibody titres in serum, and immunoglobulin and complement deposition in glomeruli. The degree of glomerular necrosis was improved and proteinuria was reduced, particularly in the earlier stages of disease. Late treatment by CTLA4-Fc starting one day after challenge with sheep anti-mouse GBM did not affect antibody production and did not attenuate glomerulonephritis. The low level of crescent formation found in BALB/c mice developing glomerulonephritis was not prevented by the administration of CTLA4-Fc. These results demonstrate that CTLA4-Fc is of benefit in this model of glomerulonephritis by its capacity to attenuate antibody production, without affecting the minor degree of cell-mediated glomerular injury. PMID:12067297

Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice.

PubMed

Kitching, A R; Huang, X R; Ruth, A-J; Tipping, P G; Holdsworth, S R

2002-06-01

The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in BALB/c mice. This strain of mice develops antibody and complement dependent glomerulonephritis under this protocol. Sensitized BALB/c mice developed high levels of circulating autologous antibody titres, intense glomerular deposition of mouse immunoglobulin and complement, significant proteinuria, renal impairment, significant glomerular necrosis and a minor component of crescent formation 10 days after challenge with a nephritogenic antigen (sheep anti-GBM globulin). Early treatment during the primary immune response, or continuous treatment throughout the disease with CTLA4-Fc, significantly suppressed mouse anti-sheep globulin antibody titres in serum, and immunoglobulin and complement deposition in glomeruli. The degree of glomerular necrosis was improved and proteinuria was reduced, particularly in the earlier stages of disease. Late treatment by CTLA4-Fc starting one day after challenge with sheep anti-mouse GBM did not affect antibody production and did not attenuate glomerulonephritis. The low level of crescent formation found in BALB/c mice developing glomerulonephritis was not prevented by the administration of CTLA4-Fc. These results demonstrate that CTLA4-Fc is of benefit in this model of glomerulonephritis by its capacity to attenuate antibody production, without affecting the minor degree of cell-mediated glomerular injury.

Anti–LAMP-2 Antibodies Are Not Prevalent in Patients With Antineutrophil Cytoplasmic Autoantibody Glomerulonephritis

PubMed Central

Brown, Michael C.; Smith, Rex Neal; Badhwar, Anshul K.; Parente, Oscar; Chung, Hyun chul; O’Dell, Donna; Bunch; McGregor, JulieAnne G.; Hogan, Susan L.; Hu, Yichun; Yang, Jia-Jin; Berg, Elisabeth A.; Niles, John; Jennette, J. Charles; Preston, Gloria A.; Falk, Ronald J.

2012-01-01

Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti–LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti–LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti–LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti–proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti–LAMP-2 titers, respectively. There was no correlation between anti–LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti–LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti–LAMP-2 antibodies and ANCA glomerulonephritis. PMID:22021709

Application of the solid phase C1q and Raji cell radioimmune assays for the detection of circulating immune complexes in glomerulonephritis.

PubMed Central

Tung, K S; Woodroffe, A J; Ahlin, T D; Williams, R C; Wilson, C B

1978-01-01

The C1q solid phase and Raji cell radioimmune assays were used to determine the frequency of detectable circulating immune complexes in patients with glomerulonephritis. In this study, 46% of 56 patients with glomerulonephritis had evidence of circulating immune complexes. More important, circulating immune complexes were associated with some, but not other, types of glomerulonephritis. Thus, immune complexes were detected in lupus glomerulonephritis (9/9 patients), rapidly progressive glomerulonephritis (5/6 patients), and acute nephritis (5/6 patients), but not in IgA-IgG glomerulonephritis (0/7 patients), or membranous glomerulonephritis (0/8 patients). The Raji cell radioimmune assay and the C1q solid phase radioimmune assay showed concordance of 79% in the detection of circulating immune complexes. Serial determinations, in general, showed either persistence of a negative or positive result of conversion of positive to negative. PMID:659639

Psychometric properties of the Italian version of the Cognitive Reserve Scale (I-CRS).

PubMed

Altieri, Manuela; Siciliano, Mattia; Pappacena, Simona; Roldán-Tapia, María Dolores; Trojano, Luigi; Santangelo, Gabriella

2018-05-04

The original definition of cognitive reserve (CR) refers to the individual differences in cognitive performance after a brain damage or pathology. Several proxies were proposed to evaluate CR (education, occupational attainment, premorbid IQ, leisure activities). Recently, some scales were developed to measure CR taking into account several cognitively stimulating activities. The aim of this study is to adapt the Cognitive Reserve Scale (I-CRS) for the Italian population and to explore its psychometric properties. I-CRS was administered to 547 healthy participants, ranging from 18 to 89 years old, along with neuropsychological and behavioral scales to evaluate cognitive functioning, depressive symptoms, and apathy. Cronbach's α, corrected item-total correlations, and the inter-item correlation matrix were calculated to evaluate the psychometric properties of the scale. Linear regression analysis was performed to build a correction grid of the I-CRS according to demographic variables. Correlational analyses were performed to explore the relationships between I-CRS and neuropsychological and behavioral scales. We found that age, sex, and education influenced the I-CRS score. Young adults and adults obtained higher I-CRS scores than elderly adults; women and participants with high educational attainment scored higher on I-CRS than men and participants with low education. I-CRS score correlated poorly with cognitive and depression scale scores, but moderately with apathy scale scores. I-CRS showed good psychometric properties and seemed to be a useful tool to assess CR in every adult life stage. Moreover, our findings suggest that apathy rather than depressive symptoms may interfere with the building of CR across the lifespan.

Coexistence of Anti-Glomerular Basement Membrane Glomerulonephritis and Membranous Nephropathy in a Female Patient with Preserved Renal Function.

PubMed

Ogawara, Aoi; Harada, Makoto; Ichikawa, Tohru; Fujii, Kazuaki; Ehara, Takashi; Kobayashi, Mamoru

2017-12-01

Renal prognosis for anti-glomerular basement membrane (GBM) glomerulonephritis is poor. The greater the amount of anti-GBM antibody binding the antigen (type IV collagen of the glomerular basement membrane), the greater the number of crescents that develop in glomeruli, resulting in progression of renal impairment. Immunofluorescence staining reveals linear IgG depositions on glomerular capillary walls. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in middle-aged to elderly patients. Immune complex is deposited in the sub-epithelial space of the glomerulus resulting in the development of a membranous lesion. Immunofluorescence staining reveals granular IgG depositions on glomerular capillary walls. Coexisting anti-GBM glomerulonephritis and MN are rare and, here we report a case of coexisting anti-GBM glomerulonephritis and MN with preserved renal function. There are some cases of coexisting anti-GBM glomerulonephritis and MN do not show severely decreased renal function. A 76-year-old Japanese woman presented with nephrotic syndrome, microscopic hematuria, and was positive for anti-GBM antibody. Kidney biopsy revealed linear and granular IgG depositions in glomerular capillary walls, crescent formations, and electron-dense deposits in the sub-epithelial space. She was diagnosed with anti-GBM glomerulonephritis and MN. Steroid and cyclosporine therapy achieved complete remission, and kidney function was preserved. In conclusion, coexisting anti-GBM glomerulonephritis and MN can have preserved renal function. IgG subclass of deposited anti-GBM antibody may be associated with the severity of anti-GBM glomerulonephritis. In addition, in the case of nephrotic syndrome with hematuria, we should consider the possibility of coexisting anti-GBM glomerulonephritis and MN.

Annual tendency of research papers used ICR mice as experimental animals in biomedical research fields.

PubMed

Kim, Ji Eun; Nam, Jung Hoon; Cho, Joon Young; Kim, Kil Soo; Hwang, Dae Youn

2017-06-01

Institute of Cancer Research (ICR) mice have been widely used in various research fields including toxicology, oncology, pharmacology, and pharmaceutical product safety testing for decades. However, annual tendency of research papers involving ICR mice in various biomedical fields has not been previously analyzed. In this study, we examined the numbers of papers that used ICR mice as experimental animals in the social science, natural science, engineering, medicine-pharmacy, marine agriculture-fishery, and art-kinesiology fields by analyzing big data. Numbers of ICR mouse-used papers gradually increased from 1961 to 2014, but small decreases were observed in 2015 and 2016. The largest number of ICR-used papers were published in the medicine-pharmacy field, followed by natural science and art-kinesiology fields. There were no ICR mouse-used papers in other fields. Furthermore, ICR mice have been widely employed in cell biology studies within the natural science field as well as in biochemistry and pathology in the medicine-pharmacy field. Few ICR mouse-used papers were published in exercise biochemistry and exercise nutrition in the art-kinesiology field. Regardless in most fields, the total numbers of published papers involving ICR mice were higher in 2014 than in other years, although the numbers in some fields including dentistry, veterinary science, and dermatology were high in 2016. Taken together, the present study shows that various ICR stocks, including Korl:ICR mice, are widely employed as experimental animals in various biomedical research fields.

Annual tendency of research papers used ICR mice as experimental animals in biomedical research fields

PubMed Central

Kim, Ji Eun; Nam, Jung Hoon; Cho, Joon Young; Kim, Kil Soo

2017-01-01

Institute of Cancer Research (ICR) mice have been widely used in various research fields including toxicology, oncology, pharmacology, and pharmaceutical product safety testing for decades. However, annual tendency of research papers involving ICR mice in various biomedical fields has not been previously analyzed. In this study, we examined the numbers of papers that used ICR mice as experimental animals in the social science, natural science, engineering, medicine-pharmacy, marine agriculture-fishery, and art-kinesiology fields by analyzing big data. Numbers of ICR mouse-used papers gradually increased from 1961 to 2014, but small decreases were observed in 2015 and 2016. The largest number of ICR-used papers were published in the medicine-pharmacy field, followed by natural science and art-kinesiology fields. There were no ICR mouse-used papers in other fields. Furthermore, ICR mice have been widely employed in cell biology studies within the natural science field as well as in biochemistry and pathology in the medicine-pharmacy field. Few ICR mouse-used papers were published in exercise biochemistry and exercise nutrition in the art-kinesiology field. Regardless in most fields, the total numbers of published papers involving ICR mice were higher in 2014 than in other years, although the numbers in some fields including dentistry, veterinary science, and dermatology were high in 2016. Taken together, the present study shows that various ICR stocks, including Korl:ICR mice, are widely employed as experimental animals in various biomedical research fields. PMID:28747984

Acute postinfectious glomerulonephritis associated with scabies in the elderly: A case report.

PubMed

Wang, Di; Li, Li; Wei, Lei; Liu, Yingying; Sun, Shiren

2017-12-01

Acute postinfectious glomerulonephritis (GN) secondary to scabies were mainly documented as early as in 1980s, and in all these published cases no histopathological evidence of renal biopsy were reported regarding scabies and renal damage. The delay in scabies treatment can result in a greater risk of secondary bacterial infections that can become invasive and/or lead to severe post-infective complications such as post-streptococcal glomerulonephritis. In diagnostic procedures, the clinical presentation of scabies is often atypical especially in elderly people patients. However, early diagnosis is necessary to prevent disease progression. Here, we present a case of acute glomerulonephritis caused by scabies in a 79-year-old male patient who presented with papular rash, asthma, haematuria, proteinuria, hypertension and variable azotaemia. The aim is to provide more details of the clinical features and the histopathologic characteristics, and to increase the vigilance among physicians in patients with acute GN. Copyright © 2017 Elsevier B.V. All rights reserved.

78 FR 33409 - Proposed Information Collection Request; Comment Request; See Item Specific ICR Titles Provided...

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2013-06-04

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The role of Th1 and Th17 cells in glomerulonephritis.

PubMed

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

2015-04-01

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

Identification and Characterization of Human Proteoforms by Top-Down LC-21 Tesla FT-ICR Mass Spectrometry.

PubMed

Anderson, Lissa C; DeHart, Caroline J; Kaiser, Nathan K; Fellers, Ryan T; Smith, Donald F; Greer, Joseph B; LeDuc, Richard D; Blakney, Greg T; Thomas, Paul M; Kelleher, Neil L; Hendrickson, Christopher L

2017-02-03

Successful high-throughput characterization of intact proteins from complex biological samples by mass spectrometry requires instrumentation capable of high mass resolving power, mass accuracy, sensitivity, and spectral acquisition rate. These limitations often necessitate the performance of hundreds of LC-MS/MS experiments to obtain reasonable coverage of the targeted proteome, which is still typically limited to molecular weights below 30 kDa. The National High Magnetic Field Laboratory (NHMFL) recently installed a 21 T FT-ICR mass spectrometer, which is part of the NHMFL FT-ICR User Facility and available to all qualified users. Here we demonstrate top-down LC-21 T FT-ICR MS/MS of intact proteins derived from human colorectal cancer cell lysate. We identified a combined total of 684 unique protein entries observed as 3238 unique proteoforms at a 1% false discovery rate, based on rapid, data-dependent acquisition of collision-induced and electron-transfer dissociation tandem mass spectra from just 40 LC-MS/MS experiments. Our identifications included 372 proteoforms with molecular weights over 30 kDa detected at isotopic resolution, which substantially extends the accessible mass range for high-throughput top-down LC-MS/MS.

The spectrum of glomerulonephritis in saudi arabia: the results of the saudi registry.

PubMed

Huraib, S; Al Khader, A; Shaheen, F A; Abu Aisha, H; Souqiyyeh, M Z; Al Mohana, F; Soliman, M; Al Wakeel, J; Mitwalli, A; Al Mohaya, S; Said, R; Al Menawy, L; Sohaibani, M; Chan, N

2000-01-01

Only few studies regarding glomerulonephritis, with relatively small numbers of patients, have so far been published from different centers in Saudi Arabia, and have reported conflicting results regarding the patterns, even in the same city. The possible reasons for these differences include the small number of patients in the different studies, differences in the indications for renal biopsies, referral bias, geographical differences, and, sometimes, the non-availability of the necessary diagnostic facilities in the reporting centers. In order to overcome these problems, a registry for glomerulonephropathy was attempted in Saudi Arabia. Six large referral hospitals from different regions of Saudi Arabia participated in this registry. Biopsy reports and clinical information of 1294 renal biopsies were obtained. There were 782 renal biopsies due to glomerulonephritis (GN) accounting for 77.2% of the total biopsies. Five hundred eighty seven (72.6%) were primary glomerulonephritidis. Focal and segmental glomerulosclerosis (FSGS) (21.3%) and membrano-proliferative glomerulonephritis (MPGN) (20.7%) were the most common types found in the primary glomerulonephritidis. Membranous glomerulonephritis (MGN) was present in only 10.6% of the cases. IgA nephropathy was found in 6.5% of the cases. Of the secondary glomerulo-nephritides, systemic lupus erythematosus (SLE) was the most common indication for biopsy (57.0%) and amyloidosis was found in only 3.2% of the biopsies. In conclusion, FSGS and MPGN were the most common forms of primary glomerulonephritis in adult patients in Saudi Arabia. MGN was not as common as in the western world. SLE was the commonest cause of secondary GN. Amyloidosis was not as common as in other Arab countries. There is a need for more centers from Saudi Arabia to join this national GN registry. Similar registries can be established in different Arab countries, which all would, hopefully, lead to a Pan-Arab GN registry.

Central venous catheter infection-related glomerulonephritis under long-term parenteral nutrition: a report of two cases.

PubMed

Okada, Mari; Sato, Mai; Ogura, Masao; Kamei, Koichi; Matsuoka, Kentaro; Ito, Shuichi

2016-03-31

Advances in long-term parenteral nutrition via indwelling central venous catheter have improved the quality of life and mortality in patients with life-threatening gastrointestinal diseases complicated with severely impaired absorption. However, infection to central venous catheter is still a common and critical complication for such patients. We encountered two patients under long-term parenteral nutrition who developed glomerulonephritis associated with central venous catheter infection. Persistent bacterial infection in indwelling medical devices placed in the blood-stream such as a ventricular-atrial shunt is known to cause glomerulonephritis, a condition termed shunt nephritis. We reported the clinical manifestations, treatment and their pathological findings in the two patients with glomerulonephritis associated with central venous catheter infection. Both patients suffered from megacystis microcolon intestinal hypoperistalsis syndrome, a form of pseudo-Hirschsprung's disease. They had been receiving home parenteral nutrition via central venous catheter because of severe malabsorption. They presented proteinuria, hematuria, hypocomplementemia and positive PR3-antineutrophilic cytoplasmic antibody accompanied by Staphylococcus epidermidis infection in the central venous catheter. Their renal biopsy revealed membranoproliferative glomerulonephritis with positive C3 deposition. One of them recovered completely following the removal of catheter and administration of antibiotics, while another did not respond to the treatments. We then treated her with methylprednisolone pulse therapy followed by prednisolone. She responded well, and achieved complete remission. As central venous catheter infection-related glomerulonephritis has a similar etiology to shunt nephritis, removal of the catheter and administration of antibiotics is fundamental to the treatment. If a patient is resistant to such conventional therapy, additional steroid and/or immunosuppressive agent

The Clinical Spectrum of Renal Insufficiency During Acute Glomerulonephritis in the Adult

PubMed Central

Lemieux, Guy; Cuvelier, Amedee A.; Lefebvre, Rene

1967-01-01

Twenty-seven adults with acute poststreptococcal glomerulonephritis were divided into two groups according to the severity of reduction in renal function: (1) 14 patients with mild depression of renal function, and (2) 13 patients with more severe renal insufficiency. In the first group the outcome was favourable, with complete clinical recovery in 11 patients. Only two patients in the second group have recovered. Five have died of renal failure and in six the chronic stage has developed. The most notable histopathological lesion observed in this group of patients was severe proliferative glomerulonephritis with a large number of epithelial crescents. According to the mode of development and time of onset of renal failure, these 13 patients could be divided into three sub-groups: (1) early renal failure without oliguria (three patients), (2) early renal failure with severe oliguria or anuria (three patients) and (3) delayed renal failure (seven patients). Although there are exceptions, the development of renal insufficiency in an adult patient suffering from acute glomerulonephritis is usually associated with a guarded prognosis. ImagesFig. 2 PMID:6021561

Epidermal growth factor receptor inhibition with erlotinib ameliorates anti-Thy 1.1-induced experimental glomerulonephritis.

PubMed

Rintala, Jukka M; Savikko, Johanna; Rintala, Sini E; Palin, Niina; Koskinen, Petri K

2016-06-01

Mesangial proliferative glomerulonephritis is a common glomerular disorder that may lead to end-stage renal disease. Epidermal growth factor (EGF) plays an important role in the regulation of cell growth, proliferation, and differentiation and in the pathology of various renal diseases. Erlotinib is a novel, oral, highly selective tyrosine kinase inhibitor of the EGF receptor. It is clinically used to treat non-small cell lung and pancreatic cancers. Here, we investigated the effect of erlotinib on the progression of mesangioproliferative glomerulonephritis in an experimental model. Mesangial glomerulonephritis was induced with anti-rat Thy-1.1 antibody in male Wistar rats weighing 150-160 g. Rats were treated with erlotinib (10 mg/kg/day p.o.) or vehicle only (polyethylene glycol). Native Wistar rat kidneys were used as histological controls. Serum creatinine levels were measured at day 7. Kidneys were harvested 7 days after antibody administration for histology. Native controls showed no histological signs of glomerular pathology. In the vehicle group, intense glomerular inflammation developed after 7 days and prominent mesangial cell proliferation and glomerular matrix accumulation was seen. Erlotinib was well tolerated and there were no adverse effects during the follow-up period. Erlotinib significantly prevented progression of the glomerular inflammatory response and glomerular mesangial cell proliferation as well as matrix accumulation when compared with the vehicle group. Erlotinib also preserved renal function. These results indicate that erlotinib prevents the early events of experimental mesangial proliferative glomerulonephritis. Therefore, inhibition of the EGF receptor with erlotinib could prevent the progression of glomerulonephritis also in clinical nephrology.

[Determination of homeostatic kidney function in the diagnosis of chronic glomerulonephritis].

PubMed

Ratner, M J

1977-12-01

The latent and hypertonic forms of the course of compensated nephritides more frequently make difficulties concerning the differential diagnosis between a chronic glomerulonephritis and a chronic pyelonephritis. According to the results achieved the determination of the renal processes furthering homoeostasis gives the possibility to demarcate the two diseases. A certain reduction of the creatinine clearance (to less than 90 ml/min) and of the maximum water diuresis (to less than 10.0 per 100 ml glomerular filtrate) is suitable for the latent form of the chronic glomerulonephritis. On the other hand, a reduction of the ammonia secretion (to less than 35 per 100 ml glomerular (filtrate) and of the total H+-ion secretion (to less than 50 per 100 ml glomerular filtrate) in the determination after Alkinton is characteristic for the chronic pyelonephritis. In the hypertensive form of the course of the chronic glomerulonephritis in contrast to the same form in chronic pyelonephritis a reduction of the maximum water diuresis to less than 7.5, of the clearance of the "osmotically free" water to less than 6.0, of the titrable acidity to less than 25 is the result. Here the ammonia quotient transgresses 45%. In chronic pyelonephritis the titrable acidity in considerably increased and the ammonia genesis relatively decreased (to less than 45%).

Complex tissue-specific epigenotypes in Russell-Silver Syndrome associated with 11p15 ICR1 hypomethylation.

PubMed

Azzi, Salah; Blaise, Annick; Steunou, Virginie; Harbison, Madeleine D; Salem, Jennifer; Brioude, Frédéric; Rossignol, Sylvie; Habib, Walid Abi; Thibaud, Nathalie; Neves, Cristina Das; Jule, Marilyne Le; Brachet, Cécile; Heinrichs, Claudine; Bouc, Yves Le; Netchine, Irène

2014-10-01

Russell-Silver Syndrome (RSS) is a prenatal and postnatal growth retardation syndrome caused mainly by 11p15 ICR1 hypomethylation. Clinical presentation is heterogeneous in RSS patients with 11p15 ICR1 hypomethylation. We previously identified a subset of RSS patients with 11p15 ICR1 and multilocus hypomethylation. Here, we examine the relationships between IGF2 expression, 11p15 ICR1 methylation, and multilocus imprinting defects in various cell types from 39 RSS patients with 11p15 ICR1 hypomethylation in leukocyte DNA. 11p15 ICR1 hypomethylation was more pronounced in leukocytes than in buccal mucosa cells. Skin fibroblast IGF2 expression was correlated with the degree of ICR1 hypomethylation. Different tissue-specific multilocus methylation defects coexisted in 38% of cases, with some loci hypomethylated and others hypermethylated within the same cell type in some cases. Our new results suggest that tissue-specific epigenotypes may lead to clinical heterogeneity in RSS. © 2014 WILEY PERIODICALS, INC.

Histopathology of humorally mediated anti-glomerular basement membrane (GBM) glomerulonephritis in mice.

PubMed

Le Hir, Michel

2004-07-01

From a diagnostic point of view it would be important to learn more about the relationship between the immune responses underlying glomerulonephritis and the patterns of glomerular lesions. A murine model of anti-GBM glomerulonephritis in which inflammation is driven by delayed-type hypersensitivity (DTH) has been studied extensively. The aim of this study was to uncover histological features that might be specific for anti-GBM glomerulonephritis driven by a humoral immune response. BALB/c mice were immunized with rabbit IgG in incomplete Freund's adjuvant. Six days later, on day 0, they received rabbit anti-GBM serum intravenously. Proteinuria was assessed with dipsticks. Mice were killed on days 4, 8 or 14. Kidneys from days 4 and 8 were processed for immunofluorescence and histology. On day 14 mice were perfusion-fixed for electron microscopy. Proteinuria started on day 3. Autologous IgG and of C3 were found along the GBM. There was only slight infiltration with macrophages and no measurable infiltration by CD4 T cells, indicating the virtual absence of DTH. Besides infiltration with neutrophils there were little histological alterations on day 4. On day 8 many loops were hyalinized. On day 14, cellular crescents were found in 23% of glomeruli. Subendothelial spaces contained hyaline material, cells and fibrin. Podocytes displayed effacement of foot processes and apical microprotrusions. Podocyte bridges were common. These alterations were identical to those reported in the standard model that produces a DTH-like inflammation. The qualitative pattern of histological damage in a murine model of anti-GBM glomerulonephritis does not depend on the underlying immunological process.

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

PubMed

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

2009-11-01

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

Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis.

PubMed

Schneider, A; Harendza, S; Zahner, G; Jocks, T; Wenzel, U; Wolf, G; Thaiss, F; Helmchen, U; Stahl, R A

1999-02-01

Monocyte chemoattractant protein-1 (MCP-1) has been shown to play a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis. Whereas a number of inflammatory mediators have been characterized that are involved in the expression of MCP-1 in renal disease, little is known about repressors of chemokine formation in vivo. We hypothesized that cyclooxygenase (COX) products influence the formation of MCP-1 and affect inflammatory cell recruitment in glomerulonephritis. The effect of COX inhibitors was evaluated in the antithymocyte antibody model and an anti-glomerular basement membrane model of glomerulonephritis. Rats were treated with the COX-1/COX-2 inhibitor indomethacin and the selective COX-2 inhibitors meloxicam and SC 58125. Animals were studied at 1 hour, 24 hours, and 5 days after induction of the disease. Indomethacin, to a lesser degree the selective COX-2 inhibitors, enhanced glomerular MCP-1 and RANTES mRNA levels. Indomethacin enhanced glomerular monocyte chemoattractant activity an the infiltration of monocytes/macrophages at 24 hours and 5 days. Our studies demonstrate that COX products may serve as endogenous repressors of MCP-1 formation in experimental glomerulonephritis. The data suggest that COX-1 and COX-2 products mediate these effects differently because the selective COX-2 inhibitors had less influence on chemokine expression.

Membranoproliferative Glomerulonephritis and Persistent Hypocomplementaemia

PubMed Central

Cameron, J. S.; Glasgow, E. F.; Ogg, C. S.; White, R. H. R.

1970-01-01

The clinical, laboratory, and histological findings of 50 patients with membranoproliferative glomerulonephritis are described. Three-quarters of the patients, who were mostly older children and young adults, presented clinically with a mixture of “nephritic” and “nephrotic” symptoms; the remaining quarter had no symptoms and were diagnosed after the discovery of proteinuria and microscopic haematuria. Though this clinical picture may occur in other forms of glomerulonephritis, the patients described here were unified as a group by their glomerular morphological appearance—namely, a combination of mesangial proliferation and capillary wall thickening, mainly due to subendothelial accumulations of mesangial matrix. In 68% serum C3 (β10-globulin) levels were reduced initially, while a further 16% subsequently showed a fall to abnormally low levels. All patients had substantial proteinuria, usually of moderately impaired selectivity, and all but one had haematuria in addition. Children frequently presented with an illness resembling acute nephritis, whereas adults usually had a nephrotic syndrome from the start. In 31 patients, followed for periods of one to eight and a half years, serial measurements of glomerular filtration rate were made. Sixteen have experienced no deterioration of renal function, though their proteinuria continues unchanged. Fifteen have shown progressive deterioration; six of them are still well, six are on regular dialysis treatment, and three have died. Treatment with corticosteroids, azathioprine, or cyclophosphamide, alone or in combination, did not seem to influence the course of the disease, and another two patients died from complications of steroid therapy. The disease usually runs a chronic course and appears to be progressive. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:4097129

[A case of Grave's disease with MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) therapy following interstitial pneumonitis].

PubMed

Saeki, T; Miyamura, S; Nakano, M; Arakawa, M

1997-03-01

A 68-year-old man who developed MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) treatment is reported. In 1986, he was diagnosed as having interstitial pneumonitis. Although he tested positive for antinuclear antibody and rheumatoid factor, he had no symptoms and was followed up without therapy. Five years later, the diagnosis of Graves's disease was made after complaints of body weight loss, diplopia and exophthalmos. Tests showed positivity for anti-thyroid stimulating hormone (TSH) receptor antibody, antithyroidperoxidase antibody and antithyroglobulin antibody. He was treated with PTU and prednisolone for four years. In November 1995, hematuria and proteinuria developed, and renal function deteriorated rapidly. A renal biopsy revealed crescentic glomerulonephritis and the serum titer of MPO-ANCA was markedly elevated. He was treated with a high dose of prednisolone and cyclophosphamide. Although the serum creatinine level gradually decreased, irreversible renal dysfunction persisted. In this patient, the presence of various autoantibodies had been recognized for several years before MPO-ANCA-associated glomerulonephritis developed. Polyclonal B-cell activation and PTU treatment may have played a role in the pathogenesis of MPO-ANCA-associated glomerulonephritis.

Vacuum Ultraviolet Photodissociation and Fourier Transform-Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry: Revisited.

PubMed

Shaw, Jared B; Robinson, Errol W; Paša-Tolić, Ljiljana

2016-03-15

We revisited the implementation of 193 nm ultraviolet photodissociation (UVPD) within the ion cyclotron resonance (ICR) cell of a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer. UVPD performance characteristics were examined in the context of recent developments in the understanding of UVPD and in-cell tandem mass spectrometry. Efficient UVPD and photo-ECD of a model peptide and proteins within the ICR cell of a FT-ICR mass spectrometer are accomplished through appropriate modulation of laser pulse timing, relative to ion magnetron motion and the potential applied to an ion optical element upon which photons impinge. It is shown that UVPD yields efficient and extensive fragmentation, resulting in excellent sequence coverage for model peptide and protein cations.

Vacuum Ultraviolet Photodissociation and Fourier Transform–Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry: Revisited

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaw, Jared B.; Robinson, Errol W.; Pasa-Tolic, Ljiljana

2016-02-16

We revisited the implementation of UVPD within the ICR cell of a FT-ICR mass spectrometer. UVPD performance characteristics were examined in the context of recent developments in the understanding of UVPD and in-cell tandem mass spectrometry. Efficient UVPD and photo-ECD of a model peptide and small protein within the ICR cell of a FT-ICR mass spectrometer are accomplished through appropriate modulation of laser pulse timing relative to ion magnetron motion and the potential applied to an ion optical element that photons impinge on. It is shown that UVPD yields efficient and extensive fragmentation resulting in excellent sequence coverage for modelmore » peptide and protein cations.« less

Developments in FT-ICR MS instrumentation, ionization techniques, and data interpretation methods for petroleomics.

PubMed

Cho, Yunju; Ahmed, Arif; Islam, Annana; Kim, Sunghwan

2015-01-01

Because of the increasing importance of heavy and unconventional crude oil as an energy source, there is a growing need for petroleomics: the pursuit of more complete and detailed knowledge of the chemical compositions of crude oil. Crude oil has an extremely complex nature; hence, techniques with ultra-high resolving capabilities, such as Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), are necessary. FT-ICR MS has been successfully applied to the study of heavy and unconventional crude oils such as bitumen and shale oil. However, the analysis of crude oil with FT-ICR MS is not trivial, and it has pushed analysis to the limits of instrumental and methodological capabilities. For example, high-resolution mass spectra of crude oils may contain over 100,000 peaks that require interpretation. To visualize large data sets more effectively, data processing methods such as Kendrick mass defect analysis and statistical analyses have been developed. The successful application of FT-ICR MS to the study of crude oil has been critically dependent on key developments in FT-ICR MS instrumentation and data processing methods. This review offers an introduction to the basic principles, FT-ICR MS instrumentation development, ionization techniques, and data interpretation methods for petroleomics and is intended for readers having no prior experience in this field of study. © 2014 Wiley Periodicals, Inc.

From Supercomputer Modeling to Highest Mass Resolution in FT-ICR.

PubMed

N Nikolaev, Evgene; N Vladimirov, Gleb; Jertz, Roland; Baykut, Gökhan

2013-01-01

Understanding of behavior of ion ensembles inside FT-ICR cell based on the computer simulation of ion motion gives rise to the new ideas of cell designs. The recently introduced novel FT-ICR cell based on a Penning ion trap with specially shaped excitation and detection electrodes prevents distortion of ion cyclotron motion phases (normally caused by non-ideal electric trapping fields) by averaging the trapping DC electric field during the ion motion in the ICR cell. Detection times of 5 min resulting in resolving power close to 40,000,000 have been reached for reserpine at m/z 609 at a magnetic field of only 7 Tesla. Fine structures of resolved 13Cn isotopic cluster groups could be measured for molecular masses up to 5.7 kDa (insulin) with resolving power of 4,000,000 at 7 Tesla. Based on resolved fine structure patterns atomic compositions can be directly determined using a new developed algorithm for fine structure processing. Mass spectra of proteins and multimers of proteins reaching masses up to 186 kDa (enolase tetramer) could be measured with isotopic resolution. For instance, at 7 Tesla resolving power of 800,000 was achieved for enolase dimer (96 kDa) and 500,000 for molecular masses above 100 kDa. Experimental data indicate that there is practically no limit for the resolving power of this ICR cell except by collisional damping in the ultrahigh vacuum chamber.

Evaluation of the ameliorative effects of immunosuppressants on crescentic glomerulonephritis in SCG/Kj mice.

PubMed

Saiga, Kan; Yoshida, Minako; Nakamura, Iwao; Toyoda, Eriko; Tokunaka, Kazuhiro; Morohashi, Hirohisa; Abe, Fuminori; Nemoto, Kyuichi; Nose, Masato

2008-09-01

The therapeutic efficacy of immunosuppressants for treating rapidly progressive glomerulonephritis (RPGN) with crescent formation remains controversial. SCG/Kj mice spontaneously develop RPGN-like symptoms, characteristic of crescentic glomerulonephritis and systemic small vessel vasculitis, associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). We evaluated the "ameliorative", not prophylactic, effects of immunosuppressive agents, deoxyspergualin (DSG), cyclophosphamide (CYC) and prednisolone (PDN), on RPGN in these mice. DSG at intraperitoneal doses of 3 and 6 mg/kg, CYC at an oral dose of 12 mg/kg, or PDN at an intraperitoneal dose of 120 mg/kg was administered once a day for 21 days to female mice "at the onset of hematuria". A set of control SCG/Kj mice received only saline injections. DSG and CYC significantly prolonged survival, improved the proteinuria, hematuria and hyperuremia, and decreased the serum level of myeloperoxidase-ANCA. Moreover, DSG significantly suppressed the formation of crescents in glomeruli. PDN failed to affect any of the parameters. DSG might be useful for inducing remission in crescentic glomerulonephritis involved in RPGN.

Snake bite complicated by acute kidney injury secondary to necrotizing glomerulonephritis.

PubMed

Al Qahtani, Mohammad A; Altheaby, Abdulrahman; Al Anazi, T; Al Saad, Khaled; Binsalih, S; Al Helail, Mohammed

2014-11-01

We present a 38-year-old man who presented to the emergency department with complaints of a snake bite. He developed acute kidney injury (AKI) and the kidney biopsy showed necrotizing glomerulonephritis, which is rarely reported in AKI after snake bite.

Establishment and characterization of a new human acinar cell carcinoma cell line, Faraz-ICR, from pancreas.

PubMed

Rezaei, Marzieh; Hosseini, Ahmad; Nikeghbalian, Saman; Ghaderi, Abbas

Basic research in the field of acinar cell carcinoma (ACC) as a rare neoplasm of the pancreas is dependent on the availability of pragmatic model such as new pancreatic cancer cell lines. Thus, establishment and characterization of new pancreatic cancer cell lines from ACC origin are deemed important. Faraz-ICR cell line was derived from a 58-years old woman with pancreatic acinar cell carcinoma by the collagenase digestion protocol. We characterized the cell line by examining its morphology and cytostructural and functional profile. Faraz-ICR has a doubling time of 35 hours and grows in soft agar with a colony-forming efficiency of 25%. The cell had nearly normal pattern of chromosomes in karyotype analysis and Comparative Genomic Hybridization (CGH) array analysis. Evaluation of cells by flowcytometry showed that Faraz-ICR is negative for EpCAM and mesenchymal markers in different passages, and has epithelial nature. Immunofluorescence staining revealed that cells were strongly positive for vimentin, desmin, ezrin, S100, nestin and they were negative for pan-cytokeratins, chromogranin and alpha smooth muscle actin. We were able to establish a new pancreatic carcinoma cell line with partial aspects of Epithelial-mesenchymal transition and aggressiveness. This cell line might be suitable for studying various anticancer drugs and protein profile aiming to see any possible tumor associated marker for ACC. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Treatment of a case of mesangioproliferative glomerulonephritis secondary to Echinococcus alveolaris with albendazole.

PubMed

Ulusoy, Sükrü; Ozkan, Gülsüm; Mungan, Sevdegül; Arslan, Mehmet; Cansu, Ayşegül; Cansiz, Muammer; Köseoğlu, Rahman; Kaynar, Kübra

2011-01-01

Parasitic infections lead to significant morbidity and mortality, especially in tropical regions. The renal damage caused by these infections occurs via various mechanisms. Two forms of parasitic echinococcus infection widely responsible for infection in humans are Echinococcus granulosus and Echinococcus multilocularis. E. multilocularis causes Alveolar echinococcus infection in humans. Alveolar echinococcus has high mortality, and the possible limits of surgery are generally exceeded by the time of diagnosis. The literature contains no case reports of comorbidity of alveolar echinococcus and glomerulonephritis. Here we discuss the treatment of a patient with comorbid mesangioproliferative glomerulonephritis and alveolar echinococcus, behaving like a tumor, using albendazole since there was no possibility of surgery. This is the first ever such case report.

Acute glomerulonephritis: a 7 years follow up of children in center of Iran.

PubMed

Sepahi, Mohsen Akhavan; Shajari, Ahmad; Shakiba, Mehrdad; Shooshtary, Fatemeh Khalife; Salimi, Mohammad Hossein

2011-01-01

Acute glomerulonephritis (AGN) is a type of renal disease which indicates the inflammation of glomerulus and nephrons. This study was carried on 94 children, <15 years old with the diagnosis of AGN who were admitted to Qom and Yazd's hospitals between 2000 and 2006. Data were collected using hospital records on admission, progression notes and outpatient follow up. Among 94 patients, 55.3% were male and 44.6% were female. Mean age of patients was 8.2±2.7 years old. Acute post streptococcal glomerulonephritis (APSGN) was reported in 92.5%, membranoproliferative glomerulonephritis in 4.2%, hemolytic uremic syndrome in 2.1% and IgA nephropathy in 1.06%. There was no significant differences between GN types and gender (P=0.54). Clinical manifestation included edema in 68.8%, oliguria in 36.3%, gross hematuria in 69.1%, HTN in 61.7% and anuria in 1.06%. Microscopic hematuria was detected in all patients. In the time of follow up none of patients had hypertension, 3.1% had proteinuria and 6.3% had microscopic hematuria. APSGN is the most common causes of AGN in Qom and Yazd's children. Early diagnosis and treatment of APSGN may protect children from long term morbidity and mortality and improve quality of life.

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

PubMed

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

2016-01-01

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

75 FR 7584 - Agency Information Collection Activities; Proposed Collection; Comment Request; EPA-ICR No. 1774...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... Program, OMB Control No. 2060-0350 AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY.... 1774.05, OMB Control No. 2060-0350. ICR status: This ICR is currently scheduled to expire on July 31...

Extracting biomolecule collision cross sections from the high-resolution FT-ICR mass spectral linewidths.

PubMed

Jiang, Ting; Chen, Yu; Mao, Lu; Marshall, Alan G; Xu, Wei

2016-01-14

It is known that the ion collision cross section (CCS) may be calculated from the linewidth of a Fourier transform ion cyclotron resonance (FT-ICR) mass spectral peak at elevated pressure (e.g., ∼10(-6) Torr). However, the high mass resolution of FT-ICR is sacrificed in those experiments due to high buffer gas pressure. In this study, we describe a linewidth correction method to eliminate the windowing-induced peak broadening effect. Together with the energetic ion-neutral collision model previously developed by our group, this method enables the extraction of CCSs of biomolecules from high-resolution FT-ICR mass spectral linewidths, obtained at a typical operating buffer gas pressure of modern FT-ICR instruments (∼10(-10) Torr). CCS values of peptides including MRFA, angiotensin I, and bradykinin measured by the proposed method agree well with ion mobility measurements, and the unfolding of protein ions (ubiquitin) at higher charge states is also observed.

2D FT-ICR MS of Calmodulin: A Top-Down and Bottom-Up Approach.

PubMed

Floris, Federico; van Agthoven, Maria; Chiron, Lionel; Soulby, Andrew J; Wootton, Christopher A; Lam, Yuko P Y; Barrow, Mark P; Delsuc, Marc-André; O'Connor, Peter B

2016-09-01

Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) allows data-independent fragmentation of all ions in a sample and correlation of fragment ions to their precursors through the modulation of precursor ion cyclotron radii prior to fragmentation. Previous results show that implementation of 2D FT-ICR MS with infrared multi-photon dissociation (IRMPD) and electron capture dissociation (ECD) has turned this method into a useful analytical tool. In this work, IRMPD tandem mass spectrometry of calmodulin (CaM) has been performed both in one-dimensional and two-dimensional FT-ICR MS using a top-down and bottom-up approach. 2D IRMPD FT-ICR MS is used to achieve extensive inter-residue bond cleavage and assignment for CaM, using its unique features for fragment identification in a less time- and sample-consuming experiment than doing the same thing using sequential MS/MS experiments. Graphical Abstract ᅟ.

Petroleum Refinery Information Collection Request (ICR) Emissions Test Report for BP-Husky Refining LLC

EPA Pesticide Factsheets

On March 31, 2011, U.S. EPA sent a Section 114 letter to the BP-Husky Refining Company in Oregon, Ohio stating that the facility was subject to the ICR and that certain information would need to be submitted by the facility to satisfy U.S. EPA’s ICR.

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model

PubMed Central

Hamano, Y; Abe, M; Matsuoka, S; Zhang, D; Kondo, Y; Kagami, Y; Ishigami, A; Maruyama, N; Tsuruta, Y; Yumura, W; Suzuki, K

2014-01-01

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80+ cells, CD3+CD4−CD8− T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80low cells were observed in crescent, while F4/80high cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80+ cells in crescents correlated significantly with F4/80+ cell numbers in PB, but not with numbers of F4/80+ cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80+ cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80+ cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis. PMID:24654803

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model.

PubMed

Hamano, Y; Abe, M; Matsuoka, S; Zhang, D; Kondo, Y; Kagami, Y; Ishigami, A; Maruyama, N; Tsuruta, Y; Yumura, W; Suzuki, K

2014-07-01

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis. © 2014 British Society for Immunology.

77 FR 58127 - Agency Information Collection Activities; Proposed Collection; Comment Request; EPA ICR No. 2104...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

... . FOR FURTHER INFORMATION CONTACT: Rachel Lentz, Office of Brownfields and Land Revitalization, (5105T.... Title: Brownfields Program--Accomplishment Reporting (Renewal). ICR numbers: EPA ICR No. 2104.04, OMB... and Brownfields Revitalization Act (Pub. L. 107-118) (``the Brownfields Amendments'') was signed into...

Focal segmental necrotizing glomerulonephritis in rheumatoid arthritis.

PubMed

Harper, L; Cockwell, P; Howie, A J; Michael, J; Richards, N T; Savage, C O; Wheeler, D C; Bacon, P A; Adu, D

1997-02-01

We report ten patients with rheumatoid arthritis (RA) who developed a focal segmental necrotizing glomerulonephritis (FSNGN) and extracapillary proliferation typical of vasculitic glomerulonephritis. Five patients also had extrarenal vasculitis. Renal presentation was with renal impairment (n = 9) (median creatinine 726 mumol/l, range 230-1592 mumol/l), microscopic haematuria (n = 8) and proteinuria (n = 10). Nine patients were seropositive for rheumatoid factor and nine had bone erosions. Serum from four of five patients tested by indirect immunofluorescence was positive for antineutrophil cytoplasmic antibody (ANCA) with perinuclear staining. Only three patients had penicillamine or gold therapy. Treatment was with prednisolone and cyclophosphamide (six patients, two of whom were also plasma-exchanged), prednisolone and azathioprine (two patients) and prednisolone alone (two patients). There was a marked improvement in renal function in eight patients. Two patients with dialysis-dependent renal failure recovered renal function, although in one patient this was transient and she required further dialysis 4 months later. Two other patients progressed to dialysis at 3 months and 1 year respectively. Four patients died, one remains dialysis-dependent, and four continue to have good renal function at 5 year follow-up (median creatinine 148.5 mumol/l, range 120-193 mumol/l). One patient was lost to follow-up at 5 years. FSNGN should be considered in all patients with RA and renal impairment, proteinuria and/or microscopic haematuria. This diagnosis appears to be more likely in patients with clinical extrarenal vasculitis, bone erosions or who are seropositive. In these cases, an urgent renal biopsy is indicated.

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

PubMed

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

2015-01-01

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

Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study

PubMed Central

Clark, William F.; Lindsay, Robert M.; Cattran, Daniel C.; Chodirker, William B.; Barnes, Colin C.; Linton, Adam L.

1981-01-01

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis. PMID:7272867

Rotation Matrix from the Mean Dynamical Equator and Equinox at J2000.0 to the ICRS

DTIC Science & Technology

2004-01-01

the ICRS is offset from its equinox by ∆o. The angle 0 is the obliquity of the ecliptic on the ICRS, that is the angle between the ICRS equator and... obliquity is caused solely by a change in the position of the pole of the mean ecliptic . Thus, the sole effect of using the rotating definition of the mean...the mean ecliptic as determined by Chapront et al. from LLR observations (23◦26′21.′′41100 ± 0.′′00005). The angle γy is the separation between the

Prevention of crescentic glomerulonephritis in SCG/Kj mice by bone marrow transplantation.

PubMed

Cherry; Engelman, R W; Wang, B Y; Kinjoh, K; El-Badri, N S; Good, R A

1998-07-01

Transplantation of MHC-compatible, T-cell-depleted, bone marrow cells has successfully treated autoimmunities, immunodeficiencies, malignancies, and developmental deficiencies of the hematopoietic system. Recombinant inbred SCG/Kj mice develop spontaneous crescentic glomerulonephritis, systemic vasculitis, and a lymphoproliferative disorder early in life. To determine whether the precipitous autoimmune disease of SCG/Kj mice could be treated by bone marrow transplantation, 30 SCG/Kj mice were engrafted with T-cell-depleted, bone marrow (TCDM) from allogeneic, MHC-compatible, autoimmune-resistant C3H/He donors, and 30 SCG/Kj mice served as controls and received TCDM from syngeneic, SCG/Kj donors. A significant survival advantage was evident from SCG/Kj mice engrafted with C3H/He TCDM (p < 0.005), and an 89% extension of median survival compared to recipients of SCG/Kj TCDM. Within 28 weeks post-transplantation, 62% of mice engrafted with SCG/Kj TCDM had died with clinical signs of fatal crescentic glomerulonephritis. This result compared with only 10% of mice engrafted with C3H/He TCDM. Mice engrafted with SCG/Kj TCDM developed significantly greater titers of autoantibodies to ss-DNA, ds-DNA, and myeloperoxidase (ANCA) (p < 0.001), had shorter latencies to the development of, and a greater incidence of proteinuria, hematuria, and peripheral lymphadenopathy, and a greater mean grade of glomerular lesion (p < 0.001), than mice engrafted with C3H/He TCDM. These findings indicate that the genetic defect of the SCG/Kj strain of mice resides within the hematopoietic stem cells and provokes the speculation that bone marrow transplantation might be a useful means of treating progressive crescentic glomerulonephritis in humans.

Monitoring the physicochemical degradation of coconut water using ESI-FT-ICR MS.

PubMed

Costa, Helber B; Souza, Lindamara M; Soprani, Letícia C; Oliveira, Bruno G; Ogawa, Elizângela M; Korres, Adriana M N; Ventura, José A; Romão, Wanderson

2015-05-01

Fresh and aged coconut water (CW) samples were introduced directly into the electrospray ionisation (ESI) source, and were combined with the Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) technique to characterise in situ chemical compounds produced during natural ageing (from 0 to 15 days) at room temperature (23 °C). The ESI-FT-ICR MS readings were acquired and the data were correlated to conventional methodologies: pH, total titratable acidity (TA), total soluble solids, microbial analyses, and ultraviolet visibility (UV-vis) spectroscopy analysis. In general, the pH and TA values changed after 3 days of storage making the CW unsuitable for consumption. The ESI(-)-FT-ICR data also showed a clear and evident change in the chemical profile of CW after 3 days of ageing in the m/z 150-250 and 350-450 regions. Initially, the relative intensity of the natural markers (the m/z 215 and 377 ions-sugar molecules) decreases as a function of ageing time, with the last marker disappearing after 3 days of ageing. New chemical species were then identified such as: citric (m/z 191), galacturonic (m/z 193), gluconic (m/z 195), and saccharic (m/z 209) acids. ESI(-)-FT-ICR MS is a powerful tool to predict the physicochemical properties of CW, such as the pH and TA, where species such as fructose, glucose, sucrose, and gluconic acid can be used as natural markers to monitor the quality of the fruits. Copyright © 2014 Elsevier Ltd. All rights reserved.

ACE Inhibition in Anti-Thy1 Glomerulonephritis Limits Proteinuria but Does Not Improve Renal Function and Structural Remodeling

PubMed Central

Westerweel, Peter E.; Joles, Jaap A.; den Ouden, Krista; Goldschmeding, Roel; Rookmaaker, Maarten B.; Verhaar, Marianne C.

2012-01-01

Background/Aims ACE inhibitor (ACE-I) treatment effectively inhibits proteinuria and ameliorates the course of various renal diseases. In experimental glomerulonephritis, however, angiotensin II (AngII) infusion has also been shown to be renoprotective. We evaluated the long-term (28 days) course of anti-Thy1 glomerulonephritis in animals with suppressed AngII formation by ACE-I treatment. Methods Brown Norway rats received perindopril (2.8 mg/kg/day, n = 12), dihydropyridine calcium-antagonist amlodipine (Ca-A; 13 mg/kg/day, n = 6) or were left untreated (n = 14). All animals were monitored for blood pressure, proteinuria, and creatinine clearance after anti-Thy1 injection. Renal histology was assessed at day 7 and 28. Results Systolic blood pressure was equally reduced by ACE-I and Ca-A treatment. AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance. After resolution of the microaneurysms, animals with suppressed AngII production showed a modest increase in glomerulosclerosis and vasculopathic thickening of intrarenal vessels. Conclusions In anti-Thy1 glomerulonephritis, suppression of AngII formation does not protect against the induction of glomerular damage and is associated with mild aggravation of adverse renal fibrotic remodeling. Proteinuria, however, is effectively prevented by ACE-I treatment. Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent. PMID:22479264

Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies

PubMed Central

2017-01-01

Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed. PMID:28573137

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

PubMed

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

2008-12-01

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

Analysis of clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in adult indigenous people of the Northern Territory of Australia.

PubMed

Ramanathan, Ganesh; Abeyaratne, Asanga; Sundaram, Madhivanan; Fernandes, David Kiran; Pawar, Basant; Perry, Greg John; Sajiv, Cherian; Majoni, Sandawana William

2017-05-01

Acute postinfectious glomerulonephritis is common in indigenous communities in the Northern Territory, Australia. It is a major risk factor for the high prevalence of chronic kidney disease. We aimed to analyse the clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in the Northern Territory. We performed a retrospective cohort analysis of all adult patients (≥18 years) who were diagnosed with acute postinfectious glomerulonephritis on native renal biopsies from 01/01/2004 to 31/05/2014. The outcome measure was end-stage renal disease requiring long-term dialysis. Forty-three of 340 patients who had renal biopsies had acute postinfectious glomerulonephritis. Most were Aboriginals (88.4%). They had co-morbidities; diabetes mellitus (60.5%), hypertension (60.5%) and smoking (56.4%). Forty-nine per cent had multiple pathologies on biopsy. Predominant histological pattern was diffuse proliferative glomerulonephritis (72%). Main sites of infections were skin (47.6%) and upper respiratory tract infection (26.2%) with streptococcus and staphylococcus as predominant organisms. Fifty per cent of patients developed end-stage renal disease. On multivariable logistic regression analysis, those on dialysis had higher baseline creatinine (P = 0.003), higher albumin/creatinine ratio at presentation (P = 0.023), higher serum creatinine at presentation (P = 0.02) and lower estimated glomerular filtration rate at presentation (P = 0.012). Overall, most patients had pre-existing pathology with superimposed acute postinfectious glomerulonephritis that led to poor outcomes in our cohort. © 2016 Asian Pacific Society of Nephrology.

Detection of viral antigens in renal tissue of glomerulonephritis patients without serological evidence of hepatitis B virus and hepatitis C virus infection.

PubMed

Kong, Dan; Wu, Di; Wang, Tianzhen; Li, Tianzhu; Xu, Shengjie; Chen, Fulai; Jin, Xiaoming; Lou, Ge

2013-07-01

Glomerulonephritis is an important extrahepatic manifestation of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. HBV and HCV infection may be occult, and they are often overlooked by both patients and doctors. The aim of this study was to assess the importance of HBV and HCV infection in glomerulonephritis patients with undetectable HBV surface antigen (HBsAg) and HCV antibody in serum. The HBsAg, the HBV core antigen (HBcAg), and the HCV antigen were detected using immunohistochemistry in frozen renal tissues of 500 glomerulonephritis patients without serological evidence of HBV and HCV infection. Electron microscopy was used to trace the virus particles, and clinicopathological features were also reviewed. HBsAg or HBcAg was positive in nine out of 500 cases (9/500, 1.8%). Three cases were HBsAg-positive and another six cases were HBcAg-positive. The HCV antigen was found in eight cases (8/500, 1.6%). There was one case of HBV and HCV co-infection (1/500, 0.2%). Under electron microscopy, virus particles were found in the base membrane and cytoplasm of endotheliocytes in the glomerulus. The most common clinical manifestation was nephrotic syndrome (9/18), followed by nephritic syndrome (7/18). Membranous nephropathy was the most common pathological diagnosis (5/18), followed by mesangioproliferative glomerulonephritis (4/18) and IgA nephropathy (4/18). Occult HBV and HCV infection might be implicated in HBV- or HCV-associated glomerulonephritis. More attention should be focused on the underlying cause. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

PubMed

Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

2011-09-01

The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. © 2011 Peripheral Nerve Society.

[Primary chronic polyarthritis with kidney involvement (mesangiocapillary glomerulonephritis)].

PubMed

Bürkle, P A

1979-01-01

A 34 year old white male patient suffering from seropositive "probable" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulo-nephritis. Rheumatoid factors (Latex test, Waaler-Rose titer) and IgM were markedly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within normal range. The rapid progression of the disease forced us to start an immunosuppressive drug therapy using azathioprine and steroids. Despite marked clinical improvement, e.g. normalisation of complement components, renal function, the disappearance of rheumatoid factor and proteinuria, the second biopsy taken two years later showed unchanged histological and immuno-histological changes of the glomerula.

Postinfectious glomerulonephritis secondary to Erythrovirus B19 (Parvovirus B19): case report and review of the literature.

PubMed

Marco, Helena; Guermah, Imane; Matas, Lurdes; Hernández, Alba; Navarro, Maruja; Lopez, Dolores; Bonet, Josep

2016-04-01

A previously healthy 32-yearold woman developed arterial hypertension, proteinuria, and hematuria (nephritic syndrome) with normal renal function and was diagnosed with post-infectious glomerulonephritis secondary to parvovirus B19 infection. The renal biopsy showed endocapillary glomerulonephritis, with positive IgG, C3, and C1q immunoreactivity in the capillary walls and ultrastructural evidence of subendothelial deposits. The diagnosis of parvovirus B19 infection was confirmed by IgG/IgM serological positivity and parvovirus DNA demonstration in both peripheral blood and kidney tissue. Glomerular involvement improved spontaneously. To be noted are the atypical signs and symptoms of our patient who, unlike previously reported cases, failed to show fever, skin rash, or affected relatives.

Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is triggered by ‘autoantigen complementarity’

PubMed Central

Reynolds, John; Preston, Gloria A.; Pressler, Barrak M.; Hewins, Peter; Brown, Michael; Roth, Aleeza; Alderman, Elizabeth; Bunch, Donna; Jennette, J. Charles; Cook, H. Terence; Falk, Ronald J.; Pusey, Charles D.

2015-01-01

‘Autoantigen complementarity’ is a theory proposing that the initiator of an autoimmune response is not necessarily the autoantigen or its molecular mimic, but may instead be a peptide that is ‘antisense/complementary’ to the autoantigen. We investigated whether such complementary proteins play a role in the immunopathogenesis of autoimmune glomerulonephritis. Experimental autoimmune glomerulonephritis, a model of anti-glomerular basement membrane (GBM) disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the α3 chain of type IV collagen. In this study, WKY rats were immunized with a complementary α3 peptide (c-α3-Gly) comprised of amino acids that ‘complement’ the well characterized epitope on α3(IV)NC1, pCol(24–38). Within 8 weeks post-immunization, these animals developed cresentic glomerulonephritis, similar to pCol(24–38)-immunized rats, while animals immunized with scrambled peptide were normal. Anti-idiotypic antibodies to epitopes from c-α3-Gly-immunized animals were shown to be specific for α3 protein, binding in a region containing sense pCol(24–38) sequence. Interestingly, anticomplementary α3 antibodies were identified in sera from patients with anti-GBM disease, suggesting a role for ‘autoantigen complementarity’ in immunopathogenesis of the human disease. This work supports the idea that autoimmune glomerulonephritis can be initiated through an immune response against a peptide that is anti-sense or complementary to the autoantigen. The implications of this discovery may be far reaching, and other autoimmune diseases could be due to responses to these once unsuspected ‘complementary’ antigens. PMID:25841937

Glomerular common gamma chain confers B- and T-cell-independent protection against glomerulonephritis.

PubMed

Luque, Yosu; Cathelin, Dominique; Vandermeersch, Sophie; Xu, Xiaoli; Sohier, Julie; Placier, Sandrine; Xu-Dubois, Yi-Chun; Louis, Kevin; Hertig, Alexandre; Bories, Jean-Christophe; Vasseur, Florence; Campagne, Fabien; Di Santo, James P; Vosshenrich, Christian; Rondeau, Eric; Mesnard, Laurent

2017-05-01

Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2 -/- , Rag2 -/- Il2rg -/- , and Rag2 -/- Il2rb -/- ) that are devoid of either T/B cells or T/B/NK cells. The Rag2 -/- Il2rg -/- or Rag2 -/- Il2rb -/- mice harbor an additional deletion of either the common gamma chain (γC) or the interleukin-2 receptor β subunit (IL-2Rβ), respectively, impairing IL-15 signaling in particular. As expected, all these strains developed severe anti-GBM-GN. Additionally, bone marrow replenishment experiments allowed us to deduce a protective role for the glomerular-expressed γC during anti-GBM-GN. Given that IL-15 has been found highly expressed in nephritic kidneys despite the absence of lymphocytes, we then studied this cytokine in vitro on primary cultured podocytes from immune-deficient mice (Rag2 -/- Il2rg -/- and Rag2 -/- Il2rb -/- ) compared to controls. IL-15 induced downstream activation of JAK1/3 and SYK in primary cultured podocytes. IL-15-dependent JAK/SYK induction was impaired in the absence of γC or IL-2Rβ. We found γC largely induced on podocytes during human glomerulonephritis. Thus, renal lesions are indeed modulated by intrinsic glomerular cells through the γC/IL-2Rβ receptor response, to date classically described only in immune cells. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Crescentic Glomerulonephritis in a Polar Bear (Ursus maritimus)

PubMed Central

BABA, Hiroshi; KUDO, Tomoo; MAKINO, Yoshinori; MOCHIZUKI, Yasumasa; TAKAGI, Takayo; UNE, Yumi

2013-01-01

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

Crescentic glomerulonephritis in a polar bear (Ursus maritimus).

PubMed

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

2013-11-01

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

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

PubMed

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

2014-02-26

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

Crescentic glomerulonephritis in non-asthmatic Churg-Strauss syndrome.

PubMed

Kaul, Anupma; Sharma, Raj Kumar; Jaisuresh, Krishna Swamy; Agrawal, Vinita

2014-03-01

A 58-year-old male presented with sensory motor polyneuropathy and rapidly progressive renal failure. Investigations revealed marked peripheral eosinophilia and elevated perinuclear antineutrophil cytoplasmic antibody titers. Renal biopsy showed pauci-immune cre-scentic glomerulonephritis with interstitial eosinophil infiltrates. He had no history of asthma. Computed tomography of the chest and X-ray of the paranasal sinuses were normal. On Day 1, the patient developed ileal perforation. Resected ileal segments showed small vessel vasculitis with extravascular eosinophils. A diagnosis of non-asthmatic variant of Churg-Strauss syndrome was made. Renal recovery was achieved in 12 weeks with a combination therapy of corticosteroid and cyclophosphamide. The patient has been relapse-free for 12 months on oral prednisolone therapy.

Top-Down Protein Identification of Proteasome Proteins with nanoLC FT-ICR MS Employing Data-Independent Fragmentation Methods

PubMed Central

Lakshmanan, Rajeswari; Wolff, Jeremy J.; Alvarado, Rudy; Loo, Joseph A.

2014-01-01

A comparison of different data-independent fragmentation methods combined with liquid chromatography (LC) coupled to high resolution Fourier-transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry (MS) is presented for top-down MS of protein mixtures. Proteins composing the 20S and 19S proteasome complex and their post-translational modifications were identified using a 15-Tesla FT-ICR mass spectrometer. The data-independent fragmentation modes with LC timescales allowed for higher duty cycle measurements that better suit on-line LC-FT-ICR-MS. Protein top-down dissociation was effected by funnel-skimmer collisionally activated dissociation (FS-CAD) and CASI (Continuous Accumulation of Selected Ions)-CAD. The N-terminus for 9 out of the 14 20S proteasome proteins were found to be modified, and the α3 protein was found to be phosphorylated; these results are consistent with previous reports. Mass measurement accuracy with the LC-FT-ICR system for the 20–30 kDa 20S proteasome proteins was 1 ppm. The intact mass of the 100 kDa Rpn1 subunit from the 19S proteasome complex regulatory particle was measured with a deviation of 17 ppm. The CASI-CAD technique is a complementary tool for intact protein fragmentation and is an effective addition to the growing inventory of dissociation methods which are compatible with on-line protein separation coupled to FT-ICR MS. PMID:24478249

Mercury in US coal: Observations using the COALQUAL and ICR data

USGS Publications Warehouse

Quick, J.C.; Brill, T.C.; Tabet, D.E.

2003-01-01

The COALQUAL data set lists the mercury content of samples collected from the in-ground US coal resource, whereas the ICR data set lists the mercury content of samples collected from coal shipments delivered to US electric utilities. After selection and adjustment of records, the COALQUAL data average 0.17 ??g Hg/g dry coal or 5.8 kg Hg/PJ, whereas the ICR data average 0.10 ??g Hg/g dry coal or 3.5 kg Hg/PJ. Because sample frequency does not correspond to the inground or produced tonnage, these values are not accurate estimates of the mercury content of either in-ground or delivered US coal. Commercial US coal contains less mercury than previously estimated, and its mercury content has declined during the 1990s. Selective mining and more extensive coal washing may accelerate the current trend towards lower mercury content in coal burned at US electric utilities.

[Effects of postnatal lambda-cyhalothrin exposure on synaptic proteins in ICR mouse brain].

PubMed

Bao, Xun-Di; Wang, Qu-Nan; Li, Fang-Fang; Chai, Xiao-Yu; Gao, Ye

2011-04-01

To evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period. Two male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot. GFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05). Early postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.

New approaches to trials in glomerulonephritis.

PubMed

Craig, Jonathan C; Tong, Allison; Strippoli, Giovanni F M

2017-01-01

Randomized controlled trials are required to reliably identify interventions to improve the outcomes for people with glomerulonephritis (GN). Unfortunately, although easier, observational studies are inherently unreliable even though the findings of both study designs agree most of the time. Currently there are ∼790 trials in GN, but suboptimal design and reporting, together with small sample sizes, mean that they may not be reliable for decision making. If the history is somewhat bleak, the future looks bright, with recent initiatives to improve the quality, size and relevance of clinical trials in nephrology, including greater patient engagement, trial networks, core outcome sets, registry-based trials and adaptive designs. Given the current state of the evidence informing the care of people with GN, disruptive technologies and pervasive culture change is required to ensure that the potential of trials to improve the health of people with this complex condition is to be realized. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

In vivo irritation study of Melastoma malabathricum cream formulation on ICR mice

NASA Astrophysics Data System (ADS)

Yasin, Rabiahtul Adarwiyah Mohd; Jemon, Khairunadwa; Nor, Norefrina Shafinaz Md

2016-11-01

Melastoma malabathricum is a traditional herb that is used to treat wound on skin. It has also been proven to have antiviral activity against Herpes Simplex virus type 1 (HSV-1). In this study, M. malabathricum cream formulation was developed by incorporating M. malabathricum aqueous extract into cream base. The safety and biocompatibility of the formulated cream was investigated by topically applying the cream onto the back of ICR mice skin. Treatment with M. malabathricum was found to accelerate wound contraction with less scar formation. The effect of M. malabathricum has prompted a possibility that M. malabathricum might contribute in enhancing the healing process of cutaneous lesion caused by HSV-1. The formulated cream did not cause any skin irritation or adverse effect to ICR mice when topically applied within seven days of exposure.

Interpolation bias for the inverse compositional Gauss-Newton algorithm in digital image correlation

NASA Astrophysics Data System (ADS)

Su, Yong; Zhang, Qingchuan; Xu, Xiaohai; Gao, Zeren; Wu, Shangquan

2018-01-01

It is believed that the classic forward additive Newton-Raphson (FA-NR) algorithm and the recently introduced inverse compositional Gauss-Newton (IC-GN) algorithm give rise to roughly equal interpolation bias. Questioning the correctness of this statement, this paper presents a thorough analysis of interpolation bias for the IC-GN algorithm. A theoretical model is built to analytically characterize the dependence of interpolation bias upon speckle image, target image interpolation, and reference image gradient estimation. The interpolation biases of the FA-NR algorithm and the IC-GN algorithm can be significantly different, whose relative difference can exceed 80%. For the IC-GN algorithm, the gradient estimator can strongly affect the interpolation bias; the relative difference can reach 178%. Since the mean bias errors are insensitive to image noise, the theoretical model proposed remains valid in the presence of noise. To provide more implementation details, source codes are uploaded as a supplement.

Fibrillary glomerulonephritis associated with monoclonal gammopathy of undetermined significance showing lambda-type Bence Jones protein.

PubMed

Nagao, Tomoaki; Okura, Takafumi; Miyoshi, Ken-Ichi; Watanabe, Sanae; Manabe, Seiko; Kurata, Mie; Irita, Jun; Fukuoka, Tomikazu; Higaki, Jitsuo

2005-09-01

A 79-year-old woman was admitted to our hospital because of leg edema due to a nephrotic syndrome. Urinary and serum immunoelectrophoresis showed positive for the lambda type of Bence Jones protein. A bone marrow aspiration test revealed mild plasmacytosis (6.4% of the total cells). These findings confirmed her diagnosis of monoclonal gammopathy of undetermined significance (MGUS). Her renal biopsy specimen revealed mild mesangial cell proliferation and an increase in the mesangial matrix. Immunofluorescence studies showed positive staining for IgG, IgA, C3, and kappa and lambda light chains in the capillary wall and mesangium area. Electron microscopy showed that the electron deposits in the thickened basement membrane were formed by randomly arranged 16- to 18-nm nonbranching fibrils. A Congo red stain for amyloid was negative. These findings corresponded with the diagnosis of fibrillary glomerulonephritis. Therefore, this case showed a rare combination of fibrillary glomerulonephritis and MGUS.

Post-infectious acute glomerulonephritis with podocytopathy induced by parvovirus B19 infection.

PubMed

Hara, Satoshi; Hirata, Masayoshi; Ito, Kiyoaki; Mizushima, Ichiro; Fujii, Hiroshi; Yamada, Kazunori; Nagata, Michio; Kawano, Mitsuhiro

2018-03-01

Human parvovirus B19 infection causes a variety of glomerular diseases such as post-infectious acute glomerulonephritis and collapsing glomerulopathy. Although each of these appears independently, it has not been fully determined why parvovirus B19 provokes such a variety of different glomerular phenotypes. Here, we report a 68-year-old Japanese man who showed endocapillary proliferative glomerulonephritis admixed with podocytopathy in association with parvovirus B19 infection. The patient showed acute onset of heavy proteinuria, microscopic hematuria and kidney dysfunction with arthralgia and oliguria after close contact with a person suffering from erythema infectiosum. In the kidney biopsy specimen, glomeruli revealed diffuse and global endocapillary infiltration of inflammatory cells, with some also showing tuft collapse with aberrant vacuolation, swelling, and hyperplasia of glomerular epithelial cells. Immunofluorescence revealed dense granular C3 deposition that resembled the "starry sky pattern". Intravenous glucocorticoid pulse therapy followed by oral prednisolone and cyclosporine combination therapy resulted in considerable amelioration of the kidney dysfunction and urinary abnormalities. The present case reveals that parvovirus B19 infection can induce different glomerular phenotypes even in the same kidney structure. This finding may provide hints useful for the further elucidation of the pathogenesis of parvovirus B19-induced glomerular lesions. © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Characterisation of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

PubMed Central

Maratou, Klio; Behmoaras, Jacques; Fewings, Chris; Srivastava, Prashant; D’Souza, Zelpha; Smith, Jennifer; Game, Laurence; Cook, Terence; Aitman, Tim

2010-01-01

Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity. PMID:21179115

THE OCCURRENCE OF A NEW GENERATION OF DBPS (BEYOND THE ICR)

EPA Science Inventory

A nationwide survey of 12 full-scale treatment plants for disinfection by-products (DBPs) was initiated in the U.S. in 2000. Approximately 50DBPs that rated a high priority for potential toxicity and were not included in the Information Collection Rule (ICR) are being quantified...

Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.

PubMed

Kim, Ju Han; Ha, Il Soo; Hwang, Chang-Il; Lee, Young-Ju; Kim, Jihoon; Yang, Seung-Hee; Kim, Yon Su; Cao, Yun Anna; Choi, Sangdun; Park, Woong-Yang

2004-11-01

Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) < 0.05] were chosen for cluster analysis. From the expression profile, acute inflammatory reactions characterized by the elevation of various cytokines, including interleukin (IL)-1 and IL-6, were identified within 3 days of disease onset. After 7 days, tissue remodeling response was prominent with highly induced extracellular-matrix (ECM) genes. Although cytokines related to lymphocyte activation were not detected, monocyte or mesangial cell proliferation-related genes were increased. Tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) pathway were consistently activated along the entire disease progression, inducing various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1. We made a large-scale gene expression time table for mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory

A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice.

PubMed

Zhuhua, Zhang; Zhiquan, Wang; Zhen, Yang; Yixin, Niu; Weiwei, Zhang; Xiaoyong, Li; Yueming, Liu; Hongmei, Zhang; Li, Qin; Qing, Su

2015-01-01

Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS.

A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura, and elevated IgA level.

PubMed

Yang, Jihyun; Seo, Min Young; Kim, Ki Tae; Lee, Jun Yong; Kim, Sun-Chul; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu; Won, Nam Hee; Cha, Ran-Hui; Cho, Eunjung

2014-01-01

Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed "lupus-like feature" glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding.

Exhaustive methylation analysis revealed uneven profiles of methylation at IGF2/ICR1/H19 11p15 loci in Russell Silver syndrome.

PubMed

Azzi, Salah; Steunou, Virginie; Tost, Jörg; Rossignol, Sylvie; Thibaud, Nathalie; Das Neves, Cristina; Le Jule, Marilyne; Habib, Walid Abi; Blaise, Annick; Koudou, Yves; Busato, Florence; Le Bouc, Yves; Netchine, Irène

2015-01-01

The structural organisation of the human IGF2/ICR1/H19 11p15 domain is very complex, and the mechanisms underlying its regulation are poorly understood. The Imprinted Center Region 1 (ICR1) contains seven binding sites for the zinc-finger protein CTCF (CBS: CTCF Binding Sites); three additional differentially methylated regions (DMR) are located at the H19 promoter (H19DMR) and two in the IGF2 gene (DMR0 and DMR2), respectively. Loss of imprinting at the IGF2/ICR1/H19 domain results in two growth disorders with opposite phenotypes: Beckwith-Wiedemann syndrome and Russell Silver syndrome (RSS). Despite the IGF2/ICR1/H19 locus being widely studied, the extent of hypomethylation across the domain remains not yet addressed in patients with RSS. We assessed a detailed investigation of the methylation status of the 11p15 ICR1 CBS1-7, IGF2DMR0 and H19DMR (H19 promoter) in a population of controls (n=50) and RSS carrying (n=104) or not (n=65) carrying a hypomethylation at the 11p15 ICR1 region. The methylation indexes (MI) were balanced at all regions in the control population and patients with RSS without any as yet identified molecular anomaly. Interestingly, patients with RSS with ICR1 hypomethylation showed uneven profiles of methylation among the CBSs and DMRs. Furthermore, normal MIs at CBS1 and CBS7 were identified in 9% of patients. The hypomethylation does not spread equally throughout the IGF2/ICR1/H19 locus, and some loci could have normal MI, which may lead to underdiagnosis of patients with RSS with ICR1 hypomethylation. The uneven pattern of methylation suggests that some CBSs may play different roles in the tridimensional chromosomal looping regulation of this locus. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Ultrahigh-resolution FT-ICR mass spectrometry characterization of a-pinene ozonolysis SOA

EPA Science Inventory

Secondary organic aerosol (SOA) of α-pinene ozonolysis with and without hydroxyl radical scavenging hexane was characterized by ultrahigh-resolution. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Molecular formulas for more than 900 negative ions were i...

[Mechanisms of immune deposit formation in glomerulonephritis].

PubMed

Bussolati, B; Camussi, G

1996-03-01

Recent experimental studies allowed the identification of several mechanisms of immune deposit formation, which are able to reproduce the morphological and clinical pattern of human glomerulonephritis. Moreover, it was shown that most of the lesions considered, in the past, as due to circulating immune complexes (IC), are instead caused by the "in situ" formation of IC. As a result of these studies, the following schematic classification was proposed: 1) immune deposits formed by glomerular localization of IC primarily formed in the circulation; 2) immune deposits formed "in situ" by reaction of circulating antibodies with fixed structural antigens; 3) immune deposits formed "in situ" by antibodies reactive with movable structural antigens; 4) immune deposits formed "in situ" by antibodies reactive with sequestered antigens leaking out of tissues; 5) IC formed "in situ" by antibodies reactive with exogenous or non-glomerular endogenous antigens planted in the glomeruli; 6) ANCA-associated glomerular disease.

75 FR 61481 - Agency Information Collection Activities; Submission of EPA ICR No. 2078.01 to OMB for Review and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

... identity or contact information unless you provide it in the body of your comment. If you send an e-mail... and other contact information in the body of your comment and with any disk or CD-ROM you submit. If..., OMB Control No. 2060-0528. ICR Status: This ICR is currently scheduled to expire on March 31, 2011. An...

A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice

PubMed Central

Zhuhua, Zhang; Zhiquan, Wang; Zhen, Yang; Yixin, Niu; Weiwei, Zhang; Xiaoyong, Li; Yueming, Liu; Hongmei, Zhang; Li, Qin; Qing, Su

2015-01-01

Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS. PMID:26134356

Collision cross section measurements for biomolecules within a high-resolution FT-ICR cell: theory.

PubMed

Guo, Dan; Xin, Yi; Li, Dayu; Xu, Wei

2015-04-14

In this study, an energetic hard-sphere ion-neutral collision model was proposed to bridge-link ion collision cross section (CCS) with the image current collected from a high-resolution Fourier transform ion cyclotron resonance (FT-ICR) cell. By investigating the nonlinear effects induced by high-order electric fields and image charge forces, the energetic hard-sphere collision model was validated through experiments. Suitable application regions for the energetic hard-sphere collision model, as well as for the conventional Langevin and hard-sphere collision models, were also discussed. The energetic hard-sphere collision model was applied in the extraction of ion CCSs from high-resolution FT-ICR mass spectra. Discussions in the present study also apply to FT-Orbitraps and FT-quadrupole ion traps.

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

PubMed

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

2016-08-01

Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

PubMed

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

2016-01-01

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

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse

PubMed Central

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

2016-01-01

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

Toxicological effects of benzo[a]pyrene on DNA methylation of whole genome in ICR mice.

PubMed

Zhao, L; Zhang, S; An, X; Tan, W; Pang, D; Ouyang, H

2015-10-30

It has been well known that alterations in DNA methylation - an important regulator of gene transcription - lead to cancer. Therefore a change in the level of DNA methylation of whole genome has been considered as a biomarker of carcinogenesis. Previously, a large number of experimental results in genetic toxicology have showed that benzo[a]pyrene could cause DNA mutation and fragmentation. However, there was little to no studies on alterations in DNA methylation of genome directly result from exposure to benzo[a]pyrene. In this paper, possible mechanisms of alterations in whole genomic DNA methylation by benzo[a]pyrene were investigated using ICR mice after benzo[a]pyrene exposure. The blood, liver, pancreas, skin, lung and bladder of ICR mice were removed and checked after a fixed time interval (6 hours) of benzo[a]pyrene exposure, and whole genomic DNA methylation level was determined by high performance liquid chromatography (HPLC). The results exhibited tissue specificity, that is, the level of whole genomic DNA methylation decreases significantly in blood and liver, rather than pancreas, lung, skin and bladder of ICR mice. This study investigated the direct relationship between aberrant DNA methylation level and benzo[a]pyrene exposure, which might be helpful to clarify the toxicological mechanism of benzo[a]pyrene in epigenetic perspectives.

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

PubMed

Ravnskov, U

2000-08-01

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

Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.

PubMed

Brosnan-Watters, G; Ogimi, T; Ford, D; Tatekawa, L; Gilliam, D; Bilsky, E J; Nash, D

2000-08-01

1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA

Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis.

PubMed

Rankin, Andrew L; Seth, Nilufer; Keegan, Sean; Andreyeva, Tatyana; Cook, Tim A; Edmonds, Jason; Mathialagan, Nagappan; Benson, Micah J; Syed, Jameel; Zhan, Yutian; Benoit, Stephen E; Miyashiro, Joy S; Wood, Nancy; Mohan, Shashi; Peeva, Elena; Ramaiah, Shashi K; Messing, Dean; Homer, Bruce L; Dunussi-Joannopoulos, Kyri; Nickerson-Nutter, Cheryl L; Schnute, Mark E; Douhan, John

2013-11-01

Autoantibody production and immune complex deposition within the kidney promote renal disease in patients with lupus nephritis. Thus, therapeutics that inhibit these pathways may be efficacious in the treatment of systemic lupus erythematosus. Bruton's tyrosine kinase (BTK) is a critical signaling component of both BCR and FcR signaling. We sought to assess the efficacy of inhibiting BTK in the development of lupus-like disease, and in this article describe (R)-5-amino-1-(1-cyanopiperidin-3-yl)-3-(4-[2,4-difluorophenoxy]phenyl)-1H-pyrazole-4-carboxamide (PF-06250112), a novel highly selective and potent BTK inhibitor. We demonstrate in vitro that PF-06250112 inhibits both BCR-mediated signaling and proliferation, as well as FcR-mediated activation. To assess the therapeutic impact of BTK inhibition, we treated aged NZBxW_F1 mice with PF-06250112 and demonstrate that PF-06250112 significantly limits the spontaneous accumulation of splenic germinal center B cells and plasma cells. Correspondingly, anti-dsDNA and autoantibody levels were reduced in a dose-dependent manner. Moreover, administration of PF-06250112 prevented the development of proteinuria and improved glomerular pathology scores in all treatment groups. Strikingly, this therapeutic effect could occur with only a modest reduction observed in anti-dsDNA titers, implying a critical role for BTK signaling in disease pathogenesis beyond inhibition of autoantibody production. We subsequently demonstrate that PF-06250112 prevents proteinuria in an FcR-dependent, Ab-mediated model of glomerulonephritis. Importantly, these results highlight that BTK inhibition potently limits the development of glomerulonephritis by impacting both cell- and effector molecule-mediated pathways. These data provide support for evaluating the efficacy of BTK inhibition in systemic lupus erythematosus patients.

Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

PubMed

Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

2015-09-01

The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50 % infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, were 2.7 ± 0.4 log10 p.f.u. for ICR mice and 3.5 ± 0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans.

Urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors of complete remission in primary glomerulonephritis.

PubMed

Chanrat, Eakkapat; Worawichawong, Supanat; Radinahamed, Piyanuch; Sathirapongsasuti, Nuankanya; Nongnuch, Arkom; Assanatham, Montira; Udomsubpayakul, Umaporn; Kitiyakara, Chagriya

2018-04-01

The balance of several cytokines likely influences the resolution of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1) is a chemokine that promotes renal inflammation whereas epidermal growth factor (EGF) stimulates protective responses. Previously, high urine MCP-1(MCP-1) and low urine EGF (EGF) levels were found to be associated with tubulointerstitial fibrosis, but there is limited information on the value of these mediators as predictors of therapeutic responses or long term outcome in primary glomerulonephritis. To determine the performance of urine EGF, MCP-1 or their ratio at baseline as biomarkers to predict complete remission, and the relationship of these mediators with subsequent renal function 24 months later in primary glomerulonephritis. This is a prospective study of patients with biopsy-proven primary glomerulonephritis. Baseline urine samples were collected at biopsy before therapy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assays and expressed as a ratio to urine creatinine (ng/mgCr) or as EGF/MCP-1 ratio (ng/ng). Proteinuria and estimated glomerular filtration rate (eGRF) were monitored after therapy. Complete remission (CR) was defined as proteinuria ≤ 0.3 g/gCr. Median follow-up was 20 months. Of all patients (n = 74), 38 patients (51.4%) subsequently achieved CR. Baseline urine EGF and EGF/MCP-1 levels were significantly higher in CR compared to Not CR. By contrast, MCP-1 was not different. High EGF (EGF > 75 ng/mgCr) was a significant predictor (OR 2.28) for CR by multivariate analysis after adjusting for proteinuria, blood pressure, baseline eGFR. In patients who completed 24 months follow-up (n = 43), baseline EGF correlated inversely with proteinuria and positively with eGFR at 24 months. High urine EGF level is a promising biomarker of CR. Baseline EGF levels correlated with kidney function at 2 years. EGF/MCP-1 was not superior to EGF alone. Further studies are necessary to

Environmental Forensics: Molecular Insight into Oil Spill Weathering Helps Advance High Magnetic Field FT-ICR Mass Spectrometry

NASA Astrophysics Data System (ADS)

McKenna, Amy

2013-03-01

The depletion of terrestrial global oil reserves has shifted oil exploration into offshore and ultra-deep water (> 5000 ft) oil reserves to meet global energy demands. Deep water reservoirs are currently in production in many parts of the world, including the Gulf of Mexico, but production is complicated by the water depth and thick salt caps that challenge reservoir characterization / production. The explosion aboard the Deepwater Horizon in April 2010 resulted in an estimated total release of ~5 million barrels (BP claims that they collected ~1M barrels, for a net release of 4 M) of light, sweet crude oil into the Gulf of Mexico and shifted attention toward the environmental risks associated with offshore oil production. The growing emphasis on deep water and ultra-deep water oil production poses a significant environmental threat, and increased regulations require that oil companies minimize environmental impact to prevent oil spills, and mitigate environmental damage when spills occur. Every oil spill is unique. The molecular transformations that occur to petroleum after contact with seawater depend on the physical and chemical properties of the spilled oil, environmental conditions, and deposition environment. Molecular-level knowledge of the composition, distribution, and total mass of released hydrocarbons is essential to disentangle photo- and bio-degradation, source identification, and long-term environmental impact of hydrocarbons released into the environment. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is unsurpassed in its ability to characterize complex mixtures at the level of elemental composition assignment. Only FT-ICR mass spectrometry can routinely achieve the required minimum resolving power necessary to elucidate molecular-level characterization of crude oil. Conversely, the spectral complexity of petroleum facilitates identification of systematic errors in the accumulation, transfer, excitation, and detection

Necrotizing crescentic glomerulonephritis related to sarcoidosis: a case report.

PubMed

Maroz, Natallia; Field, Halle

2015-12-14

Renal injury due to sarcoidosis develops in less than a quarter of patients with this systemic disease. In most cases, granulomatous tissue alters the production of vitamin D, which leads to hypercalciuria, nephrocalcinosis, and nephrolithiasis. Granulomatous interstitial nephritis is another well-recognized pathological process associated with sarcoidosis. However, a glomerular pathology is very rarely noted, and only a few cases are reported to have cellular crescentic glomerulonephritis. We describe the case of a 26-year-old African American woman with systemic sarcoidosis, with a unique constellation of renal lesions, including noncaseating epithelioid granulomatous necrotizing interstitial nephritis, cellular crescent formation, and necrotizing vasculitis. Immunosuppressive therapy was helpful for alleviating her nephrotic syndrome and maintaining the stability of her renal function over a 30-month period. Glomerular involvement of sarcoidosis needs to be considered in the differential diagnosis in cases of rapidly progressive glomerular nephritis.

Immunoadsorption in Anti-GBM Glomerulonephritis: Case Report in a Child and Literature Review.

PubMed

Dorval, Guillaume; Lion, Mathilde; Guérin, Sophie; Krid, Saoussen; Galmiche-Rolland, Louise; Salomon, Rémi; Boyer, Olivia

2017-11-01

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare autoimmune disease that is characterized by rapidly progressive glomerulonephritis that may be associated with pulmonary hemorrhage. Anti-GBM GN is caused by autoantibodies (classically type G immunoglobulin) directed against the α3 subunit of type IV collagen. Without any appropriate treatment, the disease is generally fulminant, and patient and kidney survival is poor. The current guidelines recommend the use of plasma exchanges and immunosuppressive drugs. Immunoadsorption (IA) can remove pathogenic IgGs from the circulation and do not require plasma infusions, contrary to plasma exchanges. IA has seldom been used in adult patients with good tolerance and efficiency. We report herein the first pediatric case successfully treated with IA combined with immunosuppressive drugs in a 7-year-old girl who presented acute kidney injury (estimated glomerular filtration rate 38 mL/minute/1.73 m 2 ). A kidney biopsy revealed numerous >80% glomerular crescents and linear IgG deposits along the glomerular basement membrane. Ten IA sessions led to rapid and sustained clearance of autoantibodies and improvement of kidney function until 21 months after onset (glomerular filtration rate 87 mL/minute/1.73 m 2 ). No adverse effect was noted. This report adds to the growing body of evidence suggesting IA as a therapeutic alternative to plasma exchanges in anti-GBM GN. The other 27 published pediatric cases of anti-GBM GN are reviewed. Copyright © 2017 by the American Academy of Pediatrics.

Antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis associated with rheumatoid arthritis: An unusual case report.

PubMed

Hsieh, Hsiu-Shin; Chang, Chao-Fu; Yang, An-Han; Kuo, Hsiao-Ling; Yang, Wu-Chang; Lin, Chih-Ching

2003-10-01

Clinically relevant renal lesions in rheumatoid arthritis (RA) are not common. More often renal involvement is related to complications of therapy than the disease itself. The most common forms of primary renal disease in RA are membranous glomerulonephropathy and a pure mesangial proliferative glomerulonephritis. Some studies have described the association between crescentic glomerulonephritis (crescentic GN) and RA, but they were all found to be perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positive. However, RA associated with ANCA negative pauci-immue crescentic GN has not been reported. This is a case report of a 37-year-old female with RA who initially presented with general oedema and acute deterioration of renal function. The renal biopsy revealed ANCA negative pauci-immune crescentic GN. The patient was treated with steroid pulse and plasmapheresis, but not cyclophosphamide because of severe urosepsis. Despite the use of aggressive therapy, her renal function was not improved and she underwent maintenance haemodialysis thereafter. Because ANCA negative crescentic GN may occur in RA patients without frank systemic vasculitis, but with severe clinical manifestation, a heightened suspicion for a relatively 'silent' crescentic GN would have led to the correct diagnosis and appropriate treatment.

Bartonella endocarditis with glomerulonephritis in a patient with complete transposition of the great arteries.

PubMed

Hashemi, Helen; Endicott-Yazdani, Tiana R; Oguayo, Christopher; Harmon, David M; Tran, Tuan; Tsai-Nguyen, Ginger; Benavides, Raul; Spak, Cedric W; Nguyen, Hoang-Lan

2018-01-01

We describe a patient with history of dextro-transposition of the great vessels, ventricular septal defect, and pulmonary valve replacement who presented with fatigue, prolonged fever, and leg edema. He was found to have kidney injury, pancytopenia, and liver congestion. Echocardiogram revealed thickened leaflets with prolapsing vegetation on the pulmonary valve. Given the negative blood cultures, high Bartonella henselae immunogobulin G titer (≥1:1024) and positive immunoglobulin M titer (≥1:20), he was diagnosed with Bartonella endocarditis complicated with glomerulonephritis.

Characterization of chemical constituents in Rhodiola Crenulate by high-performance liquid chromatography coupled with Fourier-transform ion cyclotron resonance mass spectrometer (HPLC-FT-ICR MS).

PubMed

Han, Fei; Li, Yanting; Mao, Xinjuan; Xu, Rui; Yin, Ran

2016-05-01

In this work, an approach using high-performance liquid chromatography coupled with diode-array detection and Fourier-transform ion cyclotron resonance mass spectrometer (HPLC-FT-ICR MS) for the identification and profiling of chemical constituents in Rhodiola crenulata was developed for the first time. The chromatographic separation was achieved on an Inertsil ODS-3 column (150 mm × 4.6 mm,3 µm) using a gradient elution program, and the detection was performed on a Bruker Solarix 7.0 T mass spectrometer equipped with electrospray ionization source in both positive and negative modes. Under the optimized conditions, a total of 48 chemical compounds, including 26 alcohols and their glycosides, 12 flavonoids and their glycosides, 5 flavanols and gallic acid derivatives, 4 organic acids and 1 cyanogenic glycoside were identified or tentatively characterized. The results indicated that the developed HPLC-FT-ICR MS method with ultra-high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents in R. crenulata. And it provides a helpful chemical basis for further research on R. crenulata. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Calibration of marginal oscillator sensitivity for use in ICR spectrometry

NASA Technical Reports Server (NTRS)

Anicich, V. G.; Huntress, W. T., Jr.

1977-01-01

A constant-reference load is utilized as Q-spoiler in calibrations of relative sensitivity variations of a marginal oscillator with frequency. Frequency-dependent effects troublesome in earlier Q-spoilers are compensated by employing a pure resistive calibration load with compensation for the small distributed capacitance of large resistors. The validity of the approach is demonstrated for a 2:1 mass ratio range, and validity for a mass ratio range greater than 10:1 is claimed. The circuit and technique were developed for use in ion cyclotron resonance (ICR) spectrometric practice.

Cyclotron Phase-Coherent Ion Spatial Dispersion in a Non-Quadratic Trapping Potential is Responsible for FT-ICR MS at the Cyclotron Frequency

NASA Astrophysics Data System (ADS)

Nagornov, Konstantin O.; Kozhinov, Anton N.; Tsybin, Yury O.

2018-01-01

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) at the cyclotron frequency instead of the reduced cyclotron frequency has been experimentally demonstrated using narrow aperture detection electrode (NADEL) ICR cells. Here, based on the results of SIMION simulations, we provide the initial mechanistic insights into the cyclotron frequency regime generation in FT-ICR MS. The reason for cyclotron frequency regime is found to be a new type of a collective motion of ions with a certain dispersion in the initial characteristics, such as pre-excitation ion velocities, in a highly non-quadratic trapping potential as realized in NADEL ICR cells. During ion detection, ions of the same m/z move in phase for cyclotron ion motion but out of phase for magnetron (drift) ion motion destroying signals at the fundamental and high order harmonics that comprise reduced cyclotron frequency components. After an initial magnetron motion period, ion clouds distribute into a novel type of structures - ion slabs, elliptical cylinders, or star-like structures. These structures rotate at the Larmor (half-cyclotron) frequency on a plane orthogonal to the magnetic field, inducing signals at the true cyclotron frequency on each of the narrow aperture detection electrodes. To eliminate the reduced cyclotron frequency peak upon dipolar ion detection, a number of slabs or elliptical cylinders organizing a star-like configuration are formed. In a NADEL ICR cell with quadrupolar ion detection, a single slab or an elliptical cylinder is sufficient to minimize the intensity of the reduced cyclotron frequency components, particularly the second harmonic. [Figure not available: see fulltext.

An outbreak of acute post-streptococcal glomerulonephritis in remote Far North Queensland.

PubMed

Scrace, Melania; Koko, Karen

2006-08-01

To observe and record an outbreak of acute post-streptococcal glomerulonephritis (APSGN) in the Lockhart River community in 2005 and the steps taken by health workers to contain the epidemic. A descriptive study of cases of APSGN and children aged from 2 to 12 years involved in the screening program. A remote indigenous community in Far North Queensland. All children aged from 2 to 12 years in the Lockhart River community. Eighty-seven children were screened. And 46% were found to have infected scabies. There were 11 confirmed cases of APSGN over four months from February to May. Infected scabies was the main preceding finding in these children.

Bartonella endocarditis with glomerulonephritis in a patient with complete transposition of the great arteries

PubMed Central

Hashemi, Helen; Endicott-Yazdani, Tiana R.; Oguayo, Christopher; Harmon, David M.; Tran, Tuan; Tsai-Nguyen, Ginger; Benavides, Raul; Spak, Cedric W.; Nguyen, Hoang-Lan

2018-01-01

ABSTRACT We describe a patient with history of dextro-transposition of the great vessels, ventricular septal defect, and pulmonary valve replacement who presented with fatigue, prolonged fever, and leg edema. He was found to have kidney injury, pancytopenia, and liver congestion. Echocardiogram revealed thickened leaflets with prolapsing vegetation on the pulmonary valve. Given the negative blood cultures, high Bartonella henselae immunogobulin G titer (≥1:1024) and positive immunoglobulin M titer (≥1:20), he was diagnosed with Bartonella endocarditis complicated with glomerulonephritis. PMID:29686571

Proliferative glomerulonephritis with monoclonal IgG deposits in two kidney allografts successfully treated with rituximab.

PubMed

Merhi, Basma; Patel, Nikunjkuma; Bayliss, George; Henriksen, Kammi J; Gohh, Reginald

2017-06-01

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposit (PGNMID), a recently described pathologic entity in native kidneys, has been recognized in kidney transplant patients, where it can present as either recurrent or de novo disease. There is no definitive treatment to date, in either population. Here, we present two cases of PGNMID in kidney allografts that illustrate the challenges of diagnostic approach and highlight the allograft outcome after treatment with rituximab as a potential treatment of this condition.

Molecular characterization and comparison of shale oils generated by different pyrolysis methods using FT-ICR mass spectrometry

USGS Publications Warehouse

Jin, J.M.; Kim, S.; Birdwell, J.E.

2011-01-01

Fourier transform ion cyclotron resonance mass spectrometry (FT ICR-MS) was applied in the analysis of shale oils generated using two different pyrolysis systems under laboratory conditions meant to simulate surface and in situ oil shale retorting. Significant variations were observed in the shale oils, particularly the degree of conjugation of the constituent molecules. Comparison of FT ICR-MS results to standard oil characterization methods (API gravity, SARA fractionation, gas chromatography-flame ionization detection) indicated correspondence between the average Double Bond Equivalence (DBE) and asphaltene content. The results show that, based on the average DBE values and DBE distributions of the shale oils examined, highly conjugated species are enriched in samples produced under low pressure, high temperature conditions and in the presence of water.

Fibrillary Glomerulonephritis in a Patient with Sjogren’s Syndrome

PubMed Central

Saleem, Tahira Sabeen; Usman, Muhammad Shariq; Chowdhury, Waliul; Kuzel, Aaron R; Iqbal, Hafiz Imran; Rahim, Mustafa

2018-01-01

Fibrillary glomerulonephritis (FGN) is an uncommon cause of primary glomerular disease. FGN is usually idiopathic; however, it has been associated with underlying malignancy or autoimmune diseases in some patients as well. The most commonly found autoimmune diseases in FGN patients include Graves’ disease, systemic lupus nephritis, Chron’s disease, and idiopathic thrombocytopenia purpura. FGN in a patient with underlying asymptomatic Sjogren’s syndrome is very rare in the literature, with only two previously reported cases of this association. We present the case of a 75-year-old female with a past medical history of asymptomatic primary Sjogren's syndrome and fibromyalgia, who presented to emergency department with a new episode of hypertension. The electron microscopy (EM) showed randomly arranged nonamyloid fibrillar deposits in the mesangium and glomerular capillary walls, confirming FGN. In this case-based review, we describe in detail the diagnostic work-up, clinical course, and complications in management. We also discuss some of the other nonamyloid fibrillary glomerular diseases. PMID:29922524

Proliferative glomerulonephritis with monoclonal IgG deposits in two kidney allografts successfully treated with rituximab

PubMed Central

Patel, Nikunjkuma; Bayliss, George; Henriksen, Kammi J.; Gohh, Reginald

2017-01-01

Abstract Proliferative glomerulonephritis with monoclonal immunoglobulin G deposit (PGNMID), a recently described pathologic entity in native kidneys, has been recognized in kidney transplant patients, where it can present as either recurrent or de novo disease. There is no definitive treatment to date, in either population. Here, we present two cases of PGNMID in kidney allografts that illustrate the challenges of diagnostic approach and highlight the allograft outcome after treatment with rituximab as a potential treatment of this condition. PMID:28616219

Renal effects of renal x irradiation and induced autoallergic glomerulonephritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rappaport, D.S.; Casarett, G.W.

1979-09-01

This study was conducted to determine what influence a single large x-ray exposure of kidney has on the development and course of an experimental autoallergic glomerulonephritis (EAG) in rats. EAG was induced in female Sprague-Dawley rats by immunization with Bordetella pertussis vaccine and homogenate of homologous kidney tissue and Freund's complete adjuvant. Progressive arteriolonephrosclerosis (ANS) was observed in right (irradiated) kidneys following unilateral renal irradiation (1500 rad). Rats were either immunized, sham-immunized, irradiated, sham-irradiated, or both immunized and irradiated. Light and immunofluorescent microscopic observation, urine protein content, and kidney weights were evaluated. In immunized-irradiated animals the effects of irradiation andmore » immunization were largely additive. Immunization did not considerably influence the development and course of ANS and irradiation did not considerably influence the development and course of EAG.« less

Gemella sanguinis endocarditis with c-ANCA/anti-PR-3-associated immune complex necrotizing glomerulonephritis with a ‘full-house’ pattern on immunofluorescence microscopy

PubMed Central

Rousseau-Gagnon, Mathieu; Riopel, Julie; Desjardins, Anne; Garceau, Daniel; Agharazii, Mohsen; Desmeules, Simon

2013-01-01

A 67-year-old man was evaluated for haematuria, with a rising creatinine level from 88 to 906 µmol/L and positive c-anti-neutrophil cytoplasm antibody (ANCA)/anti-proteinase 3 (anti-PR3). A kidney biopsy revealed necrotizing glomerulonephritis with a ‘full-house’ pattern on immunofluorescence microscopy. Echocardiography and blood cultures growing Gemella sanguinis diagnosed endocarditis. Dialysis was required for a month. Three months later, following valve replacement, glucocorticoids and 2 months of antibiotic therapy, the creatinine level decreased to 62 µmol/L and c-ANCA/anti-PR3 disappeared. This first case of c-ANCA/anti-PR3 positive glomerulonephritis with a ‘full-house’ immunofluorescence pattern due to bacterial endocarditis underlines the importance of ruling out infection with ANCA positivity or kidney biopsy suggestive of lupus nephritis. PMID:26064489

FT-ICR mass spectrometric and density functional theory studies of sulfate prenucleation clusters

NASA Astrophysics Data System (ADS)

Lemke, K. H.

2012-12-01

Recent mass spectrometric1 and relaxation spectroscopic studies2 of metal sulfate salts have demonstrated that aqueous clusters play an important role in sulfate prenucleation processes. While such studies provide evidence that that ion clusters are nucleation relevant species, ultra-high resolution mass spectrumetry, in particular, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS) can provide additional valuable information about the molecular composition and stability of individual ion clusters. Prompted by the above studies, our group has begun a systematic survey of metal sulfate clusters using FT-ICR mass spectrometry. Here, I report stoichiometries, structures and thermodynamic properties of calcium sulfate ion clusters, both "dry" and microsolvated, using electrospray ionization FT-ICR mass spectrometry in combination with semi-empirical methods and M062X/aug-cc-PVXZ level density functional theory calculations. In electrosprayed dilute aqueous solutions of CaSO4 (1-20mM), droplet desolvation results in the formation of stable doubly-charged clusters of [Ca(CaSO4)m(H2O)n]+2 (m≤10 & n≤9) as well as larger quadruply-charged ion clusters [Ca2(CaSO4)m(H2O)n]+4 with m≤23 and n≤10, demonstrating considerable sulfate nucleation potential in undersaturated electrolyte solutions. An attempt was also made to assess the extent of ion cluster aggregation in solution prior to electrospray ionization by measuring ion mass spectra at different solution concentrations. In brief, an increase in calcium sulfate concentration from 1-10mM results in a continuous increase in polynuclear ion cluster species, while smaller clusters, for instance, Ca[CaSO4]+2 and corresponding hydrated forms, become increasingly less abundant. Building on semi-empirical methods, M062X calculations have been applied to predict calcium sulfate cluster geometries, both "dry" and microsolvated, as well as the size-dependent evolution of clustering and hydration energies. 1

SCG/Kinjoh mice: a model of ANCA-associated crescentic glomerulonephritis with immune deposits.

PubMed

Neumann, Irmgard; Birck, Rainer; Newman, Mark; Schnülle, Peter; Kriz, Wilhelm; Nemoto, Kyuichi; Yard, Benito; Waldherr, Rüdiger; Van Der Woude, Fokko J

2003-07-01

Spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mice spontaneously develop crescentic glomerulonephritis (CGN), systemic vasculitis, and perinuclear ANCA (pANCA), and have been suggested as an animal model for human antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AASV). Since no systematic serologic, immunohistologic, or structural evaluation had been performed thus far, we reinvestigated the development of ANCA and CGN in these mice. SCG/Kj mice were subjected to serologic and urinary analysis, as well as histologic evaluation of the kidneys by standard light, immunofluorescence, and electron microscopy at regular intervals during the course of the disease. Perinuclear ANCA developed as early as the 6th week of life, increasing both in frequency and titer in up to 100% of animals at week 20. Crescent formation began at week 10 and peaked at week 16, maximally affecting 57% of glomeruli. Crescent formation was initiated by "activated" podocytes that formed cell bridges between tuft and Bowman's capsule. The typical picture of a diffuse immune complex nephritis was found in all animals as early as 8 weeks. Fluorescence intensity increased with age and became strongly positive for immunoglobulin (Ig)A, IgM, IgG, and C3 in the mesangium and along the peripheral capillary loops. Although ANCAs were found in the majority of animals, the massive presence of glomerular immune deposits differed from the pauci-immune pattern found in human AASV, making this model not completely representative for human ANCA-associated CGN. However, the spontaneous and concomitant development of pANCA, small vessel vasculitis, and CGN raises the opportunity to analyze pathogenetic links between these disease manifestations in vivo.

Evaluation of clinical and laboratory findings in pediatric post-streptococcal glomerulonephritis.

PubMed

Kılıc, Beltinge Demircioglu; Kara, Mehtap Akbalık; Buyukcelik, Mithat; Balat, Ayse

2018-05-05

Acute post-streptococcal glomerulonephritis (APSGN) is the most common postinfectious glomerulonephritis in childhood. In this study, we aimed to determine the possible risk factor(s), responsible for decreased glomerular filtration rate (GFR) in APSGN. The data of patients followed up with the diagnosis of APSGN in the Pediatric Nephrology Clinic of Gaziantep University Hospital between October 2014 and October 2016 were retrospectively evaluated. Total number of subjects was 75 (Male/Female:42/33) with the mean age of 8.20±3.25 years. Most common presentations were edema (86.7%), macroscopic hematuria (82.7%) and hypertension (73.3%, n=55). In laboratory examination, 28 children (37.3%) had hypoalbuminemia, 58 (77.3%) had proteinuria, 20 (26.7%) had increased C reactive protein (CRP), while 74 (98.7%) and 12 (16%) of them had decreased C3 and C4 levels, respectively. The number of children with GFR value <90 ml/min/1.73/m2 was 22 (29.3%). The risk of decreased GFR was significantly higher in patients with increased CRP (p:0.001,OR:3.58), hypoalbuminemia (p:0.006,OR:4.83), and decreased C4 level (p:0.010,OR:11.53). Additionally, white blood cell (WBC), neutrophil count, and neutrophil-lymphocyte ratio (NLR) were significantly higher (p:0.02, p:0.006, p:0.004, respectively) in patients with low GFR. Although the prognosis of APSGN in children is good, severe systemic complications and renal failure may develop during the follow-up period. We suggest that decreased C4 level, presence of hypoalbuminemia, increased inflammatory markers (WBC, CRP, neutrophil count and NLR) might be possible risk factors for severity of renal involvement. Especially decreased C4 level may be a risk factor for decreased GFR in those children. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Membranous glomerulonephritis in a child asymptomatic for hepatitis B virus. Concomitant seropositivity for HBsAG and anti-HBs.

PubMed

Hirsch, H Z; Ainsworth, S K; DeBeukelaer, M; Brissie, R M; Hennigar, G R

1981-04-01

The presence of hepatitis B surface antigen (HBsAg) in association with immunoglobulins and complement components within the glomerular basement membranes of adults having chronic active hepatitis has been well documented. In addition, investigators in Poland have demonstrated HBsAg immune complexes in glomeruli of children who did not have clinical evidence of hepatitis. More recently, a single case of childhood membranous glomerulonephritis in an asymptomatic carrier of hepatitis B virus was cited by observers in Canada. Reported here is the deposition of HBsAg immune complexes in the glomerular basement membranes of a 13-year-old black boy who had membranous glomerulopathy but not clinical evidence of hepatitis. This may be the first reported case in the United States of HbsAg-associated membranous glomerulonephritis in a child asymptomatic for hepatitis B virus, and only the second such case in North America. However, unlike previous studies of childhood glomerulopathy in association with hepatitis B virus, this patient is seropositive for both HBsAg and anti-HBs (antibody for hepatitis B surface antigen). Similar "rare" serologic findings were found for the patient's eldest male sib.

Increasing Polyaromatic Hydrocarbon (PAH) Molecular Coverage during Fossil Oil Analysis by Combining Gas Chromatography and Atmospheric-Pressure Laser Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS)

PubMed Central

Benigni, Paolo; DeBord, J. Daniel; Thompson, Christopher J.; Gardinali, Piero; Fernandez-Lima, Francisco

2016-01-01

Thousands of chemically distinct compounds are encountered in fossil oil samples that require rapid screening and accurate identification. In the present paper, we show for the first time, the advantages of gas chromatography (GC) separation in combination with atmospheric-pressure laser ionization (APLI) and ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for the screening of polyaromatic hydrocarbons (PAHs) in fossil oils. In particular, reference standards of organics in shale oil, petroleum crude oil, and heavy sweet crude oil were characterized by GC-APLI-FT-ICR MS and APLI-FT-ICR MS. Results showed that, while APLI increases the ionization efficiency of PAHs, when compared to other ionization sources, the complexity of the fossil oils reduces the probability of ionizing lower-concentration compounds during direct infusion. When gas chromatography precedes APLI-FT-ICR MS, an increase (more than 2-fold) in the ionization efficiency and an increase in the signal-to-noise ratio of lower-concentration fractions are observed, giving better molecular coverage in the m/z 100–450 range. That is, the use of GC prior to APLI-FT-ICR MS resulted in higher molecular coverage, higher sensitivity, and the ability to separate and characterize molecular isomers, while maintaining the ultrahigh resolution and mass accuracy of the FT-ICR MS separation. PMID:27212790

77 FR 2760 - Proposed Information Collection Request (ICR) for the Mining Voice in the Workplace Survey...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... DEPARTMENT OF LABOR Proposed Information Collection Request (ICR) for the Mining Voice in the...)(A)]. This program helps to ensure that required data can be provided in the desired format...' voice in mining workplaces under the jurisdiction of DOL's Mine Safety and Health Administration (MSHA...

Glomerulonephritis in a ferret with feline coronavirus infection.

PubMed

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

2015-09-01

A male domestic ferret (Mustela putorius furo), which was purchased from outside of Japan at 13 weeks of age, was euthanized at 18 months of age because of poor health. At autopsy, the liver, spleen, and mesenteric lymph node were enlarged, and white foci were observed on the outer surface of the liver. The outer surface of the mesenteric lymph node was dark red. Histologically, granulomas were observed in the liver, spleen, bone marrow, and lymph nodes, composed mainly of aggregated epithelioid macrophages, some of which were positive to an anti-feline coronavirus (FCoV; Alphacoronavirus 1) antibody in immunohistochemistry. Mesangioproliferative glomerulonephritis was observed, and periodic acid-Schiff-positive deposits were observed along glomerular capillary walls. These deposits stained pale red with periodic acid-methenamine silver stain and red with Masson trichrome stain, and were also observed in the mesangial matrix. In affected glomeruli, glomerular capillary walls and mesangial areas were positive for anti-ferret immunoglobulin G. By electron microscopy, subepithelial and mesangial electron-dense deposits were observed consistent with immune complex deposition. The deposition of immune complexes may have been associated with FCoV infection. © 2015 The Author(s).

Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice

PubMed Central

Kim, H J; Kim, D K; Kim, H; Koh, J Y; Kim, K M; Noh, M S; Lee, S; Kim, S; Park, S H; Kim, J J; Kim, S Y; Lee, C H

2008-01-01

Background and purpose: Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT2 receptor agonists compound A (4′-{[pentanoyl (phenyl) amino]methyl}-1,1′-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid). Experimental approach: A video recording was used to determine whether the BLT2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used. Key results: Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose–response curve for compound A showed peaks at around 0.005–0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT2 receptor antagonist) on the BLT2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT2 receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice. Conclusions and implications: Our present results corroborate the hypothesis that the BLT2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT2 receptor

76 FR 27363 - Proposed Information Collection Request (ICR) for the Impact Evaluation of the YouthBuild Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... characteristics? What are YouthBuild's impacts on crime and delinquency? What are the program's impacts on social... (ICR) for the Impact Evaluation of the YouthBuild Program; Comment Request AGENCY: Employment and..., collection instruments are clearly understood, and [[Page 27364

Rituximab treatment for fibrillary glomerulonephritis.

PubMed

Hogan, Jonathan; Restivo, Michaela; Canetta, Pietro A; Herlitz, Leal C; Radhakrishnan, Jai; Appel, Gerald B; Bomback, Andrew S

2014-10-01

Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Histopathological pattern in childhood glomerulonephritis.

PubMed

Moorani, Khemchand Netaram; Sherali, Afroze Ramzan

2010-12-01

To determine the histopathological pattern in childhood glomerulonephritis (CGN). This retrospective analysis of renal biopsies of 118 children with various clinical syndromes of CGN was carried out at the National Institute of Child Health (NICH) and The Kidney Center (TKC), Karachi, from July 2005 to December 2009. The age ranged from 6 months to 16 years. All biopsies were studied under light microscopy (LM) and immunoflourescence (IMF). Histopathological lesions (HPL) were classified as primary and secondary glomerular diseases. Demographic data, indications and HPL were retrieved and analyzed using descriptive statistics. Out of 118 patients, 62 (52.54%) were males and 56(47.45%) females. Mean age was 8.2 +/- 3.9 years. Major indications for biopsy were primary nephrotic syndrome (PNS 86, 72.88%). secondary GN (SGN, 17, 14.4%) and nephritic-nephrotic syndrome (NNS 13, 11%). Overall, primary glomerular diseases (PGD) accounted for 84.74% of all biopsies. Minimal change disease (MCD 38, 32.2%) and focal segmental glomerulosclerosis (FSGS 35, 29.66%) were the two most common lesions and accounted for 43% and 33.72% respectively in PNS. Other important lesions were membranous GN (MGN 10, 8.47%), membranoproliferative (MPGN 9, 7.16%), post-infective (PIGN 4, 3.38%) and IgM nephropathy (IgMN 3, 2.54%). Among secondary glomerular diseases (SGD), lupus nephritis (LN 11, 9.32%) was the most common lesion followed by Henoch-Schonlein nephritis (HSN) and haemolytic uraemic syndrome (HUS) each in 3 (2.52%). Overall, MCD and FSGS were the two most common HPL in PGD and both dominated in PNS. Lupus nephritis was the leading lesion in SGD. These histopathological pattern of CGN in our study is in conformity with the existing literature from Pakistan.

Membranoproliferative glomerulonephritis associated with autoimmune diseases.

PubMed

Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev

2014-04-01

Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.

Chemical characterization of synthetic cannabinoids by electrospray ionization FT-ICR mass spectrometry.

PubMed

Kill, Jade B; Oliveira, Izabela F; Tose, Lilian V; Costa, Helber B; Kuster, Ricardo M; Machado, Leandro F; Correia, Radigya M; Rodrigues, Rayza R T; Vasconcellos, Géssica A; Vaz, Boniek G; Romão, Wanderson

2016-09-01

The synthetic cannabinoids (SCs) represent the most recent advent of the new psychotropic substances (NPS) and has become popularly known to mitigate the effects of the Δ(9)-THC. The SCs are dissolved in organic solvents and sprayed in a dry herbal blend. However, little information is reported on active ingredients of SCs as well as the excipients or diluents added to the herbal blend. In this work, the direct infusion electrospray ionization Fourier transform ion cyclotron mass spectrometry technique (ESI-FT-ICR MS) was applied to explore the chemical composition of nine samples of herbal extract blends, where a total of 11 SCs (UR-144, JWH-073, XLR-11, JWH-250, JWH-122, AM-2201, AKB48, JWH-210, JWH-081, MAM-2201 and 5F-AKB48) were identified in the positive ionization mode, ESI(+), and other 44 chemical species (saturated and unsaturated fatty acids, sugars, flavonoids, etc.) were detected in the negative ionization mode, ESI(-). Additionally, CID experiments were performed, and fragmentation pathways were proposed to identify the connectivity of SCs. Thus, the direct infusion ESI-FT-ICR MS technique is a powerful tool in forensic chemistry that enables the rapid and unequivocal way for the determination of molecular formula, the degree of unsaturation (DBE-double bond equivalent) and exact mass (<1ppm) of a total of 55 chemical species without the prior separation step. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long-term Low-density Lipoprotein Apheresis in a Patient with Refractory Idiopathic Membranous Glomerulonephritis.

PubMed

Yabuuchi, Junko; Suwabe, Tatsuya; Mizuno, Hiroki; Ueno, Toshiharu; Hoshino, Junichi; Sekine, Akinari; Kawada, Masahiro; Yamanouchi, Masayuki; Hayami, Noriko; Hiramatsu, Rikako; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Ubara, Yoshifumi

2017-01-01

A 61-year-old Japanese man developed nephrotic syndrome (NS) due to idiopathic membranous glomerulonephritis (MGN). He received immunosuppressive therapy for two years, including prednisolone, cyclophosphamide, and cyclosporine A, but the NS persisted. Low-density lipoprotein apheresis (LDL-A) was initiated at a frequency of twice a month and continued for 9 years (203 sessions in total). His proteinuria reduced to less than 1 g daily after 9 years. LDL-A was stopped, and the NS has not relapsed for five years. This case suggests that long-term LDL-A therapy may be a treatment option for idiopathic MGN refractory to immunosuppressive therapy or short-term LDL-A.

Deletion of the Fcγ Receptor IIb in Thymic Stromal Lymphopoietin Transgenic Mice Aggravates Membranoproliferative Glomerulonephritis

PubMed Central

Mühlfeld, Anja S.; Segerer, Stephan; Hudkins, Kelly; Carling, Matthew D.; Wen, Min; Farr, Andrew G.; Ravetch, Jeffrey V.; Alpers, Charles E.

2003-01-01

Engagement of immunoglobulin-binding receptors (FcγR) on leukocytes and other cell types is one means by which immunoglobulins and immune complexes activate effector cells. One of these FcγRs, FcγRIIb, is thought to contribute to protection from autoimmune disease by down-regulation of B-cell responsiveness and myeloid cell activation. We assessed the role of FcγRIIb in a mouse model of cryoglobulin-associated membranoproliferative glomerulonephritis induced by overexpression of thymic stromal lymphopoietin (TSLP). TSLP transgenic mice were crossbred with animals deficient for FcγRIIb on the same genetic background (C57BL/6). Renal pathology was assessed in female and male animals (wild-type, FcγRIIb−/−, TSLP transgenic, and combined TSLP transgenic/FcγRIIb−/− mice) after 50 and 120 days, respectively. FcγRIIb−/− mice had no significant renal pathology, whereas overexpression of TSLP induced a membranoproliferative glomerulonephritis, as previously established. TSLP transgenic FcγRIIb−/− mice appeared sick with increased mortality. Kidney function was significantly impaired in male mice corresponding to aggravated glomerular pathology with increases in glomerular matrix and cellularity. This resulted from both a large influx of infiltrating macrophages and increased cellular proliferation. These results emphasize the important role of FcγRIIb in regulating immune responses and suggest that modulation of Fcγ receptor activation or expression may be a useful therapeutic approach for treating glomerular diseases. PMID:12937154

77 FR 6585 - Proposed Information Collection Request (ICR) for the Impact Evaluation of the YouthBuild Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-08

... job characteristics? What are YouthBuild's impacts on crime and delinquency? What are the program's... (ICR) for the Impact Evaluation of the YouthBuild Program; New Collection AGENCY: Employment and... instruments are clearly understood, and the impact of collection requirements on respondents can be properly...

IgA-dominant extracapillary proliferative glomerulonephritis following E.coli sepsis in a renal transplant recipient.

PubMed

Basic-Jukic, Nikolina; Coric, Marijana; Kastelan, Zeljko

2018-05-29

Postinfective glomerulonephritis (PIGN) generally occurs in association with staphylococcal infection. We present the first reported case of IgA-dominant PIGN after E.coli infection in a renal-transplant recipient. A 65-year-old patient with stable allograft function and E. coli urosepsis was treated with ciprofloxacin for 2 weeks with excellent response. One week later he developed proteinuria 16 g/day. Renal biopsy finding revealed IgA-dominant PIGN. He received steroid pulses and intravenous imunoglobulins without effect and had started with hemodialysis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical characteristics and outcome of pauci-immune glomerulonephritis in African Americans.

PubMed

Geetha, Duvuru; Poulton, Caroline J; Hu, Yichun; Seo, Philip; McGregor, Julie Anne G; Falk, Ronald J; Hogan, Susan L

2014-06-01

Pauci-immune glomerulonephritis is rare in African Americans (AA) and the clinical presentation and treatment outcomes of vasculitis have not been well described. We identified patients who were 2-92 years of age between 1983 and 2011 with a diagnosis of biopsy-proven pauci-immune glomerulonephritis (GN) at any point during their disease course. Comparing AA to Caucasian patients, we examined demographics, clinical features at presentation, treatment and outcomes of relapse, end-stage renal disease (ESRD), and death. Of the 672 patients, 75 were AA with the remainder being Caucasian. Compared to Caucasians, disease onset in AA was at an earlier age (52 vs. 57 years, p = 0.05) and was more often myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positive (71% vs. 54%, p = 0.01). AA patients had a shorter median time between onset of symptoms and biopsy compared to Caucasians [median (IQR): 0.23 (0.00, 1.22) months vs. 0.66 (0.00, 3.62) months, p = 0.003]. Median [Interquartile range (IQR)] follow-up in months was 28 (5, 52) in AA and 26 (10, 55) in Caucasian patients. Median estimated glomerular filtration rate was similar at presentation (21 vs. 22 ml/min/m(2)). Both groups had similar induction treatment regimens. There was less favorable treatment response among AA compared to Caucasians for initial treatment resistance (28% vs. 18%, p = 0.05) and complete remission (72% vs. 82%, p = 0.05). There were no differences in the number of renal relapses or number of deaths between the 2 groups. Overall, in multivariable analyses controlling for age, race, ANCA type, and entry serum creatinine, there were not differences by race in treatment response, renal relapse, ESRD, or death over the entire time of follow-up. AA patients with pauci-immune GN are younger and more often MPO-ANCA positive compared to Caucasians. Despite a shorter time to diagnosis for AA patients, there were no differences compared to Caucasians in treatment response, ESRD, renal

The C3aR promotes macrophage infiltration and regulates ANCA production but does not affect glomerular injury in experimental anti-myeloperoxidase glomerulonephritis

PubMed Central

Gan, Poh-Yi; Kitching, A. Richard; Holdsworth, Stephen R.

2018-01-01

The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaphylatoxin C3a signalling via the C3a receptor (C3aR) is not known. Using two different murine models of anti-myeloperoxidase (MPO) glomerulonephritis, one mediated by passive transfer of anti-MPO antibodies, the other by cell-mediated immunity, we found that the C3aR did not alter histological disease severity. However, it promoted macrophage recruitment to the inflamed glomerulus and inhibited the generation of MPO-ANCA whilst not influencing T cell autoimmunity. Thus, whilst the C3aR modulates some elements of disease pathogenesis, overall it is not critical in effector responses and glomerular injury caused by autoimmunity to MPO. PMID:29315316

Probing the Mechanisms of an Air Amplifier using a LTQ-FT-ICR-MS and Fluorescence Spectroscopy

PubMed Central

Dixon, R. Brent; Muddiman, David C.; Hawkridge, Adam M.; Fedorov, A. G.

2008-01-01

We report the first quantitative assessment of electrosprayed droplet/ion focusing enabled by the use of a voltage-assisted air amplifier between an electrospray ionization emitter and a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer (ESI-LTQ-FT-ICR-MS). A solution of fluorescent dye was electrosprayed with a stainless steel mesh screen placed in front of the MS inlet capillary acting as a gas-permeable imaging plate for fluorescence spectroscopy. Without use of the air amplifier no detectable FT-ICR signal was observed, as well as no detectable fluorescence on the screen upon imaging using a fluorescence scanner. When the air amplifier was turned ON while electrospraying the fluorescent dye, FT-ICR mass spectra with high signal to noise ratio were obtained with an average ion injection time of 21 milliseconds for an AGC target value of 5 × 105. Imaging of the screen using a fluorescence scanner produced a distinct spot of cross-sectional area ~33.5 mm2 in front of the MS inlet capillary. These experimental results provide direct evidence of aerodynamic focusing of electrosprayed droplets/ions enabled by an air amplifier, resulting in improved electrospray droplet/ion capture efficiency and reduced ion injection time. A second set of experiments was carried out to explore whether the air amplifier assists in desolvation. By electrospraying a mix of quaternary amines, ratios of increasingly hydrophobic molecules were obtained. Observation of the solvophobic effect associated with electrospray ionization resulted in a higher abundance of the hydrophobic molecule. This bias was eliminated when the air amplifier was turned ON and a response indicative of the respective component concentrations of the molecules in the bulk solution was observed. PMID:17855111

Nanoscale-alumina induces oxidative stress and accelerates amyloid beta (Aβ) production in ICR female mice

NASA Astrophysics Data System (ADS)

Shah, Shahid Ali; Yoon, Gwang Ho; Ahmad, Ashfaq; Ullah, Faheem; Amin, Faiz Ul; Kim, Myeong Ok

2015-09-01

The adverse effects of nanoscale-alumina (Al2O3-NPs) have been previously demonstrated in both in vitro and in vivo studies, whereas little is known about their mechanism of neurotoxicity. It is the goal of this research to determine the toxic effects of nano-alumina on human neuroblastoma SH-SY5Y and mouse hippocampal HT22 cells in vitro and on ICR female mice in vivo. Nano-alumina displayed toxic effects on SH-SY5Y cell lines in three different concentrations also increased aluminium abundance and induced oxidative stress in HT22 cells. Nano-alumina peripherally administered to ICR female mice for three weeks increased brain aluminium and ROS production, disturbing brain energy homeostasis, and led to the impairment of hippocampus-dependent memory. Most importantly, these nano-particles induced Alzheimer disease (AD) neuropathology by enhancing the amyloidogenic pathway of Amyloid Beta (Aβ) production, aggregation and implied the progression of neurodegeneration in the cortex and hippocampus of these mice. In conclusion, these data demonstrate that nano-alumina is toxic to both cells and female mice and that prolonged exposure may heighten the chances of developing a neurodegenerative disease, such as AD.

Antiviral therapy for HCV-associated cryoglobulinemic glomerulonephritis: case report and review of the literature.

PubMed

Fabrizi, Fabrizio; Fogazzi, Giovanni Battista; Cresseri, Donata; Passerini, Patrizia; Martin, Paul; Donato, Maria Francesca; Rumi, Maria Grazia; Messa, Piergiorgio

2012-01-01

We describe the case of a 51-year-old woman with HCV-associated cryoglobulinemic glomerulonephritis (GN). She presented mild deterioration of kidney function, non-nephrotic proteinuria, and active urinary sediment. Kidney biopsy showed features of membranoproliferative changes with some sclerosis. Sustained viral response (SVR) was obtained by 6 months of antiviral therapy (peg-IFN-α2a plus ribavirin). SVR was linked with improvement of kidney function and remission of proteinuria. Clinical and virological remission persists over a 25-month follow-up. This case report emphasizes efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis--preliminary but encouraging results exist. We identified by systematic review of the literature 9 studies (156 unique patients); the pooled estimate of frequency of sustained virological response after IFN-based therapy was 0.49 (95% confidence interval, CI: 0.21, 0.77; p < 0.0005; random effects model). Heterogeneity was found (I(2) = 98.9%, p < 0.0001). Two possible regimens should be considered for the treatment of HCV-associated cryoglobulinemic GN according to the clinical presentation. Immunosuppressive therapy is recommended for HCV-related kidney disease having aggressive course, and recent evidence supports rituximab (RTX) use with a reduced exposure to corticosteroids. We identified six studies (66 unique patients) on RTX therapy for HCV-associated kidney disease; at the end of RTX therapy, the pooled estimate of the mean decrease in proteinuria was 1.4 g/24 h (95% CI: 0.75, 2.05, p < 0.001); The p test for heterogeneity gave a value of 0.94 (I(2) = 0). Several questions related to RTX use remain. HCV-induced GN is uncommon among CKD patients of developed countries, and this clearly hampers prospective controlled clinical trials aimed to evaluate efficacy and safety of antiviral or immunosuppressive therapy in this population. Copyright © 2013 S. Karger AG, Basel.

Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis.

PubMed

Mou, Shan; Li, Jialin; Yu, Zanzhe; Wang, Qin; Ni, Zhaohui

2013-02-01

An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6-0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Restriction of dietary protein intake to 0.6-0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.

Hygiene hypothesis and prevalence of glomerulonephritis.

PubMed

Hurtado, Abdias; Johnson, Richard J

2005-08-01

The hygiene hypothesis was proposed to explain the marked increase in allergies that has been observed in industrialized (Westernized) societies. This hypothesis proposes that early and frequent exposure to bacterial and other antigens, such as is common in developing nations, leads to a normal Th1 response, but that better public hygiene and less infections observed in industrialized nations may lead to persistence of the Th2 phenotype and thereby increase our risk for developing allergies. Infection early in life with measles or hepatitis A virus, immunization with bacille Calmette-Guérin, certain gastrointestinal bacteria (lactobacillus), and environmental endotoxin exposure may protect individuals from developing allergy in adulthood. Paradoxically, infestation by parasites stimulates a Th2-cell response; however, the incidence of allergic disease is very low, perhaps due to the stimulation of T-regulatory lymphocytes that can downregulate Th1 and Th2 responses. Some types of human glomerulonephritis (GN) have Th1-predominant immune responses, including crescentic and membranoproliferative GN, whereas other types of GN have a predominant Th2 immune response, including membranous nephropathy, minimal change disease, and immunoglobulin A nephropathy. A review of the prevalence of specific GN shows that the higher prevalence of membranoproliferative GN in developing countries and the higher frequency of immunoglobulin A nephropathy and minimal change disease in industrialized countries could be explained by the hygiene hypothesis. We suggest that studies examining Th1/Th2 balance, particularly as it develops in childhood, should be performed to determine if early polarization of the immune response is responsible for the later development of specific forms of GN.

Front-End Electron Transfer Dissociation Coupled to a 21 Tesla FT-ICR Mass Spectrometer for Intact Protein Sequence Analysis

NASA Astrophysics Data System (ADS)

Weisbrod, Chad R.; Kaiser, Nathan K.; Syka, John E. P.; Early, Lee; Mullen, Christopher; Dunyach, Jean-Jacques; English, A. Michelle; Anderson, Lissa C.; Blakney, Greg T.; Shabanowitz, Jeffrey; Hendrickson, Christopher L.; Marshall, Alan G.; Hunt, Donald F.

2017-09-01

High resolution mass spectrometry is a key technology for in-depth protein characterization. High-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) enables high-level interrogation of intact proteins in the most detail to date. However, an appropriate complement of fragmentation technologies must be paired with FTMS to provide comprehensive sequence coverage, as well as characterization of sequence variants, and post-translational modifications. Here we describe the integration of front-end electron transfer dissociation (FETD) with a custom-built 21 tesla FT-ICR mass spectrometer, which yields unprecedented sequence coverage for proteins ranging from 2.8 to 29 kDa, without the need for extensive spectral averaging (e.g., 60% sequence coverage for apo-myoglobin with four averaged acquisitions). The system is equipped with a multipole storage device separate from the ETD reaction device, which allows accumulation of multiple ETD fragment ion fills. Consequently, an optimally large product ion population is accumulated prior to transfer to the ICR cell for mass analysis, which improves mass spectral signal-to-noise ratio, dynamic range, and scan rate. We find a linear relationship between protein molecular weight and minimum number of ETD reaction fills to achieve optimum sequence coverage, thereby enabling more efficient use of instrument data acquisition time. Finally, real-time scaling of the number of ETD reactions fills during method-based acquisition is shown, and the implications for LC-MS/MS top-down analysis are discussed. [Figure not available: see fulltext.

Identification of Reactive and Refractory Components of Dissolved Organic Nitrogen by FT-ICR Mass Spectrometry

NASA Astrophysics Data System (ADS)

Cooper, W. T.; Podgorski, D. C.; Osborne, D. M.; Corbett, J.; Chanton, J.

2010-12-01

Dissolved organic nitrogen is an often overlooked but potentially significant bioavailable component of dissolved organic matter. Studies of bulk DON turnover have been reported, but the compositions of the reactive and refractory components of DON are largely unknown. Here we show the unique ability of atmospheric pressure photoionization (APPI) coupled to ultrahigh resolution mass spectrometry to identify the reactive and refractory components of DON. Figure 1 is an isolated 0.30 m/z window from an ultrahigh resolution APPI FT-ICR mass spectrum of DON in surface waters draining an agricultural area in South Florida. Using this optimized, negative-ion APPI strategy we have been able to identify the reactive and refractory components of DON in these nitrogen-rich waters. Similar results were observed with samples from soil porewaters in sedge-dominated fens and sphagnum-dominated bogs within the Glacial Lake Agassiz Peatlands (GLAP) of northern Minnesota. Surprisingly, microbes appear to initially use similar enzymatic pathways to degrade DON and DOC, often with little release of nitrogen. Figure 1. Isolated 0.30 m/z window at nominal mass 432 from negative-ion APPI FT-ICR mass spectrum of DOM from waters draining an agricultural area in South Florida. Peaks marked contain nitrogen.

Top-down mass spectrometry imaging of intact proteins by laser ablation ESI FT-ICR MS.

PubMed

Kiss, András; Smith, Donald F; Reschke, Brent R; Powell, Matthew J; Heeren, Ron M A

2014-05-01

Laser ablation ESI (LAESI) is a recent development in MS imaging. It has been shown that lipids and small metabolites can be imaged in various samples such as plant material, tissue sections or bacterial colonies without any sample pretreatment. Further, LAESI has been shown to produce multiply charged protein ions from liquids or solid surfaces. This presents a means to address one of the biggest challenges in MS imaging; the identification of proteins directly from biological tissue surfaces. Such identification is hindered by the lack of multiply charged proteins in common MALDI ion sources and the difficulty of performing tandem MS on such large, singly charged ions. We present here top-down identification of intact proteins from tissue with a LAESI ion source combined with a hybrid ion-trap FT-ICR mass spectrometer. The performance of the system was first tested with a standard protein with electron capture dissociation and infrared multiphoton dissociation fragmentation to prove the viability of LAESI FT-ICR for top-down proteomics. Finally, the imaging of a tissue section was performed, where a number of intact proteins were measured and the hemoglobin α chain was identified directly from tissue using CID and infrared multiphoton dissociation fragmentation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models

PubMed Central

Karthivashan, Govindarajan; Park, Shin-Young; Kim, Joon-Soo; Cho, Duk-Yeon

2017-01-01

Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains. PMID:28792471

Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models.

PubMed

Karthivashan, Govindarajan; Park, Shin-Young; Kim, Joon-Soo; Cho, Duk-Yeon; Ganesan, Palanivel; Choi, Dong-Kug

2017-08-09

Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.

Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome.

PubMed

Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan

2006-02-01

The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.

An External Matrix-Assisted Laser Desorption Ionization Source for Flexible FT-ICR Mass Spectrometry Imaging with Internal Calibration on Adjacent Samples

NASA Astrophysics Data System (ADS)

Smith, Donald F.; Aizikov, Konstantin; Duursma, Marc C.; Giskes, Frans; Spaanderman, Dirk-Jan; McDonnell, Liam A.; O'Connor, Peter B.; Heeren, Ron M. A.

2011-01-01

We describe the construction and application of a new MALDI source for FT-ICR mass spectrometry imaging. The source includes a translational X-Y positioning stage with a 10 × 10 cm range of motion for analysis of large sample areas, a quadrupole for mass selection, and an external octopole ion trap with electrodes for the application of an axial potential gradient for controlled ion ejection. An off-line LC MALDI MS/MS run demonstrates the utility of the new source for data- and position-dependent experiments. A FT-ICR MS imaging experiment of a coronal rat brain section yields ˜200 unique peaks from m/z 400-1100 with corresponding mass-selected images. Mass spectra from every pixel are internally calibrated with respect to polymer calibrants collected from an adjacent slide.

What is new in the management of rapidly progressive glomerulonephritis?

PubMed Central

Greenhall, George H.B.; Salama, Alan D.

2015-01-01

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

Myeloperoxidase Antineutrophil Cytoplasmic Antibody (MPO-ANCA) Associated Crescentic and Necrotizing Glomerulonephritis (GN) with Membranoproliferative GN Features.

PubMed

Koda, Ryo; Nagahori, Katsuhiro; Kitazawa, Atsushi; Imanishi, Yuji; Yoshino, Atsunori; Kawamoto, Shinya; Ueda, Yoshihiko; Takeda, Tetsuro

2016-01-01

A 77-year-old man presented with a fever, non-productive cough, and edema formation. A laboratory analysis showed an elevated creatinine level (2.5 mg/dL), a high titer of myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (99 U/mL), positive reaction for antinuclear antibody (×320), hematuria, and massive proteinuria (3.33 g/day). A renal biopsy revealed crescentic and necrotizing glomerulonephritis (GN) with membranoproliferative GN features [double contour appearance of the glomerular basement membrane, granular deposition of immunoglobulin (Ig) G, IgM, and C3 along the capillary wall, subendothelial and subepithelial deposits with mesangial interposition]. A potential relationship between MPO-ANCA associated GN and membranoproliferative GN is discussed.

Organisation of lymphocytic infiltrates in ANCA-associated glomerulonephritis.

PubMed

Brix, Silke R; Noriega, Mercedes; Herden, Elisabeth M; Goldmann, Birgit; Langbehn, Ulrike; Busch, Martin; Jabs, Wolfram J; Steinmetz, Oliver M; Panzer, Ulf; Huber, Tobias B; Stahl, Rolf A K; Wiech, Thorsten

2018-06-01

Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis contributes to significant morbidity and mortality in patients. In chronic inflammation, B cells are recruited to the inflamed tissue and organised lymphoid structures have been described in several autoimmune diseases. The aim of this study was to correlate the lymphoid organisation in renal biopsies with renal outcome in ANCA-associated glomerulonephritis (GN). We investigated 112 renal biopsies from patients with newly diagnosed ANCA-associated necrotising GN. We identified four different levels of the intrarenal organisation of lymphocytes: T cells without B cells, scattered B and T cells, clustered lymphocytic infiltrates and nodular compartmentally arranged B and T cell aggregates. Almost half the patients showed clusters of B and T lymphocytes in their biopsies. In 15 of these biopsies, a higher degree of organisation with lymphocytic compartments was detected. Inflammatory cell organisation was associated with renal failure, but not with tubular atrophy and interstitial fibrosis. Patients with organised lymphocytic infiltrates in their biopsy had worse renal function during follow-up and were more likely to develop end stage renal disease. In the present study, we show that the renal lymphocytic organisation is associated with renal outcome in ANCA-associated GN. The organisation of the lymphocytic infiltrate may be a morphological correlate of a perpetual and exaggerated inflammation in renal ANCA disease. Classifying the lymphocytic infiltrate could help to predict renal outcome, and might therefore be used for individualised adjustments in the intensity and duration of immunosuppressive therapy. © 2018 John Wiley & Sons Ltd.

Epidemiology of biopsy-proven glomerulonephritis in Queensland adults.

PubMed

Jegatheesan, Dev; Nath, Karthik; Reyaldeen, Reza; Sivasuthan, Goutham; John, George T; Francis, Leo; Rajmokan, Mohana; Ranganathan, Dwarakanathan

2016-01-01

There is a paucity of data pertaining to the incidence of biopsy-proven glomerulonephritis (GN) in Australia. This retrospective study aims to review the data from all adult native renal biopsies performed in the state of Queensland from 2002 to 2011--comparing results with centres from across the world. Pathology reports of 3697 adult native kidney biopsies were reviewed, of which 2048 had GN diagnoses. Age, gender, clinical indication and histopathology findings were compared. The average age at biopsy was 48 ± 17 years. Male preponderance was noted overall (∼60%), with lupus nephritis being the only individual GN with female predilection. The average rate of biopsy was 12.04 per hundred thousand people per year (php/yr). Nephrotic and nephritic syndromes comprised approximately 75% of all clinical indications that lead to GN diagnoses. IgA nephropathy (1.41 php/yr) was the most common primary GN followed by focal segmental glomerulosclerosis (1.02 php/yr) and crescentic GN (0.73 php/yr). Diabetic nephropathy (0.84 php/yr), lupus nephritis (0.69 php/yr) and amyloidosis (0.19 php/yr) were the most commonly identified secondary GN. IgA nephropathy is the predominant primary GN in Queensland, and nephrotic syndrome the most common indication for a renal biopsy. While crescentic GN incidence has significantly increased with time, focal segmental glomerulosclerosis incidence has not shown any trend. Incidence of GN overall appears to increase with age. The annual rate of biopsy in this study appears lower than previously published in an Australian population. © 2015 Asian Pacific Society of Nephrology.

Chemical Analysis of Water-accommodated Fractions of Crude Oil Spills Using TIMS-FT-ICR MS.

PubMed

Benigni, Paolo; Marin, Rebecca; Sandoval, Kathia; Gardinali, Piero; Fernandez-Lima, Francisco

2017-03-03

Multiple chemical processes control how crude oil is incorporated into seawater and also the chemical reactions that occur overtime. Studying this system requires the careful preparation of the sample in order to accurately replicate the natural formation of the water-accommodated fraction that occurs in nature. Low-energy water-accommodated fractions (LEWAF) are carefully prepared by mixing crude oil and water at a set ratio. Aspirator bottles are then irradiated, and at set time points, the water is sampled and extracted using standard techniques. A second challenge is the representative characterization of the sample, which must take into consideration the chemical changes that occur over time. A targeted analysis of the aromatic fraction of the LEWAF can be performed using an atmospheric-pressure laser ionization source coupled to a custom-built trapped ion mobility spectrometry-Fourier transform-ion cyclotron resonance mass spectrometer (TIMS-FT-ICR MS). The TIMS-FT-ICR MS analysis provides high-resolution ion mobility and ultrahigh-resolution MS analysis, which further allow the identification of isomeric components by their collision cross-sections (CCS) and chemical formula. Results show that as the oil-water mixture is exposed to light, there is significant photo-solubilization of the surface oil into the water. Over time, the chemical transformation of the solubilized molecules takes place, with a decrease in the number of identifications of nitrogen- and sulfur-bearing species in favor of those with a greater oxygen content than were typically observed in the base oil.

Innate and adaptive immunity in experimental glomerulonephritis: a pathfinder tale.

PubMed

Artinger, Katharina; Kirsch, Alexander H; Aringer, Ida; Moschovaki-Filippidou, Foteini; Eller, Philipp; Rosenkranz, Alexander R; Eller, Kathrin

2017-06-01

The role of innate and adaptive immune cells in the experimental model of nephrotoxic serum nephritis (NTS) has been rigorously studied in recent years. The model is dependent on kidney-infiltrating T helper (TH) 17 and TH1 cells, which recruit neutrophils and macrophages, respectively, and cause sustained kidney inflammation. In a later phase of disease, regulatory T cells (Tregs) infiltrate the kidney in an attempt to limit disease activity. In the early stage of NTS, lymph node drainage plays an important role in disease initiation since dendritic cells present the antigen to T cells in the T cell zones of the draining lymph nodes. This results in the differentiation and proliferation of TH17 and TH1 cells. In this setting, immune regulatory cells (Tregs), namely, CCR7-expressing Tregs and mast cells (MCs), which are recruited by Tregs via the production of interleukin-9, exert their immunosuppressive capacity. Together, these two cell populations inhibit T cell differentiation and proliferation, thereby limiting disease activity by as yet unknown mechanisms. In contrast, the spleen plays no role in immune activation in NTS, but constitutes a place of extramedullary haematopoiesis. The complex interactions of immune cells in NTS are still under investigation and might ultimately lead to targeted therapies in glomerulonephritis.

Acute post-streptococcal glomerulonephritis in the Northern Territory of Australia: a review of 16 years data and comparison with the literature.

PubMed

Marshall, Catherine S; Cheng, Allen C; Markey, Peter G; Towers, Rebecca J; Richardson, Leisha J; Fagan, Peter K; Scott, Lesley; Krause, Vicki L; Currie, Bart J

2011-10-01

Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0-54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6-94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed.

Severe glomerulonephritis complicated by coagulopathy: treatment with anticoaguland and immunosuppresive drugs.

PubMed

Robson, A M; Cole, B R; Kienstra, R A; Kissane, J M; Alkjaersig, N; Fletcher, A P

1977-06-01

Serial determinations, using plasma fibrinogen gel chromatography as well as standard methodology, demonstrated that six children with severe glomerulonephritis, characterized on renal biopsy by glomerular necrosis and crescent formation, had persistent evidence of intravascular coagulation. Based on these observations, therapy with anticoagulants and azathicoagulants and azathioprine was instituted for one year; treatment with anticoagulants was continued for a second year. Anticoagulant therapy was initiated with heparin, followed by oral anticoagulation with phenindione and dipyridamole. In contrast to our earlier experience with similar patients, each of the present patients improved. Urinalyses returned to normal and glomerular filtration rates to near normal values in all patients at the end of the treatment period and have remained so for up to 3.9 years since treatment has been completed. Post-treatment biopsies showed remarkable improvement, with virtually no glomerulosclerosis even in patients who had had a high incidence of glomerular crescents before treatment. It is suggested that the therapeutic regimen favorably influenced the natural history of disease and that plasma fibrinogen chromatographic findings may be helpful in selecting patients likely to benefit from the use of anticoagulant therapy.

Combined optical coherence tomography and optical coherence elastography for glomerulonephritis classification

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Spectral Accuracy and Sulfur Counting Capabilities of the LTQ-FT-ICR and the LTQ-Orbitrap XL for Small Molecule Analysis

NASA Astrophysics Data System (ADS)

Blake, Samantha L.; Walker, S. Hunter; Muddiman, David C.; Hinks, David; Beck, Keith R.

2011-12-01

Color Index Disperse Yellow 42 (DY42), a high-volume disperse dye for polyester, was used to compare the capabilities of the LTQ-Orbitrap XL and the LTQ-FT-ICR with respect to mass measurement accuracy (MMA), spectral accuracy, and sulfur counting. The results of this research will be used in the construction of a dye database for forensic purposes; the additional spectral information will increase the confidence in the identification of unknown dyes found in fibers at crime scenes. Initial LTQ-Orbitrap XL data showed MMAs greater than 3 ppm and poor spectral accuracy. Modification of several Orbitrap installation parameters (e.g., deflector voltage) resulted in a significant improvement of the data. The LTQ-FT-ICR and LTQ-Orbitrap XL (after installation parameters were modified) exhibited MMA ≤ 3 ppm, good spectral accuracy (χ2 values for the isotopic distribution ≤ 2), and were correctly able to ascertain the number of sulfur atoms in the compound at all resolving powers investigated for AGC targets of 5.00 × 105 and 1.00 × 106.

Organic environments on Saturn's moon, Titan: simulating chemical reactions and analyzing products by FT-ICR and ion-trap mass spectrometry.

PubMed

Somogyi, Arpad; Oh, Chu-Ha; Smith, Mark A; Lunine, Jonathan I

2005-06-01

Laboratory simulations have been carried out to model chemical reactions that possibly take place in the stratosphere of Saturn's moon, Titan. The aerosol products of these reactions (tholin samples) have been systematically analyzed by mass spectrometry using electrospray ionization (ESI) and laser desorption (LD). A wide variety of ions with a general formula C(x)H(y)N(z) detected by ultrahigh resolution and accurate mass measurements in a Fourier transform/ion cyclotron resonance (FT-ICR) cell reflect the complexity of these polymeric products, both in chemical compositions and isomeric distributions. As a common feature, however, tandem mass spectral (MS/MS) data and H/D exchange products in the solution phase support the presence of amino and nitrile functionalities in these (highly unsaturated) "tholin" compounds. The present work demonstrates that ESI-MS coupled with FT-ICR is a suitable and "intact" method to analyze tholin components formed under anaerobic conditions; only species with C(x)H(y)N(z) are detected for freshly prepared and harvested samples. However, when intentionally exposed to water, oxygen-containing compounds are unambiguously detected.

Hydrothermal liquefaction oil and hydrotreated product from pine feedstock characterized by heteronuclear two-dimensional NMR spectroscopy and FT-ICR mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sudasinghe, Nilusha; Cort, John R.; Hallen, Richard

2014-12-01

Hydrothermal liquefaction (HTL) crude oil and hydrotreated product from pine tree farm waste (forest product residual, FPR) have been analyzed by direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) in both positive- and negative-ionization modes and high-resolution twodimensional heteronuclear 1H-13C NMR spectroscopy. FT-ICR MS resolves thousands of compounds in complex oils and provides unparalleled compositional details for individual molecules for identification of compound class (heteroatom content), type (number of rings plus double bonds to carbon or double bond equivalents (DBE) and carbon number (degree of alkylation). Heteronuclear 1H-13C NMR spectroscopy provides one-bond and multiple-bondmore » correlations between pairs of 1H and 13C chemical shifts that are characteristic of different organic functional groups. Taken together this information provides a picture of the chemical composition of these oils. Pyrolysis crude oil product from pine wood was characterized for comparison. Generally, pyrolysis oil is comprised of a more diverse distribution of heteroatom classes with higher oxygen number relative to HTL oil as shown by both positive- and negative-ion ESI FT-ICR MS. A total of 300 N1, 594 O1 and 267 O2 compounds were observed as products of hydrotreatment. The relative abundance of N1O1, N1O2, N1O3, N2, N2O1, N2O2 and O3 compounds are reduced to different degrees after hydrotreatment and other higher heteroatom containing species (O4-O10, N1O4, N1O5 and N2O3) are completely removed by hydrotreatment.« less

Acute Post-Streptococcal Glomerulonephritis in the Northern Territory of Australia: A Review of 16 Years Data and Comparison with the Literature

PubMed Central

Marshall, Catherine S.; Cheng, Allen C.; Markey, Peter G.; Towers, Rebecca J.; Richardson, Leisha J.; Fagan, Peter K.; Scott, Lesley; Krause, Vicki L.; Currie, Bart J.

2011-01-01

Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0–54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6–94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed. PMID:21976576

Corticosteroid-induced mandibular growth retardation and palatal malformation in the ICR mouse fetus.

PubMed Central

Silbermann, M; Levitan, S

1979-01-01

Pregnant ICR mice were treated with triamcinolone hexacetonide at various stages of gestation. The mandibular ramus and its condylar cartilage were studied histologically in both viable and non-viable offspring. In addition, measurements were made of the overall height of the posterior vertical dimension of the mandible and of condylar height and width. Significant changes were noted in these parameters. Concomitantly, marked changes were observed in the various zones of the condylar cartilage. A very high incidence of cleft palate was noted in newborn and stillborn mice previously treated with triamcinolone. A possible correlation between mandibular growth retardation and palatal clefting is discussed. Images Fig. 4 Fig. 5 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:489465

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

PubMed

Choi, Mi-Ran; Lee, Min Young; Hong, Ji Eun; Kim, Jeong Eun; Lee, Jae-Yong; Kim, Tae Hwan; Chun, Jang Woo; Shin, Hyun Kyung; Kim, Eun Ji

2014-10-01

The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

Analysis of the low molecular weight fraction of serum by LC-dual ESI-FT-ICR mass spectrometry: precision of retention time, mass, and ion abundance.

PubMed

Johnson, Kenneth L; Mason, Christopher J; Muddiman, David C; Eckel, Jeanette E

2004-09-01

This study quantifies the experimental uncertainty for LC retention time, mass measurement precision, and ion abundance obtained from replicate nLC-dual ESI-FT-ICR analyses of the low molecular weight fraction of serum. We used ultrafiltration to enrich the < 10-kDa fraction of components from the high-abundance proteins in a pooled serum sample derived from ovarian cancer patients. The THRASH algorithm for isotope cluster detection was applied to five replicate nLC-dual ESI-FT-ICR chromatograms. A simple two-level grouping algorithm was applied to the more than 7000 isotope clusters found in each replicate and identified 497 molecular species that appeared in at least four of the replicates. In addition, a representative set of 231 isotope clusters, corresponding to 188 unique molecular species, were manually interpreted to verify the automated algorithm and to set its tolerances. For nLC retention time reproducibility, 95% of the 497 species had a 95% confidence interval of the mean of +/- 0.9 min or less without the use of chromatographic alignment procedures. Furthermore, 95% of the 497 species had a mass measurement precision of < or = 3.2 and < or = 6.3 ppm for internally and externally calibrated spectra, respectively. Moreover, 95% of replicate ion abundance measurements, covering an ion abundance range of approximately 3 orders of magnitude, had a coefficient of variation of less than 62% without using any normalization functions. The variability of ion abundance was independent of LC retention time, mass, and ion abundance quartile. These measures of analytical reproducibility establish a statistical rationale for differentiating healthy and disease patient populations for the elucidation of biomarkers in the low molecular fraction of serum. Copyright 2004 American Chemical Society

The Acceleration of the Barycenter of Solar System Obtained from VLBI Observations and Its Impact on the ICRS

NASA Astrophysics Data System (ADS)

Xu, M. H.

2016-03-01

Since 1998 January 1, instead of the traditional stellar reference system, the International Celestial Reference System (ICRS) has been realized by an ensemble of extragalactic radio sources that are located at hundreds of millions of light years away (if we accept their cosmological distances), so that the reference frame realized by extragalactic radio sources is assumed to be space-fixed. The acceleration of the barycenter of solar system (SSB), which is the origin of the ICRS, gives rise to a systematical variation in the directions of the observed radio sources. This phenomenon is called the secular aberration drift. As a result, the extragalactic reference frame fixed to the space provides a reference standard for detecting the secular aberration drift, and the acceleration of the barycenter with respect to the space can be determined from the observations of extragalactic radio sources. In this thesis, we aim to determine the acceleration of the SSB from astrometric and geodetic observations obtained by Very Long Baseline Interferometry (VLBI), which is a technique using the telescopes globally distributed on the Earth to observe a radio source simultaneously, and with the capacity of angular positioning for compact radio sources at 10-milliarcsecond level. The method of the global solution, which allows the acceleration vector to be estimated as a global parameter in the data analysis, is developed. Through the formal error given by the solution, this method shows directly the VLBI observations' capability to constrain the acceleration of the SSB, and demonstrates the significance level of the result. In the next step, the impact of the acceleration on the ICRS is studied in order to obtain the correction of the celestial reference frame (CRF) orientation. This thesis begins with the basic background and the general frame of this work. A brief review of the realization of the CRF based on the kinematical and the dynamical methods is presented in Chapter 2

IgG3 deficiency extends lifespan and attenuates progression of glomerulonephritis in MRL/lpr mice

PubMed Central

2012-01-01

Background Antibodies of the IgG3 subclass have been implicated in the pathogenesis of the spontaneous glomerulonephritis observed in mice of the MRL/MpJ-Tnfrsf6lpr (MRL/lpr) inbred strain which have been widely studied as a model of systemic lupus erythematosus We have produced IgG3-deficient (-/-) mice with the MRL/lpr genetic background to determine whether IgG3 antibodies are necessary for or at least contributory to MRL/lpr-associated nephritis. Results The gamma3 genotype (+/+ vs. +/- vs. -/-) did not appear to significantly affect serum titers of IgG auto-antibodies specific for double-stranded DNA (dsDNA) or α-actinin. However, while substantial serum titers of IgG3 auto-antibodies specific for double-stranded DNA (dsDNA) or α-actinin were seen in gamma3 +/+ mice, somewhat lower serum titers of these IgG3 auto-antibodies were found in gamma3 +/- mice, and gamma3 -/- mice exhibited baseline concentrations of these auto-antibodies. Analysis of immunoglobulins eluted from snap-frozen kidneys obtained from mice of all three gamma3 genotypes at ~18 weeks of age revealed much higher quantities of IgG in the kidneys from gamma3 +/+ than gamma3 -/- mice, and most IgG eluted from +/+ mice was IgG3. The serum creatinine levels in gamma3 +/+ mice substantially exceeded those of age-matched gamma3 -/- mice after ~21 weeks of age. Histopathological examination of kidneys from mice sacrificed at pre-determined ages also revealed more extensive glomerulosclerosis in gamma3 +/+ or +/- mice than in -/- mice beginning at 21 weeks of age. Survival analysis for IgG3-deficient and IgG3-producing MRL/lpr mice revealed that gamma3 -/- mice lived significantly longer (p = 0.0006) than either gamma3 +/- or +/+ mice. Spontaneous death appeared to be due to irreversible renal failure, because > 85% of glomeruli in kidneys from mice that died spontaneously were obliterated by glomerulosclerosis. Conclusions The available evidence suggests that IgG3 deficiency partially protects MRL

Effect of Infection Duration on Habitat Selection and Morphology of Adult Echinostoma caproni (Digenea: Echinostomatidae) in ICR Mice.

PubMed

Platt, Thomas R; Zelmer, Derek A

2016-02-01

The course of infection of Echinostoma caproni was followed in female ICR mice, a permissive laboratory host, from infection to natural termination. Twenty-one mice were infected with 20 metacercariae via oral intubation and housed 3 per cage. Three mice from a randomly selected cage were necropsied at 1 mo intervals. A second group of 15 mice was infected approximately 1 yr later to replace mice negative at necropsy in the first group. Mice in the second group were examined weekly for the presence of eggs in the feces. Mice negative for eggs on consecutive days were killed and necropsied. The location of individual worms and worm clusters were located in 20 segments of the small intestine. Adult worms were killed and fixed in hot formalin, stained, and prepared as whole mounts. Standard measurements were taken using a compound microscope fitted with an ocular micrometer. The infection spontaneously resolved in 10 mice from 7 to 32 wk PI, indicating the host response is highly variable and extending the maximum recorded length of E. caproni infections in ICR mice to 31 wk. A moribund worm was found in the feces of an animal that continued to pass eggs for an additional 2 mo indicating individual variation in worm responses. Worms located preferentially in the ileum (segments 11-13) during the first 3 mo of the infection but shifted to the jejunum (segments 8-9) during weeks 4-6. Morphologically, worms of different ages clustered together in multivariate space, with substantial overlap between the 3- and 4-mo-old infrapopulations and between the 5- and 6-mo-old infrapopulations. Muscular structures increased in size throughout the experiment, while the gonads increased in size for the first 3 mo and then declined during the last 3 mo. The relationship between E. caproni and ICR mice is more nuanced than previously reported. The reduction in gonad size and the shift from the ileum to the jejunum in the last 3 mo likely are related. These changes might be attributable

High field FT-ICR mass spectrometry for molecular characterization of snow board from Moscow regions.

PubMed

Mazur, Dmitry M; Harir, Mourad; Schmitt-Kopplin, Philippe; Polyakova, Olga V; Lebedev, Albert T

2016-07-01

High field Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry analysis of eight snow samples from Moscow city allowed us to identify more than 2000 various elemental compositions corresponding to regional air pollutants. The hierarchical cluster analysis (HCA) of the data showed good concordance of three main groups of samples with the main wind directions. The North-West group (A1) is represented by several homologous CHOS series of aliphatic organic aerosols. They may form as a result of enhanced photochemical reactions including oxidation of hydrocarbons with sulfonations due to higher amount of SO2 emissions in the atmosphere in this region. Group A2, corresponding to the South-East part of Moscow, contains large amount of oxidized hydrocarbons of different sources that may form during oxidation in atmosphere. These hydrocarbons appear correlated to emissions from traffic, neighboring oil refinery, and power plants. Another family of compounds specific for this region involves CHNO substances formed during oxidation processes including NOx and NO3 radical since emissions of NOx are higher in this part of the city. Group A3 is rich in CHO type of compounds with high H/C and low O/C ratios, which is characteristic of oxidized hydrocarbon-like organic aerosol. CHNO types of compounds in A3 group are probably nitro derivatives of condensed hydrocarbons such as PAH. This non-targeted profiling revealed site specific distribution of pollutants and gives a chance to develop new strategies in air quality control and further studies of Moscow environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum amyloid P component gene: SAP deficiency or strain combination?

PubMed Central

Gillmore, Julian D; Hutchinson, Winston L; Herbert, Jeff; Bybee, Alison; Mitchell, Daniel A; Hasserjian, Robert P; Yamamura, Ken-Ichi; Suzuki, Misao; Sabin, Caroline A; Pepys, Mark B

2004-01-01

Human serum amyloid P component (SAP) binds avidly to DNA, chromatin and apoptotic cells in vitro and in vivo. 129\\Sv × C57BL\\6 mice with targeted deletion of the SAP gene spontaneously develop antinuclear autoantibodies and immune complex glomerulonephritis. SAP-deficient animals, created by backcrossing the 129\\Sv SAP gene deletion into pure line C57BL\\6 mice and studied here for the first time, also spontaneously developed broad spectrum antinuclear autoimmunity and proliferative immune complex glomerulonephritis but without proteinuria, renal failure, or increased morbidity or mortality. Mice hemizygous for the SAP gene deletion had an intermediate autoimmune phenotype. Injected apoptotic cells and isolated chromatin were more immunogenic in SAP–\\– mice than in wild-type mice. In contrast, SAP-deficient pure line 129\\Sv mice did not produce significant autoantibodies either spontaneously or when immunized with extrinsic chromatin or apoptotic cells, indicating that loss of tolerance is markedly strain dependent. However, SAP deficiency in C57BL\\6 mice only marginally affected plasma clearance of exogenous chromatin and had no effect on distribution of exogenous nucleosomes between the liver and kidneys, which were the only tissue sites of catabolism. Furthermore, transgenic expression of human SAP in the C57BL\\6 SAP knockout mice did not abrogate the autoimmune phenotype. This may reflect the different binding affinities of mouse and human SAP for nuclear autoantigens and\\or the heterologous nature of transgenic human SAP in the mouse. Alternatively, the autoimmunity may be independent of SAP deficiency and caused by expression of 129\\Sv chromosome 1 genes in the C57BL\\6 background. PMID:15147569

[THE USE OF THE MODEL MOUSE ICR--VARIOLA VIRUS FOR EVALUATION OF ANTIVIRAL DRUG EFFICACY].

PubMed

Titova, K A; Sergeev, Al A; Kabanov, A S; Bulychev, L E; Sergeev, Ar A; Galakhova, D O; Shishkina, L N; Zamedyanskaya, A S; Nesterov, A E; Glotov, A G; Taranov, O S; Omigov, V V; Agafonov, A P; Sergeev, A N

2016-01-01

Mice of the ICR outbred population were infected intranasally (i/n) with the variola virus (VARV, strain Ind-3a). Clinical signs of the disease did not appear even at the maximum possible dose of the virus 5.2 lg PFU/head (plaque-forming units per head). In this case, 50% infective dose (ID50) of VARV estimated by the presence or absence of the virus in the lungs three days after infection (p.i.) was equal to 2.7 ± 0.4 lg PFU/head. Taking into account the 10% application of the virus in the lungs during the intranasal infection of the mice, it was adequate to 1.7 lg PFU/lungs. This indicates a high infectivity of the VARV for mice comparable to its infectivity for humans. After the i/n infection of mice with the VARV at a dose 30 ID50/ head the highest concentration of the virus detected in the lungs (4.9 ± 0.0 lg PFU/ml of homogenate) and in nasal cavity tissues (4.8 ± 0.0 lg PFU/ml) were observed. The pathomorphological changes in the respiratory organs of the mice infected with the VARV appeared at 3-5 days p.i., and the VARV reproduction noted in the epithelial cells and macrophages were noticed. When the preparations ST-246 and NIOCH-14 were administered orally at a dose of 60 μg/g of mouse weight up to one day before infection, after 2 hours, 1 and 2 days p.i., the VARV reproduction in the lungs after 3 days p.i. decreased by an order of magnitude. Thus, outbred ICR mice infected with the VARV can be used as a laboratory model of the smallpox when evaluating the therapeutic and prophylactic efficacy of the antismallpox drugs.

Promoting effects of bile acid to intestinal tumorigenesis in gnotobiotic ICR mice.

PubMed

Iwasaki, I; Iwase, H; Yumoto, N; Ide, G

1985-11-01

Gnotobiotes were produced by administrating Lactobacillus plantarum IAM 1041 in ICR strain male germfree mice which were fed by ordinary or high fat diet. Both groups were orally administered 0.3 mg/10 g of body weight (B.W.) of methylazoxymethanol (MAM) acetate. The oral administration of 0.3 mg/10 g/B.W. once a week for 11 consecutive weeks caused a total of 68 adenomatous polyps in the large intestine (an average of 11.4/mouse) of gnotobiotic high fat diet mice and a total of 32 adenomatous polyps (an average of 5.3/mouse) of the ordinary diet mice. There were no malignancies in either of the groups. Bile acids in the feces showed higher values in the high fat diet group than in the ordinary group. Bile acids are a factor which promotes the appearance of intestinal tumors. It was also assumed that the L. plantarum promoted the activation of beta-glucuronidase and alcohol dehydrogenase in the liver and intestine.

Changes in the clinical presentation of immunoglobulin A nephropathy: data from the Spanish Registry of Glomerulonephritis.

PubMed

Gutiérrez, Eduardo; Praga, Manuel; Rivera, Francisco; Sevillano, Angel; Yuste, Claudia; Goicoechea, Marian; López-Gómez, Juan M

2018-03-01

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world, but there is little epidemiological data about possible changes in its presentation over the years. Available information about the influence of age on the form of clinical presentation is also scarce. The aim of the study was to analyse all renal biopsies performed between 1994 and 2013 and recorded in the Spanish Registry of Glomerulonephritis with a histological diagnosis of IgAN. The study was divided into five 4-year periods (1994-97, 1998-2001, 2002-05, 2006-09 and 2010-13) and patients were divided into four age groups: ≤16, 17-44, 45-64 and ≥65 years. From 20.974 renal biopsies recorded, 2961 (14.1%) corresponded to IgAN. The prevalence of IgAN remained stable, but a significant increase in age [from 37.6 (SD 17.7) in 1994-97 to 44.9 (SD 16.8) years in 2010-13; P = 0.001] and worse renal function at presentation [from serum creatinine (SCr) 1.9 (SD 1.9) in 1994-97 to 2.3 (SD 2.1) mg/dL in 2010-13; P = 0.001] were observed over the years. Nephrotic-range proteinuria and acute kidney injury (AKI) as forms of presentation were significantly more common among patients ≥65 years (17.7% and 43.2%, respectively) as compared with the other age groups [≤16 (11.4% and 13.1%, respectively), 17-44 (13.1% and 13%, respectively) and 45-64 (12.1% and 21.3%, respectively)]. Blood pressure, SCr and proteinuria were also significantly higher at presentation among elderly patients. Although the prevalence of IgAN in Spain has remained stable over the years, patients are significantly older and present with significantly worse renal function in the last years. The incidence of nephrotic-range proteinuria (17.7%) and AKI (43.2%) as forms of presentation is remarkable among patients ≥65 years of age. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The Possibility of Using the ICR Mouse as an Animal Model to Assess Antimonkeypox Drug Efficacy.

PubMed

Sergeev, Al A; Kabanov, A S; Bulychev, L E; Sergeev, Ar A; Pyankov, O V; Bodnev, S A; Galahova, D O; Zamedyanskaya, A S; Titova, K A; Glotov, A G; Taranov, O S; Omigov, V V; Shishkina, L N; Agafonov, A P; Sergeev, A N

2016-10-01

As a result of the conducted experimental studies on intranasal challenge of ICR mice, rabbits and miniature pigs (even in the maximum variant) with the doses of 4.0-5.5 lg PFU of monkeypox virus (MPXV), some clinical signs such as purulent conjunctivitis, blepharitis and ruffled fur were found only in mice. The 50% infective dose (C ID50 ) of MPXV for these animals estimated by the presence of external clinical signs was 4.8 lg PFU, and L ID50 estimated by the virus presence in the lungs of mice 7 days post-infection taking into account its 10% application in the animal respiratory tract was 1.4 lg PFU. When studying the dynamics of MPXV propagation in mice challenged intranasally with 25 L ID50 of MPXV, the maximum pathogen accumulation was revealed in nasal cavity, lungs and brain: 5.7 ± 0.1, 5.5 ± 0.1 and 5.3 ± 0.3 lg PFU/ml, respectively. The pathomorphological examination of these animals revealed the presence and replication of the pathogen in the traditional primary target cells for MPXV (mononuclear phagocyte system cells and respiratory tract epitheliocytes) as well as in some other types of cells (endothelial cells, reticular cells, connective tissue cells). Our use of these animals to assess the antiviral efficacy of some drugs demonstrated the agreement of the results (a significant positive effect of NIOCH-14 and ST-246) with those described in scientific literature, which opens up the prospects of using ICR mice as animal models for monkeypox to develop preventive antismallpox drugs. © 2015 Blackwell Verlag GmbH.

Neutrophil contribution to the crescentic glomerulonephritis in SCG/Kj mice.

PubMed

Ishida-Okawara, Akiko; Ito-Ihara, Toshiko; Muso, Eri; Ono, Takahiko; Saiga, Kan; Nemoto, Kyuichi; Suzuki, Kazuo

2004-07-01

Myeloperoxidase-specific anti-neutrophil cytoplasmic auto-antibody (MPO-ANCA) has been a useful diagnostic marker in systemic vasculitis with crescentic glomerulonephritis (CrGN). It is highly suspected that the antigenic enzyme MPO released from activated neutrophils is involved in these lesions. We evaluated the relationship between neutrophil functions including peripheral neutrophil counts and renal lesions in SCG/Kj mice as a model of ANCA-associated CrGN and vasculitis. Peripheral neutrophil counts, the plasma levels of MPO-ANCA and tumour necrosis factor alpha (TNF-alpha) were measured. The capacity of MPO release and superoxide generation were evaluated as neutrophil activity. The renal lesions were estimated by grade of proteinuria, histopathological lesion, such as glomerular neutrophil infiltration and active or chronic renal injury scores with crescent formation. MPO-ANCA and TNF-alpha levels were higher than those of normal mice C57BL/6 even before overt proteinuria; subsequently, peripheral neutrophils increased. In the phase of nephritis with low grade proteinuria, the spontaneous release of MPO from peripheral neutrophils increased, while superoxide generation increased before spontaneous MPO release occurred. In addition, the renal lesion in histological observations was aggravated with ageing and the glomerular neutrophil infiltration was positively correlated with MPO-ANCA levels, as well as with histological indices of nephritis, active renal injury score; in particular, crescent formation was correlated with spontaneous MPO release. In contrast, superoxide generation was negatively correlated with the severity of this lesion during the progression. These findings indicate that neutrophils are activated and contribute to the development of the active crescentic lesion in SCG/Kj mice.

Conducting non-commercial international clinical trials: the ICR-CTSU experience.

PubMed

Fox, Lisa; Toms, Christy; Kernaghan, Sarah; Snowdon, Claire; Bliss, Judith M

2017-09-26

Academic clinical trials play a fundamental role in the development of new treatments, the repurposing of existing treatments and in addressing areas of unmet clinical need. With cancer treatments increasingly targeted at molecular subtypes, and with priority placed on developing new treatments for rare tumour types, the need for international trial participation to access sufficient patient numbers for successful trial conduct is growing. However, lack of harmonisation of international legal, ethical and financial systems can make this challenging and the cost and effort of conducting trials internationally can be considered prohibitive, particularly where the sample size is comparatively small. The Institute of Cancer Research - Clinical Trials and Statistics Unit (ICR-CTSU) is a UK-based academic clinical trials unit that specialises in the design, conduct and analysis of clinical trials of cancer treatments with an expanding portfolio of trials in molecular subtypes of breast and urological cancers and in other rare cancer types. Implementing appropriate mechanisms to enable international participation has therefore been imperative. In this article, we explain how we have approached the challenges involved and describe examples of successful international trial conduct, achieved through robust collaborations with academic and industry partners. Conducting academic trials internationally is challenging but can and should be achieved through appropriate governance mechanisms and strong collaborations.

Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond

PubMed Central

Ma, Terry King-Wing; McAdoo, Stephen P.

2017-01-01

Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease. SYK is implicated in the pathogenesis of ANCA-associated GN. SYK, BTK, PDGFR, EFGR, DDR1 and Janus kinase are implicated in the pathogenesis of lupus nephritis. A representative animal model of IgA nephropathy (IgAN) is lacking. Based on the results from in vitro and human renal biopsy study results, a phase II clinical trial is ongoing to evaluate the efficacy and safety of fostamatinib (an oral SYK inhibitor) in high-risk IgAN patient. Various tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment. Clinical trials of TKIs in GN may be justified given their long-term safety data. In this review we will discuss the current unmet medical needs in GN treatment and research as well as the current stage of development of TKIs in GN treatment and propose an accelerated translational research approach to investigate whether selective inhibition of tyrosine kinase provides a safer and more efficacious option for GN treatment. PMID:28391340

Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond.

PubMed

Ma, Terry King-Wing; McAdoo, Stephen P; Tam, Frederick Wai Keung

2017-01-01

Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease. SYK is implicated in the pathogenesis of ANCA-associated GN. SYK, BTK, PDGFR, EFGR, DDR1 and Janus kinase are implicated in the pathogenesis of lupus nephritis. A representative animal model of IgA nephropathy (IgAN) is lacking. Based on the results from in vitro and human renal biopsy study results, a phase II clinical trial is ongoing to evaluate the efficacy and safety of fostamatinib (an oral SYK inhibitor) in high-risk IgAN patient. Various tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment. Clinical trials of TKIs in GN may be justified given their long-term safety data. In this review we will discuss the current unmet medical needs in GN treatment and research as well as the current stage of development of TKIs in GN treatment and propose an accelerated translational research approach to investigate whether selective inhibition of tyrosine kinase provides a safer and more efficacious option for GN treatment. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

[Effect of Yishen capsule on serum vascular endothelial growth factor and cell immunity in patients with chronic glomerulonephritis].

PubMed

Wu, Xi-li; Sun, Wan-sen; Zhang, Wang-gang; Qiao, Cheng-lin; Wang, Zhu; Wang, Juan

2007-11-01

To explore the effect of Yishen capsule on the serum vascular endothelial growth factor (VEGF), the cell immunity and the theraphic. Serum VEGF and T cell subsets were studied in 30 normal subjects and 83 patients before and after treatment. Compare with normal subjects, CD3, CD4, CD4/CD8 were decreased, CD8 and serum VEGF were increased obviously (P <0. 05 or P <0. 01). After three months treatment with YiShen capsule, CD4/CD8 was increased, CD8 and serum VEGF were decreased significantly (P <0.05 or P <0.01). Yishen capsule can reduce the proteinuria, increase the function of immunity and improve the clinical symptom of patients with chronic glomerulonephritis, achieved the effects of allevating chronic glomerular sclerosis ultimately.

Glomerular clusterin is associated with PKC-alpha/beta regulation and good outcome of membranous glomerulonephritis in humans.

PubMed

Rastaldi, M P; Candiano, G; Musante, L; Bruschi, M; Armelloni, S; Rimoldi, L; Tardanico, R; Sanna-Cherchi, S; Cherchi, S Sanna; Ferrario, F; Montinaro, V; Haupt, R; Parodi, S; Carnevali, M L; Allegri, L; Camussi, G; Gesualdo, L; Scolari, F; Ghiggeri, G M

2006-08-01

Mechanisms for human membranous glomerulonephritis (MGN) remain elusive. Most up-to-date concepts still rely on the rat model of Passive Heymann Nephritis that derives from an autoimmune response to glomerular megalin, with complement activation and membrane attack complex assembly. Clusterin has been reported as a megalin ligand in immunodeposits, although its role has not been clarified. We studied renal biopsies of 60 MGN patients by immunohistochemistry utilizing antibodies against clusterin, C5b-9, and phosphorylated-protien kinase C (PKC) isoforms (pPKC). In vitro experiments were performed to investigate the role of clusterin during podocyte damage by MGN serum and define clusterin binding to human podocytes, where megalin is known to be absent. Clusterin, C5b-9, and pPKC-alpha/beta showed highly variable glomerular staining, where high clusterin profiles were inversely correlated to C5b-9 and PKC-alpha/beta expression (P=0.029), and co-localized with the low-density lipoprotein receptor (LDL-R). Glomerular clusterin emerged as the single factor influencing proteinuria at multivariate analysis and was associated with a reduction of proteinuria after a follow-up of 1.5 years (-88.1%, P=0.027). Incubation of podocytes with MGN sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, serum de-complementation, or protein-A treatment. Preliminary in vitro experiments showed podocyte binding of biotinilated clusterin, co-localization with LDL-R and specific binding inhibition with anti-LDL-R antibodies and with specific ligands. These data suggest a central role for glomerular clusterin in MGN as a modulator of inflammation that potentially influences the clinical outcome. Binding of clusterin to the LDL-R might offer an interpretative key for the pathogenesis of MGN in humans.

Effect of chronic glomerulonephritis on the semen quality and cytokines in the semen of infertile males.

PubMed

Zhang, Huina; Ying, Yingfen; Chen, Yilu; Lu, Xiaosheng; Huang, Yonggang

2017-01-01

The effects of chronic glomerulonephritis (CGN) on semen quality and cytokine levels in the semen of infertile males remain undetermined. Fifty-eight semen samples from normal males and CGN males with and without infertility, respectively, were analyzed. Semen volume, semen pH, sperm density, percentage of forward movement of sperm, sperm activate rate, sperm survival rate, and rate of normal sperm morphology of infertility males with CGN were significantly lower than those of CGN males without infertility and normal males (P<.05). In addition, the blood urea nitrogen and serum creatinine levels and interleukin (IL)-17 and IL-18 levels in infertility males with CGN were significantly higher than those of CGN males without infertility and normal males (P<.05). CGN increased the blood urea nitrogen and serum creatinine levels, which induced abnormal expression of IL-17 and IL-18, and negatively affected male semen quality and might result in male infertility. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Experimental demonstration of the possible role of Acanthamoeba polyphaga in the infection and disease progression in Buruli Ulcer (BU) using ICR mice

PubMed Central

Azumah, Bright K.; Addo, Phyllis G.; Dodoo, Alfred; Awandare, Gordon; Mosi, Lydia; Boakye, Daniel A.

2017-01-01

The transmission of Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), remains puzzling although a number of hypothesis including through bites of infected aquatic insects have been proposed. We report the results of experiments using ICR mice that give credence to our hypothesis that Acanthamoeba species may play a role in BU transmission. We cocultured MU N2 and MU 1615 which expresses red fluorescent protein (RFP) and Acanthamoeba polyphaga (AP), and confirmed infected AP by Ziehl-Neelsen (ZN) staining. We tested for viability of MU inside AP and observed strong RFP signals inside both trophozoites and cysts after 3 and 42 days of coculturing respectively. ICR mice were topically treated, either on shaved intact or shaved pinpricked rumps, with one of the following; MU N2 only (2.25 x 106 colony forming units [CFU] / ml), MU N2:AP coculture (2.96 x 104 CFU: 1.6 x 106 cells/ml), AP only (1.6 x 106 cells/ml), PYG medium and sterile distilled water. Both MU N2 only and MU N2:AP elicited reddening on day (D) 31; edema on D 45 and D 44 respectively, and ulcers on D 49 at pinpricked sites only. To ascertain infectivity and pathogenicity of MU N2 only and MU N2:AP, and compare their virulence, the standard mouse footpad inoculation method was used. MU N2:AP elicited reddening in footpads by D 3 compared to D 14 with MU N2 only of the same dose of MU N2 (2.96 x 104 CFU). ZN-stained MU were observed in both thin sectioned and homogenized lesions, and aspirates from infected sites. Viable MU N2 were recovered from cultures of the homogenates and aspirates. This study demonstrates in ICR mice MU transmission via passive infection, and shows that punctures in the skin are prerequisite for infection, and that coculturing of MU with AP enhances pathogenesis. PMID:28329001

The Histone Acetyltransferase Gcn5 Regulates ncRNA-ICR1 and FLO11 Expression during Pseudohyphal Development in Saccharomyces cerevisiae

PubMed Central

Wang, Long-Chi; Montalvo-Munoz, Fernando; Tsai, Yuan-Chan; Liang, Chung-Yi; Chang, Chun-Chuan; Lo, Wan-Sheng

2015-01-01

Filamentous growth is one of the key features of pathogenic fungi during the early infectious phase. The pseudohyphal development of yeast Saccharomyces cerevisiae shares similar characteristics with hyphae elongation in pathogenic fungi. The expression of FLO11 is essential for adhesive growth and filament formation in yeast and is governed by a multilayered transcriptional network. Here we discovered a role for the histone acetyltransferase general control nonderepressible 5 (Gcn5) in regulating FLO11-mediated pseudohyphal growth. The expression patterns of FLO11 were distinct in haploid and diploid yeast under amino acid starvation induced by 3-amino-1,2,4-triazole (3AT). In diploids, FLO11 expression was substantially induced at a very early stage of pseudohyphal development and decreased quickly, but in haploids, it was gradually induced. Furthermore, the transcription factor Gcn4 was recruited to the Sfl1-Flo8 toggle sites at the FLO11 promoter under 3AT treatment. Moreover, the histone acetylase activity of Gcn5 was required for FLO11 induction. Finally, Gcn5 functioned as a negative regulator of the noncoding RNA ICR1, which is known to suppress FLO11 expression. Gcn5 plays an important role in the regulatory network of FLO11 expression via Gcn4 by downregulating ICR1 expression, which derepresses FLO11 for promoting pseudohyphal development. PMID:25922832

Cognitive Function of Artemisia argyi H. Fermented by Monascus purpureus under TMT-Induced Learning and Memory Deficits in ICR Mice

PubMed Central

Kang, Jin Yong; Lee, Du Sang; Park, Seon Kyeong; Ha, Jeong Su; Kim, Jong Min; Ha, Gi Jeong; Seo, Weon Taek

2017-01-01

The cognitive effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM), which has cellular antioxidant activity and neuronal cell viability, on trimethyltin- (TMT-) induced learning and memory impairment in Institute of Cancer Research (ICR) mice was confirmed. Tests were conducted to determine the neuroprotective effects against H2O2-induced oxidative stress, and the results showed that AAFM has protective effects through the repression of mitochondrial injury and cellular membrane damage against H2O2-induced neurotoxicity. In animal experiments, such as the Y-maze, passive avoidance, and Morris water maze tests, AAFM also showed excellent ameliorating effects on TMT-induced cognitive dysfunction. After behavioral tests, brain tissues were extracted to assess damage to brain tissue. According to the experimental results, AAFM improved the cholinergic system by upregulating acetylcholine (ACh) contents and inhibiting acetylcholinesterase (AChE) activity. AAFM effectively improved the decline of the superoxide dismutase (SOD) level and the increase of the oxidized glutathione (GSH) ratio and lipid peroxidation (malondialdehyde (MDA) production) caused by TMT-induced oxidative stress. The occurrence of mitochondrial dysfunction and apoptosis was also decreased compared with the TMT group. Finally, quinic acid derivatives were identified as the major phenolic compounds in AAFM using ultra-performance liquid chromatography quadrupole-time-of-flight (UPLC-Q-TOF) MS analysis. PMID:29081819

Cognitive Function of Artemisia argyi H. Fermented by Monascus purpureus under TMT-Induced Learning and Memory Deficits in ICR Mice.

PubMed

Kang, Jin Yong; Lee, Du Sang; Park, Seon Kyeong; Ha, Jeong Su; Kim, Jong Min; Ha, Gi Jeong; Seo, Weon Taek; Heo, Ho Jin

2017-01-01

The cognitive effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM), which has cellular antioxidant activity and neuronal cell viability, on trimethyltin- (TMT-) induced learning and memory impairment in Institute of Cancer Research (ICR) mice was confirmed. Tests were conducted to determine the neuroprotective effects against H 2 O 2 -induced oxidative stress, and the results showed that AAFM has protective effects through the repression of mitochondrial injury and cellular membrane damage against H 2 O 2 -induced neurotoxicity. In animal experiments, such as the Y-maze, passive avoidance, and Morris water maze tests, AAFM also showed excellent ameliorating effects on TMT-induced cognitive dysfunction. After behavioral tests, brain tissues were extracted to assess damage to brain tissue. According to the experimental results, AAFM improved the cholinergic system by upregulating acetylcholine (ACh) contents and inhibiting acetylcholinesterase (AChE) activity. AAFM effectively improved the decline of the superoxide dismutase (SOD) level and the increase of the oxidized glutathione (GSH) ratio and lipid peroxidation (malondialdehyde (MDA) production) caused by TMT-induced oxidative stress. The occurrence of mitochondrial dysfunction and apoptosis was also decreased compared with the TMT group. Finally, quinic acid derivatives were identified as the major phenolic compounds in AAFM using ultra-performance liquid chromatography quadrupole-time-of-flight (UPLC-Q-TOF) MS analysis.

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

PubMed

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

2015-12-01

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

The ICR96 exon CNV validation series: a resource for orthogonal assessment of exon CNV calling in NGS data.

PubMed

Mahamdallie, Shazia; Ruark, Elise; Yost, Shawn; Ramsay, Emma; Uddin, Imran; Wylie, Harriett; Elliott, Anna; Strydom, Ann; Renwick, Anthony; Seal, Sheila; Rahman, Nazneen

2017-01-01

Detection of deletions and duplications of whole exons (exon CNVs) is a key requirement of genetic testing. Accurate detection of this variant type has proved very challenging in targeted next-generation sequencing (NGS) data, particularly if only a single exon is involved. Many different NGS exon CNV calling methods have been developed over the last five years. Such methods are usually evaluated using simulated and/or in-house data due to a lack of publicly-available datasets with orthogonally generated results. This hinders tool comparisons, transparency and reproducibility. To provide a community resource for assessment of exon CNV calling methods in targeted NGS data, we here present the ICR96 exon CNV validation series. The dataset includes high-quality sequencing data from a targeted NGS assay (the TruSight Cancer Panel) together with Multiplex Ligation-dependent Probe Amplification (MLPA) results for 96 independent samples. 66 samples contain at least one validated exon CNV and 30 samples have validated negative results for exon CNVs in 26 genes. The dataset includes 46 exon CNVs in BRCA1 , BRCA2 , TP53 , MLH1 , MSH2 , MSH6 , PMS2 , EPCAM or PTEN , giving excellent representation of the cancer predisposition genes most frequently tested in clinical practice. Moreover, the validated exon CNVs include 25 single exon CNVs, the most difficult type of exon CNV to detect. The FASTQ files for the ICR96 exon CNV validation series can be accessed through the European-Genome phenome Archive (EGA) under the accession number EGAS00001002428.

[Fabry nephropathy in a female with superposed IgA glomerulonephritis].

PubMed

Pisani, A; Sessa, A; Sabbatini, M; Andreucci, M V; Fusco, C; Balletta, M; Cianciaruso, B

2005-01-01

In Anderson-Fabry disease (AFd), the kidney is affected in all hemizygous males and in some heterozygous females. Female carriers can present subtle renal abnormalities due to glycosphingolipid (GSL) accumulation within renal cells. Renal biopsy is rarely performed in female Fabry patients because clinical renal manifestations are usually lacking. However, female carriers can accumulate GSL in their renal cells despite the absence of clinically evident kidney disease. We performed a kidney biopsy in a 52-year-old female patient, a Fabry disease carrier. The patient showed normal glomerular filtration rate, persistent microhematuria and proteinuria (about 1.7 g/24 hr), cornea "verticillata", and evident left ventricular hypertrophy. The molecular study documented a missense mutation R227Q in exon 5 of the alpha-galactosidase A gene. Optical microscopy showed electron-dense mesangial deposits due IgA glomerulonephritis, as confirmed by immunofluorescence. We decided to start therapy with angiotensin-converting enzyme inhibitors (ACE-I). After 8 months of treatment, the patient demonstrated proteinuria of 0.9 g/24 hr. To decide when to start treatment using enzyme replacement therapy (ERT) with human recombinant GAL A (Fabrazyme), we decided to perform an electron microscopy study of the renal biopsy. The renal ultrastructural findings were typical GSL inclusions in all kinds of glomerular cells, in tubular epithelial cells and in endothelial cells of interstitial capillaries, confirming the hypothesis of Fabry nephropathy. Consequently, Fabrazyme was given at a standard dose of 1 mg/kg every 2 weeks. After 24 months of combined treatment (ACE-I-Fabrazyme), proteinuria decreased to 0.2 g/24 hr. The importance of performing the ultrastructural examination of the kidney biopsy is stressed, especially in heterozygous Fabry patients to evaluate the need to treat them with ERT and to evaluate the degree of renal involvement.

Rituximab Treatment for PR3-ANCA-Positive Membranoproliferative Glomerulonephritis Associated with Adult-Onset Periodic Fever Syndrome.

PubMed

Hamano, Yoshitomo; Yoshizawa, Hiromichi; Sugase, Taro; Miki, Takuya; Ohtani, Naoko; Hanawa, Shiho; Takeshima, Eri; Morishita, Yoshiyuki; Saito, Osamu; Takemoto, Fumi; Muto, Shigeaki; Yumura, Wako; Kusano, Eiji

2012-07-01

We report the case of a 36-year-old Japanese woman with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) Type I diagnosed after a 5-year history of periodic fever syndrome (PFS). Hypocomplementemia and elevation of anti-proteinase 3 anti-neutrophil cytoplasmic autoantibody (PR3-ANCA) were observed. HIV, and hepatitis B and C serology were negative. Nephrotic syndrome and periodic fever did not respond to oral steroid and intravenous steroid pulse therapies combined with cyclosporine, dipyridamole, warfarin and losartan. We tried immunotherapy using rituximab, a human-mouse chimeric monoclonal antibody directed against the CD20 antigen on mature B cells. This therapeutic approach led to improvement of renal function and remission of nephrotic syndrome and hypocomplementemia. However, it did not have a beneficial effect on periodic fever. Suspecting adult-onset hereditary PFS, we analyzed her genetic alteration of MEFV and TNFRSF1A genes. A rare genotype in intron 6 of TNFRSF1A was revealed. The etiological relationship between periodic fever and MPGN is discussed. Rituximab is a hopeful choice of induction therapy for refractory MPGN.

Childhood acute glomerulonephritis in Port Harcourt, Rivers State, Nigeria.

PubMed

Anochie, Ifeoma; Eke, Felicia; Okpere, Augustina

2009-01-01

Acute glomerulonephritis (AGN) is an important cause of renal morbidity and mortality in children. The incidence varies across the countries with lower rates in developed countries due to improved environmental hygiene and socio-economic status. A prospective study of patients admitted with the diagnosis of AGN was carried out in the Department of Paediatrics, University of Port Harcourt Teaching Hospital (UPTH) from June 2006 to June 2008. The patients' demographic data, presenting complaints; antecedent history of sore throat or skin infections, clinical findings including blood pressure; investigations, management and outcome were obtained. Data was compared with a previous study done in UPTH 14 years ago and in other countries. A total of 31 patients aged 3 to 16 years had AGN, giving an annual incidence of 15.5 cases. They comprised 16 (51.6%) males and 15 (48.4%) females with a M:F ratio of 1.1:1. There is no significant change in the annual incidence of AGN when compared with the 14.5 cases per year reported in our centre 14 years ago. Fourteen (45.2%) of the patients were between 5-10 years. The highest incidence occurred during the dry cold windy (harmattan) season of October to February in 19 (61.3%) patients. Twenty-four (77.4%) of the patients were from low socio-economic classes (social class IV and V). Sore throat was the commonest infection preceeding AGN (66.6%). Hypertensive encephalopathy with seizure occurred in 5 (16.1%) patients. There were 4 (12.9.1%) patients with nephrotic range proteinuria, and 12 (38.7%) patients had renal failure. Urinary tract infection occurred in 7 (22.6%) patients; klebsiella being the commonest organism isolated. All patients received conservative treatment while dialysis was done in 5 patients; one peritoneal dialysis (PD) and 4 haemodialysis. The recovery rate was 83.9% and a hospital mortality of 3 (9.7%). The annual incidence of AGN has remained almost the same in Port Harcourt despite the increased urbanization

Intact and Top-Down Characterization of Biomolecules and Direct Analysis Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Coupled to FT-ICR Mass Spectrometry

PubMed Central

Sampson, Jason S.; Murray, Kermit K.; Muddiman, David C.

2013-01-01

We report the implementation of an infrared laser onto our previously reported matrix-assisted laser desorption electrospray ionization (MALDESI) source with ESI post-ionization yielding multiply charged peptides and proteins. Infrared (IR)-MALDESI is demonstrated for atmospheric pressure desorption and ionization of biological molecules ranging in molecular weight from 1.2 to 17 kDa. High resolving power, high mass accuracy single-acquisition Fourier transform ion cyclotron resonance (FT-ICR) mass spectra were generated from liquid-and solid-state peptide and protein samples by desorption with an infrared laser (2.94 µm) followed by ESI post-ionization. Intact and top-down analysis of equine myoglobin (17 kDa) desorbed from the solid state with ESI post-ionization demonstrates the sequencing capabilities using IR-MALDESI coupled to FT-ICR mass spectrometry. Carbohydrates and lipids were detected through direct analysis of milk and egg yolk using both UV- and IR-MALDESI with minimal sample preparation. Three of the four classes of biological macromolecules (proteins, carbohydrates, and lipids) have been ionized and detected using MALDESI with minimal sample preparation. Sequencing of O-linked glycans, cleaved from mucin using reductive β-elimination chemistry, is also demonstrated. PMID:19185512

Prostaglandin E1 inhibits collagen expression in anti-thymocyte antibody-induced glomerulonephritis: possible role of TGF beta.

PubMed

Schneider, A; Thaiss, F; Rau, H P; Wolf, G; Zahner, G; Jocks, T; Helmchen, U; Stahl, R A

1996-07-01

To test whether or not prostaglandins mediate extracellular matrix formation in immune-mediated glomerular disease, rats with anti-thymocyte antibody-induced glomerulonephritis were treated with prostaglandin E1 (PGE1) (250 micrograms/twice daily/s.c.). Glomerular expression of collagen types III and IV was assessed by Northern blotting, immunohistology and Western blotting. Proliferation of glomerular cells was evaluated by staining for the proliferating cell nuclear antigen (PCNA) and consecutive cell counting. At day five after induction of the disease, glomerular mRNA levels of collagen types III and IV were three- to fivefold higher compared with non-nephritic controls. Similarly glomerular deposition of these collagens was markedly increased when assessed by immunohistology. The treatment of nephritic rats with PGE1 reduced the increased glomerular mRNA levels as well as the protein concentration and the deposition of extracellular collagens. The number of PCNA positive cells which was significantly higher in nephritic rats when compared with control animals (24 hr, nephritis 2.53 +/- 0.33 and Control 0.26 +/- 0.06, P = 0.011; 5 days, nephritis 5.10 +/- 1.13 and Control 0.75 +/- 0.08, cells per glomerular cross section, P = 0.03) was reduced by PGE1 (24 hr, nephritis+PGE1 0.44 +/- 0.30, P = 0.0001; 5 days, nephritis +/- PGE1 1.91 +/- 1.84 cells per glomerular cross section, P = 0.001). Prostaglandin E1 also ameliorated the glomerular infiltration of monocytes at 24 hours (nephritis 4.36 +/- 2.82, nephritis + PGE1 2.20 +/- 1.82, cells per glomerular cross section) and five days (nephritis 1.51 +/- 0.58, nephritis+PGE1 1.12 +/- 0.61, cells per glomerular cross section). To further characterize possible mechanisms by which PGE1 reduces extracellular matrix deposition, the glomerular expression of transforming growth factor (TGF-beta), and interleukin 1 beta (IL-1 beta) was assessed by Northern blotting. Nephritic glomeruli showed increased mRNA levels of TGF

Oligosaccharide composition is similar in drusen and dense deposits in membranoproliferative glomerulonephritis type II.

PubMed

D'souza, Yvonne B; Jones, Carolyn J P; Short, Colin D; Roberts, Ian S D; Bonshek, Richard E

2009-04-01

Drusen are a feature of age-related macular degeneration (AMD). Lesions similar in appearance to drusen are also found in the fundi of patients with membranoproliferative glomerulonephritis type II (dense deposit disease, DDD). The lamina densa of the glomerular basement membrane, in DDD, is transformed into an electron-dense structure by deposition of microscopically homogeneous material. Our study sought to compare the saccharide composition of drusen and dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and kidney. Six eye specimens were obtained from patients diagnosed with AMD but another eye was obtained from a patient with partial lipodystrophy, who died after renal failure presumably because of DDD. The kidney specimens were from three biopsy-proven cases of DDD. Glycosylation patterns were measured by the binding of 19 biotinylated lectins before and after neuraminidase pre-treatment. High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N-acetyl glucosamine, galactose, and sialic acid residues were found in both drusen and dense deposits. Treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study found similar pathologic oligosaccharide structures in the eye and kidney, suggesting that drusen may be a common end result of retinal and glomerular disease.

Hepatoprotective effects of litchi (Litchi chinensis) procyanidin A2 on carbon tetrachloride-induced liver injury in ICR mice

PubMed Central

Chen, Lih-Geeng; Chang, Cheng-Wei; Tsay, Jwu-Guh; Weng, Brian Bor-Chun

2017-01-01

Drug tolerance, lacking liver regenerative activity and inconclusive inhibition of steatosis and cirrhosis by silymarin treatment during chronic liver injury have increased the demand for novel alternative or synergistic treatments for liver damage. Litchi fruit is abundant in polyphenolic compounds and is used in traditional Chinese medicine for treatments that include the strengthening of hepatic and pancreatic functions. Unique polyphenolic compounds obtained from litchi pericarp extract (LPE) were studied in vitro and in vivo for hepatoprotection. Epicatechin (EC) and procyanidin A2 (PA2) of LPE were obtained by fractionated-extraction from pulverized litchi pericarps. All fractions, including LPE, were screened against silymarin in carbon tetrachloride (CCl4)-treated murine embryonic liver cell line (BNL). The effects of daily gavage-feeding of LPE, silymarin (200 mg/kg body weight) or H2O in CCl4-intoxicated male ICR mice were evaluated by studying serum chemicals, liver pathology and glutathione antioxidative enzymes. The effects of EC and PA2 on liver cell regenerative activity were investigated using a scratch wound healing assay and flow cytometric cell cycle analysis; the results of which demonstrated that LPE protected BNL from CCl4-intoxication. Gavage-feeding of LPE decreased serum glutamic oxaloacetate transaminase and glutamic pyruvic transaminase levels, and exhibited superior retention of the hexagonal structure of hepatocytes and reduced necrotic cells following liver histopathological examinations in CCl4-intoxicated ICR mice. Glutathione peroxidise and glutathione reductase activities were preserved as the normal control level in LPE groups. EC and PA2 were principle components of LPE. PA2 demonstrated liver cell regenerative activity in scratch wound healing assays and alcohol-induced liver cell injury in vitro. The present findings suggest that litchi pericarp polyphenolic extracts, including EC and PA2, may be a synergistic alternative to

Hepatoprotective effects of litchi (Litchi chinensis) procyanidin A2 on carbon tetrachloride-induced liver injury in ICR mice.

PubMed

Chen, Lih-Geeng; Chang, Cheng-Wei; Tsay, Jwu-Guh; Weng, Brian Bor-Chun

2017-06-01

Drug tolerance, lacking liver regenerative activity and inconclusive inhibition of steatosis and cirrhosis by silymarin treatment during chronic liver injury have increased the demand for novel alternative or synergistic treatments for liver damage. Litchi fruit is abundant in polyphenolic compounds and is used in traditional Chinese medicine for treatments that include the strengthening of hepatic and pancreatic functions. Unique polyphenolic compounds obtained from litchi pericarp extract (LPE) were studied in vitro and in vivo for hepatoprotection. Epicatechin (EC) and procyanidin A2 (PA2) of LPE were obtained by fractionated-extraction from pulverized litchi pericarps. All fractions, including LPE, were screened against silymarin in carbon tetrachloride (CCl 4 )-treated murine embryonic liver cell line (BNL). The effects of daily gavage-feeding of LPE, silymarin (200 mg/kg body weight) or H 2 O in CCl 4 -intoxicated male ICR mice were evaluated by studying serum chemicals, liver pathology and glutathione antioxidative enzymes. The effects of EC and PA2 on liver cell regenerative activity were investigated using a scratch wound healing assay and flow cytometric cell cycle analysis; the results of which demonstrated that LPE protected BNL from CCl 4 -intoxication. Gavage-feeding of LPE decreased serum glutamic oxaloacetate transaminase and glutamic pyruvic transaminase levels, and exhibited superior retention of the hexagonal structure of hepatocytes and reduced necrotic cells following liver histopathological examinations in CCl 4- intoxicated ICR mice. Glutathione peroxidise and glutathione reductase activities were preserved as the normal control level in LPE groups. EC and PA2 were principle components of LPE. PA2 demonstrated liver cell regenerative activity in scratch wound healing assays and alcohol-induced liver cell injury in vitro . The present findings suggest that litchi pericarp polyphenolic extracts, including EC and PA2, may be a synergistic

Circadian egg production by Echinostoma caproni (Digenea: Echinostomatidae) in ICR mice.

PubMed

Platt, Thomas R; Hussey, Gabrielle L; Zelmer, Derek A

2013-04-01

Circadian egg production by Echinostoma caproni was investigated in ICR mice. Four female mice were infected with 25 E. caproni metacercariae, maintained in individual cages on a 12:12 light:dark cycle, and provided food and water ad libitum. Twenty-eight, 51, and 58 days post-infection, mice were transferred to individual, wire-bottomed cages and feces were collected every 2 hr for 24 hr. The feces were weighed and processed immediately to estimate the number of eggs present. Fecal output and egg production were standardized to unit maxima for analysis. Standardized egg count and standardized fecal output followed distinctly circadian patterns and covaried. Egg production was highest from 2200 to 0200 hr and lowest from 1000 to 1800 hr. These correspond to the highest and lowest fecal production, and highest and lowest periods of host activity, respectively. Egg density (eggs/g of feces) covaried weakly with fecal output with an additional peak at 0800-1000 hr, suggesting E. caproni is responding to changes in host physiology in timing of the production and release of eggs into the intestine. The continuous production and release of eggs during the patent period, coupled with the circadian pattern of daily egg release by E. caproni , would result in the widest dispersal of eggs in the host environment and enhance transmission to the first intermediate host.

Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus.

PubMed

Carlson Scholz, Jodi A; Garg, Rohit; Compton, Susan R; Allore, Heather G; Zeiss, Caroline J; Uchio, Edward M

2011-10-01

The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.

The embryotoxic effects of ultrasound exposure in pregnant ICR mice.

PubMed

Kimmel, C A; Stratmeyer, M E; Galloway, W D; Laborde, J B; Brown, N; Pinkavitch, F

1983-04-01

The embryotoxicity of ultrasound exposure during pregnancy was investigated in DUB:(ICR) mice. On day 0 of gestation (day of plug), pregnant mice were assigned to one of five groups: cage control, sham exposed (0 W/cm2), 0.05 W/cm2, 0.50 W/cm2. or 1.00 W/cm2. Females were anesthetized on day 8 of gestation and their abdomens were shaved to assure good acoustic coupling. The animals were strapped on a lucite board and placed vertically into a distilled degassed water bath (30 degrees C) so that the abdomen was fully submerged and centered in the axis of the ultrasonic beam. Insonation was carried out using a PZT transducer with a radius of 1.27 cm and a frequency of 1 MHz under continuous wave conditions. Each animal was placed at a distance of 25 cm from the transducer and exposed to the appropriate intensity for 120 seconds. On day 17 of gestation, the maternal animals were killed, the uterine contents were examined, and live fetuses were weighed and then shipped in cold lactated Ringer's solution from Maryland to Arkansas. Fetuses were examined on the day following maternal sacrifice for external and visceral defects and skeletons were prepared and examined subsequently. Slight but significant differences were detected between the cage control and sham-exposed groups. No statistically significant changes were seen that could be attributed to ultrasound exposure, although there was a slight increase in the incidence of malformed fetuses and the occurrence of multiple malformations in individual fetuses as intensity of the ultrasonic exposure increased.

Diurnal migration of Echinostoma caproni (Digenea: Echinostomatidae) in ICR mice.

PubMed

Platt, Thomas R; Graf, Emily; Kammrath, Anna; Zelmer, Derek A

2010-12-01

Twenty-four female ICR mice, 12 acclimated to a 12 ∶ 12 light-dark cycle and 12 to a 12 ∶ 12 dark-light cycle for 7 days, were each infected with 10 metacercariae of Echinostoma caproni. Infected mice were maintained on their respective lighting regimes for 28 days. Six mice (3 from each group) were necropsied at 4-hr intervals beginning at 0700 hr. The small intestine was removed, opened, and the position of individual worms and worm clusters was measured to the nearest 0.1 cm. Each intestine was subsequently divided into 20 equal segments and individual worms and worm clusters were assigned to the appropriate segment based on the original measurements. All worms were found in the posterior 55% of the intestine (ileum). All posterior segments (10-20), with the exception of segment 18, harbored at least 1 worm at some time. A Monte Carlo simulation of worm abundance in segments 10-17 over all time periods indicated a random distribution, while the same analysis of segments 10-20 indicated a non-random distribution due to large numbers of worms in segment 20 and to the absence of worms in segment 18. To analyze temporal changes in worm distribution, mice were grouped by time of necropsy as follows: night (1900 and 2300 hr), morning (0300 and 0700 hr), and day (1100 and 1500 hr). During the night and morning, E. caproni was heavily concentrated in segments 10-17 and, during the day, worms were located more posteriorly, with a heavy concentration in the last segment (20).

Application of mass spectrometry in the characterization of chemicals in coal-derived liquids.

PubMed

Liu, Fang-Jing; Fan, Maohong; Wei, Xian-Yong; Zong, Zhi-Min

2017-07-01

Coal-derived liquids (CDLs) are primarily generated from pyrolysis, carbonization, gasification, direct liquefaction, low-temperature extraction, thermal dissolution, and mild oxidation. CDLs are important feedstocks for producing value-added chemicals and clean liquid fuels as well as high performance carbon materials. Accordingly, the compositional characterization of chemicals in CDLs at the molecular level with advanced analytical techniques is significant for the efficient utilization of CDLs. Although reviews on advancements have been rarely reported, great progress has been achieved in this area by using gas chromatography/mass spectrometry (GC/MS), two-dimensional GC-time of flight mass spectrometry (GC × GC-TOFMS), and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). This review focuses on characterizing hydrocarbon, oxygen-containing, nitrogen-containing, sulfur-containing, and halogen-containing chemicals in various CDLs with these three mass spectrometry techniques. Small molecular (< 500 u), volatile and semi-volatile, and less polar chemicals in CDLs have been identified with GC/MS and GC × GC-TOFMS. By equipped with two-dimensional GC, GC × GC-TOFMS can achieve a clearly chromatographic separation of complex chemicals in CDLs without prior fractionation, and thus can overcome the disadvantages of co-elution and serious peak overlap in GC/MS analysis, providing much more compositional information. With ultrahigh resolving power and mass accuracy, FT-ICR MS reveals a huge number of compositionally distinct compounds assigned to various chemical classes in CDLs. It shows excellent performance in resolving and characterizing higher-molecular, less volatile, and polar chemicals that cannot be detected by GC/MS and GC × GC-TOFMS. The application of GC × GC-TOFMS and FT-ICR MS to chemical characterization of CDLs is not as prevalent as that of petroleum and largely remains to be developed in many respects

Comparison of tribromoethanol, ketamine/acetylpromazine, Telazol/xylazine, pentobarbital, and methoxyflurane anesthesia in HSD:ICR mice.

PubMed

Gardner, D J; Davis, J A; Weina, P J; Theune, B

1995-04-01

Variation in the duration of surgical anesthesia in mice prompted an evaluation of various commonly used anesthetics. Using biotelemetric technology, we evaluated the effects of six anesthetic regimens (tribromoethanol, ketamine and acetylpromazine in combination, Telazol and xylazine in two combinations, pentobarbital, and methoxyflurane) on temperature and activity. Six groups of four male HSD:ICR mice received one of the anesthetic regimens or an equivalent volume of saline. Induction time (time from anesthetic administration until righting reflex loss) and duration of anesthesia (loss of response to interdigital toe pinch) were evaluated. Methoxyflurane and both doses of Telazol combinations resulted in the shortest and most repeatable induction times. None of the mice in the ketamine/acetylpromazine- and pentobarbital-treated groups lost the interdigital toe pinch reflex. Duration of anesthesia was superior in the two Telazol/xylazine-treated groups. A direct correlation existed between duration of anesthesia and magnitude and duration of temperature reduction. Duration of anesthesia can be used to predict extent of hypothermia.

Application of Printed Circuit Board Technology to FT-ICR MS Analyzer Cell Construction and Prototyping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leach, Franklin E.; Norheim, Randolph V.; Anderson, Gordon A.

Although Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS) remains themass spectrometry platform that provides the highest levels of performance for mass accuracy and resolving power, there is room for improvement in analyzer cell design as the ideal quadrupolar trapping potential has yet to be generated for a broadband MS experiment. To this end, analyzer cell designs have improved since the field’s inception, yet few research groups participate in this area because of the high cost of instrumentation efforts. As a step towards reducing this barrier to participation and allowing for more designs to be physically tested, we introduce amore » method of FT-ICR analyzer cell prototyping utilizing printed circuit boards at modest vacuum conditions. This method allows for inexpensive devices to be readily fabricated and tested over short intervals and should open the field to laboratories lacking or unable to access high performance machine shop facilities because of the required financial investment.« less

The crowding effect and morphometric variability in Echinostoma caproni (Digenea: Echinostomatidae) from ICR mice.

PubMed

Stillson, Lindsey L; Platt, Thomas R

2007-04-01

Population density, or crowding, was examined to determine its effect on the morphometric variability of Echinostoma caproni (Digenea) in ICR mice. Six mice were infected with 25 and 100 metacercariae, and a single mouse was infected with 300 metacercariae. All mice were infected at necropsy 22 days postinfection with recoveries of 77%, 69%, and 7.3%, respectively. Whole mounts were prepared, and 31 characters were evaluated (25 direct measurements and 6 ratios). Univariate and multivariate statistical analysis revealed significant differences between adult worms from all 3 groups. Twenty-seven of 31 characters showed significant within-group differences, with the primary differences between worms from 25/100 versus 300 metacercariae infections. Discriminant function analysis yielded a 100% correct classification based on infection size, which is consistent with studies on distinct species of Echinostoma. The low recovery from the mouse infected with 300 metacercariae suggests inflammatory expulsion of juvenile worms and the possibility of immunity as a factor in the crowding effect. These results suggest that external factors may affect morphometric variability of digenetic trematodes to a larger degree than previously recognized.

[Dense deposit nephropathy: a peculiar variant of glomerulonephritis or a distinct disease entity (author's transl)].

PubMed

Rossmann, P; Matousovic, K; Bucek, J

1975-01-01

In four renal biopsies of two patients with chronic glomerulonephritis (GN), the so-called dense deposit nephropathy (NDD) was diagnosed by means of light, electron, and immunofluorescence microscopy. In routine paraffin sections the picture approached that of the membrano-proliferative GN. In semithin sections (toluidine blue, periodic acid-Ag-methenamine) and especially in the ultrastructure there appeared extensive confluent deposits of a very dense substance, infiltrating the lamina densa of glomerular capillaries, basal membranes of both Bowman's capsules and tubules, and arteriolar walls. In this localization, a non-diffuse "psdudolinear" deposition of beta1c was detected, whereas antisera to main Ig-fractions and fibrin(ogen) were not fixed. In a biopsy performed six years later, a concentration of dense depositis towards the mesangial area and a partial regeneration of basal membranes were observed. In a part of dense deposits there appeared vacuolization, primarily in tubular and arteriolar basal membranes. In glomeruli, focal IgM deposits were apparent at an advanced stage. NDD apparently is a sequel of a particular metabolic (immune?) process, afflicting solely the renal membranous system and distinctly dns known at present. The noncharacteristic clinical presentation resembles chronic. GN, is very protracted, lengthy, and relatively benigh, with a chance of functional and possible even morphological remission.

Spontaneous extraskeletal osteosarcoma with various histological growth patterns in the abdominal wall of an ICR mouse

PubMed Central

Ito, Tsuyoshi; Katoh, Yoshitaka; Shimada, Yuko; Ohnuma-Koyama, Aya; Takahashi, Naofumi; Kuwahara, Maki; Harada, Takanori

2015-01-01

Extraskeletal osteosarcoma is extremely rare in mice. This case report demonstrates a spontaneous murine extraskeletal osteosarcoma that exhibited various histological growth patterns in an ICR mouse. At necropsy, the tumor mass was located in the abdominal wall and was 45 × 30 × 25 mm in size. Histopathologically, the tumor showed the following four growth patterns: a solid pattern of polygonal cells embedded in an osteoid eosinophilic matrix with calcification, an irregular sheet pattern of short spindle cells accompanying some eosinophilic multinucleated cells, a fascicular pattern of spindle cells and a cystic pattern lined by short spindle cells. Immunohistochemically, most of the tumor cells were positive for vimentin, proliferating cell nuclear antigen and osterix. The multinucleated cells mentioned above were desmin positive and were regarded as regenerative striated muscles but not tumor cells. Since no clear continuity with normal bone tissues was observed, the tumor was diagnosed as an “extraskeletal osteosarcoma.” PMID:26989300

Usage of FT-ICR-MS Metabolomics for Characterizing the Chemical Signatures of Barrel-Aged Whisky

PubMed Central

Roullier-Gall, Chloé; Signoret, Julie; Hemmler, Daniel; Witting, Michael A.; Kanawati, Basem; Schäfer, Bernhard; Gougeon, Régis D.; Schmitt-Kopplin, Philippe

2018-01-01

Whisky can be described as a complex matrix integrating the chemical history from the fermented cereals, the wooden barrels, the specific distillery processes, aging, and environmental factors. In this study, using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analyzed 150 whisky samples from 49 different distilleries, 7 countries, and ranging from 1 day new make spirit to 43 years of maturation with different types of barrel. Chemometrics revealed the unexpected impact of the wood history on the distillate's composition during barrel aging, regardless of the whisky origin. Flavonols, oligolignols, and fatty acids are examples of important chemical signatures for Bourbon casks, whereas a high number of polyphenol glycosides, including for instance quercetin-glucuronide or myricetin-glucoside as potential candidates, and carbohydrates would discriminate Sherry casks. However, the comparison of barrel aged rums and whiskies revealed specific signatures, highlighting the importance of the initial composition of the distillate and the distillery processes. PMID:29520358

Usage of FT-ICR-MS Metabolomics for characterizing the chemical signatures of barrel-aged whisky

NASA Astrophysics Data System (ADS)

Roullier-Gall, Chloé; Signoret, Julie; Hemmler, Daniel; Witting, Michael A.; Kanawati, Basem; Schäfer, Bernhard; Gougeon, Régis D.; Schmitt-Kopplin, Philippe

2018-02-01

Whisky can be described as a complex matrix integrating the chemical history from the fermented cereals, the wooden barrels, the specific distillery processes, ageing and environmental factors. In this study, using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analysed 150 whisky samples from 49 different distilleries, 7 countries, and ranging from 1 day new make spirit to 43 years of maturation with different types of barrel. Chemometrics revealed the unexpected impact of the wood history on the distillatés composition during barrel ageing, regardless of the whisky origin. Flavonols, oligolignols and fatty acids are examples of important chemical signatures for Bourbon casks, whereas a high number of polyphenol glycosides, including for instance quercetin-glucuronide or myricetin-glucoside as potential candidates, and carbohydrates would discriminate Sherry casks. However, the comparison of barrel aged rums and whiskies revealed specific signatures, highlighting the importance of the initial composition of the distillate and the distillery processes.

Remission of proteinuria in primary glomerulonephritis: we know the goal but do we know the price?

PubMed

Philibert, David; Cattran, Daniel

2008-10-01

Membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy are the most commonly recognized types of primary glomerulonephritis that progress to end-stage renal disease. Persistent proteinuria is a major determinant of such progression. Reduction of proteinuria slows progression of renal disease and improves renal survival, but many of the agents used to reduce proteinuria carry a considerable risk of toxicity. The assessment of benefit versus risk of these medications can be further complicated by the temporal disconnect between the onset of benefit and of serious adverse events. In addition, relapses are common in these disorders and there is often a need for retreatment. Such retreatment might lead to repeated and/or prolonged drug exposure and to the oversight or underestimation of the cumulative dose of these agents because of the potentially extended interval between relapses. Consequently, it is very important to constantly review each patient's status and take into account their age, comorbid conditions and cumulative drug exposure when assessing treatment options. The potentially delayed development of adverse events also emphasizes the need for long-term surveillance of patients who receive immunosuppressive treatment for glomerular disease, often well beyond their drug exposure period and even when the treatment has been successful.

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

PubMed

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

2016-01-01

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

The nucleotides responsible for the direct physical contact between the chromatin insulator protein CTCF and the H19 imprinting control region manifest parent of origin-specific long-distance insulation and methylation-free domains

PubMed Central

Pant, Vinod; Mariano, Piero; Kanduri, Chandrasekhar; Mattsson, Anita; Lobanenkov, Victor; Heuchel, Rainer; Ohlsson, Rolf

2003-01-01

The repression of the maternally inherited Igf2 allele has been proposed to depend on a methylation-sensitive chromatin insulator organized by the 11 zinc finger protein CTCF at the H19 imprinting control region (ICR). Here we document that point mutations of the nucleotides in physical contact with CTCF within the endogenous H19 ICR lead to loss of CTCF binding and Igf2 imprinting only when passaged through the female germline. This effect is accompanied by a significant loss of methylation protection of the maternally derived H19 ICR. Because CTCF interacts with other imprinting control regions, it emerges as a central factor responsible for interpreting and propagating gamete-derived epigenetic marks and for organizing epigenetically controlled expression domains. PMID:12629040

Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis.

PubMed

Kanaguchi, Yasuhiko; Suzuki, Yusuke; Osaki, Ken; Sugaya, Takeshi; Horikoshi, Satoshi; Tomino, Yasuhiko

2011-11-01

In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB). The urinary protein level in Tg mice decreased significantly during the acute phase (~Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with vascular thrombosis in WT mice

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

PubMed Central

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

2011-01-01

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

Petroleomics by electrospray ionization FT-ICR mass spectrometry coupled to partial least squares with variable selection methods: prediction of the total acid number of crude oils.

PubMed

Terra, Luciana A; Filgueiras, Paulo R; Tose, Lílian V; Romão, Wanderson; de Souza, Douglas D; de Castro, Eustáquio V R; de Oliveira, Mirela S L; Dias, Júlio C M; Poppi, Ronei J

2014-10-07

Negative-ion mode electrospray ionization, ESI(-), with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was coupled to a Partial Least Squares (PLS) regression and variable selection methods to estimate the total acid number (TAN) of Brazilian crude oil samples. Generally, ESI(-)-FT-ICR mass spectra present a power of resolution of ca. 500,000 and a mass accuracy less than 1 ppm, producing a data matrix containing over 5700 variables per sample. These variables correspond to heteroatom-containing species detected as deprotonated molecules, [M - H](-) ions, which are identified primarily as naphthenic acids, phenols and carbazole analog species. The TAN values for all samples ranged from 0.06 to 3.61 mg of KOH g(-1). To facilitate the spectral interpretation, three methods of variable selection were studied: variable importance in the projection (VIP), interval partial least squares (iPLS) and elimination of uninformative variables (UVE). The UVE method seems to be more appropriate for selecting important variables, reducing the dimension of the variables to 183 and producing a root mean square error of prediction of 0.32 mg of KOH g(-1). By reducing the size of the data, it was possible to relate the selected variables with their corresponding molecular formulas, thus identifying the main chemical species responsible for the TAN values.

Nuclear Factor-κB Inhibitors as Potential Novel Anti-Inflammatory Agents for the Treatment of Immune Glomerulonephritis

PubMed Central

López-Franco, Oscar; Suzuki, Yusuke; Sanjuán, Guillermo; Blanco, Julia; Hernández-Vargas, Purificación; Yo, Yoshikage; Kopp, Jeffrey; Egido, Jesús; Gómez-Guerrero, Carmen

2002-01-01

Nuclear factor (NF)-κB regulates several genes implicated in the inflammatory response and represents an interesting therapeutic target. We examined the effects of gliotoxin (a fungal metabolite) and parthenolide (a plant extract), which possess anti-inflammatory activities in vitro, on the progression of experimental glomerulonephritis. In the anti-Thy 1.1 rat model, gliotoxin (75 μg/rat/day, 10 days, n = 18 rats) markedly reduced proteinuria, glomerular lesions, and monocyte infiltration. In anti-mesangial cell nephritis in mice, parthenolide (70 μg/mouse/day, 7 days, n = 17 mice) significantly decreased proteinuria, hematuria, and glomerular proliferation. NF-κB activity, localized in glomerular and tubular cells, was attenuated by either gliotoxin or parthenolide, in association with diminished renal expression of monocyte chemoattractant protein-1 and inducible nitric oxide synthase. In cultured mesangial cells and monocytes, gliotoxin and parthenolide inhibited NF-κB activation and expression of inflammatory genes induced by lipopolysaccharide and cytokines, by blocking the phosphorylation/degradation of the IκBα subunit. In summary, gliotoxin and parthenolide prevent proteinuria and renal lesions by inhibiting NF-κB activation and expression of regulated genes. This may represent a novel approach for the treatment of immune and inflammatory renal diseases. PMID:12368222

Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice.

PubMed

Kang, Ju Hyung; Baik, Haing Woon; Yoo, Seung-Min; Kim, Joo Heon; Cheong, Hae Il; Park, Chung-Gyu; Kang, Hee Gyung; Ha, Il-Soo

2016-01-01

Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns). We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor β1 (TGF-β1), PRR, FcRn and renal metabolism of IgG in a mice model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). IgG deposition and expressions of FcRn and PRR were enhanced at glomeruli and urinary IgG levels increased in anti-GBM GN. Aliskiren attenuated anti-GBM GN with reduction of proteinuria and cortical expressions of fibronectin and TGF-β1. In addition, aliskiren suppressed the renal cortical expressions of FcRn and PRR. Aliskiren also reduced the glomerular IgG depositions and the urinary IgG levels albeit with increased circulating serum IgG levels. These results suggest that suppression of FcRn and PRR and regulation of IgG metabolism may be related to the attenuation of anti-GBM GN by aliskiren. © 2016 S. Karger AG, Basel.

Potential Interference of Oil Vehicles on Genital Tubercle Development during the Fetal Period in ICR Mice.

PubMed

Nishioka, Yasushi; Tamai, Kazuki; Onda, Masanari; Hiromori, Youhei; Kimura, Tomoki; Hu, Jianying; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

2018-01-01

Corn oil, sesame oil, and 10% ethanol in corn oil are commonly used as dosing vehicles in toxicology studies. Since these vegetable oils contain bioactive compounds, it is important for toxicology studies to characterize the toxicities of the dosing vehicles themselves. It has been recently proposed that the width of the genital tubercle (GT), the dorsal-ventral length (D-V length) of the GT, and urethral tube closure in mouse fetuses can be used as novel markers for monitoring sexual development in mice. However, how these parameters are influenced by the dosing vehicles themselves remains unclear. Therefore, we evaluated the effects of corn oil, sesame oil, and 10% ethanol in corn oil on GT width, D-V length, and GT morphology in ICR mice. Our results showed that all three vehicles influenced GT width and D-V length, but not GT morphology, suggesting that the effects of dosing vehicles themselves might need to be considered when GT width or D-V length is used as a parameter to evaluate the effects of chemicals on GT development.

Fast Profiling of Natural Pigments in Different Spirulina (Arthrospira platensis) Dietary Supplements by DI-FT-ICR and Evaluation of their Antioxidant Potential by Pre-Column DPPH-UHPLC Assay.

PubMed

Sommella, Eduardo; Conte, Giulio Maria; Salviati, Emanuela; Pepe, Giacomo; Bertamino, Alessia; Ostacolo, Carmine; Sansone, Francesca; Prete, Francesco Del; Aquino, Rita Patrizia; Campiglia, Pietro

2018-05-11

Arthrospira platensis , better known as Spirulina, is one of the most important microalgae species. This cyanobacterium possesses a rich metabolite pattern, including high amounts of natural pigments. In this study, we applied a combined strategy based on Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS) and Ultra High-Performance Liquid Chromatography (UHPLC) for the qualitative/quantitative characterization of Spirulina pigments in three different commercial dietary supplements. FT-ICR was employed to elucidate the qualitative profile of Spirulina pigments, in both direct infusion mode (DIMS) and coupled to UHPLC. DIMS showed to be a very fast (4 min) and accurate (mass accuracy ≤ 0.01 ppm) tool. 51 pigments were tentatively identified. The profile revealed different classes, such as carotenes, xanthophylls and chlorophylls. Moreover, the antioxidant evaluation of the major compounds was assessed by pre-column reaction with the DPPH radical followed by fast UHPLC-PDA separation, highlighting the contribution of single analytes to the antioxidant potential of the entire pigment fraction. β-carotene, diadinoxanthin and diatoxanthin showed the highest scavenging activity. The method took 40 min per sample, comprising reaction. This strategy could represent a valid tool for the fast and comprehensive characterization of Spirulina pigments in dietary supplements, as well as in other microalgae-based products.

Primary Glomerulonephritis with Unique C4d Deposition and Concurrent Non-infectious Intermediate Uveitis: a Case Report and Literature Review

PubMed Central

2018-01-01

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature. PMID:29713256

Close relations between podocyte injuries and membranous proliferative glomerulonephritis in autoimmune murine models.

PubMed

Kimura, Junpei; Ichii, Osamu; Otsuka, Saori; Sasaki, Hayato; Hashimoto, Yoshiharu; Kon, Yasuhiro

2013-01-01

Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa(+) and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl. MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN. Copyright © 2013 S. Karger AG, Basel.

FT-ICR MS analysis of blended pine-microalgae feedstock HTL biocrudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Jacqueline M.; Billing, Justin M.; Corilo, Yuri E.

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is utilized for direct comparison of the chemical composition of biocrudes generated from the hydrothermal liquefaction of 100% pine, 100% algae, 75:25 pine:algae, and 50:50 pine:algae feedstocks. This analysis reveals that the of the 72:25 and 50:50 pine:algal HTL biocrudes is essentially a composite of the two parent feeds (i.e., pine and algae) with a lower relative abundance of Ox species and a higher relative abundance of nitrogen-containing species than the pine HTL biocrude. Alternatively, the biocrude blends have a lower relative abundance of nitrogen-containing species where N>2 than the algalmore » HTL biocrude. The 75:25 pine:algal HTL biocrude has more elemental formulae in common with the pine HTL biocrude than the 50:50 blend; however, both blends have more elemental formulae in common with the algal HTL biocrude. Interestingly, >20% of the elemental formulae assigned to monoisotopic peaks within the 75:25 and 50:50 biocrude blends are species not present in either the pine or algal HTL biocrudes. The highest relative abundance of these new species belong to the N2O4-6 classes, which correspond to heteroatom classes with a moderate number of nitrogen atoms and higher number of oxygen atoms per molecules than the species within the pure algal HTL biocrude. Compositionally, the novel species have the same structural motif but are of higher DBE and carbon numbers than the species within the algal HTL biocrude. These original species are most likely generated from reactions between molecules from both feeds, which results in compounds wotj higher oxygen content than typically seen in the algal HTL biocrude but also higher nitrogen contents than observed in the pine HTL biocrude.« less

Long-Term Results of Cartilage Repair after Allogeneic Transplantation of Cartilaginous Aggregates Formed from Bone Marrow-Derived Cells for Large Osteochondral Defects in Rabbit Knees.

PubMed

Yoshioka, Tomokazu; Mishima, Hajime; Sakai, Shinsuke; Uemura, Toshimasa

2013-10-01

The purpose of this study was to evaluate the long-term results of cartilage repair after allogeneic transplantation of cartilaginous aggregates formed from bone marrow-derived cells. Bone marrow cells were harvested from 12-day-old rabbits. The cells were subjected to a monolayer culture, and the spindle-shaped cells attached to the flask surface were defined as bone marrow-derived mesenchymal cells. After the monolayer culture, a 3-dimensional cartilaginous aggregate was formed using a bioreactor with chondrogenesis. We created osteochondral defects, measuring 5 mm in diameter and 4 mm in depth, at the femoral trochlea of 10-week-old rabbits. Two groups were established, the transplanted group in which the cartilaginous aggregate was transplanted into the defect, and the control group in which the defect was left untreated. Twenty-six and 52 weeks after surgery, the rabbits were sacrificed and their tissue repair status was evaluated macroscopically (International Cartilage Repair Society [ICRS] score) and histologically (O'Driscoll score). The ICRS scores were as follows: at week 26, 7.2 ± 0.5 and 7.6 ± 0.8; at week 52, 7.6 ± 1.1 and 9.7 ± 0.7, for the transplanted and control groups, respectively. O'Driscoll scores were as follows: at week 26, 12.6 ± 1.9 and 10.1 ± 1.9; at week 52, 9.6 ± 3.0 and 14.0 ± 1.4, each for transplanted and control groups, respectively. No significant differences were observed between the groups. This study demonstrates that allogeneic transplantation of cartilaginous aggregates formed from bone marrow-derived cells produces comparable long-term results based on macroscopic and histological outcome measures when compared with osteochondral defects that are left untreated.

Long-Term Results of Cartilage Repair after Allogeneic Transplantation of Cartilaginous Aggregates Formed from Bone Marrow–Derived Cells for Large Osteochondral Defects in Rabbit Knees

PubMed Central

Mishima, Hajime; Sakai, Shinsuke; Uemura, Toshimasa

2013-01-01

Objective: The purpose of this study was to evaluate the long-term results of cartilage repair after allogeneic transplantation of cartilaginous aggregates formed from bone marrow–derived cells. Methods: Bone marrow cells were harvested from 12-day-old rabbits. The cells were subjected to a monolayer culture, and the spindle-shaped cells attached to the flask surface were defined as bone marrow–derived mesenchymal cells. After the monolayer culture, a 3-dimensional cartilaginous aggregate was formed using a bioreactor with chondrogenesis. We created osteochondral defects, measuring 5 mm in diameter and 4 mm in depth, at the femoral trochlea of 10-week-old rabbits. Two groups were established, the transplanted group in which the cartilaginous aggregate was transplanted into the defect, and the control group in which the defect was left untreated. Twenty-six and 52 weeks after surgery, the rabbits were sacrificed and their tissue repair status was evaluated macroscopically (International Cartilage Repair Society [ICRS] score) and histologically (O’Driscoll score). Results: The ICRS scores were as follows: at week 26, 7.2 ± 0.5 and 7.6 ± 0.8; at week 52, 7.6 ± 1.1 and 9.7 ± 0.7, for the transplanted and control groups, respectively. O’Driscoll scores were as follows: at week 26, 12.6 ± 1.9 and 10.1 ± 1.9; at week 52, 9.6 ± 3.0 and 14.0 ± 1.4, each for transplanted and control groups, respectively. No significant differences were observed between the groups. Conclusions: This study demonstrates that allogeneic transplantation of cartilaginous aggregates formed from bone marrow–derived cells produces comparable long-term results based on macroscopic and histological outcome measures when compared with osteochondral defects that are left untreated. PMID:26069678

Rapid Screening for Potential Epitopes Reactive with a Polycolonal Antibody by Solution-Phase H/D Exchange Monitored by FT-ICR Mass Spectrometry

NASA Astrophysics Data System (ADS)

Zhang, Qian; Noble, Kyle A.; Mao, Yuan; Young, Nicolas L.; Sathe, Shridhar K.; Roux, Kenneth H.; Marshall, Alan G.

2013-07-01

The potential epitopes of a recombinant food allergen protein, cashew Ana o 2, reactive to polyclonal antibodies, were mapped by solution-phase amide backbone H/D exchange (HDX) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Ana o 2 polyclonal antibodies were purified in the serum from a goat immunized with cashew nut extract. Antibodies were incubated with recombinant Ana o 2 (rAna o 2) to form antigen:polyclonal antibody (Ag:pAb) complexes. Complexed and uncomplexed (free) rAna o 2 were then subjected to HDX-MS analysis. Four regions protected from H/D exchange upon pAb binding are identified as potential epitopes and mapped onto a homologous model.

A Phthalimide Derivative That Inhibits Centrosomal Clustering Is Effective on Multiple Myeloma

PubMed Central

Shiheido, Hirokazu; Terada, Fukiko; Tabata, Noriko; Hayakawa, Ichigo; Matsumura, Nobutaka; Takashima, Hideaki; Ogawa, Yoko; Du, Wenlin; Yamada, Taketo; Shoji, Mitsuru; Sugai, Takeshi; Doi, Nobuhide; Iijima, Shiro; Hattori, Yutaka; Yanagawa, Hiroshi

2012-01-01

Despite the introduction of newly developed drugs such as lenalidomide and bortezomib, patients with multiple myeloma are still difficult to treat and have a poor prognosis. In order to find novel drugs that are effective for multiple myeloma, we tested the antitumor activity of 29 phthalimide derivatives against several multiple myeloma cell lines. Among these derivatives, 2-(2,6-diisopropylphenyl)-5-amino-1H-isoindole-1,3- dione (TC11) was found to be a potent inhibitor of tumor cell proliferation and an inducer of apoptosis via activation of caspase-3, 8 and 9. This compound also showed in vivo activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. By means of mRNA display selection on a microfluidic chip, the target protein of TC11 was identified as nucleophosmin 1 (NPM). Binding of TC11 and NPM monomer was confirmed by surface plasmon resonance. Immunofluorescence and NPM knockdown studies in HeLa cells suggested that TC11 inhibits centrosomal clustering by inhibiting the centrosomal-regulatory function of NPM, thereby inducing multipolar mitotic cells, which undergo apoptosis. NPM may become a novel target for development of antitumor drugs active against multiple myeloma. PMID:22761710

Fetal Risks and Maternal Renal Complications in Pregnancy with Preexisting Chronic Glomerulonephritis.

PubMed

Li, Yuehong; Wang, Wei; Wang, Yujuan; Chen, Qi

2018-02-18

BACKGROUND Analysis the maternal and fetal risk predictors in pregnancy in conjunction with chronic glomerulonephritis (CGN) patients are helpful to understand the influence of kidney diseases on pregnancy and the effects of pregnancy on kidney diseases. The aim of this study was to determine the predictors of adverse maternal and fetal outcomes in CGN patients. MATERIAL AND METHODS Maternal and fetal outcomes in 64 pregnancies of CGN patients were retrospectively analyzed. We randomly selected 100 low-risk-pregnancy women without chronic kidney disease (CKD) at the same time as the control group. Clinical manifestations, laboratory data, medication, and outcomes during pregnancies of these patients were analyzed by univariate and logistic regression. RESULTS CGN patients were associated with higher adverse pregnancy outcomes versus general pregnancies. The gestational ages are shorter, and the incidence of preeclampsia, gestational hypertension, and abortion were increased. The rates of premature delivery, low birth weights, and intrauterine growth restriction were higher in the CGN group. Prenatal proteinuria and blood pressure were significantly increased compared with pre-pregnancy stage. Proteinuria (0.9±0.6 g/d vs. 0.5±0.3 g/d, P=0.032) and hypertension (6.9% vs. 3.4%, P=0.021) at 6 months after delivery were aggravated. Prenatal proteinuria ≥3.5 g/d (OR 12.22, 95%CI 3.16~47.32, P=0.001) was the maternal risk predictor in pregnancy. Prenatal blood pressure ≥160/110 mmHg (OR 8.97, 95%CI 1.69~47.53, P=0.010) and uric acid ≥363 μmol/L (OR 7.35, 95%CI 1.88~28.76, P=0.004) were the fetal risk predictors in pregnancy in conjunction with CGN patients. CONCLUSIONS Maternal-fetal risks are increased in pregnancies in conjunction with CGN patients. Prenatal proteinuria ≥3.5 g/d, BP ≥160/110 mmHg, and uric acid ≥363 μmol/L were the maternal and fetal risk predictors in pregnancy.

Antiproteinuric effect of pirfenidone in a rat model of anti-glomerular basement membrane glomerulonephritis.

PubMed

Takakura, Koji; Mizukami, Kazuhiko; Mitori, Hikaru; Noto, Takahisa; Tomura, Yuichi

2014-08-15

While pirfenidone has been established as an effective anti-fibrosis remedy, whether or not its antifibrotic effect contributes to a reduction of proteinuria remains unclear. We investigated the renoprotective properties of pirfenidone in an anti-glomerular basement membrane (GBM) glomerulonephritis model both prophylactically and therapeutically to determine its profile against proteinuria. In the prophylactic regimen, pirfenidone was treated immediately after anti-serum injection. We observed a significant reduction in the progression of proteinuria (P<0.05) and decline in renal function (P<0.01) and also noted histological improvement in renal injury. These effects appeared to be due to the maintained expression of nephrin and podocin on podocytes as well as the reduced expression of profibrotic factors like transforming growth factor-β (TGF-β). The expression of nephrin mRNA was strongly negatively correlated with the amount of urinary protein excretion (R=-0.84, P<0.001), implicating podocyte damage in the outcome of proteinuria (R(2)=0.70). These results suggest that preservation of podocytes with the pirfenidone treatment may have resulted in the decrease of proteinuria. In contrast, when the therapeutic regimen was initiated 2 weeks after nephritis induction, pirfenidone had little effect on the progression of proteinuria, although the decline of renal function and fibrosis were suppressed. Taken together, present findings suggested that pirfenidone prevented the progression of proteinuria only when administered prophylactically but was still able to ameliorate the decline of renal function independent of proteinuria. In conclusion, pirfenidone as a prophylactic regimen reduces proteinuria in anti-GBM nephritis via preservation of podocytes with markedly reduced efficacy when administered as a therapeutic regimen. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis

PubMed Central

Kanaguchi, Yasuhiko; Suzuki, Yusuke; Osaki, Ken; Sugaya, Takeshi; Horikoshi, Satoshi

2011-01-01

Background. In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice. Methods. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB). Results. The urinary protein level in Tg mice decreased significantly during the acute phase (∼Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with

In vivo preventive effects of insect tea on buccal mucosa cancer in ICR mice.

PubMed

Zhao, Xin; Wang, Rui; Qian, Yu; Li, Guijie; Zhou, Yalin; Sun, Peng

2014-01-01

Insect tea is a particular drink or health product in China and it is also used as Chinese medicine now. Its functional effects need to be proved. The ICR mice buccal mucosa cancer model was established by injecting the mice with U14 cells and mice was treated with insect tea. Tumor volumes and lymph node metastasis rates were determined. And the buccal mucosa tissues and cancer cervical lymph node were also checked by histology test, real-time polymerase chain reaction, and western blot assays. The tumor volumes for the group treated with insect tea mice was smaller than those from the control mice. The sections of buccal mucosa cancer tissue showed that the canceration of insect tea mice was weaker than control mice. Insect tea significantly induced apoptosis in buccal mucosa tissues by upregulating Bax, caspases, and downregulating Bcl-2. Nuclear factor-κB, inducible nitric oxide synthase, and COX-2 gene, was significantly downregulated by insect tea, demonstrating its anti-inflammatory properties. Insect tea also exerted a great anti-metastasis effect on tissues as demonstrated by decreased expression of Matrix metalloproteinases genes and increased expression of tissue inhibitors of matrix metalloproteinases. The highest concentration of 1600 mg/kg oral gavage and 400 mg/mL smear insect tea showed the best anticancer effects. Based on the results, insect tea showed the strong in vivo buccal mucosa cancer preventive effects.

Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life.

PubMed

Hoy, Wendy E; White, Andrew V; Dowling, Alison; Sharma, Suresh K; Bloomfield, Hilary; Tipiloura, Bernard T; Swanson, Cheryl E; Mathews, John D; McCredie, David A

2012-05-01

Although unusual in western countries and in Australia in general, post-streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood. High levels of albuminuria (albumin/creatinine ratio) with increasing age were confirmed. All PSGN episodes were associated with group A streptococcal skin infections, often related to scabies. In both genders, aged 10-39 years at screening, about one in five had such a history. Among them, PSGN (5 years or more earlier) was significantly associated with higher levels of albuminuria than those without. In women, aged 30-39 years, a history of PSGN was associated with a significantly higher frequency of estimated glomerular filtration rates <60 ml/min. The adjusted odds ratios for an albumin/creatinine ratio over 34 g/mol (overt albuminuria) in males and females with a history of PSGN were 4.6 and 3.1, respectively, compared with those without a history. Thus, PSGN contributes to the very serious burden of chronic kidney disease in this community. Rigorous strategies to prevent scabies and Group A streptococcal infections will reduce this burden.

Black soybean seed coat polyphenols prevent B(a)P-induced DNA damage through modulating drug-metabolizing enzymes in HepG2 cells and ICR mice.

PubMed

Zhang, Tianshun; Jiang, Songyan; He, Chao; Kimura, Yuki; Yamashita, Yoko; Ashida, Hitoshi

2013-04-15

Black soybean seed coat is a rich source of polyphenols that have been reported to have various physiological functions. The present study investigated the potential protective effects of polyphenolic extracts from black soybean seed coat on DNA damage in human hepatoma HepG2 cells and ICR mice. The results from micronucleus (MN) assay revealed that black soybean seed coat extract (BE) at concentrations up to 25μg/mL was non-genotoxic. It is noteworthy that BE (at 4.85μg/mL) and its main components, procyanidins (PCs) and cyanidin 3-glucoside (C3G), at 10μM significantly reduced the genotoxic effect induced by benzo[a]pyrene [B(a)P]. To obtain insights into the underlying mechanism, we investigated BE and its main components on drug-metabolizing enzyme expression. The results of this study demonstrate that BE and its main components, PCs and C3G, down-regulated B(a)P-induced cytochrome P4501A1 (CYP1A1) expression by inhibiting the transformation of aryl hydrocarbon receptor. Moreover, they increased expression of detoxifying defense enzymes, glutathione S-transferases (GSTs) via increasing the binding of nuclear factor-erythroid-2-related factor 2 to antioxidant response elements. Collectively, we found that PCs and C3G, which are the main active compounds of BE, down-regulated CYP1A1 and up-regulated GST expression to protect B(a)P-induced DNA damage in HepG2 cells and ICR mice effectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Utilizing a Robotic Sprayer for High Lateral and Mass Resolution MALDI FT-ICR MSI of Microbial Cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderton, Christopher R.; Chu, Rosalie K.; Tolic, Nikola

The ability to visualize biochemical interactions between microbial communities using MALDI MSI has provided tremendous insights into a variety of biological fields. Matrix application using a sieve proved to be incredibly useful, but it had many limitations that include uneven matrix coverage and limitation in the types of matrices one could employ in their studies. Recently, there has been a concerted effort to improve matrix application for studying agar plated microbial cultures, many of which utilized automated matrix sprayers. Here, we describe the usefulness of using a robotic sprayer for matrix application. The robotic sprayer has two-dimensional control over wheremore » matrix is applied and a heated capillary that allows for rapid drying of the applied matrix. This method provided a significant increase in MALDI sensitivity over the sieve method, as demonstrated by FT-ICR MS analysis, facilitating the ability to gain higher lateral resolution MS images of Bacillus Subtilis than previously reported. This method also allowed for the use of different matrices to be applied to the culture surfaces.« less

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice.

PubMed

Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

2015-03-01

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-α, IL-1β, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage.

Migratory response of Echinostoma caproni (Digenea: Echinostomatidae) to feeding by ICR mice.

PubMed

Platt, Thomas R; Quintana, Guadalupe; Rodriguez, Arianne E; Zelmer, Derek A

2013-04-01

The migratory response of Echinostoma caproni to host feeding was examined in female ICR mice. Thirty-six mice were each infected with 20 metacercariae of E. caproni . Twenty-eight days post-infection, food, but not water, was withheld for 24 hr. Mice were haphazardly divided into 4 groups of 9, and each group received one of the following treatments: (1) 0.25 g glucose, (2) access to standard lab chow, (3) 0.5 ml saline, and (4) continued fasting. Three mice from each treatment group were killed 1, 2, and 4 hr post-treatment. The intestine of each mouse was removed, flash-frozen, and stored in a conventional freezer for later examination. Intestines were partially thawed, measured, and opened longitudinally, and the position of each worm, or worm cluster was measured. The intestine was divided into equal 5% segments based on the initial measurement and locations of worms, and worm clusters were recorded from the appropriate section of the intestine for analysis. There was no significant effect of treatment in the position of worms at 1 hr. There was a posterior shift in worm position in all treatment groups at 2 hr, except in the saline-treated mice; however, only worms in the glucose-fed mice were significantly posterior to the unfed controls. From 2 to 4 hr, there was a significant anterior movement of worms in both the glucose and chow-fed mice. The data strongly suggest that E. caproni responds to the initiation of gastric activity of the host by migrating anteriorly in the ileum. The specific stimulus for this migration is unknown.

Membranoproliferative glomerulonephritis and acute renal failure in a patient with chronic lymphocytic leukemia: Response to obinutuzumab.

PubMed

Jain, Punit; Kanagal-Shamanna, Rashmi; Wierda, William; Ferrajoli, Alessandra; Keating, Michael; Jain, Nitin

2017-09-01

Membranoproliferative glomerulonephritis (MPGN) is a common extramedullary renal presentation in chronic lymphocytic leukemia (CLL) and can present with either a frank renal failure or proteinuria. One of its etiologies has been attributed to a paraneoplastic, immune complex phenomenon occurring in CLL. Although there is no standard of care in such patients, use of anti-CD20 monoclonal antibodies like rituximab have been used before in such patients with variable responses. Obinutuzumab is a novel, type II, immunoglobulin-G1 monoclonal antibody with a higher efficacy than rituximab and has an established safely profile in patients with comorbidities and poor renal functions. There are no such reported cases of MPGN in CLL being treated with obinutuzumab. We used the standard doses of obinutuzumab in our elderly patient (78-year-old woman) with high-risk CLL due to an underlying TP53 mutation, along with a MPGN-related acute renal failure. The patient achieved complete remission after six cycles of obinutuzumab; however, she remained positive for minimal residual disease on flow cytometry. Her renal function improved completely, suggesting a complete response of her underlying MPGN. Obinutuzumab has an established safety profile in patients with CLL, but our case is the first reported case of a paraneoplastic, immune complex-mediated MPGN in CLL being treated with obinutuzumab. Obinutuzumab should be explored as a potential option in patients with CLL and MPGN. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

The BC Glomerulonephritis Network: Improving Access and Reducing the Cost of Immunosuppressive Treatments for Glomerular Diseases

PubMed Central

Barbour, Sean; Lo, Clifford; Espino-Hernandez, Gabriela; Gill, Jagbir; Levin, Adeera

2018-01-01

Glomerulonephritis (GN) is a common cause of end-stage renal disease in Canada and worldwide, and results in significant health care resource utilization and patient morbidity. However, GN has not been a traditional priority of provincial renal health care organizations, despite the known benefits to health services delivery and patient outcomes from integrated provincial care in other types of chronic kidney disease. To address this deficiency, the British Columbia (BC) Provincial Renal Agency created the BC GN Network in 2013 to coordinate provincial GN health services delivery informed by robust population-level data capture on all GN patients in the province via the BC GN Registry. This report describes the use of the BC GN Network infrastructure to systematically develop and evaluate a provincial GN drug formulary to improve patient and physician access to evidence-based immunosuppressive treatments for GN in a cost-efficient manner that successfully halted historical trends of increasing medication costs. An example is provided of using the provincial infrastructure to implement and subsequently evaluate an evidence-informed health policy of converting brand to generic tacrolimus for the treatment of GN. The BC GN Network, including the provincial drug formulary and data infrastructure, is an example of the benefits of expanding the mandate of provincial renal health administrative organizations to include the care of patients with GN, and constitutes a viable health delivery model that can be implemented in other Canadian provinces to achieve similar goals. PMID:29581884

Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.

PubMed

Maruyama, Takashi; Fukuda, Noboru; Matsumoto, Taro; Kano, Koichiro; Endo, Morito; Kazama, Minako; Kazama, Tomohiko; Ikeda, Jin; Matsuda, Hiroyuki; Ueno, Takahiro; Abe, Masanori; Okada, Kazuyoshi; Soma, Masayoshi; Matsumoto, Koichi; Kawachi, Hiroshi

2015-04-16

Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs. We examined the effects of 10(6) of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 10(6) of DFAT cells transfected with TSG-6 siRNA through tail vein. Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats. Systematic implantation of DFAT cells effectively ameliorated mAb 1

Mucosal tolerance induced by an immunodominant peptide from rat alpha3(IV)NC1 in established experimental autoimmune glomerulonephritis.

PubMed

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

2009-06-01

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the alpha 3 chain of type IV collagen, alpha3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat alpha3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 microg had no effect, a dose of 1000 microg resulted in a moderate reduction in EAG severity, and a dose of 3000 microg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of alpha3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture's disease and other autoimmune disorders.

Behavioral effects of plant-derived essential oils in the geller type conflict test in mice.

PubMed

Umezu, T

2000-06-01

The present study was conducted to further explore plant-derived essential oils that possess an anticonflict effect using the Geller type conflict test in ICR mice. The benzodiazepine anxiolytic diazepam increased the response (lever pressing) rate during the alarm period (i.e., an anticonflict effect), but the 5-HT1A partial agonist buspirone did not. Oils of juniper, cypress, geranium and jasmine did not produce any effect in this test. Frankincense oil decreased the response rate during the safe period at 1600 mg/kg, but did not exhibit any effect on the response rate during the alarm period. In contrast, lavender oil increased the response rate during the alarm period in a dose-dependent manner in the same manner as diazepam. These results indicate that not only rose oil but also lavender oil possess an anticonflict effect in mice.

Analysis of Monoclonal Antibodies in Human Serum as a Model for Clinical Monoclonal Gammopathy by Use of 21 Tesla FT-ICR Top-Down and Middle-Down MS/MS

NASA Astrophysics Data System (ADS)

He, Lidong; Anderson, Lissa C.; Barnidge, David R.; Murray, David L.; Hendrickson, Christopher L.; Marshall, Alan G.

2017-05-01

With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2-0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error 4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background.

Epidemiology of Histologically Proven Glomerulonephritis in Africa: A Systematic Review and Meta-Analysis.

PubMed

Okpechi, Ikechi G; Ameh, Oluwatoyin I; Bello, Aminu K; Ronco, Pierre; Swanepoel, Charles R; Kengne, Andre P

2016-01-01

Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50-4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2-22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3-21.1), mesangiocapillary GN (MCGN); 11.8% (9.2-14.6), crescentic GN; 2.0% (0.9-3.5) and IgA nephropathy 2.8% (1.3-4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0-18.4) and 7.7% (4.5-11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases; this could have a positive impact on chronic kidney disease evaluation and

Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

PubMed

Zhang, Qian; Luan, Hong; Wang, Le; He, Fan; Zhou, Huan; Xu, Xiaoli; Li, Xingai; Xu, Qing; Niki, Toshiro; Hirashima, Mitsuomi; Xu, Gang; Lv, Yongman; Yuan, Jin

2014-04-15

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice

PubMed Central

Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

2015-01-01

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-α, IL-1β, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage. PMID:25866750

Increased extrusion and ICRS grades at 2-year follow-up following transtibial medial meniscal root repair evaluated by MRI.

PubMed

Kaplan, Daniel J; Alaia, Erin F; Dold, Andrew P; Meislin, Robert J; Strauss, Eric J; Jazrawi, Laith M; Alaia, Michael J

2017-11-02

The purpose of the current study was to evaluate the short-term results of meniscal root repair surgery, assessing clinical and radiographic outcomes, utilizing MRI to assess root healing and extent of post-operative extrusion. This was a single-center, retrospective study evaluating patients who had undergone a medial meniscus posterior root repair using a transtibial pullout technique with two locking cinch sutures. Demographic data were collected from patient charts. Clinical outcomes were assessed with pre- and post-operative IKDC and Lysholm scores. Pre-op scores were taken at the patients' initial clinical visit, mean 1.55 months prior to surgery (± 1.8 months, min 0.3, max 7.3). Radiographic outcomes were assessed with MRI evaluation of root healing, meniscal extrusion, and cartilage degeneration using ICRS criteria. Tunnel placement was evaluated and compared to the anatomic footprint. Eighteen patients (47.2 years ± 11.9) were evaluated at mean follow-up of 24.9 months (± 7.2, min 18.4, max 35.6). The IKDC score significantly increased from 45.9 (± 12.6) pre-operatively to 76.8 (± 14.7) post-operatively (p < 0.001). Lysholm scores also increased from 50.9 (± 7.11) to 87.1 (± 9.8) (p < 0.001). Mean tunnel placement was 5.3 mm (± 3.5, range 0-11.8) away from the anatomic footprint. Mean extrusion increased from 4.74 mm (± 1.7) pre-operatively to 5.98 (± 2.8) post-operatively (p < 0.02). No patients with > 3 mm of extrusion on pre-operative MRI had < 3 mm of extrusion on post-operative MRI. Both medial femoral condyle and medial tibial plateau ICRS grades worsened significantly (p < 0.02 and p < 0.01, respectively). On MRI, one root appeared completely healed, 16 partially healed, and one not healed. Patients treated with the transtibial suture pull-out technique with two locking cinch sutures had improved clinical outcomes, but only partial healing in the majority of cases, increased extrusion

Selective pharmacological inhibition of DDR1 prevents experimentally-induced glomerulonephritis in prevention and therapeutic regime.

PubMed

Moll, Solange; Yasui, Yukari; Abed, Ahmed; Murata, Takeshi; Shimada, Hideaki; Maeda, Akira; Fukushima, Naoshi; Kanamori, Masakazu; Uhles, Sabine; Badi, Laura; Cagarelli, Thomas; Formentini, Ivan; Drawnel, Faye; Georges, Guy; Bergauer, Tobias; Gasser, Rodolfo; Bonfil, R Daniel; Fridman, Rafael; Richter, Hans; Funk, Juergen; Moeller, Marcus J; Chatziantoniou, Christos; Prunotto, Marco

2018-06-01

Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase extensively implicated in diseases such as cancer, atherosclerosis and fibrosis. Multiple preclinical studies, performed using either a gene deletion or a gene silencing approaches, have shown this receptor being a major driver target of fibrosis and glomerulosclerosis. The present study investigated the role and relevance of DDR1 in human crescentic glomerulonephritis (GN). Detailed DDR1 expression was first characterized in detail in human GN biopsies using a novel selective anti-DDR1 antibody using immunohistochemistry. Subsequently the protective role of DDR1 was investigated using a highly selective, novel, small molecule inhibitor in a nephrotoxic serum (NTS) GN model in a prophylactic regime and in the NEP25 GN mouse model using a therapeutic intervention regime. DDR1 expression was shown to be mainly limited to renal epithelium. In humans, DDR1 is highly induced in injured podocytes, in bridging cells expressing both parietal epithelial cell (PEC) and podocyte markers and in a subset of PECs forming the cellular crescents in human GN. Pharmacological inhibition of DDR1 in NTS improved both renal function and histological parameters. These results, obtained using a prophylactic regime, were confirmed in the NEP25 GN mouse model using a therapeutic intervention regime. Gene expression analysis of NTS showed that pharmacological blockade of DDR1 specifically reverted fibrotic and inflammatory gene networks and modulated expression of the glomerular cell gene signature, further validating DDR1 as a major mediator of cell fate in podocytes and PECs. Together, these results suggest that DDR1 inhibition might be an attractive and promising pharmacological intervention for the treatment of GN, predominantly by targeting the renal epithelium.

Membranous nephropathy

MedlinePlus

... glomerulonephritis; Membranous GN; Extramembranous glomerulonephritis; Glomerulonephritis - membranous; MGN Images Kidney anatomy References Appel GB, Radhakrishnan J. Glomerular disorders and nephrotic syndromes. In: Goldman L, ...

Fractionation and characterization of dissolved organic matter (DOM) in refinery wastewater by revised phase retention and ion-exchange adsorption solid phase extraction followed by ESI FT-ICR MS.

PubMed

Fang, Zhi; He, Chen; Li, Yongyong; Chung, Keng H; Xu, Chunming; Shi, Quan

2017-01-01

Although the progress of high resolution mass spectrometry in the past decade has enabled the molecular characterization of dissolved organic matter (DOM) in water as a whole, fractionation of DOM is necessary for a comprehensive characterization due to its super-complex nature. Here we proposed a method for the fractionation of DOM in a wastewater based on solubility and acidic-basic properties. Solid phase extraction (SPE) cartridges with reversed phase retention and ion-exchange adsorption capacities, namely MAX and MCX, were used in succession to fractionate a petroleum refinery wastewater into four fractions: hydrophobic acid (HOA), hydrophobic neutral (HON), hydrophobic base (HOB), and hydrophilic substance (HIS) fractions. According to the total organic carbon (TOC) analysis, 72.6% (in term of TOC) of DOM was extracted in hydrophobic fractions, in which HON was the most abundant. Hydrophobic extracts were characterized by negative and positive ion electrospray (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), respectively. Compounds with multiple oxygen atoms were predominant in the HOA, which were responded strongly in the negative ESI MS. Nitrogen containing compounds were the major detected species by positive ion ESI in all hydrophobic fractions. The molecular composition of the DOM were discussed based on the FT-ICR MS results. The fractionation provided salt free samples which enables the direct analysis of the fractions by ESI and a deep insight into the molecular composition of DOM in the wastewater. The method is potential for routine evaluation of DOM in industry wastewaters, as well as environmental water samples. Copyright © 2016. Published by Elsevier B.V.

Oral management of children with Henoch-Schönlein Purpura and associated Glomerulonephritis: a scoping review.

PubMed

Echavarría-García, A C; Pozos-Guillén, A; Tejeda-Nava, F; Flores Arriaga, J C; Garrocho-Rangel, A

2018-06-01

To perform a scoping review of the existing literature in order to gather the most relevant information in the paediatric dentistry field related to the oral management of children affected by Henoch-Schönlein Purpura and associated Glomerulonephritis (HSPG). Using scoping review methodology for the screening and selection of valid articles, the steps of this review were the following: first, to pose a research question; second, to identify relevant studies; third, to select and retrieve the studies; fourth, to chart the critical data, and finally, to collate, summarise, and report the results from the included articles. Relevant articles published over a 25-year period, up to July 31, 2017, were identified and retrieved from four Internet databases: PubMed; EMBASE/Ovid; Ebsco/Dentistry & Oral Science Source, and the Cochrane Collaboration Library. By title and abstract screening and after removing duplicates, four articles were finally included in the scoping review. According to the extracted data, the following are the most important clinical issues to be considered: (1) the disease can appear as a consequence of a dental treatment, such as those indicated for oral infectious processes; (2) children with HSPG are highly susceptible to dental caries and apical periodontitis, and (3) in affected children, oral infectious foci must be exhaustively eradicated in order to avoid the dissemination of the infection. Paediatric Dentists should be aware of HSPG, because the disease can be triggered or worsen subsequent to dental treatment. Adequate treatment of oral active infectious processes, together with an exhaustive oral preventive programme and long-term patient screening, are the best management approaches for children with HSPG.

Cage-induced stereotypies in female ICR CD-1 mice do not correlate with recurrent perseveration.

PubMed

Gross, Alexandra N; Engel, A Katarina J; Richter, S Helene; Garner, Joseph P; Würbel, Hanno

2011-01-20

Stereotypies are repetitive, unvarying, apparently purposeless behavioural patterns. They develop in animals kept in barren environments and are highly prevalent in laboratory mice (Mus musculus), yet their underlying mechanisms have remained elusive. In humans, stereotypies are associated with several psychiatric disorders and are thought to reflect dysfunction of inhibition of motor programs mediated by the corticostriatal circuitry, resulting in recurrent perseveration (=inappropriate repetition of behavioural responses). Several studies in captive animals of different species have reported a correlation between stereotypy performance and perseverative behaviour, indicating a similar dysfunction. To examine whether stereotypies in mice correlate with recurrent perseveration and whether they are causally related, we raised 40 female ICR CD-1 mice in either barren or enriched cages from three to either six or 16 weeks of age (2 × 2 factorial design) and assessed stereotypic behaviour in the home cage and recurrent perseveration on a two-choice guessing task. Enrichment significantly reduced stereotypic behaviour both at six and 16 weeks of age and recurrent perseveration increased with age. Although enriched housing reduced the number of repetitions in the guessing task significantly, there was no clear evidence for an effect on recurrent perseveration, and recurrent perseveration did not correlate positively with stereotypy level. These findings indicate either that this test did not measure recurrent perseveration or that cage stereotypies in these mice do not reflect behavioural disinhibition as measured by recurrent perseveration. Copyright © 2010 Elsevier B.V. All rights reserved.

[Acute inflammatory polyradiculoneuropathy and membranous glomerulonephritis following Epbstein-Barr virus primary infection in a 12-year-old girl].

PubMed

Meyer, P; Soëte, S; Raynaud, P; Henry, V; Morin, D; Rodière, M; Rivier, F; Roubertie, A

2010-11-01

Acute inflammatory polyradiculoneuropathy, or Guillain-Barré syndrome (GBS), is characterized by peripheral nerve demyelination, which leads to rapidly progressive weakness, loss of sensation, and loss of deep tendon reflexes. It is a prototype of postinfectious autoimmune disease, whose pathophysiology is well described in the forms provoked by certain bacteria (molecular mimicry with Campylobacter jejuni), but remains unclear for the forms related to other organisms (cytomegalovirus, Epstein-Barr virus and other herpes group viruses, Mycoplasma pneumoniae). Glomerular lesions can be associated with the neurological symptoms and have also been described after various infections, independently of any signs of polyradiculoneuropathy. We report the observation of a 12-year-old girl who presented with Guillain-Barré syndrome with facial diplegia, ataxia, and intracranial hypertension following Epstein-Barr virus (EBV) primary infection. During the course of the neurological disease, membranous glomerulonephritis (MGN) was diagnosed. The neurological impairment was regressive within 6 months after intravenous immunoglobulin treatment followed by intravenous then oral corticosteroid administration. Viremia remained high more than 6 months after the onset of symptoms. Glomerulopathy progressed independently and finally required immunosuppressant medication with cyclosporine. EBV might be the factor that triggered the autoimmune disorders, as previously reported for systemic lupus erythematosus and multiple sclerosis in children. To the best of our knowledge, this association of 3 conditions (GBS, MGN, and EBV primary infection) has never been reported in the literature. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Chronic toxicity of a mixture of chlorinated alkanes and alkenes in ICR mice.

PubMed

Wang, Fun-In; Kuo, Min-Liang; Shun, Chia-Tung; Ma, Yee-Chung; Wang, Jung-Der; Ueng, Tzuu-Huei

2002-02-01

The aim of this study was to determine the chronic toxicity of a mixture of chlorinated alkanes and alkenes (CA) consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene. These chlorinated organic solvents were present in the underground water near an electronic appliances manufactory in Taoyuan, Taiwan. Male and female weanling ICR mice were treated with low-, medium-, and high-dose CA mixtures in drinking water for 16 and 18 mo, respectively. A significant number of male mice treated with the high-dose CA mixture developed tail alopecia and deformation, which was not prominent in CA-treated female mice. Medium- and high-dose CA mixtures induced marginal increases of liver and lung weights, blood urea nitrogen, and serum creatinine levels in male mice. In female mice, the high-dose CA mixture increased liver, kidney, and uterus and ovary total weights, without affecting serum biochemistry parameters. CA mixtures had no effects on the total glutathione content or the level of glutathione S-transferase activity in the livers and kid- neys of male and female mice. Treatments with CA mixtures produced a trend of increasing frequency of hepatocelluar neoplasms in male mice, compared to male and female controls and CA-treated female mice. The high-dose CA mixture induced a significantly higher incidence of mammary adenocarcinoma in female mice. The calculated odds ratios of mammary adenocarcinoma in female mice induced by low-, medium-, and high-dose CA mixtures were 1.14, 1.37, and 3.53 times that of the controls, respectively. The low-dose CA mixture induced a higher incidence of cysts and inflammation in and around the ovaries. This study has demonstrated that the CA mixture is a potential carcinogen to male and female mice. These animal toxicology data may be important in assessing the health effects of individuals exposed to the CA mixture.

Characterization of organic matter in cloud waters sampled at the puy de Dôme mountain using FT-ICR-MS

NASA Astrophysics Data System (ADS)

Bianco, A.; Chaumerliac, N.; Vaitilingom, M.; Deguillaume, L.; Bridoux, M. C.

2017-12-01

The chemical composition of organic matter in cloud water is highly complex. The organic species result from their dissolution from the gas phase or from the soluble fraction of the particle phase. They are also produced by aqueous phase reactivity. Several low molecular weight organic species have been quantified such as aldehydes and carboxylic acids. Recently, amino acids were also detected in cloud water and their presence is related to the presence of microorganisms. Compounds presenting similarities with high molecular weight organic substances or HULIS found in aerosols were also observed in clouds. Overall, these studies mainly focused on individual compounds or functional groups rather than the complex mixture at the molecular level. This study presents a non-targeted approach to characterize the organic matter in clouds. Samples were collected at the puy de Dôme Mountain (France). Two cloud water samples (June & July 2016) were analyzed using high resolution mass spectrometry (ESI-FT-ICR-MS 9.4T). A reversed solid phase extraction (SPE) procedure was performed to concentrate dissolved organic matter components. Composer (v.1.5.3) software was used to filter the mass spectral data, recalibrate externally the dataset and calculate all possible formulas for detected anions. The first cloud sample (June) resulted from air mass coming from the North (North Sea) while the second one (July) resulted from air mass coming from the West (Atlantic Ocean). Thus, both cloud events derived from marine air masses but were characterized by different hydrogen peroxide concentration and dissolved organic carbon content and were sampled at different periods during the day. Elemental compositions of 6487 and 3284 unique molecular species were identified in each sample. Nitrogen-containing compounds (CHNO compounds), sulfur-containing compounds (CHOS & CHNOS compounds) and other oxygen-containing compounds (CHO compounds) with molecular weights up to 800 Da were detected

Epidemiology of Histologically Proven Glomerulonephritis in Africa: A Systematic Review and Meta-Analysis

PubMed Central

Okpechi, Ikechi G.; Ameh, Oluwatoyin I.; Bello, Aminu K.; Ronco, Pierre; Swanepoel, Charles R.; Kengne, Andre P.

2016-01-01

Background and aim Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. Materials and methods We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. Results Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50–4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2–22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3–21.1), mesangiocapillary GN (MCGN); 11.8% (9.2–14.6), crescentic GN; 2.0% (0.9–3.5) and IgA nephropathy 2.8% (1.3–4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0–18.4) and 7.7% (4.5–11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. Conclusions Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis.

PubMed

Vallota, E H; Forristal, J; Spitzer, R E; Davis, N C; West, C D

1971-03-01

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

Molecular-Scale Investigation with ESI-FT-ICR-MS on Fractionation of Dissolved Organic Matter Induced by Adsorption on Iron Oxyhydroxides.

PubMed

Lv, Jitao; Zhang, Shuzhen; Wang, Songshan; Luo, Lei; Cao, Dong; Christie, Peter

2016-03-01

Adsorption by minerals is a common geochemical process of dissolved organic matter (DOM) which may induce fractionation of DOM at the mineral-water interface. Here, we examine the molecular fractionation of DOM induced by adsorption onto three common iron oxyhydroxides using electrospray ionization coupled with Fourier-transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR-MS). Ferrihydrite exhibited higher affinity to DOM and induced more pronounced molecular fractionation of DOM than did goethite or lepidocrocite. High molecular weight (>500 Da) compounds and compounds high in unsaturation or rich in oxygen including polycyclic aromatics, polyphenols and carboxylic compounds had higher affinity to iron oxyhydroxides and especially to ferrihydrite. Low molecular weight compounds and compounds low in unsaturation or containing few oxygenated groups (mainly alcohols and ethers) were preferentially maintained in solution. This study confirms that the double bond equivalence and the number of oxygen atoms are valuable parameters indicating the selective fractionation of DOM at mineral and water interfaces. The results of this study provide important information for further understanding the behavior of DOM in the natural environment.

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

PubMed

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

2016-05-01

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

Oligomers, organosulfates, and nitroxy organosulfates in rainwater identified by ultra-high resolution electrospray ionization FT-ICR mass spectrometry

NASA Astrophysics Data System (ADS)

Altieri, K. E.; Turpin, B. J.; Seitzinger, S. P.

2008-09-01

Wet deposition is an important removal mechanism for atmospheric organic matter, and a potentially important input for receiving ecosystems, yet less than 50% of rainwater organic matter is considered chemically characterized. Precipitation samples collected in New Jersey, USA, were analyzed by negative ion ultra-high resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Elemental compositions of 552 unique molecular species were determined in the mass range 50 500 Da in the rainwater. Three main groups of organic compounds were identified: compounds containing carbon, hydrogen, and oxygen (CHO) only, sulfur (S) containing CHOS compounds, and S- and nitrogen containing CHONS compounds. Organic acids commonly identified in precipitation were detected, as well as linear alkylbenzene sulfonates, which are persistent pollutants commonly measured in river water, seawater, and sediments, but to our knowledge, not previously documented in atmospheric samples. Within the three main groups of compounds detected in the rainwater, oligomers, organosulfates, and nitroxy-organosulfates were identified. The majority of the compounds identified are products of atmospheric reactions and are known contributors to secondary organic aerosol (SOA) formed from gas phase, aerosol phase, and in-cloud reactions in the atmosphere. It is suggested that the large uncharacterized component of SOA is the main contributor to the large uncharacterized component of rainwater organic matter.

[Extramembranous glomerulonephritis of acquired syphilis in a patient recently infected by the hepatitis B virus. Demonstration of the treponemal antigen in the kidney by indirect immunofluorescence].

PubMed

Schillinger, F; Montagnac, R; Goclowski, C; Dine, G; Alessandri, E; Hopfner, C; Birembaut, P

1983-01-22

A 38 years old male homosexual with active secondary syphilis presented with pure nephrotic syndrome while HBs and HBe tests were positive without clinical hepatitis. He had circulating immune complexes, IgG--IgM cryoglobulinemia and high IgA, IgM and IgE levels; the C3 and C4 complement constituents were normal. Examination of renal biopsy sections under light, fluorescent and electronic microscopy showed stage I membranous glomerulonephritis the syphilitic origin of which was confirmed by indirect immunofluorescence and by rapid cure under penicillin treatment. This case calls for the following comments: (1) glomerular deposits are extramembranous rather than subendothelial in syphilitic nephrosis, a disease now classified among circulating immune complexes diseases; (2) in the kidney, the treponema antigen can be demonstrated by indirect immunofluorescence and the anti-treponema antibody, by elution; (3) the outcome of the nephrotic syndrome is always favourable, either spontaneously or after penicillin treatment; (4) syphilis and HBs antigens are frequently associated, particularly in homosexual patients; one should be looked for when the other is discovered.

Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring.

PubMed

Darebna, Petra; Novak, Petr; Kucera, Radek; Topolcan, Ondrej; Sanda, Miloslav; Goldman, Radoslav; Pompach, Petr

2017-02-05

Alternations in the glycosylation of proteins have been described in connection with several cancers, including hepatocellular carcinoma (HCC) and colorectal cancer. Analytical tools, which use combination of liquid chromatography and mass spectrometry, allow precise and sensitive description of these changes. In this study, we use MRM and FT-ICR operating in full-MS scan, to determine ratios of intensities of specific glycopeptides in HCC, colorectal cancer, and liver metastasis of colorectal cancer. Haptoglobin, hemopexin and complement factor H were detected after albumin depletion and the N-linked glycopeptides with fucosylated glycans were compared with their non-fucosylated forms. In addition, sialylated forms of an O-linked glycopeptide of hemopexin were quantified in the same samples. We observe significant increase in fucosylation of all three proteins and increase in bi-sialylated O-glycopeptide of hemopexin in HCC of hepatitis C viral (HCV) etiology by both LC-MS methods. The results of the MRM and full-MS scan FT-ICR analyses provide comparable quantitative readouts in spite of chromatographic, mass spectrometric and data analysis differences. Our results suggest that both workflows allow adequate relative quantification of glycopeptides and suggest that HCC of HCV etiology differs in glycosylation from colorectal cancer and liver metastasis of colorectal cancer. The article compares N- and O-glycosylation of several serum proteins in different diseases by a fast and easy sample preparation procedure in combination with high resolution Fourier transform ion cyclotron resonance mass spectrometry. The results show successful glycopeptides relative quantification in a complex peptide mixture by the high resolution instrument and the detection of glycan differences between the different types of cancer diseases. The presented method is comparable to conventional targeted MRM approach but allows additional curation of the data. Copyright © 2016 Elsevier B

Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring

PubMed Central

Darebna, Petra; Novak, Petr; Kucera, Radek; Topolcan, Ondrej; Sanda, Miloslav; Goldman, Radoslav; Pompach, Petr

2018-01-01

Alternations in the glycosylation of proteins have been described in connection with several cancers, including hepatocellular carcinoma (HCC) and colorectal cancer. Analytical tools, which use combination of liquid chromatography and mass spectrometry, allow precise and sensitive description of these changes. In this study, we use MRM and FT-ICR operating in full-MS scan, to determine ratios of intensities of specific glycopeptides in HCC, colorectal cancer, and liver metastasis of colorectal cancer. Haptoglobin, hemopexin and complement factor H were detected after albumin depletion and the N-linked glycopeptides with fucosylated glycans were compared with their non-fucosylated forms. In addition, sialylated forms of an O-linked glycopeptide of hemopexin were quantified in the same samples. We observe significant increase in fucosylation of all three proteins and increase in bisialylated O-glycopeptide of hemopexin in HCC of hepatitis C viral (HCV) etiology by both LC-MS methods. The results of the MRM and full-MS scan FT-ICR analyses provide comparable quantitative readouts in spite of chromatographic, mass spectrometric and data analysis differences. Our results suggest that both workflows allow adequate relative quantification of glycopeptides and suggest that HCC of HCV etiology differs in glycosylation from colorectal cancer and liver metastasis of colorectal cancer. Significance The article compares N- and O-glycosylation of several serum proteins in different diseases by a fast and easy sample preparation procedure in combination with high resolution Fourier transform ion cyclotron resonance mass spectrometry. The results show successful glycopeptides relative quantification in a complex peptide mixture by the high resolution instrument and the detection of glycan differences between the different types of cancer diseases. The presented method is comparable to conventional targeted MRM approach but allows additional curation of the data. PMID:27646713

High-field FT-ICR-MS and aromaticity equivalent approach for structural identification of water soluble organic compounds (WSOC)

NASA Astrophysics Data System (ADS)

Harir, Mourad; Yassine, Mahmoud M.; Dabek-Zlotorzynska, Ewa; Hertkorn, Norbert; Schmitt-Kopplin, Philippe

2015-04-01

Organic aerosol (OA) makes up a large and often dominant fraction, (20 to 90%) of the submicron atmospheric particulate mass, and its effects are becoming increasingly important in determining climatic and health effects of atmospheric aerosols. Despite the abundance of OA, our understanding of the sources, formation processes and atmospheric properties of OA is limited. Atmospheric OA has both primary (directly emitted) and secondary (formed in the atmosphere from precursor gases) sources, which can be natural (e.g. vegetation) and/or anthropogenic (e.g. fossil-based vehicle exhaust or biomass burning). A significant fraction of OA contains as much as 20-70% of water soluble organic compounds (WSOC). The WSOC fraction is a very complex mixture of low volatility, polyfunctional aliphatic and aromatic compounds containing carboxyl, alcohol, carbonyl, sulfo, nitro, and other functionalities. This high degree of chemical complexity of atmospheric organics has inspired a number of sophisticated approaches that are capable of identifying and detecting a variety of different analytes in OA. Accordingly, one of the most challenging areas of atmospheric particulate matter (PM) analysis is to comprehend the molecular complexity of the OA, especially WSOC fraction, a significant component of atmospheric fine PM (PM2.5). The sources of WSOC are not well understood, especially the relative contributions of primary vs. secondary organic aerosol. Therefore, the molecular characterization of WSOC is important because it allows gaining insight into aerosol sources and underlying mechanisms of secondary organic aerosols (SOA) formation and transformation. In this abstract, molecular characterization of WSOC was achieved using high-field mass spectrometry FT-ICR-MS and aromaticity equivalent approach. Aromaticity equivalent (Xc), defined recently as a new parameter calculated from the assigned molecular formulas (complementary to the aromaticity index [1]), is introduced to improve

Fragmentation analysis of water-soluble atmospheric organic matter using ultrahigh-resolution FT-ICR mass spectrometry.

PubMed

Leclair, Jeffrey P; Collett, Jeffrey L; Mazzoleni, Lynn R

2012-04-17

Isolated water-soluble atmospheric organic matter (AOM) analytes extracted from radiation fogwater samples were analyzed using collision induced dissociation with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Tandem mass analysis was performed on several mass ranges between 100 and 400 Da to characterize the functional groups of AOM species. Compounds containing nitrogen and/or sulfur were targeted because of the high number of oxygen atoms contained in their molecular formulas. Due to the large number of isobaric ions in the precursor isolation ranges, large numbers of product ions resulted from collision induced dissociation. Common neutral losses were assigned by matching the molecular formulas of the expected product ions with the detected product ions within the appropriate mass spectra. Since polar functional groups are expected to affect the hygroscopic properties of aerosols, the losses of H(2)O, CO(2), CH(3)OH, HNO(3), CH(3)NO(3), SO(3), SO(4) and combinations of these were specifically targeted. Among the 421 compounds studied, the most frequently observed neutral losses were CO(2) (54%), H(2)O (43%) and CH(3)OH (40%). HNO(3) losses were observed for 63% of the studied nitrogen containing compounds and 33% of the studied compounds containing both nitrogen and sulfur. SO(3) losses were observed for 85% of the studied sulfur containing compounds and 42% of studied compounds containing both nitrogen and sulfur. A number of molecular formulas matching those of monoterpene ozonolysis SOA were observed; they include organonitrates, organosulfates, and nitroxy-organosulfates. Overall, the results of fragmentation analysis of 400+ individual molecular precursors elucidate the complexity and multifunctional nature of the isolated water-soluble AOM.

Sirt1 activation prevents anti-Thy 1.1 mesangial proliferative glomerulonephritis in the rat through the Nrf2/ARE pathway.

PubMed

Huang, Kaipeng; Li, Ruiming; Wei, Wentao

2018-08-05

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by glomerular mesangial cells proliferation and extracellular matrix deposition in mesangial area, which develop into glomerulosclerosis. Both silent information regulator 2-related protein 1 (Sirt1) and nuclear factor erythroid 2-related factor 2/anti-oxidant response element (Nrf2/ARE) pathway had remarkable renoprotective effects. However, whether Sirt1 and Nrf2/ARE pathway can regulate the pathological process of MsPGN remains unknown. Here, we found that Sirt1 activation by SRT1720 decreased mesangial hypercellularity and mesangial matrix areas, reduced renal Col4 and α-SMA expressions, lowered 24 h proteinuria, and eventually reduced FN and TGF-β1 expressions in rats received anti-Thy 1.1 IgG. Further study showed that SRT1720 markedly enhanced the activity of Nrf2/ARE pathway including promoting the nuclear content and ARE-binding ability of Nrf2, elevating the protein levels of HO-1 and SOD1, two target genes of Nrf2, which eventually increased total SOD activity and decreased malondialdehyde level in the kidney tissues of experimental anti-Thy 1.1 MsPGN rats. Taken together, Sirt1 prevented the pathological process of experimental anti-Thy 1.1 MsPGN through promoting the activation of Nrf2/ARE pathway, which warrants further elucidation. Sirt1 might be a potential therapeutic target for treating MsPGN. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2016-01-01

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

Development of immune-complex glomerulonephritis in athymic mice: T cells are not required for the genesis of glomerular injury.

PubMed

Bagheri, Nayer; Pepple, Douglas A; Hassan, Medhat O; Harding, Clifford V; Emancipator, Steven N

2005-03-01

Chronic injection of dextran into normal mice elicits a glomerulonephritis (GN) that models IgA nephropathy (IgAN) in humans. Since athymic mice lack T cells but nonetheless develop antibodies to polysaccharide antigens such as dextran (DEX), we used athymic mice to study the role of T lymphocytes in the induction of this form of GN, independent of the role of T cells in antibody synthesis. Both mice given injections of diethylaminoethyl (DEAE)-DEX and uninjected mice had circulating IgM and IgA anti-DEX antibodies, which apparently arise as 'natural antibodies', but immune complex GN was observed only in the injected mice. All of 15 injected mice exhibited capillary staining for IgA and IgM; none of 12 control mice contained such IgA deposits and only one had capillary staining for IgM (both P<0.001). In addition, IgG and C3 were detected in injected but not control animals. By light microscopy, injected mice exhibited marked expansion of mesangial matrix relative to controls. Electron microscopy showed no glomerular abnormalities in control mice, whereas injected mice showed large organized fibrillar deposits principally in the mesangium. Hematuria and proteinuria were present in all 15 injected mice, but only one of 11 control mice showed hematuria or proteinuria (both P<0.001). These results indicate that chronic injection of DEAE-DEX into athymic mice generates the same clinical and histologic features of GN as in euthymic mice, suggesting that T cells are not necessary to promote GN in this model.

Chemical Composition of Microbe-Derived Dissolved Organic Matter in Cryoconite in Tibetan Plateau Glaciers: Insights from Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Analysis.

PubMed

Feng, Lin; Xu, Jianzhong; Kang, Shichang; Li, Xiaofei; Li, Yang; Jiang, Bin; Shi, Quan

2016-12-20

Cryoconite in mountain glaciers plays important roles in glacial ablation and biogeochemical cycles. In this study, the composition and sources of dissolved organic matter (DOM) in cryoconite from the ablation regions of two Tibetan Plateau glaciers were determined using electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and fluorescence spectrometry. A marked absorbance between 300 and 350 nm in the DOM absorption spectra was observed which was consistent with microbe-derived mycosporine-like amino acids. Fluorescence excitation-emission matrices showed that DOM had intense signals at protein-like substance peaks and weak signals at humic-like substance peaks. The high-resolution mass spectra of FT-ICR-MS showed cryoconite DOM from both glaciers contained diverse lignins, lipids, proteins, and unsaturated hydrocarbons. The lipids and proteins were consistent with material from microbial sources, and the lignins and unsaturated hydrocarbons were probably from vascular plant material supplied in atmospheric aerosols and debris from around the glaciers. Almost one-third of the identified DOM molecules had low C/N ratios (≤20), indicating their high bioavailability. Using a conservative cryoconite distribution on Chinese mountain glacier surfaces (6%) and an average debris mass per square meter of cryoconite (292 ± 196 g m -2 ), we found that the amount of DOC produced in cryoconite on Chinese glaciers as much as 0.23 ± 0.1 Gg per cryoconite formation process. This dissolved organic carbon may absorb solar radiation, accelerate glacial melting, and be an important source of bioavailable DOM to proglacial and downstream aquatic ecosystems.

Mapping the contact surfaces in the Lamin A:AIMP3 complex by hydrogen/deuterium exchange FT-ICR mass spectrometry.

PubMed

Tao, Yeqing; Fang, Pengfei; Kim, Sunghoon; Guo, Min; Young, Nicolas L; Marshall, Alan G

2017-01-01

Aminoacyl-tRNA synthetases-interacting multifunctional protein3 (AIMP3/p18) is involved in the macromolecular tRNA synthetase complex via its interaction with several aminoacyl-tRNA synthetases. Recent reports reveal a novel function of AIMP3 as a tumor suppressor by accelerating cellular senescence and causing defects in nuclear morphology. AIMP3 specifically mediates degradation of mature Lamin A (LmnA), a major component of the nuclear envelope matrix; however, the mechanism of how AIMP3 interacts with LmnA is unclear. Here we report solution-phase hydrogen/deuterium exchange (HDX) for AIMP3, LmnA, and AIMP3 in association with the LmnA C-terminus. Reversed-phase LC coupled with LTQ 14.5 T Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results in high mass accuracy and resolving power for comparing the D-uptake profiles for AIMP3, LmnA, and their complex. The results show that the AIMP3-LmnA interaction involves one of the two putative binding sites and an adjacent novel interface on AIMP3. LmnA binds AIMP3 via its extreme C-terminus. Together these findings provide a structural insight for understanding the interaction between AIMP3 and LmnA in AIMP3 degradation.

Chemical Composition and Potential Environmental Impacts of Water-Soluble Polar Crude Oil Components Inferred from ESI FT-ICR MS

PubMed Central

Liu, Yina; Kujawinski, Elizabeth B.

2015-01-01

Polar petroleum components enter marine environments through oil spills and natural seepages each year. Lately, they are receiving increased attention due to their potential toxicity to marine organisms and persistence in the environment. We conducted a laboratory experiment and employed state-of-the-art Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to characterize the polar petroleum components within two operationally-defined seawater fractions: the water-soluble fraction (WSF), which includes only water-soluble molecules, and the water-accommodated fraction (WAF), which includes WSF and microscopic oil droplets. Our results show that compounds with higher heteroatom (N, S, O) to carbon ratios (NSO:C) than the parent oil were selectively partitioned into seawater in both fractions, reflecting the influence of polarity on aqueous solubility. WAF and WSF were compositionally distinct, with unique distributions of compounds across a range of hydrophobicity. These compositional differences will likely result in disparate impacts on environmental health and organismal toxicity, and thus highlight the need to distinguish between these often-interchangeable terminologies in toxicology studies. We use an empirical model to estimate hydrophobicity character for individual molecules within these complex mixtures and provide an estimate of the potential environmental impacts of different crude oil components. PMID:26327219

Organic acid component from Taraxacum mongolicum Hand.-Mazz alleviates inflammatory injury in lipopolysaccharide-induced acute tracheobronchitis of ICR mice through TLR4/NF-κB signaling pathway.

PubMed

Yang, Nan; Li, Chao; Tian, Gang; Zhu, Maomao; Bu, Weiquan; Chen, Juan; Hou, Xuefeng; Di, Liuqing; Jia, Xiaobin; Dong, Zibo; Feng, Liang

2016-05-01

Inflammation plays an important role in the pathogenesis of acute tracheobronchitis. Taraxacum mongolicum Hand.-Mazz (TMHM) is a dietic herb for heat-clearing and detoxifying functions as well as swell-reducing and mass-resolving effect in Traditional Chinese Medicine. Studies have shown that its major ingredient organic acid component (OAC) possesses favorable anti-inflammatory activity. However, the protective effect of OAC from TMHM (TMHM-OAC) on inflammatory injury of acute tracheobronchitis and its possible mechanism remains poorly understood. In this study, HPLC-DAD was used to analyze the components of TMHM-OAC. Lipopolysaccharide of 1mg/ml was used to induce respiratory inflammation in ICR mice at the dose of 5mg/kg by intratracheally aerosol administration. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of inflammation factors such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide in serum and supernatant of trachea tissue. Western blotting (WB) and Immunohistochemistry analysis (IHC) were conducted in parallel to determine TNF-α, IL-6, inducible nitric oxide synthase (iNOS), Toll-like receptors 4(TLR4) protein expressions and nuclear factor-kappa B p65 (NF-κB p65) phosphorylation. Hematoxylin-Eosin staining (HE) was applied to evaluate pathological lesions of trachea tissue. Experimental results showed that TMHM-OAC significantly reduced the levels of the TNF-α, IL-6 and NO in serum and supernatant of tracheal of LPS-induced ICR mice. The protein expression levels of TNF-α, IL-6 and iNOS in tracheal tissue were also down-regulated significantly by the treatment of TMHM-OAC. Moreover, TMHM-OAC downregulated phosphorylation of NF-κB p65 and protein expression of TLR4. Our results indicated that TMHM-OAC could improve LPS-induced histopathological damage of tracheal tissues through the regulation of TLR4/NF-κB signaling pathway and could be beneficial for the treatment of acute tracheobronchitis

An efficient and accurate 3D displacements tracking strategy for digital volume correlation

NASA Astrophysics Data System (ADS)

Pan, Bing; Wang, Bo; Wu, Dafang; Lubineau, Gilles

2014-07-01

Owing to its inherent computational complexity, practical implementation of digital volume correlation (DVC) for internal displacement and strain mapping faces important challenges in improving its computational efficiency. In this work, an efficient and accurate 3D displacement tracking strategy is proposed for fast DVC calculation. The efficiency advantage is achieved by using three improvements. First, to eliminate the need of updating Hessian matrix in each iteration, an efficient 3D inverse compositional Gauss-Newton (3D IC-GN) algorithm is introduced to replace existing forward additive algorithms for accurate sub-voxel displacement registration. Second, to ensure the 3D IC-GN algorithm that converges accurately and rapidly and avoid time-consuming integer-voxel displacement searching, a generalized reliability-guided displacement tracking strategy is designed to transfer accurate and complete initial guess of deformation for each calculation point from its computed neighbors. Third, to avoid the repeated computation of sub-voxel intensity interpolation coefficients, an interpolation coefficient lookup table is established for tricubic interpolation. The computational complexity of the proposed fast DVC and the existing typical DVC algorithms are first analyzed quantitatively according to necessary arithmetic operations. Then, numerical tests are performed to verify the performance of the fast DVC algorithm in terms of measurement accuracy and computational efficiency. The experimental results indicate that, compared with the existing DVC algorithm, the presented fast DVC algorithm produces similar precision and slightly higher accuracy at a substantially reduced computational cost.

Glomerulonephritis

MedlinePlus

... re also more likely to recover quickly. Bacterial endocarditis. Bacteria occasionally can spread through your bloodstream and ... as a damaged or artificial heart valve. Bacterial endocarditis is associated with glomerular disease, but the connection ...

In vivo inhibition of CC and CX3C chemokine-induced leukocyte infiltration and attenuation of glomerulonephritis in Wistar-Kyoto (WKY) rats by vMIP-II.

PubMed

Chen, S; Bacon, K B; Li, L; Garcia, G E; Xia, Y; Lo, D; Thompson, D A; Siani, M A; Yamamoto, T; Harrison, J K; Feng, L

1998-07-06

Chemokines play a central role in immune and inflammatory responses. It has been observed recently that certain viruses have evolved molecular piracy and mimicry mechanisms by encoding and synthesizing proteins that interfere with the normal host defense response. One such viral protein, vMIP-II, encoded by human herpesvirus 8, has been identified with in vitro antagonistic activities against CC and CXC chemokine receptors. We report here that vMIP-II has additional antagonistic activity against CX3CR1, the receptor for fractalkine. To investigate the potential therapeutic effect of this broad-spectrum chemokine antagonist, we studied the antiinflammatory activity of vMIP-II in a rat model of experimental glomerulonephritis induced by an antiglomerular basement membrane antibody. vMIP-II potently inhibited monocyte chemoattractant protein 1-, macrophage inflammatory protein 1beta-, RANTES (regulated on activation, normal T cell expressed and secreted)-, and fractalkine-induced chemotaxis of activated leukocytes isolated from nephritic glomeruli, significantly reduced leukocyte infiltration to the glomeruli, and markedly attenuated proteinuria. These results suggest that molecules encoded by some viruses may serve as useful templates for the development of antiinflammatory compounds.

Effects of hydrolyzed Chlorella vulgaris by malted barley on the immunomodulatory response in ICR mice and in Molt-4 cells.

PubMed

Kim, Na-Hyung; Kim, Kyu-Yeob; Jeong, Hyun-Ja; Kim, Hyung-Min; Hong, Seung-Heon; Um, Jae-Young

2010-07-01

Chlorella vulgaris is a unicellular and microscopic algae that is currently used in a variety of forms of tablets, capsules and liquid as a biological response modifier. The aim of this study was to investigate the effects of hydrolyzed Chlorella vulgaris by malted barley for its potential reduction of the immobility time in ICR mice and on the cytokine regulation in human T cell line, Molt-4. After a forced swimming test, the changes in aspects of blood biochemical parameters due to the administration of hydrolyzed Chlorella vulgaris by malted barley were examined. The effect of hydrolyzed Chlorella vulgaris by the malted barley-treated group for 14 days on the immobility time was significantly reduced in comparison with that of the control group (P < 0.01). The plasma level of blood urea nitrogen was significantly decreased in hydrolyzed Chlorella vulgaris by malted barley-treated group compared with the control group (P < 0.05). In addition, hydrolyzed Chlorella vulgaris by malted barley increased interferon-gamma and interlukin-2 levels in Molt-4 cells. These results indicate that hydrolyzed Chlorella vulgaris by malted barley is useful for immune function improvements, enhanced physical stamina, and as a candidate for an anti-fatigue or antidepressant agent.

Acute nephritic syndrome

MedlinePlus

... Names Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute Images Kidney anatomy References Appel GB, Radhakrishnan J. Glomerular disorders and nephrotic syndromes. In: Goldman L, ...

Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter Syndrome

PubMed Central

Wan, Emily S.; Qiu, Weiliang; Morrow, Jarrett; Beaty, Terri H.; Hetmanski, Jacqueline; Make, Barry J.; Lomas, David A.; Silverman, Edwin K.; DeMeo, Dawn L.

2015-01-01

Klinefelter syndrome (KS) (47 XXY) is a common sex-chromosome aneuploidy with an estimated prevalence of 1 in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome-wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY), 102 male (46 XY), and 113 female (46 XX) control subjects participating in the chronic obstructive pulmonary disease (COPD) Gene Study. Empirical Bayes-mediated models were used to test for differential methylation by KS status. CpG sites with a false-discovery rate <0.05 from the first-generation HumanMethylation27K platform were further examined in an independent replication cohort of 2 KS subjects, 590 male, and 495 female controls drawn from the International COPD Genetics Network (ICGN). Differential methylation at sites throughout the genome were identified, including 86 CpG sites that were differentially methylated in KS subjects relative to both male and female controls. CpG sites annotated to the HEN1 methyltransferase homolog 1 (HENMT1), calcyclin-binding protein (CACYBP), and GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) genes were among the “KS-specific” loci that were replicated in ICGN. We therefore conclude that site-specific differential methylation exists throughout the genome in KS. The functional impact and clinical relevance of these differentially methylated loci should be explored in future studies. PMID:25988574

Determination of the lunar orbital and rotational parameters and of the ecliptic reference system orientation from LLR measurements and IERS data

NASA Astrophysics Data System (ADS)

Chapront, J.; Chapront-Touzé, M.; Francou, G.

1999-03-01

An analysis of Lunar Laser Ranging (LLR) observations from January 1972 till March 1998 is performed using the lunar theory ELP 2000-96 and the completed Moons' theory of the lunar libration. The LLR station coordinates, polar motion and Universal Time are provided by the International Earth Rotation Service (IERS). In Solution 1 the precession-nutation transformation is given by recent analytical theories, while in Solution 2 it is derived from the IERS daily corrections. Orbital and free libration parameters of the Moon, and coordinates of the reflectors are obtained in both cases. The position of the inertial mean ecliptic of J2000.0 with respect to the equator of the mean Celestial Ephemeris Pole (CEP) of J2000.0 (in Solution 1) and to the International Celestial Reference System (ICRS), the IERS celestial reference system, (in Solution 2) are fit. The position of the mean CEP equator of J2000.0 and of several dynamical reference planes and origins, with respect to ICRS, are derived from these fits (Fig. 1). The leading results are the following: 0farcs057 60+/- 0farcs000 20 (in the equator) for the separation of the origin of right ascensions in ICRS from the ascending node of the inertial mean ecliptic of J2000.0 on the reference plane of ICRS, -0farcs0460 +/- 0farcs0008 (in the ecliptic) for the separation of the latter point from the inertial dynamical mean equinox of J2000.0, -0farcs015 19+/- 0farcs000 35 (in the equator) for the separation of the inertial dynamical mean equinox of J2000.0 from the J2000.0 right ascension origin derived from IERS polar motion and Universal Time and from precise theories of precession-nutation, and 23degr26 arcmin21 farcs405 22+/- 0farcs000 07 for the inertial obliquity of J2000.0. A correction of -0farcs3437 +/- 0farcs0040 /cy to the IAU 1976 value of the precession constant is also obtained (the errors quoted are formal errors).

Immunofluorescent localization of Staphylococcos aureus antigen in acute bacterial endocarditis nephritis.

PubMed

Yum, M; Wheat, L J; Maxwell, D; Edwards, J L

1978-11-01

A 75-year-old man with Staphylococcus aureus endocarditis in whom acute diffuse proliferative glomerulonephritis developed is described. The light- and electron-microscopic changes of the glomeruli in this case were identical to those of acute poststreptococcal glomerulonephritis. Immunofluorescence revealed deposition of immunoglobulins and complement in the glomeruli. In addition, bacterial antigenic material was demonstrated in the glomeruli by indirect immunofluorescence. These observations further support the hypothesis of an immune-complex pathogenesis in this form of glomerulonephritis.

Glutathione S-transferase Mu 2-transduced mesenchymal stem cells ameliorated anti-glomerular basement membrane antibody-induced glomerulonephritis by inhibiting oxidation and inflammation

PubMed Central

2014-01-01

Introduction Oxidative stress is implicated in tissue inflammation, and plays an important role in the pathogenesis of immune-mediated nephritis. Using the anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN) mouse model, we found that increased expression of glutathione S-transferase Mu 2 (GSTM2) was related to reduced renal damage caused by anti-GBM antibodies. Furthermore, mesenchymal stem cell (MSC)-based therapy has shed light on the treatment of immune-mediated kidney diseases. The aim of this study was to investigate if MSCs could be utilized as vehicles to deliver the GSTM2 gene product into the kidney and to evaluate its potential therapeutic effect on anti-GBM-GN. Methods The human GSTM2 gene (hGSTM2) was transduced into mouse bone marrow-derived MSCs via a lentivirus vector to create a stable cell line (hGSTM2-MSC). The cultured hGSTM2-MSCs were treated with 0.5mM H2O2, and apoptotic cells were measured by terminal dUTP nick-end labeling (TUNEL) assay. The 129/svj mice, which were challenged with anti-GBM antibodies, were injected with 106 hGSTM2-MSCs via the tail vein. Expression of hGSTM2 and inflammatory cytokines in the kidney was assayed by quantitative PCR and western blotting. Renal function of mice was evaluated by monitoring proteinuria and levels of blood urea nitrogen (BUN), and renal pathological changes were analyzed by histochemistry. Immunohistochemical analysis was performed to measure inflammatory cell infiltration and renal cell apoptosis. Results MSCs transduced with hGSTM2 exhibited similar growth and differentiation properties to MSCs. hGSTM2-MSCs persistently expressed hGSTM2 and resisted H2O2-induced apoptosis. Upon injection into 129/svj mice, hGSTM2-MSCs migrated to the kidney and expressed hGSTM2. The anti-GBM-GN mice treated with hGSTM2-MSCs exhibited reduced proteinuria and BUN (58% and 59% reduction, respectively) and ameliorated renal pathological damage, compared with control mice. Mice

Glutathione S-transferase Mu 2-transduced mesenchymal stem cells ameliorated anti-glomerular basement membrane antibody-induced glomerulonephritis by inhibiting oxidation and inflammation.

PubMed

Li, Yajuan; Yan, Mei; Yang, Jichen; Raman, Indu; Du, Yong; Min, Soyoun; Fang, Xiangdong; Mohan, Chandra; Li, Quan-Zhen

2014-01-30

Oxidative stress is implicated in tissue inflammation, and plays an important role in the pathogenesis of immune-mediated nephritis. Using the anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN) mouse model, we found that increased expression of glutathione S-transferase Mu 2 (GSTM2) was related to reduced renal damage caused by anti-GBM antibodies. Furthermore, mesenchymal stem cell (MSC)-based therapy has shed light on the treatment of immune-mediated kidney diseases. The aim of this study was to investigate if MSCs could be utilized as vehicles to deliver the GSTM2 gene product into the kidney and to evaluate its potential therapeutic effect on anti-GBM-GN. The human GSTM2 gene (hGSTM2) was transduced into mouse bone marrow-derived MSCs via a lentivirus vector to create a stable cell line (hGSTM2-MSC). The cultured hGSTM2-MSCs were treated with 0.5 mM H2O2, and apoptotic cells were measured by terminal dUTP nick-end labeling (TUNEL) assay. The 129/svj mice, which were challenged with anti-GBM antibodies, were injected with 10⁶ hGSTM2-MSCs via the tail vein. Expression of hGSTM2 and inflammatory cytokines in the kidney was assayed by quantitative PCR and western blotting. Renal function of mice was evaluated by monitoring proteinuria and levels of blood urea nitrogen (BUN), and renal pathological changes were analyzed by histochemistry. Immunohistochemical analysis was performed to measure inflammatory cell infiltration and renal cell apoptosis. MSCs transduced with hGSTM2 exhibited similar growth and differentiation properties to MSCs. hGSTM2-MSCs persistently expressed hGSTM2 and resisted H2O2-induced apoptosis. Upon injection into 129/svj mice, hGSTM2-MSCs migrated to the kidney and expressed hGSTM2. The anti-GBM-GN mice treated with hGSTM2-MSCs exhibited reduced proteinuria and BUN (58% and 59% reduction, respectively) and ameliorated renal pathological damage, compared with control mice. Mice injected with hGSTM2-MSCs showed

Antitumor and antiangiogenic effects of GA-13315, a gibberellin derivative.

PubMed

Zhang, Yanli; Zhang, Hui; Chen, Jingbo; Zhao, Haixia; Zeng, Xianghui; Zhang, Hongbin; Qing, Chen

2012-02-01

This study showed that 13-chlorine-3,15-dioxy-gibberellic acid methyl ester (GA-13315), a gibberellin derivative, possessed high antitumor and antiangiogenic activity in vitro and in vivo. Cytotoxicity assays showed that GA-13315 was a potential and efficient antitumor compound, with inhibitory concentration 50 (IC(50)) values ranging from 0.13 to 30.28 μg/ml in 12 human tumor cell lines, and it showed moderate toxicity to peripheral blood mononuclear cells with an IC(50) value of 14.2 μg/ml. Administration of 0.5 or 2.5 mg/kg GA-13315 for 23 days significantly inhibited tumor growth of human non-small cell lung tumor (A549) xenografts, with relative growth rates ranging from 29.91% to 35.05%. Acute toxicity was determined in ICR mice, and the lethal dose 50 (LD(50)) was 4.19 g/kg after intragastric administration. The high antitumor potency of GA-13315 occurred in parallel with its antiangiogenic activity. In vitro, GA-13315 inhibited recombinant human epithelial growth factor-induced chemotactic motility and capillary-like tube formation of primary cultured human endothelial cells. Furthermore, GA-13315 decreased the factor VIII(+) microvessel density and vascular endothelial growth factor expression in A549 tumors, indicating its antiangiogenic efficacy in vivo. These results indicate that the antiangiogenic activity of GA-13315 contributes to its anticancer properties. Further studies are needed to investigate the use of GA-13315 as an anticancer drug.

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[The research on xiaochalhu decoction improving the inflammation of chronic glomerulonephritis patients and relieving the proteinuria].

PubMed

Ding, Shi-Yong; Zheng, Ping-Dong; He, Li-Qun; Hou, Wei-Guo; Zou, Yun; Gao, Jian-Dong

2013-01-01

To observe the balance of T help cell1/2 (Th1/Th2), the changes of correlated proinflammatory cytokines (IFN-gamma and IL-4), and regulated on activation normal T cell expressed and secreted (RANTES), and the abnormal expression of IL-17, the effector of T help cell17 (Th17) in chronic glomerulonephritis (CGN)patients with Shaoyang disease, thus revealing the mechanisms of Xiaochaihu Decoction (XD) for treating proteinuria of CGN patients according to the theory of mediating Shaoyang meridian. Totally 70 CGN patients with Shaoyang disease were randomly assigned to two groups, the treatment group (treated by XD) and the control group [treated by Shenyan Kangfu Tablet (SKT)], 35 in each group. Besides, 20 healthy volunteers were recruited as the healthy control group. Besides, routine therapy of chronic kidney disease (CKD), patients in the treatment group and the control group were treated with XD and SKT respectively for 4 weeks. The changes of Chinese medical syndrome, the effectiveness, 24-h urinary protein, renal functions, the peripheral blood IFN-gamma, IL-4, Th1/Th2, IL-17, and RANTES were compared. Before treatment the Th1/Th2, IL-17, and RANTES of the two treated groups were higher, and the IL-4 level was lower than those of the healthy control group (P < 0.05). After treatment the improvement of Chinese medical syndrome, main symptoms, the effectiveness was better in the XD group than in the SKT group (P < 0.05, P < 0.01). The proteinuria obviously decreased in the treatment group, with the efficacy superior to the SKT group (P < 0.05). The Th1/Th2, IL-17, and RANTES decreased to various degrees when compared with the SKT group (P < 0.05, P < 0.01). The IL-4 level increased more obviously in the treatment group than in the control group (P < 0.05). There was no statistical difference in the improvement of the renal function (P > 0.05). The immune disorder of the CGN patients with Shaoyang disease was correlated with Th1/Th2 imbalance, and abnormal changes

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Deriving a Mutation Index of Carcinogenicity Using Protein Structure and Protein Interfaces

PubMed Central

Hakas, Jarle; Pearl, Frances; Zvelebil, Marketa

2014-01-01

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/. PMID:24454733

Dissolved organic carbon (DOC) in soil extracts investigated by FT-ICR-MS

NASA Astrophysics Data System (ADS)

Hofmann, D.; Steffen, D.; Jablonowski, N. D.; Burauel, P.

2012-04-01

Soil drying and rewetting usually increases the release of xenobiotics like pesticides present in agricultural soils. Besides the effect on the release of two aged 14C-labeled pesticide residues we focus on the characterisation of simultaneously remobilized dissolved organic carbon (DOC) to gain new insights into structure and stability aspects of soil organic carbon fractions. The test soil (gleyic cambisol; Corg 1.2%, pH 7.2) was obtained from the upper soil layer of two individual outdoor lysimeter studies containing either environmentally long-term aged 14C residues of the herbicide ethidimuron (0-10 cm depth; time of aging: 9 years) or methabenzthiazuron (0-30 cm depth; time of aging: 17 years). Soil samples (10 g dry soil equivalents) were (A=dry/wet) previously dried (45°C) or (B=wet/wet) directly mixed with pure water (1+2, w:w), shaken (150 rpm, 1 h), and centrifuged (2000 g). This extraction procedure was repeated several individual times, for both setups. The first three individual extractions, respectively were used for further investigations. Salt was removed from samples prior analysis because of a possible quench effect in the electrospray (ESI) source by solid phase extraction (SPE) with Chromabond C18 Hydra-cartridges (Macherey-Nagel) and methanol as backextraction solvent. The so preconcentrated and desalted samples were introduced by flow injection analysis (FIA) in a fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS), equipped with an ESI source and a 7 T supra-conducting magnet (LTQ-FT Ultra, ThermoFisher Scientific). This technique is the key technique for complex natural systems attributed by their outstanding mass resolution (used 400.000 at m/z 400 Da) and mass accuracy (≤ 1ppm) by simultaneously providing molecular level details of thousands of compounds and was successful applied for the investigations of natural organic matter (NOM) different sources like marine and surface water, soil, sediment, bog and crude oil

ICR SS protozoan data site-by-site: a picture of Cryptosporidium and Giardia in U.S. surface water.

PubMed

Ongerth, Jerry E

2013-09-17

The U.S. Environmental Protection Agency (USEPA) Information Collection Rule Supplemental Survey (ICR SS) required analysis of Cryptosporidium and Giardia in 10 L surface water samples twice a week for a year by USEPA Method 1623 at 80 representative U.S. public water systems (PWS). The resulting data are examined site-by-site in relation to objectives of the Federal drinking water regulation, The Long-Term (2) Enhanced Surface Water Treatment Rule (LT2), currently under formal 6-year review by the USEPA. The data describe Cryptosporidium and Giardia in watersheds nation-wide over a single annual cycle. Due to limited recovery efficiency measurement results are not fully quantified. In the required sample volumes of 10 L no Cryptosporidium were found in 86% of samples and no Giardia were found in 67% of samples. Yet, organisms were found in enough samples at 34 of 80 sites to detail a specrtum of occurrence and variability for both organisms. The data are shown to describe indivudual site risk essential for guidance of watershed and water treatment management by PWSs. The span of median occurrence for both organisms was about 2 orders of magnitude above the limit of detection (LD), ca. 0.05 raw no's/L for Cryptosporidium and ca. 0.10 raw no's/L for Giardia. Data analysis illustrates key features of Cryptosporidium and Giardia in surface water: presence is continuous not intermittent; zeros indicate presence below the LD; occurrence level and variations depend on watershed sources; risk depends on both magnitude and variability of concentration; accurate estimation of risk requires routine measurement of recovery efficiency and calculation of concentration. The data and analysis illustrate features of Cryptosporidium and Giardia occurrence in surface water relevant to their effective regulation for public health protection.

NK026680, a novel suppressant of dendritic cell function, prevents the development of rapidly progressive glomerulonephritis and perinuclear antineutrophil cytoplasmic antibody in SCG/Kj mice.

PubMed

Saiga, Kan; Tokunaka, Kazuhiro; Ichimura, Eiji; Toyoda, Eriko; Abe, Fuminori; Yoshida, Minako; Furukawa, Hiroshi; Nose, Masato; Ono, Masao

2006-11-01

NK026680 is a newly identified type of immunosuppressive agent that inhibits dendritic cell (DC) functions and consequently reduces the mortality of mice with experimental acute graft-versus-host disease. This study was undertaken to evaluate NK026680 suppression of DC functions in preventing development of rapidly progressive glomerulonephritis (RPGN) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) in SCG/Kj mice. Oral administration of NK026680 to SCG/Kj mice began when mice were 8-10 weeks old, before the onset of disease, and continued for 56 days. The efficacy of NK026680 was evaluated using the mortality of mice, the results of urinalysis, histopathologic evaluation for glomerular injury, and immunofluorescence staining for the detection of immune complex (IC) deposition in glomeruli, and by assessing lymphadenopathy and measuring autoantibody titers. Oral administration of NK026680 at a dosage of 25 mg/kg once daily or 50 mg/kg once daily significantly suppressed 1) spontaneous mortality, 2) proteinuria and hematuria, 3) blood urea nitrogen levels, 4) glomerular damage characterized histopathologically, 5) IC deposition in glomeruli, 6) the development of pANCA and anti-DNA antibodies, and 7) lymphadenopathy. The newly identified DC inhibitor, NK026680, prevented the onset of RPGN, autoantibody production, and lymphadenopathy in SCG/Kj mice, suggesting a crucial role for DC function in these autoimmune phenotypes. NK026680 may be a potent immunosuppressive agent for the treatment of ANCA-associated renovascular disorders.

Incidences and range of spontaneous findings in the lymphoid and haemopoietic system of control Charles River CD-1 mice (Crl: CD-1(ICR) BR) used in chronic toxicity studies.

PubMed

Bradley, Alys; Mukaratirwa, Sydney; Petersen-Jones, Morven

2012-01-01

The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in the lymphoid and haemopoietic systems of control Charles River CD-1 mice (Crl: CD-1(ICR) BR). Data was collected from 2,560 mice from control dose groups (104-week and 80-week carcinogenicity studies; 13-week studies), from regulatory studies evaluated at the authors' laboratory between 2005 and 2010. Lesions of the lymphoid and hematopoietic systems were uncommon in 13-week studies but were of high incidence in the carcinogenicity studies (80- or 104-week duration). The most common finding overall was lymphoid hyperplasia within the spleen, thymus, and lymph nodes. The finding of benign lymphoid hyperplasia of the thymus is unusual in other mouse strains. The most common cause of death in the carcinogenicity studies was lymphoma. It is hoped that the results presented here will provide a useful database of incidental pathology findings in CD-1 mice on carcinogenicity studies.

Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model.

PubMed

Shimizu, Manabu; Matsumoto, Taro; Kikuta, Shinsuke; Ohtaki, Munenori; Kano, Koichiro; Taniguchi, Hiroaki; Saito, Shu; Nagaoka, Masahiro; Tokuhashi, Yasuaki

2018-03-20

Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects. Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen. DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation. Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries. Copyright © 2018 The Authors. Published by

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Characterization of fast pyrolysis products generated from several western USA woody species

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Jacqueline M. Jarvis; Deborah S. Page-Dumroese; Nathaniel M. Anderson; Yuri Corilo; Ryan P. Rodgers

2014-01-01

Woody biomass has the potential to be utilized at an alternative fuel source through its pyrolytic conversion. Here, fast pyrolysis bio-oils derived from several western USA woody species are characterized by negative-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) to determine molecular-level composition. The...

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Experimental Investigations of the Internal Energy of Molecules Evaporated via Laser-induced Acoustic Desorption into a Fourier-transform Ion Cyclotron Resonance Mass Spectrometer (LIAD/FT-ICR)

PubMed Central

Shea, Ryan C.; Petzold, Christopher J.; Liu, Ji-ang; Kenttämaa, Hilkka I.

2008-01-01

The internal energy of neutral gas-phase organic and biomolecules, evaporated by means of laser-induced acoustic desorption (LIAD) into a Fourier-transform ion cyclotron resonance mass spectrometer (FT-ICR), was investigated through several experimental approaches. The desorbed molecules were demonstrated not to undergo degradation during the desorption process by collecting LIAD-evaporated molecules and subjecting them to analysis by electrospray ionization/quadrupole ion trap mass spectrometry. Previously established gas-phase basicity (GB) values were remeasured for LIAD-evaporated organic molecules and biomolecules with the use of the bracketing method. No endothermic reactions were observed. The remeasured basicity values are in close agreement with the values reported in the literature. The amount of internal energy deposited during LIAD is concluded to be less than a few kcal/mol. Chemical ionization with a series of proton transfer reagents was employed to obtain a breakdown curve for a protonated dipeptide, val-pro, evaporated by LIAD. Comparison of this breakdown curve with a previously published analogous curve obtained by using substrate-assisted laser desorption (SALD) to evaporate the peptide suggests that the molecules evaporated via LIAD have less internal energy than those evaporated via SALD. PMID:17263513

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

...-Institutional Steam Generating Units (Renewal), EPA ICR Number 1564.08, OMB Control Number 2060-0202 AGENCY...: EPA ICR Number 1564.08, OMB Control Number 2060-0202. ICR Status: This ICR is scheduled to expire on...

Analysis and experimental kinematics of a skid-steering wheeled robot based on a laser scanner sensor.

PubMed

Wang, Tianmiao; Wu, Yao; Liang, Jianhong; Han, Chenhao; Chen, Jiao; Zhao, Qiteng

2015-04-24

Skid-steering mobile robots are widely used because of their simple mechanism and robustness. However, due to the complex wheel-ground interactions and the kinematic constraints, it is a challenge to understand the kinematics and dynamics of such a robotic platform. In this paper, we develop an analysis and experimental kinematic scheme for a skid-steering wheeled vehicle based-on a laser scanner sensor. The kinematics model is established based on the boundedness of the instantaneous centers of rotation (ICR) of treads on the 2D motion plane. The kinematic parameters (the ICR coefficient , the path curvature variable and robot speed ), including the effect of vehicle dynamics, are introduced to describe the kinematics model. Then, an exact but costly dynamic model is used and the simulation of this model's stationary response for the vehicle shows a qualitative relationship for the specified parameters and . Moreover, the parameters of the kinematic model are determined based-on a laser scanner localization experimental analysis method with a skid-steering robotic platform, Pioneer P3-AT. The relationship between the ICR coefficient and two physical factors is studied, i.e., the radius of the path curvature and the robot speed . An empirical function-based relationship between the ICR coefficient of the robot and the path parameters is derived. To validate the obtained results, it is empirically demonstrated that the proposed kinematics model significantly improves the dead-reckoning performance of this skid-steering robot.

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2010-11-01

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... Program (Renewal); EPA ICR No. 1663.07, OMB Control No. 2060-0376 AGENCY: Environmental Protection Agency... ICR No. 1663.07, OMB Control No. 2060-0376. ICR Status: This ICR is scheduled to expire on July 31...

77 FR 1930 - Agency Information Collection Activities; Proposed Collection; Comment Request; Clean Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-12

... Fine Particle Matter and Ozone (Renewal); EPA ICR No. 2152.05, OMB Control No. 2060-0570 AGENCY... Matter and Ozone (Renewal). ICR number: EPA ICR No. 2152.05, OMB Control No. 2060-0570. ICR Status: This...

Tissue distribution, excretion, and the metabolic pathway of 2,2',4,4',5-penta-chlorinated diphenylsulfide (CDPS-99) in ICR mice.

PubMed

Zeng, Xiaolan; Zhang, Xuesheng; Qin, Li; Wang, Zunyao

2015-09-15

The tissue distribution, excretion, and metabolic pathway of 2,2',4,4',5-penta-chlorinated diphenylsulfide (CDPS-99) in ICR mice were investigated after oral perfusion at 10mg/kg body weight (b.w.). Biological samples were extracted and separated and, for the first time, were determined by a novel, sensitive, and specific GC-MS method under the full scan and selected ion monitoring (SIM) modes. The results showed that the concentrations of CDPS-99 in the liver, kidneys, and serum reached a maximum after a one-day exposure and that the CDPS-99 concentration in the liver was the highest (3.43μg/g). The increase in the concentration of CDPS-99 in muscle, skin, and adipose tissue was slower, and the concentrations of CDPS-99 achieved their highest levels after 3 days of exposure. It was observed that the CDPS-99 concentration in adipose tissue was still very high (0.71μg/g) after 21 days of exposure, which suggested that CDPS-99 was able to accumulate in adipose tissue. In addition, mouse feces accounted for approximately 75% of the total gavage dose, indicating that CDPS-99 was mainly excreted via mouse feces. Metabolism analysis demonstrated that there were three possible metabolic pathways of CDPS-99 in mice: dechlorination reactions with the formation of tetra-CDPS and hydroxylation and oxidation reactions with the formation of OH-CDPS-99 and chlorinated diphenylsulfone. The present study will help to develop a better understanding of mammalian metabolism of CDPS-99. Copyright © 2015 Elsevier B.V. All rights reserved.

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2010-07-27

... Quality Standard Implementation Rule (Renewal), EPA ICR No. 2236.03, OMB Control No. 2060-0594 AGENCY...: EPA ICR No. 2236.03, OMB Control No. 2060-0594. ICR status: This ICR is scheduled to expire on July 31...

Differential Induction of Immunogenic Cell Death and Interferon Expression in Cancer Cells by Structured ssRNAs.

PubMed

Lee, Jaewoo; Lee, Youngju; Xu, Li; White, Rebekah; Sullenger, Bruce A

2017-06-07

Activation of the RNA-sensing pattern recognition receptor (PRR) in cancer cells leads to cell death and cytokine expression. This cancer cell death releases tumor antigens and damage-associated molecular patterns (DAMPs) that induce anti-tumor immunity. However, these cytokines and DAMPs also cause adverse inflammatory and thrombotic complications that can limit the overall therapeutic benefits of PRR-targeting anti-cancer therapies. To overcome this problem, we generated and evaluated two novel and distinct ssRNA molecules (immunogenic cell-killing RNA [ICR]2 and ICR4). ICR2 and ICR4 differentially stimulated cell death and PRR signaling pathways and induced different patterns of cytokine expression in cancer and innate immune cells. Interestingly, DAMPs released from ICR2- and ICR4-treated cancer cells had distinct patterns of stimulation of innate immune receptors and coagulation. Finally, ICR2 and ICR4 inhibited in vivo tumor growth as effectively as poly(I:C). ICR2 and ICR4 are potential therapeutic agents that differentially induce cell death, immune stimulation, and coagulation when introduced into tumors. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

PubMed

Strauss, J; Pardo, V; Koss, M N; Griswold, W; McIntosh, R M

1975-03-01

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.

Advanced characterisation of organic matter in oil sands and tailings sands used for land reclamation by Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS)

NASA Astrophysics Data System (ADS)

Noah, M.; Vieth-Hillebrand, A.; Wilkes, H.

2012-04-01

The Athabasca region of northern Alberta, Canada, is home to deposits of oil sands containing vast amounts (~ 173 billion barrels) of heavily biodegraded petroleum. Oil sands are recovered by surface mining or by in situ steam injection. The extraction of bitumen from oil sands by caustic hot water processing results in large volumes of fluid tailings, which are stored in on-site settling basins. There the tailings undergo a compaction and dewatering process, producing a slowly densifying suspension. The released water is recycled for extraction. The fine tailings will be reclaimed as either dry or wet landscapes. [1] To produce 1 barrel of crude oil, 2 tons of oil sand and 2 - 3 tons of water (including recycled water) are required. [2] Open pit mining and the extraction of the bitumen from the oil sands create large and intense disturbances of different landscapes. The area currently disturbed by mining operations covers about 530 km2 and the area of tailing ponds surpasses 130 km2. An issue of increasing importance is the land remediation and reclamation of oil sand areas in Canada and the reconstruction of these disturbed landscapes back to working ecosystems similar to those existing prior to mining operations. An important issue in this context is the identification of oil sand-derived organic compounds in the tailings, their environmental behaviour and the resulting chances and limitations with respect to land reclamation. Furthermore the biodegradation processes that occur in the tailings and that could lead to a decrease in hazardous organic compounds are important challenges, which need to be investigated. This presentation will give a detailed overview of our compositional and quantitative characterisation of the organic matter in oil sand, unprocessed and processed mature fine tailings samples as well as in tailings sands used as part of land reclamation. The analytical characterisation is based on the extraction of the soluble organic matter, its

ICR MICROBIAL MANUAL

EPA Science Inventory

The United States Environmental Protection Agency (U.S. EPA) instituted a formal regulation negotiation process in 1992 to develop the Disinfectant/Disinfection By-Product (D/DBP) Rule.1 The Advisory Committee that was established to negotiate the regulation included represent...

ICRS Recommendation Document

PubMed Central

Roos, Ewa M.; Engelhart, Luella; Ranstam, Jonas; Anderson, Allen F.; Irrgang, Jay J.; Marx, Robert G.; Tegner, Yelverton; Davis, Aileen M.

2011-01-01

Objective: The purpose of this article is to describe and recommend patient-reported outcome instruments for use in patients with articular cartilage lesions undergoing cartilage repair interventions. Methods: Nonsystematic literature search identifying measures addressing pain and function evaluated for validity and psychometric properties in patients with articular cartilage lesions. Results: The knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic requirements for reliability, validity, and responsiveness in cartilage repair patients. A major difference between them is that the former results in a single score and the latter results in 5 subscores. A single score is preferred for simplicity’s sake, whereas subscores allow for evaluation of separate constructs at all levels according to the International Classification of Functioning. Conclusions: Because there is no obvious superiority of either instrument at this time, both outcome measures are recommended for use in cartilage repair. Rescaling of the Lysholm Scoring Scale has been suggested, and confirmatory longitudinal studies are needed prior to recommending this scale for use in cartilage repair. Inclusion of a generic measure is feasible in cartilage repair studies and allows analysis of health-related quality of life and health economic outcomes. The Marx or Tegner Activity Rating Scales are feasible and have been evaluated in patients with knee injuries. However, activity measures require age and sex adjustment, and data are lacking in people with cartilage repair. PMID:26069575

76 FR 4655 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

... Asbestos Abatement Worker Protection; EPA ICR No. 1246.11, OMB No. 2070-0072 AGENCY: Environmental... for Asbestos Abatement Worker Protection; EPA ICR No. 1246.11, OMB No. 2070-0072. The ICR, which is... . Title: Reporting and Recordkeeping for Asbestos Abatement Worker Protection. ICR Status: This is a...

76 FR 67436 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-01

... Activities; Submission to OMB for Review and Approval; Comment Request; NESHAP for Pulp and Paper Production... FURTHER INFORMATION CONTACT: Learia Williams, Monitoring, Assistance, and Media Programs Division, Office... Production (Renewal). ICR Numbers: EPA ICR Number 1657.07, OMB Control Number 2060-0387. ICR Status: This ICR...

The parental non-equivalence of imprinting control regions during mammalian development and evolution.

PubMed

Schulz, Reiner; Proudhon, Charlotte; Bestor, Timothy H; Woodfine, Kathryn; Lin, Chyuan-Sheng; Lin, Shau-Ping; Prissette, Marine; Oakey, Rebecca J; Bourc'his, Déborah

2010-11-18

In mammals, imprinted gene expression results from the sex-specific methylation of imprinted control regions (ICRs) in the parental germlines. Imprinting is linked to therian reproduction, that is, the placenta and imprinting emerged at roughly the same time and potentially co-evolved. We assessed the transcriptome-wide and ontology effect of maternally versus paternally methylated ICRs at the developmental stage of setting of the chorioallantoic placenta in the mouse (8.5dpc), using two models of imprinting deficiency including completely imprint-free embryos. Paternal and maternal imprints have a similar quantitative impact on the embryonic transcriptome. However, transcriptional effects of maternal ICRs are qualitatively focused on the fetal-maternal interface, while paternal ICRs weakly affect non-convergent biological processes, with little consequence for viability at 8.5dpc. Moreover, genes regulated by maternal ICRs indirectly influence genes regulated by paternal ICRs, while the reverse is not observed. The functional dominance of maternal imprints over early embryonic development is potentially linked to selection pressures favoring methylation-dependent control of maternal over paternal ICRs. We previously hypothesized that the different methylation histories of ICRs in the maternal versus the paternal germlines may have put paternal ICRs under higher mutational pressure to lose CpGs by deamination. Using comparative genomics of 17 extant mammalian species, we show here that, while ICRs in general have been constrained to maintain more CpGs than non-imprinted sequences, the rate of CpG loss at paternal ICRs has indeed been higher than at maternal ICRs during evolution. In fact, maternal ICRs, which have the characteristics of CpG-rich promoters, have gained CpGs compared to non-imprinted CpG-rich promoters. Thus, the numerical and, during early embryonic development, functional dominance of maternal ICRs can be explained as the consequence of two

The Parental Non-Equivalence of Imprinting Control Regions during Mammalian Development and Evolution

PubMed Central

Bestor, Timothy H.; Woodfine, Kathryn; Lin, Chyuan-Sheng; Lin, Shau-Ping; Prissette, Marine; Oakey, Rebecca J.; Bourc'his, Déborah

2010-01-01

In mammals, imprinted gene expression results from the sex-specific methylation of imprinted control regions (ICRs) in the parental germlines. Imprinting is linked to therian reproduction, that is, the placenta and imprinting emerged at roughly the same time and potentially co-evolved. We assessed the transcriptome-wide and ontology effect of maternally versus paternally methylated ICRs at the developmental stage of setting of the chorioallantoic placenta in the mouse (8.5dpc), using two models of imprinting deficiency including completely imprint-free embryos. Paternal and maternal imprints have a similar quantitative impact on the embryonic transcriptome. However, transcriptional effects of maternal ICRs are qualitatively focused on the fetal-maternal interface, while paternal ICRs weakly affect non-convergent biological processes, with little consequence for viability at 8.5dpc. Moreover, genes regulated by maternal ICRs indirectly influence genes regulated by paternal ICRs, while the reverse is not observed. The functional dominance of maternal imprints over early embryonic development is potentially linked to selection pressures favoring methylation-dependent control of maternal over paternal ICRs. We previously hypothesized that the different methylation histories of ICRs in the maternal versus the paternal germlines may have put paternal ICRs under higher mutational pressure to lose CpGs by deamination. Using comparative genomics of 17 extant mammalian species, we show here that, while ICRs in general have been constrained to maintain more CpGs than non-imprinted sequences, the rate of CpG loss at paternal ICRs has indeed been higher than at maternal ICRs during evolution. In fact, maternal ICRs, which have the characteristics of CpG-rich promoters, have gained CpGs compared to non-imprinted CpG-rich promoters. Thus, the numerical and, during early embryonic development, functional dominance of maternal ICRs can be explained as the consequence of two

77 FR 52323 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

...- Ignition Engines (Renewal). ICR Numbers: EPA ICR No. 1695.10, OMB Control No. 2060-0338. ICR Status: This... Engines and Equipment, OMB Control Number 2060-0603) were incorporated into ICR 1695.10. This action was... Requirements for Nonroad Spark-Ignition Engines (Renewal) AGENCY: Environmental Protection Agency (EPA). ACTION...

Impact of immunofluorescence on the histological pattern of pediatric kidney biopsies from northern Pakistan.

PubMed

Ali, Akhtar; Ali, Mohammad Usman; Ali, Mahrukh Ayesha

2011-01-01

Kidney biopsy is an investigation for diagnosis and prognosis of a variety of nephritides. It also influences therapeutic options. Immunofluorescence (IMF) greatly adds in identifying the pathologies which may not be obvious on light microscopy (L/M), such as IgM, IgA nephropathy, pauci-immune glomerulonephritis, and anti-glomerular basement membrane disease. We present here data of 170 pediatric kidney biopsies from July 2005 to December 2009 from Department of Nephrology and Hypertension, Lady Reading Hospital, Peshawar, Pakistan. The study was undertaken to see whether IMF would alter the histological pattern of pediatric kidney biopsies and to compare these data with an earlier data from our department of 415 pediatric kidney biopsies done over 7-year period from 1998 to 2005, which were analyzed with L/M alone. Out of 170 kidney biopsies using L/M and IMF, IgM turns out to be most common pattern (20%), followed by minimal change disease (MCD) (17.05%), focal and segmental glomerulosclerosis (FSGS) (15.88%), chronic sclerosing glomerulonephritis (Chr. sclerosing GN) (12.35%), mesangio proliferative glomerulonephritis (MPGN) (7.65%), mesangio capillary glomerulonephritis (MCGN) (6.47%), membranous glomerulonephritis (Mem. GN) (5.29%), IgA nephropathy (5.29%), cresentic glomerulonephritis (Cres. GN) (3.53%), lupus nephritis (2.96%), and others (3.53%). Comparing these results of 170 cases with 415 renal biopsies without IMF, IgM dominated the histological pattern in IMF group whereas MCD followed by FSGS and MPGN were prominent in group without IMF. Therefore, variation in the overall histological pattern with IMF technique proved statistically significant (p < 0.0001). Addition of IMF has altered the frequency of MCD, a change from 24% (100/415) to 17% (29/170), FSGS from 18.3% (76/415) to 15.88% (27/170), and MPGN from 17.35% (72/415) to 7.65% (13/170).

Analysis and Experimental Kinematics of a Skid-Steering Wheeled Robot Based on a Laser Scanner Sensor

PubMed Central

Wang, Tianmiao; Wu, Yao; Liang, Jianhong; Han, Chenhao; Chen, Jiao; Zhao, Qiteng

2015-01-01

Skid-steering mobile robots are widely used because of their simple mechanism and robustness. However, due to the complex wheel-ground interactions and the kinematic constraints, it is a challenge to understand the kinematics and dynamics of such a robotic platform. In this paper, we develop an analysis and experimental kinematic scheme for a skid-steering wheeled vehicle based-on a laser scanner sensor. The kinematics model is established based on the boundedness of the instantaneous centers of rotation (ICR) of treads on the 2D motion plane. The kinematic parameters (the ICR coefficient χ, the path curvature variable λ and robot speed v), including the effect of vehicle dynamics, are introduced to describe the kinematics model. Then, an exact but costly dynamic model is used and the simulation of this model’s stationary response for the vehicle shows a qualitative relationship for the specified parameters χ and λ. Moreover, the parameters of the kinematic model are determined based-on a laser scanner localization experimental analysis method with a skid-steering robotic platform, Pioneer P3-AT. The relationship between the ICR coefficient χ and two physical factors is studied, i.e., the radius of the path curvature λ and the robot speed v. An empirical function-based relationship between the ICR coefficient of the robot and the path parameters is derived. To validate the obtained results, it is empirically demonstrated that the proposed kinematics model significantly improves the dead-reckoning performance of this skid–steering robot. PMID:25919370

C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy.

PubMed

Bomback, Andrew S; Santoriello, Dominick; Avasare, Rupali S; Regunathan-Shenk, Renu; Canetta, Pietro A; Ahn, Wooin; Radhakrishnan, Jai; Marasa, Maddalena; Rosenstiel, Paul E; Herlitz, Leal C; Markowitz, Glen S; D'Agati, Vivette D; Appel, Gerald B

2018-04-01

C3 glomerulonephritis (C3GN) and dense deposit disease comprise the two classes of C3 glomerulopathy. Studies from Europe and Asia have aided our understanding of this recently defined disorder, but whether these data apply to a diverse United States patient population remains unclear. We, therefore, reviewed clinical and histopathological data, including generation of a C3 Glomerulopathy Histologic Index to score biopsy activity and chronicity, to determine predictors of progression to end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD) in 111 patients (approximately 35% non-white) with C3 glomerulopathy: 87 with C3GN and 24 with dense deposit disease. Complement-associated gene variants and autoantibodies were detected in 24% and 35% of screened patients, respectively. Our C3 Glomerulopathy Histologic Index denoted higher activity in patients with C3GN and higher chronicity in patients with dense deposit disease. Over an average of 72 months of follow-up, remission occurred in 38% of patients with C3GN and 25% of patients with dense deposit disease. Progression to late-stage CKD and ESRD was common, with no differences between C3GN (39%) and dense deposit disease (42%). In multivariable models, the strongest predictors for progression were estimated glomerular filtration rate at diagnosis (clinical variables model) and tubular atrophy/interstitial fibrosis (histopathology variables model). Using our C3 Glomerulopathy Histologic Index, both total activity and total chronicity scores emerged as the strongest predictors of progression. Thus, in a large, diverse American cohort of patients with C3 glomerulopathy, there is a high rate of progression to CKD and ESRD with no differences between C3GN and dense deposit disease. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

75 FR 52734 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Cooling...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

... Facilities (Renewal), EPA ICR No. 2060.04, OMB Control No. 2040-0257 AGENCY: Environmental Protection Agency...: Cooling Water Intake Structure Phase II Existing Facilities (Renewal). ICR Numbers: EPA ICR No. 2060.04... (EPA ICR No. 2060.03) covers the last 2 years of the permit approval period (i.e., years 4 and 5 after...

75 FR 30812 - Agency Information Collection Activities: Request for Comments on Thirty-One Proposed Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-02

... 264, Subpart CC and 40 CFR Part 265). ICR Numbers: EPA ICR Number 1593.08, OMB Control Number 2060... ICR Number 1593.08, OMB Control Number 2060-0318; expiration date October 31, 2010. (6) NESHAP for..., subpart CC and 40 CFR part 265), Docket ID Number: EPA-HQ-OECA-2010-0370, EPA ICR Number 1593.08, OMB...

The Large Quasar Reference Frame (LQRF). An Optical Representation of the ICRS

DTIC Science & Technology

2009-10-01

faint regimes, both the 2MASS and the preliminary northernmost UCAC2 positions are shown of astrometry consistent with the UCAC2 main catalog, and the...is used. 2.7. 2MASS The Two Micron All-Sky Survey point source catalog (Cutri et al. 2003), hereafter 2MASS , derives from an uniform scan of the...17.1, H = 16.4, and K = 15.3. The 2MASS contains the position of 470 992 970 sources, but no proper motions. The astrometry is referred to the

Poststreptococcal glomerulonephritis (GN)

MedlinePlus

... following: Decreased urine output Rust-colored urine Swelling (edema), general swelling, swelling of the abdomen, swelling of ... A physical examination shows swelling (edema), especially in the face. ... to the heart and lungs with a stethoscope. Blood pressure ...

Glomerulonephritis (For Parents)

MedlinePlus

... a doctor right away to find the cause. Diagnosis At the doctor's office, explain your child's symptoms. ... Phosphorus Blood in the Urine (Hematuria) Living With Lupus Urine Tests Chronic Kidney Diseases Your Urinary System ...

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

....07, OMB Control Number 2060-0327 AGENCY: Environmental Protection Agency (EPA). ACTION: Notice... Anodizing Tanks (Renewal). ICR Numbers: EPA ICR Number 1611.07, OMB Control Number 2060-0327. ICR Status...

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2013-01-02

... them and without change, unless the comment contains copyrighted material, Confidentiality of Business... Combustors (Renewal) . ICR Numbers: EPA ICR Number 1900.05, OMB Control Number 2060-0423. ICR Status: This...

Permanent renal loss following tumor necrosis factor α antagonists for arthritis.

PubMed

Chen, Tzu-Jen; Yang, Ya-Fei; Huang, Po-Hao; Lin, Hsin-Hung; Huang, Chiu-Ching

2010-06-01

Tumor necrosis factor alpha (TNF-alpha) antagonists are now widely used in the treatment of aggressive rheumatoid arthritis and are generally well tolerated. Although rare, they could induce systemic lupus erythematosus, glomerulonephritis, and antineutrophil cytoplasmic antibody associated systemic vasculitis. Tumor necrosis factor alpha antagonists associated glomerulonephritis usually subsides after discontinuation of the therapy and subsequent initiation of corticosteroids and immunosuppressive agents. Here we describe crescentic glomerulonephritis progression to end-stage renal disease in a patient following two doses of TNF-alpha antagonists for the treatment of reactive arthritis. To our knowledge, dialysis dependent permanent renal loss after TNF-alpha antagonists has not yet been reported. We suggest the renal function should be closely monitored in patients treated with TNF-alpha antagonists by rheumatologists.

New effective chemically synthesized anti-smallpox compound NIOCH-14.

PubMed

Mazurkov, Oleg Yu; Kabanov, Alexey S; Shishkina, Larisa N; Sergeev, Alexander A; Skarnovich, Maksim O; Bormotov, Nikolay I; Skarnovich, Maria A; Ovchinnikova, Alena S; Titova, Ksenya A; Galahova, Darya O; Bulychev, Leonid E; Sergeev, Artemiy A; Taranov, Oleg S; Selivanov, Boris A; Tikhonov, Alexey Ya; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

2016-05-01

Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The 'therapeutic window' varied from 1 day before infection to 6 days post-infection (p.i.) to achieve 100-60 % survival rate. The administration of NIOCH-14 and ST-246 to mice resulted in a significant reduction of ectromelia virus titres in organs examined as compared with the control and also reduced pathological changes in the lungs 6 days p.i. Oral administration of NIOCH-14 and ST-246 to ICR mice and marmots challenged with monkeypox virus as compared with the control resulted in a significant reduction of virus production in the lungs and the proportion of infected mice 7 days p.i. as well as the absence of disease in marmots. Significantly lower proportions of infected mice and virus production levels in the lungs as compared with the control were demonstrated in experiments after oral administration of NIOCH-14 and ST-246 to ICR mice and immunodeficient SCID mice challenged with variola virus 3 and 4 days p.i., respectively. The results obtained suggest good prospects for further study of the chemical compound NIOCH-14 to create a new smallpox drug on its basis.

Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof-of-Concept with 7 Years of Extended Follow-Up.

PubMed

Park, Yong-Beom; Ha, Chul-Won; Lee, Choong-Hee; Yoon, Young Cheol; Park, Yong-Geun

2017-02-01

Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Patients with Kellgren-Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The stem cell-based medicinal product (a composite of culture-expanded allogeneic hUCB-MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site. Safety was assessed by the World Health Organization common toxicity criteria. The primary efficacy outcome was ICRS cartilage repair assessed by arthroscopy at 12 weeks. The secondary efficacy outcome was visual analog scale (VAS) score for pain on walking. During a 7-year extended follow-up, we evaluated safety, VAS score, International Knee Documentation Committee (IKDC) subjective score, magnetic resonance imaging (MRI) findings, and histological evaluations. Seven participants were enrolled. Maturing repair tissue was observed at the 12-week arthroscopic evaluation. The VAS and IKDC scores were improved at 24 weeks. The improved clinical outcomes were stable over 7 years of follow-up. The histological findings at 1 year showed hyaline-like cartilage. MRI at 3 years showed persistence of the regenerated cartilage. Only five mild to moderate treatment-emergent adverse events were observed. There were no cases of osteogenesis or tumorigenesis over 7 years. The application of this novel stem cell-based medicinal product appears to be safe and effective for the regeneration of durable articular cartilage in osteoarthritic knees. Stem Cells Translational Medicine 2017;6:613-621. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Protective Effect of Hydroxychloroquine on Renal Damage in Patients with Lupus Nephritis: Data from LUMINA, a Multiethnic U.S. Cohort

PubMed Central

Pons-Estel, Guillermo J.; Alarcón, Graciela S.; McGwin, Gerald; Danila, Maria I.; Zhang, Jie; Bastian, Holly M.; Reveille, John D.; Vilá, Luis M.

2010-01-01

Objective To assess if hydroxychloroquine can delay renal damage development in lupus nephritis patients. Methods Lupus nephritis patients (n=256) from LUMINA (n=635), a multiethnic cohort of African Americans, Hispanics and Caucasians, age ≥16 years, disease duration ≤5 years at baseline (T0) were studied. Renal damage was defined per the SLICC Damage Index (≥1 of the following lasting at least six months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria ≥3.5 g and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n=53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potentially confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or World Health Organization (WHO) Class glomerulonephritis were also derived. Results Sixty-three (31.0%) of 203 patients developed renal damage over a mean (standard deviation) disease duration of 5.2 (3.5) years. The most frequent renal damage domain item was proteinuria. Hydroxychloroquine-takers (79.3%) exhibited a lower frequency of WHO Class IV glomerulonephritis, lower disease activity and received lower glucocorticoid doses than non-takers. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (HR=0.12; 95% CI 0.02-0.97; p=0.0464) and reduced (HR=0.29; 95%CI 0.13-0.68; p=0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in hydroxychloroquine non-takers and in WHO Class IV glomerulonephritis (p<0.0001). Conclusions After adjusting for possible confounding factors the protective effect of hydroxychloroquine in retarding renal damage occurrence in SLE is still evident. PMID:19479701

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Motion Path of the Instant Center of Rotation in the Cervical Spine During In Vivo Dynamic Flexion-Extension: Implications for Artificial Disc Design and Evaluation of Motion Quality Following Arthrodesis

PubMed Central

Anderst, William; Baillargeon, Emma; Donaldson, William; Lee, Joon; Kang, James

2013-01-01

Study Design Case-control. Objective To characterize the motion path of the instant center of rotation (ICR) at each cervical motion segment from C2 to C7 during dynamic flexion-extension in asymptomatic subjects. To compare asymptomatic and single-level arthrodesis patient ICR paths. Summary of Background Data The ICR has been proposed as an alternative to range of motion (ROM) for evaluating the quality of spine movement and for identifying abnormal midrange kinematics. The motion path of the ICR during dynamic motion has not been reported. Methods 20 asymptomatic controls, 12 C5/C6 and 5 C6/C7 arthrodesis patients performed full ROM flexion-extension while biplane radiographs were collected at 30 Hz. A previously validated tracking process determined three-dimensional vertebral position with sub-millimeter accuracy. The finite helical axis method was used to calculate the ICR between adjacent vertebrae. A linear mixed-model analysis identified differences in the ICR path among motion segments and between controls and arthrodesis patients. Results From C2/C3 to C6/C7, the mean ICR location moved superior for each successive motion segment (p < .001). The AP change in ICR location per degree of flexion-extension decreased from the C2/C3 motion segment to the C6/C7 motion segment (p < .001). Asymptomatic subject variability (95% CI) in the ICR location averaged ±1.2 mm in the SI direction and ±1.9 mm in the AP direction over all motion segments and flexion-extension angles. Asymptomatic and arthrodesis groups were not significantly different in terms of average ICR position (all p ≥ .091) or in terms of the change in ICR location per degree of flexion-extension (all p ≥ .249). Conclusions To replicate asymptomatic in vivo cervical motion, disc replacements should account for level-specific differences in the location and motion path of ICR. Single-level anterior arthrodesis does not appear to affect cervical motion quality during flexion-extension. PMID

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Ionic current rectification in organic solutions with quartz nanopipettes.

PubMed

Yin, Xiaohong; Zhang, Shudong; Dong, Yitong; Liu, Shujuan; Gu, Jing; Chen, Ye; Zhang, Xin; Zhang, Xianhao; Shao, Yuanhua

2015-09-01

The study of behaviors of ionic current rectification (ICR) in organic solutions with quartz nanopipettes is reported. ICR can be observed even in organic solutions using quartz pipettes with diameters varied from several to dozens of nanometers, and the direction of ICR is quite different from the ICR observed in aqueous phase. The influences of pore size, electrolyte concentration, and surface charge on the ICR have been investigated carefully. Water in organic solutions affects the direction and extent of ICR significantly. Mechanisms about the formation of an electrical double layer (EDL) on silica in organic solutions with different amount of water have been proposed. An improved method, which can be employed to detect trace water in organic solutions, has been implemented based on Au ultramicroelectrodes with cathodic differential pulse stripping voltammetry.

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A refined genome-scale reconstruction of Chlamydomonas metabolism provides a platform for systems-level analyses

DOE PAGES

Imam, Saheed; Schäuble, Sascha; Valenzuela, Jacob; ...

2015-10-20

Microalgae have reemerged as organisms of prime biotechnological interest due to their ability to synthesize a suite of valuable chemicals. To harness the capabilities of these organisms, we need a comprehensive systems-level understanding of their metabolism, which can be fundamentally achieved through large-scale mechanistic models of metabolism. In this study, we present a revised and significantly improved genome-scale metabolic model for the widely-studied microalga, Chlamydomonas reinhardtii. The model, iCre1355, represents a major advance over previous models, both in content and predictive power. iCre1355 encompasses a broad range of metabolic functions encoded across the nuclear, chloroplast and mitochondrial genomes accounting formore » 1355 genes (1460 transcripts), 2394 and 1133 metabolites. We found improved performance over the previous metabolic model based on comparisons of predictive accuracy across 306 phenotypes (from 81 mutants), lipid yield analysis and growth rates derived from chemostat-grown cells (under three conditions). Measurement of macronutrient uptake revealed carbon and phosphate to be good predictors of growth rate, while nitrogen consumption appeared to be in excess. We analyzed high-resolution time series transcriptomics data using iCre1355 to uncover dynamic pathway-level changes that occur in response to nitrogen starvation and changes in light intensity. This approach enabled accurate prediction of growth rates, the cessation of growth and accumulation of triacylglycerols during nitrogen starvation, and the temporal response of different growth-associated pathways to increased light intensity. Thus, iCre1355 represents an experimentally validated genome-scale reconstruction of C. reinhardtii metabolism that should serve as a useful resource for studying the metabolic processes of this and related microalgae.« less

The Spectrum of Biopsy-Proven Glomerular Disease in China: A Systematic Review

PubMed Central

Yang, Yue; Zhang, Zheng; Zhuo, Li; Chen, Da-Peng; Li, Wen-Ge

2018-01-01

Background: Chronic kidney disease has become a leading public health concern in China, as it is associated with increased morbidity, mortality, and costs. However, the overall situation regarding common glomerular diseases in China remains unclear. Hence, the aim of this study was to assess the national profile of the common types of glomerulonephritis in China. Methods: We searched Medline, Embase, Cochrane Library, CNKI, SinoMed, VIP, and Wanfang databases for English and Chinese language articles from inception to September 2017. We also collected potentially relevant studies and reviews using a manual search. The following words in combinations are as keywords: “renal biopsy”, “kidney pathological diagnosis”, and “spectrum of pathological types”. Results: We identified 23 studies involving 176,355 patients from 15 provinces/cities in China. The detection rates of primary glomerulonephritis (PGN) and secondary glomerulonephritis (SGN) were 0.740 and 0.221, respectively. Over the past 30 years, the top five types of PGN were immunoglobulin A nephropathy (IgAN; 24.3%), mesangial proliferative glomerulonephritis (MsPGN; 10.5%), membranous nephropathy (MN; 12.6%), minimal change disease (MCD; 9.8%), and focal segmental glomerulosclerosis (FSGS; 4.6%), and the top four types of SGN were lupus nephritis (LN; 8.6%), Henoch-Schönlein purpura glomerulonephritis (4.1%), hepatitis B virus-associated glomerulonephritis (HBV-GN; 2.6%), and diabetic nephropathy (DN; 1.6%). The proportion of MN, MCD, HBV-GN, and DN tended to increase, while those of IgAN, MsPGN, FSGS, and LN tended to drop. Conclusions: Although the incidence of SGN is increasing gradually, PGN is still the leading form of kidney disease in patients undergoing renal biopsies in China. IgAN and LN are the most common types of PGN and SGN, respectively. Differences between regions are related to various factors such as nationality, environment, and diet. Furthermore, unified standards and norms for

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Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome

PubMed Central

Calvello, Mariarosaria; Tabano, Silvia; Colapietro, Patrizia; Maitz, Silvia; Pansa, Alessandra; Augello, Claudia; Lalatta, Faustina; Gentilin, Barbara; Spreafico, Filippo; Calzari, Luciano; Perotti, Daniela; Larizza, Lidia; Russo, Silvia; Selicorni, Angelo; Sirchia, Silvia M; Miozzo, Monica

2013-01-01

Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS is caused by various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis is required to reinforce the clinical diagnosis of BWS and to identify BWS patients with cancer susceptibility. This is particularly crucial prenatally because most signs of BWS cannot be recognized in utero. We established a reliable molecular assay by pyrosequencing to quantitatively evaluate the methylation profiles of ICR1 and ICR2. We explored epigenotype-phenotype correlations in 19 patients that fulfilled the clinical diagnostic criteria for BWS, 22 patients with suspected BWS, and three fetuses with omphalocele. Abnormal methylation was observed in one prenatal case and 19 postnatal cases, including seven suspected BWS. Seven cases showed ICR1 hypermethylation, five cases showed ICR2 hypomethylation, and eight cases showed abnormal methylation of ICR1 and ICR2 indicating paternal uniparental disomy (UPD). More cases of ICR1 alterations and UPD were found than expected. This is likely due to the sensitivity of this approach, which can detect slight deviations in methylation from normal levels. There was a significant correlation (p < 0.001) between the percentage of ICR1 methylation and BWS features: severe hypermethylation (range: 75–86%) was associated with macroglossia, macrosomia, and visceromegaly, whereas mild hypermethylation (range: 55–59%) was associated with umbilical hernia and diastasis recti. Evaluation of ICR1 and ICR2 methylation by pyrosequencing in BWS can improve epigenotype-phenotype correlations, detection of methylation alterations in suspected cases, and identification of UPD. PMID:23917791

Invasive cervical resorption following orthodontic treatment: Two cases involving the same patient.

PubMed

Yoshpe, Margarita; Kaufman, Arieh; Lin, Shaul; Gabay, Eran; Einy, Shmuel

2016-01-01

Invasive cervical resorption (ICR), a destructive form of external root resorption, is characterized by invasion of the fibrovascular tissue. This phenomenon is very rare and appears in 0.02% of the general population where the leading factors are orthodontics in addition to trauma, restorations, and bleaching. Heavy orthodontic force may increase the incidence to 1%. One of the main concerns regarding ICR is that it is often misdiagnosed with conventional diagnostic tools. In recent decades, a cone beam computed tomography (CBCT) imaging technique has become more common and can lead to a more accurate diagnosis and treatment plan. This case report describes a possible association between orthodontic treatment and ICR of a 14-year-old male, 18 months post orthodontic treatment. ICR in the mandibular right canine was diagnosed and verified by CBCT, and underwent combined endodontic-periodontal treatment. However, after orthodontic forced eruption was performed on this tooth to improve the bone defect, ICR was diagnosed on the mandibular right second premolar. The possible association between orthodontic treatment and ICR is discussed, as ICR was noted following orthodontic treatment on both occasions. This case report stresses the importance of ICR early detection by close attention to periodic radiographic checkups during orthodontic treatment. The use of modern diagnostic tools is highly recommended in suspicious cases. A case is described in which the patient underwent two types of orthodontic treatment in the mandible at different time periods and developed ICR in two different teeth.

Semi-Targeted Analysis of Complex Matrices by ESI FT-ICR MS or How an Experimental Bias may be Used as an Analytical Tool.

PubMed

Hertzog, Jasmine; Carré, Vincent; Dufour, Anthony; Aubriet, Frédéric

2018-03-01

Ammonia is well suited to favor deprotonation process in electrospray ionization mass spectrometry (ESI-MS) to increase the formation of [M - H] - . Nevertheless, NH 3 may react with carbonyl compounds (aldehyde, ketone) and bias the composition description of the investigated sample. This is of significant importance in the study of complex mixture such as oil or bio-oil. To assess the ability of primary amines to form imines with carbonyl compounds during the ESI-MS process, two aldehydes (vanillin and cinnamaldehyde) and two ketones (butyrophenone and trihydroxyacetophenone) have been infused in an ESI source with ammonia and two different amines (aniline and 3-chloronaniline). The (+) ESI-MS analyses have demonstrated the formation of imine whatever the considered carbonyl compound and the used primary amine, the structure of which was extensively studied by tandem mass spectrometry. Thus, it has been established that the addition of ammonia, in the solution infused in an ESI source, may alter the composition description of a complex mixture and leads to misinterpretations due to the formation of imines. Nevertheless, this experimental bias can be used to identify the carbonyl compounds in a pyrolysis bio-oil. As we demonstrated, infusion of the bio-oil with 3-chloroaniline in ESI source leads to specifically derivatized carbonyl compounds. Thanks to their chlorine isotopic pattern and the high mass measurement accuracy, (+) ESI Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) unambiguously highlighted them from the numerous C x H y O z bio-oil components. These results offer a new perspective into the detailed molecular structure of complex mixtures such as bio-oils. Graphical Abstract ᅟ.

Semi-Targeted Analysis of Complex Matrices by ESI FT-ICR MS or How an Experimental Bias may be Used as an Analytical Tool

NASA Astrophysics Data System (ADS)

Hertzog, Jasmine; Carré, Vincent; Dufour, Anthony; Aubriet, Frédéric

2018-03-01

Ammonia is well suited to favor deprotonation process in electrospray ionization mass spectrometry (ESI-MS) to increase the formation of [M - H]-. Nevertheless, NH3 may react with carbonyl compounds (aldehyde, ketone) and bias the composition description of the investigated sample. This is of significant importance in the study of complex mixture such as oil or bio-oil. To assess the ability of primary amines to form imines with carbonyl compounds during the ESI-MS process, two aldehydes (vanillin and cinnamaldehyde) and two ketones (butyrophenone and trihydroxyacetophenone) have been infused in an ESI source with ammonia and two different amines (aniline and 3-chloronaniline). The (+) ESI-MS analyses have demonstrated the formation of imine whatever the considered carbonyl compound and the used primary amine, the structure of which was extensively studied by tandem mass spectrometry. Thus, it has been established that the addition of ammonia, in the solution infused in an ESI source, may alter the composition description of a complex mixture and leads to misinterpretations due to the formation of imines. Nevertheless, this experimental bias can be used to identify the carbonyl compounds in a pyrolysis bio-oil. As we demonstrated, infusion of the bio-oil with 3-chloroaniline in ESI source leads to specifically derivatized carbonyl compounds. Thanks to their chlorine isotopic pattern and the high mass measurement accuracy, (+) ESI Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) unambiguously highlighted them from the numerous CxHyOz bio-oil components. These results offer a new perspective into the detailed molecular structure of complex mixtures such as bio-oils. [Figure not available: see fulltext.

Ions generated from uranyl nitrate solutions by electrospray ionization (ESI) and detected with Fourier transform ion-cyclotron resonance (FT-ICR) mass spectrometry.

PubMed

Pasilis, Sofie; Somogyi, Arpád; Herrmann, Kristin; Pemberton, Jeanne E

2006-02-01

Electrospray ionization (ESI) of uranyl nitrate solutions generates a wide variety of positively and negatively charged ions, including complex adducts of uranyl ions with methoxy, hydroxy, and nitrate ligands. In the positive ion mode, ions detected by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry are sensitive to instrumental tuning parameters such as quadrupole operating frequency and trapping time. Positive ions correspond to oligomeric uranyl nitrate species that can be characterized as having a general formula of [(UO(2))(n)(A)(m)(CH(3)OH)(s)](+) or [(UO(2))(n)(O)(A)(m)(CH(3)OH)(s)](+) with n = 1-4, m = 1-7, s = 0 or 1, and A = OH, NO(3), CH(3)O or a combination of these, although the formation of NO(3)-containing species is preferred. In the negative ion mode, complexes of the form [(UO(2))(NO(3))(m)](-) (m = 1-3) are detected, although the formation of the oxo-containing ions [(UO(2))(O)(n)(NO(3))(m)](-) (n = 1-2, m = 1-2) and the hydroxy-containing ions [(UO(2))(OH)(n)(NO(3))(m)](-) (n = 1-2, m = 0-1) are also observed. The extent of coordinative unsaturation of both positive and negative ions can be determined by ligand association/exchange and H/D exchange experiments using D(2)O and CD(3)OD as neutral reaction partners in the gas-phase. Positive ions are of varying stability and reactivity and may fragment extensively upon collision with D(2)O, CD(3)OD and N(2) in sustained off-resonance irradiation/collision-induced dissociation (SORI-CID) experiments. Electron-transfer reactions, presumably occurring during electrospray ionization but also in SORI-CID, can result in reduction of U(VI) to U(V) and perhaps even U(IV).

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Quantitative OCT-based longitudinal evaluation of intracorneal ring segment implantation in keratoconus.

PubMed

Pérez-Merino, Pablo; Ortiz, Sergio; Alejandre, Nicolas; Jiménez-Alfaro, Ignacio; Marcos, Susana

2013-09-09

To characterize the geometrical properties of keratoconic corneas upon intracorneal ring segments (ICRS) implantation, using custom-developed optical coherence tomography (OCT). Ten keratoconic corneas were measured pre- and post-ICRS surgery (7, 30, and 90 days). Corneal topographic and pachymetric maps were obtained from three-dimensional (3D) images acquired with OCT, provided with custom algorithms for image analysis, distortion correction, and quantification. The 3D positioning of the ICRS was also estimated longitudinally, relative to the pupil center and iris plane. Preoperatively, the average corneal radii of curvature were 7.02 ± 0.54 mm (anterior) and 5.40 ± 0.77 mm (posterior), and the minimum corneal thickness was 384 ± 60 μm. At 90 days, the average corneal radii of curvature were 7.26 ± 0.53 mm (anterior) and 5.44 ± 0.71 mm (posterior), and the minimum corneal thickness was 396 ± 46 μm. ICRS implantation produced a significant decrease of corneal power (by 1.71 ± 1.83 diopters [D] at 90 days). Corneal irregularities (defined by high order Zernike terms of the corneal elevation maps) and the corneal thickness distribution decreased in some patients and increased in others. The 3D ICRS depth matched the planned ICRS depth well (within 23.93 ± 23.49 μm). On average, ICRS showed an overall tilt of -6.8 ± 2.6° (temporal) and -2.1 ± 0.8° (superior) at 7 days. Spectral OCT (sOCT) provided with distortion correction and analysis tools, is an excellent instrument for evaluating the changes produced by ICRS in keratoconic corneas, and for analyzing the 3D ICRS position during the follow up. ICRS produced flattening on the anterior corneal surface, although the benefit for corneal surface regularization varied across patients.

[Analysis of 115 kidney biopsies performed in Dakar (Senegal)].

PubMed

Diouf, B; Ka, E F; Niang, A; Mbengue, M; Ka, M M; Diouf, M L; Pouye, A; Moreira-Diop, T

2001-01-01

Few data are now avalable concerning renal pathology in black African. That is why we under took this study as a contribution to the better knowlege of pathological aspects of kidney disease in Dakar by analysing our 6 years's experience. It was a retrospective study concerning all the patients who underwent renal biopsyfrom January 1993 to December 1998. The samples were studied on light microscopy and immunoflorescence at the nephrology unit of Necker Hospital in Paris. We performed 115 renal biopsies during this period conceming 64 males and 51 females from 5 to 60 years old (mean age 28 years). Nephrotic syndrome represented 67% of the indications, followed by lupus nephritis (13%). We found primary glomerulonephritis in 75% of all cases. Anatomicaly, 54 cases of focal and segmental hyalinosis were found (47% of all biopsies). The other lesions were extra-membranous glomerulonephritis (8,6%), minimal change glomerulonephritis 6%, endo and extra-capillary glomerulonephritis 2,6%, Mesangial glomerulonephrits, extra-capillary glomerunephrotis, IgA nephropaty represented each 1,7%. In 5% of cases the lesions did not permit a precise classification. Focal and segmental hyalinosis is the main primary lesion and lupus nephritis the main secondary one in kidney deseases biopsied in Dakar.

Overexpression of Epstein-Barr virus-induced gene 3 protein (EBI3) in MRL/lpr mice suppresses their lupus nephritis by activating regulatory T cells.

PubMed

Shinsuke, Nishimura; Hiroshi, Inoue

2013-11-01

To identify the effect of an imbalance of Th1/Th2 cytokines on the development of autoimmune glomerulonephritis (lupus nephritis), we studied the modification of pathological changes in diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN) in MRL/lpr mice, which are animal models of systemic lupus erythematosus (SLE). Transgenic MRL/lpr mice (Tg) that overexpressed Epstein--Barr virus-induced gene 3 (EBI3) showed almost normal renal function, which was demonstrated by healing of glomerulonephritis upon renal histology, as compared to the wild-type MRL/lpr (Wt) mice. The levels of anti-dsDNA antibodies and IgE decreased in the Tg mice compared to Wt mice. Quantitative real-time PCR indicated an increase in the mRNA levels of FoxP3, and a decrease in that of IFNγ in the splenocytes of Tg mice as compared to Wt mice. In addition, flow cytometric analysis showed an increase in CD4(+)CD25(+)FoxP3(+)-T cells in the former, as compared to the latter. Our findings suggest that EBI3-overexpression in MRL/lpr mice induces generation of regulatory T cells, which causes suppression of autoimmune and inflammatory reactions by affecting the Th1/Th2 cytokine balance.

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... Applicators Using 1080 Collars for Livestock Protection; EPA ICR No. 1249.09, OMB Control No. 2070-0074 AGENCY... . Title: Requirements for Certified Applicators Using 1080 Collars for Livestock Protection. ICR Numbers.... Abstract: This ICR affects approximately 40 certified pesticide applicators who utilize 1080 toxic collars...

Fourier Transform Ion Cyclotron Resonance Mass Spectrometry at the Cyclotron Frequency.

PubMed

Nagornov, Konstantin O; Kozhinov, Anton N; Tsybin, Yury O

2017-04-01

The phenomenon of ion cyclotron resonance allows for determining mass-to-charge ratio, m/z, of an ensemble of ions by means of measurements of their cyclotron frequency, ω c . In Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), the ω c quantity is usually unavailable for direct measurements: the resonant state is located close to the reduced cyclotron frequency (ω + ), whereas the ω c and the corresponding m/z values may be calculated via theoretical derivation from an experimental estimate of the ω + quantity. Here, we describe an experimental observation of a new resonant state, which is located close to the ω c frequency and is established because of azimuthally-dependent trapping electric fields of the recently developed ICR cells with narrow aperture detection electrodes. We show that in mass spectra, peaks close to ω + frequencies can be reduced to negligible levels relative to peaks close to ω c frequencies. Due to reduced errors with which the ω c quantity is obtained, the new resonance provides a means of cyclotron frequency measurements with precision greater than that achieved when ω + frequency peaks are employed. The described phenomenon may be considered for a development into an FT-ICR MS technology with increased mass accuracy for applications in basic research, life, and environmental sciences. Graphical Abstract ᅟ.

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... Gasoline (Renewal) AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: In compliance...: Detergent Gasoline (Renewal). ICR numbers: EPA ICR No. 1655.07, OMB Control No. 2060-0275. ICR Status: This... regulations is consolidated in 40 CFR part 9. Abstract: Gasoline combustion results in the formation of engine...

Idiopathic condylar resorption: The current understanding in diagnosis and treatment

PubMed Central

Young, Andrew

2017-01-01

Idiopathic condylar resorption (ICR) is a condition with no known cause, which manifests as progressive malocclusion, esthetic changes, and often pain. Cone-beam computed tomography and magnetic resonance imaging are the most valuable imaging methods for diagnosis and tracking, compared to the less complete and more distorted images provided by panoramic radiographs, and the higher radiation of 99mtechnetium-methylene diphosphonate. ICR has findings that overlap with osteoarthritis, inflammatory arthritis, physiologic resorption/remodeling, congenital disorders affecting the mandible, requiring thorough image analysis, physical examination, and history-taking. Correct diagnosis and determination of whether the ICR is active or inactive are essential when orthodontic or prosthodontic treatment is anticipated as active ICR can undo those treatments. Several treatments for ICR have been reported with the goals of either halting the progression of ICR or correcting the deformities that it caused. These treatments have varying degrees of success and adverse effects, but the rarity of the condition prevents any evidence-based recommendations. PMID:28584413

Comparison of clinical and laboratory parameters in patients with end-stage renal failure in the outcome of chronic glomerulonephritis and patients with end-stage renal failure in the outcome of other diseases.

PubMed

Popova, J A; Yadrihinskaya, V N; Krylova, M I; Sleptsovа, S S; Borisovа, N V

frequent complications of hemodialysis treatments are coagulation disorders. This is due to activation of the coagulation of blood flow in the interaction with a dialysis membrane material vascular prostheses and extracorporeal circuit trunks. In addition, in hemodialysis patients receiving heparin for years, there is depletion of stocks in endothelial cells in tissue factor inhibitor, inhibits the activity of an external blood clotting mechanism. the aim of our study was to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure. to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure and hemodialysis treatment duration conducted a study that included 100 patients observed in the department of chronic hemodialysis and nephrology hospital №1 Republican National Medical Center in the period of 2013-2016. in patients with end-stage renal failure in the outcome of chronic glomerulonephritis, a great expression of activation of blood coagulation confirm increased the mean concentration of fibrinogen, whereas in the group, which included patients with end-stage renal failure in the outcome of other diseases, such is not different from the norm, and a higher rate of hyperfibrinogenemia, identified in 2/3 patients in this group. it was revealed that the state of homeostasis in patients with end-stage renal failure in increasingly characterizes the level of fibrinogen and the activation of the hemostatic markers: soluble fibrin monomer complexes, D-dimers.

A refined genome-scale reconstruction of Chlamydomonas metabolism provides a platform for systems-level analyses.

PubMed

Imam, Saheed; Schäuble, Sascha; Valenzuela, Jacob; López García de Lomana, Adrián; Carter, Warren; Price, Nathan D; Baliga, Nitin S

2015-12-01

Microalgae have reemerged as organisms of prime biotechnological interest due to their ability to synthesize a suite of valuable chemicals. To harness the capabilities of these organisms, we need a comprehensive systems-level understanding of their metabolism, which can be fundamentally achieved through large-scale mechanistic models of metabolism. In this study, we present a revised and significantly improved genome-scale metabolic model for the widely-studied microalga, Chlamydomonas reinhardtii. The model, iCre1355, represents a major advance over previous models, both in content and predictive power. iCre1355 encompasses a broad range of metabolic functions encoded across the nuclear, chloroplast and mitochondrial genomes accounting for 1355 genes (1460 transcripts), 2394 and 1133 metabolites. We found improved performance over the previous metabolic model based on comparisons of predictive accuracy across 306 phenotypes (from 81 mutants), lipid yield analysis and growth rates derived from chemostat-grown cells (under three conditions). Measurement of macronutrient uptake revealed carbon and phosphate to be good predictors of growth rate, while nitrogen consumption appeared to be in excess. We analyzed high-resolution time series transcriptomics data using iCre1355 to uncover dynamic pathway-level changes that occur in response to nitrogen starvation and changes in light intensity. This approach enabled accurate prediction of growth rates, the cessation of growth and accumulation of triacylglycerols during nitrogen starvation, and the temporal response of different growth-associated pathways to increased light intensity. Thus, iCre1355 represents an experimentally validated genome-scale reconstruction of C. reinhardtii metabolism that should serve as a useful resource for studying the metabolic processes of this and related microalgae. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

High-rate dead-time corrections in a general purpose digital pulse processing system

PubMed Central

Abbene, Leonardo; Gerardi, Gaetano

2015-01-01

Dead-time losses are well recognized and studied drawbacks in counting and spectroscopic systems. In this work the abilities on dead-time correction of a real-time digital pulse processing (DPP) system for high-rate high-resolution radiation measurements are presented. The DPP system, through a fast and slow analysis of the output waveform from radiation detectors, is able to perform multi-parameter analysis (arrival time, pulse width, pulse height, pulse shape, etc.) at high input counting rates (ICRs), allowing accurate counting loss corrections even for variable or transient radiations. The fast analysis is used to obtain both the ICR and energy spectra with high throughput, while the slow analysis is used to obtain high-resolution energy spectra. A complete characterization of the counting capabilities, through both theoretical and experimental approaches, was performed. The dead-time modeling, the throughput curves, the experimental time-interval distributions (TIDs) and the counting uncertainty of the recorded events of both the fast and the slow channels, measured with a planar CdTe (cadmium telluride) detector, will be presented. The throughput formula of a series of two types of dead-times is also derived. The results of dead-time corrections, performed through different methods, will be reported and discussed, pointing out the error on ICR estimation and the simplicity of the procedure. Accurate ICR estimations (nonlinearity < 0.5%) were performed by using the time widths and the TIDs (using 10 ns time bin width) of the detected pulses up to 2.2 Mcps. The digital system allows, after a simple parameter setting, different and sophisticated procedures for dead-time correction, traditionally implemented in complex/dedicated systems and time-consuming set-ups. PMID:26289270

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...; Depredation Order for Blackbirds, Grackles, Cowbirds, Magpies, and Crows AGENCY: Fish and Wildlife Service... Information Collection Request (ICR) to OMB for review and approval. We summarize the ICR below and describe...-2482 (telephone). You may review the ICR online at http://www.reginfo.gov . Follow the instructions to...

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2012-08-06

... Steel Manufacturing (Renewal). ICR Numbers: EPA ICR Number 2003.05, OMB Control Number 2060-0517. ICR...: The NESHAP for Integrated Iron and Steel Manufacturing are subject to the General Provisions of the... Activities; Submission to OMB for Review and Approval; Comment Request; NESHAP for Integrated Iron and Steel...

Isopropanolic black cohosh extract and recurrence-free survival after breast cancer.

PubMed

Henneicke-von Zepelin, H H; Meden, H; Kostev, K; Schröder-Bernhardi, D; Stammwitz, U; Becher, H

2007-03-01

To investigate the influence of an isopropanolic Cimicifuga racemosa extract (iCR) on recurrence-free survival after breast cancer, including estrogen-dependent tumors. This pharmacoepidemiologic observational retrospective cohort study examined breast cancer patients treated at general, gynecological and internal facilities linked to a medical database in Germany. The main endpoint was disease-free survival following a diagnosis of breast cancer. The impact of treatment with iCR following diagnosis was analyzed by Cox-proportional hazards models, controlling for age and other confounders. Of 18,861 patients, a total of 1,102 had received an iCR therapy. The mean overall observation time was 3.6 years. Results showed that iCR was not associated with an increase in the risk of recurrence but associated with prolonged disease-free survival. After 2 years following initial diagnosis, 14% of the control group had developed a recurrence, while the iCR group reached this proportion after 6.5 years. The primary Cox regression model controlling for age, tamoxifen use and other confounders demonstrated a protractive effect of iCR on the rate of recurrence (hazard ratio 0.83, 95% confidence interval 0.69 0.99). This effect remained consistent throughout all variations of the statistical model, including subgroup analyses. TNM status was unknown but did not bias the iCR treatment decision as investigated separately. Hence, it was assumed to be equally distributed between treatment groups. Correlation analyses showed good internal and external validity of the database. An increase in the risk of breast cancer recurrence for women having had iCR treatment, compared to women not treated with iCR is unlikely.

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2011-09-20

... Activities; Submission to OMB for Review and Approval; Comment Request; NESHAP for Engine Test Cells/ Stands... Cells/Stands (Renewal) ICR Numbers: EPA ICR Number 2066.05, OMB Control Number 2060-0483. ICR Status... Hazardous Air Pollutants (NESHAP) for Engine Test Cells/Stands were proposed on May 14, 2002 (67 FR 34547...

Discrete Address Beacon System (DABS) Software System Reliability Modeling and Prediction.

DTIC Science & Technology

1981-06-01

Service ( ATARS ) module because of its interim status. Reliability prediction models for software modules were derived and then verified by matching...System (A’iCR3BS) and thus can be introduced gradually and economically without ma jor olper- ational or procedural change. Since DABS uses monopulse...lineanaly- sis tools or are ured during maintenance or pre-initialization were not modeled because they are not part of the mission software. The ATARS

Invasive cervical resorption and the oro-facial cleft patient: a review and case series.

PubMed

O'Mahony, A; McNamara, C; Ireland, A; Sandy, J; Puryer, J

2017-05-12

Introduction Invasive cervical resorption (ICR) has an unknown aetiology, yet it exhibits very aggressive behaviour compared with typical external root resorption, posing a high risk of tooth loss.Aim To investigate the number of patients at the Dublin Cleft Prosthodontic Department with an oro-facial cleft who experienced ICR and to identify any possible aetiological factors.Materials and method A retrospective investigation of all oro-facial cleft patients treated at the Dublin Cleft Prosthodontic Department, St James's Hospital, Dublin. All patients' clinical and radiological records were reviewed. Patients where tooth loss became inevitable due to Class 4 ICR were analysed.Results From 588 oro-facial cleft patients, 14 (2.38%) patients with ICR were identified. Of these eight (57%) were female and six (43%) were male. Mean age at diagnosis was 28 years (range = 16-49 years). Cleft type: six (42.1%) unilateral cleft lip and palate, eight (57.9%) bilateral cleft lip and palate. Seventeen ICR affected teeth in total, with eleven (65%) maxillary central incisors, two (12%) maxillary lateral incisors, four (23%) maxillary canines, and one (7%) central, lateral and canine affected. Some, (N = 10, 71.4%) presented with ICR resulting in immediate tooth loss. Other patients (N = 4, 28.6%) developed ICR during or following prosthodontic treatment at the Cleft Centre. Tooth loss for this cohort, though not immediate, was inevitable. All had undergone fixed orthodontic appliance treatment and twelve had received dento-alveolar bone grafts. A number (N = 7, 50%) had undergone osteotomy, two (14%) had received night guard vital dental whitening and one had a history of trauma.Conclusions ICR, given its aggressive nature and ill-understood aetiology, poses significant treatment challenges. The most severe form of ICR (Class 4) leads inevitably to tooth loss. The slow-moderate progression of ICR may explain the late presentation found in this study, reinforcing the importance

Comparison between in vivo dosimetry and barium contrast technique for prediction of rectal complications in high-dose-rate intracavitary radiotherapy in cervix cancer patients.

PubMed

Huh, Seung Jae; Lim, Do Hoon; Ahn, Yong Chan; Lee, Jeong Eun; Kang, Min Kyu; Shin, Seong Soo; Shin, Kyung Hwan; Kim, Bokyung; Park, Won; Han, Youngyih

2003-03-01

To investigate the correlation between late rectal complications and rectal dose in cervix cancer patients treated with high-dose-rate intracavitary radiotherapy (HDR ICR) and to analyze factors reducing rectal complications. A total of 136 patients with cervix cancer who were treated with external beam radiotherapy (EBRT) and HDR ICR from 1995 to 1999 were retrospectively analyzed. Radiotherapy (RT) consisted of EBRT plus HDR ICR. The median EBRT dose was 50.4 Gy, and midline block was done after 30-50 Gy of EBRT. A total of six fractions of HDR ICR with 4 Gy fraction size each were applied twice per week to the A point. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. In vivo measurement of the rectal dose was performed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 26 months (range 6-60 months). A total of 16 patients (12%) experienced rectal bleeding, which occurred 4-33 months (median 11 months) after the completion of RT. The calculated rectal doses did not differ in patients with rectal bleeding and those without, but the measured rectal doses were higher in affected patients. The differences of the measured ICR fractional rectal dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose exceeded 16 Gy, the ratio of the measured rectal dose to A point dose was > 70%; when the measured rectal BED exceeded 110 Gy(3), a high possibility of late rectal complications could be found. In vivo dosimetry using TLD during HDR ICR was a good predictor of late rectal complications. Hence, if data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.

Extensive investigation of the IGF2/H19 imprinting control region reveals novel OCT4/SOX2 binding site defects associated with specific methylation patterns in Beckwith-Wiedemann syndrome.

PubMed

Abi Habib, Walid; Azzi, Salah; Brioude, Frédéric; Steunou, Virginie; Thibaud, Nathalie; Das Neves, Cristina; Le Jule, Marilyne; Chantot-Bastaraud, Sandra; Keren, Boris; Lyonnet, Stanislas; Michot, Caroline; Rossi, Massimiliano; Pasquier, Laurent; Gicquel, Christine; Rossignol, Sylvie; Le Bouc, Yves; Netchine, Irène

2014-11-01

Isolated gain of methylation (GOM) at the IGF2/H19 imprinting control region 1 (ICR1) accounts for about 10% of patients with BWS. A subset of these patients have genetic defects within ICR1, but the frequency of these defects has not yet been established in a large cohort of BWS patients with isolated ICR1 GOM. Here, we carried out a genetic analysis in a large cohort of 57 BWS patients with isolated ICR1 GOM and analyzed the methylation status of the entire domain. We found a new point mutation in two unrelated families and a 21 bp deletion in another unrelated child, both of which were maternally inherited and affected the OCT4/SOX2 binding site in the A2 repeat of ICR1. Based on data from this and previous studies, we estimate that cis genetic defects account for about 20% of BWS patients with isolated ICR1 GOM. Methylation analysis at eight loci of the IGF2/H19 domain revealed that sites surrounding OCT4/SOX2 binding site mutations were fully methylated and methylation indexes declined as a function of distance from these sites. This was not the case in BWS patients without genetic defects identified. Thus, GOM does not spread uniformly across the IGF2/H19 domain, suggesting that OCT4/SOX2 protects against methylation at local sites. These findings add new insights to the mechanism of the regulation of the ICR1 domain. Our data show that mutations and deletions within ICR1 are relatively common. Systematic identification is therefore necessary to establish appropriate genetic counseling for BWS patients with isolated ICR1 GOM. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acute glomerular upregulation of ornithine decarboxylase is not essential for mesangial cell proliferation and matrix expansion in anti-Thy-1-nephritis.

PubMed

Ketteler, M; Westenfeld, R; Gawlik, A; de Heer, E; Distler, A

2000-01-01

Pathways of L-arginine metabolism including nitric oxide, agmatine and polyamine synthesis are upregulated during glomerular inflammation in experimental glomerulonephritis. In anti-Thy-1-glomerulonephritis L-arginine-deficient diets ameliorate the disease course in this model. However, it is unclear which metabolic pathway is affected by this substrate depletion. Since polyamines are important proproliferative molecules, we studied the effect of specific polyamine synthesis blockade in vivo on mesangial cell proliferation and glomerular fibrosis in this model. Anti-Thy-1-glomerulonephritis was induced in male Sprague-Dawley rats by single-bolus injection of monoclonal ER4-antibodies. Rats were treated with difluoromethylornithine (0.5-2% in the drinking water), a selective inhibitor of the rate-limiting enzyme of polyamine synthesis, ornithine decarboxylase (ODC). Mesangial cell proliferation and matrix expansion were evaluated in PAS-stained kidney tissues. Glomerular TGF-beta and biglycan-mRNA-expression were determined by Northern blot analysis and albuminuria was measured using a competitive ELISA. Data were compared to untreated controls. Though complete inhibition of ODC activity was achieved at any time point, difluoromethlornithine treatment had no significant effect on albuminuria, glomerular matrix protein expression and mesangial cell count in this model. The acute upregulation of glomerular ODC activity above baseline in anti-Thy1-glomerulonephritis is not pathophysiologically important for disease development however, biological effects of available polyamine pools cannot be excluded by our study.

Auraptene, a citrus coumarin, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in ICR mouse skin, possibly through suppression of superoxide generation in leukocytes.

PubMed

Murakami, A; Kuki, W; Takahashi, Y; Yonei, H; Nakamura, Y; Ohto, Y; Ohigashi, H; Koshimizu, K

1997-05-01

Coumarin-related compounds, auraptene and umbelliferone, have been isolated from the cold-pressed oil of natsumikan (Citrus natsudaidai HAYATA), and tested as inhibitors of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in Raji cells. The 50% inhibitory concentration (IC50) of auraptene (18 microM) was almost equal to that of genistein. Umbelliferone, which lacks a geranyloxyl group present in auraptene, was less active (IC50 = 450 microM). In a two-stage carcinogenesis experiment with 7,12-dimethylbenz[a] anthracene (topical application at 0.19 mumol) and TPA (topical application at 1.6 nmol) in ICR mouse skin, topical application of auraptene (at 160 nmol) significantly reduced tumor incidence and the numbers of tumors per mouse by 27% (P < 0.01) and 23% (P < 0.05), respectively. Auraptene at a concentration of 50 microM markedly suppressed superoxide (O2-) generation induced by 100 microM TPA in differentiated human promyelocytic HL-60 cells. Having no O2(-)-scavenging potential, auraptene may inhibit the multicomponent NADPH oxidase system. Inhibition of intracellular hydroperoxide formation in differentiated HL-60 cells by auraptene was also confirmed by flow-cytometric analysis using 2',7'-dichlorofluorescein diacetate as a fluorescence probe. Quantitative analyses using high-performance liquid chromatography showed the occurrence of auraptene not only in both the peels and sarcocarps of natsumikan, but also in those of hassaku orange (C. hassaku) and grapefruit (C. paradisi), and even in their bottled fresh juice form. These results indicate that auraptene is a chemopreventer of skin tumorigenesis, and implies that suppression of leukocyte activation might be the mechanism through which it inhibits tumor promotion.

Effects of a treatment with Se-rich rice flour high in resistant starch on enteric dysbiosis and chronic inflammation in diabetic ICR mice.

PubMed

Yuan, Huaibo; Wang, Wenjuan; Chen, Deyi; Zhu, Xiping; Meng, Lina

2017-05-01

Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower. Similar results were also found in NRRS-treated mice. In contrast, no significant difference was found between NR-treated and diabetic control groups. The treatments with SRRS and NRRS reduced the faecal pH values of the diabetic mice. Regarding the inflammatory factor levels, lower levels of serum C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-k-gene binding (NF-κB) and leptin (LEP) and higher adiponutrin (ADPN) levels were found in the SRRS and NRRS-treated mice compared with the diabetic and NR-treated mice. In addition, the CRP, IL-6 and NF-κB levels in the SRRS-treated mice were significantly reduced compared with those observed in the NRRS-treated mice. The reverse transcription-PCR (RT-PCR) results showed that the SRRS and NRRS-treated mice presented higher expression levels of orphan G protein-coupled receptor 41 (GPR41) and orphan G protein-coupled receptor 43 (GPR43) proteins compared with diabetic mice and NR-treated mice. These results indicate that treatments with rice high in RS exert beneficial effects by improving enteric dysbiosis and chronic inflammation. In addition, selenium and RS may exert synergistic effects on chronic inflammation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Parvovirus B19 induced lupus-like syndrome with nephritis.

PubMed

Georges, Elodie; Rihova, Zuzana; Cmejla, Radek; Decleire, Pierre-Yves; Langen, Corinne

2016-12-01

We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

Selection for growth does not affect apparent energetic efficiency of jejunal glucose uptake in mice.

PubMed

Fan, Y K; Croom, W J; Eisen, E J; Daniel, L R; Black, B L; McBride, B W

1996-11-01

Five-wk-old male mice from high growth (M16) and randomly bred control (ICR) lines, plus their reciprocal crosses, ICR x M16 and M16 x ICR, were used to investigate whether whole-body O2 consumption, jejunal respiration, jejunal glucose absorption and the apparent energetic efficiency of jejunal active glucose uptake in mice are altered by genetic selection for growth as well as by heterosis and maternal effects. Whole-body O2 consumption was measured in 12 mice from each line or cross. The mice were later killed for measurement of jejunal O2, using tissue respiration chambers and jejunal glucose transport determined by 3H-3-O-methylglucose accumulation. No heterosis or maternal effects were detected in jejunal glucose active transport and active glucose uptake. Selection for growth (M16 vs. ICR) increased daily gain (1.54 vs. 1.09 g, P < 0.001), small intestinal length and weight, but did not enhance jejunal glucose transport. The apparent energetic efficiency of jejunal active glucose uptake among lines was not different (54.0, 50.4, 51.6 and 47.1 nmol ATP expended/nmol glucose uptake for M16, ICR, M16 x ICR and ICR x M16, respectively, P > 0.63). Selection for growth in mice did not result in more energetically efficient jejunal glucose absorption.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Jacqueline M.; Sudasinghe, Nilusha M.; Albrecht, Karl O.

We apply Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for direct characterization of iron-porphyrins in hydrothermal liquefaction (HTL) biocrude oils derived from two algae: Tetraselmis sp. and cyanobacteria. The ironporphyrin compounds are shown to cause catalyst bed plugging during hydroprocessing due to iron deposition. Inductively-coupled plasma optical emission spectrometry (ICPOES) was utilized for iron quantitation in the plugged catalyst beds formed through hydroprocessing of the two HTL biocrudes and identifies an enrichment of iron in the upper five centimeters of the catalyst bed for Tetraselmis sp. (Fe=100,728 ppm) and cyanobacteria (Fe=115,450 ppm). Direct infusion FT-ICR MS analysis ofmore » the two HTL biocrudes with optimized instrument conditions facilitates rapid screening and identification of iron-porphyrins without prior chromatographic separation. With FT-ICR MS we identify 138 unique iron-porphyrin compounds in the two HTL biocrudes that are structurally similar to metal-porphyrins (e.g. Ni and V) observed in petroleum. No ironporphyrins are observed in the cyanobacteria HTL biocrude after hydroprocessing, which indicates that iron-porphyrin structures in the HTL biocrude are degraded during hydroprocessing. Hydrodemetallization reactions that occur through hydroprocessing of HTL biocrudes could be responsible for the decomposition of iron-porphyrin structures leading to metal deposition in the catalyst bed that result in catalyst deactivation and bed plugging, and must be addressed for effective upgrading of algal HTL biocrudes.« less

Dopaminergic Dysregulation in Mice Selectively Bred for Excessive Exercise or Obesity

PubMed Central

Nehrenberg, Derrick L.; Gordon, Ryan; Hua, Kunjie; Garland, Theodore; Pomp, Daniel

2010-01-01

Dysregulation of the dopamine system is linked to various aberrant behaviors, including addiction, compulsive exercise, and hyperphagia leading to obesity. The goal of the present experiments was to determine how dopamine contributes to the expression of opposing phenotypes, excessive exercise and obesity. We hypothesized that similar alterations in dopamine and dopamine-related gene expression may underly obesity and excessive exercise, as competing traits for central reward pathways. Moreover, we hypothesized that selective breeding for high levels of exercise or obesity may have influenced genetic variation controlling these pathways, manifesting as opposing complex traits. Dopamine, dopamine-related peptide concentrations, and gene expression were evaluated in dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively bred for high rates of wheel running (HR) or obesity (M16), and the non-selected ICR strain from which these lines were derived. HPLC analysis showed significantly greater neurotransmitter concentrations in DS and NA of HR mice compared to M16 and ICR. Microarray analysis showed significant gene expression differences between HR and M16 compared to ICR in both brain areas, with changes revealed throughout the dopamine pathway including D1 and D2 receptors, associated G-proteins (eg. Golf), and adenylate cyclase (eg. Adcy5). The results suggest similar modifications within the dopamine system may contribute to the expression of opposite phenotypes in mice, demonstrating that alterations within central reward pathways can contribute to both obesity and excessive exercise. PMID:20156488

The effects of intermittent calorie restriction on metabolic health: Rationale and study design of the HELENA Trial.

PubMed

Schübel, Ruth; Graf, Mirja E; Nattenmüller, Johanna; Nabers, Diana; Sookthai, Disorn; Gruner, Laura F; Johnson, Theron; Schlett, Christopher L; von Stackelberg, Oyunbileg; Kirsten, Romy; Habermann, Nina; Kratz, Mario; Kauczor, Hans-Ulrich; Ulrich, Cornelia M; Kaaks, Rudolf; Kühn, Tilman

2016-11-01

Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction (CCR), even at equal net calorie intake. Despite promising results from first trials, it remains largely unknown whether ICR-induced metabolic alterations reported from experimental studies can also be observed in humans, and whether ICR diets are practicable and effective in real life situations. Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet on five days and very low energy intake on two days per week) on metabolic parameters and body composition over one year. We will assess the effectiveness of ICR compared to CCR and a control diet over a 12-week intervention, 12-week maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking adults (50 per group, 50% women). Our primary endpoint is the difference between ICR and CCR with respect to fold-changes in expression levels of 82 candidate genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the intervention phase. The candidate genes represent pathways, which may link obesity-related metabolic alterations with the risk for major chronic diseases. In secondary and exploratory analyses, changes in metabolic, hormonal, inflammatory and metagenomic parameters measured in different biospecimens (SATb, blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging-based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study is the first randomized trial over one year testing the effects of ICR on metabolism, body composition and psychosocial factors in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimal percutaneous coronary intervention in patients with ST-elevation myocardial infarction and multivessel disease: An updated, large-scale systematic review and meta-analysis.

PubMed

Nguyen, An Vu; Thanh, Le Van; Kamel, Mohamed Gomaa; Abdelrahman, Sara Attia Mahmoud; El-Mekawy, Mohamed; Mokhtar, Mohamed Ashraf; Ali, Aya Ashraf; Hoang, Nam Nguyen Nho; Vuong, Nguyen Lam; Abd-Elhay, Fatma Abd-Elshahed; Omer, Omer Abdelbagi; Mohamed, Ahmed Abdou; Hirayama, Kenji; Huy, Nguyen Tien

2017-10-01

Our study aimed to compare three different percutaneous coronary intervention (PCI) approaches: culprit-only (COR) and complete (CR) revascularization - categorizing into immediate (ICR) or staged (SCR). We searched 13 databases for randomized controlled trials. Articles were included if they compared at least two strategies. To have more studies in each analysis, an adjusted analysis was performed using person-years to incorporate follow-up durations and obtain pooled rate ratios (RR), with their corresponding 95% confidence interval. Thirteen trials were included with a population of 2830 patients. COR significantly increased major adverse cardiac event (MACE) (adjusted RR 1.67, 95% CI: 1.27-2.19) and repeat revascularization (2.12, 1.67-2.69), which was driven by repeat PCI, without any difference in all-cause mortality and myocardial infarction (MI) compared to CR. When categorizing CR into SCR and ICR, the trend repeated with COR increased MACE (1.99, 1.53-2.6 for ICR), cardiovascular mortality (2.06, 1.07-3.96 for ICR), MI for ICR (1.72, 1.04-2.86), repeat revascularization and repeat PCI for both ICR and SCR. Non-cardiovascular mortality, stroke, nephropathy, re-hospitalization, stent thrombosis and bleeding were similar among all approaches. In MVD-STEMI patients, CR is better than COR in terms of MACE, cardiovascular mortality, repeat revascularization with no difference in safety outcomes. There was a trend towards to a reduction of cardiovascular mortality and MI in ICR compared to SCR when each matched with COR; even though there is no statistically significant difference between ICR and SCR when compared together. Copyright © 2017 Elsevier B.V. All rights reserved.

Polluted Dust Classification and Its Optical Properties Analysis Using CALIPSO Data and Simulation

NASA Astrophysics Data System (ADS)

Ding, J.; Yang, P.; Holz, R.; Vaughan, M. A.; Hu, Y.

2015-12-01

In CALIPSO Level 2 aerosol data, dust particles are classified into two subtypes, namely, pure dust and polluted dust based on lidar backscatter, depolarization ratio and surface types. In this research, the polluted dust subtype is found to have two distinct modes in terms of integrated depolarization ratio (IDR) and integrated total color ratio (ICR). Dust with smaller IDR and ICR occurs mainly over areas with strong smoke emissions such as industrial cities. This kind of polluted dust originating from East Asia is also found over the Pacific Ocean. In contrast, the other type originating from the Saharan desert with larger IDR and ICR occurs mainly over the Atlantic Ocean. The disparities of IDR and ICR may result from different pollutants. The polluted dust with smaller ICR and IDR should have stronger absorption of light and may contain black carbon. Other chemical compounds such as sea salts may account for polluted dust with larger ICR and IDR. To further separate the types of polluted dust, cluster analysis is applied to determine the centroid of each type in terms of IDR and ICR. Furthermore, scattering models of dust mixed with various pollutants are constructed to be included in a CALIPSO simulator. The simulated IDR and ICR values are compared with data to retrieve the chemical compositions of polluted dust. The difference of polluted dust over the Pacific and Atlantic Ocean provides new evidence about long-range transport of Asian dust to North America. The distribution of dust polluted by black carbon is determined, which can improve knowledge about the effect of black carbon on the earth's radiation budget.

The transition of renal histopathology after immunosuppressive therapy in a woman with renal limited ANCA-associated vasculitis: a case report and literature review.

PubMed

Li, Xiang-Yang; Liang, Ying-Shan; Pai, Pearl

2016-01-01

The kidneys are frequently involved in antineutrophil cytoplasmic autoantibody (ANCA) associated small-vessel vasculitis (AASVV). The pathological hallmark of ANCA-associated glomerulonephritis (AAGN) is a pauci-immune necrotising crescentic glomerulonephritis. The histopathology of AAGN may change during the course of the disease as a consequence of immunosuppressive therapy. Herein, we report the pathological evolution of a case of AAGN. We report a female presented with renal-limited AASVV, hypocomplementemia and nephrotic syndrome. The first renal biopsy revealed "crescentic" changes at presentation, but after treatment with immunosuppressive treatment, a second renal biopsy four years later showed "mixed" changes of AAGN and immune complex deposition mimicking a mesangial proliferative glomerulonephritis. A literature review was undertaken in order to understand these transformations and factors which determine the pathological transitions. AAGN is commonly described as a pauci-immune necrotising crescentic glomerulonephritis, but immune complex depositions have been frequently identified under electronic microscopy and is associated with greater levels of proteinuria. Acute lesions such as fibrinoid necrosis or glomerular crescent may completely disappear or reduce significantly after immunosuppressive therapy, but chronic changes may increase over time. Based on our review and the illustration of this case, the initial histopathology of an AAGN and its active fibrinoid necrosis and cellular glomerular crescent may disappear or resolve after immunosuppressive therapy with resulting non-distinctive feature. Understanding the transition may facilitate the clinical diagnosis and provide further insight into this disease.

Terahertz response of fractal meta-atoms based on concentric rectangular square resonators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Zhiqiang; Zhao, Zhenyu, E-mail: zyzhao@shnu.edu.cn; Shi, Wangzhou

We investigate the terahertz electromagnetic responses of fractal meta-atoms (MAs) induced by different mode coupling mechanisms. Two types of MAs based on concentric rectangular square (CRS) resonators are presented: independent CRS (I-CRS) and junctional-CRS (J-CRS). In I-CRS, each resonator works as an independent dipole so as to result in the multiple resonance modes when the fractal level is above 1. In J-CRS, however, the generated layer is rotated by π/2 radius to the adjacent CRS in one MA. The multiple resonance modes are coupled into a single mode resonance. The fractal level increasing induces resonance modes redshift in I-CRS whilemore » blueshift in J-CRS. When the fractal level is below 4, the mode Q factor of J-CRS is in between the two modes of I-CRS; when the fractal level is 4 or above, the mode Q factor of J-CRS exceeds the two modes of I-CRS. Furthermore, the modulation depth (MD) decreases in I-CRS while it increases in J-CRS with the increase in fractal levels. The surface currents analysis reveals that the capacitive coupling of modes in I-CRS results in the modes redshift, while the conductive coupling of modes in J-CRS induces the mode blueshift. A high Q mode with large MD can be achieved via conductive coupling between the resonators of different scales in a fractal MA.« less

Effects of TJN-598, a new selective phosphodiesterase type IV inhibitor on anti-Thy1 nephritis in rats.

PubMed

Sadakane, Chiharu; Kase, Yoshio; Koseki, Junichi; Hasegawa, Yoshihiro; Shindo, Shoichiro; Maruyama, Hirobumi; Takeda, Shuichi; Takeda, Hiroshi; Hattori, Tomohisa

2011-02-01

Phosphodiesterase type IV (PDEIV) plays an important role in the immune response and inflammation. However, it is well known that classical PDEIV inhibitors have systemic side effects, so the clinical and chronic use of these agents as therapy for glomerulonephritis is difficult. This study was performed to elucidate the anti-nephritic effects of TJN-598, a new chemical compound derived from herbal components, on experimental mesangial proliferative glomerulonephritis. We first examined the effects of TJN-598 and captopril on mesangial expansion induced by anti-Thy1 serum in rats. Second, to investigate the effects of TJN-598 and rolipram, which are typical PDEIV inhibitors, on the production of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1, glomeruli were isolated from rats with anti-Thy1 nephritis and incubated with the test drugs in vitro for 48 h. Treatment with TJN-598 prevented an increase in the mesangial area/total glomerular area, in the number of cells in the glomerular cross section and matrix index. TJN-598 also inhibited the increases in the expression of α-smooth muscle actin, the TGF-β1-positive area, in the number of ED-1 positive cells and proliferating cell nuclear antigen-positive cells in the glomeruli. Furthermore, administration of TJN-598 inhibited increases in the levels of TGF-β1 protein derived from glomeruli with anti-Thy-1 nephritis. The addition of both TJN-598 and rolipram to the culture supernatant inhibited both increased expression of TGF-β1 and increases in levels of TNF-α in glomeruli isolated from rats with anti-Thy1 nephritis in a dose-dependent manner. These results suggest that TJN-598, a PDEIV inhibitor, is effective against expansion of mesangial cells, via the suppression of secretion of TGF-β1 and TNF-α from inflamed glomeruli.

A role for the geomagnetic field in cell regulation.

PubMed

Liboff, A R

2010-08-01

We advance the hypothesis that biological systems utilize the geomagnetic field (GMF) for functional purposes by means of ion cyclotron resonance-like (ICR) mechanisms. Numerous ICR-designed experiments have demonstrated that living things are sensitive, in varying degrees, to magnetic fields that are equivalent to both changes in the general magnetostatic intensity of the GMF, as well as its temporal perturbations. We propose the existence of ICR-like cell regulation processes, homologous to the way that biochemical messengers alter the net biological state through competing processes of enhancement and inhibition. In like manner, combinations of different resonance frequencies all coupled to the same local magnetic field provide a unique means for cell regulation. Recent work on ultraweak ICR magnetic fields by Zhadin and others fits into our proposed framework if one assumes that cellular systems generate time-varying electric fields of the order 100 mV/cm with bandwidths that include relevant ICR frequencies.

Fast neutral beam ion source coupled to a Fourier transform ion cyclotron resonance mass spectrometer

NASA Astrophysics Data System (ADS)

Hill, Nicholas C.; Limbach, Patrick A.; Shomo, Ronald E., II; Marshall, Alan G.; Appelhans, Anthony D.; Delmore, James E.

1991-11-01

The coupling of an autoneutralizing SF-6 fast ion-beam gun to a Fourier transform ion cyclotron resonance (FT/ICR) mass spectrometer is described. The fast neutral beam provides for secondary-ion-type FT/ICR mass analysis [e.g., production of abundant pseudomolecular (M+H)+ ions] of involatile samples without the need for external ion injection, since ions are formed at the entrance to the ICR ion trap. The design, construction, and testing of the hybrid instrument are described. The feasibility of the experiment (for both broadband and high-resolution FT/ICR positive-ion mass spectra) is demonstrated with tetra-butylammonium bromide and a Tylenol■ sample. The ability to analyze high molecular weight polymers with high mass resolution is demonstrated for Teflon■. All of the advantages of the fast neutral beam ion source previously demonstrated with quadrupole mass analysis are preserved, and the additional advantages of FT/ICR mass analysis (e.g., high mass resolving power, ion trapping) are retained.

77 FR 40611 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

...In compliance with the Paperwork Reduction Act (PRA), this document announces that EPA is planning to submit a request to renew an existing approved Information Collection Request (ICR) to the Office of Management and Budget (OMB). This ICR is scheduled to expire on November 30, 2012. Before submitting the ICR to OMB for review and approval, EPA is soliciting comments on specific aspects of the proposed information collection as described below.

Functional Groups and Structural Insights of Water-Soluble Organic Carbon using Ultrahigh Resolution FT-ICR Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Mazzoleni, L. R.; Habib, D.; Zhao, Y.; Dalbec, M.; Samburova, V.; Hallar, G.; Zielinska, B.; Lowenthal, D.

2013-12-01

Water-soluble organic carbon (WSOC) is a complex mixture of thousands of organic compounds which may have significant influence on the climate-relevant properties of atmospheric aerosols. An improved understanding of the molecular composition of WSOC is needed to evaluate the effect of aerosol composition upon aerosol physical properties. Products of gas phase, aqueous phase and particle phase reactions contribute to pre-existing aerosol organic mass or nucleate new aerosol particles. Thus, ambient aerosols carry a complex array of WSOC components with variable chemical signatures depending upon its origin and aerosol life-cycle processes. In this work, ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was used to characterize aerosol WSOC collected during the summer of 2010 at the Storm Peak Laboratory (3210 m a.s.l.) near Steamboat Springs, CO. Approximately 4000 molecular formulas were assigned in the mass range of m/z 100-800 after negative-ion electrospray ionization. The observed trends indicate significant non-oxidative accretion reaction pathways for the formation of high molecular weight WSOC components closely associated with terpene ozonolysis secondary organic aerosol (SOA). The aerosol WSOC was further characterized using ultrahigh resolution tandem MS analysis with infrared multiphoton dissociation to determine the functional groups and structural properties of 1700 WSOC species up to m/z 600. Due to the complex nature of the WSOC, multiple precursor ions were simultaneously fragmented. The exact mass measurements of the precursor and product ions facilitated molecular formula assignments and matching of neutral losses. The most important neutral losses are CO2, H2O, CH3OH, HNO3, CH3NO3, SO3 and SO4. The presence and frequency of these losses indicate the type of functional groups contained in the precursor structures. Consistent with the acidic nature of WSOC compounds, the most frequently observed losses

Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

PubMed Central

Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei

2013-01-01

Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models. PMID:22788986

Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression.

PubMed

Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei; Zou, Xiaohui

2013-01-01

Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models.

75 FR 34110 - Agency Information Collection Activities; Proposed Collection; Comment Request; Performance...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

...; Performance Evaluation Studies on Wastewater Laboratories (Renewal) AGENCY: Environmental Protection Agency... Evaluation Studies on Wastewater Laboratories (Renewal) ICR numbers: EPA ICR No. 0234.10, OMB Control No...

Development of an Electromechanical Grade to Assess Human Knee Articular Cartilage Quality.

PubMed

Sim, Sotcheadt; Hadjab, Insaf; Garon, Martin; Quenneville, Eric; Lavigne, Patrick; Buschmann, Michael D

2017-10-01

Quantitative assessments of articular cartilage function are needed to aid clinical decision making. Our objectives were to develop a new electromechanical grade to assess quantitatively cartilage quality and test its reliability. Electromechanical properties were measured using a hand-held electromechanical probe on 200 human articular surfaces from cadaveric donors and osteoarthritic patients. These data were used to create a reference electromechanical property database and to compare with visual arthroscopic International Cartilage Repair Society (ICRS) grading of cartilage degradation. The effect of patient-specific and location-specific characteristics on electromechanical properties was investigated to construct a continuous and quantitative electromechanical grade analogous to ICRS grade. The reliability of this novel grade was assessed by comparing it with ICRS grades on 37 human articular surfaces. Electromechanical properties were not affected by patient-specific characteristics for each ICRS grade, but were significantly different across the articular surface. Electromechanical properties varied linearly with ICRS grade, leading to a simple linear transformation from one scale to the other. The electromechanical grade correlated strongly with ICRS grade (r = 0.92, p < 0.0001). Additionally, the electromechanical grade detected lesions that were not found visually. This novel grade can assist the surgeon in assessing human knee cartilage by providing a quantitative and reliable grading system.

Effects of Nesting Material on Energy Homeostasis in BALB/cAnNCrl, C57BL/6NCrl, and Crl:CD1(ICR) Mice Housed at 20 °C.

PubMed

Johnson, Jay S; Taylor, Daniel J; Green, Angela R; Gaskill, Brianna N

2017-05-01

Discrepancies exist between the preferred temperature range for mice (26 to 32 °C) and current recommendations (20 to 26 °C), which may alter metabolism and negatively affect studies using mice. Previous research indicates that nesting material can alleviate cold stress in mice; therefore, we sought to determine the effects of the amount of nesting material provided (0, 6, or 12 g) on heat energy loss and energy balance in 3 mouse strains housed at currently recommended temperatures during the daytime, a period of presumed inactivity. Groups of BALB/cAnNCrl, C57BL/6NCrl, and Crl:CD1(ICR) mice, balanced by strain and sex, were group-housed and provided 0, 6, or 12 g of nesting material. After a 3-d acclimation period, body weight was determined daily at 0800, food intake was determined at 0800 and 2000, and total heat production was evaluated from 0800 to 2000 on 4 consecutive days and used to calculate energy balance and the respiratory quotient. Although the amount of nesting material had no overall effect on food intake or heat production, mice provided 12 g of nesting material had greater weight gain than those given 0 or 6 g. This increase in body weight might have been due to improved energy balance, which was corroborated by an increased respiratory quotient in mice provided 12 g of nesting material. In summary, although heat production did not differ, providing 12 g of nesting material improved energy balance, likely leading to an increase in body weight during the 0800-2000 testing period.

Injection of Mesenchymal Stem Cells as a Supplementary Strategy of Marrow Stimulation Improves Cartilage Regeneration After Lateral Sliding Calcaneal Osteotomy for Varus Ankle Osteoarthritis: Clinical and Second-Look Arthroscopic Results.

PubMed

Kim, Yong Sang; Koh, Yong Gon

2016-05-01

To compare the clinical and second-look arthroscopic outcomes in patients undergoing arthroscopic marrow stimulation combined with lateral sliding calcaneal osteotomy for varus ankle osteoarthritis, with or without adipose-derived mesenchymal stem cell (MSC) injection. In this retrospective comparative study, 49 patients with varus ankle osteoarthritis underwent second-look arthroscopy after arthroscopic marrow stimulation combined with lateral sliding calcaneal osteotomy between January 2010 and November 2012; 23 ankles underwent marrow stimulation alone (group 1), and 26 underwent marrow stimulation with MSC injection (group 2). The decision whether to receive the MSC injection, which was free of charge, was solely up to the patients. Second-look arthroscopies were performed at a mean of 12.5 months and 12.4 months postoperatively in group 1 and group 2, respectively. Clinical outcome measures included a visual analog scale (VAS) score for pain and the American Orthopaedic Foot & Ankle Society (AOFAS) score. The radiologic outcome variable was the talar tilt angle. On second-look arthroscopy, cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) grade. The mean VAS score improved significantly from 7.3 ± 0.9 to 3.9 ± 1.2 in group 1 and from 7.4 ± 0.8 to 3.1 ± 1.5 in group 2 at final follow-up (P < .001 for both groups). The mean AOFAS score also improved significantly from 64.4 ± 4.1 to 79.6 ± 7.7 in group 1 and from 63.5 ± 4.2 to 84.2 ± 7.9 in group 2 at final follow-up (P < .001 for both groups). The VAS and AOFAS scores were significantly better in group 2 than in group 1 (P = .040 and P = .047, respectively). ICRS grades were significantly correlated with clinical outcomes in both groups (all P < .05), and there were significant differences in ICRS grades between the groups (P < .05). The mean talar tilt angle improved significantly after lateral sliding calcaneal osteotomy in both groups and was significantly

Engineering Vaccines to Reprogram Immunity against Head and Neck Cancer.

PubMed

Tan, Y S; Sansanaphongpricha, K; Prince, M E P; Sun, D; Wolf, G T; Lei, Y L

2018-06-01

The recent Food and Drug Administration's approval of monoclonal antibodies targeting immune checkpoint receptors (ICRs) for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) offers exciting promise to improve patient outcome and reduce morbidities. A favorable response to ICR blockade relies on an extensive collection of preexisting tumor-specific T cells in the tumor microenvironment (TME). ICR blockade reinvigorates exhausted CD8 + T cells and enhances immune killing. However, resistance to ICR blockade is observed in about 85% of patients with HNSCC, therefore highlighting the importance of characterizing the mechanisms underlying HNSCC immune escape and exploring combinatorial strategies to sensitize hypoimmunogenic cold HNSCC to ICR inhibition. Cancer vaccines are designed to bypass the cold TME and directly deliver cancer antigens to antigen-presenting cells (APCs); these vaccines epitomize a priming strategy to synergize with ICR inhibitors. Cancer cells are ineffective antigen presenters, and poor APC infiltration as well as the M2-like polarization in the TME further dampens antigen uptake and processing, both of which render ineffective innate and adaptive immune detection. Cancer vaccines directly activate APC and expand the tumor-specific T-cell repertoire. In addition, cancer vaccines often contain an adjuvant, which further improves APC function, promotes epitope spreading, and augments host intrinsic antitumor immunity. Thus, the vaccine-induced immune priming generates a pool of effectors whose function can be enhanced by ICR inhibitors. In this review, we summarize the major HNSCC immune evasion strategies, the ongoing effort toward improving HNSCC vaccines, and the current challenges limiting the efficacy of cancer vaccines.

Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity.

PubMed

Mathes, Wendy Foulds; Nehrenberg, Derrick L; Gordon, Ryan; Hua, Kunjie; Garland, Theodore; Pomp, Daniel

2010-07-11

Dysregulation of the dopamine system is linked to various aberrant behaviors, including addiction, compulsive exercise, and hyperphagia leading to obesity. The goal of the present experiments was to determine how dopamine contributes to the expression of opposing phenotypes, excessive exercise and obesity. We hypothesized that similar alterations in dopamine and dopamine-related gene expression may underly obesity and excessive exercise, as competing traits for central reward pathways. Moreover, we hypothesized that selective breeding for high levels of exercise or obesity may have influenced genetic variation controlling these pathways, manifesting as opposing complex traits. Dopamine, dopamine-related peptide concentrations, and gene expression were evaluated in dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively bred for high rates of wheel running (HR) or obesity (M16), and the non-selected ICR strain from which these lines were derived. HPLC analysis showed significantly greater neurotransmitter concentrations in DS and NA of HR mice compared to M16 and ICR. Microarray analysis showed significant gene expression differences between HR and M16 compared to ICR in both brain areas, with changes revealed throughout the dopamine pathway including D1 and D2 receptors, associated G-proteins (e.g., Golf), and adenylate cyclase (e.g., Adcy5). The results suggest that similar modifications within the dopamine system may contribute to the expression of opposite phenotypes in mice, demonstrating that alterations within central reward pathways can contribute to both obesity and excessive exercise. Copyright 2010 Elsevier B.V. All rights reserved.

78 FR 35287 - Agency Information Collection Activities; Proposed Collection; Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

...In compliance with the requirement for opportunity for public comment on proposed data collection projects (Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995), the Health Resources and Services Administration (HRSA) announces plans to submit an Information Collection Request (ICR), described below, to the Office of Management and Budget (OMB). Prior to submitting the ICR to OMB, HRSA seeks comments from the public regarding the burden estimate, below, or any other aspect of the ICR.

76 FR 51362 - Agency Information Collection Activities; Proposed Collection; Comment Request; Recordkeeping and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

...In compliance with the Paperwork Reduction Act (PRA) (44 U.S.C. 3501 et seq.), this document announces that EPA is planning to submit a request to renew an existing Information Collection Request (ICR) to the Office of Management and Budget (OMB). This ICR is scheduled to expire on December 31, 2011. Before submitting the ICR to OMB for review and approval, EPA is soliciting comments on specific aspects of the proposed information collection as described below.

77 FR 9233 - Agency Information Collection Activities; Proposed Collection; Comment Request; Reporting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

...In compliance with the Paperwork Reduction Act (PRA) (44 U.S.C. 3501 et seq.), this document announces that EPA is planning to submit a request to renew an existing approved Information Collection Request (ICR) to the Office of Management and Budget (OMB). This ICR is scheduled to expire on April 30, 2012. Before submitting the ICR to OMB for review and approval, EPA is soliciting comments on specific aspects of the proposed information collection as described below.

78 FR 69695 - Agency Information Collection Activities: Proposed Collection: Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

...In compliance with the requirement for opportunity for public comment on proposed data collection projects (Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995), the Health Resources and Services Administration (HRSA) announces plans to submit an Information Collection Request (ICR), described below, to the Office of Management and Budget (OMB). Prior to submitting the ICR to OMB, HRSA seeks comments from the public regarding the burden estimate, below, or any other aspect of the ICR.

75 FR 5786 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

... 2060-0038 AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: In compliance with... 2060-0038. ICR Status: This ICR is scheduled to expire on March 31, 2010. Under OMB [[Page 5787...

Experts' understanding of partial derivatives using the partial derivative machine

NASA Astrophysics Data System (ADS)

Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

2015-12-01

[This paper is part of the Focused Collection on Upper Division Physics Courses.] Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of students in STEM disciplines. In this paper, we report on an initial study of expert understanding of partial derivatives across three disciplines: physics, engineering, and mathematics. We report on the central research question of how disciplinary experts understand partial derivatives, and how their concept images of partial derivatives differ, with a focus on experimentally measured quantities. Using the partial derivative machine (PDM), we probed expert understanding of partial derivatives in an experimental context without a known functional form. In particular, we investigated which representations were cued by the experts' interactions with the PDM. Whereas the physicists and engineers were quick to use measurements to find a numeric approximation for a derivative, the mathematicians repeatedly returned to speculation as to the functional form; although they were comfortable drawing qualitative conclusions about the system from measurements, they were reluctant to approximate the derivative through measurement. On a theoretical front, we found ways in which existing frameworks for the concept of derivative could be expanded to include numerical approximation.

Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease

ClinicalTrials.gov

2014-04-16

Proteinuric Kidney Disease; Diabetic Nephropathy; Hypertensive Nephrosclerosis; IgA Nephropathy; Focal Segmental Glomerulosclerosis; Glomerulopathy (Obesity-associated); Glomerulonephritis, Membranous

Probing interaction of a fluorescent ligand with HIV TAR RNA

NASA Astrophysics Data System (ADS)

Qi, Liang; Zhang, Jing; He, Tian; Huo, Yuan; Zhang, Zhi-Qi

2017-02-01

Trans-activator of Transcription (Tat) antagonists could block the interaction between Tat protein and its target, trans-activation responsive region (TAR) RNA, to inhibit Tat function and prevent human immunodeficiency virus type 1 (HIV-1) replication. For the first time, a small fluorescence ligand, ICR 191, was found to interact with TAR RNA at the Tat binding site and compete with Tat. It was also observed that the fluorescence of ICR 191 could be quenched when binding to TAR RNA and recovered when discharged via competition with Tat peptide or a well-known Tat inhibitor, neomycin B. The binding parameters of ICR 191 to TAR RNA were determined through theoretical calculations. Mass spectrometry, circular dichroism and molecular docking were used to further confirm the interaction of ICR 191 with TAR RNA. Inspired by these discoveries, a primary fluorescence model for the discovery of Tat antagonists was built using ICR 191 as a fluorescence indicator and the feasibility of this model was evaluated. This ligand-RNA interaction could provide a new strategy for research aimed at discovering Tat antagonists.

Influence of gene dosage and autoregulation of the regulatory genes INO2 and INO4 on inositol/choline-repressible gene transcription in the yeast Saccharomyces cerevisiae.

PubMed

Schwank, S; Hoffmann, B; Sch-uller, H J

1997-06-01

Expression of structural genes of phospholipid biosynthesis in yeast is mediated by the inositol/choline-responsive element (ICRE). ICRE-dependent gene activation, requiring the regulatory genes INO2 and INO4, is repressed in the presence of the phospholipid precursors inositol and choline. INO2 and, to a less extent, INO4 are positively autoregulated by functional ICRE sequences in the respective upstream regions. However, an INO2 allele devoid of its ICRE functionally complemented an ino2 mutation and completely restored inositol/choline regulation of Ino2p-dependent reporter genes. Low-level expression of INO2 and INO4 genes, each under control of the heterologous MET25 promoter, did not alter the regulatory pattern of target genes. Thus, upstream regions of INO2 and INO4 are not crucial for transcriptional control of ICRE-dependent genes by inositol and choline. Interestingly, over-expression of INO2, but not of INO4, counteracted repression by phospholipid precursors. Possibly, a functional antagonism between INO2 and a negative regulator is the key event responsible for repression or de-repression.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, N.C.; Limbach, P.A.; Shomo, R.E. II

The coupling of an autoneutralizing SF{sup {minus}}{sub 6} fast ion-beam gun to a Fourier transform ion cyclotron resonance (FT/ICR) mass spectrometer is described. The fast neutral beam provides for secondary-ion-type FT/ICR mass analysis (e.g., production of abundant pseudomolecular (M+H){sup +} ions) of involatile samples without the need for external ion injection, since ions are formed at the entrance to the ICR ion trap. The design, construction, and testing of the hybrid instrument are described. The feasibility of the experiment (for both broadband and high-resolution FT/ICR positive-ion mass spectra) is demonstrated with {ital tetra}-butylammonium bromide and a Tylenol{sup ( )} sample.more » The ability to analyze high molecular weight polymers with high mass resolution is demonstrated for Teflon{sup ( )}. All of the advantages of the fast neutral beam ion source previously demonstrated with quadrupole mass analysis are preserved, and the additional advantages of FT/ICR mass analysis (e.g., high mass resolving power, ion trapping) are retained.« less

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Endoscopic Recurrence 6 Months After Ileocecal Resection in Children With Crohn Disease Treated With Azathioprine.

PubMed

Zarubova, Kristyna; Hradsky, Ondrej; Copova, Ivana; Rouskova, Blanka; Pos, Lucie; Skaba, Richard; Bronsky, Jiri

2017-08-01

Intestinal surgery is an important part of Crohn disease (CD) treatment in children. The aim of the present study was to compare the rate of endoscopic recurrence at the sixth month after ileocecal resection (ICR) in children with CD treated with azathioprine between patients who received prior antitumor necrosis factor alpha (anti-TNF-α) therapy and those who were not administered this therapy. Moreover, we tried to identify the potential risk factors for disease recurrence and describe the schedule of long-term follow-up after surgery. We prospectively collected data from pediatric patients with CD, who underwent ICR between October 2011 and June 2015 at our hospital and were treated with azathioprine monotherapy after ICR. We evaluated the endoscopic recurrence (Rutgeerts score) at the sixth month after ICR in all included patients. Among 21 included patients, 13 achieved endoscopic remission (Rutgeerts score < i2) at the sixth month after ICR. No difference was found between patients who received prior anti-TNF-α therapy and those who did not. We did not find any clinically relevant factors associated with endoscopic recurrence rate at the sixth month. Prior anti-TNF-α therapy does not seem to be a strong risk factor for endoscopic recurrence within 6 months after ICR. Further studies on large sample of patients are needed to identify potential predictors of disease recurrence.

Dissecting the relationship between obesity and hyperinsulinemia: Role of insulin secretion and insulin clearance.

PubMed

Kim, Mee Kyoung; Reaven, Gerald M; Kim, Sun H

2017-02-01

The aim of this study was to better delineate the complex interrelationship among insulin resistance (IR), secretion rate (ISR), and clearance rate (ICR) to increase plasma insulin concentrations in obesity. Healthy volunteers (92 nondiabetic individuals) had an insulin suppression test to measure IR and graded-glucose infusion test to measure ISR and ICR. Obesity was defined as a body mass index (BMI) ≥30 kg/m 2 , and IR was defined as steady-state plasma glucose (SSPG) ≥10 mmol/L during the insulin suppression test. Plasma glucose and insulin concentrations, ISR, and ICR were compared in three groups: insulin sensitive/overweight; insulin sensitive/obesity; and insulin resistant/obesity. Compared with the insulin-sensitive/overweight group, the insulin-sensitive/obesity had significantly higher insulin area under the curve (AUC) and ISR AUC during the graded-glucose infusion test (P < 0.001). Glucose AUC and ICR were similar. The insulin-resistant/obesity group had higher insulin AUC and ISR AUC compared with the insulin-sensitive/obesity but also had higher glucose AUC and decreased ICR (P < 0.01). In multivariate analysis, both BMI and SSPG were significantly associated with ISR. Plasma insulin concentration and ISR are increased in individuals with obesity, irrespective of degree of IR, but a decrease in ICR is confined to the subset of individuals with IR. © 2016 The Obesity Society.

An active immune defense with a minimal CRISPR (clustered regularly interspaced short palindromic repeats) RNA and without the Cas6 protein.

PubMed

Maier, Lisa-Katharina; Stachler, Aris-Edda; Saunders, Sita J; Backofen, Rolf; Marchfelder, Anita

2015-02-13

The prokaryotic immune system CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) is a defense system that protects prokaryotes against foreign DNA. The short CRISPR RNAs (crRNAs) are central components of this immune system. In CRISPR-Cas systems type I and III, crRNAs are generated by the endonuclease Cas6. We developed a Cas6b-independent crRNA maturation pathway for the Haloferax type I-B system in vivo that expresses a functional crRNA, which we termed independently generated crRNA (icrRNA). The icrRNA is effective in triggering degradation of an invader plasmid carrying the matching protospacer sequence. The Cas6b-independent maturation of the icrRNA allowed mutation of the repeat sequence without interfering with signals important for Cas6b processing. We generated 23 variants of the icrRNA and analyzed them for activity in the interference reaction. icrRNAs with deletions or mutations of the 3' handle are still active in triggering an interference reaction. The complete 3' handle could be removed without loss of activity. However, manipulations of the 5' handle mostly led to loss of interference activity. Furthermore, we could show that in the presence of an icrRNA a strain without Cas6b (Δcas6b) is still active in interference. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

An Active Immune Defense with a Minimal CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) RNA and without the Cas6 Protein*

PubMed Central

Maier, Lisa-Katharina; Stachler, Aris-Edda; Saunders, Sita J.; Backofen, Rolf; Marchfelder, Anita

2015-01-01

The prokaryotic immune system CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) is a defense system that protects prokaryotes against foreign DNA. The short CRISPR RNAs (crRNAs) are central components of this immune system. In CRISPR-Cas systems type I and III, crRNAs are generated by the endonuclease Cas6. We developed a Cas6b-independent crRNA maturation pathway for the Haloferax type I-B system in vivo that expresses a functional crRNA, which we termed independently generated crRNA (icrRNA). The icrRNA is effective in triggering degradation of an invader plasmid carrying the matching protospacer sequence. The Cas6b-independent maturation of the icrRNA allowed mutation of the repeat sequence without interfering with signals important for Cas6b processing. We generated 23 variants of the icrRNA and analyzed them for activity in the interference reaction. icrRNAs with deletions or mutations of the 3′ handle are still active in triggering an interference reaction. The complete 3′ handle could be removed without loss of activity. However, manipulations of the 5′ handle mostly led to loss of interference activity. Furthermore, we could show that in the presence of an icrRNA a strain without Cas6b (Δcas6b) is still active in interference. PMID:25512373

Interpretive Experiments: An Interpretive Experiment in Ion Cyclotron Resonance Spectroscopy.

ERIC Educational Resources Information Center

Burnier, R. C.; Freiser, B. S.

1979-01-01

Provides a discussion which is intended for chemistry college students on the ion cyclotron resonance (ICR) spectroscopy, the physical basis for ion cyclotron resonance, and the experimental methodology employed by ICR spectroscopists. (HM)

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2012-05-04

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Isolated cognitive relapses in multiple sclerosis.

PubMed

Pardini, Matteo; Uccelli, Antonio; Grafman, Jordan; Yaldizli, Özgür; Mancardi, Gianluigi; Roccatagliata, Luca

2014-09-01

While cognition can be affected during sensorimotor multiple sclerosis (MS) relapses, the relevance of isolated cognitive relapses (ICRs ie, those occurring in absence of new sensorimotor symptoms) remain poorly characterised. Here, we decided to explore the relationship between ICR, subjective evaluation of cognitive performance and long-term cognitive decline in a group of subjects with relapsing-remitting MS. We analysed the cognitive performance of 99 clinically stable relapsing-remitting MS for whom data from four consequent clinical and cognitive evaluations were available, that is, a baseline evaluation (t₀), followed in the subsequent 6 months by a second evaluation performed not later than 2 weeks after a routine brain scan positive for at least one area of gadolinium enhancement (t₁) and two gadolinium enhancement-negative follow-up evaluations after 6 months (t₂) and 1 year (t₃) from t₁. Based on published literature, we defined as a meaningful change in cognition a transient reduction of Symbol Digit Modalities Test score of at least four points at t₁ compared with t₀ and t₂. ICRs were found in 17 patients and were not associated with subjective cognitive deficits or depression. Subjects who presented with an ICR at t₁ presented with a significantly reduced cognitive performance at the follow-up evaluations compared with patients without ICR. We showed that ICRs were not associated with changes in mood, fatigue levels or cognitive performance self-evaluations. Our study introduces an operational definition of ICRs and suggests to their role as a factor for cognitive decline in MS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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[Kidney involvement in rheumatoid arthritis].

PubMed

Icardi, A; Araghi, P; Ciabattoni, M; Romano, U; Lazzarini, P; Bianchi, G

2003-01-01

Rheumatoid Arthritis (RA) is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively), followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy). Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs) nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept) are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment), followed by minimal change glomerulopathy (3-14%) and p-ANCA positive necrotizing crescentic glomerulonephritis.

Anti-GBM disease and ANCA during dengue infection.

PubMed

Lizarraga, Karlo J; Florindez, Jorge A; Daftarian, Pirouz; Andrews, David M; Ortega, Luis M; Mendoza, Jair Munoz; Contreras, Gabriel N; Nayer, Ali

2015-02-01

Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells.

PubMed

Lumsden, Amanda L; Ma, Yuefang; Ashander, Liam M; Stempel, Andrew J; Keating, Damien J; Smith, Justine R; Appukuttan, Binoy

2018-05-09

Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized. To address this issue, we undertook a comprehensive in silico analysis of the human ICR gene promoter region. We used genomic evolutionary rate profiling to identify a 115 base pair (bp) sequence within 500 bp upstream of the transcription start site of the annotated human ICR gene that was conserved across 25 eutherian genomes. A second constrained sequence upstream of the orthologous mouse gene (68 bp; conserved across 27 Eutherian genomes including human) was also discovered. Searching these elements identified 33 matrices predictive of binding sites for transcription factors known to be responsive to a broad range of pathological stimuli, including hypoxia, and metabolic and inflammatory proteins. Five phenotype-associated single nucleotide polymorphisms (SNPs) in the immediate vicinity of these elements included four SNPs (i.e. rs2569693, rs281439, rs281440 and rs11575074) predicted to impact binding motifs of transcription factors, and thus the expression of ICR and ICAM-1 genes, with potential to influence disease susceptibility. We verified that human retinal endothelial cells expressed ICR, and observed induction of expression by tumor necrosis factor-α.

Characteristics of walking, activity, fear of falling, and falls in community-dwelling older adults by residence.

PubMed

Wert, David M; Talkowski, Jaime B; Brach, Jennifer; VanSwearingen, Jessie

2010-01-01

Research focusing on community-dwelling older adults includes adults living in senior living residences (SLR) and independent community residences (ICR). Walking, physical activity, fear of falling, and fall history may differ on the basis of residence. We describe characteristics of walking, physical activity, fear of falling, and fall history between community-dwelling older adults by residence. Participants of this secondary analysis included community-dwelling older adults from independent living units within a senior life care community (SLR) and older adults recruited from the Pittsburgh community (ICR). Demographic information and physical (gait speed and physical activity), psychosocial (fear of falling and confidence in walking), and fall history measures were collected. Adults living in SLR compared with those in ICR were older, were more likely to live alone, and had greater disease burden. Compared with individuals in ICR, individuals in SLR reported less fear of falling (Survey of Activity and Fear of Falling in the Elderly tool fear results 0.24 and 0.50, respectively). Fewer older adults in SLR compared with those in ICR reported falling in the past year. Older adults living in SLR compared with those in ICR had similar physical function but differed in report of fear of falling and fall history. Recognizing the possible differences in psychosocial function by place of residence is important for health care providers and researchers conducting interventions and studies for community-dwelling older adults.

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NEPHROPATHIES IN THE EUROPEAN CAPTIVE CHEETAH (ACINONYX JUBATUS) POPULATION.

PubMed

Url, Angelika; Krutak, Verena; Kübber-Heiss, Anna; Chvala-Mannsberger, Sonja; Robert, Nadia; Dinhopl, Nora; Schmidt, Peter; Walzer, Chris

2016-09-01

According to previous studies in captive cheetah ( Acinonyx jubatus ) populations, one of the most threatening diseases besides amyloidosis, myelopathy, veno occlusive disease, and gastritis, is renal failure. Contrary to captive cheetahs in North America and South Africa, morphological data concerning renal lesions in the cheetah European Endangered Species Program (EEP) are lacking. This study details the histological characterization as well as immunohistochemical and morphometrical analysis of nephropathies in 35 captive cheetahs from the EEP, which were necropsied between 1985 and 2003. Examination of paraffin- and glycolmethacrylate-methylmethacrylate (GMA-MMA) embedded kidney samples by light microscopy revealed glomerulonephritis in 91%, with a high prevalence for glomerulosclerosis and glomerulonephritis with the histologic pattern of membranous glomerulonephritis (77%). Besides these predominating glomerulopathies, a wide range of other renal lesions, like acute tubular necrosis, interstitial nephritis, calcinosis, and amyloidosis, were present. Pathological expression of collagen type IV, complement C3, fibronectin, and IgG was demonstrated in the glomeruli of the cheetah kidneys with the use of the avidin-biotin complex method. Morphometrical analysis was performed on GMA-MMA embedded kidney samples to obtain glomerulosclerosis index and glomerulosclerosis incidence.

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Nephrology key information for internists

PubMed Central

Salim, Sohail Abdul; Medaura, Juan A.; Malhotra, Bharat; Garla, Vishnu; Ahuja, Shradha; Lawson, Nicki; Pamarthy, Amaleswari; Sonani, Hardik; Kovvuru, Karthik; Palabindala, Venkataraman

2017-01-01

ABSTRACT Hospitalists and primary care physicians encounter renal disease daily. Although most cases of acute kidney injury (AKI) are secondary to dehydration and resolve by giving fluids, many cases of AKI are due to not uncommon but unfamiliar causes needing nephrology evaluation. Common indications to consult a nephrologist on an emergency basis include hyperkalemia or volume overload in end stage renal disease patients (ESRD). Other causes of immediate consultation are cresenteric glomerulonephritis / rapidly progressive glomerulonephritis in which renal prognosis of the patient depends on timely intervention. The following evidence-based key information could improve patient care and outcomes. Abbreviations: AKI: Acute kidney injury ESRD: End stage renal disease patients PMID:28638567

Membranous nephropathy associated with familial chronic ulcerative colitis in a 12-year-old girl.

PubMed

Ridder, Regina M; Kreth, Hans W; Kiss, Eva; Gröne, Hermann J; Gordjani, Nader

2005-09-01

Glomerulonephritis is a rare complication in patients with inflammatory bowel disease. We report a case of membranous nephropathy (MN) in a 12.6-year-old girl with chronic ulcerative colitis. The girl was referred to the hospital with bloody diarrhea and arthralgia. Routine urinalysis showed 1 g/m(2) protein excretion in 24 h. Serum ANCA titers were positive. The diagnoses were confirmed by coloscopy and kidney biopsy. The patient's mother had also suffered from ulcerative colitis in adolescence. Proteinuria normalized under treatment with prednisone (60 mg/m(2)/day) and azathioprine, which was initiated to treat the colitis. Chronic ulcerative colitis can be associated with glomerulonephritis.

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... Approval; Comment Request; NSPS for Commercial and Industrial Solid Waste Incineration Units (Renewal... . Title: NSPS for Commercial and Industrial Solid Waste Incineration Units (Renewal). ICR Numbers: EPA ICR.... Abstract: The New Source Performance Standards (NSPS) for Commercial and Industrial Solid Waste...

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2011-09-21

... Activities; Proposed Collection; Comment Request; Final Authorization for Hazardous Waste Management Programs... Request (ICR) concerning final authorization for State Hazardous Waste Management Programs. This ICR is... potentially affected by this action are States. Title: Final Authorization for Hazardous Waste Management...

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2011-12-28

... Activities; Proposed Collection; Comment Request; National Pollutant Discharge Elimination System (NPDES... viruses. For additional information about EPA's public docket, visit the EPA Docket Center homepage at... Pollutant Discharge Elimination System (NPDES) Program (Renewal). ICR Number: EPA ICR No. 0229.20, OMB...

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2010-01-25

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Comprehensive Data Collected from the Petroleum Refining Sector

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76 FR 37349 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

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2011-06-27

... Vegetable Oil Production (Renewal) AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY... for Solvent Extraction for Vegetable Oil Production (Renewal). ICR Numbers: EPA ICR Number 1947.05... disclose the information. Respondents/Affected Entities: Owners or operators of vegetable oil production...

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2012-06-25

... Activities; Submission to OMB for Review and Approval; Comment Request; NESHAP for Semiconductor...: NESHAP for Semiconductor Manufacturing (Renewal). ICR Numbers: EPA ICR Number 2042.05, OMB Control Number... the owners or operators of semiconductor manufacturing plants. Estimated Number of Respondents: 1...

A database application for pre-processing, storage and comparison of mass spectra derived from patients and controls

PubMed Central

Titulaer, Mark K; Siccama, Ivar; Dekker, Lennard J; van Rijswijk, Angelique LCT; Heeren, Ron MA; Sillevis Smitt, Peter A; Luider, Theo M

2006-01-01

Background Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest. Results A new database application is presented, to detect and identify significantly differentially expressed peptides in peptide profiles obtained from body fluids of patient and control groups. The presented modular software is capable of central storage of mass spectra and results in fast analysis. The software architecture consists of 4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database, which contains all metadata, such as experiment numbers and sample codes, 3) a FTP (File Transport Protocol) server to store all raw mass spectrometry files and processed data, and 4) the software package R, which is used for modular statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test. Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that peptide-profiles of two patient groups 1) breast cancer patients with leptomeningeal metastases and 2) prostate cancer patients in end stage disease can be distinguished from those of control groups. Conclusion The database application is capable to distinguish patient Matrix Assisted Laser Desorption Ionization (MALDI-TOF) peptide profiles from control groups using large size datasets. The modular architecture of the application makes it possible to adapt the application to handle also large sized data from MS/MS- and Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry

A database application for pre-processing, storage and comparison of mass spectra derived from patients and controls.

PubMed

Titulaer, Mark K; Siccama, Ivar; Dekker, Lennard J; van Rijswijk, Angelique L C T; Heeren, Ron M A; Sillevis Smitt, Peter A; Luider, Theo M

2006-09-05

Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest. A new database application is presented, to detect and identify significantly differentially expressed peptides in peptide profiles obtained from body fluids of patient and control groups. The presented modular software is capable of central storage of mass spectra and results in fast analysis. The software architecture consists of 4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database, which contains all metadata, such as experiment numbers and sample codes, 3) a FTP (File Transport Protocol) server to store all raw mass spectrometry files and processed data, and 4) the software package R, which is used for modular statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test. Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that peptide-profiles of two patient groups 1) breast cancer patients with leptomeningeal metastases and 2) prostate cancer patients in end stage disease can be distinguished from those of control groups. The database application is capable to distinguish patient Matrix Assisted Laser Desorption Ionization (MALDI-TOF) peptide profiles from control groups using large size datasets. The modular architecture of the application makes it possible to adapt the application to handle also large sized data from MS/MS- and Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry experiments. It is expected that the

Experts' Understanding of Partial Derivatives Using the Partial Derivative Machine

ERIC Educational Resources Information Center

Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

2015-01-01

Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of…

Comparison of hybrid constructs with 2-level artificial disc replacement and 2-level anterior cervical discectomy and fusion for surgical reconstruction of the cervical spine: a kinematic study in whole cadavers.

PubMed

Liu, Baoge; Zeng, Zheng; Hoof, Tom Van; Kalala, Jean Pierre; Liu, Zhenyu; Wu, Bingxuan

2015-04-08

Multi-level cervical degeneration of the spine is a common clinical pathology that is often repaired by anterior cervical discectomy and fusion (ACDF). The aim of this study was to investigate the kinematics of the cervical spine after hybrid surgery compared with 2-level ACDF. Five freshly frozen, unembalmed whole human cadavers were used including 3 males and 2 females with a mean age of 51 ± 8 years. After evaluating the intact spine for range of motion (ROM), sagittal alignment and instantaneous center of rotation (ICR), each cadaver underwent 4 consecutive surgeries: 2-level artificial disc replacement (ADR) from C4 to C6 (ADR surgery); 2-level ACDF from C4 to C6 (ACDF surgery); hybrid C4-5 ACDF and C5-6 ADR (ACDF+ADR surgery); and hybrid C4-5 ADR and C5-6 ACDF (ADR+ACDF surgery). The ROM and ICR of adjacent intact segments (C3-4; C6-7), and whole sagittal alignment were revaluated. Two-level ACDF resulted in increased ROM at C3-4 and C6-7 compared with intact spine. ROM was significantly different to intact spine using ACDF surgery at C3-C4 and C6-C7 and ROM was increased with ACDF+ADR surgery at C6-C7 (all P<0.05). No improvement in sagittal alignment was observed with any approach. The localization of the ICR shifted upwards and anteriorly at C3-C4 after reconstruction. ICR changes at C3-C4 were greatest for ADR+ACDF surgery and were significantly different to ACDF surgery (P<0.05), but not between ADR surgery and ACDF+ADR surgery. At C6-C7, the ICR was more posterior and superior than in the intact condition. The greatest change in ICR was observed in ACDF surgery at the C6-C7 level, significantly different from the other groups (P<0.05). For 2-level reconstruction, hybrid surgery and ADR did not alter ROM and minimally changed ICR at the adjacent-level. The type of surgery had a significant impact on the ICR location. This suggests that hybrid surgery may be a viable option for 2-level cervical surgery.

Growth of etiolated barley plants in weak static and 50 Hz electromagnetic fields tuned to calcium ion cyclotron resonance

PubMed Central

Pazur, Alexander; Rassadina, Valentina; Dandler, Jörg; Zoller, Jutta

2006-01-01

Background The effects of weak magnetic and electromagnetic fields in biology have been intensively studied on animals, microorganisms and humans, but comparably less on plants. Perception mechanisms were attributed originally to ferrimagnetism, but later discoveries required additional explanations like the "radical pair mechanism" and the "Ion cyclotron resonance" (ICR), primarily considered by Liboff. The latter predicts effects by small ions involved in biological processes, that occur in definite frequency- and intensity ranges ("windows") of simultaneously impacting magnetic and electromagnetic fields related by a linear equation, which meanwhile is proven by a number of in vivo and in vitro experiments. Methods Barley seedlings (Hordeum vulgare, L. var. Steffi) were grown in the dark for 5 and 6 days under static magnetic and 50 Hz electromagnetic fields matching the ICR conditions of Ca2+. Control cultures were grown under normal geomagnetic conditions, not matching this ICR. Morphology, pigmentation and long-term development of the adult plants were subsequently investigated. Results The shoots of plants exposed to Ca2+-ICR exposed grew 15–20% shorter compared to the controls, the plant weight was 10–12% lower, and they had longer coleoptiles that were adhering stronger to the primary leaf tissue. The total pigment contents of protochlorophyllide (PChlide) and carotenoids were significantly decreased. The rate of PChlide regeneration after light irradiation was reduced for the Ca2+-ICR exposed plants, also the Shibata shift was slightly delayed. Even a longer subsequent natural growing phase without any additional fields could only partially eliminate these effects: the plants initially exposed to Ca2+-ICR were still significantly shorter and had a lower chlorophyll (a+b) content compared to the controls. A continued cultivation and observation of the adult plants under natural conditions without any artificial electromagnetic fields showed a